Laboratory Neurotoxicity and Psychopharmacology, Graduate Program in Biological Sciences: Toxicological Biochemistry, Center of Natural and Exact Sciences, Federal University of Santa Maria, Av. Roraima 1000, Camobi, Santa Maria, RS, 97105-900, Brazil.
Phytochemical Research Laboratory, Graduate Program in Pharmaceutical Sciences, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.
Naunyn Schmiedebergs Arch Pharmacol. 2019 May;392(5):513-528. doi: 10.1007/s00210-018-1594-1. Epub 2019 Jan 7.
To investigate the topical anti-inflammatory activity of the crude extract of Cariniana domestica fruit peels (CdE), its dichloromethane, n-butanol, and ethyl acetate (EtAc) fractions, and steroids (β-sitosterol, lupeol, and stigmasterol) isolated from the EtAc fraction in models of irritant contact dermatitis (ICD) croton oil-induced in mice. We induced skin inflammation by single (acute; 1 mg/ear) and multiple (chronic; 0.4 mg/ear) croton oil application. We topically applied C. domestica (CdE, fractions, and gel formulations) and β-sitosterol, lupeol, and stigmasterol immediately after applying croton oil. HPLC-DAD chromatography of the EtAc fraction and stability of the gel formulations were verified. HPLC-DAD of the EtAc fraction revealed the stigmasterol, lupeol, and β-sitosterol presence. CdE and EtAc fraction gels showed no organoleptic or pH changes at room temperatures. CdE and dichloromethane, n-butanol, and EtAc (1 mg/ear) fractions decreased the acute ear edema with maximum inhibition (I) of 97 ± 2, 86 ± 1, 81 ± 4, and 95 ± 2%, respectively. CdE and EtAc fraction gel presented similar effects, with respective I of 85 ± 6% (3%;15 mg/ear) and 82 ± 2% (1%;15 mg/ear). β-sitosterol (7.5 μg/ear), lupeol (10 μg/ear), and stigmasterol (5.7 μg/ear) also reduced this parameter by 46 ± 8, 51 ± 7, and 62 ± 7%, respectively. All topical treatments reduced the inflammatory cells' infiltration in the acute ICD model. CdE reduced the ear edema by 77 ± 4% (1 mg/ear) and the inflammatory cell infiltration in the chronic ICD model. CdE's anti-inflammatory effect was accompanied by a minimum development of adverse effects. C. domestica demonstrates a promising potential for the development of a topical anti-inflammatory agent. Graphical abstract Cariniana domestica, popularly known as jequitibá-roxo, presented topical anti-inflammatory activity in an acute and chronic irritant contact dermatitis croton oil-induced in mice. The crude extract (solutions and gel formulations) and different fractions obtained from fruit peels of C. domestica showed topical antiinflammatory activity on skin inflammation models with minimum adverse effects in preliminary toxicological studies (behavior and biochemical parameters). Moreover, the HPLC analysis revealed the presence of β-sitosterol, stigmasterol and lupeol, which also presented topical anti-inflammatory effect in the acute irritant contact dermatitis croton oil-induced. Our findings support the use of this species as a promising topical antiinflammatory agent.
为了研究 Cariniana domestica 果皮的粗提取物（CdE）、其二氯甲烷、正丁醇和乙酸乙酯（EtAc）馏分以及从 EtAc 馏分中分离出的甾体（β-谷甾醇、羽扇豆醇和豆甾醇）在小鼠刺激性接触性皮炎（ICD）模型中的局部抗炎活性，我们使用巴豆油诱导的单次（急性；1mg/耳）和多次（慢性；0.4mg/耳）巴豆油应用来诱导皮肤炎症。我们在涂抹巴豆油后立即用 C. domestica（CdE、馏分和凝胶制剂）和β-谷甾醇、羽扇豆醇和豆甾醇进行局部治疗。通过 HPLC-DAD 色谱法对 EtAc 馏分进行了验证，并对凝胶制剂的稳定性进行了验证。EtAc 馏分的 HPLC-DAD 分析显示存在豆甾醇、羽扇豆醇和β-谷甾醇。CdE 和 EtAc 馏分凝胶在室温下均未显示出感官或 pH 值变化。CdE 和二氯甲烷、正丁醇和 EtAc（1mg/耳）馏分分别降低急性耳水肿，最大抑制率（I）分别为 97±2%、86±1%、81±4%和 95±2%。CdE 和 EtAc 馏分凝胶表现出相似的效果，各自的 I 分别为 85±6%（3%；15mg/耳）和 82±2%（1%；15mg/耳）。β-谷甾醇（7.5μg/耳）、羽扇豆醇（10μg/耳）和豆甾醇（5.7μg/耳）也分别将该参数降低了 46±8%、51±7%和 62±7%。所有局部治疗均减少了急性 ICD 模型中炎性细胞的浸润。CdE 降低了急性 ICD 模型中 77±4%（1mg/耳）的耳水肿和炎性细胞浸润。CdE 的抗炎作用伴随着最小的不良反应发展。C. domestica 为开发局部抗炎药物提供了有希望的潜力。
图摘要 Cariniana domestica，俗称 jequitibá-roxo，在巴豆油诱导的小鼠急性和慢性刺激性接触性皮炎中表现出局部抗炎活性。从 C. domestica 果皮中获得的粗提取物（溶液和凝胶制剂）和不同馏分在初步毒理学研究（行为和生化参数）中表现出局部抗炎活性，且具有最小的不良反应。此外，HPLC 分析表明存在β-谷甾醇、豆甾醇和羽扇豆醇，它们在巴豆油诱导的急性刺激性接触性皮炎中也具有局部抗炎作用。我们的研究结果支持将该物种用作有前途的局部抗炎剂。
