PMID- 36678531 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230202 IS - 1424-8247 (Print) IS - 1424-8247 (Electronic) IS - 1424-8247 (Linking) VI - 16 IP - 1 DP - 2022 Dec 27 TI - Combinatory Effect and Modes of Action of Chrysin and Bone Marrow-Derived Mesenchymal Stem Cells on Streptozotocin/Nicotinamide-Induced Diabetic Rats. LID - 10.3390/ph16010034 [doi] LID - 34 AB - The purpose of this study was to see how chrysin and/or bone marrow-derived mesenchymal stem cells (BM-MSCs) affected streptozotocin (STZ)/nicotinamide (NA)-induced diabetic rats as an animal model of type 2 diabetes mellitus (T2DM). Male Wistar rats were given a single intraperitoneal (i.p.) injection of 60 mg STZ/kg bodyweight (bw) 15 min after an i.p. injection of NA (120 mg/kg bw) to induce T2DM. The diabetic rats were given chrysin orally at a dose of 100 mg/kg bw every other day, BM-MSCs intravenously at a dose of 1 x 10(6) cells/rat/week, and their combination for 30 days after diabetes induction. The rats in the diabetic group displayed impaired oral glucose tolerance and a decrease in liver glycogen content and in serum insulin, C-peptide, and IL-13 levels. They also had significantly upregulated activities in terms of liver glucose-6-phosphatase and glycogen phosphorylase and elevated levels of serum free fatty acids, IL-1beta, and TNF-alpha. In addition, the diabetic rats exhibited a significant elevation in the adipose tissue resistin protein expression level and a significant decrease in the expression of adiponectin, insulin receptor-beta subunit, insulin receptor substrate-1, and insulin receptor substrate-2, which were associated with a decrease in the size of the pancreatic islets and in the number of beta-cells and insulin granules in the islets. The treatment of diabetic rats with chrysin and/or BM-MSCs significantly improved the previously deteriorated alterations, with chrysin combined with BM-MSCs being the most effective. Based on these findings, it can be concluded that combining chrysin with BM-MSCs produced greater additive therapeutic value than using them separately in NA/STZ-induced T2DM rats. FAU - Sayed, Hesham M AU - Sayed HM AUID- ORCID: 0000-0002-8292-9272 AD - Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Beni Suef 62521, Egypt. FAU - Awaad, Ashraf S AU - Awaad AS AD - Department of Anatomy and Embryology, Faculty of Veterinary Medicine, Beni-Suef University, Beni Suef 62521, Egypt. FAU - Abdel Rahman, Fatma El-Zahraa S AU - Abdel Rahman FES AD - Department of Basic Sciences, Faculty of Oral and Dental Medicine, Nahda University, Beni Suef 62764, Egypt. FAU - Al-Dossari, M AU - Al-Dossari M AUID- ORCID: 0000-0003-0642-5117 AD - Department of Physics, Faculty of Science, King Khalid University, Abha 62529, Saudi Arabia. FAU - Abd El-Gawaad, N S AU - Abd El-Gawaad NS AUID- ORCID: 0000-0001-5606-3906 AD - Department of Physics, Faculty of Science, King Khalid University, Abha 62529, Saudi Arabia. FAU - Ahmed, Osama M AU - Ahmed OM AUID- ORCID: 0000-0003-3781-9709 AD - Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Beni Suef 62521, Egypt. LA - eng GR - KKU/RCAMS/008-22/This work was supported by the King Khalid University through a grant KKU/RCAMS/008-22 under the Research Center for Advanced Materials Science (RCAMS) at King Khalid University, Saudi Arabia./ PT - Journal Article DEP - 20221227 PL - Switzerland TA - Pharmaceuticals (Basel) JT - Pharmaceuticals (Basel, Switzerland) JID - 101238453 PMC - PMC9863970 OTO - NOTNLM OT - NA/STZ-induced diabetes mellitus OT - chrysin OT - mesenchymal stem cells COIS- The authors declared there no conflict of interest. EDAT- 2023/01/22 06:00 MHDA- 2023/01/22 06:01 PMCR- 2022/12/27 CRDT- 2023/01/21 01:48 PHST- 2022/10/11 00:00 [received] PHST- 2022/11/25 00:00 [revised] PHST- 2022/12/18 00:00 [accepted] PHST- 2023/01/21 01:48 [entrez] PHST- 2023/01/22 06:00 [pubmed] PHST- 2023/01/22 06:01 [medline] PHST- 2022/12/27 00:00 [pmc-release] AID - ph16010034 [pii] AID - pharmaceuticals-16-00034 [pii] AID - 10.3390/ph16010034 [doi] PST - epublish SO - Pharmaceuticals (Basel). 2022 Dec 27;16(1):34. doi: 10.3390/ph16010034.