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      Effect of a polyherbal formulation in streptozotocin-induced diabetic nephropathy in wistar rats

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          Abstract

          OBJECTIVES:

          Chronic kidney failure among people with diabetes mellitus (DM) is a burgeoning health problem that affects up to 25% of patients with type 2 DM. Current pharmacological treatment for diabetic nephropathy (DN) does not stop the attainment of renal complications. The intention of the current study was to explore the role of a polyherbal formulation (PHF) in diabetic-induced nephropathy in experimental animals.

          MATERIALS AND METHODS:

          Diabetic rats were grouped as follows and underwent the following treatment for about 16 weeks: Group I – normal rats – no treatment, Group II – DN rats – only vehicle (p.o), and Group III and IV – DN rats – PHF orally at 250 and 500 mg/kg, respectively. After the treatment, the animals were sacrificed, and lipid, renal function, and inflammatory markers were estimated. The observed microscopic changes in kidney were analyzed.

          RESULTS:

          Animals administered with PHF exhibited noteworthy decrease in triglycerides, total cholesterol, very low-density lipoprotein (LDL), LDL, serum creatinine, urinary protein, urinary albumin excretion rate, advanced glycation end products, type IV collagen excretion, interleukin-6, transforming growth factor-ß, and tumor necrosis factor-alpha and showed significant increase in high-density lipoprotein, urine volume, urinary urea, and urine creatinine. Histopathological examination established that administration of PHF prohibited kidney damage.

          CONCLUSION:

          Treatment with PHF showed beneficial effect on DN which may be due to the improvement of renal function parameters and hyperlipidemic and inflammatory mediators.

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          Most cited references23

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          An update on natural compounds in the remedy of diabetes mellitus: A systematic review

          Herbal medicine, phytomedicine or botanical medicine are synonymous, utilizes plants intended for medicinal purposes. Medicinal use of herbal medicine in the treatment and prevention of diseases including diabetes has a long history compared to conventional medicine. Diabetes is one of the major public health concerns over the world. Diabetes or hyperglycemia is considered to be one of the common public health hazard; optimal control of which is still not possible. Persistent hyperglycemia or uncontrolled diabetes has the potential to cause serious complications such as kidney disease, vision loss, cardiovascular disease, and lower-limb amputations which contributed towards morbidity and mortality in diabetes. There are various approaches to treat and prevent diabetes as well as its secondary complications, one of it is herbal medicines. However, the selection of herbs might depends on several factors, which include the stage of progression of diabetes, types of comorbidities that the patients are having, availability, affordability as well as the safety profile of the herbs. This review focuses on the herbal and natural remedies that play the role in the treatment or prevention of this morbid disorder – diabetes, including their underlying mechanisms for the blood glucose-lowering property and the herbal products already been marketed for the remedial action of diabetes.
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            Diabetic Kidney Disease: Pathophysiology and Therapeutic Targets

            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 understanding of how the hemodynamic, metabolic, inflammatory, and alternative pathways are all entangled in pathogenesis of DKD and detail the various therapeutic targets that may one day play a role in quelling this epidemic.
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              Stimulation of collagen gene expression and protein synthesis in murine mesangial cells by high glucose is mediated by autocrine activation of transforming growth factor-beta.

              Previous investigations have demonstrated that growing mesangial cells in high glucose concentration stimulates extracellular matrix synthesis and also increases the expression of TGF-beta. We tested whether the stimulation of extracellular matrix production is mediated by autocrine activation of TGF-beta, a known prosclerotic cytokine. Addition of neutralizing anti-TGF-beta antibody, but not normal rabbit IgG, significantly reduced the high glucose-stimulated incorporation of 3[H]proline. Denaturing SDS-PAGE revealed that mainly collagen types I and IV were stimulated by high (450 mg/dl) D-glucose. This high glucose-mediated increase in collagen synthesis was reduced by the anti-TGF-beta antibody. Treatment of mesangial cells grown in normal (100 mg/dl) D-glucose with 2 ng/ml recombinant TGF-beta 1 mimicked the effects of high glucose. Furthermore, the anti-TGF-beta antibody significantly reduced the increase in mRNA levels encoding alpha 2(I) and alpha 1(IV) collagens induced by high glucose. Thus, the high glucose-stimulated increase of collagen production in mesangial cells is mediated, at least in part, by autocrine TGF-beta activation. We postulate that the interception of the glomerular activity of TGF-beta may be an effective intervention in the management of diabetic nephropathy.
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                Author and article information

                Journal
                Indian J Pharmacol
                Indian J Pharmacol
                IJPharm
                Indian Journal of Pharmacology
                Wolters Kluwer - Medknow (India )
                0253-7613
                1998-3751
                Sep-Oct 2019
                26 November 2019
                : 51
                : 5
                : 330-336
                Affiliations
                [1] Department of Pharmacology, Raghavendra Institute of Pharmaceutical Education and Research (RIPER), Anantapuramu, Andhra Pradesh, India
                [1 ] Department of Pharmaceutics, Raghavendra Institute of Pharmaceutical Education and Research (RIPER), Anantapuramu, Andhra Pradesh, India
                Author notes
                Address for correspondence: Dr. Kanala Somasekhar Reddy, Department of Pharmacology, Raghavendra Institute of Pharmaceutical Education and Research, Chiyyedu (Post), Anantapuramu - 515 721, Andhra Pradesh, India. E-mail: somu.reddyvaru@ 123456gmail.com
                Article
                IJPharm-51-330
                10.4103/ijp.IJP_217_18
                6892015
                1f93553e-8ea9-49d2-9504-2adcf69bbc19
                Copyright: © 2019 Indian Journal of Pharmacology

                This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

                History
                : 23 April 2018
                : 11 October 2019
                : 12 October 2019
                Categories
                Research Article

                Pharmacology & Pharmaceutical medicine
                advanced glycation end products,diabetic nephropathy,polyherbal formulation,streptozotocin

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