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Research regarding the potential immunomodulatory activity of Hydrastis canadensis (goldenseal) and/or its active compounds berberine and hydrastine
This information has been complied in order to facilitate the research efforts of health care professionals and others. These statements have not been evaluated by the Food and Drug Administration and are not intended diagnose, treat, cure, prevent, mitigate, or prevent any disease. The information is presented with the latest publications first. This is an ongoing work so check back often as we will update these pages as more information becomes available. Also see the anti-parasitic and anti-diarrhea pages. Last Updated : 08/25/2008
Neutral sulfate berberine modulates cytokine secretion and increases survival in endotoxemic mice.
Li F, Wang HD, Lu
DX, Wang YP, Qi RB, Fu YM, Li CJ.
Acta Pharmacol Sin. 2006 Sep;27(9):1199-205.
Aim: Berberine is thought to be an immunomodulator, so the present study
aimed to investigate the effect of berberine on mortality, lung and
intestine injury in endotoxemic mice, and the mechanism of its action.
Methods: Mice were challenged with lipopolysaccharide (LPS, 28 mg/kg, ip),
and neutral sulfate berberine was administrated intragastrically. Mortality
was monitored every 12 h, and histology of the lungs and intestine as well
as the plasma tumor necrosis factor-alpha (TNF-alpha), interferon- gamma (IFN-gamma),
interleukin-12 (IL-12), IL-10, and nitric oxide (NO) levels were examined.
Results: Pretreatment with 50 mg/kg neutral sulfate berberine once a day for
5 days significantly decreased the mortality rate and attenuated tissue
injury of the lungs and small intestine in mice challenged with LPS. LPS
stimulated a marked increase in plasma levels of TNF-alpha, IFN- gamma,
IL-12, IL-10, and NO. The administration of berberine significantly reduced
plasma TNF-alpha, IFN- gamma, and NO levels, but did not suppress plasma
IL-12 levels in mice exposed to LPS. Furthermore, pretreatment with neutral
sulfate berberine augmented IL-10 secretion stimulated by LPS in mice.
Conclusion: Pretreatment with neutral sulfate berberine attenuates tissue
injury and improves survival in endotoxemic mice, which may be mediated, at
least in part, by the inhibition of pro-inflammatory mediator production and
upregulation of IL-10 release. These findings might provide a new strategy
for the treatment of endotoxemia.
Differential effect of Rhizoma coptidis and its main alkaloid compound berberine on TNF-alpha induced NFkappaB translocation in human keratinocytes.
Enk R, Ehehalt R,
Graham JE, Bierhaus A, Remppis A, Greten HJ.
Medizinische Klinik III,
J Ethnopharmacol. 2006 Jul 14;
The Chinese medicine Rhizoma coptidis (RC) is well established in the
treatment of common dermatological disorders although the mechanism of its'
anti-inflammatory effects have previously remained elusive. We stimulated an
inflammatory state in human keratinocyte cultures using TNF-alpha in the
presence of RC extract (RCE) and berberine, to identify the dose-dependent
anti-inflammatory role of these compounds. Control data demonstrates
significant translocation of NFkappaB into the nucleus after stimulation
with TNF-alpha. This translocation can be inhibited, and hence
anti-inflammatory effects inferred, by RCE but not by berberine. We
conclude that in dermatological disorders berberine exerts its
anti-inflammatory effects by inhibiting signal transduction pathways other
than the NFkappaB dependent pathway, while the RCE complex acts partially by
blocking the NFkappaB dependent pathway. Rhizoma coptidis extract
therefore appears to be a potent inhibitor of TNF-alpha induced inflammation
in dermatological conditions.
Chelerythrine and other benzophenanthridine alkaloids
block the human P2X7 receptor.
Shemon AN, Sluyter R, Conigrave AD, Wiley JS.
Br J Pharmacol. 2004 Jul;142(6):1015-9. Epub 2004 Jun 21.
1 Extracellular ATP can activate a cation-selective channel/pore on human
B-lymphocytes, known as the P2X7 receptor. Activation of this receptor is
linked to PLD stimulation. We have used ATP-induced 86Rb+ (K+) efflux to
examine the effect of benzophenanthridine alkaloids on P2X7 channel/pore
function in human B-lymphocytes. 2 Both ATP and the nucleotide analogue
2'-3'-O-(4-benzoylbenzoyl)-ATP (BzATP) induced an 86Rb+ efflux, which was
completely inhibited by the isoquinoline derivative
1-(N,O-bis[5-isoquinolinesulphonyl]-N-methyl-l-tyrosyl)-4-phenylpiperazine
(KN-62), a potent P2X7 receptor antagonist. 3 The benzophenanthridine
alkaloid chelerythrine, a potent PKC inhibitor, inhibited the ATP-induced
86Rb+ efflux by 73.4+/-3.5% and with an IC50 of 5.6+/-2.3 microm.
Similarly, other members of this family of compounds, sanguinarine and
berberine, blocked the ATP-induced 86Rb+ efflux by 58.8+/-4.8 and
61.1+/-8.0%, respectively. 4 Concentration-effect curves to ATP
estimated an EC50 value of 78 microm and in the presence of 5 and 10 microm
chelerythrine this increased slightly to 110 and 150 microm, respectively,
which fits a noncompetitive inhibitor profile for chelerythrine. 5
Chelerythrine at 10 microm was effective at inhibiting the ATP-induced PLD
stimulation in B-lymphocytes by 94.2+/-21.9% and the phorbol 12-myristate
13-acetate-induced PLD stimulation by 68.2+/-7.4%. 6 This study demonstrates
that chelerythrine in addition to PKC inhibition has a noncompetitive
inhibitory action on the P2X7 receptor itself.
Induction of interleukin-12 production in mouse macrophages by berberine, a benzodioxoloquinolizine alkaloid, deviates CD4+ T cells from a Th2 to a Th1 response.
Kim TS, Kang BY, Cho D, Kim SH.
Immunology. 2003 Jul;109(3):407-14.
In this study we investigated whether berberine-mediated induction of interleukin-12 (IL-12) production in antigen-presenting cells could regulate a cytokine profile of antigen-primed CD4+ T helper (Th) cells. Pretreatment with berberine induced IL-12 production in both macrophages and dendritic cells, and significantly increased the levels of IL-12 production in lipopolysaccharide-stimulated macrophages and in CD40 ligand-stimulated dendritic cells. Importantly, berberine pretreatment of macrophages increased their ability to induce interferon-gamma (IFN-gamma) and reduced their ability to induce IL-4 in antigen-primed CD4+ T cells. Berberine did not influence the macrophage cell surface expression of the class II major histocompatibility complex molecule, the co-stimulatory molecules CD80 and CD86, and intracellular adhesion molecule-1. Addition of neutralizing anti-IL-12p40 monoclonal antibody to cultures of berberine-pretreated macrophages and CD4+ T cells restored IL-4 production in antigen-primed CD4+ T cells. The in vivo administration of berberine resulted in the enhanced induction of IL-12 production by macrophages when stimulated in vitro with lipopolysaccharide or heat-killed Listeria monocytogenes, leading to the inhibition of the Th type 2 cytokine profile (decreased IL-4 and increased IFN-gamma production) in antigen-primed CD4+ T cells. These findings may point to a possible therapeutic use of berberine or medicinal plants containing berberine in the Th type 2 cell-mediated immune diseases such as allergic diseases.
Anticachectic effects of Coptidis rhizoma, an anti-inflammatory herb, on esophageal cancer cells that produce interleukin 6.
Iizuka N, Miyamoto K, Hazama S, Yoshino S, Yoshimura K, Okita K, Fukumoto T, Yamamoto S, Tangoku A, Oka M.
Cancer Lett. 2000 Sep 29;158(1):35-41.
Herbs as alternative cancer therapies have attracted a great deal of recent attention due to their low toxicity and costs. In this study, the antitumor activity and anticachectic effect of Coptidis rhizoma, an anti-inflammatory herb, were investigated in nude mice carrying a human esophageal cancer cell line YES-2, which constitutively secretes interleukin-6 (IL-6) and induces cachexia when injected into these mice. In this study, in vivo growth of YES-2 cells was not affected by an oral supplement containing the extract powder of C. rhizoma at a final concentration of 1% (CR supplement). However, in comparison with normal diet, CR supplement significantly attenuated weight loss of tumor-bearing mice without a change in food or water intake. Tumor IL-6 levels were significantly lower in mice treated with CR supplement than in control mice (P<0.001). Serum IL-6 was detectable in four (50%) of eight control mice; IL-6 was not detected in mice treated with CR supplement. We also confirmed that berberine (8-32 microM), a major component of C. rhizoma, dose-dependently inhibited secretion of IL-6 by YES-2 cells in vitro. Moreover, reverse transcription-PCR assay showed that treatment of YES-2 cells with berberine (8-32 microM) for 24 h reduced IL-6 mRNA expression. Our results suggest that C. rhizoma may have an anticachectic effect on esophageal cancer and an effect is associated with the ability of berberine to down-regulate tumor IL-6 production.
Suppression of experimental autoimmune
tubulointerstitial nephritis in BALB/c mice by berberine.
Marinova EK, Nikolova DB, Popova DN, Gallacher GB, Ivanovska
ND.
Immunopharmacology. 2000 Jun;48(1):9-16.
Berberine (BB) is a protoberberine alkaloid derived from various
representatives of the Berberidaceae family. Although used as a therapeutic
agent, it has not been applied in the treatment of immune-mediated
disorders.In the present study, BB was administered at a daily dose of 10
mg/kg for 3 consecutive days before the induction of tubulointerstitial
nephritis (TIN) by injection of bovine tubular basement membrane (TBM)
antigen in BALB/c mice. The animals were investigated 2 months after TBM
inoculation. The intensity of pathological injuries in animals with TIN+BB
decreased significantly, an effect that correlated with the improvement of
renal function. Flow cytometric analysis of peripheral blood cells showed
that BB caused a decrease in the number of CD3(+), CD4(+), CD8(+), and sIg(+)
lymphocytes in comparison with TIN mice. The same tendency was noticed in
the lymphocytes from kidney infiltrates of treated animals. The control
animals treated only with BB showed a decrease in the number of CD3(+),
CD4(+), CD8(+) T-lymphocytes in comparison with control nontreated mice.
Our results, thus, indicate that BB has an immunosuppressive effect in the
TIN model, which is an analogue of various human kidney autoimmune diseases.
Increased production of
antigen-specific immunoglobulins G and M following in vivo treatment with
the medicinal plants Echinacea angustifolia and Hydrastis canadensis.
Rehman J, Dillow JM, Carter SM, Chou J, Le B, Maisel AS.
Immunol Lett. 1999 Jun 1;68(2-3):391-5.
A number of immunomodulatory effects have been attributed to the medicinal
plants Echinacea angustifolia and Goldenseal (Hydrastis canadensis);
however, little is known about whether treatment with these plants can
enhance antigen-specific immunity. We investigated the antigen-specific in
vivo immunomodulatory potential of continuous treatment with Echinacea and
Goldenseal root extract over a period of 6 weeks using rats that were
injected with the novel antigen keyhole limpet hemocyanin (KLH) and
re-exposed to KLH after the initial exposure. Immunoglobulin production was
monitored via ELISA continuously over a period of 6 weeks. The
Echinacea-treated group showed a significant augmentation of their primary
and secondary IgG response to the antigen, whereas the Goldenseal-treated
group showed an increase in the primary IgM response during the first 2
weeks of treatment. Our results suggest that medicinal plants like Echinacea
or Goldenseal may enhance immune function by increasing antigen-specific
immunoglobulin production.
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