Topic: Shikonin? (in the Chinese herb Shiunko) RA CURE
Marnie
Frequent Contributor (5K+ posts)
Member # 773
posted
Watch for *** if not "technically" able to follow.
Received: 3 April 2008
"Abstract Objective To investigate the anti-inflammatory or immunomodulatory effect of shikonin on early stage and established murine
***collagen-induced arthritis (CIA)***.
Methods Mouse were injected intraperitoneally with shikonin (5 mg/kg) for 10 days along before or after the onset of CIA.
The arthritis response was monitored visually by macroscopic scoring. Reverse transcription-polymerase chain reaction and western blotting were employed to determine the mRNA and protein expression of cytokine in patella with adjacent synovium in CIA mouse.
Histology of knee was used to assess the occurrence of cartilage destruction and bone erosion. Results Shikonin (5 mg/kg) treatment along had no effect on macroscopic score and incidence of arthritis on early stage of CIA.
However, a pronounced amelioration of macroscopic score and cartilage destruction was found in mouse treated with shikonin on established CIA for 10 days.
Moreover, The mRNA levels of Th1 cytokines [tumor necrosis factor-α and interleukin (IL)-12] was significantly inhibited both in the synovial tissue and in the articular cartilage in treated groups compared with those in control groups, whereas the mRNA and protein levels of Th2 cytokines (IL-10 and IL-4) remained elevated throughout the treatment period.
Moreover, the inflammatory cytokine, the mRNA and protein levels of IL-6 was down-regulated in mice with established CIA after treatment with shikonin.
T-box expressed in T cells (T-bet) mRNA levels were decreased in shikonin compared with control group, and GATA-3 mRNA levels were higher than that in control group.
***Conclusion Shikonin treatment on established CIA can inhibit Th1 cytokines expression and induce Th2 cytokines expression in mice with established CIA.***
The inhibited effect of shikonin on Th1 cytokines expression may be mediated not only by inhibiting Th1 responses through T-bet mechanism, but also by inducing anti-inflammatory mediators such as IL-10 and IL-4 through a GATA-3 dependent mechanism."
And...
"Shikonin did not induce tyrosine phosphorylation of the insulin receptor, but significantly
induced both Thr-308 and Ser-473 phosphorylation of Akt."
"Akt family: Akt1, Akt2 and Akt3. These enzymes are members of the Serine/threonine-specific protein kinase family.
Akt1 is involved in cellular survival pathways, by inhibiting apoptotic processes.
Akt2 is an important signaling molecule in the Insulin signaling pathway.
The role of Akt3 is less clear, though it appears to be predominantly expressed in brain."
If one of the protein kinases is being inhibited...(such as PKCD) =
"dominant-negative PI(3)K
or kinase-dead Akt
inhibits TNF-mediated NF- B activation."
Repeating:
"Shikonin did not induce tyrosine phosphorylation of the insulin receptor, but significantly induced both Thr-308 and Ser-473 phosphorylation of Akt."
While IgG4 antibodies look to inhibit protein binding of Bb on HLA-DR...
"Elevated IgG4 titres are specific for ***auto-antibodies against citrullinated antigens*** in RA
and are indicative of a Th2-biased environment during the generation of auto-reactive plasma cells.
We discuss here an indirect role for IgG4 auto-antibodies in
hindering the elimination of auto-reactive B and plasma cells and thus driving the autoimmune process."
"Citrulline antibody: An antibody (an immune protein) directed against a circular peptide (a ring of amino acids) containing an unusual ("non-standard") amino acid called citrulline that is not normally present in peptides or proteins.
(Citrulline is formed by the body as an intermediary in the conversion of the amino acid orthithine to
arginine).
The citrulline antibody provides the basis for a test of importance in rheumatoid arthritis."
Why would we make that antibody?
Infectious B. burgdorferi strain B31 is resistant to oxidative stressors in vitro,
whereas the non-infectious isolate was sensitive due, in part, to a point mutation that converts
an arginine to a lysine
at residue 39 of BosR."
Kegg... Arginine and proline metabolism - Borrelia burgdorferi
*IF* there are too many IgG4 antibodies ultimately in the joints of RA patients and this DOES hinder the "the elimination of auto-reactive B and plasma cells"...
Ayurvedic Remedies Nityananda Rasa is very commonly used for it. 1/2 tab. to 1 tab. two times a day on empty stomach for 2 months.
Though shikonin is being heavily studied in relationship to breast cancer as a cure...
Adding more to the complexity:
IgG4 antibody abrogates (abolishes) the effector cell functions of the antibody (molecule binds to a protein) while retaining its antigen-binding properties,
antiproliferative capacity (in vitro and in vivo),
and the ability to induce apoptosis (cell death) concurrent with activation of the AKT survival pathway.
My head hurts.
[ 05. October 2008, 01:50 AM: Message edited by: Marnie ]
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