Saroglitazar

BACKGROUND AND PURPOSE: Liver fibrosis is a reversible liver injury that occurs as a result of many chronic inflammatory diseases and can lead to cirrhosis, which is irreversible and fatal. So, we studied the anti-fibrotic effects of saroglitazar on LX-2 cell lines, as a dual PPARα/γ agonist. METHODS: Cells, after 80% confluence, were treated with TGF-β (2 ng/mL) for 24 h. Then cells were treated with saroglitazar at different doses (2.5, 5, 10 µM) for 24 h...

BACKGROUND AND AIM: Vitamin E is widely prescribed for non-alcoholic steatohepatitis (NASH). Saroglitazar, a novel dual peroxisome proliferator-activator receptor ɑ/γ agonist, is approved in India for non-alcoholic fatty liver disease (NAFLD). No head-to-head comparative study for vitamin E and saroglitazar is available. We studied the efficacy and safety of saroglitazar and vitamin E in NAFLD/NASH. MATERIALS AND METHODS: We prospectively randomised 175 NAFLD patients into four arms as Saroglitazar 4 mg daily alone (n = 44), vitamin E 800IU daily alone (n = 41), vitamin E and saroglitazar combination (n = 47), and control arm (n = 43)...

Saroglitazar (SARO), a dual peroxisome proliferator activated receptor (PPAR)-α/γ agonist, has been used to treat metabolic diseases such as insulin resistance and diabetic dyslipidemia in patients with non-alcoholic fatty liver disease (NAFLD). SARO, administered at a dose of 4 mg/day, has been consistently studied in clinical trials with different time points ranging from 4 to 24 weeks with NAFLD patients. Due to its PPAR-γ agonistic action, SARO prevents adipose tissue-mediated fatty acid delivery to the liver by increasing insulin sensitivity and regulating adiponectin and leptin levels in adipose tissue...

Three peroxisome proliferator-activated receptor subtypes, PPARα, PPAR(ß/)δ, and PPARγ, exert ligand-dependent transcriptional control in concert with retinoid X receptors (RXRs) on various gene sets harboring PPAR response elements (PPREs) in their promoter regions. Ligand-bound PPAR/RXR complexes do not directly regulate transcription; instead, they recruit multiprotein coactivator complexes to specific genomic regulatory loci to cooperatively activate gene transcription. Several coactivators are expressed in a single cell; however, a ligand-bound PPAR can be associated with only one coactivator through a consensus LXXLL motif...

ETHNOPHARMACOLOGICAL RELEVANCE: Nonalcoholic fatty liver disease (NAFLD) is the most common severe liver disease globally, progressing further into nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). Vasaguduchyadi Kwatha (VK) is an Ayurvedic formulation traditionally used to treat liver diseases and other metabolic complications. This study is an ethnopharmacological approach to unravel this indigenous remedy. AIM OF THE STUDY: We aimed to discover the probable mechanism of action of VK against NASH in this study, using network pharmacology, molecular docking, in vitro study, and preclinical investigation...

Pulmonary fibrosis (PF) is a complex disorder with high morbidity and mortality. Limited efficacies of the available drugs drive researchers to seek for new therapies. Saroglitazar (Saro), a full (PPAR α/γ) agonist, is devoid of known PPAR-mediated adverse effects. Breast milk mesenchymal stem cells (BrMSCs) are contemplated to be the ideal cell type harboring differentiation/anti-inflammatory/immunosuppressive properties. Accordingly, our aims were to investigate the potential roles of Saro and/or BrMSCs in PF and to spot their underlying protective mechanisms...

BACKGROUND: Up to 40% of UDCA-treated patients do not have an adequate clinical response. Farnesoid X receptor agonists, peroxisome proliferator-activated receptor agonists, and fibroblast growth factor 19 analogs were developed as adjunctive therapy. The aim of this network meta-analysis was to compare the efficacy of these drugs as add-on therapy for patients with primary biliary cholangitis (PBC) refractory to UDCA in improving ALP levels. METHODS: We searched PubMed, Embase, Web of Science, and the Cochrane Library for eligible studies until 1 December 2023...

OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is the most common liver-related metabolic disorder in the world, with a global prevalence of 25%. Compounds with anti-inflammatory, lipid-lowering, and insulin-sensitizing properties can be used for the prevention or treatment of NAFLD. Therefore, this study was conducted to investigate the effect of saroglitazar (a dual PPARα/γ agonist) and diosmin (a flavonoid) on non-alcoholic fatty liver induced by a high-fat diet (HFD) in Wistar rats...

[This retracts the article DOI: 10.1155/2022/9565136.].

This study aimed to evaluate the possible ameliorative effects of saroglitazar (SAR) on aspects of hepatic injury in dexamethasone (DEX)-induced nonalcoholic steatohepatitis (NASH) in rats. Wistar rats received SAR (2 or 4 mg/kg/day, orally) or metformin (MET, 500 mg/kg/day, orally) for one week before and concurrently with DEX administration (8 mg/kg/day, i.p., for 6 days. Control and drug control groups received vehicle or the higher dose of SAR, respectively. At the end of the experiment, an oral glucose tolerance test (OGTT) was conducted, serum hepatic function parameters and lipid profile were assessed, and hepatic histological changes were evaluated...

We evaluated the effects of select herbal extracts ( Tinospora cordifolia [TC] , Tinospora cordifolia with Piper longum [TC + PL] , Withania somnifera [WS] , Glycyrrhiza glabra [GG] , AYUSH-64 [AY-64], and Saroglitazar [S]) on various parameters in a diet-induced obesity mouse model. After 12 weeks of oral administration of the herbal extracts in high-fat diet (HFD)-fed C57BL/6J mice, we analyzed plasma biochemical parameters, insulin resistance (IR), liver histology, and the expression of inflammatory and fibrosis markers, along with hepatic lipidome...

Non-alcoholic fatty liver disease (NAFLD) has become one of the most common causes of liver diseases globally, with a projected exponential rise. In contrast to the exponential rise in disease burden, there are limited options in the pharmacotherapeutic armamentarium against NAFLD. Saroglitazar belongs to the class of drugs known as peroxisome proliferator-activated receptor (PPAR) agonists, initially introduced for managing diabetic dyslipidemia. However, based on translational and clinical studies, it has been shown to be efficacious in NAFLD...

Saroglitazar magnesium, a dual peroxisome proliferator-activated receptor agonist, is under evaluation for treating various liver conditions. While the pharmacokinetics (PK) of saroglitazar have been extensively studied in diverse preclinical models and healthy subjects, a comprehensive assessment of its PK behavior under conditions of hepatic impairment is lacking. In this Phase 1, open-label, parallel-group study, the PK of a single dose of 4-mg saroglitazar magnesium was investigated in subjects having varying degrees of hepatic impairment with and without portal hypertension compared with appropriately matched individuals having normal hepatic function...

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has become a prevalent cause of chronic liver disease and ranks third among the causes of transplantation. In the United States alone, annual medical costs are approximately 100 billion dollars. Unfortunately, there is no Federal Drug Administration (FDA)-approved medication for its treatment. However, various clinical trials are investigating several therapeutic classes that could potentially treat NAFLD. It is valuable to have a compilation of the data available on their efficacy...

Saroglitazar is a novel medication for dyslipidemia, but its specific effects remain unclear. Therefore, we performed a systematic review and meta-analysis to assess the efficacy and safety of saroglitazar for managing dyslipidemia. The PubMed, Scopus, and EMBASE databases were systematically searched for randomized controlled trials (RCTs) comparing 2 and 4 mg of saroglitazar with placebos for treating dyslipidemia. A random-effects model calculated the pooled mean differences for continuous outcomes with 95% confidence intervals...

Alzheimer's disease (AD) is one of the most prevalent and progressive neurodegenerative disorders, hallmarked by increased amyloid-β deposition and enhanced oxidative load in the brain, ensuing cognitive decline. The present study is aimed at elucidating the neuroprotective effect of saroglitazar, a dual peroxisome-proliferator-activated receptor (PPARα/γ) agonist used in the treatment of diabetic dyslipidemia, against memory impairment induced by intraperitoneal scopolamine injection. 30 male Wistar rats were randomly divided into the following five groups: (A) Veh + Veh, (B) SGZ + Veh, (C) Veh + SCOP, (D) DPZ + SCOP, and (E) SGZ + SCOP...

No therapeutic drugs are currently available for nonalcoholic steatohepatitis (NASH) that progresses from nonalcoholic fatty liver via oxidative stress-involved pathways. Three cognate peroxisome proliferator-activated receptor (PPAR) subtypes (PPARα/δ/γ) are considered as attractive targets. Although lanifibranor (PPARα/δ/γ pan agonist) and saroglitazar (PPARα/γ dual agonist) are currently under investigation in clinical trials for NASH, the development of seladelpar (PPARδ-selective agonist), elafibranor (PPARα/δ dual agonist), and many other dual/pan agonists has been discontinued due to serious side effects or little/no efficacies...

The number of patients with nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) is increasing globally and is raising serious concerns regarding the increasing medical and economic burden incurred for their treatment. The progression of NASH to more severe conditions such as cirrhosis and hepatocellular carcinoma requires liver transplantation to avoid death. Therefore, therapeutic intervention is required in the NASH stage, although no therapeutic drugs are currently available for this...

Parkinson's disease (PD) is a neurodegenerative disorder that affects 2%-3% of the population worldwide. Clinical presentation of PD includes motor and non-motor symptoms. The interplay between pathogenic factors such as increased oxidative stress, neuroinflammation, mitochondrial dysfunction and apoptosis are responsible for neurodegeneration in PD. Intrastriatal administration of 6-hydroxy dopamine (6-OHDA) in rat brain provoked oxidative and nitrosative stress by decreasing endogenous antioxidants such as superoxide dismutase, catalase, glutathione, glutathione peroxidase and glutathione reductase...

AIM: This systematic review and meta-analysis was conducted to evaluate the efficacy and safety of 4 mg saroglitazar treatment in patients with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH). METHODS: PubMed, Embase, Scopus, Cochrane CENTRAL, medRxiv (pre-print), bioRxiv (pre-print), and ClinicalTrials.gov databases were searched for relevant studies. The primary outcome was the change in the serum alanine transaminase (ALT) level...