PMID- 33847358 OWN - NLM STAT- MEDLINE DCOM- 20220110 LR - 20240226 IS - 2042-7158 (Electronic) IS - 0022-3573 (Linking) VI - 73 IP - 9 DP - 2021 Aug 12 TI - Ganoderma lucidum ameliorates the diabetic nephropathy via down-regulatory effect on TGFbeta-1 and TLR-4/NFkappaB signalling pathways. PG - 1250-1261 LID - 10.1093/jpp/rgab058 [doi] AB - OBJECTIVES: Diabetic nephropathy (DN) is one of the most important complications of diabetes mellitus and it is considered as a principal cause for end-stage renal failure. Ganoderma lucidum (GL) has been studied for its reno-protective effect against different kidney injury models. The aim of our study is to investigate the mechanisms by which GL can improve kidney injury and consequent renal inflammation and fibrosis. METHODS: GL either in a low dose (250 mg/kg, i.p.) or high dose (500 mg/kg, i.p.) was administered to DN rat model, and nephropathy indices were investigated. KEY FINDINGS: GL treatment significantly down-regulated kidney injury molecule-1 (KIM-1) gene expression and inhibited TLR-4 (Toll-like receptor-4)/NFkappaB (nuclear factor kappa B) signalling pathway. As well, GL treatment significantly decreased the pro-inflammatory mediator; IL-1beta (interleukin-1 beta) level and fibrosis-associated growth factors; FGF-23 (fibroblast growth factor-23) and TGFbeta-1 (transforming growth factor beta-1) levels. In addition, GL remarkably inhibited (Bax) the pro-apoptotic protein and induced (Bcl-2) the anti-apoptotic protein expression in kidneys. Moreover, GL treatment significantly alleviates kidney injury indicated by correcting the deteriorated kidney function and improving oxidative stress status in DN rats. CONCLUSIONS: GL significantly improved renal function indices through dose-dependent kidney function restoration, oxidative stress reduction, down-regulation of gene expression of KIM-1 and TLR4/NFkappaB signalling pathway blockage with subsequent alleviation of renal inflammation and fibrosis. CI - (c) The Author(s) 2021. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. FAU - Hassan, Hanan M AU - Hassan HM AUID- ORCID: 0000-0003-0464-0809 AD - Department of pharmacology and Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa City, Mansoura, Egypt. FAU - Mahran, Yasmen F AU - Mahran YF AUID- ORCID: 0000-0002-6306-5616 AD - Department of Pharmaceutical Sciences, Faculty of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, Kingdom of Saudi Arabia. AD - Department of Pharmacology & Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt. FAU - Ghanim, Amal M H AU - Ghanim AMH AD - Department of Biochemistry, Faculty of Pharmacy, Fayoum University, Fayoum, Egypt. LA - eng PT - Journal Article PL - England TA - J Pharm Pharmacol JT - The Journal of pharmacy and pharmacology JID - 0376363 RN - 0 (Biological Products) RN - 0 (Cell Adhesion Molecules) RN - 0 (Havcr1protein, rat) RN - 0 (NF-kappa B) RN - 0 (Rela protein, rat) RN - 0 (Tgfb1 protein, rat) RN - 0 (Tlr4 protein, rat) RN - 0 (Toll-Like Receptor 4) RN - 0 (Transcription Factor RelA) RN - 0 (Transforming Growth Factor beta1) RN - 7Q7P4S7RRE (Fibroblast Growth Factor-23) SB - IM MH - Animals MH - Biological Products/pharmacology/therapeutic use MH - Cell Adhesion Molecules/metabolism MH - Diabetes Mellitus, Experimental/complications/drug therapy/*metabolism MH - Diabetic Nephropathies/drug therapy/*metabolism MH - Down-Regulation MH - Fibroblast Growth Factor-23/metabolism MH - Fibrosis MH - Inflammation/drug therapy/metabolism MH - Kidney/*drug effects/metabolism/pathology MH - Male MH - NF-kappa B/*metabolism MH - Oxidative Stress/drug effects MH - Rats, Sprague-Dawley MH - *Reishi MH - Signal Transduction MH - Toll-Like Receptor 4/*metabolism MH - Transcription Factor RelA/metabolism MH - Transforming Growth Factor beta1/*metabolism MH - Rats OTO - NOTNLM OT - Ganoderma lucidum OT - FGF-23 OT - TGFbeta-1 OT - diabetic nephropathy OT - inflammation OT - renal fibrosis EDAT- 2021/04/14 06:00 MHDA- 2022/01/11 06:00 CRDT- 2021/04/13 08:52 PHST- 2020/08/12 00:00 [received] PHST- 2021/03/18 00:00 [accepted] PHST- 2021/04/14 06:00 [pubmed] PHST- 2022/01/11 06:00 [medline] PHST- 2021/04/13 08:52 [entrez] AID - 6224885 [pii] AID - 10.1093/jpp/rgab058 [doi] PST - ppublish SO - J Pharm Pharmacol. 2021 Aug 12;73(9):1250-1261. doi: 10.1093/jpp/rgab058.