2. Academic Validation
  3. Arjunolic acid from Cyclocarya paliurus ameliorates diabetic retinopathy through AMPK/mTOR/HO-1 regulated autophagy pathway

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.
Xuan-Xuan Zhang 1,  Ya-Li Ji 2,  Li-Ping Zhu 3,  Zi-Han Wang 2,  Chang-Qian Fang 4,  Cui-Hua Jiang 5,  Ke Pan 3,  Jian Zhang 6,  Zhi-Qi Yin 7
Affiliations

Affiliations

  • 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].
PMID: 34688801 DOI: 10.1016/j.jep.2021.114772
Abstract

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.

Keywords

AMPK/mTOR/HO-1; Arjunolic acid; Autophagy; Cyclocarya paliurus; Diabetic retinopathy.

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