Abstract:

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.

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Investigation of nepetolide as a novel lead compound: Antioxidant, antimicrobial, cytotoxic, anticancer, anti-inflammatory, analgesic activities and molecular docking evaluation

^{Department of Pharmacology, Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan}

^{Department of Biological Sciences and Chemistry, University of Nizwa, Nizwa 616, Oman}

^{Department of Chemistry, University of Science and Technology, Bannu, Khyber Pakhtunkhwa, Pakistan}

^{STEM Biotechnology Division, Roxbury Community College, Roxbury, MA, USA}

^{College of Professional Studies, Northeastern University, 350 Huntington Avenue, Boston, USA}

Shamsher Ali: ude.uen.yksuh@mahs.ila

^{Corresponding author.}ude.uen.yksuh@mahs.ila

Shamsher Ali: ude.uen.yksuh@mahs.ila

Received 2017 Nov 3; Accepted 2017 Dec 27.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Values shown are mean ± SEM, n = 3.

Vincristine (250 µg/mL) = 91.3% tumor inhibition. Values shown are mean ± SEM, n = 3.

The results represent the values for the best solution from docking programs. The numbers in parenthesis represent Autodock results.

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Peer review under responsibility of King Saud University.

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