Article ; Online: Potent anti-angiogenic component in Kaempferia galanga L. and its mechanism of action.
2024 Volume 324, Page(s) 117811
Abstract: Ethnopharmacological relevance: Traditionally, the roots of Kaempferia galanga has been used to treat high blood pressure, chest pain, headache, toothache, rheumatism, indigestion, cough, inflammation and cancer in Asia. Nevertheless, most of its ... ...
| Abstract | Ethnopharmacological relevance: Traditionally, the roots of Kaempferia galanga has been used to treat high blood pressure, chest pain, headache, toothache, rheumatism, indigestion, cough, inflammation and cancer in Asia. Nevertheless, most of its pharmacological studies were focused on ethanolic extracts and volatile oils. The exact active chemical constituents and their underlying mechanisms are still poorly understood, especially towards its anti-cancer treatment. Inhibition of angiogenesis is an important atrategy to inhibit tumor growth. It has been reported that the low polar component of the plant possessed anti-angiogenic activity. Yet, the potent compound which is responsible for the effect and its molecular mechanism has not been reported. Aim of the study: To determine the potent anti-angiogenic component in K.galanga and its mechanism of action. Material and methods: The low polar components of the plant were concentrated using the methods of supercritical fluid extraction (SFE), subcritical extraction (SCE) and steam distillation (SD). The anti-angiogenic activity of the three extracts was evaluated using a zebrafish model. The content of the active compound in those extracts was determined with HPLC analysis. The in-vitro and in-vivo activity of the isolated compound was evaluated using human umbilical vein endothelial cells (HUVECs) model, the aortic ring assay and the matrigel plug assay, respectively. Its molecular mechanism was further studied by the western blotting assay and computer-docking experiments. Besides, its cytotoxicity on cancer and normal cell lines was evaluated using the cell-counting kit. Results: HPLC results showed that trans-ethyl p-methoxycinnamate (TEM) was the major component of the extracts. The extract of SFE showed the best effect as it has the highest content of TEM. TEM could inhibit vascular endothelial growth factor (VEGF)-induced viability, migration, invasion and tube formation in human umbilical vein endothelial cells (HUVECs) in vitro. Moreover, it inhibited VEGF-induced sprout formation ex vivo and vessel formation in vivo. Mechanistic study showed that it could suppress tyrosine kinase activity of the receptor of VEGF (VEGFR2) and alter its downstream signaling pathways. In addition, the molecular docking showed that the binding of TEM and VEGFR2 is stable, which mainly attributed to the non-covalent binding interaction. Beside, TEM possessed little toxicity to both cancer and normal cells. Conclusion: TEM is the major anti-angiogenic component present in K. galanga and its anti-angiogenic property rather than toxicity provides scientific basis for the traditional use of K. galanga in cancer treatment. |
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| MeSH term(s) | Animals ; Humans ; Vascular Endothelial Growth Factor A/metabolism ; Alpinia ; Plant Extracts/pharmacology ; Plant Extracts/therapeutic use ; Plant Extracts/chemistry ; Zebrafish ; Molecular Docking Simulation ; Zingiberaceae/chemistry ; Human Umbilical Vein Endothelial Cells ; Neoplasms/metabolism ; Angiogenesis Inhibitors/pharmacology ; Angiogenesis Inhibitors/therapeutic use ; Cell Movement ; Cell Proliferation ; Vascular Endothelial Growth Factor Receptor-2/metabolism |
| Chemical Substances | Vascular Endothelial Growth Factor A ; Plant Extracts ; Angiogenesis Inhibitors ; Vascular Endothelial Growth Factor Receptor-2 (EC 2.7.10.1) |
| Language | English |
| Publishing date | 2024-01-28 |
| Publishing country | Ireland |
| Document type | Journal Article |
| ZDB-ID | 134511-4 |
| ISSN | 1872-7573 ; 0378-8741 |
| ISSN (online) | 1872-7573 |
| ISSN | 0378-8741 |
| DOI | 10.1016/j.jep.2024.117811 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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