Anti-Inflammatory Potential of Daturaolone from Datura innoxia Mill.: In Silico, In Vitro and In Vivo Studies.
Muhammad Waleed BaigHumaira FatimaNosheen AkhtarHidayat HussianMohammad K OklaAbdulrahman Al-HashimiWahidah H Al-QahtaniHamada AbdElgawadIhsan-Ul HaqPublished in: Pharmaceuticals (Basel, Switzerland) (2021)
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 (IC 50 ) 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 IC 50 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.
Keyphrases
- nuclear factor
- molecular docking
- anti inflammatory
- blood brain barrier
- stress induced
- toll like receptor
- oxidative stress
- nitric oxide
- molecular dynamics simulations
- induced apoptosis
- diabetic rats
- signaling pathway
- chronic pain
- binding protein
- cerebral ischemia
- high glucose
- lps induced
- depressive symptoms
- nitric oxide synthase
- case control
- endothelial cells
- metabolic syndrome
- human health
- pi k akt
- cell cycle arrest
- risk assessment
- physical activity
- photodynamic therapy
- pain management
- peripheral blood
- uric acid
- sleep quality
- heat stress
- protein kinase
- spinal cord
- cell proliferation
- small molecule
- spinal cord injury
- adverse drug
- amino acid
- oxide nanoparticles