Pathak Manash Pratim, Patowary Pompy, Das Aparoop, Goyary Danswrang, Karmakar Sanjeev, Bhutia Yangchen D, Roy Probin Kumar, Das Sanghita, Chattopadhyay Pronobesh
Division of Pharmaceutical Technology, Defence Research Laboratory, Tezpur, India.
Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, India.
Clin Exp Pharmacol Physiol. 2021 Nov;48(11):1523-1536. doi: 10.1111/1440-1681.13555. Epub 2021 Aug 15.
Mast cell activation is initiated by two signalling pathways: immunoglobulin E (IgE)-dependent and IgE-independent pathway. It is reported that the IgE-independent type or pseudo-allergy pathway gets activated by G-protein-dependent activation of the mast cell. Recently, adiponectin (APN) receptors, AdipoR1, and AdipoR2 have been identified as G-protein-coupled receptors (GPCRs). Interestingly, APN replenishment is reported to activate the Nrf2/HO-1 signalling axis. However, no study has been performed interlinking the role of APN and the Nrf2/HO-1 signalling axis in pseudo-allergic reaction. In the present study, we evaluated the anti-pseudo-allergic effects of β-caryophyllene, an FDA-approved food additive, in activating AdipoR1/AdipoR2 and Nrf2/HO-1 axis signalling pathway. Compound 48/80 (C48/80)-induced systemic and cutaneous anaphylaxis-like shock in BALB/c mice was performed to assess the efficacy of β-caryophyllene (BCP). To assess the effect of BCP in anaphylactic hypotension, mean arterial pressure was measured in Wistar rats. Inhibitory properties of BCP in mast cell degranulation were estimated in rat peritoneal mast cells (RPMCs). ELISA was performed to estimate interleukin (IL)-6, tumour necrosis factor (TNF), IL-1β, IgE, ovalbumin (OVA)-IgE and APN and western blotting for protein expression of Nrf2/HO-1 and AdipoR1-AdipoR2. BCP dose-dependently inhibited systemic and cutaneous anaphylaxis-like shock induced by C48/80. BCP dose-dependently inhibited the mast cell degranulation followed by inhibition of histamine release. Also BCP dose-dependently activated the Nrf2/HO-1 and AdipoR1-AdipoR2 signalling axis pathway. Moreover, BCP reversed the drop in blood pressure when the haemodynamic parameters were accessed. Our findings suggest that BCP is a potent AdipoR1/AdipoR2-Nrf2/HO-1 axis pathway agonist that may suppress the IgE-independent pathway towards allergic response to secretagogues.
免疫球蛋白E（IgE）依赖性和IgE非依赖性通路。据报道，IgE非依赖性类型或假过敏通路通过肥大细胞的G蛋白依赖性激活而被激活。最近，脂联素（APN）受体AdipoR1和AdipoR2已被鉴定为G蛋白偶联受体（GPCR）。有趣的是，据报道补充APN可激活Nrf2/HO-1信号轴。然而，尚未有研究将APN的作用与Nrf2/HO-1信号轴在假过敏反应中的作用联系起来。在本研究中，我们评估了一种FDA批准的食品添加剂β-石竹烯在激活AdipoR1/AdipoR2和Nrf2/HO-1轴信号通路方面的抗假过敏作用。通过在BALB/c小鼠中诱导化合物48/80（C48/80）引起的全身和皮肤过敏样休克来评估β-石竹烯（BCP）的疗效。为了评估BCP在过敏性低血压中的作用，在Wistar大鼠中测量平均动脉压。在大鼠腹膜肥大细胞（RPMC）中评估BCP对肥大细胞脱颗粒的抑制特性。采用酶联免疫吸附测定（ELISA）法检测白细胞介素（IL）-6、肿瘤坏死因子（TNF）、IL-1β、IgE、卵清蛋白（OVA）-IgE和APN，并采用蛋白质印迹法检测Nrf2/HO-1和AdipoR1-AdipoR2的蛋白表达。BCP剂量依赖性地抑制C48/80诱导的全身和皮肤过敏样休克。BCP剂量依赖性地抑制肥大细胞脱颗粒，随后抑制组胺释放。此外，BCP剂量依赖性地激活Nrf2/HO-1和AdipoR1-AdipoR2信号轴通路。此外，在评估血流动力学参数时，BCP逆转了血压下降。我们的研究结果表明，BCP是一种有效的AdipoR1/AdipoR2-Nrf2/HO-1轴通路激动剂，可能抑制对促分泌剂过敏反应的IgE非依赖性通路。
