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Huangqi Guizhi Wuwu Decoction is a classic prescription in traditional Chinese medicine(TCM) and is known for its effects of tonifying Qi, warming the meridians, and promoting blood circulation to alleviate obstruction. It is primarily used to treat conditions characterized by Qi stagnation, Yang deficiency, and obstruction, and it exhibits pharmacological effects such as immune regulation, anti-inflammation, analgesia, protection of the cardiovascular and cerebrovascular systems, itch relief, reduction of frostbite symptoms, antioxidative stress, promotion of cell apoptosis, and kidney protection. In modern clinical practice, it is commonly used to treat acute myocardial infarction, sequelae of cerebral infarction, cervical spondylosis, frozen shoulder, lower limb arteriosclerosis, lower limb vascular disorders, peripheral neuropathy in diabetes, and lupus nephritis. Recent research has focused on the chemical components, pharmacological effects, and clinical applications of Huangqi Guizhi Wuwu Decoction. Based on the "five principles" of quality markers(Q-markers) in TCM, this study predicted and analyzed the Q-markers of Huangqi Guizhi Wuwu Decoction. It suggested that astragaloside â £, formononetin, kaempferol, quercetin, cinnamic acid, cinnamaldehyde, 6-gingerol, paeoniflorin, albiflorin, and gallic acid could serve as Q-markers for Huangqi Guizhi Wuwu Decoction. The findings of this study can provide references for quality control of Huangqi Guizhi Wuwu Decoction and the development of new Chinese medicinal formulations.
Assuntos
Medicamentos de Ervas Chinesas , Congelamento das Extremidades , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Astragalus propinquus , Congelamento das Extremidades/tratamento farmacológicoRESUMO
Background: The Jiawei Kongsheng Zhenzhong pill (JKZP), a Chinese herbal prescription comprised of eight Chinese crude drugs, has been historically employed to treat neurological and psychological disorders. Nevertheless, the ambiguous material basis severely hindered its progress and application. Purpose: The current study aimed to establish a rapid analytical method for identifying the chemical components of the JKZP aqueous extract and the components absorbed into the rat serum to investigate the quality markers (Q-markers) responsible for the neuroprotective effects of JKZP. Methods: The qualitative detection of the chemical components, prototype components, and metabolites of the aqueous extracts of JKZP, as well as the serum samples of rats that were administered the drug, was performed using the ultra-performance liquid chromatography- quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) technology. This analysis combined information from literature reports and database comparisons. Moreover, the study was conducted to anticipate the potential Q-markers for the neuroprotective effects of JKZP based on the "five principles" of Q-marker determination. Results: A total of 67 compounds and 111 serum components (comprising 33 prototypes and 78 metabolites) were detected and identified. Combining the principles of quality transmission and traceability, compound compatibility environment, component specificity, effectiveness, and measurability, the study predicted that five key compounds, namely, senkyunolide H, danshensu, echinacoside, loganin, and 3,6'-disinapoyl sucrose, may serve as potential pharmacological bases for the neuroprotective effects of JKZP. Conclusion: To summarize, the UPLC-Q-TOF-MS/MS technique can be employed to rapidly and accurately identify compounds in JKZP. Five active compounds have been predicted to be the Q-markers for the neuroprotective effects of JKZP. This discovery serves as a reference for improving quality, advancing further research and development, and utilizing Chinese herbal prescriptions.
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ETHNOPHARMACOLOGICAL RELEVANCE: Shenling Baizhu San (SLBZS) is a formula of traditional Chinese medicine (TCM) that enhances the functions of the qi, spleen, and lung. According to the theory of TCM, chronic obstructive pulmonary disease (COPD) is often caused by lung qi deficiency, and SLBZS is often used in the treatment of COPD and has achieved remarkable results. However, the active components of SLBZS absorbed in serum and the underlying mechanism of SLBZS in treating COPD remain unclear and require further studies. AIM OF THE STUDY: The objective of this study is to investigate the active components of SLBZS in rat serum, as well as the crucial targets and signaling pathways involved in the therapeutic effects of SLBZS for COPD. MATERIALS AND METHODS: First, the absorption components and metabolites of SLBZS in rat serum were identified using ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). Second, potential targets of SLBZS for the treatment of COPD were acquired from publicly accessible online sources. Cytoscape (v3.7.0) software was used to construct a component-target-pathway network and a protein-protein interaction (PPI) network. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of potential targets was performed using the Metascape database. The binding status of the active components in SLBZS to the potential targets was assessed with molecular docking technology. Finally, a cell model of COPD was successfully developed for experimental validation In vitro. RESULTS: A total of 108 active components were identified, including 30 prototype components and 78 metabolites. A total of 292 potential targets for the treatment of COPD were identified, including TNF, IL-6, TLR9, RELA, and others. The KEGG pathway included inflammatory mediator regulation of TRP channels, necroptosis, and the NF-κB signaling pathway, among others. The In vitro experiments showed that SLBZS-containing serum had the ability to decrease the levels of inflammatory factors and cell death. Additionally, it was observed that SLBZS-containing serum could control the expression levels of TLR9, MyD88, TRAF6, NF-κB, and IκBα at the mRNA and protein levels. These findings suggested that SLBZS-containing serum was likely to be involved in the regulation of the TLR9/NF-κB pathway. CONCLUSIONS: The mechanism of action of SLBZS on COPD was preliminarily elucidated using UPLC-Q-TOF-MS/MS, network pharmacology, and In vitro experiments. The primary active components and potential targets of SLBZS were identified, providing a scientific foundation for further research.
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Medicamentos de Ervas Chinesas , Doença Pulmonar Obstrutiva Crônica , Animais , Ratos , Espectrometria de Massas em Tandem , Farmacologia em Rede , NF-kappa B , Cromatografia Líquida de Alta Pressão , Simulação de Acoplamento Molecular , Receptor Toll-Like 9 , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológicoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Polycystic ovary syndrome (PCOS) is a prevalent female endocrine condition that significantly affects women of all age groups and is characterized by metabolic dysfunction. The efficacy of existing pharmaceutical interventions for the treatment of PCOS remains inadequate. With a rich history and cultural significance spanning thousands of years, Traditional Chinese Medicine (TCM) is extensively employed for treating a variety of ailments and can serve as a supplementary therapy for managing PCOS. Multiple clinical observations and laboratory tests have unequivocally demonstrated the substantial effectiveness and safety of TCM formulae in treating PCOS, and further investigations are currently in progress. AIM OF THE STUDY: To summarize the TCM formulae commonly employed in the clinical management of PCOS, examine their therapeutic benefits, investigate their mechanism of action, active constituents, and establish the correlation between efficacy, mechanism of action, and active constituents. MATERIALS AND METHODS: We conducted a comprehensive search on PubMed, Web of Science, and China national knowledge infrastructure (CNKI) using the following keywords: "Polycystic Ovary Syndrome", "Traditional Chinese Medicine Decoctions", "Traditional Chinese Medicine formulae", "Traditional Chinese Medicine", "Clinical Observation", "Mechanism", "Treatment", "Pharmacology", and various combinations of these terms. From January 1, 2006 until October 7, 2023, (inclusive). RESULTS: This paper summarized the clinical effectiveness, mechanism of action, and active components of 8 TCM formulae for the treatment of PCOS. Our research indicates that TCM formulae can potentially treat PCOS by enhancing the levels of hyperandrogenism and other endocrine hormones, decreasing insulin resistance and hyperinsulinemia, and controlling chronic low-grade inflammation, among other modes of action. In addition, we found an association between epigenetics and TCM formulae for the treatment of PCOS. CONCLUSION: TCM formulae have specific advantages in the treatment of Polycystic Ovary Syndrome (PCOS). They achieve therapeutic benefits by targeting several pathways and connections, attracting considerable interest and playing a vital role in the treatment of PCOS. TCM formulae can be used as an adjunctive therapy for the treatment of PCOS.
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Resistência à Insulina , Síndrome do Ovário Policístico , Feminino , Humanos , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/metabolismo , Medicina Tradicional Chinesa , Inflamação , ChinaRESUMO
BACKGROUND: Epidemiological evidence links the proprotein convertase subtilisin/kexin 7 (PCSK7) to triglyceride (TG) metabolism. We associated the known PCSK7 gain-of-function non-coding SNP rs236918 with higher levels of plasma apolipoprotein B (apoB) and the loss-of-function coding variant p.Pro777Leu (SNP rs201598301) with lower apoB and TG. Herein, we aimed to unravel the in vivo role of liver PCSK7. METHODS: We biochemically defined the functional role of PCSK7 in lipid metabolism using hepatic cell lines and Pcsk7-/- mice. Our findings were validated following subcutaneous administration of hepatocyte-targeted N-acetylgalactosamine (GalNAc)-antisense oligonucleotides (ASOs) against Pcsk7. RESULTS: Independent of its proteolytic activity, membrane-bound PCSK7 binds apoB100 in the endoplasmic reticulum and enhances its secretion. Mechanistically, the loss of PCSK7/Pcsk7 leads to apoB100 degradation, triggering an unfolded protein response, autophagy, and ß-oxidation, eventually reducing lipid accumulation in hepatocytes. Non-alcoholic fatty liver disease (NAFLD) was induced by a 12-week high fat/fructose/cholesterol diet in wild type (WT) and Pcsk7-/- mice that were then allowed to recover on a 4-week control diet. Pcsk7-/- mice recovered more effectively than WT mice from all NAFLD-related liver phenotypes. Finally, subcutaneous administration of GalNAc-ASOs targeting hepatic Pcsk7 to WT mice validated the above results. CONCLUSIONS: Our data reveal hepatic PCSK7 as one of the major regulators of apoB, and its absence reduces apoB secretion from hepatocytes favoring its ubiquitination and degradation by the proteasome. This results in a cascade of events, eventually reducing hepatic lipid accumulation, thus supporting the notion of silencing PCSK7 mRNA in hepatocytes for targeting NAFLD.