This study is designed to assess the effect of a new PPARgamma modulator on the expression and activity of the lactase enzyme in human intestinal epithelial cells. Based on their previous experimental results, the investigators hypothesized that modulating intestinal PPARgamma activity is a new pharmacological mechanism allowing the control of lactase expression and activity in the gut

Start Date16 Jul 2015

Sponsor / Collaborator

Centre Hospitalier Universitaire de Lille

[+1]

100 Clinical Results associated with Guanidinoethyldisulfide Bicarbonate

100 Translational Medicine associated with Guanidinoethyldisulfide Bicarbonate

100 Patents (Medical) associated with Guanidinoethyldisulfide Bicarbonate

Literatures (Medical) associated with Guanidinoethyldisulfide Bicarbonate

01 Apr 2024·Journal of Applied Microbiology

Effects of Guizhi and Erxian Decoction on menopausal hot flashes: insights from the gut microbiome and metabolic profiles

Article

Author: Guo, Yong ; Chen, Siyang ; Tang, Hui ; Chen, Zhenyue ; Liu, Yaqian ; Zhou, Ying ; Mao, Ting ; Ke, Xuehong ; Guo, Kaixin ; Li, Yanfang ; Zhu, Min ; Liang, Jingtao ; Huang, Lei ; Yao, Peixun ; Zong, Yun ; Zhao, Jingbing ; Lai, Yawei

AbstractAimsTo examine the influence of GED on the gut microbiota and metabolites using a bilateral ovariectomized (OVX) rat model. We tried to elucidate the underlying mechanisms of GED in the treatment of menopausal hot flashes.Methods and results16S rRNA sequencing, metabonomics, molecular biological analysis, and fecal microbiota transplantation (FMT) were conducted to elucidate the mechanisms by which GED regulates the gut microbiota. GED significantly reduced OVX-induced hot flashes and improved disturbances in the gut microbiota metabolites. Moreover, FMT validated that the gut microbiota can trigger hot flashes, while GED can alleviate hot flash symptoms by modulating the composition of the gut microbiota. Specifically, GED upregulated the abundance of Blautia, thereby increasing l(+)-ornithine levels for the treatment of menopausal hot flashes. Additionally, GED affected endothelial nitric oxide synthase and heat shock protein 70 (HSP70) levels in the hypothalamic preoptic area by changing the gut microbiota composition.ConclusionsOur study illuminated the underlying mechanisms by which GED attenuated the hot flashes through modulation of the gut microbiota and explored the regulatory role of the gut microbiota on HSP70 expression in the preoptic anterior hypothalamus, thereby establishing a foundation for further exploration of the role of the gut–brain axis in hot flashes.

01 Jul 2023·Phytomedicine

Gua Lou Er Chen decoction attenuates atherosclerosis by reducing proteoglycans accumulation and inflammation

Article

Author: Guo, Xiaochun ; Qiu, Lingyan ; Wang, Jian ; Guo, Hongya ; Li, Jianyin ; Li, Yunxing ; Zhang, Yujing

BACKGROUNDProteoglycans (PGs) accumulation and inflammation are two interactional pathological processes of atherosclerosis (AS). Up to now, there is no ideal drug for decreasing these pathological changes. Gua Lou Er Chen decoction (GED) has been used to treat AS for several years. However, if GED could treat AS through reducing PGs accumulation and inflammation remains unknown.PURPOSEThis study was designed to illustrate whether GED could attenuate AS by reducing chondroitin sulphate proteoglycan (CSPG) expressions and alleviating inflammation.METHODSIn vivo study, apolipoprotein E-deficient mice were fed a high-fat diet to induce AS. In vitro study, oxidised low-density lipoprotein (ox-LDL) and tumour necrosis factor (TNF)-α were used to induce proteoglycans accumulation and inflammation changes of vascular smooth muscle cells (VSMCs) and RAW264.7 macrophages. Oil Red O was used to stain mouse aortic lipid plaque. Haematoxylin eosin staining was used to assess the pathological changes of aortic valve and thoracic aorta. Specialised kits were used to identify blood lipids and sGAGs. Immunofluorescence and immunohistochemistry was used to identify aortic valve CSPG and versican. Western blotting, enzyme-linked immunosorbent assay and quantitative reverse transcription-polymerase chain reaction were used to measure versican, interleukin (IL)-6, TNF-α, and chondroitin sulphate (CS) synthetase expressions. CCK-8 was used to measure the cells proliferation.RESULTSIn vivo experiments revealed that GED significantly improved hyperlipidemia, lowered lipid plaque deposition in the aorta, and increased plaque stability of AS mice. In addition, further studies revealed that GED lowered the sGAGs, CSPG, and versican levels and down-regulated CS synthetase and inflammatory factor expressions. In vitro experiments revealed that GED decreased TNF-α expression in the RAW264.7 macrophage supernatant stimulated by ox-LDL; decreased versican, CS-related synthetase, and IL-6 expressions; reduced VSMC proliferation stimulated by ox-LDL; down-regulated sGAG and versican expressions of VSMCs stimulated by TNF-α.CONCLUSIONOur results demonstrated that GED could attenuate AS by reducing hyperlipidemia, hyper-expression of CSPG, and inflammation. This study might provide a novel insight into the development of innovative drug for AS.

18 May 2023·International journal of molecular sciences

PPAR-Gamma Orchestrates EMT, AGE, and Cellular Senescence Pathways in Colonic Epithelium and Restrains the Progression of IBDs.

Article

Author: Cappariello, Alfredo ; Smakaj, Amarildo ; Vetuschi, Antonella ; Sferra, Roberta ; Latella, Giovanni ; Pompili, Simona

Intestinal fibrosis, the most common complication of inflammatory bowel disease (IBD), is characterized by an uncontrolled deposition of extracellular matrix proteins leading to complications resolvable only with surgery. Transforming growth factor is the key player in the epithelial-mesenchymal transition (EMT) and fibrogenesis process, and some molecules modulating its activity, including peroxisome proliferator-activated receptor (PPAR)-γ and its agonists, exert a promising antifibrotic action. The purpose of this study is to evaluate the contribution of signaling other than EMT, such as the AGE/RAGE (advanced glycation end products/receptor of AGEs) and the senescence pathways, in the etiopathogenesis of IBD. We used human biopsies from control and IBD patients, and we used a mouse model of colitis induced by dextran-sodium-sulfate (DSS), without/with treatments with GED (PPAR-gamma-agonist), or 5-aminosalicylic acid (5-ASA), a reference drug for IBD treatment. In patients, we found an increase in EMT markers, AGE/RAGE, and senescence signaling activation compared to controls. Consistently, we found the overexpression of the same pathways in DSS-treated mice. Surprisingly, the GED reduced all the pro-fibrotic pathways, in some circumstances more efficiently than 5-ASA. Results suggest that IBD patients could benefit from a combined pharmacological treatment targeting simultaneously different pathways involved in pro-fibrotic signals. In this scenario, PPAR-gamma activation could be a suitable strategy to alleviate the signs and symptoms of IBD and also its progression.

100 Deals associated with Guanidinoethyldisulfide Bicarbonate

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Gingival Diseases	Phase 2	-	Cincinnati Children's Hospital Medical Center	-
Gingival Diseases	Phase 2	-	Inotek Pharmaceuticals Corp.	-
Gingivitis	Phase 2	US	-	-
Stomatitis	Phase 2	US	-	-
Uveitis	Phase 2	US	-	-

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


WCD2023	Phase 2	Acne Vulgaris	450	NAC-GED 5%	(rnmrqwsnxm) = lrvdyikjhu pztsfwcojv (iithlsqgzs )	Positive	04 Jul 2023
				NAC-GED 2%	(rnmrqwsnxm) = lzgbskourv pztsfwcojv (iithlsqgzs )

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