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

Nihong Lu

Nihong Lu

Department of Respiratory and Critical Care, The Third People’s Hospital of KunmingKunming, China
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Lu, Nihong
, 
Yongrui Yang

Yongrui Yang

Department of Respiratory and Critical Care, The Third People’s Hospital of KunmingKunming, China
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Yang, Yongrui
, 
Xiaofei Li

Xiaofei Li

Department of Respiratory and Critical Care, The Third People’s Hospital of KunmingKunming, China
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Li, Xiaofei
, 
Jie Li

Jie Li

Department of Respiratory and Critical Care, The Third People’s Hospital of KunmingKunming, China
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Li, Jie
, 
Jie Cheng

Jie Cheng

Department of Respiratory and Critical Care, The Third People’s Hospital of KunmingKunming, China
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Cheng, Jie
, 
Zhengxuan Lv

Zhengxuan Lv

Department of Respiratory and Critical Care, The Third People’s Hospital of KunmingKunming, China
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Lv, Zhengxuan
 e 
Yingrong Du

Yingrong Du

Department of Respiratory and Critical Care, The Third People’s Hospital of KunmingKunming, China
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Du, Yingrong
  
20 nov 2021
The protective action of piperlongumine against mycobacterial pulmonary tuberculosis in its mitigation of inflammation and macrophage infiltration in male BALB/c mice's Cover Image
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Categoria dell'articolo: Review article
Pubblicato online: 20 nov 2021
Pagine: 431 - 440
Ricevuto: 02 apr 2021
Accettato: 26 ott 2021
DOI: https://doi.org/10.2478/jvetres-2021-0061
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© 2021 N. Lu et al. published by Sciendo
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 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.
Lingua:
Inglese
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4 volte all'anno
Argomenti della rivista:
Scienze biologiche, Biologia molecolare, Microbiologia e virologia, Scienze della vita, altro, Medicina, Medicina veterinaria
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