Ginkgo biloba in the management of the COVID-19 severity

Abstract

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is linked with inflammatory disorders and the development of oxidative stress in extreme cases. Therefore, anti-inflammatory and antioxidant drugs may alleviate these complications. Ginkgo biloba L. folium extract (EGb) is a herbal medicine containing various active constituents. This review aims to provide a critical discussion on the potential role of EGb in the management of coronavirus disease 2019 (COVID-19). The antiviral effect of EGb is mediated by different mechanisms, including blocking SARS-CoV-2 3-chymotrypsin-like protease that provides trans-variant effectiveness. Moreover, EGb impedes the development of pulmonary inflammatory disorders through the diminution of neutrophil elastase activity, the release of proinflammatory cytokines, platelet aggregation, and thrombosis. Thus, EGb can attenuate the acute lung injury and acute respiratory distress syndrome in COVID-19. In conclusion, EGb offers the potential of being used as adjuvant antiviral and symptomatic therapy. Nanosystems enabling targeted delivery, personalization, and booster of effects provide the opportunity for the use of EGb in modern phytotherapy.

Keywords: Ginkgo biloba; SARS-CoV-2; complementary medicine; nanomedicines; viral proteases.

Figure 1

Natural products in coronavirus disease 2019 (COVID‐19) management.^{[ 12 ]}

Figure 2

Mild adverse effects of Ginkgo biloba products.^{[ 14 ]}

Figure 3

Anti‐inflammatory effects of Ginkgo biloba (GB): GB stimulates the release of interferon‐gamma (INF‐γ) and release of anti‐inflammatory cytokines, inhibits angiotensin II (Ang II) and release of proinflammatory cytokines. GB suppresses inflammatory mediators, including; mitogen‐activated protein kinase (MAPK), signal transducer and activator transcription 3 (STAT‐3), protein kinase C alpha (PKC‐α), and retinoic acid‐related orphan nuclear receptor (ROR‐γt) with upregulation of forkhead winged‐helix transcription factor 3 (Fox‐3).

Figure 4

Role of Ginkgo biloba (GB) in COVID‐19: GB inhibits replication of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) through inhibition of 3‐chymotrypsin like protease (3CL^pro). GB inhibits the release of proinflammatory cytokines via suppression of nuclear factor kappa B (NF‐κB) and node‐like receptor pyrin 3 (NLRP3) inflammasome. GB inhibits thrombosis and endothelial dysfunction (ED) via inhibition of angiotensin II (Ang II) and mitogen‐activated protein kinase (MAPK). Also, GB reduces the activity of cyclooxygenase (COX) and lipoxygenase (LOX) involved in releasing proinflammatory cytokines. GB antioxidant effects inhibit the expression of toll‐like receptor 4 (TLR4) and myeloid differentiation primary response (MyD88), thereby attenuating proinflammatory cytokines. GB antioxidant effects also inhibit cytokine storm and the development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). GB blocks the development of the sympathetic storm, which increases the risk of ALI, ARDS, cytokine storm, and release of proinflammatory cytokines.