Chemical composition of 1
The compounds isolated and identified from Angelica sinensis mainly include volatile oil, organic acids, polysaccharides and flavonoids.
The content of volatile oil in 1. 1 Angelica sinensis is about 1%, which is one of the main effective components of Angelica sinensis. The content of ligustilide in volatile oil is the highest, followed by butenyl phthalide. Liu Guosheng et al. (1) once divided the volatile oil of Angelica sinensis into three parts: neutral, phenolic and acidic. From the chemical structure, the main components of volatile oil are phthalide and its dimer compounds.
1. 1. 1 phthalides: phthalides are the main components in the volatile oil of Angelica sinensis, and they are also the earliest compounds isolated and identified from Angelica sinensis, including Z- ligustilide, E- ligustilide, Chuanxiong lactone A, E- butylphthalide and Z- butylphthalide. 1. 1.2 phthalide dimer: phthalide dimer is a compound isolated and identified from Angelica sinensis in recent years, mainly including Z-383'a, 7'a- tetrahydro "6,3', 7,7' a-dimerization levistolideA, with the same name, V-,.
1. 1.3 Other components: The volatile oil of Angelica sinensis also contains terpenoids represented by wormwood, cedrene and caryophyllene oxide. Alcohol compounds represented by butenyl benzene, clove oil and p-vinyl guaiacol; Alkane compounds represented by tetradecane, nonane and undecane.
1.2 Organic acid Angelica contains many organic acid compounds, the representative of which is ferulic acid. Ferulic acid is an effective component isolated from Angelica sinensis earlier. Since Lin Mao and others first extracted and separated ferulic acid from Angelica sinensis in 1979, many scholars have studied the extraction technology and content determination of ferulic acid? . At present, ferulic acid is an index component for quality control of Angelica sinensis in China Pharmacopoeia 20 10. At the same time, ferulic acid is also an index component for quality control of Ligusticum chuanxiong and Ligusticum. However, ferulic acid exists in many plants and is not a characteristic component of Angelica sinensis. In addition, acid components such as succinic acid, nicotinic acid, hexadecanoic acid, vanillic acid, phthalic acid, anisic acid, azelaic acid, palmitic acid, linoleic acid and stearic acid are returned.
1.3 polysaccharide Angelica sinensis polysaccharide (APS) is a water-soluble active ingredient in Angelica sinensis, and its content can reach 15%. At present, the mature method of extracting and separating crude polysaccharides from Angelica sinensis is water extraction and alcohol precipitation. The crude polysaccharide of Angelica sinensis can be separated by ion exchange chromatography, gel chromatography and DEAE cellulose chromatography to obtain high purity polysaccharide subcomponents. Shang Peng and others successively extracted and separated the total polysaccharide and its subcomponents from Angelica sinensis, and analyzed the composition of monosaccharides in the polysaccharide, mainly glucose, arabinose, rhamnose and galactose. The acidic polysaccharide is uronic acid. But the composition and proportion of monosaccharides are different.
1.4 Flavonoids Wang Furong et al. _ Using 75% ethanol as solvent, the yellow viscous substances in Angelica sinensis were extracted and separated by reflux, and were identified as flavonoids by metal salt reagent complexation reaction. After that, Li Gucai and others determined the best conditions of extracting total flavonoids from Angelica sinensis by ethanol through orthogonal experiments: ethanol concentration was 70%, solid-liquid ratio was 1:50, extraction temperature was 85℃, and extraction time was 2 h; The content of flavonoids in Angelica sinensis was determined by spectrophotometry as follows
1.59%。 However, so far, there is no research report on the isolation and identification of flavonoids monomer compounds from angelica sinensis.
1.5 Other ingredients Angelica sinensis contains various amino acids such as threonine, leucine and isoleucine, as well as various trace elements such as copper, iron, manganese and zinc. In addition, when it is returned, it contains uracil, adenine, vitamin E, metabolites of Penicillium, coumarins and so on.
2 pharmacological action
A large number of pharmacological research reports show that Angelica sinensis and its main chemical components have extensive biological activities and have pharmacological effects on hematopoietic system, circulatory system and nervous system.
2. 1 Influence on Hematopoietic System Angelica sinensis is called "the essential medicine for enriching blood", and its effect of enriching blood has been recognized by physicians in past dynasties. The research on the blood-enriching effect of Angelica sinensis mainly focuses on two aspects: one is the in vivo experiment to study the blood-enriching effect of Angelica sinensis on the animal model of blood deficiency; The second is to study the blood-enriching effect and mechanism of Angelica sinensis through in vitro experiments. The latter is the focus of current research work.
APS is one of the main active components of angelica sinensis in hematopoiesis, and its hematopoiesis mechanism is mainly to restore hematopoietic function by stimulating hematopoietic related cells and molecules. Recent studies show that APS can mobilize monocytes in peripheral blood and bone marrow to promote hematopoiesis. What about Hu Jing and the others? Peripheral blood mononuclear cells of male BALB/c mice mobilized by APS were infused intravenously into female allogeneic recipient mice irradiated by 8.5Gy60Co7 rays, and the source of hematopoietic reconstruction was identified by polymerase chain reaction. It was found that the survival numbers of WBC, P<, HGB and 30 days in APS group were significantly higher than those in control group and saline group (P < 0.05). It shows that the transplantation of peripheral blood hematopoietic stem/progenitor cells mobilized by APS can effectively rebuild the hematopoietic function of mice. Zhangyan et al. [19'%] found that APS can promote bone marrow mononuclear cells (BMNC) to enter the peripheral blood circulation earlier by reducing the expression of adhesion molecules on the surface of hematopoietic stem cells, and promote the repair of hematopoietic function. Further study found that APS can inhibit apoptosis by reducing the expression of P53mRNA, an apoptosis-related gene of BMNC in mice with radiation injury. And increase the expression of BMNC adhesion molecule antibodies CD44 and CD49d; Upregulating the adhesion rate of BMNC to fibronectin in extracellular matrix can accelerate the proliferation and differentiation of BMNC, thus promoting hematopoiesis.
Muscle satellite cells are the most promising source of seed cells for hematopoietic function reconstruction. Wang Xiaoling et al. used MTT method to detect the MSCs of mice cultured with bone marrow stromal cells and without culture medium, and found that MSCs cultured with bone marrow stromal cells with different concentrations of APS had significant proliferation. The conditioned medium of bone marrow stromal cells with APS intervention could effectively change the growth characteristics of MSCs and significantly promote the proliferation of MSCs and the expression of stem cell factor receptor protein.
2.2 the role of the circulatory system
2.2. Effects of1on cardiovascular system: Angelica sinensis and its volatile oil have the effects of regulating angiogenesis, inhibiting myocardial hypertrophy and resisting arrhythmia. Yeh et al. found that angelica volatile oil and n-butylphthalide had anti-angiogenesis effects; Danggui decoction can promote angiogenesis. This provides a basis for developing new angiogenesis regulators to treat cardiovascular diseases. Yuhua et al. _ Angelica injection acted on the hypertrophic cardiomyocytes induced by angiotensin N, and it was found that the protein content of cardiomyocytes decreased, which indicated that Angelica injection could effectively inhibit the hypertrophy of cardiomyocytes induced by angiotensin N. It was also found that the neutral non-rhythmic part (A3) of Angelica volatile oil had obvious antiarrhythmic effect, which could inhibit the heart beat frequency, prolong the functional refractory period, reduce the amplitude of myocardial contractility and action potential, and shorten the duration of repolarization by 20% and 90%. Its mechanism may be related to blocking the influx of Ca2+ and Na+ and promoting the outflow of K+, which is selective for K+ channels.
2.2.2 Anti-platelet aggregation: Ferulic acid in Angelica sinensis can increase the biological activity of thromboxane A:(TXA2), prostacyclin (PGI2) and the value of PGI2/TXA2, thus inhibiting platelet aggregation. Angelica injection can reduce platelet aggregation and adhesion in rats with disseminated intravascular coagulation, enhance erythrocyte deformability, and thus inhibit platelet aggregation.
2.2.3 Anti-atherosclerosis: Angelica sinensis and its organic acid component ferulic acid have anti-atherosclerosis effects. Angelica sinensis can improve the damage of high-fat serum to the morphological structure of vascular endothelial cells, reverse the decrease of TGB^ expression and the increase of bFGF expression in endothelial cells caused by high-fat serum, and achieve the effect of anti-atherosclerosis. Ferulic acid is also effective in treating atherosclerosis.
2.3 Effects on nervous system: Angelica sinensis can alleviate the degeneration of neurons during hypoxia, and has a certain regulatory effect on the activation of vascular endothelial growth factor mR-NA, suggesting that Angelica sinensis plays an important role in protecting injured nerves and promoting nerve regeneration.
Angelica injection can protect neural stem cells from intrauterine hypoxia by reducing the proliferation of neural stem cells. Zhong Xingming's research shows that Angelica injection can reduce the expression of GFAP in glial cells of young rats after intrauterine hypoxia, inhibit the expression of N- methyl-D- aspartate receptor subunit NR 1 in neonatal rats' brains, and achieve the protective effect on neonatal rats' brains after intrauterine hypoxia. In addition, Angelica injection has a certain therapeutic effect on chronic cerebral hypoperfusion and Parkinson's disease, and its mechanism may be that it upregulates the RNA and protein levels of Nrf2 in hippocampus, activates SIRT 1 through a specific signal pathway, and inhibits the apoptosis of PC 12 cells induced by hydroxydopamine.
2.4 Effect on Smooth Muscle
2.4. 1 has different effects on uterine smooth muscle: angelica volatile oil and water extract have different effects on uterine smooth muscle. The former is the main active ingredient to inhibit uterine contraction. Liu Linna et al.-Studies have shown that the volatile oil of Angelica sinensis can inhibit the contraction amplitude, frequency and activity of isolated normal uterine smooth muscle of mice, and can also inhibit the severe contraction of isolated uterine smooth muscle caused by oxytocin to restore it to normal level; It shows that the volatile oil of angelica sinensis has inhibitory effect on normal and pathological uterine smooth muscle, and has strong antispasmodic effect on uterine smooth muscle. Xiao Junhua and others further found a in the volatile oil of Angelica sinensis; So as to inhibit the best active site of uterine contraction, and its mechanism is related to its inhibition of P42/44MAPKCx43 signal transduction pathway downstream of PGF2.
On the contrary, the water extract of Angelica sinensis is the main active ingredient to excite uterus. At the concentration of 6.7mg/mL, the decoction of Angelica sinensis has an exciting effect on isolated mouse uterine muscles, which is related to the H receptor excited by Angelica sinensis, but has nothing to do with the M receptor, A receptor and prostaglandin synthase in uterine muscles. In fact, the acidic component (A 1) and the alcoholic component (A2) in the volatile oil of Angelica sinensis can also excite the uterus, but they have a dose-related two-way effect. For example, the research results of Xiao Junhua et al. showed that A 1 0~ 160mg/L had an exciting effect in normal isolated rat uterus, but it had an obvious inhibitory effect only at 320mg/L; A small dose of A2 (forget 10mg/L) has a slight excitatory effect, while a large dose (20mg/L) has an inhibitory effect.
2.4.2 Effect on bronchial smooth muscle: Angelica volatile oil can relax bronchial smooth muscle. Wang Feng, etc? It was found that the volatile oil of Angelica sinensis had obvious relaxing effect on isolated tracheal smooth muscle of guinea pigs in quiet state. Among them, 0 is the main component that plays this role; A 1 and A 1 have no obvious effects on isolated tracheal smooth muscle of guinea pigs, but there is an interaction between A 1 and A 1, which can weaken the relaxation effect of A 1 on isolated tracheal smooth muscle of guinea pigs. It is suggested that A 1 may antagonize the relaxation effect of a on isolated tracheal smooth muscle of guinea pigs.
2.4.3 Effect on gastrointestinal smooth muscle: Angelica volatile oil can relax gastrointestinal smooth muscle and reduce muscle tension. Wang Ruiqiong and others used isolated rabbit gastrointestinal smooth muscle strips to record the isometric contraction or relaxation curves of gastrointestinal smooth muscle with two kinds of physiological recorders, and calculated the change rate of muscle tension. It was found that the volatile oil of Angelica sinensis had relaxing effect on the smooth muscle of rabbit's isolated stomach bottom, stomach body, duodenum, jejunum and ileum in a concentration-dependent manner.
2.4.4 Effect on aortic smooth muscle: Angelica volatile oil can inhibit the contraction of aortic smooth muscle. Wu Guotai et al. observed the effects of angelica volatile oil on the tension of isolated rabbit thoracic aorta smooth muscle and the tension of thoracic aorta smooth muscle precontracted by norepinephrine (ne) and potassium chloride (KCl), and found that angelica volatile oil can obviously inhibit the contraction of isolated rabbit thoracic aorta smooth muscle induced by norepinephrine and KCl.
2.5 Immune Function APS is the main active component of Angelica sinensis, which can promote both specific and nonspecific immunity. Guo Zhenjun and others used ELISA to detect the secretion of TNF^a and IL ~ 4 by M9 stimulated by APS. It was found that APS could block MR-mediated phagocytosis of M9 in a dose-dependent manner. In addition, APS can up-regulate the function of dendritic cells in HBV transgenic mice. It shows that Astragalus polysaccharide can promote nonspecific immunity. APS and its subcomponents can significantly promote the proliferation of spleen cells, mixed lymphocytes and T cells. Increase the proportion of CIM cell subsets in cultured spleen cells and stimulate mice to produce specific IgG antibodies. It shows that APS has effects on both cellular immunity and humoral immunity.
2.6 Anti-tumor effect APS is the main anti-tumor component of Angelica sinensis, and its in vitro and in vivo experimental studies have shown anti-tumor activity.
In vivo, the anti-tumor effect of APS is mainly to indirectly inhibit or kill tumor cells by enhancing the immune function of the body. Wu Suzhen et al. studied the anti-tumor effect of sulfated angelica polysaccharide (SPAS) in vivo with SM mice model, and found that SPAS inhibited the tumor growth of SM mice, 40,80, 160mg/(kg? D) The tumor inhibition rates of the dose group were 27.89%, 34.69% and 39.45%, respectively, which indicated that SPAS had significant anti-tumor activity in vivo.
In vitro, Angelica sinensis can directly inhibit or kill tumor cells. Advanced? It was found that Angelica sinensis inhibited the proliferation and metastasis of lung cancer cells by decreasing MMP name, MMP4, TGF-p 1 and TIMP4, and increasing TIMP4. It was also found that APS not only inhibited SM sarcoma cells, leukemia cells and Ehrlich ascites cancer cells in vivo, but also inhibited the invasion and metastasis of liver cancer cells in vitro. ASP4d, a subcomponent of asp4d, can inhibit the proliferation of cervical cancer cells and induce their apoptosis, and its mechanism is mainly to activate the mitochondrial pathway of apoptosis.
2.7 Protective effect on organs Angelica extract has therapeutic effect on lung injury. Angelica polysaccharide is an effective component to prevent and treat pulmonary fibrosis, and can improve various pulmonary functions of pulmonary fibrosis rat model M 1. Danggui Buxue total glycoside can inhibit the abnormal proliferation, transformation and collagen expression of human embryonic lung fibroblasts induced by TGB^, and its inhibitory effect on collagen expression may be achieved by increasing the expression of metalloproteinase 4 (M2).
Angelica sinensis can prevent and treat renal ischemia-reperfusion injury, and its mechanism may be related to its regulation of TNF^, IL-6 and bFGF.
APS can intervene different chemical liver injury, reduce the salt and sAST of liver injury caused by alcohol and carbon tetrachloride, and alleviate liver injury. Nie Rong's research results suggest that APS may protect the liver by improving the antioxidant capacity of hepatocytes, enhancing the energy storage of the liver and reducing the toxicity of carbon tetrachloride to the liver.
2.8 Anti-inflammatory and analgesic effects Angelica extract has analgesic and anti-inflammatory effects, which can obviously increase the pain threshold of mice caused by thermal stimulation and inhibit the writhing reaction of mice caused by chemical stimulation. Shen Jianfen and others studied the anti-inflammatory mechanism of Angelica sinensis from the cellular and genetic levels, and found that A; It can inhibit the production of PGE, the activity of cyclooxygenase -4(COX-2) and the expression of COX mRNA and protein, suggesting that inhibiting the production of PGEi may be related to inhibiting the expression of C0X4 gene. 2.9 Other effects Angelica sinensis has anti-radiation, anti-oxidation, anti-aging and anti-psoriasis effects, and can significantly reduce blood sugar in diabetic rats, and its mechanism may be related to promoting the repair and regeneration of insulin B cells.
3 Conclusion
Angelica sinensis contains volatile oil, organic acids, polysaccharides, flavonoids and other chemical components. Its pharmacological action is extensive, involving many systems of the body. The "blood-enriching" effect of Angelica sinensis mainly acts on hematopoietic system, which is realized by stimulating hematopoietic related cells and molecules. The effect of "promoting blood circulation" of Angelica sinensis mainly acts on the circulatory system, and achieves the effect of "promoting blood circulation" by inhibiting platelet aggregation. In addition, when returned to the nervous system and immune system, it has anti-tumor, anti-radiation, anti-inflammatory and analgesic, anti-oxidation and anti-aging effects. These pharmacological research results laid a foundation for the clinical application and new product development of Angelica sinensis. In recent years, the research on the treatment of diabetes and psoriasis by Angelica sinensis is being carried out in depth. Although the mechanism is still unclear, it is believed that with the progress of science and technology, these problems will eventually be solved, and new therapeutic drugs will be found for diseases such as diabetes and psoriasis that have no definite curative effect at present. At the same time, it will also expand the clinical application scope of Angelica sinensis and improve its medicinal value.