Protective Effects of Chinese Propolis and Its Component, Chrysin, against Neuronal Cell Death via Inhibition of Mitochondrial Apoptosis Pathway in SH-SY5Y Cells

Itoh, Hiroshi; Shimazawa, Masamitsu; Tazawa, Shigemi; Araki, Yasufumi; Mishima, Satoshi; Hara, Hideaki

doi:10.1021/jf8014206

Cited by 82 publications

(49 citation statements)

References 32 publications

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“…19) Furthermore, chrysin also has the protective effect against endoplasmic stress-induced neuronal cell death. 20) These findings indicate the possibility that luteolin has the protective effects against endoplasmic reticulum stress-induced depression and/or cell damage. In the present study, we investigated the effects of luteolin against endoplasmic reticulum stress-induced neuronal cell death in vitro and depression in vivo.…”

Section: Discussionmentioning

confidence: 93%

Luteolin Shows an Antidepressant-Like Effect via Suppressing Endoplasmic Reticulum Stress

Ishisaka

Kakefuda

Yamauchi

et al. 2011

Biological & Pharmaceutical Bulletin

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In terms of mental illnesses, depression has an enormous influence in society. Major symptoms of depression are a "depressed mood" and "loss of interest and joy." Despite recent advances in the knowledge related to brain development and function, the mechanisms underlying the pathogenesis of depression remain unclear.The endoplasmic reticulum is a principal site for protein synthesis, folding, and calcium signaling.1) It is highly sensitive to alterations in calcium homeostasis and perturbations in its environment. A condition that impaired the function of the endoplasmic reticulum, collectively designated "endoplasmic reticulum stress," can lead to an accumulation of unfolded proteins in the endoplasmic reticulum lumen.2) In response to endoplasmic reticulum stress, cells have developed a self-protective signal pathway termed the unfolded protein response (UPR), leading to induction of molecular chaperones such as 78 kDa glucose-regulated protein (GRP78) and 94 kDa glucose-regulated protein (GRP94), translational attenuation, and endoplasmic reticulum associated degradation.3) However, if the damage is excessive, the UPR ultimately activates an apoptotic pathway such as CCAAT/enhancer binding protein (C/EBP)-homologous protein (CHOP) activation. 4)Recently, GRP78 and GRP94 have been found in the temporal cortex of subjects with major depressive disorder who died by suicide.5) Furthermore, in a rodent depression model, endoplasmic reticulum stress-related proteins were increased and these were attenuated by an antidepressant.6) Recently, we have reported that restraint stress increases in the expression of endoplasmic reticulum stress-related genes in the mouse brain.7) These findings indicate that endoplasmic reticulum stress may have some roles in the pathogenesis of depression.Luteolin is a common flavonoid that exists in many types of plants such as Apium graveolens L. var. dulce, 8)Petroselium crispum, 9) and Capsicum annuum L. var.'grossum.' 10) It has various pharmacological activities such as antioxidant, 11) anticancer action, 12) memory-improving, 13) and anxiolytic 14) activities, suggesting that luteolin could penetrate easily into the brain. 15) In this study, we investigated the antidepressant effects of luteolin from the green pepper leaf, as well as its mechanism, using cell death assay induced by endoplasmic reticulum stress in human neuroblastoma (SH-SY5Y) cells and animal models of depression. MATERIALS AND METHODS Purification of LuteolinLuteolin aglycon (luteolin) was provided by Theravalues (Tokyo, Japan). The purity of luteolin was 80%. In the experiments, it was dissolved in phosphate buffered saline contained 1% dimethyl sulfoxide (DMSO) or suspended in the 0.5% carboxymethylcellulose (Wako, Osaka, Japan).Cell Culture SH-SY5Y cells were purchased from the European Collection of Cell Culture (Wiltshire, U.K.) and maintained in Dulbecco's modified Eagle's medium (SigmaAldrich, St. Louis, MO, U.S.A.) containing 10% fetal bovine serum (VALEANT, Costa Mesa, CA, U.S.A.), 100 units/ml of penici...

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Section: Discussionmentioning

confidence: 93%

Luteolin Shows an Antidepressant-Like Effect via Suppressing Endoplasmic Reticulum Stress

Ishisaka

Kakefuda

Yamauchi

et al. 2011

Biological & Pharmaceutical Bulletin

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“…Previously, it has been demonstrated that BFA and TUN promote the translocation of cytochrome c from the mitochondrial matrix to the cytosol (20,21). In light of this, we further investigated the caspase-2 activity, which promotes cytosolic cleavage of Bid to tBid, acting upstream of cytochrome c release and being involved in ER stress-mediated death (22)(23)(24), and caspase-9 activity, which is involved in the cell death signals propagation triggered by mitochondria (25).…”

Section: Bfa and Tun-induced Stress Activates Er-and Mitochondria-depmentioning

confidence: 94%

ER-mediated stress induces mitochondrial-dependent caspases activation in NT2 neuron-like cells

Arduíno

Esteves²,

Domingues³

et al. 2009

BMB Reports

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Recent studies have revealed that endoplasmic reticulum (ER) disturbance is involved in the pathophysiology of neurodegenerative disorders, contributing to the activation of the ER stress-mediated apoptotic pathway. Therefore, we investigated here the molecular mechanisms underlying the ER-mitochondria axis, focusing on calcium as a potential mediator of cell death signals. Using NT2 cells treated with brefeldin A or tunicamycin, we observed that ER stress induces changes in the mitochondrial function, impairing mitochondrial membrane potential and distressing mitochondrial respiratory chain complex Moreover, stress stimuli at ER level evoked calcium fluxes between ER and mitochondria. Under these conditions, ER stress activated the unfolded protein response by an overexpression of GRP78, and also caspase-4 and-2, both involved upstream of caspase-9. Our findings show that ER and mitochondria interconnection plays a prominent role in the induction of neuronal cell death under particular stress circumstances. [BMB reports 2009; 42(11): 719-724]

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“…[36] Chinese propolis and chrysin inhibited staurosporine-induced cell death. These findings indicate that the inhibitory effects of Chinese propolis against neuronal cell death induced by endoplasmic reticulum stress or staurosporine may be exerted primarily by chrysin.…”

Section: Possible Mechanism Of Action Of Propolis and Its Compounds Ementioning

confidence: 95%

“…HT-29, A549, HEp-2, RAW 264.7, Vero Seda et al [33] Ethanolic extract (Turkey) MCF-7 Valente et al [13] Methanolic extract (Portugal) A498 Huang et al [34] Propolin G (Taiwan) C6, DBTRG-05MG Diaz-Carballo et al [35] Mucronulatol (Caribbean) HCT8, MDR1-/ MDR3+ Izuta et al [36] Chrysin, galangin, pinocembrin, caffeic acid, caffeic acid phenethyl ester (China)…”

Section: Flavonoidsmentioning

confidence: 99%

Cytotoxic constituents of propolis inducing anticancer effects: a review

Watanabe

Amarante

Conti

et al. 2011

Journal of Pharmacy and Pharmacology

190

133

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Objectives Propolis is a honeybee product used extensively in traditional medicine for its antioxidant, anti-inflammatory, immunomodulatory and anticancer effects. Propolis exhibits a broad spectrum of biological activities because it is a complex mixture of natural substances. In this review, the antitumour effects of propolis extracts and its constituents (e.g. flavonoids, terpenes and caffeic acid phenethyl ester) are discussed. Key findings The effect of propolis on experimental carcinogenesis is discussed, as well as its possible mechanisms of action against tumours, involving apoptosis, cell cycle arrest and interference on metabolic pathways. Propolis seems to be efficient against different tumour cells both in vitro and in vivo, which suggests its potential in the development of new anticancer drugs. Summary Propolis extracts may be important economically and would allow a relatively inexpensive cancer treatment. Preclinical investigations are needed to further elucidate the benefits of propolis and its antitumour properties.

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Protective Effects of Chinese Propolis and Its Component, Chrysin, against Neuronal Cell Death via Inhibition of Mitochondrial Apoptosis Pathway in SH-SY5Y Cells

Cited by 82 publications

References 32 publications

Luteolin Shows an Antidepressant-Like Effect via Suppressing Endoplasmic Reticulum Stress

Luteolin Shows an Antidepressant-Like Effect via Suppressing Endoplasmic Reticulum Stress

ER-mediated stress induces mitochondrial-dependent caspases activation in NT2 neuron-like cells

Cytotoxic constituents of propolis inducing anticancer effects: a review

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