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BACKGROUND: Sepsis causes inflammation in response to infection, often leading to acute lung injury (ALI). Yazhicao (Commelina communis L., YZC) is widely distributed in the global tropics and has good anti-respiratory inflammatory activity; however, the protection of YZC against septic-ALI has not been established. PURPOSE: The role of YZC in septic-ALI will be investigated in this study. METHODS AND RESULTS: In this study, YZC was shown to inhibit excessive inflammation and alleviate septic-ALI. Network pharmacology predicts that Quercetin, Acacetin and Diosmetin have the potential to serve as the pharmacological substance basis of YZC in alleviating septic-ALI. The metabolomics results indicated that YZC could improve the metabolic disorders caused by septic-ALI, which were mostly concerned with energy metabolism and amino acid metabolism, with Trimethylamine (TMA)/Trimethylamine N-oxide (TMAO) being potential small molecule metabolic markers for the clinical diagnosis and treatment of septic-ALI. YZC inhibits the initiation and progression of septic-ALI by controlling the TMA/TMAO metabolites. Our results also suggest that YZC protects the intestinal barrier from damage. Furthermore, our research indicated that YZC reduces TMAO synthesis by inhibiting TMA production through remodeling the intestine microbiota. We investigated the mechanism of YZC-mediated protection against septic-ALI and showed that YZC reduced the expression of proteins associated with NLRP3 inflammatory vesicles in the lung by inhibiting the expression of NF-κB. CONCLUSION: These results show that YZC inhibits the NF-κB/NLRP3 signaling pathway by regulating metabolic and intestinal flora disorders in septic-ALI mice to reduce TMAO synthesis. This study presents a theoretical groundwork for the advancement of novel medications and clinical use of YZC to enhance septic-ALI and furnishes a theoretical rationale for regulating intestinal microbiota as a therapeutic instrument to treat sepsis and septic-ALI.
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Lesão Pulmonar Aguda , Microbioma Gastrointestinal , Metabolômica , Metilaminas , Proteína 3 que Contém Domínio de Pirina da Família NLR , Sepse , Transdução de Sinais , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Transdução de Sinais/efeitos dos fármacos , Masculino , Sepse/tratamento farmacológico , Metilaminas/metabolismo , Camundongos , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Camundongos Endogâmicos C57BL , Extratos Vegetais/farmacologia , Modelos Animais de Doenças , Farmacologia em RedeRESUMO
Background: KIAA1429, a member of the RNA methyltransferase complex, is involved in cancer progression; however, the clinical significance and underlying mechanism of KIAA1429 in osteosarcoma (OS) remains to be reported. Methods: We evaluated the clinical significance of KIAA1429 in OS by performing RT-qPCR, microarray, and RNA sequencing and using published data as a reference. Two KIAA1429-targeting siRNA constructs were transfected into SW1353 cells. CCK-8 assay, colony formation assays, flow cytometry and the xenograft mouse model were conducted to investigate the biological function of KIAA1429 in OS. Results: The mRNA expression of KIAA1429 was markedly upregulated in 250 OS samples as compared to that in 71 non-cancer samples (standardized mean difference = 0.67). Summary receiver operating characteristic curve analysis revealed that KIAA1429 exhibited reliable diagnostic capacity to differentiate OS samples from non-cancer samples (area under the curve = 0.83). Further, survival analysis indicated that KIAA1429 overexpression was associated with shorter overall survival time. Knocking down KIAA1429 reduced m6A methylation levels, inhibited proliferation, prevented the growth of tumors in vivo and accelerated apoptosis of OS cells. In total, 395 KIAA1429-related genes were identified among co-expressed genes and differentially expressed genes, which were enriched in the cell cycle pathway. Protein-protein interaction network analysis showed that CDK1, CCNA2, and CCNB1 were KIAA1429-related genes, serving as major network hubs in OS. Conclusions: Our findings indicate that KIAA1429 plays an oncogenic role in OS and potentially facilitates OS progression via a mechanism that involves regulating CDK1, CCNA2, and CCNB1.
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ETHNOPHARMACOLOGICAL RELEVANCE: The genus Physalis L. (Solanaceae) is commonly used in the treatment of dermatitis, leprosy, bronchitis, pneumonia, hepatitis and rheumatism in China and other Asian countries. AIM OF THE REVIEW: This article reviews the resources, cultivation, phytochemistry, pharmacological properties, and applications of Physalis L., and proposes further research strategies to enhance its therapeutic potential in treating various human diseases. MATERIALS AND METHODS: We conducted a systematic search of electronic databases, including CNKI, SciFinder and PubMed, using the term "Physalis L." to collect information on the resources, phytochemistry, pharmacological activities, and applications of Physalis L. in China during the past ten years (2013.1-2023.1). RESULTS: So far, a variety of chemical constituents have been isolated and identified from Physalis L. mainly including steroids, flavonoids, and so on. Various pharmacological activities were evaluated by studying different extracts of Physalis L., these activities include anti-inflammatory, antibacterial, antioxidant, antiviral, antineoplastic, and other aspects. CONCLUSION: Physalis L. occupies an important position in the traditional medical system. It is cost-effective and is a significant plant with therapeutic applications in modern medicine. However, further in-depth studies are needed to determine the medical use of this plant resources and cultivation, chemical composition, pharmacological effects and applications.
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Physalis , Compostos Fitoquímicos , Physalis/química , Humanos , Animais , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Etnofarmacologia , Medicina Tradicional ChinesaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Based on the theory of traditional Chinese medicine (TCM), diabetic cardiomyopathy (DCM) belongs to the category of "Xiaoke disease" according to the symptoms, and "stasis-heat" is the main pathogenesis of DCM. The Chinese medicine Anemarrhena asphodeloides Bunge (AAB), as a representative of heat-clearing and engendering fluid, is often used clinically in the treatment of DCM. Anemarrhena asphodeloides Bunge total saponins (RATS) are the main bioactive components of AAB, the modern pharmacologic effects of RATS are anti-inflammatory, hypoglycemic, and cardioprotective. However, the potential protective mechanisms of RATS against DCM remain largely undiscovered. AIM OF THE STUDY: The primary goal of this study was to explore the effect of RATS on DCM and its mechanism of action. MATERIALS AND METHODS: Streptozotocin and a high-fat diet were used to induce DCM in rats. UHPLC/Q-TOF-MS was used to determine the chemical components of RATS. The degenerative alterations and apoptotic cells in the heart were assessed by HE staining and TUNEL. Network pharmacology was used to anticipate the probable targets and important pathways of RATS. The alterations in metabolites and main metabolic pathways in heart tissue were discovered using 1 H-NMR metabolomics. Ultimately, immunohistochemistry was used to find critical pathway protein expression. RESULTS: First of all, UHPLC/Q-TOF-MS analysis showed that RATS contained 11 active ingredients. In animal experiments, we found that RATS lowered blood glucose and lipid levels in DCM rats, and alleviated cardiac pathological damage, and decreased cardiomyocyte apoptosis. Furthermore, the study found that RATS effectively reduced inflammatory factor release and the level of oxidative stress. Mechanistically, RATS downregulated the expression levels of PI3K, AKT, HIF-1α, LDHA, and GLUT4 proteins. Additionally, glycolysis was discovered to be a crucial pathway for RATS in the therapy of DCM. CONCLUSIONS: Our findings suggest that the protective effect of RATS on DCM may be attributed to the inhibition of the PI3K/AKT/HIF-1α pathway and the correction of glycolytic metabolism.