Rheumatoid arthritis (RA) is a chronic autoimmune disorder marked by synovial inflammation and joint destruction, with Cyclooxygenase-2 (COX-2) significantly contributing to its pathogenesis. Traditional management includes NSAIDs and COX-2 inhibitors, which pose gastrointestinal and cardiovascular risks. Azadirachta indica (neem), known for its anti-inflammatory properties, was studied for its antioxidant activity, mineral content, and potential COX-2 inhibitors, emphasizing its relevance to RA treatment. Fresh leaves of neem were extracted using n-butanol and evaluated for total phenolic content (TPC), total flavonoid content (TFC), and ferric reducing antioxidant power (FRAP) using standard protocols. Mineral content was determined by atomic absorption spectroscopy, and bioactive compounds were identified using high-performance liquid chromatography (HPLC). Identified phytochemicals were subjected to in silico analyses against human COX-2. The fraction exhibited high TPC and TFC and demonstrated strong FRAP activity. HPLC analysis identified seven polyphenolic compounds, and mineral analysis revealed the presence of essential macro- and microelements, all within FAO/WHO permissible limits. E-pharmacophore screening, molecular docking, ADMET predictions, and AutoQSAR analysis identified ferulic acid as a promising COX-2 inhibitor, with ferulic acid showing the strongest binding affinity (−6.899 kcal/mol) and favorable MM-GBSA binding free energy (−34.71 kcal/mol). This study demonstrates that Azadirachta indica leaf possesses significant antioxidant activity, a beneficial mineral profile, and bioactive compounds with promising COX-2 inhibitory potential. Ferulic acid stands out for its strong binding affinity, pharmacokinetic properties, and safety profile. The combined in vitro and in silico results highlight neem’s potential as a natural anti-inflammatory agent for RA, necessitating further in vivo and clinical validation.

Background and Objective: The increasing occurrence of diabetes mellitus has spurred extensive research into natural products as potential alternative treatments. This research investigated the in vitro, in vivo, and in silico studies of the therapeutic potential of Ficus exasperata on diabetes. Aqueous and ethyl acetate extract fractions of Ficus exasperata were evaluated for antioxidant properties using standard protocols. Materials and Methods: Each of the fractions was administered at different concentrations to seven groups of Drosophila melanogaster . The in vivo inhibitory effects of the fractions were assayed for the expression of insulin-like peptide-2 (ILP-2), insulin-like receptor (InR), and Ecdysone inducible gene L2 (Imp-L2). The glucose concentration, non-protein thiol, total thiol, H₂O₂ , and nitrite activities were also evaluated. In silico studies assessed the inhibitory potentials of selected compounds on α-amylase as the target protein. All antioxidant studies were performed in triplicates, and data (Mean±SD) were statistically analyzed using one-way ANOVA with Duncan’s multiple range test (GraphPad Prism), considering p<0.05 as statistically significant. Results: The results revealed higher significant p<0.05 antioxidant contents in ethyl acetate fractions. Increased activities were also observed in rats treated with ethyl acetate fractions in comparison to acarbose administration. In silico analysis revealed naringenin and quercetin with docking scores of -7.118 and -5.898 kcal/mol, with binding energies of -41.806 and -31.715 kcal/mol, respectively, which competed with that of acarbose with the docking score and binding energy of -8.223 and -41.270 kcal/mol, respectively. Conclusion: However, the ADMET study also presented naringenin and quercetin with better physicochemical and pharmacokinetic properties. Gene expression profiling revealed ethyl acetate fractions with better upregulations in treated groups VI and VII in comparison to groups I and II. It could be recommended that ethyl acetate extract fractions of Ficus exasperata exhibited better potential efficacy in the treatment of diabetes and utility in enhancing the effectiveness of diabetic medications. APA-7 Style Shodehinde, S.A., Awojulu, V.O., Nwanna, E.E., Olubode, S.O., Bello, L., Akinnusi, P.A., Adefolalu, A., Awelewa, O.V., Olubode, S.O., Bakare, S.O., Adetokunbo, T., Egunjobi, G.D. (2025). Multimodal Assessment of Ficus exasperata in Diabetic Drosophila. International Journal of Biological Chemistry, 19(1), 36-61. https://doi.org/10.3923/ijbc.2025.36.61 ACS Style Shodehinde, S.A.; Awojulu, V.O.; Nwanna, E.E.; Olubode, S.O.; Bello, L.; Akinnusi, P.A.; Adefolalu, A.; Awelewa, O.V.; Olubode, S.O.; Bakare, S.O.; Adetokunbo, T.; Egunjobi, G.D. Multimodal Assessment of Ficus exasperata in Diabetic Drosophila. Int. J. Biol. Chem 2025, 19, 36-61. https://doi.org/10.3923/ijbc.2025.36.61 AMA Style Shodehinde SA, Awojulu VO, Nwanna EE, Olubode SO, Bello L, Akinnusi PA, Adefolalu A, Awelewa OV, Olubode SO, Bakare SO, Adetokunbo T, Egunjobi GD. Multimodal Assessment of Ficus exasperata in Diabetic Drosophila. International Journal of Biological Chemistry. 2025; 19(1): 36-61. https://doi.org/10.3923/ijbc.2025.36.61 Chicago/Turabian Style Shodehinde, Sidiqat, Adamson, Victor Oluwadamlola Awojulu, Emem Esther Nwanna, Samuel Olawale Olubode, Lateef Bello, Precious Ayorinde Akinnusi, Aderemi Adefolalu, Olamide Vincent Awelewa, Success Oluwaferanmi Olubode, Shittu Oluwafemi Bakare, Tobiloba Adetokunbo, and Gladys Diekonifelouwa Egunjobi. 2025. "Multimodal Assessment of Ficus exasperata in Diabetic Drosophila" International Journal of Biological Chemistry 19, no. 1: 36-61. https://doi.org/10.3923/ijbc.2025.36.61

Background and Objective: There has been growing interest in preventing oxidative stress, and investigating the potential of medicinal plants to combat it has gained momentum. This study explores the antioxidant properties, phenolic compositions, and mineral content of both fermented and unfermented T. catappa leaf extracts. Materials and Methods: Terminalia catappa leaves were divided into two portions of which one was wrapped with plantain leaves to facilitate fermentation. Both samples were air-dried and milled into powder. Ethanolic extracts (5 g/100 mL) of each sample were prepared to determine the above-mentioned assays. Statistical significance was evaluated using a One-way Analysis of Variance (ANOVA), followed by Dunnett’s post hoc test. Data points correspond to the mean of independent experiments and error bars; the level of significance was set at p<0.05. Results: The unfermented extract exhibited a higher significant difference (p<0.05) in antioxidant properties and phenolic contents. The HPLC analysis also followed the same trend with the presence of higher contents of quercetin, caffeic acid, ferulic acid, maleic acid, p-coumaric acid, and naringenin in unfermented T. catappa. However, the fermented extract was observed to contain additional bioactive compounds such as salicylic acid and apigenin, which are also known for antioxidant potential. In addition, the fermented extract was also observed to have a higher content (p<0.05) of potassium and manganese, while calcium, magnesium, iron, copper, sodium, and zinc were higher in the unfermented extract. The overall results of the analysis showed that the unfermented extract of T. catappa had higher antioxidant activity, phenolic contents, minerals, and HPLC-identified contents. Conclusion: However, the contents of fermented extract unique compounds suggest that fermentation not only alters the phytochemical profile but can also enhance the production of additional components that are needed for health benefits, which could be adopted in managing oxidative stress and related chronic diseases. APA-7 Style Shodehinde, S.A., Bello, L., Awojulu, O.V., Ayejuni, V.O., Omoyajowo, F.E., Fagbohun, O., Zauka, R. (2025). Phenolics, Antioxidants and Minerals in Fermented vs Unfermented Terminalia catappa. Research Journal of Medicinal Plants, 19(1), 1-11. https://doi.org/10.3923/rjmp.2025.01.11 ACS Style Shodehinde, S.A.; Bello, L.; Awojulu, O.V.; Ayejuni, V.O.; Omoyajowo, F.E.; Fagbohun, O.; Zauka, R. Phenolics, Antioxidants and Minerals in Fermented vs Unfermented Terminalia catappa. Res. J. Med. Plants 2025, 19, 1-11. https://doi.org/10.3923/rjmp.2025.01.11 AMA Style Shodehinde SA, Bello L, Awojulu OV, Ayejuni VO, Omoyajowo FE, Fagbohun O, Zauka R. Phenolics, Antioxidants and Minerals in Fermented vs Unfermented Terminalia catappa. Research Journal of Medicinal Plants. 2025; 19(1): 1-11. https://doi.org/10.3923/rjmp.2025.01.11 Chicago/Turabian Style Shodehinde, Sidiqat, Adamson, Lateef Bello, Oluwadamilola Victor Awojulu, Victoria Omojola Ayejuni, Funmilayo Esther Omoyajowo, Olasunkanmi Fagbohun, and Ruth Zauka. 2025. "Phenolics, Antioxidants and Minerals in Fermented vs Unfermented Terminalia catappa" Research Journal of Medicinal Plants 19, no. 1: 1-11. https://doi.org/10.3923/rjmp.2025.01.11

Background and Objective: In recent years, the prevention of oxidative stress and exploration of medicinal plants' potentials to combat it has driven extensive research. This study investigates the phytochemical composition, antioxidant properties, and mineral content of ethyl acetate extracts from fermented and unfermented Ficus exasperata leaves, emphasizing the effects of fermentation on these parameters. The antioxidant capacity of both extracts was evaluated using the total phenolic and flavonoid content and ferric reducing antioxidant power assay. Materials and Methods: Ficus exasperata leaf was divided into two portions in which one was wrapped with plantain leaves to facilitate fermentation. Both samples were dried at room temperature and milled into powder. Ethyl acetate extracts of each sample (5 and 5 g/100 mL of fermented and unfermented, respectively) were prepared to determine phenolic contents and antioxidant capacity. Statistical analysis was performed using One-way ANOVA followed by Dunnett's post hoc test, considering p<0.05 as significant. Results: The results showed that unfermented extract exhibited a higher significant difference (p<0.05) in antioxidant property. The HPLC analysis follows the same trend with the identification of several bioactive compounds, including caffeic acid, ferulic acid, tannic acid, salicylic acid, apigenin, and naringenin in high concentration in the unfermented extract, which are known for their antioxidant and anti-inflammatory properties. Conversely, the fermented extract displayed altered phytochemical profiles, characterized by the appearance of quercetin and an increase in caffeic acid and p-coumaric acid, alongside a reduction in ferulic acid. Mineral analysis indicated that both extracts contained essential minerals, with the unfermented extract having higher concentrations of calcium, magnesium, potassium, and sodium. Conclusion: However, the fermented extract demonstrated increased levels of iron and manganese, suggesting enhanced bioavailability of these minerals post-fermentation. The overall results of the analysis showed that the unfermented extract of F. exasperata had higher antioxidant activity, phenolic contents, minerals, and HPLC-identified contents. However, the fermented F. exasperata may offer distinct health benefits, particularly regarding mineral absorption. APA-7 Style Bello, L., Shodehinde, S.A., Arowolo, K.G., Arowolo, B.D., Adegnenga, A.G., Ayodeji, R.D., Jayeola, H.A., Awojulu, O.V., Awelewa, O.V., Ojo, E.F., Olukoju, O.A., Olubode, S.O., Sabitu, A.S. (2025). Phytochemical Analysis and Antioxidant Activity of Ficus exasperata. Asian Science Bulletin, 3(1), 102-110. https://doi.org/10.3923/asb.2025.102.110 ACS Style Bello, L.; Shodehinde, S.A.; Arowolo, K.G.; Arowolo, B.D.; Adegnenga, A.G.; Ayodeji, R.D.; Jayeola, H.A.; Awojulu, O.V.; Awelewa, O.V.; Ojo, E.F.; Olukoju, O.A.; Olubode, S.O.; Sabitu, A.S. Phytochemical Analysis and Antioxidant Activity of Ficus exasperata. Asian Sci. Bul 2025, 3, 102-110. https://doi.org/10.3923/asb.2025.102.110 AMA Style Bello L, Shodehinde SA, Arowolo KG, Arowolo BD, Adegnenga AG, Ayodeji RD, Jayeola HA, Awojulu OV, Awelewa OV, Ojo EF, Olukoju OA, Olubode SO, Sabitu AS. Phytochemical Analysis and Antioxidant Activity of Ficus exasperata. Asian Science Bulletin. 2025; 3(1): 102-110. https://doi.org/10.3923/asb.2025.102.110 Chicago/Turabian Style Bello, Lateef, Sidiqat Adamson Shodehinde, Kolapo Gabriel Arowolo, Bukola Deborah Arowolo, Adeomo Gbenga Adegnenga, Rofiyat Damilola Ayodeji, Hellen Aanuoluwapo Jayeola, Oluwadamilola Victor Awojulu, Olamide Vincent Awelewa, Emmanuel Funmilayo Ojo, Olarewaju Adewumi Olukoju, Success Oluwaferanmi Adetutu Olubode, and Abdulwasiu Sunkanmi Sabitu. 2025. "Phytochemical Analysis and Antioxidant Activity of Ficus exasperata" Asian Science Bulletin 3, no. 1: 102-110. https://doi.org/10.3923/asb.2025.102.110

Type 2 Diabetes Mellitus and MASH are converging metabolic epidemics sharing interconnected pathophysiological mechanisms. GSK-3β, a master metabolic regulator whose sustained hyperactivation drives both diseases, represents an attractive dual therapeutic target. This study employed a comprehensive in silico workflow to identify natural product-derived GSK-3β inhibitors from the Natural Products Atlas. A total of 36,545 microbial natural products were screened for drug-likeness, followed by an E-pharmacophore model derived from the GSK-3β structure (PDB ID: 4ACC). The docking protocol was validated by re-docking and enrichment analysis. Lead compounds were further evaluated using MMGBSA binding free energy calculations, Induced Fit Docking (IFD), AutoQSAR, and ADMET predictions. The validated docking protocol reproduced the 7YG crystallographic pose (RMSD = 0.8357 Å) and showed exceptional discriminatory power (ROC = 0.98; AUC = 0.97; EF₅% = 100%). NPA011425, NPA014875, NPA020257, NPA004276, NPA034843, and NPA036064 exhibited XP docking scores from − 6.858 to − 11.059 kcal/mol, superior to the co-crystallized ligand (− 6.455 kcal/mol), AR-A014418 (− 5.929 kcal/mol), and Tideglusib (− 5.895 kcal/mol). NPA014875 showed the strongest binding free energy (− 62.67 kcal/mol), comparable to the native ligand (− 63.15 kcal/mol). IFD confirmed receptor-adaptive binding, and all hits formed key hydrogen bonds with conserved hinge-region residues (Asp133, Val135, Pro136) while engaging the hydrophobic ATP-binding pocket. NPA020257 displayed predicted potency (pIC50 = 6.82). All six hits complied with Lipinski’s rules and showed favorable pharmacokinetic profiles. NPA020257, NPA034843, and NPA036064 emerged as the most balanced candidates. These findings highlight microbial natural products as promising scaffolds for GSK-3β inhibitor development, warranting further molecular dynamics, enzymatic, and cellular validation.