ABSTRACT
Tsaoko Fructus, the dried ripe fruit of Amomum tsao-ko Crevost & Lemarié, is used as both medicinal material and food additive. This review summarized the traditional uses, botany, phytochemistry, and pharmacological progress on Tsaoko Fructus. One classical prescription and the other 11 representative prescriptions containing Tsaoko Fructus were reviewed. The indications of these prescriptions are major in treating spleen and stomach disorders and epidemic febrile diseases including malaria. At least 209 compounds have been isolated and identified from Tsaoko Fructus, most of which belong to terpenoids, phenylpropanoids, and organic acids. Essential oil, crude extract, and some compounds were observed to have pharmacological activities such as anti-biotics, anti-inflammation, antioxidant, mostly via in vitro experiments. However, the mechanism of its medicinal uses remains unclear. This review provides a comprehensive understanding of Tsaoko Fructus, which will be beneficial to exploring the mechanism and potential medicinal applications of Tsaoko Fructus, as well as developing a rational quality control system for Tsaoko Fructus as a medicinal material in the future. Supplementary Information: The online version contains supplementary material available at 10.1007/s11101-021-09793-x.
ABSTRACT
Background: Deep venous thrombosis (DVT) highly occurs in patients with severe COVID-19 and probably accounted for their high mortality. DVT formation is a time-dependent inflammatory process in which NETosis plays an important role. However, whether ginsenoside Rg5 from species of Panax genus could alleviate DVT and its underlying mechanism has not been elucidated. Methods: The interaction between Rg5 and P2RY12 was studied by molecular docking, molecular dynamics, surface plasmon resonance (SPR), and molecular biology assays. The preventive effect of Rg5 on DVT was evaluated in inferior vena cava stasis-induced mice, and immunocytochemistry, Western blot, and calcium flux assay were performed in neutrophils from bone marrow to explore the mechanism of Rg5 in NETosis via P2RY12. Results: Rg5 allosterically interacted with P2RY12, formed stable complex, and antagonized its activity via residue E188 and R265. Rg5 ameliorated the formation of thrombus in DVT mice; accompanied by decreased release of Interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α in plasma; and suppressed neutrophil infiltration and neutrophil extracellular trap (NET) release. In lipopolysaccharide- and platelet-activating factor-induced neutrophils, Rg5 reduced inflammatory responses via inhibiting the activation of ERK/NF-κB signaling pathway while decreasing cellular Ca2+ concentration, thus reducing the activity and expression of peptidyl arginine deiminase 4 to prevent NETosis. The inhibitory effect on neutrophil activity was dependent on P2RY12. Conclusions: Rg5 could attenuate experimental DVT by counteracting NETosis and inflammatory response in neutrophils via P2RY12, which may pave the road for its clinical application in the prevention of DVT-related disorders.
Subject(s)
COVID-19 , Venous Thrombosis , Animals , Ginsenosides , Mice , Molecular Docking Simulation , NeutrophilsABSTRACT
The current severe situation of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not been reversed and posed great threats to global health. Therefore, there is an urgent need to find out effective antiviral drugs. The 3-chymotrypsin-like protease (3CLpro) in SARS-CoV-2 serve as a promising anti-virus target due to its essential role in the regulation of virus reproduction. Here, we report an improved integrated approach to identify effective 3CLpro inhibitors from effective Chinese herbal formulas. With this approach, we identified the 5 natural products (NPs) including narcissoside, kaempferol-3-O-gentiobioside, rutin, vicenin-2 and isoschaftoside as potential anti-SARS-CoV-2 candidates. Subsequent molecular dynamics simulation additionally revealed that these molecules can be tightly bound to 3CLpro and confirmed effectiveness against COVID-19. Moreover, kaempferol-3-o-gentiobioside, vicenin-2 and isoschaftoside were first reported to have SARS-CoV-2 3CLpro inhibitory activity. In summary, this optimized integrated strategy for drug screening can be utilized in the discovery of antiviral drugs to achieve rapid acquisition of drugs with specific effects on antiviral targets.