Flavonoid Baicalein Attenuates Activation-Induced Cell Death of Brain Microglia

Suk, Kyoungho; Lee, Heasuk; Kang, Sang Soo; Cho, Gyeong Jae; Choi, Wan Sung

doi:10.1124/jpet.102.047373

Cited by 95 publications

(64 citation statements)

References 43 publications

(41 reference statements)

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“…Thus, inhibition of these signaling pathways may explain the potent activity of celastrol as a suppressor of inflammatory mediators. Recently, various natural compounds, including baicalein, berberine, curcumin, luteolin, and resveratrol, have been reported to inhibit the overproduction of inflammatory mediators such as NO, COX-2, and TNF-α in LPS-stimulated BV-2 cells (Suk et al, 2003;Kang et al, 2004; and primary microglia (Chen et al, 2004). Interestingly, these compounds have already been shown to be potent inhibitors of the NF-κB pathway.…”

Section: Discussionmentioning

confidence: 99%

Celastrol inhibits production of nitric oxide and proinflammatory cytokines through MAPK signal transduction and NF-κB in LPS-stimulated BV-2 microglial cells

Jung

Chung²,

Kim³

et al. 2007

Exp Mol Med

118

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Excessive production of nitric oxide (NO) and proinflammatory cytokines from activated microglia play an important role in human neurodegenerative disorders. Here, we investigated whether celastrol, which has been used as a potent anti-inflammatory and anti-oxidative agent in Chinese medicine, attenuates excessive production of NO and proinflammatory cytokines such as TNF-α and IL-1β in LPS-stimulated BV-2 cells, a mouse microglial cell line. We report here that the LPS-elicited excessive production of NO, TNF-α , and IL-1β in BV-2 cells was largely inhibited in the presence of celastrol, and the attenuation of inducible iNOS and these cytokines resulted from the reduced expression of mRNAs of iNOS and these cytokines, respectively. The molecular mechanisms that underlie celastrol-mediated attenuation were the inhibition of LPS-induced phosphorylation of MAPK/ERK1/2 and the DNA binding activity of NF-κ B in BV-2 cells. The results indicate that celastrol effectively attenuated NO and proinflammatory cytokine production via the inhibition of ERK1/2 phosphorylation and NF-κ B activation in LPS-activated microglia. Thus, celastrol may be an effective therapeutic candidate for use in the treatment of neurodegenerative human brain disorders.

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Section: Discussionmentioning

confidence: 99%

Celastrol inhibits production of nitric oxide and proinflammatory cytokines through MAPK signal transduction and NF-κB in LPS-stimulated BV-2 microglial cells

Jung

Chung²,

Kim³

et al. 2007

Exp Mol Med

118

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“…Flavonoids refer to a series of naturally occurring, lowmolecular-weight plant products exhibiting a variety of biological activities such as antibacterial, antiviral, anti-inflammatory, antiallergic, and vasodilatory activities (Middleton et al, 2000;Nakamura et al, 2003;Suk et al, 2003). LYG-202 (5-hydroxy-8-methoxy-7-(4-(4-methylpiperazin-1-yl)butoxy)-2-phenyl-4H-chromen-4-one), a known synthesized flavonoid with a piperazine substitution (Fig.…”

Section: Introductionmentioning

confidence: 99%

LYG-202 Augments Tumor Necrosis Factor-α-Induced Apoptosis via Attenuating Casein Kinase 2-Dependent Nuclear Factor-κB Pathway in HepG2 Cells

Chen

Zhang

et al. 2012

Mol Pharmacol

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Tumor necrosis factor-␣ (TNF-␣) is being used as an antineoplastic agent in treatment regimens of patients with locally advanced solid tumors, but TNF-␣ alone is only marginally active. In clinical use, it is usually combined with other chemical agents to increase its tumor response rate. Our previous studies reported that LYG-202 (5-hydroxy-8-methoxy-7-(4-(4-methylpiperazin-1-yl)butoxy)-2-phenyl-4H-chromen-4-one), a synthesized flavonoid with a piperazine substitution, has antiproliferative, antiangiogenic, and proapoptotic activities in multiple cancer cell lines. Here we evaluated the antineoplastic effect of TNF-␣ and analyzed the mechanism underlying its combination with LYG-202. Our results indicated that LYG-202 significantly increased the cytostatic and proapoptotic activity of TNF-␣ in HepG2 cells and heightened the protein level of apoptosis-related genes including caspase-3, caspase-8/9, cleaved poly(ADPribose) polymerase, and Bid. The fact that LYG-202 had a fitness score similar to that of the casein kinase 2 (CK2) inhibitor naphthyridine-8-carboxylate (CX-4945) implied to us that it may serve as a potential candidate for CK2 inhibitor, and the kinase activity assay suggested that LYG-202 significantly inhibited CK2 activity. Moreover, the electrophoretic mobility shift assay and luciferase assay showed that LYG-202 blocked the TNF-␣-induced nuclear factor-B (NF-B) survival signaling pathway primarily by inactivating protein kinase CK2. In murine xenograft models, we also found that LYG-202 enhanced TNF-␣ antineoplastic activity and inhibited CK2 activity and NF-B-regulated antiapoptotic gene expression. All these results showed that LYG-202 enhanced TNF-␣-induced apoptosis by attenuating the CK2-dependent NF-B pathway and probably is a promising agent in combination with TNF-␣.

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“…40 Numerous data suggest that baicalein exhibits antiinflammatory activity through inhibition of NF-B. [40][41][42][43] Kim et al. 28 reported the anti-inflammatory effects of baicalein in human colon cancer cells.…”

Section: Modulation Of the Inflammationmentioning

confidence: 99%

Modulation of Colitis-associated Colon Tumorigenesis by Baicalein and Betaine

Kim¹,

Sung²,

Chung³

et al. 2014

Journal of Cancer Prevention

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In this review, we will summarize the current understanding of modulation of colitis-associated colon tumorigenesis by two natural products, baicalein and betaine, which have anti-inflammatory activities. Baicalein and betaine have been shown to provide various health benefits to organism in many ways. Baicalein is a phenolic flavonoid derived originally from the root of Scutellaria baicalensis Georgi. From ancient times, baicalein has widely been used in oriental medicines as an anti-inflammatory and anti-cancer therapy. Betaine, trimethylglycine, is an essential biochemical molecule of the methionine/homocysteine cycle and is synthesized by conversion of choline. Betaine is an important human nutrient obtained from various foods including sugar beet and lycium. Betaine has provided various health benefits including disease prevention. However, the action mechanisms of their activity remain poorly understood. Recent studies reported the effects of baicalein and betaine on cytotoxicity against colon cancer cells and chemically induced colitis-associated colon tumorigenesis in mice. Administrations of baicalein and betaine containing diets significantly inhibited the incidence of tumors and hyperplasia with down-regulation of inflammation. Therefore, baicalein and betaine might be applicable to the prevention of inflammation-associated colon carcinogenesis.

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Flavonoid Baicalein Attenuates Activation-Induced Cell Death of Brain Microglia

Cited by 95 publications

References 43 publications

Celastrol inhibits production of nitric oxide and proinflammatory cytokines through MAPK signal transduction and NF-κB in LPS-stimulated BV-2 microglial cells

Celastrol inhibits production of nitric oxide and proinflammatory cytokines through MAPK signal transduction and NF-κB in LPS-stimulated BV-2 microglial cells

LYG-202 Augments Tumor Necrosis Factor-α-Induced Apoptosis via Attenuating Casein Kinase 2-Dependent Nuclear Factor-κB Pathway in HepG2 Cells

Modulation of Colitis-associated Colon Tumorigenesis by Baicalein and Betaine

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