The signaling pathways of selected traditional Chinese medicine prescriptions and their metabolites in the treatment of diabetic cardiomyopathy: a review

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Июль 3, 2024

Diabetic cardiomyopathy (DCM) is a myocardial-specific microvascular disease caused by diabetes that affects the structure and function of heart considered to be leading cause morbidity death in patients with diabetes. Currently, there no specific treatment or preventive drug for DCM, an urgent need develop new drugs treat DCM. Traditional Chinese medicine (TCM) has rich experience its characteristics multi-target, multi-pathway, multi-component, few side effects can effectively deal complexity long-term nature Growing evidence suggests myocardial fibrosis, inflammation, oxidative stress, apoptosis, cardiac hypertrophy, advanced glycation end product deposition were main pathologic mechanisms According pathological mechanism this study revealed potential metabolites prescriptions TCM against DCM from perspective signaling pathways. The results showed TGF-β/Smad, NF-κB, PI3K/AKT, Nrf2, AMPK, NLRP3, Wnt/β-catenin pathways key aim was summarize update screen targets candidates provide ideas more experimental clinical use

Язык: Английский

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Mitigation of cisplatin-induced cardiotoxicity by Isorhamnetin: Mechanistic insights into oxidative stress, inflammation, and apoptosis modulation

Toxicology Reports, Год журнала: 2024, Номер 12, С. 564 - 573

Опубликована: Май 12, 2024

The flavonoid compound Isorhamnetin (IRMN) is known for its considerable pharmacological properties, which include antioxidant and anti-inflammatory effects, as well significant protective actions on heart health. However, the potential of IRMN to guard against damage caused by cisplatin (CP), a common chemotherapeutic agent, specific mechanisms involved, remain unexplored areas. This research was designed investigate how counters CP-induced toxicity. In our study, mice were orally given at 50 or 150 mg/kg/day week, followed CP injections (5 mg/kg/day) third sixth days. animals euthanized under sodium pentobarbital anesthesia (50 mg/kg, intraperitoneally) eighth day collect blood tissues further examination. Our findings reveal that administration significantly reduced elevation injury markers such cardiac troponin I, creatine kinase, lactate dehydrogenase induced CP. also effectively lowered oxidative stress markers, including reactive oxygen species malondialdehyde, while boosting ATP production antioxidants like superoxide dismutase, catalase, glutathione. compound's capability diminish levels pro-inflammatory cytokines tumor necrosis factor-alpha interleukin-6, alongside modulating apoptosis-regulating proteins (enhancing Bcl-2 suppressing Bax Caspase-3 expression), underscores cardioprotective effect. Notably, modulated p62–Keap1–Nrf2 signaling pathway, suggesting mechanism through it exerts effects injury. These insights underscore an effective adjunct in cancer therapy, offering strategy mitigate cardiotoxic side cisplatin.

Язык: Английский

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Activated Growth Factor From Platelets as Treatment for Diabetic Retinopathy Through Antioxidant-Oxidative Stress Pathway

Diabetes Metabolic Syndrome and Obesity, Год журнала: 2025, Номер Volume 18, С. 305 - 313

Опубликована: Янв. 1, 2025

Reactive oxygen species (ROS) is known to play a significant role in the activation of chronic inflammatory processes diabetic retinopathy. This study was aimed evaluate activated growth factor (AGF) from platelet for retinopathy treatment, utilizing an vivo investigation regulate antioxidant-oxidative stress pathway. The initially derived by extracting intravenous blood rats. Advanced glycation end products (AGEs), p38 mitogen protein kinase (p38 MAPK), nuclear factor-κβ (NF-κβ), reactive (ROS), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), vascular cell adhesion molecule-1 (VCAM-1), intercellular (ICAM-1), superoxide dismutase (SOD) and endothelial (VEGF) assessed using enzyme linked immunoassay (ELISA). In vivo, rat models were induced streptozotocin injection evaluated retinal funduscopy. mean diameter artery significantly reduced when with transforming factor-β concentration 10 ng/mL or 100 administered (p<0.05). tissue rats showed decline antioxidant activity due oxidative stress. AGF containing TGF-β (10 ng/mL) increased SOD administration effectively decreased proinflammatory cytokines like TNF-α IL-1β. shows that AGF, concentrations ng/mL, can reduce AGEs, p38MAPK, Nf-κβ, ROS, TNF-α, IL-1β, VCAM-1, ICAM-1, VEGF rats' tissue, while increasing concentration, suggesting may help treat reducing inflammation

Язык: Английский

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Antioxidant therapy against TGF‐β/SMAD pathway involved in organ fibrosis

Journal of Cellular and Molecular Medicine, Год журнала: 2023, Номер 28(2)

Опубликована: Дек. 2, 2023

Abstract Fibrosis refers to excessive build‐up of scar tissue and extracellular matrix components in different organs. In recent years, it has been revealed that cytokines chemokines, especially Transforming growth factor beta (TGF‐β) is involved the pathogenesis fibrosis. It shown TGF‐β upregulated fibrotic tissues, contributes fibrosis by mediating pathways are related preservation fibroblasts differentiation. There no doubt antioxidants protect against inflammatory conditions reversing effects nitrogen, oxygen sulfur‐based reactive elements. Oxidative stress a direct impact on chronic inflammation, as results, prolonged inflammation ultimately results Different types antioxidants, forms vitamins, natural compounds or synthetic ones, have proven be beneficial protection both vitro vivo. this study, we reviewed role with antioxidant activity induction inhibition TGF‐β/SMAD signalling pathway, regard such gastro‐intestinal fibrosis, cardiac pulmonary skin renal also some rare cases animal models cell lines.

Язык: Английский

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Mechanisms and Therapeutic Potential of Myofibroblast Transformation in Pulmonary Fibrosis

Deleted Journal, Год журнала: 2025, Номер 2(1), С. 10001 - 10001

Опубликована: Янв. 1, 2025

Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible, and fatal disease with an increasing incidence limited therapeutic options. It characterized by the formation deposition of excess extracellular matrix proteins resulting in gradual replacement normal lung architecture fibrous tissue. The cellular molecular mechanism IPF has not been fully understood. A hallmark fibroblast to myofibroblast transformation (FMT). During excessive repair upon exposure harmful stimuli, fibroblasts transform into myofibroblasts under stimulation cytokines, chemokines, vesicles from various cells. These mediators interact fibroblasts, initiating multiple signaling cascades, such as TGFβ1, MAPK, Wnt/β-catenin, NF-κB, AMPK, endoplasmic reticulum stress, autophagy, contributing FMT. Furthermore, single-cell transcriptomic analysis revealed significant heterogeneity among myofibroblasts, which arise cell types are adapted altered microenvironment during pathological repair. This review provides overview recent research on origins pathways driving their formation, focus interactions between epithelial cells, endothelial macrophages context fibrosis. Based these insights, targeting FMT could offer promising avenues for treatment IPF.

Язык: Английский

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Nanoparticle-Mediated Embryotoxicity: Mechanisms of Chemical Toxicity and Implications for Biological Development

Chemical Research in Toxicology, Год журнала: 2025, Номер unknown

Опубликована: Март 19, 2025

Nanoparticles, defined by their nanoscale dimensions and unique physicochemical properties, are widely utilized in healthcare, electronics, environmental sciences, consumer products. However, increasing evidence of potential embryotoxic effects during pregnancy underscores the need for a molecular-level understanding interactions embryonic development. Nanoparticles such as titanium dioxide, silver, cerium oxide, copper quantum dots can cross placental barrier interfere with crucial developmental processes. At molecular level, they disrupt signaling pathways like Wnt Hedgehog, induce oxidative stress inflammation, cause genotoxic effects, all critical sensitive phases, organogenesis. Furthermore, these nanoparticles interact directly cellular components, including DNA, proteins, lipids, impairing function viability. Innovative strategies to mitigate nanoparticle toxicity, surface modifications incorporation biocompatible coatings, discussed solutions reduce adverse interactions. Various laboratory animal models used investigate nanoparticle-induced embryotoxicity evaluated efficacy limitations, providing insights into applicability effects. This Account examines mechanisms which compromise development emphasizes importance designing safer minimize maternal-fetal exposure risks, particularly biomedical applications.

Язык: Английский

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Inhibition of 11β-hydroxysteroid dehydrogenase 1 alleviates pulmonary fibrosis through inhibition of endothelial-to-mesenchymal transition and M2 macrophage polarization by upregulating heme oxygenase-1

Cell Death and Disease, Год журнала: 2025, Номер 16(1)

Опубликована: Март 21, 2025

Abstract The intracellular enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) catalyzes the interconversion of active glucocorticoid (cortisol) and its intrinsically inert form (cortisone) in metabolic tissues. Although 11βHSD1 is considered a promising therapeutic target disorders such as 2 diabetes, obesity, nonalcoholic steatohepatitis because hepatic functions, roles other tissues have received less attention. In this study, we show that 11βHSD1-specific inhibitor J2H-1702 facilitates reversion endothelial-to-mesenchymal transition multicellular lung spheroid models encapsulating complex crosstalk among cancer cells, vascular endothelial macrophages. not only suppressed interleukin-1α (IL-1α) expression but also attenuated reactive oxygen species-induced DNA damage by upregulating heme oxygenase-1. Additionally, macrophages, which are key regulators fibrogenesis, inhibition markedly reduced IL-1β expression, thereby modulating pro-inflammatory phenotype activated mouse pulmonary fibrosis, including bleomycin-induced idiopathic model radiation-induced model, alleviated fibrosis improved efficacy nintedanib. Collectively, our data suggest holds promise clinical candidate for treatment associated with damage, transition, inflammatory responses.

Язык: Английский

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Combination of losartan with pirfenidone: a protective anti-fibrotic against pulmonary fibrosis induced by bleomycin in rats

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Апрель 16, 2024

Abstract Pirfenidone (PFD), one acceptable medication for treating idiopathic pulmonary fibrosis (IPF), is not well tolerated by patients at full doses. Hence, employing of some approaches such as combination therapy may be applicable increasing therapeutic efficacy PFD. Losartan (LOS), an angiotensin II receptor antagonist, could a suitable candidate because its stabilizing effect on the function IPF patients. Therefore, this study aimed to investigate effects LOS in with PFD bleomycin (BLM)-induced lung rats. BLM-exposed rats were treated alone or The edema, pathological changes, level transforming growth factor-β (TGF-β1), collagen content, and oxidative stress parameters assessed tissues. Following BLM exposure, inflammatory response, levels, antioxidant markers rat tissues significantly improved PFD, these LOS. findings vivo suggest that combined administration provide more potent protection against than single through boosting anti-inflammatory, anti-fibrotic, anti-oxidant effects. These results hold promise developing effective strategy fibrosis.

Язык: Английский

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Nets in fibrosis: Bridging innate immunity and tissue remodeling

International Immunopharmacology, Год журнала: 2024, Номер 137, С. 112516 - 112516

Опубликована: Июнь 20, 2024

Язык: Английский

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Cardiac tissue engineering: an emerging approach to the treatment of heart failure

Frontiers in Bioengineering and Biotechnology, Год журнала: 2024, Номер 12

Опубликована: Авг. 15, 2024

Heart failure is a major health problem in which the heart unable to pump enough blood meet body’s needs. It progressive disease that becomes more severe over time and can be caused by variety of factors, including attack, cardiomyopathy valve disease. There are various methods cure this disease, has many complications risks. The advancement knowledge technology proposed new for diseases. One promising treatments tissue engineering. Tissue engineering field research aims create living tissues organs replace damaged or diseased tissue. goal improve cardiac function reduce need transplantation. This done using three important principles cells, biomaterials signals techniques cells such as electrospinning, hydrogel synthesis, decellularization, etc. diverse. Treating through still under development research, but it hoped there will no transplants invasive surgeries near future. In study, based on most recent years, we examine power treatment failure.

Язык: Английский

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