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Objective:To summarize the clinical researches of Wumei Pill and provide reference for clinical application and follow-up research.Methods:The databases CNKI, VIP, Wanfang, CBM, PubMed, Embase were retrieved from the inception to June 30,2022. CiteSpace 6.1.R3 software was used to analyze the research hotspots and keywords in the literature. Using EndNote X9 software and Microsoft Office Excel 2013, we recorded and analyzed the published year, literature type, affiliated journal, disease treated, TCM syndrome type, single drug dose and treatment duration of the included articles.Results:212 articles were included. Diarrhea, gastritis, diabetes, insomnia were the research hotspots. The types of diseases treated by Wumei Pill mainly include digestive system, endocrine system and tumor, mainly for cold-heat syndrome and Jueyin syndrome. The average dosage of Mume Fructus was the largest, 21 g. The average treatment time was 5.78 weeks. Conclusion:At present, the overall clinical research of Wumei pill shows an increasing tendency, mainly involving gastrointestinal disease.
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Wumeiwan are recorded in the Jueyin chapter of Treatise on Cold Damage and Miscellaneous Diseases （《伤寒杂病论》）， and many doctors in the past dynasties believed that they had the effects of calming intestinal ascarid by warming Zang organs. The clinical application was limited. Since KE Qin， a doctor in the Qing dynasty， proposed that Wumeiwan were the primary prescription against Jueyin diseases， Wumeiwan have been valued by doctors， and their clinical application has also been expanded. The syndrome indicated for Wumeiwan is attributed， not only to the ascarid internal harassment， but to the abnormal Qi movement of wind and wood in Jueyin and the dysfunction of Yin and Yang. According to the functions of six meridians based on the theory of "open-close axis" in Huangdi's Internal Classic （《黄帝内经》） and the original texts of Treatise on Cold Damage and Miscellaneous Diseases， Yinshu refers to Jueyin. Wumeiwan， the primary prescription against Jueyin diseases， have the function of connecting Yin and Yang， and they can treat diseases caused by Qi disturbance of Jueyin and cold and heat in complexity. Sharing the same resource， the Secrets for Auxiliary Cultivation Life： The Essential Method of Using Herbal Medicine for the Differential Treatment of the Five Zang Organs （《辅行诀五脏用药法要》） and Treatise on Cold Damage and Miscellaneous Diseases both consult Models of the Classic of Decoction （《汤液经方》）. The formulation rules of tonic/purgative and collapse-saving prescriptions in Secrets for Auxiliary Cultivation Life follow the recorded "Tang Ye Jing Fa Tu" （an image revealing the compatibility principles of Chinese herbal drugs） and are closely related to the five elements theory. By exploring the formulation rules in "Tang Ye Jing Fa Tu" and the five elements of drugs， this study analyzed Wumeiwan and proved that Wumeiwan mainly acted on the liver， spleen， and heart. According to the Five Zang-organs Storing Spirit theory from Huangdi's Internal Classic， the above three organs are closely related to emotional adjustment. Therefore， the treatment of emotional disorders caused by qi disturbance of Jueyin and cold and heat in complexity with Wumeiwan is supported by evidence. At the end of this article， the reports on the treatment of emotional disorders with Wumeiwan in recent years were listed and reviewed. This article provides new ideas for the clinical application of Wumeiwan in the treatment of emotional disorders and expands the application range.
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ObjectiveTo investigate the effect and mechanism of Wumeiwan against Lewis lung cancer in mice with syndrome of cold and heat in complexity based on hepatocyte growth factor/mesenchymal-epithelial transition factor （HGF/C-Met） signaling pathway. MethodTwenty healthy male mice were classified into blank group， model group （equivalent volume of distilled water， ig）， cisplatin group （4.0 mg·kg-1 cisplatin， ip）， and Wumeiwan group （12.5 mL·kg-1 Wumeiwan， ig）， with 5 in each group. Lewis lung cancer with the syndrome of cold and heat in complexity was induced in mice except the blank group by gavage of propylthiouracil， Zhimu Shigaotang， and Fanxieye， ice-water swimming， and subcutaneous injection of dry yeast suspension and Lewis cell suspension under the right armpit. After modeling， administration began and lasted 6 weeks. After the experiment， the tumor weight， tumor volume， tumor inhibition rate， and lung cancer metastasis-inhibiting proportion were measured and calculated. The pathological morphology of lung tissue was observed based on hematoxylin and eosin （HE） staining. The growth state of tumor tissue was analyzed by immunohistochemistry. The mRNA expression of HGF and C-Met was detected by Real-time polymerase chain reaction （PCR）， and the protein expressions of HGF， C-Met， survivin， and X-linked inhibitor of apoptosis protein （XIAP） by Western blot. ResultCompared with the blank group， the model group showed high mRNA expression of HGF and C-Met and protein expression of HGF， C-Met， surviving， and XIAP （P<0.01）. Compared with the model group， Wumeiwan group displayed low proportion of positive cells， positive cell density， positive score （P<0.05）， histochemical score， tumor weight， tumor volume （P<0.01）， mRNA expression of HGF and C-Met （P<0.01）， and protein expression of HGF， C-Met， surviving， and XIAP （P<0.01）. Compared with the model group， the cisplatin group displayed decrease in the proportion of positive cells， density of positive cells （P<0.05）， positive score， tumor weight， tumor volume （P<0.01）， mRNA expression of HGF and C-Met （P<0.01）， and protein expression of HGF， C-Met， surviving， and XIAP （P<0.01）， and insignificant variation in the histochemical score. Wumeiwan group had high mRNA expression of HGF （P<0.01）， and insignificant variation in the proportion of positive cells， positive cell density， histochemical score， positive score， tumor weight， tumor volume， mRNA expression of C-Met， and protein expression of HGF， C-Met， surviving， and XIAP. ConclusionWumeiwan can slow down the progression of Lewis lung cancer in mice with syndrome of cold and heat I complexicity by inhibiting HGF/C-Met signaling pathway.
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ObjectiveTo observe the effects of Wumeiwan-medicated serum on the proliferation， invasion， migration， and apoptosis of human pancreatic cancer SW1990 cells and explore the underlying mechanism. MethodThe Wumeiwan-medicated serum was prepared and the pancreatic cancer SW1990 cell line was cultured in vitro. The optimal time of Wumeiwan-medicated serum was selected for subsequent experiments by cell counting kit-8（CCK-8）. SW1990 cells were divided into a control group and low- （2%）， medium- （4%）， and high-dose （8%） Wumeiwan-medicated serum groups. The colony-forming， migration， and invasion abilities were detected by clonogenic assay， wound healing assay， and transwell migration assay. Flow cytometry was used to detect the effect of Wumeiwan-medicated serum on the apoptosis of pancreatic cancer SW1900 cells. Western blot was used to detect the expression levels of apoptosis-related proteins， such as B-cell lymphoma-2（Bcl-2）， Bcl-2-associated X protein （Bax）， cytochrome C （Cyt C）， cleaved cysteinyl aspartate-specific protease-3 （cleaved Caspase-3）， cleaved cysteinyl aspartate-specific protease-9 （cleaved Caspase-9）， as well as phosphatidylinositol 3-kinase（PI3K）， phosphorylated PI3K（p-PI3K）， protein kinase B （Akt）， and phosphorylated Akt（p-Akt）in PI3K/Akt pathway in SW1990 cells. ResultCompared with blank group， Wumeiwan groups showed decreased absorbance （A） 72 h after drug intervention （P<0.01）. Compared with the low-dose group， the medium- and high-dose groups showed decreased A （P<0.01）. Compared with the medium-dose group， the high-dose group showed decreased A （P<0.01）. It indicates that Wumeiwan can inhibit SW1990 cell proliferation in a dose-dependent manner after 72 h， and the optimal action time is 72 h. Compared with the blank group， the Wumeiwan groups showed weakened invasion of SW1990 cells （P<0.01）， reduced colony-forming and migration abilities （P<0.05， P<0.01） in a dose-dependent manner， and increased total apoptosis rates （P<0.01）. The inducing effect of Wumeiwan on apoptosis increased with the increase in dosage. Compared with the blank group， the Wumeiwan groups showed decreased protein expression of Bcl-2 （P<0.01）， increased protein expression of cleaved Caspase-3， cleaved Caspase-9， Cyt C， and Bax （P<0.05， P<0.01） in a certain dose-effect relationship， reduced protein expression of p-PI3K and p-Akt （P<0.05， P<0.01） with the increase in dosage， and declining p-PI3K/PI3K and p-Akt/Akt （P<0.05， P<0.01） with the increase in dosage. ConclusionWumeiwan-medicated serum can significantly inhibit the malignant biological behaviors of pancreatic cancer SW1990 cells and induce apoptosis. The mechanism may be related to the inhibition of the PI3K/Akt signaling pathway and down-regulation of protein phosphorylation level in the PI3K/Akt signaling pathway.
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Objective:To explore the potential target and mechanism of Wumeiwan in the treatment of lung metastasis of breast cancer by network pharmacological analysis and experimental verification. Method:The databases of active ingredients and targets of Wumeiwan were established through Traditional Chinese Medicine Systems Pharmacology（TCMSP） Database and Analysis Platform，and the targets of lung metastasis of breast cancer were established through the GeneCards database and Online Mendelian Inheritance in Man（OMIM） database，and the data of Chinese medicine targets and disease targets were matched. Cytoscape 3.6.0 software was used to establish the network analysis of traditional Chinese medicine-active ingredients-therapeutic targets，and the interaction relationship between key target proteins was analyzed by STRING database. Target gene ontology（GO） analysis and Kyoto Encyclopedia of Genes and Genomes（KEGG） signal pathway enrichment analysis were performed by using the Biological Information Annotation Database. Result:A total of 108 possible important targets for Wumeiwan in the treatment of lung metastasis of breast cancer were found，including interleukin 6（IL6），cysteine aspartate-specific protease-3（CASP3），vascular endothelial growth factor A（VEGFA），epidermal growth factor receptor（EGFR），mitogen-activated protein kinase（MAPK8）， and others. GO enrichment analysis yielded 29 cell components（CC），1 218 biological processes（BP） and 125 molecular functions（MF） related to lung metastasis of breast cancer，and KEGG enrichment analysis yielded 118 pathways related to lung metastasis of breast cancer（<italic>P<</italic>0.05），including MAPK signaling pathway and apoptosis pathway. <italic>In vitro</italic> experiments showed that cinnamaldehyde， the active ingredient of Wumeiwan， could induce apoptosis，inhibit proliferation and migration of MCF7 cells，partially validating the predicted results of network pharmacology to a certain extent. Conclusion:The therapeutic effect of Wumeiwan on lung metastasis of breast cancer may be multi-target，multi-pathway and multi-mechanism. The results of this study provide more evidence for the clinical application of Wumeiwan.
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Diabetes has become one of the fastest growing public health issues in the world. Its pathological mechanism is complex and affected by multiple factors. There are trillions of microbes in the human intestine， which are roughly divided into three types： probiotics， neutral bacteria， and pathogenic bacteria. They are in a dynamic balance and constitute a complex intestinal micro-ecosystem. The balance and homeostasis of the intestinal micro-ecosystem are essential to maintain the stability of the body's environment and human health. With the rapid development of high-throughput sequencing technology， imbalanced intestinal flora distribution has been proven to be an important factor in promoting the development of insulin resistance （IR）， thus increasing the risk of diabetes. In recent years， the regulation of intestinal flora has become a new approach and new target for the prevention and treatment of diabetes and its complications. The application of traditional Chinese medicine （TCM） in treatment of metabolic diseases such as diabetes and obesity has a long history. TCM has its unique characteristics and advantages， however， the unclear mechanism of action has limited its modernization and industrialization. The harmonious symbiosis between the intestinal flora and the host is consistent with the TCM theory of "harmony between human and nature". The effect of TCM on the intestinal microflora has gradually become a hot topic in medical research today. One study believes that diabetes originates from "intestinal fever". At present， some relevant experimental researches and clinical research literatures have shown that some heat-clearing Chinese herbal compounds have a certain regulating effect on imbalanced intestinal flora. Therefore， the relationship between intestinal flora and diabetes was explored， and the mechanism of heat-clearing Chinese herbal compounds （Da Chaihutang， Gegen Qinliantang， Huanglian Jiedutang， and Wumeiwan） in preventing and treating heat syndrome of diabetes through regulation of intestinal flora was analyzed， in order to provide new theoretical basis and research clues for the further development of drugs for treating diabetes.
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Biliary tract cancers are group of highly heterogeneous malignant tumors derived from gallbladder and bile duct epithelium， including gallbladder cancer and cholangiocarcinoma， with a high degree of malignancy. When diagnosed， the course of disease often develops to the middle and late stage， with a poor prognosis. It is difficult to treat the advanced biliary tract cancers， with a lack of unified chemotherapy standard and targeted drugs. Traditional Chinese medicine（TCM） compound has multi-target， multi-link and multi-path characteristics， with effects in stabilizing tumor， alleviating clinical symptoms， alleviating side effect of radiotherapy and chemotherapy， and improving the quality of life. Especially in the treatment of advanced cancer patients， it plays an irreplaceable role. Therefore， it is concerned by many researchers. According to TCM， the pathogenesis of patients with advanced biliary tract cancers are mainly due to asthenia of healthy Qi and sthenia of pathogenic factors， Yin-Yang disharmony， and simultaneous occurrence of cold and heat. The location of the disease is related to liver， gallbladder， spleen， stomach and kidney. Because the advanced biliary tract cancers are similar to Jueyin syndrome in disease location， course and disease， Wumeiwan is often used in clinical treatment. Based on "theory， method， prescription and medicine" of TCM， Wumeiwan has the effect in regulating cold and heat， clearing the upper and lower temperature， warming the liver and supporting Yang， attacking and supplementing simultaneously， balancing the liver， spleen and kidney， which conforms to the TCM syndrome characteristics of advanced biliary tract cancers， according to modern Chinese medicine pharmacology， many effective ingredients in Wumeiwan have the effects in inducing tumor cell apoptosis， inhibiting tumor cell proliferation and reducing tumor cell proliferation， reducing inflammatory response in the body， inhibiting angiogenesis， reversing multidrug resistance of tumor cells and regulating immunity. This paper analyzes the feasibility of treatment of advanced biliary tract cancers with Wumeiwan from the perspective of traditional Chinese and Western medicine， so as to provide reference for clinical comprehensive treatment of advanced biliary tract cancers and the experimental study of TCM.
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Objective::To study the effects of Wumeiwan on blood glucose, intestinal microflora, tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10) and dietary fiber fermented by intestinal microflora in type 2 diabetic (T2DM) rats. Method::Totally 80 SD clean rats were selected as experimental subjects, and 10 of them were randomly selected as the normal group. The remaining 70 rats were given high-sugar and high-fat emulsion for 8 weeks and intraperitoneally injected with streptozotocin (STZ, 35 mg·kg-1) to establish the rat model of T2DM. The fasting blood glucose higher than 11.10 mmol·L-1 was considered as a successful model. The rats that were not successfully modeled were removed, and the remaining rats that were successfully modeled were randomly divided into model group, metformin group, high-dose Wumeiwan group, medium-dose Wumeiwan group and low-dose Wumeiwan group, with 10 rats in each group. Normal group and model group received (ig) normal saline (20 mL·kg-1·d-1), while metformin group (ig metformin 200 mg·kg-1·d-1), Wumeiwan high, medium and low dose groups (ig Wumeiwan 20, 10, and 5 g·kg-1·d-1) received corresponding drugs respectively. Blood glucose and body weight of rats were monitored regularly before and after administration of the drugs. Blood and feces were collected after four weeks of administration.16S-rDNA high-throughput sequencing technology was used for gene sequencing of intestinal flora. Enzyme linked immunoassay (ELISA) was used to detect the serum levels of inflammatory factors TNF-α and IL-10 in rats, and the contents of acetic acid, propionic acid and butyric acid in feces were detected by gas chromatography. Result::As compared with the normal group, the body weight decreased significantly (P<0.01). Bacteroidetes, Actinobacteria, Bacteroides, Clostridium increased, Firmicutes, Deltaproteobacteria, and Lactobacillus decreased, fasting blood glucose and serum TNF-α levels increased significantly (P<0.01), IL-10 level decreased (P<0.01), and the contents of acetic acid, propionic acid and n-butyric acid of short-chain fatty acids decreased(P<0.05, P<0.01) in model group. As compared with the model group, the body weight decreased; Bacteroidetes, Actinobacteria, Bacteroides and Clostridium decreased. Firmicutes, DeltaProteobacteria and Lactobacillus increased; fasting blood glucose and serum TNF-α decreased (P<0.01), and IL-10 increased (P<0.01), contents of acetic acid, propionic acid and n-butyric acid increased in Wumeiwan high-dose, medium-dose and low-dose groups and metformin group (P<0.05, P<0.01). Conclusion::Wumeiwan may prevent and treat T2DM by regulating intestinal flora, improving inflammatory response, increasing SCFAs content and reducing blood glucose.
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Objective: To observe the clinical efficacy of Wumeiwan combined with Bazhentang in the treatment of obesity type 2 diabetes with Qi and Yin deficiencies, phlegm and stasis. Method: Totally 60 patients with type 2 diabetes mellitus were randomly divided into observation group and control group, with 30 cases in each group. Observation group was given Wumeiwan combined with modified Bazhentang in addition to Western medicine (metformin hydrochloride). The control group was treated with traditional Western medicine (metformin hydrochloride). The course of treatment is eight weeks. Fasting blood sugar (FPG),2 hPG (2 hPG),glycosylated hemoglobin (HbA1c),total cholesterol (TC),triglycerin (TG),body mass index (BMI),safety indicators (three major routine,liver and kidney functions) and clinical symptoms before and after treatment between two groups were compared. The clinical efficacy of two groups was evaluated. Result: The observation group had an effective rate of 93.3% (28/30),which was significantly higher than 73.3% (22/30) of the control group,with statistically significant differences (PPPPConclusion: Modified Wumeiwan combined with Bazhentang is safe and effective in treating patients with type 2 diabetes mellitus with Qi and Yin deficiencies, phlegm and stasis,and can reduce blood sugar,blood lipid,BMI level and relieve clinical symptoms of patients, and so worth promotion.
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The effects of Wumeiwan (WMW) on TNF-α, IL-6, IL-8, IL-10 and NF-κBp65 in rats with ulcerative colitis (UC) were investigated, the curative effectiveness of WMW vs salicylazosul-fapyridine (SASP) was compared, and the action mechanism was analyzed. Fifty-Six Spra-gue-Dawley (SD) rats were randomly divided into four groups (n=14 in each group, with equal ratio of male and female): normal control group, model group, SASP group, and WMW group. Except normal control group, the rat UC models in the remaining three groups were established using the method of 2.4-dinitrochlorobenzene (DNCB) immunization and acetic acid local enema. The rats in model group, SASP group, and WMW group were treated with distilled water, SASP, and WMW re-spectively. The changes in the symptoms and signs were observed, and levels of IL-6, IL-8, TNF-α,IL-10 and the expression of NF-κBp65 in the colonic tissues were statistically analyzed. The results showed that the levels of IL-6, IL-8, and TNF-α were significantly increased (P<0.01), while those of IL-10 significantly reduced (P<0.01) after establishment of rat UC models as compared with normal control group. The levels of IL-6, IL-8, and TNF-α were obviously lower, bat the level of IL-10 was obviously higher in WMW and SASP groups than those in model group (P<0.05). The levels of IL-6,IL-8, and TNF-α were lower, while the level of IL-10 was higher in WMW group than in SASP group.NF-κBp65 was expressed negatively or weakly in normal colonic tissues. The positive expression rate of NF-κBp65 in WMW group and SASP group was obviously lower than in model group (P<0.01), and there was significant difference between WMW group and SASP group (P<0.05). It was concluded that rat UC model was established successfully. WMW could up-regulate the expres-sion oflL-10, down-regulate the expression ofTNF-α, IL-6, IL-8, and inhibit the NF-κBp65 activity to adjust immune function, indicating WMW had better curative effects on UC in rats.
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[Objective] To observe the effect of Wumei Wan on histological features of colic mucosa of rats with uleera-tive colitis. [ Methods ] Forty rats were randomly allocated to normal control group ( Group A), model group ( Group B), salicylazosulfapyridine group (Group C) and Wumei Wan group (Group D). Ulcerative colitis models were established by immune method combined with local stimulation. After gastric infusion treatment, the histological features of colic mucosa of rats were observed under light microscope and transmission electron microscope. [Results] The results of pathological slices showed histological feature of colic mucosa in Wumei Wan group was much improved as compared with Group C. [Conclusion] Wumei Wan has a certain effect in treating ulcerative colitis.