Asparagus cochinchinensis: A review of its botany, traditional uses, phytochemistry, pharmacology, and applications

Abstract

Asparagus cochinchinensis (Lour.) Merr. (A. cochinchinensis) is a traditional herbal medicine that is used to treat constipation, fever, pneumonia, stomachache, tracheitis, rhinitis, cataract, acne, urticaria. More than 90 compounds have been identified from different structural types in A. cochinchinensis, including steroidal saponins, C₂₁-steroides, lignans, polysaccharides, amino acids, etc. These bioactive ingredients make A. cochinchinensis remarkable for its pharmacological effects on anti-asthma, anti-inflammatory, anti-oxidation, anti-tumor, improving Alzheimer’s disease, neuroprotection, gut health-promoting and so on. Moreover, A. cochinchinensis also plays an important role in food, health product, cosmetic, and other fields. This review focused on the research publications of A. cochinchinensis and aimed to summarize the advances in the botany, traditional uses, phytochemistry, pharmacology, and applications which will provide reference for the further studies and applications of A. cochinchinensis.

Introduction

A. cochinchinensis is belonging to the genus Asparagus in the family Liliaceae, it is widely distributed in temperate and tropical regions, including China, Japan, Korea, and Vietnam. (Kubota et al., 2012; Pegiou et al., 2019; Pahwa et al., 2022). A. cochinchinensis is one of the most frequently used traditional herbal medicines, with documented cases of its clinical therapeutic effect in many countries. (Sheng., 2022a; Wong et al., 2022). A. cochinchinensis first appeared as a traditional Chinese medicine (TCM) in the earliest Chinese medicinal classic work Shennong’s Classic of Materia Medica (written more than 2000 years ago during the Han Dynasty), it has a long history of medicinal use and its medicinal value has been proved by clinical experience. It was included in the Pharmacopoeia of the People’s Republic of China 1977 edition as a clinical TCM in common use for the first time, and was continuously included until the latest 2020 edition. Dried roots are the main medicinal parts of A. cochinchinensis, it has been commonly used either alone or in combination with other herbal medicines to treat asthma, cough, constipation, thrombosis and inflammatory disease in China for centuries. Many classic formulas containing A. cochinchinensis have been widely used in clinic and have made important contributions to the health of people in China and other traditional medicinal systems in Asia. In addition to its medicinal value, A. cochinchinensis has various commercial applications in health products, food, and cosmetics (Safriani et al., 2022). It is commonly used as a food or nutritional supplement (Siand et al., 2015), cosmetics with whitening and anti-aging effects, and even used as a raw material for fermentation and winemaking (Kim et al., 2017; Topolska et al., 2021). Therefore, its huge potential and broad development prospects are worth exploring.

In the past few decades, A. cochinchinensis has attracted widespread attention as an important herbal medicine. Significant progress on isolation and identification of active constituents in A. cochinchinensis have been made in relevant researches. So far, more than 90 components have been isolated and identified. They mainly include steroidal saponins, C₂₁-steroids, lignans, polysaccharides, and amino acids. At present, A. cochinchinensis has a variety of pharmacological effects and has curative effects in the treatment of asthma, tumor, Alzheimer’s disease, gut diseases, inflammatory diseases (Lee et al., 2009; Lei et al., 2016; Choi et al., 2019; Zhang R. S. et al., 2021). Besides that, medicinal prescription research also has revealed that it functions synergistically in combination with various herbal medicines (Weiying et al., 2006; Jung et al., 2014). With the in-depth exploration of TCM the exploitation and utilization of traditional herbal medicine in the prevention and treatment of various diseases are steadily increasing.

With the current scientific and technological advances and the increasing international recognition of traditional herbal medicine in recent years, research on A. cochinchinensis has made significant progress. However, to the best of our knowledge, there is no review on A. cochinchinensis. It is particularly important and necessary to collate a review on A. cochinchinensis progress in recent years. This is the first review on up to date of A. cochinchinensis research developments in the fields of botany, traditional uses, phytochemistry, pharmacology, and applications. It provides an accurate overview of A. cochinchinensis research and identifies deficiencies in present studies, proposing further research targets. The authors expect this review to encourage further research into the pharmacological effects and mechanisms associated with A. cochinchinensis therapeutic effects and to provide a broader vision and new inspiration for research in current and potential applications of A. cochinchinensis.

Botany

A. cochinchinensis is a climbing perennial plant, which has the structural characteristics of pale green stalks, sickle-shaped leaves, pale green axillary flowers, red fruits, and the branches angular or narrowly winged. It usually grows on slopes, roadsides, underwoods, valleys, or wastelands, below 1750 m A. cochinchinensis is usually harvested in autumn and winter, cleaned silt, removed fibrous root, retained tuberous root, boiled in boiling water for 15 min, then peeled and cored, further dried to obtain the medicinal part of A. cochinchinensis. According to the online records of China’s flora (http://www.cn-flora.ac.cn/index.html), the medicinal part of A. cochinchinensis is fusiform, with a swelling in the middle or near the end, which is 3–5 cm long and 1–2 cm thick. A. cochinchinensis’s stem is smooth, often curved or twisted, up to 1–2 m long. A. cochinchinensis’s leafy branches are usually clustered every 3, which are flat or slightly acute triangular due to the keel shape of the midvein, slightly falcate, 0.5–8 cm long, and 1–2 mm wide. Its inflorescence usually has two axillary flowers with alternate petals. The pedicel is 2–6 mm long. The joint is generally located in the middle, the perianth is 2.5–3 mm long, and the female flowers are similar in size to the male flowers. The flowering and fruiting period is generally from May to October. When the fruit matures, it becomes red, with a diameter of 6–7 mm, with only one seed per fruit, as shown in Figure 1.

FIGURE 1.

A. cochinchinensis plant morphology. (A) The above-ground portion, (B) Flower, (C) Fruits, (D) The underground part, (E) Medicinal part.

Traditional uses

A. cochinchinensis has a long history of ethnopharmacological use and is characterized by bitter in taste and cold in nature. Since ancient times, researchers continuously explore and exploited TCM practices (Zhang X. et al., 2021; Wang et al., 2021). Dating back more than 1700 years of history, A. cochinchinensis was first documented in Shennong’s Classic of Materia Medica (Dong Han Dynasty, 25–220 A.D.), which is the earliest classic on TCM. Later, it was listed in many other well-known works on Chinese herb, including “Ming Yi Bie Lu” (Wei and Jin Dynasty, 220–420 A.D.), “Yao Xing Lun” (Tang Dynasty, 618–907 A.D.). In the folk culture, it is often used as a treatment cough, constipation, fever, pneumonia, stomachache, tracheitis, rhinitis, cataract, acne, urticaria and other diseases. In different countries, A. cochinchinensis has different therapeutic effects. It can be combined with other herb medicines to achieve a greater therapeutic effect. In Korea, extracts of formulations composed of A. cochinchinensis and other herbs were shown to have the effect of treating thrombosis (Chang et al., 2005; Lee et al., 2019). In China, the classic prescription composed of A. cochinchinensis (Qisheng pill) contains 114 chemical compounds were identified, including diosgenin, Methyl protodioscin, and ferroic acid, total saponin etc., which can inhibit the occurrence of inflammation, regulate intestinal dysfunction and improve the effect of Alzheimer disease (Xiong et al., 2022). At the same time, the herb formula water decoction composed of A. cochinchinensis can treatment of intestinal diseases, especially alleviate allergic airway inflammation and treat asthma (Luo et al., 2020). This also reflects the different therapeutic effects of A. cochinchinensis in traditional use and the broad application prospects in the future. Therefore, its clinical efficacy and function still need to be further explored.

Phytochemistry

In the past few decades, A. cochinchinensis have been investigated from a phytochemical perspective. The literature indicates the presence of multiple chemical compounds, predominantly steroidal saponin, C₂₁-steroids, amino acids, lignan, and polysaccharides. To date, more than 90 compounds have been isolated and identified from A. cochinchinensis. These compounds are summarized in Tables 1 and Table 2, and their structures are shown in Figure 2, and Figure 3, and Figure 4.

TABLE 1.

Chemical compounds isolated from A. cochinchinensis.

Number	Chemical composition	Extraction solvent	Molecular formula	Molecular weight	Reference
Steroidal Saponin
1	Dioscin	MeOH	C45H72O16	869.0436	Lee et al. (2015)
2	Prosapogenin B	70% EtOH	C39H62O12	722.9024	Liu et al. (2021)
3	(23R, 24R, 25S)-spirost-5-ene-3β,23,24-triol-3-O-α-L-rhamnopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→4)]-β-D-glucopyranoside	70% EtOH	C45H72O18	901.0424	Liu et al. (2021)
4	(24S,25S)-spirost-5-ene-3β,24-diol-3-O-α-L-rhamnopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→4)]-β-D-glucopyranoside	70% EtOH	C45H72O17	885.0430	Liu et al. (2021)
5	Methylprotodioscin	MeOH	C52H86O22	1063.2260	Liang et al. (1988)
6	(25S)-26-O-β-D-glucopyranosyl-5β-furost-20(22)-en-3β,15β,26-triol-3-O-[α-L-rhamnopyranosyl-(1-4)]-β-D-glucopyranoside	75% EtOH	C45H74O17	887.0589	Shen et al. (2011)
7	Aspacochioside C	75% EtOH; Water	C45H75O17	888.0705	Shen et al., 2011
					Kim et al. (2021)
8	3-O-[α-L-rhamnopyranosyl(1→4)-β-D-glucopyranosyl]- (25S) −5β-spirostan-3β-ol	70% MeOH	C39H64O12	724.9183	Zhu et al. (2021)
9	Asparacoside	MeOH	C49H80O21	1005.1469	Zhang et al. (2004)
10	Nicotianoside B	70% MeOH	C39H64O12	724.9183	Zhu et al. (2021)
11	Immunoside	70% MeOH	-	-	Zhu et al. (2021)
12	Shatavarin IV	70% MeOH	-	-	Zhu et al. (2021)
13	(25S)-5β-spirostan-3β-ol-3-O-α-L-rhamnopyranoside	70% MeOH	C33H54O7	562.7777	Zhu et al. (2014)
14	(25S)-5β-spirostan-3β-ol-3-O-β-D-glucopyranoside	70% MeOH	C33H54O8	578.7771	Zhu et al. (2014)
15	(23S,25R)-23-hydroxyspirost-5-en-3β-yl-O-α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranoside	70% EtOH	C39H62O13	738.9018	Liu et al. (2021)
16	Dioseptemloside F	70% EtOH	C39H62O13	738.9018	Liu et al. (2021)
17	Pseudoprotoneodioscin	75%EtOH; Water	C51H82O21	1031.1842	Shen et al., 2011
18	26-O-β-D-glucopyranosyl-(25R)-furost-5-ene-3β,22α,26-triol 3-O-(1−4)-β-D-glucopyranosyl-α-L-rhamnopyranosyl-(1−2)-[α-L-rhamnopyranosyl-(1−4)]-β-D-glucopyranoside	Water	C57H94O27	1211.3401	Zhang et al. (2021b)
19	Protodioscin	Water; 90% EtOH	C51H84O22	1049.1995	Kim et al. (2021)
					Zhang et al. (2021b)
20	15−hydroxypseudoprotodioscin	Water	C51H82O22	1047.1836	Kim et al. (2021)
21	Dioscoreside H	90% EtOH	C51H82O22	1047.1836	Zhang et al. (2021b)
22	Pseudoprotodioscin	Water	C51H82O21	1031.1842	Liang et al. (1988)
23	(25R)-26-O-β-D-glucopyranosyl-3β,20α,26-trihydroxyfurostan-5,22-diene-3-O-α-L-rhamnopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→4)]-O-β-D-glucopyranoside	90% EtOH	-	-	Zhang et al. (2021b)
24	3-O-α-L-rhamnopyranosyl(1→4)-[β-D-glucopyranosyl(1→2)]-β-D-glucopyranosyl-26-O-β-D-glucopyranosyl-(25R)-5β-furostane-3β,22α,26-triol	75% EtOH	C51H86O23	1067.2147	Jian et al. (2013)
25	3-O-β-D-xylopyranosyl(1→4)-[β-D-glucopyranosyl(1→2)]-β-D-glucopyranosyl-26-O-β-D-glucopyranosyl-(25S)-5β-furostane-3β,22α,26-triol	75% EtOH	C50H84O23	1053.1882	Jian et al. (2013)
26	3-O-β-D-glucopyranosyl(1→2)-β-D-glucopyranosyl-26-O-β-D-glucopyranosyl-(25S)-5β-furostane-3β,22α,26-triol	75% EtOH	C45H76O19	921.0735	Jian et al. (2013)
27	3-O-α-L-rhamnopyranosyl (1→4)-[β-D-xylopyranosyl(1→2)]-β-D-glucopyranosyl-26-O-β-D-glucopyranosyl-(25S)-5β-furostane-3β,22α,26-triol	60% EtOH	C50H84O22	1037.1888	Pang et al. (2021)
28	(25S)-26-O-β-D-glucopyranosyl-5β-furostan-3β,22α,26-triol-3-O-α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranoside	70% MeOH	C45H76O18	905.0741	Zhu et al. (2014)
29	(25S)-26-O-β-D-glucopyranosyl-5β-furstan-3β, 22α, 26-triol-3-O-β-D-glucopyranoside	70% MeOH	C39H66O14	758.9329	Zhu et al. (2014)
30	(25S)-5β-12-one-spirost-3β-ol-3-O-β-D-glucopyranoside	60% EtOH	C33H52O9	592.7606	Pang et al. (2021)
31	26-O-β-D-glucopyranosyl-(25S)-5β-12-one-furost-3β,26-diol-3-O-α-L-rhamnopyranosyl-(1→2)-[β-D-xylcopyranosyl-(1→4)]-β-D-glucopyranoside	60% EtOH	C50H82O23	1051.1723	Pang et al. (2021)
32	(25S)-26-O-β-D-glucopyranosyl-5β-furostan-3β,22α,26-triol-12-one-3-O-β-D-glucopyranoside	60% EtOH	C39H64O15	772.9165	Pang et al. (2021)
					Zhu et al. (2014)
33	26-O-β-D-glucopyranosyl-(25S)-Δ5(6)-12-one-furost-3β,26-diol-3-O-α-L-rhamnopyranosyl-(1→2)-[β-D-xylcopyranosyl-(1→4)]-β-D-glucopyranoside	60% EtOH	C50H80O23	1049.1564	Pang et al. (2021)
34	26-O-β-D-glucopyranosyl-(25S)-Δ5(6)-12-one-furost-3β,26-diol-3-O-α-L-rhamnopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→4)]-β-D-glucopyranoside	60% EtOH	C51H82O23	1063.1830	Pang et al. (2021)
35	(25S)-26-O-β-D-glucopyranosyl-22α-methoxy-5β-furostan-3β,26-diol-12-one-3-O-β-D-glucopyranoside	70% MeOH	C40H66O15	786.9430	Zhu et al. (2014)
36	26-O-β-D-glucopyranosyl-(25S)-5β-furost-3β,12α,26-triol-3-O-α-L-rhamnopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→4)]-β-D-glucopyranoside	60% EtOH	C39H66O15	774.9323	Pang et al. (2021)
37	Officinalisnin II	60% EtOH	-	-	Pang et al. (2021)
38	(25S)-officinalisnin-I	60% EtOH	C45H76O19	921.0735	Pang et al. (2021)
39	(25S)-26-O-β-D-glucopyranosyl-5β-furostan-3β,22α,26-triol	70% MeOH	C33H56O9	596.7923	Zhu et al. (2014)
40	Pallidifloside I	60% EtOH	C50H82O22	1035.1729	Pang et al. (2021)
41	3-O-[bis-α-L-rhamnopyranosyl-(1→2and1→4)-β-D-glucopyranosyl-25R-furost-5-ene-3β,22α,26-triol]	70% EtOH	C45H74O17	887.0589	Liu et al. (2021)
42	3-O-[{α-L-rhamnopyranosyl-(1→4)}{β-D-glucopyranosyl}]-26-O-[β-D-glucopyranosyl]-(25S)-5β-furost-20(22)-en-3β,26-diol	EtOH	C45H74O17	887.0589	Shi et al. (2004)
43	3-O-β-D-xylopyranosyl(1→4)-[β-D-glucopyranosyl(1→2)]-β-D-glucopyranosyl-26-O-β-D-glucopyranosyl-(25R)-5β-furostane-3β,22α,26-triol	75% EtOH	-	-	Jian et al. (2013)
44	3-O-[{a-L-rhamnopyranosyl-(1→4)} {β-D-glucopyranosyl}]-26-O-[β-D-glucopyranosyl]-(25S)-5β-furostane-3β,22α,26-triol	Water; EtOH	C45H76O18	905.0741	Shi et al. (2004)
45	Chamaedroside E	Water	C45H76O19	921.0735	Kim et al. (2021)
46	Furospirost-5-ene-3β,6α,23α-triol-3-O-α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranoside	70% MeOH	C40H64O14	768.9278	Liu et al. (2021)
47	16β,22,23-trihydroxycholest-5-ene-3β-yl-O-α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranoside	70% MeOH	C39H66O13	742.9335	Liu et al. (2021)
48	(24S,25R)-spirost-5-ene-3β,24-diol-3-O-α-L-rhamnopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→4)]-β-D-glucopyranoside	70% MeOH	C45H72O17	884.0430	Liu et al. (2021)
49	(24S,25S)-spirost-5-ene-3β,24-diol-3-O-α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranoside	70% EtOH	C39H62O13	738.9018	Liu et al. (2021)
50	(23S,24R,5S)–23,24-dihydroxyspirost-5-en-3β-yl-O-α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranoside	70% EtOH	C39H62O14	754.9012	Liu et al. (2021)
51	Smilagenin-3-O-α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranoside	70% EtOH	C39H64O12	724.9183	Liu et al. (2021)
52	3-O-{[β-D-glucopyranosyl-(1→2)]-[α-L-rhamnopyranosyl-(1→4)]-β-D-glucopyranosyl} -(25R)-5β-spirostan-3β-ol	70% EtOH	C45H74O17	887.0589	Liu et al. (2021)
53	(25R)-26-[(β-D-glucopyranosyl) oxy]-22α-methoxyfurost-5-en-3β-yl-O-α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranoside	70% EtOH	-	-	Liu et al. (2021)
54	Pseuprotodioscin	70% EtOH	-	-	Liu et al. (2021)
55	Dioscin F	70% EtOH	C39H60O13	736.8859	Liu et al. (2021)
56	Dioscin E	70% EtOH	C39H62O12	722.9024	Liu et al. (2021)
57	3-O-[α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranosyl]-26-O-β-D-glucopyranosyl−20, 22-seco-25R-furoene-20, 22-dione-3β, 26-diol	70% EtOH	C45H74O19	919.0577	Liu et al. (2021)
58	(23S, 24R, 25R)-spirost-5-ene-3β,23,24-triol-3-O-α-L-rhamnopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranoside	70% EtOH	C45H72O18	901.0424	Liu et al. (2021)
59	(23R, 25S)-spirost-5-ene-3β, 23-diol-3-O-α-L-rhamnopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→4)]-β-D-glucopyranoside	70% EtOH	C45H72O17	885.0430	Liu et al. (2021)
60	Dumoside	70% EtOH	C40H62O16	798.9107	Liu et al. (2021)
61	Asparacosins A	MeOH	C27H40O5	444.6035	Zhang et al. (2004)
62	Asparacosins B	MeOH	C29H46O6	490.6719	Zhang et al. (2004)
63	26-O-β-D-glucopyranosyl-(25R)-5β-furost-3β,26-diol-3-O-α-L-rhamnopyranosyl-(1→2)-[β-D-xylcopyranosyl-(1→4)]-β-D-glucopyranoside	60% EtOH	C50H84O22	1037.1888	Pang et al. (2021)
64	25-epi-officinalisnin II	60% EtOH	-	-	Pang et al. (2021)
65	Disporoside C	60% EtOH	C45H76O19	921.0735	Pang et al. (2021)
66	26-O-β-D-glucopyranosyl-(25R)-5β-furost-3β,26-diol-3-O-α-L-rhamnopyranosyl-(1→2)-[β-D-xylcopyranosyl-(1→4)]-[α-L-rhamnopyranosyl-(1→6)]-β-D-glucopyranoside	60% EtOH	C56H94O27	1199.3294	Pang et al. (2021)
67	26-O-β-D-glucopyranosyl-(25R)-5β-furost-3β,26-diol-3-O-α-L-rhamnopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→4)]-[α-L-rhamnopyranosyl-(1→6)]-β-D-glucopyranoside	60% EtOH	C57H96O27	1213.3560	Pang et al. (2021)
68	3-O-[{α-L-rhamnopyranosyl-(1→4)} {β-D-glucopyranosyl}]-26-O-[β-D-glucopyranosyl]-22α-methoxy-(25S)-5β-furostane-3β,26-diol	EtOH	C46H79O18	904.1131	Shi et al. (2004)
69	Protoneodioscin	60% EtOH	-	-	Pang et al. (2021)
70	3-O-[a-L-rhamnopyranosyl-(1→4) β-D-glucopyranosyl]-26-O-(β-D-glucopyranosyl) -(25R)-furosta-5,20-diene, -3β,26-diol	Water	-	-	Liang et al., 1988
					Liu et al. (2021)
71	5β-pregn-20-ene-3,16-diol-22-one 3-O-α-L-rhmnopyranosyl-(1→2)-β-D-glucopyranoside	70% MeOH	C34H52O12	652.7695	Zhu et al. (2021)
C21-steroide
72	3-O-β-D-xylopyranosyl(1→4)-[β-D-glucopyranosyl(1→2)]-β-Dglucopyranosyl-5β-pregna-16-ene-33β-ol-20-one	75% EtOH	C38H60O16	772.8734	Jian et al. (2013)
73	3-O-α-L-rhamnopyranosyl (1→4)- [β-D-glucopyranosyl (1→2)]-β-D-glucopyranosyl-5β-pregna-16-ene-3β-ol-20-one	75% EtOH	C33H52O12	640.7588	Jian et al. (2013)
74	3-O-β-D-glucopyranosyl (1→2)-β-D-glucopyranosyl-5β-pregna-16-ene-3β-ol-20-one	75% EtOH	C33H52O12	640.7588	Jian et al. (2013)
75	(3β,5β)-pregn-16(17)-en-3-ol-20-one 3-O-α-L-rhmnopyranosyl-(1→4)-β-D-glucopyranoside	70% MeOH	C33H52O11	624.7594	Zhu et al. (2021)
76	(3β,5β)-pregn-16(17)-en-3-ol-20-one 3-O-α-L-rhmnopyranosyl-(1→2)-β-D-glucopyranoside	70% MeOH	C33H52O11	624.7594	Zhu et al. (2021)
77	(3β,5β)-pregn-16(17)-en-3-ol-20-one 3-O-α-L-arabinopyranosyl-(1→4)-β-D-glucopyranoside	70% MeOH	C20H50O11	466.6040	Zhu et al. (2021)
78	(3β,5β)-pregn-16(17)-en-3-ol-20-one 3-O-α-L-arabipyrannosyl-(1→4)-β-D-glucopyranosyl-(1→2)-β-D-glucopyranosid	70% MeOH	C38H60O16	772.8734	Zhu et al. (2021)
79	3β-[(O-α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranosyl)oxy]pregna-5,-16-dien-20-one	70% EtOH	C33H50O11	622.7435	Liu et al. (2021)
Amino acid
80	Alanine	Water	C3H7NO2	89.0932	Choi et al., 2019
81	Glycine	Water	C2H5NO2	75.0666	Choi et al., 2019
82	Methionine	Water	C5H11NO2S	149.2113	Choi et al., 2019
83	Tryptophan	Water	C11H12N2O2	204.2252	Choi et al., 2019
Lignan
84	Iso-agatharesinol	70% EtOH	C17H18O4	286.3224	Li et al. (2012)
85	Iso-agatharesinoside	70% EtOH	C23H28O9	448.4630	Li et al. (2012)
Others
86	1-[4-hydroxyphenoxy]-5-[3-methoxy-4-hydroxyphenyl] pent-2-en-3-yne	MeOH	C18H16O4	296.3172	Zhang et al. (2004)
87	Asparenydiol	MeOH	C17H13O3	265.2839	Zhang et al. (2004)
88	3′-hydroxy-4′-methoxy-4′-dehydroxynyasol	MeOH	C18H18O3	282.3337	Zhang et al. (2004)
89	Nyasol	MeOH	C17H16O2	252.3077	Zhang et al. (2004)
90	3″-methoxynyasol	MeOH	C17H16O3	268.3071	Zhang et al. (2004)
91	1,3-bis-di-p-hydroxyphenyl-4-penten-1-one	MeOH	C17H16O3	268.3071	Zhang et al. (2004)
92	Trans-coniferyl alcohol	MeOH	C10H12O3	180.2005	Zhang et al. (2004)
93	Acrylamide	Water	C3H5NO	71.0779	Shi et al. (2009)

TABLE 2.

The structures of steroidal saponins in A. cochinchinensis.

NO	Structure
	Mother nucleus	R1	R2	R3	R4	R5
1	I	α-L-Rha (1→2)-[α-L-Rha (1→4)]-β-D-Glc	H	H	H	H
2	I	α-L-Rha (1→4)-β-D-Glc	H	H	H	H
3	I	α-L-Rha (1→2)-[α-L-Rha (1→4)]-β-D-Glc	H	H	OH	OH
4	I	α-L-Rha (1→2)-[α-L-Rha (1→4)]-β-D-Glc	H	H	H	OH
5	II	α-L-Rha (1→2)- [α-L-Rha (1→4)]-β-D-Glc	H	H	OCH3	β-D-Glc
6	III	α-L-Rha (1→4)-β-D-Glc	OH	H	H	β-D-Glc
7	III	α-L-Rha (1→4)-β-D-Glc	H	H	H	β-D-Glc
8	IV	α-L-Rha (1→4)-β-D-Glc	H	H	H	H
9	IV	β-D-Glc(1→2)-[α-L-Ara(1→4)]-[a-L-Ara(1→6)]-β-D-Glc	H	H	H	H
10	IV	α-L-Rha (1→2)-β-D-Glc	H	H	H	H
11	IV	α-L-Rha(1→2)-[α-L-Rha(1→4)]-β-D-Glc	H	H	H	H
12	IV	β-D-Glc(1→2)-[α-L-Rha(1→4)]-β-D-Glc	H	H	H	H
13	IV	α-L-Rha	H	H	H	H
14	IV	β-D-Glc	H	H	H	H
15	V	α-L-Rha (1→4)-β-D-Glc	H	H	OH	H
16	V	α-L-Rha (1→4)-β-D-Glc	α-H,β-OH	H	H	H
17	VI	α-L-Rha(1→2)-[β-D-Glc(1→4)]-β-D-Glc	H	H	H	β-D-Glc
18	VII	α-L-Rha(1→2)-[β-D-Glc(1→4)-α-L-Rha(1→4)]-β-D-Glc	H	H	OH	β-D-Glc
19	VII	α-L-Rha(1→2)-[α-L-Rha(1→4)]-β-D-Glc	H	H	OH	β-D-Glc
20	VIII	α-L-Rha(1→2)-[α-L-Rha(1→4)]-β-D-Glc	OH	H	H	β-D-Glc
21	VIII	α-L-Rha(1→2)-[α-L-Rha(1→4)]-β-D-Glc	H	H	OH	β-D-Glc
22	VIII	α-L-Rha(1→2)-[α-L-Rha(1→4)]-β-D-Glc	H	H	H	β-D-Glc
23	IX	α-L-Rha(1→2)-[α-L-Rha(1→4)]-β-D-Glc	H	H	H	β-D-Glc
24	X	β-D-Glc(1→2)-β-D-Glc	H	H	OCH3	β-D-Glc
25	X	α-L-Rha (1→4)-β-D-Glc	H	O	OH	β-D-Glc
26	X	β-D-Glc(1→2)-[α-L-Rha(1→4)]-β-D-Glc	H	H	OH	β-D-Glc
27	X	β-D-Xyl(1→2)-[α-L-Rha(1→4)]-β-D-Glc	H	H	OH	β-D-Glc
28	X	α-L-Rha (1→4)-β-D-Glc	H	H	OH	β-D-Glc
29	X	β-D-Glc	H	H	OH	β-D-Glc
30	XI	β-D-Glc	H	H	H	H
31	XII	α-L-Rha(1→2)-[β-D-Xyl(1→4)]-β-D-Glc	H	H	OH	β-D-Glc
32	XII	β-D-Glc	H	H	H	β-D-Glc
33	XIII	α-L-Rha(1→2)-[β-D-Xyl(1→4)]-β-D-Glc	H	H	OH	β-D-Glc
34	XIII	α-L-Rha(1→2)-[α-L-Rha(1→4)]-β-D-Glc	H	H	OH	β-D-Glc
35	XIII	β-D-Glc	H	H	OCH3	β-D-Glc
36	XIV	β-D-Glc	H	OH	OH	β-D-Glc
37	XIV	β-D-Glc(1→2)-[β-D-Xyl(1→4)]-β-D-Glc	H	H	OH	β-D-Glc
38	XIV	β-D-Glc(1→2)-β-D-Glc	H	H	OH	β-D-Glc
39	XIV	H	H	H	OH	β-D-Glc
40	XV	α-L-Rha(1→2)-[β-D-Xyl(1→4)]-β-D-Glc	H	H	OH	β-D-Glc
41	XV	α-L-Rha(1→2)-[α-L-Rha(1→4)]-β-D-Glc	H	H	OH	β-D-Glc
42	XVI	α-L-Rha (1→4)-β-D-Glc	H	H	H	β-D-Glc
43	XVII	β-D-Glc(1→2)-[β-D-Xyl(1→4)]-β-D-Glc	H	OH	CH3	β-D-Glc
44	XVII	α-L-Rha(1→4)-β-D-Glc	H	OH	β-methyl	β-D-Glc
45	XVII	β-D-Glc(1→4)-β-D-Glc	H	OH	α-methyl	β-D-Glc
46	XVIII	α-L-Rha (1→4)-β-D-Glc	OH	H	OH	H
47	XIX	α-L-Rha (1→4)-β-D-Glc	H	OH	OH	OH
48	XX	α-L-Rha(1→2)-[α-L-Rha(1→4)]-β-D-Glc	H	H	H	OH
49	XXI	α-L-Rha (1→4)-β-D-Glc	H	H	H	OH
50	XXI	α-L-Rha (1→4)-β-D-Glc	H	H	OH	OH
51	XXII	α-L-Rha (1→4)-β-D-Glc	H	H	H	H
52	XXII	β-D-Glc(1→2)-[α-L-Rha(1→4)]-β-D-Glc	H	H	H	H
53	XXIII	β-D-Glc(1→4)-β-D-Glc	H	H	OCH3	β-D-Glc
54	XXIV	α-L-Rha(1→2)-[α-L-Rha(1→4)]-β-D-Glc	H	H	H	β-D-Glc
55	XXV	α-L-Rha (1→4)-β-D-Glc	H	H	H	H
56	XXVI	α-L-Rha (1→4)-β-D-Glc	H	H	H	H
57	XXVII	α-L-Rha (1→4)-β-D-Glc	H	H	H	β-D-Glc
58	XXVIII	α-L-Rha(1→2)-[α-L-Rha(1→4)]-β-D-Glc	H	H	OH	OH
59	XXVIII	α-L-Rha(1→2)-[α-L-Rha(1→4)]-β-D-Glc	H	H	OH	H
60	XXIX	α-L-Rha(1→2)-[α-L-Rha(1→4)]-β-D-Glc	H	H	H	H
61	XXX	OH	OH	H	H	H
62	XXXI	H	OH	H	H	H
63	XXXII	α-L-Rha(1→2)-[β-D-Xyl(1→4)]-β-D-Glc	H	H	OH	β-D-Glc
64	XXXII	β-D-Glc(1→2)-[β-D-Xyl(1→4)]-β-D-Glc	H	H	OH	β-D-Glc
65	XXXII	β-D-Glc(1→2)-β-D-Glc	H	H	OH	β-D-Glc
66	XXXII	β-D-Glc(1→2)-[β-D-Xyl(1→4)]-[α-L-Rha(1→6)]-β-D-Glc	H	H	OH	β-D-Glc
67	XXXII	β-D-Glc(1→2)-[α-L-Rha(1→4)]-[α-L-Rha(1→6)]-β-D-Glc	H	H	OH	β-D-Glc
68	XXXIII	α-L-Rha (1→4)-β-D-Glc	H	OCH3	H	β-D-Glc
69	XXXIV	α-L-Rha(1→2)-[α-L-Rha(1→4)]-β-D-Glc	H	H	OH	β-D-Glc
70	XXXV	α-L-Rha (1→4)-β-D-Glc	H	H	CH3	β-D-Glc
71	XXXVI	α-L-Rha (1→2)-β-D-Glc	H	H	H	H

FIGURE 2.

The structures of steroidal saponins (1–71) in A. cochinchinensis.

FIGURE 3.

The structures of C₂₁-steroidals in A. cochinchinensis.

FIGURE 4.

The structures of amino acids, lignans, and other compounds in A. cochinchinensis.

Steroidal saponins

Steroidal saponins are the major chemical components in A. cochinchinensis (Lee et al., 2015). Thus far, 71 steroidal saponins (1–71) have been isolated from A. cochinchinensis in Table 2. Steroid saponins are mainly composed of steroidal saponins and sugar condensation. They are classified into spirostanol saponins, isosprirostanol saponins, pseudospirostanol saponins and furostanol saponins based on the aglycone component differences. Aglycones are composed of six rings, of which the rutile rings are usually connected in a spiroketal form. The sugar moieties in the ordinary steroidal saponins are attached to the hydroxyl groups at C₃. In a word, the structural diversity of different compounds is more reflected in the kind, length of each monosaccharide, the type of glycoside bond at the C₃ position, and the position of the substituent.

C₂₁-steroides

C₂₁-steroides are steroid derivatives with 21 carbon atoms and are one of the key compounds in A. cochinchinensis. C₂₁ steroids are mostly hydroxyl derivatives with pregnane or its isomers as the basic skeleton. According to the skeleton type, they can be divided into four types, of which 72–79 (Jian et al., 2013; Liu et al., 2021; Zhu et al., 2021) are typical C₂₁-steroides in Figure 3. In addition, there are many hydroxyl and carbonyl groups on the C₂₁-steroid mother nucleus, and most of the carbonyl groups are at C₂₀.

Amino acids

Four kinds of amino acids were isolated from A. cochinchinensis 80–83 (Choi et al., 2019), and their structures are shown in Figure 4. Amino acids are compounds containing both amino and carboxyl groups. In terms of their structure, amino acids are derivatives of carboxylic acid molecules in which amino groups replace the hydrogen in the alkyl group. According to the relative number of amino and carboxyl groups in amino acid molecules, amino acids can be divided into neutral, acidic and basic.

Lignans

Lignans are a kind of natural compounds synthesized by the polymerization of two-molecular phenylpropanoid derivatives, most of which are free, and a few are glycosides bound to a sugar. At present, a small concentration of lignans 84–85 (Li et al., 2012) was identified from A. cochinchinensis. Compared with other compounds, lignans have less structure. Therefore, future efforts should be made to isolate and characterize lignans in A. cochinchinensis.

Polysaccharides

In recent years, plant polysaccharides have attracted high research interest due to their unique biological activity and natural origin, with great potential to protect human health. Many natural products are is rich in polysaccharide resources, especially medicinal plant polysaccharides, with long application history and broad development prospects. A. cochinchinensis polysaccharides are mainly comprised of Man, Rha, Glc, Gal, Ara, Xyl, Fru, GlcUA, and GalUA, as shown in Table 3.

TABLE 3.

Composition and analysis of polysaccharides in A. cochinchinensis.

No	Name	Extraction	Analytical method	Analytical condition	Monosaccharide composition	Molecular weight (Da)	Main structure	Reference
1	ACNP	distilled water refluxed (6h)	HPLC	Sugar-pack ™column (6.5 mm × 300 mm, 10 μm) and ELSD (evaporative light scattering detector); distilled water; 0.4 ml/min; column temperature 30°C	Fru, Glc	2690	2,1-β-D-Fruf residues, ending with a (1→2) bonded α-D-Glcp	Sun et al. (2020)
			GC-MS		93.3: 6.7(area %)
2	Radix Asparagi polysaccharide	deionized water refluxed (4.5h)	CZE	40 mM sodium tetraborate buffer (pH 10.1); hydrodynamic injection (10 cm × 4 s); 14 kV	Xyl, Ara, Glc, Rha, Man, Gal, GlcUA, GalUA	-	-	Chen et al. (2015)

Other compounds

In addition to the five major phytochemical compound classes mentioned above, other bioactive constituents have also been isolated from A. cochinchinensis (Zhang et al., 2004; Shi et al., 2009). These include 1-[4-hydroxyphenoxy]-5-[3-methoxy-4-hydroxyphenyl] pent-2-en-3-yne (86), asparenydiol (87),3′-hydroxy-4′-methoxy-4′dehydroxynyasol (88), Nyasol(89), 3″-methoxynyasol(90), 1,3-bis-di-p-hydroxyphenyl-4-penten-1-one(91), trans-coniferyl alcohol(92), Acrylamide(93). The above findings illustrate the wide chemical composition of A. cochinchinensis, which is of immense future research value.

Pharmacological activities

A. cochinchinensis exerts various pharmacological activities, including anti-asthma, anti-inflammation, anti-oxidant, anti-tumor, anti-depressant, neuroprotective, improve Alzheimer’s disease and gut diseases. To illustrate the nature of the active compounds of A. cochinchinensis, the pharmacological effects and potential mechanisms of this plant on the basis of different types of extracts and compounds were summarized in Table 4. A simplified diagram of its pharmacological effects is presented in Figure 5.

TABLE 4.

Summary of pharmacological activities of A. cochinchinensis extracts/compounds.

Pharmacological activities	Extracts/Compounds	Models	Results/Mechanisms	Dosages	References
Anti-asthma	Water extract (2.5 h)	Mice (OVA-induced)	↓Number of immune cells, ↓OVA-specific Ig E level, ↓thickness of respiratory epithelium and mucus score	500 mg⋅kg−1	Choi et al. (2018b)
	Water extract	Mice (OVA-induced)	Prevent inflammation and remodeling of airway	250 and 500 mg⋅kg−1	Choi et al. (2019)
	Water extract (2.5 h)	Mice (OVA-induced)	↓Infiltration of inflammatory cells and bronchial thickness; ↓number of macrophages and eosinophils, ↓concentration of OVA-specific Ig E, and expression of Th2 cytokines	250 and 500 mg⋅kg−1	Choi et al. (2018a)
	Total saponin	Mice (OVA-induced); RAW264.7 cells (LPS-activated)	↓Number of immune cells, ↓infiltration of inflammatory cells, ↓bronchial thickness, ↓IL-4, IL-13 and COX-2	250 and 500 mg⋅kg−1; 200 µg⋅mL−1	Sung et al. (2017)
Anti-inflammatory	Distilled water extract (70°C for 5 h)	Astrocytes (stimulated with SP and LPS)	Inhibit TNF-alpha secretion by inhibiting IL-1 secretion	101–103 µg⋅mL−1	Kim et al. (1998)
	70% EtOH extract (three times, with 2 h reflux)	Mice (TPA-induced)	↓Skin thickness and tissue weight, ↓inflammatory cytokine production, ↓neutrophil-mediated MPO activity	200 mg⋅kg−1	Lee et al. (2009)
	Ethyl acetate extract (three times, with 2 h reflux)	Mice (IL-4/Luc/CNS-1 Tg)	↓Immunoglobulin E concentration, ↓epidermis thickness, ↓number of infiltrated mast cells	200 and 400 mg⋅kg−1	Sung et al. (2016)
	Ethyl acetate extract (50°C for 24 h)	RAW264.7 cells (LPS-activated)	Inhibition of NO production, COX-2 expression, ROS production, differential regulation of inflammatory cytokines cell cycle	100 and 200 µg⋅mL−1	Lee et al. (2017b)
	Methyl Protodioscin	Lung epithelial cells; Mice (airway inflammation)	Inhibited the production of proinflammatory cytokines IL-6, TNF-α, IL-1β in lung tissue	10–100 μM	Lee et al. (2015)
	Butanol extract (three times)	RAW264.7 macrophage cells (LPS-stimulated)	Inhibition of proinflammatory cytokine expression	100 and 200 µg⋅mL−1	Lee et al. (2017b)
	75% EtOH (three times, 3 h at 70°C)	BV-2 microglial cells (LPS-induced)	Inhibition of NO production	1.0 μg⋅mL−1	Jian et al. (2013)
Anti-oxidant	Water extract (three times)	Mice (D-galactose-induced aging)	↑NOS, CAT, SOD activities, ↑NO content, ↓ MDA content	0.7 g⋅mL−1	Lei et al. (2017)
	Water extract (three times)	Mice (D-galactose-induced aging)	↑NOS, CAT, SOD activities and the NO content; ↑expressions of NOS, ↑SOD and GPX	0.7 g⋅mL−1	Lei et al. (2016)
	25% ethyl acetate extract (three times, 40°C for 2 h)	CCD-966SK cell; A375.S2 cell	↑Scavenging ability, reducing power,↑anti-tyrosinase activity of DPPH	100–1000 mg⋅L−1	Wang et al. (2019)
	Water extract (1 h three times)	Mice (D-Galactose)	↑Spleen index and the SOD activity; ↓MDA content	2.66 g⋅kg−1	Xiong et al. (2011)
Anti-tumor	90% EtOH extract (80°C for 3 h)	Hep G2 cells, Hep 3B cell, LO 2 cell; mice (Tumor-Bearing)	Inhibit tumor growth and proliferation	200 mg⋅kg−1	Zhang et al. (2021b)
	70% EtOH extract (refluxing three times, 2 hours each time)	NCI-H460 cell	Inducing apoptosis and cell cycle arrest; inhibition of lung cancer cell proliferation	10, 50 and 100 μM	Liu et al. (2021)
	Water extract (decoction 3 h)	Hep G2 cells	Inhibited the TNF-alpha-induced apoptosis of Hep G2 cells	1–100 mg⋅mL−1	Koo et al. (2000)
Antidepressant and neuroprotection	Water extract (100°C for 2 h)	Mice (Ovariectomized)	↑Brain-derived neurotrophic factor	1000 and 2000 mg⋅kg−1	Kim et al. (2020)
			↑Tropomyosin receptor kinase expression levels
	MeOH extract (5 days)	Cortical neurons cell	Inhibited H2O2-induced cell death in cultured cortical neurons	0.01, 0.50 and 1.00 μM; 100 and 200 mg⋅kg−1	Jalsrai et al. (2016)
		Mice
Treat intestinal related diseases	Water extract (3 h, repeated twice)	Drosophila	↑The survival rate; ↓epithelial cell death; attenuated metal ion-induced gut morphological changes	10% w⋅v−1	Zhang et al. (2016)
	Saponin (24 h at 50°C)	Mice (loperamide-induced constipation)	↑Number of stools and gastrointestinal transit, ↑thickness of the mucosal layer, ↑flat luminal surface, ↑number of paneth cells,↑lipid droplets	1000 mg⋅kg−1	Kim et al. (2019)
Improve Alzheimer’s disease	Water extract (121°C for 45 min)	Mice	↑Nerve growth factor secretion; ↓intracellular ROS	100 mg⋅kg−1	Lee et al. (2018)

FIGURE 5.

The pharmacological activities of A. cochinchinensis.

Anti-asthma

Asthma is a common chronic and stubborn respiratory disease, clinically presenting with cough, chest tightness, wheezing, and shortness of breath (Papi et al., 2018). Non-timely treatment will lead to a series of secondary diseases, such as chronic obstructive pulmonary disease and heart failure, which can become life-threatening (Schoettler and Strek, 2020; Miller et al., 2021). At the same time, it also added a serious financial burden to the family (López-Tiro et al., 2022). Therefore, researchers found that the butanol extract of A. cochinchinensis roots, when fermented with Weissella cibaria (BAfW), was found to inhibit the development of asthma development through various potential mechanisms. Choi et al., 2018 alterations in key parameters were measured in ovalbumin (OVA)-challenged Balb/c mice treated with different BAfW dose regimens at three different time points. The results show that when the dosage of A. cochinchinensis fermentation extract was 500 mg, the number of immune cells, OVA-specific immunoglobulin E (Ig E) level, thickness of respiratory enzyme and mucus score decreased significantly in mice, and these parameters could be maintained for 48 h (Choi et al., 2018b). At the same time, researchers explored biomarkers for asthma in OVA-induced asthma mice. The extract of A. cochinchinensis was administered to the model mice at a low concentration of 250 mg/kg and a high concentration of 500 mg/kg, respectively. The changes in their metabolites were observed after administration. The results showed that the immune cells, Ig E serum concentration, the respiratory epithelium’s thickness, and inflammatory cell infiltration in the airway in mice treated with A. cochinchinensis extract recovered significantly. Notably, when assessing the endogenous metabolites, only alanine, glycine, methionine, and tryptophan were significantly recovered after A. cochinchinensis extract treatment, compared with the control group. Therefore, these four metabolites can be used as biomarkers to predict the anti-asthmatic effects (Choi et al., 2019). Moreover, the A. cochinchinensis fermentation extract was shown for the first time to accelerate the recovery from chronic asthma. It prevented airway inflammation and remodeling by restoring the cholinergic regulation of structural cells and inflammatory cells in chronic asthma models. Thus, it can further potentiate the effects of asthma treatments (Choi et al., 2018a). Furthermore, in vitro and in vivo experiments have been conducted to explore the effects of total saponins in A. cochinchinensis extract on asthma. Lipopolysaccharide (LPS) -activated RAW264.7 cells and OVA-induced mice asthma were treated with saponins-rich A. cochinchinensis extract, respectively. The result showed that the concentration of nitric oxide (NO) and mRNA levels of and cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were significantly decreased in the SEAC/LPS-treated RAW264.7 cells compared with the vehicle/LPS-treated RAW264.7 cells. At the same time, the number of immune cells, infiltration of inflammatory cells and bronchial thickness decreased, meanwhile the levels of interleukin 4 (IL-4), interleukin 13 (IL-13) decreased significantly under the treatment of A. cochinchinensis extract (Sung et al., 2017). In general, A. cochinchinensis extracts can inhibit airway inflammation and remodeling, providing an important natural medicine option for the treatment of asthma.

Anti-inflammatory

Inflammation commonly occurs due to the modern lifestyle, and its complications can detrimentally affect people’s health (Yeung et al., 2018; McInnes and Gravallese, 2021). Numerous studies have proved that A. cochinchinensis has anti-inflammatory effect. Previous research by Kim et al., 1998 showed that A. cochinchinensis could inhibit tumor necrosis factor-α (TNF-α) secretion by inhibiting interleukin 1 (IL-1) secretion and that A. cochinchinensis extracts had anti-inflammatory activity in the central nervous system (Kim et al., 1998). Another study showed that the ethanol extract of A. cochinchinensis inhibited acute and chronic inflammation. When the extract was administered at a 200 mg/kg dose, the symptoms of 12-o-tetradecanoyl-phorbol-13-acetate (TPA)-induced mice ear were significantly alleviated. In addition, the skin thickness and tissue weight, inflammatory cytokine production, neutrophil-mediated myeloperoxidase (MPO) activity and histopathological parameters were significantly decreased (Lee et al., 2009). Furthermore, researchers have found that the ethyl acetate extract of A. cochinchinensis was shown to inhibits skin inflammation. In this study, phthalic anhydride (PA) -induced skin inflammation mice were used to identify the effects of A. cochinchinensis ethyl acetate extract on inflammation. The results suggest that ethyl acetate extract of A. cochinchinensis significantly reduced the concentration of Ig E, the surface thickness and number of infiltrating mast cells, and ethyl acetate extract played a key role in the treatment process (Sung et al., 2016). Using in vitro cell experiments, the researchers showed that the A. cochinchinensis ethyl acetate extract could inhibit the LPS stimulated RAW264.7 cell NO production, COX-2 expression, reactive oxygen species (ROS) production, and the inflammatory cytokine cell cycle (Lee et al., 2017). Thus, the above research findings provide strong evidence that A. cochinchinensis extracts may have important medicinal properties for treating specific skin inflammatory diseases. Surprisingly, after fermentation with BAfW, compounds such as protodioscin were significantly enhanced. In addition, a significant suppression was observed in the expression of key members of the iNOS-mediated COX-2 induction pathway and the phosphorylation of mitogen-activated protein kinases. These observations point to the ability to inhibit inflammatory reaction occurrence (Lee et al., 2015). Furthermore, studies have shown that the compound methyl protodioscin in A. cochinchinensis can inhibit the production of pro-inflammatory factors such as interleukin 16 (IL-16), interleukin 8 (IL-8) and TNF-α in lung tissue, suggesting that the compound has therapeutic value for airway inflammatory diseases (Lee et al., 2017a). Additionally, through in vitro cell experiments, the researchers took LPS-induced microglia cell as the study model. They were found that the ethanol extract of A. cochinchinensis at 1.0 μg mL⁻¹ could significantly inhibit the production of NO in microglia cell induced by LPS, so as to play an anti-inflammatory role (Jian et al., 2013). All in all, all these studies have emphasized the potential of A. cochinchinensis extract to inhibit inflammatory reactions.

Anti-oxidant

Anti-oxidants have always played a vital role in people’s health (Milisav et al., 2018; Martemucci et al., 2022). Studies have recently confirmed the anti-oxidant effect of A. cochinchinensis extract. A. cochinchinensis is shown to significantly increase the activities of anti-oxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), nitric oxide synthase (NOS), NO, and glutathione peroxidase (GPX). Liver and kidney hematoxylin and eosin stain sections revealed that D-galactose could cause serious injury, and A. cochinchinensis treatment improved immunity and substantially protected the liver and kidney from oxidative damage in aging mice (Lei et al., 2016). In a similar experiment, compared with the Vitamin C (Vc) positive control group, 0.7 mg⋅mL⁻¹ aqueous root extract of A. cochinchinensis had similar 1,1-Diphenyl-2-picrylhydrazyl (DPPH) and 3-ethylbenzothiazoline-6-sulfonic (ABTS⁺) scavenging activities, but significantly increased superoxide anion (p < 0.05) and OH scavenging activities (p < 0.01), which suggested strong radical scavenging ability of the aqueous root extract in vitro (Lei et al., 2017). At the same time, the researchers took D-galactose -induced mice as the research object and administered intraperitoneal injection (0.2 ml/20g) to mice for 15 days to make them senile, and further explored the effect of A. cochinchinensis extract on aging mice. The study found that through the detection of mice spleen and plasma, A. cochinchinensis extract could increase the spleen index and the SOD activity, reduces malondialdehyde (MDA) content, inhibits oxidation and slows down aging (Xiong et al., 2011). Additionally, 2,2-diphenyl-1-picropylhydrazine (DPPH) plays an indispensable role in antioxidant process. In a recent study, the fermented A. cochinchinensis root extract’s effects on melanogenic factor levels in human epidermal melanocytes (HEMs) and its anti-tyrosinase activity were analyzed and compared with the unfermented extract. The results showed that the scavenging ability, reducing power, and anti-tyrosinase activity of DPPH in the fermented extract were significantly increased (Wang et al., 2019). Therefore, A. cochinchinensis can be used as a natural anti-oxidant, with broad development and application prospects in the future.

Anti-tumor

The prevention and treatment of malignant tumors and cancer is a major challenge faced in our modern societies (Liu and Dong, 2021; DiMaio et al., 2022; Mao et al., 2022). With the development of molecular biology and pharmacology, A. cochinchinensis has attracted increasing attention from domestic and foreign medical scholars working in the cancer field. Through in vitro and in vivo experiments, A. cochinchinensis extracts were mainly internalized into tumor cells through phagocytosis, but once they entered the blood, tumor cells would be quickly cleared, further inhibiting the growth and proliferation of tumor cells (Zhang R. S. et al., 2021). Another study found that the compound 3-O-{[β-D-glucopyranosyl-(1→2)]-[α-L-rhamnopyranosyl-(1→4)]-β-D-glucopyranosyl} -(25R)-5β-spirostan-3β-ol mainly exerted its effect on inhibiting the proliferation of human large cell lung cancer cells (NCI-H460) by inducing apoptosis and cell cycle arrest, with an IC₅₀ value of 1.39 μM (Liu et al., 2021). Besides that, the extract of A. cochinchinensis (1–100 mg/ml) dose-dependently not only inhibited the EtOH-induced tumor necrosis TNF-α secretion but also inhibited the EtOH and TNF-α-induced cytotoxicity. In addition, the extract of A. cochinchinensis inhibited the TNF-α -induced apoptosis of Hep G2 cells. Therefore, the above results suggest that A. cochinchinensis may prevent the EtOH-induced cytotoxicity by inhibiting the apoptosis of Hep G2 cells (Koo et al., 2000). These studies will provide a reference for further in-depth clinical application of A. cochinchinensis in cancer treatment.

Anti-depressant and neuroprotection

The risk of depression has greatly increased due to the enormous mental and physical stress people face due to modern, fast-paced lifestyles (Martins and S., 2018; Angeloni and Vauzour, 2019; Payne et al., 2022). The researchers ovariectomized rats and exposed them to a chronic stress reaction state for 4 weeks. They additionally administered A. cochinchinensis extract (1000 and 2000 mg/kg) to observe mental state alterations of the menopausal rats. The results showed that the expression of brain-derived neurotrophic factor (BDNF) and its main receptor tropomyosin receptor kinase B (TrkB) increased in rats. Thus, A. cochinchinensis extract could potentially exert anti-depressant effects (Kim et al., 2020). In addition, another study showed that the A. cochinchinensis extract, activating phosphatase 2 (Shp-2), ERK1/2, and Akt signaling pathways, could directly affect treating depression and nerve protection (Jalsrai et al., 2016). The pathogenesis of Alzheimer’s disease is unclear, but neuroprotection is shown in different studies to prevent and alleviate it. Lee et al., 2018 study showed that phenols, saponins and protodiosgenin in A. cochinchinensis extracts induced enhanced nerve growth factor secretion and decreased intracellular ROS in neurons and microglia cell lines, inhibiting the activity of acetylcholinesterase, thereby improving Alzheimer’s disease (Lee et al., 2018). This study provides novel directions for developing new drugs from A. cochinchinensis, and, more importantly, offers new insights into the treatment of Alzheimer’s disease.

Effects on the gut

Maintaining a normal gut and digestive tract function is one of the key elements to maintaining good health (Sommer et al., 2017; Fassarella et al., 2021; Nathan et al., 2021). Studies have shown that A. cochinchinensis extract can treat gut damage caused by metal ions. To evaluate such A. cochinchinensis extract effects, the metal ions Drosophila model was used. The results showed that A. cochinchinensis extract can improved the survival rate of Drosophila melanogaster, reduce the mortality of intestinal epithelial cells, and the reduce the intestinal damage caused by metal ions (Zhang L. et al., 2021). At the same time, Kim et al., 2019 found that saponins can increase stool frequency, gastrointestinal transit, mucosal layer thickness, flat luminal surface, and the number of paneth cells, thus playing a role in the treating constipation. Improvements were also observed in the levels of acetylcholine esterase activity, the phosphorylation of myosin light chains, and the expression of muscarinic acetylcholine receptors M2/M3 (Kim et al., 2019). This study provides strong evidence for A. cochinchinensis applications in treating certain gut-related diseases. However, another study showed that polysaccharides in A. cochinchinensis have a role in gut flora regulation. The impact of inulin-type fructan on gut microbiota was investigated by in vitro mediation with human fecal cultures. The results showed that inulin-type fructan was digested by gut microbiota, while the pH value in the A. cochinchinensis neutral polysaccharide (ACNP) fecal culture was greatly decreased. The total short-chain fatty acids, acetic, propionic, i-valeric, and n-valeric acids were significantly increased (Sun et al., 2020). Collectively, inulin-type fructan was shown to regulate gut microbiota beneficially (Vandeputte et al., 2017; Tao et al., 2021). Thus, it has the potential to be used as a dietary supplement or drug to improve health.

Other activities

As A. cochinchinensis is widely used as a traditional herbal medicine with high medicinal value, its safety profile is very important. A recent study evaluated the hepatotoxicity and nephrotoxicity of A. cochinchinensis toward the livers and kidneys in ICR mice. Female and male ICR mice were orally administered with 150 mg/kg, 300 mg/kg, and 600 mg/kg A. cochinchinensis extract for 14 days, respectively, and the changes in relevant markers (organ weight, urine composition, liver pathology, and kidney pathology) were observed. The results showed that Female and male ICR mice were orally administered with 150 mg/kg, 300 mg/kg, and 600 mg/kg A. cochinchinensis extract for 14 days, respectively, and the changes in relevant markers (organ weight, urine composition, liver pathology, and kidney pathology) were observed (Sung et al., 2017a). Therefore, the saponins in the A. cochinchinensis extract have no specific liver and kidney toxicity, reinforcing the excellent safety profile of A. cochinchinensis.

Applications

A. cochinchinensis embodies not only significant medicinal value in the field of TCM but also shows distinctive application value in the fields of pharmaceuticals, health care products, food, cosmetics, and others. These applications are summarized in Figure 6, and A. cochinchinensis patents in pharmaceuticals, foods, health products and cosmetics are listed in Table 5.

FIGURE 6.

The applications of A. cochinchinensis in pharmaceutical, food, health products, and cosmetics.

TABLE 5.

The patents for A. cochinchinensis.

NO	Patent name	Approval number
Pharmaceutical
1	Traditional Chinese medicine pill for treating internal injury cough	CN104013932B
2	A traditional Chinese medicine for treating old cough	CN103611141B
3	Chinese medicine for clearing lung in children	CN103550594B
4	Application and preparation method of pharyngitis tablet	CN103656415B
5	A drug and capsule for constipation	CN103948780B
6	A traditional Chinese medicine preparation for rapid cough relief	CN103028057B
7	A Chinese herbal compound for the treatment of jaundice hepatitis and cholecystitis	CN103349748B
8	A Chinese medicine combination for anti-aging and its preparation method	CN194370700B
9	A pharmaceutical composition for treating juvenile white hair loss	CN103690798B
Food
10	Radix asparagi and platycodon grandiflorum healthcare rice crust	CN103652639B
11	Rehmannia-radix asparagi beverage and preparation method thereof	CN102150912B
12	A preparation method of health jelly with algae flavor	CN103621855B
Health product
13	A medicinal wine for lowering blood pressure, blood sugar and blood lipid	CN103860903B
14	A traditional Chinese medicine health wine and its preparation method	CN103013795B
15	A longevity medicinal wine and its preparation method	CN104784474B
16	A health tea for preventing diabetes	CN102935186B
Cosmetic
17	A. cochinchinensis whitening compound soap	CN103361213B
18	Beauty antibacterial soap	CN103589537B
19	A plant combination for delaying skin aging and its preparation method	CN103550511B
20	A Traditional Chinese Medicine Composition for increasing skin moisture and its preparation method	CN101322800B
Others
21	A compound additive for cigarette and its preparation method and application	CN103549652B
22	A chrysanthemum scented snuff	CN103005679B
23	A.cochinchinensis immune adjuvant and influenza vaccine containing the adjuvant	CN101926995B

As mentioned above, A. cochinchinensis contains numerous active compounds having many promising effects in vitro and in vivo, indicating their great potential to for pharmaceutical applications (Ren et al., 2021). The pharmaceutical properties of A. cochinchinensis were recorded well in ancient Chinese medical literature. Nowadays, A. cochinchinensis has a wide range of clinical applications in the respiratory, digestive, urinary system, with diverse uses. Clinically, A. cochinchinensis is often used to treat respiratory diseases such as cough, asthma, and lung cancer. A. cochinchinensis can be used alone, in combination with other pharmaceuticals, or for external use (Hong et al., 2000; Liu et al., 2015). Health care products are becoming highly popular as people pay increasing attention to their physical health (Tabatabai and Sellmeyer, 2021). A. cochinchinensis through self-fermentation or fermentation with other Chinese herbal medicines, is marketed form of functional medicinal wine (Kim et al., 2017; Wuyts et al., 2020). It contributes to lowering blood pressure, blood sugar, and blood lipid, so it is highly sought after by middle-aged and elderly people (Sikand et al., 2015). Moreover, there are functional teas with health-promoting properties (Fu et al., 2018). A. cochinchinensis is also widely used in the food and culinary field. In the folk, people usually use A. cochinchinensis is used as the main raw material to cook porridge or paste, used to relieve cough, expectorant, tonsillitis, dry throat, sore throat, hemoptysis, and treat constipation. It is also processed into A. cochinchinensis candied fruit, that is popular, especially among young people. Certain modern A. cochinchinensis foods products have been patented, such as Radix asparagi and platycodon grandiflorum healthcare rice crust, Rehmannia-radix asparagi beverage and health jelly with algae flavor. Recent studies have shown that long-term consumption of A. cochinchinensis as a traditional edible plant can inhibit the production of pro-inflammatory cytokines interleukin-1 beta (IL-1β) and TNF-α, thereby treating various immune-related diseases (Safriani et al., 2022). Despite the currently limited research on A. cochinchinensis food products, A. cochinchinensis has great potential applications and novel future products in the food field. Interestingly, the extract obtained from fermented A. cochinchinensis is also used as a whitening facial mask and whitening soap, with increasing sales, as it can inhibit the formation of tyrosinase and melanin (Sakuma et al., 1999; Pillaiyar et al., 2017). At the same time, patents granted on A. cochinchinensis show that it has beneficial properties for improving skin aging, skin whitening, reducing skin wrinkles, and moisturizing, among others. Therefore, the potential of further A. cochinchinensis commercial applications in the cosmetics industry should be sought after with increased research efforts.

Conclusions and perspectives

In this paper, we review the botany, traditional uses, phytochemistry, applications, and pharmacology activities of A. cochinchinensis according to ancient classics and modern researches, and it will provide a new insight for future exploration of A. cochinchinensis. The root of A. cochinchinensis has been widely used to treat cough, fever, pneumonia, stomachache, tracheitis, rhinitis, cataract, acne and urticaria. Meanwhile, the root of A. cochinchinensis has a predominant therapeutic effect in diseases such as sthma, constipation, pneumonia. Interestingly, A. cochinchinensis exerts multiple functions as medicine, food, and cosmetics, which has been widely used as whitening or healthcare product. Up to now, more than 90 compounds have been isolated and identified from A. cochinchinensis. Among these constituents, steroidal saponins represent the main active ingredients. It is expected that more compounds of these categories will be discovered in the future studies. In addition, researches have shown that both extracts and active components of A. cochinchinensis possess a wide range of pharmacological activities, including anti-asthma, anti-inflammatory, anti-oxidation, anti-tumor, improving Alzheimer’s disease, nerve protection, gut health-promoting and so on. These modern pharmacological studies supported most traditional uses of A. cochinchinensis as an indispensable TCM.

However, gaps still exist in the systematic research on A. cochinchinensis. Firstly, reported studies have shown that the main chemical components of A. cochinchinensis is steroidal saponins. While other chemical constituents such as polysaccharides, lignans and amino acids extracted and isolated from A. cochinchinensis are very few compared with steroidal saponins. More chemical constituents must be obtained to explore the relationship between compounds and pharmacological effects in depth. Therefore, new separation and analysis techniques should be developed and implemented to analyze and determine A. cochinchinensis chemical composition comprehensively. Secondly, quality standards have not been adequately set. Since A. cochinchinensis has a wide variety and is easily confused with other varieties, it is very necessary to establish a complete set of quality standards to distinguish these products. This will also contribute to better-protecting people’s health and safety. Thus, it is crucial to establish the A. cochinchinensis quality analytical standards and find the appropriate markers to implement such quality control. At the same time, it is also necessary to conduct systematic and in-depth research on the toxicology of A. cochinchinensis to improve the safety profile of its clinical use. Thirdly, the main part of A. cochinchinensis used for medicinal compound extraction is its dried root, and the other parts are discarded. However, the resources of roots are relatively rare compared to the resources of leaves and fruits. In the future, in-depth research should be conducted on the leaves and fruits of A. cochinchinensis, to explore their value so that the plant can be fully utilized. This reduces the waste of plant resources and might contribute to the development of new drugs, as novel compounds might be discovered in other plant parts. Therefore, we should solve the existing problems as soon as possible, so that the future development of A. cochinchinensis will be better.

In addition, in order to further elucidate the mechanism of A. cochinchinensis in treating diseases, it is essential to establish the internal relationship between chemical components and their pharmacological activities. Pharmacokinetic studies of A. cochinchinensis can also be conducted to try to elucidate its changes including absorption, distribution, metabolism and excretion. This will further elucidate the complex relationship between chemical components and clinical effects to reveal potential mechanism of action. At the same time, A. cochinchinensis can also be used as food and nutritional supplement. People become more aware of their health, edible Chinese herbal medicines with health-promoting and therapeutic effects are becoming very popular. On this basis, in-depth research should be conducted in the fields of A. cochinchinensis health products, food, and cosmetics, which may have broader prospects for future development, providing new idea for A. cochinchinensis research.

To sum up, the root of A. cochinchinensis is an important edible medicinal herb with extensive pharmacological activities and great values in medicine, food, and cosmetics. However, more in-depth and comprehensive studies on clinical utility are needed to determine its safety and availability. Until now, multiple compounds have been discovered in A. cochinchinensis, but what we have done is far from enough. Furthermore, the precise molecular mechanisms of these active ingredients in some diseases still worth further study. Consequently, systematic studies on phytochemistry and bioactivities of A. cochinchinensis will undoubtedly be the key direction of future research. This review should provide an important reference for the development and application of A. cochinchinensis. Siand et al., 2015, Sheng, 2022b.

Author contributions

MW and HK proposed the framework of this paper. SW and ZW drafted the manuscript. SW and WH make tables and figures. BY provided some helpful suggestions in this paper. All authors read and approved the final manuscript.

Funding

This work was supported by the National Natural Science Foundation of China (No.81803686), Supporting Project of National Natural Science Foundation (No.2018PP01), University Nursing Program for Young Scholars with Creative Talents in Heilongjiang Province (No.UNPYSCT-2020225), Special Fund Project of Post doctor in Heilongjiang Province (LBH-Q20180), Chief Scientist of Qi-Huang Project of National Traditional Chinese Medicine Inheritance and Innovation “One Hundred Million” Talent Project ([2021] No.7), Heilongjiang Touyan Innovation Team Program ([2019] No.5).

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Glossary

ACNP

Asparagus cochinchinensis neutral polysaccharide

ACNVs

Asparagus cochinchinensis-derived nanovesicles

Ara

Arabinose

BDNF

Brain-derived neurotrophic factor

CAT

Catalase

COX-2

Cyclooxygenase-2

CZE

Capillary zone electrophoresis

DPPH

1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl

Fru

Fructose

Gal

Galactose

GalUA

Galacturonic acid

Glc

Glucose

GlcUA

Glucuronic acid

GPX

Glutathione peroxidase

Ig E

Immunoglobulin E

IL-4

Interleukin 4

IL-13

Interleukin 13

IL-1β

Interleukin-1 beta

iNOS

Inducible nitric oxide synthase

LPS

Lipopolysaccharide

Man

Mannose

MDA

Malondialdehyde

MPO

Myeloperoxidase

NGF

Nerve growth factor

NO

Nitric oxide

NOS

Nitric oxide synthase

OVA

Ovalbumin

PA

Phthalic anhydride

ROS

Reactive oxygen species

Rha

Rhamnose

SOD

Superoxide dismutase

SP

Substance P

TCM

Traditional Chinese medicines

Tg

Transgenic

TNF-α

Tumor necrosis factor-α

TPA

12-O-tetradecanoyl-phorbol-13-acetate

TrkB

Tropomyosin receptor kinase B

Xyl

Xylose