Dual-Stimuli-Responsive Gut Microbiota-Targeting Nitidine Chloride-CS/PT-NPs Improved Metabolic Status in NAFLD

Abstract

Background and Purpose

Nitidine chloride (NC) is a botanical drug renowned for its potent anti-inflammatory, antimalarial, and hepatocellular carcinoma-inhibiting properties; however, its limited solubility poses challenges to its development and application. To address this issue, we have devised a colon-targeted delivery system (NC-CS/PT-NPs) aimed at modulating the dysbiosis of the gut microbiota by augmenting the interaction between NC and the intestinal microbiota, thereby exerting an effect against nonalcoholic fatty liver disease.

Methods

The NC-CS/PT-NPs were synthesized using the ion gel method. Subsequently, the particle size distribution, morphology, drug loading efficiency, and release behavior of the NC-CS/PT-NPs were characterized. Furthermore, the impact of NC-CS/PT-NPs on non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD) in mice was investigated through serum biochemical analysis, ELISA, and histochemical staining. Additionally, the influence of NC-CS/PT-NPs on intestinal microbiota was analyzed using 16S rDNA gene sequencing.

Results

The nanoparticles prepared in this study have an average particle size of (255.9±5.10) nm, with an encapsulation rate of (72.83±2.13) % and a drug loading of (4.65±0.44) %. In vitro release experiments demonstrated that the cumulative release rate in the stomach and small intestine was lower than 22.0%, while it reached 66.75% in the colon. In vivo experiments conducted on HFD-induced NAFLD mice showed that treatment with NC-CS/PT-NPs inhibited weight gain, decreased serum aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and lipid levels, improved liver and intestinal inflammation, and altered the diversity of gut microbiota in mice.

Conclusion

This study provides new evidence for the treatment of NAFLD through the regulation of gut microbiota using active ingredients from traditional Chinese medicine.

Keywords:

• nanoparticles
• colonic targeting
• metabolic disorders
• gut microbiota

Acknowledgments

Thank you to everyone who has provided us with assistance during our experiments and writing papers. It is our great pleasure to acknowledge the help we have received from our supervisors, Professor Ye, who has provided us with valuable suggestions during our academic studies.

Disclosure

There are no competing financial interests or personal relationships that could influence the work reported in this study.

Additional information

Funding

This study was supported by grants from National Natural Science Foundation of China (No. 82360818), the Natural Science Foundation of Guangxi Province (No.2022GXNSFDA035063, 2023GXNSFAA026366), First-class discipline innovation-driven talent program of Guangxi Medical University, Guangxi Medical University Training Program for Distinguished Young Scholars.