Anti-Inflammatory Potential of Beesioside O: Target Prediction, Docking Studies, and Molecular Dynamics

Area of Science:

• Natural Products Chemistry
• Pharmacology
• Computational Chemistry

Background:

• Triterpenoids are promising pharmaceutical precursors for anti-inflammatory therapies.
• Beesioside O (BO), a cycloartane triterpene saponin, has known anti-HIV and anticancer activities.
• The anti-inflammatory mechanisms of BO remain largely uncharacterized.

Purpose of the Study:

• To investigate the anti-inflammatory activity of Beesioside O (BO).
• To elucidate the molecular mechanisms underlying BO's anti-inflammatory effects in LPS-induced RAW264.7 macrophages.
• To utilize computational approaches for further characterization of BO's anti-inflammatory properties.

Main Methods:

• Experimental evaluation of BO in LPS-induced RAW264.7 macrophages.
• In silico analysis including NP AI Engine predictions, molecular docking, DFT calculations, and molecular dynamics simulations.
• Preparation and evaluation of a BO derivative for anti-inflammatory activity.

Main Results:

• BO significantly inhibited the mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2).
• BO modulated the phosphorylation of extracellular signal-regulated kinase (ERK) at 3 hours.
• Computational studies characterized BO's structural and electronic properties and simulated its interaction with ERK2 kinase.

Conclusions:

• Beesioside O demonstrates significant anti-inflammatory effects in macrophages.
• The study provides mechanistic insights into BO's action, involving inhibition of iNOS and COX-2 and regulation of ERK signaling.
• BO and its derivatives hold potential for development as novel anti-inflammatory agents.