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.

INTRODUCTION: Jatropha mollissima (Pohl.) Baill is a traditional medicinal plant reputed for its hepatoprotective and nephroprotective properties. However, its potential cardioprotective and anti-inflammatory effects, both in vitro and in vivo, remain underexplored.

AIM OF THE STUDY: This study conducted a series of in vitro, in vivo, and ex vivo experiments to determine the cardioprotective properties and anti-inflammatory effect of the aqueous-methanolic leaf extract of J. mollissima. Doxorubicin-induced cardiotoxicity, thrombolytic, anticoagulant, antioxidant, vasorelaxant, anti-inflammatory, and calcium channel-blocking activities were determined.

MATERIALS AND METHODS: The study involves a phytochemical evaluation, along with HPLC analysis. The antioxidant activities of the J. mollissima extract were determined using in vitro assays, including DPPH, SOD, NO, and H2O2. In vitro and in vivo anticoagulants, antithrombolytic agents, vasorelaxants, and biochemical assays were performed to determine Jm's protective effect. Cardiac inflammatory markers (TNF-α, IL-1β, IL-6, and IL-10) were evaluated via real-time PCR. Doxorubicin was used as the positive control.

RESULTS: In an in-vitro anticoagulant experiment, J. mollissima displayed a substantial increase in activated partial thromboplastin, prothrombin, and clotting time in a dose-dependent manner (20%, 10%, and 5% dilutions) compared with heparin (250 IU/mg) and distilled water. While in-vivo anticoagulant experiment showed a substantial increment in clotting time, prothrombin time, bleeding time, and activated partial thromboplastin time in a dose-dependent manner (25 mg/kg, 50 mg/kg, and 100 mg/kg) in rats after 1-week of treatment in comparison with heparin (50 IU/mg) and distilled water. For the thrombolytic (in vivo and in vitro) experiments, dose-dependent (20%, 10%, and 5% dilutions) significant (p < 0.05) clot lysis was observed compared to streptokinase (30,000 IU) and distilled water. For antioxidant activity, doxorubicin (intraperitoneally at 10 mg/kg at 0 days) was given, blood samples were extracted (at 21st day) to determine cardiac damage by measuring DPPH, SOD, NO, CK-MB, LDH, Troponin I, serum sodium, and serum potassium in which aqueous-methanolic extract in a dose-dependent manner (600 and 400 mg/kg dilutions) displayed significant (p < 0.005-0.000) decrease in serum level. The cardiac weight-to-body weight ratio showed significant resistance to necrosis caused by the doxorubicin-induced toxic group. HPLC analysis revealed the presence of gallic acid, mandelic acid, quercetin, pyrogallol, and rutin. Gene expression analysis revealed that Jm reduced proinflammatory cytokines (TNF-α, IL-1β, and IL-6) and upregulated the anti-inflammatory cytokine IL-10, with effects comparable to those of doxorubicin.

CONCLUSION: Thus, the anticoagulant, antioxidant, cardioprotective, anti-inflammatory, and thrombolytic properties of J. mollissima are attributed to the presence of various phytochemical constituents, which may act on multiple factors. Its beneficial actions are attributed to the modulation of oxidative stress and neuroinflammatory pathways, suggesting its therapeutic potential in managing cardiotoxicity and other complications.