Constituents of the anti-asthma herbal formula ASHMI^(TM) synergistically inhibit IL-4 and IL-5 secretion by murine Th2 memory cells,and eotaxin by human lung fibroblasts in vitro

OBJECTIVE： Anti-asthma herbal medicine intervention （ASHMITM）, a combination of three tradi- tional Chinese medicinal herbs developed in our laboratory, has demonstrated efficacy in both mouse models of allergic asthma, and a double-blind placebo-controlled clinical trial in patients with asthma. This study was designed to determine if the anti-inflammatory effects of individual herbal constituents of ASHMITM exhibited synergy. METHODS： Effects of ASHMI and its components aqueous extracts of Lingzhi （Ganoderma lucidum）, Kushen （Sophora flavescens） and Gancao （Glycyrrhiza uralensis）, on Th2 cytokine secretion by murine memory Th2 cells （D10.G4.1） and eotaxin-1 secretion by human lung fibroblast （HLF-1） cells were determined by measuring levels in culture supernatants by enzyme- linked immunosorbent assay. Potential synergistic effects were determined by computing interaction indices from concentration-effect curve parameters. RESULTS： Individual Lingzhi, Kushen and Gancao extracts and ASHMI （the combination of individual extracts） inhibited production of interleukin （IL）-4 and IL-5 by murine memory Th2 cells and eotaxin-1 production by HLF-1 cells. The mean 25%-inhibitory-concentration （IC2s） values （mg/mL） forASHMI, Lingzhi, Kushen and Gancao for IL-4 production were 30.9, 79.4, 123, and 64.6, respectively; for IL-5 production were 30.2, 263, 123.2 and 100, respectively; for eotaxin-1 were 13.2, 16.2, 30.2, and 25.1, respectively. The IC50values （mg/mL） for ASHMI, Lingzhi, Kushen and Gancao for IL-4 production were 158.5, 239.9, 446.7, and 281.8, respectively; for eotaxin-1 were 38.1, 33.1, 100, and 158.5, respectively. The interaction indices of ASHMI constituents at IC25 were 0.35 for IL-4, 0.21 for IL-5 and 0.59 for eotaxin-l. The interaction indices at IC^0 values were 0.50 for IL-4 and 0.62 for eotaxin-1 inhibition. Inhibition of IL-5 did not reach IC^0 values. All interaction indices were below 1 which indicated synergy. CONCLUSION： By comparing the interaction index values, we find that constituents in ASHMITM synergistically inhibited eotaxin-1 production as well as Th2 cytokine production.

Neuroinflammation in mild respiratory COVID‑19:insights into cognitive impairment in milder cases

Severe acute respiratory syndrome coronavirus 2(SARSCoV-2)infection has been extensively shown to cause many neurological sequelae,and cognitive deficits(known as“brain fog”)may particularly and widely occur even in individuals with mild symptoms[1].Peripheral hyperinflammation as well as central nervous system(CNS)local immune responses may synergistically contribute to brain autoimmune injury.In addition to the direct neuroinvasion of SARS-CoV-2 and nonimmune effects such as severe systemic hypoxemia and vascular thrombosis,the central mechanism by which SARSCoV-2 accelerates cognitive-related symptoms may be related to immune effects[2].However,the precise neuroinflammatory mechanisms of SARS-CoV-2 infection have not been fully established.Fernández-Casta-da et al.[3]provided direct evidence and unique insights into the potential mechanism of cognitive impairment in mild respiratory coronavirus disease 2019(COVID-19)cases.