Ginsenoside Ro, an oleanolic saponin of Panax ginseng, exerts antiinflammatory effect by direct inhibiting toll like receptor 4 signaling pathway

Hong-Lin Xu,Guang-Hong Chen,Yu-Ting Wu,Ling-Peng Xie,Zhang-Bin Tan,Bin Liu,Hui-Jie Fan,Hong-Mei Chen,Gui-Qiong Huang,Min Liu,Ying-Chun Zhou 고려인삼학회 2022 Journal of Ginseng Research Vol.46 No.1

Background: Panax ginseng Meyer (P. ginseng), a herb distributed in Korea, China and Japan, exerts benefits on diverse inflammatory conditions. However, the underlying mechanism and active ingredients remains largely unclear. Herein, we aimed to explore the active ingredients of P. ginseng against inflammation and elucidate underlying mechanisms. Methods: Inflammation model was constructed by lipopolysaccharide (LPS) in C57BL/6 mice and RAW264.7 macrophages. Molecular docking, molecular dynamics, surface plasmon resonance imaging (SPRi) and immunofluorescence were utilized to predict active component. Results: P. ginseng significantly inhibited LPS-induced lung injury and the expression of proinflammatory factors, including TNF-a, IL-6 and IL-1b. Additionally, P. ginseng blocked fluorescence-labeled LPS (LPS488) binding to the membranes of RAW264.7 macrophages, the phosphorylation of nuclear factor-kB (NF-kB) and mitogen-activated protein kinases (MAPKs). Furthermore, molecular docking demonstrated that ginsenoside Ro (GRo) docked into the LPS binding site of toll like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD2) complex. Molecular dynamic simulations showed that the MD2-GRo binding conformation was stable. SPRi demonstrated an excellent interaction between TLR4/MD2 complex and GRo (KD value of 1.16 × 10<SUP>-9</SUP> M). GRo significantly inhibited LPS488 binding to cell membranes. Further studies showed that GRo markedly suppressed LPS-triggered lung injury, the transcription and secretion levels of TNF-α, IL-6 and IL-1β. Moreover, the phosphorylation of NF-kB and MAPKs as well as the p65 subunit nuclear translocation were inhibited by GRo dose-dependently. Conclusion: Our results suggest that GRo exerts anti-inflammation actions by direct inhibition of TLR4 signaling pathway.

Expression and regulation of Angiopoietins and their receptor Tie-2 in sika deer antler

Hong-Liang Zhang,Bin Guo,Zhan-Peng Yue,Lu Zhang,Zhan-Qing Yang,Shuang Geng,Kai Wang,Hai-Fan Yu 한국통합생물학회 2017 Animal cells and systems Vol.21 No.3

The cartilage vascularization and chondrocyte survival are essential for endochondral ossification which occurs in the process of antler growth. Angiopoietins (Ang) is a family of major angiogenic growth factors and involved in regulating the vascularization. However, the expression and regulation of Angs in the antler are still unknown. The aim of this study is to localize the expression of Ang-1, Ang-2 and their receptor Tie-2 in sika deer antler using in situ hybridization and focused on analyzing the regulation of testosterone, estrogen, all-trans-retinoic acid (ATRA) and 9cRA on their expression in antler chondrocytes. The results showed that Ang-1, Ang-2 and Tie-2 were highly expressed in antler chondrocytes. Administration of testosterone to antler chondrocytes led to a notable increase in the expression of Ang-1 and Tie-2, and a reduction in the expression of Ang-2. The similar result was also observed after estrogen treatment. In contrast, ATRA and 9cRA could inhibit the expression of Ang-1 in antler chondrocytes and heighten the expression of Ang-2. Simultaneously, ATRA could downregulate the expression of Tie-2 in antler chondrocytes at 12 and 24 h, while 9cRA upregulate the expression of Tie-2 at 3 and 6 h. Collectively, Ang-1, Ang-2 and Tie-2 are expressed in antler chondrocytes and their expression can be affected by testosterone, estrogen, ATRA and 9cRA.

The Lung Function Impairment in Non-Atopic Patients With Chronic Rhinosinusitis and Its Correlation Analysis

Linghao Zhang,Lu Zhang,Chun-Hong Zhang,Xiao-Bi Fang,Zhen-Xiao Huang,Qing -Yuan Shi,Li-Ping Wu,Peng Wu,Zhen-Zhen Wang,Zhi-Su Liao 대한이비인후과학회 2016 Clinical and Experimental Otorhinolaryngology Vol.9 No.4

Objectives. Chronic rhinosinusitis (CRS) is common disease in otorhinolaryngology and will lead to lower airway abnormality. However, the only lung function in CRS patients and associated factors have not been much studied. Methods. One hundred patients with CRS with nasal polyps (CRSwNP group), 40 patients with CRS without nasal polyps (CRSsNP group), and 100 patients without CRS were enrolled. The difference in lung function was compared. Meanwhile, CRSwNP and CRSsNP group were required to undergo a bronchial provocation or dilation test. Additionally, subjective and objective outcomes were measured by the visual analogue scale (VAS), 20-item Sino-Nasal Outcome Test (SNOT-20), Lund-Mackay score, Lund-Kennedy endoscopic score. The correlation and regression methods were used to analyze the relationship between their lung function and the above parameters. Results. The forced expiratory volume in 1 second (FEV1) and forced expiratory flow between 25% and 75% of forced vital capacity (FEF25-75) of CRSwNP group were significantly lower than other groups (P<0.05). On peak expiratory flow, there was no difference between three groups. In CRSwNP group, FEV1 was negatively correlated with peripheral blood eosinophil count (PBEC) and duration of disease (r=–0.348, P=0.013 and r=–0.344, P=0.014, respectively), FEF25-75 negatively with VAS, SNOT-20 (r=–0.490, P=0.028 and r=–0.478, P=0.033, respectively) in CRSsNP group. The incidence of positive bronchial provocation and dilation test was lower in CRSwNP group (10% and 0%, respectively), with both 0% in CRSsNP group. The multiple linear regression analysis indicated that change ratio of FEV1 before and after bronchial provocation or dilation test were correlated with PBEC in CRSwNP group (β=0.403, P=0.006). Conclusion. CRS leading to impaired maximum ventilation and small airway is associated with the existence of nasal polyp. Lung function impairments can be reflected by PBEC, duration, VAS, and SNOT-20. In CRSwNP patients, PBEC is independent predictor of FEV1 change ratio.

The Methylenetetrahydrofolate Reductase C677T Polymorphism Influences Risk of Esophageal Cancer in Chinese

Qu, Hong-Hong,Cui, Li-Hong,Wang, Ke,Wang, Peng,Song, Chun-Hua,Wang, Kai-Juan,Zhang, Jian-Ying,Dai, Li-Ping Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.5

Methylenetetrahydrofolate reductase (MTHFR) plays a central role in folate metabolism. This study with 381 esophageal cancer patients and 432 healthy controls was conducted to examine the association of MTHFR C677T and A1298C polymorphisms with susceptibility to esophageal cancer (EC) in a Chinese population. Compared with the CC genotype of MTHFR C677T, subjects carrying homozygote TT and variant genotypes (CT+TT) demonstrated reduced risk of EC with adjusted ORs (95% CI) of 0.44 (0.28-0.71) and 0.57 (0.37-0.88), respectively. However, no association was found between the MTHFR A1298C polymorphism and the risk of EC. Comparing to haplotype CA, haplotypes TA and TC could reduce the susceptibility to EC with adjusted ORs (95% CI) of 0.61(0.47-0.79) and 0.06 (0.01-0.43), respectively. In conclusion, the present study suggested that the MTHFR C677T polymorphism can markedly influence the risk of EC in Chinese.

Corrigendum to "Ginsenoside Ro, an oleanolic saponin of Panax ginseng, exerts anti-inflammatory effect by direct inhibiting toll like receptor 4 signaling pathway" [J Ginseng Res 46 (2022) 156-166]

Xu, Hong-Lin,Chen, Guang-Hong,Wu, Yu-Ting,Xie, Ling-Peng,Tan, Zhang-Bin,Liu, Bin,Fan, Hui-Jie,Chen, Hong-Mei,Huang, Gui-Qiong,Liu, Min,Zhou, Ying-Chun The Korean Society of Ginseng 2022 Journal of Ginseng Research Vol.46 No.2

A brain somatic RHEB doublet mutation causes focal cortical dysplasia type II

Shanshan Zhao,Zhenghui Li,Muxian Zhang,Lingliang Zhang,Honghua Zheng,Jinhuan Ning,Yanyan Wang,Feng-Peng Wang,Xiaobin Zhang,Hexia Gan,Yuanqing Wang,Xian Zhang,Hong Luo,Guojun Bu,Huaxi Xu,Yi Yao,Yun-wu 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-

Focal cortical dysplasia type II (FCDII) is a cerebral cortex malformation characterized by local cortical structure disorganization, neuronal dysmorphology, and refractory epilepsy. Brain somatic mutations in several genes involved in the PI3K/AKT/mTOR pathway are associated with FCDII, but they are only found in a proportion of patients with FCDII. The genetic causes underlying the development FCDII in other patients remain unclear. Here, we carried out whole exome sequencing and targeted sequencing in paired brain–blood DNA from patients with FCDII and identified a brain somatic doublet mutation c.(A104T, C105A) in the Ras homolog, mTORC1 binding (RHEB) gene, which led to the RHEB p.Y35L mutation in one patient with FCDII. This RHEB mutation carrier had a dramatic increase of ribosomal protein S6 phosphorylation, indicating mTOR activation in the region of the brain lesion. The RHEB p.Y35L mutant protein had increased GTPλS-binding activity compared with wild-type RHEB. Overexpression of the RHEB p. Y35L variant in cultured cells also resulted in elevated S6 phosphorylation compared to wild-type RHEB. Importantly, in utero electroporation of the RHEB p.Y35L variant in mice induced S6 phosphorylation, cytomegalic neurons, dysregulated neuron migration, abnormal electroencephalogram, and seizures, all of which are found in patients with FCDII. Rapamycin treatment rescued abnormal electroencephalograms and alleviated seizures in these mice. These results demonstrate that brain somatic mutations in RHEB are also responsible for the pathogenesis of FCDII, indicating that aberrant activation of mTOR signaling is a primary driver and potential drug target for FCDII.

cAMP induction by ouabain promotes endothelin-1 secretion via MAPK/ERK signaling in beating rabbit atria

Peng, Li-qun,Li, Ping,Zhang, Qiu-li,Hong, Lan,Liu, Li-ping,Cui, Xun,Cui, Bai-ri The Korean Society of Pharmacology 2016 The Korean Journal of Physiology & Pharmacology Vol.20 No.1

Adenosine 3',5'-cyclic monophosphate (cAMP) participates in the regulation of numerous cellular functions, including the $Na^+-K^+$-ATPase (sodium pump). Ouabain, used in the treatment of several heart diseases, is known to increase cAMP levels but its effects on the atrium are not understood. The aim of the present study was to examine the effect of ouabain on the regulation of atrial cAMP production and its roles in atrial endothelin-1 (ET-1) secretion in isolated perfused beating rabbit atria. Our results showed that ouabain ($3.0{\mu}mol/L$) significantly increased atrial dynamics and cAMP levels during recovery period. The ouabain-increased atrial dynamics was blocked by KB-R7943 ($3.0{\mu}mol/L$), an inhibitor for reverse mode of $Na^+-Ca^{2+}$ exchangers (NCX), but did not by L-type $Ca^{2+}$ channel blocker nifedipine ($1.0{\mu}mol/L$) or protein kinase A (PKA) selective inhibitor H-89 ($3.0{\mu}mol/L$). Ouabain also enhanced atrial intracellular cAMP production in response to forskolin and theophyline ($100.0{\mu}mol/L$), an inhibitor of phosphodiesterase, potentiated the ouabain-induced increase in cAMP. Ouabain and 8-Bromo-cAMP ($0.5{\mu}mol/L$) markedly increased atrial ET-1 secretion, which was blocked by H-89 and by PD98059 ($30{\mu}mol/L$), an inhibitor of extracellular-signal-regulated kinase (ERK) without changing ouabain-induced atrial dynamics. Our results demonstrated that ouabain increases atrial cAMP levels and promotes atrial ET-1 secretion via the mitogen-activated protein kinase (MAPK)/ERK signaling pathway. These findings may explain the development of cardiac hypertrophy in response to digitalis-like compounds.

Study on Anti-Proliferative Activity in Cancer Cells and Preliminary Structure–Activity Relationship of Pseudo-Peptide Chiral Thioureas

Peng Liao,Shi-Qin Hu,Hong Zhang,Liang-Bi Xu,Jing-Zi Liu,Bin He,Shang-Gao Liao,Yong-Jun Li 대한화학회 2018 Bulletin of the Korean Chemical Society Vol.39 No.3

In our previous studies, we have shown that thiourea compounds containing phosphate esters have potent antitumor activity and can be used as a novel strategy for the development of antitumor agents. Herein, a series of novel phosphonate thioureas 5–38 have been synthesized, which were fully characterized by 1H NMR, 13C NMR spectrum, elemental analysis. Three human cancer cell lines (Bcap-37, BGC-823, and PC-3) have been used to investigate these compounds’ antitumor activities. After the summarization of the structure–activity relationships, we found that the variation of R, R1, and R2 in these novel phosphonate thioureas contribute to the antitumor activities. All these SAR-guided efforts may lead to novel antitumor drugs in the market in the near future.

Arylazolyl(azinyl)thioacetanilide. Part 9#: Synthesis and Biological Investigation of Thiazolylthioacetamides Derivatives as a Novel Class of Potential Antiviral Agents

Peng Zhan,Xinyong Liu,Liu Wang,Hong Liu,Xuwang Chen,Xiao Li,Xin Jiang,Qiangqiang Zhang,Christophe Pannecouque,Lieve Naesens,Erik De Clercq,Ailin Liu,Guanhua Du 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.6

In continuation of our endeavor to develop new, potent, selective and less toxic antiviral agents, a novel series of 2-(2-amino/chloro-4-(2,4-dibromophenyl) thiazol-5-ylthio)acetamide derivatives was synthesized via an expeditious route and evaluated for their anti-HIV activities against wild-type virus and clinically relevant mutant strains, and for their anti-influenza virus activities against influenza A (H1N1 and H3N2) and influenza B in cellular assays. The selected active compounds were also assayed for their enzymic inhibitory activities. The results showed that some 2-chloro substituted thiazolylthioacetamide derivatives possessed potent activity against wild type HIV-1 and several key mutant strains (E138K, K103N, L100I) of HIV-1 in MT-4 cells with EC50 values in micromolar range. Two 2-amino substituted thiazole derivatives 8a7 and 8a8 displayed significant potency against influenza A/H1N1 in MDCK cells with EC50 values much lower than that of oseltamivir carboxylate, ribavirin, amantadine and rimantadine. Though the mechanism of actions is still unclear, these novel thiazolylthioacetamides might serve as original leads for further pharmacological investigations as potential therapeutic agents against HIV-1 or influenza virus.

A pressure-transient model for a fractured-vuggy carbonate reservoir with large-scale cave

Peng Chen,Xinhai Wang,Hong Liu,Yongmei Huang,Hao Zhang 한국자원공학회 2016 Geosystem engineering Vol.19 No.2

In the development process of fractured-vuggy carbonate reservoir with large-scale caves, the location and size of cave affect the development program. This paper takes the large-scale cave as equipotential body, treats matrix and fracture as double porous media, and establishes the flow model. Laplace transform is used to simplify the model, and then the model is solved using boundary element method. Considering the wellbore storage effect and skin effect, the bottomhole pressure-transient curve is obtained using Stefest numerical inversion method. Comparing the results of analytical solution and boundary element method in the dual porosity medium illustrate the accuracy of this model. The sensitivity of cave parameters is analyzed. It shows that the larger the cave radius is, the stronger the convex and concave of curve is. The convex is earlier and concave is sooner when cave is closer to the well. The segment of convex keeps longer and the concave margin is greater with the larger compressibility ratio. Finally, as an application example, actual test data from a large-scale cave reservoir is analyzed using this model, and the location and size of cave are obtained. It has a certain significance for the reserve evaluation and well test in this reservoir.