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Outline
To explore the protective effects of metformin plus berberine against diabetes-induced cognitive dysfunction in db/db mice.
Mice were randomly divided into model, metformin, berberine, and metformin plus berberine (MB) groups. Db/m mice born in the same litter were used as the control group. Metformin (300 mg·kg-1) and berberine (135 mg·kg-1), either alone or in combination, were administered orally for 10 weeks. Body weight, blood glucose and related indices, and behavioral, oxidative stress-related, and inflammatory factor-related indexes of db/db mice were measured. Brain tissue sections were subjected to hematoxylin-eosin (HE) staining, and pathological changes were observed via light microscopy. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was used to observe changes in the levels of small molecules in the brain tissue.
Fasting blood glucose levels were significantly lower in the MB group than in the model, metformin, and berberine groups after 8 and 10 weeks of dosing. In the Morris water maze test, escape latency and time to find the platform from the contralateral quadrant were significantly shorter in the MB group than in the model group. The number of target crossings in 90 s and residence time in the target quadrant significantly increased in the metformin plus berberine group. According to ELISA, glycated hemoglobin, 8-hydroxydeoxyguanosine, protein carbonyl, tumor necrosis factor-α, NLRP3, and interleukin-1β levels were significantly lower in the MB group than in the model group, whereas interleukin-6 levels significantly increased. In HE staining experiments, compared with the model group, the neurons in the hippocampal region in the metformin plus berberine group were arranged neatly, with more complete shape, clear nuclear staining, and clear cell boundaries. In mass spectrometry imaging experiments, brain aspartate, N-acetyl-aspartate, and glutamate levels were significantly higher in the MB group than in the model group, whereas taurine and glucose levels significantly decreased.
Oral administration of MB has protective effects on diabetes-induced cognitive dysfunction and stronger effects than using either drug alone. The mechanism of action may be related to anti-inflammatory and antioxidative stress effects and increase in excitatory amino acids levels.
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| 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 |
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