<abstract xmlns="http://www.w3.org/1999/xhtml">

<sec id="j_jvetres-2021-0061_s_005">
<h3>Introduction</h3>
<p>Piperlongumine (PL) is a bioactive alkaloid and medicinal compound of piperamide isolated from the long pepper (<italic>Piper longum</italic> Linn). It has demonstrated bactericidal action against <italic>Mycobacterium tuberculosis</italic> (MTB), the cause of pulmonary tuberculosis; nevertheless, immunomodulatory activity had not been identified for it in MTB-triggered granulomatous inflammation. This study investigated if piperlongumine could inhibit such inflammation.</p>
</sec>
<sec id="j_jvetres-2021-0061_s_006">
<h3>Material and Methods</h3>
<p><italic>Mycobacterium tuberculosis</italic> strain H37Rv was subjected to a broth microdilution assay. Piperlongumine at 5, 15, and 25 μg/mL, 0.2% dimethyl sulphoxide as control or 4 μM of dexamethasone were tested <italic>in vitro</italic> on MH-S murine alveolar macrophages. BALB/c mice were orally administered PL at 50, 100 and 150 mg/kg b.w. after trehalose-6,6-dimycolate (TDM) stimulation. Chemokine and cytokine concentrations were determined in lung supernatants. Flow cytometry and Western blot analysis were performed to determine phosphorylated spleen tyrosine kinase (Syk), c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) pathways.</p>
</sec>
<sec id="j_jvetres-2021-0061_s_007">
<h3>Results</h3>
<p>Piperlongumine inhibited inflammatory mediators and adherence of lymphocyte function-associated antigen 1 to MH-S cells following TDM activation. It also improved macrophage clearance of MTB. In TDM-stimulated MH-S cells, PL significantly influenced the macrophage inducible Ca<sup>2+</sup>-dependent lectin receptor (Mincle)-Syk-ERK signalling pathway. Oral dosing of PL effectively suppressed the development of pulmonary granulomas and inflammatory reactions in the TDM-elicited mouse granuloma model.</p>
</sec>
<sec id="j_jvetres-2021-0061_s_008">
<h3>Conclusion</h3>
<p>PL as an inhibitor of MTB-triggered granulomatous inflammation may be an effective complementary treatment for mycobacterial infection.</p>
</sec>
</abstract>

Introduction
Piperlongumine (PL) is a bioactive alkaloid and medicinal compound of piperamide isolated from the long pepper (Piper longum Linn). It has demonstrated bactericidal action against Mycobacterium tuberculosis (MTB), the cause of pulmonary tuberculosis; nevertheless, immunomodulatory activity had not been identified for it in MTB-triggered granulomatous inflammation. This study investigated if piperlongumine could inhibit such inflammation.


Material and Methods
Mycobacterium tuberculosis strain H37Rv was subjected to a broth microdilution assay. Piperlongumine at 5, 15, and 25 μg/mL, 0.2% dimethyl sulphoxide as control or 4 μM of dexamethasone were tested in vitro on MH-S murine alveolar macrophages. BALB/c mice were orally administered PL at 50, 100 and 150 mg/kg b.w. after trehalose-6,6-dimycolate (TDM) stimulation. Chemokine and cytokine concentrations were determined in lung supernatants. Flow cytometry and Western blot analysis were performed to determine phosphorylated spleen tyrosine kinase (Syk), c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) pathways.


Results
Piperlongumine inhibited inflammatory mediators and adherence of lymphocyte function-associated antigen 1 to MH-S cells following TDM activation. It also improved macrophage clearance of MTB. In TDM-stimulated MH-S cells, PL significantly influenced the macrophage inducible Ca2+-dependent lectin receptor (Mincle)-Syk-ERK signalling pathway. Oral dosing of PL effectively suppressed the development of pulmonary granulomas and inflammatory reactions in the TDM-elicited mouse granuloma model.


Conclusion
PL as an inhibitor of MTB-triggered granulomatous inflammation may be an effective complementary treatment for mycobacterial infection.

The protective action of piperlongumine against mycobacterial pulmonary tuberculosis in its mitigation of inflammation and macrophage infiltration in male BALB/c mice

Journal of Veterinary Research

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Introduction
Piperlongumine (PL) is a bioactive alkaloid and medicinal compound of piperamide isolated from the long pepper (Piper longum Linn). It has...

The protective action of piperlongumine against mycobacterial pulmonary tuberculosis in its mitigation of inflammation and macrophage infiltration in male BALB/c mice

Article Category: Review article

Published Online: Nov 20, 2021

Page range: 431 - 440

Received: Apr 02, 2021

Accepted: Oct 26, 2021

DOI: https://doi.org/10.2478/jvetres-2021-0061

Keywords
tuberculosis, piperlongumine, macrophages, inflammation, Mincle

© 2021 N. Lu et al. published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

The protective action of piperlongumine against mycobacterial pulmonary tuberculosis in its mitigation of inflammation and macrophage infiltration in male BALB/c mice

Article Category: Review article

Published Online: Nov 20, 2021

Page range: 431 - 440

Received: Apr 02, 2021

Accepted: Oct 26, 2021

DOI: https://doi.org/10.2478/jvetres-2021-0061

Keywordstuberculosis, piperlongumine, macrophages, inflammation, Mincle

© 2021 N. Lu et al. published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Keywords
tuberculosis, piperlongumine, macrophages, inflammation, Mincle