2 Department of Pharmacy, Gansu College of Traditional Chinese Medicine, Lanzhou 730000, China
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 , cardiovascular , and Alzheimer’s diseases . 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 . 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 . 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.
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 .
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 .
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 . 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 . Three polysaccharide fractions from the roots of A. sinensis, ASPF1, ASPF2, and ASPF3, are obtained through cellulose DEAE-52 column chromatography. 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 .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.
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