Chen Long, Liu Tianjun, Wang Qiangsong, Liu Juan
Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300192, China.
BMC Complement Altern Med. 2017 Apr 27;17(1):233. doi: 10.1186/s12906-017-1739-7.
Resveratrol and curcumin, as natural flavones products, have good therapeutic effect in acute and chronic inflammation; on the other hand, tetramethylpyrazine (TMP) has angiogenesis and vessel protection effect as well as anti-inflammatory function. In this paper, the anti-inflammatory effect of the tetramethylpyrazine, resveratrol and curcumin (TRC) combination in acute and chronic inflammation was reported in vivo.
The dose of the combined three natural products was optimized based on the acute paw swelling mouse model with a Uniform Design methodology. The therapeutic effect of TRC combination on chronic inflammation was investigated by using the collagen-induced arthritis (CIA) rat model based upon the following indexes: the volume of paw swelling, arthritis score, serum mediators and histological examination as well as immunohistochemical staining. The levels of alanine aminotransferase (ALT) and aspartate transaminase (AST) in serum were measured and the pathological sections of liver and kidney were analysed. LD was measured based on the acute oral toxicity (AOT) standard method.
The best formulation was the three components combined at the same mass proportion revealed by the Uniform Design methodology. This combination could significantly reduce the paw swelling in acute paw swelling mouse model, could reduce paw swelling and alleviate the damage in joint structural of ankle, cartilages and fibrous tissue in CIA rat model. The dose relationship was clear in both cases. Immunohistochemical staining of ankle tissue revealed that TRC combination was able to inhibit the expression of NF-κB p65 and TNF-α which were closely related to the inflammatory process. Analysis of serum mediators revealed TRC combination could inhibit the production of TNF-α, IL-1β, and IL-6 in the serum. Toxic study revealed this formulation was low toxic, LD was larger than 5 g/kg, both the level of ALT and AST and histopathology in the liver and kidney exhibited no distinctions between the TRC combination and the blank group, no mortality occurred at the administered doses of 5 g/kg.
The results showed this formulation could provide a novel potent treatment for acute and chronic inflammation (RA) without side effect like gastric injury occurring in NSAIDs.
白藜芦醇和姜黄素作为天然黄酮类产物，在急慢性炎症中具有良好的治疗效果；另一方面，川芎嗪（TMP）具有血管生成和血管保护作用以及抗炎功能。本文报道了川芎嗪、白藜芦醇和姜黄素（TRC）组合在体内对急慢性炎症的抗炎作用。
采用均匀设计方法，基于急性足肿胀小鼠模型优化三种天然产物的组合剂量。基于以下指标，利用胶原诱导性关节炎（CIA）大鼠模型研究TRC组合对慢性炎症的治疗效果：足肿胀体积、关节炎评分、血清介质、组织学检查以及免疫组化染色。检测血清中丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）水平，并分析肝和肾的病理切片。根据急性经口毒性（AOT）标准方法测定半数致死量（LD）。
均匀设计方法显示最佳配方是三种成分按相同质量比例组合。该组合能显著减轻急性足肿胀小鼠模型中的足肿胀，可减轻CIA大鼠模型中的足肿胀，并减轻踝关节、软骨和纤维组织的关节结构损伤。两种情况下剂量关系均明确。踝关节组织免疫组化染色显示，TRC组合能够抑制与炎症过程密切相关的NF-κB p65和TNF-α的表达。血清介质分析显示，TRC组合可抑制血清中TNF-α、IL-1β和IL-6的产生。毒性研究表明该配方毒性低，LD大于5 g/kg，TRC组合与空白组相比，肝和肾中的ALT和AST水平以及组织病理学均无差异，在5 g/kg给药剂量下未发生死亡。
结果表明该配方可为急慢性炎症（类风湿性关节炎）提供一种新型强效治疗方法，且无非甾体抗炎药所出现的如胃损伤等副作用。
