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

Abstract

OBJECTIVE:The present study aimed to investigate the mechanisms underlying the anti-inflammatory and anti-angiogenic effects of ethyl-p-methoxycinnamate isolated from Kaempferia galanga.METHODS: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.RESULTS: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.CONCLUSION: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.

Phytochemical and Pharmacological Support for the Traditional Uses of Zingiberacea Species in Suriname - A Review of the Literature

“…130,147 Both effects were probably caused, at least partially, by ethyl-p-methoxycinnamate. 148 Together, these observations support the traditional use of K. galanga leaves and rhizomes for treating mouth ulcers, headaches, sore throat, swellings, stomach ache, toothache, and rheumatism.…”

“…Microbial infections, inflammatory conditions, parasitic infections, headaches, mouth ulcers, toothache, dermatological problems, anxiety and depression 7, [126][127][128] Phenylpropanoids such as ethyl p-methoxy cinnamate; flavonols such as kaempferol; terpenoids such as 1,8-cineole 129,130 Antimicrobial, [131][132][133][134][135][136][137][138][139][140][141][142][143] antiparasitic, [136][137][138][139][140][141][142][143] antiinflammatory, antinociceptive, and sedative activity [144][145][146][147][148][149][150] Renealmia alpinia (Rottb.) Maas (ink plant; bigi masusa) Snake bites and scorpion stings, bacterial infections, gastrointestinal problems, fungal infections, convulsions and seizures, 8,[151][152][153][154]172 anxiety, 170 neurodegenerative disturbances 171 Monoterpenes such as β-pinene; labdane diterpenoids; diarylheptanoids; phenolic compounds such as coumarins and pinostrobin; desmethoxyyangonin [155][156][157]…”

Pemodelan Molekul Turunan p-Metoksi sinnamoil Hidrazida Sebagai Inhibitor Checkpoint Kinase 1 dan Inhibitor Aromatase secara In silico

“…Beberapa penelitian melaporkan bahwa aktivitas inhibisi COX-2 pada EPMS tidak hanya sebagai analgesik tetapi juga memiliki aktivitas antikanker melalui inhibisi proses angionegesis (Umar et al, 2014).…”

“…in vitro untuk aktivitas antiangiogenesis yang melibatkan hambatan enzim COX-2 berkolerasi linier dengan metode rat aortic ring assay (Umar et al, 2014), Chick Chorioallantoic Membrane (CAM) Assay (Ekowati et al, 2015;Hamid et al, 2013) dan Matrigel Assay (Donovan et al, 2001 (Meuth, 2010;Ruswanto, 2013;Putra et al, 2016). dan perkembangan sel kanker payudara (Suvannang et al, 2011;Dai et al, 2010;Winer at al., 2005;Wakeling at al., 2000).…”

Ultrasound-enhanced subcritical water extraction of essential oils from Kaempferia galangal L. and their comparative antioxidant activities

“…The constituents of the essential oils mainly include ethyl-p-methoxycinnamate, methyl cinnamate, carvone, eucalyptol and pentadecane [7], and some smaller amounts of cineol, borneol, 3-carene, camphene, kaempferal, cinnamaldehyde, kaempferide, p-methoxycinnamic acid and ethyl cinnamate. The ethyl-p-methoxycinnamate present in this plant has been reported to exhibit many bioactivities such as sedative [5] activity, anti-inflammatory effect [8], and antiangiogenic activity [9].…”