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Tuesday, 29 October 2013

Dementia Preventions - Phytochemicals Against Dementia

I. Dementia
About 5-8% of all people over the age of 65 have some form of dementia, and this number doubles every five years above that age. Dementia is the loss of mental ability that is severe enough to interfere with people's every life and Alzheimer's disease is the most common type of dementia in aging people.

II.  Phytochemicals Against Dementia
A. Rosemarinol, is a phytochemical monophenols, found in essential oil of labiate herbs like Rosemary and also in variety of other plants.
1. Chemical stabilization of fish oil
In the study of fish oil undergoes multiple changes in its physical properties and its autoxidation occurred found that rosemary extract rich in carnosic acid to ternary blends of tocopherols, ascorbyl palmitate and lecithin or Citrem significantly retarded autoxidation, according to "Chemical stabilization of oils rich in long-chain polyunsaturated fatty acids during storage" by Pop F.

2. Anti-inflammatory effects
In the research of the extract of rosemary leaves from supercritical fluid extraction and its anti inflammatory effects found that the yield of 3.92% and total phenolics of 213.5 mg/g extract obtained from the most effective extraction conditions showed a high inhibitory effect on lipid peroxidation (IC(50) 33.4 μg/mL). Both the SC-CO(2) extract and CA markedly suppressed the LPS-induced production of nitric oxide (NO) and tumor necrosis factor-α (TNF-α), as well as the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), phosphorylated inhibitor-kappaB (P-IκB), and nuclear factor-kappaB (NF-κB)/p65 in a dose-dependent manner, according to the study of "Anti-inflammatory effects of supercritical carbon dioxide extract and its isolated carnosic acid from Rosmarinus officinalis leaves" by Kuo CF, Su JD, Chiu CH, Peng CC, Chang CH, Sung TY, Huang SH, Lee WC, Chyau CC.(1)

3. Supercritical fluid
In the investigation of rosemary extract could enhance antioxidant defenses and improve antioxidant status in aged rats found that rosemary extract produced a decrease in antioxidant enzyme activity, lipid peroxidation and ROS levels that was significant for catalase activity in heart and brain, NOS in heart, and LPO and ROS levels in different brain tissues. These observations suggest that the rosemary supplement improved the oxidative stress status in old rats, according to "Protective effect of supercritical fluid rosemary extract, Rosmarinus officinalis, on antioxidants of major organs of aged rats" by Posadas SJ, Caz V, Largo C, De la Gándara B, Matallanas B, Reglero G, De Miguel E.(2)

B. Gingerole
Gingerole, is also known as gingerol, a phytochemical of Flavonoids (polyphenols) found in fresh ginger. and in variety of other plants. The herb has been used to treat nausea and vomiting of pregnancy, motion sickness, rheumatoid arthritis, relieve migraine, etc.
1. Antioxidant and anti-inflammatory effects
In the investigation of the effectiveness of chemical constituents of Zingiber officinale Rosc. (Zingiberaceae)in treating oxidative stress found that compounds [6]-gingerol, [8]-gingerol, [10]-gingerol and [6]-shogaol of the herb scavenges of 1,1-diphenyl-2-picyrlhydrazyl (DPPH), superoxide and hydroxyl radicals, inhibitsof N-formyl-methionyl-leucyl-phenylalanine (f-MLP) induced reactive oxygen species (ROS) production in human polymorphonuclear neutrophils (PMN), lipopolysaccharide induced nitrite and prostaglandin E(2) production in RAW 264.7 cells, according to the study of "Comparative antioxidant and anti-inflammatory effects of [6]-gingerol, [8]-gingerol, [10]-gingerol and [6]-shogaol" by Dugasani S, Pichika MR, Nadarajah VD, Balijepalli MK, Tandra S, Korlakunta JN(3)

2. Dementia
In the study of Ginger effectiveness in treating dementia in South Asia with A 70% aqueous/methanolic extract of dried ginger (Zo.Cr) was used. Zo.Cr tested positive for the presence of terpenoids, flavonoids, secondary amines, phenols, alkaloids and saponins found that
specific inhibition of butyrylcholinesterase (BuChE) rather than acetylcholinesterase enzyme. Different pure compounds of ginger also showed spasmolytic activity in stomach fundus, with 6-gingerol being the most potent. 6-Gingerol also showed a specific anti-BuChE effect, according to "Muscarinic, Ca(++) antagonist and specific butyrylcholinesterase inhibitory activity of dried ginger extract might explain its use in dementia" by Ghayur MN, Gilani AH, Ahmed T, Khalid A, Nawaz SA, Agbedahunsi JM, Choudhary MI, Houghton PJ.(4)

C.  Naringenin
Naringenin, a flavanone, belonging to the red, blue, purple pigments of Flavonoids (polyphenols) found predominantly in citrus fruits is considered as one of powerful antioxiant with many health benefits.
1. Antioxidant, radical scavenging and biomolecule activity
In the affirmation of the capacity of flavonoid naringenin and its glycoside naringin in the comparison of theirs antioxidant capacities, radical scavenging and biomolecule activities found that naringenin exhibited higher antioxidant capacity and hydroxyl and superoxide radical scavenger efficiency than naringin and both flavanones were equally effective in reducing DNA damage. However, they show no protective effect on oxidation of GSH, according to the study of "Antioxidant properties, radical scavenging activity and biomolecule protection capacity of flavonoid naringenin and its glycoside naringin: a comparative study" by Cavia-Saiz M, Busto MD, Pilar-Izquierdo MC, Ortega N, Perez-Mateos M, Muñiz P.(5)

2. Anti-inflammatory effects
In the evaluation of the mechanisms of action of the effective compounds. Flavone, the isoflavones daidzein and genistein, the flavonols isorhamnetin, kaempferol and quercetin, the flavanone naringenin, and the anthocyanin pelargonidin amd theirs anti-inflammatory effects found that they inhibited iNOS protein and mRNA expression and also NO production in a dose-dependent manner, according to "Anti-inflammatory effects of flavonoids: genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-kappaB activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF-kappaB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages" by Hämäläinen M, Nieminen R, Vuorela P, Heinonen M, Moilanen E.(6)

3. Immunity
In the unvestigation of Naringenin, a flavonoid in grapefruits and citrus fruits and its effec in immune system found that naringenin potently suppressed picryl chloride (PCl)-induced contact hypersensitivity by inhibiting the proliferation and activation of T lymphocytes. In vitro, both of the activated hapten-specific T cells and the T cells stimulated with anti-CD3/anti-CD28 showed growth arrest after naringenin treatment, according to "A novel regulatory mechanism of naringenin through inhibition of T lymphocyte function in contact hypersensitivity suppression" by Fang F, Tang Y, Gao Z, Xu Q.(7)

D.  Tangeritin
Tangeritin, one of the flavones, is found in tangerine and many citrus peels
1. Neuroprotective effects
In the evaluation of neuroprotective effects of a natural antioxidant tangeretin, a citrus flavonoid and its effect on Parkinson's disease found that tangeretin crosses the blood-brain barrier. The significant protection of striato-nigral integrity and functionality by tangeretin suggests its potential use as a neuroprotective agent, according to "Tissue distribution and neuroprotective effects of citrus flavonoid tangeretin in a rat model of Parkinson's disease" by Datla KP, Christidou M, Widmer WW, Rooprai HK, Dexter DT.(8)

2. Antioxidants
In the comparison of hand-pressed juice of polymethoxylated flavones (PMFs) and flavanone glycosides (FGs) and the peeled fruit of 'Sainampueng' tangerines ( Citrus reticulata Blanco cv. Sainampueng) antioxidant effects found that hand-pressed juice of C. reticulata Blanco cv. Sainampueng serves as a rich source of PMFs, FGs, carotenoids, and antioxidants: 4-5 tangerine fruits ( approximately 80 g of each fruit) giving one glass of 200 mL hand-pressed juice would provide more than 5 mg of nobiletin and tangeretin and 36 mg of hesperidin, narirutin, and didymin, as well as 30 mg of ascorbic acid, >1 mg of provitamin A active beta-cryptoxanthin, and 200 microg of alpha-tocopherol, according to "Polymethoxylated flavones, flavanone glycosides, carotenoids, and antioxidants in different cultivation types of tangerines ( Citrus reticulata Blanco cv. Sainampueng) from Northern Thailand" by Stuetz W, Prapamontol T, Hongsibsong S, Biesalski HK.(9)

E. Turmeric
Turmeric, principal curcuminoid of the popular Indian spice, a rhizomatous herbaceous perennial plant of the ginger family, Zingiberaceae, native to tropical South Asia, according to "Effects of different drying methods on the antioxidant properties of leaves and tea of ginger species" by E.W.C. Chan, Y.Y. Lim, S.K. Wong, K.K. Lim, S.P. Tan, F.S. Lianto and M.Y. Yong, posted in Science Direct. It has been used in traditional herbal medicine as an anti-inflammatory agent and to treat gastrointestinal symptoms associated with irritable bowel syndrome and other digestive disorders. Curcumin is a phytochemical found abundant in the plant. In acidic solutions (pH <7.4) it turns yellow, whereas in basic (pH > 8.6) solutions it turns bright red.
1. Alzheimer's disease and Anti-inflammatory agent
a. Alzheimer's disease
According to Aggarwal, the team determined that curcumin is more effective in inhibiting formation of the protein fragments than many other drugs being tested to treat Alzheimer's. The prevalence of the disease among older adults in India is 4.4 times less than in the U.S., suggesting that many Indians might be benefiting from having turmeric as a dietary staple.
In other study of `NSAID and antioxidant prevention of Alzheimer's disease: lessons from in vitro and animal models.`by Cole GM, Morihara T, Lim GP, Yang F, Begum A, Frautschy SA. (Source from Greater Los Angeles Healthcare System, Veterans Administration Medical Center, North Hills, CA 91343, USA. posted in US National Library of Medicine National Institutes of Health, reseachers found that the unconventional NSAID/antioxidant curcumin was effective, lowering oxidative damage, cognitive deficits, synaptic marker loss, and amyloid deposition. Curcumin proved to be immunomodulatory, simultaneously inhibiting cytokine and microglial activation indices related to neurotoxicity, but increasing an index of phagocytosis. Curcumin directly targeted Abeta and was also effective in other models, warranting further preclinical and clinical exploration.

b. Anti-inflammatory agent
According to the study of evaluation of anti-inflammatory property of curcumin (diferuloyl methane) in patients with postoperative inflammation. by Satoskar RR, Shah SJ, Shenoy SG., poated in US National Library of Medicine National Institutes of Health, researchers wrote that In this model of postoperative inflammation, the anti-inflammatory activity of curcumin (diferuloyl methane) was investigated in comparison with phenylbutazone and placebo. Phenylbutazone and curcumin produced a better anti-inflammatory response than placebo.

2. Antioxidants
In a study of `Protective Role of Curcumin Against Oxidative Stress,Immunosuppressive and Cytotoxic Effects of Lead Exposure` by Mahmoud El-sherbiny, Azza Araffa, Mona Mantawy and Hany M. Hassan (Therapeutic Chemistry Department, National Research Centre - Dokki, Giza, Egypt. Immunology Department, Animal Reproduction Research Institute (ARRI), Giza, Egypt), posted in World Applied Sciences Journal 12 (10): 1832-1838, 2011, researchers found that
ground, curcumin's benefits on tumorigenesis are thought to be mediated by its antiinflammatory activity; however, these effects have not been well characterized in a mouse model of colon cancer. Briefly, curcumin is efficacious for chronic nonbacterial prostatitis in rats and the action mechanism may be associated with its decreasing effect on the proinflammatory cytokines IL-8 and TNF-alpha in the blood and tissues. Curcumin has protective effect on DNA of pulmonary cells. There was direct evidence for an involvement of curcumin in reducing arsenic and lead induced oxidative stress in Swiss albino mice by virtue of its antioxidant potential and trapping of free radicals. The current investigation concluded that curcumin has protective role against cytotoxic, immunosuppressive , oxidative and immunosuppressive profile that perform due to lead acetate exposure.

F.  Gallic acid
Gallic acid is a phytochemical in the class of Phenolic acids, found abundantly in tea, mango, strawberries, rhubarb, soy, etc.
1. Cytotoxic and antioxidative activities
In the investigation of the bioactivity guided isolation and characterization of phytoconstituents, indicated the extract showed strong radical scavenging effects against DPPH, nitric oxide (NO) and superoxide (SO) radicals comparable to that of known antioxidants 3-t-butyl-4-hydroxyanisole, ascorbic acid (vitamin C), and quercetin in addition to its cytotoxic activities against HEP-2 (human larynx epidermoid carcinoma) and RD (human rhabdomyosarcoma) cell lines based on MTT assay for growth inhibition. The gallic acid equivalent total phenolic content of the plant was found to be 79.94mg/g dry extract. Phenylethanoid glycosides, verbascoside and calceorioside A were isolated from the most active fraction and both compounds showed strong radical scavenging activity against tested radicals and cytotoxicity against HEP-2, RD and MCF-7 (human breast adenocarcinoma) cell line, according to "Cytotoxic and antioxidative activities of Plantago lagopus L. and characterization of its bioactive compounds" by Sebnem Harput U, Genc Y, Saracoglu I.(10)

2.  Antioxidants
In the evaluation of the antioxidant, anti-inflammatory, and antiproliferative activities of organic fractions from Cystoseira sedoides (Desfontaines) C. Agardh, indicated that the F-CHCl(3) and F-AcOEt fractions showed significant total phenolic content at 55.09 and 61.30 mg gallic-acid equivalent/g dried sample, respectively. Using the DPPH method, the F-CHCl(3) and the F-AcOEt fractions exhibited the strongest radical scavenging activity, with IC(50) 120 µg/mL for F-CHCl(3) and 121 µg/mL for F-AcOEt, which approaches the activity of the powerful antioxidant standard, Trolox (IC(50) = 90 µg/mL), according to "Antioxidant, anti-inflammatory, and antiproliferative activities of organic fractions from the Mediterranean brown seaweed Cystoseira sedoides" by Mhadhebi L, Laroche-Clary A, Robert J, Bouraoui A.(11)

G. Cinnamic acid
Cinnamic acid is a phytochemical in the class of Hydroxycinnamic acids, found abundantly in cinnamon, aloe. etc.
1. Antioxidant effects
found that TPP-OH protected cells against H(2)O(2) and linoleic acid hydroperoxide-induced oxidative stress. As mitochondrial oxidative damage is associated with a number of clinical disorders, TPP-OH may be a useful lead that could be added to the family of mitochondria-targeted antioxidants that can decrease mitochondrial oxidative damage, according to "Rational discovery and development of a mitochondria-targeted antioxidant based on cinnamic acid scaffold" by Teixeira J, Soares P, Benfeito S, Gaspar A, Garrido J, Murphy MP, Borges F.(12)

2,  Anti-platelet aggregation
A series of novel ligustrazinyloxy-cinnamic acid derivatives were synthesized and evaluated for their inhibitory effect on adenosine diphosphate (ADP)-induced platelet aggregation in vitro,
found that compound 2e displayed the highest protective effect on the proliferation of the damaged ECV-304 cells (EC(50) = 0.020 mM), and compound 2f was the most active anti-platelet aggregation agent (EC(50) = 0.054 mM). Structure-activity relationships were briefly discussed, according to "Ligustrazine derivatives. Part 5: design, synthesis and biological evaluation of novel ligustrazinyloxy-cinnamic acid derivatives as potent cardiovascular agents" by Chen H, Li G, Zhan P, Liu X.(13)

H. Tyrosol
Tyrosol is a phytochemical compound, a derivative of phenethyl alcohol, belongings to the group of tyrosol esters, including found mostly in olive oil. It is best known for its antioxidants in protecting the forming of free radicals and lipid oxidation causes of heart disease. According to the study of " Tyrosol and hydroxytyrosol are absorbed from moderate and sustained doses of virgin olive oil in humans" vy E Miró-Casas, M-I Covas, M Fitó, M Farré-Albadalejo, J Marrugat and R de la Torre, posted in European Journal of Clinical Nutrition (European Journal of Clinical Nutrition (2003) 57, 186–190. doi:10.1038/sj.ejcn.1601532), researchers indicated that tyrosol and hydroxytyrosol are absorbed from realistic doses of virgin olive oil. With regard to the dose–effect relationship, 24 h urinary tyrosol seems to be a better biomarker of sustained and moderate doses of virgin olive oil consumption than hydroxytyrosol.
 1. Antioxidant
In study of " Tyrosol, the major olive oil biophenol, protects against oxidized-LDL-induced injury in Caco-2 cells." by Giovannini C, Straface E, Modesti D, Coni E, Cantafora A, De Vincenzi M, Malorni W, Masella R. (Source from Department of Metabolism and Pathological Biochemistry, Department of Food and Department of Ultrastructures, Istituto Superiore di Sanita, 00161 Rome, Italy.), posted in PubMed, researchers found that Caco-2 cell treatment (24 and/or 48 h) with oxidized LDL (0.2 g/L) resulted in cytostatic and cytotoxic effects characterized by a series of morphological and functional alterations: membrane damage, modifications of cytoskeleton network, microtubular disorganization, loss of cell-cell and cell-substrate contacts, cell detachment and cell death. The oxidized LDL-induced alterations in Caco-2 cells were almost completely prevented by tyrosol which was added 2 h before and present during the treatments.

2.  Alzheimer Disease
In a study of " Tyrosol and Hydroxytyrosol, Two Main Components of Olive Oil, Protect N2a Cells against Amyloid-β-Induced Toxicity. Involvement of the NF-κB Signaling." by St-Laurent-Thibault C, Arseneault M, Longpré F, Ramassamy C. (Source from INRS-Institut Armand Frappier, 531, boul. des Prairies, Laval, Québec, H7V 1B7, Canada., posted in PubMed, researchers found that the increase in the nuclear translocation of the NF-κB subunits after Aβ exposure was attenuated in the presence of Tyr or OH-Tyr. These results identified two individual food components of the MeDi as neuroprotective agent against Aβ and their potential involvement in the beneficial effect of the MeDi for the prevention of AD.

I.  Silymarin
Silymarin is a phytochemical in the class of Lignans (phytoestrogens), found abundantly in artichokes, milk thistle, etc.
1. Antioxidants
In the testing the effects ofEthyl acetate (100mg/kg bw) and ethanol seed extracts for S. marianum (100mg/kg bw) against the injection (i.p.) by carbon tetrachloride (2 ml/kg bw) the inducer of liver damage, found that ethanolic extract showed the most significantly decrease in the liver enzymes. For the oxidative experiments, ethyl acetate showed the most increase for glutathione level and the risk factor HDL/LDL significantly. Hepaticum was the most powerful group for the significant decreasing for malondialdehyde and fucosidase activity, according to "Silymarin, the antioxidant component and Silybum marianum extracts prevent liver damage" by Shaker E, Mahmoud H, Mnaa S.(14)

2. Neuroprotective effect
In numerous studies reported impaired cognitive and neurochemical function in diabetic patients and streptozotocin induced diabetic rodents, found that HO-1 is differently expressed in various brain regions in db/db mice when compared to lean animals. Furthermore, silibinin provides DNA protection and reduces oxidative stress in a brain specific area, in part via the activation of the HO system. Silibinin may provide a valid tool to counteract oxidative stress in the diabetic status in the central nervous system under diabetic condition, according to "Neuroprotective effect of silibinin in diabetic mice" by

Marrazzo G, Bosco P, La Delia F, Scapagnini G, Di Giacomo C, Malaguarnera M, Galvano F, Nicolosi A, Li Volti G.(15)
J. Etc.  
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