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

Abstract

In the present study, we describe various pharmacological effects and computational analysis of nepetolide, a tricyclic clerodane-type diterpene, isolated from . 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. In brine shrimp's lethality model, nepetolide potently showed cytotoxic effect, with LC 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. 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.

In Silico, Molecular Docking and In Vitro Antimicrobial Activity of the Major Rapeseed Seed Storage Proteins

“…The theoretical conformation of the ligands with the highest biological activity is presented in Table 3 and Figure 3 with favorable contacts with the attachment site presented. The docked structures were examined by using Discovery Studio 4.5 Visualizer ( Jia et al, 2015 ; Rehman et al, 2018 ; Bai et al, 2019 ; Riaz et al, 2019 ) and Chimera 1.9 ( Withana-Gamage et al, 2011 ; Nietzel et al, 2013 ; Withana Gamage, 2013 ).…”

“…The theoretical conformation of the ligands with the highest biological activity is presented in Table 3 and Figure 3 with favorable contacts with the attachment site presented. The docked structures were examined by using Discovery Studio 4.5 Visualizer (Jia et al, 2015;Rehman et al, 2018;Bai et al, 2019;Riaz et al, 2019) and FIGURE 1 | (A) Protein motif analysis of antimicrobial signatures (shown in the same color) in napin genes using the PRINTS database. BNANAPINA = Q7DMU4_BRACM = Napin (Q7DMU4) from Brassica campestris; 2SS1_BRANA = Napin-1 (P01091), 2SSI_BRANA = Napin-1A (P24565), 2SSB_BRANA = Napin-B (P27740), 2SS2_BRANA = Napin-2 (P01090), 2SS3_BRANA = Napin-3 (P80208) and 2SSE_BRANA = Napin embryo-specific protein (P09893) are from Brassica napus, ALL1_SINAL = Allergen Sin a 1 (P09893) is from Sinapis alba, and 2SS2_CAPMA = Sweet protein mabinlin-2 (P30233) and 2SS4_CAPMA =Sweet protein mabinlin-4 (P80353) are from Capparis masaikai.…”

The drug likeness analysis of anti-inflammatory clerodane diterpenoids

“…Tillifodiolide (40), isolated from Salvia tiliifolia Vahl (Lamiaceae), dosedependently inhibited paw edema in the carrageenan test [73]. Nepetolide (43), a tricyclic clerodane-type diterpenoid isolated from Nepeta suavis, reduced carrageenan-induced paw edema at the dose of 20 mg/kg [78].…”

Attenuated glutamate induced ROS production by antioxidative compounds in neural cell lines

“…21 The antioxidant activity that eliminates intercellular ROS has been widely studied, including the prevention of neuronal dysfunction and neural cell death. [22][23][24] Oxidative stress is an imbalance between free radical production and antioxidant defenses in CNS system. 25 Those compounds share common polyphenols residues in their chemical structure, which is critical for attenuating ROS production.…”