Biological Evaluation, DFT Calculations and Molecular Docking Studies on the Antidepressant and Cytotoxicity Activities of Cycas pectinata Buch.-Ham. Compounds

Abstract

Cycas pectinata Buch.-Ham. is commonly used in folk medicine against various disorders. The present study investigated the antidepressant and cytotoxicity activity of methanol extract of C. pectinata (MECP) along with quantitative phytochemical analysis by GC-MS method. Here, the GC-MS study of MECP presented 41 compounds, among which most were fatty acids, esters, terpenoids and oximes. The antidepressant activity was assessed by the forced swimming test (FST) and tail suspension test (TST) models. In contrast, MECP (200 and 400 mg/kg) exhibited a significant and dose-dependent manner reduction in immobility comparable with fluoxetine (10 mg/kg) and phenelzine (20 mg/kg). MECP showed a weak toxicity level in the brine shrimp lethality bioassay (ED₅₀: 358.65 µg/mL) comparable to the standard drug vincristine sulfate (ED₅₀: 2.39 µg/mL). Three compounds from the GC-MS study were subjected to density functional theory (DFT) calculations, where only cyclopentadecanone oxime showed positive and negative active binding sites. Cyclopentadecanone oxime also showed a good binding interaction in suppressing depression disorders by blocking monoamine oxidase and serotonin receptors with better pharmacokinetic and toxicological properties. Overall, the MECP exhibited a significant antidepressant activity with moderate toxicity, which required further advance studies to identify the mechanism.

Keywords: Cycas pectinata; DFT calculations; MAO; antidepressant; cyclopentadecanone; cytotoxicity; molecular docking; oxime; oximes; serotonin.

Figure 1

Antidepressant effect of methanol extract of C. pectinata leaves (MECP), fluoxetine and phenelzine in tail suspension test (A) and forced swimming test (B). The values are shown as mean ± standard error of the mean (SEM). * p < 0.001 statistically significant compared with the control by Dunnett’s test (n = 5).

Figure 2

Percentage of mortality of brine shrimp lethality bioassay of methanol extract of C. pectinata leaves (MECP) and standard drug vincristine sulfate (VCS) at different concentrations.

Figure 3

Optimized geometric structures of 5-chloro-1-(trimethylsilyl)-1H-indole-2,3-dione 3-[O-(trimethylsilyl)oxime] (A); cyclopentadecanone oxime (B) and trans-2-dodecen-1-ol trifluoroacetate (C).

Figure 4

Calculated 3D surface mapped of electrostatic potential for 5-chloro-1-(trimethylsilyl)-1H-indole-2,3-dione 3-[O-(trimethylsilyl)oxime] (A); cyclopentadecanone oxime (B); trans-2-dodecen-1-ol trifluoroacetate (C), respectively in (a.u), the electron density isosurface being 0.0004 (a.u).

Figure 5

HOMO-LUMO plot 5-chloro-1-(trimethylsilyl)-1H-indole-2,3-dione 3-[O-(trimethylsilyl)-oxime] (A); cyclopentadecanone oxime (B); trans-2-dodecen-1-ol trifluoroacetate (C), respectively, by B3LYP/6-31G+ (d,p) level of theory.