Gastric ulcer is a disturbing disease that impacts many people worldwide. Pioglitazone (Piog), a thiazolidinedione, and ligustrazine (Ligu), a natural component of Ligusticum chuanxiong possess gastroprotective properties. However, the underlying mechanism is not well elucidated. The present study aimed to investigate the gastroprotective effects of Piog (15 mg/kg, p.o.), Ligu (15 mg/kg, p.o.), and their combination against ethanol-induced gastric ulcer in rats. Omeprazole (10 mg/kg) was used as a standard. Pre-treatment for 7 days with Piog, Ligu, and (Piog+Ligu) effectively alleviated ethanol-predisposed oxidative stress and inflammation through restoring HO-1, GSH, and SOD tissue levels and decreasing elevated MDA, TNF-α, ICAM, I-NOS, and IL-1β contents. Moreover, Piog, Ligu, and (Piog+Ligu) markedly inhibited the ethanol-induced increase of gastric NF-KB and BAX. In contrast, this pre-treatment regimen significantly accelerated protein expression of SIRT1, Nrf2, and Bcl-2, along with autophagic proteins, ATG5 and Beclin. Interestingly, macroscopic, histopathological examination and mucin content were in harmony with previous results, where pre-treatment with Piog, Ligu, and (Piog+Ligu) showed a declined mucosal injury as evidenced by the remarkable decrease of the ulcer area percentage by 62.3%, 38.7%, and 91.2%, respectively, compared to the ethanol-ulcerated group. In conclusion, Piog and Ligu exhibited remarkable gastroprotective properties. Our study was the first to show that Piog, Ligu, and (Piog+Ligu) ameliorated oxidative stress, inflammation, and apoptosis and accelerated the autophagic process via the upregulation of the upstream SIRT1 protein. It is worth mentioning that future studies are needed to pave the way for the clinical use of Piog and Ligu as gastro-protective agents.

Myocardial infarction is classified as the irreversible myocardial cell death following ischemia. Ischemia could be initiated as a result of atherosclerotic or variable non-atherosclerotic causes. Consequent effects of ischemia are primarily caused due to oxidative stress which is the main precursor of cell death. Myocardial cell death is triggered through intrinsic or extrinsic pathways. In both pathways, apoptosis has been clearly explained through different studies but recently, necroptosis was determined to be involved. The heart has negligible ability for regeneration, thus infarcted regions are healed by replacing dead cells with scar formation. Infarct healing is triggered through an inflammatory cascade, induced by alarmins released from dying cells. Clearance of dead cells by immune cells is followed with the activation of fibroblasts to promote deposition of extracellular matrix proteins. This review discusses the events involved following ischemia including the mechanistic signalling during injury, inflammation, and repair of the infarcted heart. Moreover, the possible complications are mentioned along with the established treatment strategies and some new therapeutic approaches for myocardial infarction.

Despite the beneficial therapeutic effects of tamoxifen (TAMX) against breast cancer, long-term treatment with TAMX enhances the development of metabolic dysfunction-associated steatotic liver disease (MASLD), including steatohepatitis. Bempedoic acid (BA) is a recently approved lipid-lowering drug for dyslipidemia. Our study aimed to examine the potential impact of BA against TAMX-induced steatohepatitis in rats and underline the possible molecular pathways involved. Twenty-four adult female rats were allocated into 4 groups (n = 6): Control, TAMX (45 mg/kg), BA (15 mg/kg), and BA (30 mg/kg) groups. BA was given orally by gavage for 15 consecutive days. TAMX was administered to all rats except the normal control rats. Co-treatment of BA with TAMX showed well-organized structures of the hepatocytes in the histopathological sections. BA significantly improved liver function and lipid profile, demonstrating dose-dependent hepatoprotective effects. Mechanistically, BA significantly decreased oxidative stress by decreasing the level of malondialdehyde (MDA) and increasing the level of superoxide dismutase (SOD), significantly reduced inflammatory cytokines such as nuclear factor-kappa B (NF-κB/p65) and tumor necrosis factor-alpha (TNF-α), significantly inhibited lipogenesis by decreasing sterol regulatory element binding protein 1c (SREBP-1c), fatty acid synthetase (FAS), acetyl-coenzyme A carboxylases (ACC), ATP-citrate lyase (ACL), and significantly promoted fatty acid oxidation be enhancing carnitine palmitoyl transferase 1 significantly (CPT-1) through AMP-activated protein kinase (AMPK) activation. These findings suggest BA as a potential adjunct therapy for TAMX-induced metabolic dysfunction-associated steatohepatitis (MASH).