Insulin Mimetic Activity of 3,4-<i>Seco</i> and Hexanordammarane Triterpenoids Isolated from <i>Gynostemma longipes</i>

Pham, Ha Thanh Tung,Ha, Thi Kim Quy,Cho, Hyo Moon,Lee, Ba Wool,An, Jin Pyo,Tran, Van On,Oh, Won Keun American Chemical Society and American Society of 2018 Journal of natural products Vol.81 No.11

<P>As part of ongoing research to find new antidiabetic agents from medicinal plants, the chemical composition of <I>Gynostemma longipes</I>, an ethnomedicinal plant used to treat type 2 diabetes mellitus by local communities in Vietnam, was investigated. Ten new dammarane triterpenes, including two 3,4-<I>seco</I>-dammarane analogues, secolongipegenins S1 and S2 (<B>1</B> and <B>2</B>), a 3,4-<I>seco-</I>hexanordammarane, secolongipegenin S3 (<B>3</B>), two hexanordammarane glycosides, longipenosides ND1 and ND2 (<B>4</B> and <B>5</B>), and five other dammarane glycosides, longipenosides GL1-GL5 (<B>6</B>-<B>10</B>), were isolated from a 70% EtOH extract of the whole <I>G. longipes</I> plant. The structures of the new compounds were elucidated using diverse spectroscopic methods. All of the isolates were evaluated for their stimulatory activities on glucose uptake in differentiated 3T3-L1 adipocyte cells using 2-[<I>N</I>-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-<SMALL>D</SMALL>-glucose as a fluorescent-tagged glucose probe. The stimulant activities on glucose uptake by the test compounds were mediated via the activation of the AMPK pathway using differentiated mouse C2C12 skeletal myoblasts. Consequently, compounds <B>1</B>, <B>2</B>, and <B>4</B> enhanced glucose uptake and GLUT4 translocation significantly by regulating the AMPK signaling pathway.</P> [FIG OMISSION]</BR>

Antiviral activities of compounds from aerial parts of Salvia plebeia R. Br

Bang, S.,Quy Ha, T.K.,Lee, C.,Li, W.,Oh, W.K.,Shim, S.H. Elsevier Sequoia 2016 Journal of Ethnopharmacology Vol.192 No.-

Ethnopharmacological relevance: Salvia plebeia R. Br. is an edible plant widely spread in many countries. It has been used as a traditional medicine to treat common cold, flu, cough, hepatitis, hemorrhoids, etc. The purpose of the study is to explicate antiviral compounds responsible for its traditional use for the common cold or flu. Materials and methods: The methanolic extract of the aerial parts of S. plebeia was extracted with CHCl<SUB>3</SUB>, EtOAc, and n-BuOH, successively. The EtOAc and CHCl<SUB>3</SUB> fractions were subjected to a successive of chromatographic method, which led to the isolation of fourteen compounds. Inhibition activities of the isolated compounds were evaluated against influenza A (H1N1) neuraminidase. Results: Chemical investigation of the methanolic extracts of S. plebeia resulted in the isolation of two novel benzoylated monoterpene glycosides, named as plebeiosides A (1) and B (2), together with twelve known compounds including four flavonoids (4-5, 7, 10), two sesquiterpenoids (8, 12), four phenolics (9-10, 13-14), a steroid (6), and a triterpenoid (3). Their chemical structures were elucidated based on spectroscopic data and absolute stereochemistries of 1 and 2 were determined by comparison of optical rotations of their hydrolysates with literature values. Compounds 5, 7, 9, and 11 exhibited potent enzymatic inhibition against H1N1 neuraminidase (IC<SUB>50</SUB> values ranging from 11.18+/-1.73 to 19.83+/-2.28μM). Furthermore, two flavonoids (5 and 7) and one rosmarinic acid methyl ester (9) reduced cytopathic effects of the H1N1 virus during replication. Conclusions: The antiviral activities of the flavonoids and phenolics isolated from the extracts of S. plebeia supported the traditional application of this medicine on common cold or flu. In this study, benzoylated monoterpene glycosides were first found to exist in this species. Moreover, the present study suggested potential of three compounds (5, 7, and 9) to be new lead structures for the development of new neuraminidase inhibitors in the future.

Hypoglycemic triterpenes from <i>Gynostemma pentaphyllum</i>

Wang, Jun,Ha, Thi Kim Quy,Shi, Yan-Ping,Oh, Won Keun,Yang, Jun-Li Elsevier 2018 Phytochemistry Vol.155 No.-

<P><B>Abstract</B></P> <P>To search for bioactive gypenosides and their analogues, a saponin enriched fraction and its hydrolyzate from <I>Gynostemma pentaphyllum</I> were phytochemically investigated. Fractionation by diverse chromatographic methods, including HPLC, Sephadex LH-20, silica gel, and C18 reverse phase silica gel, led to the isolation and purification of twelve triterpenes, including five undescribed and seven known. The chemical structures of all compounds were determined as analyzed by nuclear magnetic resonance (NMR), high resolution mass spectrometry (HR-MS), infrared spectrum (IR), optical rotation, and chemical transformations. Among all isolates, nine compounds possessed a rare dammarane triterpenoid framework with A-ring modified. The relative configurations of three compounds were determined by 2D NMR for the first time. The absolute configurations of four compounds were determined by the modified Mosher's method. Two of all isolated compounds significantly enhanced 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose (2-NBDG) uptake and Glucose Transporter 4 (GLUT4) translocation via activating the AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) signaling pathway. This study provided the potential candidates for the development of antidiabetic agents.</P> <P><B>Highlights</B></P> <P> <UL> <LI> <I>Gynostemma pentaphyllum</I> is a traditional medicinal and edible plant in China. </LI> <LI> Five undescribed triterpenes were isolated. </LI> <LI> The modified Mosher's method was used to determine the absolute configurations. </LI> <LI> Their hypoglycemic activity was evaluated in differentiated 3T3-L1 adipocytes. </LI> <LI> This study provided the potential candidates for antidiabetic agents. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>Five undescribed and nine known triterpenes were isolated from the hydrolyzate and extract of <I>Gynostemma pentaphyllum.</I> Their hypoglycemic activity was evaluated.</P> <P>[DISPLAY OMISSION]</P>

<i>C</i>-Methylated Flavonoid Glycosides from <i>Pentarhizidium orientale</i> Rhizomes and Their Inhibitory Effects on the H1N1 Influenza Virus

Huh, Jungmoo,Ha, Thi Kim Quy,Kang, Kyo Bin,Kim, Ki Hyun,Oh, Won Keun,Kim, Jinwoong,Sung, Sang Hyun American Chemical Society and American Society of 2017 Journal of natural products Vol.80 No.10

<P>Thirteen C-methylated flavonoid glycosides (1-13), along with 15 previously known flavonoids (14-28), were isolated from rhizomes of Pentarhizidium orientale. Among these compounds, matteuorienates D-K (1-8) were obtained as analogues of matteuorienates A-C (14-16), which contain a characteristic 3-hydroxy-3-methylglutaryl (HMG) moiety. The structures of 1-13 were characterized by spectroscopic analysis and chemical derivatization. The isolates were evaluated for their antiviral activities against influenza virus (H1N1), with compounds 21, 22, 23, 25, and 26 showing inhibitory effects (IC50 of 23.9-30.3 mu M) against neuraminidases.</P>

Piperlongumine activates Sirtuin1 and improves cognitive function in a murine model of Alzheimer’s disease

Go, Jun,Ha, Thi-Kim-Quy,Seo, Ji Yeon,Park, Tae-Shin,Ryu, Young-Kyoung,Park, Hye-Yeon,Noh, Jung-Ran,Kim, Yong-Hoon,Hwang, Jung Hwan,Choi, Dong-Hee,Hwang, Dae Youn,Kim, Sanghee,Lee, Chul-Ho,Oh, Won Keun Elsevier 2018 Journal of Functional Foods Vol.43 No.-

<P><B>Abstract</B></P> <P>Sirtuin1 (Sirt1) is an unusual target for aging and aging-associated diseases. During the screening for Sirt1 activators from natural compounds, piperlongumine (PL), one of the major constituents of <I>Piper longum</I>, potently activated the deacetylase ability of Sirt1 <I>in vitro</I>. Treatment with PL, which regulated the gene transcription of antioxidant response element in hippocampal neurons, attenuated the cytotoxicity induced by intraneuronal Aβ<SUB>1-42</SUB> expression. The oral administration of PL, at a dose of 50 mg/kg/day for 2.5 months, significantly reduced the occupied area of beta-amyloid in parietal cortex of APP/PS1 mice. Novel object recognition and working memory impairment also markedly improved. Moreover, activated microglia and astrocytes in the cortex notably decreased, indicating the anti-inflammatory activity of PL. Finally, vesicular glutamate transporter 1 significantly increased in the hippocampus of APP/PS1 mice following PL treatment. These results suggested the beneficial effects PL and its therapeutic potential to ameliorate AD-like pathology.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Piperlongumine (PL) activates the deacetylase ability of Sirt1 <I>in vitro</I>. </LI> <LI> PL improves cognitive deficits in APP/PS1 mice. </LI> <LI> PL reduces amyloid deposition and neuro-inflammation in the brain of APP/PS1 mice. </LI> <LI> PL increases VGLUT1 level in the hippocampus of APP/PS1 mice. </LI> </UL> </P>

Oleanane Triterpenes from the Flowers of <i>Camellia japonica</i> Inhibit Porcine Epidemic Diarrhea Virus (PEDV) Replication

Yang, Jun-Li,Ha, Thi-Kim-Quy,Dhodary, Basanta,Pyo, Euisun,Nguyen, Ngoc Hieu,Cho, Hyomoon,Kim, Eunhee,Oh, Won Keun American Chemical Society 2015 Journal of medicinal chemistry Vol.58 No.3

<P>Porcine epidemic diarrhea virus (PEDV) infections have resulted in a severe economic loss in the swine industry in many countries due to no effective treatment approach. Fifteen oleanane triterpenes (<B>1</B>–<B>15</B>), including nine new ones (<B>1</B>–<B>4</B> and <B>10</B>–<B>14</B>), were isolated from the flowers of <I>Camellia japonica</I>, and their molecular structures were determined by extensive spectroscopic methods. These compounds were evaluated for their antiviral activity against PEDV replication, and the structure–activity relationships (SARs) were discussed. Compounds <B>6</B>, <B>9</B>, <B>11</B>, and <B>13</B> showed most potent inhibitory effects on PEDV replication. They were found to inhibit PEDV genes encoding GP6 nucleocapsid, GP2 spike, and GP5 membrane protein synthesis based on RT-PCR data. Western blot analysis also demonstrated their inhibitory effects on PEDV GP6 nucleocapsid and GP2 spike protein synthesis during viral replication. The present study suggested the potential of compounds <B>6</B>, <B>9</B>, <B>11</B>, and <B>13</B> as promising scaffolds for treating PEDV infection via inhibiting viral replication.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jmcmar/2015/jmcmar.2015.58.issue-3/jm501567f/production/images/medium/jm-2014-01567f_0006.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/jm501567f'>ACS Electronic Supporting Info</A></P>

Antiviral escin derivatives from the seeds of <i>Aesculus turbinata</i> Blume (Japanese horse chestnut)

Kim, Ji Won,Ha, Thi-Kim-Quy,Cho, Hyomoon,Kim, Eunhee,Shim, Sang Hee,Yang, Jun-Li,Oh, Won Keun Elsevier 2017 Bioorganic & medicinal chemistry letters Vol.27 No.13

<P><B>Abstract</B></P> <P>Porcine epidemic diarrhea virus (PEDV) causes severe diarrhea and high fatality of piglets, influencing the swine industry. Japanese horse chestnut (seed of <I>Aesculus turbinata</I>) contains many saponin mixtures, called escins, and has been used for a long time as a traditional medicinal plant. Structure-activity relationship (SAR) studies on escins have revealed that acylations at C-21 and C-22 with angeloyl or tigloyl groups were important for their cytotoxic effects. However, the strong cytotoxicity of escins makes them hard to utilize for other diseases and to develop as nutraceuticals. In this research, we investigated whether escin derivatives <B>1</B>–<B>7</B> (including new compounds <B>2</B>, <B>3</B>, <B>5</B> and <B>6</B>), without the angeloyl or tigloyl groups and with modified glycosidic linkages by hydrolysis, have PEDV inhibitory effects with less cytotoxicity. Compounds <B>1</B>–<B>7</B> had no cytotoxicity at 20μM on VERO cells, while compounds <B>8</B>–<B>10</B> showed strong cytotoxicity at similar concentrations on PEDV. Our results suggest that escin derivatives showed strong inhibitory activities on PEDV replication with lowered cytotoxicity. These studies propose a method to utilize Japanese horse chestnut for treating PEDV and to increase the diversity of its bioactive compounds.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Anti-influenza effect of the major flavonoids from <i>Salvia plebeia</i> R.Br. via inhibition of influenza H1N1 virus neuraminidase

Bang, Sunghee,Li, Wei,Ha, Thi Kim Quy,Lee, Changyeol,Oh, Won Keun,Shim, Sang Hee Informa UK (TaylorFrancis) 2018 Natural product research Vol.32 No.10

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Sesquiterpenoids with Various Carbocyclic Skeletons from the Flowers of <i>Chrysanthemum indicum</i>

Liu, Lei-Lei,Ha, Thi Kim Quy,Ha, Wei,Oh, Won Keun,Yang, Jun-Li,Shi, Yan-Ping American Society of Pharmacognosy 2017 Journal of natural products Vol.80 No.2

<P>A phytochemical investigation of the flowers of Chrysanthemum indicum yielded sesquiterpenoids 1-25 with various carbocyclic skeletons, including 10 new (1-10) and 15 known (11-25) analogues. The structures were elucidated via their physical data, while the absolute configuration of compounds 6, 8, and 10 was assessed via electronic circular dichroism analysis. The evaluation of the effect of sesquiterpenoids on porcine epidemic diarrhea virus (PEDV) replication showed that compounds 1-5, 12, 14, 16, 17, 19, and 21 increased cell viability against cell death in PEDV-injected cells. Compounds 2, 12, and 17 were selected and investigated for their inhibition of proteins required for PEDV replication. Compounds 2 and 17 significantly reduced PEDV nucleocapsid and spike protein synthesis compared with azauridin as a positive control.</P>

Effects of piperlongumine on cognitive function and amyloid pathology

Jun Go,Thi-Kim-Quy Ha,Ji Yeon Seo,Tae-Shin Park,Young-Kyoung Ryu,Hye-Yeon Park,Jung-Ran Noh,Yong-Hoon Kim,Jung Hwan Hwang,Dong-Hee Choi,Sang Hee Kim,Chul-Ho Lee,Won Keun Oh,Kyoung-Shim Kim 한국실험동물학회 2018 한국실험동물학회 학술발표대회 논문집 Vol.2018 No.1