EP is a community where members connect through shared life experiences-- like MS--and so much more. You are not defined by any one thing, so be your true self and find others just like you at
Experience Project.
Joined: Nov 08, 2004 Posts: 144 Location: Colorado
Posted: Sat Jul 19, 2008 10:50 am Post subject:
Gibbledygook
Mental Clarity - 2 caps a day - which would be 680 mg of Lions' Mane
Neorozyme - 2 caps a day - does not contain Lion's Mane
I have sent an email to New Chapter asking about the Mental Clarity and MS. I do have some concern as to the Lion's Mane stimulating the immune system. At what dosage? I do not know.
I think I shall take a trip to the library to do a little more research. References on the internet were few. I found that sites promoting products with Lion's Mane had the same message almost word for word. This has made me a little more suspicious.
Do we have any "herbal specialists" on this board?
Unfortunately nobody has come onto my board with a herbalist's expertise. I'm just trying to piece things together using pubmed. Here's some interesting info on the anti-inflammatory effects of cinnamon and other ingredients which are constituents of the ren shen yang rong tang:
Quote:
1: J Pharmacol Sci. 2007 Sep;105(1):34-40. Links
Protective effects of Guizhi-Fuling-Capsules on rat brain ischemia/reperfusion injury.Li TJ, Qiu Y, Mao JQ, Yang PY, Rui YC, Chen WS.
Department of Pharmacology, School of Pharmacy, Second Military Medical University, 325 GuoHe Road, Shanghai 200433, China.
Previous studies revealed that Guizhi-Fuling-Capsules (GZFLC), a traditional Chinese medical (Kampo) formulation composed of five kinds of medicinal plants, Cinnamomum cassia BLUME (Cinnamomi Cortex), Paeonia lactiflora PALL. (Peonies Radix), Paeonia suffruticosa ANDREWS (Moutan Cortex), Prunus persica BATSCH (Persicae Semen), and Poria cocos WOLF (Hoelen), exerts a protective effect against vascular injury and has a protective effect against glutamate- or nitro oxide-mediated neuronal damage. In the present study, the effect of GZFLC in a rat in vivo model of focal cerebral ischemia and reperfusion was investigated. Administration of GZFLC (0.3 and 0.9 g/kg, p.o.) after focal cerebral ischemia significantly decreased brain infarction and water contents in rats subjected to 2-h ischemia followed by 24-h reperfusion from 31.72 +/- 2.49%, 84.76 +/- 1.63% in the model group to 17.31 +/- 3.66%, 82.51 +/- 1.36% and 8.30 +/- 3.73%, 81.35 +/- 1.73%, respectively. Furthermore, analysis of inflammatory cytokines in ischemic brain showed that GZFLC treatment significantly down-regulated expressions of pro-inflammatory cytokines including interleukin (IL)-1beta and tissue necrosis factor-alpha and markedly up-regulated expressions of anti-inflammatory cytokines IL-10 and IL-10R both in mRNA and protein levels. The serum levels of these inflammatory cytokines were also regulated the same way. These results suggested that GZFLC may be beneficial for the treatment of brain ischemia-reperfusion injury partly due to its anti-inflammatory properties.
21/7/08
I have added today 25mg of DHEA, a steroid hormone, in which I recently showed a relatively low level. I'm also using progesterone cream from day 12 of my cycle to boost my very low progesterone levels.
I seem to have had quite a bit of tingling in the mornings recently but this seems to die down about 2 hours after my herbal breakfast.
I keep getting surges of heat, I should imagine from the capsaicin, which isn't entirely unpleasant but unusual. The dose of 2.4g of capsaicin daily is about the maximum I can take without quite severe stomach pain and bowel urgency. This dose seems to have maintained an improved bladder and bowel and spasticity although from time to time the latter doesn't seem as good as on a higher dose of capsaicin. I wonder what happens to Theiler's mice when injected with capsaicin intrathecally...
I'm still wondering about boswellia as a 5-lipoxygenase inhibtor:
Quote:
1: Brain Res. 2005 Feb 28;1035(2):206-10. Epub 2005 Jan 22. Links
Phenidone, a dual inhibitor of cyclooxygenases and lipoxygenases, ameliorates rat paralysis in experimental autoimmune encephalomyelitis by suppressing its target enzymes.Moon C, Ahn M, Wie MB, Kim HM, Koh CS, Hong SC, Kim MD, Tanuma N, Matsumoto Y, Shin T.
Department of Veterinary Medicine, Aradong 1, Cheju National University, Jeju 690-756, South Korea.
This study examined whether phenidone, a dual inhibitor of cyclooxygenase (COX) and lipoxygenase (LOX), affects the clinical symptoms of experimental autoimmune encephalomyelitis (EAE) in the rat, and the expression of both COX-1/-2 and 5-LOX in EAE spinal cords. Oral phenidone (200 mg/kg) significantly suppressed the incidence and clinical severity of EAE paralysis. Western blot analysis showed that phenidone significantly inhibited the increases in COX-1/-2 and 5-LOX in the spinal cords of rats with EAE. This finding was paralleled by immunohistochemical observations. Overall, these findings suggest that COX-1/-2 and 5-LOX are important inflammatory mediators in the pathogenesis of EAE, and that the inhibition of both COX and LOX ameliorates the autoimmune disorder of the central nervous system.
1: Brain Res. 2004 Sep 17;1021(1):140-5. Links
Experimental allergic encephalomyelitis is exacerbated in mice deficient for 12/15-lipoxygenase or 5-lipoxygenase.Emerson MR, LeVine SM.
Department of Molecular and Integrative Physiology, Ralph L. Smith Mental Retardation Research Center, University of Kansas Medical Center, Kansas City, KS 66160, USA. memers@midwestern.edu
12/15-Lipoxygenase (12/15-LO) produces 15-hydroxyeicosatetraenoic acid (15-HETE) and 13-hydroxyoctadecadienoic acid (13-HODE) which are agonists for peroxisome proliferator-activated receptor-gamma (PPARgamma). PPARgamma agonists reduce clinical severity of experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis. In contrast, 5-lipoxygenase (5-LO) produces the generally proinflammatory leukotrienes (LTs) which would be expected to worsen EAE. We tested the hypotheses that EAE severity would be exacerbated in 12/15-LO-deficient mice and attenuated in 5-LO-deficient mice. 12/15-LO deficiency conferred a significantly worse disease course, and surprisingly, 5-LO deficiency also caused significantly more severe EAE compared to control mice. These data suggest that PPARgamma-regulated gene expression and that 5-LO production of certain LTs have the ability to diminish EAE. Continued analysis will provide insight into the endogenous LO-generated effectors that assist in tempering EAE.
1: J Neuroimmunol. 2005 Sep;166(1-2):55-64. Links
Involvement of 5-lipoxygenase in spinal cord injury.Genovese T, Mazzon E, Rossi A, Di Paola R, Cannavò G, Muià C, Crisafulli C, Bramanti P, Sautebin L, Cuzzocrea S.
Dipartimento Clinico Sperimentale di Medicina e Farmacologia, Facoltà di Medicina e Chirurgia, Università di Messina, Italy.
A traumatic spinal cord injury (SCI) induces a sequelae of events which conduce biochemical and cellular alterations. Here we compare the degree of spinal cord injury caused by the application of vascular clips, in mice lacking the 5-lipoxygenase and in the corresponding wild-type mice. Biochemical, immunohistochemical and functional studies revealed respectively an increase of neutrophils infiltration, of IL-1beta, TNF-alpha immunoreactivity, apoptosis (measured by Annexin-V staining) and loss of hind legs movement in SCI operated 5-LO wild-type mice. In contrast, the degree of (1) neutrophil infiltration at different time points, (2) cytokine expression (TNF-alpha and IL-1beta), (3) histological damage, (4) apoptosis, was markedly reduced in the tissues obtained from SCI operated 5-LO deficient mice and (5) the motor recovery was ameliorated.
1: Arzneimittelforschung. 1998 Jun;48(6):668-74.Links
Effects of boswellic acids extracted from a herbal medicine on the biosynthesis of leukotrienes and the course of experimental autoimmune encephalomyelitis.Wildfeuer A, Neu IS, Safayhi H, Metzger G, Wehrmann M, Vogel U, Ammon HP.
Department of Pathology, Medical Faculty, University of Ulm, Germany.
Mixed acetylboswellic acids, pentacyclic triterpenes extracted from the gum resin of Boswellia serrata Roxb., significantly inhibited the ionophore-stimulated release of the leukotrienes (LT) B4 and C4 from intact human polymorphonuclear neutrophil leukocytes (PMNLs), with IC50 values of 8.48 micrograms/ml and 8.43 micrograms/ml, respectively. Purified acetyl-11-keto-beta-boswellic acid was about three times more potent as inhibitor of the formation of both LTB4 (IC50 = 2.53 micrograms/ml) and LTC4 (IC50 = 2.26 micrograms/ml) from human PMNLs in the same assay. The comparative agent MK 886 (3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl]- 2,2-dimethylpropanoic acid, L-663,536, CAS 118, 414-82-7) was about 10 to 100-fold more active than the boswellic acids in inhibiting the formation of 5-lipoxygenase products in human PMNLs, with IC50 values of 0.0068 microgram/ml (LTB4) and 0.49 microgram/ml (LTC4). After daily intraperitoneal dosage the extract of mixed acetylboswellic acids (20 mg/kg) significantly reduced the clinical symptoms in guinea pigs with experimental autoimmune encephalomyelitis (EAE) between days 11 and 21. However, the inflammatory infiltrates in the brain and the spinal cord were not significantly less extensive in the treated animals than in the respective control group. The multiple intraperitoneal application of boswellic acids did not inhibit the ionophore-challenged ex vivo release of leukotrienes B4 and C4 from PMNLs separated from the blood of guinea pigs with EAE. The boswellic acids have thus been characterized as selective, non-redox and potent inhibitors of the biosynthesis of leukotrienes in vitro
1: Lipids. 1997 Nov;32(11):1173-80.Links
Effect of curcumin and capsaicin on arachidonic acid metabolism and lysosomal enzyme secretion by rat peritoneal macrophages.Joe B, Lokesh BR.
Department of Biochemistry and Nutrition, Central Food Technological Research Institute, Mysore, India.
The inflammatory mediators secreted by macrophages play an important role in autoimmune diseases. Spice components, such as curcumin from turmeric and capsaicin from red pepper, are shown to exhibit antiinflammatory properties. The influence of these spice components on arachidonic acid metabolism and secretion of lysosomal enzymes by macrophages was investigated. Rat peritoneal macrophages preincubated with 10 microM curcumin or capsaicin for 1 h inhibited the incorporation of arachidonic acid into membrane lipids by 82 and 76%: prostaglandin E2 by 45 and 48%; leukotriene B4 by 61 and 46%, and leukotriene C4 by 34 and 48%, respectively, but did not affect the release of arachidonic acid from macrophages stimulated by phorbol myristate acetate. However, the secretion of 6-keto PG F1 alpha was enhanced by 40 and 29% from macrophages preincubated with 10 microM curcumin or capsaicin, respectively, as compared to those produced by control cells. Curcumin and capsaicin also inhibited the secretion of collagenase, elastase, and hyaluronidase to the maximum extent of 57, 61, 66%, and 46, 69, 67%, respectively. These results demonstrated that curcumin and capsaicin can control the release of inflammatory mediators such as eicosanoids and hydrolytic enzymes secreted by macrophages and thereby may exhibit antiinflammatory properties.
<shortened url> _________________ 1st traceable symptoms Jan 01, last edss by doctor 6.5. Feeling better on ginkgo, salvia, capsaicin, curcumin, scutellaria. Interested in other vascular strengthening herbs; pycnogenol, butcher's broom, horsechestnut, centenella, hersperidin
Posted: Mon Jul 21, 2008 8:50 am Post subject: MS and histamine dysregulation - is there a link?
My discovery that capsaicin blocks my hayfever has led me into other avenues of investigation:
Quote:
1: Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10146-51. Epub 2007 Jun 4. Links
Central histamine H3 receptor signaling negatively regulates susceptibility to autoimmune inflammatory disease of the CNS.Teuscher C, Subramanian M, Noubade R, Gao JF, Offner H, Zachary JF, Blankenhorn EP.
Departments of Medicine and Pathology, University of Vermont, Burlington, VT 05405, USA. c.teuscher@uvm.edu
Histamine (HA), a biogenic amine with a broad spectrum of activities in both physiological and pathological settings, plays a key regulatory role in experimental allergic encephalomyelitis, the autoimmune model of multiple sclerosis. HA exerts its effect through four G protein-coupled receptors designated HA receptor H1, H2, H3, and H4. We report here that, compared with wild-type animals, mice with a disrupted HA H3 receptor (H3RKO), the expression of which is normally confined to cells of the nervous system, develop more severe disease and neuroinflammation. We show that this effect is associated with dysregulation of blood-brain barrier permeability and increased expression of MIP-2, IP-10, and CXCR3 by peripheral T cells. Our data suggest that pharmacological targeting of the H3R may be useful in preventing the development and formation of new lesions in multiple sclerosis, thereby significantly limiting the progression of the disease.
1: J Immunol. 2006 Jan 1;176(1):17-26. Links
A key regulatory role for histamine in experimental autoimmune encephalomyelitis: disease exacerbation in histidine decarboxylase-deficient mice.Musio S, Gallo B, Scabeni S, Lapilla M, Poliani PL, Matarese G, Ohtsu H, Galli SJ, Mantegazza R, Steinman L, Pedotti R.
Immunology and Muscular Pathology Unit, National Neurological Institute "C. Besta," Milan, Italy.
Histamine can modulate the cytokine network and influence Th1 and Th2 balance and Ab-isotype switching. Thus, pharmacological blockade or genetic deletion of specific histamine receptors has been shown to reduce the severity of experimental autoimmune encephalomyelitis (EAE), a prototypic Th1-mediated disease with similarities to human multiple sclerosis. To study the comprehensive contribution of endogenous histamine to the expression of EAE, we attempted to induce EAE in histidine decarboxylase-deficient mice, which are genetically unable to make histamine. In this study, we show that EAE is significantly more severe in HDC-/-, histamine-deficient mice, with diffuse inflammatory infiltrates, including a prevalent granulocytic component, in the brain and cerebellum. Unlike splenocytes from wild-type mice, splenocytes from HDC-/- mice do not produce histamine in response to the myelin Ag, whereas production of IFN-gamma, TNF, and leptin are increased in HDC-/- splenocytes in comparison to those from wild-type mice. Endogenous histamine thus appears to regulate importantly the autoimmune response against myelin and the expression of EAE, in this model, and to limit immune damage to the CNS. Understanding which receptor(s) for histamine is/are involved in regulating autoimmunity against the CNS might help in the development of new strategies of treatment for EAE and multiple sclerosis.
capsaicin modulates histamine release in stressed rats:
Quote:
1: Neurosci Lett. 1999 Aug 6;270(3):181-4. Links
Activation of sensory nerves participates in stress-induced histamine release from mast cells in rats.Huang ZL, Mochizuki T, Watanabe H, Maeyama K.
Department of Pharmacology, Ehime University School of Medicine, Onsen-gun, Japan.
To elucidate the mechanism by which stress induces rapid histamine release from mast cells, Wistar rats, pretreated as neonates with capsaicin, were subjected to immobilization stress for 2 h, and histamine release was measured in paws of anesthetized rats by using in vivo microdialysis after activation of sensory nerves by electrical or chemical stimulation. Immobilization stress studies indicated that in control rats stress induced a 2.7-fold increase in the level of plasma histamine compared to that in freely moving rats. Whereas pretreatment with capsaicin significantly decreased stress-induced elevation of plasma histamine. Microdialysis studies showed that electrical stimulation of the sciatic nerve resulted in a 4-fold increase of histamine release in rat paws. However, this increase was significantly inhibited in rats pretreated with capsaicin. Furthermore, injection of capsaicin into rat paw significantly increased histamine release in a dose-dependent manner. These results suggest that activation of sensory nerves participates in stress-induced histamine release from mast cells.
1: Adv Exp Med Biol. 2007;601:423-30.Links
Mast cells, T cells, and inhibition by luteolin: implications for the pathogenesis and treatment of multiple sclerosis.Theoharides TC, Kempuraj D, Iliopoulou BP.
Department of Pharmacology, Internal Medicine and Biochemistry, Immunology Program, Tufts University School of Medicine, Tufts-New England Medical Center, Boston, MA, USA. theoharis.theoharides@tufts.edu
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) mainly mediated by Th1, but recent evidence indicates that Th2 T cells, mostly associated with allergic reactions, are also involved. Mast cells are involved in allergic and inflammatory reactions because they are located perivascularly and secrete numerous proinflammatory cytokines. Brain mast cells are critically placed around the blood-brain barrier (BBB) and can disrupt it, a finding preceding any clinical or pathological signs of MS. Moreover, mast cells are often found close to MS plaques, and the main MS antigen, myelin basic protein (MBP), can activate human cultured mast cells to release IL-8, TNF-alpha, tryptase, and histamine. Mast cells could also contribute to T cell activation since addition of mast cells to anti-CD3/anti-CD28 activated T cells increases T cell activation over 30-fold. This effect requires cell-to-cell contact and TNF, but not histamine or tryptase. Pretreatment with the flavone luteolin totally blocks mast cell stimulation and T cell activation. Mast cells could constitute a new unique therapeutic target for MS.
1: Neurology. 2006 Feb 28;66(4):572-5. Links
Allergy, histamine 1 receptor blockers, and the risk of multiple sclerosis.Alonso A, Jick SS, Hernán MA.
Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA. aalogut@alumni.unav.es
BACKGROUND: It is unclear whether allergic diseases are associated with multiple sclerosis (MS), but histamine 1 receptor blockers, used in the treatment of allergic conditions, decreased the severity of experimental autoimmune encephalomyelitis (an animal model of MS). OBJECTIVE: To assess the association of allergy history and use of histamine 1 receptor blockers with the risk of MS. METHODS: Using a case-control study nested in the United Kingdom-based General Practice Research Database cohort, the authors identified 163 incident cases of MS with at least 3 years of follow-up before their first symptoms (index date). Up to 10 controls matched to the cases by age, sex, general practice, and time in the cohort were selected. Previous history of allergic disease and use of histamine 1 receptor blockers in the 3 years before the index date were assessed through computerized medical records. RESULTS: History of any allergic condition in the 3 years before the index date was not associated with MS risk (adjusted odds ratio [OR] 1.2, 95% CI 0.8 to 1.. However, use of sedating histamine 1 receptor blockers was associated with decreased MS risk (adjusted OR 0.2, 95% CI 0.1 to 0.. CONCLUSION: These results do not support a strong link between allergic conditions and multiple sclerosis (MS) risk but suggest a possible beneficial effect of antihistamines on the onset of MS.
1: Int J Immunopathol Pharmacol. 2005 Oct-Dec;18(4):771-8.Links
A pilot, open label, clinical trial using hydroxyzine in multiple sclerosis.Logothetis L, Mylonas IA, Baloyannis S, Pashalidou M, Orologas A, Zafeiropoulos A, Kosta V, Theoharides TC.
Department of Neurology, Aristotle University, AHEPA Hospital, Thessaloniki, Greece.
Multiple sclerosis (MS) is an autoimmune disorder of myelin destruction. Blood-brain-barrier (BBB) disruption precedes pathological or clinical findings and could involve mediators from perivascular brain mast cells, such as histamine and vascular endothelial growth factor (VEGF). Mast cells could be activated by many triggers, including acute stress that has been correlated with MS exacerbations. We considered that the histamine-1 (H1) receptor antagonist hydroxyzine, which also partially inhibits brain mast cells and has anxiolytic properties, may reduce MS symptoms. This open label, pilot, clinical trial investigated the effect on MS of an oral solution of hydroxyzine (100 mg per day), together with caffeine (200 mg per day) to reduce sedation. Twenty patients (8 males; 12 females) with relapsing-remitting or relapsing-progressive MS completed the study (12 +/- 1 months) and were evaluated using disability scales. Most patients on hydroxyzine (75%) remained stable or improved neurologically and all but one showed improved mood. Hydroxyzine could be used as an adjuvant in MS, but the small number of patients enrolled and the short duration of the study precludes any definitive conclusions. A double-blind, placebo-controlled study is warranted.
1: Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1867-72. Epub 2003 Feb 7. Links
Multiple elements of the allergic arm of the immune response modulate autoimmune demyelination.Pedotti R, DeVoss JJ, Youssef S, Mitchell D, Wedemeyer J, Madanat R, Garren H, Fontoura P, Tsai M, Galli SJ, Sobel RA, Steinman L.
Department of Neurology and Neurological Science, Stanford University Medical Center, Stanford, CA 94305, USA.
Analysis of mRNA from multiple sclerosis lesions revealed increased amounts of transcripts for several genes encoding molecules traditionally associated with allergic responses, including prostaglandin D synthase, histamine receptor type 1 (H1R), platelet activating factor receptor, Ig Fc epsilon receptor 1 (Fc epsilon RI), and tryptase. We now demonstrate that, in the animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), mediated by T helper 1 (Th1) T cells, histamine receptor 1 and 2 (H1R and H2R) are present on inflammatory cells in brain lesions. Th1 cells reactive to myelin proteolipid protein expressed more H1R and less H2R than Th2 cells. Pyrilamine, an H1R antagonist, blocked EAE, and the platelet activating factor receptor antagonist CV6209 reduced the severity of EAE. EAE severity was also decreased in mice with disruption of the genes encoding Ig Fc gamma RIII or both Fc gamma RIII and Fc epsilon RI. Prostaglandin D synthase and tryptase transcripts were elevated in EAE brain. Taken together, these data reveal extensive involvement of elements of the immune response associated with allergy in autoimmune demyelination. The pathogenesis of demyelination must now be viewed as encompassing elements of both Th1 responses and "allergic" responses.
From wikipedia, pyrilamine is an old (off-patent?) anti-histamine!
Quote:
Mepyramine (INN, also known as pyrilamine) [1] is a first generation antihistamine, targeting the H1 receptor. However, it rapidly permeates the brain and so often causes drowsiness as a side effect.
It is used in over-the-counter combination products for colds and menstrual symptoms.[2]
Side effects may include sedation/drowsiness, muscle weakness, and insomnia.
upregulating histamine receptor 2 may be another useful tack:
Quote:
1: Neuroreport. 2002 Aug 7;13(11):1407-10. Links
Activation of histamine H2 receptors ameliorates experimental allergic encephalomyelitis.Emerson MR, Orentas DM, Lynch SG, LeVine SM.
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
Experimental allergic encephalomyelitis (EAE), a model of multiple sclerosis, is an autoimmune, demyelinating disease of the CNS. Pro-inflammatory cytokines (e.g. tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-12) and reactive oxygen species are implicated in promoting EAE. Since histamine H(2) receptor activation suppresses production of O(2)*-, TNF-alpha, and IL-12 by inflammatory cells, we tested the hypothesis that dimaprit, an H(2) agonist, would reduce the clinical severity and pathology of EAE. Dimaprit treatment significantly reduced clinical signs compared to vehicle in both C57BL/6 and iNOS deficient EAE mice. Furthermore, dimaprit significantly reduced CNS staining for lectin-positive macrophages and decreased extravasated albumin staining, an indicator of blood-brain barrier leakage. These data provide a rationale for exploring H2 receptor activation for therapeutic value in multiple sclerosis.
Somewhere above there's an abstract which shows that capsaicin dramatically reduces mast cells in rats and this might be useful;
Quote:
1: Int J Immunopharmacol. 2000 Sep;22(9):673-84. Links
Hydroxyzine inhibits experimental allergic encephalomyelitis (EAE) and associated brain mast cell activation.Dimitriadou V, Pang X, Theoharides TC.
Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA.
Experimental allergic encephalomyelitis (EAE) has been used as an animal model for the human demyelinating disease multiple sclerosis (MS). In acute MS or EAE, early disruption in the integrity of the blood-brain-barrier (BBB) precedes brain infiltration by inflammatory cells or any clinical evidence of disease. BBB permeability could be affected by vasoactive mediators and cytokines released from perivascular brain mast cells. We investigated the number and degree of activation of brain mast cells in EAE and the effect of the heterocyclic histamine-1 receptor antagonist hydroxyzine, a piperazine compound known to also block mast cells. Acute EAE was induced in Lewis rats by immunization with whole guinea pig spinal cord homogenate and complete Freund's adjuvant (CFA). A second group of animals were treated orally with hydroxyzine for one day before immunization and then continuously for 14 days. Control rats were treated with CFA or hydroxyzine alone. The clinical progression of EAE was assessed on days 10, 12 and 14 after immunization. The number of metachromatic mast cells and the degree of degranulation was assessed in the thalamus with light microscopy. At day 14, there was a three-fold increase in the number of brain mast cells with EAE, as compared to controls. These cells were positive for the immunoglobulin E binding protein (FcepsilonRI), while those from control rats were not. Over 40% of all thalamic mast cells studied in EAE showed partial staining or extruded secretory granule indicative of secretion. Hydroxyzine treatment inhibited (p<0.05) the progression and severity of EAE by 50% and the extent of mast cell degranulation by 70% (p<0.05). These findings indicate that brain mast cells are associated with EAE development and that inhibition of their activation correlates positively with the clinical outcome.
<shortened url> _________________ 1st traceable symptoms Jan 01, last edss by doctor 6.5. Feeling better on ginkgo, salvia, capsaicin, curcumin, scutellaria. Interested in other vascular strengthening herbs; pycnogenol, butcher's broom, horsechestnut, centenella, hersperidin
Isn't it interesting that the Prokarin idea was to give people histamine because it was depleted in the brains of MS patients: too much used up in the h2 and h1 receptors so the h3 receptors did not have what they neeeded.
Yet I have a friend who has for years used hydroxyzine for her MS based on the idea that blocking histamine would aid her as the research you cited as well. Who knows how she'd be if she'd not done it but she has progresseed.
marie
I hope you're well, somewhere above there's some data suggesting capsaicin might be good in RA. I wonder if you have tried it? I tried it by chance for my hayfever and discovered that it was fantastic at stopping me sneezing. It has also improved my bladder, bowel and spasticity but can be awful on the stomach. I have no idea if it is long term good or bad. Still nice to have a momentary reprieve. _________________ 1st traceable symptoms Jan 01, last edss by doctor 6.5. Feeling better on ginkgo, salvia, capsaicin, curcumin, scutellaria. Interested in other vascular strengthening herbs; pycnogenol, butcher's broom, horsechestnut, centenella, hersperidin
Ihave not tried it but will as soon as vitqacost cqan get me some. I eat spice like a true pepper belly, though I am Irish by genetics. I LOVE spicy food. I use capsaicin I should say on my SKIN all the time already. I like it for joint pain, it really knocks it.
I have suspected it is a wakeful thing though, do you try to take it in the morning?
marie
Yes, I take it in the morning AND the evening and I have noticed that sometimes when a bit of burning occurs in the evening that I feel a sort of rush of heat and a surge of wellbeing and also an inability to fall asleep so well. mmm. I have also realised that to my slight annoyance capsaicin stops me wanting to drink coffee and also alcohol. This is as bad as metronidazole except I don't feel nausea! I certainly think it's the drug for me for the time being. I have noticed more tingling in pre-existing sites of damage though so am not sure that this is a good sign. But it's so nice to be able to walk a bit less stiffly and to control one's bladder better...AND of course for me not to spend the summer sniffling, sneezing, sleeping with a surgical mask on, using air conditioning to clear the air of pollen. I swear that pollen in the UK gets through closed windows. _________________ 1st traceable symptoms Jan 01, last edss by doctor 6.5. Feeling better on ginkgo, salvia, capsaicin, curcumin, scutellaria. Interested in other vascular strengthening herbs; pycnogenol, butcher's broom, horsechestnut, centenella, hersperidin
Posted: Wed Jul 23, 2008 3:39 am Post subject: more stuff on anti-inflammatory effect of capsaicin
Here the capsaicin reduces ifn gamma and some other nasties but increases them after concanavalin a which is a lymphocyte mitogen and matrix metalloproteinase stimulator, according to wikipedia:
Quote:
1: Life Sci. 2007 Apr 3;80(17):1553-63. Epub 2007 Jan 27. Links
Capsicum ethanol extracts and capsaicin enhance interleukin-2 and interferon-gamma production in cultured murine Peyer's patch cells ex vivo.Takano F, Yamaguchi M, Takada S, Shoda S, Yahagi N, Takahashi T, Ohta T.
Department of Pharmacognosy and Chemistry of Natural Products, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan. takano@p.kanazawa-u.ac.jp
We investigated the effects of red pepper (Capsicum annuum Lin.) extracts (capsicum extract) and its main pungent capsaicin on T helper 1 (Th1) and 2 (Th2) cytokine production in cultured murine Peyer's patch (PP) cells in vitro and ex vivo. Direct administration of capsicum extract (1 and 10 mug/ml) and capsaicin (3 and 30 muM) resulted in suppression of interleukin (IL)-2, interferon (IFN)-gamma, IL-4 and IL-5 production. In an ex vivo experiment using PP cells removed from the mice after oral administration of capsicum extract (10 mg/kg/day for 4 consecutive days), IL-2, IFN-gamma and IL-5 increased in response to concanavalin A (Con A). Oral administration of 3 mg/kg/day capsaicin, one active constituent of the extract, also enhanced IL-2, INF-gamma and IL-4 production in response to Con A stimulation but did not influence the production of IL-5. Orally administered capsazepine (3 mg/kg/day), a selective transient receptor potential vanilloid 1 (TRPV1) antagonist, slightly enhanced IL-2 production also irrespective of Con A stimulation. The capsaicin-induced enhancement of both IL-2 and IFN-gamma production was not reduced by oral administration of capsazepine (3 mg/kg/day), suggesting a TRPV1 receptor-independent mechanism. Flow cytometric analysis revealed that the population of CD3(+) cells in the PP cells was significantly reduced while CD19(+) cells increased after oral administration of capsicum extract (1 and 10 mg/kg/day) and capsaicin (0.3 and 3 mg/kg/day). Capsazepine (3 mg/kg/day) weakly but significantly reversed these effects. Orally administered capsicum extract and capsaicin did not change the T cell subset (CD4(+) and CD8(+)), Th1 (IFN-gamma(+)) and T2 (IL-4(+)) ratio. These findings indicate that capsicum extract and capsaicin modulate T cell-immune responses, and their immunomodulatory effects on murine PP cells are partly due to both TRPV1-dependent and -independent pathway.
Concanavalin A is a lectin protein originally extracted from the jack-bean Canavalia ensiformis. It binds specifically to certain structures found in various sugars, namely internal and nonreducing terminal alpha-mannosyl groups. It is used in biology and biochemistry to characterize glycoproteins and other sugar-containing entities. It is also used in lectin affinity chromatography.
Concanavalin A is also a lymphocyte mitogen.
It has also been shown as a stimulator of several matrix metalloproteinases (MMPs).
Quote:
1: J Neuroimmunol. 2006 Feb;171(1-2):110-9. Epub 2005 Oct 18. Links
Arvanil inhibits T lymphocyte activation and ameliorates autoimmune encephalomyelitis.Malfitano AM, Matarese G, Pisanti S, Grimaldi C, Laezza C, Bisogno T, Di Marzo V, Lechler RI, Bifulco M.
Dipartimento di Scienze Farmaceutiche, Universita' di Salerno, Via Ponte don Melillo 84084 Fisciano (Salerno), Italy.
This study examined the immunomodulatory effect of arvanil, a synthetic capsaicin-anandamide hybrid. Arvanil inhibits lymphocyte proliferation and IFN-gamma production. The phenotype of activated CD4+T cells treated with arvanil shows a down-regulation of T cell activation markers such as CD25, HLA-DR and CD134/OX40. Arvanil and anandamide do not induce apoptosis on CD4+T cells. Arvanil blocks the G1/S phase transition of the cell cycle in stimulated peripheral blood mononuclear cells, inducing activation of p21waf-1/cip-1 and phosphorylation of Akt/PKB. In vivo, arvanil ameliorates experimental autoimmune encephalomyelitis in the SJL/J mouse. Our findings have relevance for the use of arvanil and related compounds as a novel immunotherapeutic approach in the treatment of multiple sclerosis.
1: Br J Pharmacol. 2003 Nov;140(6):1077-87. Epub 2003 Oct 6. Links
Signal transduction for inhibition of inducible nitric oxide synthase and cyclooxygenase-2 induction by capsaicin and related analogs in macrophages.Chen CW, Lee ST, Wu WT, Fu WM, Ho FM, Lin WW.
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
1. Although capsaicin analogs might be a potential strategy to manipulate inflammation, the mechanism is still unclear. In this study, the effects and action mechanisms of vanilloid analogs on iNOS and COX-2 expression were investigated in RAW264.7 macrophages. 2. Capsaicin and resiniferatoxin (RTX) can inhibit LPS- and IFN-gamma-mediated NO production, and iNOS protein and mRNA expression with similar IC50 values of around 10 microm. 3. Capsaicin also transcriptionally inhibited LPS- and PMA-induced COX-2 expression and PGE2 production. However, this effect exhibited a higher potency (IC50: 0.2 microm), and RTX failed to elicit such responses at 10 microm. 4. Interestingly, we found that capsazepine, a competitive TRPV1 antagonist, did not prevent the inhibition elicited by capsaicin or RTX. Nevertheless, it mimicked vanilloids in inhibiting iNOS/NO and COX-2/PGE2 induction with an IC50 value of 3 microm. RT-PCR and immunoblotting analysis excluded the expression of TRPV1 in RAW264.7 macrophages. 5. The DNA binding assay demonstrated the abilities of vanilloids to inhibit LPS-elicited NF-kappaB and AP-1 activation and IFN-gamma-elicited STAT1 activation. The reporter assay of AP-1 activity also supported this action. 6. The kinase assay indicated that ERK, JNK, and IKK activation by LPS were inhibited by vanilloids. 7. In conclusion, vanilloids can modulate the expression of inflammatory iNOS and COX-2 genes in macrophages through interference with upstream signalling events of LPS and IFN-gamma. These findings provide new insights into the potential benefits of the active ingredient in hot chilli peppers in inflammatory conditions.
<shortened url> _________________ 1st traceable symptoms Jan 01, last edss by doctor 6.5. Feeling better on ginkgo, salvia, capsaicin, curcumin, scutellaria. Interested in other vascular strengthening herbs; pycnogenol, butcher's broom, horsechestnut, centenella, hersperidin
Posted: Wed Jul 23, 2008 5:19 am Post subject: capsaicin as nerve degenerator/regenerator
I'm not sure I like the look of this:
Quote:
1: Pharmacology. 2005 Nov;75(3):116-21. Epub 2005 Sep 2. Links
ERK and STAT3 phosphorylation in sensory neurons during capsaicin-induced impairment and nerve growth factor treatment.Donnerer J, Liebmann I, Schicho R.
Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Graz, Austria. josef.donnerer@meduni-graz.at
Distinct signal transduction pathways have been shown to regulate injury responses and regeneration in peripheral nerves. In the present investigation, the time courses of the induction of phospho-MAPK/ERK1/2 and of phospho-STAT3 were investigated in the dorsal root ganglia (DRG) and in the sciatic nerve of rats following a systemic capsaicin treatment without or with concomitant intraplantar NGF injections. Western blots were probed with polyclonal antibodies that specifically detect phosphorylated ERK 1/2 and STAT3. Phosphorylation of ERK clearly peaked in the sciatic nerve and in the lumbar DRGs at 6 and 10 h after the capsaicin treatment. In the following 8 days phospho-ERK decreased to very low levels and was found recovered to basal values at the time point 16 days. An additional intraplantar nerve growth factor (NGF) injection at time points 20, 44 and 92 h after the capsaicin treatment, and collection of tissues 4 h later, markedly increased the level of phospho-ERK in the sciatic nerve as well as in the DRG, as compared to the samples taken from rats at the same time points with a capsaicin treatment only. Posphorylated STAT3, which was almost non-detectable in the control sciatic nerve, clearly peaked at 6 h after the capsaicin treatment and decreased again during the following days to almost undetectable levels. The intraplantar NGF injections slightly stimulated phosho-STAT3 in the sciatic nerve. A basal level of phosphorylated STAT3 was present in DRGs of control animals, it remained at a high level up to 6 h after the capsaicin treatment, then markedly decreased and recovered on day 8 and day 16. NGF increased STAT3 phosphorylation in DRG on day 1 and day 2 above the level observed in samples taken from rats at the same time points with a capsaicin treatment only. The present study demonstrates that a capsaicin impairment of small diameter primary sensory neurons followed by an NGF treatment evokes a characteristic pattern of ERK and STAT3 activation indicative of neuronal degeneration and regeneration. Copyright (c) 2005 S. Karger AG, Basel.
curiously in cancer cell lines capsaicin induces apoptosis in transformed cells but not normal cells
Quote:
1: Int J Cancer. 2003 Feb 10;103(4):475-82. Links
Roles of JNK-1 and p38 in selective induction of apoptosis by capsaicin in ras-transformed human breast epithelial cells.Kang HJ, Soh Y, Kim MS, Lee EJ, Surh YJ, Kim HR, Kim SH, Moon A.
College of Pharmacy, Duksung Women's University, 4129 Ssangmun-dong, Tobong-ku, Seoul 132-714, Korea.
Efforts have been made to develop a chemoprevention strategy that selectively triggers apoptosis in malignant cancer cells. Previous studies showed that capsaicin, the major pungent ingredient of red pepper, had differential effect between normal and transformed cells. As an approach to unveil the molecular mechanism by which capsaicin selectively induces apoptosis in transformed cells, we investigated the effect of capsaicin in nontransformed and ras-transformed cells of a common origin: parental (MCF10A) and H-ras-transformed (H-ras MCF10A) human breast epithelial cells. Here, we show that capsaicin selectively induces apoptosis in H-ras-transformed cells but not in their normal cell counterparts. The capsaicin-induced apoptosis, which is dependent on ras transformation, involves the activity of DEVDase (caspase-3 like). In H-ras MCF10A cells, capsaicin treatment markedly activated c-Jun N-terminal protein kinase (JNK)-1 and p38 matigen-activated protein kinase (MAPK) while it deactivated extracellular signal-regulated protein kinases (ERKs). The use of kinase inhibitors and overexpression of dominant-negative forms of MAPKs demonstrated a role of JNK-1 and p38, but not that of ERKs, in apoptosis induced by capsaicin in H-ras-transformed MCF10A cells. Based on the present study, we propose that capsaicin selectively induces apoptosis through modulation of ras-downstream signaling molecules in ras-activated MCF10A cells. Taken in conjunction with the fact that uncontrolled ras activation is probably the most common genetic defect in human cancer cells, our finding may be critical to the chemopreventive potential of capsaicin and for developing a strategy to induce tumor cell-specific apoptosis. Copyright 2002 Wiley-Liss, Inc
not sure that we want mapk p38 activation in the spinal cord:
Quote:
1: Pain. 2004 Oct;111(3):278-85. Links
Peripheral and central p38 MAPK mediates capsaicin-induced hyperalgesia.Sweitzer SM, Peters MC, Ma JY, Kerr I, Mangadu R, Chakravarty S, Dugar S, Medicherla S, Protter AA, Yeomans DC.
Department of Anesthesia, Stanford University School of Medicine, Stanford, CA 94305, USA. sweitzer@med.sc.edu
The stress-activated mitogen-activated protein kinase (MAPK) p38 is emerging as an important mediator of pain. The present study examined the possible involvement of peripheral and spinal p38 MAPK in capsaicin-induced thermal hyperalgesia. Topical capsaicin produced phosphorylation of p38 MAPK in the skin from the affected hindpaw as well as the corresponding lumbar spinal cord in a time dependent manner. Topical capsaicin produced robust C-fiber mediated thermal hyperalgesia that was inhibited by systemic, local peripheral, or central intrathecal pre-treatment with the p38 MAPK inhibitor, SD-282. Intraperitoneal SD-282 (10-60 mg/kg) significantly and dose-dependently attenuated capsaicin-induced C-fiber mediated thermal hyperalgesia. Similarly, 0.1-5mg/kg subcutaneous SD-282 in the hindpaw dose-dependently attenuated capsaicin-induced thermal hyperalgesia. Intrathecal administration of 1microg SD-282 was also anti-hyperalgesic in this model. Functionally, SD-282 decreased capsaicin-induced release of calcitonin gene related peptide in an in vitro skin release assay, consistent with a role for p38 MAPK in peripheral nerve function. These results suggest that p38 MAPK plays a role in the development of hyperalgesic states, exerting effects both centrally in the spinal cord and peripherally in sensory C fibers.
1: J Neurochem. 2007 Apr;101(2):364-76. Epub 2007 Jan 22. Links
A novel role of glia maturation factor: induction of granulocyte-macrophage colony-stimulating factor and pro-inflammatory cytokines.Zaheer A, Zaheer S, Sahu SK, Knight S, Khosravi H, Mathur SN, Lim R.
Veterans Affair Medical Center, Iowa City, Iowa, USA. asgar-zaheer@uiowa.edu
The glia maturation factor (GMF), which was discovered in our laboratory, is a highly conserved protein predominantly localized in astrocytes. GMF is an intracellular regulator of stress-related signal transduction. We now report that the overexpression of GMF in astrocytes leads to the destruction of primary oligodendrocytes by interactions between highly purified cultures of astrocytes, microglia, and oligodendrocytes. We infected astrocytes with a replication-defective adenovirus carrying the GMF cDNA. The overexpression of GMF caused the activation of p38 MAP kinase and transcription factor NF-kappaB, as well as the induction of granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA and protein in astrocytes. Small interfering RNA-mediated GMF knockdown completely blocked the GMF-dependent activation of p38 mitogen-activated protein kinase (MAPK), NF-kappaB, and enhanced expression of GM-CSF by astrocytes. Inhibition of p38 MAPK or NF-kappaB by specific inhibitors prevented GM-CSF production. The cell-free conditioned medium from overexpressing GMF astrocytes contained 320 +/- 33 pg/mL of GM-CSF, which was responsible for enhanced production and secretion of TNF-alpha, IL-1beta, IL-6, and IP-10 by microglia. Presence of these inflammatory cytokines in the conditioned medium from microglia efficiently destroyed oligodendrocytes in culture. These results suggest that GMF-induced production of GM-CSF in astrocytes is depending on p38 MAPK and NF-kappaB activation. The GM-CSF-dependent expression and secretion of inflammatory cytokine/chemokine, TNF-alpha, IL-1beta, IL-6, and IP-10, is cytotoxic to oligodendrocytes, the myelin-forming cells in the central nervous system, and as well as neurons. Our results suggest a novel pathway of GMF-initiated cytotoxicity of brain cells, and implicate its involvement in inflammatory diseases such as multiple sclerosis.
1: Eur J Immunol. 2002 Jun;32(6):1753-63. Links
Immunosuppressive activity of capsaicinoids: capsiate derived from sweet peppers inhibits NF-kappaB activation and is a potent antiinflammatory compound in vivo.Sancho R, Lucena C, Macho A, Calzado MA, Blanco-Molina M, Minassi A, Appendino G, Muñoz E.
Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Córdoba, Spain.
Capsiate and its dihydroderivatives are the major capsaicinoids of sweet pepper. These new capsaicinoids do not activate the vanilloid receptor type 1 (VR1) but they share with capsaicin (CPS)some biological activities mediated in a VR1-independent fashion. In this study we show that CPS and nordihydrocapsiate (CPT) inhibit early and late events in T cell activation, including CD69, CD25 and ICAM-1 cell surface expression, progression to the S phase of the cell cycle and proliferation in response to TCR and CD28 co-engagement. Moreover, both CPS and CPT inhibit NF-kappaB activation in response to different agents including TNF-alpha. CPS itself does not affect the DNA-binding ability of NF-kappaB but it prevents IkappaB kinase activation and IkappaBalpha degradation in a dose-dependent manner, without inhibiting the activation of the mitogen-activated protein kinases, p38, extracellular regulated kinase and c-Jun N-terminal protein kinase. Moreover, intraperitoneal pretreatment with CPT prevented mice from lethal septic shock induced by lipopolysaccharide. In a second model of inflammation CPT pretreatment greatly reduced the extensive damage in the glandular epithelium observed in the bowel of DSS-treated mice. Taken together, these results suggest that CPT and related synthetic analogues target specific pathways involved in inflammation, and hold considerable potential for dietary health benefits as well as for pharmaceutical development.
capsaicin may destroy microglia which are responsible for inflammatory cascades in the brain:
Quote:
1: J Immunol. 2006 Oct 1;177(7):4322-9. Links
Transient receptor potential vanilloid subtype 1 mediates microglial cell death in vivo and in vitro via Ca2+-mediated mitochondrial damage and cytochrome c release.Kim SR, Kim SU, Oh U, Jin BK.
Brain Disease Research Center, Ajou University School of Medicine, Suwon 443-479, Korea.
The present study examined the expression of transient receptor potential vanilloid subtype 1 (TRPV1) in microglia, and its association with microglial cell death. In vitro cell cultures, RT-PCR, Western blot analysis, and immunocytochemical staining experiments revealed that rat microglia and a human microglia cell line (HMO6) showed TRPV1 expression. Furthermore, exposure of these cells to TRPV1 agonists, capsaicin (CAP) and resiniferatoxin (RTX), triggered cell death. This effect was ameliorated by the TRPV1 antagonists, capsazepine and iodo-resiniferatoxin (I-RTX), suggesting that TRPV1 is directly involved. Further examinations revealed that TRPV1-induced toxicity was accompanied by increases in intracellular Ca(2+), and mitochondrial damage; these effects were inhibited by capsazepine, I-RTX, and the intracellular Ca(2+) chelator BAPTA-AM. Treatment of cells with CAP or RTX led to increased mitochondrial cytochrome c release and enhanced immunoreactivity to cleaved caspase-3. In contrast, the caspase-3 inhibitor z-DEVD-fmk protected microglia from CAP- or RTX-induced toxicity. In vivo, we also found that intranigral injection of CAP or 12-hydroperoxyeicosatetraenoic acid, an endogenous agonist of TRPV1, into the rat brain produced microglial damage via TRPV1 in the substantia nigra, as visualized by immunocytochemistry. To our knowledge, this study is the first to demonstrate that microglia express TRPV1, and that activation of this receptor may contribute to microglial damage via Ca(2+) signaling and mitochondrial disruption.
Microglia are a type of glial cell that acts as the first and main form of active immune defense in the central nervous system (CNS). Microglia constitute 20% of the total glial cell population within the brain. Unlike astrocytes, individual microglia are distributed in large non-overlapping regions throughout the brain and spine.[1] Microglia are constantly moving and analyzing the CNS for damaged neurons, plaques, and infectious agents.[2] The brain and spine are considered “immune privileged” organs in that they are separated from the rest of the body by a series of endothelial cells known as the blood-brain barrier, which prevents most infections from reaching the vulnerable nervous tissue. In the case where infectious agents are directly introduced to the brain or cross the blood-brain barrier, microglial cells must react quickly to increase inflammation and destroy the infectious agents before they damage the sensitive neural tissue. Due to the unavailability of antibodies from the rest of the body (antibodies are too large to cross the blood-brain barrier), microglia must be able to recognize foreign bodies, swallow them, and act as antigen-presenting cells activating T-cells. Since this process must be done quickly to prevent potentially fatal damage, microglia are extremely sensitive to even small pathological changes in the CNS.[3] They achieve this sensitivity in part by having unique potassium channels that respond to even small changes in extracellular potassium.[2]
_________________ 1st traceable symptoms Jan 01, last edss by doctor 6.5. Feeling better on ginkgo, salvia, capsaicin, curcumin, scutellaria. Interested in other vascular strengthening herbs; pycnogenol, butcher's broom, horsechestnut, centenella, hersperidin
Posted: Wed Jul 23, 2008 9:14 am Post subject: capsaicin reduces substance p in spinal dorsal horn = bad
1: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 1996 Jun;18(3):183-8.Links
[The role of substance P in the spinal dorsal horn in the pathogenesis of autoimmune diseases][Article in Chinese]
Chen J, Li S, Liu Y, Wu S, Ji H.
Institute of Basic Medical Sciences, CAMS, Beijing.
The aim of the present study is to explore the role of immunosuppression mediated by substance P (SP) in spinal dorsal horn (SDH) in the pathogenesis of the autoimmune diseases. The experimental allergic neuritis (EAN), experimental allergic encephalomyelitis (EAE) and adjuvant arthritis (AA) animal models were established in the guinea pigs and Wistar rats, respectively. The effects of alteration of SP activity in SDH on immune responses and the pathogenesis of the autoimmune diseases were observed. The results showed that decreasing activity of SP in SDH by pretreatment of capsaicin or intrathecal SP antagonist could enhance cellular and humoral immune responses and aggravate the autoimmune diseases, while intrathecal SP agonist could suppress the immunity and alleviate clinical signs. The contents of SP in SDH was elevated dramatically at the peak of immune responses. These results suggest that SDH SP might participate in the pathogenesis of the autoimmune diseases. The increase of SP contents in SDH may inhibit the immune system via unknown pathway and ease clinical severity of the autoimmune disease, where SP might act as neurotransmitter in the immunoregulation of the negative feedback. To elevate SP content in SDH might be beneficial to the autoimmune diseases.
this looks at capsaicin injected intrathecally into the spine and the reduced levels of substance p which aggravates auto immune disease:
Quote:
1: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 1995 Aug;17(4):269-73.Links
[The role of substance P in immunosuppression induced by Tripterygium wilfordii][Article in Chinese]
Liu Y, Wang W, Zhu G, Chen J, Xu C.
Institute of Basic Medical Sciences, CAMS, Beijing.
The effects of T II (extracted from Tripterygium wilfordii) and substance P (SP) on imunoregulation were investigated. It has been shown that Tripterygium wilfordii is an immunosuppresive. In order to assess the immunosuppression elicited by T II was mediated by SP in spinal dorsal horn, Wistar rats were injected intrathecally with capsaicin (CAP) to deplete SP in spinal dorsal horn prior to T II given orally. The level of interleukin 2 (IL-2) produced by splenic lymphocytes of rats and the contents of SP in some brain areas and spinal cord in mice were assayed after T II treatment. Our findings were as follows: 1. The level of IL-2 was decreased significantly after T II treatment only. However the level of IL-2 was increased markedly after CAP was given intrathecally. Moreover, CAP administration also enhanced the level of IL-2 even in immunosuppression group induced by T II treatment. 2. SP contents in spinal cord, hypothalamus and brain stem of mice were increased dramatically during immunosuppression produced by T II. The results suggested that SP in spinal dorsal horn was involved in regulation of cellular immunity, the suppressive effect of T II on cellular immunity might be mediated by SP in spinal dorsal horn.
1: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 1996 Jun;18(3):183-8.Links
[The role of substance P in the spinal dorsal horn in the pathogenesis of autoimmune diseases][Article in Chinese]
Chen J, Li S, Liu Y, Wu S, Ji H.
Institute of Basic Medical Sciences, CAMS, Beijing.
The aim of the present study is to explore the role of immunosuppression mediated by substance P (SP) in spinal dorsal horn (SDH) in the pathogenesis of the autoimmune diseases. The experimental allergic neuritis (EAN), experimental allergic encephalomyelitis (EAE) and adjuvant arthritis (AA) animal models were established in the guinea pigs and Wistar rats, respectively. The effects of alteration of SP activity in SDH on immune responses and the pathogenesis of the autoimmune diseases were observed. The results showed that decreasing activity of SP in SDH by pretreatment of capsaicin or intrathecal SP antagonist could enhance cellular and humoral immune responses and aggravate the autoimmune diseases, while intrathecal SP agonist could suppress the immunity and alleviate clinical signs. The contents of SP in SDH was elevated dramatically at the peak of immune responses. These results suggest that SDH SP might participate in the pathogenesis of the autoimmune diseases. The increase of SP contents in SDH may inhibit the immune system via unknown pathway and ease clinical severity of the autoimmune disease, where SP might act as neurotransmitter in the immunoregulation of the negative feedback. To elevate SP content in SDH might be beneficial to the autoimmune diseases.
very hard to know whether capsaicin is good or bad long term. Seems pretty good for adjuvant arthritis:
Quote:
Abstract
The prophylactic and therapeutic effects of dietary n-3 polyunsaturated fatty acids and antiinflammatory spice principles—curcumin and capsaicin on adjuvant induced arthritis in rats were studied. Rats fed codliver oil (1 mL/day/rat or 8 wt % in the diet) rich in n-3 fatty acids were found to have a decreased incidence of adjuvant induced arthritis as compared with those observed in coconut oil- or groundnut oil-fed animals. The inflammation in animals which developed adjuvant arthritis in codliver oil-fed animals was also significantly lower than that observed in the other two groups. Additional feeding of spice principles—capsaicin (from red pepper) (5 mg/kg bw/day) or curcumin (from turmeric) (30 mg/kg bw/day) along with dietary lipids delayed the onset of the disease and also lowered the extent of inflammation in arthritis arrested further progression of the disease. Curcumin and capsaicin feeding to arthritic rats also lowered paw inflammation. This beneficial effect of spice principles was observed irrespective of the nature of the dietary lipids fed to the rats. These studies indicated that the dietary n-3 polyunsaturated fatty acids, capsaicin, and curcumin can decrease the incidence, delay the onset and reduce the extent of inflammation of adjuvant-induced arthritis in rats.
http://linkinghub.elsevier.com/retrieve/pii/S0955286397000478 _________________ 1st traceable symptoms Jan 01, last edss by doctor 6.5. Feeling better on ginkgo, salvia, capsaicin, curcumin, scutellaria. Interested in other vascular strengthening herbs; pycnogenol, butcher's broom, horsechestnut, centenella, hersperidin
Forum FAQ
Search
Usergroups
Profile
Log in to check your private messages
Log in
. However, use of sedating histamine 1 receptor blockers was associated with decreased MS risk (adjusted OR 0.2, 95% CI 0.1 to 0.
