• Journal of the Korean Society of Food Science and Nutrition
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• v.36 no.1
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• pp.8-13
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• 2007

This study was conducted to investigate the effect of mycelia of Lentinus edoes mushroom-cultured Astragalus membranaceus Bunge (LAM) on proliferation of cancer cell lines (Hep3B, MCF-7 and HeLa), sarcoma 180 (S-180), and anti-allergy. In an anti-cancer test using Hep3B (hepatic cancer cell), MCF-7 (breast cancer cell) and HeLa (uterine cancer cell), LAM extract showed higher antiproliferating effect than that of Astragalus membranaceus Bunge (AM) extract. In an anti-cancer testing using Hep3B cells and MCF-7 cells, LAM extract showed growth-inhibitory effect of 65.23% at 3 mg/mL and 69.23% at 5 mg/mL, respectively. In an anti-cancer testing using HeLa cells, LAM extract showed growth-inhibitory effect of 42.01% at 5 mg/mL. In addition, LAM showed the tumor suppressive effect in mice injected with S-180 cells. The growth-inhibitory rates against tumor cells were 47% for LAM and 37% for AM. LAM inhibited histamine release from rat peritoneal mast cells activated by compound 48/80. These results suggest that Lentinus edodes mushroom-cultured herb has an antiproliferating effect against cancer cell lines (Hep3B, MCF-7 and HeLa), S-180 tumor and will be beneficial in the treatment of allergic reaction.

• Journal of Applied Biological Chemistry
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• v.64 no.4
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• pp.343-349
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• 2021

The rhizomes of Cnidium officinalis were extracted in aqueous MeOH, and the concentrate was fractionated via systematic solvent fractionation to EtOAc, n-BuOH, and aqueous fractions. The repeated column chromatography of EtOAc and n-BuOH fractions using silica gel, octadecyl silica gel, and Sephadex LH-20 as stationary phase to afford five lipids. They were identified to be methyl linoleate (1), linoleic aicd (2) 6-linoleoyl-𝛼-D-glucopyranosyl 𝛽-D-fructofuranoside (3), 1-linolenoyl-3-(𝛼-D-galactopyranosyl (1→6)-𝛽-D-galactopyranosyl) glycerol (4), and 1-linoleoyl-3-(𝛼-D-galactopyranosyl (1→6)-𝛽-D-galactopyranosyl) glycerol (5) on the basis of spectroscopic data such as IR, MS, and Nuclear magnetic resonance (NMR). Compounds 1 and 3-5 were isolated for the first time from this plant in this study. The NMR data of fatty acids 1 and 2 reported in literatures are different each other. Authors identified the NMR data without ambiguity. Compound 3, a conjugate of sucrose and fatty acid, and compounds 4 and 5, digalactosyl monoglyceride, are very rarely occurred in natural source. Through the immune enhancement and anticancer activity of the reported lipid compounds, the potential as various pharmacologically active materials of Cnidium officinalis rhizome can be expected.

• Microbiology and Biotechnology Letters
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• v.49 no.3
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• pp.458-465
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• 2021

Tubulysins are a group of bioactive secondary metabolites from myxobacteria exhibiting strong anticancer activity against various cancer cell lines. In this study, we describe the identification of putative tubulysin biosynthetic gene clusters (tubA~tubF) in the genome sequences of two tubulysin-producing myxobacterial strains, Archangium gephyra MEHO_002 and MEHO_004. The inactivation of the putative tubulysin biosynthetic genes resulted in a tubulysin-production defect. The DNA sequences of the A. gephyra MEHO_002 and MEHO_004 tubulysin biosynthetic genes were 97% identical, and the amino acid sequences of the encoded proteins shared a similarity of 97-100%. The nucleotide sequences of the tubulysin biosynthetic gene clusters in MEHO_002 and MEHO_004 were 86% identical to that in Cystobacter sp. SBCb004 known as a tubulysin-producing myxobacterium, and the organization of the clusters was identical except for the lack of a tubZ gene in the clusters in MEHO_002 and MEHO_004. The amino acid sequences of the proteins encoded by each gene were 88-97% similar to those encoded by SBCb004, and the domain compositions of the proteins were also identical.

• Journal of Life Science
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• v.31 no.4
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• pp.400-409
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• 2021

Sanguinarine, a natural benzophenanthridine alkaloid, has been considered a potential therapeutic target for the treatment of cancer because it can induce apoptosis in human cancer cells; however, the underlying mechanisms of action still remain unclear. Tumor suppressor p53 deletion or mutation is an important reason for the resistance of colorectal cancer cells to anticancer agents. Therefore, in the present study, the role of p53 during apoptosis induced by sanguinarine was investigated in p53wild type (WT, p53+/+) and p53null (p53+/+) HCT116 colon carcinoma cells. Sanguinarine significantly caused greater reductions in cell viability in HCT116 (p53+/+) cells than in HCT116 (p53-/-) cells. Consistently, sanguinarine promoted more DNA damage and apoptosis in HCT116 (p53+/+) cells than in HCT116 (p53-/-) cells while increasing the expression of p53 and cyclin-dependent kinase inhibitor p21^WAF1/CIP1. Sanguinarine increased the activity of caspase-8 and caspase-9, which are involved in the initiation of extrinsic and intrinsic apoptosis pathways, respectively, and it activated caspase-3, a typical effect caspase, in HCT116 (p53+/+) cells. Sanguinarine also increased the generation of reactive oxygen species (ROS), and the Bax/Bcl-2 ratio, while destroying the integrity of mitochondria in HCT116 (p53+/+) cells, but not in HCT116 (p53-/-) cells. Overall, the results indicate that sanguinarine induced p53-dependent apoptosis through ROS-mediated activation of extrinsic and intrinsic apoptotic pathways in HCT116 colorectal cancer cells.

• Herbal Formula Science
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• v.27 no.2
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• pp.101-120
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• 2019

PURPOSE : Euonymi Lignum Suberalatum (EL) is the stem fin of Euonymi alatus. In traditional Korean medicine, EL is used for treatment of uterine bleeding, metritis and static blood. Recently, many studies have reported several pharmacological effects of EL including anticancer, antimicrobial, antidiabetic activity, and anti-oxidative stress. However, the mechanisms underlying anti-inflammatory effects by the EL is not established. METHODS : To investigate anti-inflammatory effects of Euonymi Lignum Suberalatum Water (ELWE), Raw 264.7 cells were pre-treated with $10-300{\mu}g/mL$ of ELWE, and then exposed to $1{\mu}g/mL$ of LPS. Levels of NO, IL-6, $IL-1{\beta}$ and $TNF-{\alpha}$ were detected by ELISA kit. Expression of pro-inflammatory proteins were determined by immunoblot analysis. To evaluate the anti-inflammatory effect in vivo, rat paw edema volume, and expressions of COX-2 and iNOS proteins in carrageenan (CA)-induced rat paw edema model. RESULTS : NO production activated by LPS, was decreased by $30-300{\mu}g/mL$ of ELWE. Production of inflammatory mediators such as $TNF-{\alpha}$, ILs, $PGE_2$ were decreased by ELWE 100 and $300{\mu}g/mL$. In addition, ELWE reduced LPS-mediated iNOS and COX-2 expression. Moreover, ELWE increased $I-{\kappa}B{\alpha}$ expression in cytoplasm and decreased $NF-{\kappa}B$ expression in nucleus. In vivo study, ELWE reduced the increases of paw swelling, and expression of iNOS and COX-2 proteins in paw edema induced by CA injection. CONCLUSION : The results indicate that ELWE could inhibit the acute inflammatory response, via modulation of $NF-{\kappa}B$ activation. Furthermore, inhibition of rat paw edema induced by CA is considered as clear evidence that ELWE may be a useful source to treat acute inflammation.

• Korean Journal of Plant Resources
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• v.32 no.2
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• pp.153-159
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• 2019

In this study, we evaluated the effect of branch (STB) and leave (STL) extracts from Sageretia thea on ${\beta}-catenin$ level in human colorecal cancer cells, SW480 and lung cancer cells, A549. STB and STL dose-dependently suppressed the growth of SW480 and A549 cells. STB and STL decreased ${\beta}-catenin$ level in both protein and mRNA level. MG132 decreased the downregulation of ${\beta}-catenin$ protein level induced by STB and STL. However, the inhibition of $GSK3{\beta}$ by LiCl or ROS scavenging by NAC did not block the reduction of ${\beta}-catenin$ protein by STB and STL. Our results suggested that STB and STL may downregulate ${\beta}-catenin$ protein level independent on $GSK3{\beta}$ and ROS. Based on these findings, STB and STL may be a potential candidate for the development of chemopreventive or therapeutic agents for human colorectal cancer and lung cancer.

• Journal of Life Science
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• v.31 no.12
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• pp.1128-1141
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• 2021

'Angelica' is one of the most traditionally consumed medicinal herbs around Northeast Asia including Korea for treatments of various diseases or health care purposes like hematopoiesis, blood circulation for women, sedative, analgesic, and a tonic medicine etc. Angelica gigas Nakai, a Korean native species of Angelica, is clearly different from the others in containing a high concentration of active ingredients like pyranocoumarines including decursin, decursinol, and decursinol angelate. These compounds have various kinds of positive effects such as anti-tumor activity including the precaution of neutropenia occurred during anticancer drug administration, improvements of metabolic disorders, menstrual irregularity, impairment of renal function, respiration improvement, cognition-enhancement, anti-inflammatory effect, anti-oxidative effect, enhancing fertility and so forth. Thus it implies incredible potentialities in future development for foods and drugs. However, certain purity-related qualities and/or overdose in food products can cause side effects like toxicities; therefore, their safety profiles should also be considered. This review focuses on the positive and negative effects of three pyranocoumarines in Angelica gigas Nakai and some possibilities and considerations for future food and drug products development.

• Journal of Ginseng Research
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• v.47 no.2
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• pp.337-346
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• 2023

Background: Ginsenoside Rb2, a major active component of Panax ginseng, has various physiological activities, including anticancer and anti-inflammatory effects. However, the mechanisms underlying the rejuvenation effect of Rb2 in human skin cells have not been elucidated. Methods: We performed a senescence-associated β-galactosidase staining assay to confirm cellular senescence in human dermal fibroblasts (HDFs). The regulatory effects of Rb2 on autophagy were evaluated by analyzing the expression of autophagy marker proteins, such as microtubule-associated protein 1A/1B-light chain (LC) 3 and p62, using immunoblotting. Autophagosome and autolysosome formation was monitored using transmission electron microscopy. Autophagic flux was analyzed using tandem-labeled GFP-RFP-LC3, and lysosomal function was assessed with Lysotracker. We performed RNA sequencing to identify potential target genes related to HDF rejuvenation mediated by Rb2. To verify the functions of the target genes, we silenced them using shRNAs. Results: Rb2 decreased β-galactosidase activity and altered the expression of cell cycle regulatory proteins in senescent HDFs. Rb2 markedly induced the conversion of LC3-I to LC3-II and LC3 puncta. Moreover, Rb2 increased lysosomal function and red puncta in tandem-labeled GFP-RFP-LC3, which indicate that Rb2 promoted autophagic flux. RNA sequencing data showed that the expression of DNA damage-regulated autophagy modulator 2 (DRAM2) was induced by Rb2. In autophagy signaling, Rb2 activated the AMPK-ULK1 pathway and inactivated mTOR. DRAM2 knockdown inhibited autophagy and Rb2-restored cellular senescence. Conclusion: Rb2 reverses cellular senescence by activating autophagy via the AMPK-mTOR pathway and induction of DRAM2, suggesting that Rb2 might have potential value as an antiaging agent.

• Journal of The Korean Society of Integrative Medicine
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• v.12 no.1
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• pp.1-10
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• 2024

Purpose: Lycopene is abundantly contained in Tomatoes and is known for diverse biological activities such as antioxidant, anti-inflammatory, and anticancer effects. In this study, the antioxidative potential of lycopene was investigated through the induction of hemeoxygenase (HO)-1 by nuclear factor-erythroid 2 p45-related factor2 (Nrf2) and upstream signaling molecules, mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/Aktin RAW 264.7 cells. Methods: The antioxidative potential of lycopene against oxidative stress and its molecular mechanisms were determined by the cell viability assay, intracellular reactive oxygen species (ROS) formation assay, and Western blot analysis in RAW 264.7 cells. Results: Lycopene treatment significantly attenuated tert-butyl hydroperoxide (t-BHP) induced intracellular ROS formation in a dose-dependent manner without any cytotoxicity. In addition, 50 µM of lycopene for 6 h treatment induced potent HO-1 expression and its transcription factor, Nrf2. MAPK and PI3K/Aktwere also analyzed due to their critical roles in the regulation of cellular redox homeostasis against oxidative damage. As a result, phosphorylation of extracellular regulated kinase (ERK) was significantly induced by lycopene treatment while the activated status of c-Jun NH2-terminal kinase (JNK), p38, and Akt, were not given any effect. To confirm the antioxidative mechanism of HO-1 mediated by ERK activation, each selective inhibitor was employed in a protection assay, in which oxidative damage occurred by t-BHP. Lycopene, SnPP, and CoPP treatments reflected accelerated HO-1 expression could be a protective role against oxidative damage-initiated cell death. A selective inhibitor for ERK significantly inhibited the lycopene-induced cytoprotective effect but selective inhibitors for other signaling molecules did not attenuate the rate of t-BHP-induced cell death. Conclusion: In conclusion, lycopene potently scavenged intracellular ROS formation and enhanced the HO-1 mediated antioxidative potential through the modulation of Nrf2, MAPK signaling pathway in RAW 264.7 cells.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.402-407
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• 2023

The regulation of platelet aggregation is crucial for maintaining normal hemostasis, but abnormal or excessive platelet aggregation can contribute to cardiovascular disorders such as stroke, atherosclerosis, and thrombosis. Therefore, identifying substances that can control or suppress platelet aggregation is a promising approach for the prevention and treatment of these conditions. Artemisinin, a compound derived from Artemisia or Scopolia plants, has shown potential in various areas such as anticancer and Alzheimer's disease research. However, the specific role and mechanisms by which artemisinin influences platelet activation and thrombus formation are not yet fully understood. This study investigated the effects of artemisinin on platelet activation and thrombus formation. As a result, cAMP production were increased significantly by artemisinin, as well as phosphorylated VASP and IP₃R which are substrates to cAMP-dependent kinase by artemisinin in a significant manner. The Ca²⁺ normally mobilized from the dense tubular system was inhibited due to IP₃R phosphorylation from artemisinin, and phosphorylated VASP by artemisinin aided in inhibiting platelet activity via αIIb/β3 platelet membrane inactivation and inhibiting fibrinogen binding. Finally, artemisinin inhibited thrombin-induced thrombus formation. Therefore, we suggest that artemisinin has importance with cardiovascular diseases stemming from the abnormal platelets activation and thrombus formation by acting as an effective prophylactic and therapeutic agent.