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

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.

Discovery and characterization of the covalent SARS-CoV-2 3CLpro inhibitors from Ginkgo biloba extract via integrating chemoproteomic and biochemical approaches.

BACKGROUND: The 3C-like proteases (3CLpros) are cysteine-rich homodimeric proteins and can be covalently modified by numerous natural and synthetic compounds, which in turn, block the proteolytic activity or the formation of enzymatically active dimeric forms. Although herbal medicines have been widely used to treat COVID-19, identification of the key herbal constituents that can covalently modify the 3CLpros in ß-coronaviruses (CoVs) remains a big challenge. AIMS: To construct a comprehensive approach for efficient discovering the covalent SARS-CoV-2 3CLpro inhibitors from herbal medicines. To decipher the key anti-SARS-CoV-2 3CLpro constituents in Ginkgo biloba extract 50 (GBE50) and to study their anti-SARS-CoV-2 3CLpro mechanisms. METHODS: SARS-CoV-2 3CLpro inhibition assay including time-dependent inhibition assays and inactivation kinetic analyses were conducted using a fluorescence-based biochemical assay. The constituents in GBE50 were analyzed by UHPLC-Q-Exactive Orbitrap HRMS. The peptides modified by herbal constituents were characterized by using nanoLC-MS/MS. RESULTS: Following testing the anti-SARS-CoV-2 3CLpro effects of 104 herbal medicines, it was found that Ginkgo biloba extract 50 (GBE50) potently inhibited SARS-CoV-2 3CLpro in dose- and time-dependent manners. A total of 38 constituents were identified from GBE50 by UHPLC-Q-Exactive Orbitrap HRMS, while 26 peptides modified by 18 constituents were identified by chemoproteomic profiling. The anti-SARS-CoV-2 3CLpro effects of 18 identified covalent inhibitors were then validated by performing time-dependent inhibition assays. The results clearly demonstrated that most tested constituents showed time-dependent inhibition on SARS-CoV-2 3CLpro, while gallocatechin and sciadopitysin displayed the most potent anti-SARS-CoV-2 3CLpro effects. CONCLUSION: Collectively, GBE50 and some constituents in this herbal product could strongly inhibit SARS-CoV-2 3CLpro in dose- and time-dependent manner. Gallocatechin and sciadopitysin were identified as potent SARS-CoV-2 3CLpro inhibitors, which offers promising lead compounds for the development of novel anti-SARS-CoV-2 drugs.

Medicinal plants for the therapy of long-COVID symptoms

At the beginning of the corona pandemic, the prevailing opinion was that antiviral agents and effective vaccines were primarily needed to combat it. The extremely varied and difficult-to-grasp symptoms that result from a corona infection, resulting in Covid-19 disease, only came into the focus of science much later and are currently only insufficiently researched. The suspected spike proteins of the viral envelope are likely to cause micro blood clots and provoke autoimmune reactions affecting blood flow and function of many organs, especially central nervous system blood flow. Unfortunately, these symptoms can affect approxmately 60% of the population and can last longer than a month, although therapy can currently only be symptomatic and not causal. All long-term health consequences that can occur after infection with the SARS-CoV-2 coronavirus are summarized under the generic term "long covid", which encompasses symptoms that persist, worsen or reappear more than 4 weeks after contracting the coronavirus. Complaints that persist after 3 months and persist or recur for at least 2 months are referred to as post-Covid syndrome. In the treatment of the various symptoms, which in addition to the respiratory tract particularly affecting the central nervous system, the digestive tract and the cardiovascular system, there are excellent starting points for phytotherapeutic treatment. Depending on the symptoms, which are individually very diverse, phytotherapy can be very easily customized by combining different medicinal plants. Rhodiola rosea in particular should be highlighted as a medicinal plant for treating fatigue syndrome and Ginkgo biloba for neuronal disorders.

Ginkgolides and bilobalide for treatment of Alzheimer's disease and COVID-19: potential mechanisms of action

- Alzheimer's disease (AD) is an irreversible degenerative illness of the central nervous system with characteristic histological alterations, known as amyloid plaques and plaques and tangles in the brain induces neurotoxicity and synaptic dysfunction, ev

Identifying the Anti-MERS-CoV and Anti-HcoV-229E Potential Drugs from the Ginkgo biloba Leaves Extract and Its Eco-Friendly Synthesis of Silver Nanoparticles.

The present study aimed to estimate the antiviral activities of Ginkgo biloba (GB) leaves extract and eco-friendly free silver nanoparticles (Ag NPs) against the MERS-CoV (Middle East respiratory syndrome-coronavirus) and HCoV-229E (human coronavirus 229E), as well as isolation and identification of phytochemicals from GB. Different solvents and high-performance liquid chromatography (HPLC) were used to extract and identify flavonoids and phenolic compounds from GB leaves. The green, silver nanoparticle synthesis was synthesized from GB leaves aqueous extract and investigated for their possible effects as anti-coronaviruses MERS-CoV and HCoV-229E using MTT assay protocol. To verify the synthesis of Ag NPs, several techniques were employed, including X-ray diffraction (XRD), scan, transmission electron microscopy, FT-IR, and UV-visible spectroscopy. The highest contents of flavonoids and phenolic compounds were recorded for acetone, methanol, and ethanol as mixtures with water, in addition to pure water. HPLC flavonoids were detected as apegenin, luteolin, myricetin, and catechin, while HPLC phenolic compounds were pyrogallol, caffeic acid, gallic acid, and ellagic acid. In addition, our results revealed that Ag NPs were produced through the shift from yellow to dark brown. TEM examination of Ag NPs revealed spherical nanoparticles with mean sizes ranging from 5.46 to 19.40 nm and an average particle diameter of 11.81 nm. A UV-visible spectrophotometric investigation revealed an absorption peak at λ max of 441.56 nm. MTT protocol signified the use of GB leaves extract as an anti-coronavirus to be best from Ag NPs because GB extract had moderate anti-MERS-CoV with SI = 8.94, while had promising anti-HCov-229E, with an SI of 21.71. On the other hand, Ag NPs had a mild anti-MERS-CoV with SI = 4.23, and a moderate anti-HCoV-229E, with an SI of 7.51.

Ginkgo biloba in the relief of neurological symptoms after COVID-19

COVID-19 is a disease caused by the SARS-CoV-2 virus, multi-organ, with a wide spectrum of symptoms, the most common being pneumonia with fever, dry cough and shortness of breath. There are more and more reports of persistent long-term effects, especially after acute disease. Regardless of the way the virus enters the brain, it attacks neurons, contributing to neurological complications. The main symptoms of the central and peripheral nervous system are dizziness and headaches, impaired consciousness, sometimes acute ischemic stroke and intracranial hemorrhages, loss of taste and smell, visual disturbances, neuralgia and skeletal muscle damage. After recovery, patients experience symptoms such as persistent fatigue, diffuse muscle aches, symptoms of depression, non-renewable sleep, tinnitus, and erectile dysfunction. Early intervention and supportive care at the end of the acute phase of COVID-19 could alleviate the symptoms of the disease as well as prevent their long-term consequences. Taking into account plant raw materials, the standardized extract of Ginkgo leaves (Ginkgo biloba) may be useful at various stages of the disease: it prevents the penetration of the virus into the host cells, has anti-inflammatory, antioxidant and antithrombotic properties, and above all, it is the only plant material with proven neuroprotective and neuroregulatory properties, widely used in the treatment of Alzheimer's, Parkinson's and other diseases and disorders related to the nervous system.

A SYSTEMIC REVIEW ON OCULAR DISEASE DUE TO VIRTUAL ENVIRONMENT

As the COVID-19 epidemic continues, when it comes to studying at home or working from home, there are no escape devices. They serve as an important link in human life and learning and the working environment. As with any useful tool, certain digital devices can sometimes be "very good." The COVID-19 epidemic has led to increased use of digital devices, which poses a greater risk of developing digital eye symptoms. Eye care professionals should educate patients about screen time limitations and digital eye signage management, leading to the challenge of annual visual programs. The effects of ocular surface health and circadian rhythm abnormalities associated with ocular disease such as computer vision syndrome, dry eyes, astigmatism, near vision, muscle mass etc. are increasing. In this covid epidemic 19 the widespread use of Herbal medicine and the use of Ayurvedic medicine increases when conventional medicine does not work in the treatment of diseases. Ayurveda is considered to be one of the best remedies for disease and lead to a healthy lifestyle in ancient India. Trataka treatments and head rubbing are also a good exercise for eye health. Oncological diseases ayurvedic remedies such as Haritaki, Malaki, Vibhitaki, Alovera are widely used. Triphala is a powerful Ayurvedic tonic containing three traditional fruits that have long been used to treat various health conditions of ocular disease. This is a traditional eye procedure and is very easy to keep the eyes healthy. Ginkgo biloba is used in traditional medicine recommended to enhance vision.

Ginkgo biloba in the management of the COVID-19 severity.

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.

Therapeutic potential of plant secondary metabolites in treatment of respiratory viral diseases: A review

Respiratory viral infections are a major public health concern because of their global occurrence, ease of spread and considerable morbidity and mortality. Medical treatments for viral respiratory diseases primarily involve providing relief from symptoms like pain and discomfort rather than treating the infection. Very few antiviral medications have been approved with restrictive usage, high cost, unwanted side effects and limited availability. Plants with their unique metabolite composition and high remedial values offer unique preventive and therapeutic efficacy in treatment of viral infections. The present review is focused on the types and mode of action of plant secondary metabolites that have been used successfully ί in the treatment of infections caused by respiratory viruses like Influenza, SARS, MERS, RSV etc. Plant metabolites such as phenolics, alkaloids, terpenoids and oligosaccharides inhibit attachment and entry of the virus. Others such as flavonoids, viz quercetin and baicalein, alkaloids viz sanguinarine, berberine and emetine, specific lipids and fatty acids prevent viral replication and protein synthesis. These metabolites have the potential to be used as lead molecules that can be optimized to develop potent drugs for effectively combating pandemics caused by respiratory viruses.

Discovery of naturally occurring inhibitors against SARS-CoV-2 3CLpro from Ginkgo biloba leaves via large-scale screening.

3-Chymotrypsin-like protease (3CLpro) is a virally encoded main proteinase that is pivotal for the viral replication across a broad spectrum of coronaviruses. This study aims to discover the naturally occurring SARS-CoV-2 3CLpro inhibitors from herbal constituents, as well as to investigate the inhibitory mechanism of the newly identified efficacious SARS-CoV-2 3CLpro inhibitors. Following screening of the inhibitory potentials of eighty herbal products against SARS-CoV-2 3CLpro, Ginkgo biloba leaves extract (GBLE) was found with the most potent SARS-CoV-2 3CLpro inhibition activity (IC50 = 6.68 µg/mL). Inhibition assays demonstrated that the ginkgolic acids (GAs) and the bioflavones isolated from GBLE displayed relatively strong SARS-CoV-2 3CLpro inhibition activities (IC50 < 10 µM). Among all tested constituents, GA C15:0, GA C17:1 and sciadopitysin displayed potent 3CLpro inhibition activities, with IC50 values of less than 2 µM. Further inhibition kinetic studies and docking simulations clearly demonstrated that two GAs and sciadopitysin strongly inhibit SARS-CoV-2 3CLprovia a reversible and mixed inhibition manner. Collectively, this study found that both GBLE and the major constituents in this herbal product exhibit strong SARS-CoV-2 3CLpro inhibition activities, which offer several promising leading compounds for developing novel anti-COVID-19 medications via targeting on 3CLpro.

Evidence that Ginkgo Biloba could use in the influenza and coronavirus COVID-19 infections.

Coronavirus COVID-19 pandemic invades the world. Public health evaluates the incidence of infections and death, which should be reduced and need desperately quarantines for infected individuals. This article review refers to the roles of Ginkgo Biloba to reduce the risk of infection in the respiratory tract, the details on the epidemiology of corona COVID-19 and influenza, and it highlights how the Ginko Biloba could have been used as a novel treatment.Ginkgo Biloba can reduce the risk of infection by several mechanisms; these mechanisms involve Ginkgo Biloba contains quercetin and other constituents, which have anti-inflammatory and immune modulator effects by reducing pro-inflammatory cytokines concentrations. Cytokines cause inflammation which have been induced the injuries in lung lining.Some observational studies confirmed that Ginkgo Biloba reduced the risk of asthma, sepsis and another respiratory disease as well as it reduced the risk of cigarette smoking on respiratory symptoms. While other evidences suggested the characters of Ginkgo Biloba as an antivirus agent through several mechanisms. Ginkgolic acid (GA) can inhibit the fusion and synthesis of viral proteins, thus, it inhibit the Herpes Simplex Virus type1 (HSV-1), genome replication in Human Cytomegalovirus (HCMV) and the infections of the Zika Virus (ZIKV). Also, it inhibits the wide spectrum of fusion by inhibiting the three types of proteins that have been induced fusion as (Influenza A Virus [IAV], Epstein Barr Virus [EBV], HIV and Ebola Virus [EBOV]).The secondary mechanism of GA targeting inhibition of the DNA and protein synthesis in virus, greatly have been related to its strong effects, even afterward the beginning of the infection, therefore, it potentially treats the acute viral contaminations like (Measles and Coronavirus COVID-19). Additionally, it has been used topically as an effective agent on vigorous lesions including (varicella-zoster virus [VZV], HSV-1 and HSV-2). Ginkgo Biloba may be useful for treating the infected people with coronavirus COVID-19 through its beneficial effect. To assess those recommendations should be conducted with random control trials and extensive population studies.