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Four steroidal saponins, spirostan-25(27)-ene-1β,3α-diol-1-O-[α- L -rhamnopyranosyl-(1 → 2)-α- L -rhamnopyranoside] (fruticoside M) (6), 5α-spirost-25(27)-ene-1β,3β-diol-1-O-α- L -rhamnopyranosyl-(1 → 2)-(4-O-sulfo)-β- D -fucopyranoside (fruticoside I) (8), 26-O-β- D -glucopyranosyl-22-O-methyl-(25S)-5α-furostane-1β,3α,22ε,26-tetrol 3,26-O-β- D -glucopyranoside (9), and 26-O-β- D -glucopyranosyl-22-O-methyl-(22S)-5α-furostane-3α,22ε-26-triol-3-O-β- D -glucopyranoside (12) together with 8 phenolic compounds, 5,3′,5′-trihydroxy-3,6,7,4′-tetramethoxyflavone (1), procyanidin B2 (2), vitexin 2′′-O-rhamnoside (3), naringenin (4), 3-O-[6-trans-p-coumaryl]-β- D -glucoside (helichrysoside) (5), baicalein-6-O-β-glucuronopyranoside (7), 4′,5,7-trihydroxy-6,8-dimethylisoflavone (10) and farrerol (11) were isolated from the 70% aqueous methanolic extract of C. fruticosa (L.) A. Chev. leaves. Using HPLC-ESI/MS-MS, 46 metabolites were identified in the plant extract. They were mainly steroidal saponins and phenolics. The effect of C. fruticosa leaves' extract against doxorubicin–cisplatin-induced nephrotoxicity and hepatotoxicity in rats were evaluated. Administration of C. fruticosa extract (200 mg per kg per day) induced a significant decrease in the AST, ALT, ALP, urea, U.A. and creatinine in doxorubicin-treated rats and protected the renal tissues from necrosis induced by doxorubicin. The administration of the extract (200 mg per kg body weight) 10 days before cisplatin ingestion (5 mg per kg, single dose) in the preventive process, contributed to a pronounced protection against hepatic injury induced by cisplatin. In addition to that, the protection increased through the post prevention and treatment stages with levels of ALT and AST. The isolated compounds were examined via molecular docking as Tumor Necrosis Factor-alpha (TNF-α) inhibitors compared to silymarin as a reference drug. The obtained results could be very promising for advanced evaluations of the isolated compounds, especially the most two promising isolated compounds (6) and (9) either alone or in combination with other isolates of the extract through different in vitro and in vivo techniques for their hepatoprotective and nephroprotective effects as well. [ABSTRACT FROM AUTHOR]