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Modulatory apoptotic effects of sinomenine on Mycoplasma pneumonia through the attenuation of inflammation via ERK/JNK/NF-κB signaling pathway

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Abstract

Mycoplasma pneumoniae (MPP) induced pneumonia is a common disease of children. Sinomenine (SIN) is an isoquinoline mainly sequestered from Sinomenium acutum. It is a promising drug for treating arthritis, lung, colon, liver and gastric cancer. Hence, the present study investigated the role and mechanism of SIN treatment in MPP induced pneumonia in experimental in-vivo mice model. The BALB/c male mice were separated into four groups (n = 6 mice/group): normal, MPP, MPP + SIN (20 mg/kg bw), and SIN (20 mg/kg bw) alone. Results were expressed as mean ± SD. Data were analyzed using one way Analysis of Variance (ANOVA) with the Dunnett’s post hoc test using SPSS v 18.0. P value < 0.05 was considered significant. The total protein, cell count, inflammatory cytokines, MP–IgM, Monocyte chemo attractant protein-1 (MCP-1), and MP–DNA were measured. The protein expressions of Bax/Bcl–2, ERK, JNK, NF-κB were analyzed and histopathology of lungs was examined. SIN treatment significantly (p < 0.05) reduced the total proteins, cell counts in BALF, inflammatory cytokines, MP–IgM, MCP-1, MP–DNA and reversed the histological alterations. SIN attenuated the apoptotic pathway through the modulation of Bax/Bcl-2 expression. SIN alleviated pulmonary inflammatory mediators and apoptosis in MPP-infected mice via suppression of ERK/JNK/NF-κB signaling. SIN administration diminished inflammation and lung fibrosis by inhibiting apoptosis in MPP mice. Hence, SIN is a potential natural protective remedy for MPP.

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Data availability statement

The data sets generated during and/or analyzed during the current study can be procured from the corresponding author on reasonable request.

References

  • Abdel Sater F, Younes M, Nassar H, Nguewa P, Hamze K (2012) A rapid and low-cost protocol for the detection of B.1.1.7 lineage of SARS-CoV-2 by using SYBR Green-based RT-qPCR. Mol Biol Rep 48(11):7243–7249

    Article  Google Scholar 

  • Boddeke EW (2001) Involvement of chemokines in pain. Eur J Pharmacol 429(1–3):115–119

    Article  CAS  Google Scholar 

  • Bordon J, Aliberti S, Fernandez-Botran R, Uriarte SM, Rane MJ, Duvvuri P, Peyrani P, Morlacchi LC, Blasi F, Ramirez JA (2013) Understanding the roles of cytokines and neutrophil activity and neutrophil apoptosis in the protective versus deleterious inflammatory response in pneumonia. Int J Infect Dis 17(2):e76-83

    Article  CAS  Google Scholar 

  • Caraballo JC, Borcherding J, Thorne PS, Comellas AP (2013) Protein kinase C-ζ mediates lung injury induced by diesel exhaust particles. Am J Respir Cell Mol Biol 48(3):306–313

    Article  CAS  Google Scholar 

  • Ferrer BE, Webster J, Bruce J, Narh-Bana SA, Narh CT, Allotey NK, Glover R, Bart-Plange C, Sagoe-Moses I, Malm K, Gyapong M (2016) Integrated community case management and community-based health planning and services: a cross sectional study on the effectiveness of the national implementation for the treatment of malaria, diarrhoea and pneumonia. Malar J 15(1):340

    Article  Google Scholar 

  • Gao LW, Yin J, Hu YH, Liu XY, Feng XL, He JX, Liu J, Guo Y, Xu BP, Shen KL (2006) The epidemiology of paediatric Mycoplasma pneumoniae pneumonia in North China: 2006 to 2016. Epidemiol Infect 147:e192

    Article  Google Scholar 

  • Gao T, Hao J, Wiesenfeld-Hallin Z, Wang DQ, Xu XJ (2013) Analgesic effect of sinomenine in rodents after inflammation and nerve injury. Eur J Pharmacol 721(1–3):5–11

    Article  CAS  Google Scholar 

  • Guo L, Liu F, Lu MP, Zheng Q, Chen ZM (2015) Increased T cell activation in BALF from children with Mycoplasma pneumoniae pneumonia. Pediatr Pulmonol 50(8):814–819

    Article  Google Scholar 

  • He X, Wang J, Guo Z, Liu Q, Chen T, Wang X, Cao X (2005) Requirement for ERK activation in sinomenine-induced apoptosis of macrophages. Immunol Lett 98(1):91–96

    Article  CAS  Google Scholar 

  • Kienast K, Knorst M, Müller-Quernheim J, Ferlinz R (1996) Modulation of IL-1 beta, IL-6, IL-8, TNF-alpha, and TGF-beta secretions by alveolar macrophages under NO2 exposure. Lung 174(1):57–67

    CAS  PubMed  Google Scholar 

  • Kurai D, Nakagaki K, Wada H, Saraya T, Kamiya S, Fujioka Y, Nakata K, Takizawa H, Goto H (2013) Mycoplasma pneumoniae extract induces an IL-17-associated inflammatory reaction in murine lung: implication for mycoplasmal pneumonia. Inflammation 36(2):285–293

    Article  Google Scholar 

  • Lavazza C, Budelli S, Montelatici E, Viganò M, Ulbar F, Catani L, Cannone MG, Savelli S, Groppelli E, Lazzari L, Lemoli RM, Cescon M, La Manna G, Giordano R, Montemurro T (2022) Process development and validation of expanded regulatory T cells for prospective applications: an example of manufacturing a personalized advanced therapy medicinal product. J Transl Med 20(1):14

    Article  Google Scholar 

  • Lichtenstein DA (2015) BLUE-protocol and FALLS-protocol: two applications of lung ultrasound in the critically ill. Chest 147(6):1659–1670

    Article  Google Scholar 

  • Lin Y, Tan D, Kan Q, Xiao Z, Jiang Z (2018) The Protective effect of naringenin on airway remodeling after mycoplasma pneumoniae infection by inhibiting autophagy-mediated lung inflammation and fibrosis. Mediators Inflamm 2018:8753894

    PubMed  PubMed Central  Google Scholar 

  • Liu F, Sun GQ, Gao HY, Li RS, Soromou LW, Chen N, Deng YH, Feng HH (2013) Angelicin regulates LPS-induced inflammation via inhibiting MAPK/NF-κB pathways. J Surg Res 185(1):300–309

    Article  CAS  Google Scholar 

  • Maselli DJ, Medina JL, Brooks EG, Coalson JJ, Kannan TR, Winter VT, Principe M, Cagle MP, Baseman JB, Dube PH, Peters JI (2018) The immunopathologic effects of mycoplasma pneumoniae and community-acquired respiratory distress syndrome toxin. A primate model. Am J Respir Cell Mol Biol 58(2):253–260

    Article  CAS  Google Scholar 

  • Mu S, Kang B, Zeng W, Sun Y, Yang F (2016) MicroRNA-143-3p inhibits hyperplastic scar formation by targeting connective tissue growth factor CTGF/CCN2 via the Akt/mTOR pathway. Mol Cell Biochem 416(1–2):99–108

    Article  CAS  Google Scholar 

  • Shangguan Z, Sun Q, Zhang M, Ding J, Yi L, Gao Y, Zhan A, Zhao R, Ci X (2014) Mycoplasma pneumoniae infection in hospitalized adult patients with community-acquired pneumonia in China. J Infect Dev Ctries 8(10):1259–1266

    Article  Google Scholar 

  • Shimizu T (2016) Inflammation-inducing factors of mycoplasma pneumoniae. Front 7:414

    Google Scholar 

  • Tornatore L, Thotakura AK, Bennett J, Moretti M, Franzoso G (2012) The nuclear factor kappa B signaling pathway: integrating metabolism with inflammation. Trends Cell Biol 22(11):557–566

    Article  CAS  Google Scholar 

  • Van Hoecke L, Job ER, Saelens X, Roose K (2017) Bronchoalveolar lavage of murine lungs to analyze inflammatory cell infiltration. J vis Exp 123:55398

    Google Scholar 

  • Wang Y, Sheibani N (2006) PECAM-1 isoform-specific activation of MAPK/ERKs and small GTPases: implications in inflammation and angiogenesis. J Cell Biochem 98(2):451–468

    Article  CAS  Google Scholar 

  • Wang Y, Fang Y, Huang W, Zhou X, Wang M, Zhong B, Peng D (2005) Effect of sinomenine on cytokine expression of macrophages and synoviocytes in adjuvant arthritis rats. J Ethnopharmacol 98(1–2):37–43

    Article  CAS  Google Scholar 

  • Wang M, Wang Y, Yan Y, Zhu C, Huang L, Shao X, Xu J, Zhu H, Sun X, Ji W, Chen Z (2014) Clinical and laboratory profiles of refractory Mycoplasma pneumoniae pneumonia in children. Int J Infect Dis 29:18–23

    Article  Google Scholar 

  • Wood PR, Kampschmidt JC, Dube PH, Cagle MP, Chaparro P, Ketchum NS, Kannan TR, Singh H, Peters JI, Baseman JB, Brooks EG (2017) Mycoplasma pneumoniae and health outcomes in children with asthma. Ann Allergy Asthma Immunol 119(2):146-152.e2

    Article  Google Scholar 

  • Xu F, Li Q, Wang Z, Cao X (2019) Sinomenine inhibits proliferation, migration, invasion and promotes apoptosis of prostate cancer cells by regulation of miR-23a. Biomed Pharmacother 112:108592

    Article  CAS  Google Scholar 

  • Zhang M, Gu L, Zheng P, Chen Z, Dou X, Qin Q, Cai X (2020) Improvement of cell counting method for Neubauer counting chamber. J Clin Lab Anal 34(1):e23024

    PubMed  Google Scholar 

  • Zhao XX, Peng C, Zhang H, Qin LP (2012) Sinomenium acutum: a review of chemistry, pharmacology, pharmacokinetics, and clinical use. Pharm Biol 50(8):1053–1061

    Article  Google Scholar 

  • Zhou X, Moore BB (2017) Lung section staining and microscopy. Bio Protoc 7(10):e2286

    Article  Google Scholar 

  • Zhu Q, Sun Y, Mao L, Liu C, Jiang B, Zhang W, Li JX (2016) Antinociceptive effects of sinomenine in a rat model of postoperative pain. Br J Pharmacol 173(10):1693–1702

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Respiratory, Xi’an Children’s Hospital, Xi’an City, 710000, China

    Yao Chen, Wen Zhang, Lihong Xin & Zhen Wang

  2. Department of Emergency, Xi’an Children’s Hospital, Xi’an City, 710000, China

    Mao Zheng

  3. Department of Biochemistry, Rabiammal Ahamed Maideen College for Women, Thiruvarur, Tamil Nadu, 610001, India

    Annamalai Vijayalakshmi

Authors
  1. Yao Chen
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  2. Wen Zhang
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  3. Lihong Xin
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  4. Zhen Wang
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  5. Mao Zheng
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  6. Annamalai Vijayalakshmi
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Contributions

YC: Methodology, formal analysis, investigation, manuscript drafting, review and editing. WZ: Methodology, investigation, manuscript drafting, review and editing. LX: Conceptualization, methodology, formal analysis, manuscript drafting. ZW: Conceptualization, methodology, formal analysis, investigation, manuscript Drafting. MZ: Conceptualization, methodology, formal analysis, investigation, manuscript drafting, review and editing. AV: Conceptualization, methodology, formal analysis, manuscript drafting, review and editing.

Corresponding author

Correspondence to Mao Zheng.

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No conflicts of interest were reported.

Ethical approval

This research was approved by Xi'an Children's Hospital animal ethical committee, (Approval No. XCH202106726A).

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Communicated by Erko Stackebrandt.

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Chen, Y., Zhang, W., Xin, L. et al. Modulatory apoptotic effects of sinomenine on Mycoplasma pneumonia through the attenuation of inflammation via ERK/JNK/NF-κB signaling pathway. Arch Microbiol 204, 441 (2022). https://doi.org/10.1007/s00203-022-03039-w

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