Shin Jin A, Oh Subin, Jeong Jong-Moon
Biotechnology Research Center, Ben's Lab., Co., Ltd., 17 Wauan-gil, Bongdam-eup, Hwasung-si, Gyeonggi-do, Republic of Korea.
Department of Bioscience, College of Engineering, The University of Suwon, 17 Wauan-gil, Bongdam-eup, Hwasung-si, Gyeonggi-do, Republic of Korea.
Phytomed Plus. 2021 Nov;1(4):100058. doi: 10.1016/j.phyplu.2021.100058. Epub 2021 Mar 18.
The corona virus disease 2019 (COVID-19) pandemic has highlighted the fact that there are few effective antiviral agents for treating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Although the very recent development of vaccines is an extremely important breakthrough, it remains unclear how long-lived such vaccines will be. The development of new agents therefore remains an important goal.
Given the multifaceted pathology of COVID-19, a combinatorial formulation may provide an effective treatment. BEN815, a natural nutraceutical composed of extracts from guava leaves (), green tea leaves (), and rose petals (), had previously shown to have a therapeutic effect on allergic rhinitis. We investigated whether BEN815 possesses anti-inflammatory, antiviral and antioxidant activities, since the combination of these effects could be useful for the treatment of COVID-19.
We examined the anti-inflammatory effects of BEN815 and its principal active components quercetin and epigallocatechin gallate (EGCG) in lipopolysaccharide (LPS)-induced RAW264.7 cells and in an LPS-challenged mouse model of endotoxemia. We also assessed the antioxidant activity, and antiviral effect of BEN815, quercetin, and EGCG in SARS-CoV-2-infected Vero cells.
The principal active ingredients in BEN815 were determined and quantified using HPLC. Changes in the levels of LPS-induced pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured by ELISA. Changes in the expression levels of cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) were analyzed using western blotting. Antioxidant assay was performed using DPPH and ABTS assay. SARS-CoV-2 replication was measured by immunofluorescence staining.
BEN815 significantly suppressed the induction of IL-6 and TNF-α as well as COX-2 and iNOS in LPS-induced RAW264.7 cells. In addition, BEN815 protected against LPS-challenged endotoxic shock in mice. Two major constituents of BEN815, quercetin and EGCG, reduced the induction of IL-6 and TNF-α as well as COX-2 and iNOS synthase in LPS-induced RAW264.7 cells. BEN815, quercetin, and EGCG were also found to have antioxidant effects. Importantly, BEN815 and EGCG could inhibit SARS-CoV-2 replications in Vero cells.
BEN815 is an anti-inflammatory, antiviral, and antioxidant natural agent that can be used to prevent and improve inflammation-related diseases, COVID-19.
2019年冠状病毒病（COVID-19）大流行凸显了一个事实，即治疗严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染的有效抗病毒药物很少。尽管最近疫苗的研发是一项极其重要的突破，但这些疫苗的有效期仍不清楚。因此，开发新的药物仍然是一个重要目标。
鉴于COVID-19的多方面病理，联合制剂可能提供有效的治疗方法。BEN815是一种天然营养保健品，由番石榴叶、绿茶和玫瑰花瓣提取物组成，此前已显示对过敏性鼻炎有治疗作用。我们研究了BEN815是否具有抗炎、抗病毒和抗氧化活性，因为这些作用的组合可能对治疗COVID-19有用。
我们在脂多糖（LPS）诱导的RAW264.7细胞和LPS攻击的内毒素血症小鼠模型中研究了BEN815及其主要活性成分槲皮素和表没食子儿茶素没食子酸酯（EGCG）的抗炎作用。我们还评估了BEN815、槲皮素和EGCG在感染SARS-CoV-2的Vero细胞中的抗氧化活性和抗病毒作用。
使用高效液相色谱法（HPLC）测定并定量BEN815中的主要活性成分。通过酶联免疫吸附测定（ELISA）测量LPS诱导的促炎细胞因子白细胞介素（IL）-6和肿瘤坏死因子（TNF）-α水平的变化。使用蛋白质免疫印迹法分析环氧合酶（COX）-2和诱导型一氧化氮合酶（iNOS）表达水平的变化。使用二苯基苦味酰基自由基（DPPH）和2,2'-联氮-双-3-乙基苯并噻唑啉-6-磺酸（ABTS）测定法进行抗氧化测定。通过免疫荧光染色测量SARS-CoV-2复制。
BEN815显著抑制LPS诱导的RAW264.7细胞中IL-6和TNF-α以及COX-2和iNOS的诱导。此外，BEN815可保护小鼠免受LPS攻击的内毒素休克。BEN815的两种主要成分槲皮素和EGCG减少了LPS诱导的RAW264.7细胞中IL-6和TNF-α以及COX-2和iNOS合酶的诱导。还发现BEN815、槲皮素和EGCG具有抗氧化作用。重要的是，BEN815和EGCG可抑制Vero细胞中的SARS-CoV-2复制。
BEN815是一种抗炎、抗病毒和抗氧化的天然药物，可用于预防和改善炎症相关疾病COVID-19。
