Abstract
Inflammaging is the continuation of a mild chronic asymptomatic inflammation over a long time in the body, followed by clinical symptoms of aging as the result. This process underlies many diseases associated with aging, including cancers, diabetes, and diseases with cognitive decline. There is a variety of anti-inflammatory agents to help prevent or ameliorate the process. Best and most frequent natural sources that contain anti-inflammatory agents are the food and herbs, out of which there are some dietary supplements manufactured as well.
Major anti-inflammatory components in food include certain amino acids, vitamins, and minerals, and most importantly, polyunsaturated fatty acids. As it is hard to precisely separate food from edible herbs—since some herbs are a part of the daily diet—the great family of polyphenols is discussed as the major anti-inflammatory in herbs, despite their existence in what is called food, as well. The molecular mechanisms of the most frequent and effective agents and their role in the prevention of certain diseases related to inflammaging are discussed. And finally, briefly categorized tables are composed, to compare the sources of the compounds in more detail.
Access provided by Autonomous University of Puebla. Download chapter PDF
Similar content being viewed by others
Keywords
8.1 Inflammation
Inflammation is a process occurring in response to an infection or injury in the body. It involves many specific cell pathways and cytokine release that cope with the unusual cells; and it may come to production of cells or factors that might cause pathological conditions themselves, this is associated with the incapability of the immune system to distinguish self from non-self (Fasano 2012). This is where the inflammation can be potentially harmful. If the underlying cause of inflammation is not removed, the inflammatory processes will continue until they fall into a chronic inflammatory state.
Inflammaging refers to the condition in which a prolonged, low-grade inflammation is triggered and continued for a part of a life span, which is in this term, the aging span. It is at first subclinical, with no notable symptoms, but it will eventually show up with diseases, the predominant ones being cancers, and diseases related to cognitive decline as well as diabetes and other metabolic disorders. Table 8.1 overviews the common diseases and symptoms of inflammation. Franceschi et al. have described and discussed the pathophysiology associated with inflammaging in their review (Franceschi and Campisi 2014). As proposed by them, there are six main sources to inflammaging:
-
1.
the damaged cells and macromolecules (which should have been eliminated but accumulated); these could mimic a possible inflammatory state as they appear pathogenic to the immune system.
-
2.
products of the bacteria of the normal flora. Along with aging, the ability of the intestinal cells to prevent leakage to the inner tissues decreases, which allows more pathogenic molecules to be introduced to the immune system.
-
3.
persistently senescent cells, because they produce high amounts of proinflammatory cytokines
-
4.
Increased activation of the coagulation system
-
5.
Immunosenescence; As adaptive immunity declines with aging, the innate immune system increases its activity, which does not possess the specificity of the adaptive immunity.
-
6.
Dysregulation in the complement pathway, a cause for many degenerative diseases associated with aging
One of the most significant changes in chronic inflammation is the imbalanced ratio of proinflammatory to anti-inflammatory cytokines. Cytokines are the dominant factors in inducing or suppressing the inflammation. The mechanisms involved are generation of molecules with the ability to eliminate the undesired, such as ROS, or the iNOS protein; producer of NO, which plays an active role in inflammation in the neurons, joints, and lung (Sharma et al. 2007). Abundant ROS can cause DNA damage and genome instability, thereby inducing cancer. It also promotes tumor proliferation, angiogenesis, and survival (Wu et al. 2014). NF-κB is a protein activated by proinflammatory stimuli such as viruses, cytokines, oncogenes, toll-like receptors, etc. This protein is also tumorigenic as it mediates cell proliferation and angiogenesis (Wu et al. 2014). Moreover, the ROS, NO, cytokines, and prostaglandins are the main actors in inducing inflammation in the CNS, following different proteinopathies, which stand for the neurodegenerative state caused by over activated microglia (Glass et al. 2010).
During the subclinical period of inflammaging, lifestyle intervention, including exercise and healthy diet, contribute to prevent or delay the progression of inflammation.
Healthy diet, such as Mediterranean pattern, has been recognized as one of the best approaches to ameliorate the inflammatory status, due to the high amount of the bioactive compounds that have been found to be efficient in treatment of inflammation; some of them are also used as supplements or nutraceuticals. Many vitamins and minerals fall into this category; however, they are mainly taken by the normal daily diet. It is only of importance that necessary considerations be taken regarding the changes in the need for vitamins and minerals, especially those with an anti-inflammatory role, in the elderly.
8.2 Food
Poor nutrition contributes to many chronic aging diseases, including cardiovascular diseases, diabetes and most importantly, cancer. It is known what a poor diet might consist of; however, what exactly a “rich” or healthy diet might mean, varies upon individuals, for the beneficial and detrimental sides of the constituents might be difficult to describe. Subsequent studies at the end of the twentieth century focused on diets rich in plants and fruits, as they showed a promise to prevent cancer. These studies had focused on the radical scavenging and antioxidant characteristics of the natural constituents, including polyphenols, flavonoids, and tannins.
Dominant contents that a diet covers, which could influence the inflammatory state are vitamins, minerals, amino acids, and beneficial fats, i.e. long chain fatty acids.
8.2.1 Vitamins and Minerals
Vitamins and minerals are essential to the diet at any age; however, their amount of intake changes during aging. Some of them, such as Zinc, Folate, vitamin B12, Calcium, and vitamin D have an anti-inflammatory activity. It is only recommended that vitamins and minerals should be taken within the normal dosage range as they are normally found in a rich and healthy diet. Main mechanisms are charted in Table 8.2.
8.2.2 Amino Acids
Amino acids have a variety of functions in the body. Some have antioxidant and anti-inflammatory effects. Most effective ones are Arginine, Glutamine, L-carnitine, Tryptophan, Creatine, and Taurine. A number of in vivo studies evaluated their efficacy as a supplement/nutraceutical in reducing inflammation. Main mechanisms are charted in Table 8.3, in vivo studies in Table 8.4 as well.
8.2.3 Omega-3 Fatty Acids
Omega-3 fatty acids are polyunsaturated fatty acids (PUFA), having their last pi bond between C3 and C4. Most active biological omega-3 acids include eicosapentaenoic acid (EPA, 20:5n-3), docosapentaenoic acid (DPA, 22:5n-3), and docosahexaenoic acid (DHA, 22:6n-3). Omega 6 fatty acids are characterized by a double bond between the C6–7. These fatty acids have a major role in preventing the inflammation.
It is thought that PUFAs will integrate into the membrane of many cells, including immune cells, e.g. macrophages, lymphocytes, and neutrophils. This integration stands for the fatty acid composition, when responding to the inflammatory stimuli, i.e. the more (PUFA) in the membrane of the cells, the more they will be involved in the eicosanoid cascade (Calder 2015). This hypothesis has been proved in several studies (Healy et al. 2000; Faber et al. 2011; Thies et al. 2001; Kew et al. 2003). By an inflammatory trigger, phospholipase A2 will release the ARA from the membrane; however, it is clear that by a decreased amount of ARA, the omega-3 fatty acids will substitute the ARA, and stand as substrates for the COX and LOX enzymes. This has been further detailed below.
The cascade of biological inflammatory response involves two main pathways. The N-3 pathway results in the production of PGE3 (anti-inflammatory), the n-6 produces Dihomo-gamma-linolenic acid, which, if interrupted by the environmental factors, will be the substrate for the production of PGE1 (anti-inflammatory). But when continued, it produces Arachidonic acid, the primary substrate for COX, LOX, and CYP450 enzymes, responsible for PGE2 and leukotriene production (inflammatory). The two pathways are linked to same enzymes (mostly elongase and desaturase); but what determines the predominant pathway, will be the availability of the nutrients needed for each equation, as well as the metabolic environment (Mahan et al. 2017). Hence, a well-thought diet will have to make sure of adequate intake of n-3 fatty acids, and the supplements and minerals supporting the PGE1 and PGE3 production Table 8.5.
Apart from the role of Omega-3 fatty acids in enhancing the lipid profile, their role in the prevention of Arachidonic acid-derived products will induce the hypothesis of preventing inflammation caused by 2-series prostanoids, such as rheumatoid arthritis (RA). Some clinical trials have reported anti-inflammatory effects of omega-3 rich diets in the RA (Kremer et al. 1985, 1987; Cleland et al. 1988).
8.2.3.1 Dosage Considerations
There seems to be a threshold for the anti-inflammatory responses of n-3 fatty acids (Calder 2015). Based on a trial, an intake of more than 2 grams per day of DHA + EPA is needed to trigger the effects (Calder 2015; Rees et al. 2006). On the other hand, it is also important not to go beyond a maximum border of daily intake, this will suppress the arachidonic acid production, affecting the balance of the two pathways (Mahan et al. 2017).
8.2.3.2 Omega3 Fatty Acids in RA
A number of clinical trials supported omega-3 supplementation alongside rheumatoid medications. A trial on almost 700 patients with early RA suggests that taking higher amounts of omega 3 a year before the initiation of disease modifying antirheumatic drug (DMARD), might yield to better outcomes of the drug therapy (Lourdudoss et al. 2017). Level of omega-3 is also associated with the inflammatory/refractory pain of early RA patients receiving methotrexate for 3 months (Lourdudoss et al. 2018). A study evaluated the rate of concomitant need to analgesics after consumption of 3.6 g of EPA and 4.2 g of DHA daily for 12 weeks (Rajaei et al. 2016). They reported an improved disease state as well as a reduction in need for analgesics.
8.2.3.3 Omega3 Fatty Acids in Cardiovascular Diseases
Omega-3 can impact the cardiovascular system through several mechanisms. They are capable of decreasing blood cholesterol and triglyceride, preventing vessel stiffness and atherosclerosis. Omega-3 can relax the smooth muscle of the veins, which will enhance vasodilation. They also promote endothelial function. With their antioxidant activity besides their anti-inflammatory effects, they are considered key nutrients in cardiovascular complications of aging. Several studies have evaluated their role as nutrients in cardiovascular system (Pase et al. 2015; Casanova et al. 2017; Colussi et al. 2017).
8.2.3.4 Omega 3 Fatty Acids and Neuroinflammation
There are plenty of data on the role of omega-3 in preventing cognitive decline or maintaining metabolic status in neurodegenerative diseases. Both anti-inflammatory and antioxidant activity of omega-3 are the main mechanisms for these effects. Moreover, long-term metabolic imbalances like dyslipidemia are risk factors for the Alzheimer’s disease, which could be modulated with omega-3 supplementation.
The major neuroprotective role of omega-3 is their lipid balancing property that is discussed in studies, rather than an antioxidant activity. As amyloid precursor protein (APP) and the secretases are integrated into the lipid bilayer of the cells, lipid balance will be of importance (Grimm et al. 2017). Although trials suggest positive changes in memory function and cognition, there is no definite conclusion (Grimm et al. 2017; Shinto et al. 2014; Samieri et al. 2017; Külzow et al. 2016). Yet, as omega-3 is generally regarded as safe (GRAS), a usual and safe daily intake could be recommended, both as prevention or supplementation of an Alzheimer’s or Parkinson’s disease (AD or PD) patients (Taghizadeh et al. 2017).
8.2.4 Immunomodulating Polysaccharides
There are many natural compounds who influence the immune system, especially the innate one. Beta-glucans are polysaccharides based on glucose monomers found in the cell walls of bacteria and fungi. They can be taken orally as dietary fiber or supplement, and are well-known for their cholesterol lowering effects and immunomodulation (Liatis et al. 2009a; Behall et al. 2004). A low dose of 3 g/day of beta-glucan (available as supplements) seems to be effective in mildly reducing cholesterol (Bashir and Choi 2017). Their anti-inflammatory effects are widely used in respiratory conditions like asthma and respiratory tract infections (RTI), which is not necessarily related to aging (Bashir and Choi 2017; Sarinho et al. 2009; Talbott and Talbott 2009, 2012).
8.2.5 Chondroitin and Glucosamine
Glucosamine and chondroitin are dietary supplements used in osteoarthritis because of their cartilage building property. As osteoarthritis is a condition with which mostly elderly cope, these compounds could play a role in healthy aging. However, two reviews over their efficacy have reported no significant benefit from consumption of the supplements in treating osteoarthritis (Henrotin et al. 2012; Runhaar et al. 2017). However, as they report that more data is needed to confirm the (in) effectiveness, they could still be recommended due to the low adverse effect profile.
Their anti-inflammatory effects are carried out through inhibiting NF-κB. A trial of 18 healthy overweight individuals measured some inflammatory biomarkers, including C-reactive protein (CRP), after 30 days of 1500 mg glucosamine and 1200 mg chondroitin consumption per day (Navarro et al. 2015). 23% decrease in serum CRP was reported, and the authors concluded that this supplementation may lower systemic inflammation. However, the data still lack in this area and more trials have to be run to further investigate the effects.
8.3 Polyphenols
There are a variety of chemical compounds found in herbs and natural sources that have an anti-inflammatory role. Phenols and polyphenols are a wide group of compounds, having an anti-inflammatory activity along with antiseptic and antioxidant activities, including the simple salicylic acid, rosmarinic acid, and the complex phenolic glycosides. Phenols contain one aromatic ring, while polyphenols have more than one. They might either be unconjugated or bound to a saccharide molecule, and less often, to lipids, amino acids, etc. These compounds have been widely discussed in Chap. 7.
8.3.1 Tannins
The term “tannin” refers to phenolic substances used in tanning (dyeing brown) leather and textiles. However, the concentration of these polyphenols is too low to make them functional for conversion into leather.
Tannins are most used to tighten up loose or damaged tissues, as in burns, varices or diarrhea (to dry excess secretions). Tannins are subdivided into two major groups. Proanthocyanidin groups or condensed tannins and ellagic acid-derived.
8.3.2 Flavonoids
Flavonoids are the most common polyphenols. They are known with a 6-3-6 (no. of the ring carbons) structure. The middle ring stands for the division of the family into chalcones, anthocyanins and proanthocyanidins, dihydrochalcones, flavonones, flavonols, flavones, flavonols, and isoflavones. Many flavonoids have anti-inflammatory effects. Their mechanisms will be discussed further in the current chapter.
Fruits have an abundant amount of flavonols and proanthocyanidins. Citrus family contains further types of flavonoids like flavonones and flavones. Vegetables are rich sources of flavonols, especially quercetin, which is a great anti-inflammatory agent. Celery and lettuce contain falvones.
8.3.3 Quercetin (Meletin/Sophretin)
Quercetin is a flavanol, belonging to the flavonoid’s family. It is a well-known anti-inflammatory molecule that exerts its effects via inhibiting the NF-κB, resulting in prostanoid synthesis, cytokine production, and iNOS expression (Comalada et al. 2005; Morikawa et al. 2003). It is also thought to be a neuroprotective, preventing neuronal cells from inflammatory injuries (Chen et al. 2005). Together with its antioxidant effects, the molecule could be effective against cognitive impairment, especially in neurodegenerative diseases, where taupathy and Beta-amyloidosis are the problems, i.e. AD. A study on murine models of AD shows that quercetin can decrease Beta-amyloid and taupathy in the hippocampus and amygdala (Sabogal-Guáqueta et al. 2015). Shen et al. have proved a reduction in the rate of tau protein hyper phosphorylation induced by okadaic acid in vitro (Shen et al. 2018). Furthermore, in another AD mouse model, mitochondrial function was improved, as well as beta-amyloid plaque reduction, proved by higher levels of ROS and ATP in hippocampus mitochondria (Wang et al. 2014). Quercetin increased the AMPA protein kinase significantly, suggesting a mechanism by which it improves cognition.
The issue over this molecule is the pharmacokinetic profile. Quercetin undergoes significant first pass elimination and thus a high proportion of it is lost. Moreover, further in vivo data is needed to confirm the bioavailability of the drug to the brain, as the molecule can barely pass the blood–brain barrier (BBB) (Babaei et al. 2018).
Javadi et al. have studied the effects of 500 mg/day of quercetin for 8 weeks on women with rheumatoid arthritis. Quercetin could significantly reduce inflammatory markers and clinical symptoms, i.e. pain in the morning and after activity and the early morning stiffness (Javadi et al. 2017).
8.3.4 Isoflavonoids
Phytoestrogens are substances with estrogenic activity, though not steroids in structure, and they include isoflavones, coumarins, stilbenes, and lignans. “Isoflavonoid phytoestrogens” are extensively used and studied, due to their contribution in human health. They are commonly referred to as isoflavonoids. The most common types of isoflavonoids, Genistein (4′,5,7-trihydroxyisoflavone), daidzein (4′,7- dihydroxyisoflavone), and glycetein (4′,7-dihydroxy-6-methoxyisoflavone) are found in the soy. They are mostly referred to as antioxidants, anti-inflammatory, and antitumor agents, due to their estrogenic activity. The antioxidant characteristics are discussed in Chap. 7.
8.3.5 Actions of Isoflavonoids in Human Health
8.3.5.1 Cancer and Chronic Inflammatory Disease Prevention
Genistein is an estrogen agonist. By binding to the conventional nuclear estrogen receptor, it can mimic estrogenic effects. Moreover, there has recently been interest in its effects on G protein-coupled estrogen receptor (GPER), one of the massive study areas in breast cancer. This receptor is activated by estrogens (and probably other similar ligands) and its activation leads to phosphorylation of mitogen-activated protein kinases/extracellular signal-regulated kinases (MAPKs/ERK) pathway, involving the adenylate cyclase and phospholipase C, and will be continued through insulin-like growth factor-1 receptor (IGF-1R) and epidermal growth factor receptor (EGFR) (Kuo et al. 2010; Madeo and Maggiolini 2010; Maggiolini et al. 2004; Meyer et al. 2011; Prossnitz and Barton 2011). This can be a way to estrogen’s anti-inflammatory and antitumor activity (Blasko et al. 2009; Rettew et al. 2010), and as the receptor can be found on microglia, its effects on the nervous system. This might stand for the mechanism that genistein can modulate the inflammatory response of microglia, as it is demonstrated in a recent study by Du et al. (Du et al. 2018).
By the stimulation of microglia by the antigen, interleukin (IL)-1β, tumor necrosis factor (TNF)-alpha, and IL-6 are the major mediators produced, in which MAPKs signaling pathway, i.e. ERK, p38, and Jun N-terminal kinase (JNK) are involved. They are responsible for the release of inflammatory mediators, including NO (by iNOS) and TNF-α. Du et al.’s study on BV2 microglia demonstrated that genistein could inhibit the MAPK pathway (Du et al. 2018). Microglial stimulation will also free NF-κB, via the TLR4, and results in its nuclear translocation (Reed-Geaghan et al. 2009). NF-κBs are regulators of the immune response. They are one of the first signals activated by immunogens. ROS, heavy metals, infections, interleukins, and TNF are of the mediators that can induce their response. The NF-κB will then bind to the promoter region of these inflammatory mediators. Many studies involving the NF-κB pathway use the LPS of Gram-negative bacteria for stimulation. NF-κBs are both involved in acute and chronic inflammations, including diseases like the rheumatoid arthritis, as well as in memory and neural survival.
8.3.5.2 NF-κB and Inflammation
A study on the molecular effects of genistein reported several mechanisms through which genistein can exert anti-inflammatory effects (Jeong et al. 2014). Genistein could block the nuclear translocation of the NF-κB and thereby regulate the inflammatory response, by reduction of the reactive oxygen species. It also attenuated the production of TNF-alpha and IL-1β generation in LPS-stimulated microglia and thus the neuroinflammation. The study further declares that genistein can also inhibit both Cox-2; resulting in inhibition of inflammatory prostaglandins (PGE2), and iNOS, resulting in lower NO production.
A recent study evaluated the anti-inflammatory effects of 8-odthohydroxydaidezin (8-OHD), an analogue of genistein, on the same cell line (BV2 microglia), and compared them with genistein (Wu et al. 2018). The results demonstrated better effects with the 8-OHD rather than genistein in preventing NO production, through downregulation of iNOS expression. It was also proved that 8-OHD could more effectively reduce the ROS released by LPS-activated microglia. However, in COX-2 inhibition, genistein could be slightly more effective.
These anti-inflammatory mechanisms contribute to genistein effects on preventing breast cancer and chronic inflammatory diseases, such as R.A. There are some synthetic agents found as GPER agonists, without feminizing effects; however, genistein’s function on other estrogen receptors, including its effects on the reproductive system, has been approved as it is used in menopausal symptoms.
8.3.5.3 Prevention of Cognitive Decline
Overactivation of microglia in chronic neuroinflammation can result in neural damage and degeneration, the highly believed etiology of neurodegenerative disorders. Mechanisms are discussed further.
8.3.5.4 NF-κB and Memory
Based on the anti-inflammatory effects of estrogen, it is hypothesized that it is able to attenuate neurodegeneration (GDNF contributes to estrogen-mediated protection of midbrain dopaminergic neurons n.d.; The possible role of estrogen and selective estrogen receptor modulators in a rat model of Parkinson’s disease n.d.; Estradiol protects dopaminergic neurons in a MPP+ Parkinson’s disease model n.d.). Studies have proved the role of TLR4 and the NF-κB in the inflammation in neurodegeneration, suggesting an increase in their amount or activity, since TLR4 is able to recognize Amyloidβ (Okun et al. 2009; Liao et al. 2011; Frank et al. 2009). A study has confirmed that genistein could reverse the inflammatory effects of Amyloidβ, i.e. decreasing the production of IL-1β and iNOS in vitro (Zhou et al. 2014). In the study, cells treated with Amyloidβ showed a significant increase in NF-κB and TLR4 production, and genistein could reverse the signs by downregulating the expression of TLR4 and NF-κB (refer to NF-κB and inflammation).
Studies report that GPER activation, associated with the modulation of microglial activity, will yield to the neuroprotective effects on DA nigral neurons (Bessa et al. 2015; Bourque et al. 2012; Mendes-Oliveira et al. 2017; Zhao et al. 2016). In the study, DA neural loss by LPS-induced microglia was treated with GPER agonist, which will result in reduced NO and phagocytic activity; the pathway that is normally stimulated via the 17-β estradiol (estrogen). Moreover, blockade of GPER resulted in reduction of phagocytic activity and iNOS gene expression. Estrogen exerts its anti-inflammatory effects via the classical estrogen receptors (ER alpha and beta) too; in fact, agonizing their receptors also attenuate microglial NO production. However, the study utilized the synthetic agonists/antagonists (G1/G15), with neither feminizing effects nor difficulty passing the BBB. It has been proved that genistein can easily pass the BBB, (Mozolewski et al. 2017) but its effects on the reproductive system, might make it not so compatible as a long-term nutraceutical treatment, except for proper cases such as postmenopausal women. A recent review has proposed that polyphenols may be potentially beneficial to develop new drugs against neuroinflammation by targeting the TLR4 pathway (Rahimifard et al. 2017).
8.3.5.5 Lipid Profile and Cardiovascular Effects
Genistein can reduce the Apo lipoprotein B secretion from hepatocytes. Microsomal triglyceride transfer protein (MTP) is an essential molecule for lipoprotein assembly, which helps transfer esterified cholesterol (EC), triglyceride (TG), and phospholipid (PL) to the recently produced apolipoprotein-B (ApoB) molecules. It is thus essential for the release of ApoB. Genistein reduces both the expression and activity of MTP in the cell (Borradaile et al. 2002), meaning that in long-term use, it might be able to keep MTP at lower concentrations, resulting in lower release of VLDL and chylomicrons. It has been also demonstrated that both genistein and daidzein can decrease the rate of LDL-receptor expression and activity, which will result in higher LDL re-uptake. Genistein can also inhibit Acyl-coenzyme A (CoA): cholesterol acyltransferases (ACATs) which will prevent cholesterol from getting esterified and apolipoproteins from getting assembled. This will reduce the lipoprotein secretion, a mechanism close to 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors.
Cardioprotective effects of estrogen, especially ERβ receptor agonists, including genistein are well-known (Kararigas et al. 2014; Hsieh et al. 2015; Fliegner et al. 2010; Pedram et al. 2013). After an ischemic heart crisis, reperfusion will cause an inflammatory condition, maintained by accumulation of the leukocytes. This is triggered by some inflammatory cytokines, including TNF-a, which will increase the expression of Intracellular adhesion molecule-1 (ICAM-1) (also known as CD54) production, a factor for the leukocytes’ intercellular adhesion. Genistein can attenuate the expression of ICAM-1, by reducing TNF-α in a dose dependent manner. Thus, it is considered as a leukocyte-endothelium interaction inhibitor, resulting in the improved atherosclerotic condition (Kayisli et al. 2013).
8.3.5.6 Menopausal Symptoms and Osteoporosis
There has been a huge load of data on the estrogen-mimicking effects of genistein. It is a full agonist of ERβ, and this receptor is a negative inhibitor of ER alpha. Thus, genistein and phytoestrogens act through anti-growth properties, whereas ERalpha has pro-growth effects. Phytoestrogens are capable of ameliorating vasomotor symptoms, depressive moods, osteopenia, and vaginosis and could probably be taken in proper doses for months or years. There is also some clinical evidence that it might be effective in osteoporosis (Kayisli et al. 2013). However, data regarding vaginal atrophy still lack (Le Donne et al. 2011; Manonai et al. 2006).
8.3.5.7 Potential Adverse Effects
There might have been some concern about the feminizing effects of isoflavonoids; however, many studies do not approve reproductive problems or infertility, neither in pediatrics nor in adults. In fact, it is suggested that infants who are breastfed from mothers whose diets are soy-rich, have lower incidences of cancer, with respect to the adults with a soy-rich diet (Franke et al. 1999). A study has reported no special feminizing effects on male (Mitchell et al. 2001).
As isoflavonoids are substrates for thyroid peroxidase, high-dose isoflavonoid might be thought as an inducer of hypothyroidism. However, a recent clinical trial on almost 400 postmenopausal women who took up to 54 mg/day of genistein over 2–3 years, reported no significant decline in thyroid hormones (Bitto et al. 2010). As long as iodine storage is sufficient, no potential harm might threat thyroid conditions (Marini et al. 2012; Bruce et al. 2003).
8.3.5.8 Dietary Intake and Herbal Sources
Although there are many soy-based supplements available in the market, it is recommended to consume soy-rich diets instead, as a nutraceutical, as not to lose the other components in the plant, that would enhance the efficacy, or cause synergism. Moreover, this approach will ensure a safe amount of intake rather than supplements.
Genistein is mostly found in leguminosae plants; beans, peas, and peanuts as ones found in the normal human diet. In some fruits, flavonols are mostly found in the skin, and thus peeling will substantially reduce the intake. Other herbs containing flavonoids can be found in Table 8.3.
8.3.6 Cannabinoids
Cannabis smokers are less capable of recovering from fungal and bacterial infections. This is because the major cannabinoid found in cannabis, delta9-tetrahydrocannabinol (THC) decreases the production of proinflammatory cytokines, acting like an immunosuppressant. THC is a lipid soluble substance that will instantly distribute to different tissues, including the brain.
Cannabidiol (CBD) is a non-psychoactive cannabinoid that has anticonvulsive, sedative, anti-inflammatory, and hypnotic effects. It is thought to have a neuroprotective role in ischemic conditions. However, a systematic review has reported that it is not possible to conclude any efficacy out of it, regarding its effects on neurodegenerative disorders (Lim et al. 2017). Moreover, cannabinoids do not show any effects of note on the conditions rumored to be effective; i.e. multiple sclerosis (MS) (Sexton et al. 2014), anorexia in cancer or acquired immunodeficiency syndrome (Whiting et al. 2015), chemotherapy-induced nausea and vomiting (Whiting et al. 2015), and the pain related to cancer or rheumatism (Häuser et al. 2017).
8.4 Taken Together
Prevention of inflammation could be beneficial at any age. Many of the substances mentioned in the chapter are able to confront inflammation through several pathways, preventing cancers, diabetes dyslipidemia, atherosclerosis, etc. However, the dosage range and long-term use data for many of them still lack, and especially those thought to have effects on neurological disorders, have not proven favorable changes on the outcome. Nevertheless, most of them, including long chain PUFAs, vitamins, minerals, and isoflavonoids are regarded as safe within the normal consumption range; thus, taking a safe daily portion of them is recommended. Anti-inflammatory herbs are mostly not safe to be taken long-term daily, but per case and in courses of time. The daily intake limit for herbs shall be taken into consideration as well as their possible interactions’ profile with medications, which is a part of the life of many elderlies.
References
Akhondzadeh S, Abbasi SH (2006) Herbal medicine in the treatment of Alzheimer’s disease. Am J Alzheimers Dis Other Dement 21(2):113–118
Akhondzadeh S, Noroozian M, Mohammadi M, Ohadinia S, Jamshidi A, Khani M (2003) Salvia officinalis extract in the treatment of patients with mild to moderate Alzheimer’s disease: a double blind, randomized and placebo-controlled trial. J Clin Pharm Ther 28(1):53–59
Apaydin EA, Maher AR, Shanman R, Booth MS, Miles JN, Sorbero ME, Hempel S (2016) A systematic review of St. John’s wort for major depressive disorder. Syst Rev 5(1):148
Babaei F, Mirzababaei M, Nassiri-Asl M (2018) Quercetin in food: possible mechanisms of its effect on memory. J Food Sci 83(9):2280–2287
Bashir KM, Choi JS (2017) Clinical and physiological perspectives of β-glucans: the past, present, and future. Int J Mol Sci 18(9):1906
Basu A, Nguyen A, Betts NM, Lyons TJ (2014) Strawberry as a functional food: an evidence-based review. Crit Rev Food Sci Nutr 54(6):790–806
Behall KM, Scholfield DJ, Hallfrisch J (2004) Lipids significantly reduced by diets containing barley in moderately hypercholesterolemic men. J Am Coll Nutr 23:55–62
Bessa A, Campos FL, Videira RA, Mendes-Oliveira J, Bessa-Neto D, Baltazar G (2015) GPER: a new tool to protect dopaminergic neurons? Biochim Biophys Acta (BBA) - Mol Basis Dis 1852(10):2035–2041
Bitto A, Polito F, Atteritano M, Altavilla D, Mazzaferro S, Marini H, Adamo EB, D’Anna R, Granese R, Corrado F, Russo S (2010) Genistein aglycone does not affect thyroid function: results from a three-year, randomized, double-blind, placebo-controlled trial. J Clin Endocrinol Metabol 95(6):3067–3072
Blasko E, Haskell CA, Leung S, Gualtieri G, Halks-Miller M, Mahmoudi M, Dennis MK, Prossnitz ER, Karpus WJ, Horuk R (2009) Beneficial role of the GPR30 agonist G-1 in an animal model of multiple sclerosis. J Neuroimmunol 214(1–2):67–77
Borradaile NM, Wilcox LJ, Edwards JY, Murray WH (2002) Soya phytoestrogens, genistein and daidzein, decrease apolipoprotein B secretion from HepG2 cells through multiple mechanisms. Biochem J 366(2):531–539
Bourque M, Dluzen DE, Di Paolo T (2012) Signaling pathways mediating the neuroprotective effects of sex steroids and SERMs in Parkinson’s disease. Front Neuroendocrinol 33(2):169–178
Bruce B, Messina M, Spiller GA (2003) Isoflavone supplements do not affect thyroid function in iodine-replete postmenopausal women. J Med Food 6(4):309–316
Calder PC (2015) Marine omega-3 fatty acids and inflammatory processes: effects, mechanisms and clinical relevance. Biochim Biophys Acta, Mol Cell Biol Lipids 1851(4):469–484
Cao Z, Wang F, Xiu C, Zhang J, Li Y (2017) Hypericumperforatum extract attenuates behavioral, biochemical, and neurochemical abnormalities in aluminum chloride-induced Alzheimer’s disease rats. Biomed Pharmacother 91:931–937
Casanova MA, Medeiros F, Trindade M, Cohen C, Oigman W, Neves MF (2017) Omega-3 fatty acids supplementation improves endothelial function and arterial stiffness in hypertensive patients with hypertriglyceridemia and high cardiovascular risk. J Am Soc Hypertens 11(1):10–19
Chen JC et al (2005) Inhibition of iNOS gene expression by quercetin is mediated by the inhibition of I(kappa)B kinase, nuclear factor-kappa B and STAT1, and depends on heme oxygenase-1 induction in mouse BV-2 microglia. Eur J Pharmacol 521(1–3):9–20
Chen J, He J, Wildman RP, Reynolds K, Streiffer RH, Whelton PK (2006) A randomized controlled trial of dietary fiber intake on serum lipids. Eur J Clin Nutr 60(1):62–68
Chen W, van Wyk B, Vermaak I, Viljoen AM (2012) Cape aloes—a review of the phytochemistry, pharmacology and commercialisation of Aloe ferox. Phytochem Lett 5:1–12
Cleland LG, French JK, Betts WH, Murphy GA, Elliott MJ (1988) Clinical and biochemical effects of dietary fish oil supplements in rheumatoid arthritis. J Rheumatol 15(10):1471–1475
Cock IE (2015) The genus aloe: phytochemistry and therapeutic uses including treatments for gastrointestinal conditions and chronic inflammation. In: Novel natural products: therapeutic effects in pain, arthritis and gastro-intestinal diseases. Springer, Basel, pp 179–235
Colussi G, Catena C, Novello M, Bertin N, Sechi LA (2017) Impact of omega-3 polyunsaturated fatty acids on vascular function and blood pressure: relevance for cardiovascular outcomes. Nutr Metab Cardiovasc Dis 27(3):191–200
Comalada M et al (2005) In vivo quercitrin anti-inflammatory effect involves release of quercetin, which inhibits inflammation through downregulation of the NF-kappaB pathway. Eur J Immunol 35(2):584–592
Cugnet-Anceau C, Nazare JA, Biorklund M et al (2010) A controlled study of consumption of beta-glucan-enriched soups for 2 months by type 2 diabetic free-living subjects. Br J Nutr 103(3):422–428
de Carvalho CG, Ribeiro SM (2017) Aging, low-grade systemic inflammation and vitamin D: a mini-review. Eur J Clin Nutr 71(4):434
de Urbina JJ, San-Miguel B, Vidal-Casariego A, Crespo I, Sánchez DI, Mauriz JL, Culebras JM, González-Gallego J, Tuñón MJ (2017) Effects of oral glutamine on inflammatory and autophagy responses in cancer patients treated with abdominal radiotherapy: a pilot randomized trial. Int J Med Sci 14(11):1065
Deminice R, Rosa FT, Franco GS, Jordao AA, de Freitas EC (2013) Effects of creatine supplementation on oxidative stress and inflammatory markers after repeated-sprint exercise in humans. Nutrition 29(9):1127–1132
Du ZR, Feng XQ, Li N, Qu JX, Feng L, Chen L, Chen WF (2018) G protein-coupled estrogen receptor is involved in the anti-inflammatory effects of genistein in microglia. Phytomedicine 43:11–20
Edel AL, Rodriguez-Leyva D, Maddaford TG, Caligiuri SP, Austria JA, Weighell W, Guzman R, Aliani M, Pierce GN (2015) Dietary flaxseed independently lowers circulating cholesterol and lowers it beyond the effects of cholesterol-lowering medications alone in patients with peripheral artery disease. J Nutr 145(4):749–757
EMA/HMPC/432276/2015 (n.d.)
EMA/HMPC/55843/2011 (n.d.)
Estradiol protects dopaminergic neurons in a MPP+ Parkinson’s disease model (n.d.)
European medicine agency, committee on herbal medicinal products EMA/HMPC/680595/2013 (n.d.)
Faber J, Berkhout M, Vos AP, Sijben JW, Calder PC, Garssen J, van Helvoort A (2011) Supplementation with a fish oil-enriched, high-protein medical food leads to rapid incorporation of EPA into white blood cells and modulates immune responses within one week in healthy men and women. J Nutr 141(5):964–970
Fasano A (2012) Leaky gut and autoimmune diseases. Clin Rev Allergy Immunol 42(1):71–78
Fernandez-Martinez MN, Hernandez-Echevarria L, Sierra-Vega M, Diez-Liebana MJ, Calle-Pardo A, Carriedo-Ule D, Sahagún-Prieto AM, Anguera-Vila A, Garcia-Vieitez JJ (2014) A randomised clinical trial to evaluate the effects of Plantago ovata husk in Parkinson patients: changes in levodopa pharmacokinetics and biochemical parameters. BMC Complement Altern Med 14(1):296
Ferreroa A, Minettib A, Brasa C, Zanettia N (2007) Acute and subacute toxicity evaluation of ethanolic extract from fruits of Schinusmolle in rats. J Ethnopharmacol 113(3):441–447
Fliegner D, Schubert C, Penkalla A, Witt H, Kararigas G, Dworatzek E, Staub E, Martus P, Noppinger PR, Kintscher U, Gustafsson JÅ (2010) Female sex and estrogen receptor-β attenuate cardiac remodeling and apoptosis in pressure overload. Am J Phys Regul Integr Comp Phys 298(6):R1597–R1606
Franceschi C, Campisi J (2014) Chronic inflammation (inflammation) and its potential contribution to age-associated diseases. J Gerontol A Biomed Sci Med Sci 69(Suppl_1):S4–S9
Frank S, Copanaki E, Burbach GJ, Müller UC, Deller T (2009) Differential regulation of toll-like receptor mRNAs in amyloid plaque-associated brain tissue of aged APP23 transgenic mice. Neurosci Lett 453(1):41–44
Franke AA, Yu MC, Maskarinec G, Fanti P, Zheng W, Custer LJ (1999) Phytoestrogens in human biomatrices including breast milk. Clin Chem 23:532
Gammoh N, Rink L (2017) Zinc in infection and inflammation. Nutrients 9(6):624
GDNF contributes to estrogen-mediated protection of midbrain dopaminergic neurons (n.d.)
Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH (2010) Mechanisms underlying inflammation in neurodegeneration. Cell 140(6):918–934
Grace OM, Simmonds MSJ, Smith GF, van Wyk AE (2008) Documented utility and biocultural value of Aloe L. (Asphodelaceae): a review. Econ Bot 63(2):167–178
Grimm MO, Michaelson D, Hartmann T (2017) Omega-3 fatty acids, lipids and apoE lipidation in Alzheimer’s disease: a rationale for multi-nutrient dementia prevention. J Lipid Res 58:2083
Gruenwald J, Brendler T, Jaenicke C (2007) PDR for herbal medicines. Thomson, Reuters
Gupta A, Gupta R, Lal B (2001) Effect of Trigonella foenum-graecum (fenugreek) seeds on glycaemic control and insulin resistance in type 2 diabetes mellitus: a double-blind placebo controlled study. J Assoc Physicians India 49:1057–1061
Hallikainen M, Toppinen L, Mykkänen H et al (2006) Interaction between cholesterol and glucose metabolism during dietary carbohydrate modification in subjects with the metabolic syndrome. Am J Clin Nutr 84(6):1385–1392
Hannan JM, Rokeya B, Faruque O et al (2003) Effect of soluble dietary fiber fraction of Trigonella foenum-graecum on glycemic, insulinemic, lipidemic and platelet aggregation status of type 2 diabetic model rats. J Ethnopharmacol 88:73–77
Häuser W, Fitzcharles MA, Radbruch L, Petzke F (2017) Cannabinoids in pain management and palliative medicine: an overview of systematic reviews and prospective observational studies. Dtsch Arztebl Int 114(38):627
Healy DA, Wallace FA, Miles EA, Calder PC, Newsholme P (2000) Effect of low-to-moderate amounts of dietary fish oil on neutrophil lipid composition and function. Lipids 35(7):763–768
Hendy GN, Canaff L (2016) Calcium-sensing receptor, proinflammatory cytokines and calcium homeostasis. In: Seminars in cell and developmental biology, vol 49. Academic Press, London, pp 37–43
Henrotin Y, Mobasheri A, Marty M (2012) Is there any scientific evidence for the use of glucosamine in the management of human osteoarthritis? Arthritis Res Ther 14(1):201
Hofrichter J, Krohn M, Schumacher T, Lange C, Feistel B, Walbroel B, Heinze HJ, Crockett S, Sharbel TF, Pahnke J (2013) Reduced Alzheimer’s disease pathology by St. John’s Wort treatment is independent of hyperforin and facilitated by ABCC1 and microglia activation in mice. Curr Alzheimer Res 10(10):1057–1069
Hosseinzadeh H, Moallem SA, Moshiri M, Sarnavazi MS, Etemad L (2012) Anti-nociceptive and anti-inflammatory effects of cyanocobalamin (vitamin B12) against acute and chronic pain and inflammation in mice. Arzneimittelforschung 62(07):324–329
Hsieh DJ, Kuo WW, Lai YP, Shibu MA, Shen CY, Pai P, Yeh YL, Lin JY, Viswanadha VP, Huang CY (2015) 17β-estradiol and/or estrogen receptor β attenuate the autophagic and apoptotic effects induced by prolonged hypoxia through HIF-1α-mediated BNIP3 and IGFBP-3 signaling blockage. Cell Physiol Biochem 36(1):274–284
Hutchings A, Scott AH, Lewis G, Cunningham A (1996) Zulu medicinal plants: an inventory. University of Natal Press, Pietermaritzburg
Ionita R, Postu PA, Mihasan M, Gorgan DL, Hancianu M, Cioanca O, Hritcu L (2018) Ameliorative effects of Matricariachamomilla L. hydroalcoholic extract on scopolamine-induced memory impairment in rats: a behavioral and molecular study. Phytomedicine 47:113
Javadi F, Ahmadzadeh A, Eghtesadi S, Aryaeian N, Zabihiyeganeh M, RahimiForoushani A, Jazayeri S (2017) The effect of quercetin on inflammatory factors and clinical symptoms in women with rheumatoid arthritis: a double-blind, randomized controlled trial. J Am Coll Nutr 36(1):9–15
Jeong JW, Lee HH, Han MH, Kim GY, Kim WJ, Choi YH (2014) Anti-inflammatory effects of genistein via suppression of the toll-like receptor 4-mediated signaling pathway in lipopolysaccharide-stimulated BV2 microglia. Chem Biol Interact 212:30–39
Kararigas G, Fliegner D, Forler S, Klein O, Schubert C, Gustafsson JÅ, Klose J, Regitz-Zagrosek V (2014) Comparative proteomic analysis reveals sex and estrogen receptor β effects in the pressure overloaded heart. J Proteome Res 13(12):5829–5836
Kaul N, Kreml R, Austria JA et al (2008) A comparison of fish oil, flaxseed oil and hempseed oil supplementation on selected parameters of cardiovascular health in healthy volunteers. J Am Coll Nutr 27(1):51–58
Kayisli UA, Guzeloglu-Kayisli O, Guzel E, Arici A (2013) Genistein inhibits cell proliferation and stimulates apoptosis in human coronary artery endothelial cells. Gynecol Obstet Investig 75(4):235–242
Kazak F, Yarim GF (2017) Neuroprotective effects of acetyl-l-carnitine on lipopolysaccharide-induced neuroinflammation in mice: involvement of brain-derived neurotrophic factor. Neurosci Lett 658:32–36
Kennedy DO, Scholey AB (2006) The psychopharmacology of European herbs with cognition-enhancing properties. Curr Pharm Des 12(35):4613–4623
Kennedy DO, Pace S, Haskell C, Okello EJ, Milne A, Scholey AB (2006) Effects of cholinesterase inhibiting sage ( Salvia officinalis ) on mood, anxiety and performance on a psychological stressor battery. Neuropsychopharmacology 31(4):845–852
Kew S, Banerjee T, Minihane AM, Finnegan YE, Muggli R, Albers R, Williams CM, Calder PC (2003) Lack of effect of foods enriched with plant-or marine-derived n− 3 fatty acids on human immune function. Am J Clin Nutr 77(5):1287–1295
Kim DS, Shin MR, Kim YS, Bae WJ, Roh DH, Hwang YS, Kim EC (2015) Anti-inflammatory effects of glutamine on LPS-stimulated human dental pulp cells correlate with activation of MKP-1 and attenuation of the MAPK and NF-κB pathways. Int Endod J 48(3):220–228
Koc A, Ozkan T, Karabay AZ, Sunguroglu A, Aktan F (2011) Effect of L-carnitine on the synthesis of nitric oxide in RAW 264· 7 murine macrophage cell line. Cell Biochem Funct 29(8):679–685
Kremer J, Michalek A, Lininger L, Huyck C, Bigauoette J, Timchalk M, Rynes R, Zieminski J, Bartholomew L (1985) Effects of manipulation of dietary fatty acids on clinical manifestations of rheumatoid arthritis. Lancet 325(8422):184–187
Kremer JM, Jubiz W, Michalek A, Rynes RI, Bartholomew LE, Bigaouette J, Timchalk M, Beeler D, Lininger L (1987) Fish-oil fatty acid supplementation in active rheumatoid arthritis: a double-blinded, controlled, crossover study. Ann Intern Med 106(4):497–503
Külzow N, Witte AV, Kerti L, Grittner U, Schuchardt JP, Hahn A, Flöel A (2016) Impact of omega-3 fatty acid supplementation on memory functions in healthy older adults. J Alzheimers Dis 51(3):713–725
Kuo J, Hamid N, Bondar G, Prossnitz ER, Micevych P (2010) Membrane estrogen receptors stimulate intracellular calcium release and progesterone synthesis in hypothalamic astrocytes. J Neurosci 30:12950–12957
Le Donne M, Caruso C, Mancuso A, Costa G, Iemmo R, Pizzimenti G, Cavallari V (2011) The effect of vaginally administered genistein in comparison with hyaluronic acid on atrophic epithelium in postmenopause. Arch Gynecol Obstet 283(6):1319–1323
Lee BJ, Lin JS, Lin YC, Lin PT (2015) Antiinflammatory effects of L-carnitine supplementation (1000 mg/d) in coronary artery disease patients. Nutrition 31(3):475–479
Liao Y, Guan ZZ, Ravid R (2011) Changes of nuclear factor and inflammatory chemotactic factors in brain of patients with Alzheimer’s disease. Zhonghua bing li xue za zhi = Chin J Pathol 40(9):585–589
Liatis S, Tsapogas P, Chala E, Dimosthenopoulos C, Kyriakopoulos K, Kapantais E, Katsilambros N (2009a) The consumption of bread enriched with β-glucan reduces LDL-cholesterol and improves insulin resistance in patients with type 2 diabetes. Diabetes Metab 35:115–120
Liatis S, Tsapogas P, Chala E et al (2009b) The consumption of bread enriched with betaglucan reduces LDL-cholesterol and improves insulin resistance in patients with type 2 diabetes. Diabetes Metab 35(2):115–120
Lim K, See YM, Lee J (2017) A systematic review of the effectiveness of medical cannabis for psychiatric, movement and neurodegenerative disorders. Clin Psychopharmacol Neurosci 15(4):301
Lima CF, Carvalho F, Fernandes E et al (2004) Evaluation of toxic/protective effects of the essential oil of Salvia officinalis on freshly isolated rat hepatocytes. Toxicol in Vitro 18(4):457–465
Liu Y, Li F, Zhang L, Wu J, Wang Y, Yu H (2017) Taurine alleviates lipopolysaccharide-induced liver injury by anti-inflammation and antioxidants in rats. Mol Med Rep 16(5):6512–6517
Lourdudoss C, Wolk A, Nise L, Alfredsson L, van Vollenhoven R (2017) Are dietary vitamin D, omega-3 fatty acids and folate associated with treatment results in patients with early rheumatoid arthritis? Data from a Swedish population-based prospective study. BMJ Open 7(6):e016154
Lourdudoss C, Di Giuseppe D, Wolk A, Westerlind H, Klareskog L, Alfredsson L, van Vollenhoven RF, Lampa J (2018) Dietary intake of polyunsaturated fatty acids and pain in spite of inflammatory control among methotrexate-treated early rheumatoid arthritis patients. Arthritis Care Res 70(2):205–212
Lucas EA, Wild RD, Hammond LJ et al (2002) Flaxseed improves lipid profile without altering biomarkers of bone metabolism in postmenopausal women. J Clin Endocrinol Metab 87(4):1527–1532
Madeo A, Maggiolini M (2010) Nuclear alternate estrogen receptor GPR30 mediates 17beta-estradiol-induced gene expression and migration in breast cancer-associated fibroblasts. Cancer Res 70:6036–6046
Maggiolini M, Vivacqua A, Fasanella G, Recchia AG, Sisci D, Pezzi V, Montanaro D, Musti AM, Picard D, Ando S (2004) The G protein-coupled receptor GPR30 mediates c-fos up-regulation by 17beta-estradiol and phytoestrogens in breast cancer cells. J Biol Chem 279:27008–27016
Mahan L, Raymond J, Krause M (2017) Krause’s food & the nutrition care process. 14th ed. Elsevier, St. Louis, p 30
Maki KC, Beiseigel JM, Jonnalagadda SS et al (2010) Whole-grain ready-to-eat oat cereal, as part of a dietary program for weight loss, reduces low-density lipoprotein cholesterol in adults with overweight and obesity more than a dietary program including low-fiber control foods. J Am Diet Assoc 110(2):205–214
Manonai J, Songchitsomboon S, Chanda K, Hong JH, Komindr S (2006) The effect of a soy-rich diet on urogenital atrophy: a randomized, cross-over trial. Maturitas 54(2):135–140
Mao JJ, Xie SX, Keefe JR, Soeller I, Li QS, Amsterdam JD (2016) Long-term chamomile (Matricariachamomilla L.) treatment for generalized anxiety disorder: a randomized clinical trial. Phytomedicine 23(14):1735–1742
Marini H, Polito F, Adamo EB, Bitto A, Squadrito F, Benvenga S (2012) Update on genistein and thyroid: an overall message of safety. Front Endocrinol 3:94
Mendes-Oliveira J, Campos FL, Videira RA, Baltazar G (2017) GPER activation is effective in protecting against inflammation-induced nigral dopaminergic loss and motor function impairment. Brain Behav Immun 64:296–307
Meyer MR, Prossnitz ER, Barton M (2011) The G protein-coupled estrogen receptor GPER/GPR30 as a regulator of cardiovascular function. Vasc Pharmacol 55:17–25
Mitchell JH, Cawood E, Kinniburgh D, Provan A, Collins AR, Irvine DS (2001) Effect of a phytoestrogen food supplement on reproductive health in normal males. Clin Sci 100(6):613–618
Mohammadirad A, Aghamohammadali-Sarraf F, Badiei S, Faraji Z, Hajiaghaee R, Baeeri M, Gholami M, Abdollahi M (2013) Anti-aging effects of some selected Iranian folk medicinal herbs-biochemical evidences. Iran J Basic Med Sci 16(11):1170
Morikawa K et al (2003) Inhibitory effect of quercetin on carrageenan-induced inflammation in rats. Life Sci 74(6):709–721
Moyad MA, Robinson LE, Kittelsrud JM et al (2009) Immunogenic yeast-based fermentation product reduces allergic rhinitis-induced nasal congestion: a randomized, double-blind, placebo-controlled trial. Adv Ther 26(8):795–804
Mozolewski P, Moskot M, Jakobkiewicz-Banecka J, Wegrzyn G, Bochenska K, Banecki B, Gabig-Ciminska M (2017) Nonsteroidal anti-inflammatory drugs modulate cellular glycosaminoglycan synthesis by affecting EGFR and PI3K signaling pathways. Sci Rep 7:43154
Navarro SL, White E, Kantor ED, Zhang Y, Rho J, Song X, Milne GL, Lampe PD, Lampe JW (2015) Randomized trial of glucosamine and chondroitin supplementation on inflammation and oxidative stress biomarkers and plasma proteomics profiles in healthy humans. PLoS One 10(2):e0117534
Ng QX, Venkatanarayanan N, Ho CY (2017) Clinical use of Hypericumperforatum (St John’s wort) in depression: a meta-analysis. J Affect Disord 210:211–221
Okun E, Griffioen KJ, Lathia JD, Tang SC, Mattson MP, Arumugam TV (2009) Toll-like receptors in neurodegeneration. Brain Res Rev 59(2):278–292
Ota A, Ulrih NP (2017) An overview of herbal products and secondary metabolites used for management of type two diabetes. Front Pharmacol 8:436
Panossian AG, Gabrielian E, Manvelian V, Jurcic K, Wagner H (1996) Immunosuppressive effects of hypericin on stimulated human leukocytes: inhibition of the arachidonic acid release, leukotriene B4 and Interleukin-Iα production, and activation of nitric oxide formation. Phytomedicine 3(1):19–28
Pase MP, Grima N, Cockerell R, Stough C, Scholey A, Sali A, Pipingas A (2015) The effects of long-chain omega-3 fish oils and multivitamins on cognitive and cardiovascular function: a randomized, controlled clinical trial. J Am Coll Nutr 34(1):21–31
Pedram A, Razandi M, Korach KS, Narayanan R, Dalton JT, Levin ER (2013) ERβ selective agonist inhibits angiotensin-induced cardiovascular pathology in female mice. Endocrinology 154(11):4352–4364
Poh S, Putt KS, Low PS (2017) Folate-targeted dendrimers selectively accumulate at sites of inflammation in mouse models of ulcerative colitis and atherosclerosis. Biomacromolecules 18(10):3082–3088
Prossnitz ER, Barton M (2011) The G-protein-coupled estrogen receptor GPER in health and disease. Nat Rev Endocrinol 7:715–726
Queenan KM, Stewart ML, Smith KN, Thomas W, Fulcher RG, Slavin JL (2007) Concentrated oat beta-glucan, a fermentable fiber, lowers serum cholesterol in hypercholesterolemic adults in a randomized controlled trial. Nutr J 6:6
Raber P, Ochoa AC, Rodríguez PC (2012) Metabolism of L-arginine by myeloid-derived suppressor cells in cancer: mechanisms of T cell suppression and therapeutic perspectives. Immunol Investig 41(6–7):614–634
Rafraf M, Karimi M, Jafari A (2015) Effect of L-carnitine supplementation in comparison with moderate aerobic training on serum inflammatory parameters in healthy obese women. J Sports Med Phys Fitness 55(11):1363–1370
Rahimifard M, Maqbool F, Moeini-Nodeh S, Niaz K, Abdollahi M, Braidy N, Nabavi SM, Nabavi SF (2017) Targeting the TLR4 signaling pathway by polyphenols: a novel therapeutic strategy for neuroinflammation. Ageing Res Rev 36:11–19
Rajaei E, Mowla K, Ghorbani A, Bahadoram S, Bahadoram M, Dargahi-Malamir M (2016) The effect of omega-3 fatty acids in patients with active rheumatoid arthritis receiving DMARDs therapy: double-blind randomized controlled trial. Global J Health Sci 8(7):18
Reed-Geaghan EG, Savage JC, Hise AG, Landreth GE (2009) CD14 and toll-like receptors 2 and 4 are required for fibrillar Aβ-stimulated microglial activation. J Neurosci 29(38):11982–11992
Rees D, Miles EA, Banerjee T, Wells SJ, Roynette CE, Wahle KW, Calder PC (2006) Dose-related effects of eicosapentaenoic acid on innate immune function in healthy humans: a comparison of young and older men. Am J Clin Nutr 83(2):331–342
Rettew JA, McCall SH, Marriott I (2010) GPR30/GPER-1 mediates rapid decreases in TLR4 expression on murine macrophages. Mol Cell Endocrinol 328(1):87–92
Riesberg LA, Weed SA, McDonald TL, Eckerson JM, Drescher KM (2016) Beyond muscles: the untapped potential of creatine. Int Immunopharmacol 37:31–42
Runhaar J, Rozendaal RM, van Middelkoop M, Bijlsma HJ, Doherty M, Dziedzic KS, Lohmander LS, McAlindon T, Zhang W, Zeinstra SB (2017) Subgroup analyses of the effectiveness of oral glucosamine for knee and hip osteoarthritis: a systematic review and individual patient data meta-analysis from the OA trail bank. Ann Rheum Dis 76:1862
Sabogal-Guáqueta AM, Munoz-Manco JI, Ramírez-Pineda JR, Lamprea-Rodriguez M, Osorio E, Cardona-Gómez GP (2015) The flavonoid quercetin ameliorates Alzheimer’s disease pathology and protects cognitive and emotional function in aged triple transgenic Alzheimer’s disease model mice. Neuropharmacology 93:134–145
Saghafi N, Rhkhshandeh H, Pourmoghadam N, Pourali L, Ghazanfarpour M, Behrooznia A, Vafisani F (2018) Effectiveness of Matricariachamomilla (chamomile) extract on pain control of cyclic mastalgia: a double-blind randomised controlled trial. J Obstet Gynaecol 38(1):81–84
Samieri C, Morris MC, Bennett DA, Berr C, Amouyel P, Dartigues JF, Tzourio C, Chasman DI, Grodstein F (2017) Fish intake, genetic predisposition to Alzheimer disease, and decline in global cognition and memory in 5 cohorts of older persons. Am J Epidemiol 187(5):933–940
Santhanam S, Alvarado DM, Ciorba MA (2016) Therapeutic targeting of inflammation and tryptophan metabolism in colon and gastrointestinal cancer. Transl Res 167(1):67–79
Sarinho E, Medeiros D, Schor D, Silva AR, Sales V, Motta ME, Costa A, Azoubel A, Rizzo JA (2009) Production of interleukin-10 in asthmatic children after β-1–3-glucan. Allergol Immunopathol (Madr) 37:188–192
Sauvaire Y, Ribes G, Baccou JC, Loubatieeres-Mariani MM (1991) Implication of steroid saponins and sapogenins in the hypocholesterolemic effect of fenugreek. Lipids 26:191–197
Scholey AB, Tildesley NT, Ballard CG et al (2008) An extract of Salvia (sage) with anticholinesterase properties improves memory and attention in healthy older volunteers. Psychopharmacology 198(1):127–139
Sexton M, Cudaback E, Abdullah RA, Finnell J, Mischley LK, Rozga M, Lichtman AH, Stella N (2014) Cannabis use by individuals with multiple sclerosis: effects on specific immune parameters. Inflammopharmacology 22(5):295–303
Sharma JN, Al-Omran A, Parvathy SS (2007) Role of nitric oxide in inflammatory diseases. Inflammopharmacology 15(6):252–259
Sharma N, Suresh S, Debnath A, Jha S (2017) Trigonella seed extract ameliorates inflammation via regulation of the inflammasome adaptor protein, ASC. Front Biosci (Elite Ed) 9:246–257
Shen XY, Luo T, Li S, Ting OY, He F, Xu J, Wang HQ (2018) Quercetin inhibits okadaic acid-induced tau protein hyperphosphorylation through the Ca2+−calpain-p25-CDK5 pathway in HT22 cells. Int J Mol Med 41(2):1138–1146
Shinto L, Quinn J, Montine T, Dodge HH, Woodward W, Baldauf-Wagner S, Waichunas D, Bumgarner L, Bourdette D, Silbert L, Kaye J (2014) A randomized placebo-controlled pilot trial of omega-3 fatty acids and alpha lipoic acid in Alzheimer’s disease. J Alzheimers Dis 38(1):111–120
Sindhu G, Shyni GL, Pushpan CK, Nambisan B, Helen A (2018) Evaluation of anti-arthritic potential of Trigonella foenum-graecum L. (fenugreek) mucilage against rheumatoid arthritis. Prostaglandins Other Lipid Mediat 138:48–53
Singhal PC, Gupta RK, Joshi LD (1982) Hypocholesterolemic effect of Trigonella foenum-graecum (METHI). Curr Sci 51:136
Stark A, Madar Z (1993) The effect of an ethanol extract derived from fenugreek (Trigonella foenum-graecum) on bile acid absorption and cholesterol levels in rats. Br J Nutr 69:277–287
Sturtzel B, Dietrich A, Wagner KH, Gisinger C, Elmadfa I (2010) The status of vitamins B6, B12, folate, and of homocysteine in geriatric home residents receiving laxatives or dietary fiber. J Nutr Health Aging 14(3):219–223
Sur P, Das M, Gomes A et al (2001) Trigonella foenum-graecum (fenugreek) seed extract as an antineoplastic agent. Phytother Res 15:257–259
Taghizadeh M, Tamtaji OR, Dadgostar E, Kakhaki RD, Bahmani F, Abolhassani J, Aarabi MH, Kouchaki E, Memarzadeh MR, Asemi Z (2017) The effects of omega-3 fatty acids and vitamin E co-supplementation on clinical and metabolic status in patients with Parkinson’s disease: a randomized, double-blind, placebo-controlled trial. Neurochem Int 108:183–189
Talbott S, Talbott J (2009) Effect of β 1,3/1,6 glucan on upper respiratory tract infection symptoms and mood state in marathon athletes. J Sports Sci Med 8:509–515
Talbott SM, Talbott JA (2012) Baker’s yeast β-glucan supplement reduces upper respiratory symptoms and improved mood state in stressed women. J Am Coll Nutr 31:295–300
The possible role of estrogen and selective estrogen receptor modulators in a rat model of Parkinson’s disease (n.d.)
Thies F, Nebe-von-Caron G, Powell JR, Yaqoob P, Newsholme EA, Calder PC (2001) Dietary supplementation with γ-linolenic acid or fish oil decreases T lymphocyte proliferation in healthy older humans. J Nutr 131(7):1918–1927
Thompson Coon JS, Ernst E (2003) Herbs for serum cholesterol reduction: a systematic view. J Fam Pract 52:468–478
Torkan M, Hassan Entezari M, Siavash M (2015) Effect of flaxseed on blood lipid level in hyperlipidemic patients. Rev Recent Clin Trials 10(1):61–67
Valette G, Sauvaire Y, Baccou JC, Ribes G (1984) Hypocholesterolaemic effect of fenugreek seeds in dogs. Atherosclerosis 50:105–111
van Wyk BE, Smith G (2008) Guide to the aloes of South Africa, 2nd edn. Briza Publications, Pretoria
Wang DM, Li SQ, Wu WL, Zhu XY, Wang Y, Yuan HY (2014) Effects of long-term treatment with quercetin on cognition and mitochondrial function in a mouse model of Alzheimer’s disease. Neurochem Res 39(8):1533–1543
Whiting PF, Wolff RF, Deshpande S, Di Nisio M, Duffy S, Hernandez AV, Keurentjes JC, Lang S, Misso K, Ryder S, Schmidlkofer S (2015) Cannabinoids for medical use: a systematic review and meta-analysis. JAMA 313(24):2456–2473
Wu Y, Antony S, Meitzler JL, Doroshow JH (2014) Molecular mechanisms underlying chronic inflammation-associated cancers. Cancer Lett 345(2):164–173
Wu PS, Ding HY, Yen JH, Chen SF, Lee KH, Wu MJ (2018) Anti-inflammatory activity of 8-hydroxydaidzein in LPS-stimulated BV2 microglial cells via activation of Nrf2-antioxidant and attenuation of Akt/NF-κB-inflammatory signaling pathways, as well as inhibition of COX-2 activity. J Agric Food Chem 66(23):5790–5801
Yadav UC, Moorthy K, Baquer NZ (2004) Effects of sodium-orthovanadate and Trigonella foenum-graecum seeds on hepatic and renal lipogenic enzymes and lipid profile during alloxan diabetes. J Biosci 29:81–91
Zameer S, Najmi AK, Vohora D, Akhtar M (2017) A review on therapeutic potentials of Trigonella foenum-graecum (fenugreek) and its chemical constituents in neurological disorders: complementary roles to its hypolipidemic, hypoglycemic, and antioxidant potential. Nutr Neurosci 16:1–7
Zarvandi M, Rakhshandeh H, Abazari M, Shafiee-Nick R, Ghorbani A (2017) Safety and efficacy of a polyherbal formulation for the management of dyslipidemia and hyperglycemia in patients with advanced-stage of type-2 diabetes. Biomed Pharmacother 89:69–75
Zemestani M, Rafraf M, Asghari-Jafarabadi M (2016) Chamomile tea improves glycemic indices and antioxidants status in patients with type 2 diabetes mellitus. Nutrition 32(1):66–72
Zhao TZ, Ding Q, Hu J, He SM, Shi F, Ma LT (2016) GPER expressed on microglia mediates the anti-inflammatory effect of estradiol in ischemic stroke. Brain Behav 6(4):e00449
Zhou X, Yuan L, Zhao X, Hou C, Ma W, Yu H, Xiao R (2014) Genistein antagonizes inflammatory damage induced by β-amyloid peptide in microglia through TLR4 and NF-κB. Nutrition 30(1):90–95
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2020 Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Goudarzi, S., Abdollahi, M. (2020). Anti-Inflammatory Nutrients and Nutraceuticals for Active and Healthy Aging. In: Nabavi, S.M., D'Onofrio, G., Nabavi, S.F. (eds) Nutrients and Nutraceuticals for Active & Healthy Ageing. Springer, Singapore. https://doi.org/10.1007/978-981-15-3552-9_8
Download citation
DOI: https://doi.org/10.1007/978-981-15-3552-9_8
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-15-3551-2
Online ISBN: 978-981-15-3552-9
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)