Berberine Prevents Intestinal Mucosal Barrier Damage During Early Phase of Sepsis in Rat through the Toll-Like Receptors Signaling Pathway.

Our previous study has shown berberine prevents damage to the intestinal mucosal barrier during early phase of sepsis in rat through mechanisms independent of the NOD-like receptors signaling pathway. In this study, we explored the regulatory effects of berberine on Toll-like receptors during the intestinal mucosal damaging process in rats. Male Sprague-Dawlay (SD) rats were treated with berberine for 5 d before undergoing cecal ligation and puncture (CLP) to induce polymicrobial sepsis. The expression of Toll-like receptor 2 (TLR 2), TLR 4, TLR 9, the activity of nuclear factor-kappa B (NF-κB), the levels of selected cytokines and chemokines, percentage of cell death in intestinal epithelial cells, and mucosal permeability were investigated at 0, 2, 6, 12 and 24 h after CLP. Results showed that the tumor necrosis factor-α (TNF-α ) and interleukin-6 (IL-6) level were significantly lower in berberine-treated rats compared to the control animals. Conversely, the expression level of tight junction proteins, percentage of cell death in intestinal epithelial cells and the mucosal permeability were significantly higher in berberine-treated rats. The mRNA expression of TLR 2, TLR 4, and TLR 9 were significantly affected by berberine treatment. Our results indicate that pretreatment with berberine attenuates tissue injury and protects the intestinal mucosal barrier in early phase of sepsis and this may possibly have been mediated through the TLRs pathway.

Berberine prevents damage to the intestinal mucosal barrier during early phase of sepsis in rat through mechanisms independent of the NOD-like receptors signaling pathway.

NOD-like receptors play a crucial role in host defense against intestinal infection. We explored the regulatory effects of berberine on NLRs during the intestinal mucosal damaging process in rats. Male Sprague-Dawlay (SD) rats were treated with berberine for 5d before undergoing cecal ligation and puncture (CLP) to induce polymicrobiol sepsis. The expression of nucleotide-binding oligomerization domain 2 (NOD2), NLR family-pyrin domain containing 3 (NLRP3), the activity of nuclear factor-kappa B (NF-κB), the levels of selected cytokines and chemokines, percentage of cell death in intestinal epithelial cells, and mucosal permeability were investigated at 0h, 2h, 6h, 12h and 24h after CLP. Results showed that the Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) level in were significantly lower in berberine treated rats compared to the control animals. The tight junction proteins level, percentage of cell death in intestinal epithelial cells and the mucosal permeability were, on the other hand, significantly elevated in berberine treated rats. The expression of NOD and NLRP3, however, were not significantly affected by berberine treatment. Our results indicate that Pretreatment with berberine attenuates tissue injury and protects the intestinal mucosal barrier in early phase of sepsis but it is likely that the mechanisms of this preventive effect do not involve the NLR pathway.

[Therapeutic effects of combined enteral nutrition with Tripterygium Wilfordii poly-glycoside in remission induction of active adult Crohn's disease].

OBJECTIVE: To investigate the potential role of enteral nutrition (EN) combined with Tripterygium Wilfordii Poly-glycoside (TWP) for remission induction of active adult Crohn's disease (CD). METHODS: Clinical data of 62 adult patients with active CD treated with EN and TWP in combination (n = 42) or TWP alone (n = 20) from March 2001 to September 2008 were retrospectively analyzed. All the patients had a Crohn's Disease Activity Index (CDAI) > 150 and < 450. In TWP group, subjects received TWP tablets (1.0 - 1.5 mg x kg(-1) x d(-1)) with uncontrolled diets; while in the group of combination therapy, the patients were given total enteral nutrition (TEN) through tube feeding in addition to TWP tablets. Clinical response was defined by a decrease of at least 70 points in the CDAI from baseline after treatment, and clinical remission was defined as the absolute value of CDAI (less than 150). Patients' nutritional and disease activity index, such as CDAI score, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), were determined at 0, 4, and 12 weeks after treatment. RESULTS: The ratio of clinical response (78.6% vs. 40.0%, P = 0.003) and clinical remission (69.1% vs. 30.0%, P = 0.004) were both significantly higher in the combined treatment group than in those the TWP group at week 4. At week 12, the clinical response ratio was significantly higher in the combined treatment group (90.5% vs. 65.0%, P = 0.014); the remission ratio was also higher in the combined treatment group (76.2% vs. 55.0%, P = 0.091). The nutritional parameters improved from baseline at week 4 and 12 in the combined treatment group but not in TWP group. At week 4, blood albumin, prealbumin, and transferrin levels was higher in the combined treatment group than those in TWP group (P < 0.05); at week 12, patients in combined treatment group also had significantly higher body mass index (BMI), blood albumin, prealbumin, transferrin and hemoglobin levels (P < 0.05). CONCLUSIONS: Treatment with enteral nutrition and TWP in combination are superior to TWP alone for induction of clinical response and remission in adult Crohn's Disease. This strategy also improves patient's nutritional status and avoids the adverse effects of traditional therapy.

[Effects of perioperative combined nutritional support in Crohn disease].

OBJECTIVE: To observe the efficacy of perioperative combined nutritional support in patients with Crohn disease. METHODS: From January 2000 to June 2008, 165 patients with Crohn disease receiving perioperative nutritional support were included in this retrospective analysis. The patients were divided into three groups according to the ways of nutritional support: total enteral nutrition group, total parenteral nutrition group and combined nutrition group; there were 55 patients in each group. Each group had the same treatment except for nutritional support. The efficacy of different approaches of nutritional support was analyzed and compared among the groups. RESULTS: Compared with total enteral and total parenteral nutrition, combined nutrition supplied more sufficient energy, the nutritional status improved more significant in short time; pre-albumin, transferrin, lymphocytes and platelet count increased significantly. The disease remission rate in combined nutrition group was 80.0%, better than 76.4% in total enteral nutrition group and 74.5% in total parenteral nutrition group. The morbidity rate was 10.9% in combined nutrition group, and it was lower than that in total enteral nutrition group and total parenteral nutrition group (25.4% and 18.2%, respectively). The length of hospital stay was shorter and the treatment was more cost-effective in combined nutrition group. CONCLUSION: For patients with Crohn disease, perioperative combined nutritional support is more efficient than total enteral or parental nutrition support.

[Study of enteral nutrients transport in intestinal hypoperfused rat model].

OBJECTIVE: To study the transport of glutamine and glucose, expression of their transporters and tissue morphology in intestinal hypoperfusion. METHODS: Sprague-Dawley rats were randomized to receive 60 min of intestinal hypoperfusion (superior mesenteric artery clamp) or serve as normoxic controls (celiotomy only). At the same time, jejunal loops were randomized to receive in situ perfusion of mannitol,glucose,or glutamine.Intestinal brush border membrane vesicles (BBMV) were prepared by calcium precipitation. Sodium-dependent uptake of glucose and glutamine into BBMV were quantitated by rapid mixing and filtration. Histologic examination and immunohistochemistry were performed by pathologists blinded to the groups. RESULTS: When compared with the control group, tissue lactate concentration of the hypoperfused group increased significantly (4.9+/-0.3 vs 3.1+/-0.2), especially in the glucose perfused groups (P<0.01). Transport and transporters of glucose in brush border, but not glutamine, decreased during hypoperfusion [(76+/-10) pmol d mg(-1) d 10 s(-1) vs (290+/-13)pmol d mg(-1) d 10 s(-1)]. Tissue structural damage was most severe in glucose perfused groups during hypoperfusion. CONCLUSION: Transport and expression of transporters of glucose and glutamine in enteral nutrition are differently regulated under conditions of trauma and stress.