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Article | Open Access

In-depth exploration of bioactive constituents, biosynthetic pathways, and pharmacological mechanisms of Angelica sinensis: implications for therapeutic development

Xiumin Zhanga,b, Lijun Fub, Ruimei Zhangb, Li Liub, Yongzheng Mab, Na Zhanga()
College of Food Engineering, Harbin University of Commerce, Harbin 150028, China
Beijing Academy of Food Sciences, Beijing 100068, China

Peer review under responsibility of Tsinghua University Press.

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• Diverse Bioactive Components: The primary bioactive components in Angelica sinensis include polysaccharides, volatile oils, organic acids, and flavonoids, which play significant roles in promoting blood circulation, modulating immunity, and alleviating pain.

• Biosynthesis Pathways and Influencing Factors: The article explores the biosynthesis pathways of these bioactive components, particularly focusing on key enzymes and transcription factors, and reveals the genetic and environmental factors that influence their synthesis and accumulation.

• Bioactive Properties and Mechanisms: Research on the bioactive properties of this herb indicates that it possesses multiple health benefits, including hepatoprotection, anti-inflammatory effects, immune modulation, anti-tumor activity, circulatory enhancement, and neuroprotection, thereby supporting its potential applications as a functional food and nutraceutical product.

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Abstract

Angelica sinensis, a well-known traditional Chinese medicinal herb with the unique property of being both a medicine and an edible plant, has been widely used for promoting blood circulation, modulating immunity, and relieving pain. This review comprehensively investigates the extraction methods, structural characteristics, and biological activities of its primary bioactive components, such as polysaccharides, volatile oils, organic acids, and flavonoids. The biosynthesis pathways of these compounds, along with the key enzymes and transcription factors involved, are investigated to understand the factors influencing their synthesis and accumulation. Additionally, the biological activities of A. sinensis, including hepatoprotective, anti-inflammatory, immune-modulatory, anti-tumor, circulatory benefits, and neuroprotection, along with their underlying mechanisms are introduced. These findings provide a solid foundation for the development of A. sinensis as a valuable resource in functional foods and pharmaceutical products.

Keywords

Angelica sinensisBioactive compoundsBiosynthesis pathwaysBiological activityFunctional foods

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Food Science and Human Wellness
Volume 14 Issue 2,
February 2025
Article number: 9250498
DOI: 10.26599/FSHW.2025.9250498
Cite this article:
Zhang X, Fu L, Zhang R, et al. In-depth exploration of bioactive constituents, biosynthetic pathways, and pharmacological mechanisms of Angelica sinensis: implications for therapeutic development. Food Science and Human Wellness, 2025, 14(2): 9250498. https://doi.org/10.26599/FSHW.2025.9250498
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Detailed structural information of the reported Angelica polysaccharides.

No. Compound name Extraction method Molecular weight (Da) Monosaccharide composition Linkage mode Biological activity Reference
Note: Glc, Glucose; Gal, Galactose; Ara, Arabinose; Rha, Rhamnose; Man, Mannose; Xyl, Xylose; Fuc, Fucose; GalA, Galacturonic acid; ND, no data.
1 ASP Extracted with hot water extracting and ethanol precipitating method, then purified by Sevag method, and dried by frozen drier 1 × 104−1.1 × 105 Rha:Xyl:Ara:Glc:Gal = 1:2.2:5.8:178:12 ND ND [9]
2 WASP (water-soluble-ASP) 11 Extracted with hot water at 80 ℃, then fractionated by aion-exchange chromatography and gel filtration chromatography respectively 3.8 × 105 Glc ND ND [10]
3 WASP12 1.9 × 104 Ara, Gal
4 W-ASP3 6.2 × 104 Gal, Ara, Rha, Glc, Man, GlcA
5 AP Extracted with boiling water, precipitation with three volumes of ethanol. Then, fractionated by chromatography 5 × 104 Rha:Ara:Man:Glc:Gal = 1.00:4.54:2.98:11.09:7.45 ND Immunomodulation [11]
6 APS-1cⅠ Purified by anion-exchange and gel-filtration chromatography 1.7 × 105 Glc [→6)-α-D-Glc-(1→]n ND [12]
7 APS-1cⅡ 3.9 × 104 Glc →4)-α-D-Glc-(1→6)-α-D-Glc-(1→[→4)-α-D-Glc-(1→4)-α-D-Glc-(1→6)-α-D-Glc-(1→4)-α-D-Glc-(1→4)-α-D-Glc-(1→]n
8 APS-2a Water extraction deprotein ethanol precipitation and DEAE-sephades A-25 column chromatography respectively and was further purifed by Sephacryl S-400 and Sephadex G-100 column chromatography 7.4 × 105 Ara:Gal:Rha:Glc:GalA = 38.2:7.5:2.6:1.0:4.9 ND Antitumor [13]
9 APS-bⅡ Purified by anion exchange cellulose column and Sephadex G-100 gel column chromatography 1.3 × 104 Glc:Gal:Xyl:Ara = 8.4:2.7:1.8:1.0 ND Antitumor [14]
10 ASP Extracted with boiling water under reflux for 30 min, frozen at −70 ℃ and then lyophilised ND Saccharose (the major sugar, 18.55%), Glc and Fuc (the minor components) ND Antioxidant [15]
11 ASP3a Water extraction and ethanol precipitation, followed by purification steps including DEAE-cellulose and gel filtration chromatography 5.9 × 105 Glc:Gal:Ara:Rha:Man = 3.2:1.7:2.5:1.3:1.0 ND Antitumor [16]
12 ASP3b 2.3 × 105 Glc:Gal:Ara:Rha:Man = 2.3:5.4:6.8:1.0:1.2
13 APS3c 1.4 × 104 Glc:Gal:Ara:Rha:Man:Xyl = 6.3:4.7:6.7:6.5:1.6:1.0
14 APS-1d Extracted with hot water extracting and ethanol precipitating method, then dialyzed and lyophilized to yield APS-0. APS-0 was purified through DEAE-sephadex A-25 and Sephadex G-100 columns with NaCl gradients to obtain APS-1d 5.1 × 103 Glc:Ara = 13.8:1.0 Main chain: 1, 4-α-D-Glc; Branches: 1, 6-α-D-Glc; Terminal: β-L-Ara Antitumor [17]
15 ASP Extracted with hot water extracting and ethanol precipitating method, then purified with Sephadex G-50 column 7.29 × 103 Ara:Glc:Gal = 1:2.5:7.5 ND Hepatoprotective [18]
16 APS-2Ⅰ Extracted with hot water extracting and ethanol precipitating method, then fractionated by Sephadex A-25 column (APS-1 to APS-4) and Sephadex G-100 column (APS-1Ⅰ to APS-4Ⅱ), respectively 7.2 × 105 Man:Rha:GalA:Glc:Gal: Ara = 4:5:1:10:23:39 Main chain: →4)-α-D-GalA-(1→3)-α-L-Rha-(1→2)-α-D-Man-(1, 6→6-OMe, 4)-α-D-Gal-(1→3)-α-L-Rha-(1→2)-α-D-Man-(1, 6→α-D-T-Gal;Side chain 1: →2)-α-D-Man-(6→1)-β-D-Gal-(6→1)-β-D-Gal(→6;Side chain 2: 5→)-α-L-Ara-(1→3)-α-L-Ara-(1→3)-α-L-Ara-(1→3)-α-L-Ara-(1→4)-β-D-Gal-(1→6)-α-D-Man Antitumor [19]
17 ASP-4Ⅰ Extracted with hot water extracting and ethanol precipitating method, then fractionated by DEAE-sephadex A-25 and Sephadex G-100 column chromatography (APS-1 to APS-4), and further into APS-4Ⅰ and APS-4Ⅱ 1.61 × 104 Glc [→6)-α-Glc-(1→]n Antitumor [20]
18 APS-4Ⅱ 1.11 × 104 Glc:Gal:Ara = 3.7:1.0:2.1 →6)-α-Glc-(1→6)-α-Glc-(1→5)-α-Ara-(1→5)-α-Ara-(1→3, 5)-α-Ara-(1→3)-β-Gal-(1→3)-β-Gal1→4)-α-Gal-(1→3)-α-Ara-(1→3, 5)-α-Ara-(1→

Extraction method of polysaccharides from A. sinensis.

Extraction methods Process parameters Yield (%) Qualitative/quantitative methods References
Note: ND, no data.
Hot water extraction Solid-liquid ratio 1:5 (distilled water); extraction time 130 min; extract 5 times; anhydrous ethanol precipitation 5.6 ND [23]
Ultrasonic extraction Solid-liquid ratio 1:7, ultrasound power 180 W, extraction time 45 min, and extraction temperature 90 ℃ 6.96 ND [24]
Enzyme extraction 1.0% cellulase, extraction temperature 60 ℃, extraction time 60 min, pH 6.0, 1.0% pectinase, extraction temperature 50 ℃, extraction time 60 min, pH 5.5 24.55 (cellulase); 24.81 (pectinase) Qualitative: ND; Quantitative: ultraviolet spectrophotometer [24-25]
Microwave-assisted extraction Solid-liquid ratio 1:10, microwave high heat, extraction 3 times, each extraction for 4 min 14.1 Qualitative: ND; Quantitative: ultraviolet spectrophotometer [25]

Extraction method of volatile oils from A. sinensis.

Ingredients Extraction methods Process parameters Yield (%) Qualitative/quantitative methods References
Note: HPLC, high-performance liquid chromatography; ND, no data.
Volatile oils (LIG) Organic solvent extraction Solid-liquid ratio 1:12 (g/mL, 70% ethanol), extraction 1 h, extraction temperature 50 ℃ 1.58 Qualitative: Thin layer chromatography; Quantitative: HPLC [32]
Steam distillation Solid-liquid ratio 1:6, extraction 8 h, and the mass ratio of NaCl to the liquid is 1:5 0.42 Qualitative: ND; Quantitative: HPLC [33]
CO2 supercritical fluid extraction Extraction pressure 10 MPa, extraction temperature 50 ℃, extraction time 20 min ND Qualitative: ND; Quantitative: HPLC [34]

Extraction method of active ingredients from A. sinensis.

Ingredients Extraction methods Process parameters Yield (%) Qualitative/quantitative methods References
Note: UV, ultraviolet; ND, no data.
Organic acids (FA) Flash/ethanol reflux extraction Solid-liquid ratio 1:12 (70% ethanol), extraction 1 min for flash, and 150 min for eflux extraction 0.60 (flash); 0.69 (ethanol reflux) Qualitative: UV spectrum; Quantitative: HPLC [37]
Ultrasound extraction Solid-liquid ratio 1:8 (1% NaOH), extraction temperature 51.8 ℃, and extraction time 4.49 min 0.81 Qualitative: ND; Quantitative: HPLC [38]
Supercritical CO2 extraction Particle size was between 0.30−0.85 mm, the extraction pressure was 35 MPa, and the program of extraction temperature was 60−50−45 ℃, 80% C2H5OH as entrainer 0.0042 Qualitative: UV spectrum; Quantitative: HPLC, and GC-MS [39]
Temperature-controlled hydrophobic ionic liquids-based ultrasound/heating-assisted extraction Solid-liquid ratio 1:40, extraction temperature 60 ℃, ultrasound time 9 min, centrifugal speed 11000 r/min and the centrifugal time 5 min 0.86 Qualitative: ND; Quantitative: HPLC [40]

Extraction method of flavonoids from A. sinensis.

Extraction methods Process parameters Yield (%) Qualitative/quantitative methods References
Note: ND, no data.
Ethanol refluxing extraction Solid-liquid ratio 1:40 (80% ethanol), extraction temperature 85 ℃, extraction time 2 h 1.0 Qualitative: ND; Quantitative: ultraviolet spectrophotometer [43]
Ethanol extraction Solid-liquid ratio 1:11 (70% ethanol), extraction time of 2.5 h, and extraction temperature of 60 ℃ 0.0023 Qualitative: ND; Quantitative: ultraviolet spectrophotometer [44]
Ethanol refluxing extraction Solid-liquid ratio 1:40 (40% ethanol), extraction temperature 85 ℃, extraction time 1.5 h 9.2 Qualitative: ND; Quantitative: ultraviolet spectrophotometer [45]

Overview of cloned genes identified in A. sinensis Radix.

Gene name Classification and function Expression and effects in A. sinensis References
AsCOMT Involve in methylation, possibly participating in FA biosynthesis Expression is high in roots and flowers; low expression in leaves [64]
AsPAL Involve in phenylpropanoid metabolic pathway, responsible for controlling the rate-limiting step of biosynthesis Expression is high in roots, possibly involved in FA and coniferyl aldehyde biosynthesis [61]
As4CL Involved in the biosynthesis of various phenylpropanoid metabolites across species Expression is high in roots, stems, and leaves; likely regulates FA biosynthesis [62]
AsMYB4 MYB transcription factor family Expression is low in roots, possibly involved in regulating phenylpropanoid metabolism [67]
AsC3H Involved in the P450 family, catalyzing the hydroxylation of p-coumaric acid at the C3 position in the lignin biosynthesis pathway Expression is specific to certain tissues and may differ across tissues in response to environmental stimuli [63]
AsDXR Involved in the methylerythritol phosphate (MEP) pathway, crucial for the synthesis of terpenoids, including monoterpenoids, sesquiterpenoids, and diterpenoids Expression is high in roots and low in other tissues, suggesting a role in the MEP pathway for key metabolites [79]
AsEF-1β Involve in protein synthesis and the response to abiotic stress May be involved in the response to UV-B radiation [80]
FT, SOC1 (SOC1-4) Important flowering-related genes May be involved in the regulation of flowering time in A. sinensis [81]
GA2ox6, GA20ox1 Repress MADS-box gene expression and regulate GA biosynthesis, delaying flowering; GA20ox1 converts GA12 to GA9 May be involved in the flowering regulation pathway in coordination with hormonal signals [82]

Biological activity and potential mechanism of active ingredients in A. sinensis.

Ingredients Biological activity Mechanism References
ASP Hepatoprotective Reduce lipid accumulation and fatty regeneration [85]
ASP Hepatoprotective Alleviates chronic liver fibrosis by inhibiting hepatic stellate cell activation through the IL-22/STAT3 pathway [86]
ASP Hepatoprotective Suppress lipid peroxidation and oxidative stress, along with the inhibition of apoptosis to improve acetaminophen-induced acute liver injury [86-87]
ASP Hepatoprotective High liver specificity due to affinity for asialoglycoprotein receptors, aiding in drug delivery to the liver [88]
Angelica polysaccharide Anti-inflammatory and immunomodulatory Repress NF-κB and JAK2/STAT3 pathways by regulating miR-10a to mitigate LPS-evoked inflammatory injury [89]
ASP Anti-inflammatory and immunomodulatory Activate ERK1/2-dependent autophagy in chondrocytes to rescue SNP-induced apoptosis [90]
ASP Anti-inflammatory and immunomodulatory Inhibit myeloperoxidase activity, pro-inflammatory cytokine expression, and apoptosis to relieve dextran sodium sulfate-induced colitis [91]
ASP Anti-inflammatory and immunomodulatory Enhances activation of immune cells and cytokine secretion, acting as an immune enhancer [92]
Angelica polysaccharide Anti-inflammatory and immunomodulatory Upregulates immune cell and enhances immune response through STAT1 and STAT3 signaling pathways [93]
ASP Anti-inflammatory and immunomodulatory Stimulates strong immune responses when encapsulated with OVA in nanoparticle carriers as vaccine adjuvant [94]
ASP Anti-tumor Repress tumorigenesis of neuroblastoma cell line SH-SY5Y cells through miR-675-mediated inactivation of the PI3K/AKT and JAK/STAT pathways [95]
ASP Anti-tumor Decrease hepcidin expression, which can reduce iron burden and inhibit tumor proliferation through JAK/STAT and bone morphogenetic protein (BMP)-mothers against decapentaplegic homolog (SMAD) pathways [96]
ASP Anti-tumor Promote apoptosis of leukemia cells [19]
ASP Anti-tumor Serves as a targeted drug delivery carrier, to improve tumor microenvironment and enhance immune function, resulting in synergistic antitumor effect with chemotherapy drugs [97]
ASP Anti-tumor Serves as a drug delivery carrier targeting liver cancer, generates superior antitumor activity [98]
Z-LIG Anti-tumor Induce ovarian cancer cell death by inducing oxidative stress [99]
Z-LIG Anti-tumor Enhances tamoxifen therapy in resistant breast cancer by inhibiting autophagy. [100]
ASP Hematopoietic Prevent the JAK, SMAD and ERK pathways to down-regulate hepcidin [101]
ASP Hematopoietic Restore erythropoietin (EPO) production and improve iron availability by blocking GATA-binding factor 2 (GATA2) and NF-κB activation [102]
ASP Hematopoietic Delay oxidative stress-induced premature senescence of 5-fluorouracil-treated feeder co-cultured hematopoietic cells via down-regulation of over-activated Wnt/β-catenin signaling [103]
ASP Hematopoietic Promote the expression of cyclinD2 mRNA, downregulate the surface content of CD44 and CD49d on mononuclear cells in the bone marrow [104-106]
ASP Hematopoietic Regulate mitochondrial function to reduce ROS, MDA, and MAO levels, and inhibit excessive apoptosis of hematopoietic stem cells [107]
ASP Hematopoietic Reduce oxidative stress and apoptosis via reactivation of nuclear factor erythroid 2-related factor 2 (Nrf2) and PI3K/AKT pathways [108]
Volatile oil Vasodilation and antihypertensive Inhibit the release of calcium ions and the influx of external calcium, reduce ET-1, and increase NO to relax blood vessels [109-110]
Volatile oil Vasodilation and antihypertensive Inhibit inflammatory and oxidative pathways, suppress the generation of VCAM-1 and C-reactive protein, and enhance the levels of SOD and CAT [111]
Volatile oil Vasodilation and antihypertensive Downregulate the expression of AT1R and the vascular endothelial tissue SLC7A1 through miR122, antagonizing the renin-angiotensin system to regulate vascular endothelial signaling factors [112-113]
A. sinensis injection Vasodilation and antihypertensive Inhibit the overexpression of transforming growth factor-beta 1 (TGF-β1)/PI3K pathway in liver tissue, reduce portal vein pressure, and regulate changes in portal vein hemodynamics [114]
Volatile oil Vasodilation and antihypertensive Regulate the PI3K/Akt/endothelial nitric oxide synthase (eNOS) signaling pathway to reduce blood pressure [115]
A. sinensis Anticoagulation and anti-thrombotic Inhibit adenosine diphosphate- or arachidonic acid-induced platelet aggregation [116]
A. sinensis extract Neuroprotective Activate p38 MAPK-mediated p90 ribosomal S6 kinase (p90RSK)/phosphorylated Bcl-2-associated death promoter (p-Bad)-induced anti-apoptotic-Cytc/caspase-3-related and p90RSK/ cAMP-response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) survival signaling pathways [117]
A. sinensis extract Neuroprotective activation of p38 MAPK-mediated CREB/BDNF, glial cell line-derived neurotrophic factor (GDNF), and VEGF-A signaling pathways [118]
LIG Neuroprotective Penetrates blood-brain barrier, providing potential protective effects on the nervous system [119]
LIG Neuroprotective Induct α-processing of APP and Klotho and potential Aβ clearance [120]
Z-LIG Neuroprotective Inhibit p38 and activation of PI3K/Akt signaling pathways concurrently to improve Aβ fibrils-induced neurotoxicity [121]