Icaritin protects against oxidative stress-induced injury in cardiac H9c2 cells via Akt/Nrf2/HO-1 and calcium signalling pathways

Lei, Si Wan; Cui, Guozhen; Leung, George Pak-Heng; Luk, Sharon; Hoi, Maggie Pui Man; Wang, Liang; Mahady, Gail B.; Lee, Simon Ming‐Yuen

doi:10.1016/j.jff.2015.06.054

Cited by 15 publications

(8 citation statements)

References 44 publications

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“…Antioxidant compounds have been shown to protect against oxidative stress-induced apoptosis in this in vitro model via several mechanisms including induction of autophagy, inhibition of mitochondrial dysfunction, and activation of antioxidant enzymes (Angeloni et al 2007;Kim et al, 2014;Lei et al 2015;Lv and Zhou 2012;Movahed et al 2012;Park et al 2003;Yang et al 2012). Turner et al demonstrated that JNK inhibition was protective against oxidative stress-induced apoptosis in H9c2 cells (1998), and our previous study showed that the lingonberry extract significantly inhibited JNK activation and reduced apoptosis in a model of ischemia-reperfusion injury in H9c2 cells (Isaak et al 2015).…”

Section: R a F Tmentioning

confidence: 99%

Lingonberry anthocyanins protect cardiac cells from oxidative-stress-induced apoptosis

Isaak

Petkau

Blewett

et al. 2017

Can. J. Physiol. Pharmacol.

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Lingonberry grown in northern Manitoba, Canada, contains exceptionally high levels of anthocyanins and other polyphenols. Previous studies from our lab have shown that lingonberry anthocyanins can protect H9c2 cells from ischemia-reperfusion injury and anthocyanin-rich diets have been shown to be associated with decreased cardiovascular disease and mortality. Oxidative stress can impair function and trigger apoptosis in cardiomyocytes. This study investigated the protective effects of physiologically relevant doses of lingonberry extracts and pure anthocyanins against hydrogen-peroxide-induced cell death. Apoptosis and necrosis were detected in H9c2 cells after hydrogen peroxide treatment via flow cytometry using FLICA 660 caspase 3/7 combined with YO-PRO-1 and then confirmed with Hoechst staining and fluorescence microscopy. Each of the 3 major anthocyanins found in lingonberry (cyanidin-3-galactoside, cyanidin-3-glucoside, and cyanidin-3-arabinoside) was protective against hydrogen-peroxide-induced apoptosis in H9c2 cells at 10 ng·mL (20 nmol·L) and restored the number of viable cells to match the control group. A combination of the 3 anthocyanins was also protective and a lingonberry extract tested at 3 concentrations produced a dose-dependent protective effect. Lingonberry anthocyanins protected cardiac cells from oxidative-stress-induced apoptosis and may have cardioprotective effects as a dietary modification.

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Section: R a F Tmentioning

confidence: 99%

Lingonberry anthocyanins protect cardiac cells from oxidative-stress-induced apoptosis

Isaak

Petkau

Blewett

et al. 2017

Can. J. Physiol. Pharmacol.

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“…Icariin's derivatives have also been shown to possess significant biological activities. For example, icaritin was shown to possess osteopromotive (Yao et al, 2012 ), neuroprotective (Wang et al, 2007 ) and cardioprotective effect (Lei et al, 2015 ). The number of studies on icariside I are limited but it was reported to alleviate sexual dysfunction (Lenoble et al, 2002 ).…”

Section: Icariin and Its Derivativesmentioning

confidence: 99%

Anti-Cancer Properties of the Naturally Occurring Aphrodisiacs: Icariin and Its Derivatives

et al. 2016

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Epimedium (family Berberidaceae), commonly known as Horny Goat Weed or Yin Yang Huo, is commonly used as a tonic, aphrodisiac, anti-rheumatic and anti-cancer agent in traditional herbal formulations in Asian countries such as China, Japan, and Korea. The major bioactive compounds present within this plant include icariin, icaritin and icariside II. Although it is best known for its aphrodisiac properties, scientific and pharmacological studies suggest it possesses broad therapeutic capabilities, especially for enhancing reproductive function and osteoprotective, neuroprotective, cardioprotective, anti-inflammatory and immunoprotective effects. In recent years, there has been great interest in scientific investigation of the purported anti-cancer properties of icariin and its derivatives. Data from in vitro and in vivo studies suggests these compounds demonstrate anti-cancer activity against a wide range of cancer cells which occurs through various mechanisms such as apoptosis, cell cycle modulation, anti-angiogenesis, anti-metastasis and immunomodulation. Of note, they are efficient at targeting cancer stem cells and drug-resistant cancer cells. These are highly desirable properties to be emulated in the development of novel anti-cancer drugs in combatting the emergence of drug resistance and overcoming the limited efficacy of current standard treatment. This review aims to summarize the anti-cancer mechanisms of icariin and its derivatives with reference to the published literature. The currently utilized applications of icariin and its derivatives in cancer treatment are explored with reference to existing patents. Based on the data compiled, icariin and its derivatives are shown to be compounds with tremendous potential for the development of new anti-cancer drugs.

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“…Prenylflavonoids are reported to be a group of major active constituents present in Epimedium for the antioxidative stress, anti-inflammatory, antitumor, and antiosteoporosis activities [4–8]. Icaritin is the common aglycone with many biological effects, especially antiosteoporosis activities [5, 7].…”

Section: Introductionmentioning

confidence: 99%

“…Herba Epimedii, the dried aerial parts of Epimedium L. (Berberidaceae), are a widely used Chinese medicine for impotence, bone loss, and cardiovascular diseases [ 1 – 3 ]. Prenylflavonoids are reported to be a group of major active constituents present in Epimedium for the antioxidative stress, anti-inflammatory, antitumor, and antiosteoporosis activities [ 4 – 8 ]. Icaritin is the common aglycone with many biological effects, especially antiosteoporosis activities [ 5 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Metabolite Profiling, Pharmacokinetics, and In Vitro Glucuronidation of Icaritin in Rats by Ultra-Performance Liquid Chromatography Coupled with Mass Spectrometry

Zhang

Chen

Zhang

et al. 2017

Journal of Analytical Methods in Chemistry

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Icaritin is a naturally bioactive flavonoid with several significant effects. This study aimed to clarify the metabolite profiling, pharmacokinetics, and glucuronidation of icaritin in rats. An ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS) assay was developed and validated for qualitative and quantitative analysis of icaritin. Glucuronidation rates were determined by incubating icaritin with uridine diphosphate glucuronic acid- (UDPGA-) supplemented microsomes. Kinetic parameters were derived by appropriate model fitting. A total of 30 metabolites were identified or tentatively characterized in rat biosamples based on retention times and characteristic fragmentations, following proposed metabolic pathway which was summarized. Additionally, the pharmacokinetics parameters were investigated after oral administration of icaritin. Moreover, icaritin glucuronidation in rat liver microsomes was efficient with CLint (the intrinsic clearance) values of 1.12 and 1.56 mL/min/mg for icaritin-3-O-glucuronide and icaritin-7-O-glucuronide, respectively. Similarly, the CLint values of icaritin-3-O-glucuronide and icaritin-7-O-glucuronide in rat intestine microsomes (RIM) were 1.45 and 0.86 mL/min/mg, respectively. Taken altogether, dehydrogenation at isopentenyl group and glycosylation and glucuronidation at the aglycone were main biotransformation process in vivo. The general tendency was that icaritin was transformed to glucuronide conjugates to be excreted from rat organism. In conclusion, these results would improve our understanding of metabolic fate of icaritin in vivo.

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Icaritin protects against oxidative stress-induced injury in cardiac H9c2 cells via Akt/Nrf2/HO-1 and calcium signalling pathways

Cited by 15 publications

References 44 publications

Lingonberry anthocyanins protect cardiac cells from oxidative-stress-induced apoptosis

Lingonberry anthocyanins protect cardiac cells from oxidative-stress-induced apoptosis

Anti-Cancer Properties of the Naturally Occurring Aphrodisiacs: Icariin and Its Derivatives

Metabolite Profiling, Pharmacokinetics, and In Vitro Glucuronidation of Icaritin in Rats by Ultra-Performance Liquid Chromatography Coupled with Mass Spectrometry

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