A Review of Polygonatum Mill. Genus: Its Taxonomy, Chemical Constituents, and Pharmacological Effect Due to Processing Changes.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Polygonatum Tourn, ex Mill. contains numerous chemical components, such as steroidal saponins, polysaccharides, flavonoids, alkaloids, and others, it possesses diverse pharmacological activities, such as anti-aging, anti-tumor, immunological regulation, as well as blood glucose management and fat reducing properties. AIM OF THE REVIEW: This study reviews the current state of research on the systematic categorization, chemical composition, pharmacological effects, and processing changes of the plants belonging to the genus Polygonatum, to provide a theoretical foundation for their scientific development and rational application.
MATERIALS AND METHODS: The information was obtained by searching the scientific literature published between 1977 and 2022 on online databases (including PubMed, CNKI, SciFinder, and Web of Science) and other sources (such as the Chinese Pharmacopoeia 2020 edition, and Chinese herbal books).
RESULTS: The genus Polygonatum contains 79 species, and 233 bioactive chemical compounds were identified in them. The abundance of pharmacological activities, such as antioxidant activities, anti-fatigue activities, anti-inflammatory activities, etc., were revealed for the representatives of this genus. In addition, there are numerous processing methods, and many chemical constituents and pharmacological activities change after the unappropriated processing.
CONCLUSIONS: This review summarizes the taxonomy classification, chemical composition, pharmacological effects, and processing of the plants belonging to the genus Polygonatum, providing references and research tendencies for plant-based drug development and further clinical applications.

1. Introduction

The genus Polygonatum belongs to a perennial herbaceous plant whose English name is King Solomon’s seal, and it belongs to the Asparagaceae family. There are about 79 species of Polygonatum in the globe, which are extensively distributed in the northern hemisphere. About 39 species are recorded growing in China [1]. The genus Polygonatum has long been valued for its medicinal, diet, and healthcare values, the rhizomes are medicinal portions [2]. Polygonatumi rhizoma and Polygonatumi odorati rhizoma belong to the genus Polygonatum and have been added to the “Chinese Pharmacopeia” (2020 edition) [3]. The genus Polygonatum contains polysaccharides, flavonoids, steroids, coumarins, and other chemical components [4]. As a medicinal plant, its dried rhizome has anti-aging, anti-oxidation, immune regulation, anti-inflammatory, and anti-cancer effects, and is clinically used to treat fatigue, weakness, diabetes, cough, and loss of appetite [5]. However, the unprocessed herbs in genus Polygonatum can irritate the throat, the raw rhizomes of Polygonatum Mill. are processed by repeated steaming and drying (nine times each) in order to reduce toxic components, and improve their primary functioning, taste, and pharmaceutical effects [6].

Previously, reviews that focused on some species, P. odoratum, P. cyrtonema, P. kingianum, and P. sibiricum have been conducted. To the authors’ knowledge, no study has reviewed the taxonomy classification, chemical composition, pharmacological effect, and processing of the whole genus. This review is aimed to critically evaluate available research reports on the genus, and systematically organize and present the findings.

2. Classification of Polygonatum Mill.

The genus Polygonatum comprises 79 species. Among them, 39 species distributed in China were recorded in the Chinese monograph “Flora of China” [1], and the other 40 species were included in the World Checklist of Selected Plant Families (WCSPF, World Checklist of Selected Plant Families: Royal Botanic Gardens, Kew). The contributions and the first recorded time of the species are summarized (Table 1).

Table 1

Species of the genus Polygonatum.

Number	Species	Distribution	First Recorded Time
1	P. acuminatifolium Kom	Russian, China	1916
2	P. adnatum	China	1987
3	P. amabile	Japan	1892
4	P. angelicum	Arunachal Pradesh, Tibet	2015
5	P. arisanense	China (Taiwan)	1920
6	P. autumnale	Arunachal Pradesh	2015
7	P. annamense	Vietnam	2015
8	P. azegamii	Japan	2008
9	P. biflorum	Canada, United Mexican States	1817
10	P. brevistylum	Nepal, Darjiling	1875
11	P. buschianum	Krym	1979
12	P. campanulatum	China	2015
13	P. cathcartii	Nepal, China	1875
14	P. cirrhifolium	Himalaya, China	1839
15	P. costatum	Thailand	2015
16	P. cryptanthum	Korea, Japan	1908
17	P. curvistylum	Nepal, China	1892
18	P. cyrtonema	China	1892
19	P. daminense	China	2020
20	P. desoulavyi	Korea, Japan	1931
21	P. domonense	Japan	1970
22	P. falcatum	Korea, Japan	1859
23	P. falcatum var. hyugaense	Japan	1957
24	P. falcatum var. trichosanthum	Japan	2008
25	P. filipes	China	1980
26	P. franchetii	China	1892
27	P. geminiflorum	Pakistan, Himalaya	1844
28	P. glaberrimum	Turkey, Iran	1849
29	P. gongshanense	China, Myanmar	2014
30	P. govanianum	Pakistan, Himalaya	1839
31	P. graminifolium	Himalaya	1851
32	P. grandicaule	Korea	1998
33	P. griffithii	Arunachal Pradesh, Tibet	1875
34	P. hirtellum	China	1936
35	P. hookeri	Himalaya, China	1875
36	P. humile	Kazakhstan, Japan	1859
37	P. inflatum	Korea, Japan	1901
38	P. infundiflorum	Korea	1998
39	P. involucratum	Russian, Korea, Japan	1883
40	P. jinzhaiense	China	2000
41	P. kingianum	China	1890
42	P. lasianthum	Korea, Japan	1883
43	P. latifolium	Europe, Turkey	1807
44	P. leiboense	China	1984
45	P. longistylum	China	1990
46	P. luteoverrucosum	Arunachal Pradesh, Tibet	2015
47	P. macranthum	Japan	1919
48	P. macropodum	China	1832
49	P. megaphyllum	China	1966
50	P. mengtzense	China, Vietnam	1936
51	P. multiflorum	Europe, Caucasus	1785
52	P. nervulosum	Himalaya	1875
53	P. nodosum	China	1892
54	P. odoratum	China, Europe, Japan	1906
55	P. omeiense	China	1992
56	P. oppositifolium	Nepal, Assam	1839
57	P. orientale	Krym, Turkey, Iran	1807
58	P. prattii	China	1892
59	P. pseudopolyanthemum	Caucasus	1928
60	P. pubescens	Canada, American	1813
61	P. punctatum	Nepal, China	1850
62	P. qinghaiense	China (Qinghai)	2005
63	P. robustum	Korea	1917
64	P. roseum	Asia, China (Xinjiang)	1850
65	P. sewerzowii	Iran, Asia	1868
66	P. sibiricum	Siberia, Korea, Bhutan	1811
67	P. singalilense	Nepal, Bhutan	1965
68	P. sparsifolium	China	2002
69	P. stenophyllum	Russian, Korea	1859
70	P. stewartianum	China	1912
71	P. tessellatum	Assam, China	1936
72	P. tsinlingense	China	1949
73	P. undulatifolium	Arunachal Pradesh, Tibet	2018
74	P. urceolatum	China, Vietnam	2014
75	P. verticillatum	Europe, China	1785
76	P. wardii	Assam, Tibet	1937
77	P. yunnanense	China	1916
78	P. zanlanscianense	China	1915
79	P. zhejiangensis	China (Zhejiang)	1994

3. Chemical Constituents of Polygonatum

As mentioned in the introduction, the herbs in the genus Polygonatum contain many chemical components, such as steroidal saponins, polysaccharides, flavonoids, and alkaloids. The author summarized 233 compounds isolated from this genus from 1977 to 2022, which contained 124 steroidal saponins, 68 flavonoids, triterpenoid saponins, 16 alkaloids, 3 quinones, and 6 lignans.

3.1. Steroidal Saponins

Steroid saponins are formed by the condensation of steroid sapogenins and sugar. The carbon frame of steroid sapogenins is made up of 27 carbon atoms and is based on spirostane. According to the configuration of C25 in the spirostane structure and the cyclization state of the F ring, it is divided into spirostanol, isospirostanol, furostanol, and pseudo spirostanol types. The main pharmacological active substances are the first three types of steroidal saponins in the genus Polygonatum. The glycosyl moiety (mainly glucose, galactose, xylose, rhamnose, and fucose) is an important factor in the formation of the molecular diversity of the genus Polygonatum saponins. The details of the compounds are shown in Table 2, and the structural formulas are shown in Figure 1, Figure 2, Figure 3 and Figure 4.

Table 2

Chemical constituents of the genus Polygonatum.

No.	Compounds	Species	Parts	References
1	neoprazerigeninA-3-O-β-D-lycotetraosid	P. sibiricum	rhizome	[7]
2	(25R)-spirost-5-ene-3β,14α-diol-3-O-β-D-glucopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→3)]-Β-D-glucopyranosyl-(1→4)-β-D-galactopyranoside	P. odoratum	rhizome	[8]
3	(25S)-spirost-5-en-3-ol-3-O-β-D-glucopyranosyl-(1→3)-[β-D-fucopyranosyl-(1→2)]- β-D-glucopyranosyl-(1→4) -β-D-galactopyranoside	P. verticillatum	rhizome	[9]
4	(25S)-spirost-5-ene-3β,12β-diol-3-O-{β-D-glucopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3)]-β-D-glucopyranosyl-(1→4)} -β-D-galactopyranoside	P. cirrhifolium	rhizome	[10]
5	(25S)-Spirosta-5,14-diene-3β-ol-3-O-{β-D-glucopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3)]-β-D-glucopyranosyl-(1→4)} -β-D-galactopyranoside	P. odoratum P. cirrhifolium	rhizome	[10]
6	(25S)-spirost-5-en-3β-ol-3-O-α-L-rhamnose (1→2)-[α-L-rhamnose (1→4)]-β-D-Glucoside	P. cirrhifolium	rhizome	[10]
7	(25S)-spirost-5-ene-3β,14α-diol-3-O-{β-D-glucopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3) ]-β-D-glucopyranosyl-(1→4)}-β-D-galactopyranoside	P. odoratum P. cirrhifolium	rhizome	[10,11]
8	3-O-β-D-glucopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3)]-β-D-glucopyranosyl-(1→4)-galactopyranoside-25(S)-spirost-5(6) -en-3-ol	P. odoratum	rhizome	[11]
9	3-O-β-D-glucopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3)]-β-D-glucopyranosyl-(1→4)-galactopyranoside-25(S)-spirost-5(6) -en-3β, 14α-diol	P. odoratum	rhizome	[11]
10	neosibiricoside A	P. sibiricum	rhizome	[12]
11	neosibiricoside B	P. sibiricum	rhizome	[12]
12	neosibiricoside C	P. sibiricum	rhizome	[12]
13	polygoside A	P. odoratum	rhizome	[13]
14	(3β,14α)-3-O-β-D-glucopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3)]-β-D-glucopyranosyl-(1→4)-β-D-galactopyranoside- yamogenin	P. odoratum	rhizome	[13]
15	(25S)-spirost-5-ene-3β, 14α-dihydroxy	P. odoratum	rhizome	[13]
16	(25S)-spirost-5-en-3β-ol-3-O-β-D-glucopyranosyl-(1→4)-β-D-galactopyranoside	P. odoratum	rhizome	[13]
17	(25S)-spirost-5-en-3β-ol-3-O-β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl-(1→4)-β-D-galactopyranoside	P. odoratum	rhizome	[13]
18	polygonatumoside F	P. odoratum	rhizome	[14]
19	polygonatumoside D	P. odoratum	rhizome	[15]
20	polygonatumoside E	P. odoratum	rhizome	[15]
21	(25S)-spirost-5-en-3-O-β-D-glucopyranosyl-(1→4)-β-D-fucopyranosyl-3β, 17α-diol	P. sibiricum	rhizome	[16]
22	(25S)-spirost-5-en-3β,12β-diol-3-O-β-D-glucopyranosyl-(1→4) -β-D-fucopyranosyl	P. sibiricum	rhizome	[16]
23	(25S)-spiroster-5-en-12-one-3-OD-glucopyranosyl-(1→2)-O-[β-D-glucopyranosyl-(1→3)]-O-β-D-glucopyranosyl-(1→4)-β-D-galactopyranoside	P. cyrtonema	rhizome	[17]
24	(25S)-spirost-5-en-12-one-3-O-D-glucopyranosyl-(1→2)-O-[β-D-xylopyranosyl-(1→3)]-O-β-D-glucopyranosyl-(1→4)-β-D-galactopyranoside	P. cyrtonema	rhizome	[18]
25	(25S) -3-β-hydroxy-spirost-5-en-12-one	P. cyrtonema	rhizome	[18]
26	25S-pratioside D1	P. kingianum	rhizome	[19]
27	25S-Yunnan Polygonatum A	P. kingianum	rhizome	[19]
28	(25S)-spirost-5-ene-3β,14α-diol-3-O-β-D-glucopyranosyl-(1→2)-[β-D-glucopyranosyl- (1→3)]-β-D-glucopyranosyl-(1→4) -β-D-galactopyranoside	P. odoratum	rhizome	[7]
29	(25S)-spirost-5-en-3β-ol-3-O-β-D-glucopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→3)]-β-D-glucopyranosyl-(1→4)-β-D-galactopyranoside	P. odoratum	rhizome	[7]
30	(25S)-spirost-5-en-3β-ol-3-O-β-D-glucopyranosyl-(l→2) -[β-D-xylopyranosyl-(l→3) ]-β-D-glucopyranosyl-(l→4)-β-D-galactopyranoside	P. odoratum	Fresh rhizome	[20]
31	kingianoside H	P. kingianum	rhizome processed	[21]
32	sibiricoside B	P. sibiricum	rhizome	[7]
33	(25R)-spirost-5-en-3β-ol-3-O-α-L-rhamnose (1→2)-[α-L-rhamnose (1→4)]-β-D- Glucoside	P. cirrhifolium	rhizome	[10]
34	neosibiricoside D	P. sibiricum	rhizome	[12]
35	polygoside B	P. odoratum	rhizome	[13]
36	(25R)-spirost-5-en-3β,17α-diol-3-O-β-D-glucopyranosyl-(1→4)-β-D-fucopyranosyl	P. sibiricum	rhizome	[17]
37	(25r)-spirost-5-en-3β,17α-diol-3-O-β-D-glucopyranosyl-(1→4)-β-D-fucopyranosyl	P. sibiricum	rhizome	[17]
38	(25R)-spirost-5-en-3β,12β-diol-3-O-β-D-glucopyranosyl-(1→4)-β-D-fucopyranosyl	P. sibiricum	rhizome	[18]
39	(25R) Spiroster-5-en-12-one-3-OD-glucopyranosyl-(1→2)-O-[β-D-xylopyranosyl-(1→3)]-O-β-D-glucopyranosyl-(1→4) -β-D-galactopyranoside	P. cyrtonema	rhizome	[19]
40	cyrtonemoside A	P. cyrtonema	rhizome	[22]
41	(25r)-3-β-hydroxy-spirost-5-en-12-one	P. cyrtonema	rhizome	[23]
42	(25r) -kingianoside G	P. kingianum	rhizome	[24]
43	kingianoside K	P. kingianum	rhizome processed	[25]
44	kingianoside I	P. kingianum	rhizome processed	[25]
45	(25R)-spirost-5-ene-3β,14α-diol-3-O-β-D-glucopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3)]-β-D-glucopyranosyl-(1→4)-β-D-galactopyranoside	P. odoratum	rhizome	[9]
46	(25R)-spirost-5-ene-3β,14α-diol-3-O-β-D-glucopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→3)]-Β-D-glucopyranosyl-(1→4) -β-D-galactopyranoside	P. odoratum	rhizome	[9]
47	(25R)-spirost-5-en-3β-ol-3-O-β-D-glucopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→ 3)]- β-D-glucopyranosyl-(1→4)-β-D-galactopyranoside	P. odoratum	rhizome	[9]
48	(25R)-spirost-5-en-3β-ol-3-O-β-D-glucopyranosyl-(l→2)-[β-D-xylopyranosyl-(l→3)] -β-D-glucopyranosyl-(l→4) -β-D-galactopyranoside	P. odoratum	Fresh rhizome	[21]
49	saponin Tg	P. kingianum	rhizome processed	[23]
50	polygonatoside C1	P. kingianum	rhizome processed	[23]
51	ophiopogonin C’	P. kingianum	rhizome processed	[23]
52	Diosgenin	P. cirrhifolium	rhizome	[10]
53	(25R)-spirost-5-en-3β-ol-3-O-α-L-rhamnose (1→4)-β-D-glucoside	P. cirrhifolium	rhizome	[25]
54	pratioside D1	P. prattii P. kingianum	rhizome	[23]
55	kingianoside A	P. kingianum	rhizome	[24,26]
56	kingianoside B	P. kingianum	rhizome	[26]
57	funkioside C	P. kingianum	rhizome	[26]
58	(25R)-spirost-5-ene-3β,14α-diol-3-O-β-D-glucopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→3)]-Β-D-glucopyranosyl-(1→4) -β-D-galactopyranoside	P. odoratum	rhizome	[6]
59	Dioscin	P. kingianum P. punctatum P. cirrhifolium P. zanlanscianense	rhizome, rhizome processed	[24,25,26,27,28,29]
60	Dracaenoside F	P. cirrhifolium	roots and rhizomes	[28,30]
61	polygonatoside D	P. zanlanscianense	rhizome	[29]
62	Isobalanin-3-O-α-L-rhamnopyranosyl-(1→2)- [α-L-rhamnopyranosyl-(1→4)]-β-D-pyranosyl Glucopyranoside	P. zanlanscianense	rhizome	[29]
63	saponin Pa	P. kingianum	rhizome processed	[24]
64	prosapogenin A of dioscin	P. punctatum	rhizome	[27]
65	gracillin	P. zanlanscianense	rhizome	[30]
66	parissaponin Pb	P. zanlanscianense	rhizome processed	[29]
67	polypunctoside A	P. punctatum	rhizome	[27]
68	polypunctoside B	P. punctatum	rhizome	[27]
69	polypunctoside C	P. punctatum	rhizome	[27]
70	polypunctoside D	P. punctatum	rhizome	[27]
71	polygonatoside A	P. zanlanscianense	rhizome	[29]
72	polygonatoside B	P. zanlanscianense	rhizome	[29]
73	pratioside C	P. prattii	root	[31]
74	pratioside A	P. prattii	root	[31]
75	pratioside D1	P. prattii	root	[31]
76	pratiosides E1	P. prattii	root	[31]
77	pratiosides F1	P. prattii	root	[31]
78	isonarthogenin-3-O-β-D-glucopyranosyl-(1→2)-β-D- glucopyranosyl-(1→4) -β-D-galactopyranoside	P. zanlanscianense	rhizome	[32]
79	polygonatoside C	P. zanlanscianense	rhizome	[32]
80	saponin Tb	P. kingianum	rhizome processed	[33]
81	odospiroside	P. odoratum	rhizome	[34]
82	sibiricoside A	P. sibiricum	rhizome	[7]
83	sibiricogenin-3-O-β-lycotetraoside	P. sibiricum	rhizome	[7]
84	polygonatumoside G	P. odoratum	rhizom	[15]
85	timosaponin H1	P. odoratum	rhizom	[15]
86	(25S) -funkioside B	P. odoratum	rhizom	[15]
87	25R-22 Hydroxy-curvetoxin C	P. kingianum	rhizom	[20]
88	22-Hydroxy-curvetoxin C	P. kingianum	rhizom	[20]
89	kingianoside Z	P. sibiricum	rhizome	[35]
90	22-Hydroxy-25(R)-furost-5-en-12-one-3β,22,26-triol-26-O-β-D-glucopyranoside	P. odoratum	rhizome	[36]
91	kinginaoside E	P. kingianum	rhizome	[20]
92	25S-kinginaoside E	P. kingianum	rhizome	[20]
93	25S-kinginaoside C	P. kingianum	rhizome	[20]
94	25S-kinginaoside D	P. kingianum	rhizome	[20]
95	kingianoside C	P. kingianum	rhizome	[20]
96	kingianoside D	P. kingianum	rhizome	[20]
97	saponin Pb	P. kingianum	rhizome processed	[25]
98	25S-kinginaoside F	P. kingianum	rhizome	[20]
99	3β,26-diol-25(R)-Δ5,20(22)-diene-furosta-26-O-β- D-glucopyranoside	P. odoratum	fresh rhizome	[22]
100	(3β,23ξ, 25R)-3-{[2-O-(6-deoxy-α-L-mannopyranosyl) -β-D-glucopyranosyl]-oxy}-22-hydroxy-furost-5-en-26-yl-β-D- glucopyranoside	P. punctatum	rhizome	[28]
101	protodioscin	P. punctatum	rhizome	[28]
102	26-β-D-glucopyranosyl-22-methoxy-(25R) -furost-5-en-3β, 26-diol-3-O-[α-L-rhamnopyranosyl-(1→2)][α-L- rhamnopyranosyl-(1→4)]-β-D-glucopyranoside	P. zanlanscianense	root	[22]
103	pratioside B	P. prattii	roots	[31]
104	polygonoide A	P. sibiricum	rhizome	[33]
105	polygonoide B	P. sibiricum	rhizome	[33]
106	22-hydroxy-25(S)-furost-5-en-12-one-3β,22,26-triol-26-O-β-D -glucopyranoside	P. odoratum	rhizome	[35]
107	kingianoside F	P. kingianum	rhizome	[36]
108	ergosta-7, 22-diene-3β, 5α, 6β-triol	P. odoratum	rhizome	[14]
109	(22S)-cholest-5-ene-1β,3β,16β,22-tetrol-1-O-α-L- rhamnopyranosyl-16-O-β-D-glucopyranoside	P. odoratum	rhizome	[14]
110	(22S)-cholest-5-ene-1β,3β,16β,22-tetrol-1,16-di-O-β-D- glucopyranoside	P. odoratum	rhizome	[15]
111	(25S)-3β,14α-dihydroxy-spirost-5-ene-3-O-β-D-glucopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3)]-β-D-glucopyranosyl-(1→4)-β-D-galacopyranoside	P. odoratum	rhizome	[15]
112	(25S)3β,14α-dihydroxy-spirost-5-ene-3-O-β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl-(1→4)-β-D-galacopyranoside	P. odoratum	rhizome	[15]
113	3-O-β-D-glucopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3)]-β-D-glucopyranosyl-(1→4)-β-D-galacopyranoside-yamogenin	P. odoratum	rhizome	[15]
114	(22S)-cholest-5-ene-1β,3β,16β,22-tetrol-1-O-α-L-rhamnopyranosyl-16-O-β-D-glucopyranoside	P. odoratum	rhizome	[15]
115	polygonatumoside A	P. odoratum	rhizome	[16]
116	polygonatumoside B	P. odoratum	rhizome	[16]
117	polygonatumoside C	P. odoratum	rhizome	[16]
118	3-O-β-D-glucopyranosyl(1→4)-β-D-fucopyranosyl-(25R)-spirost-5-en-3β,17α-diol	P. sibiricum	rhizome	[37]
119	3-O-β-D glucopyranosyl (1→4)-β-D-fucopyranosyl-(25S)-spirost-5-en-3β	P. sibiricum	rhizome	[37]
120	17α-diol (2), 3-O-β-D-glucopyranosyl(1→2)-β-D-glucopyranosyl (1→4)-β-D- fucopyranosyl-(25R)-spirost-5-en-3β,17α-diol	P. sibiricum	rhizome	[37]
121	3-O-β-D glucopyranosyl(1→4)-β-D-fucopyranosyl-(25R/S)-spirost-5-en- 3β,12β-diol	P. sibiricum	rhizome	[37]
122	(25S)-spirost-5-en-3 -ol 3-O-β-D-glucopyranosyl-(1→3)- [β-Dfucopyranosyl-(1→2)]-β-D-glucopyranosyl-(1→4)-β-D-galactopyranoside	P. verticillatum	rhizome	[38]
123	26-O-β-D-glucopyranosyl-22ξ-hydroxy-(25R)-furost-5-en-3β, 26-diol, 3-O-β [xylopyranosyl (1→3) α-L-rhamnopyranosyl (1→2) β-D-glucopyranoside]	P. verticillatum	rhizome	[39]
124	3-O-β-D-xylopyranosyl (1→3) α-L-rhamnopyranosyl (1→3) β-D-glucopyranoside diosgenin	P. verticillatum	rhizome	[39]

Figure 1

Structures of spirostanol from Polygonatum Mill.

Figure 2

Structures of isosprirostanol from Polygonatum Mill.

Figure 3

Structures of furostanol from Polygonatum.

Figure 4

Structures of other steroidal saponin from Polygonatum.

3.2. Flavonoids

Flavonoids originally refer to the general term for compounds derived from 2-phenylchromone. It generally refers to a set of compounds formed by two benzene rings connected through three carbon atoms, a general term for a series of compounds with a C6-C3-C6 structure. Flavonoids mostly include flavones, flavonols, dihydroflavonoids, isoflavones, and homoisoflavonoids in Polygonatum Mill. (Table 3, Figure 5).

Table 3

Flavonoids of Polygonatuml.

No.	Compounds	Species	Parts	References
1	polygonatone B	P. odoratum	rhizome	[13]
2	polygonatone C	P. odoratum	rhizome	[13]
3	polygonatone D	P. odoratum	rhizome	[13]
4	(25S)-spirost-5-ene-3β,12β-diol-3-O-{β-D-glucopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3)]-β-D-glucopyranosyl-(1→4)}-β-D-galactopyranoside	P. odoratum	rhizome	[13]
5	(3S)-3, 5, 7-trihydroxy-6-methyl-3-(4’-methoxybenzyl) -chroma-4-one	P. odoratum	rhizome	[14]
6	5, 7-dihydroxy-3-(2’, 4’-dihydroxybenzyl) -chroma-4-one	P. odoratum	rhizome	[14]
7	(3S)-3, 5, 7-trihydroxy-6, 8-dimethyl-3-(4’-hydroxybenzyl) -chroma-4-one	P. odoratum	rhizome	[14]
8	isorhamnetin-3-O-(6″-O-α-L-rhamnopyransoyl) -β-D-glucopyranoside	P. odoratum	rhizome	[14]
9	5,4’-Dihydroxy-7-methoxy-6-methylflavonoid	P. odoratum	rhizome	[13]
10	Apigenin-7-O-β-D-glucoside	P. sibiricum	fresh rhizome	[39]
11	kaempferol	P. sibiricum P. cyrtonema	fresh rhizome	[39]
12	myricetin	P. sibiricum	fresh rhizome	[39]
13	chrysoeriol	P. odoratum	rhizome	[40]
14	(6aR, 1laR)-10-hydroxy-3,9-dimethoxy pterostane	P. kingianum	rhizome	[41]
15	neoisoliquiritin	P. kingianum	rhizome	[41]
16	5-hydroxy-7-methoxy-6, 8-dimethyl-3-(2’-hydroxy-4’-methoxybenzyl) -chroma-4-one	P. cyrtonema	rhizome	[42]
17	5, 7, 4’-trihydroxy isoflavone	P. odoratum	rhizome	[14]
18	5, 7, 4’-trihydroxy-6-methoxy isoflavone	P. odoratum	rhizome	[14]
19	5, 7, 4’-trihydroxy-6, 3’-dimethoxy isoflavone	P. odoratum	rhizome	[14]
20	2’, 7-Dihydroxy-3’, 4’-Dimethoxyisoflavan	P. kingianum	rhizome	[41]
21	isoliquiritin	P. kingianum P. alternicirrhosum	Rhizome	[41][43]
22	4’,7-Dihydroxy-3’-Methoxy Isoflavone	P. kingianum	rhizome	[43]
23	tectoridin	P. odoratum	root	[44]
24	liquiritigenin	P. kingianum P. alte-lobatum P. odoratum	rhizome	[41,43][45]
25	isomucronulatol	P. kingianum	rhizome	[46]
26	(3R)-5, 7-dihydroxy-6-methyl-3-(4’-hydroxybenzyl) -chroma-4-one	P. odoratum	rhizome	[47]
27	(3R)-5,7-Dihydroxy-6-methyl-8-methoxy-3-(4’-hydroxybenzyl)-chroman-4-one	P. odoratum	rhizome	[47]
28	polygonatone A	P. odoratum	rhizome	[13]
29	(3R)-5,7-Dihydroxy-6,8-dimethyl-3-(4’-hydroxybenzyl)-chroman-4-one	P. odoratum	rhizome	[13]
30	(3R)-5,7-Dihydroxy-6-methyl-3-(4’-hydroxybenzyl)-chroman-4-one	P. odoratum	rhizome	[13]
31	5,7-Dihydroxy-6-methyl-8-methoxy-3-(4’-methoxybenzyl)-chroman-4-one	P. odoratum	root	[13]
32	5,7-Dihydroxy-6-methyl-3-(2’,4’-dihydroxybenzyl)-chroman-4-one	P. cyrtonema	rhizome	[39]
33	disporopsin	P. odoratum	rhizome	[40]
34	5,7-Dihydroxy-6-methoxy-8-methyl-3-(4’-methylbenzyl)-chroman-4-one	P. odoratum	rhizome	[40]
35	5,7-Dihydroxy-6,8-dimethyl-3-(4’-hydroxybenzyl)-chroman-4-one	P. cyrtonema P. alte-lobatum P. odoratum	rhizomerhizomerhizome	[42][48][49]
36	5, 7-dihydroxy-6, 8-dimethyl-3-(2’-methoxy-4’-hydroxybenzyl) -chroma-4-one	P. cyrtonema	rhizome	[42]
37	5, 7-dihydroxy-6-methyl-3-(4’-hydroxybenzyl) -chroma-4-one	P. cyrtonema	rhizome	[42]
38	5, 7-dihydroxy-8-methyl-3-(4’-hydroxybenzyl) -chroma-4-one	P. cyrtonema	rhizome	[42]
39	5, 7-dihydroxy-6-methyl-3-(4’-methoxybenzyl) -chroma-4-one	P. cyrtonema	rhizome	[42]
40	5, 7-dihydroxy-6, 8-dimethyl-3-(4’-methoxybenzyl) -chroma-4-one	P. cyrtonema	rhizome	[42]
41	5, 7-dihydroxy-3-(4’-methoxybenzyl) -chroma-4-one	P. cyrtonema	rhizome	[42]
42	5, 7-dihydroxy-3-(4’-hydroxybenzyl) -chroma-4-one	P. kingianum P. cyrtonema	rhizome	[12][42]
43	5, 7-dihydroxy-3-(2’-hydroxy-4’-methoxybenzyl) -chroma-4-one	P. cyrtonema	rhizome	[42]
44	methylophiopogonanone B	P. odoratum	root	[44]
45	5,7-Dihydroxy-6-methyl-8-methoxy-3-(4’-hydroxybenzyl)-chroman-4-one	P. odoratum	root	[44]
46	ophiopogonanone E	P. odoratum	root	[44]
47	(3R)-5,7-dihydroxy-8-methoxy-3-(4-methoxybenzyl)-6-methylchrom-an-4-one	P. odoratum	rhizome	[50]
48	6-Methyl-4’,5,7-trihydroxy homoisoflavanone	P. odoratum	rhizome	[49]
49	5,7-Dihydroxy-6-methoxy-8-methyl-3-(2’,4’-dihydroxybenzyl)-chroman-4-one	P. odoratum	rhizome	[50]
50	(3R)-5,7,8-trihydroxy-3-(4-hydroxybenzyl) -6-methyl-chroma-4-one	P. odoratum	rhizome	[50]
51	5,7-Hydroxy-8-methoxy-3-(3’,4’-methylenedioxybenzyl)-chroman-4-one (Methyl Ophiopogon flavanone A)	P. cyrtonema	aboveground	[49]
52	neoliquiritin	P. kingianum	rhizome	[41]
53	hesperidin	P. odoratum	root	[44]
54	(±) 5, 7-dihydroxy-6, 8-dimethyl-3-(3’-hydroxy-4’-methoxybenzyl) -chroma-4-one	P. odoratum	root	[44]
55	(±) 5, 7-dihydroxy-6, 8-dimethyl-3-(2′-hydroxy-4′-methoxybenzyl) -chroma-4-one	P. odoratum	root	[44]
56	(3R)-5, 7-dihydroxy-6-methyl-3-(2′-hydroxy-4′-methoxybenzyl) -chroma-4-one	P. cyrtonema	rhizome	[42]
57	(3R)-5, 7-dihydroxy-8-methyl-3-(2′, 4′-dihydroxybenzyl) -chroma-4-one	P. odoratum	rhizome	[46]
58	(3R)-5, 7-dihydroxy-8-methyl-3-(4′-hydroxybenzyl) -chroma-4-one	P. odoratum	rhizome	[46]
59	(3R)-5, 7-dihydroxy-3-(2′-hydroxy-4′-methoxybenzyl) -chroma-4-one	P. odoratum	rhizome	[46]
60	(3R)-5, 7-dihydroxy-3-(4′-hydroxybenzyl) -chroma-4-one	P. odoratum	rhizome	[46]
61	(3R)-5, 7-dihydroxy-6-methoxy-8-methyl-3-(2′, 4′-dihydroxybenzyl) -chroma-4-one	P. odoratum	rhizome	[46]
62	(3R)-5, 7-dihydroxy-8-methoxy-3-(2′-hydroxy-4′-methoxybenzyl) -chroma-4-one	P. odoratum	rhizome	[46]
63	(3R)-5, 7-dihydroxy-6-methyl-8-methoxy-3-(4′-methoxybenzyl)-chroma-4-one	P. odoratum	rhizome	[46]
64	6, 8-dimethyl-5, 7-dihydroxy-3-(4′-methoxybenzyl)	P. odoratum	rhizome	[51]
65	5, 7-dihydroxy-3-(4′-hydroxybenzylidene) -chroma-4-one	P. cyrtonema	rhizome	[42]
66	€ 5, 7-dihydroxy-6, 8-dimethyl-3-(3, 4-dihydroxybenzylidene) -chroma-4-one	P. odoratum	rhizome	[44]
67	€ -7-O-β-D-glucopyranoside-5-hydroxy-3-(4′-hydroxybenzylidene) -chroma-4-one	P. odoratum	root	[44]
68	€ 5, 7-dihydroxy-8-methoxy-6-methyl-3-(3, 4-dihydroxybenzylidene) -chroma-4-one	P. odoratum	rhizome	[52]

Figure 5

Structures of flavonoid from Polygonatum.

3.3. Triterpenoid Saponins

Triterpene saponin is a class of glycosides in which aglycones are triterpenoid compounds, mainly distributed in terrestrial higher plants. Triterpenoids are a type of terpenoids. Their basic core skeleton is made up of 30 carbon atoms. They exist in plants in three forms; free, in the form of glycosides, or esters combined with sugars. The main active ingredients of many well-known Chinese herbal medicines, such as Ginseng, Glycyrrhiza uralensis, and Anemarrhena asphodeloides, have triterpene saponins. Some saponins also have valuable biological activities, such as antibacterial activity, sedation, and anticancer. The triterpenoid saponins isolated and identified from the plants of the genus Polygonatum are shown in Table 4, and structures are shown in Figure 6.

Table 4

Triterpenoid saponins of Polygonatum.

No.	Compounds	Species	Parts	References
1	(24R/S)-9,19-CycloAltin-25-ene-3β,24-diol	P. odoratum	rhizome	[10]
2	3β, 19α-dihydroxy-12-en-24, 28-dioic acid	P. odoratum	rhizome	[14]
3	ginsenoside Rb1	P. kingianum	rhizome processed	[23]
4	ginsenoside Rc	P. kingianum	rhizome processed	[25]
5	β(OH)-(3→1) glucose-(4→1) glucose-(4→1) glucose-oleanane	P. sibiricum	rhizome	[53]
6	3β(OH)-(3→1) glucose-(2→1) glucose-oleanolic acid	P. sibiricum	rhizome	[53]
7	3β(OH)-(3→1) glucose-(4→1) glucose-(28→1) arabinose-(2→1) arabinose-oleanolic acid	P. sibiricum	rhizome	[53]
8	β, 30β(OH) 2-(3→1) glucose-(2→1) glucose-oleanane	P. sibiricum	rhizome	[53]
9	polygonoide C	P. sibiricum	rhizome	[54]
10	polygonoide D	P. sibiricum	rhizome	[54]
11	polygonoides C	P. sibiricum	rhizome	[54]
12	polygonoides D	P. sibiricum	rhizome	[54]
13	polygonoides E	P. sibiricum	rhizome	[54]
14	2β, 3β, (OH) 2-(28→1) glucose-(6→1) glucose-(4→1) rhamnose-ursic acid (asiaticoside)	P. sibiricum	rhizome	[53,55]
15	2β, 3β, 6β, (OH) 3-(28→1) glucose-(6→1) glucose-(4→1) rhamnose-ursic acid Oxalin)	P. sibiricum	rhizome	[53]
16	Pseudoginsenoside F11	P. kingianum	rhizome	[55]

Figure 6

Structures of triterpenoid saponin from Polygonatum.

3.4. Alkaloids

Alkaloids are nitrogen-containing alkaline organic compounds in nature (mainly in plants, but some also exist in animals). They have a complex ring structure, and nitrogen is usually contained in the ring. It has significant biological activity and is one of the most effective ingredients in Chinese herbal medicine. Polygonatum has a low content of alkaloids and a changeable structure. Alkaloids have been found in P. odoratum, P. kingianum, P. cirrhifolium, P. verticillatum, and P. alte-lobatum (Table 5, Figure 7).

Table 5

Alkaloids of Polygonatum.

No.	Compounds	Species	Parts	References
1	N, N-bis(2,5-dihydroxybenzoyl)-2,5-dihydroxybenzamide	P. cirrhifolium	rhizome	[10]
2	soyacerebroside II	P. odoratum	rhizome	[38]
3	Polygonatum sphingolipid A	P. kingianum	rhizome	[38]
4	Polygonatum sphingolipid B	P. kingianum	rhizome	[38]
5	Polygonatum sphingolipid C	P. kingianum	rhizome	[38]
6	Polygonatum sphingolipid D	P. kingianum	rhizome	[38]
7	N-trans-feruloyltyramine	P. odoratum	rhizome	[40]
8	N-trans-feruloyloctopamine	P. odoratum	rhizome	[40]
9	3-methoxyethyl-5,6,7,8-tetrahydro-8-indolinone	P. sibiricum P. kingianum	rhizomerhizome	[56][46]
10	3-ethoxymethyl-5,6,7,8-tetrahydroindolizin-8-one	P. sibiricum	rhizome	[57]
11	kinganone	P. kingianum	rhizome	[46]
12	quinine	P. verticillatum	rhizome	[38]
13	polygonapholine	P. alte-lobatum	rhizome	[58]
14	adenosine	P. sibiricum	rhizome	[59]

Figure 7

Structures of alkaloid from Polygonatum.

3.5. Quinones

There are now three quinones isolated from P. odoratum and P. alteolobatum [13,47]. Ubiquinones with a benzoquinone structure can engage in the redox process in vivo and are a family of coenzymes considered to coenzyme Q in biological oxidation reactions. It has significant therapeutic medical value and can be used to treat cardiovascular disease, hypertension, and cancer. The tree quinones are emodin-8-O-β-D-glucopyranoside (a), polygonaquinone A (b), and polygonaquinone B (c), and their structures are in Figure 8.

Figure 8

Structures of quinone from Polygonatum, (a) emodin-8-O-β-D-glucopyranoside; (b) polygonaquinone A; (c) polygonaquinone B.

3.6. Lignans

Lignans exist in plants and belong to a kind of phytoestrogen that has antioxidation functions. Ru [56] isolated four lignans from P. sibiricum for the first time, which were (+)-syringaresinol, (+)-syringaresinol-O-β-D-glucopyranoside, liriodendrin, (+)-pinoresinol-O-β-D-glucopyranosyl-(6→1)-β-D-glucopyranoside. Gao [39] also found liriodendrin from the fresh P. sibiricum rhizome. Chen Hui et al. [60] published three lignans from the ethyl acetate layer of P. sibiricum rhizomes, namely (+)-syringaresinol, 5-hydroxy-7-methoxy-4,6-dimethyl- 2-benzofuranone, terpineol.

3.7. Polysaccharides

Polysaccharide is one of the main active ingredients of the genus Polygonatum. Due to the complexity of the structure and the relatively large molecular weight of Polygonatum Polysaccharide, there are relatively few studies on the chemical structure. At present, galactomannan galactose has two types of neutral polysaccharides (PSB-2A, PSB-1B), two types of acid polysaccharides (PSW-2A-1, PSW-3A-1), two glycoproteins (PSW-4A, PSW-5B), and neutral galactose (PSW-1B-b), separated and purified from the rhizome extract of P. sibiricum [61]. Different extraction methods result in different monosaccharide compositions. The structure of the original P. cyrtonema polysaccharide was composed of arabinose, galactose, glucose, and xylose with a molecular ratio of 1.34:7.42:54.47: 36.95 by Wu [62], and other groups also proved that cellulase-assisted extraction and hot water extracted polysaccharide of polysaccharides from P. odoratum consisted of mannose, glucosamine, rhamnose, glucose, galactose, and arabinose, with a molecular ratio of 7.80:1.08:1.63:65.93:3.58:1.00 and 11.22:0.23:0.23:17.59:2.73:9.10, respectively [63]. Interestingly, this article did not explain the specific temperature of hot water. Both 50 °C and 90 °C were hot water. Different species have different monosaccharide compositions. Zhao [64] proved that polysaccharides from P. sibiricum, P. cyrtonema, and P. kingianum were mainly composed of fructose, galacturonic acid, and galactose, with small amounts of rhamnose, arabinose, xylose, and glucose; while polysaccharides from P. odoratum mainly consisted of fructose with trace amounts of galacturonic acid, galactose, rhamnose, arabinose, xylose, and glucose.

4. Pharmacological Activities

4.1. Antioxidant Activities

The P. sibiricum (PSP) may modulate the Klotho-FGF23 endocrine axis, reduce oxidative stress, and maintain calcium and phosphorus metabolism balance [65]. Polygonatum cyrtonema polysaccharide (PCP) significantly increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and decreased malondialdehyde (MDA), indicating PCP could increase antioxidant enzyme activity to protect against lipid peroxidation and oxidative stress induced by exhaustive exercise. Additionally, PCP dramatically increased the protein levels of bone morphogenetic protein-2 (BMP-2), phosphor-Smad1, Runt-related transcription factor 2 (Runx2), and osteocalcin (OC). These findings revealed a link between PCP’s antioxidant property and its anti-fatigue function [66]. By decreasing oxidative stress, oral treatment of PSP may mitigate the aging and damage generated by D-galactose in the heart. D-gal treatment decreased reactive oxygen species (ROS) and MDA and enhanced SOD levels in the hearts of mice. By reducing the levels of 8-hydroxydeoxyguanosine (8-OHdG) and 4-hydroxy-2-nonenal, PSP also prevented oxidative stress-induced DNA damage and lipid peroxidation (4-HNE) [67]. Regarding other species, extracts of P. alte-lobatum (EPA) dose-dependently reduced exercise-induced urea nitrogen and malondialdehyde and enhanced hepatic glycogen, an essential workout fuel [68]. In addition, the surface structure of PSP was smooth and irregular, and bead-like structures were identified, suggesting that PSP could be employed for encapsulating purposes in the design of drug delivery systems [69]. In other research, PSP was used as a stabilizer to fabricate SeNPs (selenium nanoparticles) under a simple redox system. The ability of SeNPs to get rid of free radicals was greatly improved by adding PSP to the surface of the nanoparticles [70].

4.2. Anti-Fatigue Activities

The trend analysis showed that EPA supplementation improved endurance running time 1.62-fold. EPA boosted rats’ endurance time to exhaustion, showing it may increase exercise tolerance [71]. Swimming time was used to test the anti-fatigue activity of PCP. Dose- and age-dependent increases in fatigue time were seen after PCP treatment, indicating that PCP may enhance the endurance of mice during exercise. A significant correlation was found between exhaustive swimming duration and osteocalcin levels in mouse muscle fibers treated with PCP, showing that PCP’s anti-fatigue effect is linked to energy metabolism and osteocalcin signaling [72].

4.3. Anti-Inflammatory Activities

The anti-inflammatory mechanism of P. sibiricum that suppressed the production of pro-inflammatory mediators and was linked to the downregulation of the NF-B pathway was discovered [73]. In vitro anti-inflammatory effects of P. verticillatum were positively correlated with the total phenolic content, flavonoid content, and condensed tannin content. It showed that P. verticillatum had powerful antioxidant, anti-inflammatory, and cancer-preventing properties caused by the plant’s secondary metabolites [74]. Using reverse transcription-quantitative PCR and western blotting, PSP decreased body weight, blood lipids, blood glucose, insulin, resistin, adiponectin, and abdominal fat pad weight. It also reversed abnormal expression levels of inflammatory factors and lipid metabolism genes [75].

4.4. Antihypoglycemic Activities

Polygonatum Mill. has been used as herbal medicine to treat type 2 diabetes mellitus (T2DM). The polysaccharides of Polygonatum rhizoma were analyzed for their structure and bioactivity. At concentrations between 1.0 and 10.0 mg/mL, polysaccharides from Polygonatum rhizoma showed varied levels of hypoglycemic action in a dose-dependent manner [76]. The active ingredients are not just polysaccharides but also saponins. The total saponins extract from P. sibiricum could inhibit α-amylase and α-glucosidase, a in insulin resistant (IR) -HepG2 cells model [77]. In the same activity as other species, polysaccharides of P. kingianum increased the expression of insulin receptor substrate-1 (IRS-1), phosphoinositide 3-kinase (PI3K), and protein kinase B (AKT), showing that polysaccharides of P. kingianum adjust glucose metabolism by activating the PI3K/AKT signaling pathway.

4.5. Immunological Activities

The vitality of macrophages is a measure of immune activation and activator cytotoxicity [78]. In a dose-dependent way, PSP caused dendritic-like morphological alterations in RAW 264.7 cells and enhanced the production of nitric oxide, TNF-α, and IL-6. The expression of iNOS, COX-2, NF-kB, and phosphorylated p38 MAPK was increased in RAW 264.7 cells treated with PSP [79]. Different concentrations of extractants have different effects. The P. sibiricum ethanol 75 (PSE75) increased the mRNA expression of Th1 and Th2 molecular markers compared to P. sibiricum ethanol 30 (PSE30). Immunoglobulins G and M were substantially higher in PSE75 than in PSE30. The immunological regulatory action of PSE75 may be mediated by a change in the makeup of gut microbes [80]. In another study, PSP increased the expression of IL-2 and TNF-α in lymphocytes of the spleen. In addition, PSP therapy increased the dose-dependent recovery of natural killer cell activity [81]. The same as other species, P. odoratum polysaccharides (POP) also exhibit immunomodulatory activity [82]. Immunomodulation, infection prevention, gut environment enhancement, and cancer suppression of the Polygonatum genus have been studied extensively.

4.6. Other Activities of Polygonatum Mill.

P. kingianum polysaccharides (PKP) and P. kingianum aqueous extract (PKAE) alleviated uranium-induced cytotoxicity by regulating mitochondria-mediated apoptosis and the GSK-3β/Fyn/Nrf2 pathway [83]. PCP exerted antidepressant effects by regulating the oxidative stress-calpain-1- NOD-like receptor protein 3 (NLRP3) signaling axis. PCP prevented chronic unpredictable mild stress-induced changes in the calpain system and reduced depression-like behavior [84]. Moreover, methanol extract from P. odoratum administration reversed intestinal microbiota compositions, inhibiting H2S-related bacteria, a lower level of H2S, and higher content of short-chain fatty acid-related bacteria [85]. PSP also can act as a prebiotic, regulating the intestinal tract probiotics. At the phylum level, PSP treatment raised the number of Lactobacillus and decreased the abundance of Lachnospiraceae and Bacteroides (at the genus level). The make-up of microbes shifted. The PSP group increased SCFAs, such as acetic acid, propionic acid, and butyric acid than the control mice [86].

5. Processing of Polygonatum Mill.

5.1. Processing Methods of Polygonatum Mill.

There were many methods of processing the genus Polygonatum in the past to increase the curative effect and reduce toxicity. Calcium oxalate monohydrate (COM) raphides may be some of the irritating components of the genus Polygonatum. After processing, there were far fewer COM raphides. The raphide bundles that remained adhered together and were difficult to separate and most single raphides were disintegrated, particularly at their tips [87]. Some scholars believe that volatile components, such as n-hexanal and camphene, are also irritating components of the genus Polygonatum [88]. There are big differences in the processing and use of traditional Chinese medicine. According to the records of relevant documents in various regions, the processing methods of Polygonatum plants include steaming, wine steaming, and wine stewing. There are big differences in the auxiliary materials [89]. The most commonly used methods are steaming, wine steaming, and wine stewing. The “Chinese Pharmacopeia” includes wine steaming and stewing [3]. Whether steaming or stewing can achieve the purpose, using wine as an auxiliary material can increase the dissolution of certain compounds [90]. The author summarizes all methods of processing the genus Polygonatum. (Table 6).

Table 6

Processing of Polygonatum.

Processing Method	Auxiliary Dosage	Bibliography Source	References
If you take it alone, first use boiling water to remove the bitter juice, then steam and dry nine times.	-	Ming Dynasty “Introduction to Medicine”	[91]
Excellently steamed and ready to eat.	-	Qing Dynasty “Materia Medica Justice”	[92]
Remove impurities, wash, and remove; thoroughly moisten for 1 day, steam for 8 h, simmer for 12 h, take it out, sun until semi-dry, steam again for 8 h, simmer for 12 h until black, simmering, and oily, cut into thick slices, and dry.	-	“Guangdong Province Traditional Chinese Medicine Processing Regulations” 1984	[93]
Wash, stew thoroughly, or steam with wine, cut into thick slices, and dry.	For every 100 kg of Polygonatum, use 20 kg of Huangjiu	“Chinese Pharmacopoeia” 2020	[94]
A total of 400 g of Polygonatum and 2 L of black beans, cooked at the same time to remove the beans; avoid ironware.	-	Ming Dynasty “Forbidden Prescriptions in Lu Mansion”	[91]
Polygonatum Mill. is boiled until it is thin; squeeze the juice to remove the residue, and add honey.	herb: honey = 7:3/4:6	Qing Dynasty “Huizhitang Experience Prescription”	[95]

5.2. Effect of Processing on the Chemical Composition

Polysaccharides are one of the main components of the medicinal Polygonatum Mill., which changes after processing. During the nine steaming and nine drying processes of the genus Polygonatum, with the increase in steaming times, the polysaccharide content first decreases and then stabilizes. Baolai Fan [96] analyzed polysaccharide component changes in distilled and processed P. cyrtonema by PMP(1-phenyl-3-methyl-5-pyrazolone) pre-column derivatization, and high-performance liquid chromatography–mass spectrometry/mass spectrometry (HPLC–MS/MS) technology; the processed Polygonatum polysaccharide is mainly composed of galactose and mannose, followed by glucose. Moreover, other groups [97] showed that as the number of repetitions of steaming increases, polysaccharides gradually decompose into small monosaccharides. For these monosaccharides, the content after four steaming seems relatively stable [98]. All these dynamic changes in polysaccharides and monosaccharides result from the decomposition of glycosidic bonds that steaming can destroy. Others [99] revealed that the content of 5-hydroxymethyl furfural, galactose, and glucose increased after the fourth steaming and tended to be stable. Moreover, the raw rhizome’s strong numb tongue taste decreased progressively until disappearance after the fourth steaming, and the sweet taste gradually turned from slight to strong at the fourth steaming, which indicated that the toxic components were greatly reduced and the flavor was greatly developed at the fourth steaming.

During the nine steaming and nine drying processes of P. cyrtonema, the content of saponins increased first and then stabilized with the increase of steaming and drying. Since diosgenin is a prerequisite for many other saponins, some researchers have found that the content of diosgenin in P. cyrtonema after the wine is lower than that of raw products [100].

5.3. Influence of Processing on Pharmacological Effects

5.3.1. Antioxidant Activities after Processing

There are various processing methods for evaluating the antioxidant activity of P. odoratum flavones and determining which procedure could preserve such activity. The yeast fermentation had the least effect on the antioxidant activity of P. odoratum flavones, making it the optimal way of food processing for P. odoratum. In contrast, extrusion and high-pressure treatment marginally diminished the flavones’ antioxidant activity [101]. The same is true for P. odoratum flavones, and the fermentation method evaluated the antioxidant properties of flavones extracted from fermented P. odoratum samples. Lactobacillus, yeast, and Aspergillus fermentation were examined. By fermenting with Lactobacillus and yeast, the antioxidant capacity of P. odoratum flavones was found to be diminished. Fermentation with Aspergillus niger enhanced the antioxidant capacity of P. odoratum flavones [102]. The flavones are not the only compounds that have antioxidant activity. Using radical scavenging experiments, the antioxidant activity of PSP was evaluated. It was discovered that the radical scavenging activity of PSP was significantly enhanced after steaming and increased steadily with increasing numbers of steaming processes [99]. Although the polysaccharides content was decreased after steam-processing, antioxidant and hypoglycemic activities of P. cyrtonema were enhanced [103].

5.3.2. Anti-Fatigue Activities after Processing

Polysaccharides in the processed products of P. cyrtonema were the active compounds against exercise tiredness, which were more active in the plant’s processed products than in its raw materials. It offers anti-fatigue benefits for swimming exhausted mice, liver glycogen content rose, and the impact of the processed product was superior to that of the raw materials [104,105].

5.3.3. Anti-Inflammatory Activities after Processing

Lung damage caused by LPS may be treated with PSP polysaccharides and its honey-processed polysaccharides, both of which include anti-inflammatory properties. The honey-processed polysaccharides had a greater anti-inflammatory impact than raw materials polysaccharides, which inhibited the synthesis and release of IL-1, IL-6, and TNF-α [106]. In another study, raw polysaccharides and nine-steam-nine-bask processing P. cyrtonema demonstrated no toxicity and side effects on lipopolysaccharide-induced RAW264.7 cells and showed obvious inhibitory effects on the inflammatory cytokines NO, TNF-α, IL-1β, IL-6, and MCP1 in a dose-dependent manner. Thus, it is assumable that polysaccharides from raw materials and nine-steam-nine-bask processing P. cyrtonema play an anti-inflammatory role by inhibiting the expression of related inflammatory factors [107].

5.3.4. Anti-Hypoglycemic Activities after Processing

The different extractions parts from the crude and steam-processed P. cyrtonema were tested for inhibiting α-glucosidase activities from exploring potential active sites [108]. The result shows that the inhibition rate of the ethyl acetate phase of the steamed product reached 87.21%, IC50 = 1.369 mg/mL, and the inhibition rate of the ethyl acetate phase of the raw product reached 59.38%, indicating that the active ingredient in the ethyl acetate phase of the steamed product has a strong effect on α-glucose. Li [109] found that fermented P. sibiricum ameliorated the lipid accumulation in liver and white adipose tissue by inhibiting lipogenesis, enhancing lipolysis, and fatty acid oxidation. Therefore, it lowered the fasting blood glucose, insulin, total cholesterol, and triglyceride. In addition, it could reduce glycated hemoglobin in the homeostasis model after P. sibiricum was fermented. When P. sibiricum was processed using the traditional technology of “Nine-Steam-Nine-Bask”, its 70% ethanol extracts exhibited the relief of glycolipid metabolism abnormalities in type 2 diabetic mice [110].

5.3.5. Immunological Activities after Processing

As mentioned above, PCP content was considerably reduced by steaming. Compared to PCP from the raw rhizome, the immunological activities of PCP after 2 and 4 h were greater on PCP. The longer the steaming duration (6–12 h), the more PCP was destroyed, which had a detrimental effect on the immune system [111]. In another study [112], IL-2, IL-6, TNF-α, and IFN-α secretions reversed to normal levels after treatment with the water-soluble PSP extracted from crude and wine-processed PSP in the immunosuppressive model for spleen-deficient mice. PSP that had been wine-processed had more immunological effects than PSP from crude. The steam-processed PSP might be linked to the regulation of the JAK1-STAT1 pathway and the elevation of hematopoietic cytokines (erythropoietin, granulocyte colony-stimulating factor, TNF-a, and IL-6). It could also significantly increase peripheral blood cells, restore the splenic trabecular structure, and bring immune cytokines back to normal levels [113].

6. Conclusions

In conclusion, based on the current state of research, Polygonatum Mill. belongs to a renewable resource herb with many species. It has numerous chemical components and pharmacological activities. Various research studies have been conducted to evaluate the traditional uses of the genus Polygonatum, and all of the research supports the traditional claims. The authors believe that corresponding standards of Polygonatum Mill. should be established according to their various clinical applications first [6]. Secondly, an abundance of traditional uses has not been evaluated, especially in species other than P. sibiricum, P. cyrtonema, P. kingianum, and P. odoratum. Hence, further research is needed to exploit the many uses of the Polygonatum species. The final objective should be to research the usefulness of parts on the ground and fibrous roots to ensure effective protection and the sustainable development of resource applications.