Anti-oxidative Stress Activity Research Articles

Activation of cellular antioxidative stress and migration activities by purified components from immortalized stem cells from human exfoliated deciduous teeth

Although stem cell-based regenerative medicine has been extensively studied, it remains difficult to reconstruct three dimensional tissues and organs in combination with vascular systems in vitro. One clinically successful therapy is transplantation of mesenchymal stem cells (MSC) into patients with graft versus host disease. However, transplanted cells are immediately damaged and destroyed because of innate immune reactions provoked by thrombogenic inflammation, and patients need to take immunosuppressive drugs for the immunological regulation of allogeneic cells. This reduces the benefits of stem cell transplantation. Therefore, alternative therapies are more realistic options for clinical use. In this study, we aimed to take advantage of the therapeutic efficacy of MSC and use multiple cytokines released from MSC, that is, stem cells from human exfoliated deciduous teeth (SHEDs). Here, we purified components from conditioned media of immortalized SHED (IM-SHED-CM) and evaluated the activities of intracellular dehydrogenase, cell migration, and antioxidative stress by studying the cells. The immortalization of SHED could make the stable supply of CM possible. We found that the fractionated component of 50–100 kD from IM-SHED-CM had higher efficacy than the original IM-SHED-CM in terms of intracellular dehydrogenase and cell migration in which intracellular signal transduction was activated via receptor tyrosine kinases, and the glutathione peroxidase and reductase system was highly active. Although antioxidative stress activities in the fractionated component of 50–100 kD had slightly lower than that of original IM-SHE-CM, the fraction still had the activity. Thus, the use of fractionated components of 50–100 kD from IM-SHED-CM could be an alternative choice for MSC transplantation because the purified components from CM could maintain the effect of cytokines from SHED.

Liquid-Phase Adsorption Behavior of β-D-Glucooligosaccharides When Using Activated Carbon for Separation, and the Antioxidant Stress Activity of Purified Fractions.

The adsorption characteristics of β-glucooligosaccharides on activated carbon and the purification were systematically investigated. The maximum adsorption capacity of activated carbon reached 0.419 g/g in the optimal conditions. The adsorption behavior was described to be monolayer, spontaneous, and exothermic based on several models' fitting results. Five fractions with different degrees of polymerization (DPs) and structures of β-glucooligosaccharides were obtained by gradient ethanol elution. 10E mainly contained disaccharides with dp2a (G1→6G) and dp2b (G1→3G). 20E possessed trisaccharides with dp3a (G1→6G1→3G) and dp3b (G1→3G1→3G). 30E mainly consisted of dp3a and dp4a (G1→3G1→3(G1→6)G), dp4b (G1→6G1→3G1→3G), and dp4c (G1→3G1→3G1→3G). In addition to tetrasaccharides, 40E and 50E also contained pentasaccharides and hexasaccharides with β-(1→3)-linked or β-(1→6)-linked glucose residues. All fractions could inhibit the accumulation of intracellular reactive oxygen species (ROS) in H2O2-induced Caco-2 cells, and they could improve oxidative stress damage by increasing the activity of superoxide dismutase (SOD) and reduced glutathione (GSH), which were related to their DPs and structures. 50E with high DPs showed better anti-oxidative stress activity.

Microalgae Octapeptide IIAVEAGC Alleviates Oxidative Stress and Neurotoxicity in 6-OHDA-Induced SH-SY5Y Cells by Regulating the Nrf2/HO-1and Jak2/Stat3 Pathways.

Neurodegenerative diseases are characterized by the progressive loss of selectively vulnerable populations of neurons, and many factors are involved in its causes. Neurotoxicity and oxidative stress, are the main related factors. The octapeptide Ile-Ile-Ala-Val-Glu-Ala-Gly-Cys (IEC) was identified from the microalgae Isochrysis zhanjiangensis and exhibited potential anti-oxidative stress activity. In this study, the stability of α-synaptic protein binding to IEC was modeled using molecular dynamics, and the results indicated binding stabilization within 60 ns. Oxidative stress in neurons is the major cause of α-synaptic protein congestion. Therefore, we next evaluated the protective effects of IEC against oxidative stress and neurotoxicity in 6-ohdainduced Parkinson's disease (PD) model SH-SY5Y cells in vitro. In oxidative stress, IEC appeared to increase the expression of the antioxidant enzymes HO-1 and GPX through the antioxidant pathway of Nrf2, and molecular docking of IEC with Nrf2 and GPX could generate hydrogen bonds. Regarding apoptosis, IEC protected cells by increasing the Bcl-2/Bax ratio, inhibiting the caspase cascade, acting on p53, and modulating the Jak2/Stat3 pathway. The results indicated that IEC exerted neuroprotective effects through the inhibition of α-synaptic protein aggregation and antioxidant activity. Therefore, microalgal peptides have promising applications in the prevention and treatment of neurodegenerative diseases.

Changes in chemical components and hepatoprotective effect of red Panax notoginseng processed by aspartic acid impregnation treatment.

Red Panax notoginseng (RPN) is one of the major processed products of P. notoginseng (PN), with more effective biological activities. However, the traditional processing method of RPN has some disadvantages, such as low conversion rate of ginsenosides and long processing time. In this work, we developed a green, safe, and efficient approach for RPN processing by aspartic acid impregnation pretreatment. Our results showed that the optimized temperature, steaming time, and concentration of aspartic acid were 120 °C, 1 h, and 3% respectively. The original ginsenosides in PN treated by aspartic acid (Asp-PN) were completely converted to rare saponins at 120 °C within just 1 h. The concentration of the rare ginsenosides in Asp-PN was two times higher than that in untreated RPN. In addition, we examined the protective effect of RPN and Asp-PN on acetaminophen-induced liver injury in a mouse model. The results showed that Asp-PN has significantly more potent hepatoprotective action than the RPN. The hepatoprotection of Asp-PN in acetaminophen-induced hepatotoxicity may be due to its anti-oxidative stress, anti-apoptotic, and anti-inflammatory activities. These results indicated that aspartic acid impregnation pretreatment may provide an effective method to shorten the steaming time, improve the conversion rate of ginsenosides, and enhance hepatoprotective activity of RPN. © 2024 Society of Chemical Industry.

Ezetimibe treatment reduces oxidized low-density lipoprotein in biliary cirrhotic rats.

In liver cirrhosis, chronic inflammation is associated with an increase in oxidative stress, and subsequently an increase in the concentration of oxidized low-density lipoprotein (ox-LDL). Ezetimibe is a lipid-lowering agent with anti-inflammation and anti-oxidative stress activities. This study aimed to investigate the effect of ezetimibe treatment on ox-LDL in cirrhotic rats. Biliary cirrhosis was induced in Sprague-Dawley rats with common bile duct ligation (BDL). Sham-operated rats served as surgical controls. Ezetimibe (10 mg/kg/d) or vehicle was administered in the sham-operated or BDL rats for 4 weeks, after which hemodynamic parameters, biochemistry data, and oxidative stress were evaluated. Plasma and intrahepatic ox-LDL levels were also examined, and hepatic proteins were analyzed to explore the mechanism of ezetimibe treatment. The BDL rats had typical features of cirrhosis including jaundice, impaired liver function, hyperlipidemia, and elevated ox-LDL levels compared to the sham-operated rats. Ezetimibe treatment did not affect hemodynamics, liver biochemistry, or plasma lipid levels. However, it significantly reduced oxidative stress, plasma levels of ox-LDL, and tumor necrosis factor α. In addition, ezetimibe upregulated the hepatic protein expression of an ox-LDL scavenger (lectin-like ox-LDL rececptor-1), which resulted in reductions in intrahepatic ox-LDL and fat accumulation in the BDL rats. Nevertheless, ezetimibe treatment did not ameliorate hepatic inflammation or liver fibrosis. Ezetimibe reduced plasma and intrahepatic ox-LDL levels in the cirrhotic rats. Furthermore, it ameliorated intrahepatic fat accumulation and oxidative stress. However, ezetimibe did not alleviate hepatic fibrosis or inflammation in the biliary cirrhotic rats.

N-Cinnamoylpyrrole-derived alkaloids from the genus Piper as promising agents for ischemic stroke by targeting eEF1A1

BackgroundIschemic stroke (IS) is a serious cerebrovascular disease characterized by significantly elevated mortality and disability rates, and the treatments available for this disease are limited. Neuroinflammation and oxidative stress are deemed the major causes of cerebral ischemic injury. N-Cinnamoylpyrrole alkaloids form a small group of natural products from the genus Piper and have not been extensively analyzed pharmacologically. Thus, identifying the effect and mechanism of N-cinnamoylpyrrole-derived alkaloids on IS is worthwhile. PurposeThe present research aimed to explore the antineuroinflammatory and antioxidative stress effects of N-cinnamoylpyrrole-derived alkaloids isolated from the genus Piper and to explain the effects and mechanism on IS. MethodsN-cinnamoylpyrrole-derived alkaloids were isolated from Piper boehmeriaefolium var. tonkinense and Piper sarmentosum and identified by various chromatographic methods. Lipopolysaccharide (LPS)-induced BV-2 microglia and a mouse model intracerebroventricularly injected with LPS were used to evaluate the antineuroinflammatory and antioxidative stress effects. Oxygen‒glucose deprivation/reperfusion (OGD/R) and transient middle cerebral artery occlusion (tMCAO) models were used to evaluate the effect of PB-1 on IS. To elucidate the fundamental mechanism, the functional target of PB-1 was identified by affinity-based protein profiling (ABPP) strategy and verified by cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS), and circular dichroism (CD) analyses. The effect of PB-1 on the NF-κB and NRF2 signaling pathways was subsequently evaluated via western blotting and immunofluorescence staining. ResultsThe results showed that N-cinnamoylpyrrole-derived alkaloids significantly affected neuroinflammation and oxidative stress. The representative compound, PB-1 not only inhibited neuroinflammation and oxidative stress induced by LPS or OGD/R insult, but also alleviated cerebral ischemic injury induced by tMCAO. Further molecular mechanism research found that PB-1 promoted antineuroinflammatory and antioxidative stress activities via the NF-κB and NRF2 signaling pathways by targeting eEF1A1. ConclusionOur research initially unveiled that the therapeutic impact of PB-1 on cerebral ischemic injury might rely on its ability to target eEF1A1, leading to antineuroinflammatory and antioxidative stress effects. The novel discovery highlights eEF1A1 as a potential target for IS treatment and shows that PB-1, as a lead compound that targets eEF1A1, may be a promising therapeutic agent for IS.

Melanosomal localization is required for GIF-2115/2250 to inhibit melanogenesis in B16F10 melanoma cells.

Tyrosinase inhibitors suppress melanogenesis in melanocytes. During a screening for tyrosinase inhibitors, however, we noticed some discrepancies in inhibitory efficacies between melanocytes and invitro assays. The compound (S)-N-{3-[4-(dimethylamino)phenyl]propyl}-N-methyl-indan-1-amine (GIF-2115) exerts antioxidative stress activity upon accumulation in late endosomes and lysosomes. GIF-2115 was also identified as a potent antimelanogenic reagent in B16F10 mouse melanoma cells. GIF-2115 inhibited the activity of mushroom tyrosinase and the lysates of B16F10 cells. However, structure-activity relationship studies indicated that GIF-2238, which lacks the benzene ring in the aminoindan structure of GIF-2115, inhibited tyrosinase activity invitro but did not inhibit melanogenesis in B16F10 cells. The aim of the present study is to show the importance of the intracellular distribution of tyrosinase inhibitors in exerting their antimelanogenic activity in melanocytes. The intracellular distribution of compounds was monitored by linking with the fluorescent group of 7-nitro-2,1,3-benzoxadiazole (NBD). To mislocalize GIF-2115 to mitochondria, the mitochondria-preferring fluoroprobe ATTO565 was used. We reconfirmed the localization of GIF-2250 (GIF-2115-NBD) not only to matured but also to early-stage melanosomes. Although GIF-2286 (GIF-2238-NBD) maintained tyrosinase inhibitory activity, it did not show specific intracellular localization. Moreover, when GIF-2115 was linked with ATTO565, the resultant compound GIF-2265 did not inhibit melanogenesis in B16F10 cells, despite its strong tyrosinase inhibitory activity. These results suggest that melanosomal localization is essential for the antimelanogenic activity of GIF-2115, and GIF-2115 derivatives may be new guides for drugs to endosomes and lysosomes as well as melanosomes.

Time-Released Black Phosphorus Hydrogel Accelerates Myocardial Repairing through Antioxidant and Motivates Macrophage Polarization Properties.

The improvement of the myocardial microenvironment largely determines the prognosis of myocardial infarction (MI). After MI, early removal of excessive reactive oxygen species (ROS) in the microenvironment can alleviate oxidative stress injury and promote M2 phenotype polarization of macrophages, which is important for advocating myocardial repair. In this study, we combined traditional natural hydrogel materials chitosan (CS) and gelatin (Gel) to encapsulate polydopamine-modified black phosphorus nanosheets (BP@PDA). We designed an injectable composite gel (CS-Gel-BP@PDA) with a time-released ability to achieve insitu sustained-release BP@PDA in the area of MI. Utilizing the inflammation inhibition ability of CS-Gel itself and the high reactive activity of BP@PDA with ROS, continuous improvement of infarct microenvironment and myocardial repair were achieved. The studies invivo revealed that, compared with the saline group, CS-Gel-BP@PDA group had alleviated myocardial fibrosis and infarct size and importantly improved cardiac function. Immunofluorescence results showed that the ROS level and inflammatory response in the microenvironment of the CS-Gel-BP@PDA group were decreased. In conclusion, our study demonstrated the time-released ability, antioxidative stress activity and macrophage polarization modulation of the novel composite hydrogel CS-Gel-BP@PDA, which provides inspiration for novel therapeutic modalities for MI.

Synthesis and evaluation of linearly fused thiadiazolocoumarins as prospects with broad-spectrum bioactivity

Various pharmacological properties of coumarins brought them under light among the heterocyclics. Also, coumarin derivatives still approve of their importance in the medical field as a valuable building block to elicit further derivatives with diverse, potent, and interesting biological activities. Moreover, the numerous biological actions of thiadiazole-based compounds contribute to the notion of this unique synthesis of linearly fused thiadiazolocoumarins using the molecular hybridization method. This work reported the novel synthesis of seven linearly fused thiadiazolocoumarins, including Precursor N-III and TDA1-TDA6. These derivatives were characterized by their physicochemical properties and through spectrophotometric tools, including FTIR, 1H NMR, and 13C NMR. Also, their pharmacokinetics were predicted using computer-based studies by the SwissADME and PreADMET programs. Furthermore, the derivatives were checked for several biological activities, including anticancer, biosafety, anti-oxidative stress, anti-inflammatory, antimicrobial, normal flora safety, and antidiabetic activities. According to the results, TDA3 showed the greatest anticancer activity against the examined cancer cell lines, with the highest cellular biosafety. TDA3 and TDA4 showed higher anti-oxidative stress activity than the other derivatives. All the prepared derivatives showed significant inflammation-inhibitory activity toward the LOX-5 enzyme while showing poor activity towards COX enzymes. According to antimicrobial activity, TDA4 exhibited the greatest anti-gram-negative activity and also showed the best safety toward the examined normal flora. TDA1 exhibited promising activity against anaerobic bacteria, while Precursor N-III, TDA3, and TDA4 showed significant antifungal activity. Finally, TDA1 demonstrated moderate antidiabetic activity, which was the greatest activity among the other derivatives. The authors concluded from the gathered results that the linearly fused thiadiazolocoumarins represent key structures for developing compounds with versatile bioactivities.

Hederagenin Upregulates PTPN1 Expression in Aβ-Stimulated Neuronal Cells, Exerting Anti-Oxidative Stress and Anti-Apoptotic Activities.

Alzheimer's disease (AD) is a prevalently neurodegenerative disease characterized by neuronal damage which is associated with amyloid-β (Aβ) accumulation. Hederagenin is a triterpenoid saponin, exerting anti-apoptotic, anti-oxidative, anti-inflammatory, anti-tumoral, and neuroprotective activities. However, its role in AD progression is still obscure. The aim of this study was to explore the influences of hederagenin on Aβ-caused neuronal injury in vitro. Neuronal cells were treated with Aβ25-35 (Aβ) to establish a cellular model of AD. Cell viability was assessed using cell counting kit-8 (CCK-8). Oxidative stress was evaluated by detecting reactive oxygen species (ROS) generation and superoxide dismutase (SOD) activity. Apoptosis was investigated using TUNEL staining and caspase-3 activity assays. Protein tyrosine phosphatase nonreceptor type 1 (PTPN1) was screened by bioinformatics analysis. Protein levels of PTPN1 and protein kinase B (Akt) were measured by western blotting. Hederagenin (2.5, 5, and 10μM) alone did not affect viability of neuronal cells, but relieved Aβ-induced viability reduction. Hederagenin mitigated Aβ-induced increase in ROS accumulation and decrease in SOD activity. Hederagenin attenuated Aβ-induced increase in apoptotic rate and caspase-3 activity. PTPN1 was screened as a target of hederagenin against AD by bioinformatics analysis. Hederagenin treatment resisted Aβ-induced decrease in PTPN1 mRNA and protein levels in neuronal cells. PTPN1 silencing attenuated the suppressive functions of hederagenin in Aβ-stimulated oxidative stress and apoptosis. Hederagenin mitigated Aβ-induced Akt signaling inactivation by upregulating PTPN1 expression. In conclusion, hederagenin attenuates oxidative stress and apoptosis in neuronal cells stimulated with Aβ by promoting PTPN1/Akt signaling activation.

Spectrum-effect relationship analysis based on HPLC-FT-ICR-MS and multivariate statistical analysis to reveal the pharmacodynamic substances of Ling-Gui-Zhu-Gan decoction on Alzheimer's disease

Alzheimer’s disease (AD) threatens elderly human health and still lacks effective treatment. Our previous work showed that LGZGD possessed a neuroprotective effect on the Aβ25–35-induced neurotoxicity in differentiated PC12 cells, indicating that LGZGD may be a potential drug for treatment of AD. However, its pharmacodynamic substances which show anti-inflammatory and anti-oxidant stress activities are still unrevealed. This research aims to reveal the pharmacodynamic substances of LGZGD on Aβ25–35-induced PC12 cell model of AD based on a spectrum-effect relationship study by using HPLC-FT-ICR-MS method and multivariate statistical analysis. Firstly, the chemical composition spectra of different combinations of LGZGD were recorded by HPLC-FT-ICR MS. Subsequently, Aβ25–35-induced PC12 cell model of AD was established and pharmacodynamic experiments were conducted to evaluate their anti-inflammatory and anti-oxidant activities, respectively. Finally, the potential pharmacodynamic substances were screened out through spectrum-effect relationship study accompanied by multivariate statistical analysis including bivariate correlation analysis (BCA), grey relational analysis (GRA), principal component analysis (PCA), partial least squares regression analysis (PLSR). As a result, a total of 96 chemical consistents in different combinations of LGZGD were discovered. Among them, 7 components such as isoglabrolide, licorice saponin E2, licorice saponin N2 and licoisoflavanone were directly linked with the anti-inflammatory effects, and 14 constituents such as tumulosic acid, polyporenic acid C, dehydrotumulosic acid, dehydropachymic acid, and pachymic acid were directly correlated with the anti-oxidative stress activities. In conclusion, we combined the HPLC-FT-ICR-MS spectra with pharmacodynamic indicators to develop the spectrum-effect relationships of LGZGD for the first time, and successfully revealed its potential pharmacodynamic substances in the treatment of AD from the anti-inflammatory and antioxidant pathways in the cell model.

Neuroprotective Effects of Sinomenine on Experimental Autoimmune Encephalomyelitis via Anti-Inflammatory and Nrf2-Dependent Anti-Oxidative Stress Activity.

Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS). Sinomenine (SIN), a bioactive alkaloid extracted from the Chinese medicinal plant Sinomenium acutum, has powerful anti-inflammatory and immunosuppressive therapeutic benefits. In our previous research, we found that SIN increased resistance to oxidative stress via the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in PC12 neuronal cells. However, whether SIN can improve the symptoms and pathological features of experimental autoimmune encephalomyelitis (EAE), a murine model of MS, via the Nrf2 signaling pathway remains unclear. EAE was immunized followed by SIN treatment. Then we evaluated the effects of SIN in EAE. Subsequently, primary microglia were cultured to explore the effect of SIN on microglia activation. Further, the levels of Nrf2 and its downstream molecules were detected to assess the molecular mechanisms of SIN. We demonstrated that SIN effectively ameliorated the severity of EAE, accompanied by a reduction in the demyelination, axonal damage and inhibition of inflammatory cell infiltration. Mechanistically, SIN decreased the inflammatory cytokines expression, and suppressed microglia and astrocytes activation in EAE mice. Furthermore, SIN suppressed lipopolysaccharide (LPS)-induced microglial activation and the production of pro-inflammatory factors in vitro. Moreover, SIN inhibited oxidative stress via the activation of the Nrf2 signaling pathway. Our work proves that SIN exerts its neuroprotective effects by the Nrf2-dependent anti-oxidative stress and diminishing neuroinflammation, suggesting that the "antioxiflammation" effect of SIN is expected to be an ideal treatment strategy for MS/EAE.

High-Quality Indigo Naturalis Obtained with Automatic Foam Separation.

Indigo Naturalis is not only an ancient plant dye but also a famous herbal medicine with antibacterial, anti-inflammatory, and anticancer properties. In traditional processes, thousands of manual stirring separate the high-quality Indigo Naturalis from the crude pulp system. However, this method is time-consuming and labor-intensive, resulting in an unstable quality and low yield, which cannot meet the requirements of modern industrial production. In this study, foam-separation technology was used to increase the industrial applicability of high-quality Indigo Naturalis. The process parameters were optimized based on the content of active ingredients, skin irritation effects, and antioxidative stress activity. The results showed that the optimal process of the foam separation achieved the liquid level difference of 40 cm and the foaming intensity of 0.35 MPa. Compared with the original sample, the indigo and indirubin contents in purified Indigo Naturalis were 1.6 and 3 times higher, the total ash content decreased from 86 to 70%, the pH value decreased from 12.18 to 9.71, and the leachate doubled. Animal experiments suggested the significantly reduced irritation (p < 0.01) and enhanced antioxidative stress activity (p < 0.01) of Indigo Naturalis after foam separation. Therefore, the foam-separation equipment developed in this study enabled the refinement of active ingredients in Indigo Naturalis, which greatly improved the production efficiency and quality.

Therapeutic Potential of Biochanin A in Herpes Simplex Keratitis.

Herpes simplex keratitis (HSK) is a blinding eye disease that is initiated by the herpes simplex virus type 1 (HSV-1). Resistance to acyclovir (ACV) and the side effects of corticosteroid drugs have become concerning issues, so it is crucial to develop new antivirals for treating HSK. In this study, we report that biochanin A (BCA), a naturally occurring flavonoid compound, provides multifaceted protective effects with anti-viral, anti-inflammatory, anti-oxidative stress and anti-apoptotic activities to alleviate HSK. The results show that BCA significantly inhibited HSV-1 replication in vitro and further proved that BCA principally influenced the early stage of virus infection. We reveal that BCA downregulated the expression of pro-inflammatory factors triggered by HSV-1, including TNF-α, RANTES, IL-1β and IL-6. Furthermore, BCA treatment alleviated oxidative stress and apoptotic arising from HSV-1 infection. Lastly, we induced HSK in male C57BL/6 mice and treated them with either BCA or phosphate buffer solution (PBS) eye drops. We observed the ocular surface lesions; determined the virus load in the tear fluid, corneas as well as trigeminal ganglions (TGs); and detected the levels of inflammation and apoptosis in the corneas simultaneously. These results show that BCA inhibits HSV-1 and alleviates the corneal lesion degree. Our study illustrates that BCA is a promising therapeutic approach for application in treating HSK.

Protective effects of ginseng and ginsenosides in the development of osteoarthritis (Review).

Osteoarthritis (OA) is a chronic inflammatory joint disease. Traditional chinese medicine provides a resource for drug screening for OA treatment. Ginseng and the associated bioactive compound, ginsenosides, may reduce inflammation, which is considered a risk factor for the development of OA. Specifically, ginsenosides may exhibit anti-inflammatory and anti-oxidative stress activities, and inhibit extracellular matrix degradation by suppressing the NF-κB and MAPK signaling pathways. Notably, specific ginsenosides, such as compound K and Rk1, may physically interact with IκB kinase and inhibit the associated phosphorylation. Thus, ginsenosides exhibit potential as therapeutic candidates in the management of OA. However, the low water solubility limits the clinical applications of ginsenosides. Numerous effective strategies have been explored to improve bioavailability; however, further investigations are still required.

Novel pterostilbene derivatives ameliorate heart failure by reducing oxidative stress and inflammation through regulating Nrf2/NF-κB signaling pathway

Pterostilbene is a demethylated resveratrol derivative with attractive anti-inflammatory, anti-tumor and anti-oxidative stress activities. However, the clinical use of pterostilbene is limited by its poor selectivity and druggability. Heart failure is a leading cause of morbidity and mortality worldwide, which is closely related to enhanced oxidative stress and inflammation. There is an urgent need for new effective therapeutic drugs that can reduce oxidative stress and inflammatory responses. Therefore, we designed and synthesized a series of novel pterostilbene chalcone and dihydropyrazole derivatives with antioxidant and anti-inflammatory activities by the molecular hybridization strategy. The preliminary anti-inflammatory activities and structure-activity relationships of these compounds were evaluated by nitric oxide (NO) inhibitory activity in lipopolysaccharide (LPS)-treated RAW264.7 cells, and compound E1 exhibited the most potent anti-inflammatory activities. Furthermore, pretreatment with compound E1 decreased reactive oxygen species (ROS) generation both in RAW264.7 and H9C2 cells by increasing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), as well as downstream antioxidant enzymes superoxide dismutase 1 (SOD1), catalase (CAT) and glutathione peroxidase 1 (GPX1). In addition, compound E1 also significantly inhibited LPS or doxorubicin (DOX)-induced inflammation in both RAW264.7 and H9C2 cells through reducing the expression of inflammatory cytokines by inhibiting nuclear factor-κB (NF-κB) signaling pathway. Moreover, we found that compound E1 improved DOX-induced heart failure by inhibiting inflammation and oxidative stress in mouse model, which is mediated by the potential of antioxidant and anti-inflammatory activities. In conclusion, this study demonstrated the novel pterostilbene dihydropyrazole derivative E1 was identified as a promising agent for heart failure treatment.

Antioxidative effect of Periplaneta americana extract on dextran sulfate sodium-induced ulcerative colitis through activation of the Nrf2 signal

Context Periplaneta americana L. (Blattariae) is used as a treatment for ulcerative colitis (UC) in Chinese traditional medicine. Objective To evaluate the antioxidative activity of P. americana whole body ethanol extract (PAE) on UC mice and whether glycine and proline could be used for quality control and identification of active PAE components. Materials and methods NCM460 cells were pre-incubated in PAE, AA-L, AA-M, and AA-H (low, high and medium doses of proline and glycine), then treated with recombinant human TNF-α. The glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD) and reactive oxygen (ROS) levels were determined. UC mice were fed with water containing 2.5% dextran sulfate sodium (w/v) after pre-treatment with different doses of PAE once a day for 7 days. ELISA was used to detect the concentrations of inflammation-related factors. Colon tissues of mice were used to detect the activity of myeloperoxidase (MPO), GSH, MDA, and SOD. Histological changes were observed using H&E staining. The expression of target proteins was determined by western blotting. Results In vivo, PAE treatment reduced the DAI score more than in the model group, restoring the weight and colonic length. It also reduced the severity of colitis, and inflammatory and oxidative stress intensity. Additionally, western blotting showed that the Nrf2 pathway was activated by PAE. In vitro PAE significantly alleviated TNF-α-induced cell damage and oxidative stress, which is relevant to the activation of the Nrf2 pathway. Conclusions PAE may relieve oxidative stress through the Nrf2 signaling pathway, and proline and glycine may be used as active components of its antioxidative stress activity.

Protective effects of paeoniflorin on cardiovascular diseases: A pharmacological and mechanistic overview.

Background and ethnopharmacological relevance: The morbidity and mortality of cardiovascular diseases (CVDs) are among the highest of all diseases, necessitating the search for effective drugs and the improvement of prognosis for CVD patients. Paeoniflorin (5beta-[(Benzoyloxy)methyl] tetrahydro-5-hydroxy-2-methyl-2,5-methano-1H-3,4-dioxacyclobuta [cd] pentalen-1alpha (2H)-yl-beta-D-glucopyranoside, C23H28O11) is mostly derived from the plants of the family Paeoniaceae (a single genus family) and is known to possess multiple pharmacological properties in the treatment of CVDs, making it a promising agent for the protection of the cardiovascular system. Aim of the study: This review evaluates the pharmacological effects and potential mechanisms of paeoniflorin in the treatment of CVDs, with the aim of advancing its further development and application. Methods: Various relevant literatures were searched in PubMed, ScienceDirect, Google Scholar and Web of Science. All eligible studies were analyzed and summarized in this review. Results: Paeoniflorin is a natural drug with great potential for development, which can protect the cardiovascular system by regulating glucose and lipid metabolism, exerting anti-inflammatory, anti-oxidative stress, and anti-arteriosclerotic activities, improving cardiac function, and inhibiting cardiac remodeling. However, paeoniflorin was found to have low bioavailability, and its toxicology and safety must be further studied and analyzed, and clinical studies related to it must be carried out. Conclusion: Before paeoniflorin can be used as an effective therapeutic drug for CVDs, further in-depth experimental research, clinical trials, and structural modifications or development of new preparations are required.

Oral polyphenol-armored nanomedicine for targeted modulation of gut microbiota-brain interactions in colitis.

Developing oral nanomedicines that suppress intestinal inflammation while modulating gut microbiota and brain interactions is essential for effectively treating inflammatory bowel disease. Here, we report an oral polyphenol-armored nanomedicine based on tumor necrosis factor-α (TNF-α)-small interfering RNA and gallic acid-mediated graphene quantum dot (GAGQD)-encapsulated bovine serum albumin nanoparticle, with a chitosan and tannin acid (CHI/TA) multilayer. Referred to "armor," the CHI/TA multilayer resists the harsh environment of the gastrointestinal tract and adheres to inflamed colon sites in a targeted manner. TA provides antioxidative stress and prebiotic activities that modulate the diverse gut microbiota. Moreover, GAGQD protected TNF-α-siRNA delivery. Unexpectedly, the armored nanomedicine suppressed hyperactive immune responses and modulated bacterial gut microbiota homeostasis in a mouse model of acute colitis. Notably, the armored nanomedicine alleviated anxiety- and depression-like behaviors and cognitive impairment in mice with colitis. This armor strategy sheds light on the effect of oral nanomedicines on bacterial gut microbiome-brain interactions.

The Anti-Helicobacter pylori effects of Limosilactobacillus reuteri strain 2892 isolated from Camel milk in C57BL/6 mice.

Helicobacter pylori infection (H. pylori) is associated with chronic gastritis, peptic ulcers, and gastric cancer. The present study provides information on the protective effects of Limosilactobacillus reuteri strain 2892 (L. reuteri 2892) isolated from camel's milk against H. pylori-induced gastritis in the stomach tissue of animal models. Animal assays revealed that L. reuteri 2892 pretreatment significantly downregulated the virulence factor cagA gene expression. It upregulated the expression level of tight junction molecules [zona occludens (ZO-1), claudin-4] and suppressed metalloproteinase (MMP)-2 and MMP-9 expressions. L. reuteri 2892 exhibited immunomodulatory effects on cytokine profile, as it reduced the serum concentrations of pro-inflammatory cytokines interleukin (IL)-6, IL-1β, and INF-γ and increased the anti-inflammatory cytokine, IL-10. In addition, L. reuteri 2892 showed anti-oxidative stress activity by regulating the levels of oxidative stress-associated markers [superoxide dismutase (SOD) and malondialdehyde (MDA)]. Our findings suggest that L. reuteri 2892 attenuates H. pylori-induced gastritis.