Effect of a Herbal-Leucine mix on the IL-1β-induced cartilage degradation and inflammatory gene expression in human chondrocytes.
Effect of a Herbal-Leucine mix on the IL-1β-induced cartilage degradation and inflammatory gene expression in human chondrocytes.
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DOI：
10.1186/1472-6882-11-66
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发表时间：
2011-08-19
影响因子：
--
通讯作者：
Haqqi TM
中科院分区：
文献类型：
--
作者：
Akhtar N;Miller MJ;Haqqi TM
关节疾病的常规治疗通常能有效缓解症状，但也会产生显著的副作用，并不能减缓疾病的进展。几种天然物质已被证明能有效缓解骨关节炎(OA)的症状，初步证据表明，其中一些化合物可能对疾病的病程产生有利影响。本研究的目的是观察毛钩藤、博斯威利、独活、L亮氨酸等中药与氨基酸混合物对IL-1β诱导的人骨关节炎软骨细胞和软骨组织产生一氧化氮(NO)、糖胺聚糖(GAG)、基质金属蛋白酶(MMPs)、聚集素(Acan)和II型胶原(COL2A1)的影响。用中药-亮氨酸混合物(1~10μg/m l)处理原代骨性关节炎软骨细胞或骨性关节炎软骨细胞，然后用IL-1β(5 ng/m l)刺激。实时定量聚合酶链式反应(Real time-β，RT-PCR法)检测黄连对IL-1诱导的大鼠肺组织诱导型一氧化氮合酶、基质金属蛋白酶-9、基质金属蛋白酶-13、黏附分子及COL2A1基因表达的影响。使用商用试剂盒估计培养上清液中NO和GAG的释放。在这些体外实验中，HLM被发现是一种有效的抗炎药，其证据是强烈地抑制了IL-1β刺激的OA软骨细胞诱导型一氧化氮合酶、基质金属蛋白酶-9和基质金属蛋白酶-13的表达和一氧化氮的产生(p<；0.05)。支持这些基因表达结果的是，IL-1β诱导的软骨基质破坏，从软骨外植体释放的GAG来证明，也被显著阻止(p<；0.05)。此外，在中药-亮氨酸混合物的存在下，IL-1β刺激的骨性关节炎软骨细胞中Acan和COL2A1的表达也被上调(p<；0.05)。其抑制作用是通过抑制IL-1β诱导的人骨关节炎软骨细胞核因子-kB的活化而实现的。我们的数据提示，HLM可能是关节炎的软骨保护和抗炎药物，将软骨细胞的基因表达从分解代谢方向转变为合成代谢和再生方向，因此该方法可能作为一种新的辅助治疗/预防药物用于骨关节炎或损伤的修复。
Conventional treatments for the articular diseases are often effective for symptom relief, but can also cause significant side effects and do not slow the progression of the disease. Several natural substances have been shown to be effective at relieving the symptoms of osteoarthritis (OA), and preliminary evidence suggests that some of these compounds may exert a favorable influence on the course of the disease. The objective of this study was to investigate the anti-inflammatory/chondroprotective potential of a Herbal and amino acid mixture containing extract of the Uncaria tomentosa, Boswellia spp., Lepidium meyenii and L-Leucine on the IL-1β-induced production of nitric oxide (NO), glycosaminoglycan (GAG), matrix metalloproteinases (MMPs), aggrecan (ACAN) and type II collagen (COL2A1) in human OA chondrocytes and OA cartilage explants. Primary OA chondrocytes or OA cartilage explants were pretreated with Herbal-Leucine mixture (HLM, 1-10 μg/ml) and then stimulated with IL-1β (5 ng/ml). Effect of HLM on IL-1β-induced gene expression of iNOS, MMP-9, MMP-13, ACAN and COL2A1 was verified by real time-PCR. Estimation of NO and GAG release in culture supernatant was done using commercially available kits. HLM tested in these in vitro studies was found to be an effective anti-inflammatory agent, as evidenced by strong inhibition of iNOS, MMP-9 and MMP-13 expression and NO production in IL-1β-stimulated OA chondrocytes (p < 0.05). Supporting these gene expression results, IL-1β-induced cartilage matrix breakdown, as evidenced by GAG release from cartilage explants, was also significantly blocked (p < 0.05). Moreover, in the presence of herbal-Leucine mixture (HLM) up-regulation of ACAN and COL2A1 expression in IL-1β-stimulated OA chondrocytes was also noted (p < 0.05). The inhibitory effects of HLM were mediated by inhibiting the activation of nuclear factor (NF)-kB in human OA chondrocytes in presence of IL-1β. Our data suggests that HLM could be chondroprotective and anti-inflammatory agent in arthritis, switching chondrocyte gene expression from catabolic direction towards anabolic and regenerative, and consequently this approach may be potentially useful as a new adjunct therapeutic/preventive agent for OA or injury recovery.
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DOI：
10.1097/00075197-200101000-00008
发表时间：
2001-01-01
影响因子：
3.1
作者：
Kimball, SR;Jefferson, LS
通讯作者：
Jefferson, LS
DOI：
10.1128/cdli.12.5.575-580.2005
发表时间：
2005-05-01
期刊：
CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY
影响因子：
--
作者：
Chevrier, MR;Ryan, AE;Via, CS
通讯作者：
Via, CS
DOI：
10.1152/ajpendo.00510.2004
发表时间：
2005-05-01
影响因子：
5.1
作者：
Escobar, J;Frank, JW;Davis, TA
通讯作者：
Davis, TA
影响因子：
--
作者：
Miller, Mark J S;Ahmed, Salahuddin;Haqqi, Tariq M
通讯作者：
Haqqi, Tariq M
影响因子：
5.4
作者：
KULKARNI, RR;PATKI, PS;PATWARDHAN, B
通讯作者：
PATWARDHAN, B