Arjunolic acid from Cyclocarya paliurus ameliorates diabetic retinopathy through AMPK/mTOR/HO-1 regulated autophagy pathway
- J Ethnopharmacol. 2022 Feb 10:284:114772. doi: 10.1016/j.jep.2021.114772.
- 1. Department of TCMs Pharmaceuticals & Department of Natural Medicinal Chemistry, School of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing, 211198, PR China; Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, PR China; Department of Endocrinology, Nanjing Lishui District Hospital of Traditional Chinese Medicine, Nanjing, 211200, PR China.
- 2. Department of TCMs Pharmaceuticals & Department of Natural Medicinal Chemistry, School of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing, 211198, PR China; Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, PR China.
- 3. Department of TCMs Pharmaceuticals & Department of Natural Medicinal Chemistry, School of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing, 211198, PR China.
- 4. Department of Endocrinology, Nanjing Lishui District Hospital of Traditional Chinese Medicine, Nanjing, 211200, PR China.
- 5. Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, PR China.
- 6. Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, PR China. Electronic address: [email protected].
- 7. Department of TCMs Pharmaceuticals & Department of Natural Medicinal Chemistry, School of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing, 211198, PR China. Electronic address: [email protected].
Ethnopharmacological relevance: Cyclocarya paliurus (CP) is a traditional Chinese herb and possesses a variety of biological activities including anti-hyperglycemia, anti-hyperlipidemia, antioxidant and anti-inflammation. Arjunolic acid (AA) is an abundant and bioactive ingredient in CP that shows significant protection against many metabolic diseases such as diabetic complication. Diabetic retinopathy (DR) is a serious complication of diabetes and may lead to vision loss. However, the protective effects and underlying mechanisms of AA against DR is not still understood.
Aim of the study: We aimed to investigate whether AA activates AMPK/mTOR/HO-1 regulated Autophagy pathway to alleviate DR.
Materials and methods: In the study, the STZ-induced diabetic model of rats was established, and AA with 10 and 30 mg/kg dosages was given orally for ten weeks to investigate their effect on retinal injury of DR. H2O2-induced ARPE-19 cells were applied to evaluate anti-apoptosis and anti-oxidant effect of AA.
Results: The results revealed that AA could prevent STZ-induced weight loss and increase the retinal thickness and nuclei counts. The level of HO-1 protein was upregulated both in vivo and in vitro. In addition, AA prevented retinal damage and cell Apoptosis through the AMPK-mTOR-regulated Autophagy pathway. Furthermore, anti-apoptosis capacity, as well as the expression of HO-1 and LC3 protein, were effectively locked by AMPK Inhibitor dorsomorphin dihydrochloride (compound C).
Conclusions: This finding implies that AA may be a promising candidate drug by protecting retinal cells from STZ-induced oxidative stress and inflammation through the AMPK/mTOR/HO-1 regulated Autophagy pathway.