An in vitro study of apoptotic like death in Leishmania donovani promastigotes by withanolides

Chandrasekaran, Sambamurthy; Dayakar, Alti; Veronica, Jalaja; Sundar, Shyam; Maurya, Radheshyam

doi:10.1016/j.parint.2013.01.007

Cited by 49 publications

(32 citation statements)

References 20 publications

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“…Physalis peruviana L. has been known for centuries, but its potential for intensive cultivation has only recently begun to be explored, mainly due to the presence of bioactive compounds, such as ascorbic acid, phenolic compounds, phytosterols and carotenoids. Other compounds are also present in physalis, and its medicinally active components have been studied, including withanolides (Chandrasekaran, Dayakar, Veronica, Sundar, & Maurya, 2013;Fang, Liu, & Li, 2012), withaesteroides (P erez-Castorena, Luna, Martínez, & Maldonado, 2012) and physalins (Hsu et al, 2012;Soares et al, 2006). These compounds presented important pharmacological properties, including antimicrobial, antibacterial, antitumor, antinflammatory, hepatoprotective, immunomodulatory and immunosuppressive properties e in addition to demonstrating effectiveness for the inhibition of unwanted responses in autoimmune diseases and allergies as well as the transplantation of organs.…”

Section: Introductionmentioning

confidence: 99%

Osmotic dehydration of physalis (Physalis peruviana L.): Evaluation of water loss and sucrose incorporation and the quantification of carotenoids

Luchese

Gurak

Marczak

2015

LWT - Food Science and Technology

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Section: Introductionmentioning

confidence: 99%

Osmotic dehydration of physalis (Physalis peruviana L.): Evaluation of water loss and sucrose incorporation and the quantification of carotenoids

Luchese

Gurak

Marczak

2015

LWT - Food Science and Technology

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“…Our former study has shown that withanolides extracted from W. somnifera leaves exhibit potent antileishmanial activity against the promastigote stage of L. donovani parasites, but the mode of action of these withanolides has not been elucidated yet 6 . A previous study in the L. donovani showed that withaferin-A inhibits the protein kinase, which induces apoptosis through Figure 5.…”

Section: Discussionmentioning

confidence: 99%

“…The enzyme assay for LdPTR1 were performed at 30 C in the presence of NADPH (100 mM) and varied concentrations (0-120 mM) of substrate biopterin (Sigma, St. Louis, MO) in 20 mM sodium acetate buffer pH 4.8 (Sigma, St. Louis, MO). Since pteridines exhibit absorbance changes when reduced, the extinction coefficient 7,230 M À1 cm À1 was used for the coupled oxidation/reduction of NADPH/biopterin 8 6 ) were treated with withaferin A at IC 50 concentrations for different time intervals and total protein was isolated from the parasites. Briefly, the parasites were resuspended in 180 ml of milliQ water and six freeze thaw cycles were repeated at À80…”

Section: Purification Of Ptr1 Proteinmentioning

confidence: 99%

“…The failure of these drugs in chemotherapy necessitates for the development of alternative drugs. In this regard, our previous study showed the effective antileishmanial activity of withanolides through apoptotic like death mechanism 6 and withaferin A is an abundant compound among the withanolides in the W. somnifera leaves. Therefore, understanding the novel biochemical pathways in the parasite will pave path for developing selective antileishmanial drugs.…”

Section: Introductionmentioning

confidence: 96%

“…Withaferin A, an abundant withanolide, has potent anticancer and anti-proliferative activities against a wide range of cancer cell types [19][20][21] . Our previous study showed that withanolides from W. somnifera have been able to induce apoptotic like death in L. donovani promastigotes; however, the molecular mechanism of these compounds has yet to be deciphered in both stages of the parasite 6 . In our present study, we showed the antileishmanial activity of withaferin A on L. donovani promastigotes and also an attempt was made to find the mode of action from in silico analysis by retrieving the 3D structure of L. donovani.…”

Section: Introductionmentioning

confidence: 99%

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Exploring the inhibitory activity of Withaferin-A against Pteridine reductase-1 of L. donovani

Chandrasekaran

Veronica

Gundampati

et al. 2015

Journal of Enzyme Inhibition and Medicinal Chemistry

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Withaferin A is an abundant withanolide present in Withania somnifera leaves and to some extent in roots. It has been known for its profound anti-cancer properties, but its role in counteracting the Leishmania donovani infection has to be explored. Pteridine reductase 1 (PTR1) is involved in pteridine salvage and an important enzyme for the parasite growth, which could be targeted for the development of an efficient antileishmanial drug. We employed molecular docking studies to identify the binding mode of withaferin A with PTR1 in silico. We further cloned, expressed, and purified PTR1 of L. donovani and performed the enzyme kinetics using the Michaelis-Menten equation and enzyme inhibition studies with withaferin A by plotting the Lineweaver-Burk graph, which followed an uncompetitive mode of inhibition. We also showed the inhibition of the enzyme in the crude lysate of treated parasites. Thus, our study contributes towards understanding the mode of action of withaferin A against L. donovani parasite.

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Plants as Antileishmanial Agents: Current Scenario

Ullah

Nadhman

Siddiq

et al. 2016

Phytotherapy Research

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Leishmaniasis is a clinical manifestation caused by the parasites of the genus Leishmania. Plants are reservoirs of bioactive compounds, which are known to be chemically balanced, effective and least injurious as compared with synthetic medicines. The current resistance and the toxic effects of the available drugs have brought the trend to assess the antileishmanial effect of various plant extracts and their purified compound/s, which are summarized in this review. Moreover, it also highlights various traditional remedies used by local healers against leishmaniasis. A systematic cross-sectional study for antileishmanial activity of natural products was carried out using multiple literature databases. The records retrieved since 2000 till year 2016 were analysed and summarized in the form of comprehensive tables and graphs. Natural products are potential source of new and selective agents that can significantly contribute to primary healthcare and probably are promising substitutes of chemicals for the treatment of protozoan diseases like leishmaniasis. Where the researchers prefer to use alcoholic solvents for the extraction of antileishmanial agents from plants, most of the studies are limited to in vitro conditions majorly on using promastigote forms of Leishmania. Thus, there is a need to carry out such activities in vivo and in host macrophages. Further, there is a need of mechanistic studies that can help taking few of the promising pure compounds to clinical level. Copyright © 2016 John Wiley & Sons, Ltd.

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An in vitro study of apoptotic like death in Leishmania donovani promastigotes by withanolides

Cited by 49 publications

References 20 publications

Osmotic dehydration of physalis (Physalis peruviana L.): Evaluation of water loss and sucrose incorporation and the quantification of carotenoids

Osmotic dehydration of physalis (Physalis peruviana L.): Evaluation of water loss and sucrose incorporation and the quantification of carotenoids

Exploring the inhibitory activity of Withaferin-A against Pteridine reductase-1 of L. donovani

Plants as Antileishmanial Agents: Current Scenario

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