Ginkgo Biloba and Long COVID: In Vivo and In Vitro Models for the Evaluation of Nanotherapeutic Efficacy

Abstract

Coronavirus infections are neuroinvasive and can provoke injury to the central nervous system (CNS) and long-term illness consequences. They may be associated with inflammatory processes due to cellular oxidative stress and an imbalanced antioxidant system. The ability of phytochemicals with antioxidant and anti-inflammatory activities, such as Ginkgo biloba, to alleviate neurological complications and brain tissue damage has attracted strong ongoing interest in the neurotherapeutic management of long COVID. Ginkgo biloba leaf extract (EGb) contains several bioactive ingredients, e.g., bilobalide, quercetin, ginkgolides A–C, kaempferol, isorhamnetin, and luteolin. They have various pharmacological and medicinal effects, including memory and cognitive improvement. Ginkgo biloba, through its anti-apoptotic, antioxidant, and anti-inflammatory activities, impacts cognitive function and other illness conditions like those in long COVID. While preclinical research on the antioxidant therapies for neuroprotection has shown promising results, clinical translation remains slow due to several challenges (e.g., low drug bioavailability, limited half-life, instability, restricted delivery to target tissues, and poor antioxidant capacity). This review emphasizes the advantages of nanotherapies using nanoparticle drug delivery approaches to overcome these challenges. Various experimental techniques shed light on the molecular mechanisms underlying the oxidative stress response in the nervous system and help comprehend the pathophysiology of the neurological sequelae of SARS-CoV-2 infection. To develop novel therapeutic agents and drug delivery systems, several methods for mimicking oxidative stress conditions have been used (e.g., lipid peroxidation products, mitochondrial respiratory chain inhibitors, and models of ischemic brain damage). We hypothesize the beneficial effects of EGb in the neurotherapeutic management of long-term COVID-19 symptoms, evaluated using either in vitro cellular or in vivo animal models of oxidative stress.

Cognitive impairment after long COVID-19: current evidence and perspectives

“…Genomic studies can also help discover the molecular mechanisms by which the disease affects cognition. In addition, it has been suggested that certain natural compounds, including Ginkgo biloba extract, may hold promise in mitigating cognitive impairment resulting from long COVID-19 ( 72 ). However, these compounds' efficacy is yet to be firmly established, and further investigation is required to confirm their potential benefits.…”

Nanomedicine‐mediated recovery of antioxidant glutathione peroxidase activity after oxidative‐stress cellular damage: Insights for neurological long COVID

“…58,59 The free drug combination of quercetin and GB has exhibited neuroprotective effects against oxidative stress synergistically via decreasing malondialdehyde (MDA) content and increasing the levels of antioxidant enzymes, SOD, GSH, and CAT. 13,14,60 Furthermore, nanocarriers loaded with EGb extracts of GB and quercetin could modulate antioxidative signaling pathways, such as the nuclear factor (erythroid-derived 2)-like 2 (Nrf2). The neuroprotective effect of GB, delivered via biodegradable poly(ethylene glycol)-b-poly(trimethylene carbonate) (PEG-PTMC) nanoparticles (PPNPs), has been explored as a promising therapy for PD to enhance its accumulation in the blood and brain.…”

Relationship of quercetin intake and oxidative stress in persistent COVID

“…The low bioavailability of Quercetin and its poor solubility are limitations to its use leading to the reduction of the antioxidant power it possesses; restricted transport across biological barriers and transient retention are challenges to overcome, and an alternative to the above is the use of nanotherapy. The use of conjugates and nanocarriers based on different materials is an option to consider for Quercetin; these nanocarriers have been used with natural compounds such as Ginkgo Biloba as well as targeted drugs for neurodegenerative diseases ( 62 – 64 ); these nanoparticles can be organic or inorganic, organic materials (liposomes, micelles, and polymeric nanoparticles) stand out for being compatible and degradable in their entirety. Inorganic nanoparticles (iron oxide nanoparticles, gold nanoparticles, and silica nanoparticles) have smaller size, stability, higher permeability, and a controlled release period ( 65 – 67 ).…”