Journal of Traditional Chinese Medicine ›› 2022, Vol. 42 ›› Issue (6): 940-947.DOI: 10.19852/j.cnki.jtcm.2022.06.007
• Research Articles • Previous Articles Next Articles
LI Xiaoling1, SUN Fengxia1(), SHANG Zimeng1, ZHANG Yingxue1, LI Jie1, ZHANG Qiuxiang2
Received:
2021-08-12
Accepted:
2021-11-27
Online:
2022-12-15
Published:
2022-11-01
Contact:
SUN Fengxia,SHANG Zimeng,ZHANG Yingxue,LI Jie,ZHANG Qiuxiang
About author:
Pro. SUN Fengxia, Infections Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, China. sunfengxia01969@163.com, Telephone: +86-10-87906608Supported by:
LI Xiaoling, SUN Fengxia, SHANG Zimeng, ZHANG Yingxue, LI Jie, ZHANG Qiuxiang. Effect of Dangfei Liganning capsule (当飞利肝宁胶囊) on liver X receptor α/steroid regulatory element binding protein-1/fatty acid synthase signal pathway in rats with metabolic- associated fatty liver disease[J]. Journal of Traditional Chinese Medicine, 2022, 42(6): 940-947.
Group | n | Week 0 | Week 2 | Week 4 | Week 6 | Week 8 |
---|---|---|---|---|---|---|
Normal | 8 | 218±7 | 318±8 | 405±5 | 502±4 | 578±8 |
Model | 8 | 218±6 | 324±5a | 421±3a | 524±7 | 602±7 |
Dangfei-L | 8 | 216±6 | 322±4a | 418±6a | 524±7 | 601±8 |
Dangfei-M | 8 | 220±6 | 323±4a | 419±4a | 522±6 | 601±8 |
Dangfei-H | 8 | 219±3 | 313±4b | 404±4b | 476±4c | 537±4c |
Essentiale | 8 | 217±7 | 317±11b | 414±6b | 516±7 | 578±4 |
Table 1 Changes in body weight of rats in each group (g, $\bar{x} \pm s$)
Group | n | Week 0 | Week 2 | Week 4 | Week 6 | Week 8 |
---|---|---|---|---|---|---|
Normal | 8 | 218±7 | 318±8 | 405±5 | 502±4 | 578±8 |
Model | 8 | 218±6 | 324±5a | 421±3a | 524±7 | 602±7 |
Dangfei-L | 8 | 216±6 | 322±4a | 418±6a | 524±7 | 601±8 |
Dangfei-M | 8 | 220±6 | 323±4a | 419±4a | 522±6 | 601±8 |
Dangfei-H | 8 | 219±3 | 313±4b | 404±4b | 476±4c | 537±4c |
Essentiale | 8 | 217±7 | 317±11b | 414±6b | 516±7 | 578±4 |
Group | n | TG (mmol/L) | CHO (mmol/L) | HDL-C (mmol/L) | LDL-C (mmol/L) | ALT (U/L) | AST (U/L) |
---|---|---|---|---|---|---|---|
Normal | 8 | 0.33±0.12 | 2.10±0.42 | 1.06±0.16 | 0.33±0.10 | 3.40±0.81 | 10.61±1.17 |
Model | 8 | 0.89±0.23a | 5.68±0.71a | 0.61±0.14a | 0.72±0.11a | 9.98±2.26a | 23.62±4.82a |
Dangfei-L | 8 | 0.95±0.26 | 5.61±0.71 | 0.58±0.12 | 0.69±0.11 | 9.71±2.18 | 22.43±4.53 |
Dangfei-M | 8 | 1.01±0.29 | 5.47±0.65 | 0.57±0.10 | 0.70±0.10 | 9.24±1.81 | 22.34±4.19 |
Dangfei-H | 8 | 0.55±0.19b | 3.93±1.07b | 0.81±0.13b | 0.41±0.10b | 4.81±0.21bc | 13.21±0.89bc |
Essentiale | 8 | 0.56±0.13b | 3.41±0.81b | 0.78±0.11b | 0.42±0.09b | 6.42±1.88b | 16.41±3.29b |
Table 2 Changes of liver function and blood lipids of rats in each group ($\bar{x} \pm s$)
Group | n | TG (mmol/L) | CHO (mmol/L) | HDL-C (mmol/L) | LDL-C (mmol/L) | ALT (U/L) | AST (U/L) |
---|---|---|---|---|---|---|---|
Normal | 8 | 0.33±0.12 | 2.10±0.42 | 1.06±0.16 | 0.33±0.10 | 3.40±0.81 | 10.61±1.17 |
Model | 8 | 0.89±0.23a | 5.68±0.71a | 0.61±0.14a | 0.72±0.11a | 9.98±2.26a | 23.62±4.82a |
Dangfei-L | 8 | 0.95±0.26 | 5.61±0.71 | 0.58±0.12 | 0.69±0.11 | 9.71±2.18 | 22.43±4.53 |
Dangfei-M | 8 | 1.01±0.29 | 5.47±0.65 | 0.57±0.10 | 0.70±0.10 | 9.24±1.81 | 22.34±4.19 |
Dangfei-H | 8 | 0.55±0.19b | 3.93±1.07b | 0.81±0.13b | 0.41±0.10b | 4.81±0.21bc | 13.21±0.89bc |
Essentiale | 8 | 0.56±0.13b | 3.41±0.81b | 0.78±0.11b | 0.42±0.09b | 6.42±1.88b | 16.41±3.29b |
Group | n | IL-6 | TNF-α |
---|---|---|---|
Normal | 8 | 0.94±0.80 | 2.40±0.96 |
Model | 8 | 7.88±3.07a | 6.63±0.91a |
Dangfei-L | 8 | 7.55±3.17 | 6.45±0.97 |
Dangfei-M | 8 | 7.66±1.19 | 5.98±1.04 |
Dangfei-H | 8 | 1.15±0.20b | 3.99±0.81b |
Essentiale | 8 | 1.64±0.55b | 4.44±1.38b |
Table 3 Changes in the levels of inflammatory factors in rats of each group (pg/mL, $\bar{x} \pm s$)
Group | n | IL-6 | TNF-α |
---|---|---|---|
Normal | 8 | 0.94±0.80 | 2.40±0.96 |
Model | 8 | 7.88±3.07a | 6.63±0.91a |
Dangfei-L | 8 | 7.55±3.17 | 6.45±0.97 |
Dangfei-M | 8 | 7.66±1.19 | 5.98±1.04 |
Dangfei-H | 8 | 1.15±0.20b | 3.99±0.81b |
Essentiale | 8 | 1.64±0.55b | 4.44±1.38b |
Group | n | TP | ALB | GLB |
---|---|---|---|---|
Normal | 8 | 61.4±2.7 | 33.0±2.0 | 28.4±1.2 |
Model | 8 | 74.5±1.8a | 33.2±0.7 | 41.3±1.7a |
Dangfei-L | 8 | 73.3±1.6 | 33.2±0.9 | 39.9±1.9 |
Dangfei-M | 8 | 73.7±0.9 | 33.4±0.8 | 40.3±1.3 |
Dangfei-H | 8 | 61.8±1.7bc | 33.4±0.8 | 28.6±1.8bc |
Essentiale | 8 | 64.4±2.9b | 33.3±0.9 | 31.1±3.4b |
Table 4 Changes of serum protein level in rats of each group (g/L, $\bar{x} \pm s$)
Group | n | TP | ALB | GLB |
---|---|---|---|---|
Normal | 8 | 61.4±2.7 | 33.0±2.0 | 28.4±1.2 |
Model | 8 | 74.5±1.8a | 33.2±0.7 | 41.3±1.7a |
Dangfei-L | 8 | 73.3±1.6 | 33.2±0.9 | 39.9±1.9 |
Dangfei-M | 8 | 73.7±0.9 | 33.4±0.8 | 40.3±1.3 |
Dangfei-H | 8 | 61.8±1.7bc | 33.4±0.8 | 28.6±1.8bc |
Essentiale | 8 | 64.4±2.9b | 33.3±0.9 | 31.1±3.4b |
Group | n | TBIL | DBIL |
---|---|---|---|
Normal | 8 | 2.08±0.12 | 0.49±0.06 |
Model | 8 | 6.05±0.34a | 1.51±0.07a |
Dangfei-L | 8 | 6.01±0.31 | 1.45±0.06 |
Dangfei-M | 8 | 5.82±0.11 | 1.51±0.06 |
Dangfei-H | 8 | 4.00±0.21bc | 0.99±0.08b |
Essentiale | 8 | 4.43±0.20b | 1.03±0.03b |
Table 5 Changes of serum bilirubin level in rats of each group (umol/L, $\bar{x} \pm s$)
Group | n | TBIL | DBIL |
---|---|---|---|
Normal | 8 | 2.08±0.12 | 0.49±0.06 |
Model | 8 | 6.05±0.34a | 1.51±0.07a |
Dangfei-L | 8 | 6.01±0.31 | 1.45±0.06 |
Dangfei-M | 8 | 5.82±0.11 | 1.51±0.06 |
Dangfei-H | 8 | 4.00±0.21bc | 0.99±0.08b |
Essentiale | 8 | 4.43±0.20b | 1.03±0.03b |
Group | n | IL-6 | TNF-α |
---|---|---|---|
Normal | 8 | 16.3±2.0 | 40.6±3.0 |
Model | 8 | 30.6±3.6 | 85.4±3.4 |
Dangfei-L | 8 | 29.3±3.0 | 84.7±5.5 |
Dangfei-M | 8 | 28.2±3.2 | 80.8±2.9 |
Dangfei-H | 8 | 18.8±2.4a | 52.4±2.7a |
Essentiale | 8 | 19.6±1.5 | 52.4±2.1 |
Table 6 Changes of inflammatory factors in liver tissue of rats in each group (pg/mL, $\bar{x} \pm s$)
Group | n | IL-6 | TNF-α |
---|---|---|---|
Normal | 8 | 16.3±2.0 | 40.6±3.0 |
Model | 8 | 30.6±3.6 | 85.4±3.4 |
Dangfei-L | 8 | 29.3±3.0 | 84.7±5.5 |
Dangfei-M | 8 | 28.2±3.2 | 80.8±2.9 |
Dangfei-H | 8 | 18.8±2.4a | 52.4±2.7a |
Essentiale | 8 | 19.6±1.5 | 52.4±2.1 |
Figure 1 Pathological changes in rat livers according to treatment (hematoxylin and eosin staining, × 200) A: liver pathology of normal rat after HE staining (× 200); B: liver pathology of model rat after HE staining (× 200); C: liver pathology of Dangfei Liganning low-dose group rat after HE staining (× 200); D: liver pathology of Dangfei Liganning middle-dose group rat after after HE staining (× 200); E: liver pathology of Dangfei Liganning high-dose group rat after HE staining (× 200); F: liver pathology of Essentiale group rat after HE staining (× 200); The arrow points to fat vacuoles. The normal group and the model group were given the same amount of distilled water by gavage; Dangfei Liganning low, medium and high-dose group was given Dangfei Liganning 0.0675, 0.135 and 0.27 g•kg-1•d-1 by gavage; Essentiale group was given Essentiale 0.123 g•kg-1•d-1 by gavage.
Figure 2 Pathological changes in rat livers according to treatment (Oil red O staining, × 200) A: liver pathology of normal rat after Oil red O staining (× 200); B: liver pathology of model rat after Oil red O staining (× 200); C: liver pathology of Dangfei Liganning low-dose group rat after Oil red O staining (× 200); D: liver pathology of Dangfei Liganning middle-dose group rat after Oil red O staining (× 200); E: liver pathology of Dangfei Liganning high-dose group rat after Oil red O staining (× 200); F: liver pathology of Essentiale group rat after Oil red O staining (× 200). The normal group and the model group were given the same amount of distilled water by gavage; Dangfei Liganning low, medium and high-dose group was given Dangfei Liganning 0.0675, 0.135 and 0.27 g·kg-1·d-1 by gavage; Essentiale group was given Essentiale 0.123 g·kg-1·d-1 by gavage.
Group | n | LXRα | SREBP-1 | FAS |
---|---|---|---|---|
Normal | 8 | 345872±52737 | 259409±71143 | 201684±48205 |
Model | 8 | 544998±55506a | 538701±62336a | 475218±78051a |
Dangfei-H | 8 | 423402±55463b | 383871±103496b | 397673±61834b |
Essentiale | 8 | 448588±104641b | 394167±158047b | 417853±84373b |
Table 7 Changes of LXR α, SREBP-1 and FAS protein in liver tissues of rats in each group detected by immunohistochemistry ($\bar{x} \pm s$)
Group | n | LXRα | SREBP-1 | FAS |
---|---|---|---|---|
Normal | 8 | 345872±52737 | 259409±71143 | 201684±48205 |
Model | 8 | 544998±55506a | 538701±62336a | 475218±78051a |
Dangfei-H | 8 | 423402±55463b | 383871±103496b | 397673±61834b |
Essentiale | 8 | 448588±104641b | 394167±158047b | 417853±84373b |
Figure 3 Expression levels of LXR α, SREBP-1 and FAS protein in each group (×400) A: normal group LXR α; B: model group LXR α; C: Dangfei Liganning high-dose group LXR α; D: Essentiale group LXR α; E: normal group SREBP-1; F: model group SREBP-1; G: Dangfei Liganning high-dose group SREBP-1; H: Essentiale group SREBP-1; I: normal group FAS; J: model group FAS; K: Dangfei Liganning high-dose group FAS; L: Essentiale group FAS. The normal group and the model group were given the same amount of distilled water by gavage; Dangfei Liganning low, medium and high-dose group was given Dangfei Liganning 0.0675, 0.135 and 0.27 g·kg-1·d-1 by gavage; Essentiale group was given Essentiale 0.123 g·kg-1·d-1 by gavage. LXR α: liver X receptor α; SREBP-1: steroid regulatory element binding protein-1; FAS: fatty acid synthase.
Figure 4 Expression levels of LXRα, SREBP-1, FAS protein in each group 1: normal group; 2: model group; 3: Dangfei Liganning high-dose group; 4: essentiale group. The normal group and the model group were given the same amount of distilled water by gavage; Dangfei Liganning high-dose group was given Dangfei Liganning 0.27 g·kg-1·d-1 by gavage; Essentiale group was given Essentiale 0.123 g·kg-1·d-1 by gavage. LXR α: liver X receptor α; SREBP-1: steroid regulatory element binding protein-1; FAS: fatty acid synthase; GAPDH: glyceraldehyde-3-phosphate dehy-drogenase.
Group | n | LXRα | SREBP-1 | FAS |
---|---|---|---|---|
Normal | 8 | 0.79±0.28 | 0.42±0.11 | 0.43±0.12 |
Model | 8 | 1.51±0.19a | 1.14±0.45a | 1.10±0.40a |
Dangfei-H | 8 | 0.99±0.21b | 0.82±0.18b | 0.76±0.22b |
Essentiale | 8 | 1.09±0.35b | 0.83±0.20b | 0.79±0.27b |
Table 8 Changes of LXR α, SREBP-1 and FAS protein in liver tissues of rats in each group detected by Western Blot (pg/mL, $\bar{x} \pm s$)
Group | n | LXRα | SREBP-1 | FAS |
---|---|---|---|---|
Normal | 8 | 0.79±0.28 | 0.42±0.11 | 0.43±0.12 |
Model | 8 | 1.51±0.19a | 1.14±0.45a | 1.10±0.40a |
Dangfei-H | 8 | 0.99±0.21b | 0.82±0.18b | 0.76±0.22b |
Essentiale | 8 | 1.09±0.35b | 0.83±0.20b | 0.79±0.27b |
Group | n | LXRα | SREBP-1 | FAS |
---|---|---|---|---|
Normal | 8 | 1.14±0.41 | 1.52±0.51 | 1.42±0.49 |
Model | 8 | 4.29±0.52a | 6.13±1.17a | 4.35±1.97a |
Dangfei-H | 8 | 2.27±0.21b | 3.32±1.52b | 2.30±0.88b |
Essentiale | 8 | 2.25±0.34b | 2.64±1.97b | 2.61±1.81b |
Table 9 Changes of LXR α, SREBP-1 and FAS mRNA in liver tissues of rats in each group ($\bar{x} \pm s$)
Group | n | LXRα | SREBP-1 | FAS |
---|---|---|---|---|
Normal | 8 | 1.14±0.41 | 1.52±0.51 | 1.42±0.49 |
Model | 8 | 4.29±0.52a | 6.13±1.17a | 4.35±1.97a |
Dangfei-H | 8 | 2.27±0.21b | 3.32±1.52b | 2.30±0.88b |
Essentiale | 8 | 2.25±0.34b | 2.64±1.97b | 2.61±1.81b |
[1] | Gao X. New thoughts about renaming nonalcoholic fatty liver disease. Lin Chuang Gan Gan Bing Za Zhi 2020; 36: 1201-4. |
[2] | Wu J, Peng YZ. Efficacy of Dangfei Liganning capsule in nonalcoholic fatty liver disease. Shi Yong Lin Chuang Yi Xue 2018; 19: 4-6. |
[3] | Hong HW, Zhao XW, Zhang SM, et al. Clinical observation on Dangfei Liganning Capsule combined with Chinese herbal tea in treating 37 cases of non-alcoholic fatty liver with liver constraint and spleen deficiency and damp-heat accumulation syndrome. J Tradit Chin Med 2018; 59: 227-30. |
[4] | Alba B, Esther GJ, Jose AP et al. Molecular pathways in nonalcoholic fatty liver disease. Clin Exp Gastroenterol 2014; 7: 221-239. |
[5] |
Liu Y, Qiu de K, Ma X. Liver X receptors bridge hepatic lipid metabolism and inflammation. J Dig Dis 2012; 13: 69-74.
DOI URL |
[6] |
Chen G, Liang G, Ou J, et al. Central role for liver X receptor in insulinmediated activation of Srebp-1c transcription and stimulation of fatty acid synthesis in liver. Proc Natl Acad Sci USA 2004; 101: 11245-50.
DOI URL |
[7] |
Victoria J, Yongyong H, Miwon A, et al. Impact of silencing hepatic SREBP-1 on insulin signaling. PLoS One 2018; 13: e0196704.
DOI URL |
[8] | Chen LR, Zhang LP, Liu Y, et al. Effects of Chaiqi Tang on expression of SREBP-1c in rats with nonalcoholic fatty liver disease. Xi Bu Zhong Yi Yao 2016; 29: 13-7. |
[9] |
Christian VL, Stefanie L, Frank NR, et al. The human longevity gene homolog INDY and interleukin-6 interact in hepatic lipid metabolism. Hepatology 2017, 66: 616-30.
DOI PMID |
[10] |
Nati M, Haddad D, Birkenfeld A L, et al. The role of immune cells in metabolism-related liver inflammation and development of non-alcoholic steatohepatitis (NASH). Rev Endocr Metab Dis 2016; 17: 29-39.
DOI URL |
[11] | Zhang LP. Efficacy and safety of Tiopronin sodium combined with Shenxiong glucose injection in the treatment of fatty liver. Lin Chuang He Li Yong Yao Za Zhi 2021; 14: 67-9. |
[12] | Tang WJ, Yao YF, Yin JJ, et al. Effect of Huganqingzhi tablet on protein synthesis and bile metabolism in liver of Steatosis rats. Chinese Materia Medica 2014; 37: 1452-4. |
[13] |
Mitro N, Mak PA, Vargas L, et al. The nuclear receptor LXR is a glucose sensor. Nature 2007; 445: 219-23.
DOI URL |
[14] |
Yan CX, Zhang YR, Zhang XX, et al. Curcumin regulates endogenous and exogenous metabolism via Nrf2-FXR-LXR pathway in NAFLD mice. Biomed. Pharmacother 2018; 105: 274-81.
DOI URL |
[15] |
Pan YX, Zhuo MQ, Li DD, et al. SREBP-1 and LXRα pathways mediated Cu-induced hepatic lipid metabolism in zebrafish Danio rerio. Chemosphere 2019; 215: 370-9.
DOI URL |
[16] |
Yvan G, Nicolas D, Vanessa B, et al. Regulation of SREBP-1 expression and transcriptional action on HKII and FAS genes during fasting and refeeding in rat tissues. J Lipid Res 2005; 46: 697-705.
DOI PMID |
[17] |
Young AM. The SCAP/SREBP pathway: a mediator of hepatic steatosis. Endocrinol Metab 2017; 32: 6-10.
DOI URL |
[18] |
Shi L J, Shi L, Song GY, et al. Oxymatrine attenuates hepatic steatosis in non-alcoholic fatty liver disease rats fed with high fructose diet through inhibition of sterol regulatory element binding transcription factor 1 (Srebf1) and activation of peroxisome proliferator activated receptor alpha (Pparα). Eur J Pharmacol 2013; 714: 89-95.
DOI URL |
[19] |
Yang ZX, Shen W, Sun H. Effects of nuclear receptor FXR on the regulation of liver lipid metabolism in patients with non-alcoholic fatty liver disease. Hepatol Int 2010; 4: 741-8.
DOI URL |
[20] | Chen LR. Clinical retrospective study of youth non-alcoholic fatty liver disease and study of the mechanism of Chaiqi decoction on fatty liver in rats. Beijing: Beijing University of Chinese Medicine, 2017: 62-121. |
Viewed | ||||||
Full text |
|
|||||
Abstract |
|
|||||
Sponsored by China Association of Chinese Medicine
& China Academy of Chinese Medical Sciences
16 Nanxiaojie, Dongzhimen Nei, Beijing, China. 100700 Email: jtcmen@126.com
Copyright 2020 Journal of Traditional Chinese Medicine. All rights reserved.