Browsing by Author "Li, Shiming"
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- Alleviation of Collagen-Induced Arthritis by Crotonoside through Modulation of Dendritic Cell Differentiation and ActivationLin, Shih-Chao; Lin, Chi-Chien; Li, Shiming; Lin, Wan-Yi; Lehman, Caitlin W.; Bracci, Nicole R.; Tsai, Sen-Wei (MDPI, 2020-11-10)Crotonoside, a guanosine analog originally isolated from Croton tiglium, is reported to be a potent tyrosine kinase inhibitor with immunosuppressive effects on immune cells. Due to its potential immunotherapeutic effects, we aimed to evaluate the anti-arthritic activity of crotonoside and explore its immunomodulatory properties in alleviating the severity of arthritic symptoms. To this end, we implemented the treatment of crotonoside on collagen-induced arthritic (CIA) DBA/1 mice and investigated its underlying mechanisms towards pathogenic dendritic cells (DCs). Our results suggest that crotonoside treatment remarkably improved clinical arthritic symptoms in this CIA mouse model as indicated by decreased pro-inflammatory cytokine production in the serum and suppressed expression of co-stimulatory molecules, CD40, CD80, and MHC class II, on CD11c+ DCs from the CIA mouse spleens. Additionally, crotonoside treatment significantly reduced the infiltration of CD11c+ DCs into the synovial tissues. Our in vitro study further demonstrated that bone marrow-derived DCs (BMDCs) exhibited lower yield in numbers and expressed lower levels of CD40, CD80, and MHC-II when incubated with crotonoside. Furthermore, LPS-stimulated mature DCs exhibited limited capability to prime antigen-specific CD4+ and T-cell proliferation, cytokine secretions, and co-stimulatory molecule expressions when treated with crotonoside. Our pioneer study highlights the immunotherapeutic role of crotonoside in the alleviation of the CIA via modulation of pathogenic DCs, thus creating possible applications of crotonoside as an immunosuppressive agent that could be utilized and further explored in treating autoimmune disorders in the future.
- Galangin ameliorates experimental autoimmune encephalomyelitis in mice via modulation of cellular immunityTan, Kok-Tong; Li, Shiming; Panny, Lauren; Lin, Chi-Chien; Lin, Shih-Chao (2021-03-23)Multiple sclerosis (MS) causes neurologic disabilities that effect musculature, sensory systems, and vision. This is largely due to demyelination of nerve fibers caused by chronic inflammation. Corticosteroid treatments ameliorate symptoms of MS, but do not successfully cure the disease itself. In the current study, the application of galangin, a phytochemical flavonoid extracted from the ginger family of Alpinis officinarum, on experimental autoimmune encephalomyelitis (EAE; mouse model for MS) was explored. This study investigated prophylactic and therapeutic activity of the drug and mechanisms by which it acts. The results revealed that galangin at 40 and 80 mg/kg could lower the incidence rate of MS, and alleviate clinical/pathological manifestations. Mice administered galangin presented with less limb paralysis, lower levels of inflammatory cell infiltrates, and decreased demyelination compared to vehicle controls. Levels of CD4(+)IFN gamma(+) (T(H)1) and CD4(+)IL-17A(+) (T(H)17) cells in the spinal cords of EAE mice administered galangin were reduced and both cell types were not capable of expansion. More surprisingly, galangin inhibited antigen presentation and cytokine production by dendritic cells (DC). Formation of cytokines like IL-6, IL-12, and IL-23 were significantly decreased due to galangin in co-culture models of DC and T-cells. Taken together, the data lead one to conclude that galangin could potentially be used as a potent immunoregulatory agent to alleviate clinical symptoms and reduce the prevalence of MS.