Research - Immune System
Systematic exploration of Astragalus membranaceus and Panax ginseng as immune regulators: Insights from the comparative biological and computational analysis
Junqiu Liu , Shivraj Hariram Nile , Guoliang Xu , Yuesheng Wang , Guoyin Kai
Immune system plays a decisive role for defending various pathogenic microorganisms. Astragalus membranaceus (AM) and Panax ginseng (PG) are two tonic herbs used in traditional Chinese medicine (TCM) as immune booster and help to control diseases with their healthy synergistic effect on immune system.
This study was aimed to investigate the promote effect and molecular mechanisms of AM and PG on immune system as booster and to control the target diseases using animal and computational systematic study.
Computational models including absorption, distribution, metabolism, and elimination (ADME) with weighted ensemble similarity (WES) algorithm-based models and ClueGo network analysis were used to find the potential bioactive compounds targets and pathways, which were responsible for immune regulation. Viscera index analysis, proliferation activity of splenic lymphocytes and cytotoxic activity of NK cells assays were performed to validate the effect of AM and PG on immune system of long-term administrated mice. Metabonomic study of mice plasma was conducted to investigate effect of AM and PG on the endogenous metabolic perturbations, together with correlation analysis.
AM and PG simultaneously showed the ability to strengthen the immune system function including enhancement of spleen and thymus index, proliferation of splenic lymphocytes and cytotoxic activity of NK cells. Besides, the different molecular mechanisms of AM and PG on immune regulation were also investigated by analyzing the potential bioactive compounds, enzymes actions and pathways. Quercetin, formononetin and kaempferol were the main immune-related compounds in AM, while ginsenoside Ra1, ginsenoside Rh1 and kaempferol in PG. About 10 target proteins were found close to immune regulation, including acetylcholinesterase (ACHE, common target in AM and PG), sphingosine kinase 1(SPHK1), cytidine deaminase (CDA), and Choline O-acetyltransferase (CHAT). Glycerophospholipid metabolism was regulated in both AM and PG groups. Pyrimidine metabolism and sphingolipid metabolism were considered as the special pathway in AM groups. Energy metabolism and glycerolipid metabolism were the special pathways in PG groups.
A novel comprehensive molecular mechanism analysis method was established and applied to clarify the scientific connotation of AM and PG as immune regulation, with similar herbal tonic effect provided in clinical practice of TCM, which can provide a new line of research for drug development (immune booster) using AM and PG.
Source : Journal Phytomedicine
Link to Full Article
Integrated Metabolomics and Network Pharmacology Study on Immunoregulation Mechanisms of Panax ginseng through Macrophages
Junjie Hao,1,2 Huangwanyin Hu,1,2 Jing Liu,2,3 Xuan Wang,2,4 Xiaoyi Liu,2 JiaboWang,2 Ming Niu,2 Yanling Zhao,2 and Xiaohe Xiao
Panax ginseng (PG) is a widely used functional food and herbal with immunoregulation activity. Currently, immunoregulation studies of PG mainly focused on the specific actions of individual constituents. However, the integral immunoregulation mechanisms of PG need further research. In this study, an integrated metabolomics and network pharmacology approach were used to investigate it. High-content screening was used to evaluate macrophage phagocytosis activity of PG. Untargeted metabolomics profiling of murine macrophage cells with UHPLC-Q-TOF-MS and a multivariate data method were performed to discover the potential biomarkers and metabolic pathways. Then, a macrophage phenotype related “ingredients-targets-metabolites” network of PG was constructed using network pharmacology for further research. As a result, PG can significantly enhance macrophage phagocytosis of GFP-E. coli. A total of twenty potential biomarkers and ten main pathways for which levels changed markedly upon treatment were identified, including glycerophospholipid metabolism, glutathione metabolism, choline metabolism, and taurine metabolism. Twenty compounds of PG associated with metabolomic changes were selected by the network pharmacology analysis, including ginsenoside Re, ginsenoside Rg1, frutinone A, and kaempferol. The network pharmacology results also showed that PG can polarize macrophages to both M1 and M2 phenotype but may be prone to M2 phenotype. In conclusion, our results indicated that PG may be prone to polarize macrophages to M2 phenotype by mainly regulating the glutathione and choline metabolism, which was related to twenty compounds of PG.
Source : Journal Evidence Based Complementary and Alternative Medicine
Link to Full Article
Immunostimulatory effects of cordycepin‐enriched WIB‐801CE from Cordyceps militaris in splenocytes and cyclophosphamide‐induced immunosuppressed mice
Ji‐Sun Shin Soo‐Hak Chung , Woo‐Seok Lee, Je‐Young Lee, Jong‐Lae Kim, Kyung‐Tae Lee
The medicinal mushroom Cordyceps militaris has been reported to possess anticancer and immunomodulatory effects. We investigated the immunostimulatory effects of culture supernatant of C. militaris (WIB‐801CE) by examining its in vitro enhancing effects on cell proliferation and cytokine releases in splenocytes and its in vivo effects on cyclophosphamide‐induced immunosuppressed mice. WIB‐801CE enhanced normal and methotrexate‐induced cell proliferation. WIB‐801CE significantly ameliorated interleukin (IL)‐2, interferon‐γ, and tumor necrosis factor‐α secretion in methotrexate‐induced splenocytes. Oral administration of WIB‐801CE effectively increased the cyclophosphamide‐suppressed splenocyte proliferation and natural killer cytotoxic activity. WIB‐801CE effectively recovered cyclophosphamide‐induced decreases in IL‐2, interferon‐γ, tumor necrosis factor‐α, and IL‐10 level. The collective data implicate WIB‐801CE as a therapeutic candidate in ameliorating the immunosuppression through immunostimulatory properties.
Source : Journal Phytotherapy Research
Link to Full Article
Garlic (Allium sativum) Stimulates Lipopolysaccharide-induced Tumor Necrosis Factor-alpha Production from J774A.1 Murine MacrophagesAuthors
Jessica Sung, Youssef Harfouche, Melissa De La Cruz,Martha P. Zamora, Yan Liu, James A. Rego, Nancy E. Buckley
Garlic (Allium sativum) is known to have many beneficial attributes such as antimicrobial, antiatherosclerotic, antitumorigenetic, and immunomodulatory properties. In the present study, we investigated the effects of an aqueous garlic extract on macrophage cytokine production by challenging the macrophage J774A.1 cell line with the garlic extract in the absence or presence of lipopolysaccharide (LPS) under different conditions. The effect of allicin, the major component of crushed garlic, was also investigated. Using enzyme-linked immunosorbent assay and reverse transcriptase-quantitative polymerase chain reaction, it was found that garlic and synthetic allicin greatly stimulated tumor necrosis factor-alpha (TNF-α) production in macrophages treated with LPS. The TNF-α secretion levels peaked earlier and were sustained for a longer time in cells treated with garlic and LPS compared with cells treated with LPS alone. Garlic acted in a time-dependent manner. We suggest that garlic, at least partially via its allicin component, acts downstream from LPS to stimulate macrophage TNF-α secretion.
.....Therefore, we believe that our findings support the notion that garlic is beneficial to the immune system.
Source : Journal Phytotherapy Research
Link to Full Article
Anxiety About Relationships May Lower Immunity, Increase Vulnerability to Illness
Concerns and anxieties about one’s close relationships appear to function as a chronic stressor that can compromise immunity, according to new research.
In the study, researchers asked married couples to complete questionnaires about their relationships and collected saliva and blood samples to test participants’ levels of a key stress-related hormone and numbers of certain immune cells.The research focused on attachment anxiety. Those who are on the high end of the attachment anxiety spectrum are excessively concerned about being rejected, have a tendency to constantly seek reassurance that they are loved, and are more likely to interpret ambiguous events in a relationship as negative.
Married partners who were more anxiously attached produced higher levels of cortisol, a steroid hormone that is released in response to stress, and had fewer T cells – important components of the immune system’s defense against infection – than did participants who were less anxiously attached.
“Everyone has these types of concerns now and again in their relationships, but a high level of attachment anxiety refers to people who have these worries fairly constantly in most of their relationships,” said Lisa Jaremka, lead author of the study and a postdoctoral fellow in Ohio State University’s Institute for Behavioral Medicine Research (IBMR).
Though some scientists theorize that attachment anxiety can be traced to inconsistent care during one’s infancy, Jaremka noted that there is also research-based evidence that people with attachment anxiety can change.
“It’s not necessarily a permanent state of existence,” she said.
The study appears online and is scheduled for future print publication in the journal Psychological Science.
Jaremka and colleagues tested the health effects of attachment anxiety on 85 couples who had been married for an average of more than 12 years. Most participants were white, and their average age was 39 years.
The participants completed a questionnaire called The Experiences in Close Relationships scale. They also reported general anxiety symptoms and their sleep quality. Researchers collected saliva samples over three days and blood samples over two days.
Participants with higher attachment anxiety produced, on average, 11 percent more cortisol than did those with lower attachment anxiety. The more anxiously attached participants also had between 11 percent and 22 percent fewer T cells than did less anxiously attached partners. Four T-cell markers were analyzed in the study.
The combined findings make sense and are likely related, Jaremka said, because cortisol can have immunosuppressive effects – meaning it can inhibit production of these very same T cells. Previous research has suggested that reduced T-cell levels can impair the immune response to vaccines and that low levels of the cells are a hallmark of an aging immune system.
Attachment anxiety is considered a phenomenon related to childhood development, Jaremka explained. At a very young age, children learn whether or not their primary caregivers will respond when the children are in distress. If caregivers are responsive, children learn they can rely on other people. If care is inconsistent or neglectful, children can develop feelings of insecurity that might manifest as attachment anxiety later in life.
Though she knows of no research-based advice about how to shed these feelings of insecurity, Jaremka said it is clear that people can change.
“Most research that does exist in this area supports the idea that being in very caring, loving, close relationships might be a catalyst to change from being very anxious to not,” she said.
Jaremka’s research focuses on the physiological effects of dissatisfaction in relationships, or the feeling of being disconnected from other people. She also recently published a paper suggesting that loneliness can tax the immune system.
She works in the lab of Jan Kiecolt-Glaser, a professor of psychiatry and psychology at Ohio State, who was the principal investigator on a larger study in which the married couples participated. Kiecolt-Glaser, Jaremka and colleagues are continuing studies of links between health and close relationships, and are currently seeking participants for a study exploring connections between fast food and the immune system in married couples. More information is available online here: http://pni.osumc.edu/jkg/stressandhealth/couples.html.
Source : Newswise
Link to Source