The role of berberine in Covid-19: potential adjunct therapy.

Coronavirus disease 2019 (Covid-19) is a global diastrophic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Covid-19 leads to inflammatory, immunological, and oxidative changes, by which SARS-CoV-2 leads to endothelial dysfunction (ED), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and multi-organ failure (MOF). Despite evidence illustrating that some drugs and vaccines effectively manage and prevent Covid-19, complementary herbal medicines are urgently needed to control this pandemic disease. One of the most used herbal medicines is berberine (BBR), which has anti-inflammatory, antioxidant, antiviral, and immune-regulatory effects; thus, BBR may be a prospective candidate against SARS-CoV-2 infection. This review found that BBR has anti-SARS-CoV-2 effects with mitigation of associated inflammatory changes. BBR also reduces the risk of ALI/ARDS in Covid-19 patients by inhibiting the release of pro-inflammatory cytokines and inflammatory signaling pathways. In conclusion, BBR has potent anti-inflammatory, antioxidant, and antiviral effects. Therefore, it can be utilized as a possible anti-SARS-CoV-2 agent. BBR inhibits the proliferation of SARS-CoV-2 and attenuates the associated inflammatory disorders linked by the activation of inflammatory signaling pathways. Indeed, BBR can alleviate ALI/ARDS in patients with severe Covid-19. In this sense, clinical trials and prospective studies are suggested to illustrate the potential role of BBR in treating Covid-19.

5-HT/CGRP pathway and Sumatriptan role in Covid-19.

Coronavirus disease 2019 (Covid-19) is a pandemic caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). In Covid-19, there is uncontrolled activation of immune cells with a massive release of pro-inflammatory cytokines and the development of cytokine storm. These inflammatory changes induce impairment of different organ functions, including the central nervous system (CNS), leading to acute brain injury and substantial changes in the neurotransmitters, including serotonin (5-HT) and calcitonin gene-related peptide (CGRP), which have immunomodulatory properties through modulation of central and peripheral immune responses. In Covid-19, 5-HT neurotransmitters and CGRP could contribute to abnormal and atypical vascular reactivity. Sumatriptan is a pre-synaptic 5-HT (5-HT1D and 5-HT1B) agonist and inhibits the release of CGRP. Both 5-HT and CGRP seem to be augmented in Covid-19 due to underlying activation of inflammatory signaling pathways and hyperinflammation. In virtue of its anti-inflammatory and antioxidant properties with inhibition release of 5-HT and CGRP, Sumatriptan may reduce Covid-19 hyperinflammation. Therefore, Sumatriptan might be a novel potential therapeutic strategy in managing Covid-19. In conclusion, Sumatriptan could be an effective therapeutic strategy in managing Covid-19 through modulation of 5-HT neurotransmitters and inhibiting CGRP.