Chapter 21

Anti-inflammatory Dietary Ingredients, Medicinal Plants, and Herbs Exert Beneficial Health Effects in Aging

Kiran S. Panickar and Dennis E. Jewell,    Hill’s Pet Nutrition Center, Topeka, KS, United States


Nutrition plays an important role in attenuating some of the detrimental effects of aging. Aging in humans is associated with chronic and systemic low-grade inflammation as well as a decline in mobility, joint problems, weakened muscles and bones, reduced lean body mass, cancer, increased dermatological problems, decline in cognitive ability, reduced energy, decreased immune function, decreased renal function, and urinary incontinence. Strategies to reduce inappropriate chronic inflammation have included dietary modification and the use of herbal extracts in the diet or as supplements. Canines also have general aging-associated health conditions that are similar to those in humans. The underlying causes of detrimental health in aging are likely to be many, but each condition is also associated with an increase in circulating pro-inflammatory markers. An inflammatory state characterized by an increase in pro-inflammatory markers includes tumor necrosis factor α, interleukins 6 and 1 β (IL-6 and IL-1β), and C-reactive protein. All are believed to contribute to or worsen aging-related general declines in the biological mechanisms responsible for physical function. Natural botanicals have bioactive components that appear to have robust anti-inflammatory effects and may contribute to a reduction in inflammation when included in the diet. Review of all aging-associated health conditions is beyond the scope of this chapter, so we will focus on selected areas of health conditions, including immune function, renal function, dementia, and cognition in animal and human studies. We will also review the scientific data on the anti-inflammatory effects of dietary ingredients as well as the efficacy of bioactive molecules from botanicals.


Polyphenols; inflammation; cytokines; immune; botanical; inflammaging


One hallmark of aging is chronic low-grade inflammation (Brüünsgaard and Pedersen, 2003; Candore et al., 2010) that is accompanied by an increase in circulating pro-inflammatory cytokines (Roubenoff et al., 1998; Bruunsgaard, 2002, Michaud et al., 2013). A pro-inflammatory state contributes to various aging-associated dysfunctions at the cellular and molecular levels.

The immune system is a key component of inflammation and is body’s natural response to injury or infection. Immune function involves several cell types that regulate both innate and adaptive responses as well as interactions among them while responding to an antigen. Innate immune response is nonspecific and relatively immediate whereas adaptive immune response is antigen-specific and delayed. Inflammation is generally classified as acute or chronic. While many features of the acute inflammatory response may also manifest themselves in chronic inflammation, there are distinguishing features. For instance, acute inflammation, as its name indicates, is a quick response to an infection or injury and is often resolved quickly; chronic inflammation may develop in days and can be progressive. While neutrophils play an important role in acute inflammation, monocytes, macrophages, and lymphocytes play a major role in chronic inflammation. One form of early response to infection or injury is the acute phase response (APR). The APR is characterized by the production of plasma protein-derived proteins such as C-reactive protein (CRP) and serum amyloids A and P, and they complement proteins by the liver generally in response to cell-derived mediators such as prostaglandins, nitric oxide, leukotrienes, and cytokines. The goal of the early response includes (1) destroying or inhibiting the activity of foreign bodies in particular microbes, (2) exerting protective effects that may limit infection, (3) removing necrotic tissue, and (4) initiating cell repair. This response is distinct from a state of mild inflammation, which is associated with chronically elevated levels of inflammatory markers, including C-reactive protein as well as cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α).

Immunosenescence is the gradual decline of the immune system with age (Franceschi et al., 2000). Both innate and adaptive responses are dampened with aging, and there is also a decline in the diversity of the antigen repertoire and an accumulation of functionally impaired memory lymphocytes that can affect the ability to fight infection or recover from injury. While there is consensus that the immune responses decline with aging, the specific changes in the repertoire of specific cell types leading to a compromised immune system are not clear. For instance, there might be a decrease in the levels of cluster of differentiation (CD) cells CD27 and CD28 and the generation of immature B cells but an increase in CD244 and memory B cells (see Alam and Pawelec, 2012 for review). This signifies the complexity of the immune system in aging. CD244, for instance, is a cell surface receptor on natural killer (NK) cells, which might imply increased NK-mediated cytolytic activity. In addition, this receptor can also be expressed on nonlymphocytes such as eosinophils, mast cells, and dendritic cells. Whereas taking this one example in isolation would indicate an increased immune function in aging, a generalized dampened immune function in aging is likely the resultant composite function of the immune system as a whole. In canines, there does not appear to be clear consensus on the types of leukocytes that decline with aging although a general decline in immune function with aging is observed. Kearns et al. (1999) reported an age-associated decline in the proliferative capacity of lymphocytes in fox terriers and Labrador retrievers, indicating a reduced immune activity. Fleming et al. (2011) reported that older dogs died of neoplastic, traumatic, and infectious disorders, which indicates a possibly reduced immune function and ability to fight infection. Nevertheless, in older canines an ability to mount a primary humoral response to novel antigens is generally retained but the magnitude of the response is likely reduced relative to titers achieved in younger animals (Day, 2010). Aged beagle dogs have decreased neutrophil phagocytosis when compared to young ones as assessed by their ability to phagocytize Lactococcus lactis ex vivo (Hall et al., 2010). In the same study, younger dogs had significantly higher levels of messenger RNA (mRNA) for IL8R, L-selectin, and interleukin-1β-converting enzyme. While this indicates a generally depressed innate immune response in older dogs, the ability to fight infections was not assessed in the study.

Dietary modifications also can influence the immune system in elderly humans (Lesourd, 1997; Lesourd and Mazari, 1999). However, several ingredients have not had the desired beneficial immune effects although their effects in animal studies have been generally beneficial. In humans, dietary inclusions of certain ingredients including β-carotene (Santos et al., 1997) or black-currant seed oil rich in both gamma-linolenic (18:3n-6) and alpha-linolenic (18:3n-3) acids (Wu et al., 1999) have not been reported to have significant effects on the immune system in the elderly. In contrast, vitamin E (800 mg dl-α-tocopheryl acetate) appeared to enhance cell-mediated immunity in healthy elders (Meydani et al., 1990). Immunosenescence in canines can be modulated by caloric restriction (Greeley et al., 2006), and there is an important role for nutrition in regulating immune function (Sheffy and Williams, 1981). Hall et al. (2011) reported that a diet fortified with vitamins C and E and added fish oil reduced the pro-inflammatory markers, including nuclear factor kappa B (NFκB), toll-like receptors 2 and 4 (TLR-2 and TLR-4), cyclooxygenase-2, and myeloperoxidase (MPO) in the neutrophils isolated from adult and aged dogs. Consumption of high concentrations of α-tocopheryl acetate in elderly healthy dogs resulted in higher percentages of CD8+cells when compared to those consuming low concentrations (Hall et al., 2003). These studies indicate an important role of nutrition in regulating the immune function in aging.

Renal Function

A reduction in age-associated kidney function in humans has been well established (see Abdel-Rahman and Okusa, 2014, for review). In addition to a reduction in renal mass during aging (Mulder and Hillen, 2001), morphological changes in the glomeruli are associated with kidney dysfunction, including decreases in glomerular filtration rate (GFR) and renal blood flow (Anderson and Brenner, 1986; Weinstein and Anderson, 2010). Similarly, a reduction in renal function with age has also been reported in cats (Hall et al., 2014) and dogs (Hall et al., 2015). In canines, chronic renal failure (CRF) is the most common form of renal disease; while CRF may occur at all ages, its incidence increases with age (Rubin, 1997). Inflammation is associated with a decline in renal function. Costa et al. (2013) reported impaired renal function in older rats (18 months old) and significantly higher urea and creatinine as well as interferon gamma (INFγ) when compared to young rats (two months). Increased pro-inflammatory cytokines and chemokines (CCLs), including CCL3, CCL4, CCL5, CD80, TNF-α, and IL-12b are upregulated in aging rat kidney when compared to young (Xi et al., 2014). Other pro-inflammatory mediators in kidney dysfunction in aging include NFκB (Moreno et al., 2011). In canines, there was an increased expression of the cytokines IL-1α, IL-1β, transforming growth factor beta (TGF-β), and the enzyme 5-lipoxygenase (5-LO) in the venous whole blood of dogs with renal disease (Nentwig et al., 2016). There was a significant relation between serum CRP concentrations and kidney function, which indicates an important role for CRP in the pathogenesis of naturally occurring canine renal disease (Raila et al., 2011). Median CRP concentration of miniature schnauzer dogs was slightly higher than that of other breeds of dogs (Wong et al., 2011), indicating that breed specificity may also be an important factor to consider when assessing inflammation in dogs. In cats, chronic kidney disease (CKD) is the most common metabolic disease of aged domesticated cats (>12 years of age; Brown et al. (2016). Inflammation contributes to the progression of renal fibrosis in CKD in cats; when urine cytokine levels in both healthy and CKD cats were compared, significantly higher levels of IL-8 and transforming growth factor-β1 (TGF-β1) concomitant with lower vascular endothelial growth factor (VEGF) levels were reported (Habenicht et al., 2013).

A common aging effect shared by cats, dogs, and humans is declining renal function (see Panickar and Jewell, 2015 for review; Hall et al.; Hall et al., 2016a; Hall et al., 2016b). There are multiple observational studies in humans that show diets rich in fruits and vegetables reduce the risk of chronic kidney disease (Jain and Reilly, 2014). There is also a reduction in renal function when foods high in pro-inflammatory ingredients are compared to foods with high anti-inflammatory dietary ingredients; the pro-inflammatory regimen was also associated with increased systemic inflammation (Xu et al., 2015). Therefore, it is reasonable to conclude that inflammation is one pathway through which kidney function is influenced and foods that reduce inflammation may be beneficial in reducing age-associated declines in kidney function.

Nutritional intervention to reduce kidney dysfunction is important in maintaining kidney health. In evaluating the effect of anti-inflammatory ingredients and botanicals on early intervention to change age-associated declines in renal function, a food rich in antioxidants (alpha-lipoic acid, vitamins E and C), fish oil, and botanicals (fruits and vegetables) were fed to dogs for a period of six months. Dogs that did not receive the renal protective food (RPF) but were maintained on their owner’s choice food had numerically increased blood urea nitrogen (BUN) and symmetric dimethyl arginine (SDMA), while those that received the RPF decreased BUN and SDMA. The control dogs did not change blood creatinine concentration, whereas the RPF fed dogs declined in circulating creatinine concentration. These improvements in markers of renal function in geriatric dogs show the benefit of anti-inflammatory ingredients and botanicals (Hall et al., 2016b). A major role of the kidneys is to also maintain phosphorus homeostasis in the body. In general, in dogs with chronic renal failure the combination of low protein and low phosphorus in the diet appears to be beneficial. In addition, several ingredients have been demonstrated to attenuate stress associated with kidney function in aging as well as in nonaging-related kidney dysfunction. Table 21.1 provides a list of anti-inflammatory botanical extracts that may prove beneficial as nephroprotective agents when included in the diet. In cats, similar to what was observed in dogs, an RPF enriched with antioxidants (vitamins E and C), fish oil, L-carnitine, and botanicals (vegetables) had an improvement in renal function when compared to cats that did not receive nutritional intervention with the RPF. In this study, the control cats had no change in BUN and increased SDMA concentration while urine specific gravity decreased. In contrast, cats fed the RPF saw reduced concentrations of BUN, creatinine, and SDMA. Like the dog, these improvements in markers of renal function in the geriatric cats show the benefits of anti-inflammatory ingredients and botanicals (Hall et al., 2016a). Anorexia or hyporexia is a common problem in cats with CKD and may lead to cats being fed suboptimal diets for their disease (Markovich et al., 2015), indicating an importance of nutrition in cats with kidney disease.

Table 21.1

Anti-inflammatory and Immune-Modulating Effects of Some Herbal and Plant Extracts in Both In Vivo and In Vitro Models of Inflammatory Conditions

Bioactive Component or Extract Class of Compound Efficacy in Health Conditions Potential Anti-Inflammatory Mechanism References
β-caryophyllene (clove oil, rosemary, hops, basil) Sesquiterpene Neuroprotective, nephroprotective, immune modulation Inhibits pathways due to activation of toll-like receptor complex CD14/TLR4/MD2; reduces pro-inflammatory cytokines, including IL-1β, TNF-α, IL-6; exhibits synergy with μ-opioid receptor–dependent pathways; activates peroxisome proliferator-activated receptor gamma (PPARγ) pathway Bento et al., 2011; Horváth et al., 2012; Guo et al., 2014; Sharma et al., 2016
Eugenol (clove) Phenylpropene Inflammation, nephroprotective Inhibits IL-1β, IL-6, and matrix metalloproteinase 9 (MMP-9); inhibits mouse paw edema induced by carrageenan; anti-inflammatory effect on gentamycin-induced nephrotoxicity in rat kidney Valacchi et al., 2009; Said 2011; Taher et al., 2015
Zingerone, shogaols, and gingerols (ginger extract) Guaiacol (zingerone) Aging, nephroprotective Zingerone partially prevented age-related decline in PPAR expression and suppressed pro-inflammatory NFκB activity in rats; gingerol induces nephroprotective effect on gentamycin-mediated nephropathy and reduces IL-2, TNF-α, and IFN-γ. Chung et al., 2009; Kim et al., 2010; Rodrigues et al., 2014
Proanthocyanidins (grape seed extract, cinnamon extract) Polyphenol Cognition, nephroprotective Grape seed extract ameliorates renal injury in type 2 diabetic rats; proanthocyanidins from persimmon peel reduced inflammation in streptozotocin-induced diabetic rats; proanthocyanidin-rich fraction obtained from the bark of Croton celtidifolius Baill has anti-inflammatory as well as beneficial effects on cognitive functions in rats Lee et al., 2007; Moreira et al., 2010; Panickar, 2014; Bao et al., 2015
Suppressed NFkB and activator protein 1 pathways; prostaglandin E2 (PGE2), COX-2; reduction in cMyc, H-ras, and p53-related genes; inhibited signal transducer and activator of transcription 4 (STAT-4), mitogen-activated protein kinases (MAPKs); reduces TNF-α, IL-2, IL-4, IFN-γ, and chemokines (CXCL8, CCL2, CCL3, CCL4)
Ellagitannin, gallocatechin, delphinidin (pomegranate extract) Polyphenol Nephroprotective, cognition Urolithins, gut microbiota–derived metabolites of ellagitannins, inhibit LPS-induced inflammation in RAW 264.7 murine macrophages; punicalagin, a bioactive ellagitannin, inhibits LPS-induced inflammation in a macrophage cell line; consumption of pomegranate juice decreased inflammation and strengthened innate immunity in hemodialysis patients; improves cognitive performance in diabetic rats as well as in a mouse model of Alzheimer’s disease. Cambay et al. 2011; Shema-Didi et al., 2012; Xu et al., 2014; Piwowarski et al., 2015; Subash et al., 2015
Piperine (black pepper extract) Alkaloid Aging, nephroprotective Inhibits STAT-1; reduces NFκB activation, suppresses Akt, ERKs; reduces IL-2, IL-4, IL-5, iNOS, COX-2, INF-γ Kim and Lee, 2009; Bae et al., 2012
Reduces eosinophil infiltration; decreases MMP-3, MMP-13 responses
Rutin (buckwheat and citrus fruit rinds) Polyphenol Cognition Improves cognition and reduces neuroinflammation in a mouse model of Alzheimer’s disease; Improves long-term and short-term episodic memory deficits in Wistar rats Kwon et al., 2005; Koda et al., 2009; Javed et al., 2012; Ramalingayya et al., 2016
Reduces tissue levels of IFN-γ, IL-1β, IL-4, IL-5, IL-10, IL-17; IL-31, and IL-32; reduces NFκB activation, COX-2, iNOS, TNF-α; inhibits MMP-3
Carnosol (rosemary extract, sage extract) Polyphenol Cognition Rosmarinus officinalis leaf extract improves memory deficits in a rats; rosemary extract and carnosol both inhibited COX1 and COX2 activity in mice. Ozarowski et al., 2013; Emami et al., 2013
Oleocanthal, oleuropein, (olive oil) Polyphenol, phenylethanoid (oleocanthal) Nephroprotective, cognition Dietary olive oil reduces inflammation and renal injury in mice; anti-inflammatory effects of oleuropein aglycone in neurodegeneration and peripheral inflammatory disorders Casamenti et al., 2015; Aparicio-Soto et al., 2016
Rhubarb extract,rhubarb (Rheum rhabarbarum) Anthraquinones Nephroprotective Nephroprotective and anti-fibrotic activities in patients with chronic kidney disease; anthraquinones from rhubarb reduce HgCl2-induced acute renal failure in rats. Zhang et al., 2015; Gao et al., 2016
Withania somnifera Tropine and cuscohygrine (alkaloid also found in cocoa), withaferin A (steroidal lactone) Nephroprotective, cognition Oral administration of W. somnifera significantly protected against bromobenzene-induced nephrotoxicity and renal dysfunction in rats. W. somnifera extract improved cognitive and psychomotor performance in healthy male subjects. Vedi et al., 2014; Pingali et al., 2014
Magnolol (Magnolia officinalis) Lignan Mobility Anti-arthritic effects of magnolol reported in a Mycobacterium butyricum-induced arthritis model in rats Wang et al., 2012
Fenugreek extract,fenugreek (Trigonella foenum-graecum L) Alkaloids, flavonoids Nephroprotective Fenugreek oil reduced renal toxicity in alloxan-induced diabetic rats. Hamden et al., 2010; Yadav & Baquer, 2014
Black cumin (Nigella sativa) Thymoquinone, tannins Nephroprotective, cognition N. sativa administration antagonized paracetamol-induced kidney pathological damage, improved cognition in healthy adolescent males as well as in elderly human subjects. Bin Sayeed et al., 2013, 2014; Canayakin et al., 2016
Mangosteen (Garcinia mangostana) Xanthones (gartanin and α-mangostin) Cognition, nephroprotective, mobility Mangosteen attenuated the deficit in spatial memory retrieval in a mouse model of Alzheimer’s disease. α-mangosteen had a renoprotective effect in a cisplatin-induced model of nephrotoxicity in rats. Isogarcinol, isolated from Garcinia mangostana, reduced inflammation in collagen-induced arthritis in animals. Pérez-Rojas et al., 2009; Huang et al., 2014; Fu et al., 2014
Silibinin (milk thistle: Silybum marianum) Polyphenol Mobility, cognition, nephroprotective Silymarin, primarily made of three isomers—silybin, silydianin, and silychristin—exhibited significant anti-inflammatory and antiarthritic activities in the papaya latex–induced model of inflammation in rats; silymarin significantly reversed high-fat diet-induced cognitive deficits in mice; silymarin significant attenuated the nephrotoxic effects in a rat model of kidney stress. Gupta et al., 2000; Neha et al., 2014; Alcaraz-Contreras et al., 2016
Scutellaria baicalensis and Oroxylum indicum (Indian trumpetflower) Baicalein (flavonoid) Nephroprotective, cognitive, mobility Baicalein attenuated kidney injury induced by myocardial ischemia and reperfusion in rats; baicalein inhibited inflammatory process through inactivation of NF-κB and MAPK signal pathways to exert antifibrotic actions in obstructive kidney disease in mice; baicalein prevented spatial learning and memory retention deficits following whole brain irradiation in mice; baicalein attenuated expression of MMPs and ameliorated cartilage damage in rabbit model of osteoarthritis. Oh et al., 2013; Chen et al., 2015; Wang et al., 2015; Lai et al., 2016


Source: Table modified from Panickar, K.S., 2014. Anti-inflammatory properties of botanical extracts contribute to their protective effects in brain edema in cerebral ischemia. In: Watson, R., Preedy, V. (Eds), Bioactive Nutriceuticals and Dietary Supplements in Neurological and Brain Disease: Prevention and Therapy, Academic Press, New York, pp. 3−15.

The nephroprotective effects of bioactive components from dietary ingredients, including botanical extracts, in rodent studies have been reported. In rats made obese with a high-fat diet, lycopene, a major component of tomato, reduced TNF-α levels in the kidney when supplemented in the high-fat diet (Pierine et al., 2014). Anti-inflammatory effects of lycopene have been reported in the kidney of obese rats (Pierine et al., 2014), in diabetic nephropathy in mice (Guo et al., 2015), and in contrast-induced nephropathy in rats (Buyuklu et al., 2015). Inclusion of polyphenols, which generally have anti-inflammatory effects, has also been shown to have a nephroprotective effect. In a mouse model of diabetes, the low-molecular-weight polyphenol oligonol, derived from lychee fruit, reduced diabetes-induced increase in advanced glycation end product (AGE) formation and apoptosis in the kidneys (Park et al., 2014). A polyphenol-rich extract from amla (Emblica officinalis Gaertn) reduced the expression of renal nuclear factor kappa B (NFκB), inhibitory κB in cytoplasm, inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX-2) protein levels that were elevated in aged rats (Yokozawa et al., 2007).

In summary, it is apparent that a diet that includes anti-inflammatory and specific botanically active ingredients can reduce or reverse the decline in kidney function associated with aging. This effectiveness is likely due in part to the known beneficial effect of the anti-inflammatory ingredients but may also be the result of a specific action of individual botanical compounds on the kidney.

Cognitive Function

Cognitive function declines with aging, but it is not uniform; some people experience very little cognitive decline whereas others suffer from mild to moderate to severe decline in some components of cognitive function. The causes or mechanisms of this decline are not clear, but there is evidence to indicate a role for inflammation in reducing cognitive ability. In aged rats that received a single injection of lipopolysaccharide (LPS), there was an impaired reversal of learning and attentional shifts but not effect on discrimination learning (Culley et al., 2014). Further, in this study, although an increase in monocyte chemoattractant protein 1 (MCP-1) was found elevated 2 h after LPS administration, the levels returned to normal at the time of testing. Whether the increase and subsequent decrease in TNF and CCL2 following LPS injection in the rats had initiated a cascade of events that affected subsequent cognitive function is not clear but is a possibility. Increased levels of TNFα and IL1β were reported in the 24-month group (older group) when compared to the young group of rats (Gocmez et al., 2016). In another study in aged rats, following laparotomy (abdominal cavity surgery) memory and learning functions were impaired and there was a significant upregulation of TNF-α, interleukin (IL)-1β, IL-4, and IL-6 in the hippocampal tissues. However, intracisternal administration of the TNF-α receptor antagonist R-7050 during surgery attenuated these defects in cognitive function and inhibited the production of the pro-inflammatory cytokines (Ma et al., 2015).

In human subjects, a study reported that a pro-inflammatory diet at midlife might be associated with subsequent lower cognitive functioning (Kesse-Guyot et al., 2016). In the Singapore Longitudinal Aging Study, significant associations of soluble IL-2 receptor alpha chain, soluble tumor necrosis factor receptor 2, and soluble glycoprotein 130 were found along with cognitive impairment in community-dwelling older persons (Gao et al., 2016). In the Berlin Aging Study II, levels of IL-6, IL-10, and CRP were inversely associated with executive function and processing speed, but IL-6 to IL-10 ratio was not predictive for executive function and processing speed (Tegeler et al., 2016). Further, in the same study, no associations were found between inflammatory markers and verbal episodic memory. The underlying mechanisms or the neuroanatomical correlates on why certain inflammatory markers are associated with certain components of memory are not clear. In nondemented subjects aged 70–90 years, higher levels of serum macrophage inhibitory cytokine-1 (MIC-1), also called growth differentiation factor 15 (GDF15), were associated with lower global cognition (Fuchs et al., 2013). A higher intracellular cytokine production of IL-1β and IL-6 by activated monocytes were predictive of lower cognitive performance in working memory in healthy older individuals aged 55–70 years (Simpson et al., 2013). In a prospective population-based cohort study with data collected over 20 years, it was reported that higher serum CRP and IL-6 were associated with a likelihood of cognitive impairment (Wichmann et al., 2014). Nascimento et al. (2014) reported an association of pro-inflammatory cytokines, including TNF-α and IL6, with mild cognitive impairment in elderly humans. Such elevated levels of the pro-inflammatory cytokines, however, could be reduced with physical exercise, which also correlated with subsequent positive effects on cognition. Taken together, these studies indicate that an increased risk of cognitive decline is associated with age-related inflammatory conditions.

In canines, an age-dependent decline is seen in learning and memory, and neuropathological changes are also observed in canines that are generally similar to those seen in normal human aging or in early Alzheimer’s disease (Head, 2011; Vite and Head, 2014; Schütt et al., 2016). Cognitive dysfunction syndrome has also been described in canines and felines (Landsberg et al., 2012; Bosch et al., 2013). Interferon gamma (IFN-γ) expression was increased in the homogenates of dentate gyrus, a region of the limbic system involved in cognition, in aged dogs when compared to adult dogs (Hwang et al., 2008). A battery of cognitive tests were then administered to dogs that were divided into young (1–4 years), middle-aged (5–8 years), cognitively unimpaired aged (≥9 years), and cognitively impaired aged (≥9 years). The younger dogs (<9 years) successfully located the food more quickly in a food-seeking task and with more success than the aged groups (≥9 years) (González-Martínez et al., 2013). In another study with pet dogs. there were no significant effects of age on learning or retention tasks, but older dogs (≥8 years) were significantly impaired on the reversal learning task when compared with younger ones (<8 years). In addition, the trial response latency was significantly increased in aged dogs in both the initial and reversal learning tasks but not on the retention task (Mongillo et al., 2013). These studies indicate that pro-inflammatory markers are associated with a decline in cognitive function, but the facets of cognitive components affected by various inflammatory markers are yet unclear.

Diet-induced improvement in cognitive function has been demonstrated and it appears that more research is warranted. In the Whitehall II prospective cohort study, a dietary pattern with a higher intake of red and processed meat, peas, legumes and fried food, and lower intake of whole grains was associated with higher inflammatory markers and accelerated cognitive decline at older ages (Ozawa et al., 2016). Intervention studies using eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), fatty acids which have anti-inflammatory effects, to adults with mild cognitive impairment or age-related cognitive impairment have shown beneficial effects although no differences in cognitive decline between treated and nontreated participants were observed in healthy older adults (Cederholm et al., 2013). In a population-based cohort of nondemented Asian subjects aged 60–93 years, when the authors compared the Mini-Mental State Examination (MMSE) scores for three categories of regular curry (curcumin) consumption they found that those who consumed curry “occasionally” and “often or very often” had significantly better MMSE scores than did subjects who “never or rarely” consumed curry (Ng et al., 2006). The anti-inflammatory effects of curcumin have been well established in several studies (for reviews, see Boyanapalli and Tony Kong, 2015; Ghosh et al., 2015; Sahebkar et al., 2016).

In canines, higher serum vitamin E concentrations from vitamin E supplemented food correlated with improved performance on landmark-discrimination tasks in aged dogs (Ikeda-Douglas et al., 2004). Although vitamin E (generally tocopherols) has been reported to have antioxidant effects, their anti-inflammatory effects have also been reported (Betti et al., 2011; England et al., 2012). Whether the improvement in cognitive tasks was a consequence of their anti-inflammatory actions or a combination of antioxidant and anti-inflammatory actions is not clear but is a possibility. A combination of antioxidant and mitochondrial cofactor improved the performance of aged dogs in a three-choice size-discrimination task (Siwak et al., 2005). Canine puppies fed a diet rich in DHA (and with higher concentrations of vitamin E, taurine, choline, and L-carnitine) performed significantly better on cognitive tasks when compared to moderate and low DHA groups (Zicker et al., 2012). In addition to the anti-inflammatory actions of vitamin E, DHA also has been reported to have anti-inflammatory actions in beagles (Hall et al., 2011). Canines supplemented with medium-chain triglycerides (MCT) showed improved memory in some but not all of the cognitive tasks administered in aged dogs (Pan et al., 2010). The mechanisms underlying the improvement in cognitive functions in the previously mentioned studies is not clear, but certainly ingredients with anti-inflammatory potential may be important in attenuating cognitive decline.

In adult rats, anthocyanins reversed the D-galactose–induced neuroinflammation-mediated cognitive impairment (Rehman et al., 2016). In aged rats, dietary supplementation with the polyphenol-rich açaí pulps (Euterpe oleracea Mart. and Euterpe precatoria Mart.) improved cognition in aged rats and concomitantly reduced levels of TNF-α were also reported in the serum (Carey et al., 2015). In mice, supplementing a diet with resveratrol reduced the LPS-related neuroinflammation and deficits in working memory in aged mice (Abraham and Johnson, 2009). Similarly, resveratrol was effective in preventing cognitive deficit in aged rats by inhibiting the production of inflammatory cytokines (Gocmez et al., 2016). The inclusion of mushroom (Agaricus bisporus), which has anti-inflammatory effects, in the daily diet of aged rats had beneficial effects on age-related deficits in cognitive and motor function (Thangthaeng et al., 2015). Supplementation with blueberry polyphenols attenuated the kainic acid–induced increase in the expression of IL-1β, TNF-α, and NFκB, and expression of insulin-like growth factor 1 (IGF-1) and a concomitant reduction in learning impairments following the neurotoxic insult (Shukitt-Hale et al., 2008). In addition, the effects of polyphenol-rich extracts from grape, strawberry, blackberry, and plum reportedly have beneficial effects in cognition in rodent models (Shukitt-Hale et al., 2006; Shukitt-Hale et al., 2009; Cherniack, 2012). Table 21.1 lists some natural compounds that may provide beneficial health effects by reducing inflammation and may also benefit cognition. In short, the studies mentioned indicate that dietary ingredients, in particular botanical extracts with anti-inflammatory properties, may be useful in improving several components of cognitive function.


Aging-associated increases in low-grade systemic inflammation could contribute to the pathogenesis of various chronic conditions in aging, including kidney dysfunction, diminished cognition, and a reduction in an effective immune function. The causal factors for the increased systemic low-grade inflammation are not clear but likely multifactorial. Strategies to effectively combat aging-associated inflammation have included nutrition, drugs, lifestyle changes, and recently stem cell therapies to modulate the immune system. Nutritional intervention is a particularly important strategy to lower systemic inflammation in aging, and evidence for this comes from laboratory animal studies, clinical studies, and epidemiological studies. Dietary factors, including a polyphenol-rich diet from fruits, vegetables, and herbs, as well as a diet rich in ω-3 fatty acids and some vitamins appear to have beneficial effects or the potential to reduce systemic inflammation in aging. In general, there appears to be a health benefit in reducing systemic inflammation in aging. Given the complexity and breadth of the inflammatory profile, in particular in aging, it is imperative that the anti-inflammatory and immune-modulating properties of herbal or plant extracts be investigated further as part of the dietary regimen.

Conflict of Interest

The authors are employees at the Science and Technology Center of the Hillspet Nutrition Center, a Colgate-Palmolive company.


1. Abdel-Rahman EM, Okusa MD. Effects of aging on renal function and regenerative capacity. Nephron Clin Pract. 2014;127(1–4):15–20.

2. Abraham J, Johnson RW. Consuming a diet supplemented with resveratrol reduced infection-related neuroinflammation and deficits in working memory in aged mice. Rejuvenation Res. 2009;12(6):445–453.

3. Alam I, Pawelec G. Aging, nutrition and immunity – their relationship and interaction. Nutr Aging. 2012;1:151–165.

4. Alcaraz-Contreras Y, Mendoza-Lozano RP, Martínez-Alcaraz ER, et al. Silymarin and dimercaptosuccinic acid ameliorate lead-induced nephrotoxicity and genotoxicity in rats. Hum Exp Toxicol. 2016;35(4):398–403.

5. Anderson S, Brenner BM. Effects of aging on the renal glomerulus. Am J Med. 1986;80(3):435–442.

6. Aparicio-Soto M, Sánchez-Hidalgo M, Cárdeno A, et al. Dietary extra virgin olive oil attenuates kidney injury in pristane-induced SLE model via activation of HO-1/Nrf-2 antioxidant pathway and suppression of JAK/STAT, NF-κB and MAPK activation. J Nutr Biochem. 2016;27:278–288.

7. Bae GS, Kim JJ, Park KC, et al. Piperine inhibits lipopolysaccharide-induced maturation of bone-marrow-derived dendritic cells through inhibition of ERK and JNK activation. Phytother Res. 2012;26(12):1893–1897.

8. Bao L, Zhang Z, Dai X, et al. Effects of grape seed proanthocyanidin extract on renal injury in type 2 diabetic rats. Mol Med Rep. 2015;1(1):645–652.

9. Bento AF, Marcon R, Dutra RC, et al. β-Caryophyllene inhibits dextran sulfate sodium-induced colitis in mice through CB2 receptor activation and PPARγ pathway. Am J Pathol. 2011;178(3):1153–1166.

10. Betti M, Minelli A, Ambrogini P, et al. Dietary supplementation with α-tocopherol reduces neuroinflammation and neuronal degeneration in the rat brain after kainic acid-induced status epilepticus. Free Radic Res. 2011;45(10):1136–1142.

11. Bin Sayeed MS, Asaduzzaman M, Morshed H, Hossain MM, Kadir MF, Rahman MR. The effect of Nigella sativa Linn seed on memory, attention and cognition in healthy human volunteers. J Ethnopharmacol. 2013;148(3):780–786.

12. Bin Sayeed MS, Shams T, Fahim Hossain S, et al. Nigella sativa L seeds modulate mood, anxiety and cognition in healthy adolescent males. J Ethnopharmacol. 2014;152(1):156–162.

13. Bosch MN, Gimeno-Bayón J, Rodríguez MJ, Pugliese M, Mahy N. Rapid improvement of canine cognitive dysfunction with immunotherapy designed for Alzheimer’s disease. Curr Alzheimer Res. 2013;10(5):482–493.

14. Boyanapalli SS, Tony Kong AN. “Curcumin, the King of Spices”: epigenetic regulatory mechanisms in the prevention of cancer, neurological, and inflammatory diseases. Curr Pharmacol Rep. 2015;1(2):129–139.

15. Brown CA, Elliott J, Schmiedt CW, Brown SA. Chronic kidney disease in aged cats: clinical features, morphology, and proposed pathogeneses. Vet Pathol. 2016;53(2):309–326.

16. Bruunsgaard H. Effects of tumor necrosis factor-alpha and interleukin-6 in elderly populations. Eur Cytokine Netw. 2002;13(4):389–391.

17. Brüünsgaard H, Pedersen BK. Age-related inflammatory cytokines and disease. Immunol Allergy Clin North Am. 2003;23(1):15–39.

18. Buyuklu M, Kandemir FM, Ozkaraca M, et al. Benefical effects of lycopene against contrast medium-induced oxidative stress, inflammation, autophagy, and apoptosis in rat kidney. Hum Exp Toxicol. 2015;34(5):487–496.

19. Cambay Z, Baydas G, Tuzcu M, Bal R. Pomegranate (Punica granatum L.) flower improves learning and memory performances impaired by diabetes mellitus in rats. Acta Physiol Hung. 2011;98(4):409–420.

20. Canayakin D, Bayir Y, Kilic Baygutalp N, et al. Paracetamol-induced nephrotoxicity and oxidative stress in rats: the protective role of Nigella sativa. Pharm Biol. 2016;9:1–10.

21. Candore G, Caruso C, Jirillo E, Magrone T, Vasto S. Low grade inflammation as a common pathogenetic denominator in age-related diseases: novel drug targets for anti-ageing strategies and successful ageing achievement. Curr Pharm Des. 2010;16(6):584–596.

22. Carey AN, Miller MG, Fisher DR, et al. Dietary supplementation with the polyphenol-rich açaí pulps (Euterpe oleracea Mart and Euterpe precatoria Mart.) improves cognition in aged rats and attenuates inflammatory signaling in BV-2 microglial cells. Nutr Neurosci. 2015; Nov 30. [Epub ahead of print].

23. Casamenti F, Grossi C, Rigacci S, Pantano D, Luccarini I, Stefani M. Oleuropein aglycone: a possible drug against degenerative conditions in vivo evidence of its effectiveness against Alzheimer’s disease. J Alzheimers Dis. 2015;45(3):679–688.

24. Cederholm T, Salem NJr, Palmblad J. ω-3 fatty acids in the prevention of cognitive decline in humans. Adv Nutr. 2013;4(6):672–676.

25. Chen WP, Xiong Y, Hu PF, Bao JP, Wu LD. Baicalein inhibits MMPs expression via a MAPK-dependent mechanism in chondrocytes. Cell Physiol Biochem. 2015;36(1):325–333.

26. Cherniack EP. A berry thought-provoking idea: the potential role of plant polyphenols in the treatment of age-related cognitive disorders. Br J Nutr. 2012;108(5):794–800.

27. Chung SW, Kim MK, Chung JH, et al. Peroxisome proliferator-activated receptor activation by a short-term feeding of zingerone in aged rats. J Med Food. 2009;12(2):345–350.

28. Costa E, Fernandes J, Ribeiro S, et al. Aging is associated with impaired renal function, INF-gamma induced inflammation and with alterations in iron regulatory proteins gene expression. Aging Dis. 2013;5(6):356–365.

29. Culley DJ, Snayd M, Baxter MG, et al. Systemic inflammation impairs attention and cognitive flexibility but not associative learning in aged rats: possible implications for delirium. Front Aging Neurosci. 2014;6:107.

30. Day MJ. Ageing, immunosenescence and inflammageing in the dog and cat. J Comp Pathol. 2010;142(Suppl 1):S60–S69.

31. Emami F, Ali-Beig H, Farahbakhsh S, et al. Hydroalcoholic extract of Rosemary (Rosmarinus officinalis L.) and its constituent carnosol inhibit formalin-induced pain and inflammation in mice. Pak J Biol Sci. 2013;16(7):309–316.

32. England A, Valdes AM, Slater-Jefferies JL, et al. Variants in the genes encoding TNF-α, IL-10, and GSTP1 influence the effect of α-tocopherol on inflammatory cell responses in healthy men. Am J Clin Nutr. 2012;95(6):1461–1467.

33. Franceschi C, Bonafe M, Valensin S. Human immunosenescence: the prevailing of innate immunity, the failing of clonotypic immunity, and the filling of immunological space. Vaccine. 2000;18(16):1717–1720.

34. Fleming JM, Creevy KE, Promislow DE. Mortality in North American dogs from 1984 to 2004: an investigation into age-, size-, and breed-related causes of death. J Vet Internal Med. 2011;25:187–198.

35. Fu Y, Zhou H, Wang M, Cen J, Wei Q. Immune regulation and anti-inflammatory effects of isogarcinol extracted from Garcinia mangostana L against collagen-induced arthritis. J Agric Food Chem. 2014;62(18):4127–4134.

36. Fuchs T, Trollor JN, Crawford J, et al. Macrophage inhibitory cytokine-1 is associated with cognitive impairment and predicts cognitive decline-the Sydney Memory and Aging Study. Aging Cell. 2013;12(5):882–889.

37. Gao Q, Camous X, Lu YX, Lim ML, Larbi A, Ng TP. Novel inflammatory markers associated with cognitive performance: Singapore Longitudinal Ageing Studies. Neurobiol Aging. 2016;39:140–146.

38. Gao D, Zeng LN, Zhang P, et al. Rhubarb anthraquinones protect rats against mercuric chloride (HgCl2)-induced acute renal failure. Molecules. 2016;21.

39. Ghosh S, Banerjee S, Sil PC. The beneficial role of curcumin on inflammation, diabetes and neurodegenerative disease: a recent update. Food Chem Toxicol. 2015;83:111–124.

40. Gocmez SS, Gacar N, Utkan T, Gacar G, Scarpace PJ, Tumer N. Protective effects of resveratrol on aging-induced cognitive impairment in rats. Neurobiol Learn Mem. 2016;131:131–136.

41. González-Martínez A, Rosado B, Pesini P, et al. Effect of age and severity of cognitive dysfunction on two simple tasks in pet dogs. Vet J. 2013;198(1):176–181.

42. Greeley EH, Spitznagel E, Lawler DF, Kealy RD, Segre M. Modulation of canine immunosenescence by life-long caloric restriction. Vet Immunol Immunopathol. 2006;111(3–4):287–299.

43. Guo K, Mou X, Huang J, Xiong N, Li H. Trans-caryophyllene suppresses hypoxia-induced neuroinflammatory responses by inhibiting NF-κB activation in microglia. J Mol Neurosci. 2014;54(1):41–48.

44. Guo Y, Liu Y, Wang Y. Beneficial effect of lycopene on anti-diabetic nephropathy through diminishing inflammatory response and oxidative stress. Food Funct. 2015;6(4):1150–1156.

45. Gupta OP, Sing S, Bani S, et al. Anti-inflammatory and anti-arthritic activities of silymarin acting through inhibition of 5-lipoxygenase. Phytomedicine. 2000;7(1):21–24.

46. Habenicht LM, Webb TL, Clauss LA, Dow SW, Quimby JM. Urinary cytokine levels in apparently healthy cats and cats with chronic kidney disease. J Feline Med Surg. 2013;15(2):99–104.

47. Hall JA, Tooley KA, Gradin JL, Jewell DE, Wander RC. Effects of dietary n-6 and n-3 fatty acids and vitamin E on the immune response of healthy geriatric dogs. Am J Vet Res. 2003;64(6):762–772.

48. Hall JA, Chinn RM, Vorachek WR, Gorman ME, Jewell DE. Aged Beagle dogs have decreased neutrophil phagocytosis and neutrophil-related gene expression compared to younger dogs. Vet Immunol Immunopathol. 2010;137(1–2):130–135.

49. Hall JA, Chinn RM, Vorachek WR, et al. Influence of dietary antioxidants and fatty acids on neutrophil mediated bacterial killing and gene expression in healthy Beagles. Vet Immunol Immunopathol. 2011;139(2–4):217–228.

50. Hall JA, Yerramilli M, Obare E, Yerramilli M, Jewell DE. Comparison of serum concentrations of symmetric dimethylarginine and creatinine as kidney function biomarkers in cats with chronic kidney disease. J Vet Intern Med. 2014;28(6):1676–1683.

51. Hall JA, Yerramilli M, Obare E, Yerramilli M, Melendez LD, Jewell DE. Relationship between lean body mass and serum renal biomarkers in healthy dogs. J Vet Intern Med. 2015;29(3):808–814.

52. Hall JA, MacLeay J, Yerramilli M, et al. Positive Impact of nutritional interventions on serum symmetric dimethylarginine and creatinine concentrations in client-owned geriatric cats. PLoS One. 2016a;11(4):e0153654.

53. Hall JA, MacLeay J, Yerramilli M, et al. Positive impact of nutritional interventions on serum symmetric dimethylarginine and creatinine concentrations in client-owned geriatric dogs. PLoS One. 2016b;11(4):e0153653.

54. Hamden K, Masmoudi H, Carreau S, Elfeki A. Immunomodulatory, beta-cell, and neuroprotective actions of fenugreek oil from alloxan-induced diabetes. Immunopharmacol Immunotoxicol. 2010;32(3):437–445.

55. Head E. Neurobiology of the aging dog. Age (Dordr). 2011;33(3):485–496.

56. Horváth B, Mukhopadhyay P, Kechrid M, et al. β-Caryophyllene ameliorates cisplatin-induced nephrotoxicity in a cannabinoid 2 receptor-dependent manner. Free Radic Biol Med. 2012;52(8):1325–1333.

57. Huang, H.J., Chen, W.L., Hsieh, R.H., Hsieh-Li, H.M., 2014. Multifunctional effects of mangosteen pericarp on cognition in C57BL/6J and triple transgenic Alzheimer’s mice. Evid Based Complement Alternat Med, 813672.

58. Hwang IK, Lee CH, Li H, et al. Comparison of ionized calcium-binding adapter molecule 1 immunoreactivity of the hippocampal dentate gyrus and CA1 region in adult and aged dogs. Neurochem Res. 2008;33(7):1309–1315.

59. Ikeda-Douglas CJ, Zicker SC, Estrada J, Jewell DE, Milgram NW. Prior experience, antioxidants, and mitochondrial cofactors improve cognitive function in aged beagles. Vet Ther. 2004;5(1):5–16.

60. Jain N, Reilly RF. Effects of dietary interventions on incidence and progression of CKD. Nat Rev Nephrol. 2014;10:712–724.

61. Javed H, Khan MM, Ahmad A, et al. Rutin prevents cognitive impairments by ameliorating oxidative stress and neuroinflammation in rat model of sporadic dementia of Alzheimer type. Neuroscience. 2012;210:340–352.

62. Kearns RJ, Hayek MG, Turek JJ, et al. Effect of age, breed and dietary omega-6 (n-6): omega-3 (n-3) fatty acid ratio on immune function, eicosanoid production, and lipid peroxidation in young and aged dogs. Vet Immunol Immunopathol. 1999;69(2–4):165–183.

63. Kesse-Guyot E, Assmann KE, Andreeva VA, et al. Long-term association between the dietary inflammatory index and cognitive functioning: findings from the SU.VI.MAX study. Eur J Nutr. 2016; Apr 7. [Epub ahead of print].

64. Kim MK, Chung SW, Kim DH, et al. Modulation of age-related NF-kappaB activation by dietary zingerone via MAPK pathway. Exp Gerontol. 2010;45(6):419–426.

65. Lai CC, Huang PH, Yang AH, et al. Baicalein, a component of scutellaria baicalensis, attenuates kidney injury induced by myocardial ischemia and reperfusion. Planta Med. 2016;82(3):181–189.

66. Landsberg GM, Nichol J, Araujo JA. Cognitive dysfunction syndrome: a disease of canine and feline brain aging. Vet Clin North Am Small Anim Pract. 2012;42(4):749–768.

67. Lee YA, Kim YJ, Cho EJ, Yokozawa T. Ameliorative effects of proanthocyanidin on oxidative stress and inflammation in streptozotocin-induced diabetic rats. J Agric Food Chem. 2007;55(23):9395–9400.

68. Kim SH, Lee YC. Piperine inhibits eosinophil infiltration and airway hyperresponsiveness by suppressing T cell activity and Th2 cytokine production in the ovalbumin-induced asthma model. J Pharm Pharmacol. 2009;61(3):353–359.

69. Koda T, Kuroda Y, Imai H. Rutin supplementation in the diet has protective effects against toxicant-induced hippocampal injury by suppression of microglial activation and pro-inflammatory cytokines: protective effect of rutin against toxicant-induced hippocampal injury. Cell Mol Neurobiol. 2009;29(4):523–531.

70. Kwon KH, Murakami A, Tanaka T, Ohigashi H. Dietary rutin, but not its aglycone quercetin, ameliorates dextran sulfate sodium-induced experimental colitis in mice: attenuation of proinflammatory gene expression. Biochem Pharmacol. 2005;69(3):395–406.

71. Lesourd BM. Nutrition and immunity in the elderly: modification of immune responses with nutritional treatments. Am J Clin Nutr. 1997;66(2):478S–484S.

72. Lesourd B, Mazari L. Nutrition and immunity in the elderly. Proc Nutr Soc. 1999;58(3):685–695.

73. Markovich JE, Freeman LM, Labato MA, Heinze CR. Survey of dietary and medication practices of owners of cats with chronic kidney disease. J Feline Med Surg. 2015;17(12):979–983.

74. Ma Y, Cheng Q, Wang E, Li L, Zhang X. Inhibiting tumor necrosis factor-α signaling attenuates postoperative cognitive dysfunction in aged rats. Mol Med Rep. 2015;12(2):3095–3100.

75. Meydani SN, Barklund MP, Liu S, et al. Vitamin E supplementation enhances cell-mediated immunity in healthy elderly subjects. Am J Clin Nutr. 1990;52(3):557–563.

76. Michaud M, Balardy L, Moulis G, et al. Proinflammatory cytokines, aging, and age-related diseases. J Am Med Dir Assoc. 2013;14(12):877–882.

77. Mongillo P, Araujo JA, Pitteri E, et al. Spatial reversal learning is impaired by age in pet dogs. Age (Dordr). 2013;35(6):2273–2282.

78. Moreira EL, Rial D, Aguiar Jr AS, et al. Proanthocyanidin-rich fraction from Croton celtidifolius Baill confers neuroprotection in the intranasal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine rat model of Parkinson’s disease. J Neural Transm (Vienna). 2010;117(12):337–351.

79. Moreno JA, Izquierdo MC, Sanchez-Niño MD, et al. The inflammatory cytokines TWEAK and TNFα reduce renal klotho expression through NFκB. J Am Soc Nephrol. 2011;22(7):1315–1325.

80. Mulder WJ, Hillen HFP. Renal function and renal disease in the elderly Part I. Eur J Intern Med. 2001;12:86–97.

81. Nascimento CM, Pereira JR, De Andrade LP, et al. Physical exercise in MCI elderly promotes reduction of pro-inflammatory cytokines and improvements on cognition and BDNF peripheral levels. Curr Alzheimer Res. 2014;11(8):799–805.

82. Neha, Kumar A, Jaggi AS, Sodhi RK, Singh N. Silymarin ameliorates memory deficits and neuropathological changes in mouse model of high-fat-diet-induced experimental dementia. Naunyn Schmiedebergs Arch Pharmacol. 2014;387(8):777–787.

83. Nentwig A, Schweighauser A, Maissen-Villiger C, et al. Assessment of the expression of biomarkers of uremic inflammation in dogs with renal disease. Am J Vet Res. 2016;77(2):218–224.

84. Ng TP, Chiam PC, Lee T, Chua HC, Lim L, Kua EH. Curry consumption and cognitive function in the elderly. Am J Epidemiol. 2006;164(9):898–906.

85. Oh SB, Park HR, Jang YJ, Choi SY, Son TG, Lee J. Baicalein attenuates impaired hippocampal neurogenesis and the neurocognitive deficits induced by γ-ray radiation. Br J Pharmacol. 2013;168(2):421–431.

86. Ozarowski M, Mikolajczak PL, Bogacz A, et al. Rosmarinus officinalis L leaf extract improves memory impairment and affects acetylcholinesterase and butyrylcholinesterase activities in rat brain. Fitoterapia. 2013;91:261–271.

87. Ozawa M, Shipley M, Kivimaki M, Singh-Manoux A, Brunner EJ. Dietary pattern, inflammation and cognitive decline: The Whitehall II prospective cohort study. Clin Nutr. 2016; S0261-5614(16)00035-2.

88. Pan Y, Larson B, Araujo JA, et al. Dietary supplementation with medium-chain TAG has long-lasting cognition-enhancing effects in aged dogs. Br J Nutr. 2010;103(12):1746–1754.

89. Panickar KS. Anti-inflammatory properties of botanical extracts contribute to their protective effects in brain edema in cerebral ischemia. In: Watson R, Preedy V, eds. Bioactive Nutriceuticals and Dietary Supplements in Neurological and Brain Disease: Prevention and Therapy. New York: Academic Press; 2014;3–15.

90. Panickar KS, Jewell DE. The beneficial role of anti-inflammatory dietary ingredients in attenuating markers of chronic low-grade inflammation in aging. Horm Mol Biol Clin Investig. 2015;23(2):59–70.

91. Park CH, Yokozawa T, Noh JS. Oligonol, a low-molecular-weight polyphenol derived from lychee fruit, attenuates diabetes-induced renal damage through the advanced glycation end product-related pathway in db/db mice. J Nutr. 2014;144(8):1150–1157.

92. Pérez-Rojas JM, Cruz C, García-López P, et al. Renoprotection by alpha-Mangostin is related to the attenuation in renal oxidative/nitrosative stress induced by cisplatin nephrotoxicity. Free Radic Res. 2009;43(11):1122–1132.

93. Pierine DT, Navarro ME, Minatel IO, et al. Lycopene supplementation reduces TNF-α via RAGE in the kidney of obese rats. Nutr Diabetes. 2014;10(4):e142.

94. Pingali U, Pilli R, Fatima N. Effect of standardized aqueous extract of Withania somnifera on tests of cognitive and psychomotor performance in healthy human participants. Pharmacognosy Res. 2014;6(1):12–18.

95. Piwowarski JP, Kiss AK, Granica S, Moeslinger T. Urolithins, gut microbiota-derived metabolites of ellagitannins, inhibit LPS-induced inflammation in RAW 264.7 murine macrophages. Mol Nutr Food Res. 2015;59(11):2168–2177.

96. Raila J, Schweigert FJ, Kohn B. C-reactive protein concentrations in serum of dogs with naturally occurring renal disease. J Vet Diagn Investig. 2011;23(4):710–715.

97. Ramalingayya GV, Nampoothiri M, Nayak PG, et al. Naringin and rutin alleviates episodic memory deficits in two differentially challenged object recognition tasks. Pharmacogn Mag. 2016;12(Suppl 1):S63–S70.

98. Rehman SU, Shah SA, Ali T, Chung JI, Kim MO. Anthocyanins reversed D-Galactose-induced oxidative stress and neuroinflammation mediated cognitive impairment in adult rats. Mol Neurobiol. 2016; [Epub ahead of print]. PMID: 26738855.

99. Rodrigues FA, Prata MM, Oliveira IC, et al. Gingerol fraction from Zingiber officinale protects against gentamicin-induced nephrotoxicity. Antimicrob Agents Chemother. 2014;58(4):1872–1878.

100. Roubenoff R, Harris TB, Abad LW, Wilson PW, Dallal GE, Dinarello CA. Monocyte cytokine production in an elderly population: effect of age and inflammation. J Gerontol A Biol Sci Med Sci. 1998;53(1):M20–M26.

101. Rubin SI. Chronic renal failure and its management and nephrolithiasis. Vet Clin North Am Small Anim Pract. 1997;27(6):1331–1354.

102. Sahebkar A, Cicero AF, Simental-Mendía LE, Aggarwal BB, Gupta SC. Curcumin downregulates human tumor necrosis factor-α levels: a systematic review and meta-analysis ofrandomized controlled trials. Pharmacol Res. 2016;107:234–242.

103. Santos MS, Leka LS, Ribaya-Mercado JD, et al. Short- and long-term beta-carotene supplementation do not influence T cell-mediated immunity in healthy elderly persons. Am J Clin Nutr. 1997;66(4):917–924.

104. Said MM. The protective effect of eugenol against gentamicin-induced nephrotoxicity and oxidative damage in rat kidney. Fundam Clin Pharmacol. 2011;25(6):708–716.

105. Schütt T, Helboe L, Østergaard Pedersen L, Waldemar G, Berendt M, Pedersen JT. Dogs with cognitive dysfunction as a spontaneous model for early Alzheimer’s disease: a translational study of neuropathological and inflammatory markers. J Alzheimers Dis. 2016; [Epub ahead of print].

106. Sharma C, Al Kaabi J, Nurulain SM, Goyal SN, Kamal MA, Ojha S. Polypharmacological properties and therapeutic potential of β-caryophyllene: a dietary phytocannabinoid of pharmaceutical promise. Curr Pharm Des. 2016; [Epub ahead of print].

107. Sheffy BE, Williams AJ. Nutrition and the aging animal. Vet Clin North Am Small Anim Pract. 1981;11(4):669–675.

108. Shema-Didi L, Sela S, Ore L, et al. One year of pomegranate juice intake decreases oxidative stress, inflammation, and incidence of infections in hemodialysis patients: a randomized placebo-controlled trial. Free Radic Biol Med. 2012;53(2):297–304.

109. Shukitt-Hale B, Carey A, Simon L, Mark DA, Joseph JA. Effects of Concord grape juice on cognitive and motor deficits in aging. Nutrition. 2006;22(3):295–302.

110. Shukitt-Hale B, Lau FC, Carey AN, et al. Blueberry polyphenols attenuate kainic acid-induced decrements in cognition and alter inflammatory gene expression in rat hippocampus. Nutr Neurosci. 2008;11(4):172–182.

111. Shukitt-Hale B, Cheng V, Joseph JA. Effects of blackberries on motor and cognitive function in aged rats. Nutr Neurosci. 2009;12(3):135–140.

112. Simpson EE, Hodkinson CF, Maylor EA, et al. Intracellular cytokine production and cognition in healthy older adults. Psychoneuroendocrinology. 2013;38(10):2196–2208.

113. Siwak CT, Tapp PD, Head E, et al. Chronic antioxidant and mitochondrial cofactor administration improves discrimination learning in aged but not young dogs. Prog Neuropsychopharmacol Biol Psychiatry. 2005;29(3):461–469.

114. Subash S, Braidy N, Essa MM, et al. Long-term (15 mo) dietary supplementation with pomegranates from Oman attenuates cognitive and behavioral deficits in a transgenic mice model of Alzheimer’s disease. Nutrition. 2015;31(1):223–229.

115. Taher YA, Samud AM, El-Taher FE, et al. Experimental evaluation of anti-inflammatory, antinociceptive and antipyretic activities of clove oil in mice. Libyan J Med. 2015;10:28685.

116. Tegeler C, O’Sullivan JL, Bucholtz N, et al. The inflammatory markers CRP, IL-6, and IL-10 are associated with cognitive function-data from the Berlin Aging Study II. Neurobiol Aging. 2016;38:112–117.

117. Thangthaeng N, Miller MG, Gomes SM, Shukitt-Hale B. Daily supplementation with mushroom (Agaricus bisporus) improves balance and working memory in aged rats. Nutr Res. 2015;35(12):1079–1084.

118. Valacchi G, Pecorelli A, Mencarelli M, Maioli E, Davis PA. β-carotene prevents ozone-induced proinflammatory markers in murine skin. Toxicol Ind Health. 2009;25(4–5):241–247.

119. Vedi M, Rasool M, Sabina EP. Protective effect of administration of Withania somifera against bromobenzene induced nephrotoxicity and mitochondrial oxidative stress in rats. Ren Fail. 2014;36(7):1095–1103.

120. Vite CH, Head E. Aging in the canine and feline brain. Vet Clin North Am Small Anim Pract. 2014;44(6):1113–1129.

121. Xi Y, Shao F, Bai XY, Cai G, Lv Y, Chen X. Changes in the expression of the Toll-like receptor system in the aging rat kidneys. PLoS One. 2014;9(5):e96351.

122. Xu X, Yin P, Wan C, et al. Punicalagin inhibits inflammation in LPS-induced RAW264.7 macrophages via the suppression of TLR4-mediated MAPKs and NF-κB activation. Inflammation. 2014;37(3):956–965.

123. Xu H, Sjogren P, Arnlov J, et al. A proinflammatory diet is associated with systemic inflammation and reduced kidney function in elderly adults. J Nutr. 2015;145:729–735.

124. Wang JH, Shih KS, Liou JP, et al. Anti-arthritic effects of magnolol in human interleukin 1β-stimulated fibroblast-like synoviocytes and in a rat arthritis model. PLoS One. 2012;7(2):e31368.

125. Wang W, Zhou PH, Xu CG, Zhou XJ, Hu W, Zhang J. Baicalein attenuates renal fibrosis by inhibiting inflammation via down-regulating NF-κB and MAPK signal pathways. J Mol Histol. 2015;46(3):283–290.

126. Weinstein JR, Anderson S. The aging kidney: physiological changes. Adv Chronic Kidney Dis. 2010;17(4):302–307.

127. Wichmann MA, Cruickshanks KJ, Carlsson CM, et al. Long-term systemic inflammation and cognitive impairment in a population-based cohort. J Am Geriatr Soc. 2014;62(9):1683–1691.

128. Wong VM, Kidney BA, Snead EC, Myers SL, Jackson ML. Serum C-reactive protein concentrations in healthy Miniature Schnauzer dogs. Vet Clin Pathol. 2011;40(3):380–383.

129. Wu D, Meydani M, Leka LS, et al. Effect of dietary supplementation with black currant seed oil on the immune response of healthy elderly subjects. Am J Clin Nutr. 1999;70(4):536–543.

130. Yadav UC, Baquer NZ. Pharmacological effects of Trigonella foenum-graecum L in health and disease. Pharm Biol. 2014;52(2):243–254.

131. Yokozawa T, Kim HY, Kim HJ, et al. Amla (Emblica officinalis Gaertn.) attenuates age-related renal dysfunction by oxidative stress. J Agric Food Chem. 2007;55(19):7744–7752.

132. Zhang ZH, Wei F, Vaziri ND, et al. Metabolomics insights into chronic kidney disease and modulatory effect of rhubarb against tubulointerstitial fibrosis. Sci Rep. 2015;5:14472.

133. Zicker SC, Jewell DE, Yamka RM, Milgram NW. Evaluation of cognitive learning, memory, psychomotor, immunologic, and retinal functions in healthy puppies fed foods fortified with docosahexaenoic acid-rich fish oil from 8 to 52 weeks of age. J Am Vet Med Assoc. 2012;241(5):583–594.

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