Dual‐Stimuli‐Responsive Gut Microbiota‐Targeting Berberine‐CS/PT‐NPs Improved Metabolic Status in Obese Hamsters

Abstract

Gut dysbiosis has been found to be involved in the pathogenesis of energy metabolic disorders and might be a new strategy for these ailments. Berberine (BBR), a botanical medicine, shows therapeutic efficacy in patients with metabolic diseases. Numerous reports have shown BBR's modulating effect on gut microbiota, opening a new avenue to understand BBR's mechanism. In this study, a colon‐specific delivery system, BBR‐CS/PT‐NP, is investigated by the assembly of pH/gut microflora dual stimuli‐responsive nanoparticles for enhancing the interaction between BBR and gut microbiota. After oral administration, the delivering system remains stable in the stomach and small intestine, followed by a burst release of BBR after reaching the colon segment rich in intestinal bacteria. The enzymes produced by bacteria degrade the nanoparticle, causing direct exposure of BBR to gut microbiota. In the high fat diet‐induced obese hamsters, BBR‐CS/PT‐NP intervention inhibits weight‐gain and fat deposition, decreases plasma lipids and glucose levels, improves inflammation condition and insulin resistance, alleviates hepatic steatosis, at a level significantly higher than the pure BBR does. The mechanisms might be attributable to the enhanced interaction between BBR and the gut flora. The results provide a novel proof‐of‐concept for drug delivery targeting gut microbiota to ameliorate metabolic disorders.

The influence of the gut microbiota on the bioavailability of oral drugs

“…In order to prevent enzymatic degradation, stomach irritation caused by BBR and complex drug–drug interaction, Guo et al. 212 designed a microbiota-targeting and colon-specific BBR delivery system using chitosan (CS) and pectin (PT). This novel delivery system, BBR-CS/PT-NP, is pH/gut microbiota dual stimuli-responsive.…”

Berberine Relieves Metabolic Syndrome in Mice by Inhibiting Liver Inflammation Caused by a High-Fat Diet and Potential Association With Gut Microbiota

“…This indicates that colitis can be alleviated by reducing the expression of related inflammatory factors such as TNF-α, NF-κB, IL-6, and inducible nitric oxide synthase (iNOS; Li et al, 2020 ). It has been reported that berberine intervention in hamsters with HFD-induced obesity inhibits weight gain and fat deposition; reduces blood sugar, blood lipid, and cellular lipopolysaccharide levels; improves inflammation and insulin resistance; and relieves fatty liver disease and leads to increased production of short chain fatty acids (SCFA; Guo et al, 2019 ). This indicates that the metabolic regulation mechanism of berberine is likely closely related to the gut microbiota status, which represents a potential target for the development of therapeutic drugs.…”

A Naturally Derived Nanocomposite Film with Photodynamic Antibacterial Activity: New Prospect for Sustainable Food Packaging

“…Berberine is a natural isoquinoline alkaloid with hydrophobic cations from herbal plants . Long-term uses in the treatment of bacteria-related diarrhea have proven its safety and antibacterial ability . Moreover, berberine is visible light absorptive and aggregation-induced emission (AIE) active. , Perfectly opposite to the ACQ phenomenon, it shows dim fluorescence in solution but bright emission in the aggregate or solid state.…”