Laboratory of Pharmacology, Department of Physiological Sciences, Institute of Biological and Health Sciences, Federal Rural University of Rio de Janeiro (UFRRJ), BR 465, Km 07, 23890-000, Seropédica, RJ, Brazil.
Laboratory of Bioactive Natural Products Chemistry, Natural Products Research Institute (IPPN), Federal University of Rio de Janeiro (UFRJ), Av. Carlos Chagas Filho, 373, 21941-902, Rio de Janeiro, RJ, Brazil.
J Ethnopharmacol. 2020 Oct 5;260:112841. doi: 10.1016/j.jep.2020.112841. Epub 2020 Apr 5.
Cecropia Loefl. species (Urticaceae) are widely spread across the rainforest in tropical and subtropical regions of Central and South America. Inhabitants of different regions of Brazil employ leaves, fruits and sprouts of Cecropia hololeuca Miq. mainly as anti-inflammatory, anti-asthmatic, expectorant, fever suppressant, and against cough.
To evaluate the antinociceptive and anti-inflammatory activities of an aqueous leaf extract of C. hololeuca in a murine model of zymosan-induced arthritis (ZIA) and characterize compounds contributing to these effects.
The crude aqueous extract of C. hololeuca (CAE) was obtained by infusion, screened for antinociceptive and anti-inflammatory activities, and fractionated (solvent partition; RP-2 and Sephadex G-25 column chromatography), yielding fractions that were chemically and pharmacologically investigated. TLC, HPLC-DAD, HPLC-DAD-ESI-MS/MS and NMR analyses were peformed. The antinociceptive activity was assessed by means of acetic acid-induced writhing, hot-plate and rota-rod tests. ZIA was used to evaluate the anti-arthritic activity of oral treatment with CAE, butanolic (BF) and aqueous fraction (AF), as well as the fractions obtained from BF (F2, F2-A and F2-B). Rutin, a flavonoid found in C. hololeuca, was also tested. Mechanical hypernociception, joint edema, local neutrophil recruitment and articular TNF-α quantification were performed to measure the severity of arthritis and identify the anti-inflammatory potential of C. hololeuca.
CAE (0.03-1 g/kg, p.o.) showed a dose-related inhibitory effect on acetic acid-induced writhing test, but did not change the pain latency in the hotplate test, nor the first fall time on the rota-rod test. In addition, CAE (1 g/kg, p.o.) inhibited by 65% the mechanical hypernociception, 46% the joint edema, 54% the neutrophil recruitment and 53% the articular TNF-α concentration levels in ZIA. BF (0.4 g/kg, p.o.), AF (0.6 g/kg), F2 (0.1 g/kg) and F2-A (0.045 g/kg), but not F2-B (0.055 g/kg), inhibited the mechanical hypernociception, joint edema and neutrophil recruitment in ZIA. Rutin (0.001-0.03 g/kg, p.o.) produced dose-related inhibitory effects in the mechanical hypernociception, joint edema and neutrophil recruitment, and at 0.03 g/kg also inhibited articular TNF-α synthesis after intra-articular zymosan injection. Isoorientin, isovitexin, rutin and isoquercitrin were identified in the most active fraction (F2-A), along with luteolin and apigenin derivatives, tentatively identified as isoorientin-2″-O-glucoside and isovitexin-2″-O-glucoside.
This study corroborates the popular use by oral route of aqueous preparations of C. hololeuca against joint inflammatory disorders, such as rheumatoid arthritis. Our results demonstrated for the first time that oral administration of rutin shows antinociceptive and anti-inflammatory effects in ZIA, indicating that this flavonoid is one of the immunomodulatory compounds involved in the anti-arthritic activity of C. hololeuca.
Cecropia Loefl. 物种（荨麻科）广泛分布于中美洲和南美洲的热带雨林地区。巴西不同地区的居民主要使用 Cecropia hololeuca Miq. 的叶子、果实和芽作为抗炎、抗哮喘、祛痰、退烧和止咳药。
评估 Cecropia hololeuca 叶的水提物在酵母聚糖诱导的关节炎（ZIA）小鼠模型中的抗伤害感受和抗炎活性，并鉴定出对这些作用有贡献的化合物。
Cecropia hololeuca（CAE）的粗水提取物通过浸渍获得，对其进行了抗伤害感受和抗炎活性筛选，并进行了（溶剂分配；RP-2 和 Sephadex G-25 柱层析）分段，得到的各个部分进行了化学和药理学研究。进行了 TLC、HPLC-DAD、HPLC-DAD-ESI-MS/MS 和 NMR 分析。通过醋酸诱导的扭体、热板和转棒试验评估了抗伤害感受活性。使用 CAE、丁醇（BF）和水（AF）部分以及 BF 获得的部分（F2、F2-A 和 F2-B）进行口服治疗，以评估 CAE、BF 和 AF 对 ZIA 的抗关节炎活性。还测试了芦丁，芦丁是 Cecropia hololeuca 中的一种类黄酮。进行机械性痛觉过敏、关节肿胀、局部中性粒细胞募集和关节 TNF-α 定量，以测量关节炎的严重程度并确定 Cecropia hololeuca 的抗炎潜力。
CAE（0.03-1 g/kg，po）呈剂量相关地抑制醋酸诱导的扭体试验，但不改变热板试验中的疼痛潜伏期，也不改变转棒试验中的首次跌倒时间。此外，CAE（1 g/kg，po）抑制了 65%的机械性痛觉过敏、46%的关节肿胀、54%的中性粒细胞募集和 53%的关节 TNF-α浓度水平。BF（0.4 g/kg，po）、AF（0.6 g/kg）、F2（0.1 g/kg）和 F2-A（0.045 g/kg），但不是 F2-B（0.055 g/kg），抑制了 ZIA 中的机械性痛觉过敏、关节肿胀和中性粒细胞募集。芦丁（0.001-0.03 g/kg，po）在机械性痛觉过敏、关节肿胀和中性粒细胞募集方面呈剂量依赖性抑制作用，在 0.03 g/kg 时还抑制了关节内注射酵母聚糖后 TNF-α的合成。在最活跃的部分（F2-A）中鉴定出异荭草苷、异牡荆苷、芦丁和异槲皮苷，以及山奈酚和芹菜素衍生物，推测为异荭草苷-2″-O-葡萄糖苷和异牡荆苷-2″-O-葡萄糖苷。
这项研究证实了口服 Cecropia hololeuca 水提物治疗关节炎症性疾病（如类风湿性关节炎）的民间用途。我们的结果首次表明，芦丁的口服给药在 ZIA 中具有抗伤害感受和抗炎作用，表明这种类黄酮是参与 Cecropia hololeuca 抗炎活性的免疫调节化合物之一。
