Ginsenoside Rp₁, a Ginsenoside Derivative, Blocks Promoter Activation of iNOS and COX-2 Genes by Suppression of an IKKβ-mediated NF-κB Pathway in HEK293 Cells

Ting Shen,Jaehwi Lee,Myung Hwan Park,Yong Gyu Lee,Ho Sik Rho,Yi-Seong Kwak,Man Hee Rhee,Yung Chul Park,Jae Youl Cho 고려인삼학회 2011 Journal of Ginseng Research Vol.35 No.2

Ginsenoside (G) Rp₁ is a ginseng saponin derivative with anti-cancer and anti-inflammatory activities. In this study, we examined the mechanism by which G-Rp₁ inhibits inflammatory responses of cells. We did this using a strategy in which DNA constructs containing cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) promoters were transfected into HEK293 cells. G-Rp₁ strongly inhibited the promoter activities of COX-2 and iNOS; it also inhibited lipopolysaccharide induced upregulation of COX-2 and iNOS mRNA levels in RAW264.7 cells. In HEK293 cells G-Rp₁ did not suppress TANK binding kinase 1-, Toll-interleukin-1 receptor-domain-containing adapter-inducing interferon-b (TRIF)-, TRIF-related adaptor molecule (TRAM)-, or activation of interferon regulatory factor (IRF)-3 and nuclear factor (NF)-κB by the myeloid differentiation primary response gene (MyD88)-induced. However, G-Rp₁ strongly suppressed NF-κB activation induced by Iκβ kinase (IKK)β in HEK293 cells. Consistent with these results, G-Rp₁ substantially inhibited IKKβ-induced phosphorylation of Iκβα and p65. These results suggest that G-Rp₁ is a novel anti-inflammatory ginsenoside analog that can be used to treat IKKβ/NF-κB-mediated inflammatory diseases.

Nuclear Factor-κB/Signal Transducers and Activators of Transcription-1-Mediated Inflammatory Responses in Lipopolysaccharide-Activated Macrophages Are a Major Inhibitory Target of Kahweol, a Coffee Diterpene

Shen, Ting,Park, Yung Chul,Kim, Seong Hwan,Lee, Jaehwi,Cho, Jae Youl Pharmaceutical Society of Japan 2010 Biological & pharmaceutical bulletin Vol.33 No.7

<P>Diterpene kahweol, one of the major components in coffee, has anti-cancer, anti-oxidative, and anti-inflammatory activity. In this study, we explored the molecular mechanism of the anti-inflammatory activity of kahweol. Lipopolysaccharide (LPS)-activated RAW264.7 cells were used to explore the modulatory role of kahweol on nitric oxide (NO) and prostaglandin E<SUB>2</SUB> (PGE<SUB>2</SUB>) production and the activation of signaling proteins and transcription factors using immunoblotting and reverse transcription-polymerase chain reaction (RT-PCR). Kahweol diminished both the production of NO and PGE<SUB>2</SUB> and the mRNA expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2. Interestingly, this compound suppressed the phospho-signal transducers and activators of transcription (STAT)-1 and p65/nuclear factor (NF)-κB levels in the nucleus but not c-Jun and c-fos. In conjunction, the phosphorylation of Akt and Janus kinase (JAK)2 also decreased. Therefore, our data suggest that kahweol in coffee may be an anti-inflammatory modulator with NF-κB/STAT-1-targeted inhibitory properties in LPS-activated RAW264.7 cells.</P>

Hepatoprotective effect of phenylethanoid glycosides from Incarvillea compacta against CCl4-induced cytotoxicity in HepG2 cells

Ting Shen,Xueqin Li,Weicheng Hu,Lijin Zhang,Xudong Xu,Haifeng Wu,Lilian Ji 한국응용생명화학회 2015 Applied Biological Chemistry (Appl Biol Chem) Vol.58 No.4

The extraction and solvent partition of roots of Incarvillea compacta, a traditional Tibetan folk medicine, and repeated column chromatography and preparative high-performance liquid chromatography for n-butanol fraction yielded four phenylethanoid glycosides, crenatoside (1), 3000-O-methylcrenatoside (2), leucoseceptoside A (3), and martynoside (4). The chemical structures were identified on the basis of spectroscopic data analyses including NMR and MS. All compounds were isolated for the first time from the plant. Compound 1 exerted better 1,1-diphenyl-2-picrylhydrazyl free radical scavenging activity. In addition, compounds 1–4 were evaluated for their hepatoprotective activity on carbon tetrachloride (CCl4)- induced liver injury in HepG2 cells. Pretreatment of HepG2 cells with compound 1–4 significantly increased the viability on CCl4-induced cell death. Furthermore, compounds 1–4 also alleviated CCl4-induced hepatotoxicity by enhancement of the antioxidant enzyme activities of superoxide dismutase and reduction of the malondialdehyde content, intracellular ROS as well as NF-jB transactivation. Our results suggest that phenylethanoid glycosides ameliorate CCl4-induced cell injury, and this protection was likely due to antioxidative activity and down-regulation of NF-jB.

Dispersal and Control of Anammox Granular Sludge at High Substrate Concentrations

Ting-Ting Chen,Ping Zheng,Li-Dong Shen,Chong-Jian Tang,Shuang Ding 한국생물공학회 2012 Biotechnology and Bioprocess Engineering Vol.17 No.5

This paper reports about the dispersal and control of anammox granular sludge at high substrate concentrations. The results demonstrate that anammox granular sludge would turn into flocculent sludge when the substrate concentrations exceed the inhibitory threshold concentrations, with an apparent drop in the settling velocity of anammox sludge from 73.73 to 16.49 m/h. Moreover, the sludge was washed out of the reactor and a decrease in the nitrogen removal rate from 23.82 to 16.97kg N/(m3/day) was observed. The dominant anammox bacteria in the granular and flocculent sludge were Candidatus Kuenenia stuttgartiensis; however, the contents of heme c and extracellular polymeric substances in the flocculent sludge were much lower than in the granular sludge. Furthermore, the chemical composition of extracellular polymeric substances was different. The high nitrite concentrations more than the inhibitory threshold concentrations were regarded as the reason for the observed granular sludge dispersal and deterioration in reactor performance. The apparent dispersed granular sludge and malfunction of reactor performance could be recovered by means of washing out the residual substrate from the reactor and then re-running the reactor from low substrate concentrations.

Increased Cognition Connectivity Network in Major Depression Disorder: A fMRI Study

Ting Shen,Cao Li,Biao Wang,Wei-min Yang,Chen Zhang,Zhiguo Wu,Mei-hui Qiu,Jun Liu,Yi-feng Xu,Dai-hui Peng 대한신경정신의학회 2015 PSYCHIATRY INVESTIGATION Vol.12 No.2

ObjectiveaaEvidence of the brain network involved in cognitive dysfunction has been inconsistent for major depressive disorder (MDD), especially during early stage of MDD. This study seeks to examine abnormal cognition connectivity network (CCN) in MDD within the whole brain. MethodsaaSixteen patients with MDD and 16 health controls were scanned during resting-state using 3.0 T functional magnetic resonance imaging (fMRI). All patients were first episode without any history of antidepressant treatment. Both the left and right dorsolateral prefrontal cortex (DLPFC) were used as individual seeds to identify CCN by the seed-target correlation analysis. Two sample t test was used to calculate between-group differences in CCN using fisher z-transformed correlation maps. ResultsaaThe CCN was constructed by bilateral seed DLPFC in two groups separately. Depressed subjects exhibited significantly increased functional connectivity (FC) by left DLPFC in one cluster, overlapping middle frontal gyrus, BA7, BA43, precuneus, BA6, BA40, superior temporal gyrus, BA22, inferior parietal lobule, precentral gyrus, BA4 and cingulate gyrus in left cerebrum. Health controls did not show any cluster with significantly greater FC compared to depressed subjects in left DLPFC network. There was no significant difference of FC in right DLPFC network between depressed subjects and the health controls. ConclusionaaThere are differences in CCN during early stage of MDD, as identified by increased FCs among part of frontal gyrus, parietal cortex, cingulate cortex, and BA43, BA22, BA4 with left DLPFC. These brain areas might be involved in the underlying mechanisms of cognitive dysfunction in MDD.

Hepatoprotective effect of phenylethanoid glycosides from Incarvillea compacta against CCl₄-induced cytotoxicity in HepG2 cells

Shen, Ting,Li, Xueqin,Hu, Weicheng,Zhang, Lijin,Xu, Xudong,Wu, Haifeng,Ji, Lilian 한국응용생명화학회 2015 Applied Biological Chemistry (Appl Biol Chem) Vol.58 No.4

The extraction and solvent partition of roots of Incarvillea compacta, a traditional Tibetan folk medicine, and repeated column chromatography and preparative high-performance liquid chromatography for n-butanol fraction yielded four phenylethanoid glycosides, crenatoside (1), 3'''-O-methylcrenatoside (2), leucoseceptoside A (3), and martynoside (4). The chemical structures were identified on the basis of spectroscopic data analyses including NMR and MS. All compounds were isolated for the first time from the plant. Compound 1 exerted better 1,1-diphenyl-2-picrylhydrazyl free radical scavenging activity. In addition, compounds 1-4 were evaluated for their hepatoprotective activity on carbon tetrachloride ($CCl_4$)-induced liver injury in HepG2 cells. Pretreatment of HepG2 cells with compound 1-4 significantly increased the viability on $CCl_4$-induced cell death. Furthermore, compounds 1-4 also alleviated $CCl_4$-induced hepatotoxicity by enhancement of the antioxidant enzyme activities of superoxide dismutase and reduction of the malondialdehyde content, intracellular ROS as well as NF-${\kappa}B$ transactivation. Our results suggest that phenylethanoid glycosides ameliorate $CCl_4$-induced cell injury, and this protection was likely due to antioxidative activity and down-regulation of NF-${\kappa}B$.

Ginsenoside Rp₁, a Ginsenoside Derivative, Blocks Promoter Activation of iNOS and COX-2 Genes by Suppression of an IKKβ-mediated NF-κB Pathway in HEK293 Cells

Shen, Ting,Lee, Jae-Hwi,Park, Myung-Hwan,Lee, Yong-Gyu,Rho, Ho-Sik,Kwak, Yi-Seong,Rhee, Man-Hee,Park, Yung-Chul,Cho, Jae-Youl 고려인삼학회 2011 Journal of Ginseng Research Vol.35 No.2

Ginsenoside (G) $Rp_1$ is a ginseng saponin derivative with anti-cancer and anti-inflammatory activities. In this study, we examined the mechanism by which G-$Rp_1$ inhibits inflammatory responses of cells. We did this using a strategy in which DNA constructs containing cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) promoters were transfected into HEK293 cells. G-$Rp_1$ strongly inhibited the promoter activities of COX-2 and iNOS; it also inhibited lipopolysaccharide induced upregulation of COX-2 and iNOS mRNA levels in RAW264.7 cells. In HEK293 cells G-$Rp_1$ did not suppress TANK binding kinase 1-, Toll-interleukin-1 receptor-domain-containing adapter-inducing interferon-${\beta}$ (TRIF)-, TRIF-related adaptor molecule (TRAM)-, or activation of interferon regulatory factor (IRF)-3 and nuclear factor (NF)-${\kappa}$B by the myeloid differentiation primary response gene (MyD88)-induced. However, G-$Rp_1$ strongly suppressed NF-${\kappa}$B activation induced by I${\kappa}$B kinase (IKK)${\beta}$ in HEK293 cells. Consistent with these results, G-$Rp_1$ substantially inhibited IKK${\beta}$-induced phosphorylation of $I{\kappa}B{\alpha}$ and p65. These results suggest that G-$Rp_1$ is a novel anti-inflammatory ginsenoside analog that can be used to treat IKK${\beta}$/NF-${\kappa}$B-mediated inflammatory diseases.

Ginsenoside Rp1, a ginsenoside derivative, blocks promoter activation of iNOS and COX-2 genes by suppression of an IKKb-mediated NF-kB pathway in HEK293 cells

Ting Shen,Yanyan Yang,Myung Hwan Park,Yong Gyu Lee,Jueun Oh,Yi-Seong Kwak,Man Hee Rhee,Jae Youl Cho 고려인삼학회 2011 고려인삼학회 학술대회 Vol.2011 No.4

Evaluation of secondary cytoreduction surgery in platinum-resistant ovarian cancer patients within three-line recurrent: a multicenter, randomized controlled study

Ting-Ting Chen,Junfen Xu,Bairong Xia,Hui Wang,Yuanming Shen 대한부인종양학회 2024 Journal of Gynecologic Oncology Vol.35 No.1

Background: Epithelial ovarian cancer is the leading cause of death among gynecologicalmalignancies. Platinum resistance remains a dilemma and bottleneck in treatment, andsalvage chemotherapy has limited effectiveness. Recently, the role of secondar y cytoreductivesurger y (SCS) in patients with platinum-resistant recurrent ovarian cancer (ROC) has causedattention especially in patients with oligometastases. However, there is neither high-qualityevidence-based evidence nor standardized criteria for selecting SCS for patients withplatinum-resistant ROC until now. Methods: This multicenter, randomized, controlled clinical trial is to evaluate the valueof SCS and to clarif y reliable criteria of utilizing SCS in women with ROC, which is led byGynecologic Oncology Group, Women’s Hospital, Zhejiang University School of Medicine. Recruitment has started on Januar y 1st, 2023, and is scheduled to end in December 2026. One hundred and forty participants with platinum-resistant ROC who meet the “RSCScriteria” will be randomized assigned at a ratio of 1:1 to either the experimental arm or thestandard arm. Patients in the experimental arm will receive SCS followed by non-platinumsingle agent chemotherapy (paclitaxel, gemcitabine or liposomal adriamycin) for at least4 cycles while patients in the standard arm will be provided with only non-platinum singleagent chemotherapy. The primar y outcome is progression-free sur vival. The secondar youtcomes are overall sur vival, adverse events and health-related cancer-specific quality of life. Trial Registration: ClinicalTrials.gov Identifier: NCT05633199

AP-1/IRF-3 Targeted Anti-Inflammatory Activity of Andrographolide Isolated from <i>Andrographis paniculata</i>

Shen, Ting,Yang, Woo Seok,Yi, Young-Su,Sung, Gi-Ho,Rhee, Man Hee,Poo, Haryoung,Kim, Mi-Yeon,Kim, Kyung-Woon,Kim, Jong Heon,Cho, Jae Youl Hindawi Publishing Corporation 2013 Evidence-based Complementary and Alternative Medic Vol.2013 No.-

<P>Andrographolide (AG) is an abundant component of plants of the genus <I>Andrographis </I> and has a number of beneficial properties including neuroprotective, anticancer, anti-inflammatory, and antidiabetic effects. Despite numerous pharmacological studies, the precise mechanism of AG is still ambiguous. Thus, in the present study, we investigated the molecular mechanisms of AG and its target proteins as they pertain to anti-inflammatory responses. AG suppressed the production of nitric oxide (NO) and prostaglandin E<SUB>2</SUB> (PGE<SUB>2</SUB>), as well as the mRNA abundance of inducible NO synthase (iNOS), tumor necrosis factor-alpha (TNF-<I><I>α</I></I>), cyclooxygenase (COX)-2, and interferon-beta (IFN-<I><I>β</I></I>) in a dose-dependent manner in both lipopolysaccharide- (LPS-) activated RAW264.7 cells and peritoneal macrophages. AG also substantially ameliorated the symptoms of LPS-induced hepatitis and EtOH/HCl-induced gastritis in mice. Based on the results of luciferase reporter gene assays, kinase assays, and measurement of nuclear levels of transcription factors, the anti-inflammatory effects of AG were found to be clearly mediated by inhibition of both (1) extracellular signal-regulated kinase (ERK)/activator protein (AP)-1 and (2) I<I><I>κ</I></I>B kinase <I><I>ε</I></I> (IKK<I><I>ε</I></I>)/interferon regulatory factor (IRF)-3 pathways. In conclusion, we detected a novel molecular signaling pathway by which AG can suppress inflammatory responses. Thus, AG is a promising anti-inflammatory drug with two pharmacological targets.</P>