Journal of Traditional Chinese Medicine ›› 2026, Vol. 46 ›› Issue (4): 788-797.DOI: 10.19852/j.cnki.jtcm.2026.04.002
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Berberine alleviates alcoholic liver disease via activating intestinal nuclear receptor subfamily 1 group D member 1
HUANG Yuwei1, CAI Yuting1, LI Zanjin1, WU Zicong1, GUO Lianxia1, LIN Luomin1, DONG Linlin3, WU Baojian1, DONG Dong2(
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Institute of Molecular Rhythm and Metabolism ,Guangzhou University of Chinese Medicine Guangzhou 510000, China
2Department of Public Health and Preventive Medicine ,School of Medicine, Jinan University Guangzhou 510632, China
3Hebei Geo-Environment Monitoring Institute Shijiazhuang 050021, China
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Received:2025-04-25Accepted:2025-10-15Online:2026-08-15Published:2026-08-08 -
Contact:Dr. DONG Dong, Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou 510632, China. dd2015@jnu.edu.cn,Telephone: +86-18617327324
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About author:HUANG Yuwei and CAI Yuting are co-first authors and contributed equally to this work -
Supported by:Project for Young Qihuang Scholars of the National Administration of Traditional Chinese Medicine;China Postdoctoral Science Foundation-Founded Project: Mechanism Study of Circadian Rhythm in Allergic Rhinitis(2024M760666);Scientific Research Platforms and Projects of Guangdong Higher Education Institutions-founded Project: Circadian Controlled Disease and Innovative Drug Investigation Team(2023KCXTD009)
Cite this article
HUANG Yuwei, CAI Yuting, LI Zanjin, WU Zicong, GUO Lianxia, LIN Luomin, DONG Linlin, WU Baojian, DONG Dong. Berberine alleviates alcoholic liver disease via activating intestinal nuclear receptor subfamily 1 group D member 1[J]. Journal of Traditional Chinese Medicine, 2026, 46(4): 788-797.
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Figure 1 Berberine attenuated both chronic and acute alcohol induced liver injury A: levels of Biochemical parameters in CD-fed, EtOH-fed and EtOH-fed+BBR mice (n = 10); A1: plasma ALT; A2: plasma TG; A3: plasma TC; hepatic TG. B: ORO and HE staining of liver tissues in Ctrl-fed, EtOH-fed and EtOH-fed + BBR mice (n = 3); B1: CD-fed group; B2: EtOH-fed group; B3: EtOH-fed + BBR group; B4: CD-fed group; B5: EtOH-fed group; B6: EtOH-fed + BBR group; CD-fed group: control diet; EtOH-fed group: ethanol-modified diet; EtOH-fed + BBR group: ethanol-modified diet + received BBR at a dose of 100 mg/kg by gavage once every day for 16 d; ALT: alanine transaminase; TG: triglyceride; TC: triglyceride; ORO: oil Red o; HE: hematoxylin-eosin; CD-fed: control diet; EtOH-fed: ethanol-modified diet; BBR: berberine. Statistical analyses were measured using one-way analysis of variance followed by post hoc Tukey correction for multiple comparisons. Data were presented as mean ± standard deviation. Compared with the CD-fed group, aP < 0.05; compared with the EtOH-fed group, bP < 0.05.
Figure 1 Berberine attenuated both chronic and acute alcohol induced liver injury A: levels of Biochemical parameters in CD-fed, EtOH-fed and EtOH-fed+BBR mice (n = 10); A1: plasma ALT; A2: plasma TG; A3: plasma TC; hepatic TG. B: ORO and HE staining of liver tissues in Ctrl-fed, EtOH-fed and EtOH-fed + BBR mice (n = 3); B1: CD-fed group; B2: EtOH-fed group; B3: EtOH-fed + BBR group; B4: CD-fed group; B5: EtOH-fed group; B6: EtOH-fed + BBR group; CD-fed group: control diet; EtOH-fed group: ethanol-modified diet; EtOH-fed + BBR group: ethanol-modified diet + received BBR at a dose of 100 mg/kg by gavage once every day for 16 d; ALT: alanine transaminase; TG: triglyceride; TC: triglyceride; ORO: oil Red o; HE: hematoxylin-eosin; CD-fed: control diet; EtOH-fed: ethanol-modified diet; BBR: berberine. Statistical analyses were measured using one-way analysis of variance followed by post hoc Tukey correction for multiple comparisons. Data were presented as mean ± standard deviation. Compared with the CD-fed group, aP < 0.05; compared with the EtOH-fed group, bP < 0.05.
Figure 2 Berberine modulated hepatic lipid metabolism via activating the intestinal REV-ERBα A: REV-ERBα and BMAL1 protein expression of CD-fed (1), EtOH-fed (2), and EtOH-fed + BBR (3) mice in the intestine; B: REV-ERBα and BMAL1 protein expression of CD-fed (1), EtOH-fed (2), and EtOH-fed + BBR (3) mice in the liver; C: Schematic diagram of intestinal REV-ERBα controls hepatic lipid metabolism; D: FADS2 protein expression of CD-fed (1), EtOH-fed (2), and EtOH-fed + BBR (3) mice in the intestine; E: SREBP-1c, ACACA, SCD1 and ELOVL6 protein expression of CD-fed (1), EtOH-fed (2), and EtOH-fed + BBR (3) mice in the liver; CD-fed group: control diet; EtOH-fed group: ethanol-modified diet; EtOH-fed + BBR group: ethanol-modified diet + received BBR at a dose of 100 mg/kg by gavage once every day for 16 d. REV-ERBα: nuclear receptor subfamily 1 group D member 1; BMAL1: aryl hydrocarbon receptor nuclear translocator-like; FADS2: fatty acid desaturase 2; SREBP-1c: sterol regulatory element-binding protein 1; ACACA: acetyl-coenzyme A carboxylase alpha; SCD1: stearoyl-coenzyme A desaturase 1; ELOVL6: elongation of long-chain fatty acids family member 6; CD-fed: control diet; EtOH-fed: ethanol-modified diet; BBR: berberine.
Figure 2 Berberine modulated hepatic lipid metabolism via activating the intestinal REV-ERBα A: REV-ERBα and BMAL1 protein expression of CD-fed (1), EtOH-fed (2), and EtOH-fed + BBR (3) mice in the intestine; B: REV-ERBα and BMAL1 protein expression of CD-fed (1), EtOH-fed (2), and EtOH-fed + BBR (3) mice in the liver; C: Schematic diagram of intestinal REV-ERBα controls hepatic lipid metabolism; D: FADS2 protein expression of CD-fed (1), EtOH-fed (2), and EtOH-fed + BBR (3) mice in the intestine; E: SREBP-1c, ACACA, SCD1 and ELOVL6 protein expression of CD-fed (1), EtOH-fed (2), and EtOH-fed + BBR (3) mice in the liver; CD-fed group: control diet; EtOH-fed group: ethanol-modified diet; EtOH-fed + BBR group: ethanol-modified diet + received BBR at a dose of 100 mg/kg by gavage once every day for 16 d. REV-ERBα: nuclear receptor subfamily 1 group D member 1; BMAL1: aryl hydrocarbon receptor nuclear translocator-like; FADS2: fatty acid desaturase 2; SREBP-1c: sterol regulatory element-binding protein 1; ACACA: acetyl-coenzyme A carboxylase alpha; SCD1: stearoyl-coenzyme A desaturase 1; ELOVL6: elongation of long-chain fatty acids family member 6; CD-fed: control diet; EtOH-fed: ethanol-modified diet; BBR: berberine.
Figure 3 Berberine’s protection effect on alcohol-induced liver injury was lost in Rev-erbα-iKO mice A: levels of biochemical parameters in Rev-erbα-flox-EtOH, Rev-erbα-flox-BBR, Rev-erbα-iKO-EtOH and Rev-erbα-iKO-BBR mice (n = 10); A1: plasma ALT; A2: plasma TG; A3: plasma TC; B: ORO and HE staining of liver tissues in Rev-erbα-flox-EtOH, Rev-erbα-flox-BBR, Rev-erbα-iKO-EtOH and Rev-erbα-iKO-BBR mice (n = 3); B1: Rev-erbα-flox-EtOH group; B2: Rev-erbα-flox-BBR group; B3: Rev-erbα-iKO-EtOH group; B4: Rev-erbα-iKO-BBR group; C: SREBP-1c, ACACA, SCD1 and ELOVL6 protein expression of Rev-erbα-flox-EtOH (1), Rev-erbα-flox-BBR (2), Rev-erbα-iKO-EtOH (3) and Rev-erbα-iKO-BBR (4) mice in the liver; D: levels of PUFAs in Rev-erbα-flox-EtOH, Rev-erbα-flox-BBR, Rev-erbα-iKO-EtOH and Rev-erbα-iKO-BBR mice (n = 3). Rev-erbα-flox-EtOH group: Rev-erbα-flox mice received EtOH at a dose of 6 g/kg by gavage once every day for 3 d; Rev-erbα-flox-BBR group: Rev-erbα-flox-EtOH group + received BBR at a dose of 300 mg/kg by gavage once every day for 6 d; Rev-erbα-iKO-EtOH group: Rev-erbα-iKO mice received EtOH at a dose of 6 g/kg by gavage once every day for 3 d; Rev-erbα-iKO-BBR group: Rev-erbα-iKO-EtOH group + received BBR at a dose of 300 mg/kg by gavage once every day for 6 d. Rev-erbα: nuclear receptor subfamily 1 group D member 1; ALT: alanine transaminase; TG: triglyceride; TC: triglyceride; ORO: oil Red o; SREBP-1c: sterol regulatory element-binding protein 1; ACACA: acetyl-coenzyme A carboxylase alpha; SCD1: stearoyl-coenzyme A desaturase 1; ELOVL6: elongation of long-chain fatty acids family member 6; EtOH: ethanol; iKO: intestinal epithelial cell conditional knockout; BBR: berberine. Statistical analyses were measured using two-way analysis of variance followed by post hoc Tukey correction for multiple comparisons. Data were presented as mean ± standard deviation. Compared with the Rev-erbα-flox-EtOH group, aP < 0.05.
Figure 3 Berberine’s protection effect on alcohol-induced liver injury was lost in Rev-erbα-iKO mice A: levels of biochemical parameters in Rev-erbα-flox-EtOH, Rev-erbα-flox-BBR, Rev-erbα-iKO-EtOH and Rev-erbα-iKO-BBR mice (n = 10); A1: plasma ALT; A2: plasma TG; A3: plasma TC; B: ORO and HE staining of liver tissues in Rev-erbα-flox-EtOH, Rev-erbα-flox-BBR, Rev-erbα-iKO-EtOH and Rev-erbα-iKO-BBR mice (n = 3); B1: Rev-erbα-flox-EtOH group; B2: Rev-erbα-flox-BBR group; B3: Rev-erbα-iKO-EtOH group; B4: Rev-erbα-iKO-BBR group; C: SREBP-1c, ACACA, SCD1 and ELOVL6 protein expression of Rev-erbα-flox-EtOH (1), Rev-erbα-flox-BBR (2), Rev-erbα-iKO-EtOH (3) and Rev-erbα-iKO-BBR (4) mice in the liver; D: levels of PUFAs in Rev-erbα-flox-EtOH, Rev-erbα-flox-BBR, Rev-erbα-iKO-EtOH and Rev-erbα-iKO-BBR mice (n = 3). Rev-erbα-flox-EtOH group: Rev-erbα-flox mice received EtOH at a dose of 6 g/kg by gavage once every day for 3 d; Rev-erbα-flox-BBR group: Rev-erbα-flox-EtOH group + received BBR at a dose of 300 mg/kg by gavage once every day for 6 d; Rev-erbα-iKO-EtOH group: Rev-erbα-iKO mice received EtOH at a dose of 6 g/kg by gavage once every day for 3 d; Rev-erbα-iKO-BBR group: Rev-erbα-iKO-EtOH group + received BBR at a dose of 300 mg/kg by gavage once every day for 6 d. Rev-erbα: nuclear receptor subfamily 1 group D member 1; ALT: alanine transaminase; TG: triglyceride; TC: triglyceride; ORO: oil Red o; SREBP-1c: sterol regulatory element-binding protein 1; ACACA: acetyl-coenzyme A carboxylase alpha; SCD1: stearoyl-coenzyme A desaturase 1; ELOVL6: elongation of long-chain fatty acids family member 6; EtOH: ethanol; iKO: intestinal epithelial cell conditional knockout; BBR: berberine. Statistical analyses were measured using two-way analysis of variance followed by post hoc Tukey correction for multiple comparisons. Data were presented as mean ± standard deviation. Compared with the Rev-erbα-flox-EtOH group, aP < 0.05.
Figure 4 Effect of berberine on alcohol-induced injury was dosing time dependent A: levels of biochemical parameters in ZT6-Ctrl, ZT6-EtOH, ZT18-Ctrl and ZT18-EtOH mice (n = 10); A1: plasma ALT; A2: plasma TG; A3: plasma TC; A4: hepatic TG; B: ORO and HE staining of liver tissues in ZT6-Ctrl, ZT6-EtOH, ZT18-Ctrl and ZT18-EtOH mice (n = 3); B1: ZT6-Ctrl group; B2: ZT6-EtOH group; B3: ZT18-Ctrl group; B4: ZT18-EtOH; B5: ZT6-Ctrl group; B6: ZT6-EtOH group; B7: ZT18-Ctrl group; B8: ZT18-EtOH group; C: levels of biochemical parameters in EtOH-Vehicle (ZT6), EtOH-BBR (ZT6), EtOH-Vehicle (ZT18) and EtOH-BBR (ZT18) mice (n = 10); EtOH-Vehicle (ZT6) group: EtOH group + received Vehicle by gavage at ZT6 for 6 d; EtOH-BBR (ZT6) group: EtOH group + received 300 mg/kg EtOH by gavage at ZT6 for 6 d; EtOH-Vehicle (ZT18) group: EtOH group + received Vehicle by gavage at ZT18 for 6 d; EtOH-BBR (ZT18) group: EtOH group + received 300 mg/kg EtOH by gavage at ZT18 for 6 d. ALT: alanine transaminase; ZT: zeitgeber time; TG: triglyceride; TC: triglyceride; ORO: oil Red o; HE: hematoxylin-eosin; EtOH: ethanol; BBR: berberine. Statistical analyses were measured using two-way analysis of variance followed by post hoc Tukey correction for multiple comparisons. Data were presented as mean ± standard deviation. Compared with the EtOH-Vehicle (ZT6) group, aP < 0.05; compared with the EtOH-Vehicle (ZT18) group, bP < 0.05.
Figure 4 Effect of berberine on alcohol-induced injury was dosing time dependent A: levels of biochemical parameters in ZT6-Ctrl, ZT6-EtOH, ZT18-Ctrl and ZT18-EtOH mice (n = 10); A1: plasma ALT; A2: plasma TG; A3: plasma TC; A4: hepatic TG; B: ORO and HE staining of liver tissues in ZT6-Ctrl, ZT6-EtOH, ZT18-Ctrl and ZT18-EtOH mice (n = 3); B1: ZT6-Ctrl group; B2: ZT6-EtOH group; B3: ZT18-Ctrl group; B4: ZT18-EtOH; B5: ZT6-Ctrl group; B6: ZT6-EtOH group; B7: ZT18-Ctrl group; B8: ZT18-EtOH group; C: levels of biochemical parameters in EtOH-Vehicle (ZT6), EtOH-BBR (ZT6), EtOH-Vehicle (ZT18) and EtOH-BBR (ZT18) mice (n = 10); EtOH-Vehicle (ZT6) group: EtOH group + received Vehicle by gavage at ZT6 for 6 d; EtOH-BBR (ZT6) group: EtOH group + received 300 mg/kg EtOH by gavage at ZT6 for 6 d; EtOH-Vehicle (ZT18) group: EtOH group + received Vehicle by gavage at ZT18 for 6 d; EtOH-BBR (ZT18) group: EtOH group + received 300 mg/kg EtOH by gavage at ZT18 for 6 d. ALT: alanine transaminase; ZT: zeitgeber time; TG: triglyceride; TC: triglyceride; ORO: oil Red o; HE: hematoxylin-eosin; EtOH: ethanol; BBR: berberine. Statistical analyses were measured using two-way analysis of variance followed by post hoc Tukey correction for multiple comparisons. Data were presented as mean ± standard deviation. Compared with the EtOH-Vehicle (ZT6) group, aP < 0.05; compared with the EtOH-Vehicle (ZT18) group, bP < 0.05.
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