Morus alba L. (Sangzhi) alkaloids mitigate atherosclerosis by regulating M1/M2 macrophage polarization.

BACKGROUND: Atherosclerosis (AS) is an important cause of cardiovascular disease, posing a substantial health risk. Recognized as a chronic inflammatory disorder, AS hinges on the pivotal involvement of macrophages in arterial inflammation, participating in its formation and progression. Sangzhi alkaloid (SZ-A) is a novel natural alkaloid extracted from the mulberry branches, has extensive pharmacological effects and stable pharmacokinetic characteristics. However, the effects and mechanisms of SZ-A on AS remain unclear. PURPOSE: To explore the effect and underlying mechanisms of SZ-A on inflammation mediated by macrophages and its role in AS development. METHODS: Atherosclerosis was induced in vivo in apolipoprotein E-deficient mice through a high-fat and high-choline diet. We utilized macrophages and vascular endothelial cells to investigate the effects of SZ-A on macrophage polarization and its anti-inflammatory properties on endothelial cells in vitro. The transcriptomic analyses were used to investigate the major molecule that mediates cell-cell interactions and the antiatherogenic mechanisms of SZ-A based on AS, subsequently validated in vivo and in vitro. RESULTS: SZ-A demonstrated a significant inhibition in vascular inflammation and alleviation of AS severity by mitigating macrophage infiltration and modulating M1/M2 macrophage polarization in vitro and in vivo. Moreover, SZ-A effectively reduced the release of the proinflammatory mediator C-X-C motif chemokine ligand (CXCL)-10, predominantly secreted by M1 macrophages. This reduction in CXCL-10 contributed to improved endothelial cell function, reduced recruitment of additional macrophages, and inhibited the inflammatory amplification effect. This ultimately led to the suppression of atherogenesis. CONCLUSION: SZ-A exhibited potent anti-inflammatory effects by inhibiting macrophage-mediated inflammation, providing a new therapeutic avenue against AS. This is the first study demonstrating the efficacy of SZ-A in alleviating AS severity and offers novel insights into its anti-inflammatory mechanism.

Hydrolyzed Chicken Meat Extract Attenuates Neuroinflammation and Cognitive Impairment in Middle-Aged Mouse by Regulating M1/M2 Microglial Polarization.

Aging is the most common cause of several neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease. The pathological hallmarks of age-dependent neuropathology consist of chronic neuroinflammation, oxidative stress, gliosis, learning disability, and cognitive decline. A novel hydrolyzed bioactive peptide mixture extracted from chicken meat, that is, hydrolyzed chicken extract (HCE) has been previously demonstrated to exert neuroprotective effects in rodents and humans. However, the mechanism of HCE on age-related neurological disorders remains unclear. Herein, we aimed to clarify the impact and mechanism of isolated bioactive components (BCs) from HCE on age-dependent neuroinflammation and cognitive impairment in middle-aged mice. We found that both BC and HCE supplementation ameliorated age-induced memory loss, alleviated hippocampal neuroinflammation and oxidative stress, followed by promoting hippocampal neurogenesis in mice. BC and HCE treatment also ameliorated age-dependent morphological anomalies and alleviated microgliosis and astrogliosis. In parallel, BC and HCE treatment showed a significant decrease in the NF-κB p65 and p38 MAPK signaling, which were associated with the enhancement of antioxidative enzymes activities. Furthermore, BC treatment attenuated the neuroinflammatory phenotypes by the decrease in M1-polarized microglia and the increase in M2-polarized microglia in vivo and in vitro. In addition, we found that cyclo(Phe-Phe), one of the cyclopeptides purified from BC, showed notable anti-inflammatory effects in BV2 cells. Taken together, BC might be used as a dietary supplement for alleviating age-dependent neuropathology in middle-aged individuals.

The Gut Microbiota and Its Metabolites, Novel Targets for Treating and Preventing Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent metabolic disorders worldwide, along with obesity and type 2 diabetes. NAFLD involves a series of liver abnormalities from simple hepatic steatosis to non-alcoholic steatohepatitis, which can ultimately lead to liver cirrhosis and cancer. The gut-liver axis plays an important role in the development of NAFLD, which depends mainly on regulation of the gut microbiota and its bacterial products. These intestinal bacterial species and their metabolites, including bile acids, tryptophan catabolites, and branched-chain amino acids, regulate adipose tissue and intestinal homeostasis and contribute to the pathogenesis of NAFLD/non-alcoholic steatohepatitis. In this review, the current evidence regarding the key role of the gut microbiota and its metabolites in the pathogenesis and development of NAFLD is highlighted, and the advances in the progression and applied prospects of gut microbiota-targeted dietary and exercise therapies is also discussed.