"This agent has been shown to regulate numerous transcription factors, cytokines, protein kinases, adhesion molecules, redox status and enzymes that have been linked to inflammation. The process of inflammation has been shown to play a major role in most chronic illnesses, including neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. In the current review, we provide evidence for the potential role of curcumin in the prevention and treatment of various proinflammatory chronic diseases." 

"Curcuminoids which are described as natural antioxidants" 

"Curcumin may help the macrophages to clear the amyloid plaques found in Alzheimer's disease. Macrophages play an important role in the immune system. They help the body to fight against foreign proteins and then effectively clear them" . 

Alzheimer's: 

Aging and longevity: If curcumin can really help prevent heart disease, cancer and Alzheimer’s, it would have obvious benefits for longevity... But given that oxidation and inflammation are believed to play a role in aging, curcumin may have effects that go way beyond just preventing disease."

"The antioxidant effects of curcumin have been shown to attenuate adriamycin-induced cardiotoxicity and may prevent diabetic cardiovascular complications. The anti-thrombotic, anti-proliferative, and anti-inflammatory effects of curcumin and the effect of curcumin in decreasing the serum cholesterol level may protect against the pathological changes occurring with atherosclerosis. The p300-HAT inhibitory effects of curcumin have been demonstrated to ameliorate the development of cardiac hypertrophy and heart failure in animal models. The inflammatory effects of curcumin may have the possibility of preventing atrial arrhythmias and the possible effect of curcumin for correcting the Ca2+ homeostasis may play a role in the prevention of some ventricular arrhythmias."

"Curcumin has been shown to attenuate several aspects of Metabolic syndrome (MetS) by improving insulin sensitivity, suppressing adipogenesis, and reducing elevated blood pressure, inflammation, and oxidative stress. In addition, there is evidence that curcuminoids modulate the expression of genes and the activity of enzymes involved in lipoprotein metabolism that lead to a reduction in plasma triglycerides and cholesterol and elevate HDL-C concentrations. Both overweight and obesity are linked to chronic low-grade inflammation; although the exact mechanisms are not clear, it is known that pro-inflammatory cytokines are released. These cytokines are thought to be at the core of the complications associated with diabetes and cardiovascular disease. Therefore, addressing inflammation is important. In a randomized double-blind placebo-controlled trial with a parallel-group design, 117 subjects with MetS received either 1 g curcumin plus 10 mg piperine to increase absorption or a placebo plus 10 mg piperine for eight weeks. Within-group analysis revealed significant reductions in serum concentrations of TNF-α, IL-6, transforming growth factor beta (TGF-b), and monocyte chemoattractant protein-1 ( MCP-1) following curcumin supplementation (p < 0.001). In the placebo group, serum levels of TGF-b were decreased (p = 0.003) but those of IL-6 (p = 0.735), TNF-α (p = 0.138), and MCP-1 (p = 0.832) were not. Between-group comparison suggested significantly greater reductions in serum concentrations of TNF-α, IL-6, TGF-b, and MCP-1 in the curcumin versus the placebo group (p < 0.001). Apart from IL-6, changes in other parameters remained statistically significant after adjustment for potential confounders, including changes in serum lipids and glucose levels, as well as the baseline serum concentration of the cytokines. The results of this study suggest that curcumin supplementation significantly decreases serum concentrations of pro-inflammatory cytokines in subjects with MetS. In addition, the study looked at the cholesterol-lowering properties and found that curcuminoids were more effective than the placebo in reducing serum LDL-C, non-HDL-C, total cholesterol, triglycerides, and lipoprotein a (Lp(a)), in addition to elevating HDL-C concentrations." 

"Several studies have shown that curcumin exhibits anti-arthritic effects with improvement in pain and physical function scores. At a dose of 1 g/day for 8–12 weeks, the improvement in osteoarthritic pain and infammation was comparable with that of ibuprofen and diclofenac. " 

"At a dose of 1 g/day for 8–12 weeks, the improvement in osteoarthritic pain and inflammation was comparable with that of ibuprofen and diclofenac. In another study using a lecithinised formulation to increase bioavailability, 400 mg curcumin was associated with greater analgesic activity than 500 mg paracetamol, while 300 mg provided suboptimal pain relief. " 

"Gastrointestinal ulcer could be induced by infection of the stomach by a bacterium called H. pylori, by chronic ingestion of NSAIDs, and exogenous substances such as cigarette, alcohol, and fast foods. A dietary natural drug (curcumin) could be used to protector treat the inflammation induced by the ulcer effectors. The biological effect of curcumin to combat these induced pathological disorders is due to its anti-inflammatory and antioxidant activities. Therefore, this review confirmed curcumin as an antiulcer potent agent." 

In the present investigation, the oil was dominated by the linalool (32.83%) and monoterpenic ester linalyl acetate (16%) but the previous report of same plant species growing in Bangladesh dominated by the 3-carene (54.22%) and linalool (0.19%) was present as minor compound (Chowdhury et al., 2008). Other major components are Elemol (7.44%), Geranyl acetate (6.18%), Myrcene (6.12%), Allo-Ocimene (5.02%), α-Terpineol (4.9%), (E)-β-Ocimene (3.68%), Neryl acetate (3.45%) respectively. Linalool is reported to possess antibacterial, insect-repelling and toxic activities (Cardile et al., 2009 ▶).

"The antioxidant activity of curry leaf is attributed to mahanimbine, murrayanol and mahanine (Tachibana et al. 2001; Ningappa et al. 2008). Antioxidant effect of curry leaf powder in chicken and goat meat products has also been reported (Biswas et al. 2006; Das et al. 2011)...Table 1 shows the antioxidant properties of curry leaves and fenugreek extracts. Curry leaves had a significantly (P < 0.05) higher phenolic content...The reducing power was significantly (P < 0.05) higher in curry leaves than fenugreek. Palaniswamy (2001) reported that water-ethanol extract of curry leaves comprised of a high polyphenolic content and the antioxidant activity may be the result of the synergistic action of all the components, rather than of a single entity of the extract...Similar studies have reported that natural antioxidants are involved in the termination of free radical reactions and exhibit reducing capacity (Wang et al. 2003). The reducing capacity might be due to their hydrogen donating ability (Shimada et al. 1992)." 

"In the present investigation, the oil was dominated by the linalool (32.83%) and monoterpenic ester linalyl acetate (16%) but the previous report of same plant species growing in Bangladesh dominated by the 3-carene (54.22%) and linalool (0.19%) was present as minor compound (Chowdhury et al., 2008). Other major components are Elemol (7.44%), Geranyl acetate (6.18%), Myrcene (6.12%), Allo-Ocimene (5.02%), α-Terpineol (4.9%), (E)-β-Ocimene (3.68%), Neryl acetate (3.45%) respectively... One of the research reports was found that inhaling linalool can reduce stress in lab rats so the findings could form the basis of new blood tests for identifying fragrances that can soothe stress (Nakamura et al., 2009 ▶)." 

"The MKA improved the level of protective antioxidants such as glutathione peroxidase (GPx), reduced glutathione (GSH), glutathione reductase (GRD), superoxide dismutase (SOD) and catalase (CAT) in brain homogenate at higher doses (20 and 40 mg/kg, p.o.). Moreover, a dose dependent decline was noted in lipid peroxidation (LPO) and the nitric oxide assay (NO) at all doses of MKA (10, 20 and 40 mg/kg, p.o.). Interestingly, significant progress was noted with the supplementation of MKA by an improvement of the acetylcholine (ACh) levels and a reduction in the acetylcholinesterase (AChE) activity in aged mouse brain. In addition, a significant elevation of serum albumin (ALBU), alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST) and total protein as well as a decline in creatinine, total cholesterol, urea nitrogen and glucose levels with MKA also ameliorated the hepatic and renal functions in normal ageing process. The results showed the possible utility of Murraya koenigii leaves in neuroprotection against neurodegenerative disorders such as Alzheimer's disease." 

"The dichloromethane (MKD) and ethyl acetate (MKE) extracts of Murraya koenigii leaves significantly reduced the body weight gain, plasma total cholesterol (TC) and triglyceride (TG) levels significantly when given orally at a dose of 300 mg/kg/day to the high fat diet (HFD) induced obese rats for 2 weeks... Mahanimbine (1) when given orally (30 mg/kg/day) also significantly lowered the body weight gain as well as plasma TC and TG levels. These findings demonstrate the excellent pharmacological potential of mahanimbine to prevent obesity." 

"Murraya koenigii (curry leaves), against progression of high-fat diet (HFD)-induced metabolic complications in mice (male and female). Mahanimbine at 2 mg/kg (HFD + LD) and 4 mg/kg (HFD + HD) of body weight was administered daily along with HFD feeding for 12 weeks... Mahanimbine prevented HFD-induced hyperlipidemia and fat accumulation in adipose tissue and liver along with the restricted progression of systemic inflammation and oxidative stress.

"Methods: Herein, cytotoxic activity of MK was first tested on 4T1 cells in vitroby MTT assay. Then, in vivo chemopreventive study was conducted where mice were fed with extracts prior to and after inducing the tumor (inoculation). Tumor size was monitored post-4T1 inoculation. At the end of experiment, histopathology of tumor sections, T cell immunophenotyping, tumor nitric oxide level, serum cytokine level and qPCR analysis on expression of iNOS, iCAM, NF-kB and c-MYC were performed. Results: MK reduced the tumors' size and lung metastasis aside from inhibited the viability of 4T1 cells in vitro. Furthermore, it decreased the level of nitric oxide and inflammation-related cytokines and genes, including iNOS, iCAM, NF-kB and c-MYC. Conclusion: The results propose that, MK managed to inhibit the progression of tumor via immunostimulatory effect and inflammatory reaction within the tumor samples. This suggests that MKconsumption could be a savior in the search of new chemopreventive agents." 

Flaxseed contains small amounts of water-soluble and fat-soluble vitamins. Vitamin E is present as γ-tocopherol, amounting to 39.5 mg/100 g. γ-tocopherol is an antioxidant providing protection to cell proteins and fat from oxidation; promotes sodium excretion in urine, which may help in lowering of blood pressure and heart disease risks and Alzheimer disease (Morris et al. 2005; Morris 2007)."Hypertension is the single largest risk factor attributed to mortality in the world. Medications are the primary treatment for hypertension; however, adherence to drug regimens is low (~50 %). Low adherence may be a contributing factor leading to uncontrolled blood pressure in patients. An effective alternative or complement to medications in managing hypertension is through lifestyle modifications. Adopting a healthy diet is a valuable strategy. A recent, randomized controlled year-long trial observed impressive reductions in blood pressure in patients with hypertension consuming flaxseed daily. Therefore, attention has been garnered for flaxseed as a potentially valuable strategy for the management of hypertension." 

"Black pepper holds significant antioxidant activity as 50% inhibition of 13 free radicals can be achieved with 0.43mg. In some earlier studies conducted by Gulçin 14 (2005), it was observed that water and ethanol extracts (75 µg/ml) of black pepper show 15 95.5%, and 93.3% inhibition of lipid-peroxidation, respectively. The inhibition ought to 16 total phenolics content i.e. 54.3 and 42.8µg/mg, respectively. Saxena et al. (2007) 17 reported higher quantities of polypheols i.e 191mg/100g. Determination of antioxidant 18 activity through some In vitro trials generated some conclusive evidences. In this 19 regard, (Kapoor et al., 2009) observed high antioxidant activities of black pepper essential oil and oleoresins as compared to synthetic antioxidants. Likewise, Su et al. (2007) indicated that black pepper is a potential dietary source of natural antioxidants. Therefore, presence of these functional ingredients in black pepper makes it a strong candidate to ameliorate oxidative stress (Mittal and Gupta, 2000). Gulçin (2005) attributed these actions to its strong hydrogen-donating ability, metal chelating, and effectiveness to scavenge free radicals."

"Eventually, anti-inflammatory activities of black pepper are reported for the first time 26 some two decades ago. Mujumdar et al. (1990) indicated that piperine mitigate the acute 27 inflammatory process, through stimulating the pituitary adrenal axis. Later, Bang et al. 28 (2009) strengthened the anti-inflammatory activities of piperine (20 & 100 mg/kg/day) 29 through some in vitro trials. They postulated that inhibition of interlukon (IL6), matrix 30 metalloproteinase (MMPs), prostaglandin E2 (PGE2), and activator protein 1 are possible routes for their said properties. Recently, Sabina et al. (2011) reported that piperine (50/100ug/ml) suppressed the level of β-glucuronidase and lactate dehydrogenase in dose-dependent manner. Piperine along with some other components can inhibit the expression of enzymes like 5-lipoxygenase and COX-1 that are responsible for leukotriene and prostaglandin biosynthesis. These effects collectively are valuable to prevent degenerative disorders like rheumatoid arthritis too (Stohr et al., 2001; Lee et al., 2008)."

"In this regard, antioxidant potential of black pepper and its bioactive molecules is of considerable importance to improve brain function (Wattanathorn et al., 2008). Furthermore, the supplementation of piperine (5, 10 and 13 20mg/kg body/day) provides neuro-protection including improved cognitive function (Hanumanthachar and Miland, 2005; Lee et al., 2005). Li et al. (2007) previously investigated the antidepressant-like effect of piperine (2.5, 5 and 10 mg/kg). Their results revealed that piperine ameliorated the chronic mild stress due to changes in sucrose consumption, plasma corticosterone level, and open field activity. They commented that up-regulation of the progenitor cell proliferation of hippocampus, and cytoprotective activities are responsible for antidepressant-like effect of piperine. Later, Li et al. (2007) added that piperine treatment up-regulated brain-derived neurotrophic factor (BDNF) and mRNA expression. Additionally, Hu et al. (2009) indicated that piperine (10 & 20 mg/kg) improved the depression through reduction in ACTH and CRH levels thus ultimately leading to modulating hypothalamic-pituitary-adrenal (HPA) axis.. Recently, Bhutani et al. (2009) suggested to use piperine in combination with curcumin for the treatment of depressive disorders. The behavioral studies using forced swimming test (FST) and tail suspension test (TST) revealed that piperine is potent anti-depressant agent @ 10 & 20 mg/kg (Lee et al., 2005; Mohit et al., 2009; Liao 28 et al., 2009)." 

"As far absorption of piperine is concerned, it is absorbed from mucosal side (44-63%) that could be traced in intestinal tissue and serosal fluids (Suresh and Srinivasan, 2007). Piperine improves the functionality of gastrointestinal tract. The mechanisms of action include enhanced absorption of nutrients, improved enzymes synthesis, and perk-up defense capabilities. The examples include enhanced intestinal absorption of methionine & calcium ions, trace elements (selenium), vitamins B and β-carotene (Badmaev et al., 2000; Capasso et al., 2002). The amplified nutrient absorption is dependent upon the positive changes in permeability of intestinal cells membranes (Srinivasan, 2007)."

"It has been shown in a study conducted in normalmice by Panda and Kar (4) that piperine has hypo-glycemic effect... [We found that] there was significant lowering of blood glucose levels [with a peperine dose of 5 and 10 mg/kg] after 14 days ( p < 0.05... It is apparent from the above results that piper-ine has the potential to be used as an antidiabeticagent, if given repeatedly at the appropriate dosesover a period of time. Its acute effects of raising bloodglucose could also be used beneficially by using it incombination with known antidiabetics to counteracttheir adverse effect of hypoglycemia." 

"Hamsters were classified into eight groups: a normal control, atherogenic control and six other experimental groups (fed atherogenic diet supplemented with different doses of P. nigrum, P. guineense and P. umbellatum (1 and 0.25 g/kg) for 12 weeks. At the end of the feeding period the heart, liver and kidney from each group were analyzed for lipid profile and antioxidant enzymes activities. Atherogenic diet induced a significant (P<0.001) increase in the lipid profile across the board and equally significantly altered the antioxidant enzyme activities. Supplementation with Piper species significantly inhibited the alteration effect of atherogenic diet on the lipid profile and antioxidant enzymes activities. The Piper extracts may possess an antioxidant protective role against atherogenic diet induced oxidative stress in cardiac, hepatic and renal tissues." - Agbor GA, Akinfiresoye L, Sortino J, Johnson R, Vinson JA. Piper species protect cardiac, hepatic and renal antioxidant status of atherogenic diet fed hamsters. Food Chem. 2012 Oct 1;134(3):1354-9. doi: 10.1016/j.foodchem.2012.03.030. Epub 2012 Mar 23. PMID: 25005953.

"In this regard, Zhou et al. (2003) presented the evidences that the positive anticancer effects of piperine against benzo-pyrene induced lung carcinogenesis in mice model are due to its ability to 1 interaction with cytochrome P450 enzyme syste,. Later, Selvendiran et al. (2004) 2 explicated that piperine exhibited in vitro and in vivo dose-dependent inhibition of phase-I detoxification system (Bhardwaj et al., 2002). Moreover, piperine modulated the mitochondrial tricarboxylic acid cycle and glutathione-metabolizing enzymes in animal model lung carcinogenesis (Thirunavukkarasu et al., 2001; Vijayakumar et al., 2004; Suresh and Srinivasan, 2006). Later, Vellaichamy et al. (2009) examined the 7 chemopreventive potential of piperine (50mg/kg) against 7,12-8 dimethylbenz[a]anthracene (DMBA)-induced skin carcinogenesis. Piperine modulated the phase I & II detoxification system effectively thus ameliorating lipid peroxidation. In addition to aforementioned effects, the improvements in antioxidants status to normal are of significant importance for health care. Likewise, Krishnakumar et al. (2009) observed similar results in oral cancer bearing animals. Earlier, Nalini et al. (1998) observed that black pepper may protect the colon cancer by decreasing the activity of β-glucuronidase and mucinase. Pellitorine (terpinoids present in black 15 pepper) showed strong cytotoxic activities against HL60 and MCT-7 cell lines (Ee et al., 2010). Black pepper also counteracts cancer development directly (Selvendiran et al., 2004) through modification in enzyme kinetics to control the protein level in blood (Polovka and Suhaj, 2010). In another study, Bogomolny et al. (2008) supported some earlier studies that piperine owing to its potent antioxidant property can reduce protein expression thus modulating cell proliferation and transformation (Selvendiran et al., 2006). Research has revealed that pepper exerts a free-radical scavenging activity that assists in controlling the progression of some cancers. In some conditions, the same property can be useful in reducing the growth of cancer cells (Yadav and Bhatnagar, 2007). More recently, Liu et al. (2010) postulated that nearly all bioactive molecules of black pepper can suppress TNF-induced NF-kappaB activation. The extracts of black pepper at 200 microg/mL and its compounds at 25 µg/mL inhibited lipid peroxidation 27 by 45-85%, COX enzymes by 31-80% and cancer cells proliferation by 3.5-86.8%...Furthermore, black pepper and cardamom extracts collectively enhance the cytotoxic activity of 1 natural killer cells that indicate their potential anti-cancer effects (Majdalawieh and 2 Carr, 2010)."  

"[Black pepper] facilitates the digestion and reduces the food passage time in intestine by improving the digestive enzyme stimulation and saliva secretion. In addition to gastric protective functions, piperine extends its services in liver protection and bio-absorption of micronutrients, vitamins and trace elements. It helps increasing the bioavailability of many types of drugs and phytochemicals thus act as nutrient enhancer (Snyman et al., 2001; Capasso et al., 2002; Kumoro et al., 2009)."

"Objective: To evaluate and compare the analgesic and anti-inflammatory activity of pure compound, piperine along with hexane and ethanol extracts of Piper nigrum L. fruit in mice and rats.