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Targeting mitochondrial DNA-STING-NF-κB Axis-mediated microglia activation by cryptotanshinone alleviates ischemic
Wanlu Qiu1, Zhihua Zheng2, Jiaojiao Wang3
1State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Discovery of Chinese Ministry of Education (MOE), College of Pharmacy, Jinan University, Guangzhou 510632, China; Department of Ophthalmology, the First Affiliated Hospital, Jinan University, Guangzhou 510006, China.
Cryptotanshinone (CTS) alleviates ischemic retinopathy by inhibiting the STING pathway in microglia. This natural compound reduces inflammation and oxidative stress, protecting retinal structure and function.
Area of Science:
- Ophthalmology
- Neuroscience
- Pharmacology
Background:
- Ischemic retinopathy causes vision loss through oxidative stress and inflammation, with microglia playing a central role.
- Cryptotanshinone (CTS), derived from Salvia miltiorrhiza, possesses anti-inflammatory and antioxidant properties.
- The STING pathway in microglia is implicated in ischemic retinopathy pathogenesis and is a potential therapeutic target.
Purpose of the Study:
- To investigate if Cryptotanshinone (CTS) can alleviate ischemic retinopathy by modulating microglial STING signaling.
- To elucidate the underlying molecular mechanisms of CTS action in the context of ischemic retinopathy.
Main Methods:
- Utilized oxygen-induced retinopathy (OIR) mouse models and hypoxia-induced microglial cells.
- Employed fluorescein fundus angiography, electroretinogram, H&E staining, and Western blotting to assess CTS efficacy.
- Applied network pharmacology, RNA sequencing, SPR, molecular docking, and mutagenesis to identify and validate STING as the target of CTS.
Main Results:
- CTS treatment reduced microglial activation, pathological retinal angiogenesis, and improved retinal function and structure in OIR mice.
- CTS inhibited the mtDNA-STING-NF-κB signaling pathway by suppressing mtDNA release, blocking STING translocation, and enhancing its degradation.
- Synergistic effects were observed when CTS was combined with anti-VEGF therapy in suppressing neovascularization.
Conclusions:
- Cryptotanshinone (CTS) acts as a natural inhibitor of STING, effectively alleviating ischemic retinopathy.
- CTS exerts its protective effects through multifaceted mechanisms within microglia, targeting the mtDNA-STING-NF-κB pathway.
- CTS demonstrates potential as a therapeutic agent for ischemic retinopathy, particularly in combination therapies.
