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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




Targeted Mechanism





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






Inhibition of



BBB stabilization in MS.






Protective in patients with neurodegenerative diseases.




Decreased level of




neuroinflammation and neuronal degeneration.



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.


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].


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].


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.


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


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