Extract of Woodfordia fruticosa flowers ameliorates hyperglycemia, oxidative stress and improves β-cell function in streptozotocin-nicotinamide induced diabetic rats.
BACKGROUND
The art of Ayurveda and the traditional healing system in India have reflected the ethnomedicinal importance of the plant Woodfordia fruticosa Kurtz, which demonstrates its vast usage in the Ayurvedic preparations as well as in the management of diabetes by the traditional healers.


OBJECTIVE
The study aimed to ascertain the antidiabetic potential of W. fruticosa flower methanolic extract (WF) on Streptozotocin (STZ)-nicotinamide-induced diabetic rat model.


METHODS
Diabetes was induced in Sprague Dawley (SD) rats by STZ-nicotinamide and thereafter diabetic rats were treated with three different doses of WF (100, 200 and 400mg/kg body weight) respectively and glibenclamide as a positive control. Biochemical parameters such as blood glucose, serum insulin and C-peptide levels were measured with oxidative stress markers. Furthermore, histology of liver and pancreas was carried out to evaluate glycogen content and β-cell structures. Moreover, immunohistochemistry and western blot analysis were performed on kidney and pancreas tissues to determine renal Bcl-2, pancreatic insulin and glucose transporter (GLUT-2, 4) protein expression in all the experimental groups.


RESULTS
The acute toxicity study showed non-toxic nature of all the three doses of WF. Further, studies on diabetic rats exhibited anti-hyperglycemic effects by upregulating serum insulin and C-peptide levels. Similarly, WF shown to ameliorate oxidative stress by downregulating LPO levels and augmenting the antioxidant enzyme (ABTS). Furthermore, histopathological analysis demonstrate recovery in the structural degeneration of β-cells mass of pancreas tissue with increase in the liver glycogen content of the diabetic rats. Interestingly, protective nature of the extract was further revealed by the immunohistochemical study result which displayed upregulation in the insulin and renal Bcl-2 expression, the anti apoptosis protein. Moreover, western blot result have shown slight alteration in the GLUT-2 and GLUT-4 protein expression with the highest dose of WFc treatment, that might have stimulated glucose uptake in the pancreas and played an important role in attenuating the blood glucose levels.


CONCLUSIONS
The overall study result have demonstrated the potential of WF in the management of diabetes and its related complications, thus warrants further investigation on its major compounds with in depth mechanistic studies at molecular level.
Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: aditya@um.edu.my.
Aditya
A
Arya
Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Mazen M Jamil
MM
Al-Obaidi
Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Rustini Binti
RB
Karim
Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Hairin
H
Taha
Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Ataul Karim
AK
Khan
Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Nayiar
N
Shahid
Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Abu Sadat
AS
Sayem
Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Chung Yeng
CY
Looi
Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Mohd Rais
MR
Mustafa
Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Mustafa Ali
MA
Mohd
Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Hapipah Mohd
HM
Ali
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D035264:Flowers; D051273:Glucose Transporter Type 2 / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006943:Hyperglycemia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009536:Niacinamide; D018384:Oxidative Stress / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D064209:Phytochemicals / Q000032:analysis; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D031565:Woodfordia
D051273:Glucose Transporter Type 2; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007328:Insulin; D064209:Phytochemicals; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; C495683:Slc2a2 protein, rat; C495694:Slc2a4 protein, rat; D009536:Niacinamide; D013311:Streptozocin; D006003:Glycogen
Antidiabetic; Antioxidant; Bcl-2; Glycogen; Insulin; Woodfordia fruticosa