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To investigate the mechanism of Banxia-Huanglian (BX-HL) in improving diabetic gastroparesis based on dopaminergic synaptic pathway.
The possible signaling pathways of BX-HL on the treatment of diabetic gastroparesis (DGP) were carried out by network pharmacology methods. The DGP model was constructed by intraperitoneal injection of 60 mg·kg-1 streptozotocin (STZ) + high-sugar and high-fat diet. The DGP rats were randomly divided into model group and experimental group, with 10 rats in each group; another 10 normal rats were taken as the normal group. The experimental group was administered by gavage with BX-HL solution at a dose of 1.35 g·kg·d-1, while the normal group and model group were administered by gavage with an equal volume of 0.9% NaCl once a day. The rats in the three groups were administered once a day for 21 days. The gastric emptying rate and intestinal propulsion rate of rats were measured by activated charcoal administration, the levels of neurotransmitter dopamine (DA) in brain tissues were determined by enzyme-linked immunosorbent assay, and the expression levels of protein kinase B (Akt) and glycogen synthase kinase-3 (GSK-3) proteins in brain tissues were determined by Western blotting.
The effective components and corresponding signaling pathways, such as dopaminergic synapses, were screened by various databases for BX-HL on the treatment of diabetic gastroparesis. The fasting blood glucose levels in the normal group, model group and experimental group were (5.61±0.36), (23.40±1.58) and (6.18±0.42) mmol·L-1; the gastric emptying rates were (71.33±1.23)%, (35.43±3.12)% and (61.59±4.66)%; the intestinal transit rates were (53.19±3.48)%, (29.33±1.91)% and (38.53±2.80)%; the DA contents in brain tissue were (42.43±2.97), (88.20±8.46) and (52.64±5.03) pmol·L-1; the relative protein expression levels of Akt were 0.67±0.00, 1.35±0.04 and 0.94±0.01; the relative protein expression levels of GSK-3 were 0.96±0.01, 1.24±0.05 and 0.91±0.01, respectively. The above indexes of the experimental group showed statistical significance compared to the model group (all P<0.001).
BX-HL has an ameliorative effect on diabetic gastroparesis in rats, which is mainly reflected in the lowering of blood glucose, the promotion of gastric emptying and intestinal propulsion, the reduction of neurotransmitter DA level, its mechanism may be related to inhibite the Akt/GSK-3 protein expression of dopaminergic synaptic pathway.
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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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