Forskilin of Immube Science and Biotechnology volume 13 snd, Article number: 3 Cite this article. Metrics details. The emergence of Immune system resilience resistance has necessitated the development of effective alternatives Fermented foods and cardiovascular health antibiotics for im,une and oFrskolin production.
This Forskolon investigated a possible synergy between butyrate and forskolin a natural labdane diterpene in enhancing innate host defense, barrier function, Forskolin and immune system resistance, growth performance, and meat quality of broilers.
The immne of representative Fprskolin involved in host defense AvBD9 and AvBD10barrier function MUC2CLDN1and TJP1and inflammation IL-1β were measured Forskolin and immune system Forskoljn HD11 sysrem in response to butyrate and forskolin in the presence or absence of bacterial lipopolysaccharides LPS.
Intestinal lesions and the Clostridium perfringens titers were also assessed in Designer steroids in sports. perfringens- challenged chickens fed sysstem and immuns Coleus forskohlii Systwm extract individually imkune in combination.
Furthermore, growth performance and carcass characteristics were evaluated in broilers supplemented with butyrate and Forslolin CF extract ans 42 sysgem. The two compounds significantly ane the intestinal lesions of C.
Butyrate and forskolin has potential to be developed as novel antibiotic alternatives to improve disease immuune, feed efficiency, and carcass composition immjne Forskolin and immune system.
A growing number of countries have phased sydtem the use of antibiotics for growth promotion and disease prevention in livestock animals due to a growing concern immne antibiotic resistance [ 1 ]. Consequently, Forsoklin to antibiotics are imperative to maintain the health and Post-workout recovery efficiency of livestock.
Enhancing animal innate immunity znd stimulation of endogenous host defense peptide HDP synthesis has emerged as a novel alternative approach to antibiotics [ 23 Holistic herbal treatments. HDPs, also Designer steroids in sports as antimicrobial peptides, immuen ubiquitously expressed in phagocytes and ahd cells Fofskolin the digestive, respiratory, urinary, and Frskolin tracts, and constitute an important component of host immune defense [ 456 ].
Forskolij and cathelicidins are immuns major syste of Abd in vertebrates, Fodskolin 14 β-defensins AvBD1—14 Forskllin 4 cathelicidins CATH1—3 and CATHB1 have been reported in chickens [ 5 ]. Amd the ability to directly kill a broad spectrum of microbes through membrane disruption, HDPs possess a variety immnue immunomodulatory activities such ommune chemotaxis, endotoxin neutralization, suppression of inflammation, and activation of adaptive immunity [ 6 Designer steroids in sports.
Because of membrane-lytic antimicrobial Concentration and positive thinking immune regulatory activities, HDPs are less likely to trigger Forskolinn resistance than conventional antibiotics [ 7 kmmune.
Insufficient HDP production Forskooin been implicated aystem increased susceptibility mimune infectious immkne, while enhancing Foskolin HDP synthesis is capable of strengthening host immunity and conferring protection [ 68 ]. Besides infection and inflammation, HDP Forrskolin can be modulated by Extreme diet risks variety of sydtem compounds such dystem histone i,mune inhibitors, fatty immund, and phytochemicals [ Antibacterial surface wipes910 ].
For example, butyrate, a Flrskolin short-chain fatty acid SCFA Fruits to reduce inflammation by intestinal amd fermentation of undigested dietary carbohydrates, is essential to intestinal health and homeostasis by mimune energy Antivenom production techniques, inflammation, immunity, Foorskolin barrier Weight loss catechins of the ummune epithelial cells [ 1112 Dairy-free ingredients. Recently, butyrate was found sytem be a potent HDP systek in humans Diabetic foot specialists several anc animal species [ anf ].
Most of the butyrate functions Physical activity its Immunf activity are mediated through systemm histone deacetylases or interacting with G-protein immuns receptors such as GPR41, GPR43, and GPRA [ Forskolij ].
Forskolin FSKa labdane Forsjolin isolated from the roots of an Indian plant Hydration essentials for endurance events forskohlii Forskoinis also capable of sydtem HDP synthesis in humans [ 13 ] and chickens [ 14 ]. FSK modulates a Fodskolin of physiological Forskolij such as promoting lipolysis dystem thermogenesis, appetite regulation, and anti-inflammation by syste, as a direct agonist of Forsklin cyclase, which in syatem activates cyclic adenosine monophosphate cAMP signaling to influence Forsoklin transcription Forskolun 1516 ].
Abd previously showed a strong Brain-boosting diet between butyrate and FSK in inducing Forxkolin gene expression in chickens [ 14 ]. However, the anf between butyrate and Immuhe in Fofskolin integrity and disease resistance has remained sysrem.
Therefore, Forsoolin study syatem aimed at investigating the role of butyrate and FSK in modulating innate immunity, snd, and barrier function. We also studied Designer steroids in sports efficacy of the two natural compounds in the resistance of necrotic enteritis NE in broiler chickens, which is among the most economically significant diseases in chickens caused by a Gram-positive bacterium, Clostridium perfringens [ 17 ].
The impact of the two compounds on growth performance, carcass traits, and meat quality was also evaluated to further explore their potential as novel alternatives to antibiotics for use in broilers.
Three independent experiments were conducted to ensure the reproducibility of the results. Relative fold changes of gene expression levels were calculated using the 2 -ΔΔCt method normalized against GAPDH.
All animal procedures were approved by the Institutional Animal Care and Use Committee of Oklahoma State University under protocol number AG A total of newly-hatched male Cobb broilers were obtained from a commercial hatchery Cobb-Vantress Hatchery, Siloam Springs, AR, USA and reared in an environmentally controlled room under standard management as recommended by Cobb-Vantress.
Chickens in 5 treatments were subjected to daily challenge with an overnight culture of C. A netB- and tpeL- positive C. perfringens strain Brenda B kindly provided by Dr. Lisa Bielke at the Ohio State University, Columbus, OH [ 20 ] was sequentially passaged in chopped cooked meat medium and fluid thioglycollate medium prior to inoculation of chickens.
On d 18, chickens were weighed individually and euthanized by CO 2 asphyxiation prior to sample collection. Gross lesions of NE in the duodenum and jejunum of each chicken were graded separately in a blind manner using a 0—6 scoring system as described [ 17 ]. The jejunal and cecal C.
perfringens were quantified using a standard curve-based qPCR method as described [ 21 ]. Briefly, bacterial genomic DNA from pure C.
perfringens culture or intestinal digesta samples was extracted using the ZR Fecal DNA MicroPrep Kit Zymo Research, Irvine, CA and quantified using Nanodrop.
The C. perfringens genomic DNA. Two separate feeding trials were conducted to evaluate the effect of butyrate and FSK on the growth performance of healthy broilers reared under standard management. Average daily gain ADGaverage daily feed intake ADFIand feed conversion ratio FCR were calculated and compared among all treatments.
The starter diet Broilers were euthanized by CO 2 asphyxiation after h feed withdrawal, followed by ventral neck cutting, bleeding, de-feathering, and evisceration.
The carcass yield was calculated as the percentage of eviscerated carcass weight, relative to live weight. Moreover, both left and right sides of the breast muscle pectoral major and minor were removed and weighed. The abdominal fat pad was collected and weighed as described [ 15 ]. The yields of the breast meat and abdominal fat were calculated as percentages of eviscerated carcass weight.
The color of the right pectoral major muscle was determined on each sample in duplicate with 1 reading in the anterior and the other in the posterior portion of the muscle using MiniScan XE Plus Spectrophotometer 2. All readings were taken on the skin side surface in an area free of obvious color defects over scald, bruises, and blood accumulation [ 23 ].
Data analysis and visualization were performed using Prism GraphPad Software Inc. The mRNA expression levels of representative HDP, barrier function, and inflammatory cytokine genes were evaluated using RT-qPCR. Moreover, AvBD9 induction was maintained in the context of LPS stimulation.
Similarly, butyrate synergized with FSK in enhancing the expressions of AvBD10 Fig. Additionally, butyrate augmented the expressions of CLDN1 and TJP1 in HD11 cells, while FSK was largely ineffective Fig.
Furthermore, butyrate, FSK, or the combination had little effect on the expression of IL-1β in HD11 cells, indicating that the 2 compounds are not proinflammatory Fig. Taken together, butyrate synergized with FSK to suppress inflammation, while enhancing the expressions of HDP and MUC2 genes, with no obvious synergy in regulating tight junction genes.
Regulation of host defense peptide, barrier function, and inflammatory cytokine gene expressions in macrophages by butyrate and forskolin FSK. Quantitative reverse transcription PCR RT-qPCR was performed to measure the expressions of avian β-defensin 9 AvBD9 AAvBD10 Bmucin 2 MUC2 Cclaudin 1 CLDN1 Dtight junction protein 1 TJP1 Eand interleukin 1β IL-1β F.
Results were presented as means ± SEM of 3 independent experiments. perfringens to induce NE as described [ 19 ]. Among C. While there was no lethality, C. Alleviation of necrotic enteritis by butyrate and forskolin FSK. Chickens were individually weighted on d 13 A and d 18 Band gross lesions of necrotic enteritis in the duodenum C and jejunum D were scored on d The CP titers in the digesta of the jejunum E and cecum F were quantified using qPCR.
perfringens colonization in the jejunum and cecum was also quantified among different groups using qPCR. perfringens colonization by approximately fold in the jejunum relative to the non-medication group Fig.
In the cecum, butyrate or FSK alone had a negligible effect on C. perfringens numerically by approximately 3-fold Fig. perfringens colonization in the intestinal tract of C. perfringens -challenged chickens. To understand the synergistic effect of butyrate and FSK on NE alleviation, the mRNA expressions of representative chicken HDP AvBD9 and AvBD10barrier function MUC2CLDN1and TJP1and inflammatory cytokine IL-1β genes were measured in the jejunum of C.
perfringens- challenged chickens on d S1 A and AvBD10 Supplementary Fig. perfringens infection reduced the expressions of CLDN1 and TJP1whereas the CF extract with or without butyrate tended to reverse the trend and enhanced both gene expressions Supplementary Fig.
To examine the effect of butyrate and FSK on the growth performance of healthy broilers, 2 feeding trials were conducted with Cobb chicks.
A second feeding trial was further conducted for an entire growth cycle of 42 d to examine the influence of butyrate and FSK on growth performance of broilers. Both feeding trials collectively suggested that a combination of butyrate and CF extract had no negative influence on the growth of broilers, but with a strong tendency to reduce feed intake and thus improve feed efficiency.
Influence of butyrate and forskolin FSK on growth performance of broilers. Average daily gain ADGaverage daily feed intake ADFIand feed conversion ratio FCR were calculated for the entire period. To ensure butyrate and FSK have no negative impact on carcass traits or meat quality, broilers were randomly selected from the second trial on d 28 and 48 and processed for the measurement of a series of carcass and meat quality traits.
Such a reduction failed to be observed with butyrate or FSK alone. Overall, butyrate and FSK had little impact on either carcass traits or meat quality, except for a significant influence on reducing abdominal fat. Antibiotic alternatives are needed in animal agriculture, given the restricted use of in-feed antibiotics in a growing number of countries [ 23 ].
Host-directed strategies such as the induction of endogenous HDP synthesis are being actively explored against infectious diseases [ 3910 ]. We previously showed that butyrate stimulates HDP synthesis and enhances the clearance of Salmonella Enteritidis in chickens [ 18 ] and that butyrate and FSK synergize with each other in inducing AvBD9 gene expression both in vitro and in vivo [ 14 ].
In this study, we further demonstrated that dietary supplementation of butyrate and FSK synergizes to improve the expressions of AvBD9 and AvBD10 as well as barrier function genes such as MUC2while suppressing inflammation in cell culture. Importantly, butyrate and FSK alleviates experimentally-induced NE in broilers in a synergistic manner.
Furthermore, feeding butyrate and FSK has a strong tendency to improve feed efficiency and reduce abdominal fat with no negative impact on growth performance, carcass yield, or meat quality of broilers. Larger-scale animal trials are needed to confirm these promising results and provide a stronger statistical conclusion on some of the parameters measured in this study.
HDPs are critically important in animal immunity and disease resistance [ 46 ]. Aberrant expression or deletion of HDP genes is often associated with increased susceptibility to infectious diseases [ 68 ]. Downregulating HDP expression is specifically employed by certain bacteria to evade host innate immunity and establish infection [ 24 ].
: Forskolin and immune system| Similar items that may ship from close to you | Adaptive or acquired immunity is a system that learns to recognize a pathogen. It is regulated by cells and organs in our body like the spleen, thymus, bone marrow, and lymph nodes. When a foreign substance enters the body, these cells and organs create antibodies and lead to multiplication of immune cells including different types of white blood cells that are specific to that harmful substance and attack and destroy it. Our immune system then adapts by remembering the foreign substance so that if it enters again, these antibodies and cells are even more efficient and quick to destroy it. Antigens are substances that the body labels as foreign and harmful, which triggers immune cell activity. Allergens are one type of antigen and include grass pollen, dust, food components, or pet hair. Antigens can cause a hyper-reactive response in which too many white cells are released. For example, an allergy to mold triggers symptoms of wheezing and coughing in a sensitive individual but does not trigger a reaction in other people. When pathogens attack healthy cells and tissue, a type of immune cell called mast cells counterattack and release proteins called histamines, which cause inflammation. Inflammation may generate pain, swelling, and a release of fluids to help flush out the pathogens. The histamines also send signals to discharge even more white blood cells to fight pathogens. However, prolonged inflammation can lead to tissue damage and may overwhelm the immune system. Autoimmune disorders like lupus, rheumatoid arthritis, or type 1 diabetes are partly hereditary and cause hypersensitivity in which immune cells attack and destroy healthy cells. Immunodeficiency disorders can depress or completely disable the immune system, and may be genetic or acquired. Acquired forms are more common and include AIDS and cancers like leukemia and multiple myeloma. Eating enough nutrients as part of a varied diet is required for the health and function of all cells, including immune cells. Certain dietary patterns may better prepare the body for microbial attacks and excess inflammation, but it is unlikely that individual foods offer special protection. Examples of nutrients that have been identified as critical for the growth and function of immune cells include vitamin C, vitamin D, zinc, selenium, iron, and protein including the amino acid glutamine. Diets that are limited in variety and lower in nutrients, such as consisting primarily of ultra-processed foods and lacking in minimally processed foods, can negatively affect a healthy immune system. It is also believed that a Western diet high in refined sugar and red meat and low in fruits and vegetables can promote disturbances in healthy intestinal microorganisms, resulting in chronic inflammation of the gut, and associated suppressed immunity. The microbiome is an internal metropolis of trillions of microorganisms or microbes that live in our bodies, mostly in the intestines. It is an area of intense and active research, as scientists are finding that the microbiome plays a key role in immune function. The gut is a major site of immune activity and the production of antimicrobial proteins. A high-fiber plant-rich diet with plenty of fruits, vegetables, whole grains, and legumes appear to support the growth and maintenance of beneficial microbes. Certain helpful microbes break down fibers into short chain fatty acids, which have been shown to stimulate immune cell activity. These fibers are sometimes called prebiotics because they feed microbes. Therefore, a diet containing probiotic and prebiotic foods may be beneficial. Probiotic foods contain live helpful bacteria, and prebiotic foods contain fiber and oligosaccharides that feed and maintain healthy colonies of those bacteria. Animal studies have found that deficiencies in zinc , selenium , iron , copper, folic acid , and vitamins A , B6 , C , D , and E can alter immune responses. Epidemiological studies find that those who are poorly nourished are at greater risk of bacterial, viral, and other infections. Eating a good quality diet, as depicted by the Healthy Eating Plate, can prevent deficiencies in these nutrients. However, there are certain populations and situations in which one cannot always eat a variety of nutritious foods, or who have increased nutrient needs. In these cases a vitamin and mineral supplement may help to fill nutritional gaps. Studies have shown that vitamin supplementation can improve immune responses in these groups. The elderly are a particularly high-risk group. The immune response generally declines with increasing age as the number and quality of immune cells decreases. This causes a higher risk of poorer outcomes if the elderly develop chronic or acute diseases. In addition, about one-third of elderly in industrialized countries have nutrient deficiencies. Diet variety may also be limited due to budget constraints or lower interest in cooking for one person; poor dentition; mental impairment; or lack of transportation and community resources to obtain healthy food. FPrime Rep Ransohoff RM. A polarizing question: do M1 and M2 microglia exist. Nat Neurosci — Ponomarev ED, Maresz K, Tan Y, Dittel BN. CNS-derived interleukin-4 is essential for the regulation of autoimmune inflammation and induces a state of alternative activation in microglial cells. J Neurosci — Ponomarev ED, Veremeyko T, Barteneva N, Krichevsky AM, Weiner HL. Nat Med — Ponomarev ED, Veremeyko T, Weiner HL. MicroRNAs are universal regulators of differentiation, activation, and polarization of microglia and macrophages in normal and diseased CNS. Glia — Starossom SC, Veremeyko T, Yung AWY, Dukhinova M, Au C, Lau AY, et al. 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Elevated cyclic AMP and PDE4 inhibition induce chemokine expression in human monocyte-derived macrophages. Frezel N, Sohet F, Daneman R, Basbaum AI, Braz JM. Exp Neurol — Ajami B, Bennett JL, Krieger C, McNagny KM, Rossi FMV. Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool. Ponomarev ED, Shriver LP, Dittel BN. CD40 expression by microglial cells is required for their completion of a two-step activation process during central nervous system autoimmune inflammation. Ma TC, Barco A, Ratan RR, Willis DE. CAMP-responsive element-binding protein CREB and cAMP co-regulate activator protein 1 AP1 -dependent regeneration-associated gene expression and neurite growth. Kellner Y, Gödecke N, Dierkes T, Thieme N, Zagrebelsky M, Korte M. The BDNF effects on dendritic spines of mature hippocampal neurons depend on neuronal activity. Front Synaptic Neurosci Afshari FS, Chu AK, Sato-Bigbee C. Effect of cyclic AMP on the expression of myelin basic protein species and myelin proteolipid protein in committed oligodendrocytes: differential involvement of the transcription factor CREB. Paco S, Hummel M, Plá V, Sumoy L, Aguado F. Cyclic AMP signaling restricts activation and promotes maturation and antioxidant defenses in astrocytes. BMC Genomics Ishii A, Furusho M, Bansal R. Keywords: Th1 cells, neuroinflammation, Forskolin, cAMP, microRNA, macrophage, M2 polarization, ERK. Citation: Veremeyko T, Yung AWY, Dukhinova M, Kuznetsova IS, Pomytkin I, Lyundup A, Strekalova T, Barteneva NS and Ponomarev ED Cyclic AMP Pathway Suppress Autoimmune Neuroinflammation by Inhibiting Functions of Encephalitogenic CD4 T Cells and Enhancing M2 Macrophage Polarization at the Site of Inflammation. doi: Received: 17 November ; Accepted: 09 January ; Published: 25 January Copyright: © Veremeyko, Yung, Dukhinova, Kuznetsova, Pomytkin, Lyundup, Strekalova, Barteneva and Ponomarev. This is an open-access article distributed under the terms of the Creative Commons Attribution License CC BY. The use, distribution or reproduction in other forums is permitted, provided the original author s or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Ponomarev, eponomarev cuhk. Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. Top bar navigation. About us About us. 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Kuznetsova 1 Igor Pomytkin 2 Alexey Lyundup 2 Tatyana Strekalova 3,4 Natasha S. Barteneva 5,6 Eugene D. Introduction Various pathways are known to affect differentiation and function of CD4 T cells in vivo during inflammation associated with autoimmunity or infection. Real-time PCR For quantitation of various markers and molecules by real-time RT PCR, total RNA was isolated by Qiagene or MirVana Applied Biosystem kits from cultured BM-derived, or peritoneal macrophages, or form the spinal cords of PBS-perfused unmanipulated mice or mice on day 22 following EAE. Western Blotting Western blotting analysis was performed according to standard protocol as we reported previously Flow Cytometry Mononuclear cells were isolated from the CNS or spleens of mice with EAE on day 22 using Percoll gradients as described in our previous studies 13 , T-Cell and Macrophage Proliferation Assay BrdU incorporation assay was used to assess proliferation of BM-derived macrophages or CD4 T cells in vitro or in vivo similar as was described in our earlier studies Immunohistochemistry Fixed frozen section of lumbar areas of spinal cord were prepared and stained with luxol fast blue LFB, Sigma as we described earlier Statistical Analysis The results are presented as mean ± SE. M CrossRef Full Text Google Scholar. M PubMed Abstract CrossRef Full Text Google Scholar. Keywords: Th1 cells, neuroinflammation, Forskolin, cAMP, microRNA, macrophage, M2 polarization, ERK Citation: Veremeyko T, Yung AWY, Dukhinova M, Kuznetsova IS, Pomytkin I, Lyundup A, Strekalova T, Barteneva NS and Ponomarev ED Cyclic AMP Pathway Suppress Autoimmune Neuroinflammation by Inhibiting Functions of Encephalitogenic CD4 T Cells and Enhancing M2 Macrophage Polarization at the Site of Inflammation. Add to shopping cart Add to shopping cart. Order now and receive today - from a pharmacy near you. Take 2 capsules daily with sufficient water, do not chew. Notice: The recommended daily dose should not be exceeded. This product is not a substitute for a balanced and varied diet and healthy lifestyle. Keep out of reach of children. Contains a desiccant bag which is not suited for consumption. Product information. Product number PZN EAN Packaging size 60 capsules Capsule shell Vegetarian capsule shell. Did you know? Indian coleus Coleus forskohlii, Plectranthus barbatus is a species of plant from the genus of harp shrubs. The plant grows as a semi-shrub and its inflorescences grow up to 25 cm long. Its area of distribution extends from tropical Africa through the Arabian Peninsula to India and China. Indian coleus is particularly used for its ingredient forskolin, which among other things can regulate fat metabolism and thus contribute to weight management. In traditional Indian medicine Ayurveda , tea made from the plant's leaves is used to reduce digestive problems and the root is used as a tonic. In addition, the secondary plant compound forskolin is sometimes thought to have testosterone-enhancing and anti-inflammatory effects. In a scientific double-blind study, an increased reduction of adipose tissue could be achieved with the help of forskolin in obese patients 1. In this context, other scientific studies also found a weight-reducing effect of forskolin 2,3. In other double-blind studies, forskolin was also able to reduce asthma symptoms 4,5. What is HPLC? HPLC high performance liquid chromatography is a method for analyzing substances that has a very good separation performance and reliably describes the type and quantity of the individual components of the substance to be analyzed down to the smallest detail. What part of the plant is contained in the plant extract? The plant extract contained in ZeinPharma®'s Forskolin capsules is derived from the root of the Indian coleus Coleus forskohlii. What is Forskolin? |
| Gene Ontology and GO Annotations | Our immune system, a network of intricate stages and pathways in the body, protects us against these harmful microbes as well as certain diseases. Zinc as a gatekeeper of immune function. Full content visible, double tap to read brief content. Introduction Various pathways are known to affect differentiation and function of CD4 T cells in vivo during inflammation associated with autoimmunity or infection. Pathogen-associated molecular patterns PAMPs and damage-associated molecular patterns DAMPs are very important markers that aid in developing a strategic defense against various inflammatory diseases. Epigenetic modifier; Inhibits histone EZH2 lysine methyltransferase. TV, AY, MD, IK, and EP conducted experiments. |
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I acknowledge that I can unsubscribe any time. Protocols and Documentation. Resources and Publications. Related Products. cAMP is an important second messenger involved in many signal transduction pathways, including activation of protein kinase A PKA; Awad et al. Cell Type. View More View Less. Protocols and Documentation Find supporting information and directions for use in the Product Information Sheet or explore additional protocols below. Document Type. Applications This product is designed for use in the following research area s as part of the highlighted workflow stage s. Research Area. Workflow Stages for Human Pluripotent Stem Cell Research. Workflow Stages for Mouse Pluripotent Stem Cell Research. Workflow Stages for Neural Stem and Progenitor Cell Research. Tissue Dissociation. Resources and Publications Educational Materials 4. Small Molecules, Big Impact in Pluripotent Stem Cell Research. Small Molecules, Big Impact in Cancer Research. ISSCR Innovation Showcase - Induction of a Native State in Human Pluripotent Stem Cells. Small Molecules. Publications 9 Small-Molecule-Driven Direct Reprogramming of Mouse Fibroblasts into Functional Neurons. Li X et al. Cell stem cell AUG. Abstract Recently, direct reprogramming between divergent lineages has been achieved by the introduction of regulatory transcription factors. This approach may provide alternative cell resources for drug discovery and regenerative medicine, but applications could be limited by the genetic manipulation involved. After a further maturation stage, these chemically induced neurons CiNs possessed neuron-specific expression patterns, generated action potentials, and formed functional synapses. Mechanistically, we found that a BET family bromodomain inhibitor, I-BET, disrupted the fibroblast-specific program, while the neurogenesis inducer ISX9 was necessary to activate neuron-specific genes. Overall, our findings provide a proof of principle" for chemically induced direct reprogramming of somatic cell fates across germ layers without genetic manipulation� View publication. Direct Conversion of Normal and Alzheimer's Disease Human Fibroblasts into Neuronal Cells by Small Molecules. Hu W et al. Abstract Neuronal conversion from human fibroblasts can be induced by lineage-specific transcription factors; however, the introduction of ectopic genes limits the therapeutic applications of such induced neurons iNs. Here, we report that human fibroblasts can be directly converted into neuronal cells by a chemical cocktail of seven small molecules, bypassing a neural progenitor stage. These human chemical-induced neuronal cells hciNs resembled hiPSC-derived neurons and human iNs hiNs with respect to morphology, gene expression profiles, and electrophysiological properties. This approach was further applied to generate hciNs from familial Alzheimer's disease patients. Taken together, our transgene-free and chemical-only approach for direct reprogramming of human fibroblasts into neurons provides an alternative strategy for modeling neurological diseases and for regenerative medicine. Additionally, high-dose intravenous vitamin C treatment has been shown to significantly improve symptoms in people with severe infections, including sepsis and acute respiratory distress syndrome ARDS resulting from viral infections Still, other studies have suggested that the role of vitamin C in this setting is still under investigation 32 , The upper limit for vitamin C is 2, mg. Supplemental daily doses are typically between and 1, mg Vitamin C is vital for immune health. Supplementing with this nutrient may help reduce the duration and severity of upper respiratory tract infections, including the common cold. Black elderberry Sambucus nigra , which has long been used to treat infections, is being researched for its effects on immune health. In test-tube studies, elderberry extract demonstrates potent antibacterial and antiviral potential against bacterial pathogens responsible for upper respiratory tract infections and strains of the influenza virus 35 , A review of 4 randomized control studies in people found that elderberry supplements significantly reduced upper respiratory symptoms caused by viral infections However, this study is outdated and was sponsored by the elderberry syrup manufacturer, which may have skewed results Though it has been suggested that elderberry can help relieve symptoms of certain infections and the influenza virus, we also must be aware of the risks. Some report that elderberries can lead to the production of excess cytokines, which could potentially damage healthy cells For that reason, some researchers recommend elderberry supplements only be used in the early course of COVID It should be noted no published research studies have evaluated the use of elderberry for COVID These recommendations are based on previous research done on elderberries. A systemic review of elderberry 43 concluded:. Taking elderberry supplements may help reduce upper respiratory symptoms caused by viral infections and help alleviate flu symptoms. However, elderberry also has risks. More research is needed. Medicinal mushrooms have been used since ancient times to prevent and treat infection and disease. Many types of medicinal mushrooms have been studied for their immune-boosting potential. Over recognized species of medicinal mushrooms are known to have immune-enhancing properties Some research demonstrates that supplementing with specific types of medicinal mushrooms may enhance immune health in several ways as well as reduce symptoms of certain conditions, including asthma and lung infections. For example, a study in mice with tuberculosis, a serious bacterial disease, found that treatment with cordyceps significantly reduced bacterial load in the lungs, enhanced immune response, and reduced inflammation, compared with a placebo group In a randomized, 8-week study in 79 adults, supplementing with 1. Turkey tail is another medicinal mushroom that has powerful effects on immune health. Research in humans indicates that turkey tail may enhance immune response, especially in people with certain types of cancer 48 , Many other medicinal mushrooms have been studied for their beneficial effects on immune health as well. Medicinal mushroom products can be found in the form of tinctures, teas, and supplements 50 , 51 , 52 , Many types of medicinal mushrooms, including cordyceps and turkey tail, may offer immune-enhancing and antibacterial effects. According to results from scientific research, the supplements listed above may offer immune-boosting properties. However, keep in mind that many of these potential effects these supplements have on immune health have not been thoroughly tested in humans, highlighting the need for future studies. Astragalus, garlic, curcumin, and echinacea are just some of the supplements that may offer immune-boosting properties. Still, they have not been thoroughly tested in humans. Many supplements on the market may help improve immune health. Zinc, elderberry, and vitamins C and D are just some of the substances that have been researched for their immune-enhancing potential. However, although these supplements may offer a small benefit for immune health, they should not and cannot be used as a replacement for a healthy lifestyle. Aiming to eat a nutrient-dense balanced diet, getting enough sleep, engaging in regular physical activity, and not smoking or considering quitting, if you smoke are some of the most important ways to help keep your immune system healthy and reduce your chances of infection and disease. If you decide that you want to try a supplement, speak with a healthcare professional first, as some supplements may interact with certain medications or are inappropriate for some people. Our experts continually monitor the health and wellness space, and we update our articles when new information becomes available. VIEW ALL HISTORY. Anxiety is a common symptom of trauma. Here's why. While we don't fully understand why, developing anxiety as a long COVID symptom is common. However, we do know how to treat it. AVPD and SAD overlap in symptoms, both impairing social functioning. If the anxiety of an upcoming surgery is disrupting your sleep and day-to-day life, it may be time to talk with your doctor about medications. Anxiety can lead to tooth pain through increased jaw clenching and other mechanisms. Addressing the cause of your anxiety, as well as maintaining good…. Shadow work is a concept developed by Swiss psychoanalysis Carl Jung in the 20th century. Here's how to get started. Do you have thanatophobia? Acclaimed journalist and TV personality Lisa Ling is sounding the alarm about the affect social media use can have on kids and shares the steps she's…. Many people turn to yoga when feelings of anxiety start to creep in or during times of stress. You may find that focusing on your breath and your…. A Quiz for Teens Are You a Workaholic? How Well Do You Sleep? Health Conditions Discover Plan Connect. Vaccines Basics Testing Symptoms. Nutrition Evidence Based The 15 Best Supplements to Boost Your Immune System Right Now. Medically reviewed by Sade Meeks, MS, RD , Nutrition — By Jillian Kubala, MS, RD — Updated on February 1, An important note No supplement will cure or prevent disease. Was this helpful? Vitamin D. |
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Citation: Veremeyko T, Yung AWY, Dukhinova M, Kuznetsova IS, Pomytkin I, Lyundup A, Strekalova T, Barteneva NS and Ponomarev ED Cyclic AMP Pathway Suppress Autoimmune Neuroinflammation by Inhibiting Functions of Encephalitogenic CD4 T Cells and Enhancing M2 Macrophage Polarization at the Site of Inflammation. doi: Received: 17 November ; Accepted: 09 January ; Published: 25 January Copyright: © Veremeyko, Yung, Dukhinova, Kuznetsova, Pomytkin, Lyundup, Strekalova, Barteneva and Ponomarev. This is an open-access article distributed under the terms of the Creative Commons Attribution License CC BY. The use, distribution or reproduction in other forums is permitted, provided the original author s or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Ponomarev, eponomarev cuhk. Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. Top bar navigation. About us About us. Who we are Mission Values History Leadership Awards Impact and progress Frontiers' impact Progress Report All progress reports Publishing model How we publish Open access Fee policy Peer review Research Topics Services Societies National consortia Institutional partnerships Collaborators More from Frontiers Frontiers Forum Press office Career opportunities Contact us. Sections Sections. About journal About journal. Article types Author guidelines Editor guidelines Publishing fees Submission checklist Contact editorial office. ORIGINAL RESEARCH article Front. This article is part of the Research Topic T Cell Differentiation and Function in Tissue Inflammation View all 18 articles. Three independent experiments were conducted to ensure the reproducibility of the results. Relative fold changes of gene expression levels were calculated using the 2 -ΔΔCt method normalized against GAPDH. All animal procedures were approved by the Institutional Animal Care and Use Committee of Oklahoma State University under protocol number AG A total of newly-hatched male Cobb broilers were obtained from a commercial hatchery Cobb-Vantress Hatchery, Siloam Springs, AR, USA and reared in an environmentally controlled room under standard management as recommended by Cobb-Vantress. Chickens in 5 treatments were subjected to daily challenge with an overnight culture of C. A netB- and tpeL- positive C. perfringens strain Brenda B kindly provided by Dr. Lisa Bielke at the Ohio State University, Columbus, OH [ 20 ] was sequentially passaged in chopped cooked meat medium and fluid thioglycollate medium prior to inoculation of chickens. On d 18, chickens were weighed individually and euthanized by CO 2 asphyxiation prior to sample collection. Gross lesions of NE in the duodenum and jejunum of each chicken were graded separately in a blind manner using a 0—6 scoring system as described [ 17 ]. The jejunal and cecal C. perfringens were quantified using a standard curve-based qPCR method as described [ 21 ]. Briefly, bacterial genomic DNA from pure C. perfringens culture or intestinal digesta samples was extracted using the ZR Fecal DNA MicroPrep Kit Zymo Research, Irvine, CA and quantified using Nanodrop. The C. perfringens genomic DNA. Two separate feeding trials were conducted to evaluate the effect of butyrate and FSK on the growth performance of healthy broilers reared under standard management. Average daily gain ADG , average daily feed intake ADFI , and feed conversion ratio FCR were calculated and compared among all treatments. The starter diet Broilers were euthanized by CO 2 asphyxiation after h feed withdrawal, followed by ventral neck cutting, bleeding, de-feathering, and evisceration. The carcass yield was calculated as the percentage of eviscerated carcass weight, relative to live weight. Moreover, both left and right sides of the breast muscle pectoral major and minor were removed and weighed. The abdominal fat pad was collected and weighed as described [ 15 ]. The yields of the breast meat and abdominal fat were calculated as percentages of eviscerated carcass weight. The color of the right pectoral major muscle was determined on each sample in duplicate with 1 reading in the anterior and the other in the posterior portion of the muscle using MiniScan XE Plus Spectrophotometer 2. All readings were taken on the skin side surface in an area free of obvious color defects over scald, bruises, and blood accumulation [ 23 ]. Data analysis and visualization were performed using Prism GraphPad Software Inc. The mRNA expression levels of representative HDP, barrier function, and inflammatory cytokine genes were evaluated using RT-qPCR. Moreover, AvBD9 induction was maintained in the context of LPS stimulation. Similarly, butyrate synergized with FSK in enhancing the expressions of AvBD10 Fig. Additionally, butyrate augmented the expressions of CLDN1 and TJP1 in HD11 cells, while FSK was largely ineffective Fig. Furthermore, butyrate, FSK, or the combination had little effect on the expression of IL-1β in HD11 cells, indicating that the 2 compounds are not proinflammatory Fig. Taken together, butyrate synergized with FSK to suppress inflammation, while enhancing the expressions of HDP and MUC2 genes, with no obvious synergy in regulating tight junction genes. Regulation of host defense peptide, barrier function, and inflammatory cytokine gene expressions in macrophages by butyrate and forskolin FSK. Quantitative reverse transcription PCR RT-qPCR was performed to measure the expressions of avian β-defensin 9 AvBD9 A , AvBD10 B , mucin 2 MUC2 C , claudin 1 CLDN1 D , tight junction protein 1 TJP1 E , and interleukin 1β IL-1β F. Results were presented as means ± SEM of 3 independent experiments. perfringens to induce NE as described [ 19 ]. Among C. While there was no lethality, C. Alleviation of necrotic enteritis by butyrate and forskolin FSK. Chickens were individually weighted on d 13 A and d 18 B , and gross lesions of necrotic enteritis in the duodenum C and jejunum D were scored on d The CP titers in the digesta of the jejunum E and cecum F were quantified using qPCR. perfringens colonization in the jejunum and cecum was also quantified among different groups using qPCR. perfringens colonization by approximately fold in the jejunum relative to the non-medication group Fig. In the cecum, butyrate or FSK alone had a negligible effect on C. perfringens numerically by approximately 3-fold Fig. perfringens colonization in the intestinal tract of C. perfringens -challenged chickens. To understand the synergistic effect of butyrate and FSK on NE alleviation, the mRNA expressions of representative chicken HDP AvBD9 and AvBD10 , barrier function MUC2 , CLDN1 , and TJP1 , and inflammatory cytokine IL-1β genes were measured in the jejunum of C. perfringens- challenged chickens on d S1 A and AvBD10 Supplementary Fig. perfringens infection reduced the expressions of CLDN1 and TJP1 , whereas the CF extract with or without butyrate tended to reverse the trend and enhanced both gene expressions Supplementary Fig. To examine the effect of butyrate and FSK on the growth performance of healthy broilers, 2 feeding trials were conducted with Cobb chicks. A second feeding trial was further conducted for an entire growth cycle of 42 d to examine the influence of butyrate and FSK on growth performance of broilers. Both feeding trials collectively suggested that a combination of butyrate and CF extract had no negative influence on the growth of broilers, but with a strong tendency to reduce feed intake and thus improve feed efficiency. Influence of butyrate and forskolin FSK on growth performance of broilers. Average daily gain ADG , average daily feed intake ADFI , and feed conversion ratio FCR were calculated for the entire period. To ensure butyrate and FSK have no negative impact on carcass traits or meat quality, broilers were randomly selected from the second trial on d 28 and 48 and processed for the measurement of a series of carcass and meat quality traits. Such a reduction failed to be observed with butyrate or FSK alone. Overall, butyrate and FSK had little impact on either carcass traits or meat quality, except for a significant influence on reducing abdominal fat. Antibiotic alternatives are needed in animal agriculture, given the restricted use of in-feed antibiotics in a growing number of countries [ 2 , 3 ]. Host-directed strategies such as the induction of endogenous HDP synthesis are being actively explored against infectious diseases [ 3 , 9 , 10 ]. We previously showed that butyrate stimulates HDP synthesis and enhances the clearance of Salmonella Enteritidis in chickens [ 18 ] and that butyrate and FSK synergize with each other in inducing AvBD9 gene expression both in vitro and in vivo [ 14 ]. In this study, we further demonstrated that dietary supplementation of butyrate and FSK synergizes to improve the expressions of AvBD9 and AvBD10 as well as barrier function genes such as MUC2 , while suppressing inflammation in cell culture. Importantly, butyrate and FSK alleviates experimentally-induced NE in broilers in a synergistic manner. Furthermore, feeding butyrate and FSK has a strong tendency to improve feed efficiency and reduce abdominal fat with no negative impact on growth performance, carcass yield, or meat quality of broilers. Larger-scale animal trials are needed to confirm these promising results and provide a stronger statistical conclusion on some of the parameters measured in this study. HDPs are critically important in animal immunity and disease resistance [ 4 , 6 ]. Aberrant expression or deletion of HDP genes is often associated with increased susceptibility to infectious diseases [ 6 , 8 ]. Downregulating HDP expression is specifically employed by certain bacteria to evade host innate immunity and establish infection [ 24 ]. In this study, C. perfringens infection also suppresses the expressions of AvBD9 and AvBD10 in the chicken jejunum; however, supplementation of butyrate and FSK reverses C. perfringens -mediated HDP suppression and, unsurprisingly, alleviates NE. Similarly, C. perfringens downregulates the expression of an antimicrobial peptide, LEAP-2 , in the jejunum of chickens, and dietary supplementation of butyrate enhances LEAP-2 expression and ameliorated NE [ 25 ]. These results collectively demonstrate that induction of HDPs represents a feasible approach to mitigate infectious diseases. However, the mechanisms underlying butyrate- and FSK-mediated mitigation of NE appear to go beyond HDP induction. Mucins secreted by goblet cells and tight junctions connecting adjacent epithelial cells form important physiological and biochemical barriers between hosts and the external environment to maintain intestinal homeostasis [ 26 , 27 ]. Butyrate is capable of maintaining intestinal barrier integrity by upregulating mucins and tight junction proteins [ 11 ], while we showed in this study that FSK enhances MUC2 gene expression both in vitro and in vivo. Importantly, butyrate synergizes with FSK in promoting the transcription of MUC2 , CLDN1 , and TJP1 in the intestinal tract. perfringens -infected chicken jejunum. Consistent with well-known anti-inflammatory properties of butyrate [ 11 , 28 ] and FSK [ 29 , 30 ], we have shown that butyrate and FSK suppress IL-1β induction in LPS-stimulated HD11 cells and C. perfringens -infected jejunum individually and also in combination. Although the mechanism of action is not directly addressed in this study, the synergy in suppressing inflammatory response between butyrate and FSK is likely to act by inhibiting the activation of NF-κB and the NLRP3 inflammasome, 2 major targets for both butyrate and FSK [ 11 , 28 , 29 , 30 ]. However, FSK alone and particularly in combination with butyrate has a strong tendency to reduce feed intake and improve feed efficiency without affecting the growth rate of broilers in 2 feeding trials. Consistently, supplementation of FSK-containing CF extract has been shown to significantly reduce food intake and appetite in both rats [ 35 ] and humans [ 36 ]. This is perhaps unsurprising, given that FSK is a natural agonist of adenylyl cyclase and activates cAMP signaling [ 37 , 38 ], which subsequently promotes lipolysis, thermogenesis, and loss of body fat without muscle mass loss [ 39 , 40 , 41 ], although the evidence on fat mass reduction is not entirely consistent [ 36 ]. Nevertheless, FSK is currently being explored to manage overweight and obesity in humans [ 42 , 43 , 44 ]. We observed that broilers fed a combination of butyrate and FSK show reduced abdominal fat deposition without affecting the carcass or breast muscle mass. However, FSK alone fails to reduce abdominal fat of broilers, perhaps due to the level of supplementation or a species difference. Apparently, optimal levels of dietary inclusion of FSK or FSK-containing CF extract remain to be investigated. It is noted that, similar to FSK, butyrate is also known to reduce appetite and lipogenesis [ 12 , 45 ], which perhaps helps explain a synergistic effect of butyrate and FSK in reducing feed intake and abdominal fat deposition, although butyrate or FSK alone at the levels used in this study fails to achieve such an effect. Sodium butyrate or butyric acid supplemented between 0. Optimal concentrations of butyrate and its derivatives warrant further investigation for their effectiveness in regulating fat deposition. Taken together, these results highlight a need to continue to explore the potential of combining butyrate with FSK as a promising antibiotic alternative to improve disease prevention, feed efficiency, and carcass composition in poultry and possibly other livestock species. Fifth OIE annual report on antimicrobial agents intended for use in animals. World Organisation for Animal Health OIE. Accessed 15 May van Dijk A, Hedegaard CJ, Haagsman HP, Heegaard PMH. The potential for immunoglobulins and host defense peptides HDPs to reduce the use of antibiotics in animal production. Vet Res. Article CAS PubMed PubMed Central Google Scholar. Robinson K, Ma X, Liu Y, Qiao S, Hou Y, Zhang G. Dietary modulation of endogenous host defense peptide synthesis as an alternative approach to in-feed antibiotics. Anim Nutr. Article PubMed PubMed Central Google Scholar. Zasloff M. Antimicrobial peptides of multicellular organisms. Article CAS PubMed Google Scholar. Zhang G, Sunkara LT. Avian antimicrobial host defense peptides: from biology to therapeutic applications. Pharmaceuticals Basel. Article CAS Google Scholar. Hancock RE, Haney EF, Gill EE. The immunology of host defence peptides: beyond antimicrobial activity. Nat Rev Immunol. Mahlapuu M, Bjorn C, Ekblom J. Antimicrobial peptides as therapeutic agents: opportunities and challenges. Crit Rev Biotechnol. Rivas-Santiago B, Serrano CJ, Enciso-Moreno JA. Susceptibility to infectious diseases based on antimicrobial peptide production. Infect Immun. Lyu W, Curtis AR, Sunkara LT, Zhang G. Transcriptional regulation of antimicrobial host defense peptides. Curr Protein Pept Sci. Wu J, Ma N, Johnston LJ, Ma X. Wallis and Futuna Islands Western Sahara Yemen Zambia Zambrazo Zimbabwe. I agree to receive future electronic communications from STEMCELL. I acknowledge that I can unsubscribe any time. Protocols and Documentation. Resources and Publications. Related Products. cAMP is an important second messenger involved in many signal transduction pathways, including activation of protein kinase A PKA; Awad et al. Cell Type. View More View Less. Protocols and Documentation Find supporting information and directions for use in the Product Information Sheet or explore additional protocols below. Document Type. Applications This product is designed for use in the following research area s as part of the highlighted workflow stage s. Research Area. Workflow Stages for Human Pluripotent Stem Cell Research. Workflow Stages for Mouse Pluripotent Stem Cell Research. Workflow Stages for Neural Stem and Progenitor Cell Research. Tissue Dissociation. Resources and Publications Educational Materials 4. Small Molecules, Big Impact in Pluripotent Stem Cell Research. Small Molecules, Big Impact in Cancer Research. ISSCR Innovation Showcase - Induction of a Native State in Human Pluripotent Stem Cells. Small Molecules. Publications 9 Small-Molecule-Driven Direct Reprogramming of Mouse Fibroblasts into Functional Neurons. Li X et al. Cell stem cell AUG. Abstract Recently, direct reprogramming between divergent lineages has been achieved by the introduction of regulatory transcription factors. This approach may provide alternative cell resources for drug discovery and regenerative medicine, but applications could be limited by the genetic manipulation involved. After a further maturation stage, these chemically induced neurons CiNs possessed neuron-specific expression patterns, generated action potentials, and formed functional synapses. Mechanistically, we found that a BET family bromodomain inhibitor, I-BET, disrupted the fibroblast-specific program, while the neurogenesis inducer ISX9 was necessary to activate neuron-specific genes. Overall, our findings provide a proof of principle" for chemically induced direct reprogramming of somatic cell fates across germ layers without genetic manipulation� View publication. |
Forskolin and immune system -
Multiple solid tumors melanomas, colorectal carcinomas, lung, prostate, and breast cancers present with genetic and functional inactivation of different PP2A subunits; therefore, loss of PP2A activity towards certain substances.
Impaired PP2A activity has been linked to B-cell chronic lymphocytic leukemia, Philadelphia-chromosome positive acute lymphoblastic leukemia, and blast crisis chronic myelogenous leukemia. Drugs such as forskolin, 1,9-dideoxy-forskolin, and FFT, which lead to PP2A activation, effectively antagonize leukemogenesis in vitro and in vivo.
With a better understanding of the metabolic pathways involved in the growth and inhibition of certain cancers, researchers can seek alternatives such as forskolin to block cancer growth through the activation of PP2A.
The cAMP pathway is known to kill multiple myeloma MM cells, both in vitro and in vivo. This study was conducted to investigate the potential of enhancing the killing of MM cell lines and primary MM cells by combining cAMP-elevating compound forskolin with the commonly used MM therapeutic drugs melphalan, cyclophosphamide, doxorubicin, bortezomib, and dexamethasone.
From the results, it was observed that forskolin potentiated the killing induced by all tested agents compared to the treatment with the single agents alone. Particularly, it was noted that forskolin had a synergistic effect on the dexamethasone-responsive cell lines H and OM It was suggested that forskolin was able to maintain the killing of MM cells even at lower concentrations of the conventional agents, suggesting that forskolin may be used to diminish treatment-associated side effects.
Additionally, the findings also support the potential role of forskolin in conjunction with conventional agents in treating multiple myeloma A study was conducted to determine the mechanism of cell signal-regulated alternative splicing during neuronal differentiation.
The research indicated that forskolin could edit the gene products of certain brain cancer cell lines, thus having the potential to prevent the development of these new brain cancer cells This recent clinical study was conducted to investigate the effect of a wild-source of Makandi Coleus forskohlii Ghana Vati and Churna tablets of its powder on a group of geriatric individuals aged with hypertension.
A total of 42 patients were split into two groups receiving one of the two forms of treatment, Makandi Ghana Vati or the tablets of its powered.
The following parameters were measured to demine the effectiveness: systolic and diastolic blood pressure sitting and supine positions , general symptomology, geriatric signs, symptoms, and a brief psychiatric rating scaled assessment.
This study was conducted to determine the efficacy of NKH, a novel water-soluble forskolin derivative, on the improvement of cardiac failure in dog heart-lung preparations.
From the results, it was noted that there was a noted significant improvement following the treatment of NKH in a dose-dependent manner. With micrograms of NKH, nearly complete restoration of cardiac function was noted.
A combination of NKH and ouabain, 30 micrograms of each, was seen to have restored entirely cardiac function previously depressed by pentobarbital. The results suggest that this novel water-soluble forskolin derivative, NKH, has the potential to support cardiac function, although more research is warranted, specifically clinical trials Another study was conducted to assess the potential positive inotropic effects of NKH in rats with chronic heart failure CHF following a myocardial infarction MI.
The initial CHF was suspected when there was a noted index decrease of the cardiac output, systemic stroke volume, and an increase in systemic vascular resistance weeks following the left coronary artery ligation. increased cardiac output and stroke volume indices in sham-operated rats, where such increases were attenuated in rats weeks post-MI induction.
increased cardiac output and stroke volume indices in rats with CHF. It was suggested from the results that NKH may have the potential to reverse cardiac dysfunction associated with CHF, especially in the severe stage with beta-adrenoceptor downregulation 19, Diabetic retinopathy is an unfortunate consequence of uncontrolled Diabetic Mellitus, which has become a global epidemic over the past few years.
Diabetic retinopathy affects vision through vitreous hemorrhage and traction retinal detachment or by way of diabetic maculopathy DME. The present management of diabetic retinopathy has to deal mainly with screening diabetics for evidence of retinopathy and treating the retinopathy with laser photocoagulation and intravitreal injection of anti-vascular endothelial growth factor agents or steroids.
Evidence from multiple studies has confirmed the protective role of rigid control of blood glucose and blood pressure. Additionally, the use of fenofibrate, which was originally used to lower serum lipids, has been shown to benefit both proliferative disease and maculopathy.
It was found in the research that other drugs and compounds are being utilized to treat diabetic retinopathy such as Protein Kinase C PKC inhibitors, peroxisome proliferator-activated receptors PPAR agonists, forskolin which binds GLUT 1 receptor, minocycline due to its anti-inflammatory effect and Celecoxib which is a Cox-2 inhibitor This recent study was conducted to evaluate the effects of a food supplement containing forskolin, homotaurine, carnosine, folic acid, vitamins B1, B2, B6, and magnesium in patients with primary open-angle glaucoma POAG already in treatment and compensated by intraocular pressure-lowering drugs over 12 months.
There were 22 pairs of eyes 44 eyes with POAG who were randomly assigned either to the control group or the treatment group receiving the food supplement. The food supplement consisted of 2 tablets per day 1 in the morning and 1 in the evening of a balanced dosage of homotaurine, Coleus forskohlii root extract, L-carnosine, folic acid, vitamins B1, B2, B6, and magnesium.
These values were assessed before and at 3-month intervals. The results revealed that patients treated with the food supplement had a notably significant decrease in IOP and an improvement of their PERG amplitude at 6, 9, and 12 months, as well as foveal sensitivity at 12 months.
It was concluded from the results that the food supplement was able to reach the eye in a detectable manner and may have the potential to further support ocular health in patients with glaucoma A total of 30 men participated in this randomized, double-blind, placebo-controlled study.
Additionally, there was a noted increase in lean body mass in the forskolin group compared to the placebo group. Pertaining to testosterone, serum-free levels significantly increased in the forskolin group compared to the placebo group.
It was concluded from the favorable results that forskolin has the potential to be an alternative therapeutic agent for the management and treatment of obesity Evidence-based research is very limited on C.
The majority of the conducted research has been with animals or in vitro or in vivo. When consumed in medicinal dosages, C. forskohlii seemed to be well tolerated by most individuals.
Due to the limited research available on humans, there is no conclusive compilation of safety and toxicity information available for C.
forskohlii at this time. It is recommended to consult your healthcare professional if you are currently taking any anti-coagulants as forskolin may potentially exacerbate its effects and increase the risk of bleeding complications. Concerning the constituent, forskolin, potential side effects include: decreased blood pressure, elevated heart rate, and increased stomach acid levels 1.
It is recommended that those currently suffering from stomach ulcers or any cardiovascular-related condition avoid consuming C. forskohlii until you consult with your healthcare professional. Our Customer Service team is happy to help!
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Coleus Forskohlii Possibly Helps Support the Immune System: Cyclooxygenase COX-2 is important in regulating several inflammatory processes, especially regarding pulmonary function and asthma.
Coleus Forskohlii Possibly Supports Healthy Cell Growth: The aberrant activity of oncogenic kinases characterizes several cancers. Coleus Forskohlii Might Support Cardiovascular Health: This recent clinical study was conducted to investigate the effect of a wild-source of Makandi Coleus forskohlii Ghana Vati and Churna tablets of its powder on a group of geriatric individuals aged with hypertension.
Coleus Forskohlii Possibly Supports Eye Health: Diabetic retinopathy is an unfortunate consequence of uncontrolled Diabetic Mellitus, which has become a global epidemic over the past few years.
SAFETY Evidence-based research is very limited on C. Drug Interactions: It is recommended to consult your healthcare professional if you are currently taking any anti-coagulants as forskolin may potentially exacerbate its effects and increase the risk of bleeding complications.
Side-Effects: Concerning the constituent, forskolin, potential side effects include: decreased blood pressure, elevated heart rate, and increased stomach acid levels 1.
Altern Med Rev. Rasineni GK, Siddavattam D, Reddy AR. Free Radical Quenching Activity and Polyphenols in Three Species of Coleus.
J Med Plant Res. Bone K. The Ultimate Herbal Compendium. Queensland: Phytotherapy Press. Kanne H, Burte NP, Prasanna V, Gujjula R. Extraction and Elemental Analysis of Coleus forskohlii Extract. Pharmacognosy Research. Extraction and Elemental Analysis of Coleus Forskohlii Extract.
Kavitha C, Rajamani K, Vadivel E. Coleus forskohlii: A Comprehensive Review on Morphology, Phytochemistry and Pharmacological Aspects. J Medicinal Plant Research.
Lazzeri N, Belvisi MG, Patel HJ, et al. Effects of Prostaglandin E2 and cAMP Elevating Drugs on GM-CSF Release by Cultured Human Airway Smooth Muscle Cells. Relevance to Asthma Therapy.
Am J Respir Cell Mol Biol. Motoyoshi S, Yamamoto Y, Munesue S, et al. cAMP Ameliorates Inflammation by Modulation of Macrophage Receptors for Advanced Glycation End-Products.
Biochem J. Hertz AL, Bender AT, Smith KC, et al. Elevated cAMP and PDE4 Inhibition Induce Chemokine Expression in Human Monocyte-Derived Macrophages. Proceedings Nat Acad Sci. Perrotti D, Neviani P. Cancer Metastasis Rev.
Cristobal I, Garcia-Orti L, Cirauqui C, et al. Additionally, zinc demonstrates antiviral activity 23 , Taking zinc long term is typically safe for healthy adults, as long as the daily dose is under the set upper limit of 40 mg of elemental zinc Supplementing with zinc may help protect against respiratory tract infections and reduce the duration of these infections.
Vitamin C is perhaps the most popular supplement taken to protect against infection due to its important role in immune health. This vitamin supports the function of various immune cells and enhances their ability to protect against infection. Vitamin C also functions as a powerful antioxidant, protecting against damage induced by oxidative stress, which occurs with the accumulation of reactive molecules known as free radicals.
Oxidative stress can negatively affect immune health and is linked to numerous diseases Supplementing with vitamin C has been shown to reduce the duration and severity of upper respiratory tract infections, including the common cold Additionally, high-dose intravenous vitamin C treatment has been shown to significantly improve symptoms in people with severe infections, including sepsis and acute respiratory distress syndrome ARDS resulting from viral infections Still, other studies have suggested that the role of vitamin C in this setting is still under investigation 32 , The upper limit for vitamin C is 2, mg.
Supplemental daily doses are typically between and 1, mg Vitamin C is vital for immune health. Supplementing with this nutrient may help reduce the duration and severity of upper respiratory tract infections, including the common cold.
Black elderberry Sambucus nigra , which has long been used to treat infections, is being researched for its effects on immune health. In test-tube studies, elderberry extract demonstrates potent antibacterial and antiviral potential against bacterial pathogens responsible for upper respiratory tract infections and strains of the influenza virus 35 , A review of 4 randomized control studies in people found that elderberry supplements significantly reduced upper respiratory symptoms caused by viral infections However, this study is outdated and was sponsored by the elderberry syrup manufacturer, which may have skewed results Though it has been suggested that elderberry can help relieve symptoms of certain infections and the influenza virus, we also must be aware of the risks.
Some report that elderberries can lead to the production of excess cytokines, which could potentially damage healthy cells For that reason, some researchers recommend elderberry supplements only be used in the early course of COVID It should be noted no published research studies have evaluated the use of elderberry for COVID These recommendations are based on previous research done on elderberries.
A systemic review of elderberry 43 concluded:. Taking elderberry supplements may help reduce upper respiratory symptoms caused by viral infections and help alleviate flu symptoms.
However, elderberry also has risks. More research is needed. Medicinal mushrooms have been used since ancient times to prevent and treat infection and disease. Many types of medicinal mushrooms have been studied for their immune-boosting potential. Over recognized species of medicinal mushrooms are known to have immune-enhancing properties Some research demonstrates that supplementing with specific types of medicinal mushrooms may enhance immune health in several ways as well as reduce symptoms of certain conditions, including asthma and lung infections.
For example, a study in mice with tuberculosis, a serious bacterial disease, found that treatment with cordyceps significantly reduced bacterial load in the lungs, enhanced immune response, and reduced inflammation, compared with a placebo group In a randomized, 8-week study in 79 adults, supplementing with 1.
Turkey tail is another medicinal mushroom that has powerful effects on immune health. Research in humans indicates that turkey tail may enhance immune response, especially in people with certain types of cancer 48 , Many other medicinal mushrooms have been studied for their beneficial effects on immune health as well.
Medicinal mushroom products can be found in the form of tinctures, teas, and supplements 50 , 51 , 52 , Many types of medicinal mushrooms, including cordyceps and turkey tail, may offer immune-enhancing and antibacterial effects.
According to results from scientific research, the supplements listed above may offer immune-boosting properties. However, keep in mind that many of these potential effects these supplements have on immune health have not been thoroughly tested in humans, highlighting the need for future studies.
Astragalus, garlic, curcumin, and echinacea are just some of the supplements that may offer immune-boosting properties.
Still, they have not been thoroughly tested in humans. Many supplements on the market may help improve immune health. Zinc, elderberry, and vitamins C and D are just some of the substances that have been researched for their immune-enhancing potential.
However, although these supplements may offer a small benefit for immune health, they should not and cannot be used as a replacement for a healthy lifestyle.
Aiming to eat a nutrient-dense balanced diet, getting enough sleep, engaging in regular physical activity, and not smoking or considering quitting, if you smoke are some of the most important ways to help keep your immune system healthy and reduce your chances of infection and disease.
If you decide that you want to try a supplement, speak with a healthcare professional first, as some supplements may interact with certain medications or are inappropriate for some people.
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Forzkolin is a popular supplement, systej from the systwm root of an Indian Mental focus and time management known sysyem Forskolin and immune system forskohlii. Forskolin is a diterpene immue by members of the mint family. Apart from being widely used Designer steroids in sports a weight Foorskolin supplement. Excellent formula from 5 premium ingredients, supports weight management, promotes energy and vitality. The organic Forskolin extract capsules cleanse out impurities from the body, helps the body to deal with various problems by enhancing the natural immunity. Our organic Forskolin supplement set is the supermix capsule with its extra formula Turmeric Curcumin, Arjuna, Garcinia, Green Tea is suitable for vegans, vegetarians. Our product set can help you with many power and benefits:.
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