Evaluation of the protective effect of aqueous-methanolic leaf extract of Jatropha mollissima (Pohl.) Baill. on doxorubicin-induced cardiotoxicity in rats via modulating inflammatory markers and oxidative stress

Muhammad Omer Iqbal^1*Qianqian Wang²Majid Manzoor³Imran Ahmad Khan⁴Yuchao Gu¹Xiao Wu^5*Jin Chen^1*

• ¹College of Marine Science and Biological Engineering, Qingdao University of Science and Technology, Qingdao, 266042, China., Qingdao, China
• ²Ocean University of China, Qingdao, China
• ³Ningbo University, Ningbo, China
• ⁴Muhammad Nawaz Shareef University of Agriculture, Multan, Pakistan
• ⁵Qingdao Central Hospital of University of Health and Rehabilitation Sciences, Qingdao, China

Jatropha mollissima (Pohl.) Baill is a traditional medicinal plant known for hepatoprotective and nephroprotective effects, yet its cardioprotective and anti-inflammatory potential remains underexplored. This study investigated the aqueous-methanolic leaf extract of J. mollissima (Jm) through in vitro, in vivo, and ex vivo experiments to evaluate its cardioprotective, anti-inflammatory, antioxidant, anticoagulant, thrombolytic, and vasorelaxant activities. Phytochemical screening and HPLC analysis confirmed the presence of bioactive compounds including gallic acid, mandelic acid, quercetin, pyrogallol, and rutin. Antioxidant activity was assessed via DPPH, SOD, NO, and H₂O₂ assays. Doxorubicin (10 mg/kg, i.p.) was used to induce cardiotoxicity, and biochemical parameters such as CK-MB, LDH, Troponin I, serum sodium, and potassium were measured after 21 days. Jm (400–600 mg/kg) significantly (p < 0.005–0.000) reduced serum markers of cardiac damage and improved the cardiac weight-to-body weight ratio, indicating resistance to doxorubicin-induced necrosis. In vitro anticoagulant assays demonstrated a dose-dependent increase in activated partial thromboplastin, prothrombin, and clotting times (20%, 10%, and 5% dilutions) comparable to heparin. In vivo experiments (25–100 mg/kg) similarly prolonged clotting, prothrombin, and bleeding times versus controls. Thrombolytic assays showed significant (p < 0.05) clot lysis at all doses, comparable to streptokinase. Vasorelaxant and calcium channel-blocking activities further supported the cardioprotective role of Jm. Gene expression analysis revealed downregulation of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and upregulation of IL-10, comparable to doxorubicin-treated groups. These results suggest anti-inflammatory effects mediated via modulation of inflammatory signaling pathways. The combined antioxidant, anticoagulant, thrombolytic, and anti-inflammatory activities of J. mollissima, attributed to its phytochemical constituents, suggest a multifactorial mechanism underlying its cardioprotective potential. By reducing oxidative stress, modulating inflammatory responses, and protecting against cardiotoxicity, J. mollissima emerges as a promising therapeutic candidate for managing doxorubicin-induced cardiotoxicity and related cardiovascular complications.