Asperulosidic acid inhibits the PI3K/Akt/NF-κB pathway to suppress endotoxin-induced uveitis
IntroductionUveitis, a severe inflammatory disease affecting the uvea, is associated with visual impairment and irreversible blindness. Asperulosidic Acid (ASPA), derived from Hedyotis diffusa, is known for its notable anti-inflammatory and antioxidant characteristics.MethodsThe present study explor...
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Frontiers Media S.A.
2025-01-01
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| author | Yong Du Jing Lu Lujia Feng Long Zhao Ping Wu Yuxia He Linbin Zhou Xing Wang Hui Peng |
| author_facet | Yong Du Jing Lu Lujia Feng Long Zhao Ping Wu Yuxia He Linbin Zhou Xing Wang Hui Peng |
| author_sort | Yong Du |
| collection | DOAJ |
| description | IntroductionUveitis, a severe inflammatory disease affecting the uvea, is associated with visual impairment and irreversible blindness. Asperulosidic Acid (ASPA), derived from Hedyotis diffusa, is known for its notable anti-inflammatory and antioxidant characteristics.MethodsThe present study explored the potential anti-inflammatory effects and the fundamental processes of ASPA by injecting it or a placebo into the vitreous of rats with endotoxin-induced uveitis (EIU). The severity of the disease was assessed using clinical scores obtained through slit lamp examination. The study involved the examination of protein concentrations and cell count in the aqueous humor (AqH), the detection of inflammatory mediators expressed in the retina. We evaluated the expression levels of various proteins, including the tight junction protein ZO-1, the endothelial marker VE-cadherin, and the key inflammatory mediators NF-κB and its phosphorylated form, along with the regulatory proteins IκB-a and IKK in their phosphorylated and non-phosphorylated states.ResultsASPA treatment significantly reduced the clinical score of EIU, including inflammatory leukocyte penetration, protein accumulation, cellulose-like exudates, the expression of ICAM-1, IL-6, MCP-1, and TNF-α in the AqH; and adhesion of leukocytes. The activation of the PI3K/Akt/NF-κB pathway was observed in EIU. Nevertheless, pretreatment with ASPA significantly suppressed the release of ICAM-1, TNF-α, MCP-1, and IL-6.DiscussionASPA may play a role in suppressing LPS-induced inflammation by obstructing the activation of the PI3K/Akt/NF-κB signaling pathway. As a result, ASPA has shown the capacity to significantly reduce immune inflammation. |
| format | Article |
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| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| spelling | doaj-art-a0cdaf5b57f4476482aa80d6a8c5ca4e2025-08-20T02:43:38ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2025-01-011110.3389/fmed.2024.15247791524779Asperulosidic acid inhibits the PI3K/Akt/NF-κB pathway to suppress endotoxin-induced uveitisYong Du0Jing Lu1Lujia Feng2Long Zhao3Ping Wu4Yuxia He5Linbin Zhou6Xing Wang7Hui Peng8Department of Ophthalmology, Chongqing Key Laboratory for the Prevention and Treatment of Major Blinding Eye Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Ophthalmology, Chongqing Key Laboratory for the Prevention and Treatment of Major Blinding Eye Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaShenzhen Eye Hospital, Shenzhen Eye Institute, Jinan University, Shenzhen, ChinaDepartment of Ophthalmology, Chongqing Key Laboratory for the Prevention and Treatment of Major Blinding Eye Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Ophthalmology, Chongqing Key Laboratory for the Prevention and Treatment of Major Blinding Eye Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Ophthalmology, Chongqing Key Laboratory for the Prevention and Treatment of Major Blinding Eye Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, ChinaDepartment of Ophthalmology, Chongqing Key Laboratory for the Prevention and Treatment of Major Blinding Eye Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Ophthalmology, Chongqing Key Laboratory for the Prevention and Treatment of Major Blinding Eye Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaIntroductionUveitis, a severe inflammatory disease affecting the uvea, is associated with visual impairment and irreversible blindness. Asperulosidic Acid (ASPA), derived from Hedyotis diffusa, is known for its notable anti-inflammatory and antioxidant characteristics.MethodsThe present study explored the potential anti-inflammatory effects and the fundamental processes of ASPA by injecting it or a placebo into the vitreous of rats with endotoxin-induced uveitis (EIU). The severity of the disease was assessed using clinical scores obtained through slit lamp examination. The study involved the examination of protein concentrations and cell count in the aqueous humor (AqH), the detection of inflammatory mediators expressed in the retina. We evaluated the expression levels of various proteins, including the tight junction protein ZO-1, the endothelial marker VE-cadherin, and the key inflammatory mediators NF-κB and its phosphorylated form, along with the regulatory proteins IκB-a and IKK in their phosphorylated and non-phosphorylated states.ResultsASPA treatment significantly reduced the clinical score of EIU, including inflammatory leukocyte penetration, protein accumulation, cellulose-like exudates, the expression of ICAM-1, IL-6, MCP-1, and TNF-α in the AqH; and adhesion of leukocytes. The activation of the PI3K/Akt/NF-κB pathway was observed in EIU. Nevertheless, pretreatment with ASPA significantly suppressed the release of ICAM-1, TNF-α, MCP-1, and IL-6.DiscussionASPA may play a role in suppressing LPS-induced inflammation by obstructing the activation of the PI3K/Akt/NF-κB signaling pathway. As a result, ASPA has shown the capacity to significantly reduce immune inflammation.https://www.frontiersin.org/articles/10.3389/fmed.2024.1524779/fulluveitisasperulosidic acidEIUinflammationNF-κB |
| spellingShingle | Yong Du Jing Lu Lujia Feng Long Zhao Ping Wu Yuxia He Linbin Zhou Xing Wang Hui Peng Asperulosidic acid inhibits the PI3K/Akt/NF-κB pathway to suppress endotoxin-induced uveitis Frontiers in Medicine uveitis asperulosidic acid EIU inflammation NF-κB |
| title | Asperulosidic acid inhibits the PI3K/Akt/NF-κB pathway to suppress endotoxin-induced uveitis |
| title_full | Asperulosidic acid inhibits the PI3K/Akt/NF-κB pathway to suppress endotoxin-induced uveitis |
| title_fullStr | Asperulosidic acid inhibits the PI3K/Akt/NF-κB pathway to suppress endotoxin-induced uveitis |
| title_full_unstemmed | Asperulosidic acid inhibits the PI3K/Akt/NF-κB pathway to suppress endotoxin-induced uveitis |
| title_short | Asperulosidic acid inhibits the PI3K/Akt/NF-κB pathway to suppress endotoxin-induced uveitis |
| title_sort | asperulosidic acid inhibits the pi3k akt nf κb pathway to suppress endotoxin induced uveitis |
| topic | uveitis asperulosidic acid EIU inflammation NF-κB |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2024.1524779/full |
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