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Objectives Combined chemotherapy and radiotherapy usually associated with various comorbidities especially on rapidly proliferating cells as testis. This study aimed to characterize main constituents of Ocimum basilicum L. (OB) aqueous extract and examine its protective effect on doxorubicin/irradiation (DOXO/IR)‐induced testicular injury in rats. Methods Spectrophotometric analysis showed considerable amount of polyphenolic (146.31 µg/mg) and flavonoid contents (28.63 µg/mg); UPLC‐ESI‐MS/MS analysis revealed that the major flavonoid was apigenin‐O‐glucoside (7.53%) followed by luteolin (5.94%), while rosmarinic acid was the major polyphenolic (15.76%) followed by caftaric acid (9.39%); rutin and querctin were also present and were quantified using high‐performance liquid chromatography. Administration of OB extract (200 mg/kg per day; p.o.) to DOXO/IR rats resulted in marked improvement of associated testicular damage. Key findings Ocimum basilicum L. significantly decreased testicular levels of nuclear factor‐kappa B and B‐cell lymphoma‐2 (Bcl2)‐associated protein X, along with caspase‐3 immunohistochemical staining. In addition, OB elevated testicular total antioxidant capacity, nuclear erythroid‐related factor‐2, Bcl2 and testosterone contents and Ki‐67 immunohistochemical staining. Such changes were also accompanied by restoration of testicular architecture. Conclusions The study highlights the protective role of OB aqueous extract in hampering most of the harmful chemotherapy/radiotherapy‐induced outcomes via its antioxidant, antiapoptotic and cell regeneration abilities. Such findings may offer an incentive in expanding its use during chemotherapy and radiotherapy.

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Angiotensin-II (AgII) is thought to be crucial for tumor growth and progression. Moreover, hydrogen sulfide (H 2 S) performs a controversial action in cancer pathology. Zofenopril (ZF) is an angiotensin-converting enzyme (ACE) inhibitor with H 2 S donating properties. Hence, this study aims at investigating the tumor suppressor activity of ZF and elucidating the involved trajectories in Ehrlich's solid tumor (EST)-bearing mice. EST was induced by the intradermal injection of Ehrlich's ascites carcinoma cells into femoral region. All parameters were assessed after 28 days post-inoculation or one-week thereafter. ZF treatment resulted in significant reduction of tumor weights with marked decrease in IL-6 and VEGF levels in serum, and tumor Ag II and CEA contents. Additionally, the administration of ZF downregulated the tumor gene expression of cyclin-D, ACE-1, and Bcl2 and upregulated the proapoptotic gene, BAX. Moreover, ZF increased CBS gene expression, which is a major contributor to cellular H 2 S production. In addition, ZF was able to reduce the protein expression of PI3K, pAKT, pGSK-3β, and NFκB. Our study has provided novel insights into the possible mechanisms by which ZF may produce its tumor defeating properties. These intersecting trajectories involve the interference between PI3K/Akt and CBS signaling pathways.