Anti-angiogenic effect and mechanism of rhein from Rhizoma Rhei

He, Zhiheng; Zhou, Rui; He, Ming-Fang; Lau, Clara Bik‐San; Yue, Grace Gar-Lee; Ge, Wei; But, Paul Pui‐Hay

doi:10.1016/j.phymed.2010.10.006

Cited by 65 publications

(33 citation statements)

References 57 publications

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“…Recent accumulating evidence shows that several species of the Rheum genus such as Rheum emodi, Rheum undulatum L., Rhizoma Rhei, Rheum ribes, Rheum palmatum L., and Rheum rhaponticum have antiallergic, antibacterial, antioxidant, anticancer, antiangiogenesis, and anti-in ammation properties [11][12][13][14][15][16][17][18][19][20]. In relation to antioxidant capacity, anthraquinone derivates are considered to be one of the major biologically active constituents of aloeemodin, rhein, emodin, chrysophanol physcion, and danthron from the rhizomes of Rheum undulatum L. and Rheum palmatum L. [11,12,19,21]. However, antioxidant capacity of Korean rhubarb, Rheum officinale Baillon, has never been investigated in spite of the rapid growing interest in using natural antioxidants and functional ingredients in foods and dietary supplements.…”

Section: Introductionmentioning

confidence: 99%

Lipid Peroxidation and Antioxidant Activities of the Aqueous Rhizome Extract of Rheum officinale Baillon

Chang

Kim

2018

Journal of Food Quality

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Generation of reactive oxygen species (ROS) is associated with dysregulation of antioxidant defense mechanisms and incidence of human diseases. e speci c aim of this study was to investigate the lipid oxidation and antioxidant activity of aqueous extract of Rheum o cinale Baillon rhizome in order to evaluate its potential as a future novel natural antioxidant resource and a functional ingredient in food and pharmaceutical formations. Total phenolic and avonoid contents of Rheum rhizome extract were dose dependently increased. Consistent with this, radical scavenging activities of Rheum rhizome extract as determined by 2,2-diphenyl-1-picrylhydrazyl assay and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activity were signi cantly elevated as the concentration increased. In addition, the treatment of aqueous Rheum rhizome extract signi cantly increased ferric reducing and copper chelating activities. According to results of thiobarbituric acid reactive substance analysis, Rheum rhizome extract signi cantly delayed lipid oxidation. Preincubation with Rheum rhizome extract signi cantly inhibited tert-butyl hydroperoxide-(t-BHP-) induced ROS generation. Moreover, superoxide anion production was signi cantly lower in Rheum rhizome extract-treated RAW264.7 macrophage cells than t-BHP-incubated cells (p < 0.05). ese ndings suggest that Rheum o cinale Baillon rhizome extract has a potential as an excellent natural antioxidant agent.

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Section: Introductionmentioning

confidence: 99%

Lipid Peroxidation and Antioxidant Activities of the Aqueous Rhizome Extract of Rheum officinale Baillon

Chang

Kim

2018

Journal of Food Quality

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“…Rhein, as an effective component isolated from Traditional Chinese Medicine rheum, shows anti-inflammatory effects, associated with modulating matrix metalloproteinases (MMPs) involved in fatty liver [4], attenuating angiocardiopathy [5], and diabetic nephropathy [6,7]. However, direct evidences of relieving sufferings from inflammation in relation to changes in biomarkers have not been thoroughly investigated yet.…”

Section: Introductionmentioning

confidence: 99%

ER Stress, P66shc, and P-Akt/Akt Mediate Adjuvant-Induced Inflammation, Which Is Blunted by Argirein, a Supermolecule and Rhein in Rats

et al. 2011

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We investigated the anti-inflammatory activities of argirein and rhein on inflammatory edema in rat paw which was caused by complete adjuvant, compared with ibuprofen. We hypothesized that the adjuvant-induced inflammation is attributed to upregulation of activating transcript factor 6 (ATF6; a chaperone for endoplasmic reticulum (ER) stress), p66Shc (an adaptive protein modulating oxidative stress), and NADPH oxidase subunits p22phox and gp91phox in the inflamed tissues. Biomarkers were measured in the rat paw in association with monitoring swellings. The primary inflammatory edema of the injected paw occurred rapidly and sustained over a couple of days, and the secondary inflammation developed 2 weeks later. The inflammatory edema was accompanied by upregulation of cytokines including ATF6, p66Shc, p22phox, gp91phox, and MMP-2 and an increase in ratio of p-Akt/Akt in the afflicted paw. These were suppressed by either argirein and rhein or ibuprofen. These findings indicate that ER stress, upregulated p66Shc, and phosphorylated Akt are actively implicated in the inflammatory zone caused by adjuvant injection. These biomarkers were causal factors responsible for inflammation of the afflicted paw and were suppressed by a supermolecule argirein and rhein, and the anti-inflammatory activities of the two compounds were comparable to that of ibuprofen.

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“…[19][20][21][22][23][24][25][26][27][28][29] Different varieties of drugs tested in zebrafish elicit similar responses to those observed in mammalian models, [30][31][32] considering the remarkable homology in the molecular and signaling pathways involved in vessel formations between zebrafish and mammals. [33][34][35] Compared with other drug screening systems, the dominant advantages of the zebrafishbased assay include: (1) it is suitable for high-throughput drug screening; (2) it offers more relevant information to humans compared to other invertebrate models and in vitro cell lines, while it costs much less than mammalian systems.…”

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confidence: 99%

Anti-angiogenic Activity of Erxian Decoction, a Traditional Chinese Herbal Formula, in Zebrafish

Tong

Kwok

et al. 2012

Biological & Pharmaceutical Bulletin

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Erxian Decoction (EXD), a traditional Chinese herbal formula, has been used to treat menopausal symptoms and other aging diseases for several decades. Recently, our laboratory found that EXD could inhibit the proliferation of breast cancer cells. This activity may be mediated by anti-angiogenic action. To investigate the anti-angiogenic activity of EXD, its inhibitory effect on blood vessel formation was evaluated using both wild type and transgenic zebrafish embryos with fluorescent vasculature in vivo. Both semi-quantitative and real-time quantitative polymerase chain reaction (qPCR) were carried out to evaluate the effect of EXD on the expression of several genes closely associated with angiogenesis in zebrafish. EXD was found to inhibit vessel formation in zebrafish embryos in a dose-and time-dependent manner. Furthermore, it reduced the mRNA expression of vascular endothelial growth factor A (VEGF-A) and the protein level of hypoxia inducible factor 1α (HIF-1α) in the embryos, suggesting the involvement of HIF-1 mediated VEGF-A signaling pathway in the anti-angiogenic action of EXD. The anti-angiogenic activity of EXD provides new insights to its clinical application and may in the future lead to the development of potential drugs for treating various cancers, especially in menopausal period.Key words angiogenesis; zebrafish; Erxian Decoction; vascular endothelial growth factor A; hypoxia inducible factor 1αErxian Decoction (EXD), a traditional Chinese herbal formula, consists of six Chinese herbs: Epimedium sagittatum (SIEB. et ZUCC) MAXIM. (Berberidaceae, whole herb), Curculigo orchioides GAERTN. (Hypoxidaceae, rhizome), Morinda officinalis HOW (Rubiaceae, root), Angelica sinensis (OLIV.) DIELS (Umbelliferae, root), Phellodendron chinense SCHNEID. (Rutaceae, bark) and Anemarrhena asphodeloides BUNGE (Anthericaceae, rhizome). It has been used to treat osteoporotic disorders, 1) menopausal symptoms 2,3) and other aging diseases 4) in elderly patients for several decades.Angiogenesis is the formation of new blood vessels from existing ones. This complex process involves an extensive interplay between cells, soluble factors, and the extracellular matrix (ECM), which includes the proliferation and migration of endothelial cells. 5) Under particular conditions which include wound healing, embryonic development and tissue or organ regeneration, angiogenesis occurs at specific moments, which are regulated by stimulatory and inhibitory factors. 6,7)However, under certain pathological conditions such as the growth of solid tumors, tumor metastasis, rheumatoid arthritis and diabetic retinopathy, the angiogenic process takes place in a poorly controlled manner. 5,8,9) Plenty of traditional Chinese medicinal herbs are rich sources of compounds with anti-inflammatory and anti-carcinogenic properties. There are prominent evidences suggesting the co-dependence of chronic inflammation and angiogenesis. Both of them associate with the increase of cellular infiltration and proliferation, and are influenced by regulatory gro...

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Anti-angiogenic effect and mechanism of rhein from Rhizoma Rhei

Cited by 65 publications

References 57 publications

Lipid Peroxidation and Antioxidant Activities of the Aqueous Rhizome Extract of Rheum officinale Baillon

Lipid Peroxidation and Antioxidant Activities of the Aqueous Rhizome Extract of Rheum officinale Baillon

ER Stress, P66shc, and P-Akt/Akt Mediate Adjuvant-Induced Inflammation, Which Is Blunted by Argirein, a Supermolecule and Rhein in Rats

Anti-angiogenic Activity of Erxian Decoction, a Traditional Chinese Herbal Formula, in Zebrafish

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