To date, ACE2 receptor is the major known entry point for SARS-CoV-2 into human cells. The main protease (Mpro) is an essential enzyme required for the multiplication of these SARS-VoV-2 in the host cells.

Among the different classes of natural products combined, flavonoids represent the largest group of ACE2 inhibitors. In fact, several studies have previously implicated some flavonoids to possess inhibitory properties against ACE2 activity.

Supporting ingredients: epicatechin, luteolin, quercetin, taxifolin

AMPk is found in every cell in the body and serves as a “master regulating switch” in energy metabolism. It helps determine your body’s balance between energy consumption and production.

Researchers believe that as we age, AMPK activity significantly decreases which is a reason why we experience changes in appetite, body weight and energy levels.  AMPK activators are things we think of as beneficial “stressors.” These include calorie restriction, fasting and intense exercise.

Supporting ingredients: dihydromyricetin, epicatechin, luteolin, quercetin, resveratrol thymoquinone, betaine.

Apolipoprotein B, commonly known as ApoB, is the main protein found in low-density lipoproteins (LDL).  When ApoB and cholesterol particles are trapped in the arterial wall, the deposits can build up as plaque and restrict blood flow, damaging the arteries and increasing the chances of blood clots.

EGCG reduces the production of apolipoprotein B (apoB), the main protein component of LDL.

Supporting ingredients: dihydromyricetin, EGCG, epicatechin, luteolin, quercetin, resveratrol thymoquinone, betaine.

Interleukin-1β (IL-1β) is a critical regulator of the inflammatory response.

Supporting ingredients:  astaxanthin, bromelain, curcumin, dihydromyricetin, diosmin, epicatechin, quercetin, resveratrol, taxifolin, thymoquinone, betaine.

Interleukin-6 (IL-6) is a pro-inflammatory cytokine, induces the expression of a variety of proteins responsible for acute inflammation, and plays an important role in the proliferation and differentiation of cells in our bodies.

Supporting ingredients:  astaxanthin, bromelain, curcumin, dihydromyricetin, diosmin, epicatechin, luteolin, quercetin, resveratrol, taxifolin, thymoquinone.

Interleukin-8 (IL-8) is one of the major mediators of the inflammatory response and is secreted by several cell types.  It plays a key role in the recruitment of neutrophils and other immune cells to the site of infection.

Supporting ingredients:  astaxanthin, bromelain, curcumin, resveratrol.

Interleukin-10 (IL-10) is an anti-inflammatory cytokine that maintains the balance of the immune response, allowing the clearance of infection while minimizing damage to the host.

Supporting ingredients:  astaxanthin, curcumin, dihydromyricetin, quercetin, resveratrol, taxifolin, thymoquinone.

Interleukin-18 (IL-18) acts not only on the immune system but also on other systems and physiological processes, such as the endocrine system, the nervous system, and bone metabolism. Under conditions of stress, IL-18 is released from the adrenal gland, suggesting the possible involvement of IL-18 in stress-induced systemic alterations.

Supporting ingredients:  astaxanthin, quercetin, resveratrol, thymoquinone.

CD38 is a molecule that can act as an enzyme, with NAD-depleting and intracellular signaling activity. The role of CD38 in immune cells ranges from modulating cell differentiation to effector functions during inflammation, where CD38 may regulate cell recruitment, cytokine release, and NAD availability. In line with a role in inflammation, CD38 appears to also play a critical role in inflammatory processes during autoimmunity.

Supporting ingredients:  luteolin

COX-2 inhibitors mostly block pain and inflammation. NSAIDs (like ibuprofen and naproxen) usually affect both COX-1 and COX -2 enzymes. For this reason, these medications are called nonselective NSAIDs.

Because COX-2 inhibitors more precisely target COX-2 enzymes, they’re called selective NSAIDs. Ingredients in ACEND inhibit COX-2 enzymes.

Supporting ingredients:  astaxanthin, betaine, bromelain, curcumin, dihydromyricetin, diosmin, luteolin, quercetin, resveratrol, taxifolin, thymoquinone.

The gene FOXO3, one of only two for which genetic polymorphisms have exhibited consistent associations with longevity in diverse human populations.

FOXO’s are involved in energy metabolism, oxidative stress, proteostasis, apoptosis, cell cycle regulation, metabolic processes, immunity, inflammation and stem cell maintenance.

Supporting ingredients:  luteolin, quercetin, taxifolin.

IGF-1 (insulin-like growth factor 1) is a hormone that’s found in the human body and is an important hormone involved in the growth of cells and the tissues. As its name suggests, it has similar functions to insulin, though it’s not as strong in respect to its ability to influence blood sugar, it does help manage and maintain blood sugar levels.

Supporting ingredients:  epicatechin, quercetin

The expression of inducible NOS (iNOS) occurs in conditions of inflammation and ca n produce large amounts of nitric oxide (NO). In extreme conditions iNOS is regarded as a harmful enzyme and is proposed to be a major contributor to diseases.

Supporting ingredients:  astaxanthin, bromelain, curcumin, dihydromyricetin, (-)-epicatechin, thymoquinone, quercetin, resveratrol, taxifolin, betaine

JNK proteins have been shown to play several vital roles in organisms, involved in the regulation of cancer, inflammatory response, DNA repair, and even aging.

Supporting ingredients:  astaxanthin, bromelain, curcumin, dihydromyricetin, diosmin, luteolin, thymoquinone, quercetin, resveratrol, taxifolin, betaine

The MAPK signaling pathway is essential in regulating many cellular processes including inflammation, cell stress response, cell differentiation, cell division, cell proliferation, metabolism, motility, and apoptosis.

Supporting ingredients:  astaxanthin, dihydromyricetin, EGCG, epicatechin, thymoquinone, quercetin, resveratrol, SOD, taxifolin, betaine.

Supporting ingredients:  astaxanthin, bromelain, curcumin, dihydromyricetin, diosmin, luteolin, thymoquinone, quercetin, resveratrol, taxifolin, betaine

mTOR is a protein that tells cells when to grow, divide, and survive. mTOR often mutates in cancer cells, leading to uncontrolled tumor cell growth. The National Cancer Institute (NCI) supported the basic research that demonstrated the remarkable anticancer effects of mTOR inhibitors. mTOR also increases ATP production, creates new mitochondria, and increases mitochondrial metabolism by activating PGC1a.

Supporting ingredients: epicatechin, luteolin, thymoquinone, resveratrol.

NF-κB regulates multiple aspects of our immune functions and serves as a pivotal mediator of inflammatory responses. NF-κB induces the expression of various pro-inflammatory genes and plays a critical role in regulating the survival, activation and differentiation of our immune cells and inflammatory T cells.

Nuclear factor-κB (NF-κB), a transcription factor that is essential for inflammatory responses, is one of the most important molecules linking chronic inflammation to cancer, and its activity is tightly regulated by several mechanisms. Inflammation has been recognized as a hallmark of cancer and all known hallmarks of cancer involve NF-κB activation.

Supporting ingredients:  astaxanthin, bromelain, diosmin, EGCG, epicatechin, thymoquinone, quercetin, resveratrol, taxifolin, betaine

[ii] https://www.nature.com/articles/nri.2017.142

Abnormal activation of the NLRP3 inflammasome has been linked with several inflammatory disorders, which include cryopyrin-associated periodic syndromes, Alzheimer’s disease, diabetes, and atherosclerosis. The NLRP3 inflammasome is activated by diverse stimuli, and multiple molecular and cellular events, including mitochondrial dysfunction and the production of reactive oxygen species (ROS).

Supporting ingredients:  astaxanthin, bromelain, curcumin, dihydromyricetin, EGCG, thymoquinone, quercetin, resveratrol, betaine.

Nrf2 regulates the expression of antioxidant proteins and enzymes, increasing their production to help your body fight off molecules that attack your cells.  It’s known as the “master regulator” of our body’s antioxidant response. When Nrf2 is activated, it enters the nucleus and turns on several hundred genes, known collectively as “survival genes.” This, in turn, initiates the production of several of your body’s own powerful enzymes that fight free radicals. These enzymes include catalase, glutathione, and superoxide dismutase (SOD).

Supporting ingredients:  astaxanthin, curcumin, dihydromyricetin, luteolin, EGCG, (-)-epicatechin, luteolin, quercetin, resveratrol.

The PI3K/AKT/mTOR pathway is an intracellular signaling pathway important in regulating the cell cycle. It is directly related to cellular quiescence, proliferation, cancer, and longevity.

Supporting ingredients:  astaxanthin, dihydromyricetin, epicatechin, thymoquinone, quercetin, resveratrol, SOD.

A strong link has been established between the p38 pathway and inflammation. Rheumatoid arthritis, Alzheimer’s disease and inflammatory bowel disease are all postulated to be regulated in part by the p38 pathway. A variety of viral infections are related to the p38 MAPK signaling pathway, and p38 is an important host factor in virus-infected cells.

Supporting ingredients:  astaxanthin, dihydromyricetin, epicatechin, thymoquinone, quercetin, resveratrol, SOD.

Evidence shows that inhibiting PCSK9 reduces cardiovascular events, such as cardiovascular disease (CVD). This is mainly related to the pivotal role of PCSK9 in controlling low-density lipoprotein (LDL) cholesterol levels.

The influence on PCSK9 by ingredients in ACEND, are often due to activation of related pathways. Example, an ingredient may influence the expression of the SREBP pathway and thereby downregulates the expression of PCSK9.

Supporting ingredients:  curcumin, EGCG, quercetin, resveratrol, vitamin C.

It has been hypothesized that plant-derived PPARγ modulators may be able to improve insulin sensitivity without detrimental side effects.

Supporting ingredients:  astaxanthin, curcumin, luteolin, quercetin, SOD, betaine.

‘Reactive oxygen species’ (ROS) is a generic term that defines a wide variety of oxidant molecules with vastly different properties and biological functions that range from signaling to causing cell damage. ROS-related disease can be either due to a lack of ROS (e.g., certain autoimmune disorders) or a surplus of ROS (e.g., cardiovascular, and neurodegenerative diseases).

Supporting ingredients:  astaxanthin, curcumin, EGCG, (-)-epicatechin, luteolin, thymoquinone, quercetin, resveratrol, SOD, taxifolin.

SIRT1 has been connected in gene expression, metabolism, and aging. SIRT enzymes are thought to “turn off” certain genes that promote aging, such as those involved in inflammation, fat synthesis and storage, and insulin resistance.

Supporting ingredients:  dihydromyricetin, EGCG, luteolin, thymoquinone, quercetin, resveratrol.

SIRT3 has been shown to be involved in almost all aspects of mitochondrial metabolism and homeostasis, protecting mitochondria from a variety of damage. Accumulating evidence has recently documented that SIRT3 is associated with many types of human diseases, including age-related diseases, cancer, heart disease and metabolic diseases.

Supporting ingredients:  dihydromyricetin.

The activation of the sirtuins — particularly SIRT6 — is associated with an increase in both median and maximum lifespan in several life forms, and a similar increase in health span. It has emerged as an exciting target of several diseases such as cancer, neurodegenerative diseases, aging, diabetes, metabolic disorder, and heart disease.

Supporting ingredients:  luteolin, resveratrol.

The STAT 1 protein plays a key role in the immune response against viruses and other pathogens.

Supporting ingredients:  EGCG, resveratrol.

STAT-3 serves critical roles in several cellular processes, including the cell cycle, cell proliferation, cellular apoptosis and tumorigenesis.

Supporting ingredients:  EGCG, taxifolin.

STAT5 proteins regulate cellular functions such as proliferation, differentiation, and survival. STAT5 plays an important role in the maintenance of normal immune function and homeostasis,

Supporting ingredients:  dihydromyricetin, EGCG.

TLR4 is the sensor that orchestrates inflammatory responses through a series of well-characterized downstream cascades. To ensure immunity, and yet limit pathology, inflammatory responses must be confined within the proverbial “Goldilocks zone” and TLR4 does this.

Supporting ingredients:  curcumin, dihydromyricetin, EGCG, quercetin, resveratrol, betaine.

TNFa (tumor necrosis factor alpha) is produced by cells in your immune system that has many effects in promoting the inflammatory process. It is produced chiefly by macrophages, a type of white blood cell, but can be produced by other cells as well. TNFa is a major cause of the excess inflammation that drives rheumatoid arthritis (RA).

Supporting ingredients:  astaxanthin, bromelain, curcumin, dihydromyricetin, diosmin, luteolin, thymoquinone, quercetin, resveratrol, taxifolin, betaine.

VEGF is one of the most important inducers of angiogenesis (the formation of new blood vessels). It’s normally an important process that supports wound healing and supplies oxygen-rich blood to your organs and tissues. But in people with cancer, angiogenesis supports tumor growth and spread by feeding tumors with oxygen and nutrients. Blocking angiogenesis has led to great promise in the treatment of various cancers and inflammatory diseases.

Supporting ingredients:  astaxanthin, (-)-epicatechin, thymoquinone, resveratrol, taxifolin.