Angiogenesis inhibitors from natural sources Roslida Abd Hamid, Dayang Erna Zulaikha Awang Hamsin Frontiers in Drug Design and Discovery, 2016 A multi-target strategies targeting on various biochemical and physiological pathways implicated in tumour pathogenesis should be developed with the ultimate aim to manage patients with cancer and reduce the normal-tissue toxicity. Tumor angiogenesis has been recently discovered as an important strategy in treating cancer as most tumors rely on angiogenesis to survive, develop, invade and metastasize. Targeting angiogenesis to inhibit the progression of tumorigenesis has recently been a focus in developing novel anti-cancer development. This is mainly due to the specificity that anti-angiogenic possesses: it targets on newly-formed blood vessels and spares the existing ones. With that being said, inhibiting angiogenesis is now considered a promising strategy in the development and selection of new anti-cancer drug candidates. To date, there are cytotoxic drugs which also exhibit antiangiogenic activity but not angiogenesis inhibitors in whole. In this chapter, we will be discussing selected natural sources including marine products which have been investigated for their antiangiogenic activities. Various methods in validating the effects as well as their possible multiple pathways will also be contended in this chapter.
Synergistic action of compounds isolated from the hexane extract of Ardisia crispa root against tumour-promoting effect, in vitro Looi Ting Yeong, Roslida Abdul Hamid, Latifah Saiful Yazan, Huzwah Khaza'ai, Dayang Erna Zulaikha Awang Hamsin Natural Product Research, 2014 An isomeric mixture of α,β-amyrin (triterpene) and 2-methoxy-6-undecyl-1,4-benzoquinone (quinone) isolated from the Ardisia crispa root hexane (ACRH) extract was reported to possess anti-inflammatory properties in vivo. Considering the close association between inflammation and cancer, on top of the lack of antitumour study on those compounds, this study aimed to determine the potential of both compounds against tumour promotion in vitro, either as single agent or in combination. Triterpene and quinone compounds, as well as triterpene–quinone fraction (TQF) and ACRH were subjected to inhibition of Epstein–Barr virus-early antigen (EBV-EA) activation assay for that purpose. Compared with curcumin (positive control), inhibition against EBV-EA activation occurred in the order: ACRH>TQF ≥ curcumin>α,β-amyrin ≥ 2-methoxy-6-undecyl-1,4-benzoquinone. These findings reported, for the first time, the antitumor-promoting effect of α,β-amyrin and 2-methoxy-6-undecyl-1,4-benzoquinone from the roots of A. crispa, which was enhanced when both compounds act in synergy.
The hexane fraction of Ardisia crispa Thunb. A. DC. roots inhibits inflammation-induced angiogenesis Dayang Erna Zulaikha Awang Hamsin, Roslida Abdul Hamid, Latifah Saiful Yazan, Che Norma Mat Taib, Yeong Looi Ting BMC Complementary and Alternative Medicine, 2013 Background Ardisia crispa (Myrsinaceae) is used in traditional Malay medicine to treat various ailments associated with inflammation, including rheumatism. The plant’s hexane fraction was previously shown to inhibit several diseases associated with inflammation. As there is a strong correlation between inflammation and angiogenesis, we conducted the present study to investigate the anti-angiogenic effects of the plant’s roots in animal models of inflammation-induced angiogenesis. Methods We first performed phytochemical screening and high-performance liquid chromatography (HPLC) fingerprinting of the hexane fraction of Ardisia crispa roots ethanolic extract (ACRH) and its quinone-rich fraction (QRF). The anti-inflammatory properties of ACRH and QRF were tested using the Miles vascular permeability assay and the murine air pouch granuloma model following oral administration at various doses. Results Preliminary phytochemical screening of ACRH revealed the presence of flavonoids, triterpenes, and tannins. The QRF was separated from ACRH (38.38% w/w) by column chromatography, and was isolated to yield a benzoquinonoid compound. The ACRH and QRF were quantified by HPLC. The LD50 value of ACRH was 617.02 mg/kg. In the Miles vascular permeability assay, the lowest dose of ACRH (10 mg/kg) and all doses of QRF significantly reduced vascular endothelial growth factor (VEGF)-induced hyperpermeability, when compared with the vehicle control. In the murine air pouch granuloma model, ACRH and QRF both displayed significant and dose-dependent anti-inflammatory effects, without granuloma weight. ACRH and QRF significantly reduced the vascular index, but not granuloma tissue weight. Conclusions In conclusion, both ACRH and QRF showed potential anti-inflammatory properties in a model of inflammation-induced angiogenesis model, demonstrating their potential anti-angiogenic properties.
