The Important Herbal Pair for the Treatment of COVID-19 and Its Possible Mechanisms

Background: Corona Virus Disease 2019 (COVID-19) is an unprecedented disaster for people around the world. Many studies have shown that traditional Chinese medicines(TCM) are indeed effective in treating COVID-19. However, it is a hard work to find the most effective combination laws among numerous herbs as well as its potential mechanisms. The purpose of this article is to explore the combination laws of traditional Chinses medicine(TCM) prescriptions and pick out the most important herbal pair for treating COVID-19 and analyze the active components and potential mechanisms. Methods: We first systematically sorted out the TCM prescriptions recommended by leading experts for treating COVID-19 and the specific herbs they contained in different stages of disease. Next, the association rule approach was employed to examine the distribution and combination laws among these TCM prescription, and then picked out the most important herbal pair. On this basis, we further investigated the active ingredients and potential targets in the selected herbal pair by a network pharmacology approach. Result: We obtained 32 association rules for herb combinations in the process of TCM treatment for COVID-19. It was found that the combination of Amygdalus Communis Vas(ACV) and Ephedra sinica Stapf (ESS) had the highest confidence degree and lift value as well as high support degree, which can be used in almost all stages of COVID-19, so ACV and ESS (AE) was selected as the most important herbal pair. There were 26 active ingredients and 44 potential targets, which may be relate to the herbal pair of AE against COVID-19. The main active ingredients of AE against COVID-19 are quercetin, kaempferol, luteolin and the potential important targets are Interleukin 6 (IL-6), Mitogen-activated Protein Kinase 1 (MAPK)1, MAPK8, Interleukin-1β (IL-1β), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) p65 subunit (RELA) and so on. The protein-protein interaction (PPI) cluster demonstrated that IL-6 was the seed in the cluster, which plays an important role in connecting other nodes in the PPI network. The significant pathways mainly involved in tumor necrosis factor (TNF), Toll-like receptor (TLR), hypoxia-inducible factor-1 (HIF-1), nucleotide-binding oligomerization domain (NOD)-like receptor(NLRs). Conclusion: Amygdalus Communis Vas and Ephedra sinica Stapf was the most important herbal pair in the treatment of COVID-19. The main active ingredients of AE against COVID-19 were quercetin, kaempferol, luteolin and the important targets were IL-6，MAPK1, MAPK8, IL-1β, RELA and so on. AE may have therapeutic effects against COVID-19 by affecting the pathological processes such as inflammatory and immune responses, cell apoptosis, hypoxia damage and other pathological processes through multiple components, multiple targets and multiple pathways.

Ephedra sinica Stapf and Gypsum Attenuates Heat-Induced Hypothalamic Inflammation in Mice

Ephedra sinica Stapf (EH) exert toxic effects, such as excitability, cardiac arrhythmia, and others. On the contrary, in traditional herbal medicine, EH and gypsum (GF) are used most often to treat symptoms caused by external stressors. The hypothalamus plays a crucial role in thermal homeostasis. Inflammatory response in the hypothalamus by thermal stressors may affect thermal and energy homeostasis. This study investigates the effect of EH and GF against heat-induced mouse model. Mice were divided into four groups: saline, saline plus heat, EH plus heat, and GF plus heat treated groups. Heat stress was fixed at 43 °C for 15 min once daily for 3 days. Weight and ear and rectal temperature measurements were made after terminating heat stress. Hypothalamus tissue was collected to evaluate the HSP70, nuclear factor kappa-Β (NF-kB), and interleukin (IL)-1β protein expression levels. EH and GF treatment suppressed the increased body temperature. EH significantly ameliorated heat-induced body weight loss, compared to gypsum. Regulatory effects of EH and GF for body temperature and weight against heat stress were mediated by IL-1β reduction. EH showed significant HSP70 and NF-kB inhibition against heat stress. EH and GF contribute to the inhibition of heat-induced proinflammatory factors and the promotion of hypothalamic homeostasis.

Нангиад зээргэний (EphedrasinicaStapf.) биохимийн судалгаа

We have determined some biochemical properties including the moisture, ash, protein, nitrogen, cellulose, lignin, lipids and fatty acids in aerial shoot systems and root systems of the Ephedra sinica Stapf. From the test results, cellulose contents were 19.12% in aerial shoot systems and 20.23% in root systems. Thus, this indicates that the aerial shoot systems of Ephedra sinica Stapf. are promising raw materials to synthesize polysaccharides.Lipid and lipid like substance components in seeds, aerial shoot systems and root systems of the Ephedra sinica Stapf. Seed contain 71.39% of all lipid and lipid like substances other origins of Ephedra sinica Stapf contain comparatively minimum amount of all lipids. From the study of fatty acids was contained in Ephedra sinica Stapf we identified nine different fatty acids in which the biologically active fatty acids, linoleic acid was contained up to 42% in aerial shoot systems. It is possible to use it for medical treatments because it is a major ingredient in F vitamin.Analysis of amino acid contents was carried out by thin layer chromatography. As a result, total of 15 amino acids including all non substituted amino acids were identified. Metionin content (12.5%) was higher than any other amino acids in Ephedra sinica Stapf.