Institute of Experimental Pharmacology & Toxicology, Slovak Academy of Sciences, Dúbravská Cesta 9, 841 04 Bratislava, Slovakia.
Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, 832 32 Bratislava, Slovakia.
Molecules. 2017 Nov 6;22(11):1911. doi: 10.3390/molecules22111911.
Methotrexate (MTX) is still the gold standard for treatment of rheumatoid arthritis (RA). The therapeutic efficacy of low-dose of MTX can be increased by its combination with a natural substance, ferulaldehyde (FRA). The aim of this study was to evaluate the effect FRA and MTX administered alone or in combination in adjuvant arthritis. The disease was induced to Lewis male rats by intradermal injection, which contains a suspension of heat-inactivated in incomplete Freund's adjuvant. The experiment of 28 days included: healthy animals, arthritic animals, arthritic animals with administration of FRA at the oral daily dose of 15 mg/kg, arthritic animals with administration of MTX at the oral dose of 0.3 mg/kg twice a week, and arthritic animals administered with FRA and MTX. FRA in monotherapy decreased significantly only the level of interleukin-1β (IL-1β) and matrix metalloproteinase-9 in plasma. Combination of FRA and low-dose MTX was more effective than MTX alone when comparing body weight, hind paw volume, arthritic score, plasmatic levels of IL-1β, activity of γ-glutamyl transferase, and relative mRNA expression of IL-1β in the spleen. Therefore, the combination treatment was the most effective. The obtained results are interesting for future possible innovative therapy of patients with RA.
甲氨蝶呤（MTX）仍然是治疗类风湿关节炎（RA）的金标准。低剂量 MTX 与天然物质香草醛（FRA）联合使用可以提高其治疗效果。本研究旨在评估 FRA 和 MTX 单独或联合给药在佐剂性关节炎中的作用。通过皮内注射含有热失活不完全弗氏佐剂的混悬液，将疾病诱导至雄性 Lewis 大鼠。28 天的实验包括：健康动物、关节炎动物、口服每日剂量为 15mg/kg 的 FRA 治疗的关节炎动物、每周两次口服 0.3mg/kg MTX 的关节炎动物以及接受 FRA 和 MTX 治疗的关节炎动物。FRA 单独治疗仅显著降低了血浆中白细胞介素 1β（IL-1β）和基质金属蛋白酶 9 的水平。与 MTX 单独治疗相比，FRA 与低剂量 MTX 联合使用时，在体重、后爪体积、关节炎评分、血浆 IL-1β 水平、γ-谷氨酰转移酶活性和脾脏中 IL-1β 的相对 mRNA 表达方面更有效。因此，联合治疗效果最佳。这些结果对于未来 RA 患者的创新性治疗具有重要意义。
