Tetrahydropalmatine improves mitochondrial function in vascular smooth muscle cells of atherosclerosis in vitro by inhibiting Ras homolog gene family A/Rho-associated protein kinase-1 signaling pathway

Article

Author: Ding, Ke ; He, Jiaqi ; Wang, Hui ; Wang, Jiahong ; Bao, Qiying

AbstractBackgroundTetrahydropalmatine (THP) regulates mitochondrial function in vascular smooth muscle cells (VSMCs) to prevent or alleviate atherosclerosis (AS), with unclear specific mechanism.MethodsAS models were constructed by oxidized low-density lipoprotein (ox-LDL)-treated VSMCs. Cell counting kit-8 for cell viability, wound scratch assay for cell migration, and flow cytometry for cell cycle, intracellular reactive oxygen species, and mitochondrial membrane potential (MMP) were performed. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels by biochemical kits, oxygen consumption rate (OCR) by seahorse apparatus, apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay (TUNEL) staining, and apoptosis-related expression by western blot were detected. Ras homolog gene family A/Rho-associated protein kinase-1 (RhoA/ROCK1) levels were measured by western blot and ELISA. The RhoA agonist, U46619, was employed to validate mechanism of THP.ResultsTHP suppressed cell cycle progression and cell migration whereas alleviating cell viability and oxidative stress, as reduced MDA and enhanced SOD levels in ox-LDL-incubated VSMCs. THP protected mitochondrial function by higher MMP levels and OCR values. Additionally, THP decreased TUNEL-positive cells, Bax, Caspase-3, RhoA, ROCK1, and osteopontin expression, while increased Bcl-2 and smooth muscle myosin heavy chain levels. Furthermore, U46619 intervention antagonized effects of THP.ConclusionTHP improved mitochondrial function in VSMCs of AS by inhibiting RhoA/ROCK1 signaling pathway.

10 Mar 2025·International Journal of Medical Sciences

Mechanisms of Huhuang decoction in treating diabetic wounds: a network pharmacological and experimental study

Article

Author: Zhong, Shan ; Xu, Shun ; Hao, Jiaqi ; Zhang, Jie ; Yang, Peilang ; Wang, Jiaqiang ; Liu, Yan ; Gao, Min ; Chen, Yunsheng ; Shi, Yan

Background: Huhuang (HH) decoction, a composition of seven traditional Chinese medicines, has demonstrated clinical efficacy in wound healing. However, its pharmacological foundation and potential mechanisms remain unclear. This study aimed to elucidate the mechanisms of action of HH decoction in the treatment of diabetic wounds. Methods: The chemical composition of HH decoction was analysed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. The targets of the HH decoction in treating diabetic wounds were predicted using network pharmacology. The gene ontology and pathway enrichment analyses were performed using the DAVID functional annotation tool. The compound targets and PPI networks were established using Cytoscape. Molecular docking was implemented using the AutoDock Vina software. Experimental verification was performed on the target prediction of the HH decoction in treating diabetic wounds, both in vivo and in vitro. Results: The study identified 53 chemical components in HH decoction, with tetrahydropalmatine, emodin, rosmarinic acid, citric acid, berberine, and cryptotanshinone as key components for treating diabetic wounds. Twenty-one target genes were identified as core genes. Gene ontology analysis indicated that the therapeutic effects of HH on diabetic foot ulcers may occur through the regulation of cell proliferation, migration, and inflammation. Pathway enrichment was found to be mainly related to the HIF-1 and TNF signalling pathways. HH promoted proliferation, migration, and tube formation in vascular endothelial cells in vitro. Compared with the control group, the expression levels of HIF-1α, VEGF-α, cyclinD1 in the HH group were higher while the phosphorylation level of p65 in the HH group was significantly lower. The concentrations of IL-6, TNF-α, and IL-1β in wound tissue in the HH group were significantly lower than those in the control group. The expression levels of CD31, VEGF-α, Ki67 and HIF-1α in the wounds of diabetic rats in the HH group were higher than those in the control group. Conclusions: The HH decoction promotes diabetic wound healing via multiple components, targets, and pathways. It may enhance vascular endothelial cell proliferation via cyclinD1, promote vascularization through the HIF-1α/VEGF-α signalling pathway, and inhibit inflammation through NF-κB signalling pathways.

17 Feb 2025·Chemical Research in Toxicology

Inhibitory Effects of Alkaloids on OATP1B1 In Vitro and In Vivo: Prediction for Food/Herb–Drug Interactions and Hepatoprotective Effects Based on Structure–Activity Relationships

Article

Author: Wang, Fenghe ; Hu, Jiahuan ; Duan, Xiaoyan ; Tan, Huixin ; Sun, Yanhong ; Wu, Jinjin ; Hu, Jinping ; Bai, Wanting ; Bai, Jie

Alkaloids, a class of low-molecular-weight nitrogenous compounds, attract a great deal of interest because of their biological activities and therapeutic potential. Yet, surprisingly little is known about their interactions with drug transporters, especially Organic Anion Transporting Polypeptide 1B1 (OATP1B1), a liver-specific uptake transporter, which is closely associated with drug-induced liver injury (DILI). This study aims to investigate the inhibitory effects of 160 alkaloids on OATP1B1, assess the hepatoprotective effects against bosentan-induced liver injury, and elucidate the structure-activity relationships of alkaloids with OATP1B1. Four alkaloids, including dihydroberberine, deacetyltaxol, dihydrocapsaicin, and tetrahydropalmatine, significantly inhibited OATP1B1 transport activity in OATP1B1-HEK293 cells (>50%), which reduced the OATP1B1-mediated uptake of methotrexate and microcystin-LR, and consequently decreased their cell toxicity. In bosentan-induced liver injury models, 4 alkaloids reduced serum total bile acid (TBA) levels and liver concentration of bosentan to different degrees, especially deacetyltaxol, which exhibited the most potent hepatoprotective effect against bosentan. The pharmacophore model suggested that the critical pharmacophores of alkaloid inhibitors are hydrogen bond acceptors and hydrophobic groups. Our findings pave the way for predicting the potential risks of alkaloids-containing food/herb-drug interactions in humans and optimizing the alkaloid structure for alleviating OATP1B1-related DILI.

100 Deals associated with Tetrahydropalmatine sulfate

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