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    • About INDIGO
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New Publications

Scientific studies, scholarly articles, and patent information to Nuclear Receptors and Nuclear Receptor research.

Bifidobacterium species associated with breastfeeding produce aromatic lactic acids in the infant gut

ABSTRACT Breastfeeding profoundly shapes the infant gut microbiota, which is critical for early life immune development, and the gut microbiota can impact host physiology in various ways, such as through the production of metabolites. However, few breastmilk-dependent microbial metabolites mediating host–microbiota interactions are currently known. Here, we demonstrate that breastmilk-promoted Bifidobacterium species convert aromatic aminoRead More

Posted in New Publications | Tagged AhR, AhR assay | Comments Off on Bifidobacterium species associated with breastfeeding produce aromatic lactic acids in the infant gut

Olive Leaf-Derived PPAR Agonist Complex Induces Collagen IV Synthesis in Human Skin Models

Abstract Introduction Peroxisome proliferator-activated receptor (PPAR) agonists are known to modulate the synthesis of dermal lipids and proteins including collagens. Olive (Olea europaea) leaves have been reported to contain PPAR-binding ligands. Collagen IV, a major dermal-epidermal junction (DEJ) protein, degrades with both age and disease. Here, we report the formulation of a novel multi-ligand complex,Read More

Posted in New Publications | Tagged PPAR alpha assay, PPARa, PPARα | Comments Off on Olive Leaf-Derived PPAR Agonist Complex Induces Collagen IV Synthesis in Human Skin Models

Discovery of 2-(Ortho-Substituted Benzyl)-Indole Derivatives as Potent and Orally Bioavailable RORγ Agonists with Antitumor Activity

Abstract RORγ is a dual-functional drug target, which involves not only induction of inflammation but also promotion of cancer immunity. The development of agonists of RORγ promoting Th17 cell differentiation could provide a novel mechanism of action (MOA) as an immune-activating anticancer agent. Herein, we describe new 2-(ortho-substituted benzyl)-indole derivatives as RORγ agonists by scaffoldRead More

Posted in New Publications | Tagged ROR alpha, ROR alpha assay, RORa, RORg | Comments Off on Discovery of 2-(Ortho-Substituted Benzyl)-Indole Derivatives as Potent and Orally Bioavailable RORγ Agonists with Antitumor Activity

A ready-to-use, thermoresponsive, and extended-release delivery system for the paranasal sinuses

Abstract A drug delivery system for the paranasal sinuses consisting of a freeze-dried thermoresponsive hydrogel with degradable microspheres, called FD-TEMPS (Freeze Dried—Thermogel, Extended-release Microsphere-based delivery to the Paranasal Sinuses), was developed. Glass transition temperatures (Tg′) of the maximally freeze concentrated solutions consisting of poly(N-isopropylacrylamide) (pNIPAAm) and polyethylene glycol (PEG) were determined by differential scanning calorimetry,Read More

Posted in New Publications | Tagged glucocorticoid receptor assay, GR | Comments Off on A ready-to-use, thermoresponsive, and extended-release delivery system for the paranasal sinuses

Discovery of 4-Benzyloxy and 4-(2-Phenylethoxy) Chalcone Fibrate Hybrids as Novel PPARα Agonists with Anti-hyperlipidemic and Antioxidant Activities: Design, Synthesis0020and in Vitro/in Vivo Biological Evaluation

Abstract In the current work, a series of novel 4-benzyloxy and 4-(2-phenylethoxy) chalcone fibrate hybrids (10a-o) and (11a-e) were synthesized and evaluated as new PPARα agonists in order to find new agents with higher activity and fewer side effects. The 2-propanoic acid derivative 10a and the 2-butanoic acid congener 10i showed the best overall PPARαRead More

Posted in New Publications | Tagged PPAR, PPARa, PPARα | Comments Off on Discovery of 4-Benzyloxy and 4-(2-Phenylethoxy) Chalcone Fibrate Hybrids as Novel PPARα Agonists with Anti-hyperlipidemic and Antioxidant Activities: Design, Synthesis0020and in Vitro/in Vivo Biological Evaluation

Withanolide Derivative 2,3-Dihydro-3β-methoxy Withaferin-A Modulates the Circadian Clock via Interaction with RAR-Related Orphan Receptor α (RORa)

Abstract Withanolide derivatives have anticancer, anti-inflammatory, and other functions and are components of Indian traditional Ayurvedic medicine. Here, we found that 2,3-dihydro-3β-methoxy withaferin-A (3βmWi-A), a derivative of withaferin-A (Wi-A) belonging to a class of withanolides that are abundant in Ashwagandha (Withania somnifera), lengthened the period of the circadian clock. This compound dose-dependently elongated circadian rhythmsRead More

Posted in New Publications | Tagged circadian rhythm, Nr1d1, oncology, ROR, ROR alpha, RORa | Comments Off on Withanolide Derivative 2,3-Dihydro-3β-methoxy Withaferin-A Modulates the Circadian Clock via Interaction with RAR-Related Orphan Receptor α (RORa)

Accumulating evidence to support the safe and efficacious use of a proprietary blend of capsaicinoids in mediating risk factors for obesity

ABSTRACT Obesity is a significant public health concern, and finding safe and effective means for combating this condition is needed. This study investigates the safety and efficacy of supplementation of a blend of capsaicinoids on weight gain, fat mass, and blood chemistry in a high-fat diet (HFD) model of obesity in mice and on adipocyteRead More

Posted in New Publications | Tagged adipogenesis, gene expression, obesity, PPARɣ, thermogenesis | Comments Off on Accumulating evidence to support the safe and efficacious use of a proprietary blend of capsaicinoids in mediating risk factors for obesity

Synthesis and molecular targets of N-13-hydroxy-octadienoyl-ethanolamine, a novel endogenous bioactive 15-lipoxygenase-derived metabolite of N-linoleoyl-ethanolamine found in the skin and saliva

ABSTRACT N-Arachidonoyl-ethanolamine (AEA) is an endocannabinoid (eCB) and endogenous lipid mimicking many of the effects of Δ9-tetrahydrocannabinol, notably on brain functions, appetite, pain and inflammation. The eCBs and eCB-like compounds contain fatty acids, the main classes being the monoacylglycerols and the N-acyl-ethanolamines (NAEs). Thus, each long chain fatty acid likely exists under the form ofRead More

Posted in New Publications | Tagged Endocannabinoid, Inflammation, Linoleic acid | Comments Off on Synthesis and molecular targets of N-13-hydroxy-octadienoyl-ethanolamine, a novel endogenous bioactive 15-lipoxygenase-derived metabolite of N-linoleoyl-ethanolamine found in the skin and saliva

Discovery, optimization, and evaluation of non-bile acid FXR/TGR5 dual agonists

ABSTRACT Although several potent bile acid Farnesoid X receptor (FXR) and Takeda G-protein-coupled receptor 5 (TGR5, GPBAR1) dual agonists such as INT-767 have been reported, no non-bile acid FXR/TGR5 dual agonist has been investigated to date. Therefore, we attempted to discover potent non-bile acid FXR/TGR5 dual agonists and identified some non-bile acid FXR/TGR5 dual agonists,Read More

Posted in New Publications | Tagged farnesoid X receptor, FXR, NAFLD, NASH, Type 2 diabetes | Comments Off on Discovery, optimization, and evaluation of non-bile acid FXR/TGR5 dual agonists

Discovery of a novel RORγ antagonist with skin-restricted exposure for topical treatment of mild to moderate psoriasis

ABSTRACT Clinical success of IL-17/IL-23 pathway biologics for the treatment of moderate to severe psoriasis suggests that targeting RORγt, a master regulator for the proliferation and function of Th17 cells, could be an effective alternative. However, oral RORγ antagonists (VTP43742, TAK828) with high systemic exposure showed toxicity in phase I/II clinical trials and terminated development.Read More

Posted in New Publications | Tagged psoriasis, RORg, RORγ | Comments Off on Discovery of a novel RORγ antagonist with skin-restricted exposure for topical treatment of mild to moderate psoriasis
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