Astragalus membranaceus and Angelica sinensis are traditional Chinese medicines, and the drug pair composed of them is a common form of compatibility in clinical application. Astragalus membranaceus and Angelica sinensis5∶1The Danggui Buxue Decoction, which is composed of Angelica and blood, is recorded in the "theory of internal and external injuries and confusion" written by lidongyuan in the Jin and Yuan Dynasties. It is a famous prescription for replenishing qi and blood and activating blood^[1]Astragalus mongholicus is a leguminous plantAstragalus membranaceus (Fisch.) Bunge. var. mongholicus(Bge.) HsiaoOr Astragalus membranaceusA. membranaceus (Fisch.)Bge.Its dry root is sweet in taste, mild in nature, and belongs to the lung and spleen meridians. Its efficacy is to replenish qi and elevate Yang, generate fluid and nourish blood, firm the surface and stop sweating, promote stagnation and unblock arthralgia, promote diuresis and detumescence, support toxin and discharge pus, heal sores and generate muscle. Angelica sinensis (Oliv.) Diels. Astragalus membranaceus-Angelica sinensis is widely used in traditional Chinese medicine prescriptions. According to the analysis of traditional Chinese medicine application data of Angelica sinensis series drug pairs, the simultaneousAstragalus membranaceus and Angelica sinensis2780First prescription^[2]In addition, they are also widely used in modern Chinese patent medicine, such as Buzhong Yiqi Pills, Shenbao mixture, Xiaoshuan oral liquid, etc. In recent years, there has been an increasing interest in Astragalus membranaceus at home and abroad-Angelica sinensis has carried out a lot of research and achieved some results. In this paper, through the analysis of Astragalus membranaceus-This paper reviews the research progress of chemical constituents, pharmacological effects and clinical applications of Angelica sinensis, in order to lay a solid foundation for the further development and utilization of this drug pair.

1  chemical composition

The study of chemical composition is the key to reveal the material basis of drug pair efficacy, and also the prerequisite to clarify the scientific connotation of drug pair compatibility. The chemical constituents of Astragalus membranaceus and Angelica sinensis are quite different. Astragalus membranaceus mainly contains flavonoids, saponins, polysaccharides and other compounds^[3]Angelica sinensis mainly contains volatile oils and organic acids represented by esters^[4]However, the material basis on which the efficacy of a drug pair depends is not a simple addition of the chemical components of a single drug, but a community formed by the interaction of the chemical components of a single drug. Different extraction processes, compatibility ratios, and processing methods will change the content or quantity of the chemical components of the drug pair, and the absorption, distribution, metabolism, and excretion process of the drug pair after entering the body will also change the chemical components, thus affecting the efficacy of the drug pair^[5]. Fang huanle et al^[6]The compatibility of Astragalus membranaceus and Angelica sinensis can play a synergistic effect, but the material basis of its synergistic effect is not clear. Therefore, it is necessary to further study the chemical composition of this drug pair.

1.1 Qualitative and quantitative study of chemical composition

At present, many studies have shown that Astragalus membranaceus-The chemical composition of Angelica sinensis will change before and after compatibility. Guzhirong et al^[7]HPLC was used-（highperformance liquid chromatography-diode array detector，HPLC-DAD）Method for Astragalus membranaceus extracted under the same conditions-The fingerprints of Angelica sinensis and its single drug Angelica sinensis and Astragalus membranaceus were compared. The results showed that there were26Common peaks,6From Angelica sinensis,9,7They are both from Astragalus membranaceus and Angelica sinensis,4Peaks are new substances. Wang Yali et al^[8]. In addition, many studies have shown that Astragalus membranaceus-The chemical composition of Angelica sinensis will also change with different compatibility ratios. Some researchers adoptedHPLCMethod for Radix Astragali, Angelica sinensis single herb extract and Radix Astragali-The compatibility ratio of Angelica sinensis was1∶5、1∶1、5∶1The extract of18Characteristic peaks, of which11The characteristic peaks are the same as those of Astragalus membranaceus,6The characteristic peaks are the same as those of Angelica sinensis,1Three are new components after extraction, indicating that new substances are produced after the decoction of Astragalus membranaceus and Angelica sinensis, and the characteristic components change with2Changes due to different compatibility ratios of herbal medicines^[9]。

The researchers' understanding of Astragalus membranaceus-The content of chemical components in the decoction before and after the compatibility of Angelica sinensis was compared, and it was found that the compatibility ratio of Angelica sinensis and Angelica sinensis was different, and the change of component content was different. Liu Yan^[10]adoptHPLC, HPLC-Electrospray tandem mass spectrometry（HPLC-electrospray ionizationmass spectrometry，HPLC-ESI-MS）To Astragalus membranaceus-The results showed that the content of ferulic acid increased with the increase of the amount of Astragalus membranaceus in the compatibility ratio, and the content of astragaloside IV increased with the increase of the amount of Angelica. The combination of the two can improve the dissolution of ferulic acid in Angelica and astragaloside IV in Astragalus membranaceus. Some researchers used reversed-phase HPLC（reversed phase HPLC，RP-HPLC）Determination of Astragalus membranaceus by HPLC-Angelica sinensis press5∶1、1∶1、10∶1The decocting rate of ferulic acid when decocting in proportion and compatibility, it was found that Astragalus membranaceus and Angelica sinensis were decocted according to the classic proportion5∶1When compatible, the decocting rate of ferulic acid was the highest^[11]. shoudiwen et al^[12]adoptHPLCThe different compatibility ratios of Astragalus membranaceus and Angelica sinensis were determined（1∶1、2∶1、5∶1、7∶1、10∶1）It was found that the content of astragaloside IV, ferulic acid and formononetin increased with the ratio of AstragalusHigh, astragaloside IV, ferulic acid, formononetin content increased, Astragalus membranaceus-The compatibility ratio of Angelica sinensis was 0.The compatibility ratio of Angelica sinensis was 0.05% and 0.05% respectively......the compatibility ratio of Angelica sinensis was 0.05% and 0.05% and 0.05% respectively5∶1. And learnThe authors studied Astragalus membranaceus and Angelica sinensis in Danggui Buxue Decoction2Comparison of different compatibility of traditional Chinese Medicine4Astragalus membranaceus was found in all of them-WhenThe compatibility ratio of GUI5∶1The contents of astragaloside IV and formononetin in Astragalus membranaceus and ferulic acid in Angelica sinensis reached the peak, while artemisinide, a volatile oil component in Angelica sinensis, reached the lowest^[13-15]。Linetc.^[16]utilizeHPLCAccording to the chemical analysis of Danggui Buxue Decoction by HPLC, it was found that the combined decocting of Danggui Buxue Decoction produced more effective components than the single decocting medicine, which could promote the precipitation of ferulic acid, calycosin and other effective components, and the compatibility ratio of Astragalus membranaceus and Danggui was5∶1The effect is the best. But recent studies have also found that Astragalus membranaceus-Angelica sinensis1∶1and1∶5The compatibility can promote the dissolution of the main components of the two to1∶1Angelica sinensis can significantly promote the dissolution of effective components in Astragalus membranaceus when it is compatible^[17]。

In addition, the trace elements in different proportions of Huangqi Danggui Decoction were detected by spectroscopy, and it was found that Huangqi-The compatibility ratio of Angelica sinensis was 0.The compatibility ratio of Angelica sinensis was 0.05% and 0.05% respectively......the compatibility ratio of Angelica sinensis was 0.05% and 0.05% and 0.05% respectively5∶1The dissolution rates of selenium, iron, copper and other trace elements in the co Decoction of Danggui Buxue Decoction were the highest, while the dissolution rates of lead, cadmium, chromium and arsenic in the water decoction were the lowest, which further confirmed the rationality of the classic formula of Danggui Buxue Decoction and provided a scientific basis for its clinical efficacy^[18]。

1.2  Study on the in vivo process of chemical constituents

At present, for Astragalus membranaceus-Pharmacokinetic studies of Angelica sinensis mainly focused on the detection of Astragalus membranaceus-The changes of some chemical components in the blood of Angelica compound preparation, but the comparative study on the absorption, distribution and metabolism of the main components before and after its compatibility is relatively few.

Wu Ronglan et al^[19]HPLC fingerprint was used, and n-octanol-The water distribution system simulated the absorption of traditional Chinese medicine in the human body, and compared the changes of chemical composition of single decoction of Astragalus membranaceus and Angelica sinensis and the combined decoction with different ratios under different target acidity. The results showed that the acidity of different target sites and different compatibility had a great impact on the effective components, content and absorption of each component. According to the fingerprint comparison, when Astragalus membranaceus and Angelica sinensis are compatible in the same amount and the content of Astragalus membranaceus accounts for the majority in the compound, it is similar to2Compared with single drugs, more new substances appeared in the compound, and2However, there was no corresponding chromatographic peak in the compound of the components contained in each single herb. These components with changes in concentration and morphology may be potential active ingredients of traditional Chinese medicine.

Wangwenping et al^[20]Studied theThe results showed that the pharmacokinetic parameters of ferulic acid in rabbit plasma and astragaloside IV in rat plasma were almost unchanged after the compatibility of Astragalus membranaceus and Angelica sinensis, and the peak time and peak concentration of astragaloside IV in rat plasma were advanced1Times, indicating that Angelica enhanced the activity of astragaloside IV in vivo after the combination, and exerted the drug effect in advance, reflecting the adjuvant effect of Angelica officinalis. This study verified the rationality of the compatibility of Danggui Buxue Decoction from the aspect of pharmacokinetics.

The above studies suggest that Astragalus membranaceus-After Angelica Decoction, the dissolution of some components will change, and even the production of new components or the disappearance of original components, and the components of drug pairs will also change in absorption, distribution, metabolism and other links after entering the body. But there is no Astragalus at present-The report on the interaction mechanism between chemical components of Angelica sinensis when it plays a role is worth further discussion.

2  pharmacological action

Astragalus membranaceus-Angelica sinensis has a wide range of pharmacological activities, and its efficacy is closely related to the pharmacological effects of Astragalus membranaceus and Angelica sinensis. Astragalus membranaceus has significant anti-inflammatory effects^[21], regulating immune function^[22], anti-aging^[23], antiviral^[24]Cardiovascular and cerebrovascular protection^[25-26]It can inhibit the proliferation of liver cancer, lung cancer and other cells^[27-28], which can also be used to reduce blood glucose^[29]Angelica sinensis is one of the widely used traditional Chinese medicines in recent years, which has a good effect on improving anemia^[30], liver protection^[31]Immune regulation^[32], antitumor^[33], anti-inflammatory^[34]Promote blood circulation^[35]Et al. Therefore, the drug pair composed of Astragalus membranaceus and Angelica sinensis has both active ingredients, and its pharmacological effect is more extensive than that of a single drug.

2.1  Regulating immune function

Astragalus membranaceus-Angelica sinensis can be adjusted byTThe gene expression of cells and cytokines plays a role in regulating immunity, giving full play to its Qi replenishing effect, and promoting the normal life activities of the body^[36]。

As early as1997In, kongxiangying^[37]Astragalus membranaceus was studied at different levels of nonspecific immunity, humoral immunity, cellular immunity, and cyclic nucleotide levels in vivo-angelica3（5∶1、1∶1、1∶5）Effect on Immunosuppressive Model Mice and its mechanism, the results showed that3All of them could significantly enhance the immune function of the body and improve the high level of plasma cAMP5∶1The effect is most obvious when. In the cyclophosphamide induced immunocompromised mouse model, the effects of Angelica sinensis and different medicinal materials on the immune organs and macrophage phagocytosis of the model mice were studied. The spleen, thymus index, peritoneal macrophage phagocytosis rate and clearance index of the mice were detected-Angelica sinensis is one of the best compatible drug pairs^[38]. Qin Qianhua et al^[39]Astragalus membranaceus was also found-Different compatibility ratios of Angelica sinensis have different degrees of immune promoting effect on immunosuppressed mice induced by cyclophosphamide, among which Astragalus membranaceus-The compatibility ratio of Angelica sinensis was 0.The compatibility ratio of Angelica sinensis was 0.05% and 0.05% respectively......the compatibility ratio of Angelica sinensis was 0.05% and 0.05% and 0.05% respectively10∶1、1∶1It has obvious effect on improving the immunity of mice. -Auxiliary effect of Angelica sinensis on rats with Qi deficiency and blood stasis syndromeTlymphocyte1（helper T lymphocyte 1，Th1）/Th2The spleen index, thymus index and serumγ（interferon-γ，IFN-γ）, interleukin-4（interleukin-4，IL-4）Content, Astragalus membranaceus was found-Angelica compatibility can significantly increase spleen index and serumIFN-γContent, decreaseIL-4Content, showing a better immune enhancing effect, and can regulateTh1/Th2Cell balance^[40]。Gaoetc.^[41-42]The effects of Astragalus membranaceus and Angelica sinensis on stimulating immune response were studied-The compatibility ratio of Angelica sinensis was 0.The compatibility ratio of Angelica sinensis was 0.05% and 0.05% respectively......the compatibility ratio of Angelica sinensis was 0.05% and 0.05% and 0.05% respectively5∶1Can significantly induceTLymphocyte proliferationIL-2The secretion and phosphorylation of intracellular signal regulated kinase can also enhance the phagocytosis of macrophages. Astragalus membranaceus-Angelica sinensis can also regulateIFN-γIn induced mouse bone marrow cellsT-boxTranscription factors（T-box expressed in T cell，T-bet）Expression in bone marrow microenvironment, intervention of eukaryotic initiation factor2Activation of the signaling pathway, which in turn promotesTBalance of cellular immune response network^[43]。

In addition, zhaoyinli et al^[44]Astragalus membranaceus with different compatibility ratios was studied-The effect of Danggui powder on immune function of Gushi chicken was evaluated by measuring immune organ index, Newcastle disease antibody content and peripheral bloodTThe results showed that the immune enhancing effect of Astragalus membranaceus was better than that of Angelica sinensis, and Astragalus membranaceus-The compatibility ratio of Angelica sinensis was 0.The compatibility ratio of Angelica sinensis was 0.05% and 0.05% respectively......the compatibility ratio of Angelica sinensis was 0.05% and 0.05% and 0.05% respectively5∶1The effect is the best.

2.2  Regulating the blood system

Blood stasis refers to the poor operation of blood, which is manifested as viscosity, concentration, coagulation and aggregation, and also includes the change of tangible components, such as the increase of blood lipid and blood glucose levels, which makes the blood turbid and the blood flow blocked. andAstragalus membranaceus-angelicaIt can improve the hemorheology, stimulate the proliferation and differentiation of hematopoietic pluripotent stem cells and hematopoietic main cells, increase the number of white blood cells, hemoglobin and other cells in the body, and reduce the damage of harmful substances to them.

Some scholars first studied the effects of Astragalus membranaceus, Angelica sinensis and their different proportions of Decoction on the content of iron and copper in plasma of normal mice and mice with hematopoiesis inhibition caused by cyclophosphamide and hemolytic anemia caused by acetylphenylhydrazine, and found that using them can increase the content of iron and copper in plasma of mice, among which Astragalus membranaceus-The compatibility ratio of Angelica sinensis was 0.The compatibility ratio of Angelica sinensis was 0.05% and 0.05% respectively......the compatibility ratio of Angelica sinensis was 0.05% and 0.05% and 0.05% respectively5∶1The content of iron and copper in cyclophosphamide induced anemia model mice was significantly increased when the treatment was given; While Astragalus membranaceus-The compatibility ratio of Angelica sinensis was 0.The compatibility ratio of Angelica sinensis was 0.05% and 0.05% respectively......the compatibility ratio of Angelica sinensis was 0.05% and 0.05% and 0.05% respectively3∶3It also significantly increased the plasma iron and copper contents of normal mice and the plasma iron content of anemia mice induced by acetylphenylhydrazine^[45]Since iron and copper are indispensable trace elements for the body's hematopoietic function, this study is Astragalus membranaceus-Angelica sinensis, as a pair of Qi and blood tonics, provides a basis for clinical medication.

Tengjialin^[46]The acute blood stasis model was made by ice water immersion combined with epinephrine injection, and the9Astragalus membranaceus with different doses and different compatibility ratios-The effect of Angelica sinensis on platelet aggregation rate, whole blood specific viscosity and plasma specific viscosity-At a certain dose and a certain compatibility ratio, Angelica sinensis has a better effect on anti platelet aggregation and reducing the whole blood specific viscosity of blood stasis rats. Moreover, the study also found that Astragalus membranaceus-The Yiqi Huoxue effect of Angelica sinensis may also be closely related to the reduction of leukocyte adhesion and the expression of adhesion molecules.

Other scholars observed the effects of Astragalus membranaceus and Angelica sinensis alone and in combination in the treatment of vascular restenosis after endothelial denudation in rats, and found that after treatment, the hematocrit, plasma and whole blood viscosity, erythrocyte aggregation index and rigidity index were significantly lower than those of the model group, the erythrocyte deformability was significantly enhanced, and the blood flow velocity was accelerated. It can be seen that Astragalus membranaceus and Angelica sinensis may play their role in preventing and treating vascular restenosis after endothelial denudation by improving the hemorheology and ultrasound hemodynamics^[47]. by studying Astragalus membranaceus-Effects of different compatibility ratios of Angelica sinensis on blood flow and blood components of common carotid artery and renal artery in blood deficiency rats-Angelica sinensis can significantly improve red blood cells, hemoglobin and hematocrit caused by blood deficiency-The compatibility ratio of Angelica sinensis was 0.The compatibility ratio of Angelica sinensis was 0.05% and 0.05% respectively......the compatibility ratio of Angelica sinensis was 0.05% and 0.05% and 0.05% respectively1∶1The improvement effect was the best when the; Astragalus membranaceus with different compatibility ratio-Angelica sinensis can also significantly improve the blood flow reduction of common carotid artery and renal artery caused by blood deficiency-The compatibility ratio of Angelica sinensis was 0.The compatibility ratio of Angelica sinensis was 0.05% and 0.05% respectively......the compatibility ratio of Angelica sinensis was 0.05% and 0.05% and 0.05% respectively5∶1The best improvement effect was observed at the time of injection, indicating that the compatibility of traditional Chinese medicine played an important role in exerting the efficacy^[48]。

Studies have shown that Astragalus membranaceus-Angelica sinensis can resist the inhibition of bone marrow hematopoiesis induced by cyclophosphamide in mice, and its mechanism may be related to promoting the proliferation and differentiation of hematopoietic stem cells and cytokine secretion in bone marrow suppressed mice^[49-51]. Astragalus membranaceus-Angelica sinensis has the effect of increasing leukocytes. It not only has a therapeutic effect on leukopenia caused by cyclophosphamide, but also6GyExposure⁶⁰CoγThe decrease of white blood cells in mice caused by whole-body sublethal radiation can also play a role^[52-53]。

Zhang Kesheng et al^[54]To establish the aging model of hematopoietic stem cells in mice injured by tributylhydrogen peroxide, Astragalus membranaceus was observed-The effect of Angelica containing plasma, Astragalus membranaceus-The compatibility ratio of Angelica sinensis was 0.The compatibility ratio of Angelica sinensis was 0.05% and 0.05% respectively......the compatibility ratio of Angelica sinensis was 0.05% and 0.05% and 0.05% respectively1∶1The mechanism may be related to regulating the expression of cell cycle regulators and promoting cells from quiescence to proliferation. Further study found that the effects of Astragalus membranaceus and Angelica sinensis5The combination of these active ingredients can also promote the proliferation of senescent hematopoietic stem cells by regulating the cell cycle^[55]In addition, total saponins of Astragalus membranaceus and polysaccharides of Angelica sinensis had significant effects onSDRat bone marrow cells also have a significant role in promoting proliferation6∶4When combined, it has significant effect on the red blood cell count and hemoglobin content of rats inhibited by cyclophosphamideMarked elevating effect^[56]Angelica polysaccharide, astragalus polysaccharide and the combination of the two have significant effects on cytokinesIL-6、IL-3, erythropoietin（erythropoietin，EPO）The expression of et al can promote and stimulateJanuskinase2（Janus kinase 2，JAK2）, signal transducer and activator of transcription5（signal transducers and activators oftranscription 5，STAT5）The mechanism of Angelica sinensis polysaccharide and astragalus polysaccharide may be through theJAK2/STAT5Signaling pathway regulates hematopoiesis/Group stem cells to erythroid proliferation and differentiation^[57]。

2.3  Protect vascular endothelium

Blood vessel is the pipe of blood flow. The disorder or dysfunction of blood vessel wall and vascular endothelium will inevitably affect blood flow and lead to blood stasis. Astragalus membranaceus-Angelica sinensis can promote endothelial nitric oxide synthase（endothelial nitric oxide synthase，eNOS）Expression and protein kinase ofB（protein kinase B，PKB/Akt）Of phosphorylation, promoting nitric oxide（nitric oxide，NO）It can also protect vascular endothelium by inhibiting inducible nitric oxide synthase（inducible NOS，iNOS）It can also inhibit the apoptosis of vascular endothelial cells.

By studying Astragalus membranaceus-The therapeutic effect of Angelica sinensis on vascular restenosis rats was found to increaseNOSynthesis, inhibitioniNOSExpression, thereby inhibiting intimal hyperplasia caused by vascular intimal injury, and playing its role in preventing and treating restenosis after denudation of vascular endothelium^[58-59]. guoliangqing et al^[60]Astragalus membranaceus was found-The compatibility ratio of Angelica sinensis was 0.The compatibility ratio of Angelica sinensis was 0.05% and 0.05% respectively......the compatibility ratio of Angelica sinensis was 0.05% and 0.05% and 0.05% respectively3∶2Can effectively adjustNO、NOSSo as to play a role in preventing and treating vascular endothelial injury in diabetic rats.

Lei Yan et al^[61]A large number of studies have been carried out on the effects of Astragalus membranaceus, Angelica sinensis and their components on the proliferation of vascular endothelial cells. It was found that Angelica sinensis alone or in combination could promote the proliferation of vascular endothelial cellsDNASynthesis and replication and vascular endothelial growth factor（vascularendothlial growth factor，VEGF）Expression,2There is synergistic effect in the application of drug compatibility.

Astragalus membranaceus-Angelica sinensis also has a good effect of promoting vascular regeneration. Shen bin et al^[62]Astragalus membranaceus was studied-The effect of Angelica sinensis on the proliferation of rat bone marrow stem cells in vitro. It was found that Astragalus membranaceus alone or combined with Angelica sinensis could stimulate the proliferation of bone marrow stem cells in vitro, which might be related to its up regulationVEGFProtein expression, but Angelica sinensis alone has no above effect. 14 d, transplanted into the ischemic lower limb of diabetic rats, and detected the blood flow perfusion volume of the limb skin, microvessel density, and muscle tissueVEGFIt was found that Astragalus membranaceus alone or combined with Angelica can promote bone marrow stem cell transplantation in the treatment of diabetic ischemic lower limb angiogenesis, and the combination of Astragalus membranaceus and Angelica has a synergistic effect^[63]。Linetc.^[16]The angiogenic effects of Danggui Buxue Decoction and its single drug on normal zebrafish sub intestinal blood vessels were studied. The results showed that compared with single drug, Danggui Buxue Decoction could significantly promote angiogenesis and alleviate endothelial dysfunction. -Angelica sinensisC57BL/6The protective effect of Astragalus membranaceus on cardiac dysfunction in a mouse model of myocardial infarction-The compatibility ratio of Angelica sinensis was 0.The compatibility ratio of Angelica sinensis was 0.05% and 0.05% respectively......the compatibility ratio of Angelica sinensis was 0.05% and 0.05% and 0.05% respectively5∶1Can significantly improve angiogenesis^[64]The study also found that Astragalus membranaceus-The compatibility ratio of Angelica sinensis was 0.The compatibility ratio of Angelica sinensis was 0.05% and 0.05% respectively......the compatibility ratio of Angelica sinensis was 0.05% and 0.05% and 0.05% respectively5∶1It can promote the angiogenesis of chick chorioallantoic membrane^[65]。

The intimal hyperplasia model of thoracoabdominal aorta was established by balloon catheter injury of rat vascular endothelium, and Astragalus membranaceus was observed-（5∶1、2∶1、1∶1、1∶2、1∶5）On rat vascular intimaThe effect of hyperplasia was found in Astragalus membranaceus-Angelica sinensis can inhibit phosphatidylinositol- 3-kinase/（phosphatidylinositol-3-kinase，PI3K）/Aktsignaling pathway， Up regulation of smooth muscleα-Expression of actin, downregulation of proliferating cell nuclear antigen, cyclinD1, cyclinsE, collagen-Ⅰ, fibronectin, and matrix metallopeptidase-9, thereby inhibiting vascular smooth muscle cells（vascular smoothmuscle cells，VSMC）The phenotype transformation and cell proliferation of Astragalus membranaceus can further inhibit the proliferation of rat vascular intima, and Astragalus membranaceus-The compatibility ratio of Angelica sinensis was 0.The compatibility ratio of Angelica sinensis was 0.05% and 0.05% respectively......the compatibility ratio of Angelica sinensis was 0.05% and 0.05% and 0.05% respectively1∶1The effect is better when^[66]。Li Xia et al^[67-68]The network pharmacology method was usedAnalysis of Astragalus membranaceus-The mechanism of Angelica compatibility in improving the intimal hyperplasia of blood vessels revealed several possible targets and signaling pathways, which were further verified by experiments and found that Astragalus membranaceus-The compatibility ratio of Angelica sinensis was 0.The compatibility ratio of Angelica sinensis was 0.05% and 0.05% respectively......the compatibility ratio of Angelica sinensis was 0.05% and 0.05% and 0.05% respectively1∶1、5∶1Can be inhibited byPI3K/AktSignaling pathway can effectively improve intimal hyperplasia, regulate blood lipids, and regulate the phenotypic transformation and proliferation of smooth muscle in rabbits.

In addition, Astragalus membranaceus was also found-Angelica sinensis has the effect of anti apoptosis of arterial vascular endothelium, which can be exerted by different combinations, but Astragalus membranaceus-The compatibility ratio of Angelica sinensis was 0.The compatibility ratio of Angelica sinensis was 0.05% and 0.05% respectively......the compatibility ratio of Angelica sinensis was 0.05% and 0.05% and 0.05% respectively5∶1and3∶1The effect is significant, and its mechanism may be through the reduction of angiotensinⅡSpecific receptors and pro apoptotic proteinsFasLigand（Fasligand，FasL）AndBcl-2correlationXProtein（Bcl-2 associated X protein，Bax）Expression of^[69]。

2.4  antioxidant

Ferulic acid and angelica polysaccharide, as well as astragalus polysaccharide and astragaloside IV in Astragalus membranaceus, which are the effective components of Angelica sinensis, have the effect of scavenging oxygen free radicals and reducing peroxide damage.Astragalus membranaceus-Different compatibility ratios of Angelica sinensis can dose dependently increase rat embryonic myocardiumH9c2Intracellular glutathione（glutathione，GSH）And this effect can beGSHSynthetic inhibitors orGSHBlocked by regeneration inhibitors, among which Astragalus membranaceus-The compatibility ratio of Angelica sinensis was 0.The compatibility ratio of Angelica sinensis was 0.05% and 0.05% respectively......the compatibility ratio of Angelica sinensis was 0.05% and 0.05% and 0.05% respectively5∶1The effect of Danggui Buxue Decoction is the best, indicating that Danggui Buxue Decoction can enhanceGSHTo increase intracellularGSHContent, thereby exerting its anti -H9c2Role of cellular oxidative damage^[70]. studies have shown that Astragalus membranaceus-Angelica sinensis can increase serum superoxide dismutaseGSHPeroxidase levels, reducing the content of malondialdehyde^[71]。

2.5  Anti organ fibrosis

Sunlixia et al^[72]Astragalus membranaceus was studied-Effects of different compatibility ratios of Angelica sinensis on liver function and liver fibrosis in rats with immune liver injury-Angelica sinensis5∶1The mechanism may be related to the inhibition of lipid peroxidation and anti free radical injury.

Astragalus membranaceus was used-Angelica intervention in idiopathic pulmonary fibrosis mice, the results showed that Astragalus membranaceus-The compatibility ratio of Angelica sinensis was 0.The compatibility ratio of Angelica sinensis was 0.05% and 0.05% respectively......the compatibility ratio of Angelica sinensis was 0.05% and 0.05% and 0.05% respectively5∶1Group a can significantly reduce the content of hydroxyproline in lung tissue and improve alveolar structure, and can also significantly improve the quality of life of mice. Its mechanism may be related to the regulation ofTh17/TregThe expression levels of key genes of cell differentiation and genes related to tissue repair^[73-75]。

In addition, Geng Qingxia et al^[76]The effects of the optimized formula of water extract or alcohol extract of Astragalus membranaceus and Angelica sinensis on the survival of idiopathic pulmonary fibrosis mice were studied. The results showed that when the proportion of water extract of Astragalus membranaceus and alcohol extract of Angelica sinensis in the optimized formula was large, it could reduce the content of hydroxyproline in the lung and reduce transforming growth factor-β（transforming growth factor-β，TGF-β）、VEGFExpression levels, thereby improving the extent of murine pulmonary fibrosis.

By observing Astragalus membranaceus (Bge.) Bge.The effect of the treatment on the growth of the root of Astragalus membranaceus (Bge.) Bge.The growth of the root of Astragalus membranace-The effect of Angelica sinensis combined with enalapril on rats with unilateral ureteral obstruction, the results showed that the combination had a better effect on anti tubulointerstitial fibrosis^[77]。Zhangetc.^[78]The effect of Danggui Buxue Decoction on diabetic nephropathy rats was studied, and the results showed that it could inhibitTGF-β1Gene expression, thereby alleviating renal fibrosis in diabetic rats and delaying the occurrence and development of diabetic nephropathy. Other scholars found that adenine caused renal interstitial fibrosis, Astragalus membranaceus-The anti renal fibrosis mechanism of Angelica sinensis lies in the inhibition ofTGF-β1（connective tissue growthfactor，CTGF）Gene expression, different extract groups can significantly improve renal function indicators, and the effect of alcohol extract is better than that of water extract^[79]。

2.6  antiinflammatory

Yuan Ying et al^[80-82]Astragalus membranaceus was studied-Effect of Angelica sinensis on airway allergic inflammation in ratsTh1/Th2It was found that the combination of the two can reduce the concentration ofGATABinding protein3（GATAbinding protein 3，GATA3）/T-betIn nasal mucosa, lung tissue, and serumIL-4The content in lung tissue and serum increasedIFN-γLevels, and represses transcriptional activatorsSTAT6Expression of, promotingSTAT4To exert the inhibitory effect of airway allergic inflammation.Choietc.^[83]Astragalus membranaceus was studied-The compatibility ratio of Angelica sinensis was 0.The compatibility ratio of Angelica sinensis was 0.05% and 0.05% respectively......the compatibility ratio of Angelica sinensis was 0.05% and 0.05% and 0.05% respectively5∶1The results showed that Danggui Buxue Decoction, Astragalus membranaceus and Angelica sinensis could inhibit the production of allergic and inflammatory mediators, thus playing an anti allergic dermatitis role, but Danggui Buxue Decoction was better than Astragalus membranaceus and Angelica sinensis alone.

2.7  Antitumor

Sunyumin et al^[84]The effect of Danggui Buxue Decoction on tumor bearing mice was studiedEL-4It was found that it has a certain effect on tumor prevention and early treatment. In sarcomasS₁₈₀Experimental studies in mice have shown that Danggui Buxue Decoction can safely and effectively inhibit sarcomaS₁₈₀Proliferation of, which has a good application prospect^[85]. establishment of tumor bearing miceLewisThe anti-tumor effect of Astragalus membranaceus combined with Angelica sinensis was observed in animal models of lung cancer cells. It was found that the combined use of Astragalus membranaceus and Angelica sinensis could significantly inhibit tumor growth and prevent the loss of body mass and skeletal muscle^[86]In addition, Danggui Buxue Decoction can also up regulate deoxycytidine kinase and down regulate the expression of deoxycytidine kinase..the results showed that the expression of deoxycytidine kinase in the blood of the patients with chronic hepatitis B was significantly higher than that of the patients with chronic hepatitis B.the expression of deoxycytP-Glycoprotein expression to promote the antitumor effect of gemcitabine^[87]。

Astragalus membranaceus-The pharmacological effects of Angelica drug pairs are shown in table1。

3  clinical application

3.1  Astragalus membranaceus-Clinical application of Angelica sinensis

At present, Astragalus membranaceus-The mixture composed of Angelica sinensis, especially Danggui Buxue Decoction (Astragalus membranaceus-The compatibility ratio of Angelica sinensis was 0.The compatibility ratio of Angelica sinensis was 0.05% and 0.05% respectively......the compatibility ratio of Angelica sinensis was 0.05% and 0.05% and 0.05% respectively5∶1）.

3.1.1 Nephrotic syndrome  Wangyuanzhen et al^[88]The effect of Huangqi Danggui Mixture Combined with tacrolimus on renal function in patients with refractory nephrotic syndrome was observed. The results showed that the clinical efficacy of the combination of Huangqi Danggui Mixture and tacrolimus in the treatment of refractory nephrotic syndrome was better than that of tacrolimus alone, which could significantly improve the renal function of patients, and the safety was higher. Some scholars have further studied the mechanism of Astragalus and Angelica Mixture in the treatment of nephrotic syndrome, and found that Astragalus and angelica mixture can significantly improve the renal function of patients, reduce the secretion of inflammatory factors, reduce the micro inflammatory state of patients, and has significant curative effect, which is safe and reliable^[89]. Xiaoqiong^[90]Patients with nephrotic syndrome were divided into control group（32（33The control group was given conventional treatment, and the treatment group was given Huangqi Danggui decoction. The results showed that Huangqi Danggui decoction could effectively improve the overall protein metabolism disorder of patients, significantly promote the improvement of renal function, and the clinical treatment effect was significant.

3.1.2 Diabetic lesions  Zhaoxiaomei^[91]Studied the. And studies have shown that Astragalus membranaceus-. Astragalus membranaceus-WhenThe compatibility ratio was3∶2It can significantly reduce the serum of patients with early diabetic nephropathyNOandNOSLevel, and has good clinical safety^[92]。Zhaoxian^[93]take68Cases of patients with diabetic peripheral neuropathy were divided into control group and treatment group. The control group was treated with insulin and mecobalamin injection while the treatment group was treated with self-made Huangqi Danggui decoction,The results showed that the treatment group could effectively improve the hemorheological indexes of patients with diabetic peripheral neuropathy, protect nerves, and the curative effect was very good. Astragalus membranaceus-WhenreturnTreatment of qi deficiency and blood stasis type2In patients with type 2 diabetes mellitus, it was found that it can increase the patient's serum8-IsoprostanesF2αLevel, resist oxidative stress, thereby reducing the degree of macrovascular disease in patients^[94]。

3.1.3  Hematological diseases  Gao Huan et al^[95]Observation of Danggui Buxue Decoction CombinedEPOFor the clinical efficacy of renal anemia, the control group was givenEPOThe treatment group was added with Danggui Buxue Decoction on the basis of the control group. The results showed that the levels of red blood cells, hemoglobin and hematocrit in the treatment group were significantly higher than those in the control group, indicating that Danggui Buxue Decoction Combined withEPOThe treatment of renal anemia can significantly improve the clinical efficacy. Danggui Buxue Decoction Combined with recombinant humanEPOIt can also treat anemia in premature infants, reduce the incidence of anemia in premature infants at various times, improve the body immunity, and promote the growth of body mass^[96]Danggui Buxue Decoction Combined with chemical drugs also has significant curative effect in the treatment of various postoperative anemia^[97-98]。

. Chen Ping^[99]Treated with Danggui Buxue Decoction24Patients with leukemia were cured14Example: remarkable effect5Example: effective3E.g., total effective rate91.7%。

3.1.4  Perimenopausal syndrome  Some women may have a series of symptoms during the perimenopausal period, such as menstrual disorders, hot flushes, palpitations, dizziness, etc. . Using a randomized double-blind dose escalation clinical study, it was found that Danggui Buxue Decoction could significantly reduce patients' vasomotor symptoms, hot flushes and night sweats^[100]Professor Kong Li also achieved good results in treating perimenopausal vertigo with Danggui Buxue Decoction^[101]。

3.1.5 Antitumor  The role of Danggui Buxue Decoction in the clinical treatment of cancer mainly includes the enhancement and attenuation of chemotherapy, bone marrow suppression protection, immunosuppression protection and other aspects. ^[102]take392Cases of patients with malignant tumor were randomly divided into control group and treatment group. The clinical trial confirmed that the Modified Danggui Buxue Decoction had the effect of increasing efficiency and reducing toxicity on malignant tumor. Gaopeifang et al^[103]take38Cases of patients with advanced lung cancer were randomly divided into control group and treatment group. The control group was given conventional chemotherapy, and the treatment group was added with Huangqi Danggui Decoction on the basis of the control group. Results the improvement of clinical symptoms and the reduction of bone marrow suppression in the treatment group were better than those in the control groupAccording to the control group, Huangqi Danggui decoction has a significant effect on preventing and treating bone marrow suppression after chemotherapy.Chenqueting et al^[104]Patients after breast cancer surgery were randomly divided into chemotherapy group and chemotherapy drugs combined with Danggui Buxue Decoction group for treatment. The immune indexes before and after treatment were detected. The results showed that Danggui Buxue Decoction Combined with chemotherapy drugs significantly improved the immune function of the body damaged by chemotherapy.

3.1.6 other  Astragalus membranaceus-Angelica sinensis is also used in the treatment of clinical symptoms such as leukopenia, primary thrombocytopenic purpura, arthralgia, uterine dysgenesis amenorrhea, uterine fibroids, plantar pain, gingival bleeding and senile skin itching^[105]。

3.2  Astragalus membranaceus-Application of Angelica sinensis in traditional Chinese medicine compound preparation

Astragalus membranaceus-Angelica sinensis, as a pair of Qi and blood tonics, has a long history of compatibility and application. It appeared in a variety of ancient famous prescriptions, and has also been widely used in modern empirical prescriptions. Summarized the Chinese Pharmacopoeia2020See table for Chinese patent medicines containing astragalus membranaceus and Angelica sinensis collected in2。

Among them, the most representative Chinese patent medicine preparation is Danggui Buxue oral liquid, which is extracted and refined by modern technology from Astragalus membranaceus and Angelica sinensis. When used in combination, it has the effect of nourishing qi and blood. Clinically, it is mostly used to treat Qi and blood deficiency syndrome. Studies have shown that Danggui Buxue oral liquid has significant efficacy in the treatment of anemia^[106]The combination of the two can also treat chronic atrophic gastritis with dysplasia^[107], senile pruritus^[108], symptoms after hemiarthroplasty in the elderly^[109]In addition, according to the clinical symptoms and signs.

4  Conclusion and Prospect

The pharmacological effects of Astragalus membranaceus and Angelica sinensis are relatively clear, and the research on the extraction process, chemical components, pharmacological mechanism and metabolic process in vivo is also relatively in-depth-The scientific nature and necessity of the compatibility of Angelica sinensis and Angelica sinensis were elaborated from the aspects of chemical composition, pharmacological effect and clinical application. A comparative study of Danggui Buxue Decoction, a typical traditional Chinese medicine compound composed of Astragalus membranaceus and Angelica sinensis, revealed that Astragalus membranaceus-The compatibility ratio of Angelica sinensis was 0.The compatibility ratio of Angelica sinensis was 0.05% and 0.05% respectively......the compatibility ratio of Angelica sinensis was 0.05% and 0.05% and 0.05% respectively5∶1Danggui Buxue Decoction has better pharmacological effects than Astragalus and Angelica alone, indicating that Astragalus-The compatibility of Angelica sinensis has more advantages than the single drug alone.

Astragalus membranaceus-The combined application of Angelica sinensis compound preparation and Astragalus preparation is mainly aimed at the treatment of deficiency of both qi and blood. For these traditional Chinese medicine preparations with prominent pharmacological effects and significant efficacy, we should make full use of modern science and technology and means to clarify their chemical components, and further study their pharmacodynamic material basis, in vivo pharmacokinetic characteristics, pharmacological mechanism, etc., so as to lay the foundation for the development of innovative drugs and provide the basis for clinical rational drug use. -The chemical composition, pharmacological action and in vivo process of Angelica sinensis in traditional Chinese medicine compound preparations, especially in large compound preparations, are quite complex, so the disassembly method can be used to study one of them separately1To explore the contribution of various drugs in the compound compatibility to the whole prescription, and compare the effect of different dosage of drugs on the efficacy of the whole prescription. With the rapid development of analysis and testing technology and the enhancement of multidisciplinary cross penetration and complementary strength, spectrum effect relationship research, multi-target high-throughput screening, biological chromatography technology, serum medicinal chemistry, metabolomics and other methods can be applied to the study of pharmacodynamic material basis. The methods of system biology or network pharmacology can also be used for comprehensive evaluation of complex pharmacodynamics.

The modernization of traditional Chinese medicine preparations is an important part of the modernization of traditional Chinese medicine. Under the guidance of the theory of traditional Chinese medicine, combined with the new technology, new equipment, new methods and new excipients of modern pharmaceutics, some traditional dosage forms of chemical drugs have been widely used in traditional Chinese medicine. At the same time, a series of new drug delivery systems of traditional Chinese medicine with modern high-tech content have emerged, and the traditional Chinese medicine pair has also ushered in a good development opportunity. . However, the physicochemical properties of the effective components of traditional Chinese medicine are complex. The use of liposomes, polymer micelles and other dosage forms will lead to different encapsulation efficiency of different components in the drug pair, thus changing the compatibility ratio of the drug pair and Chinese drugs, and affecting the clinical efficacy. Therefore, in the development of Astragalus membranaceus-When Angelica sinensis is a new preparation, on the basis of fully understanding its material basis and physical and chemical properties, it is necessary to select a suitable new preparation process, combine the drug introduction in the drug pair with new drug delivery systems such as liposomes and polymer micelles, and developThe active "guiding" effect of the volatile drug and the passive targeting effect of the preparation can improve the targeting specificity and achieve the effect of multiple targeting; It is also necessary to combine the natural penetration enhancers in the compound with modern pharmaceutics to further promote the absorption of drugs, so as to play a greater clinical value.

In conclusion, Astragalus membranaceus-Angelica sinensis and its compound preparations have good effects in the treatment of Qi blood deficiency syndrome and other diseases. In the future, further research should be carried out on the pharmacodynamic components, metabolites and pathways, pharmacological mechanism, clinical mechanism of action and the development of new dosage forms of the drug pair, so as to make it more widely used in clinic.

References (omitted)  

Come   Source: to   ; Wan. Research progress on chemical constituents, pharmacological effects and clinical applications of Astragalus Angelica; [J] . Chinese herbal medicine, 2022, 53 (7): 2196-2213