Ethnobotany, Phytochemistry and Pharmacological Effects of Plants in Genus Cynanchum Linn. (Asclepiadaceae).

Genus Cynanchum L. belongs to the family Asclepiadaceae, which comprise more than 200 species distributed worldwide. In Chinese medical practice, numerous drugs (such as tablets and powders) containing different parts of plants of this genus are used to treat snake bites, bruises, osteoblasts, rheumatoid arthritis and tumors. A search for original articles published on the cynanchum genus was performed by using several resources, including Flora of China Official Website and various scientific databases, such as PubMed, SciFinder, the Web of Science, Science Direct, and China Knowledge Resource Integrated (CNKI). Advances in the botanical, ethnomedicinal, phytochemical, and pharmacological studies of this genus are reviewed in this paper. Results showed that more than 440 compounds, including C21 steroids, steroidal saponins, alkaloids, flavonoids and terpene, have been isolated and identified from Cynanchum plants up to now. In vivo and in vitro studies have shown that plants possess an array of biological activities, including anti-tumor, neuroprotective and anti-fungal effects. Popular traditional prescription of Cynanchum sp. was also summed up in this paper. However, many Cynanchum species have received little or no attention. Moreover, few reports on the clinical use and toxic effects of Cynanchum sp. are available. Further attention should be focused on the study of these species to gather information on their respective toxicology data and relevant quality-control measures and clinical value of the crude extracts, active compounds, and bioactive metabolites from this genus. Further research on Cynanchum sp. should be conducted, and bioactivity-guided isolation strategies should be emphasized. In addition, systematic studies of the chemical composition of plants should be enhanced.

1. Introduction

Cynanchum L. is a large genus in the Asclepiadaceae family comprising approximately 200 species. Many of these plants have been used for a long time in traditional Chinese medicine (TCM) for the treatment of common and chronic diseases. Plants of this genus are distributed worldwide, including in East Africa, the Mediterranean region, the tropical zone of Europe, and the subtropical and temperate zones of Asia [1]. A total of 53 species and 12 varieties are native to the southwestern region of China [2]. However, only 33 species of the genus Cynanchum have been systematically studied to date [3].

Cynanchum L. is an important taxonomic group in the Asclepiadaceae family because numerous species of this genus have several application prospects other than in the field of medicine. These species of Cynanchum include C. sibiricum, C. chinense, C. auriculatum, C. officinale, C. bungei, C. otophyllum, C. corymbosum, C. amplexicaule, C. forrestii, C. stauntonii, C. vincetoxicum, C. inamoenum, C. atratum (CA), C. glaucescens, C. paniculatum, C. komarovii, C. versicolor, C. chekiangense and C. mooreanum (http://frps.eflora.cn/frps/Cynanchum). These plants are traditionally used to treat snake bites, bruises, osteoblasts, rheumatoid arthritis and tumors. Some plants are poisonous; thus, they are used to kill agricultural pests and tigers because of their higher toxicity than other plants [1]. In addition, modern pharmacological studies showed that Cynanchum plants exert significant immune regulation, anti-oxidation, anti-tumor and other pharmacological effects [4].

Given the high medicinal value of anti-tumor, immune regulation and anti-oxidation of Cynanchum, a growing number of studies have been carried out on the chemical composition of the genus [5]. At present, 450 compounds from Cynanchum sp. have been isolated. Results showed that C21 steroids are the main chemical constituents of this genus, as well as acetophenones, alkaloids and certain alkyd compounds.

For our literature review, we systematically summarized the resources, folk application, chemical composition and pharmacological activity of Cynanchum, and proposed certain suggestions according to its research status to provide reference for the comprehensive development and sustainable utilization of the species in this genus.

2. Ethnomedicinal Uses

According to our review on the monographs and literature, 17 medicinal plants are included in genus Cynanchum; which are C. sibiricum, C. chinense, C. auriculatum, C. officinale, C. bungei, C. otophyllum, C. corymbosum, C. amplexicaule, C. forrestii, C. stauntonii, C. vincetoxicum, C. inamoenum, CA, C. glaucescens, C. paniculatum, C. komarovii, C. versicolor, C. chekiangense and C. mooreanum. In China, plants of genus Cynanchum are mainly distributed in the southwest, northwest and northeast provinces. In local medicine, some plant roots have been used to clear away heat evil and expel superficial evils, eliminate stasis, activate blood circulation, induce diuresis and reduce edema. This review summarizes local using of Cynanchum plants in the national medicine, as shown in Table 1.

Table 1

Traditional use of Cynanchum species in different regions of the world.

Name	Medicinal Parts	Traditional Uses	Distribution
C. sibiricum Willd.	Whole plant	Carbuncle swollen	Russia, China (Ovr Mongol, Gansu, Xinjiang)
C. chinense R. Br.	Whole plant	Wind-dispelling prescription	China (Liaoning, Hebei, Henan, Shandong, Shangxi, Ningxia, Gansu, Jiangsu, Zhejiang)
C. auriculatum Royle ex Wight	Roots	Stop coughing, cure neurasthenia, gastric and duodenal ulcers, nephritis, and so on.	India, China (Shandong, Hebei, Henan, Shanxi, Gansu, Tibet, Anhui, Jiangsu, Zhejiang, Fujian, Taiwan, Jiangxi, Hunan, Hubei, Guangxi, Guangdong, Guizhou, Sichuang, Yunnan)
C. officinale (Hemsl.) Tsiang et Zhang	Roots	Treatment of tonic analgesia, epilepsy, rabies and snake bites.	China (Shanxi, Anhui, Jiangxi, Hunan, Hubei, Guangxi, Guizhou, Sichuan, Yunnan)
C. bungei Decne.	Roots	For physically weak and insomnia, forgetful dreams, skin itching.	North Korea, China (Liaoning, OvrMongol, Hubei, Hunan, Shandong, Shanxi, Gansu).
C. otophyllum Schneid.	Roots	For rheumatoid bone pain, rubella itching, epilepsy, rabies bites, snake bites.	China (Hunan, Guangxi, Guizhou, Yunnan, Sichuan, Tibet)
C. corymbosum Wight	Whole plant	Treatment of neurasthenia, chronic nephritis, orchitis, urinary amenorrhea, tuberculosis, hepatitis and so on.	India, Burma, Laos, Vietnam, Kampuchea, Malaysia; China (Fujian, Guangxi, Guangdong, Sichuan, Yunnan)
C. wilfordii (Maxim.) Hemsl.	Roots	Injury, dysentery, infantile malnutrition, stomach pain, leucorrhea, sore ringworm.	China (Liaoning, Henan, Shandong, Shanxi, Shaanxi, Gansu, Xinjiang, Jiangsu, Anhui, Sichuan, Hunan, Hubei), North Korea, Japan.
C. amplexicaule (Sieb. et Zucc.) Hemsl. var. castaneum Makino	Whole plant	Swelling and poisoning, governance bruises, rheumatism.	North Korea, Japan, China (Heilongjiang, Liaoning)
C. forrestii Schltr. var. forrestii	Roots	Reduce pain, accelerate the healing.	Tibet, Gansu, Sichuan, Guizhou and Yunnan
C. stauntonii (Decne.) Schltr. ex Levl.	Whole plant	Treatment of lung disease, infantile malnutrition plot, cold cough and chronic bronchitis and so on.	Gansu, Anhui, Jiangsu, Zhejiang, Hunan, Jiangxi, Fujian, Guangdong, Guangxi and Guizhou.
C. vincetoxicum (L.) Pers.	Roots, seeds	Root: antiemetic; seed extract: treat cardiac failure.	China (Sichuan, Yunnan, Jiangsu and Taiwan), India and central and Western Europe
C. inamoenum (Maxim.) Loes.	Roots	Postpartum depression, pregnancy enuresis, scabies and lymphadenitis.	China (Liaoning, Hebei, Shandong, Shanxi, Anhui, Zhejiang, Hubei, Hunan, Shaanxi, Gansu, Guizhou, Sichuan, Tibet), North Korea and Japan.
C. atratum Bunge	Roots, stems	Clearing heat antitoxicant, insufficiency of vital energy and blood, fever.	China (Heilongjiang, Jilin, Shandong, Hebei, Henan, Shanxi, Shanxi, Sichuan, Guizhou, Yunnan, Guangxi, Liaoning, Guangdong, Hunan, Hubei, Fujian, Jiangxi, Jiangsu), North Korea and Japan
C. glaucesces (Decne.) Hand.-Mazz.	Roots, stems	Relieving dyspnea, antitussive and antiasthmatic.	Jiangsu, Zhejiang, Fujian, Jiangxi, Hunan, Guangdong, Guangxi and Sichuan
C. paniculatum (Bunge) Kitagawa	Roots, stems	Rheumatism, stomach pain, toothache, low back pain, flutters injury, urticaria, and eczema.	China (Liaoning, Ovr Mongol, Hebei, Henan, Shanxi, Gansu, Sichuan, Guizhou, Yunnan, Shandong, Anhui, Jiangsu, Zhejiang, Jiangxi, Shanxi, Hubei, Hunan, Guangdong and Guangxi), North Korea and Japan.
C.versicolor Bunge	Roots and stems	Reducing fever and causing diuresis, cure tuberculosis, edema, pain and so on.	China (Jilin, Liaoning, Hebei, Henan, Sichuan, Shandong, Jiangsu and Zhejiang)
C. chekiangense M. Cheng ex Tsiang et P. T. Li	Roots	Treatment of bruises, smashed topical, and scabies.	China (Zhejiang, Henan, Hunan and Guangdong)
C.mooreanum Hemsl.	Whole plant	Wash sores scabies.	China (Henan, Hubei, Hunan, Anhui, Jiangsu, Zhejiang, Jiangxi, Fujian and Guangdong)

Note: The above information was cited from the Chinese herbal and Chinese flora. References in this table was cited from the website: http://frps.eflora.cn/ and http://tool.zyy123.com/bencao/index.php.

In addition, compound medication has always been an important feature of folk medicine. Cynanchum plants and other Chinese herbs are used in a number of prescriptions, such as Baiweiwan and Baiweisan. Cynanchum plants also present a long history as a folk medicine, thus providing an important reference for clinical practice (Table 2).

Table 2

Popular traditional prescription composition of Cynanchum species.

Name	Compositions	Effect/Traditional Use	Ref.
Baiwei san	Cynanchum atratum Bunge, Zingiber officinale Rosc., Trichosanthes kirilowii Maxim., Glycyrrhiza uralensis Fisch., Mirabilite.	Antidepressant	‘Qian jin yi fang’, vol. 18
Baiwei yuan	Cynanchum atratum Bunge, Rehmannia glutinosa (Gaetn.) Libosch. ex Fisch. et Mey., Cinnamomum cassia Presl, Rubia yunnanensis Diels, Taxillus sutchuenensis (Lecomte) Danser, Dendrobium nobile Lindl., Achyranthes bidentata Blume, Ligusticum chuanxiong Hort., Saposhnikovia divaricata (Trucz.) Schischk., Panax ginseng C. A. Mey., Aristolochia fangchi Y. C. Wu ex L. D. Chow et S. M. Hwang, Cornus officinalis Sieb. et Zucc., Angelica sinensis (Oliv.) Diels, Schisandra chinensis (Turcz.) Baill.	Infertility, abortion	‘Song·tai ping hui min he ji jv fang’
Baiwei tang	Cynanchum atratum Bunge, Panax ginseng C. A. Mey., Angelica sinensis (Oliv.) Diels, Glycyrrhiza uralensis Fisch.	Depressed dizziness, and occurrence of temporary fainting.	‘Pu ji ben shi fang’, vol. 7
Baiwei wan	Cynanchum atratum Bunge, Panax ginseng C. A. Mey., Aconitum carmichaelii Debx., Rehmannia glutinosa (Gaetn.) Libosch. ex Fisch. et Mey., Cinnamomum cassia Presl, Cynanchum otophyllum Schneid., Evodia rutaecarpa (Juss.) Benth., Angelica sinensis (Oliv.) Diels, Areca catechu L.	Irregular menstruation, infertility	‘Yi lve liu shu’, vol. 27
Baiwei gao	Cynanchum atratum Bunge, Ampelopsis japonica (Thunb.) Makino, Bletilla striata (Thunb. ex A. Murray) Rchb. f., Typhonium giganteum Engl., Angelica dahurica (Fisch. ex Hoffm.) Benth. et Hook. f. ex Franch. et Sav., Paeonia lactiflora Pall., frankincense, Fraxinus chinensis Roxb.	Evil sore	‘Shen hui’, vol. 63
Baiwei shiwei wan	Cynanchum atratum Bunge, Anemarrhena asphodeloides Bunge, Cortex Lycii, Rehmannia glutinosa (Gaetn.) Libosch. ex Fisch. et Mey., Ophiopogon japonicus (L.f.) Ker-Gawl., Glycyrrhiza uralensis Fisch, Dichroa febrifuga Lour., Polygonatum odoratum (Mill.) Druce, Panax ginseng C. A. Mey.	Frail, afraid of cold, heat	‘Wai tai’, vol. 3
Baiwei wan jiawei	Saposhnikovia divaricata (Trucz.) Schischk., Notopterygium incisum Ting ex H. T. Chang, Cynanchum atratum Bunge, Tribulus terrester L., pomegranate bark, Taraxacum mongolicum Hand.-Mazz., Lonicera japonica Thunb.	Breeze heat, Nasal obstruction, headache, fever	‘Shen shi yao han’
Buyi baiwei wan	Cynanchum atratum Bunge, Dolomiaea souliei (Franch.) Shih, Angelica sinensis (Oliv.) Diels, Cinnamomum cassia Presl, Lycopuslucidus Tur-Cz. var. hirtus Regel, Achyranthes bidentata Blume, Rehmannia glutinosa (Gaetn.) Libosch. ex Fisch. et Mey., Paeonia suffruticosa Andr., Panax ginseng C. A. Mey., Ligusticum chuanxiong Hort., Atractylodes macrocephala Koidz., Citrus aurantium L., Asarum sieboldii Miq., Aconitum carmichaelii Debx., Astragalus membranaceus (Fisch.) Bunge, Dipsacus asperoides C. Y. Cheng et T. M. Ai, Evodia rutaecarpa (Juss.) Benth., Magnolia officinalis Rehd. et Wils.	Postpartum weakness, pale complexion, diet reduced, increasingly thin.	‘Pu ji fang’, vol. 350
Jiawei baiwei wan	Cynanchum atratum Bunge, Paeonia lactiflora Pall., Adenophora stricta Miq., Angelica sinensis (Oliv.) Diels, Ligusticum chuanxiong Hort., Glycyrrhiza uralensis Fisch, Astragalus membranaceus (Fisch.) Bunge.	Too much blood loss, fainting	‘Wei sheng hong bao’, vol. 5
Huachong dingdan wan	Rehmannia glutinosa (Gaetn.) Libosch. ex Fisch. et Mey., Cynanchum glaucescens (Decne.) Hand.-Mazz.	Stomach pain	‘Bian zheng lu’, vol. 2
Xuanchaung weicha san	Cynanchum atratum Bunge, Angelica dahurica (Fisch. ex Hoffm.) Benth. et Hook. f. ex Franch. et Sav., Daucus carota L., Stemona japonica (Bl.) Miq., Zanthoxylum bungeanum Maxim., Rehmannia glutinosa (Gaetn.) Libosch. ex Fisch. et Mey.	Insecticide, detoxification	‘Yi liao bao jian cha tang pu’
Jiawei baiwei tang	Cynanchum atratum Bunge, Semen Trichosanthis, Citrus maxima (Burm.) Merr., Fritillariae Thunbergii, Artemisia carvifolia, Dendrocalamopsis beecheyana (Munro) Keng var. pubescens (P. F. Li) Keng f.	Pneumonia, cough	‘Ma pei zhi yi an’
Baiwei renshen wan	Cynanchum atratum Bunge, Panax ginseng C. A. Mey., Rubia yunnanensis Diels, Achyranthes bidentata Blume, Asarum sieboldii Miq., Magnolia officinalis Rehd. et Wils., Pinellia ternata (Thunb.) Breit., Adenophora stricta Miq., Zingiber officinale Rosc., Gentiana macrophylla Pall., Zanthoxylum bungeanum Maxim., Angelica sinensis (Oliv.) Diels, Aconitum carmichaelii Debx., Saposhnikovia divaricata (Trucz.) Schischk., Aster tataricus L. f.	Irregular menstruation, infertility	‘Qian jin yi fang’, vol. 2
Guizhi huangqi baiwei kuandonghua san	Cinnamomum cassia Presl, Astragalus membranaceus (Fisch.) Bunge, Cynanchum atratum Bunge, Tussilago farfara L., Paeonia lactiflora Pall., Anemarrhena asphodeloides Bunge.	Lung malaria	‘Jie nue lun shu’
Wumei baiwei xixin wan	Dichroa febrifuga Lour., Cynanchum atratum Bunge, Clematis apiifolia DC., Anemarrhena asphodeloides Bunge, Sophora flavescens Alt., Dichroa febrifuga Lour., Glycyrrhiza uralensis Fisch, Asarum sieboldii Miq.	Liver malaria	‘Jie nue lun shu’
Baiqian san	Cynanchum glaucescens (Decne.) Hand.-Mazz., Glycyrrhiza uralensis Fisch, Panax ginseng C. A. Mey., Rehmannia glutinosa (Gaetn.) Libosch. ex Fisch. et Mey., Cannabis sativa L., Cinnamomum cassia Presl, Wolfiporia cocos, Astragalus membranaceus (Fisch.) Bunge, donkey-hide gelatin, Ophiopogon japonicus (Linn. f.) Ker-Gawl.	Pulmonary fibrosis, cough and phlegm	‘Sheng hui’, vol. 31
Baiqian tang	Cynanchum glaucescens (Decne.) Hand.-Mazz., Aster tataricus L. f., Pinellia ternata (Thunb.) Breit., Euphorbia pekinensis Rupr.	Cough, body swollen, chest tightness, throat hoarse	‘Bei ji qian jin yao fang’, vol. 18
Baiqian yin	Cynanchum glaucescens (Decne.) Hand.-Mazz., Platycodon grandiflorus (Jacq.) A. DC., Smilax china L., Amygdalus Communis Vas, Glycyrrhiza uralensis Fisch.	Weak, cough, vomit blood	‘Sheng ji zong lu’, vol. 90
Shenyan baiqian tang	Cynanchum glaucescens (Decne.) Hand.-Mazz., Pinellia ternata (Thunb.) Breit., Aster tataricus L. f., Ephedra sinica Stapf, Magnolia officinalis Rehd. etWils., Panax ginseng C. A. Mey., Glycyrrhiza uralensis Fisch.	Cough, wheezing, nausea, vomiting, belching, hiccups	‘Sheng ji zong lu’, vol. 67
Xuchangqing san	Cynanchum paniculatum (Bunge) Kitagawa, Sophora flavescens Alt., Aconitum carmichaelii Debx., Evodia rutaecarpa (Juss.) Benth., Camptotheca acuminata Decne., Asarum sieboldii Miq., Acorus calamus L., Pinellia ternata (Thunb.) Breit.	Scabies disease	‘Sheng ji zong lu’, vol. 137
Xuchangqing tang	Cynanchum paniculatum (Bunge) Kitagawa, Perotis indica (L.) Kuntze, Akebia quinata (Houtt.) Decne., Malva crispa Linn., Areca catechu L., Dianthus superbus L.	weakness of the spleen and the stomach	‘Ben cao gang mu’, vol. 13
Anwei jian	Taraxacum mongolicum Hand.-Mazz., Cynanchum otophyllum Schneid., Glycyrrhiza uralensis Fisch, Carthamus tinctorius L., Cynanchum paniculatum (Bunge) Kitagawa.	Stomach pain, blood circulation	‘Yuan zheng gang fang’
Huainan wan	Plantago asiatica L., Prunus salicina Lindl., Adiantum capillus-veneris L., Cynanchum paniculatum (Bunge) Kitagawa.	Tuberculosis, upset, headache and vomiting	‘Pu ji fang’, vol. 237

References in this table was cited from the website: http://www.wiki8.com.

3. Chemical Constituents

At present, more than 400 compounds have been isolated from genus Cynanchum. These compounds include 388 steroids, 30 benzenes and its derivatives, 13 alkaloids, 10 flavonoids, 9 terpenes and other compounds (Table 3). The chemical structures of the primary compounds are shown in Figure 1.

Table 3

Compounds isolated from Cynanchum species.

No.	Compound Name	Species	Parts	Ref.
C21 steroids
1	Cynanversicoside A	C. versicolor	Roots	[6]
2	Cynanversicoside B	C. versicolor	Roots	[6]
3	Cynanversicoside C	C. versicolor	Root/rhizome	[7]
4	Cynanversicoside D	C. versicolor	Root/rhizome	[7]
5	Cynanversicoside F	C. versicolor	Root/rhizome	[7]
6	Glaucogenin B	C. glaucescens	Roots	[8]
7	12β-O-(4-hydroxybenzoyl)-8β,14β,17β-trihydroxypregn-2,5-diene-20-one	C. wilfordii	Roots	[9]
8	12β-O-benzoyl-8β,14β,17β-trihydroxypregn-2,5-diene-20-one	C. wilfordii	Roots	[9]
9	Glaucoside A	C. glaucescens	Roots	[8]
10	Glaucoside B	C. glaucescens	Roots	[8]
11	Glaucoside C	C. glaucescens	Roots	[10]
12	Glaucoside D	C. glaucescens	Roots	[8]
13	Glaucoside E	C. glaucescens	Roots	[8]
14	Glaucoside F	C. glaucescens	Roots	[8]
15	Glaucoside G	C. glaucescens	Roots	[8]
16	Glaucoside H	C. glaucescens	Roots	[8]
17	Glaucoside I	C. glaucescens	Roots	[8]
18	Glaucoside J	C. glaucescens	Roots	[8]
19	Cynatratoside F	C. atratum	Roots	[8]
20	Cynatratoside C	C. atratum	Roots	[10]
21	Cynatratoside A	C. atratum	Roots	[11]
22	Cynatratoside B	C. atratum	Roots	[12]
23	Atratoside A	C. atratum	Roots	[13]
24	Atratoside B	C. atratum	Roots	[13]
25	Atratoside C	C. atratum	Roots	[14]
26	Atratoside D	C. atratum	Roots	[8]
27	Otophylloside A	C. forrestii C. otophyllum C. wallichii	Roots	[15]
28	Otophylloside B	C. forrestii C. otophyllum C. wallichii	Roots	[15]
29	Otophylloside C	C. otophyllum	Roots	[16]
30	Otophylloside F	C. otophyllum	Roots	[16]
31	Otophylloside H	C. otophyllum	Roots	[17]
32	Otophylloside I	C. otophyllum	Roots	[17]
33	Otophylloside J	C. otophyllum	Roots	[17]
34	Otophylloside K	C. otophyllum	Roots	[17]
35	Otophylloside L	C. otophyllum C. auriculatum	Roots	[17]
36	Otophylloside M	C. otophyllum	Roots	[17]
37	Otophylloside N	C. forrestii	Roots	[15]
38	Otophylloside O	C. forrestii	Roots	[15]
39	Otophylloside P	C. forrestii	Roots	[15]
40	Otophylloside Q	C. forrestii	Roots	[15]
41	Otophylloside R	C. forrestii	Roots	[15]
42	Otophylloside S	C. forrestii	Roots	[15]
43	Otophylloside T	C. otophyllum	Roots	[16]
44	Otophylloside U	C. otophyllum	Roots	[18]
45	Otophylloside V	C. otophyllum	Roots	[18]
46	Otophylloside W	C. otophyllum	Roots	[18]
47	Sibiricoside D	C. sibiricum	Roots	[19]
48	Sibiricoside E	C. sibiricum	Roots	[19]
49	Sibirigenin	C. sibiricum	Roots	[20]
50	Penupogenin	C. sibiricum	Roots	[20]
51	Penupogenin3-O-β-d-glucopyranosyl-(1→4)-β-l-cymaropyranosyl-(1→4)-β-d-cymaropyranosyl-(1→4)-α-l-diginopyranosyl-(1→4)-β-d-cymaropyranoside	C. bungei	Stems	[21]
52	Cynanoside A	C. atratum	Roots	[22]
53	Cynanoside B	C. atratum	Roots	[22]
54	Cynanoside C	C. atratum	Roots	[22]
55	Cynanoside D	C. atratum	Roots	[22]
56	Cynanoside E	C. atratum	Roots	[22]
57	Cynanoside F	C. atratum	Roots	[22]
58	Cynanoside G	C. atratum	Roots	[22]
59	Cynanoside H	C. atratum	Roots	[22]
60	Cynanoside I	C. atratum C. versicolor	Roots	[22]
61	Cynanoside J	C. atratum	Roots	[22]
62	Cynanoside K	C. atratum	Roots	[13]
63	Cynanoside L	C. atratum	Roots	[13]
64	Cynanoside M	C. atratum	Roots	[13]
65	Cynanoside N	C. atratum	Roots	[13]
66	Cynanoside O	C. atratum	Roots	[13]
67	Cynanosides P1	C. atratum	Roots	[14]
68	Cynanosides P2	C. atratum	Roots	[14]
69	Cynanosides P3	C. atratum	Roots	[14]
70	Cynanosides P4	C. atratum	Roots	[14]
71	Cynanosides P5	C. atratum	Roots	[14]
72	Cynanosides Q1	C. atratum	Roots	[14]
73	Cynanosides Q2	C. atratum	Roots	[14]
74	Cynanosides Q3	C. atratum	Roots	[14]
75	Cynanosides R1	C. atratum	Roots	[14]
76	Cynanosides R2	C. atratum	Roots	[14]
77	Cynanosides R3	C. atratum	Roots	[14]
78	Cynanoside S	C. atratum	Roots	[14]
79	Sublanceoside E3	C. atratum	Roots	[14]
80	Chekiangensoside A	C. chekiangense	Roots	[23]
81	Chekiangensoside B	C. chekiangense	Roots	[23]
82	Chekiangensoside C	C. chekiangense	Roots	[14]
83	Chekiangensoside D	C. chekiangense	Roots	[24]
84	Chekiangensoside E	C. chekiangense	Roots	[24]
85	Cynatroside A	C. atratum	Roots	[25]
86	Cynatroside B	C. atratum	Roots	[14]
87	Cynatroside C	C. atratum	Roots	[25]
88	Wilfoside A	C. wilfordii	Roots	[26]
89	Wilfoside B	C. wilfordii	Roots	[26]
90	Wilfoside C	C. wilfordii	Roots	[26]
91	Wilfoside D	C. wilfordii	Roots	[26]
92	Wilfoside E	C. wilfordii	Roots	[26]
93	Wilfoside F	C. wilfordii	Roots	[26]
94	Wilfoside G	C. wilfordii	Roots	[26]
95	Wilfoside H	C. wilfordii	Roots	[26]
96	Wilfoside KIN	C.wilfordii	Roots	[26]
97	Wilfoside K1GG	C. wilfordii	Roots	[27]
98	Wilfoside C1GG	C. wilfordii	Roots	[27]
99	Wilfoside C1N	C. taiwanianum	Roots	[28]
100	Wilfoside C2N	C. taiwanianum	Roots	[28]
101	Wilfoside C3N	C. auriculatum	Roots	[29]
102	Wilfoside M1N	C. auriculatum	Roots	[30]
103	Wilfoside C1G	C. auriculatum	Roots	[30]
104	Wilfoside C2G	C. otophyllum	Roots	[31]
105	Amplexicoside A	C. amplexicaule	Roots	[32]
106	Amplexicoside B	C. amplexicaule	Roots	[32]
107	Amplexicoside C	C. amplexicaule	Roots	[32]
108	Amplexicoside D	C. amplexicaule	Roots	[32]
109	Amplexicoside E	C. amplexicaule	Roots	[32]
110	Amplexicoside F	C. amplexicaule	Roots	[32]
111	Amplexicoside G	C. amplexicaule	Roots	[32]
112	Tylophoside A	C. amplexicaule	Roots	[32]
113	Hancoside A	C. amplexicaule C. komarovii	Roots	[33]
114	Hancoside	C. forrestii C. hunmkiunum	Roots	[34]
115	Neocynapanogenin F 3-O-β-d-thevetoside	C. paniculatum	Roots	[35]
116	Neocynapanogenin F	C. paniculatum	Roots	[35]
117	Neocynapanogenin F 3-O-β-d-thevetopyranoside	C. atratum.	Roots	[36]
118	Glaucogenin C	C. hunmkiunum C. atratum	Roots	[37]
119	Glaucogenin C 3-O-α-l-cymaropyranosyl-(1→4)-β-d-digitoxopyranosyl-(1→4)-β-d-canaropyranoside	C. stauntonii	root	[38]
120	Glaucogenin C 3-O-β-d-cymaropyranosyl-(1→4)-α-l-diginopyranosyl-(1→4)-β-d-thevetopyranoside	C. atratum	Roots	[39]
121	Glaucogenin C 3-O-β-d-thevetopyranoside	C. atratum	Roots	[39]
122	Glaucogenin C mono-d-thevetoside	C. stauntonii	Roots	[40]
123	Glaucogenin C 3-O-β-d-oleandropyranoside	C. atratum.	Roots	[36]
124	Glaucogenin C 3-O-α-l-diginopyranosyl-(1→4)-β-d-thevetopyranoside	C. atratum.	Roots	[36]
125	Glaucogenin C 3-O-α-l-cymaropyranosyl-(1→4)-β-d-cymaropyranosyl-(1→4)-β-d-oleandropyranoside	C. atratum.	Roots	[36]
126	Glaucogenin C 3-O-α-l-cymaropyranosyl-(1→4)-β-d-digitoxopyranosy-(1→4)-β-d-oleandropyranoside	C. atratum.	Roots	[36]
127	Glaucogenin C 3-O-β-d-cymaropyranosyl-(1→4)-α-l-diginopyranosyl-(1→4)-β-d-cymaropyranoside	C. atratum.	Roots	[36]
128	Glaucogenin C 3-O-α-d-oleandropyranosyl-(1→4)-β-d-digitoxopyranosyl-(1→4)-β-d-oleandropyranoside	C. atratum.	Roots	[36]
129	Glaucogenin C 3-O-β-d-thevetoside	C. paniculatum.	Root/rhizome	[41]
130	Glaucogenin A	C. atratum.	Roots	[36]
131	Glaucogenin A 3-O-β-d-oleandropyranoside	C. atratum.	Roots	[36]
132	Glaucogenin A 3-O-β-d-digitoxopyranoside	C. atratum.	Roots	[36]
133	Glaucogenin A 3-O-β-d-digitoxopyranosyl-(1→4)-β-d cymaropyranoside	C. atratum.	Roots	[36]
134	Glaucogenin A 3-O-β-d-glucopyranosyl-(1→4)-β-d-oleandropyranoside	C. atratum.	Roots	[36]
135	Glaucogenin A 3-O-β-d-cymaropyranosyl-(1→4)-α-l-diginopyranosyl-(1→4)-β-d-cymaropyranoside	C. atratum.	Roots	[36]
136	Glaucogenin A 3-O-α-l-cymaropyranosyl-(1→4)-β-d-digitoxopyranosyl-(1→4)-β-d-cymaropyranoside	C. atratum.	Roots	[36]
137	Glaucogenin A 3-O-α-d-oleandropyranosyl-(1→4)-β-d-digitoxopyranosyl-(1→4)-β-d-oleandropyranoside	C. atratum.	Roots	[36]
138	Glaucogenin A 3-O-α-l-cymaropyranosyl-(1→4)-β-d-digitoxopyranosyl-(1→4)-β-d-digitoxopyranoside	C. atratum.	Roots	[36]
139	Glaucogenin A 3-O-β-d-oleandropyranosyl-(1→4)-β-d-digitoxopyranosyl-(1→4)-β-d-oleandropyranoside	C. atratum.	Roots	[36]
140	Glaucogenin A 3-O-α-l-cymaropyranosyl-(1→4)-β-d-cymaropyranosyl-(1→4)-β-d-oleandropyranoside	C. atratum.	Roots	[36]
141	Glaucogenin A 3-O-α-l-cymaropyranosyl-(1→4)-β-d-cymaropyranosyl-(1→4)-β-d-cymaropyranoside	C. atratum.	Roots	[36]
142	Glaucogenin A 3-O-β-d-glucopyranosyl-(1→4)-β-d-glucopyranosyl-(1→4)-β-d-oleandropyranoside	C. atratum.	Roots	[36]
143	Glaucogenin A 3-O-α-l-oleandropyranosyl-(1→4)-β-d-digitoxopyranosyl-(1→4)-β-d-oleandropyranoside	C. atratum.	Roots	[36]
144	Glaucogenin D	C. paniculatum.	Root /rhizome	[41]
145	Stauntoside A	C. stauntoi	Roots	[42]
146	Stauntoside B	C. stauntoi	Roots	[42]
147	Stauntoside C	C. stauntonii	Roots	[43]
148	Stauntoside D	C. stauntonii	Roots	[43]
149	Stauntoside E	C. stauntonii	Roots	[43]
150	Stauntoside F	C. stauntonii	Roots	[43]
151	Stauntoside G	C. stauntonii	Roots	[43]
152	Stauntoside H	C. stauntonii	Roots	[43]
153	Stauntoside I	C. stauntonii	Roots	[43]
154	Stauntoside J	C. stauntonii	Roots	[43]
155	Stauntoside K	C. stauntonii	Roots	[43]
156	Stauntoside L	C. stauntonii	Roots	[44]
157	Stauntoside M	C. stauntonii	Roots	[44]
158	Stauntoside O	C. stauntonii	Roots	[44]
159	Stauntoside P	C. stauntonii	Roots	[44]
160	Stauntoside Q	C. stauntonii	Roots	[44]
161	Stauntoside R	C. stauntonii	Roots	[44]
162	Stauntoside S	C. stauntonii	Roots	[44]
163	Stauntoside T	C. stauntonii	Roots	[44]
164	Stauntoside UA	C. stauntonii .	Roots	[45]
165	Stauntoside UA1	C. stauntonii .	Roots	[45]
166	Stauntoside UA2	C. stauntonii .	Roots	[45]
167	Kidjoranin	C. wilfordii. C. auriculatum	Roots	[9]
168	Kidjoranin-3-O-β-d-oleandropyranosyl-(1→4)-β-d-oleandropyranosyl-(1→4)-β-d-cymaropyranosyl-(1→4)-β-d-cymaropyranoside	C. otophyllum	Roots	[46]
169	Kidjoranin 3-O-β-d-digitoxopyranoside	C. otophyllum	Roots	[47]
170	20-O-(4-hydroxybenzoyl)-kidjoranin	C. wilfordii	Roots	[9]
171	20-O-vanilloyl-kidjoranin	C. wilfordii	Roots	[9]
172	20-O-salicyl-kidjoranin	C. wilfordii	Roots	[9]
173	20-O-(4-hydroxybenzoyl)-kidjoranin	C. wilfordii.	Roots	[9]
174	12β-O-(4-hydroxybenzoyl)-8β,14β,17β-trihydroxypregn-2,5-diene-20-one	C. wilfordii.	Roots	[9]
175	Caudatin	C. auriculatum	Roots	[29]
176	caudatin-2,6-dideoxy-3-O-methy-β-d-cymaropyranoside	C. auriculatum	Roots	[48]
177	3-O-methyl-caudatin	C. wilfordii	Roots	[9]
178	Caudatin 3-O-β-d-glucopyranosyl-(1→4)-β-d-oleandropyranosyl-(1→4)-β-d-cymaropyranosyl-(1→4)-β-d-cymaropyranoside	C. forrestii	Roots	[15]
179	Caudatin 3-O-α-l-cymaropyranosyl-(1→4)-α-d-oleandropyranosyl-(1→4)-α-l-cymaropyranosyl-(1→4)-β-d-glucopyranosyl-(1→4)-α-d-oleandropyranosyl-(1→4)-β-d-oleandropyranosyl-(1→4)-β-d-diginopyranoside	C. otophyllum	Rhizome	[49]
180	Caudatin 3-O-β-d-cymaropyranosyl-(1→4)-α-d-oleandropyranosyl-(1→4)-α-l-cymaropyranosyl-(1→4)-β-d-glucopyranosyl-(1→4)-β-d-oleandropyranosyl-(1→4)-β-d-cymaropyranosyl-(1→4)-β-d-diginopyranoside	C. otophyllum	Rhizome	[49]
181	Caudatin 3-O-β-d-cymaropyranosyl-(1→4)-β-d-cymaropyranoside	C. otophyllum	Roots	[16]
182	Caudatin 3-O-β-d-glucopyranosyl-(1→4)-β-d-oleandropyranosyl-(1→4)-β-d-cymaropyranosyl-(1→4)-β-d-cymaropyranoside	C. otophyllum	Roots	[16]
183	Caudatin 3-O-β-d-glucopyranosyl-(1→4)-β-d-cymaropyranosyl-(1→4)-α-l-diginopyranosyl-(1→4)-β-d-cymaropyranoside	C. wilfordii.	Roots	[50]
184	Caudatin 3-O-β-d-cymaropyranosyl-(1→4)-β-d-oleandropyranosyl-(1→4)-β-d-cymaropyranoside	C. otophyllum	Roots	[46]
185	Caudatin-3-O-β-d-oleandropyranosyl-(1→4)-β-d-thevetopyranosyl-(1→4)-β-d-cymaropyranoside	C. otophyllum	Roots	[46]
186	Caudatin-3-O-β-d-thevetopyranosyl-(1→4)-β-d-cymaropyranosyl-(1→4)-β-d-cymaropyranoside	C. otophyllum	Roots	[46]
187	Caudatin-3-O-β-d-thevetopyranosyl-(1→4)-β-d-cymaropyranosyl-(1→4)-β-d-digitoxopyranoside.	C. otophyllum	Roots	[46]
188	Caudatin-3-O-β-d-cymaropyranosyl-(1→4)-β-d-oleandropyranosyl-(1→4)-β-d-cymaropyranosyl-(1→4)-β-d-digitoxopyranoside	C. otophyllum	Roots	[46]
189	Caudatin-3-O-α-l-cymaropyranosyl-(1→4)-α-d-cymaropyranosyl-(1→4)-α-l-cymaropyranosyl-(1→4)-β-d-digitoxopyranoside	C. otophyllum	Roots	[46]
190	Caudatin 3-O-β-d-oleandropyranosyl-(1→4)-β-d-thevetopyranosyl-(1→4)-β-d-cymaropyranosyl-(1→4)-β-d-cymaropyranoside	C. otophyllum	Roots	[46]
191	Caudatin 3-O-α-l-cymaropyranosyl-(1→4)-β-d-cymaropyranosyl-(1→4)-α-l-cymaropyranosyl-(1→4)-β-d-cymaropyranosyl-(1→4)-β-d-digitoxopyranoside.	C. otophyllum	Roots	[46]
192	Caudatin 3-O-α-l-cymaropyranosyl-(1→4)-β-d-cymaropyranosyl-(1→4)-β-d-cymaropyranosyl-(1→4)-α-l-cymaropyranosyl-(1→4)-β-d-oleandropyranosyl-(1→4)-β-d-cymaropyranoside	C. otophyllum	Roots	[46]
193	Caudatin 3-O-β-d-cymaropyranosyl-(1→4)-β-d-oleandropyranosyl-(1→4)-β-d-cymaropyranosyl-(1→4)-β-d-cymaropyranoside	C. otophyllum	Roots	[46]
194	Caudatin 3-O-β-d-oleandropyranosyl-(1→4)-β-d-digitoxopyranosyl-(1→4)-β-d-cymaropyranoside	C. otophyllum	Roots	[46]
195	Caudatin 3-O-β-d-oleandropyranosyl-(1→4)-β-d-cymaropyranosyl-(1→4)-β-d-digitoxopyranoside	C. otophyllum	Roots	[46]
196	Caudatin 3-β-d-digitoxopyranoside	C. otophyllum	Roots	[47]
197	Caudatin 3-O-α-l-diginopyranosyl-(1→4)-β-d-cymaropyranoside	C. otophyllum	Roots	[47]
198	Caudatin 3-O-β-d-glucopyranosyl-(1→4)-β-d-digitoxopyranosyl-(1→4)-β-d-diginopyranosyl-(1→4)-α-d-oleandropyranoside	C. otophyllum	Rhizome	[51]
199	Caudatin3-O-β-d-oleandropyranosyl-(1→4)-α-d-oleandropyranosyl-(1→4)-α-d-oleandropyranoside	C. otophyllum	Rhizome	[51]
200	Caudatin3-O-β-d-glucopyranosyl-(1→4)-α-d-oleandropyranosyl-(1→4)-β-d-diginopyranosyl-(1→4)-α-d-oleandropyranoside	C. otophyllum	Rhizome	[51]
201	Qingyangshengenin	C. wilfordii.	Roots	[9]
202	Qingyangshengenin 3-O-β-d-cymaropyranosyl-(1→4)-β-d-digitoxopyranoside	C. otophyllum	Roots	[16]
203	Qingyangshengenin 3-O-β-d-oleandropyranosyl-(1→4)-β-d-cymaropyranoside	C. otophyllum	Roots	[16]
204	Qingyangshengenin 3-O-β-d-oleandropyranosyl-(1→4)-β-d-cymaropyranosyl-(1→4)-β-d-digitoxopyranoside	C. otophyllum	Roots	[16]
205	Qingyangshengenin 3-O-β-d-cymaropyranosyl-(1→4)-β-d-thevetopyranosyl-(1→4)-β-d-cymaropyranosyl-(1→4)-β-d-digitoxopyranoside	C. otophyllum	Roots	[46]
206	Qingyangshengenin 3-O-α-l-cymaropyranosyl-(1→4)-β-d-oleandropyranosyl-(1→4)-β-d-cymaropyranosyl-(1→4)-β-d-cymaropyranoside	C. otophyllum	Roots	[46]
207	Qingyangshengenin 3-O-α-l-cymaropyranosyl-(1→4)-β-d-cymaropyranosyl-(1→4)-β-d-cymaropyranosyl-(1→4)-α-l-cymaropyranosyl-(1→4)-β-d-oleandropyranosyl-(1→4)-β-d-cymaropyranoside	C. otophyllum	Roots	[46]
208	Qinyangshengenin-3-O-β-d-oleandropyranosyl-(1→4)-β-d-oleandropyranosyl-(1→4)-β-d-cymaropyranosyl-(1→4)-β-d-cymaropyranoside	C. otophyllum	Roots	[52]
209	Qinyangshengenin-3-O-α-l-cymaropyranosyl-(1→4)-β-d-oleandropyranosyl-(1→4)-β-d-cymaropyranosyl-(1→4)-β-d-digitoxopyranoside	C. wallichii	Roots	[53]
210	Deacymetaplexigenin	C. wilfordii	Roots	[9]
211	12-O-vanilloyl-deacymetaplexigenin	C. wilfordii.	Roots	[9]
212	12-O-benzoyldeacymetaplexigenin	C. wilfordii.	Roots	[9]
213	17β-O-cinnamoyl-3β,8β,14β-trihydroxypregn-12,20-ether	C. wilfordii.	Roots	[9]
214	Gagamine 3-O-β-d-oleandropyranosyl-(1→4)-β-d-cymaropyranosyl-(1→4)-β-d-cymaropyranoside	C. otophyllum	Roots	[46]
215	Gagaminin 3-O-β-d-cymaropyranosyl-(1→4)-β-d-oleandropyranosyl-(1→4)-β-d-cymaropyranosyl-(1→4)-β-d-cymaropyranoside	C. wilfordii	Roots	[54]
216	Gagaminin 3-O-β-l-cymaropyranosyl-(1→4)-β-d-cymaropyranosyl-(1→4)-α-l-diginopyranosyl-(1→4)-β-d-digitoxopyranoside	C. bungei	Stems	[21]
217	Gagaminin 3-O-β-l-cymaropyranosyl-(1→4)-β-d-cymaropyranosyl-(1→4)-α-l-diginopyranosyl-(1→4)-β-d-cymaropyranoside	C. bungei	Stems	[21]
218	Gagaminine 3-O-β-d-oleandropyranosyl-(1→4)-β-d-oleandropyranosyl-(1→4)-β-d-cymaropyranoside	C. saccatum	Roots	[55]
219	Gagaminin 3-O-α-l-cymaropyranosyl-(1→4)-β-d-cymaropyranosyl-(1→4)-α-l-diginopyranosyl-(1→4)-β-d-digitoxopyranoside	C. wilfordii.	Roots	[50]
220	Gagaminin-3-O-β-d-oleandropyranosyl-(1→4)-β-d-cymaropyranosyl-(1→4)-β-d-digitoxopyranoside	C. otophyllum	Roots	[46]
221	12β-O-benzoyl-8β,14β,17β-trihydroxypregn-2,5-diene-20-one	C. wilfordii.	Roots	[9]
222	Rostratamin	C. wilfordii.	Roots	[9]
223	Rostratamine 3-O-β-d-oleandropyranosyl-(1→4)-β-d-cymaropyranosyl-(1→4)-β-d-cymaropyranoside	C. otophyllum	Roots	[16]
224	Sarcostin	C. otophyllum	Roots	[47]
225	12-O-nicotinoylsarcostin3-O-β-l-cymaropyranosyl-(1→4)-β-d-cymaropyranosyl-(1→4)-α-l-diginopyranosyl-(1→4)-β-d-cymaropyranoside	C. bungei	Stems	[21]
226	12-O-acetylsarcostin 3-O-β-lcymaropyranosyl-(1→4)-β-d-cymaropyranosyl-(1→4)-β-l-cymaropyranosyl-(1→4)-β-d-digitoxopyranosyl-(1→4)-β-d-digitoxopyranoside	C. bungei	Stems	[21]
227	12-O-acetylsarcostin3-O-β-l-cymaropyranosyl-(1→4)-β-d-digitoxopyranosyl-(1→4)-β-l-cymaropyranosyl-(1→4)-β-d-cymaropyranosyl-(1→4)-α-l-diginopyranosyl-(1→4)-β-d-cymaropyranoside	C. bungei	Stems	[21]
228	20-O-acetyl-12-O-cinnamoyl-3-O-(β-d-oleandropyranosyl-(1→4)-β-d-oleandropyranosyl-(1→4)-β-d-cymaropyranosyl)-8,14-secosarcostin-8,14-dione	C. saccatum	Roots	[56]
229	Deacylcynanchogenin	C. wilfordii	Roots	[9]
230	Cynauricuoside A	C. wilfordii	Roots	[27]
231	Cynauricuoside C	C. auriculatum	Root	[57]
232	Cynanside A	C. aniculatum	Roots	[58]
233	Cynanside B	C. aniculatum	Roots	[58]
234	Komaroside C	C. forrestii	Roots	[59]
235	Komaroside D	C. komarovii	Roots	[33]
236	Komaroside E	C. komarovii	Roots	[33]
237	Komaroside F	C. komarovii	Roots	[33]
238	Komaroside G	C. komarovii	Roots	[33]
239	Komaroside H	C. komarovii	Roots	[33]
240	Cynauricoside A	C. wilfordii.	Roots	[50]
241	Cynauricoside B	C. auriculatum	Roots	[30]
242	Cynauricoside C	C. auriculatum	Roots	[30]
243	Cynauricoside D	C. auriculatum	Roots	[30]
244	Cynauricoside E	C. auriculatum	Roots	[30]
245	Cynauricoside F	C. auriculatum	Roots	[30]
246	Cynauricoside G	C. auriculatum	Roots	[30]
247	Cynauricoside H	C. auriculatum	Roots	[30]
248	Cynauricoside I	C. auriculatum	Roots	[30]
249	Cynauricuside A	C. auriculatum	Roots	[30]
250	Cynaforroside B	C. forrestii	Roots	[59]
251	Cynaforroside C	C. forrestii	Roots	[59]
252	Cynaforroside D	C. forrestii	Roots	[59]
253	Cynaforroside E	C. forrestii	Roots	[59]
254	Cynaforroside F	C. forrestii	Roots	[59]
255	Cynaforroside G	C. forrestii	Roots	[59]
256	Cynaforroside H	C. forrestii	Roots	[59]
257	Cynaforroside I	C. forrestii	Roots	[59]
258	Cynaforroside J	C. forrestii	Roots	[59]
259	Cynaforroside K	C. forrestii	Roots	[60]
260	Cynaforroside L	C. forrestii	Roots	[60]
261	Cynaforroside M	C. forrestii	Roots	[60]
262	Cynaforroside N	C. forrestii	Roots	[60]
263	Cynaforroside O	C. forrestii	Roots	[60]
264	Cynaforroside P	C. forrestii	Roots	[60]
265	Cynaforroside Q	C. forrestii	Roots	[60]
266	Atratoglaucoside A	C. atratum C. versicolor	Roots	[39]
267	Atratoglaucoside B	C. atratum	Roots	[39]
268	Paniculatumoside A	C. paniculatum .	Roots	[61]
269	Paniculatumoside B	C. paniculatum .	Roots	[61]
270	Neohancoside C	C. hunmkiunum	Roots	[62]
271	Neohancoside D	C. hunmkiunum	Roots	[62]
272	Deoxyamplexicogenin A-3-O-yl-4-O-(4-O-α-l-cymaropyranosoyl-β-d-digitoxopyranosoyl)-β-d-canaropyranoside	C. stauntonii	Roots	[63]
273	2-deoxyamplexicogenin A	C. stauntonii	Roots	[64]
274	Amplexicogenin C-3-O-β-d-cymaropyranoside	C. amplexicaule	Roots	[65]
275	Cynascyroside A	C. ascyrifolium	Roots	[66]
276	Cynascyroside B	C. ascyrifolium	Roots	[66]
277	Cynascyroside C	C. ascyrifolium C. chekiangense	Roots	[66]
278	Cynascyroside D	C. atratum	Roots	[25]
279	Taiwanoside A	C. taiwanianum	Roots	[28]
280	Taiwanoside B	C. taiwanianum	Roots	[28]
281	Taiwanoside C	C. taiwanianum	Roots	[28]
282	Taiwanoside D	C. taiwanianum	Roots	[28]
283	Taiwanoside E	C. taiwanianum	Roots	[28]
284	Stauntonine	C. stauntonii	Roots	[40]
285	Anhydrohirundigenin	C. stauntonii	Roots	[40]
286	Anhydrohirundigenin monothevetoside	C. stauntonii	Roots	[40]
287	Auriculoside I	C. auriculatum	Roots	[29]
288	Auriculoside II	C. auriculatum	Roots	[29]
289	Auriculoside III	C. auriculatum	Roots	[29]
290	Auriculoside IV	C. auriculatum	Roots	[29]
291	Cynanauriculoside I	C. auriculatum	Roots	[29]
292	Cynanauriculoside II	C. auriculatum	Roots	[29]
293	Cynanauriculoside A	C. wallichii	Roots	[53]
294	Cynanauriculoside C	C. auriculatum	Roots	[67]
295	Cynanauriculoside D	C. auriculatum	Roots	[67]
296	Cynanauriculoside E	C. auriculatum	Roots	[67]
297	(3β,8β,9α,16α,17α)-14,16β:15,20α:18,20β-triepoxy-16α,17α-dihydroxy-14-oxo-13,14:14,15-disecopregna-5,13(18)-dien-3-yl α-cymaropyranosyl-(1→4)-α-digitoxopyranosyl-(1→4)-α-oleandropyranoside	C. paniculatum	Stems	[68]
298	(3β,8β,9α,16α,17α)-14,16β:15,20α:18,20β-triepoxy-16β:17α-dihydroxy-14-oxo-13,14:14,15-disecopregna-5,13(18)-dien-3-yl α-oleandropyranosyl-(1→4)-α-digitoxopyranosyl-(1→4)-α-oleandropyranoside	C. paniculatum	Stems	[68]
299	Cyanoauriculoside C	C. auriculatum	Roots	[69]
300	Cyanoauriculoside D	C. auriculatum	Roots	[69]
301	Cyanoauriculoside E	C. auriculatum	Roots	[69]
302	Cyanoauriculoside G	C. wilfordii.	Roots	[50]
303	Hirundoside A	C. stauntonii	Roots	[43]
304	Deacetylmetaplexigenin	C. otophyllum	Roots	[47]
305	Deacetylmetaplexigenin 3-O-β-d-oleandropyranosyl-(1→4)-α-d-oleandropyranosyl-(1→4)-α-d-oleandropyranoside	C. otophyllum	Rhizome	[70]
306	Deacetylmetaplexigenin 3-O-α-d-oleandropyranosyl-(1→4)-β-d-thevetopyranosyl-(1→4)-α-d-oleandropyranoside	C. otophyllum	Rhizome	[70]
307	Deacetylmetaplexigenin 3-O-β-d-cymaropyranosyl-(1→4)-α-d-oleandropyranoside	C. otophyllum	Rhizome	[70]
308	Cynsaccatol A	C. saccatum	Roots	[55]
309	Cynsaccatol B	C. saccatum	Roots	[55]
310	Cynsaccatol C	C. saccatum	Roots	[55]
311	Cynsaccatol D	C. saccatum	Roots	[55]
312	Cynsaccatol E	C. saccatum	Roots	[55]
313	Cynsaccatol F	C. saccatum	Roots	[55]
314	Cynsaccatol G	C. saccatum	Roots	[55]
315	Cynsaccatol H	C. saccatum	Roots	[55]
316	Cynotophylloside A	C. otophyllum.	Roots	[47]
317	Cynotophylloside B	C. otophyllum.	Roots	[47]
318	Cynotophylloside C	C. otophyllum.	Roots	[47]
319	Cynotophylloside D	C. otophyllum.	Roots	[47]
320	Cynotophylloside E	C. otophyllum.	Roots	[47]
321	Cynotophylloside F	C. otophyllum.	Roots	[47]
322	Cynotophylloside H	C.otophyllum	Roots/stems	[71]
323	Stephanoside H	C. otophyllum	Roots	[46]
324	Wallicoside	C. otophyllum	Roots	[18]
325	Wallicoside J	C. otophyllum	Roots	[46]
326	Cynawilfoside A	C. wilfordii.	Roots	[50]
327	Cynawilfoside B	C. wilfordii.	Roots	[50]
328	Cynawilfoside C	C. wilfordii.	Roots	[50]
329	Cynawilfoside D	C. wilfordii.	Roots	[50]
330	Cynawilfoside E	C. wilfordii.	Roots	[50]
331	Cynawilfoside F	C. wilfordii.	Roots	[50]
332	Cynawilfoside G	C. wilfordii.	Roots	[50]
333	Cynawilfoside H	C. wilfordii.	Roots	[50]
334	Cynawilfoside I	C. wilfordii.	Roots	[50]
335	Atratcynoside A	C. atratum	Roots	[72]
336	Atratcynoside B	C. atratum	Roots	[72]
337	Atratcynoside C	C. atratum	Roots	[72]
338	Atratcynoside D	C. atratum	Roots	[72]
339	Atratcynoside E	C. atratum	Roots	[72]
340	Atratcynoside F	C. atratum	Roots	[72]
341	Mooreanoside A	C. mooreanum	Roots	[73]
342	Mooreanoside B	C. mooreanum	Roots	[73]
343	Mooreanoside C	C. mooreanum	Roots	[73]
344	Mooreanoside D	C. mooreanum	Roots	[73]
345	Mooreanoside E	C. mooreanum	Roots	[73]
346	Mooreanoside F	C. mooreanum	Roots	[73]
347	Mooreanoside G	C. mooreanum	Roots	[73]
348	Mooreanoside H	C. mooreanum	Roots	[73]
349	Mooreanoside I	C. mooreanum	Roots	[73]
350	Mooreanoside J	C. mooreanum	Roots	[73]
351	Mooreanoside K	C. mooreanum	Roots	[73]
352	Mooreanoside L	C. mooreanum	Roots	[73]
353	Mooreanoside M	C. mooreanum	Roots	[73]
354	Mooreanoside N	C. mooreanum	Roots	[73]
355	Mooreanoside O	C. mooreanum	Roots	[73]
356	Mooreanoside P	C. mooreanum	Roots	[73]
357	Cynastauoside A	C. stauntonii	Roots	[74]
358	Cynastauoside B	C. stauntonii	Roots	[74]
359	Cynastauoside C	C. stauntonii	Roots	[74]
360	Saccatol A	C. saccatum	Roots	[56]
361	Saccatol B	C. saccatum	Roots	[56]
362	Saccatol C	C. saccatum	Roots	[56]
363	Cynanotoside A	C. otophyllum	Roots/stems	[71]
364	Cynanotoside B	C. otophyllum	Roots/stems	[71]
365	Cynanotoside C	C. otophyllum	Roots/stems	[71]
366	Cynanotoside D	C. otophyllum	Roots/stems	[71]
367	Cynanotoside E	C. otophyllum	Roots/stems	[71]
368	Mucronatoside C	C. otophyllum	Roots	[46]
369	Sinomarinoside B	C. otophyllum	Roots	[46]
370	Cynanotophylloside A	C. otophyllum	Roots	[31]
371	Cynanotophylloside B	C. otophyllum	Roots	[31]
372	Cynanotophylloside C	C. otophyllum	Roots	[31]
373	Cynanotophylloside D	C. otophyllum	Roots	[31]
374	Cynanauriculatoside A	C. otophyllum	Roots	[31]
375	3β,14β-dihydroxy-14β-pregn-5-en-20-one	C. paniculatum.	Root/rhizome	[41]
376	3-O-β-d-oleandropanyanoside	C. paniculatum.	Root/rhizome	[41]
377	Hancopregnane	C. hunmkiunum	Roots	[37]
378	Menarandroside A	C. menarandrense	Aerial parts	[75]
379	Menarandroside B	C. menarandrense	Aerial parts	[75]
380	Menarandroside C	C. menarandrense	Aerial parts	[75]
381	Menarandroside D	C. menarandrense	Aerial parts	[75]
382	Menarandroside E	C. menarandrense	Aerial parts	[75]
383	Carumbelloside I	C. menarandrense	Aerial parts	[75]
384	Carumbelloside II	C. menarandrense	Aerial parts	[75]
385	Pregnenolone-3-O-gentiobioside	C. menarandrense	Aerial parts	[75]
386	14-O-methyl-3-epi-hirundigenin	C. stauntonii	Roots	[76]
387	Stauntosaponin A	C. stauntonii	Roots	[77]
388	Stauntosaponin B	C. stauntonii	Roots	[77]
Benzene and its derivatives
389	Cynantetrone	C. taiwanianum	Rhizome	[78]
390	CynantetroneA	C. taiwanianum	Rhizome	[78]
391	Cynandione A	C. taiwanianum	Rhizome	[78]
392	Cynandione B	C. taiwanianum	Rhizome	[78]
393	2,4-Dihydroxyacetophenone	C. atratum	Roots	[25]
394	2,5-Dihydroxyacetophenone	C. bungei	Roots	[79]
395	4-Hydroxyacetophenone	C. atratum	Roots	[25]
396	4-acetylphenol	C. paniculatum	Roots	[80]
397	2,5-dihydroxy-4-methoxyacetophenone	C. paniculatum	Roots	[80]
398	2,3-dihydroxy-4-methoxyacetophenone	C. paniculatum	Roots	[81]
399	Acetoveratrone	C. paniculatum	Roots	[80]
400	2,5-dimethoxyhydroquinone	C. paniculatum	Roots	[80]
401	Resacetophenone	C. paniculatum	Roots	[80]
402	M-acetylphenol	C. paniculatum	Roots	[80]
403	Vanillic acid	C. paniculatum	Roots	[80]
404	3,5-dimethoxyhydroquinone	C. paniculatum	Roots	[80]
405	Acetovanillone	C. wilfordii	Roots	[3]
406	p-hydroxyacetophenone	C. wilfordii	Roots	[3]
407	3-(β-d-ribofuranosyl)-2,3-dihydro-6H-1,3-oxazine-2,6-dione	C. wilfordii	Roots	[3]
408	Bungeiside A	C. wilfordii	Roots	[3]
409	Cynanoneside B	C. wilfordii	Roots	[3]
410	Cynanoneside A	C. taiwanianum	Roots	[82]
411	Baishouwubenzophenone	C. auriculatum	Roots	[83]
412	3,4-dihydroxyacetophenone	C. atratum	Roots	[39]
413	4′-hydroxy-3′-methoxyacetophenone	C. wilfordii	Roots	[84]
414	Paeonol	C. auriculatum	Roots	[58]
415	Isopaeonol	C. auriculatum	Roots	[58]
416	2-hydroxy-5-methoxyacetophenone	C. auriculatum	Roots	[58]
417	Caffeic acid	C. taiwanianum	Aerial parts	[85]
418	Syringic acid	C. paniculatum	Roots	[86]
Alkaloids
419	Gagamine	C. caudatum	Roots	[87]
420	Antofine	C. vincetoxicum	Aerial parts	[88]
421	Tylophorine	C. vincetoxicum	Aerial parts	[88]
422	Vincetene	C. vincetoxicum	Aerial parts	[88,89]
423	(-)-10β,13aα-14β-hydroxyantofine N-oxide	C. vincetoxicum	Aerial parts	[90]
424	(-)-10β,13aα-secoantofine N-oxide	C. vincetoxicum	Aerial parts	[90]
425	(-)-(R)-13aα-6-O-desmethylantofine	C. vincetoxicum	Aerial parts	[91]
426	(-)-(R)-13aα-secoantofine	C. vincetoxicum	Aerial parts	[91]
427	(-)-(R)-13aα-6-O-desmethylsecoantofine	C. vincetoxicum	Aerial parts	[91]
428	(-)-10β-antofine N-oxide	C. vincetoxicum	Aerial parts	[90]
429	2,3-dimethoxy-6-(3-oxo-butyl)-7,9,10,11,11a,12-hexahydrobenzo[f]pyrrolo[1,2-b]isoquinoline	C. komarovii	Aerial parts	[92]
430	7-demethoxytylophorine	C. komarovii	Aerial parts	[92]
431	7-demethoxytylophorine N-oxide	C. komarovii	Aerial parts	[92]
Flavones
432	7-O-α-l-rhamnopyranosyl-kaempferol-3-O-β-d-glucopyranoside	C. chinese	Aerial parts	[93]
433	7-O-α-l-rhamnopyranosyl-kaempferol-3-O-α-l-rhamnopyranoside	C. chinese	Aerial parts	[93]
434	Kaempferol	C. taiwanianum	Aerial parts	[85]
435	Astragalin	C. taiwanianum	Aerial parts	[85]
436	Afzelin	C. taiwanianum	Aerial parts	[85]
437	Trifolin	C. taiwanianum	Aerial parts	[85]
438	Quercetin	C. taiwanianum	Aerial parts	[85]
439	Isoquercitrin	C. taiwanianum	Aerial parts	[85]
440	Quercitrin	C. taiwanianum	Aerial parts	[85]
441	Hyperin	C. taiwanianum	Aerial parts	[85]
Terpene
442	Neohancoside A	C. hunmkiunum	Roots	[34]
443	Neohancoside B	C. hunmkiunum	Roots	[62]
444	β-amyrin	C. paniculatum	Roots	[86]
445	α-amyrin	C. paniculatum	Roots	[86]
446	Lupeol	C. paniculatum	Roots	[86]
447	Taraxasterol	C. paniculatum	Roots	[86]
448	Ursolic acid	C. paniculatum	Roots	[86]
449	Oleanolic acid	C. paniculatum	Roots	[86]
450	Maslinic acid	C. paniculatum	Roots	[86]

Figure 1

Structures of newly isolated C21 steroid compounds from Cynanchum species in 2016–2017.

3.1. C21 Steroids

The C21 steroid compounds all have the basic skeleton of pregnane, which containing 21 carbon atoms or a derivative of its isomers. C21 steroid constituents in Cynanchum sp. can be classified into two groups on the basis of their carbon frameworks as typical and modified C21 steroids. According to the different pregnane skeletons, these compounds can be finally divided into the following five types: the normal four-ring pregnane type, 14,15-secopregnanetype, 13,14:14,15-diseco-pregnane type, aberrant 14,15-seco-pregnane type and 12,13-seco-14,18-nor-pregnane type. In C21 steroidal glycosides, sugar moiety is linked most frequently at C-3 to a hydroxyl group of the pregnane aglycone, which contains one to seven sugar units with mode of 1→4, and is generally composed of a linear (rather than a branched) oligosaccharide chain. The most common sugar residues are hexose (glucose), 6-deoxyhexose (thevetose) and 2,6-dideoxyhexoses (cymarose, oleandrose, digitoxose, diginose, sarmentose and canarose). In 2016, Gu et al. on the C21 steroid have been comprehensively and fully explained [2]. Therefore, we summarized the newly isolated compounds from Cynanchum sp. in 2016–2017 (Figure 1).

3.2. Benzene and Its Derivatives

Benzene and its derivatives are also found in Cynanchum plants. These components are mainly acetophenone derivatives, and most of them were isolated from C. paniculatum, C. auriculatum and C. stauntonii. The acetophenones in Cynanchum sp. include cynantetrone (389), cynantetrone A (390), cynandione A (391), cynandione B (392) [78], 2,4-dihydroxyacetophenone (393), 2,5-dihydroxyacetophenone (394) [79], 4-hydroxyacetophenone (395) [25], 4-acetylphenol (396), 2,5-dihydroxy-4-methoxyacetophenone (397), 2,3-dihydroxy-4-methoxyacetophenone (398) [81], acetoveratrone (399), 2,5-dimethoxyhydroquinone (400), resacetophenone (401), m-acetylphenol (402), vanillic acid (403), 3,5-dimethoxyhydroquinone (404) [80], acetovanillone (405), p-hydroxyacetophenone (406), 3-(β-d-ribofuranosyl)-2,3-dihydro-6H-1,3-oxazine-2,6-dione (407), bungeiside A (408), cynanoneside B (409) [3], cynanoneside A (410) [82], baishouwubenzophenone (411) [83], 3,4-dihydroxyacetophenone (412) [39], 4′-hydroxy-3′-methoxyacetophenone (413) [84], paeonol (414), isopaeonol (415), 2-hydroxy-5-methoxyacetophenone (416) [86], caffeic acid (417) [85] and syringic acid (418) [25]. Structures of these compounds are shown in Figure 2.

Figure 2

Structures of compounds 389–418 from Cynanchum species.

3.3. Alkaloids

Studies showed that alkaloids are only found in several plants of genus Cynanchum, and some of these alkaloids showed notable bioactivity. To date, 13 alkaloids were identified from genus Cynanchum. These alkaloids include a steroidal alkaloid gagaminine (419) [94] and fourteen phenanthroindolizidine alkaloids. The phenanthroindolizidine is an alkaloid with a basic skeleton that is a pentacyclic structure with a phenanthrene ring and a indolizidine ring, in which the phenanthrene ring contains a plurality of methoxy groups or hydroxyl groups, and some of the alkaloids also contain a methyl group or a hydroxyl group on the indolizidine ring. In this type of alkaloid, the phenanthrene ring of some compounds is not formed, and some compounds are nitrogen oxides. In addition to compound 419, compounds 420–432 have been identified as phenanthroindolizidine alkaloids. These compounds were isolated from aerial parts of C. vincetoxicum and identified as antofine (420), tylophorine (421), vincetene (422) [88], (-)-10β, 13aα-14β-hydroxyantofine N-oxide (423), (-)-10-β, 13aα-secoantofine N-oxide (424) [90], (−)-(R)-13aα-6-O-desmethylantofine (425), (−)-(R)-13aα-secoantofine (426), (−)-(R)-13aα-6-O-desmethylsecoantofine (427) [91], (-)-10β-antofine N-oxide (428) [90], 2,3-dimethoxy-6-(3-oxo-butyl)-7,9,10,11,11a,12-hexahydrobenzo[f]pyrrolo[1,2-b]isoquinoline (429), 7-demethoxytylophorine (430) and 7-demethoxy-tylophorine N-oxide (431) [92]. Structures of these compounds are shown in Figure 3.

Figure 3

Structures of compounds 419–431 from Cynanchum species.

3.4. Flavones

To date, there are few flavonoids isolated and identified from genus Cynanchum and most of them are flavonoid glycosides with 3- or 7-linked glycans. 7-O-α-l-rhamnopyranosyl-kaempferol-3-O-β-d-glucopyranoside (432) and 7-O-α-l-rhamnopyranosyl-kaempferol-3-O-α-l-rhamnopyranoside (433) were identified from C. chinense [93]. Eight flavone components kaempferol (434), astragalin (435), afzelin (436), trifolin (437), quercetin (438), isoquercitrin (439), quercitrin (440) and hyperin (441) [85] were isolated from the aerial part of C. taiwanianum. Structures of these compounds are shown in Figure 4.

Figure 4

Structures of compounds 432–441 from Cynanchum species.

3.5. Terpene

The basic skeleton of terpenoids is a type of compound composed of isoprene structural units linked. There are two monoterpene diglycosides neohancoside A (442) and B (443) are monoterpene diglycosides isolated from C. hancockianum A and B [95]. In addition, there are also seven pentacyclic triterpene compounds β-amyrin (444), α-amyrin (445), lupeol (446), taraxasterol (447), ursolic acid (448), oleanolic acid (449) and maslinic acid (450), were isolated from the roots of C. paniculatum [86]. The structures of these compounds are shown in Figure 5.

Figure 5

Structures of compounds 442–450 from Cynanchum species.

3.6. Others

In addition to the above-mentioned main components, other components, such as carboxylic acid, alcohol, ester and lignin, are foundin Cynanchum. These compounds include azelaic acid, suberic acid and succinic acid [85]; 3,3′-dimethoxy-4,9,9′-trihydroxy-benzofuranoid ligan-7′-ene-9-O-β-d-glucoside; 3,5-dihydroxybenzoic acid methyl ester; 4-dydroxybenzoic acid; 2,5-dihydroxybenzoic acid methyl ester [56]; conduritol F [3], p-menthane-1,7,8-triol, 1-p-menthane-8,9-triol, p-menthane-1,8,9-triol,trans-terpin [37], 2,6,2′,6′-tetramethoxy-4,4′-bis(2,3-epoxy-1-hydroxypropyl)-biphenyl [39] and (+)-(7S,8R,7′E)-5-hydroxy-3,5′-dimethoxy-4′,7-epoxy-8,3′-neolign-7′-ene-9,9′-diol 9′-ethyl ether [63].

4. Pharmacology

In recent years, research reports on the chemical constituents and pharmacological activities of plants of genus Cynanchum have shown an increasing trend. An increasing number of researchers show special interest in this genus and its therapeutic properties in the field of traditional Chinese medicine. In Table 4, it was summarized on the major ethnic pharmacological uses of Cynanchum sp. and the status of modern pharmacological evaluation. Its pharmacological effects are mainly anti-cancer, anti-inflammatory, anti-virus, appetite suppressing and other effects.

Table 4

Summary of pharmacological activities of the extracts/compounds from different parts of Cynanchum species.

Cynanchum Species	Extract/Isolate	Plant Part	In Vitro/In Vivo	Dosage/Duration	Model/Effect	Ref.
Anti-cancer
C. taiwanianum	Cynantetrone, cynandione B	Rhizome	In vitro		Compounds against T-24 cell lines with ED50 values of ca. 3.5 and 2.5 μg/mL, respectively, and cynandione B against PLC/PRF/5 cell lines (ED50 = 2.7 μg/mL).	[78]
C.auriculatum	Ethanol extract, Petroleumether, CHCl3, EtOAc and n-BuOH fraction	Root tubers	In vitro	1 μg/mL	The ethanol extract against K562, with the highest inhibition ratio of 24.06% at a concentration of 1 μg/mL.	[96]
			In vivo	100 mg/kg/Gavage 7 d	The ethanol extract and n-BuOH fraction showed significant antitumor activity by inhibiting the growth of sarcoma S180 in mice with an inhibition ratio of 42.22% and 41.50%.
C. auriculatum	Total glucosides		In vivo	225 mg/kg 10 d	Model: C57BL/6 mice bearing Lewis lung carcinoma. The inhibition rate of tumor weight was 38.68% the inhibition rate of lung metastasis was 63.64%.	[97]
C.auriculatum	Caudatin, caudatin-2,6-dideoxy-3-O-methy-β-d-cymaropyranoside	Root tubers	In vitro	12 μM	Model: Human tumor cell line SMMC–7721.IC50 = 24.95 μM; IC50 = 13.49 μM	[48]
			In vivo	10, 20, 40 mg/Kg 9 d	Model: Transplantable H22 tumors in mice.The growth of transplantable H22tumors in mice was inhibited.
C.auriculatum	Kidjoranin 3-O-α-diginopyranosyl-(1→4)-β-cymaropyranoside, kidjoranin 3-O-β-digitoxopyranoside, caudatin 3-O-β-cymaropyranoside	Roots	In vitro		Model: SMMC-7721 and HeLa cell lines.IC50 = 8.6 μM–58.5 μM.	[98]
C. auriculatum	Auriculoside A, auriculoside B	Roots	In vitro		Have significant cytoxicity against PC3, Hce-8693, Hela, and PAA cell lines.	[99]
C. vincetoxicum	Alkaloids	Overground	In vitro		These alkaloids inhibit growth of the hormone in dependent breast cancer cells MDA-MB 231.	[88]
C. paniculatum	Neocynapanogenin F, neocynapanogenin F 3-O-β-d-thevetoside	Roots	In vitro	100 μg/mL	These compounds exhibited significant cytotoxic activity on HL-60. The inhibitory rate (%, n = 6) was 74.18% and 97.87%, respectively.	[35]
C. paniculatum	Cynanside A, Cynanside B	Roots	In vitro		Model: SK-MEL-2 cells.IC50 values = 26.55 μM;IC50 values = 17.36 μM	[58]
C. paniculatum	Antofine	Roots	In vitro	Ellipticine: IC50 = 500 ± 25 ng/mL	Model: Human lung cancer cells A549.IC50 = 7.0 ± 0.2 ng/mL	[100]
				Ellipticine: IC50 = 340 ± 35 ng/mL	Model: Human colon cancer cells Col2.IC50 = 8.6 ± 0.3 ng/mL
C. wilfordii	20-O-salicyl-kidjoranin	Roots	In vitro	Adriamycin	Model: Human leukemia cell lines HL-60, K562 and breast cancer cell lines MCF-7.The compound can against HL-60 (IC50 = 6.72 μM) and MCF-7 (IC50 = 2.89 μM).	[9]
	Qingyangshengenin				The compound can against K-562 (IC50 = 6.72 μM).
	Rostratamin				The compound can against MCF-7 (IC50 = 2.49 μM).
C. wilfordii	Gagaminin 3-O-β-d-cymaropyranosyl-(1→4)-β-d-oleandropyranosyl-(1→4)-β-d-cymaropyranosyl-(1→4)-β-d-cymaropyranoside	Roots	In vitro	1 μM	Model: KB-V1 and MCF7/ADR cells.The compounds completely reverse the multidrug-resistance of KB-V1 and MCF7/ADR cells to Adriamycin, vinblastine, and colchicine.	[54]
C. atratum	Glaucogenin C 3-O-β-d-cymaropyranosyl-(1→4)-α-l-diginopyranosyl-(1→4)-β-d-thevetopyranoside	Roots	In vitro	Dexamethasone: 10 μM, compound: 30 μM	Model: 212 cells, RAW 264.7 mouse macrophage-like cell, N9 microglial cell.ED50 value of against 212 cells was 0.96 μg/mL and significant inhibitory on TNF-α formation.	[39]
C. vincetoxicum	(-)-10β-antofine N-oxide , (-)-10β,13aα-14β-hydroxyantofine N-oxide	Aerial parts	In vitro		Model: drug-sensitive KB-3-1 cell line and the multi-drug-resistant KB-V1 cell line.IC50 = 100 nM	[90]
C. vincetoxicum	(-)-(R)-13aα-antofine, (-)-(R)-13aα-6-O-desmethylantofine	Leaves	In vitro		Model: KB-3-1 and the KB-V1 cell line.IC50 values of 7–17 nM	[91]
C. saccatum	Cynsaccatol E	Roots	In vitro	5-FU and cisplatin	Model: HepG2 cell lines IC50 = 49.18 ± 5.67μM.	[55]
	Gagaminine 3-O-β-d-oleandropyranosyl-(1→4)-β-d-oleandropyranosyl-(1→4)-β-d-cymaropyranoside				Model: HepG2 and Hela cell lines.IC50 = 68.05 ± 4.09 μM and IC50 = 94.88 ± 9.73 μM.
	Cynsaccatol A				Model: U251 cell lines. IC50 = 35.66 ± 3.54 μM.
	Cynsaccatol D				Model: U251 cell lines. IC50 = 31.98 ± 6.55 μM
C. saccatum	Glaucogenin C-3-O-β-d-monothevetoside	Whole fresh plants	In vitro	Cisplatin: IC50 = 21.51 μM	The compound could induce HepG2 cell apoptosis via a mitochondrial pathway and IC50 value of 12.24 μM	[101]
C. paniculatum	Cynatratoside B	Roots	In vitro	5-Fluorouracil	Compound exhibited potent inhibitory activities against HL-60, HT-29, PC-3 and MCF-7 cell lines with IC50 values of 8.3, 7.5, 34.3 and 19.4 μM, respectively.	[102]
C. atratum	C21 steroids	Roots	In vitro	Cisplatin (25 μg/mL)	Model: HepG2, A549 cell lines.Compounds 1–4 displayed obvious cytotoxic activities against HepG2 cells with IC50 values ranging from 10.19 μM to 76.12 μM. Compounds 1–3 also exhibited cytotoxic effects in A549 cells with IC50 values of 30.87–95.39 μM.	[103]
Neuroprotective effect
C. wilfordii	Cynandione A	Roots	In vitro	50 μM.	Model: Neurotoxicity induced by H2O2 in cultured cortical cells. The compound could reduce neurotoxicity induced by H2O2.	[104]
C. atratum	Cynatroside A, cynatroside B, cynatroside C, cynascyroside D	Roots	In vitro	Velnacrine: IC50 = 0.4 μM.	These compounds could inhibit acetylcholinesterase activity.IC50 = 6.4 μM, IC50 = 3.6 μM, IC50 = 52.3 μM, IC50 = 52.9 μM, respectively.	[25]
C. paniculatum	2,3-dihydroxy-4-methoxyacetophenone	Roots	In vitro	Trolox (10 μM).	Model: Glutamate-induced neurotoxicity in HT22 cells. Relatively effective protection of 47.55% (at 10 μM).	[81]
C. atratum	Cynatroside B	Roots	In vivo	Donepezil: 0.032–3.2 mg/Kg body weight i.p.	The results showed that compound has both anti-AchE and anti-amnesic activities.	[105]
C. otophyllum	Cynanotoside A, cynanotoside B, cynotophylloside H	Roots and stems	In vitro		Three oxidative stress models induced by glutamate, H2O2, and homocysteic acid (HCA), respectively, in a hippocampal neuronal cell line HT22.Compounds showed significant dose-dependent protection to HCA-induced cell death ranging from 1 to 30 μM.	[71]
C. otophyllum	Otophylloside F, otophylloside B	Roots	In vivo	phenytoin sodium showed a therapeutic efficacy of 66% at 300 μM	Model: Antiseizure-like locomotor activity in the zebrafish bioassay model.The otophylloside F at a 300 μM concentration showed a therapeutic efficacy of 55%. The otophylloside B at 100 and 200 μM concentrations showed therapeutic efficacies of 77% and 90%, respectively.	[16]
C. wilfordii	Cynawilfoside A, cynauricoside A, wilfoside C1N, wilfoside K1N and cyanoauriculoside G	Roots	In vivo	Retigabine: 15.0 mg/kg	Model: MES-induced mouse seizure model.ED50 values of 48.5, 95.3, 124.1, 72.3, and 88.1 mg/kg, respectively.	[50]
C. otophyllum	Otophylloside B	Roots	In vivo	Curcumin: 100 μM	Model: AD (Alzheimer’s disease).50 μM	[106]
Antifungal ,parasitic and antiviral Activity
C. wilfordii	Wilfoside C1N, wilfoside C1G, wilfoside C1GG	Roots	In vivo	PolyoxinB (IC50 value = 71.36 μg/mL)	Model: Barley powdery mildew.The IC50 (i.e., the concentration required for 50% inhibition) were determined as 3.24 μg/mL, 12.90 μg/mL, and 28.35 μg/mL, respectively.	[27]
C. paniculatum	Ethyl acetate (EA) extracts	Roots	In vitro	Amantadine	Model: Madin-Darby bovine kidney (MDBK) cells.The tissue culture infectious dose assay (TCID50) assay.The cytotoxic concentration CC50 was 18.2 μg/mL; The EA MNTD (Maximum non-toxic dose) is 18.2 μg/mL.	[107]
C. atratum	Cynatratoside C	Roots	In vitro		Model: Grasscarp infected with I. multifiliis.0.25 mg/L.	[10]
C. paniculatum	Cynatratoside A; cynanversicoside C	Roots	In vitro		Cynatratoside A and cynanversicoside C could be 100% effective against I. multifiliis at the concentration of 10.0 mg L−1, with the median effective concentration (EC50) values of 4.6 and 5.2 mgL−1, respectively.	[11]
C. paniculatum	Essential oil	Roots	In vitro	Benzyl benzoate and DEET (diethylmethylbenzamide) 1.13 μg/cm2	LD50 were 8.93, 4.58, and 2.79. It showed more toxic than DEET (LD50 = 4.13, 3.91, and 4.87 μg/cm2) against D. farinae, D. pteronyssinus, and T. putrescentiae, respectively.	[108]
C. komarovii	7-demethoxytylophorine(1),7-demethoxytylophorine N-oxide(2)	Roots	In vitro	2,4-dioxo-hexahydro-1,3,5-triazine, showed 50% inhibition at 500 μg/mL	The alkaloid 1 exhibited 65% inhibition against the TMV at a concentration of 1.0 μg/mL. Alkaloid 2 showed 60% inhibition at 500 μg/mL	[92]
C. atratum	Cynanoside A,G,M; glaucogenin-C 3-O-β-d-cymaropyranosyl-(1→4)-α-L-diginopyranosyl-(1→4)-β-d-cymaropyranoside; glaucogenin-A 3-O-β-d-cymaropyranosyl-(1→4)-α-L-diginopyranosyl-(1→4)-β-d-cymaropyranoside	Roots	In vivo	Ningnanmycin (IC50 = 49.6 μg/mL).	IC50 = 20.5 μg/mL, IC50 = 18.6 μg/mL, IC50 = 22.0 μg/mL, IC50 = 19.2 μg/mL, IC50 = 22.2 μg/mL, respectively.	[36]
C. stauntonii	Volatile oil	Roots	In vitro	300 mg/kg 6 d	Model: Mouse influenza model. IC50 = 64 μg/mL	[109]
Immunosuppressive activity
C. chekiangense	Chekiangensosides A, cynajapogenin A, chekiangensoside B, glaucogenin A	Roots	In vitro	cyclosporin A	Model: Con A- and LPS-induced proliferation of mice splenocytes.100 μL (0.01–10 g/mL)	[23]
C. atratum	Atratcynoside A, atratcynoside B, atratcynoside C	Roots	In vitro	Cyclosporin A: 0.09 ± 0.01 μM	Model: Con A-induced proliferation of T-lymphocytes from mice.IC50 values of 3.3 μM, 7.0 μM, 6.7 μM, respectively.	[72]
Anti-inflammatory activity
C. stauntonii	Cynastauoside B; cynastauoside C	Roots	In vitro	Dexamethasone with the inhibition ratio of 83.5% at a concentration of 1 μM.	Model: C57bl/6j mouse peritoneal macrophages.The results showed 17.0% and 6.9% of inhibition rate at a concentration of 10 μM, respectively.	[74]
C. wilfordii.	Cynandione A	Roots	In vitro		Model: LPS-Induced BV-2 microglial cells. IC50 = 27.13 ± 5.38 μM.	[110]
C. stauntonii	Stauntoside V1; stauntoside V3	Roots	In vitro	Dexamethasone: IC50 = 0.3 μM	Model: C57bl/6j mouse peritoneal macrophages. IC50 values of 9.3 μM and 12.4 μM, respectively.	[111]
C. atratum	Aqueous extract	Roots	In vivo	dexamethasone	Model: Female BALB/c mice/atopicDermatitis (AD) and Human mast cell line (HMC-1).1 or 100 mg/mL.	[112]
			In vitro
C. wilfordii	Polysaccharides	Roots	In vivo	5-aminosalicylic acid (100 mg/kg)	Model: DSS (dextran sodium sulfate)-induced chroniccolitis in mice.200 mg/kg or 100 mg/kg	[113]
			In vitro		Model: LPS-induced RAW 264.7 macrophages.25 μg/mL
Anti-oxidation
C. wilfordi	Gagaminine	Roots	In vivo	Pyridoxal: IC50 = 246 μM	Model: Rat liver injury model.IC50 = 0.8 μM (0.5 μg/mL)	[94]
C. otophyllum	Otophyllosides A and B	Roots	In vivo		These compounds could protect rats from audiogenic seizures and ED50 value of 10.2 mg/kg.	[8]
Hepatoprotective activity
C. wilfordii	Cynandione A	Roots	In vitro	Silybin (100 μM)	Model: Primary cultures of rat hepatocytes injured by CCl4.50 μM	[114]
C. wilfordii	Crude extract (CWE)	Roots	In vivo	Simvastatin/10 mg/kg/day/12 weeksCWE:100 and 200 mg/kg/day/12 weeks	Model: Male C57BL/6 mice.CWE can inhibit fat accumulation in the liver. Suppressing lipid accumulation in the liver and reducing blood levels of total cholesterol and triglycerides.	[115]
Appetite suppressant effect
C.auriculatum	Wilfoside K1N	Roots	In vivo	Sibutramine15 mg/kg body weightCompound: 50 mg/kg body weight	Model: SPF female Wistar rats.	[30]
Antidepressant activity
C. auriculatum	Cynanauriculoside C, cynanauriculoside D, cynanauriculoside E, otophylloside L, cynauricuoside C	Roots	In vivo	fluoxetine (20 mg/kg)Compound: 50 mg/kg (i.g.)/twice a day/5 d Male ICR mice (18–22 g)	These compounds could significant antidepressant activity at the dosage of 50 mg/kg (i.g.)	[67]
Vasodilating activity
C. stauntonii	Stauntonine	Roots	In vivo		IC50 = 5.37 × 10−6 mol/L	[40]
C. auriculatum	Caudatin		In vitro and In vivo		Model: HUVEC human umbilical vein endothelial cell and U251 human glioma cells xenograft model.25–200 μM.	[116]
Others
C. bungei	2,5-dihydroxyacetophenone (2,5-DHAP)	Roots	In vitro and In vivo	Standard depigmenting agent: 0.2 mM	0.4 mM	[79]
C. stauntonii	Stauntosaponins A and B	Roots	In vitro	Ouabain: IC50 value of 3.5 μM. Assay of Na+/K+-ATPase inhibition	IC50 = 21 μM and IC50 = 29 μM	[77]
C. taiwanianum	Cynandione B	Plants	In vitro		Model: The formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated rat neutrophil washed rabbit platelets induced by arachidonic acid.IC50 = 1.5 ± 0.2 and 1.6 ± 0.2 μM, respectively.	[117]
	2,5-Dihydroxyacetophenone				IC50 = 4.8 μM.
C. stauntonii	Cynatratoside B	Roots	In vitro	Isoprenaline: IC50 = 0.13 μM	Model: Rat Tracheal Rings Preparation.The EC50 acetylcholine- and carbachol-induced contraction of compound were 0.67 and 0.38 μg/mL (∼0.85 and 0.48 μM), respectively.	[12]

4.1. Anti-Cancer

Crude extracts and compounds have significant activity against tumor cells, such as the SMMC-7721, MCF-7, Hela, K562, SHG44, HCT-8, A549, PC3, PLC/PRF/5, KB, T-24, A549, SK-OV-3, SK-MEL-2, HCT-15, Col2, 212, HepG2 and U251 cell lines in vitro. However, few studies have been conducted on the anti-cancer activity of Cynanchum plants in vivo.

The anti-cancer activity of the ethanol extract of C. auriculatum and different solvent extraction fractions was studied by inhibiting the growth of sarcoma S180 in mice and In vitro MTT assay. The ethanol extract inhibits K562 cell growth, with the highest inhibition ratio of 24.06% at a concentration of 1 μg/mL [96]. The inhibition rate of petroleum ether to PC3 cells at a concentration of 100 μg/mL is 33.63%. At a concentration of 100 μg/mL, the inhibition ratio of the CHCl3 fraction against K562, SHG44, HCT-8, A549 and PC3 are 35.64%, 20.61%, 31.64%, 26.99% and 52.11%, respectively. The inhibitory rates of EtOAc fraction on A549 and PC3 cells are 37.86% and 28.41%, respectively. The n-BuOH fraction shows weak cytotoxicity to other cells at the same concentration except for K562 cells. In addition, the ethanol extract and n-BuOH fraction inhibit the growth of sarcoma S180 in mice compared with the blank control (p < 0.01) at a dose of 100 mg/kg.

Compounds 389 and 392 from the rhizomes of C. taiwanianum showed significant cytotoxic effects against T-24 cell lines with ED50 values of ca. 3.5 and 2.5 mg/mL, respectively. Compound 385 also adversely affected PLC/PRF/5 cell lines (ED50 = 2.7 mg/mL) [78].

In 1992, alkaloids 420–423 extracted from C. vincetoxicum, were found to inhibit the growth of MDA-MB-231 mammary carcinoma cells. Compounds 420, 425–429 and 430, which were isolated from the aerial parts of C. vincetoxicum, are assessed In vitro using both drug-sensitive KB-3-1 and multidrug-resistant KB-V1 cancer cell lines [90,91]. The results showed that compounds 420, 425, 427 and 430 exhibited pronounced cytotoxicity against KB-3-1 and KB-V1 cell lines with IC50 (the concentration required for 50% inhibition) values in the low nanomolar range. In addition, Sang et al. found that compound 420, which is isolated from the root of C. paniculatum, inhibits the growth of A549 and Col2 cell lines with IC50 values of 7.0 ± 0.2 and 8.6 ± 0.3 ng/mL [100]. Ellipticine, as a positive control, exhibited IC50 value for A549 and Col2 cancer cells ranging from 300–500 ng/mL. Moreover, Col2 cells considerably accumulate in the G2/M cell cycle when treated with antofine (50 pg/mL) for 48 h. Therefore, this mechanism may be the main process by which antofine inhibits the growth of Col2 cells [100].

Compound 215 was isolated from the roots of C. wilfordii (CWW) and completely reverse the multidrug resistance of KB-V1 and MCF7/ADR cells to Adriamycin, vinblastine and colchicine at a concentration level of 1 μM [54].The inhibitory ratio of compound 116 isolated from ethyl acetate extract of C. paniculatum to HL-60 cells at a concentration of 10 μg/mL is 98.14% [35]. Kim et al. evaluated the anti-cancer activity of compounds 232 and 233 isolated from the roots of C. paniculatum against A549, SK-OV-3, SK-MEL-2 and HCT-15 cell lines In vitro by using the SRB bioassay [58]. Experimental results showed that compounds 232 and 233 have selective cytotoxicity on SK-MEL-2 cells with IC50 values of 26.55 and 17.36 μM, respectively.

C21 steroidal compounds, which isolated from genus Cynanchum also exhibit strong anti-cancer activity. Compound 120 isolated from the roots of CA showed significant cytotoxic effect against 212 cells, with ED50 value of 0.96 μg/mL [39].

Two C21 steroidal glycosides, namely, compounds 175 and 176 that were isolated from the roots of C. auriculatum are tested on SMMC-7721, MCF-7 and Hela cell lines. The results showed that the IC50 values of the two compounds against SMMC-7721 cells are 13.49 and 24.95 μM, respectively. Then, the in vivo assay by using solid tumor model H22 in mice was performed [48]. It was found that compounds 175 and 176 can significantly inhibit the growth of transplantable H22 tumors in mice at doses of 10, 20, and 40 mg/kg compared with positive control 5-FU.

The anti-cancer activities of 17 C21-steroidal pregnane sapogenins, namely, compounds 8, 167, 170–172, 174, 175, 177, 200, 209–212, 221, 223, 228 and 417, were evaluated by activity using HL-60, K-562 and MCF-7 cancer cells [9]. The results suggested that compound 8 shows evident cytotoxicity on HL-60 (IC50 = 6.72 μM) and MCF-7 cell lines (IC50 = 2.89 μM), whereas compounds 200 and 221 show strong inhibitory activities against K-562 (IC50 = 6.72 μM) and MCF-7 cell lines (IC50 = 2.49 μM), respectively.

Zhang et al. [46] studied the anti-cancer activity of 26 pregnane glycosides (compounds 37, 38, 43, 168, 184–195, 204–207, 214, 220, 323, 325, 368 and 369) by using three cancer cells (HepG2, Hela and U251). All of these pregnane glycosides compared with the positive compounds 5-FU and cisplatin showed cytotoxic activities (IC50 < 100 μM) in varying degrees against these cell lines except compounds 189 and 205 (IC50 > 100 μM). Moreover, the cytotoxicity of compounds 38, 219, 310–317 is evaluated against three human cancer cell lines, that is, HepG2, Hela and U251 [55].

4.2. Neuroprotective Effect

With the development of the aging population, the incidence of the neurodegenerative diseases also shows a clear upward trend [118]. Therefore, the mechanisms of prevention and early treatment of these diseases have become one of the focuses of research. Research showed that numerous compounds isolated from genus Cynanchum exhibit good neuroprotective effects, thereby indicating its potential for further development.

Compound 391 can protect cultured cortical neurons from toxicity induced by H2O2, l-glutamate and kainate. Compound 391 showed the most potent neuroprotective activity at a concentration of 50 μM. Given its significant neuroprotective effect on cultured cortical neurons, the compound can effectively protect the neurons from oxidative stress mediated by activating a-amino-3-hydroxy-5-methyl-4-isoxazolepropionate/kainate receptors [104].

The inhibitory activities of compounds 85–87 and 278 were tested against acetylcholinesterase (AChE). The result showed that compounds 85 and 86 exhibit the most potent inhibitory activity against AchE, with IC50 values of ca.6.4 and 3.6 μM, respectively. Compounds 87 and 278 also show AChE inhibition activity, with IC50 values of ca. 52.3 and 152.9 μM, respectively [25]. In addition, the anti-amnesic activity of compound 86 was investigated in passive avoidance and Morris water maze tests [105]. The results showed that compound 86 (1.0 mg/kg body weight i.p.) has significantly ameliorated the memory impairments induced in mice by scopolamine (1.0 mg/kg body weight s.c.).

The neuroprotective effect of compound 398 against glutamate-induced neurotoxicity in mouse hippocampal HT22 cells was investigated; the result revealed that this compound exerts a neuroprotective effect on glutamate-induced neurotoxicity in HT22 cells, with relatively effective protection of 47.55% at 10 μM [81]. In the hippocampal neuronal cell line HT22, compounds 363, 364 and 322 resist HCA-induced neuronal cell death within a concentration range of 1–30 μM in a concentration-dependent manner [71].

The effects of 19 compounds which have C21 steroidal structure on anti-seizure-like locomotor activity caused by pentylenetetrazole in zebrafish model were also evaluated. The results showed that compounds 30, 28 and 223 exert a significant therapeutic effect on epilepsy. The results revealed that compound 30 has a therapeutic efficacy of 55% at a concentration of 300 μM, whereas compound 28 shows therapeutic efficacies of 77% and 90% at 100 and 200 μM concentrations, respectively. Meanwhile, compound 223 showed therapeutic efficacies of 65% and 52% at 100 and 200 μM concentrations, respectively. In comparison, the positive control, phenytoin sodium, shows 66% therapeutic efficacy at a concentration of 300 μM. The results also suggested that these three compounds do not exert any nonspecific neurotoxic or sedative effects or affect locomotor activity [16].

In addition, the anti-epileptic activity of 10 C21 steroidal compounds were evaluated by Li et al. by using the mouse maximal electroshock (MES) model after oral administration. The results suggested that five compounds, namely, compounds 326, 240, 99, 96 and 302, exhibit significant protection activity in a MES-induced mouse seizure model, with ED50 values of 48.5, 95.3, 124.1, 72.3 and 88.1 mg/kg, respectively. Under identical experimental conditions, the ED50 value of the positive control retigabine is 15.0 mg/kg [50].

4.3. Anti-Fungal, Anti-Parasitic and Anti-Viral Activities

In the recent years, both compounds and the crude extracts, such as volatile oil and ethyl acetate extracts, from CWW, CA, C. komarovii and other plants were investigated for their anti-fungal, parasitic or anti-viral activity, as shown below.

Six compounds, namely, compounds 96–99, 103 and 230 isolated from CWW roots, were evaluated against barley powdery mildew In vivo and compared with the anti-fungal activity of polyoxin B. The results suggested that compounds 98, 99 and 103 exhibit potent In vivo anti-fungal activities and present disease-control values of >77% at a concentration of 63 μg/mL. The IC50 values (the concentration required for 50% inhibition) are 3.24, 12.90, and 28.35 μg/mL for compounds 99, 103 and 98, respectively [27].

Compound 20 was isolated from CA roots and was used to treat Ichthyophthirius multifiliis. This compound demonstrates 100% mortality rate of I. multifiliis in vitro after 5 h of exposure at 0.25 mg/L. The 5-hmedian effective concentration of compound to non-encysted tomonts is 0.083 mg/L [10].

Compounds 431–433 exhibit inhibitory activities against Tobacco mosaic virus (TMV). The results showed that alkaloids 432 and 433 exhibit anti-viral activities against TMV. The major active ingredient 432 exhibits 65% inhibition against the TMV at a concentration of 1.0 mg/mL. Alkaloid 433 shows 60% inhibition at 500 mg/mL, whereas compound 431 shows 15% inhibition at 500 mg/mL [92]. In comparison, 2,4-dioxo-hexahydro-1,3,5-triazine shows 50% inhibition at 500 mg/mL under the same conditions.

In addition, Yan et al. studied the anti-TMV activities of 42 compounds isolated from the roots of CA by using the conventional half-leaf method, enzyme-linked immunosorbent assay, and Western blot [36]. The results suggested that compounds 52, 58, 64, 127 and 135 show significant anti-TMV activities with IC50 values of 20.5, 18.6, 22.0, 19.2 and 22.2 μg/mL, respectively. Moreover, the anti-TMV activities of these compounds are considerably more effective than that of the positive control, ningnanmycin (IC50 = 49.6 μg/mL).

The ethyl acetate extract of C. paniculatum exert an anti-viral effect against Bovine viral diarrhea (BVD) virus. The cytotoxic concentration (CC50 for the ethyl acetate extracts is 18.2 μg/mL. In the tissue culture infectious dose assay, the BVD virus decreased when treated with 18.2 μg/mL of the ethyl acetate extracts [107].

4.4. Anti-Inflammatory and Immunosuppressive Effects

Li et al. tested four C21 steroidal glycosides, namely, compounds 81, 277, 82 and 16, for their immunological activities In vitro against concanavalin A (Con A)- and lipopolysaccharide (LPS)-induced proliferation of mice splenocytes [23]. The results showed that these compounds significantly inhibit the proliferation of Con A- and LPS-induced mice splenocytes in vitro in a dose-dependent manner.

Compound 120 has a significant inhibitory effect on TNF-α formation on the RAW 264.7 mouse macrophage-like cell line stimulated with LPS and N9 microglial cell line stimulated with LPS/IFN-γ (interferon-γ) [39].

Cho et al. investigated the anti-inflammatory effects and related molecular mechanisms of a crude polysaccharide (HMFO) which obtained from CWW in mice with dextran sulphate sodium (DSS)-induced colitis and in LPS-induced RAW 264.7 macrophages. It suggested that HMFO ameliorates the pathological characteristics of colitis and significantly reduces the production of proinflammatory cytokines in the serum [113]. Histological analysis indicated that HMFO improves the signs of histological damage. In addition, HMFO inhibits the protein expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and phosphorylates the nuclear factor-kappa B (NF-κB) p65 levels in the colon tissue of mice with DSS-induced colitis. In macrophages, HMFO inhibits several cytokines and enzymes involved in inflammation. HMFO also attenuates inflammation both in vitro and in vivo primarily by inhibiting NF-κB activation.

Zhang et al. investigated the immunosuppressive activities of compounds 335–337 and 9 isolated from 80% ethanol extract of the CA root by using an In vitro model of Con A-induced proliferation of T lymphocytes from mice. As a result, these four compounds exhibit strong inhibition on Con A-stimulated cell proliferation, showing IC50 values of 3.3, 7.0, 6.7 and 10.9 μM [72]. In addition, compounds 341–346, 348–350, 352–354 and 356 were assessed for their immunological activities in vitro against Con A-induced proliferation of mice splenocytes [73]. The results revealed that compounds 341, 342 and 354 at the concentration of 100 μmol/L, compounds 343, 352 and 354 at the concentration of 10 μmol/L and compound 353 at the concentration of 1 μmol/L exhibit weak activity against the proliferation of T lymphocyte In vitro.

Yu et al. found that compounds 358 and 359 inhibit nitric oxide production in C57bl/6j mouse peritoneal macrophages with 17.0% and 6.9% inhibition rates, respectively, at a concentration of 10 μM [74].

Fourteen steroidal glycosides were investigated by detecting the inhibitory effects of iNOS and COX-2 on RAW 246.7 murine macrophage cells stimulated by LPS [44]. The results revealed that compounds 158, 162, 156, 157, 122 and 146 can significantly inhibit iNOS expression, whereas compounds 162 and 148 can clearly inhibit COX-2 expression in RAW 246.7 cells stimulated by LPS compared with cells stimulated with LPS and not treated with other compounds.

The effects of compound 391 and extracts of CWW roots (CWE) on the expression of iNOS and proinflammatory cytokines in LPS-induced BV-2 microglial cells was investigated and the results suggested that CWE and compound 391 significantly decrease the LPS-induced NO production and the expression of iNOS in a concentration-dependent manner. Meanwhile, they did not show cytotoxic activity (CWE up to 500 μg/mL and compound 391 up to 80 μM). In addition, RT-PCR analysis and ELISA showed that compound 391 significantly attenuates the expression of TNF-α, interleukin-6, and interleukin -1β in LPS-stimulated BV-2 cells. Furthermore, compound 391 inhibits the phosphorylation of inhibitor kappa B-alpha and translocation of NF-κB to the BV-2 cell nucleus. It indicates that CWE and compound 391 may exert effective anti-inflammatory activities via NF-κB inactivation in stimulated microglial cells [110].

Choi et al. investigated the anti-atopic dermatitis (AD) effect and molecular mechanism of the aqueous extract of CA. Topical concentrations of CA at 1 and 100 mg/mL are applied to AD-like skin lesions induced by 2,4-dinitrochlorobenzene for 11 days. Scratching behavior occurrences were evaluated for 20 min. The results showed that topical application of CA attenuates the total serum IgE level [112].

4.5. Anti-Oxidizing Effect

Compound 419, a steroidal alkaloid, was isolated from CWW roots, and its effects on lipid peroxidation and the activity of aldehyde oxidase (EC. 1.2.3.1) were investigated In vitro. The results showed that it suppresses the formation of lipid peroxides in rat liver tissues significantly and potently inhibits hepatic aldehydeoxidase activity in a dose-dependent manner, with a IC50 value of 0.8 μM (0.5 μg/mL) [94].

4.6. Hepatoprotective Function

Lee et al. investigated the hepatoprotective activity of compound 391 by using primary cultures of rat hepatocytes injured by CCl4. The results suggested that compound 391 (50 μM) significantly reduces (approximately 50%) the release into the culture medium of glutamic pyruvic transaminase and sorbitol dehydrogenase from the primary cultures of rat hepatocytes exposed to CCl4. Simultaneously, this compound ameliorates lipid peroxidation by up to 50%, as demonstrated by the reduction in malondialdehyde production [114]. In addition, Jang et al. found that CWE (100 and 200 mg/Kg) can decrease fat accumulation in the liver by suppressing COX-2, NF-κB and p38 mitogen-activated protein kinase [115].

4.7. Appetite Suppressant Effect

Compound 96 isolated from C. auriculatum roots can suppress appetite and reduce body weight in rats. Moreover, appetite suppressant isolated from Hoodia gordonii shows significant appetite suppressing effect, resulting in weight loss in rats [30].

4.8. Anti-Depressant Effect

Yang et al. assessed the anti-depressant activities of compounds 294–296, 35 and 231 by using forced swimming, tail suspension and open field tests in despair mice models. The results suggested that these compounds show significant anti-depressant activities at the dosage of 50 mg/kg (i.g.). The most potential one is compound 295, with potency close to that of the positive control fluoxetine (20 mg/kg) [67].

4.9. Vasodilating Activity

Compound 284 was isolated from the C. stauntonii roots, and its vasodilatation activity was investigated. The results indicated that this compound exerts a dose-dependent relaxation effect on aortic rings with endothelium contracted by phenylepherine, with IC50 value of 5.37 × 10−6 mol/L. The inhibitory effect of this compound on aortic rings with endothelium contracted by phenylepherine was exhibited by the relaxation effect at high concentration (10−4 mol/L), with a relaxation percentage 64.8% ± 26.9%. Meanwhile, compound 28 also relaxes the aorta rings contracted by KCl at high concentration (10−4 mol/L), with a relaxation percentage 53.4% ± 7.3% [40].

Moreover, Wang et al. [116] investigated the anti-angiogenic properties of compound 175 from C. auriculatum. The results revealed that it can significantly inhibit the proliferation of HUVEC human umbilical vein endothelial cell proliferation and block the HUVEC migration, invasion and capillary-like tube formation by disturbing the vascular endothelial growth factor (VEGF)-VEGFR2-protein kinase B (AKT)/focal adhesion kinase signal axis.

4.10. Others

In addition to the pharmacological activity of the above-mentioned reviewed Cynanchum plants, compound 394 from C. bungei exerts depigmenting activity [79]. Compounds 387 and 388 from C. stauntonii exhibit anti-cardiac congestion activity [77]. Compounds 392 and 394 have an anti-platelet effect [117]. Ten-week-old female rats were ovariectomized (OVX) and treated with the aqueous extract of CWW for 1 week. The administration of CWW (200 mg/kg/d for 7 days, per os) significantly improves skin temperature increase in OVX rats [119]. Moreover, the aqueous extract of CWW inhibits the development of benign prostatic hyperplasia (BPH) in a testosterone-induced BPH rat model [120]. In addition, compound 22 showed an airway smooth muscle relaxant effect [12].

5. Conclusions

Cynanchum L. is an important genus in the Asclepiadaceae family because numerous plants in this genus show several application prospects other than in the field of medicine. Moreover, Cynanchum plants present a long history as traditional folk medicine.

At present, more than 400 compounds have been isolated from genus Cynanchum. These compounds include steroids, flavonoids, acetophenones, triterpenoids, alkaloids, phytosterols, polysaccharides and other compounds. Among these compounds, C21 steroid is the characteristic ingredient. In China, several species have been used to treat chronic diseases in TCM for thousands of years, and the roots and stems of these species have been used as a component of TCM or in combination with other Chinese medicinal plants.

Recently, increased attention has been focused on C. taiwanianum, C. auriculatum, C. paniculatum, CA, CWW, C. otophyllum and C. stauntonii because of their anti-tumor, neuroprotective, anti-fungal, parasitic and anti-viral, anti-depressant, anti-oxidant, anti-inflammatory and immunosuppressive effects. These plants also can suppress appetite, induce weight loss and expand blood vessels.

Although a number of reports on the chemical components and pharmacological activities of these plants are available, studies on the chemical composition are still not systematic enough because they only focus on the chemical components of several species of this genus. However, research on the pharmacological activities are mostly based on in vitro activity screening, and pharmacodynamic studies in vivo represent only a few reports. Therefore, further investigations are required for systematic research of the chemical composition and in vivo pharmacological activities of Cynanchum sp. We believe that this work is of particular value by providing not only the fundamental insight into the medicinal value of plants in this genus; moreover, this work can provide reference for clinical medication, sustainable development and utilization of plants in this genus.