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Saroglitazar

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https://www.readbyqxmd.com/read/29331565/saroglitazar-reduces-obesity-and-associated-inflammatory-consequences-in-murine-adipose-tissue
#1
Durgesh Kumar, Umesh Kumar Goand, Sanchita Gupta, Kripa Shankar, Salil Varshney, Sujith Rajan, Ankita Srivastava, Abhishek Gupta, Achchhe Lal Vishwakarma, Anurag Kumar Srivastava, Anil N Gaikwad
Prevailing knowledge links chronic low-grade inflammation in the adipose tissue to obesity and its associated metabolic complications. In this study, we evaluated immunometabolic effects of a recently launched dual peroxisome proliferator-activated receptor (PPAR) α & γ agonist 'Saroglitazar' in a mouse model of diet-induced obesity (DIO). Body composition analysis revealed that saroglitazar treatment promoted hepatic weight gain, while attenuated epididymal white adipose tissue (eWAT) mass in DIO. In the eWAT of saroglitazar treated mice, histological analysis showed reduced adipocyte hypertrophy and matrix deposition (picrosirius red staining)...
January 10, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29224415/preclinical-evaluation-of-saroglitazar-magnesium-a-dual-ppar-%C3%AE-%C3%AE-agonist-for-treatment-of-dyslipidemia-and-metabolic-disorders
#2
Harilal Patel, Poonam Giri, Prakash Patel, Sanjay Singh, Laxmikant Gupta, Urvesh Patel, Nirav Modi, Kalpesh Shah, Mukul R Jain, Nuggehally R Srinivas, Pankaj Patel
Saroglitazar, a novel peroxisome proliferator-activated receptor agonist (PPAR), regulates lipid and glucose metabolism. The objective of this report is to provide a preclinical evaluation (in vitro/in vivo) of ADME properties of saroglitazar. In vitro studies included determination of permeability, metabolic stability, plasma protein binding, CYP reaction phenotyping and CYP inhibitory liability. In vivo studies included oral bioavailability and pharmacokinetic assessment in mouse, rat and dog. The excretion of saroglitazar was determined in rats...
December 9, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29164820/dual-ppar%C3%AE-%C3%AE-agonist-saroglitazar-improves-liver-histopathology-and-biochemistry-in-experimental-nash-models
#3
Mukul R Jain, Suresh R Giri, Bibhuti Bhoi, Chitrang Trivedi, Akshyaya Rath, Rohan Rathod, Ramchandra Ranvir, Shekhar Kadam, Hiren Patel, Prabodha Swain, Sib Sankar Roy, Nabanita Das, Eshani Karmakar, Walter Wahli, Pankaj R Patel
BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are common clinico-pathological conditions that affect millions of patients worldwide. In this study, the efficacy of saroglitazar, a novel PPARα/γ agonist, was assessed in models of NAFLD/NASH. METHODS & RESULTS: HepG2 cells treated with palmitic acid (PA;0.75 mM) showed decreased expression of various antioxidant biomarkers (SOD1, SOD2, glutathione peroxidase and catalase) and increased expression of inflammatory markers (TNFα,IL1β and IL6)...
November 21, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/29081262/virtual-identification-of-novel-ppar%C3%AE-%C3%AE-dual-agonists-by-scaffold-hopping-of-saroglitazar
#4
Wen-Qing Jia, Zhi Jing, Xin Liu, Xiao-Yan Feng, Ya-Ya Liu, Shu-Qing Wang, Wei-Ren Xu, Jian-Wen Liu, Xian-Chao Cheng
The thiazolidinedione class PPARγ agonists as antidiabetic agents are restricted in clinical use because of the side effects such as edema, weight gain, and heart failure. The single and selective agonism of PPARγ is the main cause of side effects. The multi-target cooperative PPARα/γ dual agonist development is a hot topic in the antidiabetic medicinal chemistry field. Saroglitazar is the first approved PPARα/γ dual agonist, available in India for the treatment of diabetic dyslipidemia. It got rid of these side effects...
October 28, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29022212/effect-of-food-on-the-pharmacokinetics-of-saroglitazar-magnesium-a-novel-dual-ppar%C3%AE-%C3%AE-agonist-in-healthy-adult-subjects
#5
Maulik R Patel, Kevinkumar A Kansagra, Devang P Parikh, Deven V Parmar, Hardik B Patel, Mayur M Soni, Uday S Patil, Harilal V Patel, Jaimik A Patel, Swagat S Gujarathi, Krupi V Parmar, Nuggehally R Srinivas
BACKGROUND AND OBJECTIVE: Peroxisome proliferator-activated receptors (PPARs) have recently become a focus of interest for their important roles in glucose and lipid metabolism. In humans, PPARα activation causes a decrease in plasma triglyceride (TG) levels, enhancement of high-density lipoprotein cholesterol (HDL-C) and simultaneous enhancement of very-low-density lipoprotein (VLDL) lipolysis, whereas PPARγ agonists act as insulin sensitizers and improve insulin resistance, which is very useful in patients with type 2 diabetes mellitus (T2DM)...
October 11, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28186999/design-sythesis-and-evaluation-of-a-series-of-3-or-4-alkoxy-substituted-phenoxy-derivatives-as-ppars-agonists
#6
Jun Zhang, Xue-Jiao Wang, Xin Liu, Yi Huan, Miao-Miao Yang, Zhu-Fang Shen, Wen-Qing Jia, Zhi Jing, Shu-Qing Wang, Wei-Ren Xu, Xian-Chao Cheng, Run-Ling Wang
Peroxisome proliferators-activated receptors (PPARα, γ and δ) are potentially effective targets for Type 2 diabetes mellitus therapy. The severe effects of known glitazones and the successfully approved agents (saroglitazar and lobeglitazone) motivated us to study novelly potent PPARs drugs with improved safety profile. In this work, we received 15 carboxylic acids based on the combination principle to integrate the polar head of bezafibrate with the hydrophobic tail of pioglitazone. Another 12 tetrazoles based on the bioisosterism principle were obtained accordingly...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/27702549/thioredoxin-interacting-protein-mediates-lipid-induced-impairment-of-glucose-uptake-in-skeletal-muscle
#7
Ashok Mandala, Nabanita Das, Sudarshan Bhattacharjee, Bidisha Mukherjee, Satinath Mukhopadhyay, Sib Sankar Roy
Insulin resistance (IR) is an important determinant of type-2 diabetes mellitus (T2DM). Free fatty acids (FFAs) induce IR by various mechanisms. A surfeit of circulating FFA leads to intra-myocellular lipid accumulation that induces mitochondrial ROS generation and worsens IR. However, the molecular mechanisms behind are unclear. We identified thioredoxin interacting protein (TxNIP), which is overexpressed in T2DM, to be a promoter of ROS-induced IR. We observed upregulation of TxNIP upon palmitate treatment in skeletal muscle cells that led to ROS generation and Glut-4 downregulation resulting in impaired glucose-uptake...
October 28, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27666920/unique-interaction-of-saroglitazar-with-insulin
#8
Bipin Kumar Sethi, V Sri Nagesh, Jayant Kelwade, Ayesha Vaseem
No abstract text is available yet for this article.
December 2015: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/27646933/current-and-upcoming-pharmacotherapy-for-non-alcoholic-fatty-liver-disease
#9
REVIEW
Yaron Rotman, Arun J Sanyal
Given the high prevalence and rising incidence of non-alcoholic fatty liver disease (NAFLD), the absence of approved therapies is striking. Although the mainstay of treatment of NAFLD is weight loss, it is hard to maintain, prompting the need for pharmacotherapy as well. A greater understanding of disease pathogenesis in recent years was followed by development of new classes of medications, as well as potential repurposing of currently available agents. NAFLD therapies target four main pathways. The dominant approach is targeting hepatic fat accumulation and the resultant metabolic stress...
January 2017: Gut
https://www.readbyqxmd.com/read/27187607/quantitative-determination-of-saroglitazar-a-predominantly-ppar-alpha-agonist-in-human-plasma-by-a-lc-ms-ms-method-utilizing-electrospray-ionization-in-a-positive-mode
#10
Ashok Ghoghari, Ranjeet Dash, Chandrakant Bhatt, Kanchan Singh, Anil Jha, Harilal Patel, Rahul Gupta, Kevinkumar Kansagra, Nuggehally R Srinivas
A sensitive LC-MS/MS method was developed and validated for quantitation of saroglitazar using turboion spray interface with positive ion mode. A liquid-liquid extraction, with a mixture of dichloromethane and diethyl ether, was employed for the extraction of saroglitazar and glimepiride (IS) from human plasma. The chromatographic separation was achieved using an ACE-5, C18 (4.6 × 100 mm) column with a gradient mobile phase comprising acetonitrile and ammonium acetate buffer with trifluoracetic acid in purified water...
December 2016: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/27134886/comparison-of-effectiveness-and-safety-of-add-on-therapy-of-saroglitazar-and-fenofibrate-with-metformin-in-indian-patients-with-diabetic-dyslipidaemia
#11
Arijit Ghosh, Pranab Kumar Sahana, Chanchal Das, Ananya Mandal, Nilanjan Sengupta
INTRODUCTION: Diabetic dyslipidaemia poses a therapeutic challenge. New therapies have emerged in this patient subgroup to enhance outcome and improve compliance. AIM: The aim of this study was to compare the effectiveness and safety of add on therapy of saroglitazar and fenofibrate with metformin in Indian patients with diabetic dyslipidaemia. MATERIALS AND METHODS: Adults patients with diabetic dyslipidaemia fulfilling the inclusion criteria were randomized in two groups...
March 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/26789842/a-prospective-multicentre-open-label-single-arm-exploratory-study-to-evaluate-efficacy-and-safety-of-saroglitazar-on-hypertriglyceridemia-in-hiv-associated-lipodystrophy
#12
MULTICENTER STUDY
Alka Deshpande, Harsh Toshniwal, Shashank Joshi, Rajendrakumar H Jani
OBJECTIVE: This study was designed to explore the efficacy and safety of saroglitazar 4 mg on hypertriglyceridemia in patients with HIV associated lipodystrophy. METHODS: During this 12-week prospective, multi-centric, open-label, single arm exploratory study, 50 patients were enrolled to receive saroglitazar 4 mg orally once daily in the morning before breakfast. The primary efficacy endpoint was the percent change in triglyceride (TG) levels from baseline to Week 6 and Week 12...
2016: PloS One
https://www.readbyqxmd.com/read/26171220/saroglitazar-a-novel-ppar%C3%AE-%C3%AE-agonist-with-predominant-ppar%C3%AE-activity-shows-lipid-lowering-and-insulin-sensitizing-effects-in-preclinical-models
#13
Mukul R Jain, Suresh R Giri, Chitrang Trivedi, Bibhuti Bhoi, Akshyaya Rath, Geeta Vanage, Purvi Vyas, Ramchandra Ranvir, Pankaj R Patel
Saroglitazar is a novel nonthiazolidinediones (TZD) and nonfibric acid derivative designed to act as dual regulator of lipids and glucose metabolism by activating peroxisome proliferator-activated receptors (PPAR). These studies evaluate the efficacy and safety profile of Saroglitazar in preclinical in vitro and in vivo models. The EC50 values of Saroglitazar assessed in HepG2 cells using PPAR transactivation assay for hPPARα and hPPARγ were 0.65 pmol/L and 3 nmol/L, respectively. In db/db mice, 12-day treatment with Saroglitazar (0...
June 2015: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/25926748/saroglitazar-for-the-treatment-of-hypertrig-lyceridemia-in-patients-with-type-2-diabetes-current-evidence
#14
REVIEW
Aravind Sosale, Banshi Saboo, Bhavana Sosale
Diabetes mellitus (DM) is one of the most dreaded metabolic disorders in the world today. It is the leading cause of morbidity and mortality, and plays a cardinal role in quality of life and health economics. DM is associated with a high prevalence of microvascular and macrovascular complications. DM is a very important cardiovascular (CV) risk factor. Cardiovascular disease (CVD) has been implicated as the prime cause of mortality and morbidity in patients with DM. Hence, treatment of DM goes beyond glycemic control, and demands a multidisciplinary approach that comprehensively targets risk factors inherent in CV events...
2015: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/25820046/observational-study-to-evaluate-the-safety-and-efficacy-of-saroglitazar-in-indian-diabetic-dyslipidemia-patients
#15
MULTICENTER STUDY
Sadanand R Shetty, Soumitra Kumar, R P Mathur, Kamal H Sharma, Ashok D Jaiswal
UNLABELLED: Saroglitazar is a dual PPAR α/γ agonist approved in India for the management of diabetic dyslipidemia. AIMS: The objective of this study was to evaluate the safety and efficacy of saroglitazar 4 mg once daily in clinical practice. METHODS: This was an observational, multicenter, single-arm study. Patients with type 2 diabetes (with on-going antidiabetic medication), age above 18 years, and triglycerides ≥200 mg/dL were included...
January 2015: Indian Heart Journal
https://www.readbyqxmd.com/read/25820041/from-make-in-india-to-made-in-india-the-saroglitazar-story
#16
EDITORIAL
Sivasubramanian Ramakrishnan
No abstract text is available yet for this article.
January 2015: Indian Heart Journal
https://www.readbyqxmd.com/read/25674933/saroglitazar-for-the-treatment-of-dyslipidemia-in-diabetic-patients
#17
REVIEW
Shashank R Joshi
INTRODUCTION: Diabetes and dyslipidemia are commonly associated modifiable risk factors for cardiovascular diseases. Majority of patients with diabetes also suffer from dyslipidemia (diabetic dyslipidemia). Diabetic dyslipidemia is more atherogenic as it is commonly associated with high triglyceride (TG) levels, high proportion of small dense low-density lipoprotein cholesterol and low high-density lipoprotein cholesterol (HDL-C) level (atherogenic dyslipidemia). Currently used pharmacotherapies for the management of diabetes and dyslipidemia like thiazolidinediones (PPAR-γ agonist; for insulin resistance) and fibrates (PPAR-α agonist; for hypertriglyceridemia) have many limitations and side effects...
March 2015: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/25573251/observational-study-of-effects-of-saroglitazar-on-glycaemic-and-lipid-parameters-on-indian-patients-with-type-2-diabetes
#18
Sanjay Chatterjee, Anirban Majumder, Subir Ray
Cardiovascular risk reduction is an important issue in the management of patients with Type 2 diabetes mellitus. Peroxisome proliferator activated receptor (PPAR) agonists favourably influence glycaemic and lipid parameters in patients with Type 2 diabetes and a dual PPAR agonist is expected to have favourable effect on both parameters. In this study we have analyzed the effect of Saroglitazar, a novel dual PPAR alpha &gamma agonist, on glycaemic and lipid parameters in Indian patients with Type 2 diabetes...
2015: Scientific Reports
https://www.readbyqxmd.com/read/24944919/role-of-glitazars-in-atherogenic-dyslipidemia-and-diabetes-two-birds-with-one-stone
#19
REVIEW
Srinivasa P Munigoti, C V Harinarayan
A triad of high triglycerides, low high-density lipoprotein (HDL) cholesterol, and elevated small dense low-density lipoprotein particles occurring in a patient with type 2 diabetes is referred to atherogenic diabetic dyslipidemia (ADD). Despite statin therapy, a significant residual risk remains potentially attributable to increased triglyceride concentration and low HDL cholesterol, a characteristic hallmark of ADD. Current therapeutic options in reducing this residual risk include nicotinic acid, omega 3 fatty acids, and selective peroxisome proliferator-activated receptor-alpha (PPAR) agonists (fibrates)...
May 2014: Indian Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/24876549/a-multicenter-prospective-randomized-double-blind-study-to-evaluate-the-safety-and-efficacy-of-saroglitazar-2-and-4-mg-compared-to-pioglitazone-45-mg-in-diabetic-dyslipidemia-press-v
#20
Vikas Pai, A Paneerselvam, Satinath Mukhopadhyay, Anil Bhansali, Dinesh Kamath, V Shankar, Dhiraj Gambhire, Rajendrakumar H Jani, Shashank Joshi, Pankaj Patel
Dual PPARα/γ can improve both metabolic effects and minimized the side effects caused by either PPARα or PPARγ agonist. The PRESS V study was aimed to evaluate the safety, tolerability, and efficacy of saroglitazar 2 mg and 4 mg capsules (Lipaglyn™; Zydus Code: ZYH1) as compared to high dose pioglitazone in patients with diabetic dyslipidemia. In this 26-week double-blind, parallel arm, phase 3 study patients with hypertriglyceridemia with type 2 diabetes mellitus (BMI > 23 kg/m(2); hypertriglyceridemia: TG > 200 to 400 mg/dL; glycosylated hemoglobin [HbA1c] >7 to 9%) were enrolled from 14 sites in India...
January 2014: Journal of Diabetes Science and Technology
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