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    Research progress of modern pharmacological effects of Pueraria lobata and its compound clinical application

    2023-04-05 04:00:20LIRongSONGZongliangZHANGXiaokeWUNingjingYOUQingxiao
    Journal of Hainan Medical College 2023年2期

    LI Rong, SONG Zong-liang, ZHANG Xiao-ke, WU Ning-jing, YOU Qing-xiao

    1.Shaanxi University of Traditional Chinese Medicine, Xianyang 712046, China

    2.The Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine, Xianyang 712000, China

    Keywords:

    ABSTRACT

    1.Introduction

    Pueraria lobata is the dried root of the legume Pueraria lobata(Willd.) Ohwi or Pueraria thomsonii Benth.The former is often called "wild kudzu" and the latter is called "fen kudzu".Pueraria lobata was not only used as a food for famine relief in ancient times, but also a commonly used Chinese medicinal material in clinical practice.First recorded in "Shen Nong's Materia Medica":"Pueraria lobata, cures thirst, severe body heat, vomiting, various numbness, yin qi, detoxification.", later recorded in "Medicinal Fu": "can rise and fall, Yang Zhongyin is also.It has four uses: the appearance of typhoid fever, the relief of stomach deficiency and the quenching of thirst; the relieving of the harsh toxins of liquor,and the treatment of warm malaria.".Traditional Chinese medicine believes that Pueraria lobata is sweet, pungent, cool in nature, and returns to the spleen, stomach, and lung meridians.It is commonly used to treat exogenous fever, headache, strong back pain, measles,yin deficiency and thirst, spleen deficiency and diarrhea, chest obstruction, dizziness, etc.It is also a commonly used Chinese medicine in traditional Chinese medicine compound prescriptions.Modern pharmacological studies show that Pueraria lobata root has chemical components such as isoflavones, triterpenes, saponins,alkaloids, coumarin compounds and polysaccharides, among which isoflavones are the most content, mainly including daidzein and daidzein Yuan and puerarin, among which puerarin has the largest content [1].Modern pharmacological effects include antipyretic, antiinflammatory, anti-infection, anti-cancer, lowering blood pressure,lowering blood sugar, lowering blood fat, protecting liver, protecting heart, improving osteoporosis, improving reproductive function,etc.In recent years, many scholars have conducted research on the chemical composition, pharmacological effects, mechanism of action and clinical application of Pueraria lobata root.The author consulted reports on Pueraria lobata root at home and abroad,focusing on the review of the modern pharmacological effects and clinical application of Pueraria lobata root, and its rational use Provide reference and basis for development and utilization.

    2.Pharmacological action

    The main pharmacologically active ingredients of Pueraria lobata root are isoflavone compounds, which have antipyretic, antiinflammatory, anti-infective, anti-cancer, anti-atherosclerosis,lowering blood pressure, lowering blood sugar, lowering blood lipids, protecting liver, preventing osteoporosis, and improving reproductive function and other pharmacological effects.

    2.1 Anti-diabetes and its complications

    Puerarin can play an anti-diabetic and its complications by improving insulin resistance, protecting pancreatic β-cell function,inhibiting inflammation, regulating autophagy, resisting oxidative stress, and affecting insulin and glucagon receptor signaling pathways.

    Wang C et al.[2] used a high-fat diet (HFD)-induced diabetic mouse model with exendin-4 (GLP-1R agonist) and metformin as a positive control method to study the effect of puerarin in diabetic mice.The results showed that puerarin can significantly improve the blood glucose homeostasis of diabetic mice, and new β-cell formation markers (insulin, PDX1 and Ngn3) were observed in the pancreatic ducts of diabetic mice treated with puerarin.Puerarin can also Induces the expression of insulin and PDX1, up-regulates the expression of GLP-1R and subsequently activates β-catenin and STAT3.It is worth noting that the in vivo effects of puerarin will be eliminated by the GLP-1R antagonist exendin9-39, but exendin-4 can enhance its efficacy.It is explained that the anti-diabetic effect of puerarin is to promote β-cell regeneration through GLP-1R signal activation, thereby improving the blood glucose homeostasis and glucose tolerance of diabetic mice.This finding indicates the clinical value of puerarin as an anti-diabetic drug.

    Chen X et al [3] formed T2DM by injecting HDF into mice and intraperitoneal injection of streptozotocin (STZ).After eight weeks of puerarin treatment, blood samples were drawn from the tail veins of mice that were fasted overnight.The results show that puerarin can up-regulate the expression of key proteins in the Nrf2/HO-1 and PI3K/Akt signaling pathways, and play a significant role in lowering blood sugar and improving insulin resistance.Puerarin also exhibits lipid-lowering activity by reducing the levels of total cholesterol,triglycerides and low-density lipoproteins, and increasing the levels of high-density lipoproteins.It can also reduce the level of reactive oxygen species and increase the activity of glutathione dismutase,which has a beneficial effect on oxidative stress.

    By using the diabetic nephropathy (DN) mouse model made by STZ to study the effect of puerarin on the regulation of autophagy under endoplasmic reticulum stress (ERS) [4], in the PERK inhibition of ERS/autophagy animal model, It is suggested that puerarin promotes autophagy through the transduction of PERK/eIF2 /ATF4 signal network in the regulation of ERS-mediated autophagy to protect the structure and pathological changes of the kidney in DN.And after puerarin treatment, mitochondrial damage and basement membrane fusion were alleviated.It is proved that puerarin has a renal protective effect on patients with DN.Studies have also found that [5] puerarin upregulates miRNA-140-5p by reducing the levels of inflammatory cytokines TNF-α, IL-1β and IL-6, and preventing the activation of the TLR4/MyD88/NF-κB (p65) pathway.Reduces or prevents DN-induced impaired renal function.

    Cai Y et al.[6] used STZ to create a diabetic mouse model.By measuring the changes in blood glucose, oxidative stress and the expression of activator of transcription 3 (STAT3), the results confirmed that puerarin can lower blood sugar, increase insulin levels, and increase retinal SOD activity.Increase the content of T-AOC in the retina and reduce the content of MDA, thereby enhancing the antioxidant capacity of the retina.At the same time,puerarin can significantly inhibit the expression of STAT3, protect the retina, and improve diabetic retinopathy.

    Studies have confirmed [7] that Gegen Qinlian Decoction (GQD)promotes adipose tissue browning (BAT) and reduces lipid accumulation by activating PPAR /RXR and SIRT1 signaling pathways.GQD can make SAT differentiation and maturity,strengthen energy loss, help reduce the body's glucose and lipid metabolism disorder, and correct the symptoms of diabetes.This research provides a theoretical basis and medication basis for GQD clinical treatment of obesity-related diabetes.

    2.2 Improve cardiovascular and cerebrovascular diseases

    Puerarin has a certain effect in the treatment of myocardial ischemia-reperfusion injury, subarachnoid hemorrhage and other cardiovascular and cerebrovascular diseases.It may expand coronary and cerebral blood vessels, increase blood flow, reduce lipid accumulation, resist platelet aggregation, and improve micro The role of circulation is related.

    2.2.1 Anti-hypertension

    Long-term hypertension can damage the heart, brain, kidney and other organs, causing myocardial ischemia and cerebral hemorrhage.Shi W et al.[8] found in the study that after administering puerarin to spontaneously hypertensive rats for 2 months, the systolic and diastolic blood pressure of the rats decreased significantly, and at the same time, it also slowed the heart rate of the rats and improved NO and cGMP level.It was also found that eNOS is an important target of puerarin's mechanism of lowering blood pressure, which proves that puerarin can be used as an antihypertensive drug in clinical applications.Zhao QY et al.[9] used the total flavonoids of Pueraria lobata in the clinical observation of the curative effect of ischemic stroke and essential hypertension during the recovery period.After treatment with randomized, positive drugs and placebocontrolled, double-blind trial methods, 12 weeks It was concluded that the relative independence rate, clinical cure rate, and total effective rate of NIHSS in the Pueraria total flavonoid group were significantly higher than those in the placebo group (P<0.05).At 12,18, and 24 weeks after treatment, the blood pressure control rate of Pueraria lobata group was significantly higher than that of placebo group (P<0.01).It was finally confirmed that Pueraria lobata has a significant effect on improving patients' quality of life, neurological function and controlling hypertension.

    2.2.2 Anti-atherosclerosis

    Atherosclerosis (AS) is the main cause of coronary heart disease and cerebral infarction.Studies have shown [10] that puerarin attenuates the low-density lipoprotein-induced vascular smooth muscle cell (VSMC) proliferation by inhibiting the p38 MAPK and JNK signaling pathways, indicating that puerarin can be used as an effective drug to slow the progression of AS.At the same time,Hao D et al.[11] found that puerarin, daidzein, and tanshinone in the ethanol extract of Danlou tablets inhibit NF-κB signal and trigger PPARα/ABCA1 through apolipoprotein E-deficient mouse model and network pharmacology research.The signaling pathway plays an important role in anti-inflammatory and preventing macrophage lipid deposition in AS.Deng Y et al.[12] found in experiments that compared with HFD-only mice, the atherosclerotic lesions of the aortic root and the entire aortic cross-section of HFD mice treated with puerarin were significantly reduced, confirming that Puerarin can inhibit the adhesion of monocytes by activating the ERK5/KLF2 signaling pathway, reduce AS lesions in mice, and have a protective effect on AS.Studies have also shown that puerarin can increase the concentration of vasoactive substances, regulate the function of vascular endothelial cells, promote the re-endothelialization of blood vessels, reduce the formation of neointima, and weaken the vascular remodeling at the injured part of the artery, and further prevent the development of AS[13].

    2.2.3 Protect the heart

    Puerarin can prevent a variety of cardiovascular diseases, Chen ZQ et al.[14] established coronary artery microembolism (CME)models, CME+puerarin model rats, and measured cardiac function,myocardial histopathology and myocardial cell apoptosis index, and found that puerarin can reduce Bax and lysed caspase -3, and upregulate Bcl-2 and PI3K/Akt/GSK-3β pathway related proteins,reduce cardiomyocyte apoptosis, and significantly improve cardiac dysfunction after CME.It is proved that puerarin can protect cardiomyocytes and reduce apoptosis, thereby improving myocardial damage caused by CME.Studies have also shown that puerarin reduces inflammation by inhibiting the SIRT1/NF-κB pathway to prevent myocardial ischemia/reperfusion injury, and inhibits the activation of NLRP3 inflammasomes, confirming that puerarin is a new candidate drug for the treatment of ischemic heart disease [15].

    2.2.4 Improve cerebrovascular diseases

    Zhang Y et al.[16] tested whether puerarin can reduce brain nerve damage after subarachnoid hemorrhage (SAH), used neurological scores, brain water content, etc.to detect neurological deficits after SAH, and detect neuronal decline by TUNEL staining.The mortality rate was detected by Western Blot to detect the changes of Blc-2,Bax, cleaved caspase-3 and Sirt3, and the ROS activity and the Aslysine level of SOD2 were detected experimentally.The results proved that puerarin can improve neurological deficits in SAH mice,improve brain edema, and reduce BBB damage.It was found that the rate of neuronal apoptosis decreased after puerarin treatment of SAH.In addition, compared with vehicle-treated SAH animals,the Blc-2/Bax ratio in puerarin-treated SAH mice was significantly increased and the expression of caspase-3 was down-regulated.In addition, puerarin effectively reversed these expression changes and inhibited SAH-induced ROS production.And it can increase the activation of SOD after SAH and protect the expression of Sirt3 after SAH.It was finally confirmed that puerarin has a protective effect on SAH's damage to nerves and can be used as a new therapy for SAH.

    2.2.5 Lower blood lipids

    Lipid metabolism disorder is the pathological basis of AS, which causes cardiovascular and cerebrovascular diseases.Studies have shown [17] that puerarin can effectively reduce dyslipidemia and reduce intramuscular lipid accumulation by up-regulating the expression of a series of genes related to mitochondrial function,oxidative phosphorylation, active oxygen detoxification and fatty acid oxidation in the muscles of diabetic rats.It is proved that puerarin can improve the function of muscle mitochondria and promote the oxidation of fatty acids, reduce the accumulation of lipids, and thus play a role in lowering blood lipids.At the same time,Yang F et al.[18] used HDF feeding combined with STZ to establish a T2DM rat model.Then the rats were randomly divided into normal group, model group, metformin group, puerarin low-dose group,middle-dose group and high-dose group.After successful modeling,the rats were given corresponding drug intervention and intragastric administration for 4 weeks.The results showed that the weight of the metformin group and puerarin group decreased after 4 weeks of intervention, and the levels of FBG, TC, TG, LDL-C, ALT, AST,BUN, SCr, and UA decreased (P<0.01); at the same time, the level of HDL-C was significant Increase (P<0.05).It shows that puerarin can reduce the body weight of T2DM rats and reduce the blood lipid and blood sugar levels of T2DM rats.It is proved that puerarin can be used to control the blood sugar, blood lipids and body weight of T2DM patients in clinical practice.

    2.3 Anti-cancer

    Puerarin can inhibit tumor proliferation and induce cell apoptosis,weaken the vitality of cancer cells, prevent migration and invasion,and achieve anti-tumor effects.

    Studies have shown that puerarin can inhibit the migration,invasion and adhesion of MCF-7 and MDA-MB-231 cells induced by lipopolysaccharide (LPS) by blocking the NF-κB and Erk pathways in breast cancer cells.The experiment showed that puerarin can be used as a new type of drug for the treatment of breast cancer and inhibiting its metastasis [19].Most breast cancerrelated deaths are caused by recurrence or metastasis, so it has a certain potential for clinical value.Li J et al.[20] analyzed puerarin’s anti-colorectal cancer (CRC) targets and molecular mechanisms based on network pharmacology and found that puerarin can inhibit the proliferation of CRC cells and increase cell apoptosis in a dosedependent manner.And the down-regulation of TDP1, ALDH1A1 and proliferating cell nuclear antigen expression was detected in CRC cells treated with puerarin.Finally, it was concluded that the pharmacological molecules of TDP1 and ALDH1A1 may be new potential targets for the treatment of CRC.In addition, puerarin can regulate the circ_0020394/miR-328-3p/NRBP1 axis, downregulate circ_0020394 and increase the expression of miR-328-3p in bladder cancer, weaken cell viability, prevent migration, invasion and glycolysis, and promote bladder cancer Apoptosis of cells exerts its anti-tumor effect.It shows that Pueraria lobata can be used as a promising drug for the treatment of bladder cancer [21].

    2.4 Anti-inflammatory, anti-viral

    Puerarin exerts its anti-inflammatory and antiviral effects mainly by inhibiting the transduction of inflammatory signal pathways and the expression of pro-inflammatory factors.

    Atopic dermatitis (AD) is one of inflammatory immune diseases,and puerarin can improve many inflammatory diseases.The study found that [22] used 2,4-dinitrochlorobenzene (DNCB) to induce ADlike skin damage in BALB/c mice for 17 d, and then administered puerarin to BALB/c mice orally.It was found that puerarin can improve AD-like symptoms induced by DNCB in mice by regulating skin thickness, mast cell degranulation and serum immunoglobulin E (IgE).Experiments have confirmed that puerarin can inhibit the secretion of inflammatory cytokines and chemokines, improve ADlike skin lesions and skin inflammation by regulating various atopic and inflammatory mediators, and have protective and alleviating effects on it.Therefore, puerarin helps to treat AD and other inflammatory skin diseases.

    Qin X et al.[23] analyzed the pharmacological targets, functions,signal pathways, and mechanism of action of puerarin in the treatment of COVID-19 based on network pharmacology.The key targets of puerarin for the treatment of COVID-19 have been identified, including epidermal growth factor receptor, caspase 3, RELA proto-oncogene, Fos proto-oncogene, caspase 8,prostaglandin endoperoxidase 2, Interleukin 2, protein kinase CB,B-cell lymphoma/leukemia genes, protein kinase CA, etc.The mechanism of action is that puerarin inhibits inflammation-related signal pathways through anti-oxidative stress and inflammatory cascade response and reduction of cell apoptosis, including the regulation of apoptosis pathway, IL-17 signal pathway, mitogenactivated protein kinase signal pathway and The TNF signaling pathway achieves anti-COVID-19 effects.The effective anti-COVID-19 activity of puerarin was confirmed, suggesting that puerarin is a promising anti-COVID-19 active compound.

    Studies have shown that [24] Puerarin inhibits porcine epidemic diarrhea virus (PEDV) replication in both in vitro and in vivo experiments, and can also regulate the signaling pathway of PEDV infecting piglets, weaken the activation of NF-kB in the ileum, and regulate interferon and NF-kB signal transduction to resist PEDV infection.These results indicate that puerarin can exert antiviral and anti-inflammatory effects in piglets infected with PEDV, and may become an effective antiviral feed additive.

    2.5 Antipyretic effect

    Pueraria lobata has a history of thousands of years in China as an antipyretic for the treatment of fever.Yao XJ et al.[25] evaluated the antipyretic effect of puerarin by establishing a rat fever model made by LPS.It was found that the body temperature of fever rats given puerarin decreased significantly, and puerarin can inhibit the production of pyrogen interleukin-1β, tumor necrosis factor- ,interleukin-6, prostaglandin E(2) and nitric oxide.It shows that puerarin has a significant antipyretic effect.The study revealed that the antipyretic mechanism of Pueraria lobata root is to inhibit the production and expression of endogenous pyrogens, thereby playing a febrile effect, providing a scientific basis for the antipyretic effect of Pueraria lobata root as a traditional Chinese medicine.

    2.6 Protect the liver

    Puerarin can reduce liver steatosis and liver fibrosis through LKB1/AMPK/ACC and TGF-β/ERK1/2 pathways to protect the liver.

    Jiang B et al.[26] studied liver cell morphological changes, fibrosis and hyperplasia, fat cell infiltration and liver function changes in a mouse model experiment of liver injury caused by chronic alcoholism, and showed that Pueraria lobata can improve liver damage and prevent liver damage.The changes in microglia and neurons have a protective effect on microglia and neurons exposed to alcohol.It is proved that Pueraria lobata has a protective effect on human liver injury.Pueraria lobata can be used as a potential therapeutic drug for chronic diseases of liver dysfunction and neurological deficit.Feng R et al.[27] used a mouse model of alcoholic liver injury with chronic and single alcohol feeding and found that ethanol exposure leads to liver damage, which is mainly manifested by histopathological changes, increased lipid accumulation, liver oxidative stress and inflammation Et al.Pueraria lobata improved the above performance by up-regulating LKB1/AMPK/ACC signal to reduce alcohol-induced liver steatosis.The protective effect of Pueraria lobata on alcoholic liver steatosis and liver inflammation was confirmed.

    Liver fibrosis is a complex pathological process and an early step in the progression of liver cirrhosis, which can eventually develop into hepatocellular carcinoma.Li X et al.[28] established a model of liver fibrosis by intraperitoneal injection of thioacetamide (TAA)to study the effect of puerarin in the treatment of liver fibrosis.The results showed that puerarin treatment significantly reduced the histopathological changes and collagen fiber content of rat liver tissue samples (P<0.05).Compared with the control group,the relative protein expression levels of TGFβ1, α-SMA, type I collagen, fibronectin and p-ERK1/2 were significantly up-regulated in the TAA group (P<0.05), and puerarin treatment reversed these changes.These findings confirm that puerarin reduces liver fibrosis through the TGF-β/ERK1/2 pathway, inhibits hepatic stellate cell activation and excessive collagen deposition in liver fibrosis, and reduces the expression level of extracellular matrix proteins to delay liver cirrhosis Progress.

    2.7 Improve osteoporosis

    Puerarin improves osteoporosis by inhibiting osteoclast production and oxidative stress in bone tissue, HDAC1/HDAC3 signal transduction, and increasing the proliferation of osteoblasts.

    Studies have shown that in osteoporosis, puerarin can inhibit the expression of TRAF6 and NADPH oxidase 1, and increase the expression of antioxidant enzymes such as heme oxygenase-1 to reduce intracellular ROS levels, by inhibiting TRAF6/ROS,MAPK /NF-κB signaling pathway to inhibit osteoclast production,thereby reducing bone loss in ovariectomized mice and preventing osteoporosis.Because puerarin has little effect on breast epithelial cells, it is a potential drug candidate for the treatment of osteoclastrelated osteoporosis in postmenopausal women [29].

    Wang XH et al.[30] found in a study that high glucose can inhibit the proliferation and differentiation of osteoblasts and the expression of type I collagen mRNA in a diabetic environment, but puerarin can increase the proliferation and differentiation of osteoblasts and the expression of type I collagen mRNA.The expression indicates that puerarin has a therapeutic effect on diabetic osteoporosis(DOP), and provides a basis for the clinical treatment of DOP by puerarin.In addition, in the DOP study [31], it was also found that the administration of puerarin significantly reduced STZ-induced bone loss, anti-tartrate acid phosphatase activity and femoral tissue microstructure damage in rats.In addition, it was also found that puerarin can inhibit inflammation and cell apoptosis in STZ rats, and the overexpression of HDAC1/HDAC3 can aggravate inflammation and cell apoptosis.Puerarin can significantly eliminate cell inflammation and apoptosis by inhibiting HDAC1/HDAC3.It is proved that puerarin can prevent diabetic osteoporosis.

    2.8 Anti-Aging

    Estrogen is the key hormone that regulates skin aging homeostasis in the body.It is known as "phytoestrogens".It directly acts on dermal fibroblasts and has the effect of reducing the aging of endothelial progenitor cells.Its mechanism may be related to the ER pathway.However, the effect of puerarin on skin aging and fibroblast phenotype is still poorly understood.Kamiya Y et al.[32] studied the cytoprotective and anti-aging properties of puerarin in normal human skin fibroblasts (NHDFs) in vitro.In the experiment, normal NHDFs were subcultured and high-passage cells were selected as senescent cells.Choose low-passage cells as the method of young cell control.It was found that puerarin can increase cell proliferation and reduce the proportion of β-galactosidase-positive cells associated with aging in NHDFs culture.Moreover, puerarin treatment reduced the number of smooth muscle actin-positive myofibroblasts induced in NHDF and the expression of reticular fibroblast marker calcin-1.The results showed that the isoflavones in Pueraria lobata root can prevent the development of the aging phenotype of human skin fibroblasts and reduce the functional defects related to aging in skin fibroblasts.Based on this, new anti-skin aging drugs and treatment methods can be developed.

    2.9 Improve reproductive function

    Chen C et al.[33] made a premature ovarian failure (POF) model by randomly dividing female mice into four groups, one group was used as a control, and the other three groups were injected with cyclophosphamide and busulfan to create a premature ovarian failure (POF) model.In the POF model, the ovaries were observed.The size of the mouse decreased, the number of dominant follicles decreased, the number of atretic follicles increased significantly,and the expression of Mvh and Oct4 decreased.However, after treatment with puerarin, the ovarian morphology of the mice changed significantly.The number of follicles in the POF + puerarin group Lower than the control group, but higher than the POF group.In addition, the up-regulation of Mvh and Oct4 expression indicates that puerarin protects ovarian function by maintaining the survival of female reproductive stem cells.This experiment shows that puerarin can improve the survival rate of female germline stem cells, and play a protective effect on POF through the Wnt/β-catenin signaling pathway and alleviate oxidative stress.

    2.10 Other

    Pueraria lobata also has certain effects in protecting prostate hyperplasia, cervical spondylosis, and antidiarrheal.

    Masrudin SS et al.[34] found that Pueraria lobata extract, daidzein and genistein significantly improved prostate cells in rats induced by testosterone in a model study of testosterone-induced prostate hyperplasia in rats, indicating that Pueraria lobata is effective in the treatment of benign prostate hyperplasia.Has a protective effect.

    There have been related records of Pueraria lobata treating Xiangbi in the Qin and Han Dynasties in my country, and modern pharmacological studies have also confirmed its curative effect on cervical spondylosis.Studies believe that puerarin is the main active ingredient in the treatment of Xiangbi, which is mainly used to treat cervical spondylosis by inhibiting inflammation, inhibiting the proliferation of osteoclasts, and enhancing the vitality of osteoblasts[35].

    Zhong Lingyun et al.[36] conducted gastric emptying and small intestinal propulsion rate experiments with puerarin and daidzein,and found that both puerarin and daidzein can significantly improve the residual rate in the stomach, reduce the small intestinal propulsion rate, and reduce diarrhea.Index, and has a significant dose-effect relationship.It shows that puerarin and daidzein have a significant antidiarrheal effect, and the antidiarrheal effect is stronger after simmering.

    3.Compound application

    Compared with a single drug, Chinese herbal compound has a better clinical effect.Pueraria lobata is commonly used in the treatment of diabetes and its complications, cardiovascular and cerebrovascular diseases, gastrointestinal diseases, cervical spondylosis, etc.

    3.1 Diabetes related diseases application

    Root is a commonly used Chinese medicine in the treatment of diabetes.Studies have found that the use of Gegen Qinlian Decoction in patients with insulin resistance can improve the body's biological effect on insulin [37].The clinical efficacy and blood sugar level analysis of Gegen Qinlian Decoction in the treatment of diabetic patients clearly affirmed its blood sugar lowering effect [38].

    3.2 Application of gastrointestinal diseases

    Pueraria lobata returns to the lung and stomach meridian, has the functions of clearing away heat and detoxification, drying dampness and stopping diarrhea, and reaching the surface and clearing the inside.It is widely used in the treatment of gastrointestinal diseases in Chinese medicine.Studies have shown that Gegen Qinlian Decoction not only shortens the course of diarrhea, but also applies to various infectious diarrhea, ulcerative colitis, radiation proctitis,irritable bowel syndrome, Helicobacter pylori infection, damp-heat anal itching, etc.[39].Pueraria lobata plus Banxia decoction also has obvious curative effect in treating peptic ulcer and chronic gastritis.

    3.3 Application of respiratory diseases

    Xia Ting et al.[40] based on network pharmacology studies showed that Gegen Qinlian Decoction can effectively treat dry cough, fever and dyspnea caused by COVID-19.It also has a certain effect on chronic pharyngitis [41] and acute suppurative tonsillitis [42].

    3.4 Application of orthopedic diseases

    Gegen Decoction has the effect of relaxing tendons and relieving pain, and has significant effects in bone and joint diseases.Studies have confirmed that water needle knife combined with Gegen Decoction in the treatment of radiculopathy of cervical spondylosis can improve clinical efficacy, improve clinical symptoms and cervical function, and relieve pain [43].Guizhi plus Gegen Decoction has also achieved significant effects in the treatment of frozen shoulder, stiff neck, and acute lumbar sprain.

    3.5 Application of cardiovascular and cerebrovascular diseases

    Clinical research Gegen Qinlian Decoction has pharmacological effects such as lowering blood pressure, lowering blood sugar,lowering lipids, slowing heart rate, anti-arrhythmia, dilating coronary blood vessels, and improving heart and brain Among them, a large dose of Pueraria lobata root is the key to the effect.Often starting from 30 g, the maximum available is 120 g, which can quickly alleviate the item strength and quickly reduce blood pressure [44].It can be used alone to reduce blood pressure in the treatment of hypertension.It is often combined with Gastrodia and Uncaria Decoction, Bupleurum and Longgu Oyster Soup to lower blood pressure.Studies have found that the combination of Pueraria lobata and Ligusticum chuanxiong can effectively improve nerve function,reduce cerebral infarction, and relieve the complications of cerebral ischemic stroke, including dyslipidemia, increased blood viscosity,and thrombosis risk.It has a significant effect on cerebral ischemic stroke [45].

    3.6 Other applications

    Studies have confirmed [46] that Chaishao Gegen Decoction assists in the treatment of facial neuritis in children, by reducing the level of TNF-α and IL-6 in the body, inhibiting the inflammatory response,thereby playing a certain therapeutic effect on facial neuritis.

    4.Concluding remarks

    Pueraria lobata root has been used as an antiepileptic medicine for thousands of years.It is known as "Asian ginseng".Its clinical effects are remarkable and it has great development and utilization value.This article reviews the pharmacological effects and main clinical applications of Pueraria lobata root.The chemical components of Pueraria lobata root are mainly concentrated in isoflavones and triterpenoids.It has obvious anti-diabetic, antitumor, anti-inflammatory and other pharmacological effects, and its mechanism is mainly through regulation.Transduction of related signal pathways, inhibition of pro-inflammatory factor expression,and induction of tumor cell apoptosis have achieved their clinical effects.Pueraria lobata and its compound are now mostly used in the prevention and treatment of diabetes, cardiovascular and cerebrovascular diseases, and digestive tract diseases.Although modern research has made some progress in the research on the chemical composition and pharmacological effects of Pueraria lobata root, the research on the material basis of its pharmacological effects is still not deep enough, such as the pharmacological effects of alkaloids, coumarin compounds and polysaccharides.The structureactivity relationship and mechanism of action, the interaction relationship with other types of Chinese medicine compatibility,pharmacodynamic analysis, effective dose and other aspects are worthy of in-depth study and discussion.

    Author's contribution:

    Li Rong: Select topic, design article structure, and write articles.Song Zong-liang, Zhang Xiao-ke: Guide topic selection and article writing, scientific research guidance.Wu Ning-jing, You Qing-xiao:Provide support for revisions.

    All authors declare no conflict of interest.

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