Hugan Qingzhi tablets attenuates endoplasmic reticulum stress in nonalcoholic fatty liver disease rats by regulating PERK and ATF6 pathways
Abstract Background Endoplasmic reticulum (ER) stress, promoting lipid metabolism disorders and steatohepatitis, contributes significantly to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Hugan Qingzhi tablets (HQT) has a definite effect in the clinical treatment of NAFLD patients, b...
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | BMC Complementary Medicine and Therapies |
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| Online Access: | https://doi.org/10.1186/s12906-024-04336-1 |
| _version_ | 1827382421263220736 |
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| author | Miaoting Yang Xiaorui Yao Fan Xia Shijian Xiang Waijiao Tang Benjie Zhou |
| author_facet | Miaoting Yang Xiaorui Yao Fan Xia Shijian Xiang Waijiao Tang Benjie Zhou |
| author_sort | Miaoting Yang |
| collection | DOAJ |
| description | Abstract Background Endoplasmic reticulum (ER) stress, promoting lipid metabolism disorders and steatohepatitis, contributes significantly to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Hugan Qingzhi tablets (HQT) has a definite effect in the clinical treatment of NAFLD patients, but its mechanism is still unclear. This study aims to investigate the effects of HQT on ER stress in the liver tissues of NAFLD rats and explore the underlying mechanism. Methods The NAFLD rat model was managed with high-fat diet (HFD) for 12weeks. HQT was administrated in a daily basis to the HFD groups. Biochemical markers, pro-inflammatory cytokines, liver histology were assayed to evaluate HQT effects in HFD-induced NAFLD rats. Furthermore, the expression of ER stress-related signal molecules including glucose regulating protein 78 (GRP78), protein kinase RNA-like endoplasmic reticulum kinase (PERK), p-PERK, eukaryotic translation initiation factor 2α (EIF2α), p-EIF2α, activating transcription factor 4 (ATF4), acetyl-coenzyme A-carboxylase (ACC), activating transcription factor (ATF6), and nuclear factor-kappa B-p65 (NF-κB-p65) were detected by western blot and/or qRT-PCR. Results The histopathological characteristics and biochemical data indicated that HQT exhibited protective effects on HFD-induced NAFLD rats. Furthermore, it caused significant reduction in the expression of ERS markers, such as GRP78, PERK, p-PERK, and ATF6, and subsequently downregulated the expression of EIF2α, p-EIF2α ATF4, ACC, and NF-κB-p65. Conclusions The results suggested that HQT has protective effect against hepatic steatosis and inflammation in NAFLD rats by attenuating ER stress, and the potential mechanism is through inhibition of PERK and ATF6 pathways. |
| first_indexed | 2024-03-08T14:19:23Z |
| format | Article |
| id | doaj.art-a041cfa7af644588afee60bf6564ef6e |
| institution | Directory Open Access Journal |
| issn | 2662-7671 |
| language | English |
| last_indexed | 2024-03-08T14:19:23Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Complementary Medicine and Therapies |
| spelling | doaj.art-a041cfa7af644588afee60bf6564ef6e2024-01-14T12:11:44ZengBMCBMC Complementary Medicine and Therapies2662-76712024-01-0124111110.1186/s12906-024-04336-1Hugan Qingzhi tablets attenuates endoplasmic reticulum stress in nonalcoholic fatty liver disease rats by regulating PERK and ATF6 pathwaysMiaoting Yang0Xiaorui Yao1Fan Xia2Shijian Xiang3Waijiao Tang4Benjie Zhou5Department of Pharmacy, People’s Hospital of LonghuaDepartment of Pharmacy, Shantou Central HospitalDepartment of Pharmacy, the Seventh Affiliated Hospital, Sun Yat-sen UniversityDepartment of Pharmacy, the Seventh Affiliated Hospital, Sun Yat-sen UniversityZhujiang Hospital, Southern Medical UniversityDepartment of Pharmacy, the Seventh Affiliated Hospital, Sun Yat-sen UniversityAbstract Background Endoplasmic reticulum (ER) stress, promoting lipid metabolism disorders and steatohepatitis, contributes significantly to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Hugan Qingzhi tablets (HQT) has a definite effect in the clinical treatment of NAFLD patients, but its mechanism is still unclear. This study aims to investigate the effects of HQT on ER stress in the liver tissues of NAFLD rats and explore the underlying mechanism. Methods The NAFLD rat model was managed with high-fat diet (HFD) for 12weeks. HQT was administrated in a daily basis to the HFD groups. Biochemical markers, pro-inflammatory cytokines, liver histology were assayed to evaluate HQT effects in HFD-induced NAFLD rats. Furthermore, the expression of ER stress-related signal molecules including glucose regulating protein 78 (GRP78), protein kinase RNA-like endoplasmic reticulum kinase (PERK), p-PERK, eukaryotic translation initiation factor 2α (EIF2α), p-EIF2α, activating transcription factor 4 (ATF4), acetyl-coenzyme A-carboxylase (ACC), activating transcription factor (ATF6), and nuclear factor-kappa B-p65 (NF-κB-p65) were detected by western blot and/or qRT-PCR. Results The histopathological characteristics and biochemical data indicated that HQT exhibited protective effects on HFD-induced NAFLD rats. Furthermore, it caused significant reduction in the expression of ERS markers, such as GRP78, PERK, p-PERK, and ATF6, and subsequently downregulated the expression of EIF2α, p-EIF2α ATF4, ACC, and NF-κB-p65. Conclusions The results suggested that HQT has protective effect against hepatic steatosis and inflammation in NAFLD rats by attenuating ER stress, and the potential mechanism is through inhibition of PERK and ATF6 pathways.https://doi.org/10.1186/s12906-024-04336-1Chinese traditional medicineHugan Qingzhi tablets (HQT)Non-alcoholic fatty liver disease (NAFLD)Hepatoprotective effectEndoplasmic reticulum stress (ERS) pathway |
| spellingShingle | Miaoting Yang Xiaorui Yao Fan Xia Shijian Xiang Waijiao Tang Benjie Zhou Hugan Qingzhi tablets attenuates endoplasmic reticulum stress in nonalcoholic fatty liver disease rats by regulating PERK and ATF6 pathways BMC Complementary Medicine and Therapies Chinese traditional medicine Hugan Qingzhi tablets (HQT) Non-alcoholic fatty liver disease (NAFLD) Hepatoprotective effect Endoplasmic reticulum stress (ERS) pathway |
| title | Hugan Qingzhi tablets attenuates endoplasmic reticulum stress in nonalcoholic fatty liver disease rats by regulating PERK and ATF6 pathways |
| title_full | Hugan Qingzhi tablets attenuates endoplasmic reticulum stress in nonalcoholic fatty liver disease rats by regulating PERK and ATF6 pathways |
| title_fullStr | Hugan Qingzhi tablets attenuates endoplasmic reticulum stress in nonalcoholic fatty liver disease rats by regulating PERK and ATF6 pathways |
| title_full_unstemmed | Hugan Qingzhi tablets attenuates endoplasmic reticulum stress in nonalcoholic fatty liver disease rats by regulating PERK and ATF6 pathways |
| title_short | Hugan Qingzhi tablets attenuates endoplasmic reticulum stress in nonalcoholic fatty liver disease rats by regulating PERK and ATF6 pathways |
| title_sort | hugan qingzhi tablets attenuates endoplasmic reticulum stress in nonalcoholic fatty liver disease rats by regulating perk and atf6 pathways |
| topic | Chinese traditional medicine Hugan Qingzhi tablets (HQT) Non-alcoholic fatty liver disease (NAFLD) Hepatoprotective effect Endoplasmic reticulum stress (ERS) pathway |
| url | https://doi.org/10.1186/s12906-024-04336-1 |
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