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Abstract Title:

The Protective Action of Piperlongumine Against Mycobacterial Pulmonary Tuberculosis in Its Mitigation of Inflammation and Macrophage Infiltration in Male BALB/c Mice.

Abstract Source:

J Vet Res. 2021 Dec ;65(4):431-440. Epub 2021 Nov 20. PMID: 35111996

Abstract Author(s):

Nihong Lu, Yongrui Yang, Xiaofei Li, Jie Li, Jie Cheng, Zhengxuan Lv, Yingrong Du

Article Affiliation:

Nihong Lu

Abstract:

Introduction: Piperlongumine (PL) is a bioactive alkaloid and medicinal compound of piperamide isolated from the long pepper (Linn). It has demonstrated bactericidal action against(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: strain H37Rv was subjected to a broth microdilution assay. Piperlongumine at 5, 15, and 25μg/mL, 0.2% dimethyl sulphoxide as control or 4 μM of dexamethasone were testedon 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 Ca-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.

Study Type : Animal Study

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