In-Silico ADMET Prediction and Anti-Diabetic Potential of Morus alba Phytoconstituents

Diabetes mellitus is a major public health challenge characterised by impaired insulin secretion, reduced insulin action or both. Persistent hyperglycaemia affects carbohydrate, protein and lipid metabolism and contributes to complications involving the cardiovascular system, kidneys, eyes, blood vessels and nervous system. The increasing prevalence of type 2 diabetes has created a continuous need for safer, effective and affordable therapeutic agents. Medicinal plants remain a valuable source of structurally diverse bioactive compounds. Morus alba L., commonly known as white mulberry, belongs to the family Moraceae. Different parts of the plant, particularly the leaves and fruits, have been used in traditional systems of medicine. The leaves contain alkaloids, flavonoids, phenolic acids, anthocyanins, glycosides, polysaccharides, tannins, terpenoids and other secondary metabolites. These constituents are associated with anti-diabetic, antioxidant, anti-inflammatory and other pharmacological effects.

Among the important constituents of Morus alba, deoxynojirimycin is known for alpha-glucosidase inhibitory potential, while quercetin, kaempferol, chlorogenic acid and cyanidin are associated with antioxidant action and glucose metabolism regulation. However, biological activity alone is not sufficient for drug development. A candidate compound should also possess acceptable absorption, distribution, metabolism, excretion and toxicity characteristics. In-silico ADMET prediction offers a rapid, economical and ethically favourable approach for early-stage screening of natural compounds before extensive experimental studies. The present article reports the extraction, preliminary phytochemical screening and in-silico ADMET prediction of selected Morus alba phytoconstituents. The study combines experimental qualitative observations with computational pharmacokinetic and toxicity predictions to identify promising compounds for future anti-diabetic drug development.

Figure 1: Reported pharmacological properties of Morus alba plant.

Figure 2: Leaves and fruits of Morus alba.

Deoxynojirimycin	Quercetin	Kaempferol
Chlorogenic acid	Cyanidin

Figure 3: Chemical structures of selected Morus alba phytoconstituents

Toxicity prediction indicated that all compounds were non-hERG blockers, non-AMES toxic and non-hepatotoxic. Kaempferol, chlorogenic acid and cyanidin had higher predicted LD50 values and were placed in toxicity class 5, suggesting comparatively lower acute toxicity. Deoxynojirimycin showed toxicity class 4. Quercetin showed a lower predicted LD50 and toxicity class 3, indicating comparatively higher predicted acute toxicity and the need for careful dose optimisation.

DISCUSSION

The phytochemical screening and in-silico analysis support the therapeutic relevance of Morus alba leaves. The presence of alkaloids, flavonoids, phenolic acids and anthocyanins provides a pharmacological basis for the traditionally reported anti-diabetic and antioxidant effects of the plant. These phytochemical classes are widely associated with modulation of oxidative stress, carbohydrate digestion and glucose metabolism.

Deoxynojirimycin emerged as a promising molecule because it showed favourable molecular weight, acceptable topological polar surface area, high gastrointestinal absorption and no Lipinski violation. Its predicted safety profile was also acceptable, with absence of hepatotoxicity, mutagenicity and hERG blockade. These findings are consistent with its role as a potential alpha-glucosidase inhibitory constituent of mulberry leaves.

Quercetin and kaempferol also showed favourable drug-likeness and high gastrointestinal absorption. However, metabolic interaction alerts were observed, particularly CYP2C9 inhibition for quercetin and CYP3A4 inhibition for kaempferol. These findings do not exclude their therapeutic potential but indicate that further experimental pharmacokinetic studies are required, especially in relation to drug-drug interaction risk. Quercetin also showed comparatively higher predicted acute toxicity, suggesting the importance of controlled dosing and formulation design.

Chlorogenic acid demonstrated one Lipinski violation, a high TPSA value, lower bioavailability score and low predicted gastrointestinal absorption. These results suggest that its oral absorption may be limited. Formulation strategies such as nanoformulation, phytosomal delivery or structural optimisation could be explored to improve its bioavailability. Cyanidin showed good predicted absorption, no Lipinski violation and low acute toxicity class, supporting its inclusion as a potentially useful antioxidant and anti-diabetic phytoconstituent.

Overall, the findings indicate that the selected Morus alba constituents possess acceptable pharmacokinetic and toxicity profiles. The study also highlights the usefulness of integrated computational tools such as SwissADME, pkCSM and ProTox-II for early evaluation of phytochemicals. Nevertheless, in-silico predictions should be considered preliminary and require confirmation through in-vitro enzyme inhibition assays, cell-based safety studies and in-vivo anti-diabetic models.

CONCLUSION

The present research article demonstrates that Morus alba leaf extract contains important phytoconstituents such as deoxynojirimycin, quercetin, kaempferol, chlorogenic acid and cyanidin. In-silico ADMET prediction showed that most of these compounds possess favourable drug-likeness, acceptable gastrointestinal absorption and low predicted toxicity. Deoxynojirimycin was identified as the most balanced candidate due to its favourable absorption, drug-likeness and safety profile. Chlorogenic acid showed lower predicted bioavailability and gastrointestinal absorption, while quercetin showed relatively higher predicted acute toxicity. The study supports the anti-diabetic potential of Morus alba phytoconstituents and recommends further experimental validation for development of safe plant-based anti-diabetic therapeutics.

FUTURE PROSPECTS

Future work should include quantitative phytochemical estimation, chromatographic standardisation of the extract, in-vitro alpha-glucosidase and alpha-amylase inhibition assays, antioxidant studies, cell-line toxicity studies and in-vivo anti-diabetic evaluation. Formulation-based approaches may be used to improve the bioavailability of compounds such as chlorogenic acid. Molecular docking and molecular dynamics studies against diabetes-related targets may further clarify the mechanism of action.

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