Free radical scavenging activities of verbascoside and isoverbascoside from the leaves of Odontonema strictum (Acanthaceae).

The aqueous extract of the leaves of Odontonema strictum, a plant from tropical regions, is used by traditional physicians in Burkina Faso for its antihypertensive properties. Verbascoside and isoverbascoside, known phenylpropanoid glycosides with high solubility in water, have been isolated from the leaves. We evaluated their antioxidant properties in vitro by radical scavenging using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydrogen peroxide (H2O2). Verbascoside and isoverbascoside demonstrated high levels of DPPH radical scavenging activity, with IC50 values of 0.09 ± 0.03 µg/mL and 0.16 ± 0.07 µg/mL, respectively, compared to 0.05 ± 0.0 µg/mL for ascorbic acid as a control. These two phenylpropanoid glycosides were also more potent (2.6 ± 0.36 µg/mL and 3.0 ± 0.01 µg/mL) in scavenging H2O2 than the ascorbic acid control (4.1 ± 0.97 µg/mL). This is the first time that the antioxidant properties of verbascoside and isoverbascoside from O. strictum have been evaluated. These results can explain the use of this plant for hypertension in folk medicine.

Formulation of liposomes loading lentisk oil to ameliorate topical delivery, attenuate oxidative stress damage and improve cell migration in scratch assay.

Pistacia lentiscus L. is a sclerophyllous shrub capable of growing under harsh climatic conditions especially in the Mediterranean Basin. Different products can be obtained from this plant, such as essential oil, mastic gum or even fixed oil. The last is well known for its flavor which is mainly exploited in the food industry. Additionally, it has been traditionally used in the treatment of skin diseases, but, at the moment, any suitable formulation for skin delivery has been formulated and its biological effects was not deeply confirmed. Given that, in the present study, the lentisk oil has been formulated in liposomes at different concentrations (10, 20, 30 mg/ml) and their physicochemical, technological and main biological properties have been evaluated. Vesicles were prepared by using natural soy lecithin and a green and organic solvent free method, thus obtaining spherical, small (~ 118 nm), homogeneously dispersed (0.27) and highly negatively charged (~ -62 mV) vesicles. The used amount of oil loaded in liposomes (10, 20, 30 mg/ml) modulated the penetration ability of vesicles in the skin, favoring the deposition of the payload in the deeper strata. The loading in the vesicles potentiated the ability of oil to counteract the damaging effects caused by hydrogen peroxide in keratinocytes and fibroblasts and facilitate their migration in a cell monolayer lesion. Overall findings suggested that the incorporation of lentisk oil in liposomes made from soy lecithin can be an alternative and natural approach to exploit it in pharmaceutical ad cosmetical applications and manufacturing natural products suitable for the treatment of skin lesions.

Curcumin-Coumarin Hybrid Analogues as Multitarget Agents in Neurodegenerative Disorders.

Neurodegenerative diseases have a complex nature which highlights the need for multitarget ligands to address the complementary pathways involved in these diseases. Over the last decade, many innovative curcumin-based compounds have been designed and synthesized, searching for new derivatives having anti-amyloidogenic, inhibitory of tau formation, as well as anti-neuroinflammation, antioxidative, and AChE inhibitory activities. Regarding our experience studying 3-substituted coumarins with interesting properties for neurodegenerative diseases, our aim was to synthesize a new series of curcumin-coumarin hybrid analogues and evaluate their activity. Most of the 3-(7-phenyl-3,5-dioxohepta-1,6-dien-1-yl)coumarin derivatives 11-18 resulted in moderated inhibitors of hMAO isoforms and AChE and BuChE activity. Some of them are also capable of scavenger the free radical DPPH. Furthermore, compounds 14 and 16 showed neuroprotective activity against H2O2 in SH-SY5Y cell line. Nanoparticles formulation of these derivatives improved this property increasing the neuroprotective activity to the nanomolar range. Results suggest that by modulating the substitution pattern on both coumarin moiety and phenyl ring, ChE and MAO-targeted derivatives or derivatives with activity in cell-based phenotypic assays can be obtained.

Evaluation of Antioxidative Mechanisms In Vitro and Triterpenes Composition of Extracts from Silver Birch (Betula pendula Roth) and Black Birch (Betula obscura Kotula) Barks by FT-IR and HPLC-PDA.

Silver birch, Betula pendula Roth, is one of the most common trees in Europe. Due to its content of many biologically active substances, it has long been used in medicine and cosmetics, unlike the rare black birch, Betula obscura Kotula. The aim of the study was therefore to compare the antioxidant properties of extracts from the inner and outer bark layers of both birch trees towards the L929 line treated with acetaldehyde. Based on the lactate dehydrogenase test and the MTT test, 10 and 25% concentrations of extracts were selected for the antioxidant evaluation. All extracts at tested concentrations reduced the production of hydrogen peroxide, superoxide anion radical, and 25% extract decreased malonic aldehyde formation in acetaldehyde-treated cells. The chemical composition of bark extracts was accessed by IR and HPLC-PDA methods and surprisingly, revealed a high content of betulin and lupeol in the inner bark extract of B. obscura. Furthermore, IR analysis revealed differences in the chemical composition of the outer bark between black and silver birch extracts, indicating that black birch may be a valuable source of numerous biologically active substances. Further experiments are required to evaluate their potential against neuroinflammation, cancer, viral infections, as well as their usefulness in cosmetology.

Investigation of the Active Ingredients and Mechanism of Polygonum cuspidatum in Asthma Based on Network Pharmacology and Experimental Verification.

BACKGROUND: Polygonum cuspidatum is a Chinese medicine commonly used to treat phlegm-heat asthma. However, its anti-asthmatic active ingredients and mechanism are still unknown. The aim of this study was to predict the active ingredients and pathways of Polygonum cuspidatum and to further explore the potential molecular mechanism in asthma by using network pharmacology. METHODS: The active ingredients and their targets related to Polygonum cuspidatum were seeked out with the TCM systematic pharmacology analysis platform (TCMSP), and the ingredient-target network was constructed. The GeneCards, DrugBank and OMIM databases were used to collect and screen asthma targets, and then the drug-target-disease interaction network was constructed with Cytoscape software. A target protein-protein interaction (PPI) network was constructed using the STRING database to screen key targets. Finally, GO and KEGG analyses were used to identify biological processes and signaling pathways. The anti-asthmatic effects of Polygonum cuspidatum and its active ingredients were tested in vitro for regulating airway smooth muscle (ASM) cells proliferation and MUC5AC expression, two main symptoms of asthma, by using Real-time PCR, Western blotting, CCK-8 assays and annexin V-FITC staining. RESULTS: Twelve active ingredients in Polygonum cuspidatum and 479 related target proteins were screened in the relevant databases. Among these target proteins, 191 genes had been found to be differentially expressed in asthma. PPI network analysis and KEGG pathway enrichment analysis predicted that the Polygonum cuspidatum could regulate the AKT, MAPK and apoptosis signaling pathways. Consistently, further in vitro experiments demonstrated that Polygonum cuspidatum and resveratrol (one active ingredient of Polygonum cuspidatum) were shown to inhibit ASM cells proliferation and promoted apoptosis of ASM cells. Furthermore, Polygonum cuspidatum and resveratrol inhibited PDGF-induced AKT/mTOR activation in ASM cells. In addition, Polygonum cuspidatum decreased H2O2 induced MUC5AC overexpression in airway epithelial NCI-H292 cells. CONCLUSION: Polygonum cuspidatum could alleviate the symptoms of asthma including ASM cells proliferation and MUC5AC expression through the mechanisms predicted by network pharmacology, which provides a basis for further understanding of Polygonum cuspidatum in the treatment of asthma.

Oat polyphenol avenanthramide-2c confers protection from oxidative stress by regulating the Nrf2-ARE signaling pathway in PC12 cells.

Accumulating evidence has demonstrated that cellular antioxidant systems play essential roles in retarding oxidative stress-related diseases, such as Parkinson's disease. Because nuclear factor erythroid 2-related factor 2 (Nrf2) is a chief regulator of cellular antioxidant systems, small molecules with Nrf2-activating ability may be promising neuroprotective agents. Avenanthramide-2c (Aven-2c), avenanthramide-2f (Aven-2f) and avenanthramide-2p (Aven-2p) are the most abundant avenanthramides in oats, and they have been documented to possess multiple pharmacological benefits. In this work, we synthesized these three compounds and evaluated their cytoprotective effect against oxidative stress-induced PC12 cell injuries. Aven-2c displayed the best protective potency among them. Aven-2c conferred protection on PC12 cells by scavenging free radicals and activating the Nrf2-ARE signaling pathway. Pretreatment of PC12 cells with Aven-2c efficiently enhanced Nrf2 nuclear accumulation and evoked the expression of a set of cytoprotective molecules. The mechanistic study also supports that Nrf2 activation is the molecular basis for the cellular action of Aven-2c. Collectively, this study demonstrates that Aven-2c is a potent Nrf2 agonist, shedding light on the potential usage of Aven-2c in the treatment of neuroprotective diseases.

Structural characterization and antioxidant activity of an acetylated Cyclocarya paliurus polysaccharide (Ac-CPP0.1).

The aim of this study was to investigate the primary structure of an acetylated Cyclocarya paliurus polysaccharide (Ac-CPP0.1) and its protective effect on H2O2-treated dendritic cells. The backbone of Ac-CPP0.1 was →3)-ß-D-Galp-(1→, with some branches α-L-Araf-(1→ residues at O-6 and O-5, ß-D-Galp-(1→ and 3,5,6)-ß-D-Galf-(1 residues at O-4 and acetyl groups were substituted at the O-2 and O-6 positions of 3)-ß-D-Galp-(1 residues. The CPP0.1 and Ac-CPP0.1 significantly increased the levels of superoxide dismutase, glutathione peroxidase and catalase on H2O2-treated dendritic cells. Meanwhile, both CPP0.1 and Ac-CPP0.1 up-regulated the expression of Nrf2 (NF-E2-related factor 2) and down-regulated the Keap1 (Kelch-like ECH-associated protein-1), but Ac-CPP0.1 had a better effect on antioxidant capacity. These results indicated that potential application of Ac-CPP0.1 as an antioxidant agent.

Separation of constituents from Bergenia stracheyi (Hook. F. & Thoms.) Engl. by high-speed countercurrent chromatography with elution mode and its antidiabetic and antioxidant in vitro evaluation.

Diabetes, a metabolic disorder, is caused by a high blood sugar level. Diabetes is an increasing health issue and search for potent antidiabetic agents is desirable. Owing to its ethnomedicinal value, the Himalayan perennial herb Bergenia stracheyi (Hook. f. & Thoms.) Engl. (Saxifragaceae Juss) is used to treat diabetes. Herein, an efficient high-speed countercurrent chromatography with elution mode is reported for separation of active compounds from B. stracheyi. In current investigation, six main compounds including ß-arbutin (1), bergenin (2), 6-O-galloylarbutin (3), gallic acid (4), 11-O-galloylbergenin (5), and (-)-epicatechin 3-O-gallate (6) with above 95% purity were efficiently separated in a single run using biphasic tert-butyl methyl ether/n-butanol/methanol/water (1:3:1:5, v/v/v/v) solvent system. The structures of these compounds were characterized using spectral techniques and compared with the literature. Antidiabetic and antioxidant activities evaluation of the study samples showed that ß-arbutin (1) and 6-O-galloylarbutin (3) have a significant protective effect, especially at high dose against hydrogen peroxide induced oxidative injury. Our results might help further in-depth phytochemical and biological evaluation studies in search of potent antidiabetic compounds from B. stracheyi.

Antioxidant activity and inhibition of ultraviolet radiation-induced skin damage of Selenium-rich peptide fraction from selenium-rich yeast protein hydrolysate.

The bioactive peptides and trace element selenium (Se) both have good antioxidant activity. However, whether combined Se and bioactive peptides have more excellent antioxidant activity remain unknown. The aim of this study is to prepare a Se-rich peptide fraction containing both Se and peptides from Se-rich yeast protein hydrolysate and investigated its antioxidant activity and effect on ultraviolet B (UVB) radiation-induced skin oxidative damage. The peptide fractions with different molecular weight (MW) and Se content were obtained by enzymatically hydrolyzing normal or Se-rich yeast proteins followed by a filtration process. In vitro free radical scavenging and lipid peroxidation inhibition assays showed that Se-rich peptides fraction with lower MW of <1 kDa (sSeP) had the highest antioxidant activity compared with Se-rich peptide fractions with higher MW of <3 kDa or normal peptide fractions. Oral administration of sSeP significantly decreased the level of malonaldehyde (MDA) in liver and serum, and increased the activity of glutathione peroxidase (GPx) in liver and serum in normal mice. When topically applied on the dorsal skin of mice, sSeP effectively alleviate UVB radiation-induced skin damage and oxidative stress by increasing GPx and catalase activities and glutathione content in skin or serum. Furthermore, sSeP showed a protective effect against H2O2-induced cytotoxicity in cultured human epidermal keratinocytes (HaCaT) cells probably by increasing aquaporin-3 expression and attenuating the phosphorylation of p38 MAPK. Overall, the results showed that Se-rich yeast peptide fraction containing Se and bioactive peptides could be a promising antioxidant nutrient used as food additive to enhance the body's antioxidant ability or as cosmeceutical product to minimize the skin oxidative damage.

Enteromorpha compressa extract induces anticancer activity through apoptosis and autophagy in oral cancer.

Marine algae are an auspicious source of innovative bioactive compounds containing possible therapeutic agents against mammalian cancers. However, the mechanism by which bioactive algal compounds exhibit anticancer activity against oral squamous cell carcinoma (OSCC) is scant. The main objective of the current study was to explore the properties of the Enteromorpha compressa solvent extracts that induced autophagy and apoptosis with reference to their potent phytochemical and antioxidant properties. The presence of bioactive compounds were confirmed by UV and FT-IR spectroscopy. The free radical scavenging activity were analyzed by evaluating H2O2, DPPH, superoxide and hydroxyl activity. The anticancer activities of the extracts were investigated by employing clonogenic and scratch assay. The apoptosis potential was evaluated by DAPI and MMP by Rh123 fluorescence assay. Moreover, the CAT, SOD, GPX, APX, and GR activities were measured. The autophagy potential was evaluated by LC3 puncta formation, acridine orange in addition to LysoTracker staining. The present investigation revealed that the methanolic extract of E. compressa elicited robust free radical scavenging activity that discerns its antiproliferative potency. Moreover, the methanolic algal extract boosted intrinsic apoptosis against OSCC by downregulating protective antioxidant enzymes. Furthermore, it also revealed induction of autophagy to promote cell death in oral cancer cells. The presence of novel bioactive compounds in E. compressa has uncovered possible therapeutic value against OSCC by modulating antioxidant defense system, apoptosis and autophagy that could be used to explore very competent algal candidates for the development of potential alternative anticancer drugs.

Comparative investigation of phytochemicals among ten citrus herbs by ultra high performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry and evaluation of their antioxidant properties.

The citrus herbs have proved their important medicinal and nutritional values as medicine-food dual-purpose herbs, functional foods, or medical herbs in China. In this study, phytochemicals and antioxidant activity among ten typical citrus herbs (ethanol extracts) were investigated comprehensively. The major ingredients and their contents were analyzed by high-resolution mass spectrometry, and the differences of typical fragment ions between flavanone-7-O-rutinoside(s) and flavanone-7-O-neohesperidoside(s) were discriminated properly in negative electrospray ionization mode. Total polyphenols, total flavonoids, 1,1-diphenyl-2-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), and ferric reducing antioxidant power tests were performed, which indicated their beneficial values and antioxidant effects. The medicine-food dual-purpose herbs including Chenpi, Juluo, Daidaihua, Huajuhong, Xiangyuan, and Foshou exhibited antioxidant capacities significantly by decreasing intracellular reactive oxygen species intensity (P < 0.01), enhancing superoxide dismutase, catalase, and glutathione peroxidase activities (P < 0.01) in H2 O2 -induced RIN-m5F cells. Moreover, the functional foods Zhishi, Zhiqiao, and Qingpi showed moderate antioxidant bioactivity, while the medical herb Juhe showed weak antioxidant bioactivity, which were consistent with the multivariate analysis of their major flavonoids. The study provided a new sight for the chemical differentiation and practical application of citrus herbs as medicine-food dual-purpose herbs, functional foods, or medical herbs.

Decreasing angiogenesis vasa vasorum through Lp-PLA2 and H2O2 inhibition by PSP from Ganoderma lucidum in atherosclerosis: in vivo diabetes mellitus type 2.

Background Type 2 diabetes mellitus (T2DM) is a major risk factor of atherosclerosis. Hyperglycemia in T2DM causes advanced formation of glycation end products (AGE) which leads to oxidative stress and chronic inflammation. Oxidative stress occurs due to increased levels of reactive oxygen species (ROS) such as H2O2. On the other hand, lipoprotein-associated phospholipase (Lp-PLA2) has pro-inflammatory effects, which cause instability of atherosclerosis plaques. This condition causes hypoxemic cells to stimulate HIFα induced vasa vasorum angiogenesis. This study aims to understand the potential of PSP as an anti-angiogenic agent through decreased levels of H2O2 and Lp-PLA2 leading to the decline of vasa vasorum angiogenesis in diabetic rat model. In addition, this study also measured the lipid profile of diabetic rat model in relation to vasa vasorum angiogenesis. Methods True laboratory experiment with randomized post-test control of group design using 25 wistar rats (Rattus norvegicus) were divided into five groups; one normal group and four group with High Fat Diet (HFD) and low dose streptozotocin (30 mg/kgBW) injection sc, treated with placebo and three various doses of PSP 50, 150, 300 mg/kgBW. Results ANOVA test (p < 0.05) shows that there is a significant influence of polysaccharide peptide (PSP) feeding on the decreased amount of vasa vasorum angiogenesis (p = 0.00), lipid profile (cholesterol total and triglyceride; p = 0.01, p = 0.001), and amount of H202 (p = 0.003). The amount of Lp-PLA2 declined to (p = 0.184). This result indicates that PSP prevents inflammation in atherosclerosis. Conclusions PSP of Ganoderma lucidum is an anti-angiogenic agent in T2DM.

Preparation and in vitro antioxidant activity of some novel flavone analogues bearing piperazine moiety.

BACKGROUND: A series of eight new flavone derivatives containing a piperazine chain with different substitution were synthesized and their structures were determined. METHODS: Their antiradical and antioxidant activities were evaluated using superoxide anion radical, hydroxyl radical, 2,2-diphenyl-1-picrylhydrazyl radical, 2,2'-azino-di(3-ethylbenzthiazoline sulphonate) radical cation (ABTS+) scavenging (as measure total antioxidant status TAS), ferric reducing antioxidant power (TAC), and hydrogen peroxide decomposition. The antioxidant activities of the synthesized compounds were compared with standard antioxidants trolox, ascorbic acid, butylated hydroxytoluene (BHT) as positive controls, reference antibiotics (doxycycline, dicloxacillin), and medicinal plants (Menthae piperita, Cistus incanus). Chemiluminescence, spectrophotometry, electron spin resonance (ESR) spectroscopy in conjunction with 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) as the spin trap were the measurement techniques. RESULTS: The results show that the synthesized compounds exhibit weak, albeit a wide spectrum of antiradical and antioxidant activities. The TAS values were measured as trolox equivalents, ranging from 209.6 ± 6.1 to 391.1 ± 8.2 µM TE/g; the TAC values were in ranges from 10.8 ± 0.5 to 49.5 ± 0.5 µM TE/g being higher than that of dicloxacillin (241.0 ± 16.5 and 9.73 ± 0.8 µM TE/g, respectively), but lower than ascorbic acid, BHT, doxycycline, and medicinal plants. Best antioxidant activities were found for the piperazinyl analogues with methoxy group on phenyl piperazine ring. CONCLUSION: We suggest that the synthesized compounds may be used as lead molecules for optimization of molecular structure to maximize the antioxidant potency.

Safety evaluation and protective effects of ethanolic extract from maca (Lepidium meyenii Walp.) against corticosterone and H2O2 induced neurotoxicity.

Maca has been traditionally used to enhance sexual behavior and fertility. Recently, maca's neuroprotective effects have been reported. The purpose of this study was to investigate whether the ethanol extract of maca (EEM) (100 mg/kg/bw, 200 mg/kg/bw, 400 mg/kg/bw, p.o.) exerted neuroprotective effects in corticosterone (CORT)-induced (40 mg/kg/bw, s.c.) rats, to determine the neuroprotective effects of EEM (12.5, 25, 50 µg/ml) and macamides in H2O2-induced (50 µM) PC12 cells. The acute toxicity (2000 mg/kg/bw, p.o.) and subacute toxicity (200 mg/kg/bw, 500 mg/kg/bw, 1000 mg/kg/bw, p.o.) of EEM were evaluated by mouse models. EEM reversed CORT-induced abnormal behaviors, reduced the contents of TNF-α, IL-6 in hippocampi, and increased the positive cells of doublecortin (DCX), bromodeoxyuridine (BrdU) and DCX + BrdU in the hippocampus of rats. Moreover, EEM and 4 macamides remarkably increased the cell viability in H2O2-induced PC12 cells. EEM promoted the phosphorylation of IκBα and p65, suppressed the NF-κB activation, and inhibited the levels of pro-inflammatory cytokines such as TNF-α, IL-6 and their mRNA levels in H2O2-induced PC12 cells. In conclusion, EEM could exert neuroprotective effects in CORT-induced rats and in H2O2-induced PC12 cells. Moreover, EEM did not present relevant toxicity after exposure to single and repeated doses.

Protective and Modulatory Effects of Trapa bispinosa and Trigonella foenum-graecum on Neuroblastoma Cells Through Neuronal Nitric Oxide Synthase.

The fruits of Trapa bispinosa (TB) and seeds of Trigonella foenum-graecum (TF) are used for their nutraceutical properties in various systems of traditional medicine practiced in India. In this study aqueous and methanolic extracts of TB fruits and TF seeds were prepared and their protective effect was studied on hydrogen peroxide (H2O2)-treated neuroblastoma (NB-41) cell line. Cell viability, nitric oxide (NO) levels, mRNA, and protein profiles were analyzed and compared with untreated control. Results show that aqueous extracts of both TB and TF provide significant protection to neuroblastoma cells with TF aqueous extract offering better protection through upregulation of neuronal nitric oxide synthase (nNOS) against hydrogen peroxide generated stress. This is the first report demonstrating protection of neuronal cell lines by use of TB and TF extracts through modulation of nNOS activity.

Protective effects of five compounds from Livistona chinensis R. Brown leaves against hypoxia/reoxygenation, H2O2, or adriamycin-induced injury in H9c2 cells.

Purpose: Discovering new antimyocardial ischemia drug candidates that are highly efficient, have low toxicity, and originate from natural products is a popular trend for new cardiovascular drug development at present. The ethanol extract of Livistona chinensis leaves showed a favorable antioxidant activity in our preliminary screening test. This study aims to screen out antioxidants from the herb leaves further and evaluate their efficacy in acute myocardial ischemia treatment at the cellular level. Materials and methods: Guided with online 1, 1-diphenyl-2-picrylhydrazyl (DPPH)-high-performance liquid chromatography (HPLC) screening, antioxidants were first separated and isolated from the ethanol extract of L. chinensis leaves by preparative-HPLC. Subsequently, offline DPPH approach was used to validate the free radical scavenging activity of the components. Ultimately, the resulting antioxidants were evaluated against the hypoxia/reoxygenation (H/R)-, H2O2-, or adriamycin (ADM)-induced injury in H9c2 cells to verify their cardioprotective effects in vitro. Results: Five antioxidant ingredients, namely, orientin, isoorientin, vitexin, isovitexin, and tricin, were quickly distinguished and isolated from L. chinensis leaves. The IC50 values of these ingredients were further examined by offline DPPH assay, as follows: 15.51±0.22, 6.64±0.38, 11.86±0.24, 8.89±0.66, and 31.86±0.24 µg/mL, respectively. Out of these ingredients, isoorientin showed the strongest antioxidation, which was equivalent to that of the positive control drug (vitamin C, IC50: 6.99±0.62 µg/mL). Using H/R-, H2O2-, and ADM-induced H9c2 cell injury models, the five ingredients had different extents of cardioprotective effects in vitro. In particular, isoorientin showed the strongest protection. All the five ingredients also showed insignificant cytotoxic effect to normal H9c2 cells. Conclusion: The ethanol extract of L. chinensis leaves contained five antioxidants with low cardiac cytotoxicity. Isoorientin possessed the strongest antioxidation, which can predominantly account for the myocardial protection effects within the extract.

Qiliqiangxin Attenuates Oxidative Stress-Induced Mitochondrion-Dependent Apoptosis in Cardiomyocytes via PI3K/AKT/GSK3ß Signaling Pathway.

Qiliqiangxin capsule (QLQX) is a well-known traditional Chinese medicine that exhibits cardioprotective effects in heart failure patients. However, it remains unclear whether and by which mechanism QLQX attenuates oxidative stress-induced mitochondria-dependent myocardial apoptosis. In vivo, Sprague Dawley (SD) rats received left anterior descending coronary artery ligation for 4 weeks to establish a model of heart failure after acute myocardial infarction, and then were treated with QLQX for another 4 weeks. We evaluated cardiac function, oxidative stress injury, as well as the expressions of mitochondria-dependent apoptosis and its signaling factors. The results indicated that QLQX protected cardiac function and attenuated oxidative stress-induced myocardial apoptosis. Meanwhile, QLQX elevated the Bcl-2 expression, declined the expressions of Bax, cytochrome c, apoptotic protease activating factor-1 (Apaf-1), cleaved-caspase 9 and cleaved-caspase 3, and up-regulated the ratios of phospho-AKT/AKT and phospho-glycogen synthase kinase-3ß (GSK3ß)/GSK3ß. In vitro, H9c2 cardiomyocytes were pretreated with QLQX, then exposed to H2O2 for 24 h. QLQX promoted the proliferation of H9c2 cardiomyocytes induced by H2O2 and reversed oxidative stress damage. Moreover, QLQX inhibited the apoptosis rate and the pro-apoptosis protein expressions, but improved the Bcl-2 expression as well as the ratios of phospho-AKT/AKT and phospho-GSK3ß/GSK3ß. Meanwhile, it further ameliorated mitochondrion-related apoptosis by inhibiting the mitochondrial fission, mitochondrial permeability transition pore (MPTP) opening, and mitochondrial membrane potential (MMP) decline in H9c2 cardiomyocytes induced by H2O2. In addition, all the effects of QLQX on H2O2-induced mitochondria-dependent apoptosis could be blocked by the phosphoinositide 3-kinase (PI3K) inhibitor, LY294002. We conclude that QLQX may ameliorate oxidative stress-induced mitochondria-dependent apoptosis in cardiomyocytes through PI3K/AKT/GSK3ß signaling pathway.

Protective effect of myricetin derivatives from Syzygium malaccense against hydrogen peroxide-induced stress in ARPE-19 cells.

Purpose: Oxidative stress is implicated in the etiology of diabetes and its debilitating complications, such as diabetic retinopathy (DR). Various flavonoids have been reported to be useful in reducing DR progression. Myricetin derivatives (F2) isolated from leaf extract of Syzygium malaccense have the potential to serve as functional food as reported previously. The present study was performed with the aim of determining the antioxidant potential and protective effect of myricetin derivatives (F2) isolated from leaf extract of S. malaccense against glucose oxidase (GO)-induced hydrogen peroxide (H2O2) production that causes oxidative stress in ARPE-19 (RPE) cells. Methods: Antioxidant properties were assessed through various radical (DPPH, ABTS, and nitric oxide) scavenging assays and determination of total phenolic content and ferric reducing antioxidant power level. ARPE-19 cells were preincubated with samples before the addition of GO (to generate H2O2). Cell viability, change in intracellular reactive oxygen species (ROS), H2O2 levels in cell culture supernatant, and gene expression were assessed. Results: F2 showed higher antioxidant levels than the extract when assessed for radical scavenging activities and ferric reducing antioxidant power. F2 protected the ARPE-19 cells against GO-H2O2-induced oxidative stress by reducing the production of H2O2 and intracellular reactive oxygen species. This was achieved by the activation of nuclear factor erythroid 2-related factor 2 (Nrf2/NFE2L2) and superoxide dismutase (SOD2), as well as downregulation of nitric oxide producer (NOS2) at the transcriptional level. Conclusions: The results showed that myricetin derivatives from S. malaccense have the capacity to exert considerable exogenous antioxidant activities and stimulate endogenous antioxidant activities. Therefore, these derivatives have excellent potential to be developed as therapeutic agents for managing DR.

Baicalein protects human vitiligo melanocytes from oxidative stress through activation of NF-E2-related factor2 (Nrf2) signaling pathway.

Vitiligo is a complex disorder characterized by patchy loss of skin pigmentation due to abnormal melanocyte function. Overwhelming evidences have suggested that oxidative stress plays a major role in the loss of melanocytes thereby mediating the onset and progression of vitiligo. The nuclear factor erythroid 2-like factor 2 (Nrf2) is a master regulator of cellular redox homeostasis and the activation of Nrf2 signaling pathway is impaired in the vitiligo melanocytes. Baicalein, as flavonoid extracted from the Scutellaria baicalensis, has been proved to possess the ability to activate Nrf2 signaling pathway in other cell types and mouse model. Our previous data found that baicalein exerts a cytoprotective role in H2O2-induced apoptosis in human melanocytes cell line (PIG1). Based on these founding, we hypothesized that baicalein activates Nrf2 signaling pathway, alleviates H2O2-induced mitochondrial dysfunction and cellular damage, thereby protecting human vitiligo melanocytes from oxidative stress. In the present study, we found that baicalein effectively inhibited H2O2-induced cytotoxicity and apoptosis in human vitiligo melanocytes (PIG3V). Further results demonstrated that baicalein promoted Nrf2 nucleus translocation as well as up-regulated the expression of Nrf2 and its target gene, heme oxygenase-1 (HO-1). Moreover, the protective effects of baicalein against H2O2-induced cellular damage and apoptosis as well as mitochondrial dysfunction were abolished by Nrf2 knockdown. Additionally, we observed that Nrf2 knockdown suppressed proliferation and increased the sensitivity of PIG3V cells to H2O2 treatment. Finally, we explored the mechanism of baicalein associated with Nrf2 activation and found that the phosphorylation of Nrf2 as well as ERK1/2and PI3K/AKT signaling were not involved in the baicalein-induced activation of Nrf2. Taken together, these data clearly suggest that baicalein enhances cellular antioxidant defense capacity of human vitiligo melanocytes through the activation of the Nrf2 signaling pathway, providing beneficial evidence for the application of baicalein in the vitiligo treatment.

Physicochemical Characterization, Antioxidant and Immunostimulatory Activities of Sulfated Polysaccharides Extracted from Ascophyllum nodosum.

Polysaccharides from Ascophyllum nodosum (AnPS) were extracted and purified via an optimized protocol. The optimal extraction conditions were as follows: extraction time of 4.3 h, extraction temperature of 84 °C and ratio (v/w, mL/g) of extraction solvent (water) to raw material of 27. The resulting yield was 9.15 ± 0.23% of crude AnPS. Two fractions, named AnP1-1 and AnP2-1 with molecular weights of 165.92 KDa and 370.68 KDa, were separated from the crude AnPS by chromatography in DEAE Sepharose Fast Flow and Sephacryl S-300, respectively. AnP1-1 was composed of mannose, ribose, glucuronic acid, glucose and fucose, and AnP2-1 was composed of mannose, glucuronic acid, galactose and fucose. AnPS, AnP1-1 and AnP2-1 exhibited high scavenging activities against ABTS radical and superoxide radical, and showed protective effect on H2O2-induced oxidative injury in RAW264.7 cells. Furthermore, the immunostimulatory activities of AnP1-1 and AnP2-1 were evaluated by Caco-2 cells, the results showed both AnP1-1 and AnP2-1 could significantly promote the production of immune reactive molecules such as interleukin (IL)-8, IL-1ß, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α. Therefore, the results suggest that AnPS and its two fractions may be explored as a potential functional food supplement.