Desktop version

Home arrow Health

  • Increase font
  • Decrease font


<<   CONTENTS   >>

IMMUNOMODULATORY EFFECT OF NUTRACEUTICALS ON NEURODEGENERATION

Some nutraceuticals such as resveratrol, epigallectocatechin-3-gallate (EGCG), Vitamin-D, and Vitamin-E are potent antioxidants and have shown therapeutic effects against many diseases. A huge number of studies have evidenced the beneficial effects of nutraceuticals against various neurode- generative disorders however; the present chapter mainly focuses on nutraceuticals for which mechanistic evidences for neuroprotection are available in Table 2.1.

TABLE 2.1 Effect of different Nutraceuticals against various Neurodegenerative Diseases

SI.

No.

Nutraceuticals

Targeted Mechanism

Implications

References

1.

Resveratrol

Antioxidant properties mediated modulations of Ap processing. Increased level of 5-HT activity.

Antidepressant

properties.

[57]

2.

EGCG

Inhibition of

pro-inflammatory

signaling.

BBB stabilization in MS.

[58]

3.

Vitamin-D

Anti-inflammatory

property.

Protective in patients with neurodegenerative diseases.

[59]

4.

Vitamin-E

Decreased level of

pro-inflammatory

cytokines.

Decreased

neuroinflammation and neuronal degeneration.

[60]

IMMUNOMODULATORY ROLE OF NEUROTRANSMITTERS ON NEURODEGENERATION

CNS and immune system, mainly participates in continuous and functional crosstalk to ensure homeostasis. The catecholamine’s such as DA, serotonin, and noradrenaline, function as neuroimmunotransmitters in the sympathetic- adrenergic terminals of the autonomic nervous system, which innervates the primary and secondaiy lymphoid organs—in addition to the direct local effects that nonsynaptic varicosity secretions have on immune cells.

2.7.1 IMMUNOMODULATORY ROLE OF DOPAMINE (DA)

The immunomodulatory role of DA has a significant effect on understanding the relationship between the immune system and CNS. Reports given by various groups show the effect of DA on cytokine secretion, cell adhesion in lymphocytes of humans and rodents. It has been demonstrated that DA plays a vital role in secretion and up-regulation of cytokines like TNF-a and IL-10. Other studies revealed that D3 receptor expresses CD8+T lymphocytes selectively and stimulates the CD8T lymphocyte adhesion. Some studies deciphered that activation of circulating lymphocytes are associated with neurodegeneration in PD. The synthesis of IL-4 and IL-10 are decreased by the stimulation of D3 receptor in CD4'T lymphocytes thus promoting the production of IFN-y. Therefore, D3 receptor is an essential target for pathophysiology of PD [61]. Other related neurodegenerative diseases associated with immunomodulatory role of DA is AD. Numerous patients diagnosed with AD have a very low density of D2 receptors on lymphocytes and this event is also evidenced in postmortem analysis of AD brain. It is also suggested that lymphocytes of AD patients show an increase in inmiunoreactivity of DAp-hydroxylase and henceforth, more studies are required to determine the function of DA on lymphocytes in AD patients [61].

2.7.2 IMMUNOMODULATORY ROLE OF SEROTONIN

The association of AD is related with decrease level of serotonin as found in majority of the patients. There is a high density of 5-HT,c in natural killer cells (NK cells) and due to the increase in 5-HT,c a reduced availability of 5-HT is observed in brains of AD patients. This activation of 5-HT 2c inhibits the NK cells and make AD patients susceptible to viral infections [62]. Various selective serotonin reuptake inhibitors are used for treating the depression in AD. These inhibitors stimulated cell adhesion and lymphocyte activation whereas; another experiment observed that а 5-HT, agonist in murine model reduced amyloid production and deposition in AD brain. However, it can be stated that microglia may be associated with this complex situation as microglia expresses 5-HT, and engulfs the amyloid deposition. Thus, the above observation proved that 5-HT4 agonists play a vital role in inducing immunomodulatory effect in microglia [62].

CONCLUSIONS

Here, we tried to provide a comprehensive detail about the current research aspect of the immunomodulatory role of traditional herbs together with its potential application and mechanism of action in neurodegenerative diseases.

A single bioactive compound is not sufficient to control the complex nature of various neurodegenerative diseases. Several mechanisms such as BBB integrity, oxidative stress, immunomodulation, inflammation, and aggregation of misfolded protein have shown to be related with neurodegeneration. Since, the translational gap between in-vitro, in-vivo, and clinical studies is still a major issue especially with respect to immunomodulatory effects of the said plant extracts. Thus, careful consideration should also be made in respect to the immunomodulatory effects of plant-based extracts on neurodegeneration.

Another aspect that should be taken under consideration is that a single compound is not sufficient in controlling neurodegeneration and therefore a synergistic effect of multiple compounds as present in the extract could mutually enhance the condition of this complex disorder. In addition to this, detailed research is needed to explore the immunomodulatory effect of plant extracts along with its bioactive compounds; to elucidate the therapeutic efficacy of this extract in combating the imbalance in immunomodulatory markers in various neurodegenerative diseases. Therefore, further research should be focused on the mechanism and mode of action of herbal compound supplementation and its safe therapeutic role for preventing the imbalance of immunomodulatory markers on neurodegeneration.

KEYWORDS

  • Alzheimer’s disease
  • amyotrophic lateral sclerosis
  • blood-brain barrier
  • central nervous system
  • electron transport chain
  • epidermal growth factor

REFERENCES

  • 1. Ratheesh, G., Tian, L., et al., (2017). Role of medicinal plants in neurodegenerative diseases. Biomanufac. Rev., 2,2.
  • 2. Simen, A. A., Bordner, K. A., et al., (2011). Cognitive dysfunction with aging and the role of inflammation. Then Adv. Chronic Dis., 2, 175-195.
  • 3. Haque, M. R., Ansari, S. H., et al., (2013). Coffea Arabica seed extract stimulate the cellular immune function and cyclophosphamide induced immunosuppression in mice. Iranian. J. Pharm Res., 12,101-108.
  • 4. Mogensen, T. H., (2009). Pathogen recognition and inflammatory signaling in innate immune defenses. Clin. Microbiol. Rev., 240-273.
  • 5. Dantuma,E., Merchant, S.,etal., (2010). Stem cells for the treatment ofneurodegenerative diseases. Stem Cell Res. Then, 1, 37.
  • 6. Dunkel, P., Chai, C. L., et al., (2012). Clinical utility of neuro protective agents in neurodegenerative diseases: Current status of drug development for Alzheimer’s, Parkinson’s, and Huntington’s diseases, and amyotrophic lateral sclerosis. Expert Opin. Investig. Drugs., 21, 1267-1308.
  • 7. Dye, R. V., Miller, K. J., et al., (2012). Honnone Replacement Therapy and Risk for Neurodegenerative Diseases.
  • 8. Moraes, W. A., (2015). Current Pharmacological and Non-Pharmacological Therapies for Neurodegenerative Diseases.
  • 9. Moreno, J. A., Halliday, M., et al., (2013). Oral treatment targeting the unfolded protein response prevents neurodegeneration and chnical disease in prion-infected mice. Sci. Transl. Med.
  • 10. Weissmiller, A. M., &, Wu, C., (2012). Current advances in using neurotrophic factors to treat neurodegenerative disorders. Transl. Neurodegener., 1, 14.
  • 11. Connolly, B. S., &, Lang, A. E., (2014). Pharmacological treatment of Parkinson’s disease: A review. JAMA, 311, 1670-1683.
  • 12. Vercruysse, P., &, Vieau, D., (2018). Hypothalamic alteration in neurodegenerative diseases. Front. Mol. Neurosci.
  • 13. Beal, M. F., (1994). Neurochemistry and toxin models in Huntington’s disease. Cun: Opin. Neurol, 7, 542-547.
  • 14. Beal, M. F., (2004). Mitochondrial dysfunction and oxidative damage in Alzheimer’s and Parkinson’s diseases and coenzyme Q10 as a potential treatment. J. Bioenerg. Biomembr, 36,381-386.
  • 15. Su, K., Bourdette, D., et al., (2013). Mitochondrial dysfunction and neurodegeneration in multiple sclerosis. Front. Physiol, 4, 169.
  • 16. Wong, P. C., Pardo, C. A., et al., (1995). An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondria. Neuron., 14, 1105-1116.
  • 17. Mancuso, M., Coppede, F., et al., (2006). Mitochondrial dysfunction, oxidative stress, and neuro degeneration. J. Alzheimer’sDis., 10, 59-73.
  • 18. Rintoul, G. L., &, Reynolds, I. J., (2010). Mitochondrial trafficking and morphology in neuronal injury. Biochim. Biophys. Acta., 1802, 143-150.
  • 19. Di Filippo, M., Tozzi, A., et al., (2014). Interferon-pla protects neurons against mitochondrial toxicity via modulation of STAT1 signaling: Electrophysiological evidence. Neurobiol. Dis., 62, 387-393.
  • 20. Qi, X., Lewin, A. S., et al., (2006). Mitochondrial protein nitration primes neurodegeneration in experimental autoimmune encephalomyelitis. J. Biol. Chem., 281, 31950-31962.
  • 21. Tang, T. S., Slow, E., et al., (2005). Disturbed Ca2+ signaling and apoptosis of medium spiny neurons in Huntington’s disease. Proc. Natl. Acad. Sci. USA., 102, 2602-2607.
  • 22. Floyd, R. A., Carney, J. M., et al., (1992). Free radical damage to protein and DNA: Mechanisms involved and relevant observations on brain undergoing oxidative stress. Ann. Neurol., 32, S22-S27.
  • 23. Gilgun-Sherki, Y., Melamed, E., et al., (2001). Oxidative stress induced- neurodegenerative diseases: The need for antioxidants that penetrate the blood brain barrier. Neuropharmacology’, 40,959-975.
  • 24. Zaleska, M. M., &, Floyd, R. A., (1985). Regional lipid peroxidation in rat brain in-vitro: Possible role of endogenous iron. Neurochem. Res., 10, 397-410.
  • 25. Nunomura, A., Honda, K., et al., (2005). Alzheimer-specific epitopes of tau represent lipid peroxidation-induced conformations. Free Radic. Biol Med., 38, 746-754.
  • 26. Nunomura, A., Perry, G., et al., (1999). RNA oxidation is a prominent feature of vulnerable neurons in Alzheimer’s disease. J. Neurosci., 19,1959-1964.
  • 27. Alam, Z. I., Jenner, A., et al., (1997). Oxidative DNA damage in the Parkinsonian brain: An apparent selective increase in 8-hydroxyguanine levels in substantia nigra. J. Neurochem., 69, 1196-1203.
  • 28. Taylor, D. M., Gibbs, B. F., et al., (2007). Tryptophan 32 potentiates aggregation and cytotoxicity of a copper/zinc superoxide dismutase mutant associated with familial amyotrophic lateral sclerosis. J. Biol. Chem., 282,16329-16335.
  • 29. Ferrante, R. J., Browne, S. E., et al., (1997). Evidence of increased oxidative damage in both sporadic and familial amyotrophic lateral sclerosis. J. Neurochem., 69,2064-2074.
  • 30. Karg, E., Klivenyi, P, et al., (1999). Nonenzymatic antioxidants of blood in multiple sclerosis. J. Neurol., 246, 533-539.
  • 31. Wint, D., &, Cummings, J. L., (2016). Neuropsychiatric Aspects of Cognitive Impairment (pp. 197-208). Oxford University Press.
  • 32. https://parkinsonsnewstoday.eom/2018/02/28/8-common-treatments-parkinsons- disease-2/ (accessed on 23 June 2020).
  • 33. Harvey, A. L., Edrada-Ebel, R., et al., (2015). The re-emergence of natural products for drug discovery in the genomics era. Nat. Rev. Drug Discov, 14,111-129.
  • 34. Upadhyay, S., &, Dixit, M., (2015). Role of polyphenols and other phytochemicals on molecular signaling. Oxid. Med. Cell. Longer., 504253.
  • 35. Ghosal, S., Lai, J., et al., (1989). Immunomodulatory and CNS effects of sitoindosides IX and, X., two new glycowithanolides from Withania somnifera. Phytother Res., 3, 201-206.
  • 36. Davis, L., &, Kuttan, G., (2000). Immunomodulatory activity of Withania somnifera. J. Ethnophannacol, 71, 193-200.
  • 37. Mishra, L. C., Singh, В. B., et al., (2000). Scientific basis for the therapeutic use of Withania somnifera (ashwagandha): A review. Altem. Med. Rev, 5,334-346.
  • 38. Agarwal, R., Diwanay, S., et al., (1996). Studies on immunomodulatory activity of Withania somnifera (ashwagandha) extracts in experimental iimnune inflammation. J. Ethanopharmacol., 67, 27-35.
  • 39. Davis, L., &, Kuttan, G., (2002). Effect of Withania somnifera on cell mediated iimnune response in mice. J. Exp. Clin. Cancer Res., 21, 585-590.
  • 40. Chandel, R. S., Kulshrestha, D. K., et al., (1977). Bacogenin A3: Anew sapogenin from Bacopa monniera. Phytochemistry, 16,141-143.
  • 41. Karlowicz-Bodalska, K., Han, S., et al., (2017). Curcuma Longa as medicinal herb in the treatment of diabetic complications. Acta Pol. Pharm., 74, 605-610.
  • 42. Dhanasekaran, M., Tharakan, B., et al., (2007). Neuroprotective mechanisms of ayurvedic antidementia botanical Bacopa monniera. Phytother. Res., 21,965-969.
  • 43. Bhattacharya, S. K., Kumar, A., et al., (1995). Effects of glycowithanolides from Wtthcmia somnifera on animal model of Alzheimer’s disease and perturbed central cholinergic markers of cognition in rats. Phytother Res., 9, 110-113.
  • 44. Kuboyama, T., Tohda, C., et al., (2014). Effects of ashwagandha (roots of Withania somnifera) on neurodegenerative diseases. Biol. Pharm. Bull., 37, 892-897.
  • 45. Sandhir, R., &, Sood, A., (2017). Neuroprotective Potential of Withania somnifera (ashwagandha) in Neurological Conditions. Springer International Publishing.
  • 46. Brosseron, F., Krauthausen, M., et al., (2014). Body fluid cytokine levels in mild cognitive impairment and Alzheimer’s disease: A comparative overview. Mol. Neurobiol, 50, 534-544.
  • 47. Nagats, T., Mogi, M., et al., (2000). Cytokines in Parkinson’s disease. Advances in Research on Neurodegeneration(pp. 143-151).
  • 48. Swarup, V, Phaneuf, D., et al., (2011). Deregulation of TDP-43 in amyotrophic lateral sclerosis triggers nuclear factor kappaB-mediated pathogenic pathways. J. Exp. Med., 208, 2429-2447.
  • 49. Malik, F., Singh, J., et al., (2007). A standardized root extract of Withania somnifera and its major constituent withanolide-A elicit humoral and cell-mediated immune responses by up regulation of Thl-dominant polarization in BALB c mice. Life Sci., 80, 1525-1538.
  • 50. Kure, C., Timmer, J., et al., (2017). The immunomodulatory effects of plant extracts and plant secondary metabolites on chronic neuroinflammation and cognitive aging: A mechanistic and empirical review. Front Pharmacol., 8,117.
  • 51. Goswami, S., Saoji, A., et al., (2011). Effect of Bacopa monnieri on cognitive functions in Alzheimer’s disease patients. Int. J. Collaborative Res. Intent. Med. Public Health, 3, 285-293.
  • 52. Rama, В. P, (2018). A review on immunomodulatory effects of plant extracts. Urology and Immunology J., 2.
  • 53. Russo, A., Borrelli, F., et al., (2003). Life nitric oxide-related toxicity in cultured astrocytes: Effect of Bacopa monniera. Sci., 73,1517-1526.
  • 54. Sharma, H. S., Drieu, K., et al., (2000). Role of nitric oxide in blood-brain barrier permeability, brain edema and cell damage following hyperthermic brain injury: An experimental study using EGB-761 and Gingkolide В pretreatment in the rat. Acta Neurochir., Suppl. 76, 81-86.
  • 55. Wan, W. B., Cao, L., et al., (2014). EGb761 provides a protective effect against Apl-42 oligomer-induced cell damage and blood-brain barrier disruption in an in vjhobEnd.3 endothelial model. PLoS One, 9, ell3126.
  • 56. Jiang, J., Wang, W., et al., (2007). Neuro protective effect of curcumin on focal cerebral ischemic rats by preventing blood-brain barrier damage. Eitr. J. Pharmacol, 561, 54-62.
  • 57. Pocernich, С. B., Lange, M. L., et al., (2011). Nutritional approaches to modulate oxidative stress in Alzheimer’s disease. Cun: Alzheimer Res., 8,452-469.
  • 58. Schmitz, K., Barthelmes, J., et al., (2015). Disease modifying nutricals for multiple sclerosis. Pharmacol. Then, 148, 85-113.
  • 59. Gianforcaro, A., &, Hamadeh, M. J., (2014). Vitamin D as a potential therapy in amyotrophic lateral sclerosis. CNS Neurosci. Then, 20, 101-111.
  • 60. Betti, M., Minelli, A., et al., (2011). Dietary supplementation with a-tocopherol reduces neuro-inflammation and neuronal degeneration in the rat brain after kainic acid-induced status epilepticus. Free Radic. Res., 45, 1136-1142.
  • 61. Arreola, R., Alvarez-Herrera, S., et al., (2016). Immunomodulatory effects mediated by dopamine. J. Immunol Res., 3160486.
  • 62. Arreola, R., Becerril-Villanueva, E., et al., (2015). Immunomodulatory effects mediated by serotonin. J. Immunol Res., 354957.
 
<<   CONTENTS   >>

Related topics