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PPARγ activation by baicalin suppresses NF-κB-mediated inflammation in aged rat kidney

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Abstract

Baicalin, a herb-derived flavonoid compound, has beneficial activities, including the modulation of oxidative stress and inflammation. Nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ) is a ligand-activated transcription factor that plays an important role in regulating nuclear factor-κB (NF-κB)-induced age-related inflammation. We investigated the anti-inflammatory action of baicalin, which depends on its ability to activate PPARγ, and subsequently to suppress NF-κB. We examined baicalin-treated kidney tissue from 24-month-old Fischer 344 aged rats (10 or 20 mg/kg/day for 10 days) and baicalin-fed mice (10 mg/kg/day for 3 days) for in vivo investigations, and used endothelial YPEN-1 cells for in vitro studies. In the baicalin-fed aged rats, there was a marked enhancement of both nuclear protein levels and DNA binding activity of PPARγ, and a decreased expression of NF-κB target genes (VCAM-1, IL-1β, and IL-6) compared with non-baicalin-fed aged rats. Furthermore, to confirm the anti-inflammatory action of PPARγ activated by baicalin, we used lipopolysaccharide (LPS)-treated cells and mice. The results showed that baicalin induced PPARγ-selective activation in YPEN-1 cells, and that the effects of baicalin were blocked by the PPARγ receptor antagonist, GW9662. In addition, baicalin treatment prevented RS generation, NF-κB activation and the expression of pro-inflammatory genes, whereas it increased PPARγ expression in LPS-treated cells and mouse kidney. Our data suggest that baicalin-induced PPARγ expression reduced age-related inflammation through blocking pro-inflammatory NF-κB activation. These results indicate that baicalin is a novel PPARγ activator and that this agent may have the potential to minimize inflammation.

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Abbreviations

EMSA:

Electrophoretic mobility shift assay

H2DCF-DA:

2′,7′-Dichlorofluorescin diacetate

IL-1β:

Interukin-1β

iNOS:

Inducible nitric oxide synthase

I.P.:

Intraperitoneal

NF-κB:

Nuclear factor-κB

PPARγ:

Peroxisome proliferator-activated receptor-γ

PPRE:

Peroxisome proliferator response element

RS:

Reactive species

RXR:

Retinoid X receptor

SPF:

Specific pathogen free

TNF-α:

Tumor necrosis factor-α

TZD:

Thiazolidinedione

VCAM-1:

Vascular cell adhesion protein-1

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Acknowledgments

This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (MRC Program No. 2009-0083538) and a grant (Code # 7-19-42) from Rural Development Administration, Republic of Korea. We are grateful to the Aging Tissue Bank for providing aged rat kidney tissue. The authors thank Editage (a division of Cactus Communications Pvt. Ltd.) for valuable editing of this manuscript.

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Authors and Affiliations

  1. Molecular Inflammation Research Center for Aging Intervention (MRCA), Pusan National University, Gumjung-gu, Busan, 609-735, Republic of Korea

    Hyun Ae Lim, Eun Kyeong Lee, Ji Min Kim, Min Hi Park, Dae Hyun Kim, Yeon Ja Choi, Young Mi Ha, Jeong-Hyun Yoon & Hae Young Chung

  2. Department of Pharmacy, College of Pharmacy, Pusan National University, Gumjung-gu, Busan, 609-735, Republic of Korea

    Hyun Ae Lim, Eun Kyeong Lee, Ji Min Kim, Min Hi Park, Dae Hyun Kim, Yeon Ja Choi, Young Mi Ha, Jeong-Hyun Yoon & Hae Young Chung

  3. Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan, 619-953, Republic of Korea

    Eun Kyeong Lee

  4. Division of Food Science and Biotechnology, Pukyong National University, Busan, 608-737, Republic of Korea

    Jae Sue Choi

  5. Department of Physiology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229-3900, USA

    Byung Pal Yu

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  1. Hyun Ae Lim
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Correspondence to Hae Young Chung.

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Hyun Ae Lim and Eun Kyeong Lee contributed equally to this work.

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Lim, H.A., Lee, E.K., Kim, J.M. et al. PPARγ activation by baicalin suppresses NF-κB-mediated inflammation in aged rat kidney. Biogerontology 13, 133–145 (2012). https://doi.org/10.1007/s10522-011-9361-4

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