Realgar Alleviated Neuroinflammation Induced by High Protein and High Calorie Diet in Rats via the Microbiota-Gut-Brain Axis

Abstract

Purpose: Gastrointestinal heat retention syndrome (GHRS) often occurs in adolescents, resulting into nervous system injury. Realgar, an arsenic mineral with neuroprotective effect, has been widely used to treat GHRS. However, its mechanism of action remains unknown. Methods: A GHRS rat model was established using a high protein and high calorie diet. We performed macroscopic characterization by assessing bowel sounds, hot/cold preference, anal temperature, and fecal features. Atomic fluorescence spectroscopy was employed to evaluate brain arsenic level while hippocampal ultrastructural changes were analyzed using transmission electron microscopy. In addition, inflammatory cytokines and BBB breakdown were analyzed by western blotting, immunofluorescence assays, and immunohistochemistry staining. We also evaluated hippocampal metabolites by LC-MS while fecal microorganisms were assessed by 16S rDNA sequencing. Results: Our data showed that the high protein and high calorie diet induced GHRS. The rat model depicted decreased bowel sounds, increased fecal characteristics score, preference for low temperature zone, and increased anal temperature. In addition, there was increase in inflammatory factors IL-6, Iba-1, and NF-κB p65 as well as reduced BBB structural protein Claudin-5 and Occludin. The data also showed appearance of hippocampus metabolites disorder and fecal microbial imbalance. Realgar treatment conferred a neuroprotective effect by inhibiting GHRS-specific characteristics, neuroinflammatory response, BBB impairment, metabolites disorder, and microbial imbalance in the GHRS rat model. Conclusion: Taken together, our analysis demonstrated that realgar confers a neuroprotective effect in GHRS rats through modulation of the microbiota-gut-brain axis.

Realgar toxicity in terms of its chemical characterization, pharmacological mechanisms, and metabolic profile: A review

“…[24] However, excessive amounts of realgar can have toxic effects on the central nervous system of normal rats. [25]…”

“…[24] However, excessive amounts of realgar can have toxic effects on the central nervous system of normal rats. [25] 3.3. Antitumor mechanisms Realgar has demonstrated significant clinical efficacy in the treatment of leukemia, particularly APL, with good safety, low toxicity, and fewer adverse effects such as bone marrow suppression.…”

“…The dual nature of efficacy and toxicity of realgar has also been demonstrated. [1,25] In other words, realgar can induce redox destabilization in the cerebral cortices of normal rats, resulting in central nervous system toxicity. However, it has been found to exhibit an antagonistic effect on redox destabilization in rats with accumulated heat in the stomach and intestine syndrome, leading to beneficial therapeutic effects.…”

High-Carbohydrate Diet Consumption Poses a More Severe Liver Cholesterol Deposition than a High-Fat and High-Calorie Diet in Mice

“…The obesity-related ecological imbalance is directly associated with the high-fat diet (HFD) and manifests in a reduced overall microbiota count, a shift in bacteria species abundance, and an overall increase in gut permeability [20,21]. Also, studies have shown that a high-calorie diet in rats induced decreased bowel sounds and fecal microbial imbalance [22]. The increase in unfavorable bacteria (such as Lachnoclostridium and Desulfovibrio) was strongly associated with a disturbance of glucose and lipid metabolism [23].…”