Schapovalova Olesia, Gorlova Anna, de Munter Johannes, Sheveleva Elisaveta, Eropkin Mikhail, Gorbunov Nikita, Sicker Michail, Umriukhin Aleksei, Lyubchyk Sergiy, Lesch Klaus-Peter, Strekalova Tatyana, Schroeter Careen A
Caparica Faculdade de Ciencias e Tecnologia da Universidade Nova de Lisboa, NOVA Lisbon University, Lisbon, Portugal.
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University and Neuroplast BV, Maastricht, Netherlands.
Front Med (Lausanne). 2022 Aug 22;9:952977. doi: 10.3389/fmed.2022.952977. eCollection 2022.
While all efforts have been undertaken to propagate the vaccination and develop remedies against SARS-CoV-2, no satisfactory management of this infection is available yet. Moreover, poor availability of any preventive and treatment measures of SARS-CoV-2 in economically disadvantageous communities aggravates the course of the pandemic. Here, we studied a new immunomodulatory phytotherapy (IP), an extract of blackberry, chamomile, garlic, cloves, and elderberry as a potential low-cost solution for these problems given the reported efficacy of herbal medicine during the previous SARS virus outbreak.
The key feature of SARS-CoV-2 infection, excessive inflammation, was studied in and assays under the application of the IP. First, changes in tumor-necrosis factor (TNF) and lnteurleukin-1 beta (IL-1β) concentrations were measured in a culture of human macrophages following the lipopolysaccharide (LPS) challenge and treatment with IP or prednisolone. Second, chronically IP-pre-treated CD-1 mice received an agonist of Toll-like receptors (TLR)-7/8 resiquimod and were examined for lung and spleen expression of pro-inflammatory cytokines and blood formula. Finally, chronically IP-pre-treated mice challenged with LPS injection were studied for "sickness" behavior. Additionally, the IP was analyzed using high-potency-liquid chromatography (HPLC)-high-resolution-mass-spectrometry (HRMS).
LPS-induced release of TNF and IL-1β was reduced by both treatments. The IP-treated mice displayed blunted over-expression of SAA-2, ACE-2, CXCL1, and CXCL10 and decreased changes in blood formula in response to an injection with resiquimod. The IP-treated mice injected with LPS showed normalized locomotion, anxiety, and exploration behaviors but not abnormal forced swimming. Isoquercitrin, choline, leucine, chlorogenic acid, and other constituents were identified by HPLC-HRMS and likely underlie the IP immunomodulatory effects.
Herbal IP-therapy decreases inflammation and, partly, "sickness behavior," suggesting its potency to combat SARS-CoV-2 infection first of all via its preventive effects.
尽管已竭尽全力推广针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的疫苗接种并研发治疗方法，但目前仍没有令人满意的针对这种感染的管理措施。此外，在经济条件不利的社区中，SARS-CoV-2的任何预防和治疗措施都难以获得，这加剧了疫情的发展。鉴于在之前的SARS病毒爆发期间草药显示出的疗效，在此我们研究了一种新的免疫调节植物疗法（IP），即黑莓、洋甘菊、大蒜、丁香和接骨木果的提取物，作为解决这些问题的一种潜在低成本方案。
在应用IP的情况下，通过[具体实验名称1]和[具体实验名称2]试验研究了SARS-CoV-2感染的关键特征——过度炎症反应。首先，在脂多糖（LPS）刺激以及用IP或泼尼松龙处理后，测量人巨噬细胞培养物中肿瘤坏死因子（TNF）和白细胞介素-1β（IL-1β）浓度的变化。其次，长期用IP预处理的CD-1小鼠接受Toll样受体（TLR）-7/8激动剂瑞喹莫德，并检测促炎细胞因子在肺和脾中的表达以及血常规。最后，对长期用IP预处理并注射LPS攻击的小鼠进行“患病”行为研究。此外，使用高效液相色谱（HPLC）-高分辨率质谱（HRMS）对IP进行分析。
两种处理均降低了LPS诱导的TNF和IL-1β释放。用IP处理的小鼠在注射瑞喹莫德后，血清淀粉样蛋白A-2（SAA-2）、血管紧张素转换酶2（ACE-2）、CXC趋化因子配体1（CXCL1）和CXC趋化因子配体10（CXCL10）的过度表达减弱，血常规变化减小。注射LPS的用IP处理的小鼠表现出正常的运动、焦虑和探索行为，但强迫游泳行为无异常。通过HPLC-HRMS鉴定出异槲皮苷、胆碱、亮氨酸、绿原酸和其他成分，它们可能是IP免疫调节作用的基础。
草药IP疗法可减轻炎症，并在一定程度上减轻“患病行为”，这表明其首先通过预防作用对抗SARS-CoV-2感染的潜力。
