Astragaloside IV Pretreatment Alleviates Pulmonary Ischemia–Reperfusion Injury via the TLR4/MyD88/NF‐κB p65 Pathway in Rats
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Wiley
2025
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| author | Xiao‐rui Tian Jun‐hui Zhao Xia‐hui Yin Jia‐hui Lin Si‐min Liang Xiao‐qing Xu Ke‐ying Li Tian‐shuang Fan Ping Xiong |
| author_facet | Xiao‐rui Tian Jun‐hui Zhao Xia‐hui Yin Jia‐hui Lin Si‐min Liang Xiao‐qing Xu Ke‐ying Li Tian‐shuang Fan Ping Xiong Xiao‐rui Tian Jun‐hui Zhao Xia‐hui Yin Jia‐hui Lin Si‐min Liang Xiao‐qing Xu Ke‐ying Li Tian‐shuang Fan Ping Xiong |
| collection | Wiley Open Access |
| contents | Astragaloside IV Pretreatment Alleviates Pulmonary Ischemia–Reperfusion Injury via the TLR4/MyD88/NF‐κB p65 Pathway in Rats Xiao‐rui Tian Jun‐hui Zhao Xia‐hui Yin Jia‐hui Lin Si‐min Liang Xiao‐qing Xu Ke‐ying Li Tian‐shuang Fan Ping Xiong Phytotherapy Research ABSTRACTBackground and aim Our previous study confirmed that ASIV can protect the lung from ischemia–reperfusion injury. The aim of this study was to determine whether ASIV attenuates PIRI by inhibiting the activation of the TLR4/MyD88/NF‐κBp65 pathway. Experimental procedure In vitro, the protection of ASIV, TAK‐242, NAC, and DEX to OGD/R‐induced cell injury was compared. In vivo, the PIRI model was induced in SD rats. The lung tissue W/D ratio and pathological morphology, as well as the markers of oxidative stress, were monitored. The mRNA and protein expression levels correlated to the TLR4/MyD88/NF‐κB p65 pathway were evaluated. Furthermore, we performed molecular docking and binding affinity calculations of the interaction between ASIV and TLR4‐MD‐2, which was verified with SPR. Key results and conclusions and implications ASIV showed more effective protection than DEX or NAC, and exhibited a synergistic effect with TAK‐242. After treatment with ASIV, lung tissue and cellular damage were obviously alleviated, and the levels of T‐SOD and GSH‐PX were significantly increased, while lung MDA and MPO decreased. Moreover, the ASIV groups showed a significant down‐regulation of the TLR4, MyD88, NF‐κBp65 and p‐NF‐κBp65 proteins when compared with the PIRI model group. The prediction showed that ASIV can enter the cavity of TLR4‐MD‐2 and exhibit strong binding, with a free binding energy of −8.0 kcal·mol−1. SPR further confirmed that ASIV rapidly bound to the rhTLR4‐MD‐2 complex with a KD of 2.17 × 10−6 M. In conclusion, ASIV can specifically bind to rhTLR4‐MD‐2, thus alleviating PIRI by suppressing the activation of the TLR4/MyD88/NF‐κB65‐mediated inflammatory pathway. 10.1002/ptr.70039 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| doi_str_mv | 10.1002/ptr.70039 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_ptr_70039 |
| institution | Wiley Open Access |
| license_str_mv | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| publishDate | 2025 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Astragaloside IV Pretreatment Alleviates Pulmonary Ischemia–Reperfusion Injury via the TLR4/MyD88/NF‐κB p65 Pathway in Rats Xiao‐rui Tian Jun‐hui Zhao Xia‐hui Yin Jia‐hui Lin Si‐min Liang Xiao‐qing Xu Ke‐ying Li Tian‐shuang Fan Ping Xiong Phytotherapy Research Astragaloside IV Pretreatment Alleviates Pulmonary Ischemia–Reperfusion Injury via the TLR4/MyD88/NF‐κB p65 Pathway in Rats Xiao‐rui Tian Jun‐hui Zhao Xia‐hui Yin Jia‐hui Lin Si‐min Liang Xiao‐qing Xu Ke‐ying Li Tian‐shuang Fan Ping Xiong Phytotherapy Research ABSTRACTBackground and aim Our previous study confirmed that ASIV can protect the lung from ischemia–reperfusion injury. The aim of this study was to determine whether ASIV attenuates PIRI by inhibiting the activation of the TLR4/MyD88/NF‐κBp65 pathway. Experimental procedure In vitro, the protection of ASIV, TAK‐242, NAC, and DEX to OGD/R‐induced cell injury was compared. In vivo, the PIRI model was induced in SD rats. The lung tissue W/D ratio and pathological morphology, as well as the markers of oxidative stress, were monitored. The mRNA and protein expression levels correlated to the TLR4/MyD88/NF‐κB p65 pathway were evaluated. Furthermore, we performed molecular docking and binding affinity calculations of the interaction between ASIV and TLR4‐MD‐2, which was verified with SPR. Key results and conclusions and implications ASIV showed more effective protection than DEX or NAC, and exhibited a synergistic effect with TAK‐242. After treatment with ASIV, lung tissue and cellular damage were obviously alleviated, and the levels of T‐SOD and GSH‐PX were significantly increased, while lung MDA and MPO decreased. Moreover, the ASIV groups showed a significant down‐regulation of the TLR4, MyD88, NF‐κBp65 and p‐NF‐κBp65 proteins when compared with the PIRI model group. The prediction showed that ASIV can enter the cavity of TLR4‐MD‐2 and exhibit strong binding, with a free binding energy of −8.0 kcal·mol−1. SPR further confirmed that ASIV rapidly bound to the rhTLR4‐MD‐2 complex with a KD of 2.17 × 10−6 M. In conclusion, ASIV can specifically bind to rhTLR4‐MD‐2, thus alleviating PIRI by suppressing the activation of the TLR4/MyD88/NF‐κB65‐mediated inflammatory pathway. 10.1002/ptr.70039 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| title | Astragaloside IV Pretreatment Alleviates Pulmonary Ischemia–Reperfusion Injury via the TLR4/MyD88/NF‐κB p65 Pathway in Rats |
| topic | Phytotherapy Research |
| url | https://onlinelibrary.wiley.com/doi/10.1002/ptr.70039 |