Advanced glycation end-products inhibitors isolated from Schisandra grandiflora

Free radicals scavenging and advanced glycation end-products (AGEs) inhibitory potentials in crude chloroform extract of Schisandra grandiflora were evaluated. Bioassay-guided isolation of the chloroform extract led to the identification of 24 compounds. Among the isolates, ( ± ) gomisin M₁, arisantetralone C and D, macelignan, saurulignan B and SZ-MO displayed potent-free radical scavenging as well as AGEs inhibitory potentials. This is the first report identifying the presence of AGEs inhibitory activity and assigning AGEs inhibitory activity to these compounds. Therefore, our research finds new application of traditional medicinal plant S. grandiflora having capacity to reduce formation and accumulation of AGEs in diabetes.     

Phytochemical Analysis,Antispasmodic, Myorelaxant,and Antioxidant Effect of Dysphania ambrosioides (L.) Mosyakin and Clemants Flower Hydroethanolic Extracts and Its Chloroform and Ethyl Acetate Fractions

Dysphania ambrosioides (L.) Mosyakin and Clemants is an annual or ephemeral perennial herb used traditionally in the Mediterranean region in folk medicine to treat various illnesses, including those related to the digestive system. This study aims to assess the antispasmodic, myorelaxant, and antioxidant effects of D. ambrosioides flower hydroethanolic extract and its chloroform and ethyl acetate fractions in a comparative study to evaluate the result of the extraction type on the potential activity of the extract. Both rat and rabbit jejunum were used to evaluate the antispasmodic and myorelaxant effect, while the antioxidant effect was evaluated using DPPH, a ferric reducing power assay, and a beta-carotene bleaching test. LC/MS-MS analysis was carried out to reveal the composition of the different types of extract. Following the results, the hydroethanolic extract showed a significant myorelaxant effect (IC₅₀ = 0.39 ± 0.01 mg/mL). Moreover, it was shown that the hydroethanolic extract demonstrated the best antispasmodic activity (IC₅₀ = 0.51 ± 0.05 mg/mL), followed by the ethyl acetate (IC₅₀ = 4.05 ± 0.32 mg/mL) and chloroform (IC₅₀ = 4.34 ± 0.45 mg/mL) fractions. The antioxidant tests showed that the hydroethanolic extract demonstrated high antioxidant activity, followed by the ethyl acetate and chloroform fractions. The LC/MS-MS analysis indicates that the plant extract was rich in flavonoids, to which the extract activity has been attributed. This study supports the traditional use of this plant to treat digestive problems, especially those with spasms.     

Phytochemical analysis with the antioxidant and aldose reductase inhibitory capacities of Tephrosia humilis aerial parts’ extracts

The aerial parts of Tephrosia humilis were tested about their antioxidant potential, their ability to inhibit the aldose/aldehyde reductase enzymes and their phenolic content. The plant material was exhaustively extracted with petroleum ether, dichloromethane and methanol, consecutively. The concentrated methanol extract was re-extracted, successively, with diethyl ether, ethyl acetate and n-butanol. All extracts showed significant antioxidant capacity, but the most effective was the ethyl acetate extract. As about the aldose reductase inhibition, all fractions, except the aqueous, were strong inhibitors of the enzyme, with the n-butanolic and ethyl acetate fractions to inhibit the enzyme above 75%. These findings provide support to the ethnopharmacological usage of the plant as antioxidant and validate its potential to act against the long-term diabetic complications. The phytochemical analysis showed the presence of 1,4-dihydroxy-3,4-(epoxyethano)-5-cyclohexene(1), cleroindicin E(2), lupeol(3), methyl p-coumarate(4), methyl 4-hydroxybenzoate(5), prunin(6), 5,7,2?,5?-tetrahydroxyflavanone 7-rutinoside(7), protocatechuic acid(8), luteolin 7-glucoside(9), apigenin(10), naringin(11), rhoifolin(12) and luteolin 7-glucuronate(13).     

In vitro anti-oxidant potential of new metabolites from Hypericum oblongifolium (Guttiferae)

Phytochemical investigations on Hypericum oblongifolium led to the isolation of a flavone named folicitin (1) and a bicyclic conjugated lactone, folenolide (2) from the ethyl acetate fraction of methanolic extract. Both metabolites were characterised as new compounds based on detailed spectroscopic analyses. In vitro anti-oxidant potential of both the compounds was evaluated by the DPPH radical scavenging assay. Compound 1 exhibited significant antioxidant activity while compound 2 was found inactive.     

Ailanthus altissima (Miller) Swingle fruit - new acyl β-sitosteryl glucoside and in vitro pharmacological evaluation

β-Sitosterol-3-O-(6?-O-13?-octadecenoyl)-β-D-glucoside (1), a new acyl β-sitosteryl glucoside, along with three known compounds β-sitosterol-3-O-β-D-glucoside (2), β-sitosterol (3) and methyl gallate (4) have been isolated from the ethyl acetate soluble fraction of methanolic extract of Ailanthus altissima fruits. Their structures were elucidated through spectroscopic data including 2D NMR, ESI-MS, methanolysis and oxidative cleavage of double bond. Antibacterial, antifungal, cytotoxic, phytotoxic and insecticidal activities were evaluated of compound 1, crude extract and its fractions so far for the first time. Pharmacological activities results showed that n-butanol fraction was good active against Pseudomonas aeruginosa and Salmonella typhi bacteria, and moderate active against Microsporum canis fungus. Crude extract, n-butanol and aqueous fractions showed good cytotoxicity. Moreover, compound 1, extract and all fractions showed notable phytotoxicity at higher concentrations, whereas all inactive against assayed insects.     

Quantification of polyphenols and flavonoid content and evaluation of anti-inflammatory and antimicrobial activities of Stenocereus stellatus extracts

The hexanic, ethyl acetate and methanolic extracts from branches of Stenocereus stellatus were tested in both the 12-O-tetradecanoylphorbol-13-acetate (TPA) – induced ear oedema model and antimicrobial activity assay. The % of oedema inhibition, the Minimum Inhibitory Concentration (MIC), as well as the polyphenolic and flavonoid content were determined. Also, extracts were analysed by gas chromatography–mass spectrometry (GC–MS). In TPA model, the three extracts showed moderate oedema inhibition. In the antimicrobial activity assay, methanolic extract shows better MIC against all strains. The lowest MICs were for Candida albicans (31 μg/mL) and Rhizopus sp. (15 μg/mL). Also, 50.78 mg eq. of gallic acid/g extract of polyphenol and 115.12 mg eq. of catequine/g extract of flavonoids content were founded in ethyl acetate extract. In the chromatographic analysis, β-sitosterol, β-amyrine, betulin and some other molecules were identified. The results show that S. stellatus possess antimicrobial activities against some fungus species.     

Echinophora tenuifolia L. branches phytochemical profile and antiproliferative activity on human cancer cell lines

Abstract

The methanolic extract of Echinophora tenuifolia L. branches and its fractions were evaluated for their in vitro cell growth inhibitory activity on different human cancer cell lines (C32, LoVo and SKBr3) and the normal BJ fibroblasts. All tested samples were effective against the melanoma cell line C32, with IC₅₀ values ranging from 22.8?±?0.8 to 78.7?±?1.2?μg/mL, the antiproliferative activity of the dichloromethane fraction being significantly higher. This fraction was also effective against the LoVo adenocarcinoma cell line, with an IC₅₀ value of 53.0?±?2.1?μg/mL. The ethyl acetate and dichloromethane fractions showed the highest lipid peroxidation inhibitory activity, verified by means of the β-carotene bleaching test. The phytochemical profiles of E. tenuifolia branches extract were established by means of GC-MS and HPTLC. Overall, branches of E. tenuifolia L. could represent a rich source of bioactive compounds, potentially useful in the pharmaceutical field.     

Inhibitory effect of eleven herbal extracts on advanced glycation end-products formation and aldose reductase activity

The formation of advanced glycation end-products(AGEs) and aldose reductase(AR) activity have been implicated in the development of diabetic complications. Our study sought to characterize the capacities of eleven herbal extracts against the formation of AGEs and the AR activity. An ultrahigh performance liquid chromatography and tandem mass spectrometry(UPLC–MS/MS) method was used for the detection of AR activity and the screening of AR inhibitors in this research. The amount of sorbitol from each analyte was directly detected using the multiple reaction monitoring mode and the sorbitol level could be reduced via the addition of an inhibitor. Moreover, the BSA/glucose(fructose) system was applied to investigate their inhibitory activities of AGEs formation in glycation model reactions.Compared with other screened herbs used in our study, Flos Sophorae Immaturus and Radix Scutellariae seemed to be more effective on inhibiting the formation of AGEs and AR activity. The inhibiting capacities of herbal extracts against AR activity and AGEs formation may be correlated with the bioactive components of the herbal extracts. The differences were correlated with the amount of polyphenol and flavonoid components. In the study, we have investigated the potential anti-hyperglycemic bioactivity of eleven herbal extracts in vitro, which could provide a reference for further in vivo research in the prevention and treatment of diabetic complications.     

In vitro nonenzymatic glycation of DNA nucleobases: an evaluation of advanced glycation end products under alkaline pH

The advanced glycation end products (AGEs) of DNA nucleobases have received little attention, perhaps due to the fact that adenine, guanine, cytosine and thymine do not dissolve under mild pH conditions. To maintain nucleobases in solution, alkaline pH conditions are typically required. The objectives of this investigation were twofold: to study the susceptibility of DNA nucleobases to nonenzymatic attack by different sugars, and to evaluate the factors that influence the formation of nucleobase AGEs at pH 12, i.e., in an alkaline environment that promotes the aldo–keto isomerization and epimerization of sugars. Varying concentrations of adenine, guanine, thymine and cytosine were incubated over time with constant concentrations of D-glucose, D-galactose or D/L-glyceraldehyde under different conditions of temperature and ionic strength. Incubation of the nucleobases with the sugars resulted in a heterogeneous assembly of AGEs whose formation was monitored by UV/fluorescence spectroscopy. Capillary electrophoresis and HPLC were used to resolve the AGEs of the DNA adducts and provided a powerful tool for following the extent of glycation in each of the DNA nucleobases. Mass spectrometry studies of DNA adducts of guanine established that glycation at pH 12 proceeded through an Amadori intermediate.     

Puerariafuran, a new inhibitor of advanced glycation end products (AGEs) isolated from the roots of Pueraria lobata

A new 2-arylbenzofuran, puerariafuran (1), as well as three known compounds, coumestrol (2), daidzein (3), and genistein (4), were isolated from a MeOH extract of the roots of Pueraria lobata as active constituents, using an in vitro bioassay based on the inhibition of advanced glycation end products (AGEs) to monitor chromatographic fractionation. The structure of 1 was determined by spectroscopic data interpretation, particularly by extensive 1D and 2D NMR studies. All the isolates (1-4) were evaluated for the inhibitory activity on AGEs formation in vitro.     

Antioxidant,antimicrobial and urease inhibiting activities of methanolic extracts from Cyphostemma digitatum stem and roots

Cyphostemma digitatum stem and roots extracts were investigated for antioxidant, antimicrobial, urease inhibition potential and phytochemical analysis. Phytochemical screening of the roots and stem extract revealed the presence of secondary metabolites including flavonoids, alkaloids, coumarins, saponins, terpenoids, tannins, carbohydrates/reducing sugars and phenolic compounds. The methanolic extracts of the roots displayed highest antioxidant activity (93.518%) against DPPH while the crude methanolic extract of the stem showed highest antioxidant activity (66.163%) at 100 μg/mL concentration. The methanolic extracts of both stem and roots were moderately active or even found to be less active against the selected bacterial and fungal strains (Tables S2 and S3). The roots extract (methanol) showed significant urease enzyme inhibition activity (IC₅₀ = 41.2 ± 0.66; 0.2 mg/mL) while the stem extract was found moderately active (IC₅₀ = 401.1 ± 0.58; 0.2 mg/mL) against thiourea (IC₅₀ = 21.011; 0.2 mg/mL).     

HPLC profiling of phenolics and flavonoids of Adonidia merrillii fruits and their antioxidant and cytotoxic properties

In this study the antioxidant and cytotoxicity activity of the Adonidia merrillii fruits were investigated using different solvent polarities (methanol, ethyl acetate and water). The results showed that the total phenolic and flavonoid contents of the methanolic extract was higher compare with other extract with respective values of 17.80 ± 0.45 mg gallic acid equivalents/g dry weight (DW) and 5.43 ± 0.33 mg rutin equivalents/g DW. Beside that The RP-HPLC analyses indicated the presence of gallic acid, pyrogallol, caffeic acid, vanillic acid, syringic acid, naringin and rutin. In the DPPH, NO2 and ABTS scavenging assays, the methanolic extract exhibited higher antioxidant activity as compared to the ethyl acetate and water extracts. The extracts exhibited moderate to weak cytotoxic activity in the assays using human hepatocytes (Chang liver cells) and NIH/3T3 (fibroblasts cell) cell lines. The findings showed the Adonidia merrillii fruit extracts to possess considerable antioxidant and cytotoxicity properties. The fruit, therefore, is a potential candidate for further work to discover antioxidant and cytotoxic drugs from natural sources.     

Bioassay-Guided Isolation of Anti-Alzheimer Active Components from the Aerial Parts of Hedyotis diffusa and Simultaneous Analysis for Marker Compounds

Previous studies have reported that Hedyotis diffusa Willdenow extract shows various biological activities on cerebropathia, such as neuroprotection and short-term memory enhancement. However, there has been a lack of studies on the inhibitory activity on neurodegenerative diseases such as Alzheimer’s disease (AD) through enzyme assays of H. diffusa. Therefore, H. diffusa extract and fractions were evaluated for their inhibitory effects through assays of enzymes related to AD, including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), and β-site amyloid precursor protein cleaving enzyme 1 (BACE1), and on the formation of advanced glycation end-product (AGE). In this study, ten bioactive compounds, including nine iridoid glycosides 1–9 and one flavonol glycoside 10, were isolated from the ethyl acetate and n-butanol fractions of H. diffusa using a bioassay-guided approach. Compound 10 was the strongest inhibitor of cholinesterase, BACE1, and the formation of AGEs of all isolated compounds, while compound 5 had the lowest inhibitory activity. Compounds 3, 6, and 9 exhibited better inhibitory activity than other compounds on AChE, and two pairs of diastereomeric iridoid glycoside structures (compounds 4, 8, and 6, 7) showed higher inhibitory activity than others on BChE. In the BACE1 inhibitory assay, compounds 1–3 were good inhibitors, and compound 10 showed higher inhibitory activity than quercetin, the positive control. Moreover, compounds 1 and 3 were stronger inhibitors of the formation of AGE than aminoguanidine (AMG), the positive control. In conclusion, this study is significant since it demonstrated that the potential inhibitory activity of H. diffusa on enzymes related to AD and showed the potential use for further study as a natural medicine for AD treatment on the basis of the bioactive components isolated from H. diffusa.     

Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury

Advanced glycation end products (AGEs) are potentially harmful and heterogeneous molecules derived from nonenzymatic glycation. The pathological implications of AGEs are ascribed to their ability to promote oxidative stress, inflammation, and apoptosis. Recent studies in basic and translational research have revealed the contributing roles of AGEs in the development and progression of various aging-related pathological conditions, such as diabetes, cardiovascular complications, gut microbiome-associated illnesses, liver or neurodegenerative diseases, and cancer. Excessive chronic and/or acute binge consumption of alcohol (ethanol), a widely consumed addictive substance, is known to cause more than 200 diseases, including alcohol use disorder (addiction), alcoholic liver disease, and brain damage. However, despite the considerable amount of research in this area, the underlying molecular mechanisms by which alcohol abuse causes cellular toxicity and organ damage remain to be further characterized. In this review, we first briefly describe the properties of AGEs: their formation, accumulation, and receptor interactions. We then focus on the causative functions of AGEs that impact various aging-related diseases. We also highlight the biological connection of AGE–alcohol–adduct formations to alcohol-mediated tissue injury. Finally, we describe the potential translational research opportunities for treatment of various AGE- and/or alcohol-related adduct-associated disorders according to the mechanistic insights presented.Subject terms: Medical research, Experimental models of disease     

Inhibition of resveratrol glucosides (REs) on advanced glycation endproducts (AGEs) formation: inhibitory mechanism and structure-activity relationship

Abstract

The study on inhibitory effects of resveratrol glucosides (REs) on advanced glycation endproducts (AGEs) formation is still unmet. Herein, for the first time, the antiglycation activities of five REs in the fetal bovine serum proteins (FBS)/fructose system were evaluated, and its structure-activity relationship and antiglycation mechanism were further explored. These REs showed remarkable inhibition toward AGEs formation. Among them, Piceatannol-3'-O-glucoside (PG) exhibited highest antiglycation activity as reflected in approximately 80% inhibition of fluorescent AGEs at the concentration of 1.0?mM. The structure-activity relationship analysis indicated that glucoside attached to the B ring of resveratrol displays a superior antiglycation activity. Moreover, the results of antiglycation mechanism showed that the antiglycation activity of REs was proportional to their antioxidant capacity and methylglyoxal (MGO) trapping capacity. Therefore, the REs are promising candidates worthy of further exploration for preventing AGEs accumulation in vivo, thereby treating AGEs-associated diseases.     

Chemical composition and biological activities of Indigofera hirsuta aerial parts’ methanol fractions

Abstract

Methanol extract of Indigofera hirsuta, was evaluated for its antiradical potential and capacity in inhibiting lipoxygenase and aldose/aldehyde reductase enzymes. The ethyl acetate fraction derived from the methanol extract partition, showed the greatest antioxidant capacity, while the butanol was the strongest inhibitor of lipoxygenase enzyme. All fractions (diethyl ether, ethyl acetate, butanol and the aqueous residue) exhibited strong inhibition capacity of both aldose/aldehyde reductase enzymes, which comes in agreement with the ethnomedicinal plant utilization as an antidiabetic agent. LC-DAD-MS(ESI+) fraction analysis verified the findings above, leading to a conclusion regarding the biological activities attributed to the main compounds. Phytochemical analysis led to the identification of an indolic dimer, cinnamic acids, phenolics, flavonoid glycosides, a cyclic polyol, the rare sugar 1-methyl-β-D-glucopyranoside and glycerol. Many of these compounds were isolated for the first time in Indigofera species while the indolic dimer was isolated for the first time in the Fabaceae family.     

Isolation and identification of a new neo-clerodane diterpenoid from Teucrium chamaedrys L.

Teucrium chamaedrys L. is an aromatic and medicinal plant used as traditional medicine. Aerial parts of the plant material were dried and extracted with hexane–dichloromethane (extract 1), ethyl acetate–dichloromethane (extract 2) and methanol–dichloromethane (extract 3) in a ratio of 1:1 at rt successively. The solvents were evaporated to give crude extracts. Extract 1 was suspended in water at 60°C then partitioned successively with hexane and ethyl acetate to give hexane and ethyl acetate portions. After the column chromatography (silica gel) of ethyl acetate extract, one new and four known compounds were isolated. The new compound was named as 1(12S,18R)-15,16-epoxy-2β,6β-dihydroxy-neo-cleroda-13(16),14-dien-20,l2-olide-l8,l9-hemiacetal (teuchamaedryn D) (4). The known compounds were teucrin A (1), dihydroteugin (2), teucroxide (3), syspirensin A (5). The chromatographic methods were also applied for extract 3 to isolate verbascoside (6) and teucrioside (7). The structure of isolated compounds was elucidated by spectroscopic methods including LC-TOF/MS, 1D NMR and 2D NMR.     

Two new phenolic compounds and some biological activities of Scorzonera pygmaea Sibth. & Sm. subaerial parts

Abstract

Phytochemical composition of ethyl acetate fraction and total phenolic content, in vitro antioxidant, anti-inflammatory, antimicrobial activities of petroleum ether, chloroform, ethyl acetate and n-butanol fractions of the ethanol extract obtained from the subaerial parts of Scorzonera pygmaea Sibth. & Sm. (Asteraceae) were investigated. Nine compounds; scorzopygmaecoside (1), scorzonerol (2), cudrabibenzyl A (3), thunberginol C (4), scorzocreticoside I (5) and II (6), chlorogenic acid (7), chlorogenic acid methyl ester (8), 3,5-di-O-caffeoylquinic acid (9) were isolated and identified using spectroscopic methods. All substances were isolated for the first time from this species. Compounds 1 and 2 are new. The fractions showed high antioxidant capacity correlated with their phenolic content and no significant antimicrobial activity against tested bacteria and fungi. COX inhibition test was used to evaluate the anti-inflammatory activity and all the fractions showed low inhibition in comparison with indomethacin.     

Antioxidant,antibacterial and cytotoxic potential of the ripe fruits of Solanum lycocarpum A. St. Hil. (Solanaceae)

Ethanol extract (EE) and fractions obtained from the ripe fruits of Solanum lycocarpum were examined in order to determine their phenolic composition, antioxidant capacity, antibacterial activities and cytotoxic potential. High-performance liquid chromatography coupled with DAD analysis indicated that caffeic and chlorogenic acids were the main phenolic compounds present in the EE, dichloromethane (DCM) and ethyl acetate (Ac) fractions. The antioxidant activity assessed by the scavenging ability on 1,1-diphenyl-2-picrylhydrazyl radical was significantly more pronounced for DCM and Ac fractions than that of the commercial antioxidant 2,6-di-tert-butyl-4-methylphenol (BHT). EE and fractions exhibited selective antibacterial activity against Gram-positive bacteria, especially the hexane (Hex) and DCM fractions. EE and fractions exhibited low toxicity towards the LLC-MK2 cell line, especially the Hex, DCM and Ac fractions. This work provides the knowledge of phenolic composition in the extract and fractions from the ripe fruits of S. lycocarpum and their antioxidant, antibacterial and cytotoxic activities.     

Cytotoxic,antibacterial and antioxidant activities of extracts of the bark of Melia azedarach (China Berry)

Nature provides a variety of drugs and medicinal agents derived from plants. This study was conducted to determine antimicrobial, antioxidant and cytotoxic activities of extracts of Melia azedarach bark with methanol/water (9:1 v/v), chloroform, butanol, hexane, water and ethyl acetate. For the determination of the antimicrobial activities, the agar well diffusion method was employed. Cytotoxicity was studied by brine shrimp lethality assay; antioxidant activities were measured using 1,1-diphenyl-2-picrylhydrazyl. The chloroform extract was active against Enterobacter aerogenes and Proteus mirabilis, the ethyl acetate extract had highest antibacterial spectrum against Pseudomonas aeruginosa, the n-hexane extract had highest inhibition against E. aerogenes, the aqueous extract showed highest activities against P. mirabilis, the butanol fraction showed highest activities against E. aerogenes and the methanolic extract was highly active against P. mirabilis.