Hexavalent chromium salt, like potassium dichromate (PD), is chromium’s most precarious valence state in industrial wastes. Recently, there has been increasing interest in β-sitosterol (BSS), a bioactive phytosterol, as a dietary supplement. BSS is recommended in treating cardiovascular disorders due to its antioxidant effect. Trimetazidine (TMZ) was used traditionally for cardioprotection. Through the administration of BSS and TMZ, the cardiotoxic effects of PD were to be countered in this study, in addition to examining the precise mechanism of PD-induced cardiotoxicity. Thirty male albino rats were divided into five groups; the control group: administered normal saline daily (3 mL/kg); the PD group: administered normal saline daily (3 mL/kg); BSS group: administered BSS daily (20 mg/kg); TMZ group: administered TMZ daily (15 mg/kg); and the BSS + TMZ group: administered both BSS (20 mg/kg) and TMZ (15 mg/kg) daily. All experimental groups, except the control, received on the 19th day a single dose of PD (30 mg/kg/day, S.C.). Normal saline, BSS, and TMZ were received daily for 21 consecutive days p.o. The exposure to PD promoted different oxidative stresses, pro-inflammatory, and cardiotoxicity biomarkers. BSS or TMZ succeeded solely in reducing these deleterious effects; however, their combination notably returned measured biomarkers close to normal values. The histopathological investigations have supported the biochemical findings. The combination of BSS and TMZ protects against PD cardiotoxicity in rats by reducing oxidative stress and apoptotic and inflammatory biomarkers. It may be promising for alleviating and protecting against PD-induced cardiotoxicity in people at an early stage; however, these findings need further clinical studies to be confirmed. Highlights: • Potassium dichromate induces cardiotoxicity in rats through the upregulation of oxidative stress, proinflammatory, and apoptotic pathways biomarkers. • β-Sitosterol possesses a possible cardioprotective effect by modulating several signaling pathways. • Trimetazidine, the antianginal agent, has a potential cardioprotective impact on PD-intoxicated rat model. • The combination of β-Sitosterol and trimetazidine was the best in modulating different pathways involved in PD cardiotoxicity in rats via the interplay between NF-κB/AMPK/mTOR/TLR4 and HO-1/NADPH signaling pathways. Graphical

Oxalis corniculata (O. corniculata) is a member of Oxalidaceae family, widely distributed in Asia, Europe, America, and Africa, used extensively as food and its traditional folkloric uses include management of epilepsy, gastric disorders, and neurodegenerative diseases, together with its use in enhancing health. Numerous pharmacological benefits of O. corniculata are linked to its anti-inflammatory and antioxidant abilities. One of the most prevalent neurodegenerative disorders is Alzheimer's disease (AD) in which neuroinflammation and oxidative stress are its main pathogenic processes. Our research aimed to study the neuroprotective effect of the methanolic extract of Oxalis corniculata Linn. (O. corniculata ME), compared to selenium (Se) against AlCl₃-induced AD. Forty male albino rats were allocated into four groups (Gps). Gp I a control group, the rest of the animals received AlCl₃ (Gp II-Gp IV). Rats in Gp III and IV were treated with Se and O. corniculata ME, respectively. The chemical profile of O. corniculata ME was studied using ultraperformance liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry, allowing the tentative identification of sixty-six compounds, including organic acids, phenolics and others, cinnamic acid and its derivatives, fatty acids, and flavonoids. AlCl₃ showed deterioration in short-term memory and brain histological pictures. Our findings showed that O. corniculata ME and selenium helped to combat oxidative stress produced by accumulation of AlCl₃ in the brain and in prophylaxis against AD. Thus, Selenium (Se) and O. corniculata ME restored antioxidant defense, via enhancing Nrf2/HO-1 hub, hampered neuroinflammation, via TLR4/NF-κβ/NLRP3, along with dampening apoptosis, Aβ generation, tau hyperphosphorylation, BACE1, ApoE4 and LRP1 levels. Treatments also promoted autophagy and modulated Wnt 3/β-catenin/GSK3β cue. It was noted that O. corniculata ME showed a notable ameliorative effect compared to Se on Nrf2/HO-1, TLR4/NF-κβ/NLRP3, APOE4/LRP1, Wnt 3/β-catenin/GSK-3β and PERK axes.