Curcumin prevents against osteoarthritis

doi:10.3969/j.issn.2095-4344.2015.02.022

Abstract

Abstract:

BACKGROUND: Curcumin is proved to possess anti-inflammatory, antioxidant and anti-apoptotic roles.
OBJECTIVE: To summarize and discuss the mechanisms and effects of curcumin used for the treatment of osteoarthritis
METHODS: PubMed, Embase, Elseveir databases were retrieved for relevant articles published from 1973 to 2014, with the key words of “osteoarthritis, curcumin, chondrocyte, articular cartilage” in English. After the quality of the included studies was evaluated, valid data were extracted and analyzed.
RESULTS AND CONCLUSION: Curcumin prevents the occurrence and development osteoarthritis by inhibiting oxidative enzyme and scavenging free radicals. Curcumin increases production of collagen type 2 through suppressing the reduction of cartilage matrix by matrix metalloproteinases. Anti-inflammatory reaction of curcumin can be achieved by inhibiting cytosolic phospholipase A2, cyclooxygenase-2, and 5-lipoxygenase. Curcumin inhibits interleukin-1β-induced apoptosis of chondrocytes and mitochondrial swelling. Results from clinical trials suggest that curcumin or its derivatives can reduce joint pain and improve the function of knee joints in patients with osteoarthritis. High-concentration curcumin in vitro have been demonstrated toxic effects.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

全文链接：

Key words: Osteoarthritis, Curcumin, Chondrocytes

CLC Number:

R318

Zhang Rui, Liu Shi-qing. Curcumin prevents against osteoarthritis[J]. Chinese Journal of Tissue Engineering Research, 2015, 19(2): 277-282.

Figures/Tables 5

姜黄素的生物利用度很低，当口服摄入姜黄素后，其吸收和代谢的分子在胃肠道内迅速被转化，仅一小部分会到达血液循环。临床试验证明：口服姜黄素的生物利用度相对较低[5]。姜黄素能迅速转变为姜黄素葡糖苷酸和姜黄素硫酸盐或者在小肠和肝内降解为六氢姜黄素[6]。姜黄素的代谢衍生品不具备与原来相同的生物活性，在某研究中，姜黄素的代谢产物比姜黄素对人结肠癌细胞产生前列腺素E2的抑制作用弱[7]。它易溶于甲醇、乙醇、丙酮、醋酸乙酯和碱液中，不溶于水，是一种光敏性很强的物质[8]。因此为了得到姜黄素溶液，它必须溶解在如乙醇、二甲亚砜、丙酮等有机溶剂中[9-10]。许多学者的体外实验都证实了姜黄素能溶解在二甲基亚砜中。 2.2 姜黄素在保护关节软骨及抑制骨关节炎的作用及相关机制 2.2.1 姜黄素能抗氧化骨关节炎软骨细胞的退化是由于一系列的机械因素、炎性介质、生化因素，尤其是基质金属蛋白酶和活性氧等共同作用导致的[11]。姜黄素在体外已被证明是一种有效地活性氧清除剂和活性氮提供剂[12-13]。Benqmark[14]认为姜黄素抗氧化效应强于常规维生素。姜黄素的很多功能基团都具有抗氧化作用。Priyadarsini等[15]指出酚基团对于姜黄素清除氧自由基是必要的，甲氧基的存在进一步的增加其抗氧化活性。有人认为，姜黄素在体内外可以清除自由基，其原因是通过抑制炎症相关的酶比如基质金属蛋白酶9的活性[16]，或者增强谷胱甘肽的合成实现抗氧化作用的[17]。在骨关节炎的病理和进展中，主要的活性氧物质为一氧化氮、过氧硝酸盐、超氧化物阴离子[18]。这些因素不仅是参与软骨细胞凋亡的有毒物质，而且是细胞代谢重要的信号分子[19]。通过抑制氧化作用的酶，清除自由基，螯合金属离子，完成抗氧化作用[20]。此外姜黄素的抗氧化活性还与其能够抑制脂质过氧化反应，增加超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化酶等的活性有关。Yang等[21]实验证实了这一点，姜黄素通过增加超氧化物歧化酶和过氧化氢酶的活性，并同时降低丙二醛的含量来完成抗氧化作用，见图2。 2.2.2 姜黄素可抗分解代谢研究表明，白细胞介素1β下调软骨细胞Ⅱ型胶原的表达，这一过程能够被姜黄素逆转。除了对Ⅱ型胶原的作用外，姜黄素还能逆转白细胞介素1β诱导的整合素β1的下调[22]。来自风湿性关节炎患者滑膜成纤维细胞培养研究表明巨噬细胞迁移抑制因子(MIF)上调了编码基质金属蛋白酶的信使RNA，这一过程可以被姜黄素抑制[23]。细胞因子白细胞介素 6超家族成员抑瘤素M(OSM)在骨关节炎患者中升高，与白细胞介素1β一起通过基质金属蛋白酶促进软骨退变[24]。姜黄素能通过抑制转录因子核因子kB的激活和核易位来抑制白细胞介素1β和抑瘤素M诱导的人软骨细胞基质金属蛋白酶1、基质金属蛋白酶3、基质金属蛋白酶9、基质金属蛋白酶13等基因的表达[25]。Mathy-Hartert等[26]揭示了高生物利用度的姜黄素通过抑制基质金属蛋白酶3从而对抗软骨细胞的分解，但却不能改变蛋白多糖的产生。新研究表明，姜黄素能抑"

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