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

Background: 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...

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Main Authors: Heeseung Oh, Wonjun Cho, Seung Yeon Park, A.M. Abd El-Aty, Ji Hoon Jeong, Tae Woo Jung
Format: Article
Language:English
Published: Elsevier 2023-05-01
Series:Journal of Ginseng Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1226845322001531
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author Heeseung Oh
Wonjun Cho
Seung Yeon Park
A.M. Abd El-Aty
Ji Hoon Jeong
Tae Woo Jung
author_facet Heeseung Oh
Wonjun Cho
Seung Yeon Park
A.M. Abd El-Aty
Ji Hoon Jeong
Tae Woo Jung
author_sort Heeseung Oh
collection DOAJ
description Background: 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.
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spelling doaj.art-e6a94ce1952d45b8bc823b409eee2fe42023-05-20T04:29:38ZengElsevierJournal of Ginseng Research1226-84532023-05-01473400407Ginsenoside Rb3 ameliorates podocyte injury under hyperlipidemic conditions via PPARδ- or SIRT6-mediated suppression of inflammation and oxidative stressHeeseung Oh0Wonjun Cho1Seung Yeon Park2A.M. Abd El-Aty3Ji Hoon Jeong4Tae Woo Jung5Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of KoreaDepartment of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of KoreaDepartment of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea; Department of Global Innovative Drugs, Graduate School of Chung-Ang University, Seoul, Republic of KoreaDepartment of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt; Department of Medical Pharmacology, Medical Faculty, Ataturk University, Erzurum, TurkeyDepartment of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea; Department of Global Innovative Drugs, Graduate School of Chung-Ang University, Seoul, Republic of KoreaDepartment of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea; Corresponding author. Department of Pharmacology, College of Medicine, Chung-Ang University, 221, Heuksuk-dong, Dongjak-gu, Seoul, 06974, Republic of Korea.Background: 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.http://www.sciencedirect.com/science/article/pii/S1226845322001531Rb3podocytesapoptosisPPARδSIRT6renal injury
spellingShingle Heeseung Oh
Wonjun Cho
Seung Yeon Park
A.M. Abd El-Aty
Ji Hoon Jeong
Tae Woo Jung
Ginsenoside Rb3 ameliorates podocyte injury under hyperlipidemic conditions via PPARδ- or SIRT6-mediated suppression of inflammation and oxidative stress
Journal of Ginseng Research
Rb3
podocytes
apoptosis
PPARδ
SIRT6
renal injury
title Ginsenoside Rb3 ameliorates podocyte injury under hyperlipidemic conditions via PPARδ- or SIRT6-mediated suppression of inflammation and oxidative stress
title_full Ginsenoside Rb3 ameliorates podocyte injury under hyperlipidemic conditions via PPARδ- or SIRT6-mediated suppression of inflammation and oxidative stress
title_fullStr Ginsenoside Rb3 ameliorates podocyte injury under hyperlipidemic conditions via PPARδ- or SIRT6-mediated suppression of inflammation and oxidative stress
title_full_unstemmed Ginsenoside Rb3 ameliorates podocyte injury under hyperlipidemic conditions via PPARδ- or SIRT6-mediated suppression of inflammation and oxidative stress
title_short Ginsenoside Rb3 ameliorates podocyte injury under hyperlipidemic conditions via PPARδ- or SIRT6-mediated suppression of inflammation and oxidative stress
title_sort ginsenoside rb3 ameliorates podocyte injury under hyperlipidemic conditions via pparδ or sirt6 mediated suppression of inflammation and oxidative stress
topic Rb3
podocytes
apoptosis
PPARδ
SIRT6
renal injury
url http://www.sciencedirect.com/science/article/pii/S1226845322001531
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