Neuroprotective effects of saffron on the late cerebral ischemia injury through inhibiting astrogliosis and glial scar formation.

PMID: 

Biomed Pharmacother. 2020 Feb 26 ;126:110041. Epub 2020 Feb 26. PMID: 32113053

Abstract Title: 

Neuroprotective effects of saffron on the late cerebral ischemia injury through inhibiting astrogliosis and glial scar formation in rats.

Abstract: 

This study is to explore the neuroprotective effects and involved glial scar of saffron (Crocus sativus L.) on the late cerebral ischemia in rats. Focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in Sprague Dawley rats that were randomly divided into sham group, MCAO group, edaravone group (as a positive control) and saffron groups (saffron extract 30, 100, 300 mg/kg). Saffron was administered orally at 2 h at the first day and once daily from day 2 to 42 after ischemia. Behavioral changes were detected from day 43 to 46 after ischemia to evaluate the effects of saffron. Infarct volume, survival neuron density, activated astrocyte, and the thickness of glial scar were also detected. GFAP, neurocan, phosphocan, neurofilament expressions and inflammatory cytokine contents were detected by Western-blotting and ELISA methods, respectively. Saffron improved the body weight loss, neurological deficit and spontaneous activity. It also ameliorated anxiety-like state and cognitive dysfunction, which were detected by elevated plus maze (EPM), marble burying test (MBT) and novel object recognition test (NORT). Toluidine blue staining found that saffron treatment decreased the infarct volume and increased the neuron density in cortex in the ischemic boundary zone. The activated astrocyte number and the thickness of glial scar in the penumbra zone reduced after saffron treatment. Additionally, saffron decreased the contents of IL-6 and IL-1β, increased the content of IL-10 in the ischemic boundary zone. GFAP, neurocan, and phosphocan expressions in ischemic boundary zone and ischemic core zone all decreased after saffron treatment. Saffron exerted neuroprotective effects on late cerebral ischemia, associating with attenuating astrogliosis and glial scar formation after ischemic injury.

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Prevalence of comorbidities in the novel Wuhan coronavirus (COVID-19) infection: a systematic review and meta-analysis.

PMID: 

Int J Infect Dis. 2020 Mar 12. Epub 2020 Mar 12. PMID: 32173574

Abstract Title: 

Prevalence of comorbidities in the novel Wuhan coronavirus (COVID-19) infection: a systematic review and meta-analysis.

Abstract: 

BACKGROUND: An outbreak of Novel Coronavirus (COVID -19) in Wuhan, China, the epidemic is more widespread than initially estimated, with cases now confirmed in multiple countries.AIMS: The aim of the meta-analysis was to assess the prevalence of comorbidities in the COVID-19 infection patients and the risk of underlying diseases in severe patients compared to non-severe patients.METHODS: A literature search was conducted using the databases PubMed, EMBASE, and Web of sciences until February 25, 2020. Risk ratio (OR) and 95% confidence intervals (CIs) were pooled using random-effects models.RESULTS: Eight studies were included in the meta- analysis, including 46248 infected patients. The result showed the most prevalent clinical symptom was fever ( 91 ± 3, 95% CI 86-97% ), followed by cough (67 ± 7, 95% CI 59-76%), fatigue ( 51 ± 0, 95% CI 34-68% ) and dyspnea ( 30 ± 4, 95% CI 21-40%). The most prevalent comorbidity were hypertension (17 ± 7, 95% CI 14-22%) and diabetes ( 8 ± 6, 95% CI 6-11% ), followed by cardiovascular diseases ( 5 ± 4, 95% CI 4-7% ) and respiratory system disease( 2 ± 0, 95% CI 1-3% ). Compared with the Non-severe patient, the pooled odds ratio of hypertension, respiratory system disease, cardiovascular disease in severe patients were (OR 2.36, 95% CI: 1.46-3.83), (OR 2.46, 95% CI: 1.76-3.44) and (OR 3.42, 95% CI: 1.88-6.22)respectively.CONCLUSION: We assessed the prevalence of comorbidities in the COVID-19 infection patients and found underlying disease, including hypertension, respiratory system disease and cardiovascular, may be a risk factor for severe patients compared with Non-severe patients.

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Ferulic acid alleviates atopic dermatitis-like symptoms in mice via its potent anti-inflammatory effect.

PMID: 

Immunopharmacol Immunotoxicol. 2020 Apr ;42(2):156-164. Epub 2020 Mar 3. PMID: 32122212

Abstract Title: 

Ferulic acid alleviates atopic dermatitis-like symptoms in mice via its potent anti-inflammatory effect.

Abstract: 

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by the interactions between multiple genetic and environmental factors. The pathogenesis of AD is still not completely clear. Steroid topical therapy has severe side effects for chronic AD symptoms and new therapeutic options are urgently needed. Ferulic acid (FA) is a novel natural dietary polyphenol with anti-oxidative and anti-inflammatory effects.FA was assessed in BALB/c mice with AD-like lesions resulted from repetitive applications of 2,4-dinitrochlorobenzene (DNCB). Molecular and serological properties of the AD lesions as well as the overall symptomatic score were evaluated.FA ameliorated the overall symptoms of AD, including the severity of skin lesion and incidence of scratching behavior. Systemically, FA markedly decreased DNCB-induced Th2 cytokines and IgE in the peripheral blood. In the local tissue with AD lesions, FA suppressed DNCB-stimulated mRNA production of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-6, and IL-31. In THP-1 cells, a human monocyte model, FA dose-dependently suppressed DNCB-elicited up-regulation of CD54 and CD86 at cell surface, secretion of pro-inflammatory cytokines IL-6 and TNF-α, and NFκB signaling activation.Our findings demonstrated that FA could serve as a promising therapeutic agent in AD treatment.

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These findings suggest that ferulic acid may protect H9c2 cells against ischemia/reperfusion injury.

PMID: 

Front Pharmacol. 2020 ;11:103. Epub 2020 Feb 25. PMID: 32161543

Abstract Title: 

Ferulic Acid Attenuates Hypoxia/Reoxygenation Injury by Suppressing Mitophagy Through the PINK1/Parkin Signaling Pathway in H9c2 Cells.

Abstract: 

Ferulic acid protects against cardiac injury by scavenging free radicals. However, the role of mitophagy in ferulic acid-induced cardioprotection remains obscure. In the present study, H9c2 cells were exposed to hypoxia/reoxygenation and ferulic acid treatment during hypoxia. We illustrated the impact of ferulic acid on oxidative damage in H9c2 cells. Our results showed that ferulic acid significantly attenuated apoptosis induced by hypoxia/reoxygenation injury and reduced mitochondrial dysfunction, evidenced by a decline in the overproduction of reactive oxygen species and ATP depletion and recovery of the membrane potential. We also found that mitophagy, a selective form of autophagy, was excessively activated in H9c2 cells subjected to hypoxia/reoxygenation. Ferulic acid reduced the binding of mitochondria to lysosomes, down-regulated the PINK1/Parkin pathway, and was accompanied by increased p62 and decreased LC3-II/LC3-I levels. Ferulic acid also antagonistically reduced the activation of mitophagy by rapamycin. These findings suggest that ferulic acid may protect H9c2 cells against ischemia/reperfusion injury by suppressing PINK1/Parkin-dependent mitophagy. Accordingly, our findings may provide a potential target and powerful reference for ferulic acid in clinical prevention and treatment of hypoxia/reoxygenation injury.

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Gastrodin can inhibit H2O2-induced ferroptosis through its antioxidative effect in C6 cells.

PMID: 

Biol Pharm Bull. 2020 ;43(3):480-487. PMID: 32115506

Abstract Title: 

Gastrodin Inhibits HO-Induced Ferroptosis through Its Antioxidative Effect in Rat Glioma Cell Line C6.

Abstract: 

Ferroptosis is a form of necrosis caused by iron-induced accumulation of lipid hydroperoxide, involving several molecular events, and has been implicated in Parkinson's disease. Gastrodin is a component of Gastrodia elata Blume with strong antioxidant activity. We examined whether gastrodin can prevent HO-induced cytotoxicity in rat glioma cell line C6. For this purpose, C6 cells were pretreated with gastrodin (1, 5, 25 µM) and then exposed to 100 µM HO. Results showed that pretreatment of C6 cells with gastrodin decreased HO-induced lactate dehydrogenase (LDH) release and cell death. Moreover, gastrodin decreased intracellular malondialdehyde (MDA) level, whereas increased glutathione peroxidase (GPX) activity and glutathione (GSH) level after HOtreatment. In addition, treatment of deferoxamine (DFO), ferrostatin-1, and liproxstatin-1 abolished ferroptosis induced by HOor erastin pretreatment. Treatment with gastrodin attenuated HO-induced ferroptosis and decreased lipid reactive oxygen species (ROS) (C11-BODIPY) production in C6 cells. Moreover, gastrodin increased the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), GPX4, ferroportin-1 (FPN1), and heme oxygenase-1 (HO-1) in C6 cells treated with HO. RSL3, a GPX4 inhibitor, inhibited GPX4 protein level in cells co-treated with gastrodin and 100 µM HO. These findings indicate that gastrodin can inhibit HO-induced ferroptosis through its antioxidative effect in C6 cells.

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Gastrodin improves preeclampsia-induced cell apoptosis by regulation of TLR4/NF-κB.

PMID: 

Food Sci Nutr. 2020 Feb ;8(2):820-829. Epub 2020 Jan 10. PMID: 32148791

Abstract Title: 

Gastrodin improves preeclampsia-induced cell apoptosis by regulation of TLR4/NF-κB in rats.

Abstract: 

To explain gastrodin improved cell apoptosis induced by preeclampsia in vivo and in vitro study. The PE and normal rats were injected with normal saline (Model), low-dose gastrodin (Gas-L), medium-dose gastrodin (Gas-M), and high-dose gastrodin (Gas-H) groups at 50, 100, or 200 mg/kg per day. The rat blood pressure and 24-hr urine protein level were measured at pregnant days 10, 16, and 20. Evaluating pathology by H&E staining, the cell apoptosis by TUNEL, and MyD88 and NF-κB (p65) proteins by IHC assay using H/R to simulate PE cell model. Measuring cell proliferation, apoptosis, and MyD88 and NF-κB (p65) protein expression by MTT, flow cytometry, and WB assay. The SBP, DBP, and 24-hr urine protein levels were significantly different in PE rats ( 

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A history of smoking may lead to a more severe coronavirus infection.

PMID: 

Chin Med J (Engl). 2020 Feb 28. Epub 2020 Feb 28. PMID: 32118640

Abstract Title: 

Analysis of factors associated with disease outcomes in hospitalized patients with 2019 novel coronavirus disease.

Abstract: 

BACKGROUND: Since early December 2019, the 2019 novel coronavirus disease (COVID-19) has caused pneumonia epidemic in Wuhan, Hubei province of China. This study aims to investigate the factors affecting the progression of pneumonia in COVID-19 patients. Associated results will be used to evaluate the prognosis and to find the optimal treatment regimens for COVID-19 pneumonia.METHODS: Patients tested positive for the COVID-19 based on nucleic acid detection were included in this study. Patients were admitted to 3 tertiary hospitals in Wuhan between December 30, 2019, and January 15, 2020. Individual data, laboratory indices, imaging characteristics, and clinical data were collected, and statistical analysis was performed. Based on clinical typing results, the patients were divided into a progression group or an improvement/stabilization group. Continuous variables were analyzed using independent samples t-test or Mann-Whitney U test. Categorical variables were analyzed using Chi-squared test or Fisher exact test. Logistic regression analysis was performed to explore the risk factors for disease progression.RESULTS: Seventy-eight patients with COVID-19-induced pneumonia met the inclusion criteria and were included in this study. Efficacy evaluation at 2 weeks after hospitalization indicated that 11 patients (14.1%) had deteriorated, and 67 patients (85.9%) had improved/stabilized. The patients in the progression group were significantly older than those in the disease improvement/stabilization group (66 [51, 70] vs. 37 [32, 41] years, U = 4.932, P = 0.001). The progression group had a significantly higher proportion of patients with a history of smoking than the improvement/stabilization group (27.3% vs. 3.0%, χ = 9.291, P = 0.018). For all the 78 patients, fever was the most common initial symptom, and the maximum body temperature at admission was significantly higher in the progression group than in the improvement/stabilization group (38.2 [37.8, 38.6] vs. 37.5 [37.0, 38.4]°C, U = 2.057, P = 0.027). Moreover, the proportion of patients with respiratory failure (54.5% vs. 20.9%, χ = 5.611, P = 0.028) and respiratory rate (34 [18, 48] vs. 24 [16, 60] breaths/min, U = 4.030, P = 0.004) were significantly higher in the progression group than in the improvement/stabilization group. C-reactive protein was significantly elevated in the progression group compared to the improvement/stabilization group (38.9 [14.3, 64.8] vs. 10.6 [1.9, 33.1] mg/L, U = 1.315, P = 0.024). Albumin was significantly lower in the progression group than in the improvement/stabilization group (36.62 ± 6.60 vs. 41.27 ± 4.55 g/L, U = 2.843, P = 0.006). Patients in the progression group were more likely to receive high-level respiratory support than in the improvement/stabilization group (χ = 16.01, P = 0.001). Multivariate logistic analysis indicated that age (odds ratio [OR], 8.546; 95% confidence interval [CI]: 1.628-44.864; P = 0.011), history of smoking(OR, 14.285; 95% CI: 1.577-25.000; P = 0.018), maximum body temperature at admission (OR, 8.999; 95% CI: 1.036-78.147, P = 0.046), respiratory failure (OR, 8.772, 95% CI: 1.942-40.000; P = 0.016), albumin (OR, 7.353, 95% CI: 1.098-50.000; P = 0.003), and C-reactive protein (OR, 10.530; 95% CI: 1.224-34.701, P = 0.028) were risk factors for disease progression.CONCLUSIONS: Several factors that led to the progression of COVID-19 pneumonia were identified, including age, history of smoking, maximum body temperature on admission, respiratory failure, albumin, C-reactive protein. These results can be used to further enhance the ability of management of COVID-19 pneumonia.

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Fucoidan ameliorates oxidative stress, inflammation, DNA damage, and hepatorenal injuries in diabetic rats.

PMID: 

Oxid Med Cell Longev. 2020 ;2020:9316751. Epub 2020 Feb 10. PMID: 32104544

Abstract Title: 

Fucoidan Ameliorates Oxidative Stress, Inflammation, DNA Damage, and Hepatorenal Injuries in Diabetic Rats Intoxicated with Aflatoxin B.

Abstract: 

The current study was carried out to evaluate the ameliorative effect of fucoidan against aflatoxicosis-induced hepatorenal toxicity in streptozotocin-induced diabetic rats. Sixty-four Wister albino male rats were randomly assigned into eight groups (8 rats each) that received normal saline, fucoidan (FUC) at 100 mg/kg/day orally for 4 weeks, streptozotocin (STZ) at 50 mg/kg/i.p. single dose, STZ plus FUC, aflatoxin B(AFB) at 50 g/kg/i.p. after one month of the beginning of the experiment for 2 weeks, AFBplus FUC, STZ plus AFB, or STZ plus AFBand FUC. Injection of rats with STZ induced hyperglycemia. Rats with STZ-induced diabetes, with or without AFBintoxication, had significantly elevated activities of serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase, and levels of serum urea, creatinine, cholesterol, 8-oxo-2'-deoxyguanosine, interleukin-1, interleukin-6, and tumor necrosis factor-. In addition, these rats exhibited increased lipid peroxidation and reduced glutathione concentration and activities of superoxide dismutase, catalase, and glutathione peroxidase enzymes in the hepatic and renal tissues. In contrast, administration of FUC to diabetic rats, with or without AFBintoxication, ameliorated the altered serum parameters, reduced oxidative stress, DNA damage, and inflammatory biomarkers, and enhanced the antioxidant defense system in the hepatic and renal tissues. These results indicated that FUC ameliorated diabetes and AFB-induced hepatorenal injuries through alleviating oxidative stress, DNA damage, and inflammation.

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Micro RNA Expression after Ingestion of Fucoidan; A Clinical Study.

PMID: 

Mar Drugs. 2020 Feb 28 ;18(3). Epub 2020 Feb 28. PMID: 32121066

Abstract Title: 

Micro RNA Expression after Ingestion of Fucoidan; A Clinical Study.

Abstract: 

Fucoidans are a class of fucose-rich sulfated polysaccharides derived from brown macroalgae that exert a range of biological activities in vitro and in vivo. To generate an unbiased assessment of pathways and processes affected by fucoidan, a placebo-controlled double-blind pilot study was performed in healthy volunteers. Blood samples were taken immediately before and 24 h after ingestion of a single dose of 1 g offucoidan (UPF) or placebo. Levels of isolated miRNAs were analyzed using Taqman Open Array Human MicroRNA panels. Out of 754 miRNAs screened, UPF affected a total of 53 miRNAs. Pathway analysis using the TALOS data analysis tool predicted 29 different pathways and processes that were largely grouped into cell surface receptor signaling, cancer-related pathways, the majority of which were previously associated with fucoidans. However, this analysis also identified nine pathways and processes that have not been associated with fucoidans before. Overall, this study illustrates that even a single dose of fucoidans has the potential to affect the expression of genes related to fundamental cellular processes. Moreover, it confirms previous data that fucoidans influence immunity, cancer cells, inflammation, and neurological function.

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