In the present study, we describe various pharmacological effects and computational analysis of
nepetolide, a tricyclic
clerodane-type
diterpene, isolated from Nepeta suavis.
Nepetolide concentration-dependently (1.0-1000 µg/mL) exhibited 1,1-diphenyl,2-picrylhydrazyl
free radical scavenging activity with maximum effect of 87.01 ± 1.85%, indicating its
antioxidant potential, as shown by standard drug,
ascorbic acid. It was moderately active against bacterial strain of Staphylococcus aureus. In brine shrimp's lethality model,
nepetolide potently showed cytotoxic effect, with LC50 value of 8.7 µg/mL. When evaluated for antitumor activity in potato disc
tumor assay,
nepetolide exerted
tumor inhibitory effect of 56.5 ± 1.5% at maximum tested concentration of 1000 µg/mL.
Nepetolide at 20 mg/kg reduced
carrageenan-induced
inflammation (P < .001 vs. saline group) in rat paw.
Nepetolide dose-dependently (100-500 mg/kg) decreased
acetic acid evoked writhes, as exhibited by
diclofenac sodium. In-silico investigation of
nepetolide was carried out against
cyclooxygenase-2,
epidermal growth factor receptor and
lipoxygenase-2 targets. Virtual screening through Patchdock online docking server identified primarily hydrophobic interactions between
ligand nepetolide and receptors
proteins. Enhanced hydrogen bonding was predicted with Autodock showing 6-8 hydrogen bonds per target. These results indicate that
nepetolide exhibits
antioxidant, antibacterial, cytotoxic, anticancer, anti-inflammatory and
analgesic activities and should be considered as a lead compound for developing drugs for the remedy of oxidative stress-induced disorders, microbial
infections,
cancers,
inflammations and
pain.