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The modulation of cAMP/PKA pathway by asiaticoside ameliorates high glucose-induced inflammation and apoptosis of retinal pigment epithelial cells

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Abstract

Asiaticoside, the major bioactive constituent purified from Centella asiatica, is a pentacyclic triterpene saponin with sugar moieties (glucose-glucose-rhamnose). Its biological activities including anti-inflammation and antioxidant have been widely reported. This study aimed to investigate the role of asiaticoside in diabetic retinopathy (DR). Human retinal pigment epithelium (RPE) cells ARPE-19 were induced by high glucose. Then, cell survival rate, expression of inflammatory factors, oxidative stress, and apoptosis were measured by MTT method, western blot, oxidative stress detection kits and TUNEL respectively. To uncover the underlying mechanism, the levels of cyclic AMP (cAMP) and protein kinase A (PKA) were measured by Enzyme linked immunosorbent assay (ELISA) and PKA activities were detected by the Kemptide phosphorylation assay. Furthermore, cAMP inhibitor SQ22536 was also used to validate the mechanism. Asiaticoside suppressed the inflammation and apoptosis of ARPE-19 cells, and the activities of cAMP and PKA were inhibited upon HG induction while again released after further administration of asiaticoside. However, these effects were all abolished by SQ22536. In conclusion, we have demonstrated in this paper that asiaticoside ameliorates high glucose-induced inflammation and apoptosis of RPE cells by activating cAMP/PKA signaling pathway. asiaticoside-mediated activation of cAMP/PKA signaling pathway may serve as a potential target for the management of DR.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Ophthalmology, Wanzhou aier eye hospital, Chongqing, 404100, China

    Yixia Zhang & Xindan Meng

  2. Department of Surgery, Northern Kuanren Hospital, The Second Affiliated Hospital of Chongqing Medical University, Yubei District, 69 Renhe Xingguang Avenue, Chongqing, 401120, China

    Keyu Liu

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  1. Yixia Zhang
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  2. Xindan Meng
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  3. Keyu Liu
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Correspondence to Keyu Liu.

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Zhang, Y., Meng, X. & Liu, K. The modulation of cAMP/PKA pathway by asiaticoside ameliorates high glucose-induced inflammation and apoptosis of retinal pigment epithelial cells. J Bioenerg Biomembr 54, 9–16 (2022). https://doi.org/10.1007/s10863-021-09929-w

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  • DOI: https://doi.org/10.1007/s10863-021-09929-w

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