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To explore the mechanism by which processed Radix Hedysari and vinegar-processed Rhizoma Curcumae inhibit angiogenesis in colitis-associated colorectal cancer (CAC).
Sixty SPF-grade C57BL/6J mice were randomly divided into six groups (A-F), A: Blank control; B: Model group [Azoxymethane (AOM)/Dextran sodium sulfate (DSS) AOM/DSS group]; C: Sulfasalazine group; D: Fried Astragalus group; E: Fried Astragalus-Vinegar Curcuma (4∶1) group; F: Curcuma zedoaria group. Each group contained 10 mice. A CAC mouse model was induced using combined AOM and DSS. Simultaneously, each treatment group received intervention, the blank group received 0.9% sodium chloride solution. The experiment concluded after 17 weeks of intervention. Collagen fiber area expression in colon tissues was assessed using Masson’s trichrome staining. Microvascular density in colon tissues was determined via immunohistochemistry. Serum vascular endothelial growth factor(VEGF) and nitric oxide(NO) levels were measured using enzyme linked immunosorbent assay(ELISA). Key proteins in the phosphatidylinositol-3-kinase/ protein kinase B(PI3K/AKT) pathway and VEGF expression were detected by Western blotting (WB).
After 17 weeks of pharmacological intervention, the microvessel counts in the blank group, model group, sulfasalazine group, honey-fried Radix Hedysari-vinegar-processed Rhizoma Curcumae (4:1) group, honey-fried Radix Hedysari group, and vinegar-processed Rhizoma Curcumae group were (23.20±4.21), (73.60±13.52), (44.80±2.78), (33.40±6.31), (41.60±3.36), and (47.80±7.29), respectively. The serum VEGF concentrations were (83.03±24.13), (153.61±18.69), (115.08±11.43), (87.03±25.24), (91.33±32.37), and (101.93±19.74) pg·mL-1, respectively. The serum NO levels were (28.46±5.91), (40.62±2.28), (30.62±6.54), (29.18±5.37), (30.87±5.30), and (32.29±3.43) μmol·L-1, respectively. Compared with the blank group, the model group exhibited significant increases in the collagen fiber staining area and microvessel density in colonic tissue, markedly elevated serum VEGF and NO levels, and significantly enhanced phosphorylation of PI3K, AKT, and mTOR as well as upregulated VEGF expression in colonic tissue. In comparison with the model group, the honey-fried Radix Hedysari-vinegar-processed Rhizoma Curcumae (4∶1) group, honey-fried Radix Hedysari group, and vinegar-processed Rhizoma Curcumae group demonstrated significant reductions in the collagen fiber area and microvessel count in colonic tissue, decreased serum VEGF and NO concentrations, and markedly suppressed phosphorylation of PI3K, AKT, and mTOR along with downregulated VEGF expression in colonic tissue (P<0.05 or P<0.01).
The combined use of processed Radix Hedysari and vinegar-processed Rhizoma Curcumae exerts a better anti-CAC effect than the single herb. Its mechanism is closely related to regulating the expressions of key proteins in the PI3K/AKT signaling pathway, thereby inhibiting angiogenesis in colitis-associated colorectal cancer.
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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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