PMID- 36144196 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220928 IS - 2218-1989 (Print) IS - 2218-1989 (Electronic) IS - 2218-1989 (Linking) VI - 12 IP - 9 DP - 2022 Aug 25 TI - Metabolic Profiling of Jasminum grandiflorum L. Flowers and Protective Role against Cisplatin-Induced Nephrotoxicity: Network Pharmacology and In Vivo Validation. LID - 10.3390/metabo12090792 [doi] LID - 792 AB - Cisplatin (CP) is a powerful chemotherapeutic agent; however, its therapeutic use is restricted due to its nephrotoxicity. In this work, we profiled the phytoconstituents of Jasminum grandiflorum flower extract (JGF) using LC-MS/MS and explored the possible molecular mechanisms against acute renal failure through pharmacological network analysis. Furthermore, the possible molecular mechanisms of JGF against acute renal failure were verified in an in vivo nephrotoxicity model caused by cisplatin. LC-MS analysis furnished 26 secondary metabolites. Altogether, there were 112 total hit targets for the identified metabolites, among which 55 were potential consensus targets related to nephrotoxicity based on the network pharmacology approach. Upon narrowing the scope to acute renal failure, using the DisGeNET database, only 30 potential targets were determined. The computational pathway analysis illustrated that JGF might inhibit renal failure through PI3K-Akt, MAPK signaling pathway, and EGFR tyrosine kinase inhibitor resistance. This study was confirmed by in vivo experiment in which kidneys were collected for histopathology and gene expression of mitogen-activated protein kinase 4 (MKK4), MKK7, I-CAM 1, IL-6, and TNF receptor-associated factor 2 (TRAF2). The animal-administered cisplatin exhibited a substantial rise in the expression levels of the MMK4, MKK7, I CAM 1, and TRFA2 genes compared to the control group. To summarize, J. grandiflorum could be a potential source for new reno-protective agents. Further experiments are needed to confirm the obtained activities and determine the therapeutic dose and time. FAU - Alqahtani, Moneerah J AU - Alqahtani MJ AUID- ORCID: 0000-0003-3013-1354 AD - Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia. FAU - Mostafa, Sally A AU - Mostafa SA AD - Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University, Mansoura 35511, Egypt. FAU - Hussein, Ismail A AU - Hussein IA AUID- ORCID: 0000-0001-6033-7359 AD - Department of Pharmacognosy and Medicinal Plants, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt. FAU - Elhawary, Seham AU - Elhawary S AD - Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt. FAU - Mokhtar, Fatma A AU - Mokhtar FA AD - Department of Pharmacognosy, Faculty of Pharmacy, ALSalam University, Al Gharbiya, Kafr El Zayat 31616, Egypt. FAU - Albogami, Sarah AU - Albogami S AUID- ORCID: 0000-0003-0774-5550 AD - Department of Biotechnology, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia. FAU - Tomczyk, Michal AU - Tomczyk M AUID- ORCID: 0000-0002-4063-1048 AD - Department of Pharmacognosy, Medical University of Bialystok, ul. Mickiewicza 2a, 15-230 Bialystok, Poland. FAU - Batiha, Gaber El-Saber AU - Batiha GE AUID- ORCID: 0000-0002-7817-425X AD - Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, Egypt. FAU - Negm, Walaa A AU - Negm WA AUID- ORCID: 0000-0003-0463-8047 AD - Department of Pharmacognosy, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt. LA - eng PT - Journal Article DEP - 20220825 PL - Switzerland TA - Metabolites JT - Metabolites JID - 101578790 PMC - PMC9502427 OTO - NOTNLM OT - LC-MS/MS OT - MAPK pathway OT - enrichment analysis OT - gene expression OT - network pharmacology OT - protein-protein interaction COIS- The authors declare no conflict of interest. EDAT- 2022/09/24 06:00 MHDA- 2022/09/24 06:01 PMCR- 2022/08/25 CRDT- 2022/09/23 01:34 PHST- 2022/07/27 00:00 [received] PHST- 2022/08/15 00:00 [revised] PHST- 2022/08/22 00:00 [accepted] PHST- 2022/09/23 01:34 [entrez] PHST- 2022/09/24 06:00 [pubmed] PHST- 2022/09/24 06:01 [medline] PHST- 2022/08/25 00:00 [pmc-release] AID - metabo12090792 [pii] AID - metabolites-12-00792 [pii] AID - 10.3390/metabo12090792 [doi] PST - epublish SO - Metabolites. 2022 Aug 25;12(9):792. doi: 10.3390/metabo12090792.