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Khaya anthotheca(卫矛科)水提物对钒诱导的小鼠焦虑、记忆丧失和大脑及卵巢病变的改善作用。

Ameliorative effects of the aqueous extract of Khaya anthotheca (Welw.) C.DC (Meliaceae) in vanadium induced anxiety, memory loss and pathologies in the brain and ovary of mice.

机构信息

Department of Animal Biology and Physiology, Faculty of Science, University of Yaounde I, P.O. Box 812, Yaounde, Cameroon; Department of Psychology, Faculty of Arts, Letters and Social Science, University of Yaounde I, P.O. Box 7011, Yaounde, Cameroon.

Department of Veterinary Anatomy, Faculty of Veterinary Medicine, University of Ibadan, Ibadan, 20001, Nigeria.

出版信息

J Ethnopharmacol. 2021 Jul 15;275:114099. doi: 10.1016/j.jep.2021.114099. Epub 2021 Apr 5.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Ethnobotanical enquiries have revealed that Khaya anthotheca (Welw.) C.DC (Meliaceae) has anxiolytic properties and is used to alleviate vaginal dryness in postmenopausal women in Cameroon. The aim of this study was to evaluate the ameliorative effects of the aqueous extract of K. anthotheca in vanadium induced anxiety, memory loss and pathologies in the brain and ovary of mice.

MATERIAL AND METHODS

Forty neonatal female mice were used in this study. All animals received vanadium (3 mg/kg BW/72 h, by lactation and i.p.) for 20 weeks except the Control group. At 16 weeks old, mice were divided into 5 groups (n = 8): Control group received distilled water; V-group received vanadium (V) (3 mg/kg BW every 72 h i.p.), V + Vit E group received vitamin E (500 mg/kg BW/72 h) and vanadium (V) (3 mg/kg BW/72 h i.p, simultaneously). V + KA 125 and V + KA 250 groups received K. anthotheca extract at the doses of 125 and 250 mg/kg BW/day respectively and vanadium (V) (3 mg/kg BW/72 h i.p, simultaneously).The treatment was done per os at 10 mL/kg of volume of administration for 4 weeks. To evalute anxiolytic effects and spatial working memory improved by the extract in mice, the elevated open space test and Y maze test were used respectively. After sacrifice, brains were harvested and pathologies were assessed using cresyl violet stainning and immunohistochemistry (GFAP, Iba-1 and MBP), while pathologies in the ovaries were assessed using immunohistochemistry (Collagen type 1) and H&E stainning.

RESULTS

Results in the three sessions of elevated open space test showed that vanadium exposure resulted in a significant (p < 0.05; p < 0.01) increase of the latency of first entry in the slopes and a significant (p < 0.05; p < 0.01; p < 0.001) decrease of the time spent and number of entries in the slopes however, Khaya anthotheca treatment induced a significant (p < 0.05; p < 0.01) decrease of the latency of first entry in the slopes and a significant (p < 0.05; p < 0.01) increase of the time spent and number of entries in the slopes. In the Y maze test, vanadium exposure resulted in a significant decrease (p < 0.01) in the percentage of correct alternation, K. anthotheca extract at the dose of 250 mg/kg BW however induced a significant (p < 0.05) increase of this percentage of correct spontaneous alternation. In the brain, degeneration induced by vanadium exposure was marked by an increase of GFAP-immunoreactive cells, microgliosis and demyelination. The treatment with Khaya anthotheca extract at the dose of 250 mg/kg BW resulted in the preservation of cellular integrity in the same anatomical regions with reduced astroglial and microglial activation and prevented demyelination. In addition, vanadium exposure decreased Collagen type 1 expression in the ovaries and induced a deterioration of tertiary follicle. Khaya anthotheca treatment at the dose of 250 mg/kg BW induced an increase of expression of Collagen type 1 and alleviated deterioration of the microarchitecture of tertiary follicle induced by vanadium.

CONCLUSION

These effects induced by K. anthotheca extract could justify the traditional use of this plant in Cameroonian traditional medicine to manage anxiety. Therefore, to minimise vanadium induced toxicity, the plant should be given more emphasis as a candidate in developing a modern phytodrug.

摘要

民族药理学相关性

民族植物学研究表明,Khaya anthotheca(卫矛科)具有抗焦虑特性,用于缓解喀麦隆绝经后妇女的阴道干燥。本研究旨在评估 K. anthotheca 水提物对钒诱导的焦虑、记忆丧失以及小鼠大脑和卵巢病变的改善作用。

材料和方法

本研究使用了 40 只新生雌性小鼠。除对照组外,所有动物均通过哺乳和腹腔内注射(i.p.)接受 3 毫克/千克体重/72 小时的钒(V)处理 20 周。在 16 周龄时,将小鼠分为 5 组(n=8):对照组接受蒸馏水;V 组接受钒(V)(3 毫克/千克体重,每 72 小时 i.p.);V+Vit E 组接受维生素 E(500 毫克/千克体重/72 小时)和钒(V)(3 毫克/千克体重,同时 i.p.);V+KA 125 和 V+KA 250 组分别给予 K. anthotheca 提取物 125 和 250 毫克/千克体重/天的剂量,并同时接受钒(V)(3 毫克/千克体重,每 72 小时 i.p.)。治疗方法为口服给药,体积为 10 毫升/千克体重,持续 4 周。为评估提取物对小鼠的抗焦虑作用和空间工作记忆的改善作用,分别使用高架十字迷宫测试和 Y 迷宫测试。处死小鼠后,用 cresyl violet 染色和免疫组织化学(GFAP、Iba-1 和 MBP)评估大脑病理变化,用免疫组织化学(胶原类型 1)和 H&E 染色评估卵巢病理变化。

结果

高架十字迷宫测试的三个阶段的结果表明,暴露于钒会导致第一次进入斜坡的潜伏期显著增加(p<0.05;p<0.01),并且在斜坡上花费的时间和进入的次数显著减少(p<0.05;p<0.01;p<0.001);然而,K. anthotheca 处理会导致第一次进入斜坡的潜伏期显著减少(p<0.05;p<0.01),并且在斜坡上花费的时间和进入的次数显著增加。在 Y 迷宫测试中,暴露于钒会导致正确交替的百分比显著减少(p<0.01),但 K. anthotheca 提取物的剂量为 250 毫克/千克体重会导致正确自发交替的百分比显著增加(p<0.05)。在大脑中,钒暴露引起的变性表现为 GFAP-免疫反应细胞的增加、小胶质细胞增生和脱髓鞘。用 250 毫克/千克体重的 K. anthotheca 提取物治疗会导致同一解剖区域的细胞完整性得到保护,减少星形胶质细胞和小胶质细胞的激活,并防止脱髓鞘。此外,钒暴露会降低卵巢中胶原类型 1 的表达,并导致三级卵泡恶化。用 250 毫克/千克体重的 K. anthotheca 提取物处理会增加胶原类型 1 的表达,并减轻钒引起的三级卵泡微结构恶化。

结论

K. anthotheca 提取物的这些作用可以证明这种植物在喀麦隆传统医学中用于治疗焦虑的传统用途。因此,为了最小化钒引起的毒性,应该更加重视这种植物作为开发现代植物药的候选药物。

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