背景:肿瘤坏死因子-α(TNF-α)是一种关键的促炎细胞因子,其异常产生与几种免疫介导的炎性疾病(IMID)有关。生物抗TNF-α治疗包括用单克隆抗体如英夫利昔单抗治疗,其已被证明是成功的,并且在大多数患者中具有良好的耐受性。不幸的是,一些患者可能对治疗无反应(原发性无应答者),或者随着时间的推移可能对生物制剂失去敏感性(早期和晚期继发性无应答者).天然产物可以减少炎症,并与小分子或生物制剂协同作用,尽管证据仍然有限。这项研究旨在调查补充和替代医学(CAM)是否可以在英夫利昔单抗无反应者中发挥作用。据报道,由于其抗炎特性,肉桂可以帮助管理慢性炎症。
方法:我们使用两步方法研究了肉桂和英夫利昔单抗在体外的协同作用。首先,我们调查了肉桂和英夫利昔单抗是否具有协同作用.第二,我们选择了支持与英夫利昔单抗有统计学显著协同作用的条件,并研究了与英夫利昔单抗无应答相关的几种基因的mRNA表达.我们使用肉桂水提取物(aCE)从肉桂,浙青,和肉桂和生物活性反式肉桂醛(TCA),肉桂酸(CA),和丁香酚在成纤维细胞(L929)和单核细胞(U937)细胞系中使用生物测定法研究英夫利昔单抗和aCE/生物活性化合物之间的协同作用,其次是qPCR的分子水平的见解。TCA,C.决明子,和泽兰梭菌aCE显示与英夫利昔单抗的剂量依赖性协同作用。此外,我们看到粘附分子的差异基因表达,凋亡因子,信号分子,和在存在和不存在aCE/生物活性物质的情况下的基质重塑剂。
结果:补充CAM对肉桂aCE最有效,其中观察到所有测试基因的协同作用,特别是MMP-1,BcL-xL,Bax和JAK2,其次是TCA,除了TLR-2、MMP1、MMP3、TIMP-1和BAX,和C.zeylanicumaCE,不影响ICAM-1、VCAM-1、TLR-2、TLR-4、MMP1、MMP3、TIMP-1和STAT3。
结论:结论:当用作提取物时,肉桂与英夫利昔单抗协同作用以减轻炎症。纯化的生物活性TCA也显示出协同活性。因此,CE,或肉桂生物活性物质可用作CAM,以改善患者的生活质量。
BACKGROUND: Tumor necrosis factor-alpha (TNF-α) is a critical pro-inflammatory cytokine, and its abnormal production is associated with several immune mediated inflammatory diseases (IMID). Biological anti-TNF-α therapy includes treatment with monoclonal antibodies such as infliximab which have proven successful and are well-tolerated in most patients. Unfortunately, some patients may not respond to therapy (primary non-responders) or may lose sensitivity to the biological agent over time (early and late secondary non-responders). Natural products can reduce inflammation and act synergistically with small molecules or biologics, although evidence remains limited. This study aimed to investigate whether complementary and alternative medicine (CAM) could play a role in infliximab non-responders. Reportedly, cinnamon can help manage chronic inflammatory conditions owing to its anti-inflammatory properties.
METHODS: We studied the synergistic effects of cinnamon and infliximab in vitro using a two-step approach. First, we investigated whether cinnamon and infliximab act synergistically. Second, we selected conditions that supported statistically significant synergy with infliximab and studied the mRNA expression of several genes involved in non-response to infliximab. We used aqueous cinnamon extract (aCE) from Cinnamomum cassia, Cinnamomum zeylanicum, and Cinnamomum loureiroi and bioactive trans-cinnamaldehyde (TCA), cinnamic acid (CA), and eugenol to study the synergy between infliximab and aCE/bioactive compounds using bioassays in fibroblast (L929) and monocytic (U937) cell lines, followed by qPCR for molecular-level insights. TCA, C. cassia aCE, and C. zeylanicum aCE demonstrated a dose-dependent synergistic effect with infliximab. Moreover, we saw differential gene expression for adhesion molecules, apoptotic factors, signaling molecules, and matrix remodelers in presence and absence of aCE/bioactives.
RESULTS: CAM supplementation was most effective with C. cassia aCE, where a synergistic effect was observed for all the tested genes specifically for MMP-1, BcL-xL, Bax and JAK2, followed by TCA, which affected most of the tested genes except TLR-2, MMP1, MMP3, TIMP-1, and BAX, and C. zeylanicum aCE, which did not affect ICAM-1, VCAM-1, TLR-2, TLR-4, MMP1, MMP3, TIMP-1, and STAT3.
CONCLUSIONS: In conclusion, cinnamon acted synergistically with infliximab to mitigate inflammation when used as an extract. Purified bioactive TCA also showed synergistic activity. Thus, aCE, or cinnamon bioactive may be used as a CAM to improve patients\' quality of life.