Protective mechanisms of 3-caffeoyl, 4-dihydrocaffeoyl quinic acid from Salicornia herbacea against tert-butyl hydroperoxide-induced oxidative damage.
Salicornia herbacea has been used as a folk medicine for disorders such as constipation, obesity, diabetes, and cancer. Recent studies have shown that S. herbacea has antioxidative, anti-inflammatory, immunomodulatory, antihyperglycemic, and antihyperlipidemic activities. In the present work, we investigated the protective effects of the chlorogenic acid derivative, 3-caffeoyl, 4-dihydrocaffeoyl quinic acid (CDCQ), which was isolated from S. herbacea, against tert-butyl hydroperoxide (t-BHP)-induced hepatotoxicity in Hepa1c1c7 cells. Pretreatment of Hepa1c1c7 cells with CDCQ significantly reduced t-BHP-induced generation of ROS, caspase-3 activation, and subsequent cell death. Also, CDCQ up-regulated heme oxygenase-1 (HO-1) expression, which conferred cytoprotection against oxidative injury induced by t-BHP. Moreover, CDCQ-induced nuclear translocation of the transcription factor NF-E2-related factor 2 (Nrf2), which is upstream of CDCQ-induced HO-1 expression, and PI3K/Akt activation, a pathway that is involved in induced Nrf2 nuclear translocation. Taken together, these results suggest that the protective effects of CDCQ against t-BHP-induced hepatotoxicity may be due, at least in part, to its ability to scavenge ROS and to regulate the antioxidant enzyme HO-1 via the PI3K/Akt-Nrf2 signaling pathways.
Hwang
Yong Pil
YP
College of Pharmacy, Chosun University, Gwangju, Republic of Korea.
Yun
Hyo Jeong
HJ
Chun
Hyo Kon
HK
Chung
Young Chul
YC
Kim
Hyung Keun
HK
Jeong
Myung Ho
MH
Yoon
Taek Rim
TR
Jeong
Hye Gwang
HG
D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D019663:Chenopodiaceae / Q000737:chemistry*; D002726:Chlorogenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051267:NF-E2-Related Factor 2 / Q000235:genetics; D018384:Oxidative Stress; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020122:tert-Butylhydroperoxide / Q000633:toxicity*
C544671:3-caffeoyl-4-dihydrocaffeoylquinic acid; D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D002726:Chlorogenic Acid; D020122:tert-Butylhydroperoxide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3