COVID-19: Is There Evidence for the Use of Herbal Medicines as Adjuvant Symptomatic Therapy?

Background: Current recommendations for the self-management of SARS-Cov-2 disease (COVID-19) include self-isolation, rest, hydration, and the use of NSAID in case of high fever only. It is expected that many patients will add other symptomatic/adjuvant treatments, such as herbal medicines. Aims: To provide a benefits/risks assessment of selected herbal medicines traditionally indicated for “respiratory diseases” within the current frame of the COVID-19 pandemic as an adjuvant treatment. Method: The plant selection was primarily based on species listed by the WHO and EMA, but some other herbal remedies were considered due to their widespread use in respiratory conditions. Preclinical and clinical data on their efficacy and safety were collected from authoritative sources. The target population were adults with early and mild flu symptoms without underlying conditions. These were evaluated according to a modified PrOACT-URL method with paracetamol, ibuprofen, and codeine as reference drugs. The benefits/risks balance of the treatments was classified as positive, promising, negative, and unknown. Results: A total of 39 herbal medicines were identified as very likely to appeal to the COVID-19 patient. According to our method, the benefits/risks assessment of the herbal medicines was found to be positive in 5 cases (Althaea officinalis, Commiphora molmol, Glycyrrhiza glabra, Hedera helix, and Sambucus nigra), promising in 12 cases (Allium sativum, Andrographis paniculata, Echinacea angustifolia, Echinacea purpurea, Eucalyptus globulus essential oil, Justicia pectoralis, Magnolia officinalis, Mikania glomerata, Pelargonium sidoides, Pimpinella anisum, Salix sp, Zingiber officinale), and unknown for the rest. On the same grounds, only ibuprofen resulted promising, but we could not find compelling evidence to endorse the use of paracetamol and/or codeine. Conclusions: Our work suggests that several herbal medicines have safety margins superior to those of reference drugs and enough levels of evidence to start a clinical discussion about their potential use as adjuvants in the treatment of early/mild common flu in otherwise healthy adults within the context of COVID-19. While these herbal medicines will not cure or prevent the flu, they may both improve general patient well-being and offer them an opportunity to personalize the therapeutic approaches

Activation of the mouse IL-2 gene by okadaic acid: synergy with interleukin-1

Interleukin-1 (IL-1) has potent immunoregulatory and inflammatory functions. Its activity is mediated by an 80-kDa receptor on the cell surface and leads to activation of other genes. The underlying molecular events are largely unknown. We investigated the role of phosphatases in activation of the IL-2 gene in EL4 thymoma cells. We found that the protein phosphatase PP1 and PP2A inhibitor okadaic acid (OA) alone was able to significantly stimulate IL-2 production by the IL-1-responsive EL4 subline EL4 5D3 and also by the IL-1-nonresponsive EL4 subline EL4D6/76. In the IL-1-responsive cell line OA strongly synergized with phorbol myristate acetate (PMA) and IL-1. In the IL-1-nonresponsive cell line OA synergized with PMA but not with IL-1. Under suboptimal conditions of PMA/OA synergy an additional synergistic effect of IL-1 was shown. This was true for IL-2 and IL-6 production. Sphingomyelinase or sphingosine had no detectable effect. The kinetics of OA- and PMA-induced expression of IL-2 mRNA and IL-2 protein was different. PMA induced maximal expression between 6 and 12 h and was almost undetectable at 24 h. OA-induced expression was first obvious at 12 h and continued longer than 36 h. In both cases IL-1 caused no shift in kinetics, but potentiated the effects of the different tumor promoters. Utilizing IL-2 promoter-CAT constructs we showed in transfection experiments that the synergistic effect was also evident on the transcriptional level. We conclude from the data that phosphatases play an important role for IL-2 expression and that IL-1 can use additional pathways of activation that are different from events induced by PMA or OA

Pleiotropic effect of okadaic acid on maturing mouse oocytes

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Induction of M-phase entry of prophase-blocked mouse oocytes through microinjection of okadaic acid, a specific phosphatase inhibitor

We report that a specific inhibitor of types 1 and 2A phosphatases, okadaic acid (OA), induces germinal vesicle break down (GVBD) and chromosome condensation when microinjected into denuded mouse oocytes maintained in prophase block by analogs of cAMP, inhibitors of phosphodiesterase, or a tumor-promoting phorbol ester. GVBD and chromosome condensation are also observed when incompetent oocytes are similarly injected with OA, this effect being dependent on the oocyte diameter. Marked changes in cell shape, cytoskeletal organization, and chromosome condensation with abnormal or abortive spindle formation are associated with such injections. The polar body is not formed. These results led to the conclusions that in mouse oocytes, OA acts distal to both the cAMP-modulated pathway involved in meiotic arrest and the inhibitory action exerted by tumor-promoting phorbol esters