Pain healing potential of famous traditional fermented Rhododendron ( <i>Lali-Guras</i> ) beverages from Indo-Nepal Himalaya: <i>In vitro</i> and <i>in silic</i> <i>o</i> evaluation

Abstract This in vitro and in silico study was designed to validate acclaimed anti-inflammatory or pain-relieving properties of fermented ethnic beverages prepared from Rhododendron or Guras flowers in the Singalila ridge- the famous Rhododendron growing region of the Himalayas. Traditional beverages Guras wine and its distilled version Guras Raksi were considered in this study which were collected from Gairibas, a village situated in Indo-Nepal Singalila Ridge of the Himalayas. In vitro protein (albumin) denaturation inhibition assay was conducted to evaluate anti-inflammatory activity of the samples and later GC-MS analysis was carried out to identify anti-inflammatory compounds present in those beverages. From GC-MS results, eleven major metabolites such as 5-hydroxymethylfurfural; quinic acid; clionasterol; l-(+)-ascorbic acid, 2,6-dihexadecanoate; d-sorbitol; cis-cinnamic acid; tyrosol; lupeol; methyl commate A; 2-hydroxy-gamma-butyrolactone; and 1,3-propanediol, 2-(hydroxymethyl)- 2-nitro- were chosen for molecular docking with human cyclooxygenase-1 (hCOX-1), an important targets in the drug-design for nonsteroidal anti-inflammatory drugs. Among all query compounds, phytosterol- clionasterol and triterpenoid- lupeol and methyl commate A exhibited considerably high binding energy scores (&lt;-8 kcal/mol) even compared to anti-inflammatory drugs- acetaminophen and ibuprofen. Outcome of this research affirmed the potential of Guras based traditional drinks in the healing of different forms of high-altitudinal stress induced pain.