Prevention of infections of the upper respiratory tract.

PMID: 

Laryngorhinootologie. 2018 Aug ;97(8):529-536. Epub 2018 Aug 6. PMID: 30081415

Abstract Title: 

[Prevention of Infections of the Upper Respiratory Tract].

Abstract: 

Because of its high prevalence acute respiratory diseases have a significant impact on the population. The focus of this review was the current state of knowledge for the prophylactic efficacy of: zinc, vitamin C, Echinacea preparations, garlic and carrying out physical measures. Furthermore, the benefits of pneumococcal and influenza vaccine were elicited. In the synopsis, the physical measures proved to be the most effective, cost-effective method to prevent infections. The intake of zinc, Echinacea preparations (for example: E. purpurea), vitamin C and garlic showed moderate success in the prevention of infection and must be elicited individually. Pneumococcal and annual influenza vaccines in family practice should be given furthermore accordingly topical STIKO-recommendation. Nevertheless, the prophylactic effect from influenza vaccines on usual cold illnesses is unsettled.

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Pharmacologic ascorbate as a pro-drug for hydrogen peroxide release to kill mycobacteria.

PMID: 

Biomed Pharmacother. 2019 Jan ;109:2119-2127. Epub 2018 Nov 27. PMID: 30551469

Abstract Title: 

Pharmacologic ascorbate as a pro-drug for hydrogen peroxide release to kill mycobacteria.

Abstract: 

BACKGROUND AND PURPOSE: Tuberculosis is one of the most highly fatal diseases worldwide, and one-third of the world's population has been infected with Mycobacterium tuberculosis (M. tuberculosis). A previous study showed that M. tuberculosis was highly susceptible to being killed by ascorbate (i.e. vitamin C, VC), but the molecular mechanisms of the bactericidal activity of VC against M. tuberculosis are still not well understood.EXPERIMENTAL APPROACH: We assayed the effects of VC as an anti-tuberculosis drug against mycobacteria (i.e. M. bovis BCG or M. tuberculosis H37Rv) in macrophages (i.e. RAW 264.7 cells). Relative global protein expression changes in 5 mM VC-treated and control samples of H37Rv were investigated by Tandem mass tag (TMT)-based quantitative proteomic analysis. qRT-PCR was also used to measure the differential expression of six intracellular stress response mycobacteria genes.KEY RESULTS: Quantitative proteomic analysis showed that 11 peptide components including rip3, fdxA, Rv2028c, mtp, LH57_00670, hspX, pfkB, Rv1824, Rv1813c, LH57_08410 and Rv2030c were up-regulated and 17 peptide components were down-regulated in 5 mM VC-treated H37Rv compared with the control samples. qRT-PCR also verified that VC could induce the expression of six genes (hsp, fdxD, furA, devR, hspX, and dnaB) in BCG and H37Rv. We also found that exosomes from RAW 264.7 cells treated with pharmacologic VC could kill M. bovis BCG in vitro.CONCLUSION AND IMPLICATIONS: Our results demonstrated that the bactericidal activity of VC against mycobacteria, as a pro-drug for hydrogen peroxide formation (HO), was dependent on reactive oxygen species production and the activated oxidative stress pathway, which suggested that pharmaceutical VC and exosomes from macrophages treated with VC could be used as potential anti-tuberculosis drugs.

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Alternate pathway to ascorbate induced inhibition of Mycobacterium tuberculosis.

PMID: 

Tuberculosis (Edinb). 2018 07 ;111:161-169. Epub 2018 Jun 21. PMID: 30029903

Abstract Title: 

Alternate pathway to ascorbate induced inhibition of Mycobacterium tuberculosis.

Abstract: 

Ascorbate has been demonstrated to interfere with the growth of Mycobacterium tuberculosis. It scavenges oxygen in the culture medium to induce dormancy of M. tuberculosis. It kills the mycobacteria by generating reactive oxygen intermediates via iron mediated Fenton reactions. In this study, we observed that ascorbate can inhibit M. tuberculosis isocitrate lyase (MtbICL) with an ICof 2.15 mΜ. MtbICL is an essential enzyme for the survival of M. tuberculosis under dormancy. We studied the effect of ascorbate on the growth of M. tuberculosis H37Rv metabolizing through citric acid cycle or glyoxylate cycle with glucose or acetate respectively as the sole carbon source. It was observed that 4 mM ascorbate inhibited ∼89% of the growth in glucose medium, which was confirmed to be mediated by Fenton reaction, as the inhibition was significantly lesser (61%) under low iron condition. On the other hand, in acetate medium, ∼97% of the growth was inhibited and the inhibition wasuninfluenced by the iron levels. 3-nitropropionate, a known inhibitor of MtbICL, was seen to cause significantly higher inhibition in the acetate medium than in the glucose medium; however it was indifferent to iron levels in either medium. Molecular docking and dynamic simulation studies confirmedstable binding of ascorbate to MtbICL leading to its inhibition. These observations suggest an additional pathway for ascorbate induced inhibition of M. tuberculosis through inhibition of glyoxylate cycle. Since human immune cells can accumulate ascorbate in millimolar concentrations, the in vitroactivity range (1-4 mM) of ascorbate against M. tuberculosis could be extrapolated in vivo. Our result supports the possible benefits of adding high vitamin C diet in TB-treated patients.

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The role of physiological vitamin C concentrations on key functions of neutrophils isolated from healthy individuals.

PMID: 

Nutrients. 2019 Jun 17 ;11(6). Epub 2019 Jun 17. PMID: 31212992

Abstract Title: 

The Role of Physiological Vitamin C Concentrations on Key Functions of Neutrophils Isolated from Healthy Individuals.

Abstract: 

Vitamin C (ascorbate) is important for neutrophil function and immune health. Studies showing improved immune function have primarily used cells from scorbutic animals or from individuals with infectious conditions or immune cell disorders. Few studies have focused on the requirements of neutrophils from healthy adults. Therefore, we have investigated the role of vitamin C, at concentrations equivalent to those obtained in plasma from oral intakes (i.e., 50-200µmol/L), on key functions of neutrophils isolated from healthy individuals. Cells were either pre-loaded with dehydroascorbic acid, which is rapidly reduced intracellularly to ascorbate, or the cells were activated in the presence of extracellular ascorbate. We measured the effects of enhanced ascorbate uptake on the essential functions of chemotaxis, oxidant production, programmed cell death and neutrophil extracellular trap (NET) formation. We found that neutrophils isolated from healthy individuals already had replete ascorbate status (0.35 nmol/10cells), therefore they did not uptake additional ascorbate. However, they readily took up dehydroascorbic acid, thus significantly increasing their intracellular ascorbate concentrations, although this was found to have no additional effect on superoxide production or chemotaxis. Interestingly, extracellular ascorbate appeared to enhance directional mobilityin the presence of the chemoattractant formyl-methionyl-leucyl-phenylalanine (fMLP). Stimulation of the cells in the presence of ascorbate significantly increased intracellular ascorbate concentrations and, although this exhibited a non-significant increase in phosphatidylserine exposure, NET formation was significantly attenuated. Our findings demonstrate the ability of neutrophils to regulate their uptake of ascorbate from the plasma of healthy humans to maintain an optimal level within the cell for proper functioning. Higher oral intakes, however, may help reduce tissue damage and inflammatory pathologies associated with NET formation.

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Schisandrae Chinensis Fructus inhibits behavioral deficits induced by sleep deprivation and chronic unpredictable mild stress.

PMID: 

Phytother Res. 2019 Dec ;33(12):3177-3190. Epub 2019 Aug 30. PMID: 31468620

Abstract Title: 

Schisandrae Chinensis Fructus inhibits behavioral deficits induced by sleep deprivation and chronic unpredictable mild stress via increased signaling of brain-derived neurotrophic factor.

Abstract: 

The present study was undertaken to explore the interactions between sleep deprivation (SD) and Schisandrae Chinensis Fructus (SCF) treatment in the antidepressant-like effects. We observed that SD aggravated the anxiety-like behavior induced by chronic unpredictable mild stress (CUMS) in the elevated plus maze test. However, the forced swimming test and sucrose preference test showed that SD (12 hr) alleviated the depressive symptoms and SD (72 hr) has the opposite effects. Administration of SCF showed a promising therapeutic effect on depression and anxiety induced by CUMS and SD. Moreover, SCF could potential strengthen the antidepressant-like effects of SD (12 hr) according to the behavioral tests. In addition, the BDNF level in hippocampus was elevated by SD (12 hr) and SCF treatment and together with the upregulation of TrkB/CREB/ERK and PI3K/AKT/GSK3β/mTOR signaling pathways. Besides, the protein levels of p70S6K and PSD95, which are downstream targets of mTOR, also increased by the treatment. These results indicated that the antidepressant-like effect of SCF in the CUMS depends on the activation of BDNF and the modulation of TrkB/CREB/ERK andPI3K/AKT/GSK3β/mTOR signaling cascades, and SD (12 hr) shared a common etiology consisting of complex bidirectional interactions with SCF.

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S. chinensis fruit extract is a potential herbal drug candidate for the amelioration and prevention of Parkinson’s disease.

PMID: 

Nutrients. 2019 Jul 21 ;11(7). Epub 2019 Jul 21. PMID: 31330885

Abstract Title: 

Neuroprotective Effect of Schisandra Chinensis on Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Induced Parkinsonian Syndrome in C57BL/6 Mice.

Abstract: 

(Turcz.) Baill. () is a well-known botanical medicine and nutritional supplement that has been shown to have potential effects on neurodegeneration. To investigate the potential neuroprotective effect offruit extract, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to induce behavioral disorders and dopaminergic neuronal damage in mice, and biochemical indicators were examined. Male C57BL/6 mice were used to establish the MPTP-induced parkinsonian syndrome model. Open field and rotarod tests were performed to evaluate the overall manifestation of motor deficits and rodent motor coordination. The mice were divided into 8 groups as follows: normal control; MPTP alone (25 mg/kg, i.p.);extract pretreatment (0.5, 1.5, 5 g/kg, p.o.); andextract treatment (0.5, 1.5, 5 g/kg, p.o.). Liquid chromatography coupled to electrochemical detection was used to monitor neurochemicals in the striatum. Tyrosine hydroxylase content was measured by immunohistochemistry, and biochemical antioxidative indicators were used to evaluate the potential neuroprotective effects offruit extract. The results demonstrated that treatment withfruit extract ameliorated MPTP-induced deficits in behavior, exercise balance, dopamine level, dopaminergic neurons, and tyrosine hydroxylase-positive cells in the striatum of mice. Among the pretreated and treatment groups, a high dose offruit extract was the most effective treatment. In conclusion,fruit extract is a potential herbal drug candidate for the amelioration and prevention of Parkinson's disease.

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Schisandra chinensis acidic polysaccharide partialy reverses acetaminophen-induced liver injury.

PMID: 

J Pharmacol Sci. 2019 Jul ;140(3):248-254. Epub 2019 Jul 24. PMID: 31400930

Abstract Title: 

Schisandra chinensis acidic polysaccharide partialy reverses acetaminophen-induced liver injury in mice.

Abstract: 

Schisandra chinensis is a hepatoprotective herb that has been used for centuries in China. Polysaccharide is one of the major active components in S. chinensis, which has been reported to improve liver injuries induced by carbon tetrachloride, alcohol, or high-fat diet. In this study, we observed the effects and corresponding mechanisms of the secondary component of Schisandra polysaccharide (acidic polysaccharide, SCAP) on a murine model of severe acute liver injury induced by acetaminophen (APAP). SCAP significantly decreased the serum alanine aminotransferase (ALT), aspartate aminotransferas (AST), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) levels, and was found to alleviate hepatic pathological alterations in the mouse model. Meanwhile, SCAP revealed a protective effects on the liver injury-related enzymes and factors, such as significantly diminished malondialdehyde (MDA) levels and glutathione (GSH) depletion, reduced ratio of B-cell lymphoma-2 (Bcl-2)-associated X protein (Bax)/Bcl-2, prohibited cleaved caspase-3 expression, and elevated the expression of p-AMPK, p-Akt, p-glycogen synthase kinase 3β (GSK 3β), nuclear factor erythroid 2-derived-like 2 (Nrf 2) and heme oxygenase-1 (HO-1) proteins in the liver tissues of the mouse model. In conclusion, we speculated that the protective activities of SCAP on the APAP-induced mouse model of acute liver injury might be related to its antioxidation, anti-inflammation and anti-apoptosis properties.

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