Ethnobotany, Phytochemistry, and Pharmacology of Angelica decursiva Fr. et Sav.

Md Yousof Ali; Su Hui Seong; Susoma Jannat; Hyun Ah Jung; Jae Sue Choi

doi:10.20307/nps.2019.25.3.181

Abstract

Angelica decursiva Fr. et Sav. (Umbelliferae) has traditionally been used to treat different diseases due to its antitussive, analgesic, and antipyretic activities. It is also a remedy for thick phlegm, asthma, and upper respiratory infections. Recently, the leaf of A. decursiva has been consumed as salad without showing any toxicity. This plant is a rich in different types of coumarin derivatives, including dihydroxanthyletin, psoralen, dihydropsoralen, hydroxycoumarin, and dihydropyran. Its crude extracts and pure constituents possess anti-inflammatory, anti-diabetic, anti-Alzheimer disease, anti-hypertension, anti-cancer, antioxidant, anthelmintic, preventing cerebral stroke, and neuroprotective activities. This valuable herb needs to be further studied and developed not only to treat these human diseases, but also to improve human health. This review provides an overview of current knowledge of A. decursiva metabolites and their biological activities to prioritize future studies.

Introduction

The genus Angelica belongs to the family Apiaceae (alt. Umbelliferae), commonly known as parsley family. It comprises more than 90 species of medicinally important biennial or perennial herbs.1 2 3 Many analytical techniques such as high-performance liquid chromatography (HPLC), Ultra high-pressure liquid chromatography (UPLC), gas chromatography (GC), and nuclear magnetic resonance spectroscopy (NMR) have been used to evaluate the quality and distinguish different species of Angelica.4 5 6 7 According to traditional Chinese medicine (TCM), Angelica decursiva (A. decursiva) belongs to Plantae, Angiospermea Phylum, Dicotyledoneae Class. Umbelliflorae Order, Apiaceae Family, Angelica Genus.8 It grows throughout Japan, China and Korea. It is mainly distributed in the hillside, grassland, or sparse forest. It is called ‘Jahwajeonho’ in Korean and ‘Zi hua qian hu’ in Chinese and Zenko in Japanese. It is widely employed in traditional medicine in Japan, China and Korea to cure diseases such as cough from pathogenic wind-heat and accumulation of phlegm and heat in lungs.9 A. decursiva is also used in Korea as a salad without showing any toxicity.10 The usage of roots of A. decursiva has a long history in China to clean heat, resolve summer heat, and stop bleeding. It is also officially listed in the Chinese pharmacopeia. Both in vitro and in vivo studies have indicated that A. decursiva exhibits a variety of pharmacological activities, including inhibition of airway inflammation, reducing allergic lung inflammation, therapy for ischemia-induced brain damage, anti-diabetic, anti-Alzheimer disease, anti-cancer, antioxidant, and neuroprotective activities.11 12 13 14 15 16 17 18 19 20 This plant is rich source in different types of coumarin derivatives, including furanocoumarin, psoralen, dihydropsoralen, angelicin, dihydroangelicin, pyranocoumarin, dihydroxanthyletin, and dihydroseselin.4 5 6 7 11 13 14 21 22 23 24 25 The available information on A. decursiva was collected using several different resources, including classic books on Chinese herbal medicine and a number of scientific databases, PubMed, SciFinder, the Web of Science and Science Direct.

This review herein summaries progress regarding chemical analysis of A. decursiva for the first time, primarily focusing on the development of phytochemistry, botanical aspects, ethnopharmacological, and pharmacological effects of A. decursiva. A. decursiva species is rich sources of different types of coumarin derivatives that exhibited number of biological activities and may be potentially impact human health. Unfortunately, A. decursiva has not been developed as a pharmaceutical agent. The main objective of this review a summary of the studies published to date on this promising plant, with a solid platform to design and conduct of clinical studies.

Botanical profile and taxonomy

The genus Angelica belongs to the family Apiaceae commonly known as parsley family. It comprises more than 90 species of medicinally important biennial or perennial herbs distributed widely in Asia, Europe, and North America.1 2 About 20 species of Angelica genus have been found in Korea.26 Among them, A. decursiva is a perennial herb growing up to 1.5 m. Photographs of A. decursiva are shown in Figure 1. It grows throughout Japan, China, and Korea. It is mainly distributed in the hillside, grassland, or sparse forest.27 Its roots are conical with a few branches. They are 1 – 2 cm in diameter. Their appearance is brownish yellow to tan, with a strong odor.28 Their roots and stems have long stalks. These stalks are 13 – 36 cm long. Their base is swelled into rounded purple leaf sheaths, clasped, and glabrous outside.29 Their flowers are conical-shaped. Petals are obovate or elliptic-lanceolate. Fruits are oblong to ovateoblong, 4 – 7 mm long, 3 – 5 mm wide, glabrous, and sulcate.30 There are 1 – 3 oil pipes inside and 4–6 joint oil pipes. The ventral surface of the endosperm is slightly concave. These species are hermaphrodite (having both male and female organs). They are pollinated by insects. The plant is self-fertile. Light (sandy), medium (loamy), and heavy (clay) soils are suitable for its growth. Acid, neutral, and basic (alkaline) soils are all suitable for its growth. It can grow in semi-shade (light woodland) or no shade. It prefers moist soil. Its roots are called anterior which contains many active ingredients. They have been used as a remedy for fever, headache fever, bronchitis, cough fever, cough, heat stroke, chronic asthma breathing, and thick yellow phlegm.9 They are also used for nerve pain and painkiller as a folk drug.

Traditional uses and ethnopharmacology

European folkloric reputation of the genus Angelica had a mythological belief that in the middle ages when Europe was almost destroyed by the plague, apparently an angel came to a monk and offered a herb that could cure the disease. Since then, this herb has a name called Angelica. Reports on traditional medicinal uses of Angelica species can be found in various ancient literature. The folklore of all North European countries depicts a common belief in their merits as a protection against contagion, for purifying blood, and for curing every conceivable ailment. In China, A. decursiva has been primarily used as traditional medicines to treat cough caused by pathogenic wind heat and accumulation of phlegm and heat in lungs.9 Additionally, the root of A. decursiva (local name: Zi-Hue Qian-Hu) has been used to treat respiratory diseases and pulmonary hypertension.5 11 Moreover, the usage of roots of A. decursiva has a long history in China to clean heat, resolve summer heat, and stop bleeding. It is also officially listed in the Chinese pharmacopeia. In Korea, the root of A. decursiva, local name Radix Peucedani (Qianhu), has been primarily used to dispel wind-heat, relieve cough, reduce sputum, treat cold and headache, dyspneal fullness and tightness in the chest, respiratory diseases, and pulmonary hypertension.31 In Korean traditional medicines, it has been used as an antitussive, analgesic, antipyretic, and cough remedy.11 A. decursiva is also used in Korea as a salad without toxicity.10 In addition to medicinal preparations of A. decursiva, fairly large quantities are used in the confectionery and liquor industries. As a result, A. decursiva has now emerged as one of commercially important species.

Phytochemistry

Several compounds have been isolated from A. decursiva, mainly different categories of coumarin derivatives and other constituents. They are listed in Table 1. Chemical structures of these main compounds are presented in Figures 2, 3, 4, 5, 6, 7. Coumarins are among the most effective constituents present in A. decursiva. They are biologically active, possessing a wide range of pharmacological properties such as anti-diabetic, anti-Alzheimer disease, anti-cancer, antioxidant, anti-inflammatory, and neuroprotective activities. Coumarins are widely distributed in nature. They are found in all parts of plants. Coumarins belong to the benzopyrone group, with a benzene ring connected to a pyrone moiety. Coumarin derivatives have been studied for their availability, low toxicity, relatively low expense, presence in the diet, and multiple bioactivities.32 Dietary exposure to coumarin is quite significant than exposure to other compounds because they are widely found in Citrus fruits, vegetables, seeds, nuts, and higher plants. Previous phytochemical investigations on A. decursiva have led to the identification of over 64 compounds, including coumarins 1 – 58 and others (59 – 64). Analysis of the whole A. decursiva plant has shown the presence of various compounds, including decursinol (1), 4-hydroxy Pd-C-III (4), 4′-methoxy Pd-C-I (5), Pd-C-I (6), Pd-C-II (7), Pd-C-III (8), decursidine (11), nodakenin (23), nodakenetin (24), isorutarine (25), (+)-trans-decursidinol (2), 2′-isopropyl psoralene (37), edulisin II (44), umbelliferone (46), umbelliferone 6-carboxylic acid (47), 6-formyl umbelliferone (48), cis-3′-acetyl-4′-angeloylkhellactone (54), (3′R)-O-acetyl-(4′S)-O tigloylkhellactone (55), para-hydroxy benzoic acid (62), and vanillic acid (63).11 13 14 16 Roots of A. decursiva contain (−)-cis-decursidinol (3), Pd-C-IV (9), Pd-C-V (10), (+)-3′S-decursinol (12), decursin (13), AD-I (14), AD-II (15), (−)-methoxydecursidinol (16), alsaticol (17), Pd-D-V (18), decursitin B (19), decursitin C (20), decursitin D (21), decursitin F (22), decuroside I (26), decuroside II (27), decuroside III (28), decuroside IV (29), decuroside V (30), decuroside VI (31), imperatorin (32), isoimperatorin (33), bergapten (34), (+)-oxypeucedanin hydrate (35), (+)-oxypeucedanin (36), oreoselon (38), deltoin (39), columbianadin (40), bakuchicin (41), libanoridin (42), edultin (43), edulisin III (45), umbelliprenin (49), ostruthin (50), ostenol (51), suberosin (52), scopoletin (53), selinidin (56), peujaponisinol A (57), peujaponisinol B (58), β-sitosterol (59), β-sitosterol-β-D-glucoside (60), crocatone (61), and decursidate (64).4 5 6 7 22 23 24 25

Biological and pharmacological activities

Numerous studies have investigated pharmacological activities of various A. decursiva extracts. Table 2 summarizes its pharmacological features that have been observed, including antidiabetic, anti-inflammatory, anticancer, antioxidant, anti-hypertension, prevention of cerebral stroke, anti-Alzheimer's disease, and anthelmintic properties. Coumarins isolated from A. decursiva are structurally diverse. They exhibit multiple pharmacological properties, suggesting that these compounds contribute to therapeutic effects of A. decursiva (Table 3).

Anti-inflammatory activity

The root of A. decursiva has been frequently used in traditional medicine as anti-inflammatory, antitussive, and analgesic agents and expectorant, especially for treating cough, asthma, bronchitis, and upper respiratory tract infections. Nitric oxide (NO) is a mutagen that affects microbial and mammalian cells due to the production of free radical. The 70% EtOH extract from root of A. decursiva and ethyl acetate (EtOAc), dichloromethane (CH₂Cl₂), and n-butanol (n-BuOH) fractions from an MeOH extract of the whole plant of A. decursiva have shown inhibitory effects on lipopolysaccharide (LPS)-induced NO production in MH-S and RAW 264.7 cells, respectively.11 12 Interleukin 6 (IL-6) is a pro-inflammatory cytokine that has pathological effect on chronic inflammation. Pretreatment with aqueous (H₂O) or 70% EtOH root extract of A. decursiva can inhibit IL-6 production in a dose-dependent (50 – 200 µg/ml) manner in IL-1β treated A549 cells.12 Additionally, 70% EtOH and H₂O root extract can reduce cell number in the bronchoalveolar lavage fluid (BALF) of LPS-induced acute lung injury in mice.12 Another in vivo study has shown that 70% EtOH extract can markedly reduce mucus production, inhibit eosinophils, neutrophils, macrophages, lymphocytes, and type 2 cytokines (IL-4, IL-5, IL-13, and eotaxin-3), histamine secretion, and IgE levels, It can also down-regulate Th2 (T helper) cells activation and diminish activated CD4 T cell and GATA-3 levels in the lung.17 Three major coumarins (nodakenin, umbelliferone, and nodakenetin) from A. decursiva inhibited NO and IL-6 production.11 12 Nodakenin is a major coumarin glycoside from A. decursiva. Effect of nodakenin in suppressing airway inflammation, hyperresponsiveness, and remodeling in a murine model of chronic asthma has been investigated.33 Pre-treatment with nodakenin (20 mg/kg) markedly inhibited airway inflammation, hyper-responsiveness, and remodeling. It improved subepithelial fibrosis, smooth muscle hypertrophy, and goblet cell hyperplasia. It also decreased levels of interleukin (IL)-4, IL-5, IL-13, and matrix metalloproteinase-2/-9 in bronchoalveolar lavage fluid as well as serum level of OVA-specific IgE. In addition, NF-κB DNA-binding activity in lung tissues was decreased by nodakenin treatment.33 As a rare hydroxycoumarin, umbelliferone 6-carboxylic acid could inhibit NO, reactive oxygen species (ROS), iNOS, cyclooxygenase-2 (COX-2), and NF-κB activity.34 It also reduced TNF-α and PGE2 production and dose-dependently (25, 50 mg/kg) inhibited carrageenan-induced mouse paw edema.34 Columbianadin, a psoralen type coumarin from A. decursiva, exhibits potent anti-inflammatory activity through inhibition of NO, IL-6, and iNOS expression level in MH-S cells. In in vivo study, columbianadin at concentrations of 20 – 60 mg/kg also decreased cell numbers in BALF and LPS-induced alveolar macrophage, dendritic cell, neutrophil, and interstitial macrophage.12 Recently, Ishita et al. (2015) have investigated the anti-inflammatory activity of different dihydroxanthyletin-type coumarins.13 Among them, decursidin, Pd-C-I, Pd-C-II, Pd-C-III, and 4-hydroxy Pd-C-III can inhibit NO and TNF-α production and expression levels of iNOS and COX-2. Edulisin II also inhibited NO and TNF-α production and expression levels of iNOS and COX-2 in RAW 264.7 cells.13

Antioxidant activity

Natural products are highly promising sources of antioxidants. A wide range of bioactive constituents of plants has antioxidant activities. Based on various assay methods and activity indices, antioxidant activities and nutraceutical and therapeutic effects of traditional Chinese medicines as well as mechanisms underlying such activities and effects have been investigated.35 Generation of free radicals can result in damage to the cellular machinery. Whole plants of MeOH extract and EtOAc, CH₂Cl₂, n-BuOH, and H₂O fractions of A. decursiva have exhibited 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), and peroxynitrite (ONOO⁻) scavenging activities.11 Among these tested fractions, EtOA fraction was found as the most active one, with IC₅₀ value of 45.50 µg/ml for DPPH, 15.20 µg/ml for ABTS, and 1.58 µg/ml for ONOO⁻ assays.11 Coumarin umbelliferone 6-carboxylic acid exhibits potent antioxidant activity by scavenging DPPH (IC₅₀ = 681.86 µg/ml), ABTS (IC₅₀ = 11.20 µg/ml), and ONOO⁻ (IC₅₀ = 8.04 µg/ml). It also dose-dependently (12.5 − 100 µM) inhibited ONOO⁻ -mediated tyrosine nitration.16 Vanilic acid, a phenolic compound, also possesses antioxidant activity by scavenging DPPH (IC₅₀ = 725.79 µg/ml) and ABTS (IC₅₀ = 1.39 µg/ml).11 It can also inhibit NO production, with IC₅₀ value of 23.38 µg/ml.11 Coumarins 4-hydroxy Pd-C-III, 4′-methoxy Pd-C-I, decursidine, decursinol, and 2′-isopropyl psoralene can also inhibit ONOO⁻-mediated tyrosine nitration in a dose-dependent manner at concentrations ranging from 12.5 µM to 100 µM.16

Antidiabetic activity

Protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase are two key enzymes that are effective in treating diabetes mellitus (DM). PTP1B can negatively regulate insulin signaling pathway. It is a promising target for the treatment of type II DM.36 MeOH extract of A. decursiva whole plant has inhibitory activities against PTP1B and α-glucosidase. Out of 12 coumarins from this extract, decursinol, 4-hydroxy Pd-C-III, 4′-methoxy Pd-C-I, decursidine, 2′-isopropyl psoralene, and umbelliferone 6-carboxylic acid exhibited the highest inhibitory activities against PTP1B, with IC₅₀ values of 5.39 − 58.90 µM.14 16 Kinetic studies revealed that coumarins, 4-hydroxy Pd-C-III, umbelliferone 6-carboxylic acid, and 2′-isopropyl psoralene were competitive inhibitors against PTP1B. They showed tight binding with the active site of PTP1B by hydrogen bond interactions.16 Moreover, α-glucosidases can aid in carbohydrate digestion and glucose release. Increased activity of these enzymes can lead to hyperglycemia and development of type II diabetes. Currently, α-glucosidase inhibitors can suppress the onset of this disorder. Several coumarins such as decursinol, 4-hydroxy Pd-C-III, 4′-methoxy Pd-C-I, decursidine, 2′-isopropyl psoralene, and (3′R)-O-acetyl-(4′S)-O tigloylkhellactone have α-glucosidase inhibitory activity, with IC₅₀ values below 93 µM when 4-nitrophenyl-alpha-D-glucopyranoside is used as the substrate. Such IC₅₀ values are considerably lower than the IC₅₀ value (201 µM) of acarbose as a control drug.14 16 Kinetic studies have revealed that coumarins decursinol, 4-hydroxy Pd-C-III, 4′-methoxy Pd-C-I, decursidine, and 2′-isopropyl psoralene show different modes of inhibition against α-glucosidase.16

Hyperglycemia is considered a vital initiator of several complications associated with diabetes by activating various metabolic pathways such as polyol pathway and formation of advanced glycation end products (AGE).37 Thus, inhibiting aldose reductase (AR) and AGE formation has been used as a therapeutic strategy for diabetic complications.38 39 Several coumarins derivatives including 4-hydroxy Pd-C-III, 4′-methoxy Pd-C-I, decursidine, (+)-trans-decursidinol, Pd-C-I, Pd-C-II, and Pd-C-III show potent human recombinant aldose reductase (HRAR) and AGE inhibitory activities, with IC₅₀ values of 1.03 – 21.31 µM against HRAR and 0.41 – 5.56 µM against AGE.19 Kinetic studies have revealed that coumarins 4-hydroxy Pd-C-III, Pd-C-I, Pd-C-II, and (+)-trans-decursidinol are competitive inhibitors against HRAR. Molecular analysis has shown that these coumarins have high affinity and tight binding capacities for the HRAR active site.19 Ali et al. (2015) have also investigated inhibitory activities of serval coumarins and their derivatives against rat lens aldose reductase (RLAR) and found that their IC₅₀ values range from 107.89 µM to 266.39 µM.14

Anticancer activity

A. decursiva root extract possesses anticancer activity in vitro by inhibiting cell proliferation and inducing apoptosis.8 40 41 42 It has been shown that 95% EtOH extract of A. decursiva root can induce apoptosis of various cancer cells, including C6 rat glioma cells40, FaDu human head and neck squamous cell carcinoma cells41, Saos2 human osteogenic sarcoma cells8, and human oral cancer cell line KB.42 Procaspase-9 activated via a mitochondrial pathway can subsequently activate other executioner caspases such as caspases-3, -6, and -7.40 These caspases also play an important role in the initiation and execution of apoptosis induced by various stimuli.43 44 Cho et al. (2009) have reported that A. decursiva extract possesses cytotoxic (IC₅₀ = 0.19 µg/mL) activity by inducing cell death in a concentration- (0.01 − 300 µg/m1) and time-dependent (1 – 3 days) manner and upregulating expression levels of proteolytic caspase genes such as caspase-3, -7, -9.40 In another study, Shin et al. (2010) have found that 95% EtOH extract of A. decursiva has anti-cancer activity in FaDu human head and neck squamous cell carcinoma cells by inducing cell death (IC₅₀ = 0.23 µg/mL) in a concentration- (0.01 – 10 µg/m1) and time-dependent (1 – 3 days) manner.41 It also increased expression levels of proteolytic genes of caspase-3, -7, and -9.41 Moreover, ethanol extract of A. decursiva root can suppress growth of Saos2 human osteogenic sarcoma cells and induce apoptotic cell death (IC₅₀ = 1.4 µg/ml) in a concentration (0.01–10 µg/m1)-dependent manner.8 Furthermore, proteolytic processing and activities of caspase-3 and -7 in Saos2 cells are increased by treatment with A. decursiva extract.8 Additionally, ethanol extract of A. decursiva root possesses cytotoxic (IC₅₀ = 0.21 µg/mL) activity and induces cell death of human oral cancer cell line KB.42 Treatment of KB cells with extract of A. decursiva induced apoptotic cell death in both dose- and time-dependent manner. It also decreased levels of procaspase-7 and -9 and activation of caspase-7.42 MeOH extract of A. decursiva and its different fractions also exhibit cytotoxic activity against HeLa cells.45 Columbianadin as a coumarin also possesses anticancer activity by inhibiting cell proliferation and inducing apoptosis and necroptosis of HCT116 colon cancer cells.46 Columbianadin exhibited cytotoxic activity (IC₅₀ = 32.4 µM), increased sub-G1 phase and expression levels of caspases-9, caspase-3, Bax, and p53, and down-regulated expression levels of Bcl-2, Bim, and BH3 in HTC116 cells. In addition, pretreatment with columbianadin at concentration of 50 µM increased apoptosis (annexin V+/PI+) and necroptosis (annexin V−/PI+). In addition, columbianadin suppressed cleaved caspase-8 but increased levels of RIP-3, activated PARP, and cleaved PARP in a concentration (12.5 − 50 µM) dependent manner. Furthermore, columbianadin induced the accumulation of ROS and imbalance of intracellular antioxidant enzymes such as SOD-1, SOD-2, catalase, and GPx-1.46

Anti-Alzheimer's disease activity

Acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) are three key enzymes that are effective in treating Alzheimer's disease (AD). MeOH extract of whole plant of A. decursiva and its solvent-soluble fractions have been tested for their AChE and BChE inhibitory activities using Elman's method. Butanol and ethyl acetate fractions at a final concentration of 100 µg/mL significantly inhibited AChE activity, with IC₅₀ values of 6.01 ± 0.09 and 9.67 ± 0.73 µg/mL, respectively. Butanol (IC₅₀ = 0.42 ± 0.01 µg/mL), dichloromethane (IC₅₀ = 2.35 ± 0.74 µg/mL), and ethyl acetate (IC₅₀ = 5.47 ± 0.38 µg/mL) fractions also exhibited potent inhibitory activities against BChE. Furthermore, butanol fraction (IC₅₀ = 9.1 ± 0.46 µg/mL) significantly inhibited β-secretase (BACE1) activity.14 Nodakenin, the major coumarin from A. decursiva, showed significant inhibitory activities against AChE, BChE, and BACE1, with IC₅₀ values of 33.67, 54.6, and 147.7 µM, respectively.14 Additionally, nodakenin (1.0mg/kg) improved memory impairment, enhanced proliferation and survival of newborn immature neuronal cells, and significantly increased phosphorylation level of Akt and expression level of GSK-3β.47 In addition, coumarins umbelliferone 6-carboxylic acid, 6-formyl umbelliferone, 4′-methoxy Pd-C-I, decursidine, 4-hydroxy Pd-C-III, Pd-C-I, Pd-C-II, and Pd-C-III that displayed strong anti-AD activities by inhibiting AChE, BChE, and BACE1 enzymes were isolated from this plant.14 15 16 Moreover, nodakenetin, umbelliferone, 3′(R)-O-acetyl-4′(S)-O-tigloylkhellactone, 2′-isopropyl psoralene, para-hydroxybenzoic acid, isorutarine, and cis-3′-acetyl-4′-angeloylkhellactone exhibited significant anti-AD activities by inhibiting AChE and BChE.14 15

Other activities

MeOH extract of A. decursiva root and its EtOA, chloroform, n-BuOH, and H₂O fractions exhibited anti-parasitic effects for the control of Dyschirius intermedius.48 Especially, its chloroform fraction (100 – 350 mg/L) exhibited the highest inhibitory activity against D. intermedius (EC₅₀ = 240.4 mg/l; EC₉₀ = 433.9 mg/l). Coumarin decursidine also displayed anaphylactic activity by decreasing ⁴⁵Ca uptake induced by concanavalin A into rat mast cells.49 It has been reported that 70% ethanol extract (25 – 800 µg/m1) of A. decursiva dried root possesses vasorelaxant effects on phenylephrine and KCl in vivo.50 The vasorelaxant effect of the extract was inhibited by pre-treatment (25 – 200 µg/m1) with glibenclamide, an ATP-sensitive K⁺ channel blocker. Furthermore, the extract of A. decursiva concentration-dependently (100 – 400 µg/m1) inhibited Ca²⁺ supplementation-induced vasoconstriction of aortic rings pretreated with phenylephrine or KCl in the presence of Ca²⁺.50 Recently, MeOH extract of A. decursiva root has been investigated for its potential to prevent or treat cerebral stroke.51 In vivo study showed that the extract (at concentrations of 60 mg/kg) significantly decreased infract lesions in C57BL/6 mice. Additionally, pretreatment with the extract at 200 mg/kg effectively suppressed expression levels of iNOS, reactive oxygen species (ROS), and malondialdehyde (MDA) and pro-inflammatory cytokines such as IL-1β and TNF-α in brain tissues of mice with MCAO-induced brain injury.51

Conclusion and perspectives

As presented in this review, pharmacological studies on A. decursiva and its putative active compounds, especially coumarins, support that several biological activities of A. decursiva can potentially impact human health. Coumarins can be effectively isolated and purified from A. decursiva root and its whole plant with various extraction analytical methods, mainly separation-based methods using TLC, HPLC, high-speed counter-current chromatography (HSCCC), and column chromatography (silica gel, reverse-phase, and Sephadex). Coumarins derived from A. decursiva have a wide range of crucial bioactivities, including anti-inflammatory, anti-diabetic, anti-Alzheimer's disease, anti-hypertension, anti-cancer, antioxidant, anthelmintic, prevention of cerebral stroke, and neuroprotective activities. Despite these reported biological activities of A. decursiva and coumarins derivatives, in vivo studies in animals and clinical studies must be conducted to understand effects of coumarins metabolites on human health because effects of these coumarins on human tissues and cells measured by in vitro do not accurately recapitulate their actual in vivo effects. Thus, there are still opportunities and challenges for research of coumarins. The number of modern studies on bioactive coumarins is increasing in biomedicine, suggesting that these compounds might have great medical significance in the future. This review presents a summary of studies published to date on this promising plant.