Scientists unlock the potential of fenugreek-based lipid nanoparticles to improve diabetes treatment, offering a promising alternative for enhanced drug delivery and long-term stability.
Fenugreek (Trigonella foenum-graecum) seed closeup. Study: Fenugreek seeds as a natural source of L-arginine-encapsulated lipid nanoparticles against diabetes. Image Credit: Valery Prokhozhy / Shutterstock
In a recent article in the journal Scientific Reports, researchers investigated the role of L-arginine, a conditionally essential amino acid, in managing diabetes. They also evaluated the efficacy of lipid nanocarriers derived from fenugreek seed oil to improve drug delivery.
Their conclusions indicate that L-arginine shows promising potential as an anti-diabetic agent by exhibiting strong molecular interactions with key diabetes-related proteins, though further validation is required to confirm its clinical efficacy. The study also highlights the role of lipid nanocarriers in improving the bioavailability, stability, and targeted delivery of L-arginine. These advancements could pave the way for better diabetes treatments, although further validation through in vivo studies and clinical trials is required.
Background
Scientists estimate that over 10% of adults under 80 years old around the world have diabetes, with approximately half being unaware that they have the condition. The prevalence of diabetes in adults increased from 4.7% in 1980 to 8.5% in 2021, and the number of cases worldwide is expected to rise to 783 million in 2045.
To address this surge, researchers are exploring novel treatment strategies, as the long-term effectiveness, bioavailability, and drug stability of current therapies remain limited. Plant-based treatments, which have long been used in traditional medicine, are now being investigated for anti-diabetic properties.
Fenugreek, which is grown across North Africa, Europe, and Asia, has hypoglycemic properties. It contains phytochemicals that decrease oxidative stress and increase insulin sensitivity. Phytochemical screening in this study confirmed the presence of key bioactive compounds, including alkaloids, flavonoids, and phenols, which contribute to fenugreek’s therapeutic properties. Specific compounds such as Daidzein, 4-hydroxyisoleucine, and diosgenin were identified as having potential anti-diabetic effects.
Animal models suggest that fenugreek extracts can reduce blood glucose levels. L-arginine may also have therapeutic value as it enhances the production of nitric oxide, which benefits blood flow and vascular function and protects pancreatic beta cells, which are responsible for producing insulin. These cells can be damaged by glucotoxicity (high blood sugar) and high-fat levels (lipotoxicity).
However, the poor bioavailability of L-arginine means that the body absorbs it inefficiently, and it is often removed from the body too quickly, reducing its effectiveness for long-term treatment. A solution to this problem is encapsulating L-arginine in lipid carriers, which may improve stability, making the drug last longer in the body. It may also enable targeted delivery, ensure it reaches the right tissues, and allow controlled release, maintaining steady levels of the drug over time. The nanoparticles synthesized in this study exhibited a neutral zeta potential (-9.37 mV), which contributes to their stability and biocompatibility in biological systems.
About the Study
In this study, researchers combined L-arginine with lipid nanoparticles synthesized from fenugreek seed oil, exploring the potential of this dual-action system to enhance drug stability and targeted delivery while also harnessing the bioactive properties of fenugreek extracts. They aimed to strengthen the delivery and effectiveness of diabetes drugs by studying network pharmacology (how drugs interact with multiple biological pathways) and phytoinformatics (analyzing plant-based compounds for drug potential).
After obtaining 250g of fenugreek seeds, the research team processed them through Soxhlet and methanol extraction to derive seed oil and bioactive compounds.
The Collective Molecular Activities of Useful Plants (CMAUP) database provided resources to identify the active compounds, while other resources were utilized to search for genes associated with type 2 diabetes mellitus (T2DM) and standardize gene targets. Researchers identified 172 compounds in fenugreek and focused on two key candidates: L-arginine and Daidzein. A network analysis using Cytoscape software revealed how these compounds interact with diabetes-related genes.
Molecular docking studies compared L-arginine, Daidzein, and Metformin (a common diabetes drug) to assess their binding strength to diabetes-related proteins. L-arginine exhibited the strongest binding interactions, forming multiple hydrogen bonds with CYP1A2, CYP2C19, and NFKB, which play key roles in diabetes regulation. However, further biological validation is required to confirm the therapeutic impact of these interactions.
Additionally, the team evaluated the absorption, metabolism, and drug-likeness of active compounds and used phytochemical screening to detect and measure the content of compounds such as alkaloids, saponins, phenols, tannins, terpenoids, quinones, flavonoids, and glycosides.
Finally, lipid nanoparticles were created by mixing methanolic fenugreek extract and seed oil; L-arginine was incorporated into nanoparticles using centrifugation and high-speed stirring. This was characterized using ultraviolet-visible spectroscopy to confirm nanoparticle formation and scanning electron microscopy for structural analysis.
Findings
Using the CMAUP database, the research team identified L-arginine and Daidzein as the most promising bioactive compounds for diabetes treatment. They also identified 14,327 gene/protein targets, including 10 for L-arginine and 55 for Daidzein. Three common targets were found between these compounds and T2DM-related genes.
Molecular docking studies revealed that L-arginine demonstrated stronger binding interactions with diabetes-related proteins than both Daidzein and Metformin, suggesting a promising mechanism of action. However, molecular docking alone does not confirm therapeutic effectiveness, and further in vivo testing is necessary.
Researchers then looked at Daidzein and L-arginine's toxicity, excretion, metabolism, distribution, and absorption properties. While both compounds showed favorable absorption, L-arginine demonstrated no major safety concerns, whereas Daidzein exhibited reactivity in 5 out of 11 toxicity tests.
Phytochemical screening of the fenugreek seed and oil extracts confirmed the presence of alkaloids, flavonoids, and phenols, with the seed extract showing higher phenolic and flavonoid content. The lipid nanoparticle synthesis also revealed that a particle size of 100.2 nm was optimal for targeted drug delivery in diabetes treatment; the nanoparticles were moderately stable with an amorphous to semi-crystalline structure, which may enhance bioavailability compared to crystalline forms.
The L-arginine-loaded nanoparticles exhibited strong antioxidant (84.44% inhibition), anti-inflammatory (81.10% albumin denaturation inhibition), and anti-diabetic (89.30% α-amylase inhibition) properties, surpassing Metformin’s effectiveness in these assays.
Conclusions
This research demonstrates the potential of L-arginine as an anti-diabetic agent, particularly when encapsulated in lipid nanoparticles that improve stability, bioavailability, and controlled release. These nanoparticles exhibited superior antioxidant and anti-inflammatory activity compared to conventional treatments.
However, long-term stability, in vivo validation, and clinical safety assessments must be conducted before scaling up production and developing patient-specific formulations. Further research should assess the environmental impact, regulatory requirements, and optimization of nanoparticle surface modifications for improved stability.
This study lays the foundation for the development of novel diabetes treatments utilizing lipid nanoparticle-encapsulated bioactive compounds, potentially revolutionizing targeted drug delivery for metabolic disorders.