Resveratrol: A Potential Protector Against Benzo[a]pyrene- Induced Lung Toxicity.

<b>Background and Objective:</b> Benzo[a]pyrene (B[a]P), a major component of lipophilic pollutants then can be translated to diffluent substances. The aim of t he present article was to investigate protective activity of resveratrol against lung toxicity induced by B[a]P. Material and Methods: Male Sprague-Dawley rats were randomly assigned to 6 groups (6 animals/group): 3 negative control groups, control positive, B[a]P (20 mg kg¹ b.wt., resveratrol (50 mg kg¹ b.wt.)-B[a]P and vitamin C (1 g kg¹ b.wt.)-B[a]P groups. <b>Results:</b> The daily oral administration of the resveratrol (50 mg kg¹ b.wt.) and vitamin C (1 g kg¹ b.wt.) for 30 days to rats treated with B[a]P (20 mg kg¹ b.wt.) resulted in a significant improve plasma cholesterol, triglyceride and HDL-C as well as serum TNF-α, TBARS, IL-2,IL-6, haptoglobin, histamine, IgA, Ig E,Ig G and Ig M in B[a]P treated rats. On the other hand oral administration of resveratrol elevated the SOD, GPx and GR gene expression in lung rats treated with B[a]P. Furthermore, resveratrol and vitamin C nearly normalized these effects in lung histoarchitecture. <b>Conclusion:</b> The obtained biochemical, molecular biology and histological results of this study proved the lung protective activity of resveratrol against B[a]P induced lung toxicity in rats.

Screening for the Active Anti-Inflammatory and Antioxidant Polyphenols of Gaultheria procumbens and Their Application for Standardisation: From Identification through Cellular Studies to Quantitative Determination.

Aerial parts, leaves, and stems of Gaultheria procumbens are polyphenol-rich herbal medicines with anti-inflammatory and antioxidant effects. The present study focused on identifying active markers of the G. procumbens extracts in an integrated approach combining phytochemical and biological capacity tests. The target compounds, representing all classes of Gaultheria polyphenols, were pre-selected by LC-ESI-PDA-MS/MS. For unambiguous identification, the key analytes, including a rare procyanidin trimer (cinnamtannin B-1), miquelianin potassium salt, and two new natural products: quercetin and kaempferol 3-O-ß-d-xylopyranosyl-(1→2)-ß-d-glucuronopyranosides, were isolated by preparative HPLC and investigated by spectroscopy (HR-ESI-MS, UV-vis, CD, 1D- and 2D-NMR), thiolysis, flame photometry, optical rotation experiments, and absolute configuration studies. The significant contribution of the pre-selected compounds to the biological effects of the extracts was confirmed in vitro: the analytes significantly and in a dose-dependent manner down-regulated the pro-oxidant and pro-inflammatory functions of human neutrophils ex vivo (inhibited the release of reactive oxygen species, IL-1ß, TNF-α, and neutrophils elastase, ELA-2), inhibited two key pro-inflammatory enzymes (cyclooxygenase, COX-2, and hyaluronidase), and most of them, except gaultherin, exerted potent direct antioxidant activity (ferric reducing antioxidant power and superoxide anion scavenging capacity). Moreover, cellular safety was confirmed for all compounds by flow cytometry. Eventually, as these mechanisms have been connected to the health benefits of G. procumbens, 11 polyphenols were accepted as active markers, and a simple, accurate, reproducible, and fully validated RP-HPLC-PDA method for standardisation of the target extracts was proposed.

In vivo Antimalarial, Antioxidant Activities and Safety of Carapa procera DC. (Meliaceae).

Background and Objectives: Carapa procera is a popular herb used by traditional healers in the western part of Burkina Faso. In a previous study, Carapa procera showed interesting antiplasmodial activity in vitro against P. falciparum. The present study aimed to evaluate its in vivo potential against malaria parasites and its safety in mice. Materials and Methods: The antimalarial activity of the ethanolic extract was evaluated on Plasmodium berghei Anka in the Naval Medical Research Institute (NMRI) mice using the Peters 4-day suppressive test. The acute toxicity was performed according to the Lorke method and sub-acute toxicity following the Seewaboon method. The polyphenols and flavonoids were determined by colorimetric methods. The antioxidant activity of the extract was evaluated in vitro by Ferric Reducing Antioxidant Power (FRAPP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) methods. Results: Carapa procera had a good antiplasmodial activity at a dose of 250 mg kg¹ b.wt. Phytochemical screening revealed the presence of polyphenols and flavonoids in the extracts. Soxhlet ethanolic extracts had the highest content in polyphenols and flavonoids. The antioxidant activity of Soxhlet ethanolic extracts was better than macerated extract by DPPH method and FRAP method. Besides, no mortality in mice was recorded with the soxhlet ethanolic extract. No toxic signs were observed in animals in the sub-acute toxicity test. Conclusion: Carapa procera soxhlet ethanolic stem bark extract had a good in vivo antimalarial activity against Plasmodium berghei infection in mice and the extract was relatively safe when administered orally in mice.

A hypolipoprotein sepsis phenotype indicates reduced lipoprotein antioxidant capacity, increased endothelial dysfunction and organ failure, and worse clinical outcomes.

OBJECTIVE: Approximately one-third of sepsis patients experience poor outcomes including chronic critical illness (CCI, intensive care unit (ICU) stay > 14 days) or early death (in-hospital death within 14 days). We sought to characterize lipoprotein predictive ability for poor outcomes and contribution to sepsis heterogeneity. DESIGN: Prospective cohort study with independent replication cohort. SETTING: Emergency department and surgical ICU at two hospitals. PATIENTS: Sepsis patients presenting within 24 h. METHODS: Measures included cholesterol levels (total cholesterol, high density lipoprotein cholesterol [HDL-C], low density lipoprotein cholesterol [LDL-C]), triglycerides, paraoxonase-1 (PON-1), and apolipoprotein A-I (Apo A-I) in the first 24 h. Inflammatory and endothelial markers, and sequential organ failure assessment (SOFA) scores were also measured. LASSO selection assessed predictive ability for outcomes. Unsupervised clustering was used to investigate the contribution of lipid variation to sepsis heterogeneity. MEASUREMENTS AND MAIN RESULTS: 172 patients were enrolled. Most (~ 67%, 114/172) rapidly recovered, while ~ 23% (41/172) developed CCI, and ~ 10% (17/172) had early death. ApoA-I, LDL-C, mechanical ventilation, vasopressor use, and Charlson Comorbidity Score were significant predictors of CCI/early death in LASSO models. Unsupervised clustering yielded two discernible phenotypes. The Hypolipoprotein phenotype was characterized by lower lipoprotein levels, increased endothelial dysfunction (ICAM-1), higher SOFA scores, and worse clinical outcomes (45% rapid recovery, 40% CCI, 16% early death; 28-day mortality, 21%). The Normolipoprotein cluster patients had higher cholesterol levels, less endothelial dysfunction, lower SOFA scores and better outcomes (79% rapid recovery, 15% CCI, 6% early death; 28-day mortality, 15%). Phenotypes were validated in an independent replication cohort (N = 86) with greater sepsis severity, which similarly demonstrated lower HDL-C, ApoA-I, and higher ICAM-1 in the Hypolipoprotein cluster and worse outcomes (46% rapid recovery, 23% CCI, 31% early death; 28-day mortality, 42%). Normolipoprotein patients in the replication cohort had better outcomes (55% rapid recovery, 32% CCI, 13% early death; 28-day mortality, 28%) Top features for cluster discrimination were HDL-C, ApoA-I, total SOFA score, total cholesterol level, and ICAM-1. CONCLUSIONS: Lipoproteins predicted poor sepsis outcomes. A Hypolipoprotein sepsis phenotype was identified and characterized by lower lipoprotein levels, increased endothelial dysfunction (ICAM-1) and organ failure, and worse clinical outcomes.

Comparison of the efficacy of multiple antioxidant and hyperbaric oxygen treatments in the prevention of ischemia and necrosis of local random McFarlane skin flap.

OBJECTIVE: The aim of this study was to compare the efficacy of multiple antioxidant (Proxeed Plus (PP) with Carnitine, Selenium, Zinc, Coenzyme Q10, Vitamin C, Folic Acid, Vitamin B12) on local random skin flap healing with the hyperbaric oxygen (HBO) therapy. METHODS: Fourty rats were equally divided into five groups (Control, PP, HBO, HBO + PP, PP + HBO + PP). Local random McFarlane skin flap was applied to all rats. Following the applications, evaluations were made biochemical (TAS, TOS, OSI, IL-1ß, IL-6, TNF-α, TGF-ß, VEGF) and histopathological parameters. RESULTS: Necrosis percentage was found to be lower in the PP + HBO + PP group than all other groups whereas the necrosis percentages of PP and HBO groups were similar. Oxidative stress rates were significantly higher in the control group compared to the other groups whereas it was lower in the PP + HBO + PP group than all other groups. The inflammation parameters were the highest in the control group and the lowest in the PP + HBO + PP group. Growth factors were higher in the PP + HBO + PP group than all other groups. Epithelialization and wound healing were better in the HBO and PP groups than in the control group. The greatest healing, epithelialization and vascularization was seen in the PP + HBO + PP group. The histopathological findings in the PP + HBO + PP group were better in each inner region than in the other groups. CONCLUSION: Biochemical and histopathological parameters have shown that PP reduces ischemia and necrosis and increases oxygenation in flap healing by providing significant improvement thanks to the multiple molecular structures in its content.

Mortality in septic patients treated with vitamin C: a systematic meta-analysis.

BACKGROUND: Supplementation of vitamin C in septic patients remains controversial despite eight large clinical trials published only in 2020. We aimed to evaluate the evidence on potential effects of vitamin C treatment on mortality in adult septic patients. METHODS: Data search included PubMed, Web of Science, and the Cochrane Library. A meta-analysis of eligible peer-reviewed studies was performed in accordance with the PRISMA statement. Only studies with valid classifications of sepsis and intravenous vitamin C treatment (alone or combined with hydrocortisone/thiamine) were included. RESULTS: A total of 17 studies including 3133 patients fulfilled the predefined criteria and were analyzed. Pooled analysis indicated no mortality reduction in patients treated with vitamin C when compared to reference (risk difference - 0.05 [95% CI - 0.11 to - 0.01]; p = 0.08; p for Cochran Q = 0.002; I2 = 56%). Notably, subgroup analyses revealed an improved survival, if vitamin C treatment was applied for 3-4 days (risk difference, - 0.10 [95% CI - 0.19 to - 0.02]; p = 0.02) when compared to patients treated for 1-2 or > 5 days. Also, timing of the pooled mortality assessment indicated a reduction concerning short-term mortality (< 30 days; risk difference, - 0.08 [95% CI - 0.15 to - 0.01]; p = 0.02; p for Cochran Q = 0.02; I2 = 63%). Presence of statistical heterogeneity was noted with no sign of significant publication bias. CONCLUSION: Although vitamin C administration did not reduce pooled mortality, patients may profit if vitamin C is administered over 3 to 4 days. Consequently, further research is needed to identify patient subgroups that might benefit from intravenous supplementation of vitamin C.

Scientific Papers and Patents on Substances with Unproven Effects.

It is evident from reviewing scientific literature that the quality of argumentation in some areas of medical research has deteriorated during the last decades. Publication of a series of questionable reliability has continued without making references to the published criticism; examples are discussed in this review. Another tendency is that drugs without proven efficiency are advertised, corresponding products patented and marketed as evidence-based medications. Professional publications are required to register drugs and dietary supplements to obtain permissions for the practical use; and such papers appeared, sometimes being of questionable reliability. Several examples are discussed in this review when substances without proven effects were patented and introduced into practice being supported by publications of questionable reliability. Some of the topics are not entirely clear; and the arguments provided here can induce a constructive discussion.

Report: Comparison of qualitative, quantitative analysis and antioxidant potential between wild and cultivated Borago officinalis leaves from palestine.

Borago officinalis plant is an important plant of high medicinal and nutritional values. This study designed to evaluate antioxidant activity, screen the existence of phytogenic chemical compounds and to determine the total flavonoid and phenol contents of wild and cultivated Borago officinalis. Total flavonoid contents of the wild and cultivated Borago officinalis were determined by using rutin reference standard method and total phenols determined by using Folin Ciocalteu's method while antioxidant activity evaluated by using 2, 2-diphenyl-1-picryl-hydrazyl-hydrate assay. Phytochemical analyses indicated the presence of carbohydrate, phenols, flavonoids, phytosteroids tannins and volatile oil. The total flavonoid content of the methanolic extract from the wild borage plant was 22.4mg RU/g this value was reduced to 13.1mg RU/g for the cultivated methanolic extract as well as the total phenols contents was dropped from 5.21mg GA/g to 2.37mg GA/g methanolic extracts. Total tannins content of the wild growing borage plant was 13.7mg GA/g methanolic extract. This value was higher in the cultivated borage with 21.33mg GA/g methanolic extract. The wild leaves extract had IC50 =6.3µg/mL for wild leaves extract was closer to IC50 value of Trolox (standard reference with high antioxidant activity), while the cultivated leaves extract had higher IC50= 8.7µg/mL which mean lower antioxidant activity than the wild growing one. The data of this study showed that the extracts of Borago officinalis possess antioxidant and free radical scavenging activities. Variation was clear between wild and cultivated species, these findings propose that such plant extract could have a wide range of applications in both food and pharmaceutical industries. Therefore, more research is necessary to investigate different cultural practices on the efficiency of borage plant.

Comparison of the chromatographic fingerprint, multicomponent quantitation and antioxidant activity of Salvia miltiorrhiza Bge. between sweating and nonsweating.

Salvia miltiorrhiza Bge. is a traditional Chinese medicine applied in the treatment of various diseases in clinical practice. In the course of its processing, S. miltiorrhiza Bge. is usually processed by sweating. This study employed 10-component contents determination coupled with high-performance liquid chromatography (HPLC) fingerprint and antioxidant activity to investigate the effect of sweating on S. miltiorrhiza Bge. so as to evaluate the quality of S. miltiorrhiza Bge. The HPLC method was performed using C18 and 0.05% phosphoric acid aqueous solution-acetonitrile with a gradient elution system. It was validated for linearity, precision, repeatability, stability and recovery. Similarity analysis, principal components analysis and antioxidant activity assays were used to compare sweated S. miltiorrhiza Bge. (SSM) and nonsweated S. miltiorrhiza Bge. (NSSM). SSM and NSSM showed good similarities in HPLC fingerprint (>0.9), but principal components analysis could classify the HPLC fingerprint and 10-component quantitation analysis. Meanwhile, the antioxidant activity of SSM was significantly higher than that of NSSM (p < 0.01). The results of this study indicated that sweating could alter the content of chemical constituents in S. miltiorrhiza Bge., and could also improve its antioxidant activity. In addition, the method not only affords a viable strategy for comparing SSM and NSSM and assessing the quality of S. miltiorrhiza Bge., but also provides a reference for other herbal medicine that suffers from sweating.