Ginsenoside Rb3 ameliorates podocyte injury under hyperlipidemic conditions via PPARδ- or SIRT6-mediated suppression of inflammation and oxidative stress

Journal of Ginseng Research

Available online 26 November 2022

Journal of Ginseng ResearchAuthor links open overlay panelHighlights•

Ginsenoside Rb3 suppresses inflammation and oxidative stress, thereby attenuating apoptosis in podocytes under hyperlipidemic conditions.

Rb3 attenuates inflammation and oxidative stress via PPARδ or SIRT6 -dependent pathway.

PPARδ or SIRT6 contributes to the effects of Rb3 on hyperlipidemia-induced podocyte apoptosis.

AbstractBackground

Rb3 is a ginsenoside with anti-inflammatory properties in many cell types and has been reported to attenuate inflammation-related metabolic diseases such as insulin resistance, nonalcoholic fatty liver disease, and cardiovascular disease. However, the effect of Rb3 on podocyte apoptosis under hyperlipidemic conditions, which contributes to the development of obesity-mediated renal disease, remains unclear. In the current study, we aimed to investigate the effect of Rb3 on podocyte apoptosis in the presence of palmitate and explore its underlying molecular mechanisms.

Methods

Human podocytes (CIHP-1 cells) were exposed to Rb3 in the presence of palmitate as a model of hyperlipidemia. Cell viability was assessed by MTT assay. The effects of Rb3 on the expression of various proteins were analyzed by Western blotting. Apoptosis levels were determined by MTT assay, caspase 3 activity assay, and cleaved caspase 3 expression.

Results

We found that Rb3 treatment alleviated the impairment of cell viability and increased caspase 3 activity as well as inflammatory markers in palmitate-treated podocytes. Treatment with Rb3 dose-dependently increased PPARδ and SIRT6 expression. Knockdown of PPARδ or SIRT6 reduced the effects of Rb3 on apoptosis as well as inflammation and oxidative stress in cultured podocytes.

Conclusions

The current results suggest that Rb3 alleviates inflammation and oxidative stress via PPARδ- or SIRT6-mediated signaling, thereby attenuating apoptosis in podocytes in the presence of palmitate. The present study provides Rb3 as an effective strategy for treating obesity-mediated renal injury.

Keywords

Rb3

podocytes

apoptosis

PPARδ

SIRT6

renal injury

© 2022 The Korean Society of Ginseng. Publishing services by Elsevier B.V.

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