Bioflavonoid combination attenuates diabetes-induced nephropathy in rats via modulation of MMP-9/TIMP-1, TGF-β, and GLUT-4-associated pathways
Ritu,
Yifan Xiong,
Hanuman Prasad Sharma,
Ramesh K. Goyal,
Sonia Narwal,
Ajay Berwal,
Sourabh Jain,
Meher Priya,
Manisha Singh,
Gaurav Agarwal,
Xiaoyan Wang,
Bairong Shen,
Rajeev K. Singla
Affiliations
Ritu
Department of Pharmacology, Delhi Pharmaceutical Sciences & Research University, Mehrauli-Badarpur Road, Pushp Vihar Sector-3, New Delhi, 110017, India
Yifan Xiong
Department of Pathology, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Chengdu, 610500, Sichuan, China
Hanuman Prasad Sharma
Ocular Pharmacology and Pharmacy Division, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India; Bioanalytics Facility, Centralized Core Research Facility (CCRF), All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India
Ramesh K. Goyal
Department of Pharmacology, Delhi Pharmaceutical Sciences & Research University, Mehrauli-Badarpur Road, Pushp Vihar Sector-3, New Delhi, 110017, India; Corresponding author. Department of Pharmacology, School of Pharmaceutical Science, Delhi Pharmaceutical Science and Research University, New Delhi, 110017, India.
Sonia Narwal
Department of Pharmacy, Panipat Institute of Engineering and Technology, Samalkha, Panipat, 132102, Haryana, India
Ajay Berwal
Geeta Institute of Pharmacy, Geeta University, Naultha, Panipat, 132145, Haryana, India
Sourabh Jain
Kewalshri Institute of Pharmacy, Khandwa Road, Indore, 452020, Madhya Pradesh, India
Meher Priya
School of Medical and Allied Sciences, KR Mangalam University, Sohna Road, Gurugram, 122103, Haryana, India
Manisha Singh
School of Medical and Allied Sciences, KR Mangalam University, Sohna Road, Gurugram, 122103, Haryana, India
Gaurav Agarwal
Department of Pharmacy, Panipat Institute of Engineering and Technology, Samalkha, Panipat, 132102, Haryana, India
Xiaoyan Wang
Department of Pathology, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Chengdu, 610500, Sichuan, China; Corresponding author.
Bairong Shen
Joint Laboratory of Artificial Intelligence for Critical Care Medicine, Department of Critical Care Medicine and Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
Rajeev K. Singla
Joint Laboratory of Artificial Intelligence for Critical Care Medicine, Department of Critical Care Medicine and Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China; School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, 144411, India
Background: Diabetic nephropathy represents a significant microvascular complication of diabetes, characterized by extracellular matrix accumulation, loss of cell-cell junctions, microalbuminuria, and diminished creatinine clearance. Despite its prevalence, therapeutic options dedicated to this condition are currently lacking. Natural products like bioflavonoids have garnered attention for their potential therapeutic benefits. The present study aimed to evaluate the efficacy of a bioflavonoid combination, including ginger extract, soy extract, and hesperetin, in a diabetic rat model. Methods: Diabetes was initiated in the rat pups via intraperitoneal injection of streptozotocin on the fifth postnatal day. After six weeks, rats exhibiting blood sugar levels exceeding 160 mg/dL were allocated into diabetic control and treatment groups, with eight animals each. A subset of rats received citrate buffer as a control. The treatment group received the bioflavonoid combination orally for twenty-four weeks. Various parameters, including glycemic levels, urinary parameters, antioxidant status, mRNA expression via Western blot, gel zymography, and immunohistochemistry, were assessed at the study's conclusion. Results: The bioflavonoid combination demonstrated significant reductions in hyperglycemia and various urinary parameters compared to controls. Notably, it modulated MMP-9/TIMP-1 expression, upregulated GLUT-4, and downregulated TGF-β. Additionally, the combination enhanced total antioxidant capacity, indicating potential antioxidative benefits. Conclusions: This study highlights the therapeutic potential of a bioflavonoid combination (ginger extract, soy extract, and hesperetin) in improving renal function in diabetic nephropathy. By modulating key factors such as MMP-9/TIMP-1, TGF-β, and GLUT-4, this combination presents a promising avenue for further exploration in managing diabetic nephropathy. These findings underscore the importance of natural products as potential therapeutic agents in addressing diabetic complications.
