RESUMO
BACKGROUND: Massa Medicata Fermentata (MMF) is one of the most commonly used traditional fermented Chinese medicines. MMF is widely used for the treatment of digestive diseases such as dyspepsia and flatulence in traditional Chinese medicine (TCM). However, the therapeutic mechanism of MMF is not well understood. METHOD: In this study, SD rats received 0.1% iodoacetamide either alone or in combination with water platform sleep deprivation to induce functional dyspepsia and were administered MMF (1 or 3 g/kg/d, ig), mosapride citrate (Mosa., 2 mg/kg/d, ig) or saline for 21 days. After treatment, the sucrose preferences and gastric emptying rates of the rats were assessed; HE staining was used to detect the pathological changes in the rat duodenum; ELISA kits were used to detect motilin (MTL) in the rat duodenum and the serum contents of Interferon-λ (IFN-λ), Interleukin 6 (IL-6), and Tumor Necrosis Factor-α (TNF-α). An approach based on 16S rDNA amplicon sequencing was utilized to explore the intestinal microflora in the colon contents of rats and the metabolism of the microflora to assess the potential mechanisms of MMF in ameliorating functional dyspepsia (FD). In addition, gas chromatography-mass spectrometry (GC/MS) was used to detect changes in short fatty acids (SCFAs) in the colon contents of rats. RESULTS: MMF reduced the serum levels of TNF-α, and IFN-λ, improved the morphology of duodenal intestinal villi and ameliorated intestinal mucosal lamina propria injury in FD rats, and the sucrose preference increased and the gastric emptying rate decreased in FD rats. MMF alleviated intestinal microflora disturbance and exerted a regulatory effect on Bacteroidetes, Proteobacteria, and Firmicutes, reduced total SCAFs, Butyric Acid, Propionic acid-2-methyl, Butanoic Acid-3-methyl, and Hexanoic acid. CONCLUSIONS: These results showed that the effect of MMF on the intestinal flora and its metabolites may provide a new treatment strategy for FD.
Assuntos
Dispepsia , Microbioma Gastrointestinal , Ratos , Animais , Dispepsia/tratamento farmacológico , Dispepsia/microbiologia , Microbioma Gastrointestinal/genética , Fator de Necrose Tumoral alfa/metabolismo , Ratos Sprague-DawleyRESUMO
Headache is a common clinical complication of ischemic stroke. As a precursor of stroke, headache occurs repeatedly in the convalescent period of ischemic stroke, leading to secondary stroke and seriously hindering patients' rehabilitation. Currently, it is believed that the pathogenesis of ischemic stroke-related headache is associated with the abnormal release of vasoactive substances, high platelet aggregation, and stimulation of intracranial pain-sensitive structures. The active ingredients in traditional Chinese medicines(TCM) with the effects of activating blood to resolve stasis and clearing heat to release exterior can protect brain tissue and relieve headache by reducing the release of inflammatory cytokines, alleviating antioxidant stress, inhibiting neuronal apoptosis and so on. This paper introduces the research progress in the potential mechanism and TCM treatment of ischemic stroke-related headache, aiming to provide reference for further research and drug development of this complication.
Assuntos
Isquemia Encefálica , Medicamentos de Ervas Chinesas , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , AVC Isquêmico/tratamento farmacológico , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Medicina Tradicional Chinesa , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico , Cefaleia/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêuticoRESUMO
Resveratrol is a natural polyphenol found in various plants. It has been widely studied on cardiovascular disorders. It is known that resveratrol can activate Sirtuin proteins and participate in cellular energy metabolism through a Sirtuin-dependent pathway. Here, we hypothesized that resveratrol may protect against myocardial ischemia/reperfusion injury (MIRI) through the target of Sirt1/Sirt3 on mitochondrial dynamics, cardiac autophagy, bioenergetics and oxidative damage in hypoxia/reoxygenation (H/R)-induced neonatal rat cardiomyocytes. We observed that resveratrol could activate the Sirt1/Sirt3-FoxO pathway on myocardial mitochondria in H/R cardiomyocytes. Subsequently, we found that resveratrol repaired the fission-fusion balance, autophagic flux and mitochondrial biosynthesis compared by H/R group. These changes were followed by increased functional mitochondrial number, mitochondrial bioenergetics and a better mitochondrial antioxidant enzyme system. Meanwhile, these effects were antagonized by co-treatment with Selisistat (Ex527), a Sirtuin inhibitor. Together, our findings uncover the potential contribution of resveratrol in reestablishing a mitochondrial quality control network with Parkin, Mfn2 and PGC-1α as the key nodes.
Assuntos
Traumatismo por Reperfusão Miocárdica , Sirtuína 3 , Sirtuínas , Animais , Mitocôndrias Cardíacas/metabolismo , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Miócitos Cardíacos , Ratos , Resveratrol/metabolismo , Resveratrol/farmacologia , Sirtuína 1/metabolismo , Sirtuína 3/metabolismo , Sirtuínas/metabolismo , Ubiquitina-Proteína Ligases/metabolismoRESUMO
To explore the potential molecular mechanism of Mongolian medicine Bawei Sanxiang San in the treatment of chronic heart failure(CHF) through network pharmacology and molecular docking technology. The active ingredients and potential targets of Bawei Sanxiang San were collected by applying TCMSP, BATMAN databases and literature mining. CHF-related genes were collected through TTD, GeneCards and CTD databases. After the potential common targets between Bawei Sanxiang San and CHF were disco-vered, the interaction network diagram of "compound-target-pathway" was constructed using Cytoscape. The intersecting targets were imported into the DAVID database for GO function and KEGG pathway enrichment analysis. Finally, the Autodock_vina software was used to molecularly dock the selected proteins with the active ingredients of Bawei Sanxiang San. The results showed that there were 60 active ingredients in Bawei Sanxiang San that might be used to treat CHF, involving 311 target genes and 7 signaling pathways that directly related to CHF, such as HIF-1 signaling pathway, TNF signaling pathway, adrenergic signaling in cardiomyocytes, aldosterone-regulated sodium reabsorption, calcium signaling pathway, cGMP-PKG signaling pathway, renin secretion. Additionally, molecular docking showed that the bioactive compounds had good binding activity with the protein receptors of key target genes. Bawei Sanxiang San might exert therapeutic effects on CHF by regulating cardiomyocytes, angiogenic and inflammation related targets and pathways in a multi-component, multi-target and multi-pathway manner.
Assuntos
Medicamentos de Ervas Chinesas , Insuficiência Cardíaca , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/genética , Humanos , Medicina Tradicional Chinesa , Medicina Tradicional da Mongólia , Simulação de Acoplamento MolecularRESUMO
BACKGROUND: Non-small cell lung cancer (NSCLC) is associated with extremely high morbidity and mortality rates worldwide. Citrullus colocynthis (L.) Schrad, widely distributed in Asian and African countries, is used to treat cancers in traditional Uyghur medicine. HYPOTHESIS/PURPOSE: The combination of Cucurbitacin E (CuE) and Myricetin (Myr) of C. colocynthis could treat NSCLC by targeting autophagy. STUDY DESIGN: The potential anti-cancer components (CuE and Myr) of C. colocynthis were identified using in-silico methods and further in vitro explored the anti-NSCLC properties of the combination of CuE and Myr. METHODS: Network pharmacology and molecular docking were used to identify potential therapeutic compounds of C. colocynthis for the treatment of NSCLC. In A549 cells, the anti-cancer activities and synergy of CuE and Myr were studied using CompuSyn, their mechanism behind autophagy regulation was determined by western blotting and immunofluorescence staining. RESULTS: CuMy-12 (CuE: 0.5 µM, Myr: 20 µM), a combination of CuE and Myr from C. colocynthis, inhibited A549 cell proliferation and colony formation, and induced apoptosis and cell cycle arrest in the G0/G1 phase, exhibiting a synergistic effect. Furthermore, CuMy-12 inhibited autophagy and activation of the PI3K/AKT/mTOR signaling pathway, which was characterized by a decrease in Beclin 1, AKT, and phospho-AKT proteins. CONCLUSION: CuMy-12 can be considered a natural candidate with anticancer activity for autophagy-based regulation, but mechanistic and clinical studies are required to validate its potential.