Background/Purpose Numerous antioxidants derived from plants have been shown in recent studies to provide defense against neurodegenerative illnesses connected to inflammation, apoptosis, and metal toxicity. Therefore, assessing the effectiveness of diosmin, a natural bioflavonoid, on aluminum chloride (AlCl 3 )-induced neurotoxicity in mice was the primary goal of the current investigation. Materials and Methods Four groups of mice were randomly selected. The normal control group received 5 mL/kg p.o. of distilled water; the second group received 100 mg/kg of AlCl 3 orally from the 2nd week to the end of the 6th week; and the third group received AlCl 3 + diosmin (100 mg/kg) from week 2 to week 6. AlCl 3 + diosmin (200 mg/kg) was administered to the fourth group from the 2nd week until the trial’s conclusion. Results We found that, in comparison to rats treated with AlCl 3 , diosmin at both dosages (100 and 200 mg/kg) considerably increased the spontaneous alteration and improved the discrimination index, as well as locomotion of AlCl 3 -challenged mice. Diosmin also considerably improved the endogenous antioxidant activity and reduced nitric oxide levels in the brain tissue homogenate. Moreover, we observed there was a significant decline in acetylcholinesterase activity and levels of inflammatory cytokines after diosmin treatment in the mouse brain. Conclusion Hence, we can conclude that our outcomes showed that diosmin exhibits a promising protective effect against AlCl 3 -induced neurotoxicity in mice.
Background Calycosin, the primary active compound of Astragalus membranaceus, has demonstrated potential protective effects against myocardial ischemia–reperfusion injury (MIRI). However, its underlying molecular mechanisms remain incompletely understood. Purpose This study aimed to investigate the potential mechanisms underlying the protective effects of calycosin against MIRI using network pharmacology, molecular docking, and in vitro experimental validation. Methods Calycosin-associated targets were retrieved from the STITCH, TCMSP, HERB, and SwissTargetPrediction databases, while MIRI-related targets were collected from GeneCards, OMIM, and DrugBank. Core targets were identified through protein–protein interaction (PPI) network construction and topological analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the associated biological processes and signaling pathways. A drug–target–signaling pathway network was constructed, and molecular docking was conducted to evaluate the interactions between calycosin and key targets. Finally, the effects of calycosin on H9C2 cells subjected to oxygen–glucose deprivation/reoxygenation (OGD/R) were investigated using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Results PPI network topology analysis identified 37 core targets. GO and KEGG enrichment analyses revealed that these targets were primarily associated with inflammation and angiogenesis. Molecular docking demonstrated favorable binding affinities between calycosin and key targets, including AKT1, SRC, STAT3, IL6, IL1β, and MAPK1, with binding energies below −6.0 kcal/mol. In OGD/R-treated H9C2 cells, calycosin significantly increased the mRNA expression of AKT1, SRC, and STAT3 while decreasing the mRNA expression of IL6, IL1β, and MAPK1. Conclusion Calycosin may exert protective effects against MIRI through multiple molecular targets and signaling pathways, potentially involving anti-inflammatory and angiogenesis-related mechanisms. These findings provide a theoretical basis for further mechanistic investigation and in vivo validation of calycosin as a potential therapeutic agent for MIRI.
Background Liver cancer, a formidable global health issue, is characterized by its high mortality rates, making it the third major cause of cancer-associated deaths worldwide. The 5-year survival rate for liver cancer remains dismally low, particularly in advanced stages, emphasizing an urgent need for more effective therapeutic methods.Purpose The present study evaluated how asperuloside eliminates liver cancer cells by inhibiting viability and enhancing apoptosis in HepG2 cells.Materials and Methods An MTT assay was employed to evaluate the effect of asperuloside on the proliferation of liver cancer HepG2 cells. The asperuloside-induced cell damage in the HepG2 cells was evaluated by the lactate dehydrogenase (LDH) release assay utilizing kits. The apoptotic levels in the HepG2 cells were examined using a dual staining technique. The levels of phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway proteins in the untreated and asperuloside-treated HepG2 cells were assessed using kits.Results The MTT assay results indicated a notable decrease in HepG2 cell growth after treatment with diverse concentrations of asperuloside. Asperuloside treatment induced cell damage in the HepG2 cells, as evidenced by increased LDH activity. The findings of the dual staining assay confirmed the initiation of apoptosis in the asperuloside-exposed HepG2 cells. Moreover, the asperuloside treatment markedly decreased the PI3K, AKT, and mTOR levels in the HepG2 cells.Conclusion The present findings indicate that asperuloside significantly inhibits viability and promotes apoptosis in liver cancer HepG2 cells via downregulating the PI3K/AKT/mTOR pathway. Consequently, it possesses the capacity to serve as an effective anti-cancer agent to treat liver cancer.
Background As the predominant contributor to global mortality, cardiovascular diseases (CVDs) are fundamentally driven by cardiomyocyte lipotoxicity.Purpose This study investigates the cardioprotective mechanism of apigenin through c-Jun N-terminal kinase (JNK)/Beclin-1 pathway-mediated autophagy regulation, aiming to establish novel therapeutic strategies for metabolic cardiovascular disorders.Methods Utilizing an H9c2 rat cardiomyocyte model, experimental groups were categorized as: control, apigenin (graded concentrations), palmitic acid (PA)-induced lipotoxic model, SP600125 (JNK inhibitor), RAP (mammalian target of rapamycin (mTOR) inhibitor), apigenin+3-MA (autophagy inhibitor), and apigenin+SP600125+3-MA groups. Comprehensive assessments included cell viability, apoptosis, oxidative stress markers, and immunoblotting of AMP-activated protein kinase (AMPK)/mTOR signaling components (AMPK, p-AMPK, mTOR, p-mTOR) along with apoptosis/autophagy regulators (Beclin-1, Bcl-2, Bax, cleaved caspase-3).Results PA administration induced dose-dependent cardiomyocyte damage, evidenced by suppressed viability. After 24 h of PA treatment, intracellular reactive oxygen species levels increased significantly, malondialdehyde content increased, and superoxide dismutase activity decreased accordingly. Apigenin treatment (50 & micro;M) effectively attenuated these abnormalities by activating the JNK/Beclin-1 pathway, and the validation experiment confirmed that apigenin activated this pathway to mediate autophagy.Conclusion Our findings elucidate that apigenin mitigates lipid-overload cardiomyocyte injury by potentiating JNK/Beclin-1-mediated autophagic clearance, providing the first evidence of apigenin's dual regulatory capacity in harmonizing lipid homeostasis and autophagic flux, advancing phytochemical-based therapeutics for metabolic CVDs. However, future studies are required to evaluate whether it plays similar roles in cardiomyocyte injury in patients with CVDs.
Background Hepatocellular carcinoma (HCC) is a highly aggressive malignancy with limited clinical treatment options. Although the natural compound curcumin has demonstrated potential anti-tumor effects, its specific regulatory mechanisms in HCC remain incompletely understood.Purpose This study aimed to investigate the molecular mechanism by which curcumin suppresses the malignant biological characteristics of HCC through microRNA (miR)-134 targeting nitric oxide synthase 3 (Nos3), thereby regulating the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway.Materials and Methods Cells were divided into a blank control group (Group A), an HCC group (Group B), and a curcumin intervention group (Group C). Group A consisted of normal human hepatocyte L-02 cells without treatment; Group B comprised human HCC BEL-7402 cells without treatment; Group C involved BEL-7402 cells treated with 50 & micro;mol/L curcumin. Cells were cultured for 48 h. Cell proliferation was assessed using the cell counting kit-8 (CCK-8) assay, protein expression by Western blot, messenger ribonucleic acid (mRNA) levels by quantitative polymerase chain reaction (qPCR), and migration and invasion abilities by the Transwell assay.Results Compared with Group B, Group C exhibited reduced cell proliferation, decreased migration and invasion, elevated expression of apoptotic proteins (Fas, BCL2-associated X protein [Bax], Fas ligand [FasL]), and lower B-cell lymphoma 2 (Bcl-2) expression. Group C showed higher relative expression of miR-134 and Nos3 protein, while AKT and PI3K mRNA and protein levels were lower than in Group B.Conclusion Curcumin may target Nos3 via miR-134, reducing HCC cell viability, suppressing proliferation, migration, and invasion, and inducing apoptosis. Its mechanism may involve modulation of the PI3K/AKT signaling pathway.
