PAIN RECEPTOR MEDI ANTI-INFLAMMATORY ACTIV. OF ECHINACEA, HYPERICUM SPECIES/WURTE

TRP(瞬时受体电位)、CB(大麻素)和ASCI(酸感)通道被认为起作用 一起感知、传递和整合疼痛反应和相关的炎症反应。 特别是，TRPV1与多种内源和外源分子和刺激相互作用，并 被认为是整合炎症性疼痛的关键组成部分。项目3将调查关系 在活性紫锥菊和金丝桃组分与TRPV1等通道之间。它将测试 假设紫锥菊和金丝桃含有对一系列TRPV1-1具有生物活性的成分 相关受体，以及紫锥菊的生化成分通过 其作用机制与TRPV1激动剂辣椒素不同。在建议的研究中，离子通道 将使用瞬时表达两个模型来检测生物活性：1)青蛙卵母细胞系统 筛选多个植物组分，以及2)人类HEK293T细胞模型，用于更详细地评估 植物成分在整合炎性疼痛中的作用。具体目标1：评估广度 紫锥菊和金丝桃对Trp、CB和ASCI通道的生物活性。这些实验将揭示 这些提取是否激活了TRPV1以外的通道，以及每个活动是否由 植物成分的明显互补。具体目标2：确定松果菊属成分(S)和 金丝桃属，利用生物活性引导的分级来激发TRPV1通道反应。摘录将会是 反复分级，测试TRPV1的活性，并对化学成分进行分析评估。 我们的目标是确定诱导TRPV1生物活性的特定化合物和植物化合物类别。 具体目标3：通过紫锥菊成分鉴定TRPV1生物活性的机制。炎症和 痛苦是错综复杂的相互联系。在这个目标中，我们试图描述紫锥菊提取物和 成分与其他激动剂和拮抗剂相互作用。此外，转录本分析，平行 通过抗炎和促炎反应的分析，将揭示基因和信号网络受到 紫锥菊成分以TVPR1依赖的方式。总而言之，这些研究将解决 这些植物药可能影响TRPV1/介导的疼痛和神经系统整合的细胞机制 炎症反应。

TRP (transient receptor potential), CB (cannabinoid) and ASCI (acid-sensing) channels are thought to act together to sense, transmit, and integrate the pain response and the associated inflammatory responses. TRPV1, in particular, interacts with a multiple endogenous and exogenous molecules and stimuli, and is considered a key component in the integration of inflammatory pain. Project 3 will investigate relationships between bioactive Echinacea and Hypericum constituents and TRPV1 and other channels. It will test the hypotheses that Echinacea and Hypericum contain constituents with bioactivity against a range of TRPV1- related receptors, and that biochemical constituents of Echinacea induce pain-receptor responses by mechanisms distinct from those of capsaicin, a TRPV1 agonist. For the proposed studies, ion channel bioactivity will be assayed using transient-expression two models: 1) a frog oocyte system for initial screenings of multiple plant fractions, and 2) a human HEK293t cell model for more detailed evaluation of the role of the plant constituents in integration of inflammatory pain. Specific Aim 1: Evaluate the breadth of bioactivity of Echinacea and Hypericum on TRP, CB, and ASCI channels. These experiments will reveal whether these extracts activate channels other than TRPV1, and whether each activity is invoked by a distinct complement of botanical constituents. Specific Aim 2: Identify constituent(s) of Echinacea and Hypericum that evoke TRPV1-channel responses using bioactivity-guided fractionation. Extracts will be iteratively fractionated, tested for TRPV1 activation, and analytically evaluated for chemical composition. Our goal is to identify particular compounds and classes of plant compounds that induce TRPV1 bioactivity. Specific Aim 3: Identify mechanisms of TRPV1 bioactivity via Echinacea constituents. Inflammation and pain are complexly interrelated. In this aim, we seek to characterize how Echinacea extracts and constituents interact with other agonists and antagonists. Furthermore, transcriptomic analyses, in parallel with assays of anti- and pro- inflammatory responses, will reveal genetic and signaling networks affected by Echinacea constituents in a TVPR1-dependent manner. Taken together, these studies will address the cellular mechanisms by which these botanicals might influence TRPV1/-mediated integration of pain and inflammatory responses.