Evaluation of Antimycobacterial and Synergistic Activity of Plants Selected Based on Cheminformatic Parameters

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Abstract

Background:

Drug resistance is a major public health problem and a threat to progress made in bovine tuberculosis care and control worldwide. This study aimed at evaluating anti-mycobacterial and synergistic activity of some medicinal plants that were selected by cheminformatics studies against Mycobacterium bovis.

Methods:

Considering the strong synergistic antimycobacterial action of oleanolic acid in combination with tuberculosis drugs, NCBI database was explored to find the compounds with over 80% similarity to oleanolic acid, called S1. Plants containing S1-type compounds were traced to and resulted in five plants, including Datura stramonium, Boswellia serrata Lavandula stoechas, Rosmarinus officinalis, and Thymus vulgaris, as experimental samples. Crude extracts were prepared by percolation using 80% ethanol or as the product of a pharmaceutical company. The extracts were screened against Mycobacterium bovis using broth microdilution method and Alamar Blue Assay. Extracts from these plants were used in combination with isoniazid and ethambutol to investigate the possibility of synergy with respect to antimycobacterial activity.

Results:

The extracts from D. stramonium, B. serrata a, L. stoechas, R. officinalis, and T. Thymus vulgaris showed antimycobacterial activity of 375, 125, 250, 187.5, 500 µg/ml, respectively. The best synergistic results were for L. stoechas and D. stramonium in combination with ethambutol, the fractional inhibitory concentration index was 0.125 µg/ml for both.

Conclusion:

The observed antimycobacterial and synergistic activities are completely novel and obtained from targeted screening designed according to cheminformatics strategy. As for the synergistic action of the extracts, they could be used as supplements in bTB treatment.

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Most cited references 22

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Anticonflict effects of lavender oil and identification of its active constituents.

Hiroyasu Ito, Misao Sakaniwa, Masatoshi Morita … (2006)

The pharmacological effects of lavender oil were investigated using two conflict tests in ICR mice, and then the active constituents were identified. Lavender oil produced significant anticonflict effects at 800 and 1600 mg/kg in the Geller conflict test and at 800 mg/kg in the Vogel conflict test, suggesting that the oil has an anti-anxiety effect. Analysis using GC/MS revealed that lavender oil contains 26 constituents, among which alpha-pinene (ratio, 0.22%), camphene (0.06%), beta-myrcene (5.33%), p-cymene (0.3%), limonene (1.06%), cineol (0.51%), linalool (26.12%), borneol (1.21%), terpinene-4-ol (4.64%), linalyl acetate (26.32%), geranyl acetate (2.14%) and caryophyllene (7.55%) were identified. We examined the effects of linalool, linalyl acetate, borneol, camphene, cineol, terpinen-4-ol, alpha-pinene and beta-myrcene using the Geller and Vogel conflict tests in ICR mice. Cineol, terpinen-4-ol, alpha-pinene and beta-myrcene did not produce any significant anticonflict effects in the Geller test. Linalyl acetate did not produce any significant anticonflict effects in either test. Both borneol and camphene at 800 mg/kg produced significant anticonflict effects in the Geller, but not in the Vogel conflict test. Linalool, a major constituent of lavender oil, produced significant anticonflict effects at 600 and 400 mg/kg in the Geller and Vogel tests, respectively, findings that were similar to those of lavender oil. Thus, we concluded that linalool is the major pharmacologically active constituent involved in the anti-anxiety effect of lavender oil.

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The evaluation of forty-three plant species for in vitro antimycobacterial activities; isolation of active constituents from Psoralea corylifolia and Sanguinaria canadensis.

Sudagar S. Gurcha, Michelle Newton, Clara Lau … (2001)

Extracts from forty-three plant species were selected on account of reported traditional uses for the treatment of TB and/or leprosy. These were assayed for antimycobacterial activities. A simple in vitro screening assay was employed using two model species of mycobacteria, M. aurum and M. smegmatis. Crude methanolic extracts from three of the plants, C. mukul, P. corylifolia and S. canadensis, were found to have significant antimycobacterial activity against M. aurum only (MIC=62.5 microg/ml). Bioassay guided fractionation led to the isolation of two known benzophenanthridine alkaloids, sanguinarine (1) and chelerythrine (2), from the roots S. canadensis and the known phenolic meroterpene, bakuchiol (3) from the seeds of P. corylifolia. The fractionation of the resin of C. mukul lead to a decrease in antimycobacterial activity and hence further work was not pursued. Compound (2) was the most active against M. aurum and M. smegmatis (IC(50)=7.30 microg/ml [19.02 microM] and 29.0 microg/ml [75.56 microM], respectively). M. aurum was the most susceptible organism to all three compounds. No significant difference in antimycobacterial activity was observed when the two alkaloids were tested for activity in media of differing pH values. The activities of the pure compounds against M. aurum were comparable with those against M. bovis BCG with compound (2) being the most active (M. bovis BCG, IC(50)=14.3 microg/ml [37.3 microM]). These results support the use of these plants in traditional medicine.

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Treatment of osteoarthritis with a herbomineral formulation: a double-blind, placebo-controlled, cross-over study.

R. R. Kulkarni, P S Patki, V P Jog … (2015)

The clinical efficacy of a herbomineral formulation containing roots of Withania somnifera, the stem of Boswellia serrata, rhizomes of Curcuma longa and a zinc complex (Articulin-F), was evaluated in a randomized, double-blind, placebo controlled, cross-over study in patients with osteoarthritis. After a one-month single blind run-in period, 42 patients with osteoarthritis were randomly allocated to receive either a drug treatment or a matching placebo for a period of three months. After a 15-day wash-out period the patients were transferred to the other treatment for a further period of three months. Clinical efficacy was evaluated every fortnight on the basis of severity of pain, morning stiffness, Ritchie articular index, joint score, disability score and grip strength. Other parameters like erythrocyte sedimentation rate and radiological examination were carried out on a monthly basis. Treatment with the herbomineral formulation produced a significant drop in severity of pain (P less than 0.001) and disability score (P less than 0.05). Radiological assessment, however, did not show any significant changes in both the groups. Side effects observed with this formulation did not necessitate withdrawal of treatment.

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Author and article information

Journal

Journal ID (nlm-ta): Iran Biomed J

Journal ID (iso-abbrev): Iran. Biomed. J

Title: Iranian Biomedical Journal

Publisher: Pasteur Institute (Iran )

ISSN (Print): 1028-852X

ISSN (Electronic): 2008-823X

Publication date (Print): November 2018

Volume: 22

Issue: 6

Pages: 401-407

Affiliations

[1 ]Department of Agricultural Biotechnology Engineering, Payam-e-Noor University, Tehran 19395, Iran

[2 ]Drug Design and Bioinformatics Unit, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran 13164, Iran

Author notes

Corresponding Author: Soroush Sardari Drug Design and Bioinformatics Unit, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran 13164, Iran; Tel.: (+98-912) 2632484; Fax: (+98-21) 66480780; E-mail: ssardari@ 123456hotmail.com

Article

Publisher ID: IBJ-22-401

DOI: 10.29252/.22.6.401

PMC ID: 6305812

PubMed ID: 29510602

SO-VID: 6bd950e6-51b1-4306-8b63-d7166c570d5c

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License, ( http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 03 July 2017

Date revision received : 22 August 2017

Date accepted : 04 September 2017

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Evaluation of Antimycobacterial and Synergistic Activity of Plants Selected Based on Cheminformatic Parameters

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Most cited references 22

Anticonflict effects of lavender oil and identification of its active constituents.

The evaluation of forty-three plant species for in vitro antimycobacterial activities; isolation of active constituents from Psoralea corylifolia and Sanguinaria canadensis.

Treatment of osteoarthritis with a herbomineral formulation: a double-blind, placebo-controlled, cross-over study.

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