INTERESTING TIMES

Ursolic acid ameliorates autoimmune arthritis via suppression of Th17 and B cell differentiation.
Baek SY1, Lee J1, Lee DG1, Park MK1, Lee J2, Kwok SK2, Cho ML1, Park SH2.
Abstract

AIM:
Ursolic acid (UA) is a pentacyclic triterpenoid found in most plant species, which has been shown anti-inflammatory and anti-oxidative activities. In this study, we examined the effects of UA on collagen-induced arthritis (CIA) in mice, and to identify the mechanisms underlying the effects.

METHODS:
CIA was induced in mice. Two weeks later, the mice were treated with UA (150 mg/kg, ip, 3 times per week) for 4 weeks. The expression of cytokines and oxidative stress markers in joint tissues was measured with immunohistochemistry. The numbers of CD4+IL-17+, CD4+CD25+Foxp3+ and pSTAT3 cells in spleens were determined using confocal immunostaining or flowcytometric analyses. Serum antibody levels and B cell-associated marker mRNAs were analyzed with ELISAs and qRT-PCR, respectively. CD4+ T cells and CD19+ B cells were purified from mice spleens for in vitro studies.

RESULTS:
UA treatment significantly reduced the incidence and severity of CIA-induced arthritis, accompanied by decreased expression of proinflammatory cytokines (TNF-α, IL-1β, IL-6, IL-21 and IL-17) and oxidative stress markers (nitrotyrosine and iNOS) in arthritic joints. In CIA mice, UA treatment significantly decreased the number of Th17 cells, while increased the number of Treg cells in the spleens, which was consistent with decreased expression of pSTAT3, along with IL-17 and RORγt in the splenocytes. In addition, UA treatment significantly reduced the serum CII-specific IgG levels in CIA mice. The inhibitory effects of UA on Th17 cells were confirmed in an in vitro model of Th17 differentiation. Furthermore, UA dose-dependently suppressed the expression of B cell-associated markers Bcl-6, Blimp1 and AID mRNAs in purified CD19+ B cells pretreated with IL-21 or LPS in vitro.

CONCLUSION:
UA treatment significantly ameliorates CIA in mice via suppression of Th17 and differentiation. By targeting pathogenic Th17 cells and autoantibody production, UA may be useful for the treatment of autoimmune arthritis and other Th17-related diseases.
PMID: 25087995 [PubMed - in process] PMCID: PMC4155530

SOURCE
http://www.ncbi.nlm.nih.gov/pubmed/25087995
Acta Pharmacol Sin. 2014 Sep;35(9):1177-87. doi: 10.1038/aps.2014.58. Epub 2014 Aug 4.

No time to work out, you say? Have to clear out the sink? OK then, try this. The asana for dishwashing is the Fierce pose, Utkatasana. Basically you put your feet hipwidth or narrower and parallel, and bend your legs like you were going to sit into a chair. But there is no chair. Keep your spine straight, not hunched, head up. Pull in your belly. Put your weight into your heels. Drop lower into your seat. Arms go straight overhead for the full expression of the asana, but you can wash a few dishes in between. This asana is warming, and if you persist for more than a minute or two your breathing and heart rate will increase, and your legs will begin to burn. You can hold it longer than you think you can. This asana is one of the best for back pain, both the kind that is between your shoulderblades, and the low back kind.

Francis Brinker ND
1981 NCNM grad, prof at SCNM and U of Az College of Med
Botanical Pharmacokinetic Interactions with Drugs and Botanical Adjuncts
with NSAIDS & Analgesics for Arthritis
Useful Website: http://medicine.iupui.edu/clinpharm/DDIs/table.aspx
**print interaction summary page from moodle
consumer info: http://WWW.DRUGDIGEST.ORG/WPS/PORTAL/DDIGEST
arthritis part of talk at the very end, first part of talk all about drug interactions
interactions with St John's Wort, Ginkgo, Ginseng, Garlic, Peppermint, and as usual Grapefruit
( notes )

MIDTERM IS WEEK 5
bring fasting info page for Thea
don't mobilize hands/wrists in case of arthritis until you have a firm dx
know the disease process
don't do grade 3+ if inflamed
( notes on Frangos' lab class 2-5pm )

Which condition demonstrates nonuniform joint space narrowing, osteophytes, subchondral sclerosis, & subchondral cysts?
( more )

Kitten is passed out on the couch. I have never seen her sprawl exactly there and like that before....she seems to be getting more comfortable. She does not have to hide from the little canine anymore. She is exhausted from last night's excitement. I closed the door to the Crow's Nest last night while she was still out prowling. She could come into that room, but no farther, and she could not get to me. The idea was that I wanted to sleep all night and wake up without her stomping on me and muttering me awake.
( mental download )