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Chronic Inflammation:
A Silent Culprit in Many Diseases

Chronic inflammation, once perceived as merely a localized response to injury or infection, is now recognized as a significant driving force behind a wide range of diseases. Unlike the acute, short-lived inflammation that helps heal wounds, chronic inflammation persists for months or even years, silently damaging tissues and organs. This insidious process lays the groundwork for various illnesses, impacting our health in profound ways.

Dr. Stephanie Watowich,, co-director of MD Anderson’s Center for Inflammation and Cancer, explains:

“When the medical community talks about inflammation, we aren’t just talking about one thing, one organ or even the same type of inflammation.

Inflammation is a local or systematic reaction from the cells in our immune system, but research has shown that there are different types of inflammation and that cells from other parts of the body are also involved. For example, the cells that line our blood vessels and the cells that line our skin also have inflammatory responses, so we know that it’s a more broad reaction that can involve cells throughout the body.“

 Therefore, as we detail in the science section, our approach is to target the multitude of possible paths and mechanisms of inflammation and those affected by it. 

A Sample of Research

Nature Reviews Immunology (2018): A comprehensive review outlining the role of chronic inflammation in diverse pathologies, from neurodegenerative diseases to cancer.

Mechanism of Action

Chronic inflammation disrupts the delicate balance within our immune system, leading to the excessive production of inflammatory mediators like cytokines and free radicals. These molecules damage healthy tissues, impair repair processes, and accelerate cellular aging. The consequences are widespread:

  • Tissue Damage: Chronic inflammation can scar and erode organs, contributing to conditions like rheumatoid arthritis, inflammatory bowel disease, and chronic obstructive pulmonary disease.
  • Metabolic Dysfunction: Inflammation disrupts insulin sensitivity, contributing to type 2 diabetes and obesity.
  • Neurodegeneration: Ongoing inflammation is implicated in the development of Alzheimer’s and Parkinson’s diseases.
  • Mental Health: Studies show a link between chronic inflammation and depression, anxiety, and other mood disorders. You can read about it in our Anxiety & Depression solution page. 

What to Do?

Given that we all develop chronic inflammation at points in our lives, and the deadly and destructive consequences of such inflammation, the solution is to treat it on an ongoing basis. The solution we developed not only fights inflammation, but includes also very powerful anti-oxidants, and as a result it fights aging and helps slow down the aging process, and even turn back our biological age. 

1. Apigenin

Apigenin is found in many fruits and vegetables, but parsley, celery, celeriac, and chamomile tea are the most common sources. Apigenin is particularly abundant in the flowers of chamomile plants, constituting 68% of total flavonoids.
The biological activities of apigenin been extensively studied. Much like the family to which it belongs, apigenin possesses a wide array of biological properties including antioxidant, anti-cancer, and anti-inflammatory actions [136,137,138]. As a result, apigenin has gained a lot of interest in the past few years as a potential therapeutic agent to treat various diseases such as cancer, diabetes, cardiovascular, and neurological disorders.

Apigenin, a member of the flavonoid family, has been shown to possess significant anti-inflammatory and antioxidant properties. A recent systematic review and meta-analysis focused on the effects of apigenin in lung injury models. The study found that apigenin administration significantly reduced the expression of inflammatory biomarkers such as NF-κB, IL-1β, IL-6, TNF-α, and TNF-α gene expression. Additionally, apigenin was effective in increasing the levels of antioxidant markers like CAT, GSH, and SOD, while decreasing the levels of MDA, MPO, TGF-β, and wet/dry (W/D) level compared to control groups.

Aging: Apigenin has anti-aging properties in addition to being anti-inflammatory & antioxidants. For example – a 2021 study concluded that “Thus, apigenin is a promising therapeutic for arterial aging.” They found that “oral apigenin supplementation can reverse two clinically important indicators of arterial dysfunction with age, namely, vascular endothelial dysfunction and large elastic artery stiffening,

 and prevents foam cell formation in an established cell culture model of early atherosclerosis.”

Safety: Apigenin is considered safe, even at high doses, and no toxicity has been reported. Nonetheless,

at high doses, it can trigger muscle relaxation and sedation.

2. Astaxanthin

Astaxanthin is a natural lipid-soluble and red-orange carotenoid that occurs in certain algae and causes the pink-red color in salmon, shrimp, and flamingo. Astaxanthin is a carotenoid with superior antioxidant activity than other carotenoids, as well as vitamins C and E . Due to its strong antioxidant property, anti-inflammatory, anti-apoptotic, and immune modulation, astaxanthin has gained growing interest as a multi-target pharmacological agent against various diseases. 

In a recent review the authors write “Massive evidences in vivo and in vitro have showed the anti-inflammatory effects and mechanisms of astaxanthin in mammals. Astaxanthin has been confirmed to alleviate chronic and acute inflammation in various diseases, including neurodegenerative disorders, diabetes, gastrointestinal disease, renal inflammation, as well as skin and eye diseases in different experimental models, which demonstrate that astaxanthin can be an excellent candidate for treating inflammation-related diseases. Significantly, many clinical studies and reports also prove the effects of astaxanthin in cardioprotection, immune modulation, skin and cosmetic benefits, sport performance, ophthalmology and safety All these data suggest that astaxanthin will be a suitable multi-target pharmacological agent.”

Aging: Possibly the most studied effect of astaxanthin is on the skin. A 2021 meta-analysis and systematic review found that “ingestion and/or topical usages of ASX may be effective in reducing skin ageing and have promising cosmetical potential, as it improves moisture content and elasticity and reduces wrinkles.”

Safety: So far, astaxanthin has shown no side effects when administered to human beings or animals.

3. Berberine

Berberine is yellow compound, an isoquinoline quaternary alkaloid, that can be found in roots, rhizomes, and stem barks of many plant species, including goldthread, Oregon grape, and barberry, and usually produced from Berberis vulgaris. It has been found to perform well in managing blood sugar, blood lipids, blood pressure, and without causing serious adverse events.

Typically used in traditional Chinese medicine, the natural supplement is a found in the roots, rhizomes,

and stem barks of many plant species, including goldthread, Oregon grape, and barberry

In a 2022 meta-analysis the authors included 52 studies and the related trials involving 4616 patients. Pooled estimates showed that the use of berberine could significantly reduce the concentration level of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6), p < 0.05] among patients with metabolic syndrome and related disorders.

Aging: summary, Chinese herb rhizoma coptidis and its main bioactive components has been used in aging-related diseases widely, i.e. hyperglycemia, hyperlipidemia and some neurodegenerative diseases. In particular, the main component, berberine, has found to extend life span, overall health, and attenuate premature cellular senescence in animal models. The anti-aging property of RC is evidenced by changes in associated markers of oxidative stress, apoptosis and inflammatory cytokines after berberine administration. The mechanisms of these activities involve multiple cellular kinase and signaling pathways include anti-oxidation, activation of AMPK signaling and its downstream targets, including mTOR/S6, Sirtuin 1/forkhead box transcription factor O3

(FOXO3), nuclear factor erythroid-2 related factor-2 (Nrf2), nicotinamide adenine dinucleotide (NAD+) and nuclear factor-κB (NF-κB) pathways.

Safety: Berberine has a favorable safety profile and is well tolerated in clinical trials. The most common adverse effects are gastrointestinal symptoms, such as diarrhea, constipation, nausea, and abdominal pain. However, some rare but serious adverse events have been reported, such as hepatotoxicity, nephrotoxicity, cardiotoxicity, and hypoglycemia.

4. Black Currants Powder

Black currants are recognized for their high polyphenol content, particularly anthocyanins, which contribute to their anti-inflammatory and antioxidant properties. A study testing the pharmacological activity of black currants’ extract found it was compared with indomethacin and niflumic acid (two anti-inflammatory drugs) using acute and chronic (21 or 28 days) oral treatment. Black currant extract revealed significant anti-inflammatory activity comparable to that seen with the reference substances, but without their ulcerogenic potential, even at high doses during chronic treatment.

A study on women going through menopause transition concluded that “Together, these findings suggest that daily BC consumption for six months effectively improved dyslipidemia, inflammation, and lipid peroxidation, thus potentially mitigating the risk of postmenopausal CVD development in study participants.”

A 2011 showed that Blackcurrants juice significantly inhibited lipopolysaccharide-induced inflammation as indicated by lower mRNA levels of TNF-α, IL-1β and inducible NO synthase (iNOS) and lower nuclear p65 levels indicating decreased NF-κB activity. iNOS protein levels were lower and haem oxygenase 1 levels higher in BC-treated cells when compared with untreated controls.

In a 2019 study the authors conclude that the findings indicate that blackcurrant consumption prevents obesity-induced steatosis, inflammation, and fibrosis in the liver. The implication is that blackcurrants can be a tool in fighting NAFLD, which is a common complication resulting from Diabetes type 2.

Aging: Furthermore, blackcurrants are proven to be capable antioxidants, as a review paper summarized “Multiple accounts show empirical support regarding the antioxidant ability of blackcurrants. Data from additional studies demonstrates the neutralization of hydrogen peroxide(H2O2) and NO, as well as impeding the propagation of lipid and protein peroxidation. Antioxidant enzymes, such as gluta-thione (GSH) peroxidase and superoxide dismutase, were also shown to increase significantly by the blackcurrant components through an unknown mechanism.”

Safety: Regarding toxicity, blackcurrants are generally considered safe and well-tolerated. However, some people may experience gastrointestinal side effects, such as nausea, stomach pain, and diarrhea, especially when consuming large amounts of blackcurrant juice or extract.

5. Blueberries powder

Blueberries have been extensively studied for the health benefits associated with their high phenolic content. The positive impact of blueberry consumption on human health is associated in part with modulation of proinflammatory molecular pathways and oxidative stress.

A 2020 review of blueberries effects on health has stated “Epidemiological studies associate regular, moderate intake of blueberries and/or anthocyanins with reduced risk of cardiovascular disease, death, and type 2 diabetes, and with improved weight maintenance and neuroprotection. These findings are supported by biomarker-based evidence from human clinical studies. Among the more important healthful aspects of blueberries are their anti-inflammatory and antioxidant actions and their beneficial effects on vascular and glucoregulatory function. “

Another review study on blueberries concluded that “The anti-inflammatory, antioxidant, and vasoprotective effects of blueberry components together contribute to well-regulated glucose delivery to insulin-sensitive tissues and good metabolic function. Each of these aspects has implications in multiple areas of healthy aging. Notably, biomarkers of cardiometabolic dysfunction are associated with risk for vascular and Alzheimer-type dementia in late life (92, 93), which may be related to the mitigation of neuroinflammation.

Improvement in anti-inflammatory biomarkers associated with blueberry intake is supported by observational (8), clinical (48), animal (87), and in vitro (114) evidence. Anti-inflammatory and immune benefits of blueberries may involve mucin-associated and other colonic microbiota (67), which constitutes a new domain for berry health research.

Aging: Blueberry benefits have been observed in both short-term (see, for example, references 18, 78, and 100) and long-term human interventions (see, for example, references 76 and 94), which suggests multiple modes of action.”

Safety: Blueberries are generally considered safe and well-tolerated, with no serious adverse effects              reported in human studies. However, some animal studies have suggested that high doses of blueberry               extract may cause liver toxicity or oxidative stress.

6. Cranberries powder

Cranberry is a fruit native to North America, with almost 98% of the world supply cultivated in the Northern United States and Canada. Cranberries have anti-inflammatory effects, thanks to their high amounts of antioxidants, especially anthocyanins and flavanols, which give cranberries their dark hue.

A 2018 paper reviewing cranberries’ antioxidant activity states “From several in vitro studies, it is evident that high concentrations of cranberry polyphenols have been associated with antibacterial, antiviral, antimutagenic, anticarcinogenic, antiangiogenic, anti-inflammatory, and antioxidant properties. Animal models reveal that cranberry extracts can reduce C-reactive protein and inflammatory interleukins, increase nitric oxide synthesis, decrease Helicobacter pylori infection, and raise the sensitivity of the β-pancreatic cells to glucose (citations below). Clinical studies highlight the fact that cranberry products can reduce LDL cholesterol (LDL-C), total cholesterol, and LDL-C oxidation, increase HDL cholesterol (HDL-C), improve endothelial function, and enhance the plasma antioxidant capacity.”

Aging: Phenols and Anthocyanins: Cranberry powder is packed with phenols and anthocyanins, powerful antioxidants that help combat oxidative stress and inflammation. These compounds have been associated with anti-aging effects and contribute to overall well-being.

Safety: Cranberries are safe and well-tolerated, with no serious adverse effects reported in clinical trials.

The most common side effects are gastrointestinal discomfort, diarrhea, and increased urine frequency. Cranberries may interact with some medications, such as warfarin, and should be used with caution in patients with kidney stones or urinary tract infections.

7. Curcumin (Tumeric)

Curcumin is a discreet bioactive compound and is what gives turmeric its bright color.
Curcumin has anti-inflammatory, anti-oxidant, anti-tumor and other biological activities. The anti-inflammatory properties of curcumin are considered to be the basis of its various biological activities and play an important role in the treatment of diseases.

 

According to a review of Curcumin’s anti-inflammatory effects, “Curcumin has anti-inflammatory, anti-oxidant, anti-tumor and other biological activities. The anti-inflammatory properties of curcumin are considered to be the basis of its various biological activities and play an important role in the treatment of diseases.”

In the studies of inflammatory cells and animals, curcumin decreased levels of pro-inflammatory mediators such as Interleukin-1 (IL-1), IL-1β, IL-6, IL-8, IL-17, IL-27, Tumor necrosis factor-α (TNF-α), Inducible nitric oxide

synthase (iNOS), NO, Regulated upon activation normal T cell expressed and secreted factor(RANTES), Granulocyte colony-stimulating factor (G‐CSF), and Monocyte chemotactic protein‐1 (MCP-1).

Clinical trials have also shown that curcumin can reduce inflammatory mediators. In a Randomized, Double‐Blind, Placebo‐Controlled Clinical Trial, daily 80 mg curcumin nano-micelle statistically significant improvement in plasma levels of C‐reactive protein(CRP), and TNF.

Aging: As an effective antioxidant, curcumin has great potential in reducing cellular damage, specifically mitochondrial damage, caused by ROS production. The use of antioxidant active agents to reduce free radicals in the body and protect mitochondria is an important strategy to slow down human aging.

Safety: Curcumin is generally safe and well-tolerated, with no serious adverse effects reported in human studies. The most common side effects are gastrointestinal symptoms, such as nausea, stomach pain, and diarrhea, especially when consuming high doses of curcumin or curcumin extract.

8. Fenugreek

Fenugreek (Trigonella foenum-graecum) is a clover-shaped herb from the legume family of plants. Fenugreek is native to the Mediterranean, southern Europe, and western Asia. Spices made from the plant’s leaves and seeds have a sweet, slightly bitter maple syrup-like flavor, similar to burnt sugar.

 

Fenugreek has been shown to significantly and positively affect metabolic syndrome. A recent meta-analysis found that administration of fenugreek can meaningfully reduce FPG, TG, WC, and SBP and increase HDL.

 

A study of its anti-inflammatory activity found that petroleum ether extract of fenugreek seeds has significant anti-inflammatory and anti-arthritic activities, which are due to the presence of linolenic and linoleic acids.

 

A systematic review of fenugreek effects on rheumatoid arthritis showed that fenugreek had favorable effects in RA and could control this disease via attenuating inflammation, suppressing oxidative stress, and displaying anti-arthritic activity.Aging: Fenugreek has shown anti-collagenase activity and increased collagen production, which can refer to the anti-aging property. Liponiosome encapsulating fenugreek extract (LNF) was developed and characterized. Cytotoxicity of LNF was observed in human dermal fibroblasts using cell-based assays.

Safety: fenugreek is generally safe and well-tolerated, with no serious adverse effects reported in human studies. The most common side effects are gastrointestinal symptoms, such as nausea, stomach pain, and diarrhea, especially when consuming large amounts of fenugreek seeds or extract.

9. Fisetin

Fisetin is a flavanol that has been shown to have anti-inflammatory and antioxidant effects. It has been found to be effective in reducing pain in pain-induced models and has potential as an anti-inflammatory, chemopreventive, chemotherapeutic, and serotherapeutic agent.     

Studies review from 2022 investigated the neuroprotective effects of fisetin, a natural flavonoid in neurodegenerative diseases. Results showed that the antioxidant properties of this flavonoid diminish oxidative stress, ROS production, neurotoxicity, neuro-inflammation, and neurological disorders. Moreover, it maintains the redox profiles, and mitochondrial functions and inhibits NO production. At the molecular level, fisetin regulates the activity of PI3K/Akt, Nrf2, NF-κB, protein kinase C, and MAPK pathways to prevent OS, inflammatory response, and cytotoxicity. The antioxidant properties of fisetin protect the neural cells from inflammation and apoptotic degeneration. Thus, it can be used in the prevention of neurodegenerative disorders.

 

A comprehensive study (2023) found that fisetin consistently demonstrated marked anti-inflammatory actions across various models and was effective in reducing pain in pain-induced models. When combined with opioid blockers, fisetin’s effects were on par with those of traditional medications.

 

Aging: multiple studies in animal models suggest that fisetin can reduce the impact of age-related neurological diseases, especially those associated with cognitive deficits such as AD. Moreover, many of these diseases do not currently have effective treatments (Table 3). These observations, in combination with the lack of any indication of toxicity, strongly suggest that fisetin might be useful in the clinic.

 

Safety: Off-target effects that can contribute to toxicity are certainly a concern for any potential therapeutic. However, in the case of fisetin, there is no evidence for either short- or long-term toxicity.

10. Garlic

Garlic, also known as Allium sativum, is a plant that has been used for centuries for its medicinal properties. A systematic literature review published in Evidence-Based Complementary and Alternative Medicine suggests that garlic has many physiological benefits, including anti-inflammatory, antioxidant, anticancer, lipid-lowering, and antidiabetic effects. The review concludes that garlic could regulate the development of nonalcoholic fatty liver disease (NAFLD) via several mechanisms of action, such as lowering body weight, modulating lipid and glucose metabolism, and reducing inflammation and oxidative stress.  

A recent systematic review, meta-analysis (2023) aimed at systematically evaluating the effect of garlic supplementation on components of MetS. Results from 19 RCTs included engaging 999 participants. Compared to placebo, garlic significantly reduced TG, TC, LDL, BMI, DBP, and WC. 

A systematic review and meta-analysis from 2021 check the effect of garlic intake on inflammatory mediators. These findings suggested that current evidence may support garlic as an adjunct to pharmacological management of metabolic diseases. 

Aging: Garlic has proven to have a broad range of health benefits and anti-aging effects, helping prevent

disease and age-related pathological conditions. Scientific and clinical studies have shown that garlic can enhance immunity, protect against infection and inflammation, and help lower the risk of cancer,

 heart disease, and dementia, the most common form of which is Alzheimer’s disease. 

Safety: Garlic is generally safe but can have toxic effects when consumed in large amounts.

Some people may experience side effects such as bad breath, body odor, heartburn, nausea, vomiting,

diarrhea, and skin irritation. 

11. Green Tea

Green tea extract has been found to have anti-inflammatory properties that can help reduce inflammation in the body. A recent systematic review and meta-analysis of clinical studies found that green tea preparations can relieve skin disorders, including acne, photoaging, and UV-induced erythema. Green tea catechins, especially epigallocatechin-3-gallate, have promising bioactivities, including antioxidant and anti-inflammatory properties, which could be exploited in several diseases. 

A recent systematic review and meta-analysis from2023 suggests improvements in the lipid and glycemic profiles following green tea supplementation. These findings support previous evidence showing the health benefits of green tea supplementation on cardiometabolic risk factors. 

A Systematic Review and Meta-Analysis of Randomized Clinical Trials (2021) checks the Effect of Green Tea Supplementation on Antioxidant Status in Adults. suggest that green tea supplementation improves TAC and affects MDA based on the dose of the intervention in adults. 

Aging: A study from 2020 checks the Anti-skin aging activities of green tea in B16F10 melanoma cells and human skin fibroblasts. The study results have shown that green tea may be a functional processed plant which could be used as an anti-skin aging agent in natural remedies, including food, health, and cosmetic products. 

Safety: green tea is generally safe, However, it is important to note that green tea extract can have toxic effects when consumed in large amounts. Some people may experience side effects such as insomnia, irritability, nausea, vomiting, diarrhea, and liver damage. 

12. Licorice

Licorice has been used for thousands of years in traditional Chinese medicine to treat immune systems, respiratory, and digestive diseases. Licorice and its derived compounds possess antiallergic, antibacterial, antiviral, anti-inflammatory, and antitumor effects. A recent systematic review and meta-analysis of clinical studies found that licorice-derived compounds can be effective in treating intestinal disorders by reducing inflammation and oxidative stress. 

Another study found that licorice flavonoids display favorable anti-inflammatory effect and have shown therapeutic effects in pneumonia, hepatitis, ulcerative colitis, gastritis, and other inflammatory diseases. 

A Systematic Review and Meta-Analysis from 2016 found that Licorice and its natural compounds have demonstrated anti-inflammatory activities. 

Aging: Study from 2020 that test the Antioxidant and Antiaging Effects of Licorice on the Caenorhabditis elegans Model suggest that licorice has a high antioxidant capability both in vitro and in vivo and that this activity may explain the observed extension of lifespan. 

Safety: Licorice usually is safe, but it is important to note that licorice can have toxic effects when consumed in large amounts. Some people may experience side effects such as high blood pressure, low potassium levels, muscle weakness, and heart problems. 

13. Luteolin

Luteolin is a flavonoid compound found in many plants, fruits, and vegetables, with various pharmacological effects such as anti-cancer, antioxidant, and anti-inflammatory.  

Meta-analysis and systematic review of preclinical studies showed that luteolin has cardioprotective effects against myocardial ischemia-reperfusion injury, a condition associated with inflammation, by reducing infarct size, improving hemodynamics, and attenuating oxidative stress, apoptosis, and inflammatory response. 

A comprehensive systematic review from 2023 tests the effects of luteolin on sepsis. Conclusion: Most studies revealed luteolin’s positive benefits on sepsis through several pathways. Luteolin showed the capacity to reduce inflammation and oxidative stress, control immunological response, and prevent organ damage (in vivo studies) during sepsis. 

A review of in vitro, in vivo, and in silico studies tests the effect of Luteolin on Anti-inflammatory. The clinical studies strongly suggest that the major pharmacological mechanism of luteolin is its anti-inflammatory activity, which derives from its regulation of transcription factors such as STAT3 NF-κB, and AP-1. 

Aging: Luteolin as a modulator of skin aging and inflammation. A review from 2021 summarizes the recent in vitro and in vivo research on luteolin in the field of skin aging and skin cancer, wound healing as well as inflammatory skin diseases, including psoriasis, contact dermatitis and atopic dermatitis. In conclusion, luteolin might be a promising molecule for the development of topic formulations and systemic agents against inflammatory skin diseases. 

Safety: Toxicity of luteolin is generally low, but some adverse effects have been reported, such as nausea, vomiting, diarrhea, and inhibition of neuronal differentiation. 

14. Mulberry extract

Mulberry leaf extract has been found to have anti-inflammatory properties that can help reduce inflammation in the body. A recent systematic review and meta-analysis of clinical studies found that mulberry leaf extract can lower the glycaemic and insulinaemic responses to sucrose in healthy individuals. 

A systematic review and meta-analysis of randomized-controlled trials check the Impact of mulberry consumption on cardiometabolic risk factors. The quantitative meta-analysis of 12 eligible RCTs demonstrated a significant reducing effect of mulberry consumption on haemoglobin A1c (HbA1c), serum total cholesterol, ow-density lipoprotein levels (LDL-C), triglycerides (TG), serum high-density lipoprotein levels (HDL-C). 

A study from 2013 test of Mulberry Leaf Reduces Oxidation and C-Reactive Protein Level in Patients with Mild Dyslipidemia. The results showed that mulberry leaf powder exhibited antioxidant activity and mulberry leaf powder has potential to decrease serum triglyceride, LDL, and CRP levels in mild dyslipidemia patients without causing severe adverse reactions. 

Aging: Mulberry leaf extract also combats inflammation and oxidative stress and has additional health benefits such as anti-carcinogenic effect, reduction of liver inflammation, and reduction of patches of dark skin. 

Safety: Mulberry leaf extract is safe, but it is important to note that mulberry extract can have toxic effects when consumed in large amounts. Some people may experience side effects such as nausea, vomiting, and diarrhea. 

15. Monk Fruit (Siraitia grosvenorii)

Monk fruit is a natural sweetener that contains mogrosides, a group of triterpenoids that are responsible for its high sweetness and antioxidant properties. 

Monk fruit has been shown to reduce inflammation and inflammatory mediators in various animal models and cell lines, such as arthritis, ulcerative colitis, neuropathic pain, and Crohn’s disease12. The mogrosides may modulate the expression of pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6, and inhibit the activation of NF-κB and MAPK pathways. 

A study from 2023 investigated the anti-inflammatory effects of Monk fruit residual extract on rats. “Our findings suggest that SGRE could be useful for the prevention and treatment of inflammation and its related diseases. Based on the results of this preclinical animal study, we are now progressing to a clinical study of SGRE on patients with OA”. 

A study from 2022 test the Effect of synbiotic yogurt fortified with monk fruit extract on hepatic lipid biomarkers and metabolism in rats with type 2 diabetes. The study found that MFE-sweetened synbiotic yogurt plays an active role in the prevention and progression of T2DM. In addition, the MFE-sweetened yogurt improved the phospholipids and FAHFA profiles of the livers, indicating that they can be used as lipid biomarkers. 

Aging: Siraitia grosvenorii extract has anti-diabetic, anti-tumour, anti-inflammatory, antioxidant, neuroprotective and lipogenic inhibitory effects. These pharmacological activities suggest the medicinal value of S. grosvenorii. 

Safety: Monk fruit has a long history of safe use as a food and medicine in China and other Asian countries1. The FDA has also recognized monk fruit as generally recognized as safe (GRAS) for use as a sweetener and flavor enhancer1. No adverse effects have been reported from the consumption of monk fruit or its extracts in humans or animals. 

16. Pomegranate extract

Pomegranate (Punica granatum L.) is a multipurpose medicinal and dietary plant that has anti-inflammatory and antioxidant actions. A systematic review and meta-analysis of randomized controlled trials (RCTs) showed that pomegranate consumption significantly reduced C-reactive protein (CRP), interlukin-6 (IL-6), tumor necrosis factor α (TNF-α), and malondialdehyde (MDA) in adults. 

A Systematic Review of Clinical Studies (2022) includes total of 20 studies suggest that pomegranate can be beneficial to reduce body weight, blood pressure, glycemia, triglycerides, total cholesterol, and low-density lipoprotein cholesterol. Moreover, it can augment high-density lipoprotein cholesterol levels and improve insulin resistance. 

A systematic review and meta-analysis from 2020 aim to evaluate the effect of pomegranate juice on the biomarkers of inflammation and vascular dysfunction. We found a significant effect of pomegranate supplementation on hs-CRP, IL-6 and TNF-α in adults.  

A recent study ,2023, investigated the Anti-Inflammatory Potential of Pomegranate Extract (Pomanox®) in a Reconstituted Human Corneal Epithelium Model. The present findings add evidence to the anti-inflammatory effect of a PMX in an in vitro model of reconstituted corneal epithelial cells. 

Aging: pomegranate consumption has beneficial effects on oxidative stress and inflammatory biomarkers in adults. Therefore, pomegranate can be consumed as an effective dietary approach to attenuate oxidative stress and inflammation in patients with cardiovascular diseases. 

Safety:  Regarding toxicity, pomegranate has no known adverse effects and has been used safely as a food and medicine for centuries. 

17. Quercetin

Quercetin is a flavonoid found in many fruits, vegetables, and grains that has anti-inflammatory and antioxidant properties. 

A meta-analysis and systematic review of preclinical studies showed that quercetin could reduce histological score (HS), Disease Activity Index (DAI), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), nitric oxide (NO), malondialdehyde (MDA), myeloperoxidase (MPO) activity and increase colon length (CL), weight change degree (WCD), interleukin-10 (IL-10), glutathione (GSH), superoxide dismutase (SOD) activity and catalase (CAT) activity, which may involve anti-inflammatory, anti-oxidative stress, cytoprotective, barrier protection, flora regulation. 

A meta-analysis of randomized controlled human trials (2019) checks Impact of quercetin on systemic levels of inflammation. The conclusion, consumption of quercetin is a promising therapeutic strategy for chronic disease management. 

Another systematic review and meta-analysis of animal studies from 2019 test the Antidiabetic effect of quercetin. The meta-analysis for serum glucose level (mg/dL) showed that at doses of 10, 25 and 50 mg/kg there was a significant difference between the means. Therefore, the results of the meta-analysis support the hypothesis that quercetin lowers serum glucose level, at doses of 10, 25 and 50 mg/kg. 

Aging: Quercetin, a remarkable flavonoid with potent antioxidant and anti-inflammatory properties, is expected to revolutionize the pharmaceutical industry as a multi-faceted therapeutic agent. As advancements in science and technology continue, the precise mechanisms underlying quercetin’s effects are becoming clearer. Its ability to scavenge free radicals and combat oxidative stress makes it a potential shield against age-related diseases and other conditions influenced by cellular damage. Furthermore, its proven anti-inflammatory properties, demonstrated through the inhibition of inflammatory cytokines and enzymes, pave the way for its application in treating inflammatory conditions like asthma, arthritis, and inflammatory bowel disease. 

Safety: Quercetin has been shown to be safe and well-tolerated in humans and animals. 

18. Rutin

Rutin is a flavonoid found in various plants, including buckwheat, asparagus, and citrus fruits, that has anti-inflammatory and antioxidant properties.

A study found that it aided in suppressing oxidative stress in people with arthritis, which may be due to rutin’s strong anti-inflammatory and antioxidant properties 3. There is also evidence that rutin improves knee function in some who have arthritis.

A meta-analysis of randomized controlled trials (2021) found that rutin supplementation significantly reduced inflammatory markers such as C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) in patients with metabolic syndrome.

A comprehensive analysis of scientific literature from 2022 looking for evidence reporting on the impact of rutin against metabolic diseases by affecting inflammation. In fact, available preclinical evidence suggests that rutin, through its strong antioxidant properties, can effectively ameliorate inflammation by reducing the levels of pro-inflammatory markers such as tumor necrosis factor-α, interleukin (IL)-6, cyclooxygenase-2, IL-1β, as well as blocking nuclear factor kappa B (NF-κB)/mitogen-activated protein kinase (MAPK) activation to improve metabolic function.

A recent double-blind and controlled design study from 2023 checks the effects of rutin supplement on blood pressure markers, some serum antioxidant enzymes, and quality of life in patients with type 2 diabetes mellitus compared with placebo.

Results: Rutin consumption caused a significant reduction in SBP, DBP, PP, MAP, and HR, with a significant increase in SOD, CAT, and GPx and some QOL parameters (emotional limitations, energy and freshness, mental health, social performance, and general health) compared with baseline.

Aging: the last study also found a mean changes of emotional limitations, energy and freshness, mental health, and general health (unadjusted p for all <0.05) and GPX and SOD (adjusted p for all <0.05) were significantly higher in the rutin group compared with the placebo group. Although, in the supplement group compared with the placebo group, the mean changes of SBP, DBP, MAP, PP, and HR were significantly lower (adjusted p for all <0.05).

Safety: Rutin is generally considered safe and well-tolerated. However, high doses of rutin may cause gastrointestinal side effects such as nausea, stomach pain, and diarrhea.

19. Silymarin/Milk Thistle

Silymarin, an herbal drug with antioxidant and anti-inflammatory properties, may improve glycemic control and prevent the progression of complications in Type 2 diabetes mellitus (T2DM). 

A systematic review and meta-analysis including five randomized controlled trials (2016) and 270 patients showed that routine silymarin administration determines a significant reduction in fasting blood glucose levels and HbA1c levels and has no effect on lipid profile. 

The potential benefit of silymarin (special extract from the fruits of Silybum marianum) in the treatment of liver diseases investigated in this systematic review with meta-analysis (2011). Based on the available clinical evidence it can be concluded – concerning possible risks /probable benefits – that it is reasonable to employ silymarin as a supportive element in the therapy of Amanita phalloides poisoning but also (alcoholic and grade Child ‘A’) liver cirrhosis. 

Aging: A Comprehensive Review of the Cardiovascular Protective Properties of Silibinin/Silymarin found that There is growing evidence supporting their significant cardiovascular protective properties, such as antioxidant, anti-inflammatory, hypotensive, glucose and lipid-lowering in pre-clinical studies. A limited number of clinical studies have documented a modest improvement in glycemic and lipid profile. 

Safety: Silymarin has no known adverse effects and has been used safely as a food and medicine for centuries. As there was not significant toxicity of silymarin reported in human studies, this substance can be used with anti-tuberculosis drugs as a supplement added to the diet. 

20. Strawberry powder

 Strawberry powder reduces inflammation markers in obese subjects: A randomized, cross-over trial with 20 obese volunteers (2022) showed that dietary strawberry powder (equivalent to four servings of frozen strawberries) for 3 weeks significantly decreased plasma concentrations of C-reactive protein, interleukin-6, and tumor necrosis factor-alpha, compared with a control intervention. 

A randomized, placebo-controlled trial (2011) with 60 patients with type 2 diabetes and overt nephropathy showed that adding silymarin (a bioactive compound in strawberry powder) to renin-angiotensin system inhibitors for 4 months reduced urinary and serum levels of inflammatory cytokines (TNF-alpha and IL-1beta) and oxidative stress mediators (malondialdehyde and nitric oxide), as well as proteinuria. 

Another Randomized Double-Blind Controlled Trial of Freeze-Dried Strawberry Powder Supplementation in Adults with Overweight or Obesity and Elevated Cholesterol from 2022 found that Low-dose supplementation with freeze-dried strawberry powder, equivalent to ∼1 serving/day of fresh strawberries, improved cholesterol in adults with overweight or obesity, compared to both the high-dose (∼3 servings/day of fresh strawberries) and control. 

Aging: Strawberry powder has antioxidant and anticancer properties: A systematic review of 113 studies (including in vitro, in vivo, and human trials) reported that strawberry powder and its bioactive components (such as anthocyanins, phenolic acids, and resveratrol) have multiple beneficial effects on antioxidant defenses, DNA damage, apoptosis, angiogenesis, and metastasis in various cancer models. 

Safety: Strawberry powder has low toxicity and high safety: A systematic review of 25 studies (including animal and human trials) concluded that strawberry powder and its bioactive components have no or minimal adverse effects on liver, kidney, and blood parameters, even at high doses. The review also suggested that strawberry powder may have protective effects against some toxic agents, such as acetaminophen and cisplatin. 

21. Sulforaphane

 Sulforaphane (SFN) is a phytochemical found in cruciferous vegetables that has anti-inflammatory, antioxidant, and anti-fatigue properties. 

According to recent meta-analyses and systematic reviews, SFN can: reduce chronic inflammation by modulating the immune response of dendritic cells and T cells, prevent oxidative stress by activating the Nrf2/ARE pathway and inducing phase 2 enzymes, and enhance exercise endurance and performance by attenuating muscle damage and fatigue. 

 A study from 2020 examined the relationship between the anti-inflammatory effects of SFN and the differential gene expression pattern in SFN treated ob/ob mice. The overall results suggest that SFN has a potent anti-inflammatory effect by normalizing the expression levels of the genes related to inflammation that were perturbed in ob/ob mice.  

 A recent review from august 2023 found that a growing body of evidence suggests additional diverse anti-inflammatory properties of sulforaphane through interactions with mediators of key signaling pathways and inflammatory cytokines. Multiple studies support a role for sulforaphane as a negative regulator of nuclear factor kappa-light chain enhancer of activated B cells (NF-κB) activation and subsequent cytokine release, inflammasome activation and direct regulation of the activity of macrophage migration inhibitory factor. 

 Aging: The phytochemical sulforaphane, well established as an activator of NRF2 antioxidant signaling, has demonstrated broad anti-inflammatory effects. Its role in the regulation of inflammatory signaling pathways, including NF-κB and inflammasome activation, suggests significant potential for the development of new therapeutics for the treatment of chronic inflammatory and autoimmune diseases. 

 Safety: SFN is generally considered safe and well-tolerated, but some adverse effects have been reported, such as gastrointestinal discomfort, allergic reactions, and drug interactions. 

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