<i>Garcinia cambogia</i> Ameliorates Non-Alcoholic Fatty Liver Disease by Inhibiting Oxidative Stress-Mediated Steatosis and Apoptosis through NRF2-ARE Activation
Excessive free fatty acids (FFAs) causes reactive oxygen species (ROS) generation and non-alcoholic fatty liver disease (NAFLD) development. <i>Garcinia cambogia</i> (<i>G. cambogia</i>) is used as an anti-obesity supplement, and its protective potential against NAFLD has bee...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-07-01
|
| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/10/8/1226 |
| _version_ | 1797524822019801088 |
|---|---|
| author | Joo-Hui Han Min-Ho Park Chang-Seon Myung |
| author_facet | Joo-Hui Han Min-Ho Park Chang-Seon Myung |
| author_sort | Joo-Hui Han |
| collection | DOAJ |
| description | Excessive free fatty acids (FFAs) causes reactive oxygen species (ROS) generation and non-alcoholic fatty liver disease (NAFLD) development. <i>Garcinia cambogia</i> (<i>G. cambogia</i>) is used as an anti-obesity supplement, and its protective potential against NAFLD has been investigated. This study aims to present the therapeutic effects of <i>G. cambogia</i> on NAFLD and reveal underlying mechanisms. High-fat diet (HFD)-fed mice were administered <i>G. cambogia</i> for eight weeks, and steatosis, apoptosis, and biochemical parameters were examined in vivo. FFA-induced HepG2 cells were treated with <i>G. cambogia</i>, and lipid accumulation, apoptosis, ROS level, and signal alterations were examined. The results showed that <i>G. cambogia</i> inhibited HFD-induced steatosis and apoptosis and abrogated abnormalities in serum chemistry. <i>G. cambogia</i> increased in NRF2 nuclear expression and activated antioxidant responsive element (ARE), causing induction of antioxidant gene expression. NRF2 activation inhibited FFA-induced ROS production, which suppressed lipogenic transcription factors, C/EBPα and PPARγ. Moreover, the ability of <i>G. cambogia</i> to inhibit ROS production suppressed apoptosis by normalizing the Bcl-2/BAX ratio and PARP cleavage. Lastly, these therapeutic effects of <i>G. cambogia</i> were due to hydroxycitric acid (HCA). These findings provide new insight into the mechanism by which <i>G. cambogia</i> regulates NAFLD progression. |
| first_indexed | 2024-03-10T09:03:02Z |
| format | Article |
| id | doaj.art-1b425cdbaae74850a20bf33b7bcf42a3 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T09:03:02Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-1b425cdbaae74850a20bf33b7bcf42a32023-11-22T06:35:58ZengMDPI AGAntioxidants2076-39212021-07-01108122610.3390/antiox10081226<i>Garcinia cambogia</i> Ameliorates Non-Alcoholic Fatty Liver Disease by Inhibiting Oxidative Stress-Mediated Steatosis and Apoptosis through NRF2-ARE ActivationJoo-Hui Han0Min-Ho Park1Chang-Seon Myung2Department of Pharmacology, College of Pharmacy, Chungnam National University, Daejeon 34134, KoreaInstitute of Drug Research and Development, College of Pharmacy, Chungnam National University, Daejeon 34134, KoreaDepartment of Pharmacology, College of Pharmacy, Chungnam National University, Daejeon 34134, KoreaExcessive free fatty acids (FFAs) causes reactive oxygen species (ROS) generation and non-alcoholic fatty liver disease (NAFLD) development. <i>Garcinia cambogia</i> (<i>G. cambogia</i>) is used as an anti-obesity supplement, and its protective potential against NAFLD has been investigated. This study aims to present the therapeutic effects of <i>G. cambogia</i> on NAFLD and reveal underlying mechanisms. High-fat diet (HFD)-fed mice were administered <i>G. cambogia</i> for eight weeks, and steatosis, apoptosis, and biochemical parameters were examined in vivo. FFA-induced HepG2 cells were treated with <i>G. cambogia</i>, and lipid accumulation, apoptosis, ROS level, and signal alterations were examined. The results showed that <i>G. cambogia</i> inhibited HFD-induced steatosis and apoptosis and abrogated abnormalities in serum chemistry. <i>G. cambogia</i> increased in NRF2 nuclear expression and activated antioxidant responsive element (ARE), causing induction of antioxidant gene expression. NRF2 activation inhibited FFA-induced ROS production, which suppressed lipogenic transcription factors, C/EBPα and PPARγ. Moreover, the ability of <i>G. cambogia</i> to inhibit ROS production suppressed apoptosis by normalizing the Bcl-2/BAX ratio and PARP cleavage. Lastly, these therapeutic effects of <i>G. cambogia</i> were due to hydroxycitric acid (HCA). These findings provide new insight into the mechanism by which <i>G. cambogia</i> regulates NAFLD progression.https://www.mdpi.com/2076-3921/10/8/1226<i>Garcinia cambogia</i>non-alcoholic fatty liver disease (NAFLD)steatosisapoptosisreactive oxygen speciesantioxidant |
| spellingShingle | Joo-Hui Han Min-Ho Park Chang-Seon Myung <i>Garcinia cambogia</i> Ameliorates Non-Alcoholic Fatty Liver Disease by Inhibiting Oxidative Stress-Mediated Steatosis and Apoptosis through NRF2-ARE Activation Antioxidants <i>Garcinia cambogia</i> non-alcoholic fatty liver disease (NAFLD) steatosis apoptosis reactive oxygen species antioxidant |
| title | <i>Garcinia cambogia</i> Ameliorates Non-Alcoholic Fatty Liver Disease by Inhibiting Oxidative Stress-Mediated Steatosis and Apoptosis through NRF2-ARE Activation |
| title_full | <i>Garcinia cambogia</i> Ameliorates Non-Alcoholic Fatty Liver Disease by Inhibiting Oxidative Stress-Mediated Steatosis and Apoptosis through NRF2-ARE Activation |
| title_fullStr | <i>Garcinia cambogia</i> Ameliorates Non-Alcoholic Fatty Liver Disease by Inhibiting Oxidative Stress-Mediated Steatosis and Apoptosis through NRF2-ARE Activation |
| title_full_unstemmed | <i>Garcinia cambogia</i> Ameliorates Non-Alcoholic Fatty Liver Disease by Inhibiting Oxidative Stress-Mediated Steatosis and Apoptosis through NRF2-ARE Activation |
| title_short | <i>Garcinia cambogia</i> Ameliorates Non-Alcoholic Fatty Liver Disease by Inhibiting Oxidative Stress-Mediated Steatosis and Apoptosis through NRF2-ARE Activation |
| title_sort | i garcinia cambogia i ameliorates non alcoholic fatty liver disease by inhibiting oxidative stress mediated steatosis and apoptosis through nrf2 are activation |
| topic | <i>Garcinia cambogia</i> non-alcoholic fatty liver disease (NAFLD) steatosis apoptosis reactive oxygen species antioxidant |
| url | https://www.mdpi.com/2076-3921/10/8/1226 |
| work_keys_str_mv | AT joohuihan igarciniacambogiaiamelioratesnonalcoholicfattyliverdiseasebyinhibitingoxidativestressmediatedsteatosisandapoptosisthroughnrf2areactivation AT minhopark igarciniacambogiaiamelioratesnonalcoholicfattyliverdiseasebyinhibitingoxidativestressmediatedsteatosisandapoptosisthroughnrf2areactivation AT changseonmyung igarciniacambogiaiamelioratesnonalcoholicfattyliverdiseasebyinhibitingoxidativestressmediatedsteatosisandapoptosisthroughnrf2areactivation |