Anti-Inflammatory Potential of Daturaolone from Datura innoxia Mill.: In Silico, In Vitro and In Vivo Studies

Abstract

Exploration of leads with therapeutic potential in inflammatory disorders is worth pursuing. In line with this, the isolated natural compound daturaolone from Datura innoxia Mill. was evaluated for its anti-inflammatory potential using in silico, in vitro and in vivo models. Daturaolone follows Lipinski’s drug-likeliness rule with a score of 0.33. Absorption, distribution, metabolism, excretion and toxicity prediction show strong plasma protein binding; gastrointestinal absorption (Caco-2 cells permeability = 34.6 nm/s); no blood–brain barrier penetration; CYP1A2, CYP2C19 and CYP3A4 metabolism; a major metabolic reaction, being aliphatic hydroxylation; no hERG inhibition; and non-carcinogenicity. Predicted molecular targets were mainly inflammatory mediators. Molecular docking depicted H-bonding interaction with nuclear factor kappa beta subunit (NF-κB), cyclooxygenase-2, 5-lipoxygenase, phospholipase A2, serotonin transporter, dopamine receptor D1 and 5-hydroxy tryptamine. Its cytotoxicity (IC50) value in normal lymphocytes was >20 µg/mL as compared to cancer cells (Huh7.5; 17.32 ± 1.43 µg/mL). Daturaolone significantly inhibited NF-κB and nitric oxide production with IC50 values of 1.2 ± 0.8 and 4.51 ± 0.92 µg/mL, respectively. It significantly reduced inflammatory paw edema (81.73 ± 3.16%), heat-induced pain (89.47 ± 9.01% antinociception) and stress-induced depression (68 ± 9.22 s immobility time in tail suspension test). This work suggests a possible anti-inflammatory role of daturaolone; however, detailed mechanistic studies are still necessary to corroborate and extrapolate the findings.

Ethnobotanical uses and phytochemical, biological, and toxicological profiles of Datura metel L.: A review

“…Daturaolone is a potential compound found in D. metel; in a study, it was found that this compound can inhibit cyclooxygenase and lipoxygenase to provide anti-inflammatory and analgesic activity ( Rauf et al, 2016 ); the basic mechanism is to inhibit cyclooxygenase COX-1 and COX-2 and lipoxygenase; this inhibition causes the suppression of prostaglandin synthesis or might be the narcotic effects of Datura species ( Chandan et al, 2021 ; Jaafar et al, 2018 ). In the process of inflammation, arachidonic acid is crucial because it serves as a building block for the creation of two different types of vital compounds, prostaglandins and leukotrienes, in the body, and daturaolone inhibits the production of prostaglandins and leukotrienes by cyclooxygenase 1 and 2 and lipoxygenase inhibition ( Samuelsson, 1987 , Baig et al, 2021 ), as shown in Fig. 7 .…”

Combination therapy with Hordeum vulgare, Elettaria cardamomum, and Cicer arietinum exhibited anti-diabetic potential through modulation of oxidative stress and proinflammatory cytokines

“…To compare the experimental and theoretical binding affinity of the compounds with the target site, docking studies were carried out [ 34 ]. The structure of all compounds was drawn by using ChemDraw 16.0.…”

Antioxidant, Antimicrobial, and Protein Kinase Inhibition Profiling of C. ambrosioides Seed Extracts along with RP-HPLC

“…Protein Kinase Inhibition Assay. Protein kinase inhibition potential of sample extracts was evaluated according to the procedure reported previously [16,18]. The 24-hour regenerated Streptomyces culture (100 μl) in Trypton soy broth spread to small-scale ISP4 plates on the lawn.…”