The niacin receptor HCAR2 prevents sleep deprivation-induced cognitive impairment by inhibiting microglia-mediated neuroinflammation in mice.

Sleep loss has become a common occurrence nowadays, posing significant concerns to public health by increasing risks of various diseases. Studies have shown that sleep loss can cause neuroinflammation and cognitive decline, yet its exact mechanisms and reliable prevention strategies remain unclear. Hydroxycarboxylic acid receptor 2 (HCAR2) is a G protein-coupled receptor expressed in various immune cells, and its activation shows beneficial anti-inflammatory effects in some peripheral and central inflammatory diseases.

Uncovering the mechanism of Buyang Huanwu Decoction in regulating mitochondrial dysfunction to alleviate atherosclerosis: BTK, PREPL, and P2RX7 proteins play key roles.

The purpose of this study was to uncover key target proteins and corresponding active ingredients of Buxue Huanwu Decoction (BYHWD) on improving mitochondrial function to alleviate atherosclerosis (AS) via construction of a novel strategy based on in silico virtual screening, UHPLC-Q-TOF-MS/MS, and experimental verification. Firstly, 57 compounds of BYHWD were identified using UHPLC-Q-TOF-MS/MS technology, followed by the selection of 13 candidate compounds using Druggability predictions. Subsequently, a combination of differentially expressed genes (DEGs), weighted gene co-expression network analysis (WGCNA), and machine learning methods were employed to identify three hub genes associated with mitochondrial function and AS, including BTK, P2RX7 and PREPL.

Xylan acetate ester ameliorates ulcerative colitis through intestinal barrier repair and inflammation inhibition via regulation of macrophage M1 polarization.

Ulcerative colitis (UC) is a chronic inflammatory disease resulting from abnormal immune response to gut microflora translocating through damaged intestinal barrier. Xylan acetate ester (XylA) can increase colon short-chain fatty acids (SCFAs) levels and alleviate kidney disease by inhibiting inflammation through the G protein-coupled receptor pathway. Here, we synthesized and purified XylA, and then the effects and mechanisms of XylA on dextran sodium sulfate-induced UC in mice were investigated.

Discovery of NAFLD-Improving Agents by Promoting the Degradation of Keap1.

Activating Nrf2 through inhibiting Keap1 has been proven to alleviate oxidative stress and related diseases, including nonalcoholic fatty liver disease (NAFLD). Traditional Keap1 inhibitors could not avoid the "off-target" effects, but using proteolysis targeting chimera (PROTAC) technology to induce Keap1 degradation might be an effective strategy to find potential NAFLD improving agents. Thus, several PROTACs were designed and synthesized by harnessing CDDO as the Keap1 ligand in this study.

Dopamine D2 receptor agonist Bromocriptine ameliorates Aβ-induced memory deficits and neuroinflammation in mice.

Alzheimer's Disease (AD) is the most common neurodegenerative disease, which lacks disease-modifying therapeutics so far. Studies have shown that the dysfunction of the dopaminergic system is related to a variety of pathophysiology of AD, and the expression of Dopamine D2 receptor (DRD2) in the brains of AD patients and animal models is significantly downregulated, suggesting that DRD2 may represent a therapeutic target for AD. However, the strategy of targeting DRD2 for AD treatment still lacks some key experimental evidences.

DRD1 agonist A-68930 improves mitochondrial dysfunction and cognitive deficits in a streptozotocin-induced mouse model.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder characterized by irreversible cognitive deficits and memory dysfunction. Dopamine is the most abundant catecholaminergic neurotransmitter in the brain which regulates motivation, reward, movement, and cognition. Recently, increasing evidences have shown that dopaminergic system is disturbed in AD conditions, and pharmacological interventions targeting dopamine D1 receptor (DRD1) exhibit certain therapeutic benefits in AD models.

GPR40 receptor agonist TAK-875 improves cognitive deficits and reduces β-amyloid production in APPswe/PS1dE9 mice.

Rationale: Alzheimer's disease (AD) is an age-related neurodegenerative disease characterized by progressive cognitive dysfunction and memory impairment. G protein-coupled receptor 40 (GPR40) is expressed in brain in addition to periphery and is associated with cognitive function such as space orientation, memory, and learning. However, the effects and mechanisms of GPR40 agonist in improving the AD progression remain largely unknown.

Dopamine D1 receptor agonist A-68930 ameliorates Aβ-induced cognitive impairment and neuroinflammation in mice.

Alzheimer's disease (AD) is an irreversible neurodegenerative disease characterized by progressive cognitive dysfunction and memory impairment. Dopamine is an important catecholaminergic neurotransmitter that controls movement, reward, motivation, and cognition. Recently, dopamine receptors were reported to regulate immune system in both periphery and central nervous system.

The modulatory role of dopamine receptors in brain neuroinflammation.

Neuroinflammation is a general pathological feature of central nervous system (CNS) diseases, primarily caused by activation of astrocytes and microglia, as well as the infiltration of peripheral immune cells. Inhibition of neuroinflammation is an important strategy in the treatment of brain disorders. Dopamine (DA) receptor, a significant G protein-coupled receptor (GPCR), is classified into two families: D1-like (D1 and D5) and D2-like (D2, D3 and D4) receptor families, according to their downstream signaling pathways.

The ameliorative effects and underlying mechanisms of dopamine D1-like receptor agonist SKF38393 on Aβ-induced cognitive impairment.

Alzheimer's disease (AD) is an age-related neurodegenerative disease characterized by extracellular amyloid plaques and intracellular neurofibrillary tangles. It is the most common form of human cognitive decline and dementia. In this study, we aim to systematically investigate the ameliorative effects of dopamine D1-like receptor agonist SKF38393 on cognitive dysfunction and explore its underlying mechanisms.