Gastrodin attenuates diabetic cardiomyopathy characterized by myocardial fibrosis by inhibiting the KLK8-PAR1 signaling axis DOI Creative Commons

MingShan Zhang,

Yufei Zhang,

Jinggang He

et al.

Chinese Medicine, Journal Year: 2024, Volume and Issue: 19(1)

Published: Nov. 22, 2024

Abstract Background Diabetic cardiomyopathy (DCM), characterized by myocardial fibrosis, is a major cause of mortality and morbidity in diabetic patients; the inhibition cardiac fibrosis fundamental strategy for treating DCM. Gastrodin (GAS), compound extracted from Gastrodia elata protects against DCM, but molecular mechanism underlying its antifibrotic effect has not been elucidated. Methods In vivo, effects GAS were investigated using C57BL/6 mice with which was induced administering high-sugar, high-fat (HSF) diet streptozotocin (STZ). We assessed function these detected histopathological changes their hearts degree fibrosis. vitro, neonatal rat fibroblasts (CFs) transformed into myofibroblasts exposing them to high glucose combined palmitic acid (HG-PA), CFs pEX-1 (pGCMV/MCS/EGFP/Neo) plasmid-mediated overexpression KLK8, contains KLK8 gene. The siRNA knocked down study on CF differentiation, collagen synthesis, cell migration specific mechanisms action GAS. Results attenuated pathological DCM mice, rescued impaired function, Additionally, results docking analysis showed that binds kinin-releasing enzyme-related peptidase 8 (KLK8) inhibit increase protease-activated receptor-1 (PAR-1), thus attenuating Specifically, transformation exposed HG-PA. Overexpressing promoted migration, HG-PA-induced migration. Further studies revealed PAR-1 antagonist, PAR-2 could attenuate inhibited upregulation PAR1 activation, blocking HG-PA-exposed triggering TGF-β1/Smad3 signaling. Conclusion alleviated model an HSF STZ. mediated CFs. inhibiting KLK8-PAR1 signaling axis, process TGF-β1 Smad3 are involved. Graphical

Language: Английский

Epigenetics-targeted drugs: current paradigms and future challenges DOI Creative Commons

Wanlin Dai,

Xinbo Qiao, Yuanyuan Fang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Nov. 26, 2024

Epigenetics governs a chromatin state regulatory system through five key mechanisms: DNA modification, histone RNA remodeling, and non-coding regulation. These mechanisms their associated enzymes convey genetic information independently of base sequences, playing essential roles in organismal development homeostasis. Conversely, disruptions epigenetic landscapes critically influence the pathogenesis various human diseases. This understanding has laid robust theoretical groundwork for developing drugs that target epigenetics-modifying pathological conditions. Over past two decades, growing array small molecule targeting such as methyltransferase, deacetylase, isocitrate dehydrogenase, enhancer zeste homolog 2, have been thoroughly investigated implemented therapeutic options, particularly oncology. Additionally, numerous epigenetics-targeted are undergoing clinical trials, offering promising prospects benefits. review delineates epigenetics physiological contexts underscores pioneering studies on discovery implementation drugs. include inhibitors, agonists, degraders, multitarget agents, aiming to identify practical challenges avenues future research. Ultimately, this aims deepen epigenetics-oriented strategies further application settings.

Language: Английский

Citations

35
Oxymatrine alleviates ALD-induced Cardiac Hypertrophy by regulating autophagy via activation Nrf2/SIRT3 signaling pathway DOI

Dingchun Lu,

Shun Wu,

Xueting Wang

et al.

Phytomedicine, Journal Year: 2025, Volume and Issue: 138, P. 156389 - 156389

Published: Jan. 13, 2025

Language: Английский

Citations

2
Qiliqiangxin: A multifaceted holistic treatment for heart failure or a pharmacological probe for the identification of cardioprotective mechanisms? DOI Creative Commons
Milton Packer

European Journal of Heart Failure, Journal Year: 2023, Volume and Issue: 25(12), P. 2130 - 2143

Published: Oct. 25, 2023

The active ingredients in many traditional Chinese medicines are isoprene oligomers with a diterpenoid or triterpenoid structure, which exert cardiovascular effects by signalling through nutrient surplus and deprivation pathways. Qiliqiangxin (QLQX) is commercial formulation of 11 different plant ingredients, whose compounds include astragaloside IV, tanshione IIA, ginsenosides (Rb1, Rg1 Re) periplocymarin. In the QUEST trial, QLQX reduced combined risk death heart failure hospitalization (hazard ratio 0.78, 95% confidence interval 0.68-0.90), based on 859 events 3119 patients over median 18.2 months; benefits were seen taking foundational drugs except for sodium-glucose cotransporter 2 (SGLT2) inhibitors. Numerous experimental studies diverse cardiac injuries have yielded highly consistent findings. marked abrupt injury, mitigated injury upregulating PI3K/Akt/mTOR/HIF-1α/NRF2 pathway; abrogated suppression PI3K, Akt, mTOR, HIF-1α NRF2. contrast, prolonged measured stress (as chronic failure), ameliorated oxidative stress, maladaptive hypertrophy, cardiomyocyte apoptosis, proinflammatory profibrotic pathways, while enhancing mitochondrial health promoting glucose fatty acid oxidation ATP production. These achieved an action to upregulate SIRT1/AMPK/PGC-1α enhanced autophagic flux. particular, appears enhance interaction PGC-1α PPARα, possibly direct binding RXRα; silencing SIRT1, RXRα favourable heart. Since PGC-1α/RXRα also downstream effector Akt/mTOR signalling, actions may explain its both acute stress. Intriguingly, individual - ginsenosides, IIA share QLQX's PGC-1α/RXRα/PPARα signalling. QXQL contains periplocymarin, glycoside that inhibits Na

Language: Английский

Citations

19
1,8-Cineole ameliorates diabetic retinopathy by inhibiting retinal pigment epithelium ferroptosis via PPAR-γ/TXNIP pathways DOI Open Access

Zhangnian Liu,

Shiquan Gan,

Lingyun Fu

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 164, P. 114978 - 114978

Published: June 2, 2023

1,8-Cineole, the main component of volatile oil in aromatic plants, has diverse pharmacological properties, including antioxidant, anti-inflammatory, and anti-cancer properties. Diabetic retinopathy (DR) is a common microvascular complication diabetes mellitus (DM). Here, we investigated protective effect 1,8-cineole on DR found that treatment could alter expression several genes both high glucose (HG)-induced ARPE-19 cells retinal tissues DM mice, as well inhibit ferroptosis. Subsequent investigations into molecular mechanisms underlying this inhibition revealed thioredoxin-interacting protein (TXNIP) was significantly upregulated while peroxisome proliferator-activated receptor γ (PPAR-γ) downregulated HG-induced cells, with effectively reverse these changes. Treatment PPAR-γ agonist (rosiglitazone), alone or combined 1,8-cineole, inhibited transcription TXNIP ferroptosis cells. Conversely, pretreatment GW9662, inhibitor, cells; failed to expression. To explore relationships, constructed adenovirus shRNA elucidate negative regulation by PPAR-γ. Taken together, present findings indicate tissue plays an essential role pathogenesis DR, which can be ameliorated 1,8-cineole.

Language: Английский

Citations

17
SIRT1 regulates endoplasmic reticulum stress-related organ damage DOI Creative Commons
He Hu,

Weichao Xu,

Yan Li

et al.

Acta Histochemica, Journal Year: 2024, Volume and Issue: 126(1), P. 152134 - 152134

Published: Jan. 1, 2024

Endoplasmic reticulum (ER) stress plays a key role in the pathogenesis of several organ damages. Studies show that excessive ER (ERS) can destroy cellular homeostasis, causing cell damage and physiological dysfunction various organs. In recent years, Sirtuin1 (SIRT1) has become research hotspot on ERS. Increasing evidence suggests SIRT1 positive ERS-induced via multiple mechanisms, including inhibiting apoptosis promoting autophagy. also alleviate liver, heart, lung, kidney, intestinal by We discuss possible mechanism SIRT1, explore potential therapeutic targets diseases, provide theoretical basis for treating ERS-related diseases.

Language: Английский

Citations

4
Recent advances of traditional Chinese medicine against cardiovascular disease: overview and potential mechanisms DOI Creative Commons

Junting Dai,

Lulu Qiu,

Yimin Lu

et al.

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 30, 2024

Cardiovascular disease (CVD) is the leading cause of human mortality worldwide. Despite Western medicine having made encouraging results in clinical management CVD, morbidity, mortality, and disability rates remain high. Modern pharmacology has confirmed that traditional Chinese (TCM), characterized by its multi-component, multi-target, integrity, plays a positive important role prevention treatment various CVDs China, which notable advantages stabilizing disease, improving heart function, enhancing quality life. Importantly, TCM gradually being accepted international community due to low cost, high safety, versatile bioactivity, toxicity. Unfortunately, comprehensive studies on therapeutic effect CVD mechanisms are very limited, may restrict application CVD. Therefore, this review performed analyze pathogenesis including inflammatory response, oxidative stress, mitochondrial dysfunction, pyroptosis, ferroptosis, dysbiosis gut microbiota, etc. Moreover, we summarized latest progress (formulas, extracts, compounds) curing according published literature from 2018 2023, as well evidence. In conclusion, expected provide useful information reference for further drug development

Language: Английский

Citations

4
Maintaining the Mitochondrial Quality Control System Was a Key Event of Tanshinone IIA against Deoxynivalenol-Induced Intestinal Toxicity DOI Creative Commons
Cong Zhang,

Youshuang Wang,

Xinyu Zhang

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(1), P. 121 - 121

Published: Jan. 18, 2024

Deoxynivalenol (DON) is the one of most common mycotoxins, widely detected in various original foods and processed foods. Tanshinone IIA (Tan IIA) a fat-soluble diterpene quinone extracted from Salvia miltiorrhiza Bunge, which has multi-biological functions pharmacological effects. However, whether Tan protective effect against DON-induced intestinal toxicity unknown. In this study, results showed treatment could attenuate IPEC-J2 cell death. DON increased oxidation product accumulation, decreased antioxidant ability disrupted barrier function, while reversed function impairment oxidative stress. Furthermore, dramatically improved mitochondrial via quality control. upregulate biogenesis fusion as well downregulate fission unfolded protein response. addition, significantly attenuated mitophagy caused by DON. Collectively, presented potential underlying mechanisms were involved control–mediated mitophagy.

Language: Английский

Citations

3
Signaling pathways behind the biological effects of tanshinone IIA for the prevention of cancer and cardiovascular diseases DOI

Homa Shahrokhi,

Javad Asili,

Zahra Tayarani-Najaran

et al.

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 12, 2025

Language: Английский

Citations

0
Traditional Chinese medicine in the prevention of diabetes mellitus and cardiovascular complications: mechanisms and therapeutic approaches DOI Creative Commons
Caixia Chen,

Hui Gao,

Ying Wei

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 11, 2025

Diabetes mellitus (DM) is a chronic endocrine and metabolic disorder characterized by persistent hyperglycemia that poses serious threats to human health quality of life. The morbidity, disability, mortality rates cardiovascular complications stemming from are primary factors affecting the lifespan patients with diabetes. Currently, there no cure for DM. Standard biomedical treatments mostly control symptoms using insulin injections or oral hypoglycemic drugs. Although effect standard therapy remarkable, its long-term use prone toxic side effects. Numerous studies have recently found Traditional Chinese Medicine (TCM) has strong advantages in prevention treatment DM (DACC). collection, processing, preparation clinical TCM guided theory follow “holistic concept.” Multiple components, pathways, targets form basis treating multiple parts organs body simultaneously. mainly derived natural medicines their processed products fewer clinically used as compound prescriptions, botanical drugs, monomers. TCM, either independently combination treatments, shown unique therapeutic advantages. This review aimed explore reported mechanisms action DACC. These findings will aid optimization current formation schedule integrated treatments.

Language: Английский

Citations

0
Post-translational acylation of proteins in cardiac hypertrophy DOI
Yingqi Liu, Qin Yang, Guo‐Wei He

et al.

Nature Reviews Cardiology, Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

Language: Английский

Citations

0