The present study investigated the antidiabetic properties of the extracts and fractions from leaves and stem bark of M. glabra based on dipeptidyl peptidase-4 (DPP-4) and α-Amylase inhibitory activity assays. The chloroform extract of the leaves was found to be most active towards inhibition of DPP-4 and α-Amylase with IC50 of 169.40 μg/mL and 303.64 μg/mL, respectively. Bioassay-guided fractionation of the leaves’ chloroform extract revealed fraction 4 (CF4) as the most active fraction (DPP-4 IC50: 128.35 μg/mL; α-Amylase IC50: 170.19 μg/mL). LC-MS/MS investigation of CF4 led to the identification of trans-decursidinol (1), swermirin (2), methyl 3,4,5-trimethoxycinnamate (3), renifolin (4), 4′,5,6,7-tetramethoxy-flavone (5), isorhamnetin (6), quercetagetin-3,4′-dimethyl ether (7), 5,3′,4′-trihydroxy-6,7-dimethoxy-flavone (8), and 2-methoxy-5-acetoxy-fruranogermacr-1(10)-en-6-one (9) as the major components. The computational study suggested that (8) and (7) were the most potent DPP-4 and α-Amylase inhibitors based on their lower binding affinities and extensive interactions with critical amino acid residues of the respective enzymes. The binding affinity of (8) with DPP-4 (−8.1 kcal/mol) was comparable to that of sitagliptin (−8.6 kcal/mol) while the binding affinity of (7) with α-Amylase (−8.6 kcal/mol) was better than acarbose (−6.9 kcal/mol). These findings highlight the phytochemical profile and potential antidiabetic compounds from M. glabra that may work as an alternative treatment for diabetes.

Melicope glabra (Blume) T. G. Hartley from the Rutaceae family is one of the richest sources of plant secondary metabolites, including coumarins and flavanoids. This study investigates the free radical scavenging and antibacterial activities of M. glabra and its isolated compounds. M. glabra ethyl acetate and methanol extracts were prepared using the cold maceration technique. The isolation of compounds was performed with column chromatography. The free radical scavenging activity of the extracts and isolated compounds were evaluated based on their oxygen radical absorbance capacity (ORAC) activities. The extracts and compounds were also subjected to antibacterial evaluation using bio-autographic and minimal inhibitory concentration (MIC) techniques against two oral pathogens, Enterococcus faecalis and Streptococcus mutans. Isolation of phytoconstituents from ethyl acetate extract successfully yielded quercetin 3, 5, 3’-trimethyl ether (1) and kumatakenin (2), while the isolation of the methanol extract resulted in scoparone (3), 6, 7, 8-trimethoxycoumarin (4), marmesin (5), glabranin (6), umbelliferone (7), scopoletin (8), and sesamin (9). The study is the first to isolate compound (1) from Rutaceae plants, and also the first to report the isolation of compounds (2–5) from M. glabra. The ORAC evaluation showed that the methanol extract is stronger than the ethyl acetate extract, while umbelliferone (7) exhibited the highest ORAC value of 24 965 μmolTE/g followed by glabranin (6), sesamin (9) and scopoletin (8). Ethyl acetate extract showed stronger antibacterial activity towards E. faecalis and S. mutans than the methanol extract with MIC values of 4166.7 ± 1443.4 μg/ml and 8303.3 ± 360.8 μg/ml respectively. Ethyl acetate extract inhibited E. faecalis growth, as shown by the lowest optical density value of 0.046 at a concentration of 5.0 mg/mL with a percentage inhibition of 95%. Among the isolated compounds tested, umbelliferone (7) and sesamin (9) exhibited promising antibacterial activity against S. mutans with both exhibiting MIC values of 208.3 ± 90.6 μg/ml. Findings from this study suggests M. glabra as a natural source of potent antioxidant and antibacterial agents.

Context Melicope latifolia (DC.) T. G. Hartley (Rutaceae) was reported to contain various phytochemicals including coumarins, flavonoids, and acetophenones. Objective This study investigates the antidiabetic and antioxidant effects of M. latifolia bark extracts, fractions, and isolated constituents. Materials and methods Melicope latifolia extracts (hexane, chloroform, and methanol), fractions, and isolated constituents with varying concentrations (0.078–10 mg/mL) were subjected to in vitro α-amylase and dipeptidyl peptidase-4 (DPP-4) inhibitory assay. Molecular docking was performed to study the binding mechanism of active compounds towards α-amylase and DPP-4 enzymes. The antioxidant activity of M. latifolia fractions and compounds were determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging and β-carotene bleaching assays. Results Melicope latifolia chloroform extract showed the highest antidiabetic activity (α-amylase IC 50 : 1464.32 μg/mL; DPP-4 IC 50 : 221.58 μg/mL). Fractionation of chloroform extract yielded four major fractions (CF 1 –CF 4 ) whereby CF 3 showed the highest antidiabetic activity (α-amylase IC 50 : 397.68 μg/mL; DPP-4 IC 50 : 37.16 μg/mL) and resulted in β-sitosterol ( 1 ), halfordin ( 2 ), methyl p -coumarate ( 3 ), and protocatechuic acid ( 4 ). Isolation of compounds 2 – 4 from the species and their DPP-4 inhibitory were reported for the first time. Compound 2 showed the highest α-amylase (IC 50 : 197.53 μM) and β-carotene (88.48%) inhibition, and formed the highest number of molecular interactions with critical amino acid residues of α-amylase. The highest DPP-4 inhibition was exhibited by compound 3 (IC 50 : 911.44 μM). Discussion and conclusions The in vitro and in silico analyses indicated the potential of M. latifolia as an alternative source of α-amylase and DPP-4 inhibitors. Further pharmacological studies on the compounds are recommended.

Scopoletin has previously been reported as a biomarker for the standardization of Paederia foetida twigs. This study is the first report on the determination and quantification of scopoletin using quantitative nuclear magnetic resonance (qNMR) in the different extracts of Paederia foetida twigs. The validated qNMR method showed a good linearity (r2 = 0.9999), limit of detection (LOD) (0.009 mg/mL), and quantification (LOQ) (0.029 mg/mL), together with high stability (relative standard deviation (RSD) = 0.022%), high precision (RSD < 1%), and good recovery (94.08–108.45%). The quantification results of scopoletin concentration in chloroform extract using qNMR and microplate ultraviolet-visible (UV-vis) spectrophotometer was almost comparable. Therefore, the qNMR method is deemed accurate and reliable for quality control of Paederia foetida and other medicinal plants without extensive sample preparation.

Melicope glabra­ (Blume) T. G. Hartley is a plant of Rutaceae family. The present study aimed to evaluate the in vivo hypoglycemic effect of M. glabra leaves extract on diabetic rats and identify its bioactive components. The induction of diabetes in Sprague-Dawley rats was done by a combination of high-fat diet and low-dose streptozotocin injection. The M. glabra extracts and standard sitagliptin were orally administered once daily to the diabetic rats for 28 days. The diabetic rats showed drastic weight loss, hyperglycemia, poor glucose tolerance, hyperlipidemia, and disturbances in the liver and kidney functions. However, oral administration of M. glabra extracts to the diabetic rats significantly lowered the DPP-4 level and increased glucagon-like peptide-1 (GLP-1) level. Scopoletin, pachypodol, and stigmasterol were revealed as the active DPP-4 and α-amylase inhibitors. This study revealed novel findings which suggest the