The genus Rumex (Polygonaceae): an ethnobotanical, phytochemical and pharmacological review.

Rumex L., a genus in Polygonaceae family with about 200 species, is growing widely around the world. Some Rumex species, called "sorrel" or "dock", have been used as food application and treatment of skin diseases and hemostasis after trauma by the local people of its growing areas for centuries. To date, 29 Rumex species have been studied to contain about 268 substances, including anthraquinones, flavonoids, naphthalenes, stilbenes, diterpene alkaloids, terpenes, lignans, and tannins. Crude extract of Rumex spp. and the pure isolates displayed various bioactivities, such as antibacterial, anti-inflammatory, antitumor, antioxidant, cardiovascular protection and antiaging activities. Rumex species have important potential to become a clinical medicinal source in future. This review covers research articles from 1900 to 2022, fetched from SciFinder, Web of Science, ResearchGate, CNKI and Google Scholar, using "Rumex" as a search term ("all fields") with no specific time frame set for the search. Thirty-five Rumex species were selected and summarized on their geographical distribution, edible parts, traditional uses, chemical research and pharmacological properties.

Introduction

Rumex L., the second largest genus in the family Polygonaceae, with more than 200 species, is mainly distributed in the northern temperate zone [1]. It is mostly perennial herbs with sturdy roots, paniculate inflorescences, and triangular fruits that are enveloped in the enlarged inner perianth. The name "Rumex" originated from the Greek word–"dart" or "spear", alluding to the shape of leaves [2]. The other explanation from Rome–"rums" alludes to the function that the leaves could be sucked to alleviate thirst [3]. R. acetosa, a typical vegetable and medicinal plant, whose name 'acetosa' originated from the Latin word "acetum", described the taste of the plant as vinegar. Currently, many oxalic acids have been reported from Rumex, verifying its sour tastes [4].

Rumex species have had a valued place as global folk medicine, e.g., in Southern Africa, America, India, China, and Turkey. The earliest medicinal record of Rumex spp. in China was in "Shennong's Herbal Classic", in which Rumex was recorded for the treatment of headed, scabies, fever, and gynecological diseases. Roots of Rumex, also called dock root, have been reported for its therapeutic capacity of bacterial infections, inflammatory, tumor and cardiovascular diseases [5, 6]. Recently, pharmacological study showed that Rumex species displayed apparent antibacterial and antifungal effects [7], and were employed in the management of skin scabies and inflammation [8, 9]. The processed Rumex exhibited different chemical profiles and bioactivities [10, 11]. Leaves, flowers and seeds of some Rumex plants are edible as vegetables, while in some regions, the Rumex plants are regarded as noxious weeds because oxalic acid makes them difficult to be digested [12].

To date, 268 components from 29 Rumex species have been reported. Anthraquinones, flavonoids, tannins, stilbenes, naphthalenes, diterpene alkaloids, terpenes, and lignans were as the main chemical components, with a broad spectrum of pharmacological activities, such as anti-inflammatory, antioxidant, antibacteria, antitumor, and antidiabetic activities [13-17]. In addition to important role of Rumex in the traditional applications, researchers also regard Rumex as a potential effective medicine of many diseases. This article has reviewed a comprehensive knowledge on the distribution, traditional uses, chemistry and bioactivity progress of Rumex, and their therapeutic applications and utilizations were provided.

Geographical distributions, local names, parts used and traditional uses

The genus Rumex with more than 200 species, is distributed widely in the world and has been used traditionally in many regions, e.g., Asia, America, Europe and other continents. Many of them known as "sorrel" or "dock" have a long history of food application and medicinal uses for the treatment of skin diseases, and hemostasis after trauma by the local people of its growing areas. For example, R. acetosa is commonly used medicinally for diuretics around the world [4]. R. maritimus and R. nepalensis, used as laxatives, have long-term medicinal applications in India as substitutes for Rheum palmatum (Polygonaceae), which is usually used to regulate the whole digestive system. Moreover, Indians have also recorded nine Rumex plants as astringent agents, including R. acetosa, R. acetosella, R. crispus, R. dentatus, R. hastatus, R. maritimus, R. nepalensis, R. scutatus, and R. vesicarius [18]. All seven species included R. acetosa, R. trisetifer, R. patientia, R. crispus, R. japonicus, R. dentatus and R. nepalensis, called "jinbuhuan", have been used for hemostasis remediation in China [19]. R. thyrsiflorus, rich in nutrition, has been used as food by Europeans in history and as folk medicine due to its obvious anti-inflammatory activity [20]. R. lunaria has been used to treat diabetes by Canarian medicine [16]. The leaves of more than 14 Rumex spp., such as R. acetosa, R. hastatus, R. thyrsiflorus, R. aquaticus, R. crispus, R. gmelini, R. patientia, R. vesicarius, R. ecklonianus, R. abyssinicus, R. confertus, R. hymenosepalus, R. alpinus and R. sanguineus (Table 1) could be eaten freshly or cooked as vegetables in the folk of many places [5, 6]. In Table 1, the geographical distributions, local names, parts used and traditional uses of 35 Rumex species are summarized.

Table 1

Traditional uses of Rumex plants

No	Species	Local names	Country	Parts used	Traditional uses	Ref
R1	Rumex acetosa L	Sorrel, garden sorrel, common dock, broad-leaved sorrel, English sorrel, sheep’s sorrel, red sorrel, sour weed, field sorrel	South Africa, North America, Europe, Yemen, Czech Repubilc, Korea, Britain, Ireland, China, Hungary, Romania and Bulgaria	Leaf, flower, whole plant, fruit, root and seed	Gastrointestinal disorders (constipation, cramping, diarrhea, tenesmus), antiscorbutic, hemostasis, dermatological, tumors, cramping, sore throats, warts, dysentery, gonorrhea, ulcer, scabies, kidney diseases (diuretic), fever, worm, abscesses. Seed: astringent	[4, 18, 19, 57, 135, 192, 198]
R2	R. hastatus D. Don	Heartwing sorrel, hastate-leaved dock, sour dock, khatimal	China, India, Nepal, Bhutan, Pakistan and Afghanistan	Leaf, flower, seed, root, whole plant, anile part and contemporary tuber	Astringent, sexually transmitted diseases (AIDs), constipation, tonic agent, diuretic, rheumatism, dermatological, piles, bleeding of the lungs, cough, headache, fever, blood pressure, abdominal pain, sore throat, tonsillitis diseases, worm, wounds	[18, 58, 191, 195]
R3	R. thyrsiflorus Fingerh	Compact dock, thyrse sorrel	China, Kazakhstan and Russia, and Europe	Leaf	For food	[59, 198]
R4	R. aquaticus L	Red dock, western dock	China, Japan, Kazakhstan, Russia and Europe	Leaf	Disinfection, constipation, fever, diarrhea, stomach problems, edema, jaundice	[60, 201]
R5	R. Chalepensis Mill		Asia, Middle East, Morocco and Africa	–	–	[40, 61, 202]
R6	R. crispus L	Curled dock, curly dock, yellow dock, narrow-leaf dock	Asia, Europe, North America, Northern Africa, Colombia and India	Leaf, root, stem, seed	Antidysentery, hemostasis, ulcers, cough. Root: laxative, astringent, skin eruptions, skin diseases, scrofula, scurvy, intermittent fevers, congested liver and jaundice. Seed: astringent	[18, 19, 62, 195, 197]
R7	R. dentatus L	Toothed dock	Asia, Middle East and Southeast Europe and Pakistan	Whole plant	Cutaneous disorders, stomach problems. Plant: astringent, hemostasis	[18, 19, 28, 63, 195]
R8	R. gmelini Turcz. ex Ledeb		China, Japan, North Korea, Russia, Mongolia and Siberia	Leaf	Tumor, bacterial infection	[31, 64]
R9	R. japonicus Houtt		China, Japan, North Korea and Russia	Whole plant	Hemostasis, fever, constipation	[19, 65, 199]
R10	R. maritimus L	Golden dock	Bangladesh, India, North Africa and America	Leaf, root and seed	Leaf and root: laxative; externally applied to burns. Seed: aphrodisiac	[18, 66]
R11	R. nepalensis Spreng		Asia, Europe and Africa, Ethiopia, Nepal, Pakistan and India	Leaf, root and whole plant	Hemostasis, stomach problems, itch, astringent, paralysis, tonsillitis, ascariasis, uterine bleeding, as an abortifacient, joint pain. Leaf: colic; externally applied to syphilitic ulcers. Root: constipation	[18, 19, 33, 67, 195, 196]
R12	R. obtusifolius L	Broad-leaf dock, bitter dock, blunt-leaf dock	China, Japan, Europe, Africa and Ireland	Whole plant	Nettle, depurative, astringent, constipation, tonic agent, sores, blisters, hyperglycemic, burns, tumors	[62, 193, 194]
R13	R. patientia L	Herb patience, garden patience, patience dock, spinach dock	Asia, Europe, North India, Bulgaria and Ukraine	Leaf	Hemostasis, diarrhoea, diarrhoea in cows	[4, 19, 68, 192, 198]
R14	R. cristatus DC	Greek dock	France, Turkey and Spain	–	–	[69–71]
R15	R. vesicarius L	Bladder dock, country sorrel	South Asia, Egypt and North Africa	Leaf, seed and whole plant	Plant: astringent, antiscorbutic, stomach problems, diuretic. Seed: antidysentery	[18, 72, 73, 203]
R16	R. luminiastrum Jaub & Spach		Europe	–	–	[42]
R17	R. pictus Forssk	Veined dock	Egypt, Gulf States, Kuwait, Lebanon-Syria, Libya, Palestine, Saudi Arabia, Sinai and Israel	Whole plant	For food	[41, 74, 75] [76, 203]
R18	R. bucephalophorus L		North America and Libya	Whole plant	Laxative	[77, 204]
R19	R. tingitanus L	Koressa	Europe, Asia and Africa	Whole plant	Hepatoprotective, antidepression, blood purifcation, constipation, tonic	[78, 186]
R20	R. ecklonianus Meissner	South African dock	South Africa	Young leaf	Anemia, chlorosis	[79]
R21	R. abyssinicus Jacq	Spinach rhubarb, mekmeko	Europe, Africa and Spinach	Young shoot, leaf, fresh or dried plant	Brest cancer, stomach problems, gonorrhea, liver diseases, wounds, diabetes, cough, hypertension, sores, rheumatism, hemorrhoids, scabies, diarrhoea	[80, 123]
R22	R. confertus Willd	Russian dock, Asiatic dock, mossy sorrel	Russia, Kazakhstan, China, Hungary, Slovakia, Romania, Italy, Europe, Finland, Norway, Sweden, Lithuania, Britain,Canada, north Dakota,Bulgaria and Ukraine	Leaf, root and rhubarb	Diarrhoea, diarrhoea in cows	[81–91, 198]
R23	R. hymenosepalus Torr	Canaigre, canaigre dock, desert rhubarb, wild rhubarb, sand dock	Australia, American California, Sonoran and Mexico	Leaf, tuber and rhubarb	Throat infections	[92, 93, 205, 206]
R24	R. alpinus L	Alpine dock, monk's rhubarb	Europe and Asia	Leaf and rhubarb	For food	[94]
R25	R. rugosus Campd		North America, Europe	Leaf	For food	[95, 96, 200]
R26	R. nervosus Vahl	Ithrib	Himalayas, Nilgiri, Nainital, East Africa and Arab	Leaf	Microbial infections, anticoccidial	[97, 98, 207]
R27	R. maderensis Lowe	Azedas, madeira sorrel	Portugal	Leaf	Blood depurative, dermatosis, diuretic, simulated gastrointestinal digestion, antidiabetic	[99, 100]
R28	R. chinensis Campd. (Syn. = R. trisetifer)		Vietnam, China	–	Microbial infections	[101]
R29	R. algeriensis Barratte & Murb. (Syn. = R. elongatus)		Algeria	–	–	[102]
R30	R. tunetanus		Tunisia	–	–	[103, 104]
R31	R. rechingerianus Losinsk. (Syn. = R. pamiricus)		Trans-Ili Ala-Tau	–	–	[61]
R32	R. lunaria L		Canarian	–	Diabetes	[16]
R33	R. rothschildianus Aarons		Palestine	Whole plant	Constipation, diarrhea, wound, diuretic, eczema and for food	[105]
R34	R. sanguineus L	Bloody dock, red veined dock, red-veined dock, red veined sorrel, red-veined sorrel	America, Canada, Chile and Italy	Young leaf	Wound, bacterial infections and abscesses	[61, 106]
R35	R. acetosella Linn	Sheep sorrel	Asia and Colombia	Root, the aerial part and leaf	Diuretic, constipation, diaphoretic, antiscorbutic. Fresh plant: urinary and kidney diseases	[18, 195]

– unknown

Chemical constituents

To date, 268 compounds including 56 quinones (1–56), 57 flavonoids (57–113), 25 tannins (114–138), 6 stilbenes (139–144), 22 naphthalenes (145–166), 6 terpenes (167–172), 3 diterpene alkaloids (173–175), 14 lignans (176–189) and 79 other types of components (190–268) were isolated and reported from 29 Rumex species (Table 2).

Table 2

The summary of compounds in Rumex

No	Compounds	Formula	Species	Plant parts	Ref
Quinones
1	Chrysophanol	C15H10O4	R2, R5, R7, R8, R9, R11, R13, R21, R22, R23, R28, R31	Rh, R, WP, T, A, S, F	[23, 35, 45, 46, 50, 51, 63, 80, 93, 101, 113, 125, 128, 129]
2	Chrysophanol-1-O-β-D-glucoside	C21H20O9	R8, R31	R, S	[64, 128]
3	Chrysophanol-8-O-β-D-glucoside (chrysophanein)	C21H20O9	R8, R9, R13, R21, R28	A, S, R, WP	[32, 46, 54, 101, 123, 129, 130]
4	Chrysophanol-8-O-β-D-galactoside	C21H20O9	R8, R14	R	[52, 112]
5	Chrysophanol-1-O-(4-O-β-D-galactosyl)-α-L-rhamnoside	C27H30O13	R2	WP	[184]
6	6'-Acetyl-chrysophanol-8-O-β-D-glucoside	C23H22O10	R8	R	[32, 112, 113]
7	Chrysophanol anthrone	C15H12O3	R1	R	[29]
8	Emodin (1,6,8-trihydroxy-3-methylanthraquinone)	C15H10O5	R2, R5, R6, R8, R9, R11, R13, R21, R28, R31	Rh, R, WP, A, S, F, L	[23, 32, 34, 35, 40, 45–47, 51, 54, 80, 101, 112, 113, 128, 129]
9	Emodin-1-O-β-D-glucoside	C21H20O10	R7, R8	R, A	[14, 64]
10	Emodin-1-O-β-D-glucosyl-α-L-rhamnoside	C27H30O14	R5, R31	R, S, L	[128, 131]
11	Emodin-6-O-β-D-glucoside	C21H20O10	R13	R	[54, 130]
12	Emodin-8-O-β-D-glucoside (PMEG)	C21H20O10	R4, R6, R8, R9, R13, R28	WP, A, R, S	[23, 32, 34, 38, 46, 47, 101, 112, 129, 130]
13	Aloe-emodin	C15H10O6	R2, R8, R13	R, WP, L	[23, 27, 35, 112]
14	6-Hydroxy-emodin (citreorosein)	C15H10O6	R9, R21	WP	[50, 123]
15	6-Acetoxy-aloe-emodin	C17H12O6	R1	R	[29]
16	Emodin dimethylether	C17H14O5	R13	WP	[23]
17	Emodin anthrone	C15H12O4	R1	R	[29]
18	Physcion (rheochrysin, emodin 3-methyl ether)	C16H12O5	R2, R8, R9, R11, R13, R21, R23, R28	Rh, R, WP, T, A	[23, 35, 46, 50, 51, 54, 80, 93, 101, 113, 129]
19	Physcion-8-O-β-D-glucoside (physcionin)	C22H22O10	R8, R9, R13, R21, R28	A, F, R, WP	[45, 101, 123, 129, 130]
20	Physcion anthrone	C16H14O4	R1	R	[29]
21	Rumejaposide A	C22H22O11	R9	R	[26]
22	Rumejaposide B	C22H22O11	R9	R	[26]
23	Rumejaposide C	C22H22O12	R9	R	[26]
24	Rumejaposide D	C22H22O13	R9	R	[26]
25	Rumejaposide E	C21H22O10	R7, R9	R	[26, 28]
26	Rumejaposide F	C21H22O10	R7, R13	L, R	[27, 28]
27	Rumejaposide G	C21H22O9	R7	R	[28]
28	Rumejaposide H	C21H22O9	R7	R	[28]
29	Rumejaposide I	C21H22O10	R7, R13	L, R	[27, 28]
30	Xanthorin-5-methylether	C17H14O6	R13	WP	[23, 24]
31	Rumexone	C17H16O4	R6	R	[30]
32	Rhein	C15H8O6	R2	R	[35]
33	Rhein-8-O-β-D-glucoside	C21H18O11	R9	WP	[50]
34	Cassialoin	C21H22O9	R7, R13	L, R	[27, 28]
35	Phallacinol (telochistin)	C16H12O6	R11	R	[51]
36	1,8-Dihydroxyanthraquinone	C14H8O4	R1	R	[29]
37	Martianine	C42H42O17	R11	R	[132]
38	Rumoside A	C42H42O16	R8, R13	R	[32, 112]
39	10-Hydroxyaloin A	C21H22O10	R8	R	[31]
40	10-Hydroxyaloin B	C21H22O10	R8	R	[31]
41	6-Methoxyl-10-hydroxyaloin A	C22H24O11	R8	R	[32]
42	6-Methoxyl-10-hydroxyaloin B	C22H24O11	R8	R	[32]
43	10-Hydroxycascaroside C	C27H32O14	R11	R	[132]
44	10-Hydroxycascaroside D	C27H32O14	R11	R	[132]
45	Obtusifolate A	C39H42O8	R12	R	[25]
46	Obtusifolate B	C34H34O7	R12	R	[25]
47	Rumexpatientoside A	C22H24O10	R11	R	[133]
48	Rumexpatientoside B	C22H24O10	R11	R	[133]
49	Nepalenside A	C21H22O11	R11	R	[33]
50	Nepalenside B	C21H22O11	R11	R	[33]
51	Helminthosporin	C15H12O5	R21	Rh	[80]
52	1,3,5-Trihydroxy-7-methylanthraquinone	C15H10O5	R13	R	[130]
53	1,5-Dihydroxyanthraquinone	C14H8O4	R6	R	[30]
54	1,3,7-Trihydroxy-6-methylanthraquinone	C15H10O5	R2	WP	[134]
55	Przewalskinone B	C16H12O5	R2	WP	[134]
56	Rumpictusoide A	C21H19O10	R17	WP	[183]
Flavonoids
57	Vitexin	C21H20O10	R1	A	[57]
58	Isovitexin	C21H20O10	R15	A	[185]
59	Orientin	C21H20O11	R1, R16	A, WP	[42, 57]
60	Acetyl-orientine	C23H22O12	R16	WP	[42]
61	Iso-orientine	C21H20O11	R1	A	[57]
62	Quercetin-3-O-β-D-galactoside (hyperoside)	C21H20O11	R1, R7, R13, R31	S, R, WP	[36, 44, 47, 49]
63	Kaempferol	C15H10O6	R2, R6, R7, R13	WP, R, A	[14, 23, 34, 35]
64	Kaempferol-3-O-β-D-glucoside	C21H20O11	R4, R7, R13	WP, A	[14, 23, 36–38]
65	Kaempferol-3-O-α-L-rhamnoside	C21H20O10	R1, R6	L, WP	[34, 39]
66	Kaempferol-3-O-α-L-rhamnosyl-(1 → 6)-β-D-galactoside	C27H30O15	R5, R7	L, WP	[36, 40]
67	Kaempferol-3-O-α-L-arabinosyl-(1 → 6)-β-D-galactoside	C26H28O15	R17	A	[41]
68	Kaempferol-3-O-[2''-O-acetyl-α-L-arabinosyl]-(1 → 6)-β-D-galactoside	C28H30O16	R17	A	[41]
69	Kaempferol-7-O-β-D-glucoside	C21H20O11	R16	WP	[42]
70	Kaempferol-7-O-α-L-rhamnoside	C21H20O10	R16	WP	[42]
71	Quercetin	C15H10O7	R2, R5, R7, R8, R13	F, S, R, A	[14, 35, 45, 47, 48]
72	Quercetin-3-O-β-D-glucoside (isoquercetin, ECQ, QGC)	C21H20O12	R4, R5, R7, R13	A, WP, L, S	[14, 23, 27, 37, 38, 46, 47]
73	Quercetin-3-O-β-D-glucuronide	C21H18O13	R7, R13	A	[14, 46]
74	Quercetin-3-β-D-glucosyl-(1 → 4)-β-D-galactoside	C27H30O17	R5	L	[40]
75	Quercetin-3-O-α-L-rhamnoside (quercitrin)	C21H20O11	R4, R5, R9, R13, R31	L, WP, R, A	[27, 38, 40, 49, 50]
76	Isorhamnetol	C16H12O7	R13	WP,	[23, 37]
77	Isorhamnetol-3-O-rutinoside	C28H32O16	R7	WP	[36]
78	Isorhamnetol-3-O-β-D-galactoside	C22H22O12	R7	WP	[36]
79	Isorhamnetol-3-O-β-D-glucoside	C22H22O12	R7	WP	[36]
80	Quercetin-3-O-α-L-arabinoside	C20H18O11	R4, R16	WP, A	[38, 42, 43]
81	Quercetin-3-O-α-L-arabinosyl-(1 → 6)-β-D-galactoside	C26H28O16	R17	A	[41]
82	Quercetin-3-O-[2''-O-acetyl-α-L-arabinosyl]-(1 → 6)-β-D-galactoside	C28H30O17	R17	A	[41]
83	Quercetin-7-O-β-D-glucoside	C21H20O12	R13, R16	S, WP	[42, 44, 47]
84	Quercetin-7-O-α-L-rhamnoside	C21H20O11	R16	WP	[42]
85	Rutin	C21H30O16	R5, R8, R31	R, L	[32, 40, 49, 112]
86	5-Hydroxy-4'-methoxyflavone-7-O-β-D-rutinoside	C28H32O14	R13	WP	[23, 37]
87	Apigenin	C15H10O5	R1	R	[53]
88	Luteolin (cyanidenon)	C15H10O6	R1, R19, R35	L, WP, A	[136, 186–188]
89	Luteolin-7-O-β-D-glucoside	C21H20O11	R16	WP	[42]
90	7-Hydroxy-2,3-dimethyl-chromone	C11H10O3	R14	R	[52]
91	5-Methoxy-7-hydroxy-1(3H)-chromone	C10H8O4	R13	R	[53]
92	5,7-Dihydroxy-1(3H)-chromone	C9H6O4	R13	R	[53]
93	Mikanin (3,5-dihydroxy-4',6,7-trimethoxyflavone)	C18H16O7	R13	L	[27]
94	3,5-Dihydroxy-6,7,3',4'-tetramethoxyflavone	C19H18O8	R13	L	[27]
95	2,5-Dimethyl-7-hydroxychromone-7-O-β-D-glucoside	C17H20O8	R8	R	[31]
96	2,5-Dimethyl-7-hydroxychromone	C11H10O3	R11	R	[51]
97	3-O-Methyl quercetin	C16H12O7	R8	F	[45]
98	Tricin-7-O-β-D-glucoside	C23H24O12	R22	R	[137]
99	2-(2'-Hydroxypropyl)-5-methyl-7-hydroxychromone	C13H14O4	R13	R	[138]
100	2-(2'-Hydroxypropyl)-5-methyl-7-hydroxychromone-7-O-β-D-glucoside	C19H24O9	R13	R	[138]
101	Maackiain	C16H12O5	R13	A	[46]
102	Maackiain-3-O-β-D-glucoside	C22H22O10	R13	A	[46]
103	Aloesin	C19H22O9	R11	R	[33]
104	4'-p-Acetylcoumaroyl luteolin	C26H18O9	R19	L	[78]
105	Catechin	C15H14O6	R1, R6, R13, R19, R31	R, WP	[34, 49, 53, 54]
106	6-Cl-catechin	C15H13ClO5	R13, R19	R	[54]
107	Epicatechin	C15H14O6	R1, R6, R14, R31	R, WP	[34, 49]
108	(+)-Epigallocatechin	C15H14O7	R1	R	[135]
109	(−)-Epigallocatechin	C15H14O7	R1	R	[135]
110	Epicatechin-3-O-gallate	C22H18O10	R1, R31	A, R	[49, 56]
111	Epigallocatechin-3-O-gallate	C22H18O11	R1	A	[56]
112	Isokaempferide	C16H12O6	R4	A, R	[148]
113	Quercetin-3,3'-dimethylether	C17H14O7	R4	A, R	[148]
Tannins
114	Epiafzelechin-(4β → 8)-epicatechin-(4β → 8)-epicatechin	C45H38O17	R1	A	[56]
115	Epicatechin-(4β → 8)-epicatechin-(4β → 8)-catechin	C45H38O18	R1	A	[56]
116	Epicatechin-(4β → 8)-epicatechin-(4β → 8)-epicatechin (Procyanidin C1)	C45H38O18	R1	A	[56]
117	Epicatechin-3-O-gallate-(4β → 8)-epicatechin-3-O-gallate-(4β → 8)-epicatechin-3-O-gallate	C66H50O30	R1	A	[56]
118	Epicatechin-(4β → 8)-epicatechin-(4β → 8)-epicatechin-(4β → 8)-epicatechin	C60H50O24	R1	A	[56]
119	Epicatechin-3-O-gallate-(4β → 8)-epicatechin-3-O-gallate	C44H34O20	R1	A	[139]
120	Epicatechin-(4β → 6)-epicatechin (procyanidin B5)	C30H26O12	R1	A	[56]
121	Epicatechin-(4β → 6)-catechin	C30H26O12	R1	A	[56]
122	Epicatechin-(4β → 8)-catechin (procyanidin B1)	C30H26O12	R1	A	[56, 107]
123	Catechin-(4α → 8)-catechin (procyanidin B3)	C30H26O12	R1	A	[56, 107]
124	Catechin-(4α → 8)-epicatechin (procyanidin B4)	C30H26O12	R1	A	[56, 107]
125	Epiafzelechin-(4β → 8)-epicatechin (procyanidin B2)	C30H26O11	R1	A	[56, 107]
126	Epicatechin-(4β → 8)-epicatechin-3-O-gallate	C37H30O16	R1	A	[56]
127	Epiafzelechin-(4β → 8)-epicatechin-3-O-gallate	C37H30O15	R1	A	[56]
128	Epicatechin-(4β → 6)-epicatechin-3-O-gallate	C37H30O16	R1	A	[56]
129	Epicatechin-3-O-gallate-(4β → 6)-epicatechin-3-O-gallate	C44H34O20	R1	A	[56]
130	Epiafzelechin-3-O-gallate-(4β → 8)-epicatechin-3-O-gallate	C44H34O19	R1	A	[56]
131	Epicatechin-(2β → 7, 4β → 8)-epicatechin-(4β → 8)-epicatechin (cinnamtannin B1)	C45H36O18	R1	A	[56]
132	Epicatechin-(2β- > 7, 4β → 8)-epiafzelechin-(4α → 8)-epicatechin	C45H36O17	R1	A	[56]
133	Epicatechin-3-O-gallate-(2β → 7,4β → 8)-epicatechin-(4β → 8)-epicatechin (cinnamtannin B1-3-O-gallate)	C52H40O22	R1	A	[56]
134	Epicatechin-(2β → 7, 4β → 8)-epicatechin-(4β → 8)-phloroglucinol	C36H28O14	R1	A	[56]
135	Epiafzelechin-(4β → 6)-epicatechin-3-O-gallate	C37H30O15	R1	A	[56]
136	Parameritannin A1	C60H48O24	R1	A	[56]
137	Epicatechin-3-O-gallate-(4β → 8)-epicatechin-3-O-gallate-phloroglucinol	C50H38O25	R1	A	[56]
138	Epicatechin-(2β → 7, 4β → 8)-epicatechin	C30H26O12	R1	A	[56]
Stilbenoids
139	Resveratrol	C14H12O3	R2, R8	R, F	[32, 35, 45, 112]
140	(Z)-Resveratrol	C14H12O3	R1	R	[124]
141	Polydatin (resveratrol-3-O-β-D-glucoside, piceid)	C20H22O8	R7, R8	R, A	[14, 32, 112]
142	5,4'-Dihydroxy-3-methoxystilbene	C15H14O3	R18	R	[77]
143	3,5-Dihydroxy-4'-methoxystilbene	C15H14O3	R18	R	[77]
144	5,4'-Dihydroxystilbene-3-O-α-arabinoside	C19H20O7	R18	R	[77]
Naphthalenes
145	Nepodin (musizin)	C13H12O3	R2, R8, R9, R13	R	[32, 35, 112, 113, 130]
146	Nepodin-8-O-β-D-glucoside	C19H22O8	R1, R2, R4, R7, R8, R13, R17	R, L, A	[27, 31, 38, 46, 63, 74, 110, 130]
147	Nepodin-8-O-β-D-(6'-O-acetyl)-glucoside	C21H24O9	R2	R
148	Neposide	C19H22O8	R2, R22, R24	R, WP	[140, 141]
149	2-Acetyl-3-methyl-6-methoxyl-8-hydroxy-1,4-naphthoquinone	C14H12O5	R9	WP	[141]
150	Torachrysone (TRA, 2-acetyl-1,8-dihydroxy-3-methyl-6-methoxyl-naphthalene)	C14H14O4	R13	WP	[141]
151	Torachrysone-8-O-β-D-glucoside	C20H24O9	R2, R7, R9, R13	L, R, A	[27, 46, 53, 63]
152	2-Methoxystypandrone (MSD, 6-acetyl-7-methyl-2-methoxyl-5-hydroxy-1,4-naphthoquinone)	C14H12O5	R9, R10	L, S, R	[115, 116]
153	3-Acetyl-2-methyl-1,5-dihydroxyl-2,3-epoxynaphthoquinol	C13H12O5	R9, R11	R,	[51, 65]
154	Rumexoside	C20H22O10	R2	R	[110]
155	2-Acetyl-4-chloro-1,8-dihydroxy-3-methylnaphthalene-8-O-β-D-glucoside (patientoside A)	C19H21O8Cl	R13	R	[117]
156	Patientoside B	C17H18O7Cl2	R13	R	[117]
157	4,4''-Binaphthalene-8,8''-O,O-di-β-D-glucoside	C36H42O16	R13	R	[120]
158	6-Hydroxymusizin-8-O-β-D-glucopyranoside	C15H14O6	R2	R	[110]
159	3-Acetyl-2-methyl-1,4,5-trihydroxyl-2,3-epoxynaphthoquinol	C13H14O5	R13	R	[118]
160	3-Acetyl-2-methyl-1,5-dihydroxyl-7-methoxyl-2,3-epoxynaphthoquinol	C14H14O6	R13	WP	[119]
161	Rumexone A	C14H18O4	R11	R	[142]
162	Rumexneposide A	C23H26O9	R11	R	[143]
163	Rumexneposide B	C22H26O10	R11	R	[143]
164	Hastatuside B	C21H24O9	R2, R13	L, R	[114] [27]
165	Epi-isoshinanolone	C11H12O3	R13	R	[138]
166	Isoshinanolone	C11H12O3	R9, R13	R, WP	[50, 138]
Terpenes
167	Tormentic acid	C30H48O5	R9	ST	[121]
168	Myrianthic acid	C30H48O6	R9	ST	[121]
169	2α,3α,19α-Trihydroxy-24-norurs-4(23),12-dien-28-oic acid	C29H44O5	R9	ST	[121]
170	4(R),23-Epoxy-2α,3α,19α-trihydroxy-24-norurs-12-en-28-oic acid	C29H44O6	R9	ST	[121]
171	Taraxasterol acetate	C32H52O2	R2	R	[35]
172	Lupeol	C30H50O	R11	A	[189]
Diterpene alkaloids
173	7,11,14-Trihydroxy-2,13-dioxohetisane (orientinine)	C20H23NO5	R17	A	[75]
174	6,13,15-Trihydroxyhetisane (acorientine)	C20H27NO3	R17	A	[75]
175	6-Hydroxy-11-deoxy-13-dehydrohetisane (panicudine)	C20H25NO3	R17	A	[75]
Lignans
176	Arctiin	C27H34O11	R13	WP	[23]
177	3-Hydroxyarctiin	C27H34O10	R13	WP	[23]
178	3-Methoxyarctiin-4''-O-β-D-xyloside	C27H34O11	R13	WP	[23]
179	4-Ketopinoresinol	C20H20O7	R13	L	[27]
180	Syringaresinol	C22H26O8	R9, R13	L, WP	[27, 50]
181	Manassantin A	C42H52O11	R13	L	[27]
182	Balanophonin	C22H22O7	R13	L	[27]
183	Schizandriside	C28H32O6	R2	WP	[111]
184	(−)-Isolariciresinol-9-O-β-D-xylopyranoside	C25H34O10	R2	WP	[111]
185	(−)-5-Methoxyisolariciresinol-9-O-β-D-xylopyranoside	C26H36O11	R2	WP	[111]
186	(+)-5-Methoxyisolariciresinol-9-O-β-D-xylopyranoside	C26H36O11	R2	WP	[111]
187	(+)-Lyoniside	C27H38O12	R2	WP	[111]
188	Nudiposide	C27H38O12	R2	WP	[111]
189	(+)-Lyoniresinol-3α-O-β-D-glucoside	C28H38O13	R11	R	[33]
Others
190	Phenylethyl-O-α-L-arabinopyransy-(1 → 6)-O-β-D-glucoside	C19H28O10	R8	R	[31]
191	Methylorsellinate	C11H14O4	R11	R	[51]
192	Ferulic acid	C10H10O4	R11	R	[51]
193	Methyl 2-acetyl-3,5-dihydroxyphenylacetate	C11H12O5	R11	R	[51]
194	1-(2-Hydroxy-5-methyl-phenyl)-ethanon	C9H10O2	R11	R	[51]
195	Methyl syringate	C10H12O5	R11	R	[51]
196	1-(2,4-Dihydroxy-6-methylphenyl)-ethanon	C9H10O3	R11	R	[51]
197	4-Hydroxybenzene ethanol	C8H10O2	R11	R	[51]
198	Isovanillin	C8H8O3	R11	R	[51]
199	p-Coumaricacid-n-eicosanyl ester	C31H52O3	R13	S	[47]
200	Z-Octadecyl caffeate	C27H44O4	R13	S	[47]
201	Dibutylphthalate	C16H22O4	R11	R	[132]
202	2-Methoxyhydroquinone	C7H8O3	R11	R	[132]
203	Batiansuanmol	C14H18O5	R13	R	[138]
204	Orcinol	C7H8O2	R13	R	[54]
205	p-Hydroxybenzoic acid	C7H6O3	R1, R9	L,	[26, 39]
206	p-Coumaric acid	C9H8O3	R1, R2, R7	L, R, WP, A	[39, 48, 134, 144]
207	Methyl 3,4-dihydroxyphenylpropionate	C10H12O4	R1	L	[39]
208	Vanillic acid	C8H8O4	R1	L	[39]
209	Isovanillic acid	C8H8O4	R1, R7	L, R	[39, 48]
210	Gallic acid	C7H6O5	R2, R7, R13	R,	[35, 48, 53]
211	Methyl gallate	C8H8O5	R2	R	[35]
212	2,6-Dimethoxy-4-hydroxyl benzoic acid	C9H10O5	R9	A	[26]
213	Pyrocatechin	C6H6O2	R9	A	[145]
214	Syringic acid	C9H10O5	R9	A	[145]
215	3,4-Dihydroxybenzaldehyde	C7H6O3	R9	A	[145]
216	Ethyl 3,4-dihydroxybenzoate	C9H10O4	R9	A	[145]
217	Ethyl gallate	C9H11O4	R9	A	[145]
218	Rumexin	C15H20O8	R4	A	[38]
219	Caffeic acid	C9H8O4	R4	A	[38]
220	1-O-caffeoylglucose	C15H18O9	R4	A	[38]
221	1-Methyl caffeic acid	C10H10O4	R4	A	[38]
222	Neochlorogenic acid	C16H18O9	R27	L	[146]
223	(S)-4′-Methylnonyl benzoate	C17H26O2	R7	A	[14]
224	5-Methoxy-7-hydroxy-1(3H)-benzofuranone	C9H8O4	R11	R	[51]
225	5,7-Dihydroxy-1(3H)-benzofuranone	C9H6O4	R13	R	[53]
226	5-Methoxyl-1(3H)-benzofuranone-7-glucoside	C15H18O9	R8	R	[31]
227	Sinapic acid	C11H12O5	R1	FL	[147]
228	Protocatechuic acid	C7H6O4	R1	L	[55]
229	p-Hydroxycinnamic acid	C9H8O3	R8	R	[190]
230	Streptokordin	C8H9NO2	R11	R	[132]
231	Hastatuside A	C16H18O9	R2	R	[114]
232	β-Sitosterol	C29H50O	R1, R6, R7, R11, R13, R28	A, R, S, L, WP	[34, 39, 47, 48, 53, 101, 189]
233	Daucosterol	C35H60O6	R1, R7, R8, R13, R28	A, R, F, L	[39, 45, 48, 53, 101, 138, 190]
234	Ergosta-6,22-diene-3,5,8-triol	C28H46O3	R21	WP	[123]
235	Nonadecanoic acid-2,3-dihydroxypropyl ester	C22H44O4	R13	R	[53]
236	Hexadecanoic acid 2,3-dihydroxypropyl ester	C19H38O4	R7	R	[48]
237	1-Stearoylglycerol	C21H42O4	R4	A, R	[148]
238	Triacontanol	C30H62O	R13	S	[47]
239	Dotriacontanol	C32H66O	R13	S	[47]
240	Hexacosanoic acid	C26H52O2	R6, R13	S, WP	[34, 47]
241	Dotriacontane	C32H66	R13	S	[47]
242	Glyceryl 1,3-dipalmitate	C35H68O5	R13	S	[47]
243	(2E)-8-Hydroxy-2,6-dimethyl-2-octenoic acid	C10H18O3	R11	R,	[132]
244	Tetratriacontane	C34H70	R13	S	[149]
245	Ceryl alcohol	C26H54O	R20	A	[125]
246	Oxalic acid	C2H2O4	R1	A	[56]
247	Cardozin	C10H20O6	R7	R	[48]
248	Succinic acid	C4H6O4	R7	R	[48]
249	Sucrose	C12H22O11	R8	R	[190]
250	Rebeccamycin	C27H21Cl2N3O7	R1	L	[9]
251	Vitamin C	C6H8O6	R1	L	[9]
252	Calcium oxalate	C2H2O4 Ca	R1	L	[9]
253	Tartaric acid	C4H6O6	R1	L	[9]
254	β-carotene	C40H56	R13, R15	R, L	[126, 129]
255	Lutein	C40H56O2	R15, R25	L	[95, 126]
256	Anhydrolutein I	C40H54O	R25	L	[95]
257	Anhydrolutein II	C40H54O	R25	L	[95]
258	Riboflavin	C17H20N4O6	R13	R	[129]
259	2-O-methyl inositol	C7H14O6	R13	A	[46]
260	Stigmasterol	C29H48O	R13	WP	[23]
261	α-Asarone	C12H16O3	R13	WP	[23]
262	7-Hydroxy-5-methoxyphthalide	C9H8O4	R11	R	[51]
263	4-Ethyl heptyl benzoate	C16H24O2	R26	R	[150]
264	Glucosylceramide	C40H77NO8	R12	L	[151]
265	Helonioside A	C32H38O17	R7	R	[48]
266	1-O-β-D-(2,4-dihydroxy-6-methoxyphenyl)-6-O-(4-hydroxy-3,5-dimethoxybenzoyl)-glucoside	C22H26O13	R1	A	[56]
267	1-O-β-D-(3,5-Dimethoxy-4-hydroxyphenol)-(6-O-galloyl)-glucoside	C21H24O13	R11	R	[33]
268	RA-P (Polysaccharide (D-glucose-—-D-arabinose)		R1	R	[127]

Rh rhizomes, R roots, WP whole plants, T tubers, A the aerial part, S seeds, L leaves, F fruits, S stems, FL flowers

Quinones

Quinones are widely found in Rumex, particularly accumulated in the roots. 56 quinones (Fig. 1) including anthraquinones, anthranones, and seco-anthraquinones and their glycosides and dimers were isolated and identified from more than 17 Rumex species (Table 2). Among them, anthraquinone O- and C- glycosides with glucose, galactose, rhamnose, and 6-hydroxyacetylated glucose as commonly existing sugar moieties, were normally found in Rumex. Three anthraquinones, chrysophanol (1), emodin (8) and physcion (18) are commonly used indicators to evaluate the quality of Rumex plants [22]. Some new molecules were also reported. For example, xanthorin-5-methylether (30) was isolated from R. patientia for the first time [23, 24], and two new antioxidant anthraquinones, obtusifolate A (45) and B (46) were isolated from R. obtusifolius [25].

Fig. 1

Structures of quinones (1–56)

The anthranones often existed in pairs of enantiomers, whose meso-position is commonly connected with a C-glycosyl moiety. The enantiomers, rumejaposides A (21) and B (22), E (25) and F (26), G (27) and H (28) were reported from R. dentatus, R. japonicus, R. nepalensis and R. patientia [26-28]. Three hydroxyanthrones, chrysophanol anthrone (7), emodin anthrone (17), physcion anthrone (20), whose C-10 were reduced as an alphatic methylene, were isolated from the roots of R. acetosa for the first time [29], while a new anthrone, rumexone (31) was reported from the roots of R. crispus [30]. Two anthranones, 10-hydroxyaloins A (39) and B (40) were reported from Rumex for the first time [31]. A new 8-ionized hydroxylated 9,10-anthraquinone namely, rumpictusoide A (56) was isolated from the whole plant of R. pictus [183]. Moreover, two new oxanthrone C-glucosides 6-methoxyl-10-hydroxyaloins A (41) and B (42) were isolated from the roots of R. gmelini [32].

Seco-anthraquinones are oxidized anthraquinones with a loop opened at C-10, resulting in the fixed planar structure of anthraquinone destroyed and causing of a steric hindrance between the two left benzene rings. So far, only two seco-anthraquinone glucosides, nepalensides A (49) and B (50) were reported from the roots of R. nepalensis [33].

Flavonoids

Flavonoids are one of the most important bioactive components existing widely in plant kingdom. To date, 57 flavonoids (57–113) including flavones, flavanols, chromones and their

glycosides were reported from Rumex (Fig. 2, Table 2). They are mostly derived from kaempferol (63) and quercetin (71) connecting with glucosyl, rhamnosyl, galactosyl and arabinosyl moieties at different positions. For example, kaempferol (63) together with seven glycosides, -3-O-β-D-glucoside (64), -3-O-α-L-rhamnoside (65), -3-O-α-L-rhamnosyl-(1 → 6)-β-D-galactoside(66), -3-O-α-L-arabinosyl-(1 → 6)-β-D-galactoside (67), -3-O-(2''-O-acetyl-α-L-arabinosyl)-(1 → 6)-β-D-galactoside (68), -7-O-β-D-glucoside (69) and -7-O-α-L-rhamnoside (70) [14, 23, 34–42], and quercetin (71) together with 11 derivatives, -3-O-β-D-glucoside (72), -3-O-β-D-glucuronide (73), -3-O-β-D-glucosyl(1 → 4)-β-D-galactoside (74), -3-O-α-L-rhamnoside (75), -3-O-α-L-arabinoside (80), -3-O-α-L-arabinosyl-(1 → 6)-β-D-galactoside (81), -3-O-[2''-O-acetyl-α-L-arabinosyl]-(1 → 6)-β-D-galactoside (82), -7-O-β-D-glucoside (83), -7-O-α-L-rhamnoside (84), 3-O-methyl quercetin (97) and -3,3'-dimethylether (113) [14, 23, 27, 35, 37, 38, 40–50, 148], were reported from several Rumex plants.

Fig. 2

Structures of flavonoids (57–113)

Moreover, a new chromone glucoside, 2,5-dimethyl-7-hydroxychromone-7-O-β-D-glucoside (95) was isolated from the root of R. gmelini [31], and five chromones, 7-hydroxy-2,3-dimethyl-chromone (90), 5-methoxy-7-hydroxy-1(3H)-chromone (91), 5,7-dihydroxy-1(3H)-chromone (92), 2,5-dimethyl-7-hydroxychromone-7-O-β-D-glucoside (95) and 2,5-dimethyl-7-hydroxychromone (96) were reported from R. gmelini, R. nepalensis, R. patientia and R. cristatus [31, 51–53].

Catechin (105) and epicatechin (107) are commonly distributed in R. patientia, the roots of R. rechingerianus, the whole plant of R. crispus, and the leaves of R. acetosa [34, 37, 39, 49, 54, 55]. Moreover, a variety of flavan-3-ols, 105, 107, epicatechin-3-O-gallate (110), epigallocatechin-3-O-gallate (111) were isolated from R. acetosa [49, 56].

Tannins

Tannins, which may be involved with the hemostasis activity, are abundant in Rumex plants. So far, 25 condensed tannins (114–138) (Fig. 3, Table 2) were reported from the genus Rumex.

Fig. 3

Structures of tannins (114–138)

Chemical investigations on the EtOAc fraction of acetone–water extract of the aerial parts of R. acetosa showed that R. acetosa was rich in tannins. Five new condensed tannin dimers, epiafzelechin-(4β → 8)-epicatechin-3-O-gallate (127), cinnamtannin B1-3-O-gallate (132) and epiafzelechin-(4β → 6)-epicatechin-3-O-gallate (135), and trimers, epiafzelechin-(4β → 8)-epicatechin-(4β → 8)-epicatechin (114), and epicatechin-(2β → 7, 4β → 8)-epiafzelechin-(4α → 8)-epicatechin (132), were reported. In addition, some procyanidins and propelargonidins, epiafzelechin-(4β → 8)-epicatechin-(4β → 8)-epicatechin (114), epicatechin-(4β → 8)-epi-catechin-(4β → 8)-catechin (115), procyanidin C1 (116), epicatechin-(4β → 6)-catechin (121), procyanidin B1-B5 (120, 122–125), and epicatechin-(4β → 8)-epicatechin-3-O-gallate (126), were also isolated [56, 107].

Stilbenes

So far, 6 stilbenes have been separated from Rumex (139–144) (Fig. 4, Table 2). Resveratrol (139) isolated from R. japonica Houtt was found for the first time from the Polygonaceae family [108]. It has been widely applied in cardiovascular protection and as antioxidation agent [109]. Resveratrol (139), (Z)-resveratrol (140) and polydatin (141) were obtained from Rumex spp. [14, 32, 35, 45, 110, 111]. 5,4'-Dihydroxy-3-methoxystilbene (142), 3,5-dihydroxy-4'-methoxystilbene (143) and 5,4'-dihydroxy-stilbene-3-O-α-arabinoside (144) were separated from the roots of R. bucephalophorus [77].

Fig. 4

Structures of stilbenes (139–144) and naphthalenes (145–166)

Naphthalenes

Naphthalenes are also widely distributed in Rumex. At present, 22 naphthalenes including naphthol, α-naphthoquinones and their derivatives have been identified from Rumex (145–166) (Fig. 4, Table 2). Nepodin (145) and nepodin-8-O-β-D-glucoside (146) are widespread in Rumex [31, 45, 112, 113]. In addition, 145, nepodin-8-O-β-D-(6'-O-acetyl)-glucoside (147), rumexoside (154), 6-hydroxymusizin-8-O-β-D-glucopyranoside (158) and hastatuside B (164) were isolated from R. hastatus [35, 110, 114]. 2-Methoxystypandrone (152) was isolated from R. japonicus and R. maritimus [115, 116]. Notably, some naphthalenes containing Cl, 2-acetyl-4-chloro-1,8-dihydroxy-3-methylnaphthalene-8-O-β-D-glucoside (155) and patientoside B (156) were isolated from R. patientia [117]. Moreover, 3-acetyl-2-methyl-1,5-dihydroxyl-2,3- epoxynaphthoquinol (153), 3-acetyl-2-methyl-1,4,5-trihydroxyl-2,3-epoxy-naphtho-quinol (159) and 3-acetyl-2-methyl-1,5-dihydroxyl-7-methoxyl-2,3-epoxynaphthoquinol (160), which contain the ethylene oxide part of the structure, were rarely found in Rumex, and they were reported from R. patientia, R. japonicus and R. nepalensis [51, 65, 118, 119]. 4,4''-Binaphthalene-8,8''-O,O-di-β-D-glucoside (157) was isolated from R. patientia [120].

Terpenes

Until now, only six terpenes have been reported from Rumex (Fig. 5, Table 2). Four pentacyclic triterpenes, i.e., tormentic acid (167), myrianthic acid (168) and 2α,3α,19α-trihydroxy-24-norurs-4(23), 12-dien-28-oic acid (169) and (4R)-23-epoxy-2α,3α,19α-trihydroxy-24-norurs-12-en-28-oic acid (170) were obtained from the EtOAc fraction of the stems of R. japonicus. Of them, 169 and 170 were two new 24-norursane type triterpenoids, whose C-12 and C-13 were existed as double bonds [121]. A ursane (α-amyrane) type triterpene, taraxasterol acetate (171) was isolated from R. hastatus. [63]. And lupeol (172) was isolated from the roots of R. nepalensis for the first time [122].

Fig. 5

Structures of terpenes (167–172)

Diterpene alkaloids

So far, only three hetisane-type (C-20) diterpene alkaloids, orientinine (7,11,14-trihydroxy-2,13-dioxohetisane, 173), acorientine (6,13,15-trihydroxyhetisane, 174) and panicudine (6-hydroxy-11-deoxy-13-dehydrohetisane, 175) were reported from the aerial part of R. pictus. They might be biosynthesized from tetra- or penta-cyclic diterpenes [75] (Fig. 6, Table 2).

Fig. 6

Structures of diterpene alkaloids (173–175)

Lignans

Fourteen lignans (176–189) were summarized from Rumex (Fig. 7, Table 2). A new lignan, 3-methoxyarctiin-4''-O-β-D-xyloside (178), and two known ones, arctiin (176) and 3-hydroxy-arctiin (177), were obtained from R. patientia [23]. Six lignan glycosides, schizandriside (183), (-)-isolariciresinol-9-O-β-D-xylopyranoside (184), (-)-5-methoxyisolariciresinol-9-O-β-D-xylopyranoside (185), (+)-5-methoxyisolariciresinol-9-O-β-D-xylopyranoside (186), (+)-lyoniside (187) and nudiposide (188) were reported from R. hastatus for the first time [111].

Fig. 7

Structures of lignans (176–189)

Other compounds

Up to now, 79 coumarins, sterides, alkaloids, glycosides and polysaccharide were found in Rumex (190–268) (Fig. 8, Table 2). Phenylethyl-O-α-L-arabinopyransy-(1 → 6)-O-β-D-glucoside (190) and 5-methoxyl-1(3H)-benzofuranone-7-glucoside (226) were isolated from R. gmelini for the first time [31]. p-Hydroxybenzoic acid (205), p-coumaric acid (206), methyl 3,4-dihydrophenylpropionate (207), vanillic acid (208) and isovanillic acid (209) were isolated from the leaves of R. acetosa [39]. β-Sitosterol (232) and daucosterol (233) are commonly distributed in R. acetosa, R. chinensis, R. crispus and R. gmelini [31, 34, 39, 101]. 2,6-Dimethoxy-4-hydroxyl benzoic acid (212) was isolated from R. japonicus [26]. Moreover, rumexin (218), caffeic acid (219), 1-O-caffeoylglucose (220) and 1-methyl caffeic acid (221) were isolated from the aerial parts of R. aquatica [38]. Recently, one new compound (S)-4′-methylnonyl benzoate (223) was reported from R. dentatus [14]. Ergosta-6,22-diene-3,5,8-triol (234) was isolated from the EtOAc fraction of R. abyssinicus for the first time [123]. Conventional techniques and supercritical fluid extraction (SFE) were compared and the latter yielded great efficiency of phenolics from the roots of R. acetosa [124].

Fig. 8

Structures of other compounds (190–268) (Note:268 not given)

Ceryl alcohol (245) from R. ecklonianus [125], and β-carotene (254) and lutein (255) from R. vesicarius [126] were reported. Moreover, anhydroluteins I (256) and II (257) were separated from R. rugosus together with 255 [95]. From the roots of R. dentatus, helonioside A (265) was isolated for the first time [48]. One new phloroglucinol glycoside 1-O-β-D-(2,4-dihydroxy-6-methoxyphenyl)-6-O-(4-hydroxy-3,5-dimethoxybenzoyl)-glucoside (266) was isolated from R. acetosa [56]. It was the first time that 1-O-β-D-(3,5-dimethoxy-4-hydroxyphenol)-(6-O-galloyl)-glucoside (267) was isolated from R. nepalensis [33].

Rumex polysaccharides have rarely been studied, and only one polysaccharide, RA-P (268), which has a 30 kDa molecular weight and consists of D-glucose and D-arabinose, was reported from R. acetosa [127].

LC–MS analysis

The chemical compositions of Rumex spp. were also analyzed by LC–MS techniques. Untargeted metabolomic profiling via UHPLC-Q-TOF–MS analysis on the flowers and stems of R. tunetanus resulted in the identification of 60 compounds, 18 of which were reported from the Polygonaceae family for the first time. Quercetin-3-O-β-D-glucuronide (73) was found to be the most abundant phenolic compound in flowers and epicatechin-3-O-gallate (110) in stems [103]. Moreover, 44 bioactive components classified as sugars, flavanols, tannins and phenolics were clarified from the flowers and stems of R. algeriensis based on RP-HPLC–DAD-QTOF-MS and MS–MS [102]. The analysis of sex-related differences in phenolics of R. thyrsiflorus has shown female plants of R. thyrsiflorus contain more bioactive components than males, such as phenolic acids and flavonoids, especially catechin (105) [20].

Bioactivity

Rumex has been used as food and medicine in the folk. In addition to important role of Rumex in the traditional application, during the past few decades, it was subjected to scientific investigations of the structure of isolated chemical components and their clinical applications by several research groups. Pharmacological studies on Rumex extracts and its pure components revealed a wide range of bioactivities, involving antimicrobial, anti-inflammatory, antiviral, renal and gastrointestinal protective effects, antioxidant, antitumor and anti-diabetes effects.

Antimicrobial

Bioassay-guided isolation on the whole plants of R. abyssinicus yielded six antimicrobial quinones, chrysophanol (1) and its 8-O-β-D-glucoside (3), emodin (8), 6-hydroxyemodin (14), physcion (18) and its 8-O-β-D-glucoside (19), with MIC values of 8—256 μg/mL [123].

Proanthocyanidin-enriched extract from the aqueous fraction of the acetone–water (7: 3) extract of the aerial parts of R. acetosa (5 μg/mL—15 μg/mL) could interfered with the adhesion of Porphyromonas gingivalis (ATCC 33,277) to KB cells (ATCC CCL-17) both in vitro and in situ. In silico docking assay, a main active constituent from R. acetosa, epiafzelechin-3-O-gallate-(4β → 8)-epicatechin-3-O-gallate (130) exhibited the ability to interact with the active side of Arg-gingipain and the hemagglutinin from P. gingivalis [139].

A bacteriostasis experiment of two naphthalenes, torachrysone (150) and 2-methoxy-stypandrone (152) isolated from R. japonicus roots, showed inhibitory effect on both gram-negative and gram-positive bacteria [152]. The antibacterial (Bacillus subtilis, Escherichia coli, Moraxella catarrhalis, etc.) potential of the n-hexane, chloroform, aqueous fractions of 14 Rumex from Carpathian Basin (R. acetosella, R. acetosa, R. alpinus, R. aquaticus, R. crispus, R. patientia, R. pulcher, R. conglomeratus, R. thyrsiflorus, etc.) were investigated by the disc diffusion method. It showed that the n-hexane and chloroform fractions of roots of R. acetosa, R. alpinus, R. aquaticus, R. conglomeratus and R. patientia exhibited stronger activity against bacteria (inhibition zones > 15 mm). Naphthalenes (145, 146, 151, 152) exhibited antibacterial capacity against several bacterial strains (MIC = 48—57.8 μM, in case of M. catarrhalis; MIC = 96—529.1 μM, in case of B. subtilis) than anthraquinones (1, 3, 8, 12, 14, 18), flavonoids (62, 71, 80, 105, 112, 113), stilbenes (139, 141) and 1-stearoylglycerol (237), etc., which were isolated from R. aquaticus [148].

Antimicrobial study demonstrated that R. crispus and R. sanguineus have the potential for wound healing due to their anti-Acinetobacter baumannii activities (MIC = 1.0—2.0 mg/mL, R. crispus; 1.0—2.8 mg/mL, aerial parts of R. sanguineus; 1.4—4.0 mg/mL, roots of R. sanguineus) [106].

Anti-inflammatory

The potential effects of anti-inflammatory of AST2017-01 composing of processed R. crispus and Cordyceps militaris which was widely used in folk medicines in Korea, as well as chrysophanol (1) on the treatment of ovalbumin-induced allergic rhinitis (AR) rats were investigated. The serum and tissue nasal mucosa levels of IgE, histamine, TSLP, TNF-α, IL-1, IL-4, IL-5 and IL-13 were both decreased by treatment with AST2017-01 and 1 (positive control: dexamethasone), indicating that R. crispus and 1 has the ability to prevent and treat AR [153]. The aqueous extract of roots of R. patientia has anti-inflammatory action in vivo. The higher dose of extract (150 mg/kg) showed inhibition (41.7%) of edema in rats compared with the positive control, indomethacin (10 mg/kg, 36.6%) [21]. Methanolic extracts of the roots and stems of R. roseus exhibited anti-inflammatory functions in intestinal epithelial cells, reducing TNF-α-induced gene expression of IL-6 and IL-8 [154].

The ethanol extract of the roots of R. japonicus could be a therapeutic agent for atopic dermatitis. Skin inflammation in Balb/c mice was alleviated with the extract in vivo. Moreover, an in vitro experiment showed that the extract of R. japonicus decreased the phosphorylation of MAPK and stimulated NF-κB in TNF-α in HaCaT cells [155]. The methanolic extract of R. japonicus inhibited dextran sulfate sodium (DSS)-induced colitis in C57BL/6 N mice by protecting tight junction connections in the colonic tissue. It was observed that R. japonicus has the potential to treat colitis [156]. Ethyl acetate extract of the roots of R. crispus showed anti-inflammatory activity in inhibiting NO production and decreasing the secretion of proinflammatory cytokines [157].

Antivirus

1,4-Naphthoquinone and naphthalenes from R. aquaticus presented antiviral activity against herpes simplex virus type 2 (HSV-2) replication infected Vero cells. In which, musizin (145) showed dose dependent inhibitory property, causing a 2.00 log10 reduction in HSV-2 at 6.25 μM, on a traditional virus yield reduction test and qPCR assay. It suggested that R. aquaticus had the potential to treat HSV-2 infected patients [158].

Acetone–water extract (R2, which contains oligomeric, polymeric proanthocyanidins and flavonoids) from the aerial parts of R. acetosa showed obvious antiviral activities via plaque reduction test and MTT assay on Vero cells. R2 was 100% against herpes simplex virus type-1 at concentrations > 1 μg/mL (IC50 = 0.8 ± 0.04 μg/mL). At concentrations > 25 μg/mL (CC50 = 78.6 ± 12.7 μg/mL), cell vitality was more than 100% reduced by R2 [107].

The function in kidney and gastrointestinal tract

It is noted that quercetin-3-O-β-D-glucoside (72, QGC) from R. aquaticus could alleviate the modle that indomethacin (nonsteroidal anti-inflammatory drugs) induced gastric damage of rats and ethanol extract of R. aquaticus had a protective effect on the inflammation of gastric epithelial cells caused by Helicobacter pylori. In vivo research suggested that QGC pretreatment could decrease gastric damage by increasing mucus secretion, downregulating the expression of intercellular adhesion molecule-1 and decreasing the activity of myeloperoxidase. The in vitro test found that flavonoids including QGC could inhibit proinflammatory cytokine expression and inhibit the proliferation of an adenocarcinoma gastric cell line (AGS) [159, 160]. The cytoprotective effect of QGC against hydrogen peroxide-induced oxidative stress was noticed in AGS [161]. Moreover, QGC also showed protective efficiency in a rat reflux esophagitis model in a dose-dependent manner (1—30 mg/kg) [162].

Ten anthraquinones chrysophanol (1), chrysophanol-8-O-β-D-glucoside (3), 6'-acetyl-chrysophanol-8-O-β-D-glucoside (6), emodin (8), emodin-8-O-β-D-glucoside (12), physcion (18), aloe-emodin (13), rumexpatientosides A (47) and B (48) and nepalenside A (49) from R. patientia, R. nepalensis, R. hastatus not only inhibited the secretion of IL-6, but also decreased collagen IV and fibronectin production at a concentration of 10 µM in vitro. On which concentration, they were nontoxic to cells [133]. It suggested that anthraquinones have great potential to treat kidney disease.

Antioxidant properties

An extraction technology to obtain the total phenolics of R. acetosa was optimized and the antioxidant activity of different plant parts of R. acetosa was well investigated. It was found that the 80% methanol extract of the roots (IC50 = 118.8 μM) showed higher scavenging activity to DPPH free radicals than the other parts (leaves: IC50 = 201.6 μM, flowers and fruits: IC50 = 230.1 μM, stems: IC50 = 411.2 μM) [163]. The roots of R. thyrsiflorus [164], ethanol extracts of R. obtusifolius and R. crispus showed antioxidant ability on DPPH, ABTS+ and FRAP assays [165]. Moreover, R. tingitanus leaves, R. dentatus, R. rothschildianus leaves, R. roseus and R. vesicarius also showed antioxidant activity on DPPH assay [13, 78, 105, 154, 166, 167]. Phenolics isolated from R. tunetanus flowers and stems displayed antioxidant properties on DPPH and FRAP assays [103]. DPPH, ABTS+, NO2− radical scavenging and phosphomolybdate antioxidant assays verified that R. acetosella has antioxidant properties [168]. Phenolic constitutions from R. maderensis dispalyed antioxidant activity after the gastrointestinal digestion process. These components are known as dietary polyphenols and have the potential to be developed as functional products [99].

Moreover, the total antioxidant capacities of R. crispus were found to be 49.4%—86.4% on DPPH, ABTS+, NO, phosphomolybdate and SPF assays, which provided the basis to develop R. crispus as antioxidant, antiaging and skin care products [169]. Later on, the ripe fruits of R. crispus were studied and the aqueous extract showed antioxidant activity in vitro [170]. Dichloromethane and ethyl acetate extracts of R. crispus exhibited stronger antioxidant activity, which were associated with the concentration of polyphenols and flavonoids [157]. The antioxidant activities of chrysophanol (1), 1,3,7-trihydroxy-6-methylanthraquinone (54), przewalskinone B (55) and p-coumaric acid (206) isolated from R. hastatus were investigated on a nitric oxide radical scavenging assay, whose IC50 values were 0.39, 0.47, 0.45, and 0.45 mM, respectively [134].

Antitumor properties

MTT assays on HeLa (human cervical carcinoma), A431 (skin epidermoid carcinoma) and MCF7 (human breast adenocarcinoma) cell lines showed that R. acetosa and R. thyrsiflorus could inhibit the tumor cell proliferation [171]. The fruit of R. crispus showed cytotoxicity on HeLa, MCF7 and HT-29 (colon adenocarcinoma) cells in vitro [170]. The methanolic extract of R. vesicarius was assessed for hepatoprotective effects in vitro. CCl4-induced hepatotoxicity was observed at 100 mg/kg bw and 200 mg/kg bw. The plant also has cytotoxicity in HepG2 (human hepatoma cancer) cell lines [172]. Dichloromethane extract of R. crispus roots inhibited the growth and induced cellular apoptosis of HepG2 cells [157]. The hexane fraction of R. rothschildianus leaves showed 98.9% and 97.4% inhibition of HeLa cells and MCF7 cells at a concentration of 4 mg/mL [105].

Different plant parts (stems, roots, flowers and leaves) of R. vesicarius were screened for their cytotoxicity by the MTS method on MCF7, Lovo and Caco-2 (human colon cancer), and HepG2 cell lines. The stems displayed stronger cytotoxicity in vitro and with nontoxicity on zebrafish development, with IC50 values of 33.45—62.56 μM. At a concentration of 30 µg/mL, the chloroform extract of the stems inhibited the formation of  ≥ 70% of intersegmental blood vessels and 100% of subintestinal vein blood vessels when treated zebrafish embryos, indicating the chloroform extract of R. vesicarius stems has apparent antitumor potential [15].

2-Methoxystypandrone (152) from R. japonicus exhibited antiproliferative effect on Jurkat cells and the potential to treat leukemia, by reducing the mitochondrial membrane potential and increasing the accumulation of mitochondrial reactive oxygen, as shown by flow cytometry [116]. The phenolic extract from the flower parts of R. acetosa exhibited in vitro antiproliferative effects on HaCaT cells. When increasing of the extract concentration from 25 μg/mL to 100 μg/mL, the proliferation ability on HaCaT cells gradually decreased [147].

Antidiabetes activities

Chrysophanol (1) and physcion (18) from the roots of R. crispus showed inhibition on α-glucosidase, with IC50 values of 20.1 and 18.9 μM, respectively [180]. The alcohol extract of R. acetosella displayed stronger inhibitory activity on α-glucosidase (roots, IC50 = 12.3 μM; aerial parts, IC50 < 10 μM), compared to the positive control, acarbose (IC50 = 605 μM, p < 0.05), revealing R. acetosella could be developed as an antidiabetic agent [168]. Moreover, the methanolic extract of R. lunaria leaves displayed remarkable kinetic of -α-glucosidase activity from the concentration of 3 μM by comparison with blank control [16], and the acetone fraction of R. rothschildianus leaves showed inhibitory activity against α-amylase and α-glucosidase (IC50 = 19.1 ± 0.7 μM and 54.9 ± 0.3 μM, respectively) compared to acarbose (IC50 = 28.8, 37.1 ± 0.3 μM, respectively) [105].

The hypoglycemic effects of oral administration of ethanol extract of R. obtusifolius seeds (treatment group) were compared to the control group (rabbits with hyperglycemia). The treatment group could decrease fasting glucose levels (57.3%, p < 0.05), improve glucose tolerance and increase the content of liver glycogen (1.5-fold, p < 0.01). It also not only reduced the total cholesterol, low-density lipoprotein cholesterol levels and liver enzyme levels, but increased the high-density lipoprotein cholesterol levels. The results showed that R. obtusifolius has great potential to treat diabetes [173]. In addition, phenolic components of R. dentatus showed the ability to ameliorate hyperglycemia by modulating carbohydrate metabolism in the liver and oxidative stress levels and upregulating PPARγ in diabetic rats [14].

Other biological activities

The vasorelaxant antihypertensive mechanism of R. acetosa was investigated in vivo and in vitro. Intravenous injection (50 mg/kg) of the methanol extract of R. acetosa (Ra.Cr) leaves caused a mean arterial pressure (MAP) (40 mmHg) in normotensive rats with a decrease of 27.88 ± 4.55% and a MAP (70 mmHg) in hypertensive rats with a decrease of 48.40 ± 4.93%. In endothelium intact rat aortic rings precontracted with phenylephrine (1 μM), Ra.Cr induced endothelium-dependent vasorelaxation with EC50 = 0.32 mg/mL (0.21—0.42), while in denuded endothelial rat aortic rings, EC50 = 4.22 mg/mL (3.2—5.42), which was partially blocked with L-NAME (10 μM), indomethacin (1 μM) and atropine (1 μM). In isolated rabbit aortic rings precontracted with phenylephrine (1 μM) and K+ (80 mM), Ra.Cr induces vasorelaxation and the movement of Ca2+ [174].

The acetone extract of R. japonicus showed protective activity against myocardial apoptosis, through the regulation of oxidative stress levels in cardiomyocytes (LDH, MDA, CK, SOD) and the suppression of the expression of apoptosis proteins (caspase-3, Bax, Bcl-2) on in vitro H2O2-induced myocardial H9c2 cell apoptosis [175].

The antiplatelet activity of R. acetosa and the protective mechanism on cardiovascular system were investigated yet. The extract of R. acetosa showed inhibition of the collagen-induced platelet aggregation by modulating the phosphorylation of MAPK, PI3K/Akt, and Src family kinases and inhibited the ATP release in a dose dependent manner (25—200 μg/mL) [176]. The absorption of fexofenadine was inhibited by the ethanol extract of R. acetosa to decrease the aqueous solubility of fexofenadine [177]. The hepatoprotective effect of R. tingitanus was investigated by an in vivo experiment, in which the ethanol extract protected effectively the CCl4-damaged rats by enhancing the activity of liver antioxidant enzymes. Moreover, the extract could reduce the immobility time of mice, comparable of the positive drug, clomipramine. The results indicated that R. tingitanus has antidepressant-like effects [78].

Stimulating the ERK/Runx2 signaling pathway and related transcription factors could induce the differentiation of osteoblasts. Fortunately, chrysophanol (1), emodin (8) and physcion (18) from the aqueous extract of R. crispus could suppress the RANKL-induced osteoclast differentiation by suppressing the MAPK/NF-κB/NFATc1 signaling axis and increas the inhibitory factors of NFATc1 [178].

Moreover, the ethanol extract of R. crispus could reduce the degradation of collagen by inhibiting matrix metalloproteinase (MMP-1, MMP-8, MMP-13), indicating that R. crispus exhibited the antiaging function [169].

The anti-Alzheimer effect of helminthosporin (51) from R. abyssinicus was investigated in PAMPA-BBB permeability research, showing that 51 inhibited obviously AChE and BChE with IC50 values < 3 μM. Compound 51 could not only cross the BBB with high BBB permeability, but also bind with the peripheral anion part of the cholinesterase activity site by molecular docking [80].

It is noted, R. crispus, a traditional medicinal herb in the folk with rich retinol, ascorbic acid and α-tocopherol in the leaves, could be used as a complementary diet [179]. Moreover, chrysophanol (1) and physcion (18) from R. crispus roots showed obvious inhibitory activity on xanthine oxidase (IC50 = 36.4, 45.0 μg/mL, respectively) [180].

Inhibition of human pancreatic lipase could reduce the hydrolysis of triacylglycerol into monoacylglycerol and free fatty acids [181]. Chrysophanol (1) and physcion (18) from R. nepalensis with good inhibitory activity on pancreatic lipase (Pearson's r = 0.801 and 0.755, respectively) showed the obvious potential to treat obesity [182].

Conclusion

The genus Rumex distributing widely in the world with more than 200 species has a long history of food and medicinal application in the folk. These plants with rich secondary metabolites, e.g., quinones, flavonoids, tannins, stilbenes, naphthalenes, terpenes, diterpene alkaloids, lignans and other type of components, showed various pharmacological activities, such as antimicrobial, anti-inflammatory, antiviral, renal and gastrointestinal protective effects, antioxidant, antitumor and anti-diabetes effects. Particularly, quinones as the major components in Rumex showed stronger antibacterial activities and exerted the potential to treat kidney disease. However, detailed phytochemical studies are needed for many Rumex species, in order to clarify their bioactive components. Further studies and application may focus on the antitumor, anti-diabetes, anti-microbial, hepatoprotective, cardiovascular and gastrointestinal protective effects. Moreover, the toxicity or side effects for Rumex plants and their chemical constituents should be evaluated, in order to make the uses of Rumex more safety.