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Anti-inflammatory/Anti-oxidative Stress Activities and Differential Regulation of Nrf2-Mediated Genes by Non-Polar Fractions of Tea Chrysanthemum zawadskii and Licorice Glycyrrhiza uralensis

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Abstract

Accumulating evidence from epidemiological studies indicates that chronic inflammation and oxidative stress play critical roles in neoplastic development. The aim of this study was to investigate the anti-inflammatory, anti-oxidative stress activities, and differential regulation of Nrf2-mediated genes by tea Chrysanthemum zawadskii (CZ) and licorice Glycyrrhiza uralensis (LE) extracts. The anti-inflammatory and anti-oxidative stress activities of hexane/ethanol extracts of CZ and LE were investigated using in vitro and in vivo approaches, including quantitative real-time PCR (qPCR) and microarray. Additionally, the role of the transcriptional factor Nrf2 (nuclear erythroid-related factor 2) signaling pathways was examined. Our results show that CZ and LE extracts exhibited potent anti-inflammatory activities by suppressing the mRNA and protein expression levels of pro-inflammatory biomarkers IL-1β, IL-6, COX-2 and iNOS in LPS-stimulated murine RAW 264.7 macrophage cells. CZ and LE also significantly suppressed the NO production of LPS-stimulated RAW 264.7 cells. Additionally, CZ and LE suppressed the NF-κB luciferase activity in human HT-29 colon cancer cells. Both extracts also showed strong Nrf2-mediated antioxidant/Phase II detoxifying enzymes induction. CZ and LE induced NQO1, Nrf2, and UGT and antioxidant response element (ARE)-luciferase activity in human hepatoma HepG2 C8 cells. Using Nrf2 knockout [Nrf2 (−/−)] and Nrf2 wild-type (+/+) mice, LE and CZ showed Nrf2-dependent transactivation of Nrf2-mediated antioxidant and phase II detoxifying genes. In summary, CZ and LE possess strong inhibitory effects against NF-κB-mediated inflammatory as well as strong activation of the Nrf2-ARE-anti-oxidative stress signaling pathways, which would contribute to their overall health promoting pharmacological effects against diseases including cancer.

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Acknowledgments

The authors thanks Mr. Curtis Krier at the Cancer Institute of New Jersey (CINJ) Core Expression Array Facility for his assistance with the microarray analyses. This work was supported in part by: Institutional Funds, NIH R01-CA094828 of A.N.K. and a grant (Code # 20070301034039) from Biogreen 21 Program, Rural Development Administration, Republic of Korea.

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Authors and Affiliations

  1. Graduate Program in Pharmaceutical Science, Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA

    Tien-Yuan Wu & Ah-Ng Tony Kong

  2. Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Room 228, 160 Frelinghuysen Road, Piscataway, New Jersey, 08854, USA

    Tin Oo Khor, Constance Lay Lay Saw & Ah-Ng Tony Kong

  3. Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA

    Stephanie C. Loh, Alvin I. Chen & Li Cai

  4. Department of Food Science and Nutrition, Hallym University, Chuncheon, South Korea

    Soon Sung Lim & Jung Han Yoon Park

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  1. Tien-Yuan Wu
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Correspondence to Ah-Ng Tony Kong.

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Wu, TY., Khor, T.O., Saw, C.L.L. et al. Anti-inflammatory/Anti-oxidative Stress Activities and Differential Regulation of Nrf2-Mediated Genes by Non-Polar Fractions of Tea Chrysanthemum zawadskii and Licorice Glycyrrhiza uralensis . AAPS J 13, 1–13 (2011). https://doi.org/10.1208/s12248-010-9239-4

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