PMID: Front Med (Lausanne). 2019 ;6:165. Epub 2019 Jul 25. PMID: 31403046 Abstract Title: Boosting the Immune System, From Science to Myth: Analysis the Infosphere With Google. Abstract: The concept that one can"boost"immunity is a popular one. Although the only evidence-based approach to this is vaccination, the lay public is exposed to a wide range of information on how to boost immunity. The aim of this study was to analyze such information available on the Internet.We visited 185 webpages returned from a Google search on"boost immunity"and classified them by typology (blogs, commercial, government, no-profit, news, professional, scientific journals) and by using standard indicators of health information quality (JAMA score, HONCode). We then analyzed their content in terms of disease and"boosters"mentioned. Commercial and news websites represented one third of the results each. Of the 37 approaches to boost immunity recorded, the top ones were diet (77% of webpages), fruit (69%), vitamins (67%), antioxidants (52%), probiotics (51%), minerals (50%), and vitamin C (49%). Interestingly, vaccines ranked 27th, with only 12% of webpages mentioning them.Commercial websites are an important component of the information available to the public on the topic, and thus contribute providing biased information.
PMID: Sci Transl Med. 2020 Feb 26 ;12(532). PMID: 32102933 Abstract Title: High-dose vitamin C enhances cancer immunotherapy. Abstract: Vitamin C (VitC) is known to directly impair cancer cell growth in preclinical models, but there is little clinical evidence on its antitumoral efficacy. In addition, whether and how VitC modulates anticancer immune responses is mostly unknown. Here, we show that a fully competent immune system is required to maximize the antiproliferative effect of VitC in breast, colorectal, melanoma, and pancreatic murine tumors. High-dose VitC modulates infiltration of the tumor microenvironment by cells of the immune system and delays cancer growth in a T cell-dependent manner. VitC not only enhances the cytotoxic activity of adoptively transferred CD8 T cells but also cooperates with immune checkpoint therapy (ICT) in several cancer types. Combination of VitC and ICT can be curative in models of mismatch repair-deficient tumors with high mutational burden. This work provides a rationale for clinical trials combining ICT with high doses of VitC.
PMID: J Nutr Biochem. 2020 Mar ;77:108240. Epub 2019 Oct 30. PMID: 31841960 Abstract Title: Micronutrients in autoimmune diseases: possible therapeutic benefits of zinc and vitamin D. Abstract: A functional immune system is essential for healthy life. This is achieved by the coordinate activation and interaction of different immune cells. One should be aware that activation of the immune response is as important as its deactivation when the pathogens are cleared, as otherwise host tissue can be damaged up to life-threatening levels. Autoimmune diseases (AID) represent a phenomenon of immune cells attacking host cells and tissue. Five to eight percent of the world's population are currently affected by 80-100 AID. In recent years, the incidence has been constantly increasing, reaching alarmingly high numbers particularly for type 1 diabetes mellitus, Crohn's disease, rheumatoid arthritis, Sjogren's syndrome and multiple sclerosis. This indicates a higher societal burden of AID for the future. This article provides an overview of general concepts of triggers and underlying mechanisms leading to self-destruction. Lately, several original concepts of disease etiology were revised, and there is a variety of hypotheses on triggers, underlying mechanisms and preventive actions. This article concentrates on the importance of nutrition, especially zinc and vitamin D, for balancing the immune function. Homespun nutritional remedies seem to reenter today's therapeutic strategies. Current treatment approaches are largely symptomatic or suppress the immune system. However, recent studies reveal significant benefits of nutrition-related therapeutic approaches including prevention and treatment of established disease, which offer a cost-efficient and trigger-unspecific alternative addressing balancing rather than suppression of the immune system. Zinc and vitamin D are currently the best studied and most promising candidates for therapeutic intervention.
High doses of vitamin C are well-documented as being effective against viral infections, so why don't you hear about it more often?
Originally published on www.orthomolecular.org
PMID: J Int Med Res. 2010 Mar-Apr;38(2):386-414. PMID: 20515554 Abstract Title: Essential role of vitamin C and zinc in child immunity and health. Abstract: With the progressive elimination of dietary protein-energy deficits, deficiencies of micronutrients are emerging as the limiting factors in ensuring children's optimal health. Data from several countries in Asia and Latin America indicate that deficiencies of vitamin C and zinc continue to be at alarming levels. This article reviews the roles of vitamin C and zinc in supporting children's growth and development, with a particular focus on the complementary roles they play in supporting immune functions and combating infections. The contemporary relevance of vitamin C and zinc deficiency in the Asian and Latin American regions, both undergoing a rapid nutritional transition, are also discussed. Overall, there is increasing evidence that deficiency of vitamin C and zinc adversely affects the physical and mental growth of children and can impair their immune defences. Nutrition should be the main vehicle for providing these essential nutrients; however, supplementation can represent a valid support method, especially in developing regions.
PMID: J Am Coll Nutr. 2011 Aug ;30(4):248-58. PMID: 21917705 Abstract Title: Dietary intake and supplement use of vitamins C and E and upper respiratory tract infection. Abstract: OBJECTIVE: Antioxidants are regulators of immune function and may play a role in upper respiratory tract infections (URTI). We investigated the potential effects of dietary intake from food and supplement use of vitamins C and E on the risk of self-reported URTI.METHODS: We conducted a population-based cohort study of 1509 Swedish men and women ages 20 to 60 with a follow-up period of 4 months. Participants reported a total of 1181 occurrences of URTI. Poisson regression model was used to control for age, sex, and other confounding factors.RESULTS: Among women, we found that the incidence rate ratio (IRR) for high intake of vitamin C (>200 mg/d) from food was 0.69 (95% CI 0.49-0.98) compared with low intake (150 mg/d) compared with low intake (
Effect of ascorbic acid and alpha tocopherol on immune status of male Sprague Dawley rats exposed to chronic restraint stress.
PMID: J Ayub Med Coll Abbottabad. 2012 Jul-Dec;24(3-4):31-5. PMID: 24669603 Abstract Title: Effect of ascorbic acid and alpha tocopherol on immune status of male Sprague Dawley rats exposed to chronic restraint stress. Abstract: BACKGROUND: The immune system provides protection against infectious diseases or other insults. Psychological stress may alter antibody production through neurobiological pathways. Antioxidant supplementation is thought to improve immune status and thereby reduce infectious morbidity. The aim of this study was to determine the preventive effect of ascorbic acid and alpha tocopherol on immune status of rats exposed to chronic restraint stress.METHODS: A total of 150 healthy male Sprague Dawley rats were included in the study. They were divided into 5 groups, each comprised of 30 rats. Group I was the control group on normal diet. Group II rats were exposed to chronic restraint stress for 6 hours daily for 15 days, without antioxidant supplementation, whereas rats of groups III, IV and V were given supplementation of ascorbic acid or alpha tocopherol or both respectively, for one month prior to exposure of rats to chronic restraint stress. Total leukocyte count (TLC) and lymphocyte counts was done, and serum immuno-globulins (IgG, IgA, IgM, and IgE) levels were estimated using ELISA.RESULTS: Total leukocyte and lymphocyte counts and serum IgA, IgE, IgG, and IgM levels were found significantly (p 0.001) decreased in rats exposed to chronic restraint stress compared to the rats not exposed to the restraint stress. The combined supplementation of ascorbic acid and alpha tocopherol significantly (p 0.001) prevented the decline in total leukocyte and lymphocyte counts and serum immuno-globulins compared to the administration of either of the two antioxidants.CONCLUSION: Antioxidants (ascorbic acid and alpha tocopherol) given in combination produce greater beneficial effect in improving the immune status of rats exposed to chronic stress than individual supplementation of either ascorbic acid or alpha tocopherol.
Effect of interaction of vitamin C on macrophage immune response to infection with Mycobacterium bovis.
PMID: Cell Mol Biol (Noisy-le-grand). 2012 May 15 ;58 Suppl:OL1688-94. Epub 2012 May 15. PMID: 22762523 Abstract Title: Effect of interaction of vitamin C on macrophage immune response to infection with Mycobacterium bovis. Abstract: Bovine tuberculosis is a chronic infectious disease caused by Mycobacterium bovis affecting humans and livestock. Like Mycobacterium tuberculosis (M.tb), M. bovis can persist in cattle without causing overt symptoms after entering a non-replicating persistent (NRP) state. Given that M.tb enters NRP under stress conditions, we sought to find the effects of vitamin C (VC) on M. bovis in vitro and in vivo (VC could mimic stresses like hypoxia by O2 scavenging and acidic conditions in phagosome). M. bovis was cultured in a medium with VC for 48 h. The differential expression of five genes (dosR, dosS, dosT, icl, and hspX of M. bovis) implicated in the M. bovis NRP state was measured with real-time quantitative PCR. Expression of all five genes was increased by VC. Relative to the control, VC-exposed bacteria appeared smaller and more rounded in shape with a much thicker inner envelope. A lower number of viable bacteria were found in comparison with those of the control. We infected macrophage cell line ANA-1 with M. bovis and cultured it in VC-added medium (MC group) for 24h and 48 h. Expression of il-10, il-6, tnf-α, and il-β was examined and compared with expression by cells infected by M. bovis only without VC treatment (MB group), uninfected cells in the medium treated with VC (VC group), and cells in the medium only without VC. Il-1β, tnf-α, and il-6 transcription were up-regulated significantly in MCgroup. IL-10 gene expression in MB and MC groups was less than in the control at 24h, but that of MC group increased more than the MB group at 48 h. The numbers of intracellular M. bovis in the MC group were lower than that in the other groups. Slower growth was found in VC-treated M. bovis, and macrophages were more bactericidal for intracellular VC-stimulated M. bovis than for M. bovis with no VC treatment.
PMID: Antioxid Redox Signal. 2013 Dec 10 ;19(17):2054-67. Epub 2013 Feb 5. PMID: 23249337 Abstract Title: Vitamin C promotes maturation of T-cells. Abstract: AIMS: Vitamin C (ascorbic acid) is thought to enhance immune function, but the mechanisms involved are obscure. We utilized an in vitro model of T-cell maturation to evaluate the role of ascorbic acid in lymphocyte development.RESULTS: Ascorbic acid was essential for the developmental progression of mouse bone marrow-derived progenitor cells to functional T-lymphocytes in vitro and also played a role in vivo. Ascorbate-mediated enhancement of T-cell development was lymphoid cell-intrinsic and independent of T-cell receptor (TCR) rearrangement. Analysis of TCR rearrangements demonstrated that ascorbic acid enhanced the selection of functional TCRαβ after the stage of β-selection. Genes encoding the coreceptor CD8 as well as the kinase ZAP70 were upregulated by ascorbic acid. Pharmacologic inhibition of methylation marks on DNA and histones enhanced ascorbate-mediated differentiation, suggesting an epigenetic mechanism of Cd8 gene regulation via active demethylation by ascorbate-dependent Fe(2+) and 2-oxoglutarate-dependent dioxygenases.INNOVATION: We speculate that one aspect of gene regulation mediated by ascorbate occurs at the level of chromatin demethylation, mediated by Jumonji C (JmjC) domain enzymes that are known to be reliant upon ascorbate as a cofactor. JmjC domain enzymes are also known to regulate transcription factor activity. These two mechanisms are likely to play key roles in the modulation of immune development and function by ascorbic acid.CONCLUSION: Our results provide strong experimental evidence supporting a role for ascorbic acid in T-cell maturation as well as insight into the mechanism of ascorbate-mediated enhancement of immune function.
Curcumin restores innate immune Alzheimer's disease risk gene expression to ameliorate Alzheimer pathogenesis.
PMID: Neurobiol Dis. 2019 07 ;127:432-448. Epub 2019 Apr 2. PMID: 30951849 Abstract Title: Curcumin restores innate immune Alzheimer's disease risk gene expression to ameliorate Alzheimer pathogenesis. Abstract: Alzheimer's disease (AD) genetics implies a causal role for innate immune genes, TREM2 and CD33, products that oppose each other in the downstream Syk tyrosine kinase pathway, activating microglial phagocytosis of amyloid (Aβ). We report effects of low (Curc-lo) and high (Curc-hi) doses of curcumin on neuroinflammation in APPsw transgenic mice. Results showed that Curc-lo decreased CD33 and increased TREM2 expression (predicted to decrease AD risk) and also increased TyroBP, which controls a neuroinflammatory gene network implicated in AD as well as phagocytosis markers CD68 and Arg1. Curc-lo coordinately restored tightly correlated relationships between these genes' expression levels, and decreased expression of genes characteristic of toxic pro-inflammatory M1 microglia (CD11b, iNOS, COX-2, IL1β). In contrast, very high dose curcumin did not show these effects, failed to clear amyloid plaques, and dysregulated gene expression relationships. Curc-lo stimulated microglial migration to and phagocytosis of amyloid plaques both in vivo and in ex vivo assays of sections of human AD brain and of mouse brain. Curcumin also reduced levels of miR-155, a micro-RNA reported to drive a neurodegenerative microglial phenotype. In conditions without amyloid (human microglial cells in vitro, aged wild-type mice), Curc-lo similarly decreased CD33 and increased TREM2. Like curcumin, anti-Aβ antibody (also reportedto engage the Syk pathway, increase CD68, and decrease amyloid burden in human and mouse brain) increased TREM2 in APPsw mice and decreased amyloid in human AD sections ex vivo. We conclude that curcumin is an immunomodulatory treatment capable of emulating anti-Aβ vaccine in stimulating phagocyticclearance of amyloid by reducing CD33 and increasing TREM2 and TyroBP, while restoring neuroinflammatory networks implicated in neurodegenerative diseases.
PMID: Inflammopharmacology. 2019 Oct ;27(5):885-900. Epub 2019 May 28. PMID: 31140036 Abstract Title: Curcumin: a modulator of inflammatory signaling pathways in the immune system. Abstract: Curcumin is a natural compound derived from the spice, turmeric, that has been extensively reported for its efficacy in controlling or treatment of several inflammatory diseases. There is a growing body of literature that recognizes the anti-inflammatory effects of curcumin in the immune system. On the other hand, the role of inflammatory signaling pathways has been highlighted in the pathogenesis of several inflammatory diseases, and signaling molecules involved in these pathways are considered as valuable targets for new treatment approaches. We aimed to provide a comprehensive overview of the modulatory effects of curcumin on inflammatory signaling pathways which leads to inhibition of inflammation in different types of immune cells and animal models. In this comprehensive review, we elaborate on how curcumin can effectively inhibit multiple signaling molecules involved in inflammation including NF-κB, JAKs/STATs, MAPKs, β-catenin, and Notch-1.
Antiviral and immunomodulatory effects of polyphenols on macrophages infected with dengue virus serotypes 2 and 3 enhanced or not with antibodies.
PMID: Infect Drug Resist. 2019 ;12:1833-1852. Epub 2019 Jul 1. PMID: 31303775 Abstract Title: Antiviral and immunomodulatory effects of polyphenols on macrophages infected with dengue virus serotypes 2 and 3 enhanced or not with antibodies. Abstract: There is a lack of specific antiviral therapy against dengue virus (DENV) in current use. Therefore, a great proportion of dengue cases progress to severe clinical forms due to a complex interplay between virus and host immune response. It has been hypothesized that heterotypic non-neutralizing antibodies enhance DENV infection in phagocytic cells, and this induces an inflammatory response that is involved in the pathogenesis of severe dengue.To identify the antiviral and immunomodulatory effects of polyphenols on dengue virus infection.Human U937-DC-SIGN macrophages were infected with DENV serotypes 2 or 3 in the presence or not of enhancing antibody 4G2. Viral titers and the secretion of tumor necrosis factor-alpha, IL-6, IL-10 and interferon-alpha were analyzed timely.DENV infection alone induced high production of IL-6 and TNF-α, but in the presence of 4G2 antibody, viral titers and TNF-α secretion were potentiated. Based on anti-inflammatory antecedents, the polyphenols curcumin, fisetin, resveratrol, apigenin, quercetin and rutin were tested for antiviral and immunomodulatory properties. Only quercetin and fisetin inhibited DENV-2 and DENV-3 infection in the absence or presence of enhancing antibody (>90%,
PMID: Phytother Res. 2019 Nov ;33(11):2798-2820. Epub 2019 Aug 19. PMID: 31429161 Abstract Title: Therapeutic effects of curcumin on sepsis and mechanisms of action: A systematic review of preclinical studies. Abstract: Sepsis is a complex disease that begins with an infectious disorder and causes excessive immune responses. Curcumin is considered as an active component of turmeric that can improve the condition in sepsis due to its anti-inflammatory and antioxidant properties. PubMed, Embase, Google Scholar, Web of Science, and Scopus databases were searched. Searching was not limited to a specific publication period. Only English-language original articles, which had examined the effect of curcumin on sepsis, were included. At first, 1,098 articles were totally found, and 209 articles were selected after excluding duplicated data; 46 articles were remained due to the curcumin effects on sepsis. These included 23 in vitro studies and 23 animal studies. Our results showed that curcumin and various analogs of curcumin can have an inhibitory effect on sepsis-induced complications. Curcumin has the ability to inhibit the inflammatory, oxidative coagulation factors, and regulation of immune responses in sepsis. Despite the promising evidence of the therapeutic effects of curcumin on the sepsis complication, further studies seem necessary to investigate its effect and possible mechanisms of action in human studies.
PMID: Endocr Metab Immune Disord Drug Targets. 2019 Aug 23. Epub 2019 Aug 23. PMID: 31441735 Abstract Title: Curcumin Suppresses Epithelial Growth Factor Receptor (EGFR) and Proliferative Protein (Ki 67) in Acute Lung Injury and Lung Fibrosis In Vitro and In Vivo. Abstract: BACKGROUND: Acute lung injury is one of the common condition caused due to bleomycin therapy which leads to pulmonary fibrosis, which is one of the severe interstitial lung disease most commonly affecting the elderly individuals. EGFR and Ki67 are can be marked as beneficial markers for detecting pulmonary fibrosis based on which clinicians can guide therapy.OBJECTIVE: The aim of the study was to evaluate effect of curcumin as an intervention on two prognostic markers EGFR and Ki67 in bleomycin induced basal alveolar epithelial cells and C57BL/6 mice. Protein expressions and pathological expressions of EGFR and Ki67 were evaluated to analyze the effect of curcumin on it both in in vitro and in vivo approaches.METHODS: The effect of curcumin was investigated both on cell lines (A549) and animal model (both normal and bleomycin induced mice, n=6) via techniques like western blotting for protein expression. Techniques like immunofluorescence and immunohistochemistry was carried out and examined under confocal microscopy and phase contrast microscope to analyze the expressions of the said biomarkers. Bleomycin was used as a causative agent to induce inflammation.KEY FINDINGS: The natural polyphenol curcumin could downregulate the expressions levels of Ki67 and EGFR both in vitro and in vivo. Immunofluorescence analysis on proliferative marker Ki67 showed reduced expression on curcumin treatment in vitro. The pathological sections from treated lungs showed significant decrease in EGFR and Ki67 levels when exposed to curcumin.CONCLUSION: We conclude that curcumin, well-known natural bioactive compound holds strong anti-proliferative on Ki67 and EGFR expressions.We observed that, a clinical outcome in diagnosis of pulmonary fibrosis remains to be unconvincing so far. Curcumin can be considered as a potential therapeutic.
PMID: Immune Netw. 2019 Oct ;19(5):e35. Epub 2019 Oct 17. PMID: 31720046 Abstract Title: Curcumin Elevates TCells and Germinal Center B Cell Response for Antibody Production in Mice. Abstract: Curcumin is a natural product extracted from. It has been reported as a potent antioxidant and anti-inflammatory compound. Previous studies have demonstrated that curcumin suppresses pro-inflammatory cytokine production via inhibition of NF-κB in macrophages. However, its role in adaptive immune cells such as T cells,, has not clearly been elucidated. Here, we examined the effects of curcumin in T follicular helper (T) cells and on Ab production during NP-ovalbumin immunization in mice. The results revealed that curcumin administered daily significantly increased CXCR5B-cell lymphoma 6Tcells and CD95GL-7germinal center (GC) B cells in draining lymph nodes. In addition, curcumin treatment in mice induced total Ab production as well as high affinity IgG1 and IgG2b Ab production. Collectively, these results suggest that curcumin has positive regulatory roles in Tcell functions and GC responses. Thus, this could be an advantageous supplement to enhance humoral immunity against infectious diseases and cancer.
PMID: Biochem Pharmacol. 2020 Jan 24:113824. Epub 2020 Jan 24. PMID: 31987852 Abstract Title: Using curcumin to turn the innate immune system against cancer. Abstract: Curcumin has been at the center of vigorous research and major debate during the past decade. Inspired by its anti-inflammatory properties, many curcumin-based products are being sold now to manage various forms of arthritis. Parallel preclinical studies have established its role in dissolving beta-amyloid plaques, tau-based neurofibrillary tangles, and also alpha-synuclein-linked protein aggregates typically observed in Parkinson's disease. In cancer research, most cancer cells in culture are eliminated by curcumin at an IC50 of 15-30 µM, whereas the maximum in vivo curcumin concentration achieved in humans is only about 6 µM. Additionally, a decade ago, no improvement over the placebo groups was observed in clinical studies using free curcumin as an anticancer agent. The lack of anticancer efficacy was attributed to its lowbioavailability, which results from the low water-solubility and high metabolic rate in vivo. Newer lipid-complexed or antibody-targeted forms have been used and these studies have revealed an exciting property of curcumin, which involves repolarization of the tumor-promoting, tumor-associated microglia/macrophages (TAMs) into a tumoricidal form and recruitment of natural killer cells from the periphery. This review will cover some efforts to explore the effect of appropriately-delivered curcumin to dramatically alter the tumor microenvironment, thereby launching an indirect attack on the tumor cells and the tumor stem cells. Reviewing some aspects of immunotherapy, this article will argue for the use of the innate immune cells in cancer therapy.
PMID: Biomed Pharmacother. 2020 May ;125:109946. Epub 2020 Jan 28. PMID: 32004976 Abstract Title: Curcumin regulates the differentiation of naïve CD4+T cells and activates IL-10 immune modulation against acute lung injury in mice. Abstract: OBJECTIVES: Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is one type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs. Curcumin has been reported to be an anti-inflammatory factor through enhancing the function of regulatory T cells (Tregs). This study aimed to explore the effect of curcumin on the differentiation of Tregs and the role of curcumin in ALI/ARDS.METHODS: A cecal ligation and puncture (CLP)-induced acute lung injury mouse model was used to explore the effect of curcumin in ALI/ARDS. The severity of lung injury was evaluated. Immunohistochemistry of IL-17A and MPO in lung tissue was examined. Treg-related cytokine levels in serum and bronchoalveolar lavage fluid (BALF) were tested. The expression of nuclear factor-kappa B (NF-κB) in lung tissue was detected. Macrophages in lung tissue were detected by immunofluorescence. Splenic CD4+CD25+FOXP3+ Tregs were quantified, and the differentiation of Tregs from naïve CD4 + T cell and STAT5 was evaluated. The expression of IL-10 during naïve CD4 + T cell differentiation in vitro was tested.RESULTS: Curcumin alleviated lung injury in the induced CLP mouse model and suppressed inflammation. IL-17A, MPO-producing neutrophils, and NF-κB p65 expression in lungs of CLP mice decreased significantly after pretreatment with curcumin. We found curcumin could regulate M1/M2 macrophage levels in lungs of CLP mice. This may have been through regulating the differentiation of Tregs and the production of Treg-derived IL-10. Treg-derived IL-10 is the main factor that could affect macrophage polarization. We found curcumin could increase Treg proportions in vivo and up-regulate IL-10 expression in serum and BALF of CLP mice. In our in vitro experiments, we found curcumin could promote Treg differentiation and increase the production of IL-10.CONCLUSIONS: Curcumin can reduce the degree of severity of ALI and uncontrolled inflammation through promoting the differentiation of naïve CD4 + T cells to CD4+ CD25+ FOXP3+ Tregs. Curcumin promotes the conversion of macrophages from M1 to M2. The differentiation of Tregs induced by curcumin may be one source of IL-10 immune modulation.
PMID: S Afr Med J. 1980 Dec 13 ;58(24):974-7. PMID: 7444701 Abstract Title: The effect of ascorbate on cellular humoral immunity in asthmatic children. Abstract: Ten White children with bronchial asthma and exercise-induced bronchoconstriction were assessed immunologically before and 1, 3 and 6 months after the commencement of standard therapy supplemented with ascorbate 1 g/d. The tests of cellular immune function were neutrophil chemotaxis, phagocytosis and resting and stimulated nitroblue tetrazolium reduction, and lymphocyte mitogen-induced transformation. Humoral functions measured were secretory IgA, serum immunoglobulins, alpha 1-antitrypsin, C3, C4 and total haemolytic complement, antistreptolysin O (ASO) and C-reactive protein. Radio-allergosorbent testing to the common allergens Cynodon dactylon (grass), Dermatophagoides pteronyssinus (mite), house dust and cat epithelium was performed on each child before and 3 and 6 months after treatment. Two children had depressed neutrophil motility, 4 had depressed lymphocyte transformation, and 7 had elevated levels of ASO. These functions normalized after 6 months of ascorbate-supplemented therapy. Serum total IgE levels but not specific IgE levels were likewise reduced after 6 months of therapy. Reduced levels of serum alpha 1-antitrypsin were observed in 2 children, and remained unchanged throughout the study.
The mechanistic activity of Chinese skullcap may make it a useful herb for treating periodontal disease.
PMID: Complement Ther Med. 2018 Jun ;38:11-18. Epub 2018 Mar 26. PMID: 29857875 Abstract Title: Protective role of flavonoid baicalin from Scutellaria baicalensis in periodontal disease pathogenesis: A literature review. Abstract: INTRODUCTION: Periodontal disease is characterized by a chronic infection, leading to the irreversible destruction of tissues supporting the teeth. Bacteria, pro-inflammatory mediators and host immune response play important role in the progress of periodontal disease. Baicalin is a bioactive flavone extracted from the dry raw root of Scutellaria baicalensis, with pharmaceutical actions of anti-inflammation, anti-oxidants, anti-tumor, antivirus, and so on. The present review summarizes the efficacy of baicalin in periodontal treatment.METHODS: A computer-based literature search was carried out using Pubmed, Scopus and Web of Science to identify papers published until 2017. Keywords used in the search were"baicalin"/"baicalein"and various words related to periodontal disease (periodontal, periodontitis, periodontal tissue, gingival, gingivitis, gingival tissue, periodontal disease, gingival disease, gingiva, periodontium).RESULTS: A total of 28 original studies were found, including 3 bacteriological studies, 7 zoological studies and 18 cytological studies. 15 of them were published in English and 13 of them were published in Chinese. Results from these 28 studies could not be pooled to conduct meta-analysis due to the heterogeneity. The pharmacological properties and mechanisms of baicalin for treating periodontal disease is mainly focused on five aspects: antibacterial effect on putative periodontopathic bacteria, protective effect on periodontal tissues, regulatory effect on pro-inflammatory mediators and matrix metalloproteinases, and regulatory effect on innate immune response.CONCLUSIONS: Baicalin have been shown to possess multiple pharmacological activities in periodontal tissues. However, the underlying mechanisms have not been fully defined. Further researches are needed to provide more scientific evidence for the clinical periodontal treatment.
Chinese skullcap regulates free fatty acid metabolism to ameliorate nonalcoholic fatty liver disease.
PMID: J Nat Med. 2018 Jun ;72(3):655-666. Epub 2018 Mar 14. PMID: 29542003 Abstract Title: Scutellaria baicalensis regulates FFA metabolism to ameliorate NAFLD through the AMPK-mediated SREBP signaling pathway. Abstract: Scutellaria baicalensis has been reported to improve the lipid metabolism of high-fat diet-induced liver dysfunction, but direct evidence is rare. This study aimed to explore the effects and mechanisms of S. baicalensis and its major constituent baicalin on hepatic lipotoxicity. KK-Amice and orotic acid (OA)-induced nonalcoholic fatty liver disease (NAFLD) rats were used to evaluate lipid metabolism regulatory effects. Sodium oleate-induced triglyceride-accumulated HepG2 cells were used for the mechanism study, pretreated with or without compound C or STO-609 or transfected with liver kinase B1 (LKB1) siRNA. In KK-Amice, S. baicalensis extract showed a decreased effect on serum and hepatic triglycerides, total cholesterols, and free fatty acid (FFA) levels after 8 weeks of treatment. In OA-induced NAFLD rats, 18 days of treatment with baicalin significantly inhibited hepatic lipid accumulation, attenuating hepatocyte hypertrophy, vacuolization and necrosis. S. baicalensis and baicalin treatment significantly suppressed the sterol regulatory element bindingprotein-1c (SREBP-1c) transcriptional program with downregulation of gene and protein expression of SREBP-1c (both precursor and mature fraction) and acetyl-CoA carboxylase, fatty acid synthase and stearoyl-CoA desaturase, and upregulation of AMP-activated protein kinase (AMPK), carnitine palmitoyltransferase 1 and nuclear respiratory factor 2 in the liver. Furthermore, activation of AMPK by baicalin was observed to be relative to the increase in phosphorylation of calmodulin-dependent protein kinase kinase. Taken together, S. baicalensis conferred preventive effects against FFA-induced lipotoxicity through the AMPK-mediated SREBP signaling pathway.
PMID: Int Immunopharmacol. 2015 Dec ;29(2):269-277. Epub 2015 Nov 11. PMID: 26578286 Abstract Title: The investigation of anti-inflammatory activity of volatile oil of Angelica sinensis by plasma metabolomics approach. Abstract: Angelica sinensis (AS) is an important medicinal plant, and volatile oil is the main pharmacologically active ingredient. This study was aimed to investigate the anti-inflammatory activity of the volatile oil of A. sinensis (VOAS) and explore its potential anti-inflammatory mechanism by plasma metabolomics approach. Rat acute inflammation was induced by subcutaneous injection of carrageenan in hind paws. Paw edema, histamine (HIS) and 5-hydroxytryptamine (5-HT) were detected. Then, we analyzed plasma metabolic profiling of acute inflammation and performed pathway analysis on the metabolite markers reversed after VOAS administration and further integration of metabolic networks. The results showed that VOAS could alleviate the paw edema and decrease plasma HIS and 5-HT levels. Fourteen metabolite markers of acute inflammation were screened, and the levels were all reversed to different degrees after VOAS administration. These metabolite markers mainly related to linoleic acid metabolism, ascorbate and aldarate metabolism, arachidonic acid metabolism, glyoxylate and dicarboxylate metabolism, and glycine, serine and threonine metabolism. In metabolic networks, glycine and arachidonic acid were node molecules. It indicated that VOAS could significantly inhibit systemic inflammatory response triggered by acute local stimulation and it exerted anti-inflammatory activity mainly through regulating the disturbed metabolic networks centered on glycine and arachidonic acid.
Angelica sinesis extracts display antiproliferative, anti-inflammatory, anti-mutagenic effects in vitro.
PMID: Zhongguo Zhong Yao Za Zhi. 2018 Mar ;43(6):1235-1240. PMID: 29676134 Abstract Title: [Colorectal cancer preventive effect of combined administration of phenolic acids and supercritical extracts from Angelica sinensis]. Abstract: This study aimed to investigate the colorectal cancer preventive effect of the combined administration of phenolic acids and supercritical extracts from Angelica sinensis. The AOM/DSS model in mice was adopted. Phenolic acids were administrated orally in the initial stage of the model at a dose of 1 g·kg⁻¹ BW, which was combined withtherectal administration with three doses of supercritical extracts (15, 30, 60 g·kg⁻¹ BW). PCNA, 8-oxoguaine, γ-H2AX, iNOS and COX-2 were tested by immunohistochemistry and Western blot assays. The results showed that the combined administration of phenolicacids and supercritical extracts from A. sinensis suppressed the tumor growth and cell proliferation, and DNA damages and inflammatory responses were reduced in a dose-dependent manner. These results indicate that the combined administration of phenolic acids and supercritical extracts from A. sinensis have a certain effect in preventing carcinogenesis.
Angelica whole plant and leaf display the highest anxiolytic activity whereas the root, fruit, intermediate, and stem display the least.
PMID: J Tradit Complement Med. 2012 Jul ;2(3):235-41. PMID: 24716138 Abstract Title: Anti-anxiety Activity of Methanolic Extracts of Different Parts of Angelica archangelica Linn. Abstract: Angelica archangelica Linn.is a herb distributed in tropical and subtropical regions of the world. In Indian and Chinese system of medicine, it is used for nervous disorders and cerebral diseases. Previously the aqueous extract of the A. archangelica was evaluated for anxiolytic activity and was found to have significant potential for the same. The present study is aimed to evaluate the anxiolytic activity of methanol extract of root (MER), stem (MES), leaf (MEL), fruit (MEF) and whole plant (MEW) of Angelica archangelica Linn. All the extracts (MER, MES, MEL, MEF and MEW) were evaluated for anxiolytic effects using elevated plus maze test (EPM) model in rats. Methanol extracts of different parts of A.archangelica had increased number of entries and time spent in open arms while they decreased the number of entries and duration of time spent in closed arm of the EPM. In a similar fashion, the diazepam increased the percentage of time spent and percentage of arm entries in the open arms (*P
PMID: Prog Neuropsychopharmacol Biol Psychiatry. 2013 Jan 10 ;40:180-6. Epub 2012 Aug 29. PMID: 22960104 Abstract Title: Coumarins from Angelica archangelica Linn. and their effects on anxiety-like behavior. Abstract: UNLABELLED: TRADITIONAL RELEVANCE: Angelica archangelica Linn. (Apiaceae) is an herb distributed in tropical and subtropical regions of the world. Both in Chinese and Indian system of medicine, it is used for nervous disorders including anxiety, anorexia, migraine and other cerebral diseases.AIM OF STUDY: To evaluate the anxiolytic potential of non polar coumarins isolated from A. archangelica Linn.METHODS AND RESULTS: A. archangelica Linn. (1 kg) was subjected to extraction in a soxhlet apparatus with petroleum ether (40-60°C), yield 6.9% w/w. The extract of petroleum ether produced a yellow colored precipitate (YP) which was evaluated for anxiolytic like effect using EPM test and was found significant (**P
Angelica root displays antiviral activity against herpes simplex virus-1 and coxsackievirus B3 infections.
PMID: Food Chem Toxicol. 2017 Nov ;109(Pt 2):1026-1031. Epub 2017 May 6. PMID: 28487231 Abstract Title: Antiviral effect of compounds derived from Angelica archangelica L. on Herpes simplex virus-1 and Coxsackievirus B3 infections. Abstract: The dichloromethane extract from fruits of Angelica archangelica L. was separated by the modern high-performance countercurrent chromatography (HPCCC). The extract and five pure compounds: xanthotoxin, bergapten, imperatorin, phellopterin and isoimperatorin, and the mixture of imperatorin and phellopterin, have been studied as the potential antiviral agents against Herpes simplex virus type l and Coxsackievirus B3. The cytotoxicity was measured using the MTT method. Compounds were tested for the in vitro antiviral activity using the cytopathic effect (CPE) inhibitory assay and by the virus titre reduction assay. Real-time PCR was used to quantify the relative inhibition of the HSV-1 replication. The results indicate that the highest activity was demonstrated by the extract, imperatorin, phellopterin and the mixture of imperatorin and phellopterin, reducing the HSV-1 replication by 5.61 log, 4.7 log, 3.01 log and 3.73 log, respectively. The influence of isolated compounds on the CVB3 replication was not significant. Only the extract caused the decrease in the titre of virus in relationto the virus control. Our results show that coumarins of A. archangelica L. might be a potential candidate for the development of the alternative natural anti- HSV-1 compound. Moreover, the presence of isopentenyloxy moiety at C-8 position significantly improves their activity.
This paper describes traditional Chinese herbs used to clear heat that have been demonstrated to possess anti-inflammatory and antimicrobial activity.
PMID: J Tradit Complement Med. 2014 Apr ;4(2):93-8. PMID: 24860732 Abstract Title: Anti-inflammatory and Antimicrobial Effects of Heat-Clearing Chinese Herbs: A Current Review. Abstract: Inflammation is a normal immune response; but if the body's regulation of inflammation is dysfunctional, then it will have an adverse effect on the body. Although use of modern drugs for inflammation has a relieving effect, it is still unsatisfactory. Moreover, the emergence of drug-resistant strains and even new kinds of microorganisms is causing significant morbidity and mortality. Recently, more attention has been focused on herbal medicine to treat various diseases because of the ability of the herbs to affect multiple target signaling pathways and their multiple mechanisms of action. Thus, a large number of studies have reported on the anti-inflammatory and antimicrobial effects of the traditional Chinese herbs. Literature survey was performed by conducting systematic electronic search in PubMed, Science Direct, Google Scholar, and in books. This review has listed 11 heat-clearing Chinese herbs (HCCHs) including Scutellaria baicalensis ( Huáng Qín), Coptis chinensis ( Huáng Lián), Flos Lonicerae ( Jīn Yín Hūa), Forsythia suspensa ( Lián Qiào), Isatidis Folium ( Dà Qīn Yè), Radix Isatidis ( Bǎn Lán Gēn), Viola yedoensis ( Zǐ Huā Dì Dīn), Pulsatilla Radix ( Bái Tóu Wēn), Andrographis paniculata ( Chuān Xīn Lián), Houttuynia cordata ( Yú Xīng Cǎo), and Patrinia Herba ( Bài Jiàn Cǎo), which have anti-inflammatory and antimicrobial effects, and has described their effects through different mechanisms of action and multiple targets. Their ability to affect multiple target signaling pathways and their potential mechanisms of action contributing to their anti-inflammatory and antimicrobial activity may be related to their action of removing heat and counteracting toxicity. Further studies are needed on the collection of HCCHs to know the detailed mechanism of action of herbs in this group for the assessment of effective drug.
The US Gov. Health Statistics Agency Directs Hospitals to Confirm Suspected COVID-19 Deaths As Confirmed
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While the hysteria and panic over COVID-19's presumed lethality grow, so do serious questions about whether the government and media are accurately reporting on the scale of the threat. A document has surfaced revealing that the government's own health statistics agency is now directing hospitals to define deaths merely suspected to be linked to COVID-19 as confirmed on death certificates.
PMID: J Periodontol. 2006 Feb ;77(2):271-9. PMID: 16460254 Abstract Title: Inhibition of proinflammatory activities of major periodontal pathogens by aqueous extracts from elder flower (Sambucus nigra). Abstract: BACKGROUND: Prolonged induction of excessive levels of inflammatory mediators contributes to the pathogenesis of chronic disease states, such as periodontitis. It is thus important to develop safe and effective anti-inflammatory strategies for therapeutic reasons. In this study, we determined the ability of aqueous extracts from elder flower (Sambucus nigra) to inhibit the proinflammatory activity of major virulence factors from the periodontal pathogens Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans.METHODS: Monocytes/macrophages or neutrophils were incubated with whole cells of P. gingivalis, A. actinomycetemcomitans, or purified components thereof (lipopolysaccharide and fimbriae) in the absence or presence of elder flower extract and were assayed for cytokine production, integrin activation, or induction of the oxidative burst.RESULTS: The elder flower extract was found to potently inhibit all proinflammatory activities tested. Investigation of the underlying mechanisms revealed that the anti-inflammatory extract inhibited activation of the nuclear transcription factor kappaB and of phosphatidylinositol 3-kinase.CONCLUSION: The elder flower extract displays useful anti-inflammatory properties that could be exploited therapeutically for the control of inflammation in human periodontitis.
Elderberry and elderflower extracts inhibit nitric oxide production in lipopolysaccharide-activated macrophages.
PMID: Int J Mol Sci. 2017 Mar 8 ;18(3). Epub 2017 Mar 8. PMID: 28282861 Abstract Title: Elderberry and Elderflower Extracts, Phenolic Compounds, and Metabolites and Their Effect on Complement, RAW 264.7 Macrophages and Dendritic Cells. Abstract: Modulation of complement activity and inhibition of nitric oxide (NO) production by macrophages and dendritic cells may have therapeutic value in inflammatory diseases. Elderberry and elderflower extracts, constituents, and metabolites were investigated for their effects on the complement system, and on NO production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages and murine dendritic D2SC/I cells. The EtOH crude extracts from elderberry and elderflower and the isolated anthocyanins and procyanidins possessed strong complement fixating activity and strong inhibitory activity on NO production in RAW cells and dendritic cells. Phenolic compounds in the range of 0.1-100µM showed a dose-dependent inhibition of NO production, with quercetin, rutin, and kaempferol as the most potent ones. Among the metabolites, caffeic acid and 3,4-dihydroxyphenylacetic acid showed the strongest inhibitory effects on NO production in both cell lines, without having cytotoxic effect.Only 4-methylcatechol was cytotoxic at the highest tested concentration (100 µM). Elderberry and elderflower constituents may possess inflammatory modulating activity, which increases their nutritional value.