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Methotrexate (MTX) is a chemotherapeutic agent and an immunosuppressant used to treat cancer and autoimmune diseases. However, its use is limited by its multi-organ toxicity, including nephrotoxicity, which is related to MTX-driven oxidative stress. Silencing oxidative stressors is therefore an important strategy in minimizing MTX adverse effects. Medicinal plants rich in phenolic compounds are probable candidates to overcome these oxidants. Herein, C . pentandra ethyl acetate extract showed powerful in vitro radical-scavenging potential (IC 50 = 0.0716) comparable to those of the standard natural (ascorbic acid, IC 50 = 0.045) and synthetic (BHA, IC 50 = 0.056) antioxidants. The effect of C . pentandra ethyl acetate extract against MTX-induced nephrotoxicity in rats was evaluated by administering the extract (400 mg/kg/day) or the standard antioxidant silymarin (100 mg/kg/day) orally for 5 days before and 5 days after a single MTX injection (20 mg/kg, i.p.). C. pentandra showed slight superiorities over silymarin in restoring the MTX-impaired renal functions, with approximately twofold decreases in overall kidney function tests. C. pentandra also improved renal antioxidant capacity and reduced the MTX-induced oxidative stress. Moreover, C. pentandra inhibited MTX-initiated apoptotic and inflammatory cascades, and attenuated MTX-induced histopathological changes in renal tissue architecture. Phytochemical investigation of the extract led to the purification of the phenolics quercitrin ( 1 ), cinchonains 1a ( 2 ) and 1b ( 3 ), cis -clovamide ( 4 ), trans -clovamide ( 5 ), and glochidioboside ( 6 ); a structurally similar with many of the reported antioxidant and nephroprotective agents. In conclusion, these data demonstrate that C. pentandra exhibits nephroprotective effect against MTX-induced kidney damage via its antioxidant, antiapoptotic and anti-inflammatory mechanisms. Taxonomy Functional Disorder, Traditional Medicine, Herbal Medicine.

Further phytochemical investigation of the fruits of Kigelia pinnata DC. has yielded a new phenylpropanoid derivative identified as 6-p-coumaroyl-sucrose (1) together with ten known phenylpropanoid and phenylethanoid derivatives (2-11) and a flavonoid glycoside (12). The structures of the isolated compounds were elucidated using various techniques of NMR and MS spectral analysis.