Inhibitory effects of Scutellaria baicalensis extract on hepatic stellate cells through inducing G2/M cell cycle arrest and activating ERK-dependent apoptosis via Bax and caspase pathway

Pan, Tai‐Long; Wang, Pei Wen; Leu, Yann Lii; Wu, Tong; Wu, Tian Shung

doi:10.1016/j.jep.2011.12.028

Cited by 69 publications

(62 citation statements)

References 33 publications

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“…Scutellaria baicalensis extract was found to prevent hepatic fibrosis by promoting ERK-p53 pathways, which in turn caused G2/M cell cycle arrest and activation of the caspase system resulting in apoptosis. It may also induce Bax expression with concomitant decrease in Bcl-2 and MAPK signaling in HSC-T6 cells (30). Here, we also found that sustained activation of ERKs is involved in the C. majus L. extract-induced growth inhibition and apoptosis in A431 cells.…”

Section: Discussionsupporting

confidence: 67%

Chelidonium majus L. extract induces apoptosis through caspase activity via MAPK-independent NF-κB signaling in human epidermoid carcinoma A431 cells

Park

Kim

et al. 2014

Oncology Reports

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Abstract. Chelidonium majus L. (C. majus L.) is known to possess certain biological properties such as anti-inflammatory, antimicrobial, antiviral and antitumor activities. We investigated the effects of C. majus L. extract on human epidermoid carcinoma A431 cells through multiple mechanisms, including induction of cell cycle arrest, activation of the caspase-dependent pathway, blocking of nuclear factor-κB (NF-κB) activation and involvement in the mitogen-activated protein kinase (MAPK) pathway. C. majus L. inhibited the proliferation of A431 cells in a dose-and time-dependent manner, increased the percentage of apoptotic cells, significantly decreased the mRNA levels of cyclin D1, Bcl-2, Mcl-1 and survivin and increased p21 and Bax expression. Exposure of A431 cells to C. majus L. extract enhanced the activities of caspase-3 and caspase-9, while co-treatment with C. majus L., the pancaspase inhibitor Z-VAD-FMK and the caspase-3 inhibitor Z-DEVE-FMK increased the proliferation of A431 cells. C. majus L. extract not only inhibited NF-κB activation, but it also activated p38 MAPK and MEK/ERK signaling. Taken together, these results demonstrate that C. majus L. extract inhibits the proliferation of human epidermoid carcinoma A431 cells by inducing apoptosis through caspase activation and NF-κB inhibition via MAPK-independent pathway. IntroductionChelidonium majus is commonly known as greater celandine. It belongs to the family Papaveraceae and is widely distributed in Europe and western Asia. Extracts of Chelidonium majus L.(C. majus L.) have been shown to exhibit a variety of biological effects including anti-inflammatory, antimicrobial, antiviral and antitumor activities (1,2). The antitumor, antigenotoxic and hepatoprotective effects of C. majus L. extract suggest that it may be potentially useful as an anticancer therapeutic agent (3).Apoptosis is mediated through at least 3 major pathways, which are regulated by death receptors, mitochondria and the endoplasmic reticulum. Activation of the apoptosis pathway is a key mechanism by which cytotoxic drugs kill tumor cells. Defects in apoptosis signaling contribute to the drug resistance of tumor cells (4,5). The Bcl-2 family consists of important apoptotic regulators of programmed cell death. This family of proteins includes both anti-apoptotic molecules such as Bcl-2 and pro-apoptotic molecules such as Bax (6). Bcl-2 and Bcl-X L are members of the Bcl-2 family and are regulated by nuclear factor-(NF)-κB. These proteins can prevent release of cytochrome c and activation of caspases (7).Mitogen-activated protein kinase (MAPK) cascades are involved in the signaling pathways that regulate various cellular responses such as inflammation, proliferation and cell death (8). Three major mammalian MAPK subfamilies have been described: extracellular signal-regulated kinases (ERKs), c-Jun N-terminal kinases and p38 kinases. Each MAPK is activated through a specific phosphorylation cascade (9,10). The ERK cascade is activated through receptor-mediated signaling stimuli and is...

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Section: Discussionsupporting

confidence: 67%

Chelidonium majus L. extract induces apoptosis through caspase activity via MAPK-independent NF-κB signaling in human epidermoid carcinoma A431 cells

Park

Kim

et al. 2014

Oncology Reports

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“…Long-term liver damage and the wound-healing process resulted in liver fibrosis, in which the hepatic stellate cell (HSC) played a key role during fibrogenesis. The extract of Scutellaria baicalensis could prevent hepatic fibrosis by promoting ERK-p53 pathways, which may in turn cause G2/M cell cycle arrest and activate the Caspase system, finally resulting in apoptosis of HSC-T6 cells [122]. As a result, Scutellaria baicalensis might be beneficial for the amelioration of liver fibrosis.…”

Section: Scutellaria Baicalensismentioning

confidence: 99%

Natural Products for the Prevention and Treatment of Hangover and Alcohol Use Disorder

Wang

Zhang

et al. 2016

Molecules

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Alcoholic beverages such as beer, wine and spirits are widely consumed around the world. However, alcohol and its metabolite acetaldehyde are toxic and harmful to human beings. Chronic alcohol use disorder or occasional binge drinking can cause a wide range of health problems, such as hangover, liver damage and cancer. Some natural products such as traditional herbs, fruits, and vegetables might be potential dietary supplements or medicinal products for the prevention and treatment of the problems caused by excessive alcohol consumption. The aim of this review is to provide an overview of effective natural products for the prevention and treatment of hangover and alcohol use disorder, and special emphasis is paid to the possible functional component(s) and related mechanism(s) of action.

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“…Scutellaria, the root of Scutellariae baicalensis Georgi, is a popular Chinese herb widely used in Asia for the treatment of brain diseases, hepatic disorders, inflammatory diseases and cancer [1][2][3][4]. Baicalin (Fig.…”

Section: Introductionmentioning

confidence: 99%

Baicalin attenuates proinflammatory cytokine production in oxygen–glucose deprived challenged rat microglial cells by inhibiting TLR4 signaling pathway

Hou

Wang

Zhang

et al. 2012

International Immunopharmacology

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Inhibitory effects of Scutellaria baicalensis extract on hepatic stellate cells through inducing G2/M cell cycle arrest and activating ERK-dependent apoptosis via Bax and caspase pathway

Cited by 69 publications

References 33 publications

Chelidonium majus L. extract induces apoptosis through caspase activity via MAPK-independent NF-κB signaling in human epidermoid carcinoma A431 cells

Chelidonium majus L. extract induces apoptosis through caspase activity via MAPK-independent NF-κB signaling in human epidermoid carcinoma A431 cells

Natural Products for the Prevention and Treatment of Hangover and Alcohol Use Disorder

Baicalin attenuates proinflammatory cytokine production in oxygen–glucose deprived challenged rat microglial cells by inhibiting TLR4 signaling pathway

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