**11.** *Berberine* **from** *Berberis aristata* **DC**

Berberine **(33)** has been shown to be neuroprotective through the Nrf2 upregulation and also alleviates rotenone-induced cytotoxicity by antioxidation and activation of PI3K/Akt signaling pathway in SH-SY5Y cells [82]. Neuroprotective effects of berberine have also been confirmed in animal models of Alzheimer's disease [83]. Berberine nanoparticles have shown protective effect against LPS-induced neurodegenerative changes [84]. Berberine confers neuroprotection in coping with focal cerebral ischemia by targeting inflammatory cytokines [85]. Berberine had also shown protective effect against the altered intrinsic properties of the CA1 neurons induced by Aβ neurotoxicity [86]. There are many pathways by which berberine acts to protect neurons and has recently been reviewed. Authors have concluded that it being a potential candidate for combating neurodegenerative diseases [87, 88].

#### **12. Garcinol from** *Garcinia indica* **Choisy**

Garcinol **(34)** is one of the major constituents of *Garcinia indica* (a plant found in the region of Western Ghats of India). Garcinol can effectively restore the balance between the neurotransmitters glutamate and the γ-aminobutyric acid (GABA), rescue neural precursor cells, and promote their rapid growth. It regulates the expressions of glutamic acid decarboxylase 65 and GABAA receptors, preventing hyperactivation of NMDA receptor and the resultant excitotoxicity. It enhances memory and cognition in C57BL/6 mice, significantly lowering epileptic seizure scores [89, 90]. It also serves as a strong inhibitor of histone acetyltransferases (HAT), thus contributing protection against rapid neurodegeneration in parkinsonian brain [91, 92]. Garcinol helps in restoration of dopamine potency and has homocysteine lowering ability as well as have been shown to counter LDOPA-induced dyskinesia in PD model, demonstrate its worthiness as a potential drug candidate against Parkinson's Disease [93, 94]. Garcinol also exhibits desirable anti-cholinesterase properties by inhibiting the enzyme acetyl

*Bioactive Molecules from Indian Medicinal Plants as Possible Candidates for the Management… DOI: http://dx.doi.org/10.5772/intechopen.92043*

#### **Figure 5.**

*Structures of compounds present in various plants for neuroprotective activity.*

cholinesterase with an IC50 value of 0.66 μM, and it improves the neuronal count in hippocampal regions following administration of pentylenetetrazole (PTZ). In cultured rat cortical progenitor cells, garcinol can reduce cell death associated with growth factor deprivation. It also promotes neurite outgrowth in epidermal growth factor-responsive neural precursor cells and supports the survival of neurons [90]. In unilaterally 6-hydroxydopamine (6-OHDA)-lesioned hemi parkinsonian mice, 5 mg/kg of garcinol co-treatment with L-DOPA effectively controlled the axial, limb, and orofacial (ALO) score for dyskinesia analysis. Following the administration of garcinol, a decreased expression of c-Fos, FRA-2, and ARC genes has been visualized [94], which is usually over-activated in L-DOPA induced dyskinesia [95]. Moreover, methanolic extract of *G. indica*, which is known to contain garcinol, effectively elevates dopamine level in the striatum and confers neuroprotection to dopaminergic neurons in 6-OHDA lesioned experimental rats [96]. Even pharmacological inhibition of HATs by garcinol can notably suppress MPP+-induced cell death due to reduction in ATP content [97]. *In silico* studies on the molecular interaction between garcinol and the active sites of COMT and MAO-B revealed that garcinol can potentially inhibit the activity of the two enzymes, similar to their known inhibitors [93]. In conclusion, garcinol may prove to be a dependable remedial measure in PD therapeutics since its inhibition of MAO-B and COMT can be correlated to increase the availability of dopamine as well as prevent the generation of toxic dopamine metabolites including homocysteine, 3-omethyldopa, 3-methoxytyramine, and 3,4-dihydroxyphenylacetaldehyde [98] (**Figure 5**).

#### **13.** *Nardostachys jatamansi* **(D. Don)DC.(Jatamansi)**

The plant *Nardostachys jatamansi* is well exploited in Ayurvedic system of medicine for its role in neurological disorders. Various phytochemicals have been reported from this plant by various authors. Its sedative and antidepressant activity, its mechanism (inhibition of MAO and GABA), and its role in rat cerebral ischemia have been documented [99]. Anticonvulsant activity and neurotoxicity profile of the plant have been generated [100]. The extracts of *N. jatamansi* have been found to attenuate 6-hydroxydopamine-induced parkinsonism in rats, as proven by behavioral,

neurochemical, and immunohistochemical studies [101]. It also improves learning and memory in mice. It also has stress modulating antioxidant effect. Its formulation was also found to enhance the learning and memory process in rats [102–104]. It has shown neuroprotective efficacy in conjunction with selenium in cognitive impairment [105]. *N. jatamansi* root extract was found to modulate the growth of IMR-32 and SK-N-MC neuroblastoma cell lines through MYCN-mediated regulation of MDM2 and p53 [106]. Novel Sesquiterpeniods and Anti-neuroinflammatory metabolites from *N. jatamansi* have also been isolated [107]. Compounds such as Desoxo-narchinol A **35** and Narchinol B **36** isolated from *N. jatamansi* have been shown to exert anti-neuroinflammatory effects by upregulating nuclear transcription factor erythroid-2-related factor 2/heme oxygenase-1 signaling [108].
