Dihydroxy berberine from Tinospora cordifolia: In silico evidences for the mechanism of anti-inflammatory action through dual inhibition of Lipoxygenase and Cyclooxygenase

Abstract

The non-steroidal anti-inflammatory drugs in clinical use have been implicated with side effects on prolonged use. This implies the dearth of a safer alternative to these drugs and can be easily sourced from the huge resources available to us through Ayurveda. Tinospora cordifolia has been used in the preparation of traditional Ayurvedic formulations, with reported anti-inflammatory activities. Molecular docking studies have been used in an attempt to identify and elucidate the mechanism of action of the bioactive compounds in T. cordifolia with dual inhibition of 5-Lipoxygenase (5-LOX) and Cyclooxygenase-2 (COX-2) enzymes for identification of lead compounds. A screening of the compounds identified in the bioactive fraction of T. cordifolia was carried out using the drug-likeness score and the selected compounds were docked with the Glide module of Schrödinger suite 2014 with Maestro 9.3. Dihydroberberine (TC1) was found to be a potent inhibitor of both 5-Lipoxygenase and Cyclooxygenase-2 enzymes. The binding energy of the compounds to the free enzyme was better than when co-crystallized with substrate indicating preference to the enzyme active site. Dihydroberberine can be evaluated further as a promising candidate to develop a safer anti-inflammatory drug.