title: Protective efficacy of piperine against Mycobacterium tuberculosis.
abstract: Piperine a trans-trans isomer of 1-piperoyl-piperidine was evaluated for its immunomodulatory activity to enhance the efficacy of rifampicin in a murine model of Mycobacterium tuberculosis infection. In-vitro immunomodulation of piperine was tested on mouse splenocytes for lymphocyte proliferation, cytokine production and macrophage activation. Protective efficacy of piperine was tested in a mice infection model of M. tuberculosis for the activation of Th-1 response and synergistic combination efficacy with rifampicin. Murine splenocytes exposed to piperine exhibited proliferation of T and B cell, increased Th-1 cytokines and enhanced macrophage activation. Piperine (1 mg/kg) in mice infected with M. tuberculosis activated the differentiation of T cells into Th-1 sub-population (CD4+ / CD8+ subsets). There was an increase in secretion of Th-1 cytokines (IFN-γ and IL-2) by these cells. The qRT-PCR studies revealed corresponding increases in the mRNA transcripts of IFN-γ and IL-2 in the infected lung tissues. Combination of piperine and rifampicin (1 mg/kg) exhibited better efficacy of and resulted in additional 1.4 to 0.8 log reduction in lung cfu as compared to rifampicin alone. The up-regulation of Th1 immunity by piperine can be synergistically combined with rifampicin to improve its therapeutic efficacy in immune-compromised TB patients.
authors.affiliation: Clinical Microbiology Division, Indian Institute of Integrative Medicine (CSIR), Canal Road, Jammu Tawi 180 001, India.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Clinical Microbiology Division, Indian Institute of Integrative Medicine (CSIR), Canal Road, Jammu Tawi 180 001, India.
authors.forename: Nitin Pal
authors.initials: NP
authors.lastname: Kalia
authors.affiliation: Pharmacology Division, Indian Institute of Integrative Medicine (CSIR), Canal Road, Jammu Tawi 180 001, India.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Suden
authors.affiliation: Pharmacology Division, Indian Institute of Integrative Medicine (CSIR), Canal Road, Jammu Tawi 180 001, India.
authors.forename: Prashant Singh
authors.initials: PS
authors.lastname: Chauhan
authors.affiliation: Clinical Microbiology Division, Indian Institute of Integrative Medicine (CSIR), Canal Road, Jammu Tawi 180 001, India.
authors.forename: Manoj
authors.initials: M
authors.lastname: Kumar
authors.affiliation: Clinical Microbiology Division, Indian Institute of Integrative Medicine (CSIR), Canal Road, Jammu Tawi 180 001, India.
authors.forename: Anshu Beulah
authors.initials: AB
authors.lastname: Ram
authors.affiliation: Pharmacology Division, Indian Institute of Integrative Medicine (CSIR), Canal Road, Jammu Tawi 180 001, India.
authors.forename: Anamika
authors.initials: A
authors.lastname: Khajuria
authors.affiliation: Pharmacology Division, Indian Institute of Integrative Medicine (CSIR), Canal Road, Jammu Tawi 180 001, India.
authors.forename: Sarang
authors.initials: S
authors.lastname: Bani
authors.affiliation: Clinical Microbiology Division, Indian Institute of Integrative Medicine (CSIR), Canal Road, Jammu Tawi 180 001, India. Electronic address: iakhan@iiim.res.in.
authors.forename: Inshad Ali
authors.initials: IA
authors.lastname: Khan
mesh_terms: D000470:Alkaloids / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000995:Antitubercular Agents / Q000494:pharmacology / Q000627:therapeutic use*; D052117:Benzodioxoles / Q000494:pharmacology / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D015169:Colony Count, Microbial; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical / Q000379:methods; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D008168:Lung / Q000382:microbiology; D008213:Lymphocyte Activation / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development; D009569:Nitric Oxide / Q000096:biosynthesis; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D053284:Polyunsaturated Alkamides / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics; D012293:Rifampin / Q000627:therapeutic use; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*
chemical_list: D000470:Alkaloids; D000995:Antitubercular Agents; D052117:Benzodioxoles; D004338:Drug Combinations; D007376:Interleukin-2; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D012333:RNA, Messenger; D009569:Nitric Oxide; D007371:Interferon-gamma; C008922:piperine; D012293:Rifampin
keywords: Bioavailability; Cell proliferation; Immune-modulation; Immune-phenotyping; Rifampicin