title: Upregulation of insulin secretion and downregulation of pro-inflammatory cytokines, oxidative stress and hyperglycemia in STZ-nicotinamide-induced type 2 diabetic rats by Pseuduvaria monticola bark extract.
abstract: The current study aimed to ascertain the antidiabetic potential of Pseuduvaria monticola bark methanolic extract (PMm) using in vitro mechanistic study models. In particular, the study determined the effect of PMm on cellular viability, 2-NBDG glucose uptake, insulin secretion, and NF-κB translocation in mouse pancreatic insulinoma cells (NIT-1). Furthermore, in vivo acute toxicity and antidiabetic studies were performed using streptozotocin (STZ)-induced type 1 and STZ-nicotinamide-induced type 2 diabetic rat models to evaluate various biochemical parameters and markers of oxidative stress and pro-inflammatory cytokines. Five isoquinoline alkaloids and three phenolic compounds were tentatively identified in the PMm by LC/MS Triple TOF. The study results showed that PMm is non-toxic to NIT-1 cells and significantly increased the glucose uptake and insulin secretion without affecting the translocation of NF-κB. Moreover, the non-toxic effects of PMm were confirmed through an in vivo acute toxicity study, which revealed that the serum insulin and C-peptide levels were significantly upregulated in type 2 diabetic rats and that no significant changes were observed in type 1 diabetic rats. Similarly, PMm was found to downregulate the levels of oxidative stress and pro-inflammatory cytokines in type 2 diabetic rats by alleviating hyperglycemia. Therefore, we conclude that PMm may be developed as an antidiabetic agent for the treatment of type 2 diabetes-associated conditions.
authors: Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors: Hairin
authors: H
authors: Taha
authors: Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: aditya@um.edu.my.
authors: Aditya
authors: A
authors: Arya
authors: Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors: Mohammadjavad
authors: M
authors: Paydar
authors: Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors: Chung Yeng
authors: CY
authors: Looi
authors: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors: Won Fen
authors: WF
authors: Wong
authors: Department of Pathology, International Medical University, Kuala Lumpur, Malaysia.
authors: C R
authors: CR
authors: Vasudeva Murthy
authors: Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors: M I
authors: MI
authors: Noordin
authors: Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors: Hapipah Mohd
authors: HM
authors: Ali
authors: Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors: A M
authors: AM
authors: Mustafa
authors: Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors: A Hamid A
authors: AH
authors: Hadi
mesh_terms: D000818:Animals; D029061:Annonaceae / Q000737:chemistry*; D016207:Cytokines / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D015536:Down-Regulation; D018836:Inflammation Mediators / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D009536:Niacinamide; D018384:Oxidative Stress; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D013311:Streptozocin; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D007328:Insulin; D010936:Plant Extracts; D009536:Niacinamide; D013311:Streptozocin
keywords: Antioxidant; Cytokines; Diabetes mellitus; Oxidative stress; Pseuduvaria monticola; Type 2 diabetes