β-Caryophyllene Ameliorates Cyclophosphamide Induced Cardiac Injury: The Association of TLR4/NFκB and Nrf2/HO1/NQO1 Pathways

Background: β-caryophyllene (BCP), a natural sesquiterpene, is extensively present in the essential oils of several plants. Cyclophosphamide (CYC) is an anticancer drug. However, its clinical usage is inadequate due to its cardiotoxicity. The aim of this study was to study the effects of BCP on cardiac injury induced by CYC exposure, and to identify the underlying mechanism of action. Methods: Five groups of Wistar rats were allocated. Group I (Normal), II (BCP), and III (CYC) acted as controls. Group IV, V (CYC + BCP) received BCP in two doses (100 and 200 mg/kg, orally, respectively) for 14 days after CYC challenge. CYC groups received 200 mg/kg, i.p. of the drug once on the first day of experiments. Results: CYC group displayed numerous ECG and histological irregularities and cardiac markers elevation. CYC induced lipid peroxidation and oxidative stress intensification, as well as inflammatory and apoptotic markers escalation. Treatment with BCP resulted in modified ECG traces and histological sections. BCP mitigated cardiac markers and lipid peroxidation whereas intensified antioxidant capacity. BCP activated Nrf2, with subsequent HO1 and NQO1 amplification. BCP diminished TLR4/NFκB pathway, which consequently lessened the inflammatory and apoptosis responses. Conclusion: BCP administration was associated with activated Nrf2/HO1/NQO1 and inhibited TLR4/NFκB pathways with subsequent enhanced anti-oxidative capacity and diminished inflammatory and apoptosis responses