The Antioxidant Carrichtera annua DC. Ethanolic Extract Counteracts Cisplatin Triggered Hepatic and Renal Toxicities

Abstract

Cisplatin is a powerful anti-neoplastic drug that displays multi-organ toxicity, especially to the liver and kidneys. Consumption of phytomedicines is a promising strategy to overcome the side effects of chemotherapy. Carrichtera annua extract proved to possess potent antioxidant activity. Its protective potential against cisplatin-induced hepato–nephrotoxicity was scrutinized. Moreover, a phytochemical study was conducted on C. annua ethyl acetate fraction which led to the isolation of five known phenolic compounds. Structure determination was achieved utilizing 1H- and 13C-NMR spectral analyses. The isolated phytochemicals were trans-ferulic acid (1), kaempferol (2), p-coumaric acid (3), luteolin (4) and quercetin (5). Regarding our biological study, C. annua has improved liver and kidney deteriorated functions caused by cisplatin administration and attenuated the histopathological injury in their tissues. Serum levels of ALT, AST, blood urea nitrogen and creatinine were significantly decreased. C. annua has modulated the oxidative stress mediated by cisplatin as it lowered MDA levels while enhanced reduced-GSH concentrations. More importantly, the plant has alleviated cisplatin triggered inflammation, apoptosis via reduction of INFγ, IL-1β and caspase-3 production. Moreover, mitochondrial injury has been ameliorated as remarkable increase of mtDNA was noted. Furthermore, the MTT assay proved the combination of cisplatin—C. annua extract led to growth inhibition of MCF-7 cells in a notable additive way. Additionally, we have investigated the binding affinity of C. annua constituents with caspase-3 and IFN-γ proteins using molecular simulation. All the isolated compounds exhibited good binding affinities toward the target proteins where quercetin possessed the most auspicious caspase-3 and IFN-γ inhibition activities. Our results put forward that C. annua is a promising candidate to counteract chemotherapy side effects and the observed activity could be attributed to the synergism between its phytochemicals.

Thonningia sanguinea Extract: Antioxidant and Cytotoxic Activities Supported by Chemical Composition and Molecular Docking Simulations

“…In a continuing effort to discover biologically active phytochemicals from medicinal plants [21][22][23][24][25], our group focused on the study of T. sanguinea, a locally well-known medicinal plant widely distributed throughout the forest zones of tropical Africa. T. sanguine is rich in phenolic compounds, such as brevifolin carboxylic acid and gallic acid [26].…”

The effect of Usnea longissima extract on chemotherapy-associated multi-organ damage in rats

“…Apart from this, it reacts with hydrogen peroxide and organic peroxides to show antioxidant effect [31,32]. Previous studies show that decrease in GSH levels result in doxorubicin and cisplatin associated heart [33,34], liver [33,35], kidney [33,35] and [36,37] damage. The decrease in tGSH levels in ovarian, heart, liver and kidney tissues of the doxorubicin and cisplatin given rats in our study supports the literature.…”

“…Various studies showed that overproduction of reactive oxygen species induces the synthesis of proin ammatory cytokines and causes tissue damage [8,33,35]. LPO associated oxidative stress increases the production of TNF-α and IL-6 to increase tissue damage [39,40].…”

Potential Gonado-Protective Effect of Cichorium endivia and Its Major Phenolic Acids against Methotrexate-Induced Testicular Injury in Mice

“…Since oxidative stress, inflammation, and apoptosis are the main mechanisms by which MTX induces toxicity and causes the loss of spermatocytes, as well as the atrophy of seminiferous tubules [ 70 ], agents that have antioxidant, anti-inflammatory, and antiapoptotic effects would be beneficial to ameliorate such germ cell toxicity. Many plants are the main sources for bioactive compounds that can be used to relieve diseases [ 81 ]. For instance, phytomedicine and plant-derived antioxidants are considered a prosperous strategy for alleviating chemotherapy-induced organ toxicities [ 28 , 82 , 83 , 84 , 85 ].…”