Preventive Effect and Safety of a Follicle Stimulating Hormone Inhibitory Formulation Containing a Mixture of <i> Coicis Semen</i> and <i> Artemisia capillaris</i> for Precocious Puberty: A Preliminary Experimental Study Using Female Rats

Trinh, Tuy An,Park, Seung Chan,Oh, Jihong,Kim, Chang-Eop,Kang, Ki Sung,Yoo, Hwa Seung,Lee, Hye Lim Hindawi 2017 Evidence-based Complementary and Alternative Medic Vol.2017 No.-

<P><B>Background</B></P><P> Precocious puberty is a common endocrine disease in children. Inappropriate activation of hypothalamic–pituitary–gonadal axis leads to the development of secondary sexual characteristics at an earlier age than normal children and causes short stature in adulthood.</P><P><B> Objectives</B></P><P> The aim of this study is to evaluate the preventive effects of a herbal formulation containing a mixture of<I> Coicis Semen</I> and<I> Artemisia capillaris</I> (hEIF extract) on precocious puberty.</P><P><B> Methods</B></P><P> The preventive effect of hEIF extract on precocious puberty in rats was evaluated by measuring blood component after 3 weeks of treatment via oral administration. Network pharmacological analyses were performed to predict the bioactive components of hEIF extract.</P><P><B> Results</B></P><P><I> In vivo</I> studies showed that hEIF extract significantly reduced follicle stimulating hormone (FSH) levels. After treatment with 200 mg/kg of hEIF extract, the FSH level was 5.33 ± 1.10 ng/mL, whereas the FSH level in the vehicle group was 46.73 ± 0.80 ng/mL. Moreover, the use of hEIF extract did not stimulate body growth and bone accretion in rats. The network pharmacological analysis led to the identification of multiple targets of hEIF extract related to lipolysis and the female sex hormone-related pathways.</P><P><B> Conclusion</B></P><P> hEIF extract can be used as an FSH inhibitor for the treatment of precocious puberty. </P>

Estrogenic Activity of Sanguiin H-6 through Activation of Estrogen Receptor a Coactivator-binding Site

Tuy An Trinh,박은지,이다혜,송지훈,이혜림,김기현,김영훈,정기원,강기성,유정은 한국생약학회 2019 Natural Product Sciences Vol.25 No.1

A popular approach for the study of estrogen receptor a inhibition is to investigate the protein-protein interaction between the estrogen receptor (ER) and the coactivator surface. In our study, we investigated phytochemicals from Rubus coreanus that were able to disrupt ERa and coactivator interaction with an ERa antagonist. The E-screen assay and molecular docking analysis were performed to evaluate the effects of the estrogenic activity of R. coreanus extract and its constituents on the MCF-7 human breast cancer cell line. At 100 mg/mL, R. coreanus extract significantly stimulated cell proliferation (574.57 ? 8.56%). Sanguiin H6, which was isolated from R. coreanus, demonstrated the strongest affinity for the ERa coactivator-binding site in molecular docking analysis, with a binding energy of -250.149. The initial results of the study indicated that sanguiin H6 contributed to the estrogenic activity of R. coreanus through the activation of the ERa coactivator-binding site.

Effects of estrogen inhibition formula herbal mixture for danazol-induced precocious puberty in female rats: an experimental study with network pharmacology

Seung Chan Park,Tuy An Trinh,Won-Yung Lee,Ji Yun Baek,Seung Yong Lee,Kyu Hee Choi,Jaewon Ha,Chang-Eop Kim,Ki Sung Kang,Hye Lim Lee 한국한의학연구원 2021 Integrative Medicine Research Vol.10 No.3

Background: This study aimed at determining the effect of the herbal mixture estrogen inhibition formula (EIF) and its possible mechanisms by precocious puberty animal models and network pharmacology-based analysis. Methods: Precocious puberty animal models were established by a single injection of 300 μg danazol, then female rats were administered EIF, vaginal openings were monitored, uterus and pituitary indices were determined. The levels of ALP, E2, LH, and FSH were measured using ELISA kits. Real-time PCR was performed to evaluate the mRNA expression of GnRH, UNC5C, and netrin-1 in hypothalamic tissues. We applied network pharmacological analysis to predict potential targets and pathways of EIF. Results: EIF delayed danazol-induced early vaginal opening. In the onset model, EIF reduced the increased levels of serum ALP, E2, LH, and FSH; as well as mRNA expressions of GnRH, Netrin-1, and UNC5C. Moreover, long-term administration of EIF not only diminished all impaired factors but also had no effect on the normal development of the animals. The gene set enrichment analysis showed that the targets of EIF are mainly associated with the GnRH signaling and ovarian steroidogenesis pathways. Conclusion: EIF could be used in preclinical research for the treatment of precocious puberty by the inhibition of HPGA pre-maturation.

Curcuzedoalide contributes to the cytotoxicity of <i>Curcuma zedoaria</i> rhizomes against human gastric cancer AGS cells through induction of apoptosis

Jung, Eun Bee,Trinh, Tuy An,Lee, Tae Kyoung,Yamabe, Noriko,Kang, Ki Sung,Song, Ji Hoon,Choi, Sungyoul,Lee, Sanghyun,Jang, Tae Su,Kim, Ki Hyun,Hwang, Gwi Seo Elsevier 2018 Journal of Ethnopharmacology Vol.213 No.-

<P><B>Abstract</B></P> <P><B>Ethnopharmacological relevance</B></P> <P> <I>Curcuma zedoaria</I> Roscoe (Zingiberaceae), also known as white turmeric or zedoaria, has been used in Ayurveda and traditional Chinese medicine to treat various cancers, and it possesses several sesquiterpenoid compounds.</P> <P><B>Objective</B></P> <P>This study aimed to evaluate the therapeutic effects of a methanolic (MeOH) extract of <I>C. zedoaria</I> rhizomes, as well as its active constituents, against gastric cancer, which is a frequently diagnosed cancer in South Korea.</P> <P><B>Materials and methods</B></P> <P>Repeated column chromatography, together with semi-preparative HPLC purification, was used to separate the bioactive constituents from the <I>C. zedoaria</I> MeOH extract. The cytotoxic effects of the <I>C. zedoaria</I> MeOH extract and its active compounds were measured in human gastric cancer AGS cells. Expression of proteins related to apoptosis was evaluated using Western blotting analysis.</P> <P><B>Results</B></P> <P>The MeOH extract of <I>C. zedoaria</I> rhizomes exerted a cytotoxic effect on AGS cells (IC<SUB>50</SUB>: 96.60 ± 4.87μg/mL). Based on the bioactivity-guided fractionation for antiproliferative activity, a chemical investigation of the MeOH extract led to the isolation of five sesquiterpenes including isoprocurcumenol (<B>1</B>), germacrone (<B>2</B>), curzerenone (<B>3</B>), curcumenol (<B>4</B>), and curcuzedoalide (<B>5</B>). Among these, curcuzedoalide demonstrated the strongest effect in suppressing gastric cancer cell proliferation in a dose-dependent manner with an IC<SUB>50</SUB> value of 125.11±2.77μM. Western blotting analysis showed that curcuzedoalide inhibited AGS human gastric cancer cell viability by activating caspase-8, caspase-9, caspase-3, and PARP, which contributed to apoptotic cell death in AGS human gastric cancer cells.</P> <P><B>Conclusion</B></P> <P>These data indicate that curcuzedoalide contributed to the cytotoxicity of <I>C. zedoaria</I> by activating the cleavage of caspases and PARP, which are representative markers for apoptosis. Therefore, curcuzedoalide is a positive candidate for the development of novel chemotherapeutics.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Bioactivity-based analysis and chemical characterization of anti-inflammatory compounds from <i>Curcuma zedoaria</i> rhizomes using LPS-stimulated RAW264.7 cells

Lee, Tae Kyoung,Trinh, Tuy An,Lee, Seoung Rak,Kim, Sil,So, Hae Min,Moon, Eunjung,Hwang, Gwi Seo,Kang, Ki Sung,Kim, Ji Hwan,Yamabe, Noriko,Kim, Ki Hyun Elsevier 2019 Bioorganic chemistry Vol.82 No.-

<P><B>Abstract</B></P> <P>Inflammation is not only a self-defense response of the innate immune system, but also the pathogenesis mechanism of multiple diseases such as arthritis, neurodegeneration, and cancer. <I>Curcuma zedoaria</I> Roscoe (Zingiberaceae), an indigenous plant of India, has been used traditionally in Ayurveda and folk medicine. As part of our ongoing efforts to screen traditional medicinal plants exhibiting pharmacological potential and to characterize the compounds involved, we examined the anti-inflammatory effects of the MeOH extract of <I>C. zedoaria</I> rhizomes using lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophage cells and found that MeOH extract inhibited the synthesis of nitric oxide (NO) in a dose-dependent manner (IC<SUB>50</SUB>: 23.44 ± 0.77 μg/mL). In our efforts to characterize the compounds responsible for these anti-inflammatory effects, bioactivity-guided fractionation of the MeOH extract and chemical investigation of its active hexane-soluble fraction led to the successful isolation of five sesquiterpenes (<B>1</B>–<B>5</B>), the structures of which were elucidated by NMR spectroscopic analysis and LC/MS analysis. Among them, curcuzedoalide (<B>5</B>) exhibited potent inhibitory effects on NO synthesis (IC<SUB>50</SUB>: 12.21 ± 1.67 μM) and also suppressed pre-inflammatory protein expression of iNOS and COX-2. Curcuzedoalide (<B>5</B>) was thus determined to be a contributor to the anti-inflammatory effect of <I>C. zedoaria</I> rhizomes and could be a potential candidate for therapeutic applications.</P> <P><B>Highlights</B></P> <P> <UL> <LI> MeOH extract of <I>Curcuma zedoaria</I> rhizomes inhibited the synthesis of nitric oxide (NO). </LI> <LI> Five sesquiterpenes (<B>1</B>–<B>5</B>) were isolated using bioactivity-based analysis. </LI> <LI> Curcuzedoalide (<B>5</B>) exhibited potent inhibitory effects on NO synthesis. </LI> <LI> The compound (<B>5</B>) suppressed pre-inflammatory protein expression of iNOS and COX-2. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Regulation of appetite-related neuropeptides by Panax ginseng: A novel approach for obesity treatment

Hung Manh Phung,Dongyeop Jang,Tuy An Trinh,Donghun Lee,Quynh Nhu Nguyen,Chang-Eop Kim,Ki Sung Kang 고려인삼학회 2022 Journal of Ginseng Research Vol.46 No.4

Obesity is a primary factor provoking various chronic disorders, including cardiovascular disease, diabetes,and cancer, and causes the death of 2.8 million individuals each year. Diet, physical activity,medications, and surgery are the main therapies for overweightness and obesity. During weight losstherapy, a decrease in energy stores activates appetite signaling pathways under the regulation ofneuropeptides, including anorexigenic [corticotropin-releasing hormone, proopiomelanocortin (POMC),cholecystokinin (CCK), and cocaine- and amphetamine-regulated transcript] and orexigenic [agoutirelatedprotein (AgRP), neuropeptide Y (NPY), and melanin-concentrating hormone] neuropeptides,which increase food intake and lead to failure in attaining weight loss goals. Ginseng and ginsenosidesreverse these signaling pathways by suppressing orexigenic neuropeptides (NPY and AgRP) and provokinganorexigenic neuropeptides (CCK and POMC), which prevent the increase in food intake. Moreover,the results of network pharmacology analysis have revealed that constituents of ginseng radix,including campesterol, beta-elemene, ginsenoside Rb1, biotin, and pantothenic acid, are highly correlatedwith neuropeptide genes that regulate energy balance and food intake, including ADIPOQ, NAMPT, UBL5,NUCB2, LEP, CCK, GAST, IGF1, RLN1, PENK, PDYN, and POMC. Based on previous studies and networkpharmacology analysis data, ginseng and its compounds may be a potent source for obesity treatment byregulating neuropeptides associated with appetite.

Chemical Identification of Isoflavonoids from a Termite-Associated <i>Streptomyces</i> sp. RB1 and Their Neuroprotective Effects in Murine Hippocampal HT22 Cell Line

Lee, Seoung Rak,Song, Ji Hoon,Song, Jae-Hyoung,Ko, Hyun-Jeong,Baek, Ji Yun,Trinh, Tuy An,Beemelmanns, Christine,Yamabe, Noriko,Kim, Ki Hyun MDPI 2018 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.19 No.9

<P>Insect-associated bacteria have been recognized as a very promising natural resource for discovering bioactive secondary metabolites with diverse pharmacological effects. One new isoflavonoid glycoside, termisoflavone D (<B>1</B>), together with seven known isoflavonoids (<B>2</B>–<B>8</B>), were identified from MeOH extracts of the fungus-growing termite-associated <I>Streptomyces</I> sp. RB1. The chemical structure of the new compound <B>1</B> was elucidated using comprehensive spectroscopic methods including 1D and 2D NMR, along with LC/MS analysis. The existence of two rhamnose moieties in <B>1</B> was determined with comparative NMR analysis, and the absolute configuration was elucidated using chemical reactions. The neuroprotective activities of compounds <B>1</B>–<B>8</B> were thoroughly investigated using the murine hippocampal HT22 cell line. Compound <B>5</B> prevented glutamate-induced HT22 cell death by blocking intracellular reactive oxygen species (ROS) accumulation. The present study provides the first experimental evidence for the potential use of isoflavonoids from termite-associated bacteria as lead compounds that can prevent neuronal damage induced by glutamate.</P>