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Huanglian Jiedu Decoction (HLJDT) is a classic fever-clearing detoxification prescription, with clear clinical evidence to support its anti-tumor activity. However, its effect on melanoma metastasis and its potential molecular mechanism have not been systematically clarified. In this study, network pharmacology is used to predict the potential active components, therapeutic targets and key signaling pathways of HLJDT that may have an anti-melanoma transfer effect. Based on these findings, a mouse melanoma lung metastasis model was established, and in vivo and in vitro experiments were carried out to verify the anti-transfer effect of HLJDT and explore its potential mechanism. The results show that network pharmacology analysis indicates that HLJDT contains multiple potential anti-melanoma active ingredients and may exert a synergistic anti-tumor effect by regulating multiple key signaling pathways, including cancer-related pathways and JAK-STAT pathways. In vivo experiments showed that HLJDT significantly inhibited melanoma lung metastasis, reduced the number of lung metastasis nodules, and enhanced the anti-tumor immune response. In vitro experiments further confirmed that HLJDT significantly inhibits the proliferation and migration of melanoma cells and induces cell apoptosis, which is closely related to the enhancement of ROS generation and mitochondrial membrane potential destruction. Mechanism research shows that HLJDT inhibits the activation of signal transducer and activator of transcription 3 (STAT3) and its phosphorylation, downgrades the expression of PD-L1 and N-cadherin, and upregulates the expression of E-cadherin, thus inhibiting the invasion and metastasis of melanoma cells and improving the immune microenvironment of tumors. Overall, these findings show that HLJDT has potential in inhibiting melanoma metastasis and reshaping the tumor immune microenvironment, providing a systematic experimental basis for its application as an auxiliary treatment of malignant tumors. This experiment was approved by the Experimental Animal Ethics Committee of Shandong University of Traditional Chinese Medicine (approval No.: SDUTCM20220302025).
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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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