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A Paeonol derivative, YPH-PA3 promotes the differentiation of monocyte/macrophage lineage precursor cells into osteoblasts and enhances their autophagy.
Abstract Previous studies have indicated that paeonol inhibits RANKL-induced osteoclastogenesis by inhibiting the ERK, p38, and NF-κB pathway. We modified paeonol to form a new compound, YPH-PA3, and found that it promoted osteoclastogenesis rather than inhibited it the way paeonol does. The aim of this study is to investigate the mechanisms involved in YPH-PA3-promoted osteoclastogenesis. YPH-PA3-promoted differentiation of RAW264.7 cells (human monocytes) into osteoclasts is activated through ERK/p38/JNK phosphorylation, affecting c-FOS, NF-κB, and NFATc2. Real-time quantitative PCR and western blot revealed a...
Source: European Journal of Pharmacology - May 18, 2018 Category: Drugs & Pharmacology Authors: Tsai CH, Hsu MH, Huang PH, Hsieh CT, Chiu YM, Shieh DC, Lee YJ, Tsay GJ, Wu YY Tags: Eur J Pharmacol Source Type: research

Suppressing autophagy enhances disulfiram/copper-induced apoptosis in non-small cell lung cancer.
Abstract Autophagy, a cellular survival mechanism, is thought to allow the recycling of cellular breakdown products when cancer cells are subjected to chemotherapy, thus decreasing drug-induced apoptosis. Disulfiram (DSF), a drug widely used to control alcoholism, possesses anticancer activity by inducing apoptosis in vitro and in vivo in a copper (Cu)-dependent manner. Our previous studies proved that DSF/Cu exerts increased anti-tumor effects on non-small cell lung cancer (NSCLC) xenograft models, and inhibits NSCLC recurrence driven by ALDH-positive cancer stem cells. The present study is designed to investigat...
Source: European Journal of Pharmacology - March 13, 2018 Category: Drugs & Pharmacology Authors: Wu X, Xue X, Wang L, Wang W, Han J, Sun X, Zhang H, Liu Y, Che X, Yang J, Wu C Tags: Eur J Pharmacol Source Type: research

Inhibition of protein tyrosine phosphatase 1B in spinal cord dorsal horn of rats attenuated diabetic neuropathic pain.
Abstract Protein tyrosine phosphatase 1B (PTP1B) has been shown to dephosphorylate and inactivate insulin receptors, which contributes to the pathogenesis of diabetes. Neuropathic pain is one of the severe complications that results from diabetic neuropathy. However, whether PTP1B was involved in the development of diabetic neuropathic pain is largely unknown. The current study illustrated that PTP1B was located in spinal cord dorsal horn neurons of Sprague-Dawley rats. Western blot analysis demonstrated that the diabetic neuropathic pain induced by intraperitoneal injection of streptozotocin was associated with a...
Source: European Journal of Pharmacology - March 8, 2018 Category: Drugs & Pharmacology Authors: Zhao JY, Yang L, Bai HH, Liu JP, Suo ZW, Yang X, Hu XD Tags: Eur J Pharmacol Source Type: research

Interferon-stimulated gene 15 promotes cholesterol efflux by activating autophagy via the miR-17-5p/Beclin-1 pathway in THP-1 macrophage-derived foam cells.
In conclusion, these findings suggest that ISG15 reduces miR-17-5p levels and thereby promotes Beclin-1-mediated autophagy, resulting in increased cholesterol efflux from THP-1 macrophage-derived foam cells. PMID: 29518394 [PubMed - as supplied by publisher]
Source: European Journal of Pharmacology - March 5, 2018 Category: Drugs & Pharmacology Authors: Huang C, Yu XH, Zheng XL, Ou X, Tang CK Tags: Eur J Pharmacol Source Type: research

MEHP promotes the proliferation of cervical cancer via GPER mediated activation of Akt.
Abstract Cervical cancer is the fourth leading cause of cancer death in females worldwide and the second leading cause of mortality among women. Estrogenic signals can regulate the progression of cervical cancer, however, little is known about the mono-2-ethyhexyl phthalate (MEHP), an environmental xenoestrogen, on the development of cervical cancers. Our present data showed that nanomolar concentrations of MEHP can trigger the proliferation, while not invasion, of cervical cancer HeLa and SiHa cells, which was confirmed by the results that MEHP can also increase the expression of proliferating cell nuclear antige...
Source: European Journal of Pharmacology - January 27, 2018 Category: Drugs & Pharmacology Authors: Yang W, Tan W, Zheng J, Zhang B, Li H, Li X Tags: Eur J Pharmacol Source Type: research

(-)-Epicatechin stimulates mitochondrial biogenesis and cell growth in C2C12 myotubes via the G-protein coupled estrogen receptor.
Abstract We have reported on the capacity of (-)-epicatechin ((-)-EPI) to stimulate mitochondrial biogenesis (MiB) in mouse skeletal muscle (SkM). However, the mechanisms mediating the effects of (-)-EPI are not fully understood. We previously identified a role of the G-protein coupled estrogen receptor (GPER) in modulating the vascular effects of (-)-EPI. We therefore tested the hypothesis that GPER mediates (at least in part) the stimulatory effects of (-)-EPI on MiB in SkM cells. As an in vitro model, we employed mouse SkM-derived C2C12 myoblasts differentiated into myotubes. Using confocal microscopy, we detec...
Source: European Journal of Pharmacology - January 16, 2018 Category: Drugs & Pharmacology Authors: Moreno-Ulloa A, Miranda-Cervantes A, Licea-Navarro A, Mansour C, Beltrán-Partida E, Donis-Maturano L, De la Herrán HCD, Villarreal F, Álvarez-Delgado C Tags: Eur J Pharmacol Source Type: research

LOX-1 mediated phenotypic switching of pulmonary arterial smooth muscle cells contributes to hypoxic pulmonary hypertension.
In conclusion, our data uncovers an important role of LOX-1 in the maintenance of PASMCs phenotype. Therapeutic targeting of LOX-1/ERK1/2-Elk-1/MRTF-A/SRF signaling axis would be exploited to treat hypoxic PH. PMID: 29069578 [PubMed - as supplied by publisher]
Source: European Journal of Pharmacology - October 22, 2017 Category: Drugs & Pharmacology Authors: Zhang W, Zhu T, Wu W, Ge X, Xiong X, Zhang Z, Hu C Tags: Eur J Pharmacol Source Type: research

Cinnamaldehyde protects human dental pulp cells against oxidative stress through the Nrf2/HO-1-dependent antioxidant response.
This study examined the intracellular signaling mechanisms of CA on the oxidative stress response in human dental pulp cells (hDPCs). The results showed that CA did not have any cell cytotoxicity or cause morphological changes at concentrations up to 50µM. A CA treatment strongly up-regulated the cellular protein level of heme oxygenase-1 (HO-1) and promoted Nrf2 translocation to the nucleus. CA-mediated Nrf2/HO-1 activation reduced the level of reactive oxygen species and protected the hDPCs from H2O2-induced oxidative stress, which induces apoptosis. Moreover, HO-1 depletion by siRNA attenuated the CA-mediated cell prot...
Source: European Journal of Pharmacology - September 4, 2017 Category: Drugs & Pharmacology Authors: Kim NY, Ahn SG, Kim SA Tags: Eur J Pharmacol Source Type: research

Activation of PPAR γ inhibits HDAC1-mediated pulmonary arterial smooth muscle cell proliferation and its potential mechanisms.
Activation of PPARγ inhibits HDAC1-mediated pulmonary arterial smooth muscle cell proliferation and its potential mechanisms. Eur J Pharmacol. 2017 Aug 31;: Authors: Li F, Zhu Y, Wan Y, Xie X, Ke R, Zhai C, Pan Y, Yan X, Wang J, Shi W, Li M Abstract The downstream targets of histone deacetylase 1 (HDAC1) mediation of platelet-derived growth factor (PDGF)-induced pulmonary arterial smooth muscle cell (PASMC) proliferation are still unclear, and it is also unknown whether activation of peroxisome proliferator-activated receptor γ (PPARγ) modulates HDAC1 and its down-stream targets in PASMCs. The pres...
Source: European Journal of Pharmacology - August 31, 2017 Category: Drugs & Pharmacology Authors: Li F, Zhu Y, Wan Y, Xie X, Ke R, Zhai C, Pan Y, Yan X, Wang J, Shi W, Li M Tags: Eur J Pharmacol Source Type: research

Danshensu accelerates angiogenesis after myocardial infarction in rats and promotes the functions of endothelial progenitor cells through SDF-1 α/CXCR4 axis.
Danshensu accelerates angiogenesis after myocardial infarction in rats and promotes the functions of endothelial progenitor cells through SDF-1α/CXCR4 axis. Eur J Pharmacol. 2017 Aug 29;: Authors: Yin Y, Duan J, Guo C, Wei G, Wang Y, Guan Y, Mu F, Yao M, Xi M, Wen A Abstract The present study was performed to investigate the the potential role of Danshensu in therapeutic angiogenesis in ischemic myocardium and endothelial progenitor cells (EPCs) function. The rat model of myocardial infarction (MI) injury was induced by left anterior descending coronary artery ligation for 14 days. Danshensu signific...
Source: European Journal of Pharmacology - August 29, 2017 Category: Drugs & Pharmacology Authors: Yin Y, Duan J, Guo C, Wei G, Wang Y, Guan Y, Mu F, Yao M, Xi M, Wen A Tags: Eur J Pharmacol Source Type: research

Losartan protects against cerebral ischemia/reperfusion-induced apoptosis through β-arrestin1-mediated phosphorylation of Akt.
In this study, we investigated whether losartan protected against cerebral I/R injury by reducing apoptosis and the possible signaling pathways. Wistar rats were pretreated for 14 days with 5mg/kg losartan, and then subjected to middle cerebral artery occlusion (MCAO) for 2h followed by reperfusion. Meanwhile, PC12 cells pretreated with losartan were exposed to oxygen-glucose deprivation-reoxygenation (OGD/R), an in vitro model of cerebral ischemia. Our results showed that administration of losartan significantly inhibited the apoptosis by decreasing the number of apoptotic cells, decreasing the protein level of cleaved ca...
Source: European Journal of Pharmacology - August 24, 2017 Category: Drugs & Pharmacology Authors: Chen L, Ren Z, Wei X, Wang S, Wang Y, Cheng Y, Gao H, Liu H Tags: Eur J Pharmacol Source Type: research

PTPN21 protects PC12 cell against oxygen-glucose deprivation by activating cdk5 through ERK1/2 signaling pathway.
In this study, we investigated the neuroprotective effects and potential mechanism of PTPN21 on oxygen glucose deprivation (OGD)-injured PC12 cells. The ischemic stroke model of PC12 cells was made by OGD for 2h, after transfection of the PTPN21 siRNA and pcDNA 3.1 PTPN21(+). Cell viability was tested using the MTT and CCK-8 assay. Apoptotic cells were estimated by Annexin V-FITC/PI staining and caspase-3 activity using the Caspase-3 Assay Kit; the PTPN21, cdk5, ERK1/2 and p-ERK1/2 levels were estimated by qRT-PCR and Western blot. We found that the PTPN21 markedly increased cell viability, inhibited apoptosis. We also fou...
Source: European Journal of Pharmacology - August 23, 2017 Category: Drugs & Pharmacology Authors: Cui N, Lu H, Li M, Yan Q Tags: Eur J Pharmacol Source Type: research

Inhibition of lipolysis by ilexgenin A via AMPK activation contributes to the prevention of hepatic insulin resistance.
Abstract Adipose dysfunction links tightly to hepatic insulin resistance and gluconeogenesis. Ilexgenin A is reported with the ability to regulate lipid profile and protect the liver against high fat diet (HFD) -induced impairment. Here, we propose that ilexgenin A ameliorates hepatic insulin signaling and gluconeogenesis by regulating lipolysis in white adipose tissue (WAT). Pyruvate tolerance test and biochemical analysis coupled with the ex vivo siRNA knockdown and co-culture studies demonstrate that ilexgenin A suppresses inflammation-associated lipolysis in epididymal fat pad via 5'-AMP-activated protein kina...
Source: European Journal of Pharmacology - July 21, 2017 Category: Drugs & Pharmacology Authors: Li LZ, Zhang T, Yang L, Zhang L, Wang L, Liu B, Liu K Tags: Eur J Pharmacol Source Type: research

Aristeromycin and DZNeP cause growth inhibition of prostate cancer via induction of mir-26a.
Abstract Most prostate cancers initially respond to androgen deprivation therapy, but then progress from androgen-dependent to androgen-independent prostate cancers. In the present study, a differential cytotoxicity screen of hormone-resistant prostate cancer LNCaP-hr cells and the parental LNCaP-FGC cells against normal MRC5 fibroblast cells, identified a small molecule compound, Aristeromycin (a derivative of 3-deazaneplanocin A (DZNeP)). The molecular target was shown to be S-adenosylhomocysteine hydrolase (AHCY), which catalyzes reversible hydrolysis of S-adenosylhomocysteine (SAH) to adenosine and L-homocyste...
Source: European Journal of Pharmacology - July 10, 2017 Category: Drugs & Pharmacology Authors: Uchiyama N, Tanaka Y, Kawamoto T Tags: Eur J Pharmacol Source Type: research

Tenuigenin inhibits LPS-induced inflammatory responses in microglia via activating the Nrf2-mediated HO-1 signaling pathway.
In conclusion, the results of this study indicated that TGN inhibited LPS-induced inflammatory responses in microglia via activating the Nrf2-mediated HO-1 signaling pathway. PMID: 28478071 [PubMed - as supplied by publisher]
Source: European Journal of Pharmacology - May 3, 2017 Category: Drugs & Pharmacology Authors: Wang X, Li M, Cao Y, Wang J, Zhang H, Zhou X, Li Q, Wang L Tags: Eur J Pharmacol Source Type: research

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