提取自Nyctanthes arbor-tritis和Tagetes patula的类胡萝卜素复方制剂保护D-半乳糖诱导的小鼠皮肤衰老
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Saraswathi Vidya Bhavan's College of Pharmacy, Kalyan Shil Road, Sonarpada, Dombivli (E), Maharashtra 421204, India

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Formulation Containing Phytosomes of Carotenoids from Nyctanthes arbor-tristis and Tagetes patula Protect D-galactose Induced Skin Aging in Mice
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Saraswathi Vidya Bhavan's College of Pharmacy, Kalyan Shil Road, Sonarpada, Dombivli (E), Maharashtra 421204, India

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    摘要:

    背景:类胡萝卜素在延缓衰老中发挥重要作用。Nyctanthes arbor-tristis的橙色管状花萼所含藏红花素属于一类脱辅基胡萝卜素,是藏红花柱头的主要成分。由于藏红花素存在于桔黄色的管状萼中,它可替代藏红花,应用在医药和美容产品中。Tagetes patula L花瓣中的叶黄素是另一种普遍的类胡萝卜素,具有抗氧化和诸多有益健康的作用。类胡萝卜素暴露在空气中很不稳定,采用磷脂复合物包埋是提高这类成分稳定性的一种常用方法。制备磷脂复合物具有提高分子稳定性和生物利用度的双重优势。目的:本研究将富含藏红花素和叶黄素的提取物包埋在磷脂复合物中,以提升制剂的稳定性和功效。方法:从Nyctantes arbor-tristis L.管状花萼和Tagetes patula L.花瓣获得富含类胡萝卜素的提取物(藏红花素和叶黄素含量标准化),利用水化脂质膜技术制备包埋了富含类胡萝卜素提取物的磷脂复合物,然后将该复合物掺入凝胶基质中,并根据ICH指南评估凝胶制剂的稳定性。通过D-半乳糖诱导的衰老模型评价该制剂的功效。对白化小鼠给予D-半乳糖(100 mg/kg bwsc.)连续42天,诱导皮肤老化。局部施用凝胶制剂42天。通过相关生化参数,即谷胱甘肽和丙二醛(MDA)的变化,以及对局部治疗后皮肤样品的组织病理学分析,来评估该制剂对皮肤老化的影响。通过RT-PCR检测皮肤样品中 I型胶原蛋白和elastin基因的表达。结果:磷脂复合物中藏红花素和叶黄素的包埋率(%w/w)分别为60.20%和50.81%。加速稳定性研究表明,类胡萝卜素(即藏红花素和叶黄素)的稳定性均有改善,三个月后制剂中藏红花素和叶黄素的含量在99.98% w/w至99.85% w/w之间。与未治疗组相比,复方制剂组显著增厚真皮和表皮层(P < 0.05)并提高皮肤的GSH水平,显示出强效抗衰老活性。凝胶制剂局部治疗上调I型胶原蛋白和elastin的基因表达。与未治疗组相比,治疗组MDA水平下调,表明脂质过氧化显著降低。结论:藏红花素和叶黄素可能通过上调I型胶原蛋白和elastin基因表达防止皮肤老化。这些基因上调导致表皮和真皮层厚度增加,同时缓解皮肤氧化应激。将富含类胡萝卜素的Nyctanthes arbor-tritis和Tagetes patula提取物包埋在磷脂复合物中,提高了制剂的稳定性和功效。

    Abstract:

    Background: Carotenoids play important role in delay of aging process. Orange coloured tubular calyx of flowers of Nyctanthes arbor-tristis contains crocin, an apocarotenoid which forms a major component of stigma of saffron. Due to presence of crocin in orange coloured tubular calyx of Nyctanthes arbor-tristis, it can be used as an economical substitute to saffron for its medicinal and cosmetic utilities. Lutein from flower petals of Tagetes patula L., is another popular carotenoid which has antioxidant effect and many health benefits. The carotenoids are highly unstable when exposed to atmosphere. One of the ways to improve stability of these phytoconstituents, is their entrapment in phytosomes. Preparation of phytosomes will have dual advantages of improving stability as well as bioavailability of molecule. Objective: In the present study crocin and lutein rich extracts were entrapped into phytosomes to improve stability and efficacy of topical preparation. Methods: The phytosomes of Carotenoid rich extract of tubular calyx of Nyctanthes arbor-tristis L. and the petals of Tagetes patula L. (standardized for crocin and lutein content) were prepared using lipid film hydration technique and these phytosomes were then incorporated into gel base. The gel formulation was evaluated for stability as per ICH guidelines. Efficacy of formulation was evaluated by d-galactose induced aging model. Aging in skin was induced by administration of d-galactose (100 mg/kg bwsc.) to albino mice for 42 days. The gel formulation was applied topically for 42 days. Then the effect of formulation on skin aging was evaluated by estimation of biochemical parameters viz. glutathione and malondialdehyde (MDA) and histopathological studies of treated skin samples. Expression of COL type I and elastin genes in skin samples was also carried out by RT-PCR. Results: Percent entrapment (%w/w) of crocin and lutein in phytosomes were found to be 60.20% and 50.81%, respectively. Accelerated stability studies showed improvement in stability of carotenoids viz. crocin and lutein and the content of crocin and lutein in formulation was found in the range of 99.98% w/w to 99.85% w/w at the end of three months. The formulation containing extract of Phytosomes of carotenoid rich extracts of Nyctanthes arbor-tristis L. and the petals of Tagetes patula L. exhibited potent antiaging activity through significant (P < 0.05) increase in dermal and epidermal layers, and increase in GSH levels of skin as compared to the untreated group. The treatment with the gel formulation revealed upregulation of collagen type I and elastin genes. There was significant reduction in lipid peroxidation as revealed through reduction in MDA levels as compared to untreated group. Conclusion: Crocin and lutein have potential to prevent skin aging via upregulation of collagen type I gene and elastin gene. Upregulation of genes resulted into increase in the thickness of epidermal and dermal layer along with reduction in oxidative stress in skin. Entrapment of carotenoid rich extracts of Nyctanthes arbor-tristis and Tagetes patula in phytosomes enhanced the stability and efficacy of the formulation.

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  • 在线发布日期: 2023-11-21
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