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Xiaoke formula (XKF) is a classic formula for the treatment of insulin resistance (IR), but there is still unclear on bioactive equivalent combinatorial components (BECC) of XKF. In this study, based on the previous research of our team, three components, berberine, astragaloside Ⅳ and chlorogenic acid, were selected as the BECC of XKF, and their efficacy and mechanism were investigated. A high-fat diet-induced IR mouse model was used to detect blood glucose, insulin sensitivity, lipid metabolism, immune & inflammatory factors, etc., and staining of pathology sections was used to detect histopathological changes. Network pharmacology was used to predict the potential targets and signaling pathways of XKF and its BECC, and the results of the network were verified by Western blot. The animal welfare and experimental procedures followed the regulations of the Laboratory Animal Ethics Committee of Beijing MDKN Biotech Company (MDKN-2023-019). The results showed that BECC, which was composed of berberine, astragaloside Ⅳ and chlorogenic acid in the ratio of the original formula of XKF, was comparable to XKF in improving the glycemia, insulin sensitivity, histopathological damage, dyslipidemia, and immuno-inflammation in IR mice. The results of network pharmacology and Western blot suggested that the BECC of XKF and XKF might alleviate IR by promoting the activation of hepatic phosphatidylinositol 3-kinase (PI3K), phosphorylation of protein kinase B (AKT), and inhibiting the expression of glucose-6-phosphate phosphatase (G6PC) and phosphoenolpyruvate carboxykinase 1 (PCK1), the key limiting enzymes of hepatic gluconeogenesis. The above results suggest that berberine, astragaloside Ⅳ and chlorogenic acid can be used as the potential BECC of XKF to improve IR, and can regulate lipid metabolism, immuno-inflammation, and promote hepatic PI3K/AKT signaling to inhibit hepatic gluconeogenesis, regulate glucose homeostasis, and improve IR in mice.
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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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