ABSTRACT
The present study evaluated three green extraction methods, accelerated solvent extraction (ASE), ultrasound-assisted extraction (UAE), and laser irradiation extraction (LE), for the polyphenolic compounds and vitamin C extraction of Cornus mas L. and Crataegus monogyna fruit extracts. The polyphenols and vitamin C of extracts were quantified using HPLC-DAD, and the total phenolic content, flavonoid content, antioxidant activity (DPPH and reducing power), and antidiabetic activity were also studied. The antidiabetic activity was examined by the inhibition of α-amylase and α-glucosidase, and in vitro on a beta TC cell line (ß-TC-6). The results showed significant differentiation in the extraction yield between the methods used, with the ASE and LE presenting the highest values. The C. mas fruit extract obtained by ASE exhibited the best antioxidant activity, reaching an IC50 value of 31.82 ± 0.10 µg/mL in the DPPH assay and 33.95 ± 0.20 µg/mL in the reducing power assay. The C. mas fruit extracts obtained by ASE and LE also have the highest inhibitory activity on enzymes associated with metabolic disorders: α-amylase (IC50 = 0.44 ± 0.02 µg/mL for the extract obtained by ASE, and 0.11 ± 0.01 µg/mL for the extract obtained by LE at combined wavelengths of 1270 + 1550 nm) and α-glucosidase (IC50 of 77.1 ± 3.1 µg/mL for the extract obtained by ASE, and 98.2 ± 4.7 µg/mL for the extract obtained by LE at combined wavelengths of 1270 + 1550 nm). The evaluation of in vitro antidiabetic activity demonstrated that the treatment with C. mas and C. monogyna fruit extracts obtained using ASE stimulated the insulin secretion of ß-TC-6 cells, both under normal conditions and hyperglycemic conditions, as well. All results suggest that C. mas and C. monogyna fruit extracts are good sources of bioactive molecules with antioxidant and antidiabetic activity.
Subject(s)
Antioxidants , Cornus , Crataegus , Fruit , Hypoglycemic Agents , Plant Extracts , alpha-Amylases , Crataegus/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry , Antioxidants/pharmacology , Antioxidants/chemistry , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/chemistry , Cornus/chemistry , Fruit/chemistry , alpha-Amylases/antagonists & inhibitors , alpha-Amylases/metabolism , Glycoside Hydrolase Inhibitors/pharmacology , Glycoside Hydrolase Inhibitors/chemistry , Glycoside Hydrolase Inhibitors/isolation & purification , Animals , alpha-Glucosidases/metabolism , Polyphenols/pharmacology , Polyphenols/chemistry , Cell Line , Flavonoids/pharmacology , Flavonoids/chemistry , Flavonoids/isolation & purification , Phenols/pharmacology , Phenols/chemistry , Chromatography, High Pressure Liquid , Ascorbic Acid/pharmacologyABSTRACT
A talented endophytic Streptomyces sp. PH9030 is derived from the medicinal plant Kadsura coccinea (Lem.) A.C. Smith. The undescribed naphthoquinone naphthgeranine G (5) and seven previously identified compounds, 6-12, were obtained from Streptomyces sp. PH9030. The structure of 5 was identified by comprehensive examination of its HRESIMS, 1D NMR, 2D NMR and ECD data. The inhibitory activities of all the compounds toward α-glucosidase and their antibacterial properties were investigated. The α-glucosidase inhibitory activities of 5, 6, 7 and 9 were reported for the first time, with IC50 values ranging from 66.4 ± 6.7 to 185.9 ± 0.2 µM, as compared with acarbose (IC50 = 671.5 ± 0.2 µM). The molecular docking and molecular dynamics analysis of 5 with α-glucosidase further indicated that it may have a good binding ability with α-glucosidase. Both 9 and 12 exhibited moderate antibacterial activity against methicillin-resistant Staphylococcus aureus, with minimum inhibitory concentration (MIC) values of 16 µg/mL. These results indicate that 5, together with the naphthoquinone scaffold, has the potential to be further developed as a possible inhibitor of α-glucosidase.
Subject(s)
Anti-Bacterial Agents , Glycoside Hydrolase Inhibitors , Molecular Docking Simulation , Naphthoquinones , Phenazines , Streptomyces , alpha-Glucosidases , Streptomyces/chemistry , Naphthoquinones/chemistry , Naphthoquinones/pharmacology , Naphthoquinones/isolation & purification , Glycoside Hydrolase Inhibitors/chemistry , Glycoside Hydrolase Inhibitors/pharmacology , Glycoside Hydrolase Inhibitors/isolation & purification , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , alpha-Glucosidases/metabolism , alpha-Glucosidases/chemistry , Phenazines/chemistry , Phenazines/pharmacology , Phenazines/isolation & purification , Microbial Sensitivity Tests , Endophytes/chemistry , Molecular Structure , Molecular Dynamics Simulation , Methicillin-Resistant Staphylococcus aureus/drug effectsABSTRACT
Isoxerophilusins A (1) and B (2), two unprecedented diterpene heterodimers biogenetically from ent-atisanes and abietanes, were isolated from the rhizomes of Isodon xerophilus. Their structures were determined by extensive spectroscopic analysis and single-crystal X-ray diffraction. Selective esterification of 1 generated 11 new derivatives. All derivatives showed excellent α-glucosidase inhibitory activity in comparison to acarbose. Compounds 12 and 13 demonstrated significant inhibition against α-glucosidase with IC50 values of 4.92 and 3.83 µM, respectively.
Subject(s)
Diterpenes , Glycoside Hydrolase Inhibitors , Isodon , alpha-Glucosidases , Glycoside Hydrolase Inhibitors/chemistry , Glycoside Hydrolase Inhibitors/pharmacology , Glycoside Hydrolase Inhibitors/isolation & purification , Diterpenes/chemistry , Diterpenes/pharmacology , Diterpenes/isolation & purification , alpha-Glucosidases/metabolism , Molecular Structure , Isodon/chemistry , Dimerization , Crystallography, X-Ray , Structure-Activity Relationship , Rhizome/chemistryABSTRACT
Condensed tannins were isolated from the bark of Ficus altissima and fractionated into four subcomponents on a Sephadex LH-20 column with 60 %, 80 %, 100 % methanol, and 70 % acetone, separately. Their structures were characterized by MALDI-TOF MS coupled with HPLC-ESI-MS and confirmed to be polymers of B-type procyanidin glucosides, procyanidins, and prodelphinidin glucosides. The degree of polymerization (DP) of these polymers was as high as 21, and the mDPs of the four subcomponents were calculated as 2.4, 6.6, 10.5 and 13.4, respectively. They competitively or noncompetitively suppressed the activities of tyrosinase and α-glucosidase through hydrogen bonding and hydrophobic interaction. And they also showed a powerful antioxidative activity. Correlation analyses verified that the anti-tyrosinase capacity exhibited a significant positive correlation (R2monophenolase = 0.9167 and R2diphenolase = 0.9302) with mDP within the methanol-water system, and the anti-α-glucosidase activity also showed a significant positive correlation with the mDP (R2 = 0.9187). In contrast, the antioxidant capability showed a significant negative correlation with the mDP (R2DPPH = 0.9258, R2ABTS = 0.9372). This study confirmed that condensed tannins from the bark of F. altissima were desirable anti-tyrosinase, anti-α-glucosidase, and antioxidant agents, and elucidated the relationships of their mDP (molecular weight) and activities, which provided a scientific basis for the comprehensive utilization of these polymers in the food, cosmetics, medicine and other fields.
Subject(s)
Antioxidants , Ficus , Plant Bark , Polymerization , Proanthocyanidins , Ficus/chemistry , Plant Bark/chemistry , Antioxidants/chemistry , Antioxidants/pharmacology , Proanthocyanidins/chemistry , Proanthocyanidins/isolation & purification , Proanthocyanidins/pharmacology , Monophenol Monooxygenase/antagonists & inhibitors , Monophenol Monooxygenase/metabolism , alpha-Glucosidases/metabolism , Glycoside Hydrolase Inhibitors/pharmacology , Glycoside Hydrolase Inhibitors/chemistry , Glycoside Hydrolase Inhibitors/isolation & purification , Plant Extracts/chemistry , Plant Extracts/pharmacology , Tannins/chemistry , Tannins/isolation & purification , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/isolation & purificationABSTRACT
This study investigated the chemical constituents, antioxidant potential, and in vitro and in silico antidiabetic activity of Gymnema sylvestre. Column chromatography and spectroscopic techniques identified twelve compounds from the methanol extract, including 4 sterols (1-4), 5 triterpenoids (5-9), and 3 flavonoids (10-12). The chemophenetic significance of all compounds was also investigated. The antioxidant capacity of the extract and compounds (1-4) was evaluated using FRAP and DPPH assays. The extract exhibited strong free radical scavenging activity (IC50 = 48.34⯵g/mL), while compounds (1-4) displayed varying degrees of efficacy (IC50 = 98.30-286.13⯵g/mL). The FRAP assay indicated significant reducing power for both extract and compounds (58.54, 47.61, 56.61, and 49.11â¯mg Eq.VitC/g for extract and compounds 1 & 2, 3, and 4, respectively). The antidiabetic potential was assessed through α-amylase and α-glucosidase enzyme inhibition assays. The crude extract demonstrated the most potent inhibition (IC50 = 218.46 and 57.42⯵g/mL for α-glucosidase and α-amylase respectively) suggesting its potential for managing postprandial hyperglycaemia. In silico studies employed molecular docking and dynamics simulations to elucidate the interactions between identified compounds and α-amylase/α-glucosidase enzymes. The results revealed promising binding affinities between the compounds and target enzymes, with compound 6 demonstrating the highest predicted inhibitory activity with -10â¯kcal/mol and -9.1â¯kcal/mol for α-amylase and α-glucosidase, respectively. This study highlights the presence of diverse bioactive compounds in Gymnema sylvestre. The extract exhibits antioxidant properties and inhibits carbohydrate-digesting enzymes, suggesting its potential as a complementary therapeutic approach for managing hyperglycaemia associated with type 2 diabetes.
Subject(s)
Antioxidants , Computer Simulation , Glycoside Hydrolase Inhibitors , Gymnema sylvestre , Hypoglycemic Agents , Molecular Docking Simulation , Plant Extracts , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/isolation & purification , Hypoglycemic Agents/chemistry , Antioxidants/pharmacology , Antioxidants/isolation & purification , Gymnema sylvestre/chemistry , Plant Extracts/pharmacology , Glycoside Hydrolase Inhibitors/pharmacology , Glycoside Hydrolase Inhibitors/isolation & purification , alpha-Amylases/antagonists & inhibitors , alpha-Amylases/metabolism , alpha-Glucosidases/metabolism , Secondary MetabolismABSTRACT
Diabetes is a significant global health challenge, affecting circa 540 million adults worldwide. Dioscorea dumetorum, a Nigerian folkloric antidiabetic plant is severely understudied in terms of its bioactive phytochemical constituents. Antidiabetic guided isolation of the tubers and peels of D. dumetorum afforded three phytoecdysteroids bearing a cis-fused A/B ring junction including two new ones: 24-hydroxymuristerone A (1) and 24-hydroxykaladasterone (2), alongside the known muristerone A (3). Additionally, 2,2',7,7'-tetramethoxy-[1,1'-biphenanthrene]-4,4',6,6'-tetraol (4), batatasin I (5), and dihydroresveratrol (6) were isolated. Structural elucidation relied on spectroscopic, spectrometric methods, and comparison with existing literature. The ethyl acetate extracts of both the tubers and peels of D. dumetorum exhibited the highest phenolic content, correlating with potent antioxidant activity. Compounds 4 (IC50 = 0.10 mg/mL) and 6 (IC50 = 0.22 mg/mL) demonstrated superior inhibitory effects against α-glucosidase compared to acarbose (IC50 = 0.63 mg/mL). In contrast, compounds 3, 4, and 5 showed reduced α-amylase inhibition, with IC50 values of 2.58, 3.78, and 1.12 mg/mL, respectively, compared to acarbose (IC50 = 0.42 mg/mL). These observed bioactivities validate the traditional use of D. dumetorum and contribute valuable phytochemical data to the scientific literature of the species.
Subject(s)
Antioxidants , Dioscorea , Hypoglycemic Agents , Phytochemicals , Plant Tubers , Dioscorea/chemistry , Antioxidants/pharmacology , Antioxidants/isolation & purification , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/isolation & purification , Hypoglycemic Agents/chemistry , Molecular Structure , Phytochemicals/pharmacology , Phytochemicals/isolation & purification , Plant Tubers/chemistry , Ecdysteroids/isolation & purification , Ecdysteroids/pharmacology , Ecdysteroids/chemistry , Nigeria , Plant Extracts/pharmacology , Plant Extracts/chemistry , Glycoside Hydrolase Inhibitors/pharmacology , Glycoside Hydrolase Inhibitors/isolation & purification , alpha-Glucosidases/metabolism , alpha-Amylases/antagonists & inhibitorsABSTRACT
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease mainly caused by insulin resistance, which can lead to a series of complications such as cardiovascular disease, retinopathy, and its typical clinical symptom is hyperglycaemia. Glucosidase inhibitors, including Acarbose, Miglitol, are commonly used in the clinical treatment of hypoglycaemia. In addition, Protein tyrosine phosphatase 1B (PTP1B) is also an important promising target for the treatment of T2DM. Gynostemma pentaphyllum is a well-known oriental traditional medicinal herbal plant, and has many beneficial effects on glucose and lipid metabolism. In the present study, three new and nine known dammarane triterpenoids isolated from G. pentaphyllum, and their structures were elucidated by spectroscopic methods including HR-ESI-MS,1H and 13C NMR and X-ray crystallography. All these compounds were evaluated for inhibitory activity against α-glucosidase, α-amylase and PTP1B. The results suggested that compounds 7â¼10 were potential antidiabetic agents with significantly inhibition activity against PTP1B in a dose-dependent manner.
Subject(s)
Dose-Response Relationship, Drug , Enzyme Inhibitors , Gynostemma , Protein Tyrosine Phosphatase, Non-Receptor Type 1 , Protein Tyrosine Phosphatase, Non-Receptor Type 1/antagonists & inhibitors , Protein Tyrosine Phosphatase, Non-Receptor Type 1/metabolism , Gynostemma/chemistry , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/isolation & purification , Molecular Structure , Structure-Activity Relationship , alpha-Glucosidases/metabolism , Humans , alpha-Amylases/antagonists & inhibitors , alpha-Amylases/metabolism , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/isolation & purification , Models, Molecular , Crystallography, X-Ray , Triterpenes/pharmacology , Triterpenes/chemistry , Triterpenes/isolation & purification , Glycoside Hydrolase Inhibitors/pharmacology , Glycoside Hydrolase Inhibitors/chemistry , Glycoside Hydrolase Inhibitors/isolation & purificationABSTRACT
Seven previously undescribed flavonol glycosides including four rare flavonol glycoside cyclodimers, dicyclopaliosides A-C (1-3) with truxinate type and dicyclopalioside D (4) with truxillate type, as well as three kaempferol glycoside derivatives cyclopaliosides A-C (5-7), were obtained from the leaves of Cyclocarya paliurus. Their structures were elucidated by extensive spectroscopic methods and chemical analyses. All compounds were evaluated for their inhibitory α-glucosidase activities. Among them, compounds 1-4 display strong inhibitory activities with IC50 values of 82.76 ± 1.41, 62.70 ± 4.00, 443.35 ± 16.48, and 6.31 ± 0.88 nM, respectively, while compounds 5-7 showed moderate activities with IC50 values of 4.91 ± 0.75, 3.64 ± 0.68, and 5.32 ± 0.53 µΜ, respectively. The structure-activity relationship analysis assumed that the cyclobutane cores likely contribute to the enhancement of α-glucosidase inhibitory activities of dimers. Also, the interaction mechanism between flavonol glycoside dimers and α-glucosidase were explored by the enzyme kinetic assay, indicating that compounds 1-3 exhibited mixed-type inhibition, while 4 showed uncompetitive inhibition. Additionally, the active compounds have also undergone molecular docking evaluation.
Subject(s)
Flavonols , Glycoside Hydrolase Inhibitors , Glycosides , Juglandaceae , alpha-Glucosidases , Glycoside Hydrolase Inhibitors/chemistry , Glycoside Hydrolase Inhibitors/pharmacology , Glycoside Hydrolase Inhibitors/isolation & purification , Glycosides/chemistry , Glycosides/pharmacology , Glycosides/isolation & purification , Flavonols/chemistry , Flavonols/pharmacology , Flavonols/isolation & purification , Juglandaceae/chemistry , Kinetics , alpha-Glucosidases/metabolism , Structure-Activity Relationship , Molecular Docking Simulation , Molecular Structure , Plant Leaves/chemistry , Dose-Response Relationship, DrugABSTRACT
The Hippophae rhamnoides L. pomace was generated in the production process for juice, wine of food industry. To expand the application of pomace, the extraction process optimization, enrichment and identification of triterpene acids were performed in this study. The extraction yield was 14.87% under optimal ultrasound-assisted extraction techniques performed via response surface methodology. The extract was subsequently purified to obtain the triterpenoid acid enrichment fraction (TPF) with the content of 75.23% ± 1.45%. 13 triterpenoid acids were identified via UPLC-Triple-TOF MS/MS and further semi-quantified through comparison with triterpenoid acid standards. TPF exhibited a strong inhibitory effect on α-glucosidase with IC50 value of 5.027 ± 0.375 µg/mL, as determined via enzyme inhibition experiment and molecular docking. Additionally, the TPF significantly reduced postprandial glucose levels, as revealed via carbohydrate tolerance tests, as well as ameliorate serum lipid profiles. Therefore, pomace may be a promising resource of functional food components with therapeutic and commercial values.
Subject(s)
Hippophae , Hypoglycemic Agents , Plant Extracts , Triterpenes , Triterpenes/chemistry , Triterpenes/pharmacology , Triterpenes/isolation & purification , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/isolation & purification , Hippophae/chemistry , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Animals , alpha-Glucosidases/chemistry , alpha-Glucosidases/metabolism , Male , Glycoside Hydrolase Inhibitors/chemistry , Glycoside Hydrolase Inhibitors/pharmacology , Glycoside Hydrolase Inhibitors/isolation & purification , Tandem Mass Spectrometry , Blood Glucose/metabolism , Rats , Humans , Molecular Docking Simulation , Chromatography, High Pressure LiquidABSTRACT
Labdanum resin or "gum" can be obtained from Cistus ladanifer L. by two different extraction methods: the Zamorean and the Andalusian processes. Although its main use is in the fragrance and perfumery sectors, ethnobotanical reports describe its use for medicinal purposes in managing hyperglycemia and mental illnesses. However, data concerning the bioactivities and pharmacological applications are scarce. In this work, it was found that the yield of labdanum resin extracted by the Andalusian process was 25-fold higher than the Zamorean one. Both resins were purified as absolutes, and the Andalusian absolute was purified into diterpenoid and flavonoid fractions. GC-EI-MS analysis confirmed the presence of phenylpropanoids, labdane-type diterpenoids, and methylated flavonoids, which are already described in the literature, but revealed other compounds, and showed that the different extracts presented distinct chemical profile. The potential antidiabetic activity, by inhibition of α-amylase and α-glucosidase, and the potential neuroprotective activity, by inhibition of acetylcholinesterase, were investigated. Diterpenoid fraction produced the higher α-amylase inhibitory effect (~30% and ~40% at 0.5 and 1 mg/mL, respectively). Zamorean absolute showed the highest α-glucosidase inhibitory effect (~14% and ~24%, at 0.5 and 1 mg/mL, respectively). Andalusian absolute showed the highest acetylcholinesterase inhibitory effect (~70% and ~75%, at 0.5 and 1 mg/mL, respectively). Using Caco-2 and HepG2 cell lines, Andalusian absolute and its purified fractions showed moderate cytotoxic/anti-proliferative activity at 24 h exposure (IC50 = 45-70 µg/mL, for Caco-2; IC50 = 60-80 µg/mL, for HepG2), whereas Zamorean absolute did not produce cytotoxicity (IC50 ≥ 200.00 µg/mL). Here we show, for the first time, that labdanum resin obtained by the Andalusian process, and its fractions, are composed of phytochemicals with anti-diabetic, neuroprotective and anti-proliferative potential, which are worth investigating for the pharmaceutical industry. However, toxic side-effects must also be addressed when using these products by ingestion, as done traditionally.
Subject(s)
Cistus , Hypoglycemic Agents , Neuroprotective Agents , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/chemistry , Neuroprotective Agents/pharmacology , Neuroprotective Agents/chemistry , Neuroprotective Agents/isolation & purification , Humans , Cistus/chemistry , Resins, Plant/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry , Cell Proliferation/drug effects , Glycoside Hydrolase Inhibitors/pharmacology , Glycoside Hydrolase Inhibitors/chemistry , Glycoside Hydrolase Inhibitors/isolation & purification , Hep G2 Cells , Flavonoids/pharmacology , Flavonoids/chemistry , Flavonoids/isolation & purificationABSTRACT
BACKGROUND: The present study aimed to investigate the in-vitro anti-diabetic, anti-cholinesterase, and anti-inflammatory potential of extracts from different parts of Ficus benghalensis, including leaves, stem, and roots, as well as isolated column fractions (F-B-1 C, F-B-2 C, F-B-3 C, and F-B-4 C). METHODS: The extracts and subsequent fractions were evaluated for their inhibitory activity against key enzymes involved in diabetes [α-glucosidase and α-amylase], neurodegenerative diseases [acetylcholinesterase and butyrylcholinesterase], and inflammation (cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX)). RESULTS: The results showed that F. benghalensis leaf extract exhibited the highest α-glucosidase inhibitory activity (73.84%) and α-amylase inhibitory activity (76.29%) at 1000 µg/mL. The stem extract (65.50%) and F-B-2 C fraction (69.67%) also demonstrated significant α-glucosidase inhibitory activity. In terms of anti-cholinesterase activity, the extracts of roots, leaves, and stem showed promising inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), with half maximal inhibitory concentration (IC50) values ranging from 50.50 to 474.83 µg/mL. The derived fractions (F-B-1 C, F-B-2 C, F-B-3 C, and F-B-4 C) also exhibited notable inhibition of AChE and BChE, with IC50 values from 91.85 to 337.94 µg/mL. Moreover, the F-B-3 C fraction demonstrated the highest COX-2 inhibitory potential (85.72%), followed by F-B-1 C (83.13%), the stem extract (80.85%), and the leaves extract (79.00%). The F-B-1 C fraction showed the highest 5-LOX inhibitory activity (87.63%), while the root extract exhibited the lowest inhibition (73.39%). CONCLUSIONS: The results demonstrated promising bioactivity, suggesting the potential of F. benghalensis as a source of natural compounds with therapeutic applications. Further studies are required to identify and isolate the active components responsible for these effects and to evaluate their in-vivo efficacy and safety.
Subject(s)
Anti-Inflammatory Agents , Cholinesterase Inhibitors , Ficus , Hypoglycemic Agents , Plant Extracts , Ficus/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/isolation & purification , Cholinesterase Inhibitors/chemistry , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/chemistry , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/isolation & purification , Plant Leaves/chemistry , Butyrylcholinesterase/metabolism , Glycoside Hydrolase Inhibitors/pharmacology , Glycoside Hydrolase Inhibitors/isolation & purification , alpha-Amylases/antagonists & inhibitors , Lipoxygenase Inhibitors/pharmacology , Lipoxygenase Inhibitors/isolation & purification , Acetylcholinesterase/metabolism , Arachidonate 5-Lipoxygenase/metabolism , Plant Roots/chemistryABSTRACT
Alpinia officinarum is a commonly used spice with proven folk uses in various traditional medicines. In the current study, six compounds were isolated from its rhizomes, compounds 1-3 were identified as diarylheptanoids, while 4-6 were identified as flavonoids and phenolic acids. The isolated compounds were subjected to virtual screening against α-glucosidase, butyrylcholinesterase (BChE), and acetylcholinesterase (AChE) enzymes to evaluate their potential antidiabetic and anti-Alzheimer's activities. Molecular docking and dynamics studies revealed that 3 exhibited a strong binding affinity to human a α- glucosidase crystal structure compared to acarbose. Furthermore, 2 and 5 demonstrated high potency against AChE. The virtual screening results were further supported by in vitro assays, which assessed the compounds' effects on α-glucosidase, cholinesterases, and their antioxidant activities. 5-Hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-phenylheptan-3-one (2) showed potent antioxidant effect in both ABTs and ORAC assays, while p-hydroxy cinnamic acid (6) was the most potent in the ORAC assay. In contrary, kaempferide (4) and galangin (5) showed the most potent effect in metal chelation assay. 5-Hydroxy-1,7-diphenylhepta-4,6-dien-3-one (3) and 6 revealed the most potent effect as α-glucosidase inhibitors where compound 3 showed more potent effect compared to acarbose. Galangin (5) revealed a higher selectivity to BChE, while 2 showed the most potent activity to (AChE).
Subject(s)
Acetylcholinesterase , Alpinia , Antioxidants , Butyrylcholinesterase , Cholinesterase Inhibitors , Glycoside Hydrolase Inhibitors , Molecular Docking Simulation , Rhizome , Alpinia/chemistry , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/chemistry , Cholinesterase Inhibitors/isolation & purification , Glycoside Hydrolase Inhibitors/pharmacology , Glycoside Hydrolase Inhibitors/chemistry , Glycoside Hydrolase Inhibitors/isolation & purification , Antioxidants/pharmacology , Antioxidants/chemistry , Antioxidants/isolation & purification , Rhizome/chemistry , Butyrylcholinesterase/metabolism , Acetylcholinesterase/metabolism , alpha-Glucosidases/metabolism , Quantitative Structure-Activity Relationship , Flavonoids/chemistry , Flavonoids/pharmacology , Flavonoids/isolation & purification , Hydroxybenzoates/pharmacology , Hydroxybenzoates/chemistry , Hydroxybenzoates/isolation & purification , HumansABSTRACT
Quantitative analysis of Rumex nepalensis var. remotiflorus revealed that its roots contain rich anthraquinones, which has emodin, chrysophanol, and physcion contents of up to 0.30, 0.67, and 0.98 mg/g, respectively. Further phytochemical study led to the isolation and purification of seven undescribed phenolic constituents, including one flavan derivative with a 13-membered ring, polygorumin A (1), two dianthrone glucosides, polygonumnolides F and G (2, 3), two diphenylmethanones, rumepalens A and B (4, 5), and a pair of epimeric oxanthrone C-glucosides, rumejaposides K and L (6a, 6b) from the roots of R. nepalensis var. remotiflorus. Furthermore, 1 undescribed natural product, 1-ß-D-glucoside-6'-[(2E)-3-(4-hydroxy-3-methoxyphenyl)-2-propenoate]-3-hydroxy-5-methylphenyl (19), and 21 known phenolic compounds were obtained from the aforementioned plant for the first time. Their structures were elucidated through extensive spectroscopic data analysis. Notably, compounds 1, 4-5, and 7-9 exhibited inhibitory activity on α-glucosidase with IC50 values ranging from 1.61 ± 0.17 to 32.41 ± 0.87 µM. In addition, the isolated dianthrone, chrysophanol bianthrone (14), showed obvious cytotoxicity against four human cancer cell lines (HL-60, SMMC-7721, A-549, and MDA-MB-231) with IC50 values ranging from 3.81 ± 0.17 to 35.15 ± 2.24 µM. In silico target prediction and molecular docking studies demonstrated that the mechanism of the anticancer activity of 14 may be related to the interaction with protein kinase CK2.
Subject(s)
Antineoplastic Agents, Phytogenic , Glycoside Hydrolase Inhibitors , Phenols , Rumex , alpha-Glucosidases , Humans , Phenols/pharmacology , Phenols/chemistry , Phenols/isolation & purification , Glycoside Hydrolase Inhibitors/pharmacology , Glycoside Hydrolase Inhibitors/chemistry , Glycoside Hydrolase Inhibitors/isolation & purification , Rumex/chemistry , alpha-Glucosidases/metabolism , alpha-Glucosidases/drug effects , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Molecular Structure , Drug Screening Assays, Antitumor , Molecular Docking Simulation , Structure-Activity Relationship , Cell Line, Tumor , Plant Roots/chemistry , Dose-Response Relationship, Drug , Cell Proliferation/drug effectsABSTRACT
Aspergillus versicolor, an endophytic fungus associated with the herbal medicine Pedicularis sylvatica, produced four new polyketides, aspeversins A-D (1-2 and 5-6) and four known compounds, O-methylaverufin (2), aversin (3), varilactone A (7) and spirosorbicillinol A (8). Their structures were elucidated by extensive spectroscopic data analysis, and their absolute configurations were determined by calculated electronic circular dichroism (ECD) and Mo2(AcO)4-induced CD data. Compound 5 was found to exhibit α-glucosidase inhibitory activity with an IC50 value of 25.57 µM. An enzyme kinetic study indicated that 5 was a typical uncompetitive inhibitor toward α-glucosidase, which was supported by a molecular docking study. Moreover, compounds 1-3 and 5 also improved the cell viability of PC12 cells on a 1-methyl-4-phenylpyridinium (MPP+)-induced Parkinson's disease model, indicating their neuroprotective potential as antiparkinsonian agents.
Subject(s)
Aspergillus , Glycoside Hydrolase Inhibitors , Molecular Docking Simulation , Neuroprotective Agents , Polyketides , alpha-Glucosidases , Aspergillus/chemistry , Neuroprotective Agents/pharmacology , Neuroprotective Agents/chemistry , Neuroprotective Agents/isolation & purification , Polyketides/pharmacology , Polyketides/chemistry , Polyketides/isolation & purification , Glycoside Hydrolase Inhibitors/pharmacology , Glycoside Hydrolase Inhibitors/chemistry , Glycoside Hydrolase Inhibitors/isolation & purification , PC12 Cells , Animals , Rats , alpha-Glucosidases/metabolism , Cell Survival/drug effects , Molecular StructureABSTRACT
Five pairs of new merosesquiterpenoid enantiomers, named dauresorcinols A-E (1-5), were isolated from the leaves of Rhododendron dauricum. Their structures were elucidated by comprehensive spectroscopic data analysis, quantum chemical calculations, Rh2(OCOCF3)4-induced ECD, and single-crystal X-ray diffraction analysis. Dauresorcinols A (1) and B (2) possess two new merosesquiterpene skeletons bearing an unprecedented 2,6,7,10,14-pentamethyl-11-oxatetracyclo[8.8.0.02,7.012,17]octadecane and a caged 15-isohexyl-1,5,15-trimethyl-2,10-dioxatetracyclo[7.4.1.111,14.03,8]pentadecane motif, respectively. Plausible biosynthetic pathways of 1-5 are proposed involving key oxa-electrocyclization and Wagner-Meerwein rearrangement reactions. (+)/(-)-1 and 3-5 showed potent α-glucosidase inhibitory activity, 3 to 22 times stronger than acarbose, an antidiabetic drug targeting α-glucosidase. Docking results provide a basis to design and develop merosesquiterpenoids as potent α-glycosidase inhibitors.
Subject(s)
Glycoside Hydrolase Inhibitors , Rhododendron , Rhododendron/chemistry , Stereoisomerism , Glycoside Hydrolase Inhibitors/chemistry , Glycoside Hydrolase Inhibitors/pharmacology , Glycoside Hydrolase Inhibitors/isolation & purification , Molecular Structure , Structure-Activity Relationship , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacology , Sesquiterpenes/isolation & purification , alpha-Glucosidases/metabolism , Molecular Docking Simulation , Humans , Dose-Response Relationship, Drug , Plant Leaves/chemistry , Crystallography, X-Ray , Models, MolecularABSTRACT
Five new components including two new isoflavones, 5, 7, 2', 3'-tetrahydroxy-6-methoxyisoflavone (1), 5, 7, 2', 3'-tetrahydroxy-8-methoxyisoflavone (2), one flavonol 3, 5, 3', 4'-tetrahydroxy-7, 2'-dimethoxyflavonol (3), one flavanone (2S)-5, 7, 3'-trihydroxy-2'-methoxyflavanone (4), and one flavanonol (2R, 3R)-3, 5, 3', 4'-tetrahydroxy-7, 2'-dimethoxyflavanonol (5), along with nine known flavonoids (6-14) were isolated from under ground parts of Iris tenuifolia Pall. Their structures were elucidated by NMR and HRESIMS data and by comparison of CD spectra with compounds having similar structure. The separated compounds were evaluated for in vitro antioxidant activities by DPPH and ABTS. The α-glucosidase inhibitory activity of the compounds were evaluated with the pNPG method, the results indicated flavonoids were potential inhibitors of α-glucosidase. Moreover, in vitro anti-oxidative assay using flow cytometry indicated that compounds 1-5 showed strong oxidation resistance ability on C8D1A cells without affecting the cell viability.
Subject(s)
Antioxidants , Flavonoids , Glycoside Hydrolase Inhibitors , Iris Plant , Molecular Structure , Flavonoids/pharmacology , Flavonoids/isolation & purification , Flavonoids/chemistry , Iris Plant/chemistry , Glycoside Hydrolase Inhibitors/pharmacology , Glycoside Hydrolase Inhibitors/isolation & purification , Glycoside Hydrolase Inhibitors/chemistry , Antioxidants/pharmacology , Antioxidants/isolation & purification , Isoflavones/pharmacology , Isoflavones/isolation & purification , Isoflavones/chemistry , Phytochemicals/pharmacology , Phytochemicals/isolation & purificationABSTRACT
Phytochemical investigations of the twig and leaf extracts of Uvaria dac Pierre ex Finet & Gagnep. resulted in the isolation and identification of five new highly oxygenated cyclohexenes, uvaridacols M - Q (1-3, 5, and 6), and six known compounds (4 and 7-11). All new structures were elucidated by spectroscopic methods and HRESITOFMS data. The absolute configuration of 1, 5, and 6 was confirmed by single X-ray diffraction analysis with Cu Kα radiation. In contrast, other compounds were established by comparing their specific rotation and ECD spectra with those of known compounds. Some of the isolated compounds with sufficient quantity were evaluated for their α-glucosidase inhibitory activity. Of these, (-)-1,6-desoxypipoxide (10) showed α-glucosidase inhibitory activity with an IC50 value of 28.6 µM. The in silico molecular docking of active compounds was also studied.
Subject(s)
Cyclohexenes , Glycoside Hydrolase Inhibitors , Molecular Docking Simulation , Phytochemicals , Plant Leaves , Uvaria , Glycoside Hydrolase Inhibitors/pharmacology , Glycoside Hydrolase Inhibitors/isolation & purification , Glycoside Hydrolase Inhibitors/chemistry , Molecular Structure , Uvaria/chemistry , Plant Leaves/chemistry , Phytochemicals/pharmacology , Phytochemicals/isolation & purification , Cyclohexenes/isolation & purification , Cyclohexenes/pharmacology , Cyclohexenes/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Stems/chemistry , ChinaABSTRACT
In this study, bioactive compounds were isolated and characterized from the leaves and root-barks extracts of S.latifolius, with subsequent in vitro experimental investigations for antihyperglycemic potentials on α-amylase and α-glucosidase enzymes. Thirteen bioactive compounds were identified, including 10-Hydroxystrictosamide (2) and Quinovic acid-3-O-α-L-rhamnosyl-28-O-ß-d-glucopyranosyl ester (8), using chromatographic, nuclear magnetic resonance spectroscopy (NMR), and mass spectrometry (MS) techniques. Experimental assays revealed that compounds 1-4 exhibited potent inhibition of α-amylase and α-glucosidase, with compound 2 demonstrating the most potent α-amylase inhibition (IC50 value of 0.52 ± 0.003 µg/mL). Compound 8 showed a lower IC50 value (0.098 ± 0.016 µg/mL) against α-glucosidase compared to compound 2 and acarbose. Synergistic effects among the compounds could enhance their inhibitory actions on the enzymes, positioning them as potential anti-hyperglycemia agents. Compound 2 displayed the highest binding affinity (-7.970 kcal/mol) when docked against α-amylase (PDB ID: 2QV4), comparable to acarbose (-8.515 kcal/mol). It also ranked among the top ligands against α-glucosidase (PDB ID 3TOP), although compound 13 and acarbose had higher docking scores. All compounds exhibited ideal ADMET properties, suggesting good bioavailability and low toxicity. In conclusion, the isolated compounds exhibit promising antihyperglycemic potential and favourable safety profiles for further exploration.
Subject(s)
Glycoside Hydrolase Inhibitors , Hypoglycemic Agents , Molecular Docking Simulation , Phytochemicals , Plant Leaves , Plant Roots , alpha-Amylases , Phytochemicals/pharmacology , Phytochemicals/isolation & purification , Plant Leaves/chemistry , alpha-Amylases/antagonists & inhibitors , Glycoside Hydrolase Inhibitors/pharmacology , Glycoside Hydrolase Inhibitors/isolation & purification , Plant Roots/chemistry , Molecular Structure , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/isolation & purification , alpha-Glucosidases/metabolism , Plant Extracts/pharmacology , Plant Extracts/chemistry , Computer SimulationABSTRACT
An intensive phytochemical investigation into the fruits of Schisandra chinensis afforded 28 triterpenoids incorporating diverse backbones with methyl-migration, ring-expansion and ring-opening features. Among them, ten compounds (1-10) including three likely extracting artefacts (8-10) were described for the first time. Their structures were fully characterized by comprehensive spectroscopic analyses, with the absolute configurations established via electronic circular dichroism and Mosher's NMR techniques. Preliminary biological evaluations revealed that nine isolates showed inhibitory activity against the hyperglycemic target α-glycosidase and 12 compounds exerted cytotoxicity toward three female tumor cell lines (Hela (cervical), MDA-MB231 and MCF-7 (breast)). Compound 6 exhibited the most promising potency on all the three tested cancer cells, and further assessment demonstrated that it could induce significant cell apoptosis and cycle arrest, as well as suppress cell migration, by regulating relevant proteins in MDA-MB231 cells.
Subject(s)
Antineoplastic Agents, Phytogenic , Apoptosis , Fruit , Glycoside Hydrolase Inhibitors , Phytochemicals , Schisandra , Triterpenes , Schisandra/chemistry , Humans , Fruit/chemistry , Molecular Structure , Triterpenes/pharmacology , Triterpenes/isolation & purification , Triterpenes/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Glycoside Hydrolase Inhibitors/pharmacology , Glycoside Hydrolase Inhibitors/isolation & purification , Apoptosis/drug effects , Phytochemicals/pharmacology , Phytochemicals/isolation & purification , Cell Movement/drug effects , Cell Line, Tumor , ChinaABSTRACT
Three new oleanane-type triterpene saponins, named camphanosides A-C (1-3), along with five known compounds, chikusetsusaponin IVa (4), spinasaponin A 28-O-glucoside (5), (-)-epicatechin (6), (-)-epicatechin 3-O-gallate (7), and (-)-epigallocatechin 3-O-gallate (8) were isolated from the leaves Camellia phanii Hakoda & Ninh. Their structures were established by 1D and 2D-NMR and mass spectral analysis and chemical methods. Moreover, compounds 1-5 were also evaluated for α-glucosidase inhibitory activity. Compounds 1-3 exhibited moderate α-glucosidase inhibitory activity with IC50 values of 230.7±18.0, 251.4±22.7, and 421.4±25.6â µM, respectively.