Therapeutic effect and mechanism of Daikenchuto in a model of methotrexate-induced acute small intestinal mucositis.

BACKGROUND: Daikenchuto (DKT) has positive therapeutic effects on improving various gastrointestinal disorders. The present study investigated whether or not DKT has a potential therapeutic effect on chemotherapy-induced acute small intestinal mucositis (CIM) in a rat model. METHODS: Intraperitoneal injection of 10 mg/kg methotrexate (MTX) every 3 days for a total of 3 doses was used for induction of CIM in a rat model. The MTX and DKT-MTX groups were injected with MTX as above from the first day, and the DKT-MTX and DKT groups were administered 2.7% DKT via the diet at the same time. The rats were euthanized on day 15. RESULTS: The DKT-MTX group showed an improvement in the body weight and conditions of gastrointestinal disorders as well as increased levels of diamine oxidase in plasma and in the small intestinal villi. The pathology results showed that small intestinal mucosal injury in the DKT-MTX group was less severe than that in the MTX group. Immunohistochemistry for myeloperoxidase and malondialdehyde and quantitative real-time polymerase chain reaction (RT-qPCR) for TGF-ß1 and HIF-1α showed that DKT attenuated peroxidative damage. The crypts in the DKT-MTX group contained more Ki-67-positive cells than MTX group. The zonula occluden-1 and claudin-3 results showed that DKT promoted repair of the mucosal barrier. RT-qPCR for the amino acid transporters EAAT3 and BO+AT also confirmed that DKT promoted mucosal repair and thus promoted nutrient absorption. CONCLUSION: DKT protected against MTX-induced CIM in a rat model by reducing inflammation, stimulating cell proliferation, and stabilizing the mucosal barrier.

How the cost-effectiveness results change in the China health policy environment: an economic evaluation of glycopyrrolate/formoterol for the treatment of COPD.

OBJECTIVE: To investigate the cost-effectiveness of glycopyrrolate/formoterol compared with tiotropium bromide for the treatment of moderate-to-severe COPD in China and discuss the influence of healthcare policies on the economic evaluation. METHODS: A Markov model with seven disease states was built to evaluate the lifetime cost-effectiveness of glycopyrrolate/formoterol from the perspective of the Chinese healthcare sector. Drug prices both before and after the negotiation were applied to discuss the influence on the economic evaluation results. Exacerbation and adverse event were included in each cycle. The improvement of forced expiratory volume in 1 second (FEV1) and incidence rate of exacerbation were derived from pooled PINNACLE analysis. Mortality rates from Chinese life tables were adjusted using hazard ratios. Direct medical costs were modeled in accordance with the perspective chosen. Health resource utilization were derived from previous studies and expert's opinions. Life-years gained, quality-adjusted life years (QALYs), and incidence of exacerbation were simulated as the health outcomes. One-way sensitivity analysis and probability analysis were conducted to explore the robustness of the base case results. Several scenario analyses were also designed. RESULTS: Glycopyrrolate/formoterol generated an additional 0.0063 LYs and 0.0032 QALYs with lower lifetime costs compared with tiotropium (CNY 27,854 vs. CNY 33,189) and was proved to be the dominant strategy in the base case analysis. The one-way sensitivity analysis confirmed the robustness of the base case results. The probabilities of glycopyrrolate/formoterol being cost-effective were 96.5, 95.7, and 93.0% when CNY 72,000 (1 time GDP per capital), CNY 108,000, and CNY 216,000 were used as thresholds, respectively. Compared with the scenario where price before negotiation was used, the cost-effectiveness based on current price was significantly increased. CONCLUSION: Glycopyrrolate/formoterol was demonstrated to be a clinically and cost-effective treatment for moderate-to-severe COPD in China using the latest price. The negotiation policy could increase the cost-effectiveness and benefit the patients.

Reversine and herbal Xiang-Sha-Liu-Jun-Zi decoction ameliorate thioacetamide-induced hepatic injury by regulating the RelA/NF-κB/caspase signaling pathway.

This study investigated the anti-fibrotic effects of reversine and Chinese medicine Xiang-Sha-Liu-Jun-Zi decoction (XSLJZD) on thioacetamide (TAA)-induced hepatic injury. Sprague-Dawley rats were intraperitoneally administered with TAA, then injected with reversine intraperitoneally, and/or orally provided with XSLJZD. TAA resulted in liver injury with increases in the liver index and levels of serum aspartate aminotransferase (AST) and alanine aminotransferase. Reversine alleviated the liver index and AST level and improved TAA-induced pathological changes but decreased TAA-induced collagen deposition, and α-smooth muscle actin and transforming growth factor-ß1 expression. Reversine also modulated the mRNA levels of inflammatory cytokines, such as RelA, interleukin (IL)-17A, IL-22, IL-1ß, IL-6, NLR family pyrin domain containing 3, platelet-derived growth factor, and monocyte chemoattractant protein, and suppressed nuclear factor (NF)-κB (p65) phosphorylation and caspase 1 activation. Meanwhile, XSLJZD protected TAA-injured liver without increasing fibrosis and enhanced the regulating effect of reversine on RelA, IL-17A, IL-1ß, and MCP-1 cytokines. In conclusion, reversine ameliorates liver injury and inhibits inflammation reaction by regulating NF-κB, and XSLJZD protects the liver through its synergistic effect with reversine on regulating inflammatory cytokines.