Anti-Inflammatory Activity and Docking Analysis of Synephrine Isomers via Inhibition COX-2 for Possible Benefit in Arthritis: In vitro and In-silico Analysis

The current study aims to examine the pharmacological capabilities of different isomers of Synephrine in treating arthritis. At first, the several forms of Synephrine (ortho, meta, and para) were examined for their ability to inhibit the COX enzyme (COX-1 and COX-2). The results indicate that all isomers of synephrine showed significant inhibition of COX-2 in comparison to COX-1. Among them, p-synephrine exhibited the most powerful inhibitory action, with an IC50 value of 8.32 µM. During a docking investigation with COX-2, it was observed that p-Synephrine was located in the active site of COX-2, which is surrounded by specific amino acid residues including Ala199, Leu390, Trp387, Thr206, His207, Phe210, Asn382, His386, Gln203, and His388. These residues play a crucial role in the binding of p-Synephrine to COX-2. The anti-inflammatory properties of p-Synephrine were assessed by many bioassays, including protein denaturation, lipoxygenase, and anti-proteinase activity. The results demonstrated that p-Synephrine effectively inhibited these parameters in a concentration-dependent way. Our study conclusively showed that p-Synephrine has a strong anti-inflammatory impact, which could potentially be beneficial in treating Arthritis. This effect is achieved by specifically inhibiting COX-2.