Preventive Effects against Retinal Degeneration by Centella asiatica Extract (CA-HE50) and Asiaticoside through Apoptosis Suppression by the Nrf2/HO-1 Signaling Pathway

Abstract

Age-related macular degeneration (AMD) is caused by the chronic and gradual oxidative degeneration of the retina. Unfortunately, the general purpose of current treatments is to slow AMD progression, as the retina cannot be restored to its pre-AMD condition. We aimed to identify natural products that can be potential treatments that prevent AMD and can delay the development of late-AMD and selected Centella asiatica extract (CA-HE50), which shows excellent efficacy in cytoprotection. In animal experiments using N-methyl-N-nitrosourea (MNU), CA-HE50 dramatically increased the thickness of photoreceptors and the outer nuclear layer (ONL) and the number of nuclei in the ONL (p < 0.05). Using retinal epithelial ARPE-19 cells showed that CA-HE50 inhibited apoptosis through inhibition of the intrinsic apoptosis signaling pathway and cell cycle regulation (p < 0.05). The anti-apoptotic efficacy was confirmed to be due to activation of the Nrf2/HO-1 antioxidation pathway (p < 0.05). These results were also observed with asiaticoside, a functional substance of CA-HE50. In addition, the accumulation of oxidized-N-retinylidene-N-retinylethanolamine (A2E), which induces AMD, was inhibited by CA-HE50, resulting in increased ARPE-19 cell viability (p < 0.05). This study demonstrates that CA-HE50 is worth further research and human application tests, to develop it as a raw material for treatment or dietary supplement for the prevention of AMD.

Asiaticoside delays senescence and attenuate generation of ROS in UV‑exposure cells through regulates TGF‑β1/Smad pathway

“…With the improvement of understanding of asiaticoside, multiple functions of asiaticoside have been revealed. Not only capacity of anti-aging in UV damaged cells as reported in the present study, but also capability against retinal degradation and ameliorate inflammation through Nrf2/HO-1 pathway and TLR4/NF-κB pathway, respectively (57,58). Furthermore, asiaticoside-contained foam dressing, nano-composite and nanofibrous scaffold have been developed for traumatic treatment, showing great potential of asiaticoside in wound healing (14,59,60).…”

Protective effects of Lycium barbarum L. berry extracts against oxidative stress-induced damage of the retina of aging mouse and ARPE-19 cells

“…48 Natural product Centella Asiatica extract suppresses RPE cell apoptosis and protects the retina from degeneration by up-regulating the Nrf2/HO-1 signalling pathway. 49 The current in vitro cell experiments showed that the LBW-95E could significantly improve the survival rate of ARPE-19 cells from oxidative stress which was the main active fraction of LBW. Its mechanism might be related to promoting the translocation of Nrf2 into the nucleus, increasing the levels of intracellular HO-1, SOD and GSH and reducing the level of intracellular ROS.…”

A Comparative Study of the Hepatoprotective Effect of Centella asiatica Extract (CA-HE50) on Lipopolysaccharide/d-galactosamine-Induced Acute Liver Injury in C57BL/6 Mice

“…CA-HE50 showed a protective effect by inhibiting the expression of inflammatory genes in an APAP-induced liver injury model [29]. Moreover, in a study on the prevention of retinal degeneration of CA-HE50, it was confirmed that CA-HE50 and its active compound, asiaticoside, promote the Nrf2/HO-1 signaling pathway [61]. Judging from the results of these studies, the hepatoprotective efficacy of CA-HE50 shown in the LPS/D-gal-induced ALF animal model is expected to occur through the Nrf2/HO-1 signaling pathway, a well-known antioxidant mechanism.…”