• Biomolecules & Therapeutics
• /
• v.28 no.5
• /
• pp.414-422
• /
• 2020

Fangchinoline (FAN) is a bisbenzylisoquinoline alkaloid that is widely known for its anti-tumor properties. The goal of this study is to examine the effects of FAN on arthritis and the possible pathways it acts on. Human fibroblast-like synovial cells (FLS), carrageenan/kaolin arthritis rat model (C/K), and collagen-induced arthritis (CIA) mice model were used to establish the efficiency of FAN in arthritis. Human FLS cells were treated with FAN (1, 2.5, 5, 10 µM) 1 h before IL-1β (10 ng/mL) stimulation. Cell viability, reactive oxygen species measurement, and western blot analysis of inflammatory mediators and the MAPK and NF-κB pathways were performed. In the animal models, after induction of arthritis, the rodents were given 10 and 30 mg/kg of FAN orally 1 h before conducting behavioral experiments such as weight distribution ratio, knee thickness measurement, squeaking score, body weight measurement, paw volume measurement, and arthritis index measurement. Rodent knee joints were also analyzed histologically through H&E staining and safranin staining. FAN decreased the production of inflammatory cytokines and ROS in human FLS cells as well as the phosphorylation of the MAPK pathway and NF-κB pathway in human FLS cells. The behavioral parameters in the C/K rat model and CIA mouse model and inflammatory signs in the histological analysis were found to be ameliorated in FAN-treated groups. Cartilage degradation in CIA mice knee joints were shown to have been suppressed by FAN. These findings suggest that fangchinoline has the potential to be a therapeutic source for the treatment of rheumatoid arthritis.

• Archives of Pharmacal Research
• /
• v.25 no.4
• /
• pp.522-527
• /
• 2002

The antimetastatic effect of BCG-CWS, which was emulsified in an oil-in-water form with either Drakeol 6VR mineral oil (BCG-CWS/DK) or squalane (BCG-CWS/SQA), on lung metastasis produced by highly metastatic murine tumor cells, Colon26-M3.1 carcinoma cells and B16-BL6 melanoma cells, was investigated in syngeneic mice. An intravenous (i.v.) administration of BCG-CWS (100 mg/mouse) 1 day after tumor inoculation significantly inhibited tumor metastasis of both Colon26-M3.1 carcinoma and B16-BL6 melanoma cells in experimental lung metastasis models. No differences in the antitumor activity of the two oil-based formulations (BCG-CWS/DK and BCG-CWS/SQA) were obverved. However, BCG-CWS/SQA administered through subcutaneous (s.c.) route was shown to be effective only when it was consecutively injected (3 times) after tumor inoculation. An in vivo analysis for tumor-induced angiogenesis shwed that a single i.v. administration of BCG-CWS/SQA inhibited the number of tumor-induced blood vessels and suppressed tumor growth. Furthermore, the multiple administration of BCG-CWS/SQA given at on week intervals led to a significant reduction in spontaneous lung metastasis of B16-BL6 melanoma cells in a spontaneous metastasis model. These results suggest that BCG-CWS emulsified with squalane is a potent inhibitory agent of lung metastasis, and that the anti metastatic effect of BCG-CWS is related to the suppression of tumor growth and the inhibition of tumor-induced angiogenesis.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.17 no.3
• /
• pp.605-610
• /
• 2003

According to the Leukemia and Lymphoma Society, leukemia is a malignant disease (cancer) that originates in a cell in the marrow. It is characterized by the uncontrolled growth of developing marrow cells. There are two major classifications of leukemia: myelogenous or lymphocytic, which can each be acute or chronic. The terms myelogenous or lymphocytic denote the cell type involved. Thus, four major types of leukemia are: acute or chronic myelogenous leukemia and acute or chronic lymphocytic leukemia. Leukemia, lymphoma and myeloma are considered to be related cancers because they involve the uncontrolled growth of cells with similar functions and origins. The diseases result from an acquired (not inherited) genetic injury to the DNA of a single cell, which becomes abnormal (malignant) and multiplies continuously. In the United States, about 2,000 children and 27,000 adults are diagnosed each year with leukemia. Treatment for cancer may include one or more of the following: chemotherapy, radiation therapy, biological therapy, surgery and bone marrow transplantation. The most effective treatment for leukemia is chemotherapy, which may involve one or a combination of anticancer drugs that destroy cancer cells. Specific types of leukemia are sometimes treated with radiation therapy or biological therapy. Common side effects of most chemotherapy drugs include hair loss, nausea and vomiting, decreased blood counts and infections. Each type of leukemia is sensitive to different combinations of chemotherapy. Medications and length of treatment vary from person to person. Treatment time is usually from one to two years. During this time, your care is managed on an outpatient basis at M. D. Anderson Cancer Center or through your local doctor. Once your protocol is determined, you will receive more specific information about the drug(s) that Will be used to treat your leukemia. There are many factors that will determine the course of treatment, including age, general health, the specific type of leukemia, and also whether there has been previous treatment. there is considerable interest among basic and clinical researchers in novel drugs with activity against leukemia. the vast history of experience of traditional oriental medicine with medicinal plants may facilitate the identification of novel anti leukemic compounds. In the present investigation, we studied 31 kinds of anti leukemic medicinal plants, which its pharmacological action was already reported through many experimental articles and oriental medical book: 『pharmacological action and application of anticancer traditional chinese medicine』 In summary: Used leukemia cellline are HL60, HL-60, Jurkat, Molt-4 of human, and P388, L-1210, L615, L-210, EL-4 of mouse. 31 kinds of anti leukemic medicinal plants are Panax ginseng C.A Mey; Polygonum cuspidatum Sieb. et Zucc; Daphne genkwa Sieb. et Zucc; Aloe ferox Mill; Phorboc diester; Tripterygium wilfordii Hook .f.; Lycoris radiata (L Her)Herb; Atractylodes macrocephala Koidz; Lilium brownii F.E. Brown Var; Paeonia suffruticosa Andr.; Angelica sinensis (Oliv.) Diels; Asparagus cochinensis (Lour. )Merr; Isatis tinctoria L.; Leonurus heterophyllus Sweet; Phytolacca acinosa Roxb.; Trichosanthes kirilowii Maxim; Dioscorea opposita Thumb; Schisandra chinensis (Rurcz. )Baill.; Auium Sativum L; Isatis tinctoria, L; Ligustisum Chvanxiong Hort; Glycyrrhiza uralensis Fisch; Euphorbia Kansui Liou; Polygala tenuifolia Willd; Evodia rutaecarpa (Juss.) Benth; Chelidonium majus L; Rumax madaeo Mak; Sophora Subprostmousea Chunet T.ehen; Strychnos mux-vomical; Acanthopanax senticosus (Rupr.et Maxim.)Harms; Rubia cordifolia L. Anti leukemic compounds, which were isolated from medicinal plants are ginsenoside Ro, ginsenoside Rh2, Emodin, Yuanhuacine, Aleemodin, phorbocdiester, Triptolide, Homolycorine, Atractylol, Colchicnamile, Paeonol, Aspargus polysaccharide A.B.C.D, Indirubin, Leonunrine, Acinosohic acid, Trichosanthin, Ge 132, Schizandrin, allicin, Indirubin, cmdiumlactone chuanxiongol, 18A glycyrrhetic acid, Kansuiphorin A 13 oxyingenol Kansuiphorin B. These investigation suggest that it may be very useful for developing more effective anti leukemic new dregs from medicinal plants.

• Journal of Mushroom
• /
• v.11 no.4
• /
• pp.254-260
• /
• 2013

The objective of this study was to evaluate antioxidant effect and tyrosinase inhibitory activity of methanol extracts from Hypsizygus marmoreus. The Hypsizygus marmoreus was divided into two parts (pileus and stipe) and extracted with methanol. Total polyphenolics and flavonoids in the methanol extracts were measured by spectrophotometric methods and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities have been determined for antioxidant activities. The total polyphenolics and flavonoids contents of methanol extract of the pileus were higher than methanol extract of the stipes. The total polyphenolics contents in methanol extracts of the pileus and stipes were 8.7 ug/mg and 5.6 ug/mg, respectively. The total flavonoids contents in methanol extracts of the pileus and stipes were 2.8 ug/mg and 1.4 ug/mg, respectively. The tyrosinase inhibitory activity was proportional to concentration of methanol extract. The tyrosinase inhibitory activity of the methanol extract (200 mg/ml) of pileus (66.9%) and stipe (57.97%) was lower than those of positive control 2% arbutin. The DPPH radical scavenging activity of the methanol extract (20 mg/ml) of pileus and stipes was 52.55% and 30.35%, respectively. Moreover, the effects of methanol extarcts on cell proliferation of B16BL6 mouse melanoma cells were investigated using WST-1 assay (4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulphonate) and B16BL6 mouse melanoma cells treated with methanol extract of 200-2,000 ug/ml were higher proliferation rate than those of 0.04% adenosine.

• Food Science and Preservation
• /
• v.24 no.8
• /
• pp.1149-1157
• /
• 2017

Inflammation is the first response of the immune system to infection or irritation in our body. The use of medicinal plants has been widely applied as an alternative source for drug development. One of marine natural resources, the anti-inflammatory effect of Ishige sinicola ethanol extract (ISEE), was evaluated by using LPS-induced RAW 264.7 cell and mice model. As a result, the production of nitric oxide (NO) and pro-inflammatory cytokines (IL-6, IL-$1{\beta}$, TNF-${\alpha}$) were inhibited with increasing concentration of ISEE without any cytotoxicity. Furthermore, ISEE suppressed the expression of not only inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-kappa B (NF-${\kappa}B$) p65, and mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK) 1/2, p38, and c-Jun N-terminal kinase (JNK) in a dose-dependent manner. In mice ear edema test, the formation of edema was reduced at the highest dosage of ISEE and the reduction of the number of infiltrated mast cells was observed in histological analysis. These results indicate that ISEE has a potent anti-inflammatory activity and can be used as a pharmaceutical material for many kinds of inflammatory disease.

• Journal of Life Science
• /
• v.28 no.6
• /
• pp.648-655
• /
• 2018

Enhancement mechanistic actions of testosterone (TS) productions in mouse Leydig TM3 cells by the eritadenine (EA) and/or the Agaricus blazei mycelial liquid culture extract (ABMLCE). Productions of TS in TM3 cells were investigated in normal and oxidative-stressed culture conditions. In the normal culture condition, TM3 cells grown in a Dulbecco's Modified Eagle's Medium (DMEM) were treated with EA (0~100 ppm) and ABMLCE (10 ppm) + EA (0~50 ppm) for 24 hr, and in the oxidative-stressed culture condition, the cells grown in DMEM containing $50{\mu}M$ $H_2O_2$ to induce oxidative stress for 4 h were treated with the same as those in the normal culture condition. TS content, $3{\beta}$-hydroxysteroid dehydrogenase 2 (HSD3B2) enzyme activity, $5{\alpha}$-reductase 2 ($5{\alpha}-R2$) enzyme activity, and free-radical nitric oxide (NO) content in the culture media were measured using their corresponding assay kits. EA, ABMLCE, and ABMLCE + EA significantly, p<0.05, enhanced TS productions in both cultural conditions, relative to control treatment. The activity of the HSD3B2 enzyme, which is involved in the production of precursors for TS production, was elevated by EA, ABMLCE, and ABMLCE + EA treatments in both culture conditions. The activity of the $5{\alpha}-R2$ enzyme, which converts TS to dihydroxytestosterone (DHT), was not significantly affected in either culture condition by EA, ABMLCE, or ABMLCE + EA treatments. The treatments included reduced NO content. These results indicate that EA, ABMLCE, and EA + ABMLCE treatments elevated TS in TM3 cells via the enhancements of HSD3B2 activity and the reduction of NO production, and also imply that EA and ABMLCE or EA + ABMLCE could be useful materials for the production of TS in humans.

• Microbiology and Biotechnology Letters
• /
• v.44 no.3
• /
• pp.268-277
• /
• 2016

This study aimed to investigate the anti-inflammatory effect of the ethanol extract from Chondrus ocellatus Holmes (COHEE) in RAW 264.7 cells and in a mouse ear edema model, by measuring the production of lipopolysaccharide-induced inflammatory response mediators. There were no cytotoxic effects on the proliferation of macrophages treated with COHEE compared with the control. COHEE inhibited the production of nitric oxide and pro-inflammatory cytokines [interleukin (IL)-6, tumor necrosis factor-α, and IL-1β]. The extract also reduced the expression of inducible nitric oxide synthase, cyclooxygenase-2, nuclear factor-κB p65, and phosphorylated mitogen-activated protein kinase in a dose-dependent manner. In the croton-oil-induced ear edema model, COHEE decreased the formation of mouse ear edema at the highest dose compared with the control, and histological analysis revealed that the epidermal/dermal tissue thickness and mast cell numbers were reduced. Therefore, these results suggest that COHEE may be a promising topical anti-inflammatory therapeutic material through its action of modulating NF-κB and the MAPK signaling pathway.

• Development and Reproduction
• /
• v.10 no.2
• /
• pp.105-113
• /
• 2006

Reactive oxygen species(ROS) generated in cellular metabolism have an effect on cell maturation and development. In human reproductive tract, oxidative injury by ROS may induce female infertility. Also, oxidative injury may be responsible for developmental retardation and arrest of mammalian preimplantation embryos. Activating transcription factor 4(ATF4) is a member of the cyclic-AMP response element-binding(CREB) familiy of basic region- leucine zipper(bZip). ATF4 is known to regulate stress response to protect cell from various stress factors and inducer of apoptisis. The purpose of this study was to investigate whether ATF4 is involved in the defensive mechanism in oxidative stress condition during the development of mouse preimplantation embryos. To verify the expression of ATF4 in oxidative stress condition, 2-cell stage embryos were cultured in HTF media containing 0.1mM, 0.5mM or 1mM hydrogen peroxide($H_2O_2$) for 1hr(2-cell), 8hr(4-cell), 17hr(8-cell), 24hr(morula), 48hr(early blastocyst) or 64hr(late blastocyst). The developmental rate decreased in the 0.1mM $H_2O_2$ treated group compared with control group. In embryos treated with 0.5mM and 1mM $H_2O_2$ showed 2-cell block. As a results of the semi-quantitative RT-PCR analysis of SOD1, ATF4 and Bax gene expression, SOD1, ATF4 and Bax genes were increased in 0.1mM, 0.5mM, 1mM $H_2O_2$ treated groups compared with control group. In 2-cell embryos, expression of SOD1, ATF4 and Bax genes were notably increased in 0.1mM, 0.5mM, 1mM $H_2O_2$ treated groups compared with control group. Immunofluorescence analysis showed that ATF4 protein was localized at the cytoplasm of preimplantation embryos. The increase in ATF4 immunoreactivety was observed in the 0.1mM, 0.5mM, 1mM $H_2O_2$ treated groups compared with control group. It suggests that oxidative stress by $H_2O_2$ induces expression of ATF4 and may be involved in protection mechanism in preimplantation embryos from oxidative injury.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
• /
• v.37 no.1
• /
• pp.1-16
• /
• 2024

Objectives : We aimed to study the effect of Smilax China L.(SCL), which has anti-inflammatory, antioxidant, and anticancer effects, on the growth of skin cancer cells. Methods : HaCaT cells, a normal human cell line, and skin cancer cells including A431, SK-MEL-5 and SK-MEL-28 cells were treated with Smilax China L. ethanol extract(SCL-EtOH) at concentrations of 5, 10, 20 and 40㎍/㎖. Meanwhile, JB6 Cl41, a normal mouse epithelial cell line, was treated with epidermal growth factor(EGF) and phorbol 12-myristate 13-acetate(TPA), an inflammatory factor, to induce cell transformation and treated with SCL-EtOH. In addition, we treated SK-MEL-5 and SK-MEL-28 cells with SCL-EtOH at various concentrations and checked the effect on the cell cycle. Results : As a result, it showed no toxicity to HaCaT cells up to the highest concentration of 40㎍/㎖, and significant cell growth inhibition to A431, SK-MEL-5 and SK-MEL-28 cells in a time- and concentration-dependent manner. In addition, as a result of checking the shape of skin cancer cells according to SCL-EtOH treatment, it was observed that as the concentration increased, the number of normally attached and growing cells decreased and the shape of the cells changed. Colony formation was significantly reduced in a concentration-dependent manner in JB6 Cl41 cells treated with EGF or TPA. Flow cytometry analysis with propidium iodide(PI) staining showed that SCL-EtOH induced the G2/M phase arrest. We further confirmed the decrease in Cyclin B1 expression and increase in p27 expression associated with the G2/M phase of the cell cycle through western blot analysis. Flow cytometry analysis confirmed that SCL-EtOH induced cell apoptosis. Furthermore, through Western blot analysis, it was observed that the expression of cleaved-caspase-7, which is related to apoptosis, increased. Finally, it was confirmed that the expression of COX-2, an inflammatory marker protein, decreased in a concentration-dependent manner with SCL-EtOH. Conclusions : Through the above results, we have established a basis for applying SCL to the treatment of skin cancer.

• Journal of Ginseng Research
• /
• v.39 no.3
• /
• pp.189-198
• /
• 2015

Background: Antiallergic effect of 20(S)-protopanaxatriol (PPT), an intestinal metabolite of ginseng saponins, was investigated in guinea pig lung mast cells and mouse bone marrow-derived mast cells activated by a specific antigen/antibody reaction. Methods: Increasing concentrations of PPT were pretreated 5 min prior to antigen stimulation, and various inflammatory mediator releases and their relevant cellular signaling events were measured in those cells. Results: PPT dose-dependently reduced the release of histamine and leukotrienes in both types of mast cells. Especially, in activated bone marrow-derived mast cells, PPT inhibited the expression of Syk protein, cytokine mRNA, cyclooxygenase-1/2, and phospholipase $A_2$ ($PLA_2$), as well as the activities of various protein kinase C isoforms, mitogen-activated protein kinases, $PLA_2$, and transcription factors (nuclear factor-${\kappa}B$ and activator protein-1). Conclusion: PPT reduces the release of inflammatory mediators via inhibiting multiple cellular signaling pathways comprising the $Ca^{2+}$ influx, protein kinase C, and $PLA_2$, which are propagated by Syk activation upon allergic stimulation of mast cells.