Phillygenin Attenuated Colon Inflammation and Improved Intestinal Mucosal Barrier in DSS-induced Colitis Mice via TLR4/Src Mediated MAPK and NF-κB Signaling Pathways.

Ulcerative colitis (UC) is a chronic, relapsing, and nonspecific inflammatory bowel disease (IBD). Phillygenin (PHI), a natural bioactive ingredient, isolated from Forsythiae Fructus, exhibits anti-inflammatory, anti-oxidative, and hepatoprotective activities. However, few reports provide direct evidence on the efficacy of PHI in improving colitis mice. The present study elucidated that the symptoms of DSS-induced colitis mice were alleviated after PHI administration, including body weight loss, the disease activity index, colon length shortening, colonic pathological damage, splenomegaly, and hepatomegaly. PHI treatment improved the intestinal mucosal barrier by protecting goblet cells, promoting gene expressions of Clca1, Slc26a3, and Aqp8, increasing tight junction proteins (TJs), and reducing epithelial cell apoptosis. In addition, the levels of oxidative stress (MPO, SOD, and MDA) and inflammatory cytokines (TNF-α, IL-1ß, IL-6, and IL-10) were reversed by PHI in colitis mice. According to transcriptome and network pharmacology analysis, inflammatory pathway might be an important mechanism for PHI to improve colitis. Western blotting displayed that the PHI inhibited the activation of tyrosine kinase Src mediated by TLR4, and then reduced the phosphorylation of downstream proteins p38, JNK, and NF-κB in colitis mice. In summary, our results suggested that PHI might be an appropriate and effective drug candidate to protect colitis.

[A controlled study on the treatment of acute progressive cerebral infarction by continuous anticoagulation with small doses of heparin].

OBJECTIVE: To discuss the treatment of acute progressive cerebral infarction by continuous anticoagulation with small doses of heparin. METHODS: A prospective, randomized, and controlled clinical research was conducted. Three hundred and fifty-one patients were randomly divided into three groups. Group A (n=119) was treated with heparin, which was controlled by an infusion pump with a speed of 18 U×kg(-1)×h(-1) for 24 hours, and the dosage was regulated according to the changes in activated partial thromboplastin time (APTT) which was determined every 8 hours. Group B (n=115) was treated with intravenous drip of 12,500 U of heparin with a speed of 18 U×kg(-1)×h(-1) once a day. Group C (n=117) was treated with 5000 U of low-molecular-weight heparin calcium injection twice a day. After 14 days, nerve function defect according to the National Institutes of Heath stroke scale (NIHSS) score was determined, the adverse events (e.g. intracranial hemorrhage, subcutaneous ecchymosis, gingival bleeding, hematuria and occult blood in stools) were observed. After 6 months, the recurrence rate and Barthel index (BI) would be determined. RESULTS: The total efficiency in group A (95.80%) was significantly higher than that in group B (85.22%) and group C (85.47%). Recurrence rate in group A (1.68%) was significantly lower than group B (8.70%) and group C (8.33%) with significant differences (P<0.05 or P<0.01), while there was no significant difference between group B and group C (both P>0.05). The BI of group A (89.27±8.56) was significantly higher than group B (72.57±9.77) and group C (71.66±9.37) with significant difference (both P<0.01), while there was no significant difference between group B and group C (P>0.05). Adverse event rate in group A (5.88%) was slightly higher than that of group B (3.48%) and group C (4.27%), but the difference was not significant (both P>0.05). CONCLUSIONS: Continuous infusion of low dosage of heparin could significantly reduce neurologic impairment score in patients with progressive cerebral infarction, increase cure rate, reduce the recurrence rate, and raise the BI of patients, and it dose not increase the risk of intracranial and extracranial hemorrhage.