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抗疟原虫和抗炎作用的一种抗疟疗法从 Wayana 美洲印第安人,法属圭亚那: takamalaimë (番樱桃 Psidium acutangulum Mart. 前直流。,桃金娘科)。

Antiplasmodial and anti-inflammatory effects of an antimalarial remedy from the Wayana Amerindians, French Guiana: takamalaimë (Psidium acutangulum Mart. ex DC., Myrtaceae).

机构信息

CNRS - UMR Ecologie des Forêts de Guyane (EcoFoG), Institut Pasteur de la Guyane, 23 Avenue Pasteur, BP6010, 97306 Cayenne Cedex, French Guiana.

Museum National d'Histoire Naturelle, UMR 208 PALoc, MNHN-IRD, BP 165, 97323 Cayenne Cedex, French Guiana.

出版信息

J Ethnopharmacol. 2015 May 26;166:279-85. doi: 10.1016/j.jep.2015.03.015. Epub 2015 Mar 16.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Field investigations highlighted the use of Psidium acutangulum Mart. ex DC (syn. P. persoonii McVaugh), a small tree used by the Wayana Amerindians in Twenke-Taluhwen and Antecume-Pata, French Guiana, for the treatment of malaria, and administered either orally in the form of a decoction or applied externally over the whole body. This use appears limited to the Wayana cultural group in French Guiana and has never been reported anywhere else. Our goal was to evaluate the antimalarial and anti-inflammatory activities of a P. acutangulum decoction to explain the good reputation of this remedy.

MATERIALS AND METHODS

Interviews with the Wayana inhabitants of Twenke-Taluhwen and Antecume-Pata were conducted within the TRAMAZ project according to the TRAMIL methodology, which is based on a quantitative and qualitative analysis of medicinal plant uses. A decoction of dried aerial parts of P. acutangulum was prepared in consistency with the Wayana recipe. In vitro antiplasmodial assays were performed on chloroquine-resistant FcB1 ([(3)H]-hypoxanthine bioassay) and 7G8 (pLDH bioassay) P. falciparum strains and on chloroquine sensitive NF54 ([(3)H]-hypoxanthine bioassay) P. falciparum strain. In vitro anti-inflammatory activity (IL-1β, IL-6, IL-8, TNFα) was evaluated on LPS-stimulated human PBMC and NO secretion inhibition was measured on LPS stimulated RAW murine macrophages. Cytotoxicity of the decoction was measured on L6 mammalian cells, PBMCs, and RAW cells. A preliminary evaluation of the in vivo antimalarial activity of the decoction, administered orally twice daily, was assessed by the classical four-day suppressive test against P. berghei NK65 in mice.

RESULTS

The decoction displayed a good antiplasmodial activity in vitro against the three tested strains, regardless to the bioassay used, with IC50 values of 3.3µg/mL and 10.3µg/mL against P. falciparum FcB1 and NF54, respectively and 19.0µg/mL against P. falciparum 7G8. It also exhibited significant anti-inflammatory activity in vitro in a dose dependent manner. At a concentration of 50µg/mL, the decoction inhibited the secretion of the following pro-inflammatory cytokines: TNFα (-18%), IL-1β (-58%), IL-6 (-32%), IL-8 (-21%). It also exhibited a mild NO secretion inhibition (-13%) at the same concentration. The decoction was non-cytotoxic against L6 cells (IC50>100µg/mL), RAW cells and PBMC. In vivo, 150µL of the decoction given orally twice a day (equivalent to 350mg/kg/day of dried extract) inhibited 39.7% average parasite growth, with more than 50% of inhibition in three mice over five. The absence of response for the two remaining mice, however, induced a strong standard deviation.

CONCLUSIONS

This study highlighted the in vitro antiplasmodial activity of the decoction of P. acutangulum aerial parts, used by Wayana Amerindians from the Upper-Maroni in French Guiana in case of malaria. Its antioxidant and anti-inflammatory potential, which may help to explain its use against this disease, was demonstrated using models of artificially stimulated cells.

摘要

民族药理学相关性

实地调查强调了 Psidium acutangulum Mart. ex DC(同义词 P. persoonii McVaugh)的使用,这种小树被法属圭亚那的 Wayana 美洲原住民在 Twenke-Taluhwen 和 Antecume-Pata 用于治疗疟疾,无论是口服形式的汤剂还是全身外用。这种用法似乎仅限于法属圭亚那的 Wayana 文化群体,在其他任何地方都没有报道过。我们的目标是评估 Psidium acutangulum 汤剂的抗疟和抗炎活性,以解释这种疗法的良好声誉。

材料和方法

根据 TRAMIL 方法,在 TRAMAZ 项目中对 Twenke-Taluhwen 和 Antecume-Pata 的 Wayana 居民进行了访谈,该方法基于对药用植物用途的定量和定性分析。按照 Wayana 的配方制备了干燥的 Psidium acutangulum 地上部分的汤剂。在体外抗疟活性试验中,采用氯喹耐药 FcB1([(3)H]-次黄嘌呤生物测定)和 7G8(pLDH 生物测定)恶性疟原虫株以及氯喹敏感 NF54([(3)H]-次黄嘌呤生物测定)恶性疟原虫株对干汤剂进行了检测。在体外抗炎症活性(IL-1β、IL-6、IL-8、TNFα)方面,采用 LPS 刺激的人 PBMC 进行了评估,并通过 LPS 刺激的 RAW 鼠巨噬细胞测量了 NO 分泌抑制作用。采用 L6 哺乳动物细胞、PBMC 和 RAW 细胞测量了汤剂的细胞毒性。通过经典的为期四天的对 P. berghei NK65 的抑制试验,初步评估了该汤剂在体内的抗疟活性,每日口服两次。

结果

该汤剂在体外对三种测试菌株均显示出良好的抗疟活性,无论使用哪种生物测定方法,其对恶性疟原虫 FcB1 和 NF54 的 IC50 值分别为 3.3µg/mL 和 10.3µg/mL,对恶性疟原虫 7G8 的 IC50 值为 19.0µg/mL。它还表现出显著的体外抗炎活性,呈剂量依赖性。在 50µg/mL 浓度下,汤剂抑制了以下促炎细胞因子的分泌:TNFα(-18%)、IL-1β(-58%)、IL-6(-32%)、IL-8(-21%)。在相同浓度下,它还表现出轻度的 NO 分泌抑制(-13%)。该汤剂对 L6 细胞(IC50>100µg/mL)、RAW 细胞和 PBMC 无细胞毒性。在体内,每天口服两次 150µL 汤剂(相当于 350mg/kg/天的干提取物)抑制了平均 39.7%的寄生虫生长,其中 5 只小鼠中有 3 只超过 50%的抑制率。然而,其余 2 只老鼠没有反应,导致标准差很大。

结论

本研究强调了法属圭亚那上马罗尼的 Wayana 美洲原住民在治疗疟疾时使用的 Psidium acutangulum 地上部分汤剂的体外抗疟活性。其抗氧化和抗炎潜力,这可能有助于解释它对这种疾病的使用,通过人工刺激细胞的模型得到了证明。

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