Front. Pharmacol. Frontiers in Pharmacology Front. Pharmacol. 1663-9812 Frontiers Media S.A. 1068858 10.3389/fphar.2022.1068858 Pharmacology Review Asparagus cochinchinensis: A review of its botany, traditional uses, phytochemistry, pharmacology, and applications Wang et al. 10.3389/fphar.2022.1068858 Wang Meng Wang Shuang Hu Wenjing Wang Zhibin Yang Bingyou Kuang Haixue * Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Ministry of Education, Heilongjiang University of Chinese Medicine, Harbin, China

Edited by: Zheng Xiang, Liaoning University, China

Reviewed by: Xingbin Yin, Beijing University of Chinese Medicine, China

Zijia Zhang, Shanghai University of Traditional Chinese Medicine, China

Changfu Wang, Guangdong Pharmaceutical University, China

 *Correspondence: Haixue Kuang, hxkuang@hljucm.net

This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology

 30 11 2022 2022 13 1068858 13 10 2022 15 11 2022 Copyright © 2022 Wang, Wang, Hu, Wang, Yang and Kuang. 2022 Wang, Wang, Hu, Wang, Yang and Kuang

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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.

Asparagus cochinchinensis (Lour.) Merr traditional uses phytochemistry pharmacology applications National Natural Science Foundation of China10.13039/501100001809 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.

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.

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)

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

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

The structures of C21-steroidals in A. cochinchinensis.

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.

 C<sub>21</sub>-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.

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.

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)

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.

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

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.

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T. Li H. Z. (2014). Steroidal saponins from the roots of Asparagus cochinchinensis. Chin. J. Nat. Med. 12 (3), 213–217. 10.1016/S1875-5364(14)60035-2 Zhu G. L. Hao Q. Xing L. Yang X. Q. Xie S. D. Zhao P. (2021). C21, C22 pregnane glycosides and cytotoxic C27 spriostanol steroids from Asparagus cochinchinesis. Steroids 172, 108874. 10.1016/j.steroids.2021.108874 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