Antioxidant and urease inhibitory C-glycosylflavonoids from Celtis africana

Two new C-glycosylflavonoids celtisides A (1) and B (2) have been isolated from n-butanol-soluble fraction of Celtis africana, along with five known C-glycosylflavonoids vitexin (3), orientin (4), isoswertiajaponin (5), isoswertisin (6), and 2″-O-rhamnosyl vitexin (7) reported for the first time from this species. Their structures were assigned from 1D and 2D NMR spectra. These compounds were investigated for biological activities and showed significant antioxidant and urease inhibitory activities.     

A New Flavonoid C-Glycoside from Celtis australis L. and Celtis occidentalis L. Leaves and Potential Antioxidant and Cytotoxic Activities

A major development over the past two decades has been the realization that free radical induced lipid peroxidation and DNA damage are associated with major health problems, e.g. cancer and ageing. Plant-derived antioxidants are increasingly found beneficial in protecting against these diseases. Celtis australis L. and Celtis occidentalis L. are two plants that have a variety of uses in folk medicine but have not been evaluated before for their antioxidant and cytotoxic properties. Therefore, the extracts of both plants’ leaves were investigated for these activities, as well as isolation of the bioactive compounds responsible for the activities. Molecular structures of the compounds were elucidated by UV, HRESIMS, 1D (¹H and ¹³C) and 2D (¹H-¹³C HSQC and ¹H-¹³C HMBC) NMR analyses. The ethanolic and aqueous extracts, n-butanol fractions and the isolated major compound were tested for their antioxidant activity using DPPH radical scavenging assay, xanthine oxidase-induced generation of superoxide radical and lipid peroxidation assay by thiobarbituric acid-reactive substances (TBARS) method using rat tissue homogenates. Cytotoxic activities were studied using standard MTT assay. A novel flavonoid C-triglycoside, 4‴-α-rhamnopyranosyl-2″-O-β-d-galactopyranosylvitexin, was isolated from both plants’ leaves, together with seven known flavonoids. The n-butanol fractions and the major compound 2″-O-β-galactopyranosylvitexin showed significant antioxidant activities, more pronounced than the tested standards BHT and dl-α-tocopherol in most tests. All extracts showed variable cytotoxic activities. This study provides strong evidence for the antioxidant and cytotoxic activities of the extracts of Celtis australis L. and Celtis occidentalis L. leaves, which were attributed to the polar n-butanol fractions and the major isolated flavonoid 2″-galactosylvitexin.     

Urease inhibitory constituents from Daphne retusa

The bioassay-guided fractionation of Daphne retusa Hemsl. has led to the isolation of a new aryl tetrahydronaphthalene lignan derivative named as daphnretusic acid (1), along with six new source compounds such as 5,7-dihydroxyflavone (2), 7-hydroxyflavone (3), 6-methoxyflavone (4), (+) pinoresinol (5), (+) sesamin (6), and β-sitosterol-3-O-β-D-glucopyranoside (7). Their structures were elucidated by ¹H NMR, ¹³C NMR, 1D, 2D NMR, UV, IR, and EIMS analyses. All the fractions (n-hexane, CHCl₃, AcOEt, CH₃OH, and water) and pure compounds (1–7) were subjected to the assay of urease and α-chymotrypsin inhibitory activities. Chloroform and methanol soluble fractions showed moderate urease inhibition. Compound 2 exhibited significant urease inhibition with IC₅₀ value 60.4 ± 0.72 μM, whereas compounds 1 and 3–7 remained inactive during urease inhibition and α-chymotrypsin bioassays.     

Antioxidant and angiotensin converting enzyme (ACE) inhibitory activities of ethanol extract and pure flavonoids from Adinandra nitida leaves

Context: Adinandra nitida Merr. ex. H.L. Li (Theaceae) is an indigenous plant in south China. Its leaves have been reported to have many curative effects such as reducing blood pressure, as well as antibacterial, antioxidant, and analgesic properties, which could be used in foods and medicines.

Objective: The antioxidant and angiotensin converting enzyme (ACE) inhibitory activities of the main flavonoids and ethanol extract (EE) of A. nitida leaves were investigated for the first time.

Materials and methods: The main flavonoids of A. nitida leaves (camellianin A, camellianin B) were prepared and their contents in EE were determined by HPLC. The antioxidant activities of the samples were measured by DPPH radical scavenging assay and Rancimat test. The ACE inhibitory activities of the samples were carried out by using an assay kit with hippuryl-glycyl-glycine as substrate.

Results: The contents of camellianin A, camellianin B and apigenin in EE were determined as 41.98, 2.67, and 1.73%, respectively. The antioxidant activities of the flavonoids were far lower than that of EE in DPPH radical scavenging and Rancimat assays. However, the ACE-inhibitory activities of camellianin A, camellianin B and apigenin were higher than that of EE.

Discussion and conclusion: The flavonoid content of EE was more than 45%. The high activities of EE in DPPH scavenging and Rancimat assay could be mainly attributed to compounds other than flavonoids. However, the ACE-inhibitory activity of EE could be mainly attributed to the presence of the flavonoids.     

Analgesic and anti-inflammatory effects of the methanol stem bark extract of Prosopis africana

Prosopis africana (Guill. & Perr.) Taub. (Mimosoideae) is a shrub used for menstrual and general body pain in Nupe land in north central Nigeria. In this study, the methanol extract of the stem bark of Prosopis africana (at doses of 62.5, 125, and 250?mg/kg) was evaluated for analgesic and anti-inflammatory activities using acetic acid-induced writhing assay and carrageenan-induced inflammation in rats. The extract significantly (P <0.05) attenuated the acetic acid-induced writhing with the highest activity observed at the highest dose, 250?mg/kg (76.89%) comparable to that of piroxicam (83.16%) the standard agent used. In the carrageenan-induced inflammation assay, the extract showed significant anti-inflammatory activity (P <0.001) from the third hour. The preliminary phytochemical screening revealed the presence of flavonoids, saponins, carbohydrates, cardiac glycosides, tannins, and alkaloids. The oral median lethal dose was found to be 3807.9?mg/kg in mice and > 5000?mg/kg in rats. This study supports the folkloric claim of the use of Prosopis africana in the management of pain.     

伏康树籽挥发油的GC-MS分析

目的:分析伏康树籽的挥发油成分。方法:采用水蒸气蒸馏法提取伏康树籽挥发油,通过气相色谱-质谱联用技术对其成分进行鉴定,同时采用面积归一法测定其含量。结果:分离出32种物质,鉴定出22个化合物,占总馏出组分的97.85%,其中脂肪酸类百分含量为80.93%。结论:伏康树籽挥发油主要成分为油酸(30.46%),棕榈酸(28.65%),亚油酸(12.31%)等。通过对伏康树籽挥发油成分的分析鉴定,为进一步开发利用其资源提供科学依据。     

Synthesis,enzyme inhibitory kinetics,and computational studies of novel 1‐(2‐(4‐isobutylphenyl) propanoyl)‐3‐arylthioureas as Jack bean urease inhibitors

In this article, synthesis of a novel 1‐(2‐(4‐isobutylphenyl)propanoyl)‐3‐arylthioureas ( 4a–j) as jack bean urease inhibitors has been described. Freshly prepared 2‐(4‐isobutylphenyl) propanoyl isothiocyanate was treated with substituted aromatic anilines in one pot using anhydrous acetone. The compounds 4e, 4h, and 4j showed IC₅₀ values 0.0086 nm , 0.0081 nm , and 0.0094 nm , respectively. The enzyme inhibitory kinetics results showed that compound 4h inhibit the enzyme competitively while derivatives 4e and 4j are the mixed type inhibitors. The compound 4h reversibly binds the urease enzyme showing Ki value 0.0012 nm . The Ki values for 4e and 4j are 0.0025 nm and 0.003 nm , respectively. The antioxidant activity results reflected that compounds 4b, 4i, and 4j showed excellent radical scavenging activity. Moreover, the cytotoxic activity of the target compounds was evaluated using brine shrimp assay and it was found that all of the synthesized compounds exhibited no cytotoxic effects to brine shrimps. The computational molecular docking and molecular dynamic simulation of title compounds were also performed, and results showed that the wet laboratory findings are in good agreement to the dry laboratory results. Based upon our results, it is proposed that compound 4h may act as a lead candidate to design the clinically useful urease inhibitors.     

Evaluation of Antiaris africana methanol extract and compounds for antioxidant and antitumor activities

A methanol extract from the stem bark of Antiaris africana Engler (Moraceae), as well as compounds isolated and identified as betulinic acid (1), 3β-acetoxy-1β,11α-dihydroxy-olean-12-ene (2), ursolic acid (3), oleanolic acid (4), strophanthidol (5), periplogenin (6), convallatoxin (7), strophanthidinic acid (8), methyl strophanthinate (9), and 3,3′-dimethoxy-4′-O-β-d-xylopyronosylellagic acid (10), were tested for their antioxidant and anticancer activities. The DPPH radical scavenging assay was used for the antioxidant test while the potato disk tumor induction and XTT assays were used to detect antitumor activities. The antioxidant test showed that the methanol extract and compounds 1, 9, and 10, as well as vitamin C, used as reference antioxidant drug, were able to interact with more than 50% DPPH. The results of the potato disk tumor induction assay also indicated a pronounced tumor reducing activity of the methanol extract (83.12%) and compound 10 (96.64%). Samples showing more than 20% inhibition of Crown gall tumors were then tested against human DU-145 and hepatocarcinoma Hep G2 cells. The results showed inhibitory activities of 64.12% and 73.62%, respectively, on DU-145 and Hep G2 cells for the methanol extract. Compound 10 showed the highest inhibition potency on both cell lines with more than 70% inhibition at 50?μg/mL. The methanol extract showed an IC₅₀ value lower than this at 30?μg/mL, a threshold value for potential antineoplastic extracts. The results of the present study provide supportive data for the traditional anticancer use of A. africana and indicate that the methanol extract as well as compound 10 represent a potential source of medicine for the treatment of cancer, having also interesting antioxidant properties.     

1,3,4-Thiadiazole and 1,2,4-triazole-5-thione derivatives bearing 2-pentyl-5-phenyl-2,4-dihydro-3H-1,2,4-triazole-3-one ring: Synthesis,molecular docking,urease inhibition,and crystal structure

Two series of 1,3,4-thiadiazole ( 40a–o ) and 1,2,4-triazole-5-thione ( 41a–l ) derivatives bearing a 2-pentyl-5-phenyl-1,2,4-triazole-3-one ring were synthesized and then studied for their urease inhibitory activities using thiourea as a standard drug. Among the two groups, the first group ( 40a–o ) did not show good activity while the second group ( 41a–l ) showed excellent activity. Compound 41j (1091.24 ± 14.02 µM) of the second series of compounds showed lower activity than thiourea, while the remaining 11 compounds ( 41a–i , k , and l ) showed better activity than thiourea (183.92 ± 13.14 µM). Among the 11 compounds, 41b (15.96 ± 2.28 µM) having the 3-F group on the phenyl ring showed the highest inhibitory activity. Urease kinetic studies of 41b , which is the most active compound, determined it to have an un-competitive inhibition potential. Moreover, in silico analysis against urease from jack bean with 27 new heterocyclic compounds and the reference molecule was carried out to see the necessary interactions responsible for urease activity. The docking calculations of all compounds supported stronger binding to the receptor than the reference molecule, with high inhibition constants. In addition, compound 40m was characterized by single-crystal X-ray diffraction analysis. X-ray analysis reveals that the structures of the compound 40m crystallize in the monoclinic P21/c space group with the cell parameters: a = 10.2155(9) Å, b = 22.1709(18) Å, c = 21.4858(17) Å, β = 99.677(8)°, V = 4797.0(7) ų. X-ray diffraction analyses were also performed to gain insights into the role of weak intermolecular interactions and C-H…X (halogen) interactions in compound 40m that influence the crystal packing.     

Preliminary screening of acetylcholinesterase inhibitory and antioxidant activities of Anatolian Heptaptera species

The ethyl acetate and methanol extracts prepared from the fruits, aerial parts, and roots of Heptaptera anatolica (Boiss.) Tutin, (Umbelliferae), H. anisoptera (DC.) Tutin, H. cilicica (Boiss. & Balansa) Tutin (endemic), and H. triquetra (Vent.) Tutin were tested for their acetylcholinesterase (AChE) inhibitory and antioxidant activities. AChE inhibition was evaluated using ELISA microplate reader at 500, 1000, and 2000 μg mL^?1. Antioxidant activity was determined by 2,2-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging test and Fe⁺²-ferrozine test system for metal chelating power at the same concentrations. Total phenol contents of the extracts were determined using Folin-Ciocalteu reagent. At 2000 μg mL^?1, only the aerial parts and fruits of H. anatolica showed moderate anti-AChE effect (61.97% and 49.80%, respectively), while the aerial parts and fruits of H. triquetra had the highest DPPH scavenging effect (80.48% and 86.19%, respectively). All of the methanol extracts exhibited significant ferrous ion-chelating effect varying between 72.97% and 92.36%, whereas only four of the ethyl acetate extracts exerted chelating effect over 70%. These results indicate that Heptaptera species could be a good source for antioxidant compounds.     

Antioxidant constituents from Cotoneaster racemiflora

A new lignan rhamnoside, racemiside (1), has been isolated from the ethyl acetate-soluble fraction of Cotoneaster racemiflora, along with scopoletin (2), 7,8-dimethoxy-6-hydroxycoumarin (3), 3,3′,4′-tri-O-methylellagic acid (4), and cereotagloperoxide (5), reported for the first time from this species. All of them showed profound antioxidative activities in the DPPH assay.     

Biochemical characterization of a novel antioxidant and angiotensin I-converting enzyme inhibitory peptide from Struthio camelus egg white protein hydrolysis

A peptide from ostrich (Struthio camelus) egg white protein hydrolysate (OEWPH) was purified, characterized, and its antioxidant and enzyme inhibitory properties were evaluated. The OEWPH was prepared using pepsin and pancreatin, and then fractionated using reversed-phase high performance liquid chromatography. The antioxidant activity of the WG-9 peptide was investigated based on its scavenging capacity for 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, 2,20-azinobis (3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS), superoxide ( O2•-), hydroxyl (OH^•−), and lipid peroxidation inhibition. The angiotensin-converting enzyme (ACE) inhibitory activity and kinetic parameters of the peptide were determined using N-[3-(2-Furyl)acryloyl]-L-phenylalanyl-glycyl-glycine (FAPGG) as a substrate. Tandem mass spectrometry analysis of the purified peptide revealed a sequence of WESLSRLLG (MW: 1060 Da; WG-9). This peptide inhibited linoleic acid oxidation and acted as a DPPH (IC₅₀ = 15 ± 0.4 μg/mL), ABTS (IC₅₀ = 130 ± 4.5 μg/mL), superoxide (IC₅₀ = 160 ± 6.4 μg/mL), and hydroxyl (IC₅₀ = 150 ± 6.7 μg/mL) radical scavenger. The ACE-inhibitory activity and kinetic parameters of the WG-9 peptide were determined, showing an ACE inhibitory activity with IC₅₀ of 46.7 ± 1.4 μg/mL. The parameters of peptide/ACE interactions were investigated by molecule docking. Furthermore, viability assays showed that the identified peptide had no cytotoxicity against an HFLF-PI-5 cell line. In conclusion, the WG-9 peptide showed potent antioxidant and ACE-inhibitory activity.     

Antioxidant Enzymes and Weight Gain in Drug-naive First-episode Schizophrenia Patients Treated with Risperidone for 12 Weeks: A Prospective Longitudinal Study

Background: Oxidative stress plays an important role in weight gain induced by antipsychotics in schizophrenia (SCZ). However, little is known about how antioxidant enzymes are involved in weight gain caused by risperidone monotherapy in antipsychotics-naïve first-episode (ANFE) patients with SCZ. Therefore, the main purpose of this study was to investigate the effects of risperidone on several antioxidant enzymes in patients with ANFE SCZ and the relationship between weight gain and changes in antioxidant enzyme activities.Objective: The activities of plasma superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as the levels of malondialdehyde (MDA) were measured in 225 ANFE patients and 125 healthy controls.Methods: Patients were treated with risperidone monotherapy for 12 weeks. Clinical symptoms, antioxidant enzyme activities, and MDA levels were measured at baseline and during follow-up.Results: Compared with healthy controls, the patients showed higher activities of SOD and CAT but lower MDA levels and GPx activity. At baseline, the CAT activity was associated with body weight or BMI. Further, based on a 7% weight increase from baseline to follow-up, we found 75 patients in the weight gain (WG) group and 150 patients in the non-WG group. Comparing SOD, CAT, GPx activities and MDA levels between the WG group and the non-WG group at baseline and during the 12-week follow-up, it was found that after treatment, the SOD activity in the WG group increased while the MDA level decreased in the non-WG group. Moreover, baseline SOD and GPx activities were predictors of weight gain at 12-week follow-up.Conclusion: These results suggest that the antioxidant defense system may have predictive value for the weight gain of ANFE SCZ patients after risperidone treatment.     

Synthesis,molecular structure and urease inhibitory activity of novel bis-Schiff bases of benzyl phenyl ketone: A combined theoretical and experimental approach

BackgroundUrease belongs to the family of amid hydrolases with two nickel atoms in their core structure. On the basis of literature survey, this research work is mainly focused on the study of bis-Schiff base derivatives of benzyl phenyl ketone nucleus.ObjectiveSynthesis of benzyl phenyl ketone based bis-Schiff bases in search of potent urease inhibitors.MethodIn the current work, bis-Schiff bases were synthesized through two steps reaction by reacting benzyl phenyl ketone with excess of hydrazine hydrate in ethanol solvent in the first step to get the desired hydrazone. In last, different substituted aromatic aldehydes were refluxed in catalytic amount of acetic acid with the desired hydrazone to obtain bis-Schiff base derivatives in tremendous yields. Using various spectroscopic techniques including FTIR, HR-ESI-MS, and ¹H NMR spectroscopy were used to clarify the structures of the created bis-Schiff base derivatives.ResultsThe prepared compounds were finally screened for their in-vitro urease inhibition activity. All the synthesized derivatives (3–9) showed excellent to less inhibitory activity when compared with standard thiourea (IC₅₀ = 21.15 ± 0.32 µM). Compounds 3 (IC₅₀ = 22.21 ± 0.42 µM), 4 (IC₅₀ = 26.11 ± 0.22 µM) and 6 (IC₅₀ = 28.11 ± 0.22 µM) were found the most active urease inhibitors near to standard thiourea among the synthesized series. Similarly, compound 5 having IC₅₀ value of 34.32 ± 0.65 µM showed significant inhibitory activity against urease enzyme. Furthermore, three compounds 7, 8, and 9 exhibited less activity with IC₅₀ values of 45.91 ± 0.14, 47.91 ± 0.14, and 48.33 ± 0.72 µM respectively. DFT used to calculate frontier molecular orbitals including; HOMO and LUMO to indicate the charge transfer from molecule to biological transfer, and MEP map to indicate the chemically reactive zone suitable for drug action. The electron localization function (ELF), non-bonding orbitals, AIM charges are also calculated. The docking study contributed to the analysis of urease protein binding.     

Lipoxygenase inhibitory sphingolipids from Launaea nudicaulis

Four new sphingolipids: nudicaulin A [(2S,3S,4R,14E)-2-{[octadecanoyl]amino}tetraeicos-14-ene-1,3,4-triol; 1], nudicaulin B [(2S,3S,4R,14E)-2-{[(2R)-2-hydroxyoctadecanoyl]amino}tetraeicos-14-ene-1,3,4-triol; 2], nudicaulin C [(2S,3S,4R,14E)-2-{[(2R)-2-hydroxyoctadecanoyl]amino}tetraeicos-14-ene-1,3,4-triol-1-O-β-d-glucopyranoside; 3], and nudicaulin D [(2S,3S,4R)-2-{[(2R,3S,12E)-2,3-dihydroxyeicos-12-enoyl]amino}octadecane-1,3,4-triol; 4] together with 1-hexatriacontanol, β-sitosterol, octadecyl 4-hydroxycinnamate, elaidic acid, cholesta-5,22-diene-3,7-diol, oleanolic acid, apigenin, and β-sitosterol 3-O-β-d-glucopyranoside were isolated from the methanolic extract of the whole plant of Launaea nudicaulis. Their structures were elucidated using ¹H and ¹³C NMR spectra and 2D NMR analyses (HMQC, HMBC, and COSY) in combination with mass spectrometry (EI-MS, HR-EI-MS, FAB-MS, and HR-FAB-MS) experiments and comparison with literature data of related compounds. Compounds 1–4 displayed moderate inhibitory potential against enzyme lipoxygenase in concentration-dependent manner with IC₅₀ value ranges 103–193 μM.     

Antioxidant potential and radical scavenging effects of various extracts from Abutilon indicum and Abutilon muticum

Abutilon indicum L. (Malvaceae) and Abutilon muticum DC. (Malvaceae) are traditional medicinal herbs used for analgesic, anthelmintic, hepatoprotective, and hypoglycemic properties. These effects may be correlated with the presence of antioxidant compounds. Extracts in organic solvents from the aerial parts and roots of both species were prepared and evaluated for their total antioxidant capacity (TAC), total phenolic content, and total flavonoid content. The Trolox equivalent antioxidant capacity (TEAC) of all the extracts of both plants was found, employing ABTS and FRAP assays. TEAC values ranged from 3.019 to 10.5?μM for n-hexane and butanol fractions of Abutilon indicum and from 2.247 to 14.208?μM for n-hexane and butanol fractions of Abutilon muticum, respectively, using the ABTS assay. The FRAP assay showed reducing powers of the fractions in the order of butanol > ethyl acetate > chloroform > n-hexane and butanol > chloroform > hexane > ethyl acetate for Abutilon indicum and Abutilon muticum, respectively. EC₅₀ and T_EC50 values for the extracts of both plants were determined using the DPPH free radical assay. The reaction kinetics with this free radical indicated the presence of both slow reacting and fast reacting antioxidant components in the extracts of both plants. The antioxidant/radical scavenging capacity of the extracts was found to be a dose-dependent activity. The results obtained in the present study indicate that both Abutilon species are potential sources of natural antioxidants.     

Isolation,characterization, and in silico,in vitro and in vivo antiulcer studies of isoimperatorin crystallized from Ostericum koreanum

Context: Ostericum koreanum (Maxim.) Kitagawa (Apiaceae) roots are traditionally used as an analgesic and antiulcer agent. However, the antiulcer potential of isoimperatorin isolated from O. koreanum has not yet been explored.

Aim: To evaluate the antiulcer activity of isoimperatorin isolated from the roots of O. koreanum.

Materials and methods: Isoimperatorin was isolated as cubic crystals by repeated column chromatography of the ethyl acetate fraction and structure was verified with ¹H NMR, ¹³C NMR and high-resolution mass spectrometry (HRMS-FAB). The crystals obtained were analyzed with the single crystal X-ray method. The MTT assay was used to determine its cytotoxicity against chondrocytes at different concentrations (0.0–737.74?μM, 24?h). The in vivo antiulcer activity of isoimperatorin (40?mg/kg) was determined against ethanol-, indomethacin- and pyloric ligation-induced ulcers in Sprague-Dawley rats. Furthermore, the effect of isoimperatorin (0.0–737.74?μM, 24?h) on the expression of type II collagen in chondrocytes was determined using western blot method. The in vitro urease inhibitory activity of isoimperatorin (0–80?μM) and molecular docking was also performed against urease.

Results and discussion: Isoimperatorin demonstrated significant inhibitory activity (IC₅₀ 36.43?μM) against urease as compared to the standard drug thiourea (IC₅₀ 33.57?μM) without cytotoxic effects. It provided 70.9%, 67.65% and 54.25% protection in ulcer models induced by ethanol, indomethacin and pyloric ligation, respectively. Isoimperatorin showed the highest expression level of type II collagen at 368.87?μM. The docking results confirmed strong binding affinity with the target protein.

Conclusion: Isoimperatorin may be used to develop antiulcer drugs with decreased side effects.     

Sorbicins A and B, new urease and serine protease inhibitory triterpenes from Sorbus cashmiriana

Two new lupene-type triterpenes, sorbicins A and B, have been isolated from the chloroform-soluble fraction of the MeOH extract from the whole plant of Sorbus cashmiriana, and their structures were elucidated by spectroscopic techniques including 2D NMR. Both compounds displayed urease and α-chymotrypsin inhibitory potential.