EGCG – American ME and CFS Society

Feasibility Study of Developing a Saline-Based Antiviral Nanoformulation Containing Lipid-Soluble EGCG: A Potential Nasal Drug to Treat Long COVID

Abstract:

A recent estimate indicates that up to 23.7 million Americans suffer from long COVID, and approximately one million workers may be out of the workforce each day due to associated symptoms, leading to a USD 50 billion annual loss of salary. Post-COVID (Long COVID) neurologic symptoms are due to the initial robust replication of SARS-CoV-2 in the nasal neuroepithelial cells, leading to inflammation of the olfactory epithelium (OE) and the central nervous system (CNS), and the OE becoming a persistent infection site.

Previously, our group showed that Epigallocatechin-3-gallate-palmitate (EC16) nanoformulations possess strong antiviral activity against human coronavirus, suggesting this green tea-derived compound in nanoparticle formulations could be developed as an intranasally delivered new drug to eliminate the persistent SARS-CoV-2 infection, leading to restored olfactory function and reduced inflammation in the CNS. The objective of the current study was to determine the compatibility of the nanoformulations with human nasal primary epithelial cells (HNpECs).

Methods: Nanoparticle size was measured using the ZetaView Nanoparticle Tracking Analysis (NTA) system; contact antiviral activity was determined by TCID50 assay for cytopathic effect on MRC-5 cells; post-infection inhibition activity was determined in HNpECs; and cytotoxicity for these cells was determined using an MTT assay. The rapid inactivation of OC43 (a β-coronavirus) and 229E (α-coronavirus) viruses was further characterized by transmission electron microscopy.

Results: A saline-based nanoformulation containing 0.1% w/v EC16 was able to inactivate 99.9999% β-coronavirus OC43 on direct contact within 1 min. After a 10-min incubation of infected HNpECs with a formulation containing drug-grade EC16 (EGCG-4′ mono-palmitate or EC16m), OC43 viral replication was inhibited by 99%. In addition, all nanoformulations tested for their effect on cell viability were comparable to normal saline, a regularly used nasal irrigation solution. A 1-min incubation of an EC16 nanoformulation with either OC43 or 229E showed an altered viral structure.

Conclusion: Nanoformulations containing EC16 showed properties compatible with nasal application to rapidly inactivate SARS-CoV-2 residing in the olfactory mucosa and to reduce inflammation in the CNS, pending additional formulation and safety studies.

Source: Frank N, Dickinson D, Garcia W, Liu Y, Yu H, Cai J, Patel S, Yao B, Jiang X, Hsu S. Feasibility Study of Developing a Saline-Based Antiviral Nanoformulation Containing Lipid-Soluble EGCG: A Potential Nasal Drug to Treat Long COVID. Viruses. 2024; 16(2):196. https://doi.org/10.3390/v16020196 https://www.mdpi.com/1999-4915/16/2/196 (Full text)

Epigallocatechin gallate ameliorates behavioral and biochemical deficits in rat model of load-induced chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome is a heterogeneous disorder with unknown pathogenesis and etiology, characterized by tiredness, difficulty in concentration and memory, and concomitant skeletal and muscular pain, thus affecting both mental and physical domains. The pathogenesis of chronic fatigue syndrome is multifactorial and involves increased oxido-nitrosative stress along with generation of pro-inflammatory cytokines such as TNF-α.

In the present study chronic fatigue was produced in rats by plunging a load of 10 ± 2% body weight and subjecting them to forced swim inside a rectangular jar daily for 28 days. Endurance capacity and post-swim fatigue were assessed on 1st, 7th, 14th, 21st and 28th days. EGCG was administered daily by oral gavage 30 min before forced swim session. On the 29th day, after assessment of various behavioral parameters, blood was collected through tail vein, and animals were sacrificed to harvest the brains, spleens and thymus.

Chronic fatigue group exhibited significant behavioral alterations along with enhanced oxido-nitrosative stress and serum TNF-α level as compared to naive group. Chronic treatment with EGCG restored all the behavioral and biochemical alterations associated with chronic fatigue syndrome. The present study signifies the therapeutic potential of EGCG for the treatment of chronic fatigue syndrome.

Source: Sachdeva AK, Kuhad A, Chopra K. Epigallocatechin gallate ameliorates behavioral and biochemical deficits in rat model of load-induced chronic fatigue syndrome. Brain Res Bull. 2011 Oct 10;86(3-4):165-72. doi: 10.1016/j.brainresbull.2011.06.007. Epub 2011 Jul 28. https://www.ncbi.nlm.nih.gov/pubmed/21821105

Protective effect of epigallocatechin gallate in murine water-immersion stress model of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a specific clinical condition that characterizes unexplained disabling fatigue. In the present study, chronic fatigue was produced in mice by subjecting them to forced swim inside a rectangular jar of specific dimensions for 6 min. daily for 15 days.

Epigallocatechin gallate (EGCG; 25, 50 and 100 mg/kg, p.o.) was administered daily 30 min. before forced swim session. Immobility period and post-swim fatigue was assessed on alternate days. On the 16th day, after assessment of various behavioural parameters, mice were killed to harvest the brain, spleen and thymus.

There was significant increase in oxidative-nitrosative stress and tumour necrosis factor-alpha levels in the brain of mice subjected to water-immersion stress as compared with naive group. These behavioural and biochemical alterations were restored after chronic treatment with EGCG. The present study points out that EGCG could be of therapeutic potential in the treatment of chronic fatigue.

Source: Sachdeva AK, Kuhad A, Tiwari V, Arora V, Chopra K. Protective effect of epigallocatechin gallate in murine water-immersion stress model of chronic fatigue syndrome. Basic Clin Pharmacol Toxicol. 2010 Jun;106(6):490-6. doi: 10.1111/j.1742-7843.2009.00525.x. Epub 2010 Jan 18. http://onlinelibrary.wiley.com/doi/10.1111/j.1742-7843.2009.00525.x/full (Full article)

Epigallocatechin gallate ameliorates chronic fatigue syndrome in mice: behavioral and biochemical evidence

Abstract:

Three decades after the coining of the term chronic fatigue syndrome, the diagnosis of this illness is still symptom based and the aetiology remains elusive. Chronic fatigue syndrome pathogenesis seems to be multifactorial and the possible involvement of immune system is supported. The present study was designed to evaluate the effects of the epigallocatechin gallate in a mouse model of immunologically induced chronic fatigue.

On 19th day, after lipopolysaccharide/Brucella abortus administration, the mice showed significant increase in immobility period, post swim fatigue and thermal hyperalgesia. Behavioral deficits were coupled with enhanced oxidative-nitrosative stress as evident by increased lipid peroxidation, nitrite levels and decreased endogenous antioxidant enzymes (superoxide dismutase, reduced glutathione and catalase) and inflammation (increased levels of tumor necrosis factor-alpha and tissue growth factor-beta).

Chronic treatment with epigallocatechin gallate restored these behavioral and biochemical alterations in mice. The present study points out towards the beneficial effect of epigallocatechin gallate in the amelioration of chronic fatigue syndrome and thus may provide a new, effective and powerful strategy to treat chronic fatigue syndrome.

Source: Sachdeva AK, Kuhad A, Tiwari V, Chopra K. Epigallocatechin gallate ameliorates chronic fatigue syndrome in mice: behavioral and biochemical evidence. Behav Brain Res. 2009 Dec 28;205(2):414-20. doi: 10.1016/j.bbr.2009.07.020. Epub 2009 Jul 28. https://www.ncbi.nlm.nih.gov/pubmed/19643148