H2O2-induced Oxidative Damage Research Articles

New Insight into the Potential Protective Function of Sulforaphene against ROS-Mediated Oxidative Stress Damage In Vitro and In Vivo.

Sulforaphene (SFE) is a kind of isothiocyanate isolated from radish seeds that can prevent free-radical-induced diseases. In this study, we investigated the protective effect of SFE on oxidative-stress-induced damage and its molecular mechanism in vitro and in vivo. The results of cell experiments show that SFE can alleviate D-gal-induced cytotoxicity, promote cell cycle transformation by inhibiting the production of reactive oxygen species (ROS) and cell apoptosis, and show a protective effect on cells with H2O2-induced oxidative damage. Furthermore, the results of mice experiments show that SFE can alleviate D-galactose-induced kidney damage by inhibiting ROS, malondialdehyde (MDA), and 4-hydroxyalkenals (4-HNE) production; protect the kidney against oxidative stress-induced damage by increasing antioxidant enzyme activity and upregulating the Nrf2 signaling pathway; and inhibit the activity of pro-inflammatory factors by downregulating the expression of Toll-like receptor 4 (TLR4)-mediated inflammatory response. In conclusion, this research shows that SFE has antioxidant effects, providing a new perspective for studying the anti-aging properties of natural compounds.

5-(3′,4′-dihydroxyphenyl)-γ-valerolactone, a microbiota metabolite of flavan-3-ols, activates SIRT1-mediated autophagy to attenuate H₂O₂-induced inhibition of osteoblast differentiation in MC3T3-E1 cells

Phenolic compounds are promising agents for the prevention of osteoporosis. 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone (DHPV) is the major microbiota metabolite of the flavan-3-ols phenolic compound. Herein, we aimed to investigate the potential mechanisms underlying the effects of DHPV on an osteoblast cell model with H2O2-induced oxidative injury. The MC3T3-E1 cell cultured with H2O2 was used as an oxidative injury model after pretreating with DHPV. Pretreatment with DHPV significantly attenuated cell viability decline, enhanced the activity of alkaline phosphatase and mineralization capacity in MC3T3-E1 cells. Reduced reactive oxygen species (ROS) and malondialdehyde (MDA) levels as well as increased in mitochondrial membrane potential and superoxide dismutase (SOD) activities indicated that DHPV affected both the oxidative and antioxidative processes in the cells. DHPV administration increased the LC3-II/I ratio and Beclin-1 protein levels, thereby promoting autophagy, which perhaps contributes to ROS elimination. However, the inhibition of Sirtuin 1 (SIRT1) by SIRT1 small interfering RNA reduced the protective effect of DHPV or SRT1720, as revealed by the increased ROS and MDA levels and decreased SOD, LC3-II/I ratio and Beclin-1 levels. DHPV may promote autophagy and reduce oxidative stress through the SIRT1-mediated pathway, thereby protecting MC3T3-E1 cells from H2O2-induced oxidative damage.

Exosomes secreted by mesenchymal stem cells delay brain aging by upregulating SIRT1 expression

The increase in the aging population has seriously affected our society. Neurodegenerative diseases caused by aging of the brain significantly impact the normal life of the elderly, and delaying brain aging is currently the focus of research. SIRT1 is a viable therapeutic target, and there is mounting evidence that it plays a significant role in the aging process. Mesenchymal stem cell-derived exosomes (MSC-Exos) have gained widespread interest as nanotherapeutic agents because of their ability to be injected at high doses to reduce the immune response. The present study focused on the ameliorative effect of MSC-Exos on aging mice and the potential mechanisms of this effect on cognitive impairment and brain aging. In this study, we first tested the neuroprotective effects of MSC-Exos in vitro on H2O2-induced oxidative damage in BV2 cells. An in vivo SAMP8 rapid senescence mouse model showed that MSC-Exos significantly increased SIRT1 gene expression in senescent mice. In addition, MSC-Exos also had an anti-apoptotic effect and reduced oxidative stress in the brains of SAMP8 senescent mice. In conclusion, MSC-Exos may exert neuroprotective effects and help prevent brain senescence in SAMP8 mice by activating the SIRT1 signaling pathway.

Neuroprotective effects of idebenone on hydrogen peroxide-induced oxidative damage in retinal ganglion cells-5.

To investigate the neuroprotective effect of idebenone against hydrogen peroxide (H2O2)-induced oxidative damage in retinal ganglion cells-5 (RGC-5 cells). RGC-5 cells were pre-treated with various idebenone concentrations (5, 10, and 20µM) for 12h and were then subjected to 300µM H2O2 for a further 12h. Apoptosis in RGC-5 was measured by flow cytometry. The changes of mitochondrial membrane potential (MMP) were detected by JC-1 staining. Autophagy in RGC-5 cells was observed by transmission electron microscopy. Western blots were used to measure the expression of autophagy-related protein light chain 3 (LC3), Beclin-1, and the release of Cytochrome c (Cyt-c). Flow cytometry showed that the apoptosis rates in the normal control group, H2O2 group, and idebenone groups were 6.48 ± 0.55%, 27.3 ± 0.51%, 22.8 ± 0.52%, 15.45 ± 0.81%, and 12.59 ± 0.58%, respectively (F = 559.7, P < 0.0001). After incubation with H2O2, the number of autophagosomes increased significantly, whereas it was decreased in the idebenone groups. After incubation of RGC-5 cells with H2O2, MMP levels were significantly decreased, while idebenone could prevent the decrease in MMP levels. Compared with that in the normal control group, LC3 II/I, the expression levels of Beclin-1 and Cyt-c were increased significantly in the H2O2 group (P < 0.05). Compared with that in the H2O2 group, LC3 II/I, the expression of Beclin-1 and Cyt-c was significantly decreased in idebenone groups (P < 0.05). Idebenone protects RGC-5 cells against H2O2-induced oxidative damage by reducing mitochondrial damage and autophagic activity.

Proteomic and Mutant Analysis of Hydrogenase Maturation Protein Gene hypE in Symbiotic Nitrogen Fixation of Mesorhizobium huakuii.

Hydrogenases catalyze the simple yet important redox reaction between protons and electrons and H2, thus mediating symbiotic interactions. The contribution of hydrogenase to this symbiosis and anti-oxidative damage was investigated using the M. huakuii hypE (encoding hydrogenase maturation protein) mutant. The hypE mutant grew a little faster than its parental 7653R and displayed decreased antioxidative capacity under H2O2-induced oxidative damage. Real-time quantitative PCR showed that hypE gene expression is significantly up-regulated in all the detected stages of nodule development. Although the hypE mutant can form nodules, the symbiotic ability was severely impaired, which led to an abnormal nodulation phenotype coupled to a 47% reduction in nitrogen fixation capacity. This phenotype was linked to the formation of smaller abnormal nodules containing disintegrating and prematurely senescent bacteroids. Proteomics analysis allowed a total of ninety differentially expressed proteins (fold change > 1.5 or <0.67, p < 0.05) to be identified. Of these proteins, 21 are related to stress response and virulence, 21 are involved in transporter activity, and 18 are involved in energy and nitrogen metabolism. Overall, the HypE protein is essential for symbiotic nitrogen fixation, playing independent roles in supplying energy and electrons, in bacterial detoxification, and in the control of bacteroid differentiation and senescence.

Hepatoprotective effect of cyanidin-3-O-glucoside–lauric acid ester against H2O2-induced oxidative damage in LO2 cells

Hepatoprotective effect of cyanidin-3-O-glucoside–lauric acid ester against H2O2-induced oxidative damage in LO2 cells

Cath-DM-NT, a peptide derived from the skin of Duttaphrynus melanostictus, shows dual lectin-like and antioxidant activity

Chansu, a mixture extracted from Duttaphrynus melanostictus or Bufo gargarizans Cantor, is a traditional Chinese medicine with a broad range of medical applications. However, the peptides/proteins in it have not received adequate attention. Herein, a Cathelicidin-DM-derived peptide named Cath-DM-NT was identified from the skin of D. melanostictus. Previous studies have shown that Cathelicidin-DM has significant antibacterial activity, while Cath-DM-NT has no antibacterial activity. In this study, Cath-DM-NT is found to have lectin-like activity which can agglutinate erythrocytes and bacteria, and bind to lipopolysaccharide (LPS). In addition, Cath-DM-NT has antioxidant activity, which can scavenge 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), 1,1-diphenyl-2-picrylhydrazyl (DPPH), and nitric oxide (NO) radicals and reduce Fe3+. Consistently, Cath-DM-NT can protect PC12 cells from H2O2-induced oxidative damage and carrageenan-induced paw edema, reduce malondialdehyde (MDA) and reactive oxygen species (ROS) accumulation, and restore superoxide dismutase (SOD) and glutathione (GSH) levels. Our study suggests that Cath-DM-NT can serve as a lead compound for the development of drugs with dual lectin and antioxidant effects.

Mechanism of action of platinum nanoparticles implying from antioxidant to metabolic programming in light-induced retinal degeneration model

Photoreceptors (PRs) degeneration is central to visual impairment and loss in most blind retinal diseases, including age-related macular disease (AMD) and diabetic retinopathy (DR). PRs are susceptible to oxidative stress owing to their unique metabolic features. Accumulating evidence has demonstrated that the targeting oxidative stress is a promising treatment strategy for PR degeneration. Herein, we introduced potent antioxidative platinum nanoparticles (Pt NPs) to treat PRs degeneration in this study. The Pt NPs exhibited multi-enzymatic antioxidant activity and protected PRs from H2O2-induced oxidative damage in vitro assays. Based on the same mechanism, the intravitreal injection of Pt NPs significantly reduced cell apoptosis, maintained retinal structure and preserved retinal function in a mouse model of light-induced retinal degeneration (LIRD). Most importantly, the results of RNA sequencing showed that the transcription of antioxidative genes was upregulated, and metabolic reprogramming occurred in the LIRD-retina after treatment with Pt NPs, both of which benefited retinal survival from oxidative damage. The results indicated that Pt NPs were indeed potent therapeutic candidates for PRs degeneration in blind retinal diseases.

Persulfidation of mitoKv7.4 channels contributes to the cardioprotective effects of the H2S-donor Erucin against ischemia/reperfusion injury

BackgroundHydrogen sulfide (H2S) is a gasotransmitter deeply involved in cardiovascular homeostasis and implicated in the myocardial protection against ischemia/reperfusion. The post-translational persulfidation of cysteine residues has been identified as the mechanism through which H2S regulates a plethora of biological targets. Erucin (ERU) is an isothiocyanate produced upon hydrolysis of the glucosinolate glucoerucin, presents in edible plants of Brassicaceae family, such as Eruca sativa Mill., and it has emerged as a slow and long-lasting H2S-donor. AimIn this study the cardioprotective profile of ERU has been investigated and the action mechanism explored, focusing on the possible role of the recently identified mitochondrial Kv7.4 (mitoKv7.4) potassium channels. ResultsInterestingly, ERU showed to release H2S and concentration-dependently protected H9c2 cells against H2O2-induced oxidative damage. Moreover, in in vivo model of myocardial infarct ERU showed protective effects, reducing the extension of ischemic area, the levels of troponin I and increasing the amount of total AnxA1, as well as co-related inflammatory outcomes. Conversely, the pre-treatment with XE991, a blocker of Kv7.4 channels, abolished them. In isolated cardiac mitochondria ERU exhibited the typical profile of a mitochondrial potassium channels opener, in particular, this isothiocyanate produced a mild depolarization of mitochondrial membrane potential, a reduction of calcium accumulation into the matrix and finally a flow of potassium ions. Finally, mitoKv7.4 channels were persulfidated in ERU-treated mitochondria. ConclusionsERU modulates the cardiac mitoKv7.4 channels and this mechanism may be relevant for cardioprotective effects.

18-α-glycyrrhetinic acid alleviates oxidative damage in periodontal tissue by modulating the interaction of Cx43 and JNK/NF-κB pathways.

Objective: Periodontitis is a common chronic inflammatory disease in which oxidative stress is one of the key pathogenic factors. Connexin43 (Cx43) is the most critical and widely distributed connexin isoform. When the organism undergoes a severe and sustained stress response, Cx43-mediated gap junctions (GJs) are believed to underlie the biology of tissue injury exacerbation and amplification. Notably, 18-α-glycyrrhetinic acid (GA) is a classical pharmacological inhibitor of GJs and has antioxidant potential. However, the regulatory role of GA in the redox signaling of periodontal tissues and the potential mechanisms of Cx43 in the pathogenesis of periodontitis remain uncertain. Methods: In this study, we evaluated the effects and mechanisms of GA in alleviating oxidative damage of periodontal tissues and cells by constructing an H2O2-induced oxidative stress model in human periodontal ligament cells (hPDLCs) and a periodontitis model in rats. Results: Cellular experiments showed that GA effectively attenuated H2O2-induced oxidative damage in hPDLCs by inhibiting the expression and function of Cx43. In addition, pretreatment of hPDLCs with either GA or SP600125 (a JNK inhibitor) inhibited the Cx43/JNK/NF-κB pathway, restored cell viability, and reduced apoptosis. Animal experiment results showed that GA intervention reduced alveolar bone resorption and periodontal tissue destruction, inhibited osteoclast differentiation, improved mitochondrial structural abnormalities and dysfunction in periodontal tissue, and decreased oxidative stress levels and apoptosis in rats with periodontitis. Conclusion: Overall, our findings suggest that the Cx43/JNK/NF-κB pathway may play a vital role to promote periodontitis progression, while GA reduces oxidative stress and apoptosis by inhibiting the interaction of Cx43 and JNK/NF-κB pathways, thus alleviating oxidative damage in the periodontal tissues.

Bezafibrate reduces the damage, activation and mechanical properties of lung fibroblast cells induced by hydrogen peroxide.

In pulmonary fibrosis, the proliferation of fibroblasts and their differentiation into myofibroblasts is often caused by tissue damage, such as oxidative damage caused by reactive oxygen species, which leads to progressive rupture and thus destruction of the alveolar architecture, resulting in cell proliferation and tissue remodeling. Bezafibrate (BZF) is an important member of the peroxisome proliferator-activated receptor (PPARs) family agonists, used in clinical practice as antihyperlipidemic. However, the antifibrotic effects of BZF are still poorly studied. The objective of this study was to evaluate the effects of BZF on pulmonary oxidative damage in lung fibroblast cells. MRC-5 cells were treated with hydrogen peroxide (H2O2) to induce oxidative stress activation and BZF treatment was administered at the same moment as H2O2 induction. The outcomes evaluated were cell proliferation and cell viability; oxidative stress markers such as reactive oxygen species (ROS), catalase (CAT) levels and thiobarbituric acid reactive substances (TBARS); col-1 and α-SMA mRNA expression and cellular elasticity through Young's modulus analysis evaluated by atomic force microscopy (AFM). The H2O2-induced oxidative damage decreased the cell viability and increased ROS levels and decreased CAT activity in MRC-5 cells. The expression of α-SMA and the cell stiffness increased in response to H2O2 treatment. Treatment with BZF decreased the MRC-5 cell proliferation, ROS levels, reestablished CAT levels, decreased the mRNA expression of type I collagen protein (col-1) and α-smooth muscle actin (α-SMA), and cellular elasticity even with H2O2 induction. Our results suggest that BZF has a potential protective effect on H2O2-induced oxidative stress. These results are based on an in vitro experiment, derived from a fetal lung cell line and may emerge as a possible new therapy for the treatment of pulmonary fibrosis.

Mitochondrial-targeted and ROS-responsive nanocarrier via nose-to-brain pathway for ischemic stroke treatment

Oxidative stress injury and mitochondrial dysfunction are major obstacles to neurological functional recovery after ischemic stroke. The development of new approaches to simultaneously diminish oxidative stress and resist mitochondrial dysfunction is urgently needed. Inspired by the overproduced reactive oxygen species (ROS) at ischemic neuron mitochondria, multifunctional nanoparticles with ROS-responsiveness and mitochondrial-targeted (SPNPs) were engineered, achieving specific targeting delivery and controllable drug release at ischemic penumbra. Due to the nose-to-brain pathway, SPNPs which were encapsulated in a thermo-sensitive gel by intranasal administration were directly delivered to the ischemic penumbra bypassing the blood‒brain barrier (BBB) and enhancing delivery efficiency. The potential of SPNPs for ischemic stroke treatment was systematically evaluated in vitro and in rat models of middle cerebral artery occlusion (MCAO). Results demonstrated the mitochondrial-targeted and protective effects of SPNPs on H2O2-induced oxidative damage in SH-SY5Y cells. In vivo distribution analyzed by fluorescence imaging proved the rapid and enhanced active targeting of SPNPs to the ischemic area in MCAO rats. SPNPs by intranasal administration exhibited superior therapeutic efficacy by alleviating oxidative stress, diminishing inflammation, repairing mitochondrial function, and decreasing apoptosis. This strategy provided a multifunctional delivery system for the effective treatment of ischemic injury, which also implies a potential application prospect for other central nervous diseases.

The Transport and Uptake of Resveratrol Mediated via Glucose Transporter 1 and Its Antioxidant Effect in Caco-2 Cells.

Resveratrol has anti-inflammatory, anti-cancer, and anti-aging pharmacological activities. There is currently a gap in academic research regarding the uptake, transport, and reduction of H2O2-induced oxidative damage of resveratrol in the Caco-2 cell model. This study investigated the role of resveratrol in the uptake, transport, and alleviation of H2O2-induced oxidative damage in Caco-2 cells. In the Caco-2 cell transport model, it was observed that the uptake and transport of resveratrol (10, 20, 40, and 80 μM) were time dependent and concentration dependent. Different temperatures (37 °C vs. 4 °C) could significantly affect the uptake and transportation of resveratrol. The apical to basolateral transport of resveratrol was markedly reduced by STF-31, a GLUT1 inhibitor, and siRNA intervention. Furthermore, resveratrol pretreatment (80 μM) improves the viability of Caco-2 cells induced by H2O2. In a cellular metabolite analysis combined with ultra-high performance liquid chromatography-tandem mass spectrometry, 21 metabolites were identified as differentials. These differential metabolites belong to the urea cycle, arginine and proline metabolism, glycine and serine metabolism, ammonia recycling, aspartate metabolism, glutathione metabolism, and other metabolic pathways. The transport, uptake, and metabolism of resveratrol suggest that oral resveratrol could prevent intestinal diseases caused by oxidative stress.

Design, Synthesis, and Biological Activity of Donepezil: Aromatic Amine Hybrids as Anti-Alzheimerss Drugs.

In this study, benzylpiperidine, the active group of donepezil (DNP), was connected with the neurotransmitter phenylethylamine by square amide, in which the fat chain of phenylethylamine was reduced and the benzene rings were substituted. A series of multifunctional hybrid compounds, including DNP-aniline hybrids (1-8), DNP-benzylamine hybrids (9-14), and DNP-phenylethylamine hybrids (15-21) were obtained and their cholinesterase inhibitory activity and neuroprotection of the SH-SY5Y cell line were determined. Results showed that compound 3 exhibited excellent acetylcholinesterase inhibitory activity with an IC50 value of 4.4 μM, higher than that of positive control DNP and significant neuroprotective effects against H2O2-induced oxidative damage in SH-SY5Y cells with 80.11% viability rate at 12.5 μM, much higher than that of the model group (viability rate = 53.1%). The mechanism of action of compound 3 was elucidated by molecular docking, reactive oxygen species (ROS), and immunofluorescence analysis. The results suggest that compound 3 could be further explored as a lead compound for the treatment of Alzheimer's disease. In addition, molecular docking research indicated that the square amide group formed strong interactions with the target protein. Based on the above analysis, we believe that square amide could be an interesting construction unit in anti-AD agents.

Protective mechanisms of intra- and extracellular polysaccharides from Schizophyllum commune on H2O2-induced oxidative damage of human skin fibroblasts

ABSTRACT Schizophyllum commune is a fungus with applications both in medicine and foods, which produces IPS and EPS. However, there is no comparative study on the activity comparison of IPS and EPS and its mechanism of antioxidant effect. In this study, the antioxidant activities of the two polysaccharides were measured in biochemical, cellular and molecular levels, and H2O2 induced oxidative damage model of HSFs was established to explore the protective effects of EPS and IPS. We found IPS and EPS both achieved a good antioxidant effect. They can also improve the cellular levels of SOD and reduce MDA. Insights regarding the molecular mechanism were studied, we found that both EPS and IPS could increase the expression of Nrf2 in Keap1-Nrf2/ARE signaling pathway. At the same time, they could inhibit the expression of the negative feedback gene Keap1 and promote the expression of downstream gene GCLC, Gstt-1, Nqo1 and Ho-1.

Revealing of Intracellular Antioxidants in Dendrobium nobile by High Performance Liquid Chromatography-Tandem Mass Spectrometry

The medicinal plant Dendrobium nobile is an important natural antioxidant resource. To reveal the antioxidants of D. nobile, high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was employed for metabolic analysis. The H2O2-induced oxidative damage was used in human embryonic kidney 293T (H293T) cells to assess intracellular antioxidant activities. Cells incubated with flower and fruit extracts showed better cell survival, lower levels of reactive oxygen species (ROS), and higher catalase and superoxide dismutase activities than those incubated with root, stem, and leaf extracts (p &lt; 0.01). A total of 13 compounds were newly identified as intracellular antioxidants by association analysis, including coniferin, galactinol, trehalose, beta-D-lactose, trigonelline, nicotinamide-N-oxide, shikimic acid, 5′-deoxy-5′-(methylthio)adenosine, salicylic acid, isorhamnetin-3-O-neohespeidoside, methylhesperidin, 4-hydroxybenzoic acid, and cis-aconitic acid (R2 &gt; 0.8, Log2FC &gt; 1, distribution &gt; 0.1%, and p &lt; 0.01). They showed lower molecular weight and higher polarity, compared to previously identified in vitro antioxidants in D. nobile (p &lt; 0.01). The credibility of HPLC-MS/MS relative quantification was verified by common methods. In conclusion, some saccharides and phenols with low molecular weight and high polarity helped protect H293T cells from oxidative damage by increasing the activities of intracellular antioxidant enzymes and reducing intracellular ROS levels. The results enriched the database of safe and effective intracellular antioxidants in medicinal plants.

Antioxidant Capacity and Protective Effects on H2O2-Induced Oxidative Damage in PC12 Cells of the Active Fraction of Brassica rapa L.

Brassica rapa L. (BR), a traditional biennial herb belonging to the Brassica species of Brassicaceae, has been widely used for functions of anti-inflammatory, antitumor, antioxidation, antiaging, and regulation of immunity. In this study, antioxidant activity and protective effects on H2O2-induced oxidative damage in PC12 cells of the active fractions of BR were investigated in vitro. Among all active fractions, the ethyl acetate fraction of ethanol extract from BR (BREE-Ea) showed the strongest antioxidant activity. Additionally, it was noted that BREE-Ea and n-butyl alcohol fraction of ethanol extract from BR (BREE-Ba) both have protective effects in oxidatively damaged PC12 cells, while BREE-Ea displayed the best protective effect in all determined experimental doses. Furthermore, flow cytometry (DCFH-DA staining) analysis indicated that BREE-Ea could reduce the H2O2-induced apoptosis in PC12 cells by reducing the production of intracellular reactive oxygen species (ROS) and increasing enzymatic activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Moreover, BREE-Ea could decrease the malondialdehyde (MDA) content and reduce the release of extracellular lactic dehydrogenase (LDH) from H2O2-induced PC12 cells. All these results demonstrate that BREE-Ea has a good antioxidant capacity and protective effect on PC12 cells against apoptosis induced by H2O2 and that it can be used as a good edible antioxidant to improve the body's endogenous antioxidant defense.

Hindakia tetrachotoma ME03 (Chlorophyta) has high phenolic content, antioxidant capacity, and attenuates H2O2-induced oxidative stress and apoptosis in human cells

ABSTRACT Oxidative stress damages cellular components and may lead to cell death when it is not effectively counterbalanced by the endogenous antioxidant mechanisms. Exogenous sources of antioxidants are also necessary to cope with high levels of free radicals. Microalgae are rich sources of diverse metabolites with high antioxidant potential. In this study, metabolites of Hindakia tetrachotoma ME03, a green microalga previously isolated from thermal springs in Türkiye, were chemically fractionated using four solvents (ethanol-water, ethyl acetate, hexane and water). The extracts were evaluated for their antioxidant capacities, total phenolics, flavonoids and carotenoids. The highest antioxidant capacity, phenolic and carotenoid contents were obtained in the ethanol-water extracts. The antioxidant capacity in the ethanol-water extracts was measured as 12.42 ± 1.21 μmol Trolox g–1 DW and 67.98 ± 3.45 μmol Trolox g–1 DW by DPPH and FRAP assays, respectively. Twelve different phenolic compounds in the ethanol-water and ethyl acetate extracts were quantified by reverse phase high pressure liquid chromatography. Quercetin and rutin were the most abundant phenolics in the ethanol-water extracts, whereas the ethyl acetate extract was rich in phenolic precursor, benzoic acid. Finally, the cytoprotective effect of ethanol-water extracts of H. tetrachotoma ME03 against H2O2-induced oxidative damage was investigated using an in vitro cell line model of human breast adenocarcinoma (MCF7). Hindakia tetrachotoma ME03 extracts significantly decreased the intracellular reactive oxygen species levels and the percentage of apoptotic and necrotic cells in MCF7 cells. These findings suggest the strong cytoprotective activity of H. tetrachotoma ME03 extracts, which may be conferred by its antioxidative properties.

Effects of saponins isolated from Polygonatum sibiricum on H2O2-induced oxidative damage in RIN-m5F cells and its protective effect on pancreas.

The damage of islet cells caused by oxidative stress is closely related to diabetes. The aim of this study is to investigate the protective effect of saponins isolated from polygonatum sibiricum (PSS) on pancreas injury by using in vitro and in vivo models. The oxidative stress model of RIN-m5F cells induced by H2O2 was established. We found that PSS could decrease the apoptosis of RIN-m5F cells under oxidative stress. After PSS treatment, ROS and MDA levels in cells significantly decreased. Moreover, the levels of SOD and GSH were significantly increased. PSS could increase the insulin secretion level of cells under oxidative stress. The expression level of intracellular Bcl-2 increased, and the expression levels of Bax, caspase-3, caspase-8, and caspase-9 decreased significantly. In addition, the type 2 diabetes mouse model was established. The results showed that PSS had a protective effect on the injury of the pancreas in T2DM mice. PSS can relieve oxidative stress and high glucose-mediated pancreas cytotoxicity. PSS may be a promising candidate for diabetes intervention and functional foods.

Discovery of phenylcarbamoyl xanthone derivatives as potent neuroprotective agents for treating ischemic stroke.

Compounds of natural sources are widespread discovered in the treatment of ischemic stroke. Alpha-mangostin, a natural prenylated xanthone, has been found to display a therapeutic potential to treat ischemic stroke. However, the direct application of α-mangostin is limited due to its cytotoxicity and relatively low efficacy. Herein, structural modification of α-mangostin was necessary to improve its drug-ability. Currently, 34 α-mangostin phenylcarbamoyl derivatives were synthesized and evaluated for their neuroprotective activities by glutamate-induced excitotoxicity and H2O2-induced oxidative damage models in vitro. The results showed that compound 2 had the most therapeutic potential in both models. Whereafter, 2 has been proved to have powerful therapeutic effects by the MCAO ischemic stroke model in rats, which might be due to inhibition of inflammatory reaction and free radical accumulation. Besides, acute toxicity assay in rats showed that compound 2 had excellent safety. Overall, 2 could be a promising neuroprotective agent for the treatment of ischemic stroke deserving further investigations.