The novel herbal cocktail MA128 suppresses tumor growth and the metastatic potential of highly malignant tumor cells

KIM, AEYUNG,IM, MINJU,YIM, NAM-HIU,HWANG, YOUN-HWAN,YANG, HYE JIN,MA, JIN YEUL Spandidos Publications 2015 ONCOLOGY REPORTS Vol.34 No.2

<P>MA128, a novel herbal medicine, was previously identified and its effectiveness in the treatment of asthma and atopic dermatitis (AD) was demonstrated. In particular, post-inflammatory hyperpigmentation (PIH) in AD mice was improved by treatment with MA128. In addition, MA128 exhibited anti-melanogenic activity by inhibiting tyrosinase activity via the p38 MAPK and protein kinase A signaling pathways in B16F10 cells. In the present study, we examined whether oral administration of MA128 suppressed the in vivo tumor growth of HT1080 cells in athymic nude mice. The results showed that the daily oral administration of 75 and 150 mg/kg MA128 suppressed the tumorigenic growth of HT1080 cells efficiently. Since metastasis is a major cause of cancer-associated mortality and the greatest challenge during cancer treatment, we investigated the effect of non-toxic concentrations of MA128 on the metastatic potential of HT1080 cells. MA128 inhibited anchorage-independent colony formation, migration and invasion. Matrix metalloproteinase-9 (MMP-9) activity under resting and PMA-stimulated conditions was decreased in a dose-dependent manner by MA128 in HT1080 cells. In addition, the daily oral administration of MA128 at doses of 75 and 150 mg/kg efficiently blocked the lung metastasis of B16F10 cells that had been injected into the tail veins of C57BL/6 mice. In particular, none of the mice treated with MA128 exhibited systemic toxicity, such as body weight loss or liver and kidney dysfunction. MA128 also inhibited tumor-induced angiogenesis. Taken together, the results suggest that MA128 is a potential therapeutic agent and a safe herbal medicine for controlling malignant and metastatic cancer.</P>

Anti-melanogenic activity of the novel herbal medicine, MA128, through inhibition of tyrosinase activity mediated by the p38 mitogen-activated protein kinases and protein kinase signaling pathway in B16F10 cells

Kim, Aeyung,Ma, Jin Yeul Medknow PublicationsMedia Pvt Ltd 2014 Pharmacognosy magazine Vol.10 No.39

<P><B>Background:</B></P><P>Recently, our research group developed MA128, a novel herbal medicine, and demonstrated that MA128 is effective for the treatment of asthma and atopic dermatitis (AD). In particular, postinflammatory hyper-pigmentation in AD mice was improved with MA128 treatment. Thus, in this study, we determined the effect of MA128 on melanogenesis and its underlying mechanism in murine B16F10 melanoma cells.</P><P><B>Materials and Methods:</B></P><P>After treatment with MA128 at 100 and 250 μg/mL and/or alpha-melanocyte stimulating hormone (α-MSH) (1 μM), cellular melanin content and tyrosinase activity in B16F10 cells were measured. Using western blotting, expression levels of tyrosinase, tyrosinase-related protein-1 (TRP-1), TRP-2, microphthalmia-associated transcription factor (MITF), and activation of c-AMP-dependent protein kinase (PKA), c-AMP-related element binding protein (CREB) and mitogen-activated protein kinases (MAPKs) were examined.</P><P><B>Results:</B></P><P>MA128 significantly inhibited melanin synthesis and tyrosinase activity in a resting state as well as α-MSH-stimulating condition, and significantly decreased the expression of tyrosinase, TRP-1, TRP-2 and MITF. In addition, phosphorylation of PKA and CREB by α-MSH stimulation was efficiently blocked by MA128 pretreatment. Moreover, MA128 as an herbal mixture showed synergistic anti-melanogenic effects compared with each single constituent herb.</P><P><B>Conclusion:</B></P><P>MA128 showed anti-melanogenic activity through inhibition of tyrosinase activity mediated by p38 MAPK and PKA signaling pathways in B16F10 cells. These results suggest that MA128 may be useful as an herbal medicine for controlling hyper-pigmentation and as a skin-whitening agent.</P>

Oral Administration of Novel Oriental Medicine, KIOM-C, Protect against Influenza Virus

Jin Yeul Ma, Eun Ha Kim, Jun Han Lee, Min-Suk Song, Yun Hee Baek, Young Ki Choi 충북대학교 동물의학연구소 2012 Journal of Biomedical and Translational Research Vol.13 No.2

The influenza virus is an important respiratory risk affecting humans, and effective treatments are needed. Some oriental medicines are currently applied for treatment of common colds as well as influenza infection. Previous studies have reported that the therapeutic properties of MA-128 are effective for treatment of psoriasis antiasthmatic and atopic dermatitis. In this study, we investigated the therapeutic properties of the novel herbal medicine, MA-128, for treatment of influenza virus infection by oral administration. MA-128 is an active natural biological compound from herbal-marine origin. The results showed that oral administration of MA-128 in mice could confer a survival benefit against Type A influenza virus infection. Daily oral administration of MA- 128 resulted in delayed death in infected mice for three days against mouse adapted H3N2 (A/Philippines/2/82). However, it protected more than 60% of mice from lethal infection of 2009 pandemic H1N1 (A/Korea/CJ01/2009) influenza virus. In addition, lung viral titers were significantly reduced at seven days post infection (~100 times) compared with mock-treated mice and viruses were cleared at 9 dpi only in the MA-128 treated groups. This study demonstrated the potential of the novel herbal medicine, MA-128, as an herbal remedy against influenza A viruses.

Vibrio parahemolyticus에 대한 한방처방 [方藥合編] 및 그 단미제의 항균활성에 관한 연구

마진열,김진숙,신순식,정규용,박갑주 한국한의학연구원 1999 한국한의학연구원논문집 Vol.5 No.1

Vibrio are become prevailing if superficial temperature of ocean is raised and their activities of area are expanded and most of ocean creatures (fishes, oysters etc) are polluted with vibrio. The one who has taken these polluted fishes and aysters uncooked caused foodpoisoning and diarrhea from Vibrio. Frequencise of these diseases breakout is disposed in westsea shore of Korea. According to ancient and traditional Korean medical book -『Bangyak Happyeon』(Collection of Local Medicines, 1884) - and their single prescibes, we carried out experiment check the activities of natural medicinal effects on Vibrio parahemolyticus. The prescriptions of trial materials are processed from extraction boiling water and 80% methanol and followed freeze dried and adsorbed to every discs in dosage of 10mg. Gentamycin of 10mg were used for control. The result of compound prescription displayed special diseases in antimicrobial activities of boiling water and MeOH extraction compared with control. In compound prescription, extraction MeOH of Sashinhwan(clear zone : 17mm) presented extraordinaire antimicrobial activity. In single prescription, extraction of boiling water (clear zone : 16mm) and MeOH(clear zone : 18mm) of Fructus Chebulae presented extraordinaire antimicrobial activity. The MBC of Fructus Chebulae extracts was expressed in boiling water (1.28mg/ml) and MeOH(0.64mg/ml).

Monoamine Oxidase 의 활성 변화에 의한 기미론 연구

黃今熙,마진열,金仁洛 대한본초학회 1999 大韓本草學會誌 Vol.14 No.1

To explain the theory of KIMI which is the theory of therapeutics in oriental medicine, the monoamine oxidase(MAO) activities were determined in the brain and liver of mouse which was orally adminstered cold and hot drugs, and forced swimming in cold and hot water. The MAO plays a central role in the metabolism of many amines including the neurotransmetter monoamines. MAO is a flavoprotein found exclusively in the mitochondrial outer membrane, occuring in the MAO-A and MAO-B subtypes. MAO-A deaminates serotonin and noradrenaline, whereas MAO-B prefers penylethylamine and benzylamine as substrates. Serotonin is important neurotransmetter for the control of body temperature. Coptis japonica Makino was selected as the cold drug, and Radix Aconiti lateralis preparata was as the hot drug. Coptis japonica Makino elevated the MAO-A activity which was increased by cold stress, whereas it inhibited the MAO-B activity which was increased by cold stress. Coptis japonica Makino elevated the MAO-A activity which was decreased by heat stress, whereas it inhibited the MAO-B activity which was increased by heat stress. Radix Aconiti lateralis preparata inhibited the MAO-A activity which was increased by cold stress, whereas it inhibited the MAO-B activity which was increased by heat stress.

多樣한 黃芩藥鍼製劑의 安全性 및 效能에 關한 硏究

김호경,마진열,전원경,윤수영,강은정,주혜정,고병섭 한국한의학연구원 1997 한국한의학연구원논문집 Vol.3 No.1

In order to detect the safety and effect of various aqua-acupunctures from Scutellariae Radix, the modifications of boiling, filtration and dilution were employed for the manufacture of aqua-acupunctures. We injected 0.2cc of aqua-acupunctures into Joksamri(足三里) of rat, repeatedly. we compared subacute toxicity of them with saline group, distilled water(D.W.) group, acupuncture group and control group. The results were summarized as follows: 1. The groups were all healthy and alive, and there was no special abnormality in physical condition and autopsy. And there were not any toxic symptoms in repeating application of aqua-acupunctures to the rat, including changes of body weight, organ weight, haematological examination and serum biochemical test. 2. There was slight change of body weight in acupuncture group : We could see significance after 3 days (p<0.05) and after 7 days (p<0.001) in body weight loss. After 9 days, all tested groups were suppressed in body weight increment. 3. Result of organ weight: In Palking aqua-acupuncture(D-2 group), saline group and acupuncture group there were some statistical significance. Especially, acupuncture group revealed significant result in liver and spleen than aqua-acupunctures. From this result, we could suggest that the efficacy of acupuncture was preceded herbal medicine. 4. In serum biochemical test, we examined glucose(GLU), triglyceride(TG) and cholesterol(CHOL). In comparison with control group, the diluted 10 times of hwanggum aqua-acupuncture (× 10 group) was recognized significant decrease of glucose, but the diluted 100 times of Hwanggum aqua-acupuncture (× 100 group), D-2 group, saline group were confirmed significant increment. There was not any meaningful change of CHOL in all of tested group, excepting the acupuncture group was exhibited statistically significant decrease(p<0.05). In TG level all tested group except complex injection of standard compound (CPA group) and HG, there were significant value in statistically. The diluted solution was more significant decrease than Hwanggaum aqua-acupuncture(HG). The mutual relationship of components of aqua-acupuncture tended to decrease level of TG, regardless of its concentration. In acupuncture group, we gained some interesting result in meaningful decrease in TG. 5. Haematological examination showed significant increment of gramulocytes(GR) in all tested groups except Hwanggum aqua-acupuncture. And the diluted solutions of HG expressed very high increment of them(p<0.001). The GR and Mean Corpuscular Volume(MCV) of acupuncture group showed statistical significance.

煎湯에 의한 黃芩 成分 移行率에 관한 硏究I

고병섭,주혜정,마진열,박갑주,안상우 한국한의학연구원 1996 한국한의학연구원논문집 Vol.2 No.1

In order to improve the qualities of boiling extract the availability of standard compounds was investigated in extract of Scutellariae Radix. The standard compounds used baicalin(1), baicalein(2), and wogonin(3). The availabilities were analyzed by thin layer chromatography(TLC) and high performance liquid chromatography(HPLC) on C18 column. The extract of RS-4(W/V=10g/100ml) showed the highest availabilities as 7.95% of baicalin(1), 1.04% of baicalein(2), and 0.31% of wogonin(3).

Fermented Herbal Formulas KIOM-MA128 Ameliorate IL-6-Induced Intestinal Barrier Dysfunction in Colon Cancer Cell Line

Park, Kwang Il,Kim, Dong Gun,Lee, Bo Hyoung,Ma, Jin Yeul Hindawi Publishing Corporation 2016 MEDIATORS OF INFLAMMATION Vol.2016 No.-

<P>Inflammatory bowel disease (IBD) comprises Crohn's disease (CD) and ulcerative colitis (UC). IBD increases the risk of colorectal cancer (CRC), depending on the extent and duration of intestinal inflammation. Increased IL-6 expression has been reported in IBD patients, which may be associated with intestinal barrier function through discontinuous tight junction (TJ). KIOM-MA is a specific agent for allergic diseases and cancer, and it is composed of several plants; these herbs have been used in traditional oriental medicine. We fermented KIOM-MA, the product of KIOM-MA128, using probiotics to improve the therapeutic efficacy via the absorption and bioavailability of the active ingredients. In this study, we demonstrated that KIOM-MA/MA128 exhibited anticolitis effects via the modulation of TJ protein. Interleukin-6 resulted in a dose-dependent decrease in the TER and an increase in the FITC-dextran permeability; however, pretreatment with 400 <I>µ</I>g/ml KIOM-MA/MA128 resulted in a significant increase in the TER and a decrease in the FITC-dextran permeability via IL-6 induction. Furthermore, protein and mRNA TJ levels remained stable after pretreatment with 400 <I>µ</I>g/ml KIOM-MA/MA128. Moreover, KIOM-MA/MA128 suppressed the expression of PLC<I>γ</I>1 and PKC. Taken together, these findings suggest novel information and clue of the anticolitis effects of KIOM-MA128 via regulation of tight junction.</P>

A Novel Herbal Medicine KIOM-MA Exerts an Anti-Inflammatory Effect in LPS-Stimulated RAW 264.7 Macrophage Cells

Oh, You-Chang,Cho, Won-Kyung,Jeong, Yun Hee,Im, Ga Young,Kim, Aeyung,Hwang, Youn-Hwan,Kim, Taesoo,Song, Kwang Hoon,Ma, Jin Yeul Hindawi Publishing Corporation 2012 Evidence-based Complementary and Alternative Medic Vol.2012 No.-

<P>KIOM-MA was recently reported as a novel herbal medicine effective for atopic dermatitis and asthma. In this study, we have demonstrated the inhibitory effect of KIOM-MA on proinflammatory mediator produced in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. KIOM-MA significantly inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as nitric oxide (NO) and prostaglandin E<SUB>2</SUB> (PGE<SUB>2</SUB>). Consistent with the inhibitory effect on PGE<SUB>2</SUB>, KIOM-MA suppresses the LPS-induced migration of macrophages and gelatinase activity and the expression of matrix metalloprotease-9 (MMP-9) in a dose-dependent manner. Additionally, KIOM-MA showed a strong suppressive effect on the inflammatory cytokines production such as tumor necrosis factor-<I><I>α</I></I> (TNF-<I><I>α</I></I>) and interleukin-6 (IL-6). We also found that KIOM-MA inhibits the activation of nuclear factor-<I><I>κ</I></I>B (NF-<I><I>κ</I></I>B) and represses the activity of extracellular signal-regulated kinase (ERK), p38, and c-Jun NH<SUB>2</SUB>-terminal kinase (JNK) mitogen-activated protein kinases (MAPKs). Taken together, we elucidated the mechanism of anti-inflammatory effect of KIOM-MA using RAW 264.7 cells stimulated by LPS.</P>

Determination of Matrine in Rat Plasma after Oral Administration of Novel Korean Herbal Medicine KIOM-MA128 and Application of PK

Back, Hyun-moon,Song, Byungjeong,Chae, Jung-woo,Yun, Hwi-yeol,Ma, Jin Yeul,Kwon, Kwang-il Hindawi Publishing Corporation 2015 Journal of analytical methods in chemistry Vol.2015 No.-

<P>KIOM-MA128 is a novel Korean herbal medicine with antiatopic, anti-inflammatory, and antiasthmatic effects. Matrine is thought to be a potential chemical marker of KIOM-MA128, but pharmacokinetic studies on KIOM-MA128 had not been performed. This study describes a simple and rapid method using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to determine the concentration of matrine in rats plasma after administration of KIOM-MA128. The isocratic mobile phase consisted of methanol and distilled water, and the flow rate was 0.15 mL/min. The accuracy and precision of the assay, as well as stability tests, were performed in accordance with FDA regulations for the validation of bioanalytical methods. The half-life and <I>T</I><SUB>max</SUB> of matrine after administration of KIOM-MA128 were 4.29 ± 2.20 h and 1.8 ± 1.23 h, respectively. <I>C</I><SUB>max</SUB> and AUC<SUB>inf</SUB> of matrine after administration of KIOM-MA128 at 4 g/kg and 8 g/kg were 595.10 ± 182.91 ng/mL, 5336.77 ± 1503.84 ng/mL·h and 850.46 ± 120 ng/mL, 9583.10 ± 888.92 ng/mL·h, respectively. The validated method was successfully applied to a pharmacokinetic study in rats after oral administration of KIOM-MA128.</P>