Α-glucosidase Inhibitory Activity Research Articles

A New Benzofuran from the Roots of Eupatorium chinense L. and Its α-glucosidase and PTP1B Inhibitory Activities

A New Benzofuran from the Roots of Eupatorium chinense L. and Its α-glucosidase and PTP1B Inhibitory Activities

Extraction and Quantification of Flavonoids from Vietnamese Dicranopteris linearis Leaves Using Green Method and Determination of their α-Glucosidase Inhibitory Activity

Extraction and Quantification of Flavonoids from Vietnamese Dicranopteris linearis Leaves Using Green Method and Determination of their α-Glucosidase Inhibitory Activity

Effect of processing and simulated digestion on phenolics, antioxidant and hypoglycemic potential of winter jujube

The wellknown winter jujube (Zizyphus jujuba Mill. cv. Dongzao), has been proved to contain a series of bioactive compounds. To investigate the impact of processing and digestion on its phenolics, winter jujube was processed (steaming and freeze-drying) and digested. The treated winter jujubes' phenolic content, antioxidant capacity, and hypoglycemic potential were assessed. The results showed that processing reduced the number of total phenolics/flavonoids, antioxidant, and α-glucosidase inhibitory activity by 0.74 ∼ 25.26%. With the exception of α-glucosidase inhibitory activity, which increased by 16.67 ∼ 19.25% after digestion, these declines were more pronounced. After processing, the six discovered phenolics in winter jujube were mostly constant, but after digestion, their contents dropped by 6.72 ∼38.64 %. These results suggested that following processing and digestion, the phenolic content and activity of winter jujube remained high (61.36 ∼ 97.93%), indicating that freeze-drying and steaming are viable approaches to prepare and consume winter jujube.

Insights into the culturable fungal endophytes of Dioscorea bulbifera L. in terms of their diversity, antidiabetic and antioxidant activity

The research on endophytes is focused on understanding the complex microbiome compositions, their interactions with host plants and their bioactive potential. Our study provided an overview of the diversity, distribution and bioactivities of culturable endophytic fungi associated with fungal endophytes of Dioscorea bulbifera L. The phylogenetic analysis depicted the evolutionary relationship among taxa of endophytic fungal isolates. The isolated fungal endophytes belonged to twenty-five genera and thirty-eight species. Further, diversity indices demonstrated significant diversity of fungal endophytes in the different tissues: stem, leaf, tuber and bulbil. A higher consistency of endophytic fungal isolates in the bulbils was found using Shannon index. Furthermore, Simpson's index revealed that the leaf tissue harboured highly diverse fungal endophytes. Likewise, Margalef's index depicted high taxonomic richness in bulbils. The isolates such as Acrocalymma medicaginis, Curvularia lycoperscii, Talaromyces macrospora, Fusarium laceratum, Paecilomyces formosus and Microascus cirrosus isolated in this study have been reported as endophytes for the first time from any plant. In-vitro antioxidant and antidiabetic activities of the ethyl acetate extracts revealed that Nigrospora oryzae (Z2) effectively inhibited α-glucosidase activity with IC50 value of 0.6 µg/ml whereas IC50 value of the acarbose, the positive control was reported to be 0.040 µg/ml. The results of antioxidant activity demonstrated that H15A (Acrocalymma medicaginis) and BD5 (Phomopsis longicolla) could be used as potential sources of antioxidant agents. Moreover, H15A (Acrocalymma medicaginis) was reported to produce 687.1 ± 0.17 µg GAE/mg of TPC and 78.55 ± 0.29 µg QE/mg of TFC quantitatively. These findings suggest that the potential endophytes could be explored using systematic bio-guided investigations to further discover novel natural products. Our study provides an important resource for a deeper understanding of endophyte-plant interactions at molecular and genetic levels.

Investigation of Phytochemical Composition, Radical Scavenging Potential, Anti-Obesogenic Effects, and Anti-Diabetic Activities of Kaempferia parviflora Rhizomes.

Kaempferia parviflora or commonly known as "Kunyit hitam" by locals, is an edible plant, native to tropical regions, has been extensively utilized for culinary and medicinal applications. The present study aimed to investigate the phytochemical composition and biological activities of the rhizomes of K. parviflora. The ethanol crude and fractionated extracts (hexane and chloroform) of the rhizomes were evaluated for their total phenolic content, total steroidal content, as well as antioxidant, anti-obesogenic, and anti-diabetic activities. The chloroform extract demonstrated the highest concentration of plant sterols (432±0.23 mg BSE/g extract) and a substantial amount of phenolic compounds (1.19×103±0.41 mg GAE/g extract). Gas chromatography-mass spectrometry (GC/MS) analysis revealed that the chloroform extract of the rhizomes is predominantly composed of bioactive flavonoids including tectochrysin (1), 5,7-dimethoxyflavone (2), 3,5,7-trimethoxyflavone (3), 3,4',5,7-tetramethoxyflavone (4), and 4',5,7-trimethoxyflavone (5). Furthermore, the chloroform extract exhibited the highest overall radical scavenging and α-glucosidase inhibitory activities, which can be attributed to the presence of compounds 1-5 in the extract. Collectively, these findings suggest that the chloroform extract of the rhizomes of K. parviflora is a potentially valuable source of bioactive compounds with antioxidant, anti-obesogenic, and anti-diabetic properties, with potential application in therapeutics and functional foods.

'Bhim Kol (Musa Balbisiana)' Wine: Chemical Profiling and Antidiabetic Properties with MD Simulation Insights.

Musa balbisiana (Bhim Kol), an exotic fruit that offers numerous benefits can be fermented to obtain a unique indigenous wine. This study explores the fermentation of Musa balbisiana (Bhim Kol) fruit to produce a unique indigenous wine using strain of Saccharomyces cerevisiae and sugar over a 21-day period. Chemical profiling via GC-MS analysis revealed the presence of major volatile compounds such as butan-1-ol, propanoic acid, 2-phenylethanol, oxolane-2,5-dione etc. The wine exhibited in vitro α-glucosidase inhibition activity with an IC50 value of 8.56±0.14 μg/mL and antioxidant properties (DPPH⋅ scavenging activity (AAR) of 1.29±0.18 mM TRE). Molecular docking and simulation studies indicated potential binding of volatile compounds like 4-Hydroxy-3-methoxybenzoic acid, 2-phenylethanol, butan-1-ol and butane-2,3-diol with α-glucosidase enzyme. The study suggests the medicinal potential of the wine and its suitability for commercial production in the winery industry. Further studies are warranted to explore its full medicinal benefits.

Coconut Testa Flour Sub-Fractions: Correlation Between FTIR Spectral Data and α-Glucosidase Inhibitory Activities

Fourier-transform infrared spectroscopy (FTIR) serves as a rapid analytical technique to characterize food specimens chemically. The purpose of this study was to investigate the potential of FTIR combined with multivariate statistics to detect Alpha-glucosidase (Alpha-glu) inhibitory activities of a non-cereal flour-like coconut testa flour (CTF). CTF of five distinct local cultivars was sequentially extracted with hexane, ethyl acetate (EtOAc), and methanol (MeOH) to assay the Alpha-glu inhibitory activity. FTIR spectra of CTF extracts were obtained within the range of 4000–500 cm−1 and the prominent spectral peaks obtained for both hexane and EtOAc extracts were roughly similar but some additional peaks were observed in EtOAc extracts representing phenolic constituents. The major absorbance peaks found in MeOH extracts were primarily indicative of the occurrence of the hydroxyl group associated with carbohydrates and phenolic compounds. The multivariate predictive models developed using partial least squares (PLS) and orthogonal partial least squares (OPLS) regression analyses indicated a strong correlation between Alpha-glu inhibitory activity and spectral data. Models developed for the spectral regions 3700–2800 cm−1 and 1800–500 cm−1 exerted the highest regression coefficients with the lowest root mean square errors. In OPLS regression analysis, the model obtained with third-derivative spectral data was identified as the best, exhibiting the highest regression coefficients and the lowest root mean square errors. Both PLS and OPLS regression analyses indicated a potential correlation of Alpha-glu inhibitory activity with FTIR spectral regions. Notably, OPLS models offered enhanced interpretability of the model parameters. This study suggests that the application of multivariate regression analysis of FTIR spectral data on coconut-based products could help to detect Alpha-glu inhibitory activities.

Biological Potential of Asphodelus microcarpus Extracts: α-Glucosidase and Antibiofilm Activities In Vitro

Type 2 diabetes (T2D), characterized by insulin resistance and β-cell dysfunction, requires continuous advancements in management strategies, particularly in controlling postprandial hyperglycemia to prevent complications. Current antidiabetics, which have α-amylase and α-glucosidase inhibitory activities, have side effects, prompting the search for better alternatives. In addition, diabetes patients are particularly vulnerable to yeast infections because an unusual sugar concentration promotes the growth of Candida spp. in areas like the mouth and genitalia. Asphodelus microcarpus contains bioactive flavonoids with potential enzyme inhibitory properties. This study investigates α-amylase and α-glucosidase inhibitory activities and antioxidant and antimycotic capacity of ethanolic extracts from different parts of A. microcarpus. Results show that extracts significantly inhibit α-glucosidase, with the IC50 value being up to 25 times higher than for acarbose, while exerting low α-amylase activity. The extracts also demonstrated strong antioxidant properties and low cytotoxicity. The presence of phenolic compounds is likely responsible for the observed biological activities. Molecular docking analysis of 11 selected compounds identified emodin and luteolin as significant inhibitors of α-glucosidase. Additionally, the extracts demonstrated significant antibiofilm action against an MDR strain of Candida albicans. These findings suggest that A. microcarpus is a promising source of natural compounds for T2D management.

Proximate, Mineral, Amino Acid Composition, and Bioactive Properties of Dough Meals Supplemented with African Walnut Flour

This study investigated the impact of African walnut flour supplementation on the nutritional and bioactive properties of dough meals formulated with varying proportions of plantain flour. The proximate composition, mineral content, amino acid profile, color characteristics, antioxidant and anti-diabetic properties were analyzed for five different formulations: 100% plantain flour (P100), 95% plantain flour with 5% African walnut flour (PAW95), 90% plantain flour with 10% African walnut flour (PAW90), 85% plantain flour with 15% African walnut flour (PAW85), and 80% plantain flour with 20% African walnut flour (PAW80). The proximate analysis revealed significant variations, with moisture content ranging from 53.71% to 71.89%, ash content from 0.77% to 1.28%, and protein content from 3.38% to 11.14%. Notably, PAW80 showed the highest protein content. Mineral analysis showed that calcium, potassium, and magnesium levels varied significantly across the samples, with the highest calcium content observed in PAW80 (32.55 mg/kg) and the highest potassium content in PAW95 (47.80 mg/kg). Amino acid analysis indicated that essential amino acids, particularly leucine, valine, and lysine, were present in higher concentrations in the supplemented samples compared to P100. Antioxidant assays indicated that PAW80 had the highest 2,2-diphenyl-1-picrylhydrazyl (DPPH) (67.22%) and hydroxyl (73.66%) free radical scavenging activities. The in vitro anti-diabetic assays revealed that α-amylase and α-glucosidase inhibitory activities were enhanced with higher walnut flour supplementation. These findings suggest that African walnut flour can significantly enhance the nutritional quality and bioactive properties of plantain-based dough meals, and thus make it a functional food with potential health benefits.

Preparation, identification and α-glucosidase inhibitory activity of a high-methoxyl HG-type pectin from Liangping pomelo (Citrus maxima cv. Liangpin Yu) peel.

The peel from Liangping pomelo (Citrus maxima cv. Liangpin Yu) is generally discarded as waste during post-harvest handling and process, resulting in environmental pollution and waste. Pectin is the major component in pomelo peels and yields significant economic advantages. Thus, developing pomelo peel pectin (PPs) might be a feasible strategy to reduce environmental pollution caused by pomelo peel. The optimized PPs yield was 156.5 ± 2.5 g kg-1 under the inoculum size of 100 mg g-1, liquid-solid ratio of 31 mL g-1, fermentation time of 64 h, and fermentation temperature of 39 °C. PPs-6Aa, a pectin fraction from PPs purified with DEAE-52 cellulose, Sephadex G-100 and Sephadex G-75 column chromatography, showed higher α-glucosidase inhibitory activity, with an IC50 of 0.12 ± 0.03 mg mL-1. It was a high-methoxyl HG-type pectin of 42.8 kDa, and its repeat unit was →4)-α-GalpA-6-OMe-(1→4)-α-GalpA-6-OMe-(1→. Additionally, its α-glucosidase inhibitory activity might be related to hydrogen bonds formed with Lys-156, Glu-277, His-280, Asp-307, Arg-315, Asn-350, Asp-352 and Glu-411, and to hydrophobic interactions formed with Ser-157, Tyr-158, Asp-233, Gln-239, Ser-240, Phe-303, Thr-306, Leu-313, Phe-314, Gln-353 and Arg-442. These findings provide structural and bioactivity information on pectin from Liangping pomelo peel, which could be beneficial for the development of functional foods and pharmaceuticals. © 2024 Society of Chemical Industry.

Phytochemical profiling from Dioscorea bulbifera L. bulbils using LC-MS, proximate analysis and antidiabetic activity: in vitro and in silico approaches

ABSTRACT The nutritional value and medicinal properties of highly edible Bulbils of Dioscorea bulbifera L are still unexplored. This study reported the nutritional and medicinal values by In vitro, and In silico studies along with chemical profiling using LC-MS. The proximate analysis was conducted by the AOAC method. The antioxidant and antidiabetic activities were assessed using DPPH and α- α-glucosidase enzyme inhibition assay. Molecular docking was used to do an In silico examination of the identified molecules, and ADMET analysis of the hit candidate was also performed. The result showed that bulbils of D. bulbifera were found to have a higher percentage of protein (8.83%), fat (0.96%), and fiber (5.40%). It exhibited significant levels of phenolic and flavonoid content 106.93 ± 0.02 mg GAE/g and 11.51 ± 0.02 mg QE/g, respectively. The ethyl acetate fraction of D. bulbifera showed potent antioxidants with an IC 50 = 13.75 ± 0.6 μg/mL. Furthermore, the methanol extract showed more than 50 % inhibition activity with IC 50 values of 26.29 ± 0.6 μg/mL and 191.2 ± 0.7 μg/mL against α-glucosidase and α-amylase, respectively. The ethyl acetate fraction showed higher α-glucosidase and α-amylase inhibitory activity with an IC 50 of 14.42 ± 0.4 μg/mL and 171.5 ± 0.4 μg/mL, respectively, compared to the standard acarbose (p < 0.05). Chemical profiling of most bio-active ethyl acetate fraction was done using LC-MS analysis, where eleven compounds were annotated. In conclusion, bulbils of D. bulbifera demonstrate promising anti-diabetic activity through In vitro and In silico studies.

Bioactive Lipids in Dunaliella salina: Implications for Functional Foods and Health.

Dunaliella salina is a green microalga extensively explored for β-carotene production, while knowledge of its lipid composition is still limited and poorly investigated. Among lipids, polar lipids have been highlighted as bioactive phytochemicals with health-promoting properties. This research aimed to provide an in-depth lipidome profiling of D. salina using liquid and gas chromatography coupled with mass spectrometry. The lipid content was 6.8%, including phospholipids, glycolipids, betaine lipids, sphingolipids, triglycerides, diglycerides, and pigments. Among the total esterified fatty acids, 13.6% were 18:3 omega-3 and 14.7% were 18:1 omega-9. The lipid extract of D. salina showed anti-inflammatory activity by inhibiting cyclooxygenase-2 activity at 100 µg/mL, dose-dependent antioxidant scavenging activity, and antidiabetic activity by inhibiting α-glucosidase activity at 25 and 125 µg/mL. In conclusion, the lipid extract of D. salina has the potential to be used as a functional food ingredient or in the nutraceutical and cosmeceutical industries.

Synthesis of newly designed hydrazones, in vitro and in silico studies, and structure-activity relationship

Herein, new N'-(substituted benzylidene)-3,5-dihydroxybenzohydrazide (1–13) series were synthesized, and their antioxidant, anticholinesterase, anti-tyrosinase, anti-urease, and antidiabetic activities were investigated together with in silico studies. The synthesized derivates were characterized using molecular spectroscopy, and the structure-activity relationships (SAR) were discussed for all tested biological assays. According to activity results, compound 3 exhibited excellent antioxidant activity in all tests, while compound 1 demonstrated the best acetylcholinesterase (AChE) inhibitory and butyrylcholinesterase (BChE) inhibitory activities. On the other hand, compound 11 showed excellent tyrosinase inhibitory (IC50:3.02±0.10 mM) and urease inhibitory (IC50:9.21±0.27 µM) activity. Moreover, among the synthesized compounds, compound 6 was detected as the best antidiabetic compound by inhibiting α-amylase (IC50:30.68±0.94 µM) and α-glycosidase (IC50:41.35±0.03 µM) enzymes, which were related with the antidiabetic activity. Molecular docking analysis confirmed AChE, BChE, tyrosinase, urease, α-amylase, and α-glucosidase inhibitory activities. In line with the findings obtained from in vitro bioactivity results and molecular docking analysis, hydrazone compounds are a suitable class of organic compounds for developing acetylcholinesterase, butyrylcholinesterase, urease, α-amylase, and α-glucosidase inhibitors.

Aristolactams and Flavanones from Dasymaschalon wallichii (Hook.f. &amp; Thomson) Jing Wang &amp; R.M.K.Saunders and Their α-Glucosidase Inhibitory Activity

The first phytochemical investigation of the twig and leaf extracts of Dasymaschalon wallichii led to the isolation and identification of 10 compounds, including 6 airstolactam alkaloids (1-6), 3 flavonoids (7-9) and one chalcone (10). The structures were elucidated through the analysis of NMR spectroscopic data and comparisons with those reported in the literature. Compounds 1-4 and 7-10 were evaluated for their α-glucosidase inhibitory activity. Among them, aristolactam AII (1) and 8-formyl-5,7dihydroxyflavanone (8) showed α-glucosidase inhibitory activity with IC50 values of 62.9 and 83.9 μM, respectively, which are better than the positive control (acarbose, IC50 = 178.2 μM). The potential binding modes of active compounds with α-glucosidase were also analyzed by molecular docking. HIGHLIGHTS The first phytochemical investigation of Dasymaschalon wallichii resulted in the isolation and identification of 10 compounds. Compounds 1 and 8 showed α-glucosidase inhibitory activity with IC50 values of 62.9 and 83.9 μM, respectively. The molecular docking of compounds 1 and 8 were studied. GRAPHICAL ABSTRACT

Anti-Hyperglycemic Effects of Thai Herbal Medicines

This study aims to investigate selected medicinal plants’ anti-oxidative and antihyperglycemic activities to develop an effective remedy for lowering blood glucose levels and/or reducing diabetes complications. Thai medicinal plants, reported to have blood sugar-lowering effects, were selected for the study: Coccinia grandis, Gymnema inodorum, Gynostemma pentaphyllum, Hibiscus sabdariffa, Momordica charantia, Morus alba, and Zingiber officinale. Each species was extracted by Soxhlet’s extraction using ethanol as solvent. The ethanolic crude extract of each species was then evaluated for its phytochemicals, anti-oxidant, and antihyperglycemic activities. The results showed that the extract of Z. officinale gave the highest values of total phenolic and total flavonoid content (167.95 mg gallic acid equivalents (GAE)/g and 81.70 mg CE/g, respectively). Anti-oxidant activity was determined using DPPH and ABTS radical scavenging activity. Among the ethanolic extracts, Z. officinale exhibited the highest anti-oxidant activity with IC50 values of 19.16 and 8.53 µg/mL, respectively. The antihyperglycemic activity was assessed using α-glucosidase inhibitory and glucose consumption activities. M. alba and G. pentaphyllum demonstrated the highest α-glucosidase inhibitory activity among the ethanolic extracts, with IC50 values of 134.40 and 329.97 µg/mL, respectively. Z. officinale and H. sabdariffa showed the highest percentage of glucose consumption activity in induced insulin-resistant HepG2 cells at a concentration of 50 µg/mL with 145.16 and 107.03%, respectively. The results from α-glucosidase inhibitory and glucose consumption activities were developed as an effective antihyperglycemic remedy. Among the remedies tested, the R1 remedy exhibited the highest potential for reducing blood glucose levels, with an IC50 value of 122.10 µg/mL. Therefore, the R1 remedy should be further studied for its effects on animals.

Triterpenoid Saponins and Flavonoid Glycosides from the Flower of Camellia flavida and Their Cytotoxic and α-Glycosidase Inhibitory Activities

Camellia flavida var. flavida, commonly known as “Jinhua Tea”, has its flowers and leaves traditionally utilized as tea and functional food sources. However, there is limited knowledge about its bioactive components and their biological activities. This study isolated ten previously unidentified glycoside compounds from the flowers of Camellia flavida, including three oleanane-type triterpenoid saponins (compounds 1–3) and seven flavonoid glycosides (compounds 4–10), collectively named flavidosides A–J. This study assessed the cytotoxicity of these compounds against a panel of human cancer cell lines and their α-glucosidase inhibitory activities. Notably, flavidoside C showed significant cytotoxicity against BEL-7402 and MCF-7 cell lines, with IC50 values of 4.94 ± 0.41 and 1.65 ± 0.39 μM, respectively. Flavidoside H exhibited potent α-glucosidase inhibitory activity, with an IC50 value of 1.17 ± 0.30 mM. These findings underscore the potential of Camellia flavida in the development of functional foods.

Synthesis, α-Glucosidase, α-Amylase, and Aldol Reductase Inhibitory Activity with Molecular Docking Study of Novel Imidazo[1,2-a]pyridine Derivatives.

Inhibition ofaldose reductase (AR), α-glycosidase (α-GLY), and α-amylase (α-AMY) are some of the essential targets in diabetes mellitus (DM). Here, a series of imidazo[1,2-a]pyridine-based 1,3,4-thiadiazole derivatives (8a-k) were successfully synthesized and characterized using 1H NMR, 13C NMR, and HRMS spectroscopic techniques. The inhibition effects of the synthesized derivatives against AR, α-GLY, and α-AMY were evaluated using both in vitro and in silico methods. In vitro studies revealed that the derivatives (8a-k) showed significant inhibition activity. The results showed that the novel derivatives (8a-k) demonstrated potential inhibitory activity, with K I values covering the following ranges: 23.47 ± 2.40 to 139.60 ± 13.33 nM for AR and 6.09 ± 0.37 to 119.80 ± 12.31 μM for α-GLY, with IC50 values 81.14 to 153.51 μM for α-AMY. Furthermore, many of these compounds exhibited high inhibition activity, while some of them showed higher potency than the reference compounds. Molecular docking of the target compounds was carried out in the active sites of AR (PDB ID: 4JIR) and α-GLY (PDB ID: 5NN8).

Phytochemical Profile and Antioxidant, Enzyme-Inhibitory, and Cytotoxic Potential of Endemic Cynoglottis chetikiana subsp. chetikiana

Background Cynoglottis chetikiana subsp. chetikiana, an endemic Boraginaceae plant growing in Turkey, has not been previously studied in terms of pharmacognosy. However, related species, such as Anchusa, Symphytum, and Rindera, have been known for their pharmacological effects attributed to compounds such as flavonoids, terpenoids, and other phenol derivatives. Purpose This study aimed to reveal the phytochemical composition and potential biological activity of C. chetikiana. Methods Phytochemical profiling analysis was performed by using the liquid chromatography–high-resolution mass spectrometry (LC–HRMS) system. The cytotoxic effects of the extracts were evaluated on the MCF-7 mammalian breast cancer cell line by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method. The in vitro α-glucosidase and tyrosinase enzyme inhibitory activities were assessed using literature methods. Additionally, antioxidant properties were investigated, leading to the bioactivity-guided isolation of the most active substance. Results LC–HRMS analysis revealed 27 major phenolic compounds and 2 pyrrolizidine alkaloids in C. chetikiana. Bioactivity-guided studies led to the isolation of a flavonoid, rutin. The n-butanol extract of the plant exhibited high antioxidant capacity and was rich in phenolic compounds. The methanol extract of C. chetikiana demonstrated low-moderate α-glucosidase inhibitory activity (IC50 = 608.62 ± 7.01 µg/mL). Moreover, the methanol extract showed significant anti-tyrosinase enzyme activity (195.84 ± 5.81 mg Kojic acid equivalent/g extract), and the petroleum ether extract displayed the highest cytotoxicity on MCF-7 cells (IC50 = 76.91 ± 3.12 µg/mL). Conclusion This is the first phytomedicinal study report for C. chetikiana, which gives promising insight for further pharmaceutical research.

Enzyme Inhibitory Activities and RP-HPLC Analysis of Geranium And Erodium Species.

The genera Geranium and Erodium (Geraniaceae) have been documented to possess diverse ethnopharmacological uses, including diabetes mellitus. Relevant to their ethnopharmacological use, the current study aimed to evaluate the α-glucosidase, α-amylase, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) enzyme inhibitory activity of ethanol extracts from 46 samples belonging to thirty-one species of Geranium (20) and Erodium (11) collected throughout Türkiye. The majority of the extracts displayed a marked α-glucosidase and α-amylase inhibitory activity. Besides, 23 extracts out of 46 exhibited a concentration-dependent inhibitory effect over 50% towards AChE. The highest AChE inhibition was found in G. subcaulescens collected from Konya with an IC50 value of 4.73 ± 2.96 µg/mL. E. somanum, E. leucanthum, and E. sipthorpianum exhibited the most potent α-glucosidase inhibitory activity, while E. birandianum and E. pelargoniiflorum were the most active extracts against AChE and BChE, respectively. Three extracts that had inhibitory activity over 50% against four of the enzymes were selected and proceeded to RP-HPLC analysis. Geraniin and ellagic acid were identified as major compounds in the active extracts. Most of the species screened in the current study were examined for the first time against α-glucosidase, α-amylase, AChE, and BChE.

Analysis of the Setomimycin Biosynthetic Gene Cluster from Streptomyces nojiriensis JCM3382 and Evaluation of Its α-Glucosidase Inhibitory Activity Using Molecular Docking and Molecular Dynamics Simulations.

The formation of atroposelective biaryl compounds in plants and fungi is well understood; however, polyketide aglycone synthesis and dimerization in bacteria remain unclear. Thus, the biosynthetic gene cluster (BGC) responsible for antibacterial setomimycin production from Streptomyces nojiriensis JCM3382 was examined in comparison with the BGCs of spectomycin, julichromes, lincolnenins, and huanglongmycin. The setomimycin BGC includes post-polyketide synthase (PKS) assembly/cycling enzymes StmD (C-9 ketoreductase), StmE (aromatase), and StmF (thioesterase) as key components. The heterodimeric TcmI-like cyclases StmH and StmK are proposed to aid in forming the setomimycin monomer. In addition, StmI (P-450) is predicted to catalyze the biaryl coupling of two monomeric setomimycin units, with StmM (ferredoxin) specific to the setomimycin BGC. The roles of StmL and StmN, part of the nuclear transport factor 2 (NTF-2)-like protein family and unique to setomimycin BGCs, could particularly interest biochemists and combinatorial biologists. α-Glucosidase, a key enzyme in type 2 diabetes, hydrolyzes carbohydrates into glucose, thereby elevating blood glucose levels. This study aimed to assess the α-glucosidase inhibitory activity of EtOAc extracts of JCM 3382 and setomimycin. The JCM 3382 EtOAc extract and setomimycin exhibited greater potency than the standard inhibitor, acarbose, with IC50 values of 285.14 ± 2.04 μg/mL and 231.26 ± 0.41 μM, respectively. Molecular docking demonstrated two hydrogen bonds with maltase-glucoamylase chain A residues Thr205 and Lys480 (binding energy = -6.8 kcal·mol-1), two π-π interactions with Trp406 and Phe450, and one π-cation interaction with Asp542. Residue-energy analysis highlighted Trp406 and Phe450 as key in setomimycin's binding to maltase-glucoamylase. These findings suggest that setomimycin is a promising candidate for further enzymological research and potential antidiabetic therapy.