This paper describes the anti-nociceptive activity of isolated di-naphthodiospyrols from Diospyros lotus L., Ebenaceae. The roots of D. lotus were collected from the surroundings of Razagram, Pakistan. Six dimeric di-naphthodiospyrols were isolated by column chromatography and identified as follows: 5,4-dihydroxy-1-methoxy-6,6-dimethyl-7,3-binaphthyl-1,4,5,8-tetraone (1), 5,8-dihydroxy-5-methoxy-6,6-dimethyl-7,3-binaphthyl-1,4,1,4-tetraone (2), 8,5,8-trihydroxy-6,6-dimethyl-7,3-binaphthyl1,4,1,4-tetraone (3), 5′,8′-dihydroxy-6,6′-dimethyl-7,3′-binaphthyl-1,4,1′,4′-tetraone (4), 5′,8′-dihydroxy-5,8-dimethoxy-6,6′-dimethyl-7,3′-binaphthyl-1,4,1′,4′-tetraone (5), and 5,8,5-trihydroxy-8-methoxy-6,6-dimethyl-7,3-binaphthyl-1,4,1,4-tetraone (6). They were subjected to anti-nociceptive assay by the hot plate test. Results revealed that compounds 3 and 4 significantly increased the latency time and can be considered an evidence for the anti-nociceptive effect of the studied plant material. Molecular docking study was also performed against cyclooxygenase (COX) isomers (type 1 and 2) in order to assess the possible binding mechanism of compounds 3 and 4, which established various significant electrostatic interactions with critical residues in both enzymatic targets. These results suggest that di-naphthodiospyrols are natural products that could be considered to have a good anti-nociceptive potential. [Figure not available: see fulltext.]
