Anemoside B4 protects against Klebsiella pneumoniae- and influenza virus FM1-induced pneumonia via the TLR4/Myd88 signaling pathway in mice

Abstract Background: Pneumonia refers to the inflammation of the terminal airway, alveoli and pulmonary interstitium, which can be caused by pathogenic microorganisms, physical and chemical factors, immune damage, and drugs. Anemoside B4, the major ingredient of Pulsatilla chinensis (Bunge) Regel, exhibited anti-inflammatory activity. However, the therapeutic effect of anemoside B4 on pneumonia has not been unraveled. This study aims to investigate that anemoside B4 attenuates the inflammatory responses in Klebsiella pneumonia (KP)- and influenza virus FM1 (FM1)-induced pneumonia mice model.Methods: The network pharmacology and molecular docking assays were employed to predict the targets of anemoside B4’s treatment of pneumonia. Two models (bacterial KP-infected mice and virus FM1-infected mice) were employed in our study. BALB/c mice were divided into six groups: control, model group (KP- induced pneumonia or FM1-induced pneumonia), anemoside B4 (B4)-treated group (2.5, 5, 10 mg/kg), and positive drug group (Ribavirin or Ceftriaxone Sodium Injection). Blood samples were collected for hematology analysis. The effects of B4 on inflammation-associated mediators were investigated by Enzyme-linked immunosorbent assay (ELISA) and hematoxylin and eosin staining (HE) staining. Proteins expression was quantified by western blotting.Results: The network results indicated that many pro-inflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) participated in anemoside B4’s anti-inflammatory activity. The counts of neutrophil (NEU) and white blood cell (WBC), the level of myeloperoxidase (MPO), and the release of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 increased by KP or FM1 infection, which were reversed by anemoside B4. In addition, anemoside B4 significantly suppressed the FM1-induced expression of Toll-like receptor 4 (TLR4), myeloid differential protein-88 (MyD88), and myeloid differentiation protein-2 (MD-2), which were further validated by molecular docking data that anemoside B4 bound to bioactive sites of TLR4. Therefore, anemoside B4 exhibited a significant therapeutic effect on pneumonia via the TLR4/MyD88 pathway.Conclusion: Our findings demonstrated that anemoside B4 attenuates pneumonia via the TLR4/Myd88 signaling pathway, suggesting that anemoside B4 is a promising therapeutic candidate for bacterial-infected or viral-infected pneumonia.

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Anemoside B4 protects against Klebsiella pneumoniae- and influenza virus FM1-induced pneumonia via the TLR4/Myd88 signaling pathway in mice

10.21203/rs.3.rs-27002/v1 ◽

2020 ◽

Author(s):

Jia He ◽

Renyikun Yuan ◽

Xiaolan Cui ◽

Yushun Cui ◽

Shan Han ◽

...

Keyword(s):

Influenza Virus ◽

Molecular Docking ◽

Signaling Pathway ◽

Therapeutic Effect ◽

Inflammatory Cytokines ◽

Inflammatory Activity ◽

Tnf Α ◽

Anti Inflammatory ◽

Myd88 Signaling ◽

Pro Inflammatory Cytokines

Abstract Background Pneumonia refers to the inflammation of the terminal airway, alveoli and pulmonary interstitium, which can be caused by pathogenic microorganisms, physical and chemical factors, immune damage, and drugs. Anemoside B4, the major ingredient of Pulsatilla chinensis (Bunge) Regel, exhibited anti-inflammatory activity. However, the therapeutic effect of anemoside B4 on pneumonia has not been unraveled. This study aims to investigate that anemoside B4 attenuates the inflammatory responses in Klebsiella pneumonia (KP)- and influenza virus FM1 (FM1)-induced pneumonia mice model.Methods The network pharmacology and molecular docking assays were employed to predict the targets of anemoside B4’s treatment of pneumonia. Two models (bacterial KP-infected mice and virus FM1-infected mice) were employed in our study. BALB/c mice were divided into six groups: control, model group (KP- induced pneumonia or FM1-induced pneumonia), anemoside B4 (B4)-treated group (2.5, 5, 10 mg/kg), and positive drug group (Ribavirin or Ceftriaxone Sodium Injection). Blood samples were collected for hematology analysis. The effects of B4 on inflammation-associated mediators were investigated by Enzyme-linked immunosorbent assay (ELISA). Proteins expression was quantified by western blotting.Results The network results indicated that many pro-inflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) participated in anemoside B4’s anti-inflammatory activity. The counts of neutrophil (NEU) and white blood cell (WBC), the level of myeloperoxidase (MPO), and the release of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 increased by KP or FM1 infection, which were reversed by anemoside B4. In addition, anemoside B4 significantly suppressed the FM1-induced expression of Toll-like receptor 4 (TLR4), myeloid differential protein-88 (MyD88), and myeloid differentiation protein-2 (MD-2), which were further validated by molecular docking data that anemoside B4 bound to bioactive sites of TLR4. Therefore, anemoside B4 exhibited a significant therapeutic effect on pneumonia via the TLR4/MyD88 pathway.Conclusion Our findings demonstrated that anemoside B4 attenuates pneumonia via the TLR4/Myd88 signaling pathway, suggesting that anemoside B4 is a promising therapeutic candidate for bacterial-infected or viral-infected pneumonia.

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Irisin Ameliorates Hypoxia/Reoxygenation-Induced Inflammation and Apoptosis in PC12 Cells by Inhibiting TLR4/MYD88 Signaling Pathway

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.17:329-336 ◽

2019 ◽

Vol 17 (3) ◽

pp. 329-336

Author(s):

Wang Jinli ◽

Xu Fenfen ◽

Zheng Yuan ◽

Cheng Xu ◽

Zhang Piaopiao ◽

...

Keyword(s):

Ischemic Stroke ◽

Signaling Pathway ◽

Pc12 Cells ◽

Major Complication ◽

Lactic Dehydrogenase ◽

Dependent Manner ◽

Cerebral Ischemic Stroke ◽

Cerebral Ischemic ◽

Myd88 Signaling ◽

Hypoxia Reoxygenation

Cardiovascular disease including cerebral ischemic stroke is the major complication that increases the morbidity and mortality in patients with diabetes mellitus as much as four times. It has been well established that irisin, with its ability to regulate glucose and lipid homeostasis as well as anti-inflammatory and anti-apoptotic properties, has been widely examined for its therapeutic potentials in managing metabolic disorders. However, the mechanism of irisin in the regulation of cerebral ischemic stroke remains unclear. Using PC12 cells as a model, we have shown that hypoxia/reoxygenation inhibits cell viability and increases lactic dehydrogenase. Irisin, in a dose-dependent manner, reversed these changes. The increase in inflammatory mediators (IL-1β, IL-6, and TNF-α) by hypoxia/reoxygenation was reversed by irisin. Furthermore, the cell apoptosis promoted by hypoxia/reoxygenation was also inhibited by irisin. Irisin suppressed TLR4/MyD88 signaling pathway leading to amelioration of inflammation and apoptosis in PC12 cells. Thus, inhibition of TLR4/MyD88 signaling pathway via irisin could be an important mechanism in the regulation of hypoxia/reoxygenation-induced inflammation and apoptosis in PC12 cells.

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