<shortened url>1: FEBS Lett. 2001 Jun 29;500(1-2):52-5. Links
The flavonoid baicalin inhibits superantigen-induced inflammatory cytokines and chemokines.Krakauer T, Li BQ, Young HA.
Department of Immunology and Molecular Biology, United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702-5011, USA. email@example.com
Excessive release of proinflammatory cytokines mediates the toxic effect of superantigenic staphylococcal exotoxins (SE). Baicalin, a flavone isolated from the Chinese herb Scutellaria baicalensis Georgi and used in China to treat infectious diseases, inhibited SE-stimulated T-cell proliferation (by 98%) and production of interleukin 1beta, interleukin 6, tumor necrosis factor, interferon gamma, monocyte chemotactic protein 1, macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta mRNA and protein by human peripheral blood mononuclear cells. These data suggest that baicalin may be therapeutically useful for mitigating the pathogenic effects of SE by inhibiting the signaling pathways activated by superantigens.
<shortened url>1: Biomed Pharmacother. 2008 Feb 27. [Epub ahead of print] Links
Up-regulation of Toll-like receptor 4 was suppressed by emodin and baicalin in the setting of acute pancreatitis.Li Z, Xia X, Zhang S, Zhang A, Bo W, Zhou R.
Department of General Surgery, the Second Affiliated Hospital of Medical School, Xi'an Jiaotong University, No.157, Xiwu Road, Xi'an, Shaanxi Province 710004, PR China.
Acute pancreatitis (AP) activates the systemic inflammatory response and is potentially lethal. Recent studies demonstrated that pancreatic enzymes could induce cytokine expression via Toll-like receptor 4 (TLR4) signal pathway, indicating a possible role of TLR4 in local pancreatic injury and systemic inflammatory response. Emodin, an anthraquinone derivative from Radix et Rhizoma Rhei, and baicalin, a flavone from Scutellaria baicalensis Georgi, both have been reported to possess anti-inflammatory activities. In present study, we investigated the combined effect of emodin and baicalin on pancreatic damage and pancreatitis associated lung injury, as well as tissue TLR4 expression in the setting of AP. The results showed that combination of emodin and baicalin significantly reduced serum amylase, tumor necrosis factor-alpha and interleukin-6, attenuated pancreatic and pulmonary damage, also suppressed TLR4 expression in pancreas and lung. It could be speculated that amelioration of pancreatic and pulmonary damage by emodin and baicalin might contribute, in part at least, to the suppression of TLR4 expression. The present study provides beneficial evidence as to simultaneous treatment for AP, and also suggests an important role of TLR4 in pathophysiology of AP.
<shortened url>1: J Clin Immunol. 2008 May 8. [Epub ahead of print] Links
15-Deoxy-Delta(12,14)-Prostaglandin J(2) and Curcumin Modulate the Expression of Toll-like Receptors 4 and 9 in Autoimmune T Lymphocyte.Chearwae W, Bright JJ.
Neuroscience Research Laboratory, Methodist Research Institute at Clarian Health, 1800 North Capitol Avenue, Noyes Building E-504C, Indianapolis, IN, 46202, USA.
INTRODUCTION: Experimental allergic encephalomyelitis (EAE) is a T cell-mediated autoimmune disease model for multiple sclerosis (MS). We have shown earlier that 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) and curcumin ameliorate EAE by modulating inflammatory signaling pathways in T lymphocytes. Toll-like receptors (TLRs), expressed primarily in innate immune cells, play critical roles in the pathogenesis of EAE. T lymphocytes also express TLRs and function as costimulatory receptors to upregulate proliferation and cytokine production in response to specific agonists. DISCUSSION: In this study, we show that naïve CD4(+) and CD8(+) T cells express detectable levels of TLR4 and TLR9 and that increase after the induction of EAE in SJL/J and C57BL/6 mice by immunization with PLPp139-151 and MOGp35-55 antigen, respectively. It is interesting to note that in vivo treatment with 15d-PGJ2 or curcumin results in a significant decrease in TLR4 and TLR9 expression in CD4(+) and CD8(+) T cells in association with the amelioration of EAE. CONCLUSION: Although the exact mechanisms are not known, the modulation of TLR expression in T lymphocytes by 15d-PGJ(2) and curcumin suggests new therapeutic targets in the treatment of T cell-mediated autoimmune diseases.
<shortened url>1: J Immunol. 2004 Dec 1;173(11):7070-7. Links
TLR4 contributes to disease-inducing mechanisms resulting in central nervous system autoimmune disease.Kerfoot SM, Long EM, Hickey MJ, Andonegui G, Lapointe BM, Zanardo RC, Bonder C, James WG, Robbins SM, Kubes P.
Immunology Research Group, Department of Physiology and Biophysics, University of Calgary, Alberta, Canada.
Environmental factors strongly influence the development of autoimmune diseases, including multiple sclerosis. Despite this clear association, the mechanisms through which environment mediates its effects on disease are poorly understood. Pertussis toxin (PTX) functions as a surrogate for environmental factors to induce animal models of autoimmunity, such as experimental autoimmune encephalomyelitis. Although very little is known about the molecular mechanisms behind its function in disease development, PTX has been hypothesized to facilitate immune cell entry to the CNS by increasing permeability across the blood-brain barrier. Using intravital microscopy of the murine cerebromicrovasculature, we demonstrate that PTX alone induces the recruitment of leukocytes and of active T cells to the CNS. P-selectin expression was induced by PTX, and leukocyte/endothelial interactions could be blocked with a P-selectin-blocking Ab. P-selectin blockade also prevented PTX-induced increase in permeability across the blood-brain barrier. Therefore, permeability is a secondary result of recruitment, rather than the primary mechanism by which PTX induces disease. Most importantly, we show that PTX induces intracellular signals through TLR4, a receptor intimately associated with innate immune mechanisms. We demonstrate that PTX-induced leukocyte recruitment is dependent on TLR4 and give evidence that the disease-inducing mechanisms initiated by PTX are also at least partly dependent on TLR4. We propose that this innate immune pathway is a novel mechanism through which environment can initiate autoimmune disease of the CNS.
<shortened url>1: Clin Mol Allergy. 2007 Nov 26;5:5. Links
Baicalein inhibits IL-1beta- and TNF-alpha-induced inflammatory cytokine production from human mast cells via regulation of the NF-kappaB pathway.Hsieh CJ, Hall K, Ha T, Li C, Krishnaswamy G, Chi DS.
Departments of Internal Medicine, James H, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee 37614, USA. firstname.lastname@example.org.
ABSTRACT: BACKGROUND: Human mast cells are multifunctional cells capable of a wide variety of inflammatory responses. Baicalein (BAI), isolated from the traditional Chinese herbal medicine Huangqin (Scutellaria baicalensis Georgi), has been shown to have anti-inflammatory effects. We examined its effects and mechanisms on the expression of inflammatory cytokines in an IL-1beta- and TNF-alpha-activated human mast cell line, HMC-1. METHODS: HMC-1 cells were stimulated either with IL-1beta (10 ng/ml) or TNF-alpha (100 U/ml) in the presence or absence of BAI. We assessed the expression of IL-6, IL-8, and MCP-1 by ELISA and RT-PCR, NF-kappaB activation by electrophoretic mobility shift assay (EMSA), and IkappaBalpha activation by Western blot. RESULTS: BAI (1.8 to 30 muM) significantly inhibited production of IL-6, IL-8, and MCP-1 in a dose-dependent manner in IL-1beta-activated HMC-1. BAI (30 muM) also significantly inhibited production of IL-6, IL-8, and MCP-1 in TNF-alpha-activated HMC-1. Inhibitory effects appear to involve the NF-kappaB pathway. BAI inhibited NF-kappaB activation in IL-1beta- and TNF-alpha-activated HMC-1. Furthermore, BAI increased cytoplasmic IkappaBalpha proteins in IL-1beta- and TNF-alpha-activated HMC-1. CONCLUSION: Our results showed that BAI inhibited the production of inflammatory cytokines through inhibition of NF-kappaB activation and IkappaBalpha phosphorylation and degradation in human mast cells. This inhibitory effect of BAI on the expression of inflammatory cytokines suggests its usefulness in the development of novel anti-inflammatory therapies.
<shortened url>1: Braz J Med Biol Res. 2007 Jul;40(7):1003-10. Links
Baicalin reduces the severity of experimental autoimmune encephalomyelitis.Zeng Y, Song C, Ding X, Ji X, Yi L, Zhu K.
Department of Neurology, The First Affiliated Hospital, Nanjing Medical University, China.
Scutellaria baicalensis Georgi is one of the important medicinal herbs widely used for the treatment of various inflammatory diseases in Asia. Baicalin (BA) is a bioactive anti-inflammatory flavone found abundantly in Scutellaria baicalensis Georgi. To explore the therapeutic potential of BA, we examined the effects of systemic administration of the flavone (5 and 10 mg/kg, ip) on relapsing/remitting experimental autoimmune encephalomyelitis (EAE) induced by proteolipid protein 139-151 in SJL/J mice, an experimental model of multiple sclerosis. The mice treated with PBS or BA at day -1 and for 3 consecutive days were observed daily for clinical signs of disease up to 60 days after immunization. In the PBS-EAE group, neurological scores were: incidence (100%), mean day of onset (8.0 +/- 0.73), peak clinical score (3.0 +/- 0.4), and cumulative disease index (141.8 +/- 19.4). In the BA-EAE group (5 or 10 mg kg(-1) day(-1), respectively), incidence (95 or 90%), mean day of onset (9.0 +/- 0.80 or 9.2 +/- 0.75; P = 0.000), peak clinical score (2.2 +/- 0.3 or 2.0 +/- 0.3; P = 0.000), and cumulative disease index (75.9 +/- 10.1 or 62.9 +/- 8.4; P = 0.000) decreased, accompanied by the histopathological findings (decrease of dense mononuclear infiltration surrounding vascellum) for the spinal cord. Additionally, the in vitro effects of BA (5, 10, and 25 microM) on mononuclear cells collected from popliteal and inguinal lymph nodes of day-10 EAE mice were evaluated using an MTT reduction assay for cell proliferation, and ELISA to measure IFN-gamma and IL-4 cytokines. Compared with the control group, BA caused an increase in IL-4 (EAE-DMSO: 3.56 +/- 0.42 pg/mL vs EAE-BA (5, 10, and 25 microM): 6.03 +/- 1.1, 7.83 +/- 0.65, 10.54 +/- 1.13 pg/mL, respectively; P < 0.001); but inhibited IFN-gamma (EAE-DMSO: 485.76 +/- 25.13 pg/mL vs EAE-BA (5, 10, and 25 microM): 87.08 +/- 9.24, 36.27 +/- 5.44, 19.18 +/- 2.93 pg/mL, respectively; P < 0.001) and the proliferation of mononuclear cells (EAE-DMSO: 0.73 +/- 0.021 vs EAE-BA (5, 10, and 25 microM): 0.41 +/- 0.015, 0.31 +/- 0.018, 0.21 +/- 0.11, respectively; P < 0.001) in a concentration-dependent manner. The results suggest that BA might be effective in the treatment of multiple sclerosis.