RESUMEN
Farnesol is a natural acyclic sesquiterpene alcohol, found in various essential oils such as, lemon grass, citronella, tuberose, neroli, and musk. It has a molecular mass of 222.372 g/mol and chemical formula of C15H26O. The main objective of this study was to assess the effect of farnesol on mTOR and its two downstream effectors, p70S6K and eIF4E, which are implicated in the development of cancer, via molecular dynamic simulation, and docking analysis in an in silico study. A multilayer, primarily computer-based analysis was conducted to assess farnesol's anticancer potential, with a focus on primary cancer targets. From the calculations performed, farnesol showed a binding affinity of - 9.66 kcal/mol, followed by binding affinity of - 7.4 kcal/mol and - 7.8 kcal/mol for mTOR, p70S6K and eIF4E respectively. Rapamycin showed the binding affinity of - 10.45 kcal/mol for mTOR, for p70S6K and eIF4E the calculated binding affinity was - 10.65 kcal/mol and 8.16 kcal/mol respectively. The binding affinity of farnesol was comparable to the standard drug rapamycin indicating its potential as an mTOR inhibitor. Molecular dynamics simulations suggest that the ligands (farnesol and rapamycin) were well trapped within the active site of the protein over a time gap of 50 ns. It is clear that farnesol showed relatively stable MD simulation results, with minor fluctuations and maintains a consistent binding orientation, suggesting a strong and stable interaction with the target proteins when compared to simulation data of standard drug. This study explores the potential of farnesol as an anticancer agent through an in-silico approach, focusing on its interaction with mTOR and its downstream effectors. Inhibition of mTOR signaling pathway may be responsible for the anticancer effect of farnesol. As this pathway plays a crucial role in cell proliferation and survival, making it a significant target in cancer research.
RESUMEN
Ajuga bracteosa (Ab) has tremendous medicinal value with long-established disease curing potential. The present study aimed to assess the hepatoprotective potential of Ab extracts in paracetamol-induced hepatotoxicity in mice. Group I (normal control) were treated with saline 1 ml/kg BW orally for 7 days while Group II (toxicant control) received saline 1 ml/kg BW for 6 days and Paracetamol (1000 mg/kg BW) on day7of the treatment. Group III received Standard drug silymarin (100 mg/kg BW) for 6 days and Paracetamol (1000 mg/kg BW) on day 7of treatment. Groups IV andV were administered with methanol extract (ME) 200 mg/kg BW and aqueous extract (AE) 1000 mg/kg BW for 6 days and Paracetamol (1000 mg/kg BW) on day 7th of the study. Both extracts showed hepatoprotective potential against the toxic effects of paracetamol, evidenced by serum analysis of biomarkers involved in liver injury and histopathological findings. Hepatotoxic mice pretreated with Ab plant extract or silymarin exhibited significant decrease in ALP, AST, and ALT enzyme level while GSH levels were markedly increased. According to histological observations, groups treated with PCM (toxicant control) showed significant necrosis and lymphocyte infiltration, while groups treated with silymarin and Ajuga bracteosa plant extract showed preservation of the normal liver structural features. The phytochemical analysis of ME and AE of Ab showed the presence of glycosides, phenolic compounds, tannins, fats, saponins, flavonoids, terpenes, oils, and fats. The antioxidant activity of these two extracts was determined by nitric oxide assay, DPPH assay, and ferric reducing power assay. The methanolic extract exhibited the highest antioxidant potential (78.09 ± 0.0806). The antioxidant potential of aqueous extract was 73.08 ± 0.248. The reducing power for methanolic extract and ascorbic acid (standard) 500 µg/ml was 0.933 and 0.987 respectively. The anti-inflammatory activity of both extracts was demonstrated by in vitro methods, namely albumin denaturation, proteinase inhibition, and membrane stabilization assays. The study suggests that Ab extracts have competence for attenuating inflammation, oxidants, and hepatotoxicity.