TH17 cells, oleanolic acid

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TH17 cells, oleanolic acid

Postby gibbledygook » Thu Apr 11, 2013 3:10 am

A recent successful bone marrow transplant study for MS revealed that significantly diminished T helper 17 cells (TH17) was the cause of the arrested disease and recovery of patients as per this article: http://www.ottawacitizen.com/health/Ottawa+doctors+behind+breakthrough+report/8180666/story.html

And Holy Basil or ocimum tenuiflorum contains an advertisable degree of oleanolic acid. This suppresses TH17 as per below articles. I think the Holy Basil pills which I have been trying for the last few days are doing something positive. HOORAY!!! FOR ONCE!!!!!

Br J Pharmacol. 2012 Jul;166(5):1708-23. doi: 10.1111/j.1476-5381.2012.01869.x.
Natural triterpenes modulate immune-inflammatory markers of experimental autoimmune encephalomyelitis: therapeutic implications for multiple sclerosis.
Martín R, Hernández M, Córdova C, Nieto ML.
Source
Instituto de Biología y Genética Molecular, CSIC-Universidad de Valladolid, Spain.
Abstract
BACKGROUND AND PURPOSE:
Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are inflammatory demyelinating diseases that develop as a result of deregulated immune responses causing glial activation and destruction of CNS tissues. Oleanolic acid and erythrodiol are natural triterpenes that display strong anti-inflammatory and immunomodulatory activities. Oleanolic acid beneficially influences the course of established EAE. We now extend our previous observations to erythrodiol and address the efficacy of both compounds to protect against EAE, given under different regimens.
EXPERIMENTAL APPROACH:
The utility of both triterpenes in disease prevention was evaluated at a clinical and molecular level: in vivo through their prophylactic administration to myelin oligodendrocyte protein-immunized C57BL/6 mice, and in vitro through their addition to stimulated-BV2 microglial cells.
KEY RESULTS:
These triterpenes protected against EAE by restricting infiltration of inflammatory cells into the CNS and by preventing blood-brain barrier disruption. Triterpene-pretreated EAE-mice exhibited less leptin secretion, and switched cytokine production towards a Th2/regulatory profile, with lower levels of Th1 and Th17 cytokines and higher expression of Th2 cytokines in both serum and spinal cord. Triterpenes also affected the humoral response causing auto-antibody production inhibition. In vitro, triterpenes inhibited ERK and rS6 phosphorylation and reduced the proliferative response, phagocytic properties and synthesis of proinflammatory mediators induced by the addition of inflammatory stimuli to microglia.
CONCLUSIONS AND IMPLICATIONS:
Both triterpenes restricted the development of the characteristic features of EAE. We envision these natural products as novel helpful tools for intervention in autoimmune and neurodegenerative diseases including MS.
© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.
PMID: 22260389 [PubMed - indexed for MEDLINE] PMCID: PMC3419913 [Available on 2013/7/1]
http://www.ncbi.nlm.nih.gov/pubmed/22260389

Sci Rep. 2011;1:201. doi: 10.1038/srep00201. Epub 2011 Dec 19.
Triterpenoid modulation of IL-17 and Nrf-2 expression ameliorates neuroinflammation and promotes remyelination in autoimmune encephalomyelitis.
Pareek TK, Belkadi A, Kesavapany S, Zaremba A, Loh SL, Bai L, Cohen ML, Meyer C, Liby KT, Miller RH, Sporn MB, Letterio JJ.
Source
Department of Pediatrics/Division of Pediatric Hematology-Oncology, University Hospitals Case Medical Center and The Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA.
Abstract
Inflammatory cytokines and endogenous anti-oxidants are variables affecting disease progression in multiple sclerosis (MS). Here we demonstrate the dual capacity of triterpenoids to simultaneously repress production of IL-17 and other pro-inflammatory mediators while exerting neuroprotective effects directly through Nrf2-dependent induction of anti-oxidant genes. Derivatives of the natural triterpene oleanolic acid, namely CDDO-trifluoroethyl-amide (CDDO-TFEA), completely suppressed disease in a murine model of MS, experimental autoimmune encephalomyelitis (EAE), by inhibiting Th1 and Th17 mRNA and cytokine production. Encephalitogenic T cells recovered from treated mice were hypo-responsive to myelin antigen and failed to adoptively transfer the disease. Microarray analyses showed significant suppression of pro-inflammatory transcripts with concomitant induction of anti-inflammatory genes including Ptgds and Hsd11b1. Finally, triterpenoids induced oligodendrocyte maturation in vitro and enhanced myelin repair in an LPC-induced non-inflammatory model of demyelination in vivo. These results demonstrate the unique potential of triterpenoid derivatives for the treatment of neuroinflammatory disorders such as MS.
http://www.ncbi.nlm.nih.gov/pubmed/22355716

Toxicol Appl Pharmacol. 2013 Mar 13;269(1):72-80. doi: 10.1016/j.taap.2013.03.001. [Epub ahead of print]
Oleanolic acid acetate inhibits atopic dermatitis and allergic contact dermatitis in a murine model.
Choi JK, Oh HM, Lee S, Park JW, Khang D, Lee SW, Lee WS, Rho MC, Kim SH.
Source
CMRI, Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea.
Abstract
Atopic dermatitis (AD) and allergic contact dermatitis (ACD) are common allergic and inflammatory skin diseases caused by a combination of eczema, scratching, pruritus, and cutaneous sensitization with allergens. This paper examines whether oleanolic acid acetate (OAA) modulates AD and ACD symptoms by using an existing AD model based on the repeated local exposure of mite extract (Dermatophagoides farinae extract, DFE) and 2,4-dinitrochlorobenzene to the ears of BALB/c mice. In addition, the paper uses a 2,4-dinitrofluorobenzene-sensitized local lymph node assay (LLNA) for the ACD model. The oral administration of OAA over a four-week period attenuated AD symptoms in terms of decreased skin lesions, epidermal thickness, the infiltration of immune cells (CD4+ cells, eosinophils, and mast cells), and serum IgE, IgG2a, and histamine levels. The gene expression of Th1, Th2, Th17, and Th22 cytokines was reduced by OAA in the lymph node and ear tissue, and the LLNA verified that OAA suppressed ACD. The oral administration of OAA over a three-day period attenuated ACD symptoms in terms of ear thickness, lymphocyte proliferation, and serum IgG2a levels. The gene expression of Th1, Th2, and Th17 cytokines was reduced by OAA in the thymus and ear tissue. Finally, to define the underlying mechanism, this paper uses a TNF-α/IFN-γ-activated human keratinocyte (HaCaT) model. OAA inhibited the expression of cytokines and chemokines through the downregulation of NF-κB and MAPKs in HaCaT cells. Taken together, the results indicate that OAA inhibited AD and ACD symptoms, suggesting that OAA may be effective in treating allergic skin disorders.
Copyright © 2013 Elsevier Inc. All rights reserved.
PMID: 23499868 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23499868
3 years antibiotics, 06/09 bilateral jug stents at C1, 05/11 ballooning of both jug valves, 07/12 stenting of renal vein, azygos & jug valve ballooning,
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Re: TH17 cells, oleanolic acid

Postby CureOrBust » Thu Apr 11, 2013 6:03 am

OK, so what do you think you have noticed personally?
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Re: TH17 cells, oleanolic acid

Postby gibbledygook » Thu Apr 11, 2013 6:31 am

Well, my symptoms remain much as they were but the pain in my left foot is lower and the tingling is more subdued so now it feels more numb rather than crawling. The right leg is stronger but this is likely as result of coming off the tizanidine/benzodiazepines and instead drinking whiskey to kill the night spasms. Again coming off tizanidine and the benzos is probably why the night spasms seem milder. The tingling in my legs feels different. The strength in my right arm is greater as I can do the weights now which a week ago I could not, however this is again likely due to cessation of tizanidine/benzodiazepine.
3 years antibiotics, 06/09 bilateral jug stents at C1, 05/11 ballooning of both jug valves, 07/12 stenting of renal vein, azygos & jug valve ballooning,
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Re: TH17 cells, oleanolic acid

Postby LR1234 » Thu Apr 11, 2013 8:40 am

Hey gg thanks for the info. I also noticed it lowers cortisol levels which I think may also be beneficial.
Let us know you get on xx
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Re: TH17 cells, oleanolic acid

Postby gibbledygook » Thu Apr 11, 2013 8:44 am

Yes, I will try to find some more objective measures than the tingling stuff but I am quite encouraged to have found that "Holy Basil" has such exciting properties, no wonder they call it Holy.
3 years antibiotics, 06/09 bilateral jug stents at C1, 05/11 ballooning of both jug valves, 07/12 stenting of renal vein, azygos & jug valve ballooning,
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Re: TH17 cells, oleanolic acid

Postby lyndacarol » Thu Apr 11, 2013 5:25 pm

Perhaps here is another mechanism for Holy Basil – cortisol… I am a regular viewer of The Dr. Oz Show. A recent guest, Dr. Natasha Turner, was speaking about hormones; she mentioned that the plant Holy Basil – the plant leaf itself, or supplements, or tea – reduces cortisol levels.

http://www.doctoroz.com/episode/deadly- ... ideo=17201

If Holy Basil reduces cortisol, it ultimately reduces insulin, too. For those people who test and find a high level of cortisol, the fasting blood insulin test may find a high level of insulin also; Holy Basil may help the situation (and even MS symptoms).
My hypothesis: excess insulin (hyperinsulinemia) plays a major role in MS, as developed in my initial post: http://www.thisisms.com/forum/general-discussion-f1/topic1878.html "Insulin – Could This Be the Key?"
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Re: TH17 cells, oleanolic acid

Postby leonardo » Mon Oct 14, 2013 12:37 pm

I take holy basil for stress. It works for me (but nothing revolutionary).
It also gives me giant appetite which is good for me.

Do you still take it gibbledygook?

Anyone else tried it?
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Re: TH17 cells, oleanolic acid

Postby gibbledygook » Tue Oct 15, 2013 12:52 am

oh hi Leonardo, well you know I have now tried quite a few herbs this year which have all had a significant but not necessarily helpful effect on my legs. So I tried the Holy Basil for several weeks in pulse format, so 10 days on, 10 days off. I noticed that after the first 2 pulses my leg was actually weaker on the herb after an hour or so of consuming it. So I backed off the Holy Basil. I noticed that in Pub MEd about 80% of the articles suggest that it would be helpful but a worrying 20% or so suggested that it would do things like increase interferon gamma. I think the latter is meant to help kill off viruses and is firmly in the TH1 cell division and this is the autoimmune camp whereas Th2 cells are more in the allergy camp. ANYWAY the long and short of it is I don't think I can handle the added interferon gamma, AT PRESENT. Now I have just started taking crocin from saffron and this doesn't increase interferon gamma, at least in the pubmed articles which I have managed to read and it does provide intense anti oxidation, again according to some in vitro and some in vivo mouse studies. So I will see how I go on that and update this in the regimens section. I also very recently tried nigella sativa but again I think this upregulates TH1 inflammatory pathways and I had a much worse left foot numbness develop on that herb. I also tried anatabine from the tobacco plant but it looks like abolishing tumour necrosis factor alpha as anatabine does would actually and perhaps counter-intuitively be bad in MS. In fact many RA patients who use anti - TNF products end up getting neurological problems like MS and an MS trial involving anti-TNF ended up stopping early as most participants felt noticeably worse. MULTIPLE SCLEROSIS IS A BUGGER! So, no I haven't continued with the Holy Basil.
3 years antibiotics, 06/09 bilateral jug stents at C1, 05/11 ballooning of both jug valves, 07/12 stenting of renal vein, azygos & jug valve ballooning,
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