BChE Inhibitory Activity Research Articles

Investigation of the chemical composition, antioxidant, and enzyme inhibitory activities of Ononis natrix subsp. natrix, performance of in silico analyses of its major compounds

In this study, phytochemical composition, antioxidant, anti-Alzheimer, anti-diabetic, tyrosinase activities and in silico analyses of methanol, ethyl acetate and water extracts obtained from the aerial parts of Ononis natrix subsp. natrix, which is naturally distributed in the flora of Mediterranean area, were performed. The extracts were first analyzed for their phytochemical composition using quantitative chromatographic techniques. As a result of spectrophotometric analyses (Agilent Technologies 1260 Infinity liquid chromatography system with 6420 Triple Quad mass spectrometer), it was determined that the methanol extract was the richest in terms of total phenolics (74.60 mg GAEs/g dry weight), while the water extract was found to be richest in terms of total flavonoids (27.88 mg REs/g dry weight). As a result of quantitative phytochemical analyses, taxifolin, hyperoside, eriodictiol and quercetin were found to be present in high concentrations. As a result of quantitative phytochemical analyses, taxifolin, hyperoside, eriodictyol, and quercetin were found to be present in high concentrations. The methanol extract displayed higher activity in all test systems except for DPPH radical scavenging activity. The results from the phosphomolybdenum, ABTS radical scavenging, CUPRAC, FRAP, and metal chelating tests for the methanol extract were: 1.71, 1.07, 1.02 mg, 0.91, and 1.47 mg /ml, respectively. When the AChE, BChE and α-glucosidase inhibitory activity tests were evaluated in terms of IC50, the methanol extract showed higher activity with IC50 values of 1.02, 1.70 and 1.02 mg/ml, respectively. In contrast, the ethyl acetate extract showed higher activity in the tyrosinase and α-amylase tests, with IC50 values of 1.42 and 1.78 mg/ml, respectively. It was found that there was a strong correlation between the total phenolic and flavonoid contents of the extracts and their antioxidant and enzyme inhibitor activities. The study also conducted in silico molecular docking, MM/GBSA, drug-likeness, and ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) analyses to describe the pharmacokinetic and pharmacodynamic properties of bioactive compounds with potential pharmacological action present in O. natrix subsp. natrix extracts. The compounds studied were eriodictyol, hyperoside, quercetin, and taxifolin. Researchers have found that, based on molecular docking, MM/GBSA, and key interactions within the enzyme active sites, hyperoside may inhibit α-amylase and BChE, eriodictyol may inhibit α-glucosidase and AChE, and both hyperoside and eriodictyol may inhibit tyrosinase. The presented data on antioxidant and enzyme inhibitory activity, along with in silico studies, represent the first recorded findings in the literature.

Synthesis, Molecular Docking, Anti-cholinesterase Activity, Theoretical Investigation, and Catalytic Effect of New Encumbered N-benzyladamantyl Substituted Imidazolidin-2-ylidene Carbene Pd-PEPPSI Complexes

Abstract: This study aimed to describe the preparation of novel PEPPSI type Pd(II)-NHC complexes bearing N-benzyladamantyl substituted imidazolidin-2-ylidene group. All synthesized compounds were characterized by using 1H-NMR and 13C-NMR spectroscopies, FTIR, and elemental analysis techniques. One of the objectives of this study was the synthesis of Pd-NHC complexes with AChE/BChE inhibition activities. Among all the tested compounds, complexes 4b and 4c were found to have the most high potential AChE and BChE inhibitory activities with IC50 values of 21.57 ± 0.23 Mm and 15.78 ± 0.39 Mm, respectively. Conducting molecular docking studies helped us in gathering crucial information about the main binding interactions of inhibitors and enzymes, and the results were in agreement with the biological evaluation. The synthesized Pd-NHC complexes were employed for catalyzing the direct C2- and C5-arylation reaction between aryl (hetero) halide and a variety of heterocyclic systems. In both cases (C2 and C5-arylation), Pd-NHC complexes catalysts provided access to the arylated heterocycles in good to high yields in the presence of 1 mol% catalyst loading at 150°C. The DFT theoretical investigation showed that the Pd-NHC complexes were of ML2X2 type, where the the Pd(II) cation had a square planar geometry. The interaction energies obtained by energy decomposition analysis (EDA) demonstrated that the 4d and 4e complexes were more stable in the presence of more methyl substituents. The chemical indicators demonstrated that the less stable 4c complex was more reactive in regard to the chemical hardness, chemical potential, and electrophilicity values.

Variation of the essential oil components of Citrus aurantium leaves upon using different distillation techniques and evaluation of their antioxidant, antidiabetic, and neuroprotective effect against Alzheimer’s disease

Citrus fruit essential oil is considered one of the widely studied essential oils while its leaves attract less attention although being rich in nearly the same composition as the peel and flowers. The leaves of bitter orange or sour orange (Citrus aurantium L.) were extracted using three different techniques namely; hydrodistillation (HD), steam distillation (SD), and microwave-assisted distillation (MV) to compare their chemical composition. The three essential oil samples were analyzed through GC/FID and GC/MS analyses. The samples were tested in vitro using different antioxidant techniques (DPPH, ABTS, CUPRAC, FRAP, PBD, and MCA), neuroprotective enzyme inhibitory activities (acetylcholine and butyl choline enzymes), and antidiabetic activities (α-amylase and α-glucosidase). The results showed that thirty-five volatile ingredients were detected and quantified. Monoterpenes represented the most abundant class in the three essential oils followed by sesquiterpenes. C. aurantium essential oil carried potential antioxidant activity where SD exhibited the highest antioxidant activity, with values arranged in the following order: FRAP (200.43 mg TE/g), CUPRAC (138.69 mg TE/g), ABTS (129.49 mg TE/g), and DPPH (51.67 mg TE/g). SD essential oil also presented the most potent α-amylase (0.32) inhibition while the MV essential oil showed the highest α-glucosidase inhibition (2.73 mmol ACAE/g), followed by HD (2.53 mmol ACAE/g), and SD (2.46 mmol ACAE/g). The SD essential oil exhibited the highest BChE and AChE inhibitory activities (3.73 and 2.06 mg GALAE/g), respectively). Thus, bitter orange essential oil can act as a potential source of potent antioxidant, antidiabetic, and neuroprotective activities for future drug leads.

Benzofuran Derivatives from Cortex Mori Radicis and Their Cholinesterase-Inhibitory Activity.

The phytochemical investigation of Cortex Mori Radicis led to the isolation and identification of a new prenylated benzofuranone (1) and four ring-opening derivatives (2-5) named albaphenol A-E, as well as nigranol A (6), together with ten 2-arylbenzofuran derivatives (7-16). The characterization of the structures of the new compounds and the structural revision of nigranol A (6) were conducted using the comprehensive analysis of spectroscopic data (1D/2D NMR, HRESIMS, CD, and XRD). Compounds 1-16 were tested for their inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Compounds 1 and 4 showed weak BChE-inhibitory activity (IC50 45.5 and 61.0 μM); six 2-arylbenzofuran derivatives showed more-potent BChE-inhibitory activity (IC50 2.5-32.8 μM) than the positive control galantamine (IC50 35.3 μM), while being inactive or weakly inhibitory toward AChE. Cathafuran C (14) exhibited the most potent and selective inhibitory activity against BChE in a competitive manner, with a Ki value of 1.7 μM. The structure-activity relationships of the benzofuran-type stilbenes were discussed. Furthermore, molecular docking and dynamic simulations were performed to clarify the interactions of the inhibitor-enzyme complex.

Synthesis, computational docking and molecular dynamics studies of a new class of spiroquinoxalinopyrrolidine embedded chromanone hybrids as potent anti-cholinesterase agents.

Novel structurally intriguing heterocycles embedded with spiropyrrolidine, quinoxaline and chromanone units were synthesized in good yields using a [Bmim]Br accelerated multicomponent reaction strategy. The key step of the reaction is 1,3-dipolar cycloaddition involving highly functionalized dipolarophile, viz. 3-benzylidenechroman-4-one, to afford spiroquinoxalinopyrrolidine embedded chromanone hybrid heterocycles. The formation of spiro products occurs via two C-C, two N-C and one C-N bonds possessing four adjoining stereogenic centers, two of which are spiro carbons. The newly synthesized spiro compounds showed potent acetylcholinesterase and butyrylcholinesterase inhibitory activities. Moreover, compounds with fluorine displayed the highest AChE (3.20 ± 0.16 μM) and BChE (18.14 ± 0.06 μM) inhibitory activities. Further, docking studies, followed by all-atom molecular dynamics, showed results that are consistent with in vitro experimental findings. Although docking scores for the synthesized derivatives were higher than those of the standard drug, MD MMPBSA results showed better binding of synthesized derivatives (-93.5 ± 11.9 kcal mol-1) compared to the standard drug galantamine (-66.2 ± 12.3 kcal mol-1) for AChE but exhibited similar values (-98.1 ± 11.2 and -97.9 ± 11.5 kcal mol-1) for BChE. These differences observed in drug binding with AChE/BChE are consistent with RMSD, RMSF, LIG plots, and FEL structural analysis. Taken together, these derivatives could be potential candidates as inhibitors of AChE and BChE.

New Imidazo[1,2-a]pyridin-2-yl Derivatives as AChE, BChE, and LOX Inhibitors; Design, Synthesis, and Biological Evaluation

Background: Inhibition of cholinesterase enzyme has been recognized as an important target in the symptomatic treatment of Alzheimer’s disease. Objective: In the current work, a series of new N-(4-(imidazo[1,2-a]pyridin-2-yl)phenyl)cinnamamide derivatives were synthesized and their inhibitory activities against acetyl cholinesterase, butrylcholines terase, and Lipoxygenase were evaluated. Methods: The target compounds were synthesized as the literature reported with some modifications. The AChE, BChE, and LOX inhibitory activities of the synthesized compounds were evaluated using in vitro methods. The docking and kinetic studies were performed for the most potent compounds to evaluate the inhibition mechanism. Results: The structural elucidation of the synthesized imidazo-pyridine derivatives was performed by different spectroscopic techniques including IR, NMR, and Mass. Most of the synthesized compounds demonstrated good AChE, BChE, and LOX inhibitory activities. The most active AChE, BChE, and sLOX-1 inhibitors were found for compounds 4a, 4g, and 4l, respectively. The docking study also revealed that the three compounds, 4a, 4g, and 4l, have important binding interactions with the AChE, BChE, and sLOX-1 enzyme active sites, respectively. Conclusion: The results of current study shows imidazo[1,2-a]pyridine derivatives have potential for development of novel drug candidate for AD as AChE, BChE and sLOX-1 inhibitors.

Active Components of Rosa laevigata Michx. Isolated Using Activity‐Guided Methods Based on LC‐MS/MS for Treating Alzheimer's Disease through Multitarget Mechanisms

AbstractRosa laevigata Michx., a member of the Rosaceae family, is a famous traditional Chinese medicine and edible food in Asian countries. The major active ingredient is triterpenoid, which has anti‐Alzheimer's Disease (AD), antioxidant and neuroprotection properties. However, the properties of “multi‐component structure” and “multi‐directional target” make it impossible to explain the molecular mechanism by conventional ways. The present study aimed to predict the multi‐target mechanisms of triterpenoids in R. laevigata against AD using high performance liquid chromatography equipped with quadrupole time‐of‐flight mass spectrometer (HPLC‐Q‐TOF MS) approach, network pharmacology analysis, dynamics simulation (MDs) and validation of the predicted results with straight‐target tests as well as neuroprotection model. Firstly, bioassay‐guided fractionation of R. laevigata integrated with LC‐MS/MS analysis of the most prospective enriched fractions in terms of anti‐AD efficacy was commenced. Subsequently, multi‐level network model of “multi components‐multi‐targets‐multiple pathways” was established based on the identification of 69 triterpenoids. Complementarily, 64 AD‐related targets were identified through various databases. Network structure analysis illuminated that the intricate pharmacological mechanisms improving cognitive dysfunction of AD was superiorly combined with the crucial targets of APP, APOE, VEGFA, IL1B, MAPT, PSEN1 and BACE and further regulation of principal pathways as HIF‐1 and Calcium signaling pathways. In addition, AChE, BChE and BACE inhibitory activities in vitro showed that nine compounds exhibited potential inhibitory activities. The neuroprotective effects also had a similar effect on H2O2‐induced SH‐SY5Y cell injury. The results show that R. laevigata and its bioactive triterpenoids can pave the way for potential application as inhibitors for treatment of AD.

The biguanide–sulfonamide derivatives: synthesis, characterization and investigation of anticholinesterase inhibitory, antioxidant and DNA/BSA binding properties

A number of new biguanidine-sulfonamide derivatives (1–16) were synthesized and their structures were characterized by spectroscopic and analytical methods. Crystal structures of the compounds 1, 4, 8, 10 and 14 were determined by single crystal X-ray diffraction studies. X-ray crystallographic data showed the π-electron delocalization through the biguanide units. The AChE and BChE cholinesterase inhibitor, DPPH antioxidant and DNA/BSA binding properties of the synthesized compounds were evaluated. Results of cholinesterase inhibitory properties have shown that the compounds containing electron-withdrawing (–F, –Cl) groups have higher AChE/BChE inhibitory and antioxidant activities. Compound 3 showed higher BChE inhibitory activity than tacrine with IC50 value of 28.4 µM. The compounds interact with DNA via minor groove binding mode. The compounds with a naphthyl group in its structure strongly binds with DNA/BSA biomolecules. Communicated by Ramaswamy H. Sarma

Green Chemistry Based Synthesis of Zinc Oxide Nanoparticles Using Plant Derivatives of Calotropis gigantea (Giant Milkweed) and Its Biological Applications against Various Bacterial and Fungal Pathogens.

Nanotechnology is a burning field of scientific interest for researchers in current era. Diverse plant materials are considered as potential tool in green chemistry based technologies for the synthesis of metal nanoparticles (NPs) to cope with the hazardous effects of synthetic chemicals, leading to severe abiotic climate change issues in today's agriculture. This study aimed to determine the synthesis and characterization of metal-based nanoparticles using extracts of the selected plant Calotropis gigantea and to evaluate the enzyme-inhibition activities and antibacterial and antifungal activity of extracts of metal-based zinc nanoparticles using C. gigantea extracts. The crystal structure and surface morphology were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). C. gigantea was examined for antimicrobial activity against clinical isolates of bacteria and fungi. The water, ethanolic, and acetone extracts of C. gigantea were studied for their antagonistic action against bacterial strains (E. coli, S. aureus, P. multocida, and B. subtilis) and selected fungal strains (A. paracistic, F. solani, A. niger, S. ferrugenium, and R. nigricans). In vitro antimicrobial activity was determined by the disc diffusion method, where C. gigantea wastested for AChE and BChE inhibitory activity using Ellman's methodology. The kinetic analysis was performed by the proverbial Berthelot reaction for urease inhibition. The results showed that out of all the extracts tested, ethanolic and water extracts possessed zinc nanoparticles. These extracts showed the maximum zone of inhibition against F. solani and P. multocida and the lowest against S. ferrugenium and B. subtilis. A potential source of AChE inhibitors is certainly provided by the abundance of plants in nature. Numerous phyto-constituents, such as AChE and BChE inhibitors, have been reported in this communication. Water extract was active and has the potential for in vitro AChE and BChE inhibitory activity. The urease inhibition with flower extracts of C. gigantea revealed zinc nanoparticles in water extracts that competitively inhibited urease enzymes. In the case of cholinesterase enzymes, it was inferred that the water extract and zinc nanoparticles have more potential for inhibition of BChE than AChE and urease inhibition. Furthermore, zinc nanoparticles with water extract are active inthe inhibition of the bacterial strains E. coli, S. aureus, and P. multocida and the fungal strains A. paracistic, F. solani, and A. niger.

Synthesis, Characterization and Biological Evaluation of Novel Thiourea Derivatives

Objective: A new series of 4-[3-(substitutedphenyl)thioureido]-N-(6-chloropyrazin-2-yl)benzenesulfonamide were synthesized from sulfaclozine. Methods: All compounds were characterized by IR, 1H-NMR spectroscopic methods and elemental analysis. In addition to the antioxidant activity of the synthesis series, enzyme inhibition activities such as anticholinesterase, tyrosinase, α-amylase and α-glycosidase were determined for the first time in this study. Results: According to these biological activity test results, compound 2a in the DPPH, 2c in the ABTS˙+ assay exhibited more antioxidant activity than reference standard. All thiourea derivatives demonstrated good BChE inhibitory activity than galantamine. Among the compounds, 2e and 2f showed the best tyrosinase enzyme inhibition activity, while 2g had the best α-amylase and α-glucosidase enzyme inhibition activity. In addition, we evaluated the druglikeness properties of compounds and their oral bioavailability were also found to be high. Conclusion: Thiourea derivatives exhibited remarkable antioxidant activity and enzyme inhibition activity against tyrosinase, cholinesterase, α-amylase and α-glucosidase.

Design, synthesis, and biological evaluation of thienopyrimidine and thienotriazine derivatives as multitarget anti-Alzheimer agents.

A series of tetrahydrobenzothienopyrimidines and tetrahydrobenzothienotriazines incorporating a pharmacophore from donepezil molecule were designed and synthesized. The 12 newly synthesized compounds were screened for their inhibition activity against acetylcholinesterase enzyme (AChE). Compounds that exerted the most potent AChE inhibitory action were further evaluated for their BChE inhibitory activity. In addition, the inhibitory effects of all newly synthesized compounds on Aβ and reactive oxygen species were assessed. Compounds 4d, 10b, and 10c showed potent inhibitory activity on AChE comparable to donepezil. Compound 10b (IC50 = 0.124 ± 0.006 nM) showed the greatest AChE inhibitory action and the most potent BChE inhibitory action (IC50 = 0.379 ± 0.02 nM). These three compounds showed more inhibitory action on Aβ accumulation than donepezil. Moreover, they showed potent antioxidant activity. The binding pattern of compounds 4d and 10b into AChE active site rationalized their remarkable AChE inhibitory activity. Taken together, these results indicated that these derivatives could be promising multifunctional agents for Alzheimer's disease management.

Isosteroidal alkaloids of Fritillaria taipaiensis and their implication to Alzheimer's disease: Isolation, structural elucidation and biological activity

Four undescribed and five known isosteroidal alkaloids were isolated from the bulbs of Fritillaria taipaiensis and their structures were elucidated on the basis of HR-ESI-MS, 1D and 2D NMR spectroscopic data analyses. The undescribed compounds were designated taipainines A−D. Of these, taipainine D presented a unique structure having the D/E trans (H-13α/H-17β) and E/F cis (β-axial lone pair of the N atom/H-22β) ring junctions. Possible biosynthetic pathway to taipainine D is proposed. Four compounds showed significant BChE inhibitory activities similar or better than the positive control galantamine. In addition, the preliminary structure−activity relationships (SARs) of these isosteroidal alkaloids were also investigated.

Identification of sulfonamide-based butyrylcholinesterase inhibitors using machine learning.

Aim: Thisstudy reports the designing of BChE inhibitors through machine learning (ML), followed by in silico and in vitro evaluations. Methodology: ML technique was used to predict the virtual hit, and its derivatives were synthesized and characterized. The compounds were evaluated by using various in vitro tests and in silico methods. Results: The gradient boosting classifier predicted N-phenyl-4-(phenylsulfonamido) benzamide as an active BChE inhibitor. The derivatives of the inhibitor, i.e., compounds 34, 37 and 54 were potent BChE inhibitors and displayed blood-brain barrier permeability with no significant AChE inhibition. Conclusion: The ML prediction was effective, and the synthesized compounds showed the BChE inhibitory activity, which was also supported by the in silico studies.

Design, synthesis, AChE/BChE inhibitory activity, and molecular docking of spiro[chromeno[4,3-b]thieno[3,2-e]pyridine]-7-amine tacrine hybrids

A new series of 12 examples of spiro[chromeno[4,3-b]thieno[3,2-e]pyridine]-7-amines tacrine hybrids (3) were designed and synthesized as cholinesterase inhibitors. These new compounds were synthesized at 20-33% yields by a one-pot two-step cyclocondensation reaction of 2-aminothiophene-3-carbonitriles (1) with spiro[chroman-2,10-cycloalkan]-4-ones (2) using AlCl3 as the catalyst without solvent and under conventional thermal heating. Subsequently, these new tacrine hybrids were subjected to AChE and BChE inhibitory activity evaluation and molecular docking studies. In vitro cholinesterase assays and in silico docking indicated that all new tacrine analogs 3 were not AChE inhibitors. However, the molecules without a carbocyclic moiety geminated to the thiophene ring, i.e., spiro scaffolds that originated from cyclopentanone (3aa), cyclohexanone (3ba), and cycloheptanone (3ca) showed the highest inhibitory potency against the BChE enzyme, thereby proving to be promising candidates for evaluation in Alzheimer's disease synthetic models.

Phenolic profile, antioxidant and enzyme inhibitory properties of phenolic-rich fractions from the aerial parts of Mentha pulegium L.

This study investigated into the phenolic profile and biological properties of Mentha pulegium L. based on the antioxidant and enzyme inhibitory activities. Total phenolic and flavonoid contents were spectrophotometrically quantified. The phenolic profile was analyzed by RP-HPLC-PDA. Galvinoxyl radical (GOR), 2,2′-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS), 1,1-diphenyl-2-picrylhydrazyl (DPPH), ferric reducing activity, cupric reducing and β-carotene bleaching methods were performed to evaluate antioxidant potential. Enzyme inhibitory activity was tested towards alpha-glucosidase, alpha-amylase, acetylcholinesterase and butyrylcholinesterase. The results indicated that ethyl acetate fraction exhibited the strongest antioxidant potential with its higher phenolic and flavonoid contents. This fraction also exerted the highest alpha-glucosidase (IC50 of 61.85 ± 1.69 μg/mL), alpha-amylase (IC50 of 16.37 ± 0.11 μg/mL), AChE (IC50 of 3.13 ± 0.05 μg/mL) and BChE (IC50 of 12.97 ± 0.20 μg/mL) inhibitory activities, its activity was higher than that of acarbose and galantamine used as standard drugs. Gallic acid, p-coumaric acid, ferulic acid, naringenin and quercetin were identified in this fraction. Hence, these findings suggest that M. pulegium is a promising source of bioactive compounds, which could be helpful in the management of oxidative stress associated diseases including diabetes and Alzheimer's disease.

Heterocyclic Schiff base derivatives containing pyrazolone moiety: Synthesis, characterization, and in vitro biological studies

AbstractIn this study, some pyrazolone‐based Schiff base derivatives 2a‐e (except 2a) were synthesized for the first time and structurally illuminated by some spectroscopic techniques (1H, 13C NMR, FT‐IR) and elemental analysis. All synthesized molecules were screened for their anticancer and antioxidant activities, as well as AChE, BChE, and tyrosinase inhibitory properties. The obtained results exhibited that compounds 1b (IC50 = 9.497 μΜ) and 2a (IC50 = 30.49 μΜ) significantly decreased the proliferation of HeLa cells. On the other hand, the apoptotic effects of these two compounds were investigated with acridine orange/propidium iodide double staining. The apoptotic cell ratios of the molecules treated with these two compounds were determined as 60 and 64%. Compound 2b (IC50 = 17.95 ± 0.47 μΜ) was determined to be a very active substance in the ABTS assay. Compound 2e (A0.5 = 43.75 ± 0.62 μM) indicated the closest antioxidant activity to the standard compound α‐TOC (A0.5 = 50.58 ± 0.39 μM) in the cupric reducing antioxidant capacity (CUPRAC) assay. In inhibition studies of enzymes, it was determined that compound 2c had a very active molecule in AChE, BChE, and tyrosinase inhibitory activities with 82.79 ± 1.03, 91.39 ± 1.06, and 92.60 ± 1.80% inhibition, respectively. It was determined that the target molecules 2a‐e showed better antioxidant and enzyme inhibitory activities than those of ester derivatives 1a‐e.

Draba cemileae (Karaer): Phytochemical composition, antioxidant and enzyme inhibitory activity

Plant polyphenols have always attracted the attention of researchers with their excellent biological activity potentials. In this study, roots, leaves and seeds of Draba cemileae (Karaer) were evaluated for their chemical compositions and biological activities. Spectrophotometric analysis showed that phenolics and flavonoids were present in high quantities in leaf and seed extracts (22.84 mg GAEs/g and 23.32 mg REs/g, respectively). Chromatographic analysis showed that the p-hydroxybenzoic acid and chlorogenic acid contents of the extracts were significantly high. The seed extract also contained 550 mg/g of rosmarinic acid. While the leaf extract showed high activity in phosphomolybdenum, CUPRAC, FRAP and ferrous ion chelating activity tests (0.88, 2.23, 1.73 and 3.68 mg/ml, respectively), DPPH and ABTS scavenging activity tests resulted in the superiority of the seed extract (3.75 and 2.53 mg/ml, respectively). The leaf extract also showed the highest activity in α-amylase and tyrosinase inhibitory activity tests (1.78 and 4.99 mg/ml, respectively). On the other hand, the seed extract exhibited higher activity than the others in α-glucosidase, AChE and BChE inhibitory activity tests (7.14, 1.13 and 5.11 mg/ml, respectively). Correlation coefficients between the composition and the biological activities were over 0.9. It was concluded that D. cemileae could be a new and effective source of antioxidant and enzyme inhibitory phytochemicals in medicine, food and cosmetics industries.

Nutraceutical extracts from some endemic Onosma ( O. ci rcinnata , O. bornmuelleri , and O. angustissima ) species: LC–ESI‐MS/MS–based polyphenol profile, antioxidant and enzyme inhibition activities

This study aimed to determine the chemical composition of methanol extracts from Onosma circinnata, Onosma bornmuelleri, and Onosma angustissima and to investigate their antioxidant and enzyme inhibitory activities. Spectrophotometric analysis showed that the extracts were found to be rich in chlorogenic acid, luteolin 7-glucoside, rosmarinic acid, and apigenin 7-glucoside. While O. bornmuelleri showed the highest activity in DPPH, ABTS, and FRAP tests, O. circinnata was more effective in CUPRAC, phosphomolybdenum, and ferrous ion chelating tests. While O. angustissima showed significant inhibitory activities on AChE, BChE, and tyrosinase, O. bornmuelleri and O. circinnata showed the highest inhibitory activities on α-amylase and α-glucosidase. It was concluded that O. circinnata and O. bornmuelleri are effective antioxidant agents and O. angustissima can be considered as an alternative agent in the medical and cosmetic industries due to its ChE and tyrosinase inhibitory activities. Novelty impact statement Biological activities of Onosma species were brought to the literature for the first time with this study. O. circinnata showed remarkable antioxidant activity. O. angustissima exhibited the highest AChE, BChE and tyrosinase inhibitory activity.

New secondary metabolites with immunosuppressive and BChE inhibitory activities from an endophytic fungus Daldinia sp. TJ403-LS1

Five new acetylenic phenol derivatives (1–4 and 7), one new benzofuran derivative (8), one new naphthol derivative (9), and two known analogues (5 and 6), were isolated and identified from an endophytic fungus Daldinia sp. TJ403-LS1 that was isolated from the medicinally valuable plant Anoectochilus roxburghii. Their structures were elucidated by means of extensive spectroscopic analyses and electronic circular dichroism (ECD) calculations. In addition, compound 1 exhibited remarkable immunosuppressive activity against LPS and anti-CD3/anti-CD28 mAbs activated murine splenocytes proliferation with the same IC50 values of 0.06 μM and BChE inhibitory activity with an IC50 value of 6.93 ± 0.71 μM, and compounds 6, 8 and 9 showed excellent BChE inhibitory activity with IC50 values of 16.00 ± 0.30, 23.33 ± 0.55, and 15.53 ± 0.39 μM, respectively (positive drug neostigmine, IC50 = 49.60 ± 6.10 μM), highlighting the promising potentials to be designed and developed as immunosuppressive and BChE inhibitory agents.

Phytochemical profiles and antioxidant, anticholinergic, and antidiabetic activities of Odontites serotina (Lam.) Dum

IntroductionOdontites serotina is a medicinal plant primarily distributed in northern China. To the best of our knowledge, no previous study has investigated the bioactivities of this plant. The present study investigated the active constituent contents and bioactivities of the 95% ethanol crude extract (ECE) of O. serotina and its fractions. MethodsThe total phenol/flavonoid/iridoid glycoside contents were examined by spectrophotometric methods. DPPH/ABTS assays were used to evaluate the antioxidant activities. α-Glycosidase/α-amylase/AChE/BChE-inhibitory assays were performed to evaluate antidiabetic and anticholinergic activities. Correlations were determined via Pearson's correlation analyses. ResultsThe total phenol/flavonoid contents of the ethyl acetate fraction (EAF) and n-butanol fraction (NBF) and the total iridoid glycoside content of the NBF were determined to be significantly higher than those of the ECE. The EAF and NBF exhibited strong antioxidant and potent inhibitory effects on acetylcholinesterase (AChE), and they also exhibited butylcholinesterase (BChE)/α-glucosidase-inhibitory effects. No sample demonstrated any effects against α-amylase. The correlation analyses indicated strong positive correlations between total phenol content and antioxidant activity and between total flavonoid content and antioxidant/AChE/BChE/α-glucosidase-inhibitory activities. The isolation of the EAF resulted in the acquisition of acteoside (1), emodin (2), benzoic acid (3) and β-sitosterol (4). Acteoside showed moderate antioxidant and BChE/α-glucosidase-inhibitory activities, and emodin exhibited moderate BChE-inhibitory activity. ConclusionThe EAF and NBF are rich in phenols, flavonoids and iridoid glycosides and have antioxidant and dual AChE/BChE and selective α-glycosidase-inhibitory activities. O. serotina has potential in the development of new drugs to treat Alzheimer's disease (AD) and diabetes.