Jiangzhi granule attenuates non-alcoholic steatohepatitis through modulating bile acid in mice fed high-fat vitamin D deficiency diet
Vitamin D deficiency is a common phenomenon in non-alcoholic fatty liver disease (NAFLD) and the progressive non-alcoholic steatohepatitis (NASH). Jiangzhi Granule (JZG) formula is a Traditional Chinese medicine prescription, and has been found effective against NAFLD/NASH. Here we showed that vitam...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-05-01
|
| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S075333222200213X |
| _version_ | 1811299868325445632 |
|---|---|
| author | Ying Cao Xiangbing Shu Meng Li Siyu Yu Chunlin Li Guang Ji Li Zhang |
| author_facet | Ying Cao Xiangbing Shu Meng Li Siyu Yu Chunlin Li Guang Ji Li Zhang |
| author_sort | Ying Cao |
| collection | DOAJ |
| description | Vitamin D deficiency is a common phenomenon in non-alcoholic fatty liver disease (NAFLD) and the progressive non-alcoholic steatohepatitis (NASH). Jiangzhi Granule (JZG) formula is a Traditional Chinese medicine prescription, and has been found effective against NAFLD/NASH. Here we showed that vitamin D deficiency could accelerate NASH development, and reduce vitamin D receptor (VDR) expression. JZG treatment alleviated high-fat vitamin D deficient (HF-VDD) diet-induced NASH in C57BL/6 J mice, and up-regulated both the liver and intestinal VDR expression independent of 1,25-dihydroxy-vitamin D3 level. We analyzed the fecal BA profile using liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-TQMS) -based metabolomics, and found that JZG modulated fecal BA profile, predominantly increased the ratio of secondary BA species, as well as the expression of tight junction proteins Zona occludens 1(ZO-1) and occludin in the colon. In vitro experiment further confirmed the representative secondary BA species lithocholic acid (LCA) and keto-LCA upregulated the expression of and ZO-1 through VDR in LPS-stressed Caco-2 cells. Our results identified the endogenous VDR activation by JZG through modulating BA species in vitamin D deficiency-related NASH mice, thus providing evidence for the clinical application of JZG in treating NASH. |
| first_indexed | 2024-04-13T06:42:59Z |
| format | Article |
| id | doaj.art-798dce8a482b45a0bf823b4857fa5d0f |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-13T06:42:59Z |
| publishDate | 2022-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-798dce8a482b45a0bf823b4857fa5d0f2022-12-22T02:57:41ZengElsevierBiomedicine & Pharmacotherapy0753-33222022-05-01149112825Jiangzhi granule attenuates non-alcoholic steatohepatitis through modulating bile acid in mice fed high-fat vitamin D deficiency dietYing Cao0Xiangbing Shu1Meng Li2Siyu Yu3Chunlin Li4Guang Ji5Li Zhang6Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, ChinaDepartment of Geratology, Baoshan Branch of Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201999, ChinaInstitute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, ChinaInstitute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, ChinaInstitute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, ChinaInstitute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; Corresponding authors.Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; Corresponding authors.Vitamin D deficiency is a common phenomenon in non-alcoholic fatty liver disease (NAFLD) and the progressive non-alcoholic steatohepatitis (NASH). Jiangzhi Granule (JZG) formula is a Traditional Chinese medicine prescription, and has been found effective against NAFLD/NASH. Here we showed that vitamin D deficiency could accelerate NASH development, and reduce vitamin D receptor (VDR) expression. JZG treatment alleviated high-fat vitamin D deficient (HF-VDD) diet-induced NASH in C57BL/6 J mice, and up-regulated both the liver and intestinal VDR expression independent of 1,25-dihydroxy-vitamin D3 level. We analyzed the fecal BA profile using liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-TQMS) -based metabolomics, and found that JZG modulated fecal BA profile, predominantly increased the ratio of secondary BA species, as well as the expression of tight junction proteins Zona occludens 1(ZO-1) and occludin in the colon. In vitro experiment further confirmed the representative secondary BA species lithocholic acid (LCA) and keto-LCA upregulated the expression of and ZO-1 through VDR in LPS-stressed Caco-2 cells. Our results identified the endogenous VDR activation by JZG through modulating BA species in vitamin D deficiency-related NASH mice, thus providing evidence for the clinical application of JZG in treating NASH.http://www.sciencedirect.com/science/article/pii/S075333222200213XVitamin D deficiencyVitamin D receptorNon-alcoholic steatohepatitisTight junctionJiangzhi Granule |
| spellingShingle | Ying Cao Xiangbing Shu Meng Li Siyu Yu Chunlin Li Guang Ji Li Zhang Jiangzhi granule attenuates non-alcoholic steatohepatitis through modulating bile acid in mice fed high-fat vitamin D deficiency diet Biomedicine & Pharmacotherapy Vitamin D deficiency Vitamin D receptor Non-alcoholic steatohepatitis Tight junction Jiangzhi Granule |
| title | Jiangzhi granule attenuates non-alcoholic steatohepatitis through modulating bile acid in mice fed high-fat vitamin D deficiency diet |
| title_full | Jiangzhi granule attenuates non-alcoholic steatohepatitis through modulating bile acid in mice fed high-fat vitamin D deficiency diet |
| title_fullStr | Jiangzhi granule attenuates non-alcoholic steatohepatitis through modulating bile acid in mice fed high-fat vitamin D deficiency diet |
| title_full_unstemmed | Jiangzhi granule attenuates non-alcoholic steatohepatitis through modulating bile acid in mice fed high-fat vitamin D deficiency diet |
| title_short | Jiangzhi granule attenuates non-alcoholic steatohepatitis through modulating bile acid in mice fed high-fat vitamin D deficiency diet |
| title_sort | jiangzhi granule attenuates non alcoholic steatohepatitis through modulating bile acid in mice fed high fat vitamin d deficiency diet |
| topic | Vitamin D deficiency Vitamin D receptor Non-alcoholic steatohepatitis Tight junction Jiangzhi Granule |
| url | http://www.sciencedirect.com/science/article/pii/S075333222200213X |
| work_keys_str_mv | AT yingcao jiangzhigranuleattenuatesnonalcoholicsteatohepatitisthroughmodulatingbileacidinmicefedhighfatvitaminddeficiencydiet AT xiangbingshu jiangzhigranuleattenuatesnonalcoholicsteatohepatitisthroughmodulatingbileacidinmicefedhighfatvitaminddeficiencydiet AT mengli jiangzhigranuleattenuatesnonalcoholicsteatohepatitisthroughmodulatingbileacidinmicefedhighfatvitaminddeficiencydiet AT siyuyu jiangzhigranuleattenuatesnonalcoholicsteatohepatitisthroughmodulatingbileacidinmicefedhighfatvitaminddeficiencydiet AT chunlinli jiangzhigranuleattenuatesnonalcoholicsteatohepatitisthroughmodulatingbileacidinmicefedhighfatvitaminddeficiencydiet AT guangji jiangzhigranuleattenuatesnonalcoholicsteatohepatitisthroughmodulatingbileacidinmicefedhighfatvitaminddeficiencydiet AT lizhang jiangzhigranuleattenuatesnonalcoholicsteatohepatitisthroughmodulatingbileacidinmicefedhighfatvitaminddeficiencydiet |