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Cited by 26Respiratory Support and MechanismsImmune Response and InflammationNatural Compounds in Disease Treatment

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Madecassoside Protects Against LPS-Induced Acute Lung Injury via Inhibiting TLR4/NF-κB Activation and Blood-Air Barrier Permeability

Open access
Peng, Lu-Yuan, Shi, Hai-Tao, Yuan, Meng, Li, Jing-He, Song, Ke, Huang, Jiang-Ni, Yi, Peng-Fei, Shen, Hai-Qing, Fu, Ben-Dong·2020·Frontiers in Pharmacology

Abstract

Madecassoside (MA), a crucial ingredient of Centella asiatica, has been reported to exhibit a variety of bioactivities, including anti-pulmonary fibrosis, and anti-inflammatory effects. Here we aimed to elucidate the protective activity and underlying mechanisms of MA with a focus on acute lung injury (ALI). The mice were received intratracheal of LPS to establish the ALI model and treated with MA. Then we measured the pathological changes by haematoxylin and eosin staining, the levels of pro-inflammatory cytokines and myeloperoxidase (MPO) by ELISA, the transcriptional level of tight junction proteins by qRT-PCR, as well as the expression of Toll-likereceptor4/Nuclear factor kappa-B (TLR4/NF-κB) pathway by western blot. The results indicated that MA significantly inhibited LPS-induced pathological damages, lung edema, MPO activity, and pro-inflammatory cytokines production. Furthermore, MA obviously reduced alveolar epithelium permeability which showed by reduced secretion of total proteins in the BALF and enhanced mRNA expression of tight junction as Occludin and zonula occludens-1 (ZO-1) comparing to LPS. Further research indicated that the LPS stimulation up-regulated the TLR4/NF-κB signaling pathway and the up-regulation were reversed by MA. In conclusion, these data supported that MA had protective effects on LPS-induced ALI. The therapeutic possibility may be associated with reducing the alveolar epithelium permeability and inflammatory response via repressing the activation of TLR4/NF-κB pathway.

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Figures

Figure 1 Pathohistological evaluations of lung tissues and lung injury scoring. Hematoxylin and eosin (H&E) staining of lung tissues in (A) control, (B) Madecassoside (MA) alone, (C) Lipopolysaccharides (LPS) and (D–F) LPS+MA (40, 20, 10 mg/kg) groups. (G) Lung injury score of all groups. Mean ± S.D. (n=8). ## p < 0.01: significantly different from control; * p < 0.05 and ** p < 0.01: significantly different from the LPS group.
Figure 1 Pathohistological evaluations of lung tissues and lung injury scoring. Hematoxylin and eosin (H&E) staining of lung tissues in (A) control, (B) Madecassoside (MA) alone, (C) Lipopolysaccharides (LPS) and (D–F) LPS+MA (40, 20, 10 mg/kg) groups. (G) Lung injury score of all groups. Mean ± S.D. (n=8). ## p < 0.01: significantly different from control; * p < 0.05 and ** p < 0.01: significantly different from the LPS group.CC BY · PubMed Central
Figure 2 Myeloperoxidase (MPO) assay of lung injury was measured by ELISA. Mean ± S.D. (n=8). ## p<0.01: significantly different from control; ** p < 0.01: significantly different from the lipopolysaccharides (LPS) group.
Figure 2 Myeloperoxidase (MPO) assay of lung injury was measured by ELISA. Mean ± S.D. (n=8). ## p<0.01: significantly different from control; ** p < 0.01: significantly different from the lipopolysaccharides (LPS) group.CC BY · PubMed Central
Figure 3 Wet weight to dry weight ratio of lung tissues. Mean ± S.D. (n=8). ## p < 0.01: significantly different from control; * p < 0.05 and ** p < 0.01: significantly different from the lipopolysaccharides (LPS) group.
Figure 3 Wet weight to dry weight ratio of lung tissues. Mean ± S.D. (n=8). ## p < 0.01: significantly different from control; * p < 0.05 and ** p < 0.01: significantly different from the lipopolysaccharides (LPS) group.CC BY · PubMed Central
Figure 4 Air-blood barrier permeability examination. (A) Total protein in bronchoalveolar lavage fluid (BALF) and (B) mRNA expression of ZO-1 and Occludin in lung tissues were detected to access the integrity of air-blood barrier. Mean ± S.D. (n=8). ## p < 0.01: significantly different from control; ** p < 0.01: significantly different from the lipopolysaccharides (LPS) group.
Figure 4 Air-blood barrier permeability examination. (A) Total protein in bronchoalveolar lavage fluid (BALF) and (B) mRNA expression of ZO-1 and Occludin in lung tissues were detected to access the integrity of air-blood barrier. Mean ± S.D. (n=8). ## p < 0.01: significantly different from control; ** p < 0.01: significantly different from the lipopolysaccharides (LPS) group.CC BY · PubMed Central
Figure 5 The measurement of TNF-α and IL-1β in lung tissues. Lung tissue was homogenized in PBS and the concentrations of (A) TNF-α and (B) IL-1β (pg per mg protein) measured in the supernatant. Mean ± S.D. (n=8). ## p < 0.01: significantly different from control; ** p < 0.01: significantly different from the lipopolysaccharides (LPS) group.
Figure 5 The measurement of TNF-α and IL-1β in lung tissues. Lung tissue was homogenized in PBS and the concentrations of (A) TNF-α and (B) IL-1β (pg per mg protein) measured in the supernatant. Mean ± S.D. (n=8). ## p < 0.01: significantly different from control; ** p < 0.01: significantly different from the lipopolysaccharides (LPS) group.CC BY · PubMed Central
Figure 6 Inflammatory cell infiltration in bronchoalveolar lavage fluid (BALF). Mean ± S.D. (n=8). ## p < 0.01: significantly different from control; * p < 0.05 and ** p < 0.01: significantly different from the lipopolysaccharides (LPS) group.
Figure 6 Inflammatory cell infiltration in bronchoalveolar lavage fluid (BALF). Mean ± S.D. (n=8). ## p < 0.01: significantly different from control; * p < 0.05 and ** p < 0.01: significantly different from the lipopolysaccharides (LPS) group.CC BY · PubMed Central
Figure 7 TNF-α and IL-1ß concentrations in bronchoalveolar lavage fluid (BALF). The secretion of (A) TNF-α and (B) IL-1β were measured by ELISA kits. Mean ± S.D. (n=8). ## p < 0.01: significantly different from control; * p < 0.05 and ** p < 0.01: significantly different from the lipopolysaccharides (LPS) group.
Figure 7 TNF-α and IL-1ß concentrations in bronchoalveolar lavage fluid (BALF). The secretion of (A) TNF-α and (B) IL-1β were measured by ELISA kits. Mean ± S.D. (n=8). ## p < 0.01: significantly different from control; * p < 0.05 and ** p < 0.01: significantly different from the lipopolysaccharides (LPS) group.CC BY · PubMed Central
Figure 8 The activation of TLR4/NF-κB pathway. (A) TLR4/NF-κB protein samples were analyzed by Western blot with TLR4, IκB, p-IκB, p65, p-p65 antibodies. β-actin was used as a control. (B) Quantification of TLR4 proteins and (C) p-p65, (D) p-IκB protein was determined by densitometry. Mean ± S.D. (n=8). ## p < 0.01: significantly different from control; ** p < 0.01: significantly different from the lipopolysaccharides (LPS) group.
Figure 8 The activation of TLR4/NF-κB pathway. (A) TLR4/NF-κB protein samples were analyzed by Western blot with TLR4, IκB, p-IκB, p65, p-p65 antibodies. β-actin was used as a control. (B) Quantification of TLR4 proteins and (C) p-p65, (D) p-IκB protein was determined by densitometry. Mean ± S.D. (n=8). ## p < 0.01: significantly different from control; ** p < 0.01: significantly different from the lipopolysaccharides (LPS) group.CC BY · PubMed Central

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Citations

Cites

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Metadata

Authors
Peng, L.-Y., Shi, H.-T., Yuan, M., Li, J.-H., Song, K., Huang, J.-N., Yi, P.-F., Shen, H.-Q., & Fu, B.-D.
Affiliations
Jilin University (CN)
Corresponding author
Fu, Ben-Dong
Venue
Frontiers in Pharmacology
Published
2020-06-05
Volume
11
Pages
807-807
ISSN
1663-9812 (ISSN-L)
OpenAlex
W3033663687
Cited by
26
References
1
Citations by year
2026: 3 · 2025: 5 · 2024: 3 · 2023: 5 · 2022: 5 · 2021: 5
FWCI
2.11
Type
journal article
Language
en
Open access
Locations
  • Frontiers in Pharmacology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (201403051, 31972724, 31372470)
  • Special Fund for Agro-scientific Research in the Public Interest (201403051)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory Support and Mechanisms
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
Keywords
madecassoside, Centella asiatica, acute lung injury, lipopolysaccharide, TLR4/NF-κB signaling, tight junction proteins, occludin, ZO-1, alveolar epithelium, inflammatory cytokines, myeloperoxidase, pulmonary edema, anti-inflammatory activity

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CoChat. (2026). Citation check: Madecassoside Protects Against LPS-Induced Acute Lung Injury via Inhibiting TLR4/NF-κB Activation and Blood-Air Barrier Permeability. https://app.cochat.ai/papers/10.3389/fphar.2020.00807
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Peng, L.-Y., Shi, H.-T., Yuan, M., Li, J.-H., Song, K., Huang, J.-N., Yi, P.-F., Shen, H.-Q., & Fu, B.-D. (2020). Madecassoside Protects Against LPS-Induced Acute Lung Injury via Inhibiting TLR4/NF-κB Activation and Blood-Air Barrier Permeability. Frontiers in Pharmacology. https://doi.org/10.3389/fphar.2020.00807

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