Last update 01 Nov 2024

PTGES2

Last update 01 Nov 2024

Basic Info

Synonyms

C9orf15, chromosome 9 open reading frame 15, FLJ14038

+ [9]

Introduction

Isomerase that catalyzes the conversion of PGH2 into the more stable prostaglandin E2 (PGE2) (in vitro) (PubMed:12804604, PubMed:18198127, PubMed:17585783). The biological function and the GSH-dependent property of PTGES2 is still under debate (PubMed:18198127, PubMed:17585783). In vivo, PTGES2 could form a complex with GSH and heme and would not participate in PGE2 synthesis but would catalyze the degradation of prostaglandin E2 H2 (PGH2) to 12(S)-hydroxy-5(Z),8(E),10(E)-heptadecatrienoic acid (HHT) and malondialdehyde (MDA) (PubMed:17585783) (By similarity).

Drugs associated with PTGES2

Compound 3(University of Salerno)

Target

PTGES2

Mechanism

PTGES2 modulators

Active Org.

Sun Pharma Advanced Research Company Ltd. [+1]

Originator Org.

University of Salerno

Active Indication

Pancreatic Ductal Adenocarcinoma [+1]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with PTGES2

100 Translational Medicine associated with PTGES2

0 Patents (Medical) associated with PTGES2

1,818

Literatures (Medical) associated with PTGES2

01 Jan 2025·Gene

Prostaglandin E2 suppresses KCNH1 gene expression and inhibits the proliferation of CaSki cervical cells through its four prostanoid PTGER subtypes

Article

Author: Cortes-Hernández, Ulises ; Larrea, Fernando ; Javier Noriega-Mejía, Bryan ; Avila, Euclides ; González-Macías, Jocelyn ; García-Quiroz, Janice ; Misael Lizardi-Aguilera, Tomas ; Díaz, Lorenza ; Noriega-Mejía, Bryan Javier ; Lizardi-Aguilera, Tomas Misael

The main risk factor for cervical cancer is the persistent infection of high-risk HPV subtypes, notably HPV16. Another contributing factor is proinflammatory prostaglandin E₂ (PGE₂), a lipid abundantly found in seminal fluid. PGE₂, along with its receptors (PTGER1-4), contributes to cancer development; however, its specific role in the proliferation of cervical cancer models with high HPV16 copy numbers remains unclear. In this study, we investigated the effects of PGE₂ on the proliferation of CaSki cells, a cell line with a high HPV16 viral load. Surprisingly, PGE₂ inhibited CaSki cell proliferation, while it increased the proliferation of SiHa, HeLa, and C-33 A cervical cancer cells. The effect of PGE₂ on CaSki cell proliferation was specific, as estradiol increased cell growth. Furthermore, PGE₂ suppressed expression and promoter activity of the cervical tumoral marker KCNH1. To discern the specific role of each receptor in cell proliferation, we generated stable CaSki cell lines overexpressing each receptor alongside control cells with an empty vector. Notably, PGE₂ significantly inhibited cell proliferation in all stable transfected CaSki cells, suppressing oncogenic KCNH1 expression and its promoter activity. In conclusion, our findings indicate that PGE₂ inhibits the proliferation of CaSki cervical cancer cells with a high HPV16 load, at least in part, by suppressing the expression of the oncogenic KCNH1 gene.

01 Jan 2025·Progress in Neuro-Psychopharmacology and Biological Psychiatry

Cannabidiol exerts antipyretic effects by downmodulating inflammatory mediators in LPS-induced fever

Article

Author: Nascimento, Glauce C ; Andres, Emilly S.S. ; Branco, Luiz G.S. ; Trajano, Isis P ; Marques, Lucas Miranda ; Nascimento, Glauce C. ; Branco, Luiz G S ; Soriano, Renato Nery ; Andres, Emilly S S ; Trajano, Isis P. ; Santos, Wanderson S ; Del-Bel, Elaine ; Santos, Wanderson S. ; Passaglia, Patrícia

Contrasting to tetrahydrocannabinol (THC), cannabidiol (CBD) has virtually no psychoactive effects and thus presents a minor risk for abuse. Furthermore, emerging preclinical and clinical evidence indicates that CBD exerts several beneficial pharmacological effects, including anti-inflammatory and antioxidant properties. Even though fever is one of the responses associated with systemic inflammation, no previous study assessed the putative impact of CBD on lipopolysaccharide (LPS)-induced fever. The present study aimed to evaluate whether CBD exerts effects on febrile responses, by modulating the hypothalamic-pituitary-adrenal (HPA) axis, and the inflammatory reflex, in this response. CBD caused no change in euthermic mice, indicating that it does not alter euthermia. Conversely, CBD blunted all the assessed systemic inflammation parameters including fever (a hallmark of infection), plasma pro-inflammatory cytokines and prostaglandin E₂ (PGE₂) surges, and hypothalamic PGE₂ (the proximal mediator of fever) synthesis. Moreover, CBD also reduced LPS-induced increase in plasma corticosterone levels and spleen TNF-α. These data are consistent with the notion that CBD has antipyretic effects, reducing peripheral febrigenic signaling (plasma pro-inflammatory cytokines levels), and eventually down-modulating hypothalamic PGE₂ production, possibly in a corticosterone- and inflammatory reflex-dependent manner.

01 Jan 2025·Journal of Ethnopharmacology

Screening bioactive compounds from Fangji Huangqi decoction for treating rheumatoid arthritis via COX-2 magnetic ligand fishing combined with in vivo validation

Article

Author: Duan, Ao ; Zhou, Zishan ; Li, Ping ; Yu, Qianqian ; Zhu, Quanhong ; Pan, Dongmei ; Zhu, Yongyan ; Tao, Huaming ; Tian, Shuo

ETHNOPHARMACOLOGICAL RELEVANCEFangji Huangqi Decoction (FHD) is a classical Chinese compound formula for treating rheumatoid arthritis (RA) with satisfactory effects. FHD is reputed for its ability to tonify qi with strengthening exterior, and dispel wind while removing dampness, but its mechanisms and bioactive compounds for treating RA remain unclear.AIM OF THE STUDYThe aim of this study was to explore the key target and bioactive compounds that were responsible for FHD-mediated improvements in RA.MATERIALS AND METHODSUsing network pharmacology, we discovered that cyclooxygenase-2 (COX-2) was the key target of FHD against RA. We utilized a ligand fishing technique with COX-2 immobilized magnetic beads to recognize the bioactive components that act on COX-2. Then we carried out an in vitro assay of COX-2 enzyme inhibition and in vivo assay of carrageenan-induced inflammation and collagen-induced arthritis (CIA) to validate the bioactive effects of these captured ingredients. In the CIA assay, micro-CT, hematoxylin‒eosin staining and safranin-O/fast green staining were employed to assess the influence of the captured ligand on bone damage, pathological injury and cartilage destruction, respectively. Immunohistochemistry (IHC) and enzyme-linked immunosorbent assays (ELISAs) were used to detect the expression of COX-2 target in the ankle joint. interleukin-6 (IL-6) levels in the serum were also detected by ELISA. Molecular docking was used to reveal the binding mechanism of the COX-2 protein and the captured ligand.RESULTSEleven ligands, including tetrandrine, fangchinoline, cyclanoline, licochalcone B, ononin, calycosin and liquiritin, were specifically bound to the COX-2 protein, as determined by ultrahigh-performance liquid chromatography-mass spectrometry (UPLC-MS), seven of which were present at high levels. One ligand, tetrandrine, not only had a great inhibitory effect on COX-2 enzyme activity but also significantly reduced carrageenan-induced inflammation. In the CIA assay, middle- and high-dose tetrandrine (25 and 50 mg/kg) had effects comparable to those of FHD and celecoxib on ameliorating RA symptoms in CIA mice via the COX-2 target. Furthermore, compared with the low-dose tetrandrine group (12.5 mg/kg), the FHD group exhibited significantly lower arthritis index scores and serum IL-6 expression, although the content of tetrandrine in FHD extract solution was approximately 0.1% of that in the low-dose tetrandrine group.CONCLUSIONSHence, we inferred that tetrandrine was the main bioactive component responsible for the effects of FHD against RA by suppressing the expression of the COX-2 protein and inhibiting the enzyme catalytic activity of COX-2. The reason for these effects may be that tetrandrine can interact with the residue Tyr385 of COX-2, the enzymatic catalytic site of COX-2 to transform arachidonic acid (AA) to prostaglandin E2 (PGE2), and thereby reduce the production of prostaglandins and inflammatory metabolites. Moreover, in addition to tetrandrine, FHD contains other compounds that could supplement the activity of tetrandrine when FHD was used to treat RA, which is manifested the "multi-component" characteristic of how Traditional Chinese Medicine formulas treat diseases.

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PTGES2

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