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Targeting Stearoyl-CoA Desaturase-1 (SCD1) by the Drug–Nutraceutical Combination of Montelukast and Bixin in Ameliorating Steatotic NAFLD

Year: 2025

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome, which progresses from simple fat accumulation (steatosis) to nonalcoholic steatohepatitis (NASH), fibrosis, and eventually liver cancer. Stearoyl-CoA desaturase 1 (SCD1), a key lipogenic enzyme, plays a significant role in the progression of NAFLD by promoting the accumulation of fat in the liver. This study investigated the drug-nutraceutical combination of Montelukast (a synthetic anti-inflammatory drug) and Bixin (an apo-carotenoid) as SCD1 inhibitors for treating fatty liver disease. Bixin was identified through virtual screening of a curated carotenoid database (carotenoid DB) targeting lipogenic enzyme SCD1. In the in vitro model of steatotic HepG2 cells, the combination treatment of Montelukast and Bixin showed a marked reduction ( P < 0.05) in SCD1 gene expression (41%), protein expression (61%), and SCD1 enzyme activity (56.22%). The combination treatment showed a significant reduction of 21.64% ( P < 0.05) in lipid accumulation relative to individual treatment with Bixin or Montelukast and was comparable with the reference drug Aramchol (21.83%). The markers of oxidative stress were also significantly reduced ( P < 0.05), evidenced by decreased MDA (42.25%), RNS levels (32.59%), and ROS levels (30.72%) in the combination group. These findings suggest that Bixin and Montelukast in combination hold potential for managing the multiple aspects in the pathophysiology of NAFLD development and progression.

Source: ACS Omega

DOI: 10.1021/acsomega.5c05345

Authors: Sonakshi Puri, Shivani Kirad, Shubhashree Dash, Pankaj Kumar Sharma, Murugesan Sankaranarayanan, Perinkulam Ravi Deepa

Institutions: Department of Biological Sciences, Department of Biological Sciences, Birla Institute of Technology and Science, Pilani

Language: English

Topic: Liver Disease Diagnosis and Treatment

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,935