In recent years, the incidence of thyroid cancer has been increasing globally, with papillary thyroid cancer (PTCa) being the most prevalent pathological type, accounting for approximately 80% of all cases. Although PTCa has been regarded to be slow growing and has a good prognosis, in some cases, PTCa can be aggressive and progress despite surgery and radioactive iodine treatment. In addition, most cancer treatment drugs have been shown to be cytotoxic and nonspecific to cancer cells, as they also affect normal cells and consequently cause harm to the body. Therefore, searching for new targets and therapies is required. Herein, we explored a bioinformatics analysis to identify important theranostic markers for THCA. Interestingly, we identified that the DPP4/CTNNB1/MET gene signature was overexpressed in PTCa, which, according to our analysis, is associated with immuno-invasive phenotypes, cancer progression, metastasis, resistance, and unfavorable clinical outcomes of thyroid cancer cohorts. Since most cancer drugs were shown to exhibit cytotoxicity and to be nonspecific, herein, we evaluated the anticancer effects of the antidiabetic drug sitagliptin, which was recently shown to possess anticancer activities, and is well tolerated and effective. Interestingly, our in silico molecular docking results exhibited putative binding affinities of sitagliptin with DPP4/CTNNB1/MET signatures, even higher than standard inhibitors of these genes. This suggests that sitagliptin is a potential THCA therapeutic, worthy of further investigation both in vitro and in vivo and in clinical settings.

This research attempts to establish the antihyperglycemic potential of Eremomastax speciosa, a medicinal plant utilized in traditional West African diabetes therapy, through virtual simulation. While numerous reports have validated its biological potency, studies on the drug-likeness and antidiabetic properties of its compounds are limited. The in silico pharmacological, and toxicological profile of aqueous, methanolic/methylene phytochemicals from previously reported work was analyzed using Swiss ADME and Protox II online server. The docking process was performed using PyRx-0.8, coupled with AutoDock Vina. Phytochemicals that aligned with Lipinski’s rules for drugs were then subjected to a virtual docking simulation. This simulation replicated the inhibitory effects of E. speciosa phytochemicals on sodium-glucose co-transporters (SGLT2) and α-amylase, similar to metformin, an FDA-approved antidiabetic medicine utilized as a control. Phytochemicals such as 8, 9,10-dimethyltricyclo[4.2.1.1(2,5)]decane-9,10-diol (-6.6 kcal/mol), 11-isopropylidenetricyclo[4.3.1.1(2,5)]undec-3-en-10-one (-7.9 kcal/mol), 4-(1,5-dihydroxy-2,6,6-trimethylcyclohex-2-enyl)but-3-en-2-one (-7.3 kcal/mol), and N-methyl-N-4-[2-acetoxymethyl-1-pyrrolidyl]-2-butynyl]-acetamide (-7.5 kcal/mol) exhibits superior binding affinities to the specific proteins targeted, compared to metformin, implying that E. speciosa is a source of druggable antidiabetic molecules that can be enhanced to achieve better efficacy.

Citrus spp., including their essential oils, have been studied for their antidiabetic potential; however, their modulatory mechanism on dipeptidyl peptidase-4 (DPP4) remains elusive. This study profiled citrus essential oils' (CEOs) constituents using gas chromatography-mass spectrophotometry and evaluated the DPP4 inhibitory potential of the oils and their metabolites using in vitro, machine learning (ML), and molecular dynamics simulation methods. Of the six CEOs investigated, only Citrusreticulata (18.21 μg/mL) had lower half maximal inhibitory concentration (IC₅₀) than the reference standard [sitagliptin (22.88 μg/mL)]. A total of 64 metabolites were curated into a library from the chemical profiles of the oils. Machine learning analysis highlighted the principal component and hierarchical clustering of the top 35 abundant metabolites and correlated metabolites abundances with in vitro DPP4 inhibition of the oils. The ML characterization of DPP4 inhibition using docking scores and molecular descriptor of the metabolites yielded a regression model (R²) of 0.682 (root mean square error of 0.409), with strong correlations (Pearson r = 0.82, Spearman ρ = 0.93) between docking scores and binding free energy values. Structural activity analysis of the metabolites revealed that while beta-terpineol (-35.78 kcal/mol) presented superior binding free energy than sitagliptin (-34.80 kcal/mol) and the other CEO metabolites, it also had better binding stability and interaction with the catalytic residues of DPP4, which is critical for modulating the enzyme activity. Kinetic analysis indicated beta-terpineol's competitive inhibition pattern against DPP4. Findings from this study show that relative abundance of metabolites does not directly translate into their biological activities and CEOs and their metabolites, especially beta-terpineol, possess potential anti-DPP4 effects. Nevertheless, further studies such as in vivo validation and lead optimization are necessary to fully establish the antidiabetic potential of the investigated CEOs and their metabolites.

Background: The purpose of this study was to determine the phytochemical composition and antimicrobial potential of crude n-hexane, ethyl-acetate, methanol and aqueous extracts of Calotropis procera leaves against food spoilage microorganisms. Methods: Standard protocols were employed for the analysis of qualitative phytochemical compositions of the extracts, and antimicrobial activities against Staphylococcus aureus, Bacillus cereus, Pseudomonas aerugenosa and Aspergillus niger. Results: Phytochemical analysis revealed the presence of tannin, saponin, alkaloids, flavonoids, reducing sugar and phenolics. Terpenoids were absent in ethyl acetate and n-hexane extracts while cardiac glycoside was absent in all extracts. All extracts produced antimicrobial activity at a varying zone of inhibition. The widest inhibition zone was produced by methanol extract (21.35±0.43 mm) on staphylococcus aureus while the lowest inhibition zone (12.05±0.45 mm) was observed in the n-hexane fraction. Similarly, the widest inhibition zone (17.24±0.95 mm) was produced by methanol on A. niger while the lowest inhibition zone (5.45±0.42 mm) was produced on n-hexane on A. niger. However, the ethyl acetate extract showed no visible inhibitory zone on all the tested microorganisms. The minimum inhibitory concentration ranged from 32 mg/ml (S. aureus and B. cereus) for ethanol extracts to 128 mg/ml (B. cereus, P. aerugenosa and A. niger) for n-hexane extract. Conclusion: The result shows that the plant is a good source of bioactive compounds that can be used as a natural alternative to a chemical agent in preserving and controlling food poisoning organisms.

Background: In rural areas of KwaZulu-Natal and Eastern Cape Provinces, South Africa, women have traditionally used bark extracts from Cassipourea flanaganii, C. malosana, and C. gummiflua for skin lightening and sun protection. This study investigates the anti-tyrosinase and antioxidant activities of methanolic bark extracts from these species, aiming to validate their traditional use and identify potential lead compounds for the treatment of skin hyperpigmentation. Methods: Anti-tyrosinase activity was evaluated using half-maximal inhibitory concentration (IC₅₀) values, and antioxidant capacity was measured through FRAP, DPPH, and TEAC assays. Polyphenol and flavanol contents were quantified using Folin-Ciocalteu method. Potential lead compounds were identified through molecular docking, pharmacokinetic analysis, and molecular dynamics (MD) simulations. Statistical analyses, including ANOVA and post-hoc tests, compared extract activities. Results: C. flanaganii exhibited the most potent anti-tyrosinase activity (IC₅₀: 37.10 μg/mL), though statistical differences among species were non-significant. C. gummiflua showed the highest polyphenol (143.68 mg GAE/g) and flavanol (14.67 mg QE/g) content, correlating with superior antioxidant activity (FRAP: 526.07 μmol AAE/g; DPPH: 390.26 μmol TE/g; TEAC: 596.98 μmol TE/g). The isolated compound 7-methoxygeranin A demonstrated lower anti-tyrosinase activity (IC₅₀: 45.16 μg/mL) compared to C. flanaganii extract, suggesting the presence of more potent metabolites. Molecular docking and MD simulations identified emodin 6,8-dimethyl ether as a thermodynamically stable lead compound (binding free energy: − 39.88 kcal/mol), interacting with key catalytic residues over 150 ns. The compound demonstrated prolonged residence at the active site of tyrosinase, indicating strong-binding stability. Conclusion: While C. flanaganii demonstrated the strongest anti-tyrosinase activity, C. gummiflua showed the highest antioxidant potential. Emodin 6,8-dimethyl ether emerged as a promising candidate for skin-lightening applications, warranting further in vitro and in vivo validation. These findings support the traditional use of Cassipourea species and highlight their potential for developing natural skin health products. Further studies are needed to explore the pharmacokinetics, safety, and efficacy of these compounds in clinical settings.