Search

Hydroxypyranone and hydroxypyridinone are important oxygen-containing or nitrogen-containing heterocyclic nucleus and attracted increasing attention in medicinal chemistry and drug discovery over the past decade. Previous literature reports revealed that hydroxypyranone and hydroxypyridinone derivatives exhibit a wide range of pharmacological activities such as antibacterial, antifungal, antiviral, anticancer, anti-inflammatory, antioxidant, anticonvulsant, and anti-diabetic activities. In this review, we systematically summarized the literature reported biological activities of hydroxypyranone and hydroxypyridinone derivatives. In particular, we focus on their biological activity, structure-activity relationship (SAR), mechanism of action, and interaction mechanisms with the target. The collected information is expected to provide rational guidance for the development of clinically useful agents from these pharmacophores., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Skin damage, especially the extensive full-thickness wound, is seriously affecting people's daily life and health. Meanwhile, wound healing is always challenged by bacterial infection. In this study, for the purpose of developing a disinfectant wound dressing, we designed a novel multi-functional nanofiber mats via electrospinning combining chitosan derivations and stereocomplex crystallite (SC). The SC membrane of poly (lactic acid)/chitosan derivatives were prepared via warming at 80 °C for 1 h. The thermal and mechanical properties of the heated mats were strengthened owing to the formation of SC, which restricted the lactide chains mobility. In vivo wound healing test revealed that the SC mats have better wound repair ability than the control group with a wound healing rate of 100 % within 15 days. In a word, the biomass-based mats with enhanced thermal and mechanical properties, antibacterial effect and antioxidant activity, providing a potential multi-functional platform for designing of disinfectant wound dressings., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Exogenous antioxidants are considered as a promising therapeutic approach to treat neurodegenerative diseases since they could prevent and/or minimize the neuronal damage by oxidation., Objective: Three series of lipophilic compounds structurally based on scutellarein (2), which is one metabolite of scutellarin (1) in vivo, have been designed and synthesized., Methods: Their antioxidant activity was evaluated by detecting the 2-thiobarbituric acid reactive substance (TBARS) produced in the ferrous salt/ascorbate-induced autoxidation of lipids, which were present in microsomal membranes of rat hepatocytes. The lipophilicity of these compounds indicated as partition coefficient between n-octanol and buffer was investigated by ultraviolet (UV) spectrophotometer., Results: This study indicated that compound 5e which had a benzyl group substituted at the C4'- OH position showed a potent antioxidant activity and good lipophilicity., Conclusion: 5e could be an effective candidate for preventing or reducing the oxidative status associated with the neurodegenerative processes., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The objective of this study consisting of 2 trials was to investigate the antioxidant role of conjugated linoleic acid (CLA) isomers (c9, t11-CLA and t10, c12-CLA) and the underlying mechanism by which they act in modulating redox status in a primary laying hen hepatocyte culture. In trial 1, the cytotoxicity of CLA isomers or linoleic acid (LA) (0, 25, 50, 100, 200, 400, 800 μmol/L) was evaluated by 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT) assay. The concentration of CLA isomers or LA (25, 50, 100 μmol/L) for proper antioxidant activity was evaluated by measuring the antioxidant enzyme activity. In trial 2, there were 5 groups: control group, cells were untreated; H2O2 group, cells were exposed to 4 mmol/L H2O2 for 2 h; c9, t11 or t10, c12 or LA group, cells were treated with c9, t11-CLA or t10, c12-CLA or LA for 24 h and then exposed to 4 mmol/L H2O2 for 2 h. Trial 1 showed that the non-toxic dose range for CLA isomers was 0 to 200 μmol/L. The optimum concentration of c9, t11-CLA and t10, c12-CLA for trial 2 was 100 μmol/L. In trial 2, pretreatment with t10, c12-CLA but not c9, t11-CLA attenuated the increase in reactive oxygen species (ROS) compared to hydrogen peroxide (H2O2) group (P < 0.05). t10, c12-CLA elevated the superoxide dismutase (SOD) and catalase (CAT) activities compared with the H2O2 group (P < 0.05). In addition, t10, c12-CLA up-regulated the mRNA expression of nuclear factor E2-related factor-2 (Nrf2) as well as its target genes, Cu-Zn superoxide dismutase (SOD1) and CAT (P < 0.05). Pretreatment with t10, c12-CLA but not c9, t11-CLA decreased Nrf2 protein expression in the cytoplasm and increased Nrf2 protein expression in the nucleus compared with the H2O2 group (P < 0.05). The results indicate that t10, c12-CLA exhibits a stronger antioxidant capacity than c9, t11-CLA in primary cultured laying hen hepatocytes. t10, c12-CLA increases the activity and mRNA expression of antioxidant enzymes via facilitating nuclear translocation of Nrf2.

Four polysaccharides, PTP-1, PTP-2, PTP-3 and PTP-4, were obtained from the water extraction of the stems of P. tricuspidata by anion exchange chromatography and gel filtration. The antioxidant activities of four PTPs were investigated, exhibiting different antioxidant activities, in which PTP-4 performed noticeable, with strong superoxide radical activity (comparable to BHT), high DPPH radical activity (78.53% at 1250 μg/mL), moderate hydroxyl radical scavenging activity and reducing power activity. Furthermore, the chemical structure of PTP-4 was measured by FT-IR, GC, 1 H and 13 C NMR spectra, indicating its mainly composition of the arabinose, xylose, galactose, glucuronic acid, and mannose. Thus, the stems of P. tricuspidata could be used as a potential source for natural antioxidant., (Copyright © 2018. Published by Elsevier B.V.)

Three series of scutellarein derivatives have been designed and synthesized based on metabolic mechanism of scutellarin (1) in vivo. Their thrombin inhibition activities were tested through the analyzation of prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB). The antioxidant activities of these target products were assessed by 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) assay and the ability to protect PC12 cells against H2 O2 -induced cytotoxicity, and their solubilities were evaluated by ultraviolet (UV) spectrophotometer. The results showed that the two isopropyl groups substituted derivative (18c) demonstrated stronger anticoagulant activity, better water solubility, and good antioxidant activity compared with scutellarein (2), which warrants further development of 18c as a promising agent for ischemic cerebrovascular disease treatment., (© 2016 John Wiley & Sons A/S.)

In order to improve the biological activity and water solubility of scutellarin (1), some derivatives of its main metabolite (scutellarein) were designed and synthesized. All the compounds were tested for their thrombin inhibition activity through the analyzation of thrombin time (TT), activated partial thromboplastin time (APTT), prothrombin time (PT) and fibrinogen (FIB). Their antioxidant activities were assessed by measuring their scavenging capacities toward 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and the ability to protect PC12 cells against H2O2-induced cytotoxicity, their water solubility were also assessed by ultraviolet (UV) spectrophotometer. The results showed that compound 8b demonstrated stronger anticoagulant and antioxidant activity, better water solubility compared with scutellarein (2), which warrants it as a promising agent for the treatment of ischemic cerebrovascular disease., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Bisphenol A (BPA) is a well-known endocrine-disrupting chemical (EDC) that has received particular attention because of its widespread distribution in humans. Due to its chemical similarity to diethylstilbestrol, which is carcinogenic to mammals, the possible genotoxicity of BPA has already largely been evaluated. However, the results are still inconclusive and controversial. To investigate the genotoxic effects of BPA in rat germ cells and the potential protective action of melatonin against these effects, adult male Sprague-Dawley rats were orally administered BPA at a dose of 200mg/kg body weight per day for ten consecutive days with or without melatonin pretreatment. The thiobarbituric acid reactive substances (TBARS) level and superoxide dismutase (SOD) activity in the testes were evaluated. Subsequently, their spermatocytes were isolated, and DNA damage was assessed using an alkaline comet assay and the meiotic spread method. BPA administration did not significantly affect the weights of rats and their reproductive organs, and no alteration in sperm count was found. However, we demonstrated that BPA administration induced a significant increase in TBARS levels and a decrease in SOD activity that were concomitant with an increase in DNA migration within male germ cells and γH2AX foci formation on the autosomes of pachytene spermatocytes. Furthermore, a decrease in the proportion of 4C-cells was observed. These BPA effects were significantly alleviated by melatonin pretreatment. Nevertheless, the genotoxic effects of BPA were not accompanied by apoptosis in germ cells and morphological changes in the testes. These results indicate that BPA exposure may induce DNA damage accumulation in germ cells via oxidative stress. Moreover, melatonin may be a promising pharmacological candidate for preventing the potential genotoxicity of BPA following occupational or environmental exposure., (Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Methyl helicterate is a triterpenoid isolated from Helicteres angustifolia (Sterculiaceae), one of the valuable traditional Chinese herbs. Antifibrotic activities of H. angustifolia have been extensively proved., Aim of the Study: The purpose of this study was to investigate the effect of methyl helicterate (MH) on liver fibrosis in rats induced by carbon tetrachloride (CCl(4)) and to explore its underlying mechanism., Materials and Methods: Hepatic fibrosis was induced in male Sprague-Dawley (SD) rats by intragastric administration with 2 ml/kg CCl(4) (mixed 1:1 in peanut oil) twice a week for 12 weeks. To evaluate the effect of MH (16.72, 33.45, 66.90 mg/kg) on hepatic fibrosis, liver function, histological study and hepatic fibrosis evaluation were performed. Liver function was assessed by determining the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (Alb) and total protein (TP). The biomarkers such as hydroxyproline (Hyp), hyaluronic acid (HA), type III precollagen (PCIII) and laminin (LN) were examined for the evaluation of hepatic fibrosis. The underlying mechanism was investigated by measuring oxidative stress level and detecting the expression of TGF-β1 mRNA and Smad3 protein., Results: MH (33.45, 66.90 mg/kg) treatment significantly inhibited the loss of body weight and the increase of liver index in rats induced by CCl(4). MH also improved the liver function as indicated by decreasing serum enzymatic activities of ALT, AST, TP and Alb (P<0.05). Histological results indicated that MH alleviated liver damage and reduced the formation of fibrous septa. Moreover, MH significantly decreased liver Hyp, HA, LN and PCIII (P<0.05). Research on mechanism showed that MH could markedly reduce liver malondialdehyde (MDA) concentration, increase activities of liver superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and inhibit the expression of TGF-β1 mRNA and Smad3 protein (P<0.05)., Conclusions: Our findings indicated that MH can inhibit CCl(4)-induced hepatic fibrosis, which may be ascribed to its radical scavenging action, antioxidant activity, and modulation of TGF-β-Smad3 signaling pathway., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

This study was to investigate the possibility of enhancing the anti-fibrotic effect by using a combination therapy with taurine, epigallocatechin gallate and genistein in a rat liver fibrosis model induced by alcohol, and to explore its underlying mechanism. Hepatic fibrosis was induced by intragastric administration with various amount of alcohol (5.0-9.5 g/kg) within 24 weeks in rats. The model group received alcohol only, and treatment groups received the corresponding drugs plus alcohol respectively, while the normal control group received an equal volume of saline. The antifibrotic effects of combination therapy were assessed directly by hepatic histology, and indirectly by measurement of serum biochemical markers, the fibrosis markers and related key cytokines/proteins. The results showed that combination therapy could significantly improve the liver function, as indicated by decreasing levels of alanine transaminase, aspartate transaminase, alkaline phosphatase, γ-glutamyltransferase, interleukin-6 and tumor necrosis factor-α. Moreover, combination therapy could effectively suppress the serum levels of fibrosis markers and hepatic hydroxyproline content, inhibit collagen deposition and reduce the pathological tissue damage. Research on mechanism showed that combination therapy was able to markedly reduce lipid peroxidation and recruit the anti-oxidative defense system, and inhibit the expression of B-cell lymphoma 2, α-smooth muscle actin, transforming growth factor β(1) and small mothers against decapentaplegic homolog 3 proteins. Our results showed that combination therapy is effective in attenuating hepatic injury and fibrosis in the alcohol-induced rat model. The improved efficacy of the combination therapy with its good safety profile could represent a new protective approach for liver fibrosis.

This study was designed to investigate the protective effects of the polysaccharide isolated from Tarphochlamys affinis (PTA) against CCl4-induced hepatotoxicity in rats. Liver injury was induced in rats by the administration of CCl4 twice a week for 2 weeks. During the experiment, the model group received CCl4 only; the treatment groups received various drugs plus CCl4, whereas the normal control group received an equal volume of saline. Compared with the CCl4 group, PTA significantly decreased the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in the serum and increased the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) in the liver. Moreover, the content of hepatic malondialdehyde (MDA) was reduced. Histological findings also confirmed the anti-hepatotoxic characterisation. In addition, PTA significantly inhibited the proinflammatory mediators, such as prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and myeloperoxidase (MPO). Further investigation showed that the inhibitory effect of PTA on the pro-inflammatory cytokines was associated with the down-regulation of nuclear factor-kappa B (NF-κB). In brief, our results show that the protective effect of PTA against CCl4-induced hepatic injury may rely on its ability to reduce oxidative stress and suppress inflammatory responses.

Purpose: PS-341 (bortezomib, Velcade), the first proteasome inhibitor approved by the Food and Drug Administration for the treatment of patients with relapsed multiple myeloma, induces apoptosis in human cancer cell lines. Vitamin C (ascorbic acid) is an essential water-soluble vitamin required for many normal physiologic functions and has to be obtained through diet or supplemental tablets in humans. Here we studied the potential effect of vitamin C on the anticancer activity of PS-341 in human cancer cell lines., Experimental Design: The effects of vitamin C on apoptosis induction by PS-341 alone and by PS-341 combined with tumor necrosis factor-related apoptosis-inducing ligand were studied. In addition, the effects of vitamin C and other antioxidants on PS-341-mediated proteasome inhibition were also examined. Finally, the direct chemical interaction between vitamin C and PS-341 was determined., Results: Vitamin C abrogated the ability of PS-341 to induce apoptosis in various human cancer cell lines, to induce G(2)-M arrest, and to augment apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand. Moreover, vitamin C suppressed PS-341-mediated inhibition of proteasome activity. PS-341 itself did not induce generation of intracellular reactive oxygen species whereas other antioxidants failed to abrogate its biological activity. Importantly, we detected a direct chemical interaction between vitamin C and PS-341., Conclusion: Vitamin C directly binds to PS-431, thus inactivating PS-341 independent of its antioxidant activity. Our findings suggest that vitamin C may have a negative effect on PS-341-mediated anticancer activity.

The correlations between the antioxidant activity and hindered phenolic antioxidants bonded with para bridge structures in polyamide 6 (PA6) were studied by comparing the antioxidant properties of three hindered phenolic antioxidants bonded with different bridging groups. The antioxidant properties of the pure PA6 and stabilized PA6 were investigated in terms of mechanical properties, rheological properties, crystallization properties, chemical structure, and the migration resistance of antioxidants. The radical scavenging activity and capacity of hindered phenolic antioxidants were also compared. The results showed that the hindered phenolic bonded with the aromatic ring exhibits the best activity and capacity in scavenging radical and the best migration resistance in PA6. Therefore, the tensile strength of PA6/HPAP remains at 117 % of the unaged sample after 12 days of thermal oxygen aging at 150 °C, and the notch impact strength of PA6/HPAP remains at 68 % of the unaged sample. The mechanical properties of PA6/HPAP are comparable to PA6/1098 (a commonly used commercial antioxidant in PA) after 12 days of thermal oxygen aging. The mechanism of the hindered phenolic antioxidants bonded with para bridge structure in scavenging PA6 free radicals and inhibiting the aging of PA6 macromolecular chains was explored in this article. [Display omitted] • The correlations between the antioxidant activity and structure in polyamide 6 (PA6) were studied. • The bonding mode and bonding structure of the bridging groups have an impact on the radical scavenging ability. • The aromatic bonded with HP exhibits better antioxidant activity and capacity, it exhibits the best antioxidant activity. [ABSTRACT FROM AUTHOR]

The proteolytic enzyme β‐secretase (BACE1) plays a central role in the synthesis of the pathogenic β‐amyloid peptides (Aβ) in Alzheimer's disease (AD), antioxidants could attenuate the AD syndrome and prevent the disease progression. In this study, BACE1 inhibitors (D1–D18) with free radical‐scavenging activities were synthesized by molecular hybridization of 2‐aminopyridine with natural antioxidants. The biological activity evaluation showed that D1 had obvious inhibitory activity against BACE1, and strong antioxidant activity in 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) and 2,2′‐azinobis‐(3‐ethylbenzthiazoline‐6‐sulphonate) (ABTS+•) assay, which could be used as a lead compound for further study. [ABSTRACT FROM AUTHOR]

Scutellarin (1) possesses protective effects against neuronal injury, while 6-O-methyl-scutellarein (3), as the main metabolite of scutellarin in vivo, has not been reported about its protective effects previously. The present study mainly investigated whether the neural injury caused by ischemia/reperfusion would be influenced by different doses of 6-O-methyl-scutellarein (3). The results of behavioral, neurological, and histological examinations indicated that 6-O-methyl-scutellarein (3) could improve neuronal injury, and exhibit significant difference among the various doses. More importantly, 6-O-methyl-scutellarein (3) had better protective effects than scutellarin in rat cerebral ischemia. [ABSTRACT FROM AUTHOR]

In this study, Super Critical CO 2 (SCC) was applied to extract the active ingredients from Multi-herbal formula Chaihu Shugan San (CSS). Response Surface Methodology (RSM) coupled with an improved chaotic Gray Wolf Optimization (ACGWO) was employed to the experimental design. After gas chromatography–mass spectrometer (GC–CI/EI-MS) detection, liquid chromatography–mass spectrometry- ion trap-time of flight (LC–MS-IT-ToF) further indicated that several phthalides are mainly responsible for the SCC extract; the next is α-Cyperone in Cyperus rotundus ; and Meranzin hydrate, Isomeranzin in Citrus reticulata Blanco again. Further pharmacological tests were also performed for the SCC extracts. THP-1 macrophages were used to observe the anti-inflammatory effects. The expression of IL-6 was obviously suppressed by the SCC extract from CSS, through a positive correlation with the dose. Then, ROS content in a cell model was used to detect the antioxidant capacities. The results showed that the SCC extract from CSS, exert dose-dependent inhibitory effects on the oxidative stress of the cells. [ABSTRACT FROM AUTHOR]

Objectives. To establish a new method for determination of antioxidant capacity of human urine based on the redox couple I2/KI and to evaluate the redox status of healthy and diseased individuals. Methods. The method was based on the linear relationship between oxidation reduction potential (ORP) and logarithm of concentration ratio of I2/KI. ORP of a solution with a known concentration ratio of I2/KI will change when reacted with urine. To determine the accuracy of the method, both vitamin C and urine were reacted separately with I2/KI solution. The new method was compared with the traditional method of iodine titration and then used to measure the antioxidant capacity of urine samples from 30 diabetic patients and 30 healthy subjects. Results. A linear relationship was found between logarithm of concentration ratio of I2/KI and ORP (R2=0.998). Both vitamin C and urine concentration showed a linear relationship with ORP (R2=0.994 and 0.986, resp.). The precision of the method was in the acceptable range and results of two methods had a linear correlation (R2=0.987). Differences in ORP values between diabetic group and control group were statistically significant (P<0.05). Conclusions. A new method for measuring the antioxidant capacity of clinical urine has been established. [ABSTRACT FROM AUTHOR]