Traditional Chinese medicine Lingguizhugan decoction ameliorate HFD-induced hepatic-lipid deposition in mice by inhibiting STING-mediated inflammation in macrophages
Abstract Background Stimulator of IFN genes (STING) is highly expressed in the livers of non-alcoholic fatty liver disease (NAFLD) patients and high fat diet (HFD) induced NAFLD mice model. The STING signaling-mediated inflammation has been shown to play a critical role in metabolic disorders. Lingg...
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| Format: | Article |
| Language: | English |
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BMC
2022-01-01
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| Series: | Chinese Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13020-021-00559-3 |
| _version_ | 1830372336960798720 |
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| author | Lin Cao Erjin Xu Rendong Zheng Zhili Zhangchen Rongling Zhong Fei Huang Juan Ye Hongping Sun Yaofu Fan Shaofeng Xie Yu Chen Yijiao Xu Jing Cao Wen Cao Chao Liu |
| author_facet | Lin Cao Erjin Xu Rendong Zheng Zhili Zhangchen Rongling Zhong Fei Huang Juan Ye Hongping Sun Yaofu Fan Shaofeng Xie Yu Chen Yijiao Xu Jing Cao Wen Cao Chao Liu |
| author_sort | Lin Cao |
| collection | DOAJ |
| description | Abstract Background Stimulator of IFN genes (STING) is highly expressed in the livers of non-alcoholic fatty liver disease (NAFLD) patients and high fat diet (HFD) induced NAFLD mice model. The STING signaling-mediated inflammation has been shown to play a critical role in metabolic disorders. Lingguizhugan decoction (LGZG), a Traditional Chinese herbal decoction, has been applied to treat metabolic disorders for many years. However, whether LGZG can alleviate the progression of NAFLD through inhibiting inflammation remains unclear. This study was to determine the role of STING-mediated inflammation in the HFD-induced hepatic-lipid deposition treated with LGZG. Methods The anti-inflammatory and anti-steatotic effects of LGZG in vivo were detected by H&E staining, immunofluorescence and immuno-chemistry. Mice bone-marrow-derived macrophages (BMDMs) and primary liver macrophages were treated with STING-specific agonist (DMXAA), LGZG and its critical components respectively. The treated culture supernatant of BMDMs and primary liver macrophages from each group was co-cultured with palmitic acid-treated mouse primary hepatocytes or mouse liver cell line AML-12 respectively to detect whether the activation of STING-mediated pathway is involved in the anti-steatotic effect of LGZG. The hepatocyte lipid deposition in vivo and in vitro were detected by oil red staining. Mitochondrial DNA release of mouse liver extracts were detected by real time PCR. The expression of proteins and inflammatory cytokines related to STING-TBK1-NF-κB pathway was detected by western blotting and ELISA. Results LGZG significantly ameliorated HFD induced hepatic steatosis, oxidative stress, hepatic mitochondrial damage and mitochondrial DNA release, which was correlated with reduction of the expression level of STING as well as the infiltration of STING-positive macrophages in the livers of HFD fed mice. The critical components of LGZG directly inhibited the activation of STING-TBK1-NF-κB pathway in liver macrophages induced by DMXAA, LPS, thereby reducing the release of IFNβ and TNFα. Co-incubating the culture supernatant of LGZG treated liver macrophages and PA-stimulated hepatocytes significantly inhibited the PA-induced lipid deposition. Conclusion This study demonstrates that LGZG can ameliorate HFD-induced hepatic-lipid deposition through inhibiting STING-TBK1-NF-κB pathway in liver macrophages, which provides novel insight for elucidating the molecular mechanism of LGZG alleviating HFD induced hepatic steatosis. |
| first_indexed | 2024-12-20T07:01:09Z |
| format | Article |
| id | doaj.art-fb588b0ee38240ac86081d10a8b0f00e |
| institution | Directory Open Access Journal |
| issn | 1749-8546 |
| language | English |
| last_indexed | 2024-12-20T07:01:09Z |
| publishDate | 2022-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Chinese Medicine |
| spelling | doaj.art-fb588b0ee38240ac86081d10a8b0f00e2022-12-21T19:49:13ZengBMCChinese Medicine1749-85462022-01-0117111610.1186/s13020-021-00559-3Traditional Chinese medicine Lingguizhugan decoction ameliorate HFD-induced hepatic-lipid deposition in mice by inhibiting STING-mediated inflammation in macrophagesLin Cao0Erjin Xu1Rendong Zheng2Zhili Zhangchen3Rongling Zhong4Fei Huang5Juan Ye6Hongping Sun7Yaofu Fan8Shaofeng Xie9Yu Chen10Yijiao Xu11Jing Cao12Wen Cao13Chao Liu14Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese MedicineAffiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese MedicineAffiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese MedicineAffiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese MedicineAffiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese MedicineSuzhou Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese MedicineAffiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese MedicineAffiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese MedicineAffiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese MedicineAffiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese MedicineAffiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese MedicineAffiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese MedicineAffiliated Hospital of Nanjing University of Chinese MedicineThe Affiliated Jiangning Hospital of Nanjing Medical UniversityAffiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese MedicineAbstract Background Stimulator of IFN genes (STING) is highly expressed in the livers of non-alcoholic fatty liver disease (NAFLD) patients and high fat diet (HFD) induced NAFLD mice model. The STING signaling-mediated inflammation has been shown to play a critical role in metabolic disorders. Lingguizhugan decoction (LGZG), a Traditional Chinese herbal decoction, has been applied to treat metabolic disorders for many years. However, whether LGZG can alleviate the progression of NAFLD through inhibiting inflammation remains unclear. This study was to determine the role of STING-mediated inflammation in the HFD-induced hepatic-lipid deposition treated with LGZG. Methods The anti-inflammatory and anti-steatotic effects of LGZG in vivo were detected by H&E staining, immunofluorescence and immuno-chemistry. Mice bone-marrow-derived macrophages (BMDMs) and primary liver macrophages were treated with STING-specific agonist (DMXAA), LGZG and its critical components respectively. The treated culture supernatant of BMDMs and primary liver macrophages from each group was co-cultured with palmitic acid-treated mouse primary hepatocytes or mouse liver cell line AML-12 respectively to detect whether the activation of STING-mediated pathway is involved in the anti-steatotic effect of LGZG. The hepatocyte lipid deposition in vivo and in vitro were detected by oil red staining. Mitochondrial DNA release of mouse liver extracts were detected by real time PCR. The expression of proteins and inflammatory cytokines related to STING-TBK1-NF-κB pathway was detected by western blotting and ELISA. Results LGZG significantly ameliorated HFD induced hepatic steatosis, oxidative stress, hepatic mitochondrial damage and mitochondrial DNA release, which was correlated with reduction of the expression level of STING as well as the infiltration of STING-positive macrophages in the livers of HFD fed mice. The critical components of LGZG directly inhibited the activation of STING-TBK1-NF-κB pathway in liver macrophages induced by DMXAA, LPS, thereby reducing the release of IFNβ and TNFα. Co-incubating the culture supernatant of LGZG treated liver macrophages and PA-stimulated hepatocytes significantly inhibited the PA-induced lipid deposition. Conclusion This study demonstrates that LGZG can ameliorate HFD-induced hepatic-lipid deposition through inhibiting STING-TBK1-NF-κB pathway in liver macrophages, which provides novel insight for elucidating the molecular mechanism of LGZG alleviating HFD induced hepatic steatosis.https://doi.org/10.1186/s13020-021-00559-3Lingguizhugan decoction (LGZG)Hepatic steatosisSTINGInflammation |
| spellingShingle | Lin Cao Erjin Xu Rendong Zheng Zhili Zhangchen Rongling Zhong Fei Huang Juan Ye Hongping Sun Yaofu Fan Shaofeng Xie Yu Chen Yijiao Xu Jing Cao Wen Cao Chao Liu Traditional Chinese medicine Lingguizhugan decoction ameliorate HFD-induced hepatic-lipid deposition in mice by inhibiting STING-mediated inflammation in macrophages Chinese Medicine Lingguizhugan decoction (LGZG) Hepatic steatosis STING Inflammation |
| title | Traditional Chinese medicine Lingguizhugan decoction ameliorate HFD-induced hepatic-lipid deposition in mice by inhibiting STING-mediated inflammation in macrophages |
| title_full | Traditional Chinese medicine Lingguizhugan decoction ameliorate HFD-induced hepatic-lipid deposition in mice by inhibiting STING-mediated inflammation in macrophages |
| title_fullStr | Traditional Chinese medicine Lingguizhugan decoction ameliorate HFD-induced hepatic-lipid deposition in mice by inhibiting STING-mediated inflammation in macrophages |
| title_full_unstemmed | Traditional Chinese medicine Lingguizhugan decoction ameliorate HFD-induced hepatic-lipid deposition in mice by inhibiting STING-mediated inflammation in macrophages |
| title_short | Traditional Chinese medicine Lingguizhugan decoction ameliorate HFD-induced hepatic-lipid deposition in mice by inhibiting STING-mediated inflammation in macrophages |
| title_sort | traditional chinese medicine lingguizhugan decoction ameliorate hfd induced hepatic lipid deposition in mice by inhibiting sting mediated inflammation in macrophages |
| topic | Lingguizhugan decoction (LGZG) Hepatic steatosis STING Inflammation |
| url | https://doi.org/10.1186/s13020-021-00559-3 |
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