• Herbal Formula Science
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• v.29 no.4
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• pp.239-252
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• 2021

Objectives : This study is to effect of improving muscle atrophy through water extract on the solid-phase fermentation extraction with Phellinus linteus of discarded Schisandra chinensis in an atorvastatin-induced atrophy C2C12 cell. Methods : C2C12 myoblast were differentiated into myotube by 2% horse serum medium for 6 days, and then treated solid-phase fermentation(S-P) extract at different concentrations for 24h. To investigate the effect of S-P extract on the induction of muscle atrophy and expression of atrophy-related genes and apoptosis in differentiated C2C12 myotubes using a GSH, ROS, real-time PCR, western blots analysis. Results : As a result of treatment with atorvastatin at concentrations of 5, 10, and 20 uM on the 6th day of differentiation in C2C12 myotube cells, it was confirmed that the cell morphology was damaged in a concentration-dependent manner, and the length and thickness of the myotube also decreased in a concentration-dependent manner. Treatment with S-P extract (50, 100 and 200 ㎍/㎖) increased of GSH and inhibited ROS in the atorvastatin-induced muscle atrophy cell model at a concentration that did not induce toxicity. In addition, it was confirmed that it has an effect on muscle reduction by inhibiting apoptosis of muscle cells as well as being involved in protein production and degradation of muscle cells. Conclusions : Atorvastatin-induced atrophy C2C12 cell, S-P extract activates related to differentiation/generation and proteolysis, and inhibits cell death of atrophy in C2C12 cell. Based on this, it is necessary to prove its effectiveness through animal models and human application test, but it is considered to be discarded Schisandra chinensis can present the potential for development as a recycling industrial material.

• Nutrition Research and Practice
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• v.15 no.6
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• pp.686-702
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• 2021

BACKGROUND/OBJECTIVES: Schisandrae Fructus, the fruit of Schisandra chinensis Baill., has traditionally been used as a medicinal herb for the treatment of various diseases, and has proven its various pharmacological effects, including anti-inflammatory and antioxidant activities. In this study, we investigated the inhibitory effect of Schisandrae Fructus ethanol extract (SF) on inflammatory and oxidative stress in particulate matter 2.5 (PM2.5)-treated RAW 264.7 macrophages. MATERIALS/METHODS: To investigate the anti-inflammatory and antioxidant effects of SF in PM2.5-stimulated RAW 264.7 cells, the levels of pro-inflammatory mediator such as nitric oxide (NO) and prostaglandin E₂ (PGE₂), cytokines including interleukin (IL)-6 and IL-1β, and reactive oxygen species (ROS) were measured. To elucidate the mechanism underlying the effect of SF, the expression of genes involved in the generation of inflammatory factors was also investigated. We further evaluated the anti-inflammatory and antioxidant efficacy of SF against PM2.5 in the zebrafish model. RESULTS: The results indicated that SF treatment significantly inhibited the PM2.5-induced release of NO and PGE₂, which was associated with decreased inducible NO synthase and cyclooxygenase-2 expression. SF also attenuated the PM2.5-induced expression of IL-6 and IL-1β, reducing their extracellular secretion. Moreover, SF suppressed the PM2.5-mediated translocation of nuclear factor-kappa B (NF-κB) from the cytosol into nuclei and the degradation of inhibitor IκB-α, indicating that SF exhibited anti-inflammatory effects by inhibiting the NF-κB signaling pathway. In addition, SF abolished PM2.5-induced generation of ROS, similar to the pretreatment of a ROS scavenger, but not by an inhibitor of NF-κB activity. Furthermore, SF showed strong protective effects against NO and ROS production in PM2.5-treated zebrafish larvae. CONCLUSIONS: Our findings suggest that SF exerts anti-inflammatory and antioxidant effects against PM2.5 through ROS-dependent down-regulating the NF-κB signaling pathway, and that SF can be a potential functional substance to prevent PM2.5-mediated inflammatory and oxidative damage.

• Journal of Life Science
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• v.25 no.2
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• pp.249-255
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• 2015

Schisandrae fructus [Schizandra chinensis (Turcz.) Baillon] is a medicinal herb widely used for treating various inflammatory and immune diseases in East Asian countries. The Schisandrae Semen essential oil (SSeo) from this plant has pharmacological activities, including antioxidant, antimicrobial, and antitumoral activities. Nevertheless, the biological activities and underlying molecular mechanisms of the potential anti-cancer effects of this oil remain unclear. In the present study, we investigated the potential inhibition of apoptosis signaling pathways by SSeo in human leukemia U937 cells and evaluated the underlying molecular mechanism. Exposure to SSeo resulted in a concentration-dependent growth inhibition due to apoptosis, which was verified by DNA fragmentation, the presence of apoptotic bodies, and an increase in the sub-G1 ratio. Induction of apoptotic cell death by SSeo was correlated with the down-regulation of members of the inhibitor of apoptosis protein (IAP) family (including X-linked inhibitor of apoptosis protein (XIAP), cIAP-1, and surviving) and anti-apoptotic Bcl-2, and with up-regulation of death receptor (DR) 4 and DR5, depending on dosage. SSeo treatment also induced Bid truncation, mitochondrial dysfunction, proteolytic activation of caspase-3, -8 and -9, and concomitant degradation of activated caspase-3 target proteins such as poly (ADP-ribose) polymerase. Taken together, these findings suggest that SSeo may be a potential chemotherapeutic agent for use in the control of human leukemia cells. Further studies are needed to identify its active compounds.

• Journal of Life Science
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• v.14 no.5
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• pp.800-808
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• 2004

Resveratrol, a phytoalexin found at high levels in grapes and in grape products such as red wine, has been reported to possess a wide range of biological and pharmacological activities including antioxident, anti-inflammatory, anti-mutagenic, and anti-carcinogenic effects. According to recent studies, this compound is an effective inhibitor of cell growth in general, triggers partial arrest of the cell cycle and induce apoptosis. In this study, the anti-proliferative effects of resveratrol in A549 human lung carcinoma cells were investigated. It is shown that resveratrol induced the growth inhibition in a time-dependent manner and morphological changes of A549 cells, which were associated with induction of S phase arrest of the cell cycle and apoptotic cell death. The Bcl-$X_L$levels were markedly down-regulated in resveratrol treated cells, however, Bax and Bcl-2 were remained unchanged. Resveratrol treatment induced the proteolytic degradation of Sp-l and proliferating cell nuclear antigen protein, and inhibited the expression of $\beta$-catenin protein. Resveratrol treatment also induced a marked up-regulation of cyclin-dependent kinase (Cdk) inhibitor p21 and inhibited the kinase activities of Cdk2 and Cdk4. In addition, resveratrol treatment inhibited the levels of cyclooxygenase (COX)-2 mRNA and protein, and the release of prostagladin E2 without alteration of COX-1 expression. Taken together, these findings suggest that resveratrol may be a potential chemotherapeutic agent for the control of human lung carcinorma cells.

• Journal of Life Science
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• v.25 no.11
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• pp.1235-1243
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• 2015

Hwangheuk-san (HHS) is a Korean multi-herb formula comprising four medicinal herbs. HHS, which was recorded in “Dongeuibogam,” has been used to treat patients with inflammation syndromes and digestive tract cancer for hundreds of years. However, little is known about its anti-tumor efficacy. The present study investigated the pro-apoptotic effect and mode of action of HHS against AGS human gastric carcinoma cells. HHS inhibited the cell growth of AGS cells in a dose-dependent manner, which was associated with the induction of apoptotic cell death, as evidenced by the formation of apoptotic bodies, chromatin condensation, and an accumulation of cells in the sub-G1 phase. HHS-induced apoptotic cell death was associated with the up-regulation of pro-apoptotic Bax protein expression, down-regulation of antiapoptotic Bcl-2 protein, and the release of cytochrome c from mitochondria to the cytosol. The treatment of AGS cells with HHS significantly elevated the generation of reactive oxygen species (ROS). Additionally, apoptosis-inducing concentrations of HHS induced the activation of both caspase-9 and -8, initiator caspases of the mitochondrial-mediated intrinsic and death receptor-mediated extrinsic pathways, respectively, and caspase-3, accompanied by proteolytic degradation of poly (ADP-ribose)-polymerase. However, ROS scavenger and pan-caspases inhibitor significantly blocked HHS-induced growth inhibition and apoptosis. Taken together, these findings suggest that HHS induces apoptosis through ROS- and caspase-dependent mechanisms and that HHS may be a potential chemotherapeutic agent for the control of human gastric cancer.

• Journal of Life Science
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• v.25 no.11
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• pp.1255-1264
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• 2015

Cnidium officinale, a traditional herb, has diverse beneficial pharmacological activities, such as anti-inflammatory, antioxidant, anticancer, and antiangiogenesis effects. However, the cellular and molecular mechanisms of apoptosis by C. officinale are poorly defined. The present study investigated the proapoptotic effects of water, ethanol, and methanol extract of C. officinale (WECO, EECO, and MECO, respectively) in human leukemia U937 cells. The antiproliferative activity of EECO was higher than that of WECO and MECO. The antiproliferative effect of EECO treatment in U937 cells was associated with the induction of apoptotic cell death, including increased populations of annexin-V positive cells, the formation of apoptotic bodies, DNA fragmentation, and increased numbers of cells with a loss of mitochondrial membrane potential (MMP, Δψm). EECO-induced apoptotic cell death was associated with upregulation of death receptor 4 (DR4) and down-regulation of cellular inhibitor of apoptosis protein-1 (cIAP-1), Bcl-2, and total Bid. The EECO treatment also induced the proteolytic activation of caspases (-3, -8, and -9), and degradation of caspase-3 substrate proteins, such as poly(ADP-ribose) polymerase (PARP), β-catenin, and phospholipase C-γ1 (PLCγ1). In addition, the EECO treatment effectively activated the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. However, compound C, a specific inhibitor of AMPK, significantly reduced EECO-induced apoptosis. These results indicate that AMPK is a key regulator of apoptosis in response to EECO in human leukemia U937 cells.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.6
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• pp.714-720
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• 2008

Cordyceps militaris is a medicinal fungus which has been used for patient suffering from cancer in Oriental medicine. It was previously reported that C. militaris extracts are capable of inhibiting tumor growth and inducing apoptosis; however, the anti-poliferative effects of human cancer cells have been poorly understood. In this study, to elucidate the anti-cancer mechanisms of human cancer cells by treatment with aqueous extract of C. militaris (AECM), we investigated the anti-proliferative effects of AECM in human hepatocarcinoma Hep3B cells. AECM treatment inhibited the growth of Hep3B cells and induced the apoptotic cell death in a concentration-dependent manner such as formation of apoptotic bodies and increased populations of apoptotic-sub G1 phase. The induction of apoptosis by AECM was connected with a proteolytic activation of caspase-3 and caspase-8. and concomitant degradation of poly (ADP-ribose) polymerase (PARP) and ${\beta}$-catenin proteins. Furthermore, caspase-3 inhibitor, z-DEVD-fmk, significantly inhibited AECM-induced apoptosis demonstrating the important role of caspase-3 in the bserved cytotoxic effect. Taken together, these findings suggest that AECM-induced inhibition of human hepatocarcinoma cell proliferation is associated with the induction of apoptotic cell death via activation of caspase-3 and C. militaris may have therapeutic potential in human cancer.

• Korean Journal of Plant Resources
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• v.32 no.5
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• pp.442-447
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• 2019

In this study, we evaluated the effect of Rodgersia podophylla leave extracts (RPL) on ${\beta}-catenin$ level in human cancer cells. RPL dose-dependently inhibited cell proliferation in SW480, A549, MDA-MB-231, PC-3 and AsPC-1 cells. RPL dramatically decreased ${\beta}-catenin$ protein level in all cancer cells. However, decreased level of ${\beta}-catenin$ mRNA expression was observed in A549 and AsPC-1 cells. In addition, RPL dramatically attenuated cyclin D1 mRNA expression in all cancer cells. MG132 decreased the downregulation of ${\beta}-catenin$ protein level induced by RPL in all cancer cells, while RPL-induced downregulation of ${\beta}-catenin$ was inhibited by the inhibition of $GSK-3{\beta}$ by LiCl in MDA-MB-231 cells. RPL phosphorylated ${\beta}-catenin$ and $GSK-3{\beta}$. In addition, the inhibition of $GSK-3{\beta}$ by LiCl attenuated RPL-induced ${\beta}-catenin$ phosphorylation. Based on these findings, RPL may be a potential candidate for the development of chemopreventive or therapeutic agents for human cancer.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.213-220
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• 2023

The most common skin disease, acne, often occurs in adolescence, but it is also detected/observed in adults due to air pollution and drug abuse. One of the causative agents of acne, Cutibacterium acnes (C. acnes) plays a role in the development of skin acne by inducing inflammatory mediators. Torreya nucifera (TN) is an evergreen tree of the family Taxaceae, having well reported antioxidant, anti-proliferative, liver protection, and nerve protection properties. Improvement of these bioactive properties of natural products is one of the purposes of natural product chemistry and pharmaceuticals. We believe biorenovation could be one improvement strategy that utilizes microbial metabolism to produce unique derivatives having enhanced bioactivity. Therefore, in this study, the C. acnes-induced RAW264.7 inflammation model was used to evaluate the anti-inflammatory activity of the biorenovated Torreya nucifera product (TNB). The results showed improved viability of TNB-treated cells compared to TN-treated cells in the concentration range of 50, 100, and 200 ㎍/mL. At non-toxic concentrations, TNB inhibited the production of nitric oxide and prostaglandin E2 by suppression of inducible nitric oxide synthase and cyclooxygenase-2 protein expression. TNB also attenuated the expression of interleukin-1β, interleukin-6, interleukin-8, and tumor necrosis factor-α induced by C. acnes. Furthermore, TNB inhibited the nuclear factor-κB signaling pathway, a transcription factor known to regulate inflammatory mediators. Based on these results, this study suggests the potential of using TNB as natural material for the treatment of acnes and thus, supporting our postulation of biorenovation as an bioactivity improvement strategy.

• The Journal of Internal Korean Medicine
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• v.32 no.4
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• pp.565-583
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• 2011

Objectives : This study investigated the biochemical mechanisms of anti-proliferative and pro-apoptotic effects of the water extract of Dan-Seon-Tang (DST) in human leukemia U937 cells. Methods : U937 cells were exposed to DST and growth inhibition was measured by MTT assay. Results : Exposure of U937 cells to DST resulted in the growth inhibition in a concentration-dependent manner. This inhibitory effect was associated with morphological changes and apoptotic cell death such as formation of apoptotic bodies, increased populations of apoptotic-sub G1 phase and induction of DNA fragmentation. The induction of apoptotic cell death in U937 cells by DST was associated with up-regulation of death receptor 4 (DR4) and down-regulation of Bid, surviving and cellular inhibition of apoptosis protein-2 (cIAP-2) expression. DST treatment also induced the proteolytic activation of caspase-3, caspase-8 and caspase-9, and a concomitant degradation of caspase-3 substrate proteins such as poly (ADP-ribose) polymerase (PARP), phospholipase (PLC)-${\gamma}1$, ${\beta}$-catenin and DNA fragmentation factor 45/inhibotor of caspase activated DNAse (DFF45/ICAD). Furthermore, apoptotic cell death by DST was significantly inhibited by caspase-3 specific inhibitor z-DEVD-fmk, demonstrating the important role of caspase-3. Conclusions : These findings suggest that herb prescription DST may be a potential chemotherapeutic agent for the control of human leukemia U937 cells; further study is needed to identify the active compounds.