Zwitterionic polymer-functionalized mulberry-derived lipid nanoparticles (PpC@DNJ-LNPs) encapsulating 1-deoxynojirimycin demonstrate synergistic hypoglycemic, anti-inflammatory, antioxidant, and epithelial barrier-restoring effects for oral treatment of diabetic colitis.
Key Findings
Background
Artificial intelligence was used to identify 1-deoxynojirimycin (DNJ) as a therapeutic candidate for diabetic colitis.
AI-based approach was leveraged to identify the therapeutic potential of DNJ for addressing diabetic colitis.
DNJ was selected based on its capacity to address key pathophysiological hallmarks: hyperglycemia, intestinal barrier disruption, immune dysregulation, and microbial metabolic imbalance.
This represents a computational drug-disease matching strategy prior to experimental validation.
Methods
Mulberry-derived lipid nanoparticles were successfully functionalized with zwitterionic polymer PpC and loaded with DNJ to create PpC@DNJ-LNPs.
The nanoparticles were derived from mulberry as the lipid source.
Surface functionalization with zwitterionic polymer (PpC) was used to improve stability and gastrointestinal traversal.
DNJ encapsulation within PpC@DNJ-LNPs was designed to improve bioavailability and efficacy compared to free DNJ.
The formulation was engineered for oral administration and controlled drug release.
Results
PpC@DNJ-LNPs efficiently traversed the gastrointestinal tract following oral administration and enabled controlled DNJ release.
The zwitterionic surface functionalization facilitated passage through the gastrointestinal tract.
Controlled release of DNJ was achieved from the nanoparticle platform.
The nanoparticles reached the colonic target site following oral delivery.
Results
PpC@DNJ-LNPs inhibited α-glucosidase activity to regulate glucose homeostasis in a diabetic colitis model.
Alpha-glucosidase inhibition is a known mechanism of DNJ action.
The nanoparticle formulation conferred hypoglycemic effects.
Glucose homeostasis regulation was identified as one of the synergistic therapeutic effects of PpC@DNJ-LNPs.
The improved bioavailability from encapsulation was intended to enhance this pharmacological effect compared to free DNJ.
The nanotherapeutics promoted intestinal immune balance through modulation of colonic mucosa-microbiome interaction.
Microbiota remodeling was identified as one of the key mechanisms of action.
These effects contributed to reshaping the intestinal microecology.
Immune dysregulation and microbial metabolic imbalance were targeted as key pathophysiological hallmarks of diabetic colitis.
Results
PpC@DNJ-LNPs exerted synergistic hypoglycemic, anti-inflammatory, antioxidant, and epithelial barrier-restoring effects in diabetic colitis.
Four synergistic therapeutic effects were identified: hypoglycemic, anti-inflammatory, antioxidant, and epithelial barrier-restoring.
These effects collectively addressed the key pathophysiological hallmarks of diabetic colitis.
The combination of effects was attributed to both the DNJ payload and the mulberry-derived lipid nanoparticle carrier.
Epithelial barrier restoration addressed the intestinal barrier disruption characteristic of diabetic colitis.
Conclusions
PpC@DNJ-LNPs were demonstrated to be a safe and effective oral therapeutic platform for diabetic colitis.
Safety was established as a key characteristic of the nanotherapeutic platform.
The study demonstrates 'translational potential of PpC@DNJ-LNPs as a safe and effective oral therapeutic platform for diabetic colitis.'
The platform was evaluated in the context of type 2 diabetes-associated gastrointestinal complications.
Oral administration route was maintained, which is clinically favorable for gastrointestinal conditions.
What This Means
This research suggests that a new nanoparticle drug delivery system made from mulberry-derived fats can effectively treat diabetic colitis, a serious gut complication of type 2 diabetes. The researchers used artificial intelligence to identify a natural compound called 1-deoxynojirimycin (DNJ), found in mulberries, as a promising treatment candidate. They then packaged DNJ inside specially designed nanoparticles coated with a zwitterionic polymer (a material with both positive and negative charges) to help the particles survive the harsh environment of the digestive tract and reach the colon where they are needed most.
When given orally to animal models of diabetic colitis, these nanoparticles (called PpC@DNJ-LNPs) produced multiple beneficial effects simultaneously: they lowered blood sugar by blocking a glucose-processing enzyme, reduced inflammation, fought oxidative stress, helped repair the gut lining, and rebalanced the gut microbiome. This combination of effects addressed all the major features of diabetic colitis, which is typically difficult to treat because it involves both metabolic and inflammatory problems at the same time.
This research suggests that combining natural plant-derived materials with advanced nanotechnology could offer a practical oral treatment strategy for diabetic colitis, a condition that currently has limited therapeutic options. The use of mulberry-derived components and a naturally occurring compound like DNJ also points toward a potentially more tolerable treatment approach, and the authors note the platform showed a favorable safety profile, supporting its potential for future clinical development.
Cao Y, Xu H, Xu C, Zu M, Sun J, Xiong D, et al.. (2026). Zwitterionic Lipid Nanotherapeutics from Mulberry for Oral Treatment of Diabetic Colitis.. ACS nano. https://doi.org/10.1021/acsnano.5c17183