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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
, 
Yongrui Yang
Yongrui Yang
, 
Xiaofei Li
Xiaofei Li
, 
Jie Li
Jie Li
, 
Jie Cheng
Jie Cheng
, 
Zhengxuan Lv
Zhengxuan Lv
 and 
Yingrong Du
Yingrong Du
   | Nov 20, 2021
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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
© 2021 N. Lu et al. published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Fig. 1

Effect of piperlongumine (PL) on cell viability in MH-S (6 × 105) cells cultured for 48 h with and without PL (2.5–45 μg/mL). Dimethyl sulphoxide (DMSO) was used as internal reference for comparison. Data are expressed as mean ± SD and show no significant differences between DMSO and PL treated cells
Effect of piperlongumine (PL) on cell viability in MH-S (6 × 105) cells cultured for 48 h with and without PL (2.5–45 μg/mL). Dimethyl sulphoxide (DMSO) was used as internal reference for comparison. Data are expressed as mean ± SD and show no significant differences between DMSO and PL treated cells

Fig. 2a

In vitro effects of piperlongumine (PL) on the inhibition production of TNF-α and IL-6 in trehalose 6,6-dimycolate (TDM)-activated MH-S cells. Data are expressed as mean ± SD of three experiments. DMSO – dimethyl sulphoxide; P1 –PL at 5 μg/mL; P2 – PL at 15 μg/mL; P3 – PL at 25 μg/mL; DEX – dexamethasone; ns – non-significant, P > 0.05; * P < 0.05; ** P < 0.01; *** P < 0.001 vs TDM-treated group
In vitro effects of piperlongumine (PL) on the inhibition production of TNF-α and IL-6 in trehalose 6,6-dimycolate (TDM)-activated MH-S cells. Data are expressed as mean ± SD of three experiments. DMSO – dimethyl sulphoxide; P1 –PL at 5 μg/mL; P2 – PL at 15 μg/mL; P3 – PL at 25 μg/mL; DEX – dexamethasone; ns – non-significant, P > 0.05; * P < 0.05; ** P < 0.01; *** P < 0.001 vs TDM-treated group

Fig. 2b

In vitro effects of piperlongumine (PL) on the inhibition of production of C-C motif chemokine ligand 2 (CCL-2), C-C motif chemokine ligand 10 (CXCL-10), C-C motif chemokine ligand 5 (CCL-5) and keratinocyte-derived chemokine (KC) in trehalose 6,6-dimycolate (TDM)-activated MH-S cells. Data are expressed as mean ± SD of three experiments. DMSO – dimethyl sulphoxide; P1 – PL 5 μg/mL; P2 – PL 15 μg/mL; P3 – PL 25 μg/mL; DEX – dexamethasone; ns – non-significant, P > 0.05; * P < 0.05; ** P < 0.01; *** P < 0.001 vs TDM-treated group
In vitro effects of piperlongumine (PL) on the inhibition of production of C-C motif chemokine ligand 2 (CCL-2), C-C motif chemokine ligand 10 (CXCL-10), C-C motif chemokine ligand 5 (CCL-5) and keratinocyte-derived chemokine (KC) in trehalose 6,6-dimycolate (TDM)-activated MH-S cells. Data are expressed as mean ± SD of three experiments. DMSO – dimethyl sulphoxide; P1 – PL 5 μg/mL; P2 – PL 15 μg/mL; P3 – PL 25 μg/mL; DEX – dexamethasone; ns – non-significant, P > 0.05; * P < 0.05; ** P < 0.01; *** P < 0.001 vs TDM-treated group

Fig. 3

Enhancing effect of piperlongumine (PL) on the clearance of mycobacterium from alveolar macrophages. Data are expressed as mean ± SD of three experiments. TDM – trehalose-6,6-dimycolate; DMSO – dimethyl sulphoxide; P1 – PL at 5 μg/mL; P2 – PL at 15 μg/mL; P3 – PL at 25 μg/mL; DEX – dexamethasone; ns – non-significant, P > 0.05; ** P < 0.01; *** P < 0.001 vs M. tuberculosis H37Rv strain infection group
Enhancing effect of piperlongumine (PL) on the clearance of mycobacterium from alveolar macrophages. Data are expressed as mean ± SD of three experiments. TDM – trehalose-6,6-dimycolate; DMSO – dimethyl sulphoxide; P1 – PL at 5 μg/mL; P2 – PL at 15 μg/mL; P3 – PL at 25 μg/mL; DEX – dexamethasone; ns – non-significant, P > 0.05; ** P < 0.01; *** P < 0.001 vs M. tuberculosis H37Rv strain infection group

Fig. 5

Diminution by piperlongumine of trehalose 6,6-dimycolate (TDM)-stimulated pulmonary granulomatous inflammation in BALB/c mice. Data are expressed as mean ± SD of three experiments. A) Haematoxylin and eosin-stained granulomatous response in BALB/c mice after 4–7 days of piperlongumine (PL) treatment after TDM challenge. B) Inflammatory intensity level in lungs removed from TDM-challenged mice on days 4 and 7. P1 – PL at 50 mg/mL; P2 – PL at 100 mg/mL; P3 – PL at 150 mg/mL; DEX – dexamethasone; ns – non-significant, P > 0.05; * P < 0.05; ** P < 0.01; *** P <0.001 vs TDM-treated group
Diminution by piperlongumine of trehalose 6,6-dimycolate (TDM)-stimulated pulmonary granulomatous inflammation in BALB/c mice. Data are expressed as mean ± SD of three experiments. A) Haematoxylin and eosin-stained granulomatous response in BALB/c mice after 4–7 days of piperlongumine (PL) treatment after TDM challenge. B) Inflammatory intensity level in lungs removed from TDM-challenged mice on days 4 and 7. P1 – PL at 50 mg/mL; P2 – PL at 100 mg/mL; P3 – PL at 150 mg/mL; DEX – dexamethasone; ns – non-significant, P > 0.05; * P < 0.05; ** P < 0.01; *** P <0.001 vs TDM-treated group

Fig. 6

Effect of piperlongumine on trehalose 6,6-dimycolate (TDM)-stimulated pulmonary granulomatous inflammation in BALB/c mice. Data are expressed as mean ± SD of three experiments. Graphs show production of tumour necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 10 (IL-10), keratinocyte-derived cytokine (KC), C-C motif chemokine ligand 5 (CCL-5), C-C motif chemokine ligand 10 (CXCL-10) and C-C motif chemokine ligand 2 (CCL-2) in pulmonary homogenates after 4 and 7 days of TDM stimulation with or without piperlongumine (PL) treatment. P1 – PL at 50 mg/mL; P2 – PL at 100 mg/mL; P3 – PL at 150 mg/mL; DEX – dexamethasone; ns – non-significant, P > 0.05; * P < 0.05; ** P < 0.01; *** P < 0.001 vs TDM-treated group
Effect of piperlongumine on trehalose 6,6-dimycolate (TDM)-stimulated pulmonary granulomatous inflammation in BALB/c mice. Data are expressed as mean ± SD of three experiments. Graphs show production of tumour necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 10 (IL-10), keratinocyte-derived cytokine (KC), C-C motif chemokine ligand 5 (CCL-5), C-C motif chemokine ligand 10 (CXCL-10) and C-C motif chemokine ligand 2 (CCL-2) in pulmonary homogenates after 4 and 7 days of TDM stimulation with or without piperlongumine (PL) treatment. P1 – PL at 50 mg/mL; P2 – PL at 100 mg/mL; P3 – PL at 150 mg/mL; DEX – dexamethasone; ns – non-significant, P > 0.05; * P < 0.05; ** P < 0.01; *** P < 0.001 vs TDM-treated group

Fig. 7

Inhibition by piperlongumine (PL) of leukocyte infiltration in trehalose 6,6-dimycolate (TDM)-stimulated pulmonary granulomatous inflammation in BALB/c mice. Data are expressed as mean ± SD of three experiments. A) CD11b+ Ly6G−macrophages. B) CD11b+ lymphocyte antigen 6 complex locus G6D (Ly6G+)–neutrophils. C) chemokine receptor type 3 (CCR3)+ CD16/32−eosinophils. Bar charts represent quantitative measurement of positively stained cells. P1 – PL at 50 mg/mL; P2 – PL at 100 mg/mL; P3 –PL at 150 mg/mL; DEX – dexamethasone; ns – non-significant, P > 0.05; * P < 0.05; ** P < 0.01; *** P < 0.001 vs TDM-treated group
Inhibition by piperlongumine (PL) of leukocyte infiltration in trehalose 6,6-dimycolate (TDM)-stimulated pulmonary granulomatous inflammation in BALB/c mice. Data are expressed as mean ± SD of three experiments. A) CD11b+ Ly6G−macrophages. B) CD11b+ lymphocyte antigen 6 complex locus G6D (Ly6G+)–neutrophils. C) chemokine receptor type 3 (CCR3)+ CD16/32−eosinophils. Bar charts represent quantitative measurement of positively stained cells. P1 – PL at 50 mg/mL; P2 – PL at 100 mg/mL; P3 –PL at 150 mg/mL; DEX – dexamethasone; ns – non-significant, P > 0.05; * P < 0.05; ** P < 0.01; *** P < 0.001 vs TDM-treated group
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