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Hyperlipidemia, or elevated serum lipid levels, is an important root cause of cardiovascular problems and other related disorders. The condition may worsen if enzymes such as lipoprotein lipase (LPL) and 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase are impaired. Drugs like fibrates, thiazolidinediones (TZDs), NO-1886, and statins are known to pose side effects. Ursolic acid (UA) found in different medicinal plants has been shown to possess antihyperlipidemic activity. In the current investigation, UA derivatives were designed and the potent derivative selected through molecular docking was synthesized for discovering its anti-hyperlipidemic activity using in silico and in vivo approaches. Molecular docking for the designed derivatives was investigated in the active region of the LPL protein using AutoDock to study their interactions and energies. Anti-hyperlipidemic activities were determined in mice with hyperlipidemia caused by triton WR-1339 or tyloxapol (TY). LPL protein molecular docking results showed that among the 18 UA derivatives, 1a forms hydrogen bonds with the Threonine 238 residue, with a − 9.36 kcal/mol binding energy and non-bonded interaction with other residues. A UA derivative was synthesized under optimized conditions and confirmed using spectroscopic methods including 1H/13C NMR. Treatment with UA and its derivative, 1a, significantly improved the lipid profile and LPL activity and reduced liver HMG-CoA reductase activity. In conclusion, UA and its derivative, 1a, show anti-hyperlipidemic activity. These findings suggest that phenylethyl-based UA derivatives are possibly good lead agents for the development of new antihyperlipidemic agents. Comprehending the mechanism of action and bioavailability of UA derivatives to improve their efficacy requires further investigation.

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In Silico and In Vivo Evaluation of Synthesized Ursolic Acid Derivative as Anti-hyperlipidemic Agent

  • 会议论文

  • 发表日期：

    2025年

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  • Laishram Dhanakumar Singh,
  • Yadav Laxmi Rani,
  • Munmee Goswami,
  • Pooja Paul,
  • Baphilinia Jones Mylliemngap,
  • Rishanlang Nongkhlaw,
  • Suktilang Majaw

摘要

Hyperlipidemia, or elevated serum lipid levels, is an important root cause of cardiovascular problems and other related disorders. The condition may worsen if enzymes such as lipoprotein lipase (LPL) and 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase are impaired. Drugs like fibrates, thiazolidinediones (TZDs), NO-1886, and statins are known to pose side effects. Ursolic acid (UA) found in different medicinal plants has been shown to possess antihyperlipidemic activity. In the current investigation, UA derivatives were designed and the potent derivative selected through molecular docking was synthesized for discovering its anti-hyperlipidemic activity using in silico and in vivo approaches. Molecular docking for the designed derivatives was investigated in the active region of the LPL protein using AutoDock to study their interactions and energies. Anti-hyperlipidemic activities were determined in mice with hyperlipidemia caused by triton WR-1339 or tyloxapol (TY). LPL protein molecular docking results showed that among the 18 UA derivatives, 1a forms hydrogen bonds with the Threonine 238 residue, with a − 9.36 kcal/mol binding energy and non-bonded interaction with other residues. A UA derivative was synthesized under optimized conditions and confirmed using spectroscopic methods including 1H/13C NMR. Treatment with UA and its derivative, 1a, significantly improved the lipid profile and LPL activity and reduced liver HMG-CoA reductase activity. In conclusion, UA and its derivative, 1a, show anti-hyperlipidemic activity. These findings suggest that phenylethyl-based UA derivatives are possibly good lead agents for the development of new antihyperlipidemic agents. Comprehending the mechanism of action and bioavailability of UA derivatives to improve their efficacy requires further investigation.