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Leonotis ocymifolia (Burm.f.) Iwarsson aerial parts aqueous extract mitigates cisplatin-induced nephrotoxicity via attenuation of inflammation, and DNA damage

Affiliation
Laboratory of Biotechnology and Biomonitoring of the Environment and Oasis Ecosystems ,Faculty of Sciences of Gafsa ,University of Gafsa ,Gafsa ,Tunisia
Mufti, Afoua;
Affiliation
Laboratory of Biotechnology and Biomonitoring of the Environment and Oasis Ecosystems ,Faculty of Sciences of Gafsa ,University of Gafsa ,Gafsa ,Tunisia
Feriani, Anouar;
Affiliation
AgroBioSciences Program ,College for Sustainable Agriculture and Environmental Science ,Mohammed VI Polytechnic University ,Ben Guerir ,Morocco
Ouchari, Wafae;
Affiliation
School of Life and Medical Sciences ,University of Hertfordshire Hosted By Global Academic Foundation ,Cairo ,Egypt
Mandour, Yasmine M.;
Affiliation
Institut Supérieur des Sciences et Technologies de L’Environnement ,Université de Carthage ,Carthage ,Tunisia
Tlili, Nizar;
Affiliation
Department of Biochemistry ,Ahmadu Bello University ,Zaria ,Nigeria
Ibrahim, Mohammed Auwal;
Affiliation
Department of Pharmacology and Toxicology ,Faculty of Pharmacy ,Zagazig University ,Zagazig ,Egypt
Mahmoud, Mona F.;
Affiliation
AgroBioSciences Program ,College for Sustainable Agriculture and Environmental Science ,Mohammed VI Polytechnic University ,Ben Guerir ,Morocco
Sobeh, Mansour

Herein, we explored the protective effect of Leonotis ocymifolia (Burm.f.) Iwarsson aerial parts extract (LO) against cisplatin (CP)-induced nephrotoxicity in rats and profiled their phytocontents. A total of 31 compounds belonging to organic and phenolic acids and their glycosides as well as flavonoids and their O - and C -glycosides were identified through LC-MS/MS. The DPPH and FRAP assays revealed that the extract had powerful antioxidant properties. The in vivo results demonstrated that administering LO extract for 30 days (40 and 80 mg/kg b. w.) significantly improved the altered renal injury markers via reducing creatinine (high dose only) and uric acid levels compared to the Cp-group. The deleterious action of cisplatin on renal oxidative stress markers (GSH, MDA, SOD, and CAT) were also mitigated by LO-pretreatment. The reduction of the inflammatory marker (IL-6), and inhibition of DNA fragmentation, highlighted the prophylactic action of LO in kidney tissue. Molecular docking followed by a 100 ns molecular dynamic simulation analyses revealed that, amongst the 31 identified compounds in LO, chlorogenic and caffeoylmalic acids had the most stable binding to IL-6. The nephroprotective effects were further confirmed by histopathological observations, which showed improvement in ultrastructural changes induced by cisplatin. The observed findings reinforce the conclusion that L. ocymifolia extract exerts nephroprotective properties, which could be related to its antioxidant and anti-inflammatory activities. Further studies are required to determine the therapeutic doses and the proper administration time.

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License Holder: Copyright © 2023 Mufti, Feriani, Ouchari, Mandour, Tlili, Ibrahim, Mahmoud and Sobeh.

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