Chinese Journal of Natural Medicines  2015, Vol. 13 Issue (4): 0241-0249  
0

Cite this article as: 

MA Jian-Ping, GUO Zhi-Bing, JIN Ling, LI Ying-Dong. Phytochemical progress made in investigations of Angelica sinensis (Oliv.) Diels [J]. Chinese Journal of Natural Medicines, 2015, 13(4): 0241-0249.
[Copy]

Research funding

This work was supported by the National Science & Technology Supporting Program for the 12th Five-year Plan (2011BAI05B02) and the National Training Program of Innovation and Entrepreneurship for Undergraduates (201210731022).

Corresponding author

Tel: 86-931-2976650, Fax: 86-9312973367, E-mail: majp@fudan.edu.cn

Article history

Received on: 19-Apr.-2014
Phytochemical progress made in investigations of Angelica sinensis (Oliv.) Diels
MA Jian-Ping1 , GUO Zhi-Bing1, JIN Ling2, LI Ying-Dong2    
1 College of Life Science and Technology,Lanzhou University of Technology, Lanzhou 730050, China;
2 Department of Pharmacy, Gansu College of Traditional Chinese Medicine, Lanzhou 730000, China
[Abstract] The phytochemical progress on Angelica sinensis (Oliv.) Diels over the past decades is summarized. Since 1970s, 165 chemical constituents, including phthalides, phenylpropanoids, terpenoids and essential oils, aromatic compounds, alkaloids, alkynes, sterols, fatty acids, and polysaccharides have been isolated or detected from the various parts of the title plant.
[Key words] Angelica sinensis    Chemical constituents    Phthalides    Phenylpropanoids    Terpenoids and essential oils    Aromatic compounds    Sterols    Fatty acids    Polysaccharides    
Introduction

Angelica sinensis (Oliv.) Diels (Apiaceae), commonly called Danggui or Dong Quai, is a well-known medicinal plant cultivated mainly in the northwestern China. Its dried root is one of the most important crude drugs in traditional Chinese medicine, and has been used commonly for the treatment of gynecopathia, including anemia, dysmenorrhea, amenorrhea, premenstrual, and menopausal syndromes [1, 2], as well as for the management of cancer [3], cardiovascular [4], and Alzheimer’s diseases [5]. It is considered a “magic” drug due to the various effects of different medicinal parts of the herbal plant.

Angelica root is used to replenish and invigorate blood, stop pain, and moisten the intestines. The head of the roots is more effective for nourishing blood, the tail for moving blood, and the body for invigorating and nourishing blood [6]. A number of chemical constituents have been associated with the biological activities and clinical applications. Z-Ligustilide and ferulic acid have been officially used as marker compounds to characterize the quality of Dang Gui according to the current Chinese Pharmacopoeia (Committee for the Pharmacopoeia of China, 2010). Ligustilide has been extensively investigated, revealing an impressive pharmacological profile that includes, inter alia, reduction of cerebral infarct volume and improvement of neurobehavioral deficits, attenuation of lipopolysaccaride (LPS)-induced endotoxic shock, inhibition of vascular smooth muscle cell proliferation, anti-apoptotic, and analgesic effects [7]. Ferulic acid possesses many physiological functions, including antimicrobial and anti-cancer activities, and also protects against coronary disease, lowers cholesterol and increases sperm viability, ameliorates memory, enhances cholinergic activities and cerebral blood flow[8, 9]. Both compounds have anti oxidant, antithrombotic, and anti-inflammatory activities. However, this is insufficient to explain the pharmacological pleiotropy of Dang Gui by simply using ferulic acid and Z-ligustilide. In this review, the phytochemical progress made in researches of A. sinensis over the past decades is summarized.

Since 1970s, 165 chemical constituents, including phthalides, phenylpropanoids, terpenoids and essential oils, aromatic compounds, alkaloids, alkynes, sterols, fatty acids, and polysaccharides, have been isolated or detected from the various parts of the title plant (Table1), their structures are shown in Fig.1.

Table 1 Chemical constituents isolated from Angelica sinensis
Fig.1
Results

Twenty four phthalide monomers (1-24) are isolated from A. sinensis [5, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23]. To date, twenty dimeric phthalides have been obtained. Most of them are composed of two ligustilide units both having the Z-configuration (25, 27-29, 32, 35, 37, 40, 44), or one Z- form and one E- form (30, 33-34, 36, 38, 43), or both having the E- configura- tion (31, 39) [10, 11, 12, 14, 15, 20, 24, 25, 26, 27, 28, 29, 30]. Other compounds are consisted of one 3Z-ligustilide and one n-butylidenephthalide monomer (26, 41, 42) [11, 12, 14, 20, 24, 25]. The connection positions of the two moieties are labeled in the structures.

Ferulic acid (45) is found to be another one of the effective components in the rhizomes of A. sinensis [9, 11, 15, 17, 18, 19, 20, 21, 31, 32, 33, 45]. Six phenylpropenoids (46-51) and their esters (52-57), one lignan (58), and six coumarins (59-64) arealso isolated from the various parts of A. sinensis [9, 11, 15, 17, 20, 21, 22, 28, 31, 32, 33, 34, 35, 36, 37].

Monoterpenoids and sesquiterpenoids are the major constituents of the essential oil. Fourteen monoterpenoids (65-74, 82, 83, 85, 86), twelve sesquiterpenoids (75-81, 84, 87-90), and an alkane (91), alkene (92), and alkyl ketone (93) are distributed in the essential oil of A. sinensis [31, 35, 38, 39, 40, 41].

Thirty-two phenyl derivatives (94-125) which mainly consisted of mono-, di-, tri-, and tetra-substituted benzenes [11, 15, 20, 21, 33, 34, 35, 36, 39, 41, 42], and three flavonoid glycosides (126-128) are isolated from the aerial parts and roots of A. sinensis [33, 34].

To date, five polyynes (129-133) have been obtained from the roots of A. sinensis which exhibit antimicrobial, antibacterial, antifungal, antiproliferative, cytotoxic, and anti-TB activities [10, 11, 20, 33, 36, 43].

Three β-carboline type alkaloids (134-136), nicotinic acid (138), and choline (139) are isolated from the roots of A. sinensis [15, 28, 33, 44]. A new phenylpentanamine alkaloid (137) has been produced by an endophyte Bacillus subtilis from the surface-sterilized root of A. sinensis [44].

A triterpene (140) and four steroids (141-144) are isolated from the aerial parts and roots of A. sinensis [11, 15, 19, 33, 34].

Three fatty alcohol (145-147), twelve fatty acids, and their esters (148-159) are isolated from roots of A. sinensis [11, 13, 15, 18, 21, 22, 28, 35, 37, 41].

Six other types of compounds, including four nucleotides (160-163) and two furfural derivatives (164-165) are isolated from the various parts of this plant [15, 18, 20, 22, 34]. Amino acids, such as aspartic acid, glutamic acid, histidine, methionine, and tyrosine, among others, are also detected from the aqueous extract of A. sinensis radix as measured by amino acid analysis [15].

In addition to the low-molecular weight constituents mentioned above, the polysaccharides isolated from A. sinensis have drawn the attention of researchers and patients due to their remarkable biological activities [46, 47, 48, 49, 50]. An arabinoglucan, named APS-ld, having a backbone composed of (1, 4)-α-Dglucopyranosyl (Glcp) residues, and branches composed of (1, 6)-α-D-Glcp residues with a terminal β-L-arabofuranose (Araf) residue, is extracted from roots of A. sinensis [51, 52]. An Angelica polysaccharide which is isolated from the roots is composed of rhamnose, galacturonic acid, glucose, galactose, and arabinose in a molar ratio of 0.05 : 0.26 : 14.47 : 1.00 : 1.17. Glucose is the predominant monosaccharide in the Angelica polysaccharide [53]. An analytical method involving high performance capillary electrophoresis (HPCE) has been developed to simultaneously separate and identify the component monosaccharides of A. sinensis polysaccharide fractions (APFs), named APF1, APF2, and APF3. The predominant sugars in APFs are identified as arabinose, glucose, rhamnose, galactose, and galacturonic acid, as well as trace amounts of mannose and glucuronic acid [54]. Three polysaccharide fractions from the roots of A. sinensis, ASPF1, ASPF2, and ASPF3, are obtained through cellulose DEAE-52 column chromatography[55]. A novel polysaccharide, named A. sinensis polysaccharide (ASP), has been obtained from the powdered and defatted roots of A. sinensis. The molecular weight of ASP is determined to be 78 kDa and with 95.0% sugars, mostly consisting of arabinose, glucose, and galactose with a molar ratio of 1 : 5.68 : 3.91 [56].

Conclusion

In summary, phytochemical studies on A. sinensis have revealed that the typical constituents are phthalide monomers and dimers, phenylpropanoids, aromatic compounds, terpenoids and essential oils, and polysaccharides. Current research focuses mainly on the mechanisms of the pharmacological effects associated with A. sinensis crude extract, and of the main, active, low-molecular weight components [57, 58], structural elucidation and activity assessment of the polysaccharides and their derivatives [50, 59], the development and validation of chromatographic methods with various detection methodologies for the determination of active or toxic components from Dang Gui or biosamples [60, 61, 62]. This review, to a certain extent, provides a necessary foundation for further research and development of medicines containing A. sinensis and related preparations.

References
[1] Sarker SD, Nahar L. Natural medicine: the genus Angelica [J]. Curr Med Chem, 2004, 11: 1479-1500.
[2] Monograph: Angelica sinenesis (Dong Quai) [J]. Altern Med Rev, 2004, 9(4): 429-433.
[3] Su ZY, Khor TO, Shu LM, et al. Epigenetic reactivation of Nrf2 in murine prostate cancer TRAMP C1 cells by natural phytochemicals Z-ligustilide and radix Angelica sinensis via promoter CpG demethylation [J]. Chem Res Toxicol, 2013, 26(3): 477-485.
[4] Tsai NM, Chen YL, Lee CC, et al. The natural compound n-butylidenephthalide derived from Angelica sinensis inhibits malignant brain tumor growth in vitro and in vivo [J]. J Neurochem, 2006, 99(4): 1251-1262.
[5] Ho CC, Kumaran A, Hwang LS. Bio-assay guided isolation and identification of anti-Alzheimer active compounds from the root of Angelica sinensis [J]. Food Chem, 2009, 114: 246-252.
[6] Fang L, Xiao XF, Liu CX, et al. Recent advances in studies on Angelica sinensis [J]. Chin Herb Meds, 2012, 4(1): 12-25.
[7] Yang JY, Chen HH, Wu J, et al. Advances in studies on pharmacological functions of ligustilide and their mechanisms [J]. Chin Herb Meds, 2012, 4(1): 26-32.
[8] Lin Z, Gu J, Xiu J, et al. Traditional Chinese medicine for senile dementia [J]. J Evid-Based Compl Alt Med, 2012: 1-13.
[9] Hsien MT, Tsai FH, Lin YC, et al. Effects of ferulic acid on the impairment of inhibitory avoidance performance in rats [J]. Planta Med, 2002, 68(8): 754-756.
[10] Chen QC, Lee JP, Jin WY, et al. Cytotoxic constituents from Angelicae sinensis radix [J]. Arch Pharm Res, 2007, 30(5): 565-569.
[11] Deng SX, Chen SN, Yao P, et al. Serotonergic activity-guided phytochemical investigation of the roots of Angelica sinensis [J]. J Nat Prod, 2006, 69(4): 536-541.
[12] Lü JL, Duan JA, Tang YP, et al. Phthalide mono- and dimers from the radix of Angelica sinensis [J]. Biochem Syst Ecol, 2009, 37: 405-411.
[13] Wang YL, Liang YZ, Chen BM, et al. LC-DAD-APCI-MS- based screening and analysis of the absorption and metabolite components in plasma from a rabbit administered an oral solution of Dang Gui [J]. Anal Bioanal Chem, 2005, 383(2): 247-254.
[14] Li WD, Wu Y, Liu XD, et al. Isolation, identification and screen of lactone compounds from Angelica sinensis [J]. Chin Tradit Pat Med, 2011, 33(12): 2114-2118.
[15] Chen YZ, Zhang HD. Analysis of the chemical ingredients of Angelica sinensis, Analysis of non-volatile constituents of roots [J]. Chem J Chin Univ, 1984, 5(4): 515-520.
[16] Lu XH, Liang H, Zhao YY. Isolation and identification of the ligustilide compounds from the root of Angelica sinensis [J]. China J Chin Mat Med, 2003, 28(5): 423-425.
[17] Lao SC, Li SP, Kan KKW, et al. Identification and quantification of 13 components in Angelica sinensis (Dang Gui) by gas chromatography-mass spectrometry coupled with pressurized liquid extraction [J]. Anal Chim Acta, 2004, 526(2): 131-137.
[18] Lin M, Zhu GD, Sun QM, et al. Chemical studies of Angelica sinensis [J]. Acta Pharm Sin, 1979, 14(9): 529-534.
[19] Wang HY, Chen RX, Xu HZ. Studies on chemical constituents of radix Angelicae sinensis [J]. China J Chin Mat Med, 1998, 23(3): 167-169.
[20] Song QY, Fu YB, Liu J, et al. Chemical constituents from An- gelica sinensis [J]. Chin Tradit Herb Drugs, 2011, 42(10): 1900-1904.
[21] Lu XH, Zhang JJ, Liang H, et al. Chemical constituents of Angelica sinensis [J]. J Chin Pharm Sci, 2004, 13(1): 1-3.
[22] Huang WH, Song CQ. Studies on the chemical constituents of Angelica sinensis [J]. Acta Pharm Sin, 2003, 38(9): 680-683.
[23] Hu CY, Ding XL. Isolation and identification of lactone compounds from the essential oil of Angelica sinensis [J]. Chin Tradit Herb Drugs, 2004, 35(4): 383-384.
[24] Deng SX, Chen SN, Lu J, et al. GABAergic phthalide dimers from Angelica sinensis (Oliv,) Diels [J]. Phytochem Anal, 2006, 17(6): 398-405.
[25] Lu XH, Zhang JJ, Zhang XX, et al. Study on biligustilides from Angelica sinensis [J]. China J Chin Mat Med, 2008, 33(19): 2196-2201.
[26] Li XN, Chen YY, Cheng DP, et al. Two phthalide dimers from the radix of Angelica sinensis [J]. Nat Prod Res, 2012, 26(19): 1782-1786.
[27] Su DM, Yu SS, Qin HL. New dimeric phthalide derivative from Angelica sinensis [J]. Acta Pharm Sin, 2005, 40(2): 141-144.
[28] Nguyen THV, Nguyen THA, Tran VS, et al. Studies on chemical composition of Angelica sinensis, Part VI-Angelicolide and three other compounds [J]. Tap Chi Hoa Hoc, 2005, 43(6): 749-752.
[29] Chen YZ, Zhang HD, Chen NY, et al. Analysis of the chemical ingredients of Angelica sinensis, Structural elucidation of angelicide [J]. Chin Sci Bull, 1983, 19: 1206-1207.
[30] Lin LZ, He XG, Lian LZ, et al. Liquid chromatographic- electrospray mass spectrometric study of the phthalides of Angelica sinensis and chemical changes of Z-ligustilide [J]. J Chromatogr A, 1998, 810: 71-79.
[31] Jiang W, Wang CH, Wang ZT. Water-soluble chemical constituents of Angelica sinensis (Oliv,) Diels [J]. Chin Pharm J, 2010, 45(2): 101-103.
[32] Xue WX, Hua YL, Guo YS, et al. Changes of composition in different parts of Angelica sinensis based on geoherbs [J]. J Gansu Agric Univ, 2012, 47(1): 149-154.
[33] Zhao XJ, Wang HF, Zhao DQ, et al. Isolation and identification of the chemical constituents from roots of Angelica sinensis (Oliv,) Diels [J]. J Shenyang Pharm Univ, 2013, 30(3): 182-185, 221.
[34] Zhou GS, Yang NY, Tang YP, et al. Chemical constituents from the aerial parts of Angelica sinensis and their bioactivities [J]. Chin J Nat Med, 2012, 10(4): 295-298.
[35] Chen YZ, Chen NY, Ma XY, et al. Analysis of the ingredients of Angelica sinenesis, Identification of the volatile components from the roots of Angelica sinensis by capillary GC-MS [J]. Chem J Chin Univ, 1984, 5(1): 125-128.
[36] Nguyen THV, Nguyen THA, Tran VS, et al. Chemical study of Angelica sinensis [J]. Tap Chi Hoa Hoc, 2005, 43(4): 494-498.
[37] Chen F, Yao C. Advances in studies on chemical constituents of Angelica sinensis [J]. Chongqing J Res Chin Drugs Herbs, 2002, (1): 49-53.
[38] Yang NY, Zhou GS, Tang YP, et al. Two new alpha-pinene derivatives from Angelica sinensis and their anticoagulative activities [J]. Fitoterapia, 2011, 82(4): 692-695.
[39] Chen YZ, Li HQ, Chen NY, et al. Analysis of the volatile components from the leaves of Angelica sinensis by capillary GC-MS [J]. J Lanzhou Univ (Med Sci), 1985, 21(3): 130-132.
[40] Liu GS, Lu FS. Chemical analysis of the essential oil from Angelica sinensis and TLC comparasion of its constituents with those from Levisticum officinale [J]. Chin Pharm J, 1979, 14(8): 375-377.
[41] Liu LN, Mei QB, Cheng JF. Analysis of the chemical components of the essential oil from Angelica sinensis (Oliv,) Diels [J]. Chin Tradit Pat Med, 2005, 27(2): 204-206.
[42] Yi LZ, Liang YZ, Wu H, et al. The analysis of radix Angelicae sinensis (Dang Gui) [J]. J Chromatgr A, 2009, 1216: 1991-2001.
[43] Deng SX, Wang YH, Inui T, et al. Anti-TB polyynes from the roots of Angelica sinensis [J]. Phytother Res, 2008, 22: 878-882.
[44] Yang NY, Jiang S, Shang EX, et al. A new phenylpentanamine alkaloid produced by an endophyte Bacillus subtilis isolated from Angelica sinensis [J]. J Chem Res, 2012, 36(11): 647.
[45] Ou SY, Kwok KC. Ferulic acid: pharmaceutical functions, preparation and applications in foods [J]. J Sci Food Agric, 2004, 84: 1261-1269.
[46] Yang TH, Jia M, Zhou SY, et al. Antivirus and immune enhancement activities of sulfated polysaccharide from Angelica sinensis [J]. Int J Biol Macromol, 2012, 50: 768-772.
[47] Chen Y, Duan JA, Qian DW, et al. Assessment and comparison of immunoregulatory activity of four hydrosoluble fractions of Angelica sinensis in vitro on the peritoneal macrophages in ICR mice [J]. Int Immunopharmacol, 2010, 10: 422-430.
[48] Ye YN, So HL, Liu ESL, et al. Effect of polysaccharides from Angelica sinensis on gastric ulcer healing [J]. Life Sci, 2003, 72: 925-932.
[49] Shang P, Qian AR, Yang TH, et al. Experimental study of antitumor effects of polysaccharides from Angelica sinensis [J]. World J Gastroenterol, 2003, 9(9): 1963-1967.
[50] Lee JG, Hsieh WT, Chen SU, et al. Hematopoietic and myeloprotective activities of an acidic Angelica sinensis polysaccharide on human CD34+ stem cells [J]. J Ethnopharmacol, 2012, 139: 739-745.
[51] Cao W, Li XQ, Liu L, et al. Structural analysis of water-soluble glucans from the root of Angelica sinensis (Oliv,) Diels [J]. Carbohydr Res, 2006, 341: 1870-1877.
[52] Cao W, Li XQ, Liu L, et al. Structure of an anti-tumor polysaccharide from Angelica sinensis (Oliv,) Diels [J]. Carbohydr Polym, 2006, 66: 149-159.
[53] Zhou SY, Zhang BL, Liu XY, et al. A new natural Angelica polysaccharide based colon-specific drug delivery system [J]. J Pharm Sci, 2009, 98(12): 4756-4768.
[54] Yang XB, Zhao Y, Zhou YJ, et al. Component and antioxidant properties of polysaccharide fractions isolated from Angelica sinensis (Oliv,) Diels [J]. Biol Pharm Bull, 2007, 30(10): 1884-1890.
[55] Ai ST, Fan XD, Fan LF. Extraction and chemical characterization of Angelica sinensis polysaccharides and its antioxidant activity [J]. Carbohydr Polym, 2013, 94: 731-736.
[56] Liu JY, Zhang Y, You RX, et al. Polysaccharide isolated from Angelica sinensis inhibits hepcidin expression in rats with iron deficiency anemia [J]. J Med Food, 2012, 15(10): 923-929.
[57] Yang YQ, Chin A, Zhang LK, et al. The role of traditional Chinese medicines in osteogenesis and angiogenesis [J]. Phytother Res, 2014, 28(1): 1-8.
[58] Li WD, Wu Y, Liu XD, et al. Antioxidant properties of cis-Z, Z'-3a,7a', 7a,3a'-dihydroxy ligustilide on human umbilical vein endothelial cells in vitro [J]. Molecules, 2013, 18: 520-534.
[59] Yang TH, Jia M, Zhou SY, et al. Antivirus and immune enhancement activities of sulfated polysaccharide from Angelica sinensis [J]. Int J Biol Macromol, 2012, 50: 768-772.
[60] Zhang XY, Qiao H, Shi YB, et al. HPLC method with fluorescence detection for the determination of ligustilide in rat plasma and its pharmacokinetics [J]. Pharm Biol, 2014, 52(1): 21-30.
[61] Yang YL, Yang T, Yang YH, et al. Determination of light toxic compound coumarin in enrichment Angelica pills and Angelica sinensis by ultra performance liquid chromatography [J]. Chin J Anal Chem, 2013, 41(11): 1744-1748.
[62] Li Y, Wang SW, Tu HH, et al. Simultaneous quantification of six main active constituents in Chinese Angelica by high-performance liquid chromatography with photodiode array detector [J]. Pharmacog Mag, 2013, 9(34): 114-119.