Chittasupho Chuda, Umsumarng Sonthaya, Srisawad Kamonwan, Arjsri Punnida, Phongpradist Rungsinee, Samee Weerasak, Tingya Wipawan, Ampasavate Chadarat, Dejkriengkraikul Pornngarm
Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand.
Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai 50100, Thailand.
Pharmaceutics. 2024 Jun 2;16(6):751. doi: 10.3390/pharmaceutics16060751.
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- (Family Euphorbiaceae), (Family Combretaceae), and (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 (, , , and ) ( < 0.05). Mechanistically, nanotriphala and its active compounds notably attenuated the expression of inflammasome machinery proteins (NLRP3, ASC, and Caspase-1) ( < 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.
由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起的2019冠状病毒病大流行对全球健康构成了重大威胁。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2019冠状病毒病患者出现炎症风暴。三果木，一种古老的阿育吠陀药物，由三种植物的干果组成——（大戟科）、（使君子科）和（使君子科）——在解决炎症方面显示出前景。然而，其三果木乙醇提取物的水溶性有限，阻碍了其生物利用度。在本研究中，我们旨在开发负载三果木提取物的纳米颗粒，称为“纳米三果木”，作为一种药物递送系统。此外，我们研究了纳米三果木及其主要化合物，即没食子酸、诃子鞣酸和诃子次酸，在由CoV2-SP诱导的肺上皮细胞（A549）中的体外抗炎特性。纳米三果木制剂采用溶剂置换法制备。基于总酚含量，三果木在纳米三果木中的包封率测定为87.96±2.60%。在体外释放方面，纳米三果木表现出双相释放曲线，在0-8小时内呈零级动力学。用纳米三果木或其活性化合物处理A549细胞，然后用100 ng/mL的刺突S1亚基（CoV2-SP）诱导。结果表明，诃子鞣酸和诃子次酸是纳米三果木中的活性化合物，它们显著降低了细胞因子释放（IL-6、IL-1β和IL-18），并抑制了炎症基因（、、、和）的表达（P<0.05）。从机制上讲，纳米三果木及其活性化合物显著减弱了炎性小体机制蛋白（NLRP3、ASC和半胱天冬酶-1）的表达（P<0.05）。总之，三果木的纳米颗粒制剂提高了其稳定性，并对CoV2-SP诱导表现出抗炎特性。这是通过抑制炎症介质和NLRP3炎性小体机制实现的。因此，纳米三果木有望作为一种支持性预防性抗炎疗法用于治疗与2019冠状病毒病相关的慢性炎症。
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