An extract of Pueraria tuberosa tubers attenuates diabetic nephropathy by upregulating matrix metalloproteinase-9 expression in the kidney of diabetic rats
Background
Currently, no drug is available to directly target the signaling molecules involved in the pathogenesis of diabetic nephropathy (DN); only antihypertensive and antidiabetic drugs are in clinical use. In the present study, the therapeutic effects of a active fraction of tubers from Pueraria tuberosa (hereafter referred to as PTY-2) were investigated in streptozotocin (STZ)-diabetic rats with DN, with particular emphasis on its effects on extracellular matrix (ECM) accumulation and matrix metalloproteinase (Mmp)-9 expression in kidney tissue.
Methods
Rats were injected with 55 mg/kg, i.p., STZ. After 40 days, rats were divided into groups as follows (n = 6 per group): Group 1, age-matched rats not injected with STZ (non-diabetic control); Group 2, STZ-diabetic DN rats; and Group 3, PTY-2 (30 mg/100 g, p.o.)-treated DN rats. After 20 days treatment, the effects of PTY-2 on serum urea and creatinine concentrations, urinary levels of glucose, creatinine, protein, and ketone bodies, and urine pH were determined. Kidney tissue was evaluated for Mmp-9 expression and histological changes.
Results
Blood glucose, serum urea, creatinine, and urine protein levels were significantly higher, and creatinine clearance was significantly lower, in Group 2 versus Group 1 rats. There was a higher degree of glomerulosclerosis, expansion of the mesangial matrix, and excess ECM deposition and eosinophilic casts in kidneys from Group 2 versus Group 1 rats. Furthermore, Mmp-9 activity and expression were significantly reduced in kidney homogenate of Group 2 versus Group 1 rats. Interestingly, PTY-2 treatment significantly reversed all these changes in DN rats.
Conclusion
Treatment of DN rats with PTY-2 significantly attenuated the severity of DN by increasing the expression and activity of Mmp-9, consequently degrading the ECM accumulated in kidney tissue.
#2Barij Nayan Sinha(BIT Mesra: Birla Institute of Technology, Mesra)H-Index: 19
Last. Venkatesan Jayaprakash(BIT Mesra: Birla Institute of Technology, Mesra)H-Index: 22
view all 3 authors...
Objectives: Curcumin, a known hMAO-A (human Monoamine oxidase-A) inhibitor from Curcuma longa has never been recognized for this property due to its poor permeability and extensive metabolism. Thus, the main objective of this study is to incorporate structural features of Curcumin in the pyrazoline scaffold as an attempt to get potent, selective hMAO-isoform inhibitors with improved permeability. Methods: A series of twelve novel 4, 4'-(4, 5-dihydro-1H-pyrazole-3,5-diyl)bis(2-methoxyphenol) deri...
Diabetic Nephropathy (DN) is believed to be a major microvascular complication of diabetes. The hallmark of DN includes deposition of Extracellular Matrix (ECM) proteins, such as, collagen, laminin and fibronectin in the mesangium and renal tubulo-interstitium of the glomerulus and basement membranes. Such an increased expression of ECM leads to glomerular and tubular basement membranes thickening and increase of mesangial matrix, ultimately resulting in glomerulosclerosis and tubulointerstitial...
Diabetes is a worldwide epidemic that has led to a rise in diabetic kidney disease (DKD). Over the past two decades, there has been significant clarification of the various pathways implicated in the pathogenesis of DKD. Nonetheless, very little has changed in the way clinicians manage patients with this disorder. Indeed, treatment is primarily centered on controlling hyperglycemia and hypertension and inhibiting the renin-angiotensin system. The purpose of this review is to describe the current...
#1Mostafa A. Elfawal(UMass: University of Massachusetts Amherst)H-Index: 7
#2Melissa J. Towler(WPI: Worcester Polytechnic Institute)H-Index: 19
Last. Stephen M. Rich(UMass: University of Massachusetts Amherst)H-Index: 31
view all 5 authors...
Abstract Pharmaceutical monotherapies against human malaria have proven effective, although ephemeral, owing to the inevitable evolution of resistant parasites. Resistance to two or more drugs delivered in combination will evolve more slowly; hence combination therapies have become the preferred norm in the fight against malaria. At the forefront of these efforts has been the promotion of Artemisinin Combination Therapy, but despite these efforts, resistance to artemisinin has begun to emerge. I...
Pueraria tuberosa (Willd.) DC is a perennial herb commonly known as ‘vidarikanda’, distributed throughout south east Asia. The plant's tuber is widely used in ethanomedicine as well as in traditional systems of medicine, particularly in ayurveda. It has been used in various ayurvedic formulations as restorative tonic, antiaging, spermatogenic and immune booster and has been recommended for the treatment of cardiovascular diseases, hepatosplenomegaly, fertility disorders, menopausal syndrome, sex...
#1Xiaoxuan Xu(CSU: Central South University)H-Index: 13
#2Li Xiao(CSU: Central South University)H-Index: 22
Last. Lin Sun(CSU: Central South University)H-Index: 27
view all 8 authors...
Matrix metalloproteinases (MMPs) are proteolytic enzymes belonging to the family of zinc-dependent endopeptidases that are capable of degrading almost all the proteinaceous components of the extracellular matrix (ECM). It is known that MMPs play a role in a number of renal diseases, such as, various forms of glomerulonephritis and tubular diseases, including some of the inherited kidney diseases. In this regard, ECM accumulation is considered to be a hallmark morphologic finding of diabetic neph...
#1Nidhi Pandey(IMS-BHU: Institute of Medical Sciences, Banaras Hindu University)H-Index: 10
#2Durgavati Yadav(IMS-BHU: Institute of Medical Sciences, Banaras Hindu University)H-Index: 4
Last. Yamini B. Tripathi(IMS-BHU: Institute of Medical Sciences, Banaras Hindu University)H-Index: 26
view all 4 authors...
Changing life style and over-nutrition causes low-grade inflammation (LGI), with obesity and hyper-lipidemia as basic factors. The physiological state polarizes macrophages to classical type (M1), which is pro-inflammatory and promotes ectopic fat deposition in the body. Both factors induce inflammatory cascade, where free radicals (FRs) play an important role. Thus, pharmacological and non-pharmacological interventions would be effective in the management of LGI and plant products would be used...
Diabetes mellitus is heterogeneous primary disorder of carbohydrate metabolism with multiple etiologic factors that generally involves absolute or relative insulin deficiency or insulin resistance or both, which results in hyperglycemia. According to WHO projection; it will be the single largest non-communicable disease worldwide by the year 2025 with the largest diabetic population in India. India leads the world with largest diabetic population thus, being termed the ‘‘Diabetes Capital of the ...
Functional foods provide health benefit beyond basic nutrition. Functional foods fortified with plant ingredients are well known. Ayurveda (Indian System of Medicine) has found several ways in which the medicinal benefits of herbs can be conveyed via certain foods as carriers. Milk is one such carrier which has been effectively used to deliver phytochemicals for targeted health benefits. Indian Kudzu or Pueraria tuberosa Linn. (Fabaceae) is an important medicinal plant of Ayurveda, and experimen...
Last. Jiangang Shen(GU: Guangzhou University)H-Index: 50
view all 7 authors...
Abstract Objective The present study was undertaken to investigate the therapeutic effect and underlying mechanisms of lumbrokinase on diabetic nephropathy. Methods Type I diabetes was induced in male Sprague-Dawley rats via intraperitoneal injection of Streptozotocin (STZ). Lumbrokinase was administered to the diabetic rats at a dose of 600,000 U/kg body weight by gavage. As a positive control, perindopril, an angiotensin-converting enzyme inhibitor (ACEI), was given to diabetic rats at a dose ...
#1Priya Shree(IMS-BHU: Institute of Medical Sciences, Banaras Hindu University)H-Index: 4
#2Priyanka Mishra(IMS-BHU: Institute of Medical Sciences, Banaras Hindu University)H-Index: 1
Last. Yamini B. Tripathi(IMS-BHU: Institute of Medical Sciences, Banaras Hindu University)H-Index: 26
view all 8 authors...
COVID-19 pandemic was started in Wuhan city of China in December 2019; immensely affected global population. Herein, an effort was made to identify potential inhibitors from active phytochemicals of Pueraria tuberosa (PTY-2) via molecular docking study. Our study showed five potential inhibitors (Robinin, Genistin, Daidzin, Hydroxytuberosone, Tuberostan) against Mpro and five inhibitors (Robinin, Anhydrotuberosin, Daidzin, Hydroxytuberosone, Stigmasterol) against TMPRSS2. Out of these, Robinin, ...
#1Huayu Yang(Capital Medical University)H-Index: 2
#2Haiping Chen(Capital Medical University)H-Index: 3
Last. Qing Ma(Capital Medical University)H-Index: 5
view all 4 authors...
BACKGROUND Matrix metalloproteinases-9 (MMP-9) can regulate extracellular matrix deposition in diabetic glomerular injury. However, it remains unknown whether MMP-9 is involved in the renal tubular injury. Meanwhile, neutrophil gelatinase-associated lipocalin (NGAL), defined as a biomarker of proximal tubular injury, may influence MMP-9 by forming the MMP-9/NGAL complex. The aim of this study was to investigate MMP-9 expression in proximal renal tubules and the relationship of MMP-9 and NGAL in ...
As the current treatment of chronic kidney disease (CKD) is limited, it is necessary to seek more effective and safer treatment methods, such as Chinese herbal medicines (CHMs). In order to clarify the modern theoretical basis and molecular mechanisms of CHMs, we reviewed the knowledge based on publications in peer-reviewed English-language journals, focusing on the anti-inflammatory, antioxidative, anti-apoptotic, autophagy-mediated and antifibrotic effects of CHMs commonly used in kidney disea...
Pueraria tuberosa (Roxb. ex Willd.) DC. (Fabaceae), also known as Indian Kudzu (vidari kand) is a perennial herb distributed throughout India and other Asian Countries. Traditionally, tuber and leaves of this plant have extensively been reported for nutritional and medicinal properties in Ayurveda as well as in Chinese traditional practices. The objective of the present review is to compile and update the published data on traditional uses, pharmacological potential, and phytochemistry of compou...
BACKGROUND: Enhanced expression of PTY-2 dipeptidyl-peptidase-IV (DPP-IV) has been found to improve has been found in various intestinal diseases. Pueraria tuberosa tuber water extract-2 (PTY-2) is already known to have DPP-IV inhibitory potential. At the mRNA level, this inhibition has not yet been investigated. Increased incretin secretion due to inhibition of DPP-IV could lead to the suppression of stress and apoptosis of intestinal cells. AIM: In this research, we tried to study the antioxid...
Last. E. G. Kovaleva(UrFU: Ural Federal University)H-Index: 8
view all 6 authors...
Abstract The anti-diabetic effect of isoflavone-rich kudzu extract obtained using natural deep eutectic solvent was assessed in diabetic wistar rats treated at doses of 100 mg/kg or 200 mg/kg for 28 days. Effect of treatment was based on weight, glucose tolerance, fasting glucose and glycated haemoglobin level, hepatic biochemical parameters, expression of anti-insulin and Ki67 antibodies, and histopathological evaluation of pancreas and kidney tissues. We found overall improvement in weight in ...
Last. Dragan Djuric(University of Belgrade)H-Index: 21
view all 6 authors...
Diabetes mellitus (DM) is a metabolic disorder that causes severe complications. Thus, the aims of this study were to investigate the influence of DM and folic acid treatment on liver and renal bio...
#1Harsh Pandey(IMS-BHU: Institute of Medical Sciences, Banaras Hindu University)H-Index: 3
#2Shivani Srivastava(IMS-BHU: Institute of Medical Sciences, Banaras Hindu University)H-Index: 17
Last. Yamini BhusanTripathi(IMS-BHU: Institute of Medical Sciences, Banaras Hindu University)H-Index: 1
view all 4 authors...
Abstract Objective The present study was undertaken to investigate the safe doses of Pueraria tuberosa water extract (PTWE) on different organs. Methodology Haematoxylin and eosin staining was used to study the morphological alterations in heart, intestine, testis, adrenal gland and spleen. Followed the OECD guidelines 407 of repeated toxicity with respect to the selection of dose and days for different organs. The selected doses of PTWE were 250, 500, 1000 and 2000 mg/kg bw and the durations se...
Enhanced DPP-IV expression is found to get enhanced in various intestinal diseases. PTY-2 has already been known to have DPP-IV inhibitory potential. This inhibition has not yet been studied at mRNA level. Increased incretin secretion due to DPP-IV inhibition could lead to suppression of stress & intestinal cells apoptosis. Through histological analysis, we have found morphological damage of intestine after STZ injection (65 mg/kg bw) to male Charles foster rats. mRNA expressions were analyzed b...
Last. Zhiguo Zhang(SJTU: Shanghai Jiao Tong University)H-Index: 53
view all 6 authors...
The purpose of this study was to explore the protective effect of protopanaxatriol (PPT) on acute liver injury induced by concanavalin A (ConA). In this study, mice were randomly separated into four groups. The first group received PBS (i.v.). The second group was given PPT (50 mg/kg body weight, i.p.) for 3 days before PBS (i.v.) injection. The third group received ConA (15 mg/kg body weight, i.v.). The fourth group was administered PPT (50 mg/kg body weight, i.p.) for 3 days before ConA (i.v.)...