Ethyl-p-methoxycinnamate isolated from kaempferia galanga inhibits inflammation by suppressing interleukin-1, tumor necrosis factor-α, and angiogenesis by blocking endothelial functions

• Published in: Clinics (São Paulo, Brazil) Vol. 69; no. 2; pp. 134 - 144
• Main Authors: Umar, Muhammad Ihtisham, Asmawi, Mohd Zaini, Sadikun, Amirin, Majid, Amin Malik Shah Abdul, Al-Suede, Fouad Saleih R., Hassan, Loiy Elsir Ahmed, Altaf, Rabia, Ahamed, Mohamed B. Khadeer
• Format: Journal Article
• Language: English; Portuguese
• Published: Brazil Elsevier España, S.L.U 01.02.2014; Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo; Faculdade de Medicina / USP; Elsevier España
• Subjects: Analysis of Variance; Angiogenesis Inhibitors - isolation & purification; Angiogenesis Inhibitors - pharmacology; Animals; Anti-Inflammatory Agents - isolation & purification; Anti-Inflammatory Agents - pharmacology; Basic Research; Cell Migration Assay; Cell Proliferation - drug effects; Cinnamates - pharmacology; Cotton Pellet Granuloma; Cytokine Inhibition Assay; Enzyme-Linked Immunosorbent Assay; Human Umbilical Vein Endothelial Cells - drug effects; Humans; Interleukin-1 - analysis; Male; MEDICINE, GENERAL & INTERNAL; Plant Extracts - pharmacology; Rat Aortic Ring Assay; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Tail Flick Assay; Tube Formation Assay; Tumor Necrosis Factor-alpha - analysis; Tumor Necrosis Factor-alpha - drug effects; U937 Cells - drug effects; Vascular Endothelial Growth Factor A - analysis; Vascular Endothelial Growth Factor A - drug effects; Zingiberaceae - chemistry; Rat Aortic Ring Assay; Tail Flick Assay; Cotton Pellet Granuloma; Cell Migration Assay; Tube Formation Assay; Cytokine Inhibition Assay
• ISSN: 1807-5932; 1980-5322; 1980-5322
• DOI: 10.6061/clinics/2014(02)10

The present study aimed to investigate the mechanisms underlying the anti-inflammatory and anti-angiogenic effects of ethyl-p-methoxycinnamate isolated from Kaempferia galanga. The anti-inflammatory effects of ethyl-p-methoxycinnamate were assessed using the cotton pellet granuloma assay in rats, whereby the levels of interleukin-1 and tumor necrosis factor-α were measured in the animals' blood. In addition, the levels of interleukin, tumor necrosis factor, and nitric oxide were measured in vitro using the human macrophage cell line (U937). The analgesic effects of ethyl-p-methoxycinnamate were assessed by the tail flick assay in rats. The anti-angiogenic effects were evaluated first by the rat aortic ring assay and, subsequently, by assessing the inhibitory effects of ethyl-p-methoxycinnamate on vascular endothelial growth factor, proliferation, migration, and tube formation in human umbilical vein endothelial cells. Ethyl-p-methoxycinnamate strongly inhibited granuloma tissue formation in rats. It prolonged the tail flick time in rats by more than two-fold compared with the control animals. The inhibition of interleukin and tumor necrosis factor by ethyl-p-methoxycinnamate was significant in both in vivo and in vitro models; however, only a moderate inhibition of nitric oxide was observed in macrophages. Furthermore, ethyl-p-methoxycinnamate considerably inhibited microvessel sprouting from the rat aorta. These mechanistic studies showed that ethyl-p-methoxycinnamate strongly inhibited the differentiation and migration of endothelial cells, which was further confirmed by the reduced level of vascular endothelial growth factor. Ethyl-p-methoxycinnamate exhibits significant anti-inflammatory potential by inhibiting pro-inflammatory cytokines and angiogenesis, thus inhibiting the main functions of endothelial cells. Thus, ethyl-p-methoxycinnamate could be a promising therapeutic agent for the treatment of inflammatory and angiogenesis-related diseases.