PDF(Pubmed)
Abstract：
The COVID-19 pandemic, caused by SARS-CoV-2, poses a significant global health threat. The spike glycoprotein S1 of the SARS-CoV-2 virus is known to induce the production of pro-inflammatory mediators, contributing to hyperinflammation in COVID-19 patients. Triphala, an ancient Ayurvedic remedy composed of dried fruits from three plant species-Emblica officinalis (Family Euphorbiaceae), Terminalia bellerica (Family Combretaceae), and Terminalia chebula (Family Combretaceae)-shows promise in addressing inflammation. However, the limited water solubility of its ethanolic extract impedes its bioavailability. In this study, we aimed to develop nanoparticles loaded with Triphala extract, termed \"nanotriphala\", as a drug delivery system. Additionally, we investigated the in vitro anti-inflammatory properties of nanotriphala and its major compounds, namely gallic acid, chebulagic acid, and chebulinic acid, in lung epithelial cells (A549) induced by CoV2-SP. The nanotriphala formulation was prepared using the solvent displacement method. The encapsulation efficiency of Triphala in nanotriphala was determined to be 87.96 ± 2.60% based on total phenolic content. In terms of in vitro release, nanotriphala exhibited a biphasic release profile with zero-order kinetics over 0-8 h. A549 cells were treated with nanotriphala or its active compounds and then induced with 100 ng/mL of spike S1 subunit (CoV2-SP). The results demonstrate that chebulagic acid and chebulinic acid are the active compounds in nanotriphala, which significantly reduced cytokine release (IL-6, IL-1β, and IL-18) and suppressed the expression of inflammatory genes (IL-6, IL-1β, IL-18, and NLRP3) (p < 0.05). Mechanistically, nanotriphala and its active compounds notably attenuated the expression of inflammasome machinery proteins (NLRP3, ASC, and Caspase-1) (p < 0.05). In conclusion, the nanoparticle formulation of Triphala enhances its stability and exhibits anti-inflammatory properties against CoV2-SP-induction. This was achieved by suppressing inflammatory mediators and the NLRP3 inflammasome machinery. Thus, nanotriphala holds promise as a supportive preventive anti-inflammatory therapy for COVID-19-related chronic inflammation.
摘要：
COVID-19大流行，由SARS-CoV-2引起的，构成了重大的全球健康威胁。已知SARS-CoV-2病毒的刺突糖蛋白S1可诱导促炎介质的产生，导致COVID-19患者的炎症过度。Triphala,一种古老的阿育吠陀疗法，由来自三种植物种类的干果组成-Emblicaofficinalis（大齿科），Terminaliabellerica(FamilyCombretaceae),和Terminaliachebula（Combretaceae家族）-显示出解决炎症的希望。然而,其乙醇提取物的有限水溶性阻碍了其生物利用度。在这项研究中,我们的目标是开发装载Triphala提取物的纳米粒子，被称为“纳米无名氏”，作为药物输送系统。此外,我们研究了纳米无名氏及其主要化合物的体外抗炎特性，即没食子酸,鹰嘴豆酸,和chebulinic酸,在CoV2-SP诱导的肺上皮细胞（A549）中。使用溶剂置换法制备纳米无名氏制剂。基于总酚含量,测定Triphala在纳米arphala中的包封效率为87.96±2.60%。在体外释放方面，nanotarphala在0-8小时内表现出具有零级动力学的双相释放曲线。A549细胞用nanotarphala或其活性化合物处理，然后用100ng/mL的spikeS1亚基（CoV2-SP）诱导。实验结果表明，在纳米丝珠中，有活性的化合物是滑谷花酸和滑谷酸，显着减少细胞因子释放（IL-6，IL-1β，和IL-18）并抑制炎症基因（IL-6，IL-1β，IL-18和NLRP3)(p<0.05)。机械上,纳米丝路及其活性化合物显着减弱了炎症体机械蛋白的表达(NLRP3，ASC，和Caspase-1)(p<0.05)。总之,Triphala的纳米颗粒制剂增强了其稳定性，并具有抗CoV2-SP诱导的抗炎特性。这是通过抑制炎症介质和NLRP3炎性体机制来实现的。因此，纳米法拉有望作为COVID-19相关慢性炎症的支持性预防性抗炎治疗。
