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Exploration of anti-Malassezia potential of Nyctanthes arbor-tristis L. and their application to combat the infection caused by Mala s1 a novel allergen.

ABSTRACT: BACKGROUND:Malassezia commensal yeasts along with multitude of antigens have been found to be associated with various skin disorders including Pityriasis versicolor (PV). Amongst them Mala s1, a 37 kDa protein has been proved to be a major allergen reacting with a large panel of sera. However, there exists no therapeutic alternative to combat such problems in form of plant based natural compounds. The purpose of this study is in the first place, to determine the anti-Malassezia activity of Nyctanthes arbor-tristis L. (NAT) ethanolic leaf extract through turbidimetric growth curves, disruption of plasma membrane and secondly, it aims to present in silico validation of its active constituents over Mala s1a novel allergen. METHODS:The antifungal susceptibility 50 % ethanolic extract of NAT was determined by broth microdilution method according to CLSI guidelines. Further MICs and IC50 were determined spectrophotometrically using the software SoftMax® Pro-5 (Molecular Devices, USA). Active constituents mediated disruption of plasma membrane was studied through flowcytometry by permeabilization of fluorescent dye Propidium Iodide (PI). Antioxidant activity of the extract was determined using the DPPH stable radical. Molecular validation of fungal DNA from the extract was observed using PCR amplification. In silico analysis of its active constituents over Mala s1 was performed using HEX software and visualized through Pymol. RESULTS:The anti-Malassezia potential of NAT leaf extracts reflected moderate MIC 1.05 ?g/?l against M. globosa, while least effective against M. restricta with MIC 1.47 ?g/?l. A linear correlation coefficient R (2) = 0.866 was obtained in case of M. globosa while minimum was observed in M. restricta with R (2) = 0.732. The flow cytometric data reveal?~ 75 % cell death when treated with active constituents ?-Sitosterol and Calceolarioside A. The docking confirmations and the interaction energies between Mala s1 and the active constituents (?-Sitosterol and Calceolarioside A) from extracts showed an effective binding which suggests Mala s1 as efficient allergen for site specific targeting. CONCLUSIONS:This study revealed that Nyctanthes arbor-tristis L. (NAT) extracts possess high anti-Malassezia potential which is driven mainly by disruption of plasma membrane. Also in silico validation and molecular modeling studies establishes Mala s1 as a novel allergen that could be a potential target in disease treatment. Our results would also provide a foundation for the development of new therapeutic approach using NAT extract as lead compound with high antioxidant property as an added trait for skin care.

SUBMITTER: Mishra RK

PROVIDER: S-EPMC4815214 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Exploration of anti-Malassezia potential of Nyctanthes arbor-tristis L. and their application to combat the infection caused by Mala s1 a novel allergen.

Mishra Rohit K RK Mishra Vani V Pandey Anand A Tiwari Amit K AK Pandey Himanshu H Sharma Shivesh S Pandey Avinash C AC Dikshit Anupam A

BMC complementary and alternative medicine 20160331

<h4>Background</h4>Malassezia commensal yeasts along with multitude of antigens have been found to be associated with various skin disorders including Pityriasis versicolor (PV). Amongst them Mala s1, a 37 kDa protein has been proved to be a major allergen reacting with a large panel of sera. However, there exists no therapeutic alternative to combat such problems in form of plant based natural compounds. The purpose of this study is in the first place, to determine the anti-Malassezia activity ...[more]

PMID: 27036961

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Project description:BackgroundAn unceasing threat of drug resistance continuously poses demand for new antimalarial drugs. A scientific assessment of traditionally used antimalarial plants through reverse pharmacology is crucial for a fast track drug discovery. An Ayurvedic plant Nyctanthes arbor-tristis Linn. - (Parijat) is being used in clinical practice and had shown antimalarial activity, with a parasite clearance in 76.6% of 120 patients, in an earlier clinical study.ObjectiveTo further explore antimalarial potential of the plant through additional objective markers.Materials and methodsAn open-labelled observational study was conducted at M.A. Podar Hospital - Ayurveda (MAPH-A) after ethics committee approval. Administration of a paste of 5 fresh leaves, thrice a day for a week was a standard practice for management of malaria at MAPH-A. Clinical activity of N. arbor-tristis was evaluated by monitoring pyrexia, parasitemia and morbidity score (MS) in twenty patients. In addition, immune and biochemical markers and organ functions were monitored for objective markers of response. Student's paired-'t' test was applied to assess statistical significance.ResultsTen out of 20 patients showed both fever and parasite clearance, which was confirmed by polymerase chain reaction. Remaining ten patients had persistent but decreasing parasitemia. Four of them needed chloroquine as a fail-safe procedure. Irrespective of the degree of parasitemia all the patients showed decrease in MS. There was also an increase in platelet count and normalization of plasma lactic acid. There was a good clinical tolerability and an improvement in organ function. The inflammatory cytokines showed a reduction; particularly in TNF-α within a day.ConclusionsAt the given dosage, N. arbor-tristis showed disease-modifying activity; early clinical recovery with a decline of TNF-α and a gradual parasite clearance. Further studies with a standardised formulation for dose-searching and optimizing the treatment schedule are needed in a larger sample size.Clinical trial registration noThe process of trial registration had not begun when the study was conducted in 2000.

Dataset Information

Exploration of anti-Malassezia potential of Nyctanthes arbor-tristis L. and their application to combat the infection caused by Mala s1 a novel allergen.

Publications

Exploration of anti-Malassezia potential of Nyctanthes arbor-tristis L. and their application to combat the infection caused by Mala s1 a novel allergen.

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