Extraction, purification, structure characteristics, biological activities and pharmaceutical application of Bupleuri Radix Polysaccharide: A review.

Abstract Traditional Chinese medicine (TCM) has been widely used for several centuries for metabolic diseases, including non-alcoholic fatty liver disease (NAFLD). At present, NAFLD has become the most prevalent form of chronic liver disease worldwide and can progress to non-alcoholic steatohepatitis (NASH), cirrhosis, and even hepatocellular carcinoma. However, there is still a lack of effective treatment strategies in Western medicine. The development of NAFLD is driven by multiple mechanisms, including genetic factors, insulin resistance, lipotoxicity, mitochondrial dysfunction, endoplasmic reticulum stress, inflammation, gut microbiota dysbiosis, and adipose tissue dysfunction. Currently, certain drugs, including insulin sensitizers, statins, vitamin E, ursodeoxycholic acid and betaine, are proven to be beneficial for the clinical treatment of NAFLD. Due to its complex pathogenesis, personalized medicine that integrates various mechanisms may provide better benefits to patients with NAFLD. The holistic view and syndrome differentiation of TCM have advantages in treating NAFLD, which are similar to the principles of personalized medicine. In TCM, NAFLD is primarily classified into five types based on clinical experience. It is located in the liver and is closely related to spleen and kidney functions. However, due to the multi-component characteristics of traditional Chinese medicine, its application in the treatment of NAFLD has been considerably limited. In this review, we summarize the advances in the pathogenesis and treatment of NAFLD, drawn from both the Western medicine and TCM perspectives. We highlight that Chinese and Western medicine have complementary advantages and should receive increased attention in the prevention and treatment of NAFLD. 

Integrated traditional Chinese and Western medicine in the prevention and treatment of non-alcoholic fatty liver disease: future directions and strategies

Xiaoyao san (XYS) plays an important role in treatment of non-alcoholic fatty liver disease (NAFLD) with liver stagnation and spleen deficiency, but its specific mechanism is still unclear. This study aimed to investigate the material basis and mechanism by means of network pharmacology, metabolomics, systems biology and molecular docking methods. On this basis, NAFLD rat model with liver stagnation and spleen deficiency was constructed and XYS was used to intervene, and liver histopathology, biochemical detection, enzyme-linked immunosorbent assay, quantitative PCR assay and western blotting were used to further verify the mechanism. Through the above research methods, network pharmacology study showed that there were 94 targets in total for XYS in the treatment of NAFLD. Metabolomics study showed that NAFLD with liver depression and spleen deficiency had a total of 73 differential metabolites. Systems biology found that PTGS2 and PPARG were the core targets; Quercetin, kaempferol, naringenin, beta-sitosterol and stigmasterol were the core active components; AA, cAMP were the core metabolites. And molecular docking showed that the core active components can act well on the key targets. Animal experiments showed that XYS could improve liver histopathology, increase 5HT and NA, decrease INS and FBG, improve blood lipids and liver function, decrease AA, increase cAMP, down-regulate PTGS2, up-regulate PPARG, and decrease PGE2 and 15d-PGJ2. In conclusion, XYS might treat NAFLD with liver depression and spleen deficiency by down-regulating PTGS2, up-regulating PPARG, reducing AA content, increasing cAMP, improving insulin resistance, affecting glucose and lipid metabolism, inhibiting oxidative stress and inflammatory response.Communicated by Ramaswamy H. Sarma.

Mechanism of Xiaoyao San in treating non-alcoholic fatty liver disease with liver depression and spleen deficiency: based on bioinformatics, metabolomics and in vivo experiments.

The Radix Bupleuri and Radix Paeoniae Alba herb-pair (RRH) are the most classic compatible drug pair for the treatment of hepatitis. However, the underlying mechanism remains unclear. Therefore, network pharmacology and molecular docking were conducted to investigate the prospective therapeutic constituents, targets, and pharmacological mechanisms of RRH in the treatment of hepatitis. The active components of RRH from the TCMSP database and disease-related targets from the OMIM, PharmGkb, GeneCards, TTD, and DrugBank databases were identified. The “drug-target-disease” network diagram and protein–protein interaction (PPI) network were constructed using Cytoscape (v3.8.0) and Online STRING 11.0. GO and KEGG pathway enrichment analyses were performed using R version 4.1.2, and molecular docking was performed to verify the results. We placed 176 overlapping cross genes into Online STRING 11.0 and obtained 14 core targets. A “Component-Target-GO-KEGG” network diagram was constructed, which was composed of 7 components, 14 targets, 10 biological processes, and 10 signal pathways. A total of 2413 GO biological processes and 174 KEGG pathways were explored for hepatitis treatment. Quercetin, kaempferol, isorhamnetin, and beta-sitosterol, which are the main bioactive components, were employed to bind the disease's hub targets, ensuring fulfillment of spatial and energy matching. The anti-hepatitis mechanism of RRH may be associated with several targets including RELA, AKT1, JUN, MAPK1, TP53, CCND1, MYC, NFKBIA, CDKN1A, and their respective signaling pathways. The main bioactive components in RRH, including quercetin, kaempferol, isorhamnetin, and beta-sitosterol, were used to bind the hub targets of the disease, which may provide insights into drug development for hepatitis.

Network pharmacology and molecular docking technology for exploring the effect and mechanism of Radix Bupleuri and Radix Paeoniae Alba herb-pair on anti-hepatitis: A review

Background: Yuquan Pill (YQW) is a modern concentrated pill preparation of six herbs, namely, Ge Gen (Pueraria lobata Ohwi), Di huang (Rehmannia glutinosa Libosch.), Tian Huafen (Trichosanthes kirilowii Maxim.), Mai Dong (Ophiopogon japonicus (L. f.) Ker Gawl.), Wu Weizi (Schisandra chinensis (Turcz.) Baill.) and Gan Cao (Glycyrrhiza uralensis Fisch.). It is extensively used to treat type 2 diabetes-related glucose and lipid metabolism disorders. But what’s the pharmacodynamic substance and how it works in the treatment of Type 2 diabetes mellitus (T2DM) are still unclear.Purpose: The purpose of this study is to determine the likely pharmacological components and molecular mechanism of YQW’s intervention on T2DM by combining serum pharmacochemistry, network analysis and transcriptomics.Methods: The efficacy and prototypical components of blood entry were determined after oral administration of YQW aqueous solution to T2DM rats induced by high-fat feed and low-dose streptozotocin (STZ), and the key targets and pathways for these compounds to intervene in T2DM rats were predicted and integrated using network analysis and transcriptomics techniques.Results: In diabetic rats, YQW can lower TG, CHO, NO, and MDA levels (p < 0.05) while increasing HDL-C levels (p < 0.01), and protecting the liver and kidney. 22 prototype components (including puerarin, daidzein, 3′-methoxypuerarin, and liquiritigenin, among others) were found in the serum of rats after oral administration of YQW for 90 min, which might be used as a possible important ingredient for YQW to intervene in T2DM rats. 538 YQW pharmacodynamic components-related targets and 1,667 disease-related targets were projected through the PharmMapper database, with 217 common targets between the two, all of which were engaged in regulating PI3K-Akt, MAPK, Ras and FoxO signal pathway. Finally, the mRNA expression profiles of liver tissues from rats in the control, model, and YQW groups were investigated using high-throughput mRNA sequencing technology. YQW can regulate the abnormal expression of 89 differential genes in a disease state, including 28 genes with abnormally high expression and 61 genes with abnormally low expression. Five common genes (Kit, Ppard, Ppara, Fabp4, and Tymp) and two extensively used regulatory pathways (PI3K-Akt and MAPK signaling pathways) were revealed by the integrated transcriptomics and network analysis study.Conclusion: The mechanism of YQW’s intervention in T2DM rats could be linked to 22 important components like puerarin, daidzein, and glycyrrhetinic acid further activating PI3K-Akt and MAPK signaling pathways by regulating key targets Kit, Ppard, Ppara, Fabp4, and Tymp, and thus improving lipid metabolism disorder, oxidative stress, and inflammation levels in T2DM rats. On the topic, more research into the pharmacological ingredient foundation and mechanism of YQW intervention in T2DM rats can be done.

Elucidating the pharmacodynamic mechanisms of Yuquan pill in T2DM rats through comprehensive multi-omics analyses

Xiaoyao Powder in the treatment of non-alcoholic fatty liver disease: A systematic review and meta-analysis.

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Xiaoyao Powder in the treatment of non-alcoholic fatty liver disease: A systematic review and meta-analysis.