This study aimed to investigate the hepatoprotective effects of the combination of berberine (BBR) and stachyose (Sta) in spontaneous type 2 diabetic KKAy mice. KKAy mice were randomly divided into four groups (n = 14 per group): Model control (model), stachyose (Sta, 200 mg·kg-1), berberine (BBR, 100 mg·kg-1), and BBR + Sta (100 mg·kg-1 BBR + 200 mg·kg-1 Sta), with oral gavage of water, Sta, BBR, and BBR + Sta respectively for eight weeks. At the end of the experiment, serum and liver tissues were collected, the liver weight was measured, and liver index was calculated. Lipid content and oxidative stress-related indicators in liver were measured. Meanwhile, the levels of lipid, transaminase, and oxidative stress in serum were determined. The expression levels of genes related to lipid metabolism and inflammation in the hepatic tissues were detected using qPCR. The number of macrophages in the liver tissues was measured by flow cytometry. Our findings revealed that the combination of BBR and Sta significantly reduced the liver index, decreased hepatic contents of triglyceride (TG), total cholesterol (TC), nitric oxide (NO), inducible nitric oxide synthase (iNOS), and malonaldehyde (MDA), improved liver histomorphology, attenuated lipid deposition, lowered serum lipids and alanine aminotransferase (ALT) levels, and suppressed the expression of lipid synthesis-related genes [fatty acid synthetase (Fasn), sterol regulatory element-binding protein 1c (Srebp1c)] and inflammation-related genes [interleukin-6 (Il-6), tumor necrosis factor-α (Tnf-α), monocyte chemoattractant protein-1 (Mcp-1)] in hepatic tissues. Furthermore, the combination treatment reduced the total number of hepatic macrophages (CD11b+F4/80+) and M1 macrophages (F4/80+CD11c+), and attenuated the antigen-presenting capacity of macrophages. Notably, BBR combined with Sta was superior to BBR alone in reducing blood lipids and inhibiting the expression of hepatic pro-inflammatory genes Il-6. However, no significant difference was observed between the two groups in alleviating hepatic macrophage infiltration and improving oxidative stress indicators. Collectively, the combination of BBR and Sta exerts anti-MASLD (metabolic dysfunction-associated steatotic liver disease) effects by ameliorating hepatic lipid accumulation, inflammation, and oxidative stress, as well as reducing macrophage number and weakening its function. Furthermore, the effects of the combination in improving MASLD are better than BBR alone. These findings suggest that BBR combined with Sta is a potential effective strategy for the treatment of MASLD. The animal experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College.
| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |