The potential role of Ginkgo biloba L. folium extract in the management of COVID-19

By Bhavana KunkalikarReviewed by Danielle Ellis, B.Sc.Jun 13 2022

In a recent study published in Archiv der Pharmazie, researchers explored the effectiveness of Ginkgo biloba L. folium extract (EGb) in the management of coronavirus disease 2019 (COVID-19) severity.

Background

COVID-19 is associated with several inflammatory disorders as well as the manifestation of oxidative stress in severe cases. Therefore, the development of therapeutic approaches against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that target inflammation and oxidation can help alleviate COVID-19 complications.

Antiviral activity of EGb

Various studies have highlighted the broad‐spectrum antiviral activity of EGb and its impact on viral life cycle stages, such as viral binding, viral entry, expression of proteins, as well as assembly and release of proteins. This antiviral activity is mainly observed under the cytotoxic threshold. EGb is also known to have an inhibitory effect against influenza A and B viruses via disruption of the hemagglutinin (HA) to the host cells.

In the present study, the team noted that the transmissibility of the influenza A virus depends on the interactions between HA and neuraminidase (NA) with sialic acid present in the cell surface receptor. Ginkgetin, a natural biflavone isolated from GB, can effectively block the sialidase activity of the influenza virus, thus preventing viral adsorption on the host's cell surface. Furthermore, EGb has been found to have a substantial antiviral effect against the H3N2 influenza virus as well as the hepatitis B virus.

The antiviral effect of GB is reported to be due to the disruption of viral fusion and the protective effect induced by GB on the host cells by improving its stability and reducing its permeability. Furthermore, studies showed that isorhamnetin, a flavonoid present in EGb, can inhibit NA and HA found in the H1N1 virus. This flavonoid also reduced autophagy induced by a viral infection, production of reactive oxygen species, and the phosphorylation of mitogen-activated protein kinase.

Anti-inflammatory activity of EGb

EGb and its components have also displayed anti-inflammatory effects via the inhibition of proinflammatory cytokines and the activation of anti-inflammatory cytokines. Various studies have noted that biflavones present in EGb, such as ginkgetin, significantly reduce the abnormal expression of Akt and p38 pathways in the basal epithelial cells. Biflavones also suppressed the expression of messenger ribonucleic acid (mRNA) of respiratory tract mucin, which could lead to mucociliary clearance failure.

EGb was also found to reduce the inflammation of the airway in asthmatic patients by decreasing the infiltration of the inflammatory cells, such as lymphocytes and eosinophils. It also suppressed the activity of protein kinase alpha (PKC‐α) of lymphocytes, thus preventing the secretion of interleukin 5 (IL-5) in the epithelial cells of the respiratory system. Additionally, a diterpene trilactone of GB called ginkgolide B also reduced the inflammatory reactions incident in the airway of patients who have asthma by reducing the secretion of platelet-activating factor (PAF).

EGb and COVID-19

Evidence shows that the 3‐chymotrypsin‐like protease (3CL^pro) enzyme plays a crucial role in SARS-CoV-2 replication and is considered an effective target against SARS-CoV-2. GA and a bioflavone called sciadopitysin present in EGb can sufficiently block 3CL^pro. Moreover, glycosylated flavonoids found in EGb also display inhibitory effects on SARS-CoV-2 replication by suppressing the function of 3CL^pro. The team also noted that a glycosylated derivative of kaempferol present in EGb has one of the highest binding energies to 3CL^pro in SARS-CoV-2. Kaempferol inhibited the 3CL^pro by exerting modularity effects on the extracellular as well as intercellular signaling pathways.              

Furthermore, the papain‐like protease (PL^pro) was also inhibited by quercetin, the primary component of the EGb flavonoids. This inhibition led to the suppression of SARS-CoV-2 replication through the inhibition of both PL^pro and CL^pro, which further resulted in the mitigation of coagulopathy, hyperinflammatory reactions as well as prothrombotic conditions. Moreover, the channel blocking activity of quercetin and kaempferol inhibited the SARS-CoV-2 envelope (E) protein, thus reducing viral activity and proliferation.

Various studies have highlighted the important role of lipoxygenase (LOX) and cyclooxygenase (COX) enzymes in worsening bronchial inflammatory reactions as well as the progression of acute lung injury (ALI) in patients experiencing severe COVID-19. Ginkgetin effectively inhibits leukotriene and prostaglandin pathways as a result of the reduction in phospholipase A2 enzyme activity. Altogether, this indicated that EGb showed great potential as a therapeutic approach against ALI.

Conclusion

Overall, the study findings showed that GB preparations could serve as effective potential candidates in the management of COVID-19 and its disease severity. The researchers believe that further clinical trial studies could verify the effectiveness of EGb against COVID-19 disease progression.