Antileishmanial and lung adenocarcinoma cell toxicity of Withania somnifera (Linn.) dunal root and fruit extracts

Abstract

This study aims to evaluate the anti-Leishmania major and the lung adenocarcinoma (A549) cytotoxicity of Withania somnifera root and fruit. The total extracts were obtained by homogenisation in aqueous MeOH, and the sub-extracts [n-hexane, ethyl acetate (EtOAc), nbutanol (n-BuOH), and methanol (MeOH)] were obtained by flash chromatography. The activity evaluation showed that n-BuOH sub-extracts from root and fruit exhibited noticeable antileishmanial promastigote properties. The n-hexane and EtOAc sub-extracts from both organs, and the MeOH sub-extract from the fruit exerted mild to moderate effects on the promastigotes.In-vitro growth-inhibitory test results on axenic amastigote and cytotoxicity testing on macrophages (RAW264.7), the parasite-host at the amastigote stage, revealed that the activity was mainly concentrated in the root EtOAc and n-BuOH sub-extracts and to a lesser extent the fruit MeOH and EtOAc, and the root n-hexane sub-extracts. Only the roots' EtOAc and n-BuOH sub-extracts demonstrated low cytotoxicity on the A549 cell line.

Identification of Potential Leishmania N-Myristoyltransferase Inhibitors from Withania somnifera (L.) Dunal: A Molecular Docking and Molecular Dynamics Investigation

“…The development of new medications with enough safety and affordability is immediately needed to tackle this disease. W. somnifera is a perennial shrub found in open fields and deserts from the Mediterranean region to Southeast Asia [ 1 ]. A reasonable level of safety has been supported by up to 30 clinical studies; there were no obvious side effects or changes in hematological, biochemical, or vital indicators.…”

“…The introduction of promastigote into the body, the blood circulation of amastigote, phagocytosis and macrophage cell growth, lysis, and blood flow as amastigote once more are among the steps that occur in Leishmania infection [ 1 ]. However, NMT inhibitors obtained by synthesis from various research groups were unable to kill parasites inside macrophages at reasonable therapeutic doses, as shown by in vivo assay [ 2 ].…”

“…Leishmaniasis is a serious neglected tropical disease that causes several illnesses connected to immune-system dysfunction and poverty, which are sometimes associated with high fatality rates [ 1 ]. The disease is manifested in three different ways: Cutaneous leishmaniasis (CL), which is characterized by lesions at the site of infection; mucocutaneous leishmaniasis, which is characterized by invasion and destruction of the mucosa; and visceral leishmaniasis, which is the most severe form because the infection spreads to other organs like the spleen and liver [ 2 ].…”

“…Each year, around two million new cases are reported worldwide, with cutaneous leishmaniasis accounting for 75% of these infections. The primary cause of cutaneous leishmaniasis is Leishmania major, and out of the 89 countries where it is present, Afghanistan, Brazil, Iran, Peru, Saudi Arabia, and Syria account for 90% of CL cases [ 1 , 3 ]. Despite the long history of the disease, no vaccine is available, and all of the current medications are either ineffective, have unfavorable side effects, or are losing efficacy as resistance emerges [ 4 ].…”

“…Screening of W. somnifera from different geographical regions has shown that methanolic extract exhibits in vitro antileishmanial action against free-living promastigotes [ 25 , 26 ] and intracellular amastigotes of L. major [ 26 ]. Investigation of a solvent-soluble fraction of root and fruit hydromethanolic extracts demonstrated significant antileishmanial promastigote properties of the butanol-soluble fraction from roots and fruits, whereas in vitro growth-inhibitory assessment on axenic amastigotes revealed promising activity of the root ethyl acetate-soluble and butanol-soluble fractions [ 1 ]. Further bio-guided fractionation revealed that the withanolide-enriched fraction from W. somnifera ethanolic extract was effective [ 17 ].…”