Inhibition of phorbol ester‐induced COX‐2 expression by some edible African plants

Abstract

Cancer bush (CB, Sutherlandia frutescens), Devil's claw (DEV, Harpagophytum procumbens), Rooibos tea (RT, Aspalathus linearis), and Bambara groundnut (BB, Vignea subterranean) have been used to treat some malignancies and inflammatory disorders in Africa. However, biochemical basis for chemopreventive effects of these medicinal plants remains unclear. An abnormally elevated expression of cyclooxygenase-2 (COX-2) has been implicated in pathogenesis and progression of carcinogenesis. In the present study, we found that the methanol extracts of CB, DEV, RT, and BB inhibited, to a different extent, 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced COX-2 expression in human breast epithelial (MCF10A) cells and in mouse skin in vivo. To determine the molecular mechanism of COX-2 inhibition by the above medicinal plants, we examined their effects on activation of NF-kappaB which is one of the major transcription factors responsible for regulating COX-2 expression. Methanol extracts of both CB and BB inhibited the DNA binding of NF-kappaB activated by TPA in MCF10A cells in a dose-dependent manner. Based on above findings, CB and BB are likely to inhibit TPA-induced COX-2 expression through suppression of DNA binding of NF-kappaB, which may contribute to the chemopreventive or chemoprotective activity of these African plants.

Anti-Inflammatory Effects of Aspalathus linearis and Cyclopia spp. Extracts in a UVB/Keratinocyte (HaCaT) Model Utilising Interleukin-1α Accumulation as Biomarker

“…Rooibos and honeybush also possess antioxidant and anti-inflammatory properties that have been implicated in the photoprotective and anti-carcinogenic mechanisms in skin [38][39][40]. The anti-inflammatory activity against cytokine production by quercetin, rutin and luteolin, also present in rooibos, has been shown to involve inhibition of pro-inflammatory cytokine synthesis of via suppression of transcription factors and MAP kinases [31,46].…”

“…Modulation of inflammation by the polyphenolic constituents has been proposed as a key mode of action underlying the protective activity of the extracts. The anti-inflammatory properties of rooibos and honeybush against UVB and PMA-induced COX-2 expression and oedema have been demonstrated and implicated in the anti-tumour activity of the herbal tea extracts in skin [39,40]. However, the modulatory activity of the herbal teas against primary cytokines involved in the early stages of UVB-induced inflammation as well as the effect on cell growth parameters still needs to be elucidated.…”

South African herbal teas: Aspalathus linearis, Cyclopia spp. and Athrixia phylicoides—A review

“…In vitro Methanol extract Extract (1, 5, 10 g/ml) inhibited TPA-induced COX-2 expression in human epithelial (MCF10A) cells Na et al (2004) Inhibited TPA-induced COX-2 expression through suppression of DNA binding of NF-B Fermented…”

Harpagoside suppresses lipopolysaccharide-induced iNOS and COX-2 expression through inhibition of NF-κB activation

“…Interestingly, a harpagoside-free extract also markedly inhibited inducible NO synthase expression and in contrast to pure harpagoside exerted strong antioxidative activity (Kaszkin et al, 2004). Recently, it was shown that a methanolic extract of devil's claw inhibited TPA (12-Otetradecanoylphorbol-13-acetate)-induced COX-2 expression in human breast epithelial cells and in mouse skin in vivo by inhibiting DNA-binding of NF-B activated by TPA (Na et al, 2004). Topical application of the extract also inhibited TPA-induced activation of activator protein-1 and attenuated the expression of its key component c-Fos (Kundu et al, 2005).…”