Effects of curcumin on memory follicular T cells in obese mice with colitis / 药学学报

This study evaluated the regulatory effect of curcumin on memory follicular T cells (mTf) in obese mice with ulcerative colitis on the basis of determining its effective treatment of ulcerative colitis in obese mice. Forty male leptin mutant (ob/ob) mice were randomly divided into control group, control + curcumin group, dextran sodium sulfate (DSS) group and DSS + curcumin group, with 10 mice in each group. Mice in the DSS group and the DSS + curcumin group were induced by DSS to establish chronic ulcerative colitis model, and mice in the control + curcumin group and the DSS + curcumin group were given curcumin (200 mg·kg-1·d-1) by intragastric administration. Mice were sacrificed under anesthesia, and colon mass index, colon length and other conditions were observed in each group. Pathological injury of colonic was performed after HE staining. The levels of memory follicular helper T cells (mTfh) and memory follicular regulatory T cells (mTfr) in spleen of mice were detected by flow cytometry. The expression levels of interleukin-10 (IL-10) and interleukin-17A (IL-17A) in colon tissue were detected by ELISA. The results showed that curcumin significantly increased the body weight and colon length of obese mice with colitis, and decreased the colon weight, colon mass index and pathological score (P < 0.05). Curcumin significantly reduced the levels of central memory follicular T cells (cmTf), mTfh1, mTfh17 cells and the content of pro-inflammatory cytokine IL-17A (P < 0.01). The levels of effector memory follicular T cells (emTf) and mTfr and the content of anti-inflammatory cytokine IL-10 were increased (P < 0.05, P < 0.01). Therefore, curcumin may treat colitis in obese mice by regulating the balance of mTf cell subsets.

Regulatory Effect of Xiangshenwan on TLR/NF-κB Signal in Colonic Mucosa of Mice with Colitis / 中国实验方剂学杂志

Objective:To explore the effect and mechanism of Xiangshenwan on ulcerative colitis （UC） induced by dextran sulfate sodium （DSS） in mice based on the classic Toll-like receptor （TLR）/nuclear factor kappa B （NF-<italic>κ</italic>B） signaling pathway. Method:The experimental mice were divided into a normal group， a model group， a Xiangshenwan group， and a mesalazine group. The mice， except for those in the normal group， received 3% DSS solution for 7 days to establish the acute UC model and were treated with Xiangshenwan （5 g·kg^-1） and mesalazine （300 mg·kg^-1） continuously from the 1st day to the 10th day of modeling. The body weight， disease activity index （DAI）， colon weight， intestinal weight index， colon length， colon weight per unit length， and pathological changes of mice were evaluated respectively. The protein expression of TLR5， myeloid differentiation factor 88 （MyD88）， interleukin-1 receptor-associated kinase 4 （IRAK4）， tumor necrosis factor receptor-associated factor 6 （TRAF6）， transforming growth factor <italic>β</italic>-activated kinase 1 （TAK1）， p38 mitogen-activated protein kinase （MAPK）， NF-<italic>κ</italic>B， IRAK1， TAK1-binding protein 1 （TAB1）， TAB2， mitogen-activated protein kinase kinase 3 （MKK3）， MKK6 and cyclic adenosine monophosphate response element-binding protein （CREB） in colon tissues of mice was detected by Western blot. Result:Compared with the normal group， the model group showed decreased body weight of mice， increased DAI scores， elevated colon weight， intestinal weight index， and colon weight per unit length， shortened colon length， severe colonic mucosal injury， and up-regulated protein expression of TLR5， MyD88， IRAK4， TRAF6， TAK1， p38 MAPK， NF-<italic>κ</italic>B， IRAK1， TAB1， TAB2， MKK3， MKK6， and CREB in colon tissues （<italic>P</italic><0.05，<italic> P</italic><0.01<bold>）.</bold> Compared with the model group， the Xiangshenwan group and the mesalazine group displayed increased body weight of mice， decreased DAI scores， declining colon weight， intestinal weight index， and colon weight per unit length， increased colon length， improved colonic mucosal injury， and down-regulated protein expression of TLR5， MyD88， IRAK4， TRAF6， TAK1， p38 MAPK， NF-<italic>κ</italic>B， IRAK1， TAB1， TAB2， MKK3， MKK6， and CREB in colon tissues （<italic>P</italic><0.05，<italic> P</italic><0.01）. Conclusion:Xiangshenwan can effectively treat DSS-induced UC presumedly by the inhibition of TLR/NF-<italic>κ</italic>B signaling pathway.

Regulatory Effect of Volatile Oil from Sishenwan on TLR/MyD88 Signaling Pathway in Mice with Chronic Ulcerative Colitis / 中国实验方剂学杂志

Objective:To explore the underlying mechanism of volatile oil from Sishenwan in treating chronic ulcerative colitis through the Toll-like receptor （TLR）/myeloid differentiation factor 88 （MyD88） signaling pathway. Method:The BALB/c mice were randomly divided into a normal group （normal）， a model group ［dextran sodium sulfate （DSS）］， a Sishenwan volatile oil group， an Ershen pill volatile oil group， a Wuweizi powder volatile oil group， and a mesalazine control group. The chronic ulcerative colitis model was induced by DSS in mice. Seven days after intragastric administration， the efficacy was evaluated based on the body weight， colon weight， colon weight index， colon length， and pathological damage score under colonoscopy. The levels of interleukin （IL）-4， IL-10， IL-17A， IL-21， and interferon-<italic>γ </italic>（IFN-<italic>γ</italic>） in the supernatant of colon tissues were detected by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the expression levels of proteins related to the TLR/MyD88 signaling pathway in the colon mucosa of mice， including TLR2， MyD88， Ras-related C3 botulinum toxin substrate 1 （Rac1）， IL-1 receptor-associated kinase 4 （IRAK4）， IRAK1， tumor necrosis factor receptor （TNFR）-associated factor 6 （TRAF6）， transforming growth factor-<italic>β</italic>-activated kinase 1 binding protein 1 （TAB1）， TAB2， mitogen-activated protein kinase kinase 6 （MKK6）， p38 mitogen-activated protein kinase （p38 MAPK）， and cyclic adenosine monophosphate response element-binding protein （CREB）. Result:Compared with the normal group， the model group showed decreased colon length， increased colon weight， colon weight index， and pathological damage score under colonoscopy， decreased IL-10 level in the colon tissues， increased IL-4， IL-17A， IL-21， and IFN-<italic>γ</italic> levels （<italic>P<</italic>0.05， <italic>P<</italic>0.01）， and up-regulated protein expression of TLR2， MyD88， Rac1， IRAK4， IRAK1， TRAF6， TAB1， TAB2， MKK6， p38MAPK， and CREB （<italic>P<</italic>0.01）. Compared with the model group， the Sishenwan volatile oil group showed increased colon length， reduced colon weight， colon weight index， and pathological damage score under colonoscopy， elevated IL-10 level in the colon tissues， decreased IL-4， IL-17A， IL-21， and IFN-<italic>γ</italic> levels （<italic>P<</italic>0.05， <italic>P<</italic>0.01），and down-regulated protein expression of TLR2， MyD88， Rac1， IRAK4， IRAK1， TRAF6， TAB1， TAB2， MKK6， p38MAPK， and CREB （<italic>P<</italic>0.05， <italic>P<</italic>0.01）. Conclusion:The volatile oil from Sishenwan can effectively improve the inflammatory response of chronic ulcerative colitis， which may be achieved by regulating the TLR/MyD88 signaling pathway.

Study on monogalactosylmonoacylglycerol in marine algae (Sargassum fusiforme) / 中草药

Objective To indentify monogalactosylmonoacylglycerol (MGMG) and analyze the chemical characteristics of sn-1 and sn-2 type isomers in Marine TCM Sargassum fusiforme. Methods The MGMG compounds were isolated by multiple chromatography methods and their structures were determined by spectroscopic methods such as NMR and HRESI-MS. The interconversion and chromatography-mass spectrometry feature of MGMG positional isomers were analyzed through HPLC and HPLC-ESI-MS/MS. Results Five MGMGs were isolated from Sargassum fusiforme, and the fatty acyl compositions were stearidonoyl, linolenoyl, arachidoyl, linoleyl, and oleyl. The sn-1 and sn-2 type of MGMG were unstable. The interconversion tended to be sn-1 type rapidly, and kept balanced content at 85:15. The relative retention time of sn-2 type was less than sn-1 type on C18 reverse phase chromatography. The abundant fragment ions of MS/MS were significantly differences. The base peak was [M+Na-Gal]+ (100%), and the peak intensity of [M+Na-RCOOH]+ was always more than 50% from sn-2 type while less than 20% from sn-1 type. Conclusion Five MGMGs were isolated from brown algae for the first time. This was the first report about the interconversion and chromatography-mass spectrometry feature of sn-1 and sn-2 type. It can use to determine the fatty acyl attachment in each MGMG.