**4.** *Terminalia chebula* **Retz**

*Terminalia chebula* (Combretaceae) commonly called *Haritaki*, is used in ayurvedic formulations, also reported to demonstrate neuroprotective activities. The principle constituents in pericarp of *T. chebula* fruits are phenolics (chebulic acid (**7**), chebulagic acid (**8**), chebulinic acid (**9**), ellagic acid (**10**), gallic acid (**11**)) [10] and triterpenoid glycosides chebuloside II (**12**) (**Figure 2**) [11]. Pericarp of fruits of *T. chebula* constitutes *Triphala* (one of the popular formulations of ayurvedic system of medicine). The methanolic (70%) extract of the fruit *Fructus chebulae* has been shown to rescue cerebral ischemia by protecting neurons from degeneration. The in-vitro study and in-vivo studies have shown promising results [12]. Also, there is a promising decrease in the levels of malondialdehyde (MDA), NO, and microglial death stimulated by lipopolysaccharide (LPS) in the cells after treating with the extract [13]. The underlying mechanism might be the inhibition of inflammatory and oxidative processes. *T. chebula* constituents such as chebulagic acid, chebulinic acid, and ellagic acid have shown to be neuroprotective on various cell lines by showing its effect on various targets [14–16].

### **5. Honey and** *Jaggery*

Both Honey and *Jaggery* are used in making of many ayurvedic preparations, and they constitute major part of many formulations [4]. Honey, a sweet and viscous substance, is produced by the honey bees (*Apis* spp.). It contains sugar and others such as minerals, proteins, essential oils, and flavonoids. Dietary polyphenols found in honey as well as other food and plant materials can prevent neurodegenerative disease in various ways [17–22]. These include oxidative protection of neurons [17], enhancement of neuronal function and regeneration [18], protection of neurons from Aβ-induced neuronal injury and neurotoxicity [19], protection of hippocampal cells against nitric oxide-induced toxicity [20], and modulation of neuronal and glial cell signaling pathways [21]. Luteolin (**13**) shows neuroprotective activity via prevention of microglia-associated inflammation in the hippocampus of aged rats [22]. Other flavonoids such as quercetin (**14**) and kaempferol (**1**) have also shown to be neuroprotective in various models. Kaempferol's (**15**) neuroprotective effect was confirmed by the histochemical findings where it prevented the loss of TH-positive neurons induced by MPTP [23–25]. Luteolin **13,** a flavone, has a significant role in treating CNS disorders through various mechanisms [26]. The activity of luteolin **13**

**Figure 2.** *Structures of compounds present in* T. chebula.

was also reported at its microglial transcriptome level for the treatment of CNS disorders via anti-inflammatory activity [27]. Pretreatment of mice with luteolin **13** was expected to reduce the frequency of seizure in the PTZ mice model [28]. Luteolin **13** also has the potential to improve the activity of oxygen-glucose deprivation/reperfusion (OGD/R) induced neurons in a dose-dependent manner by enhancing the Na+/ K+-ATPase activity suggesting a potential molecule to treat cerebral ischemia [29]. Apigenin (**16**), a trihydroxyflavone, was reported to inhibit the release of glutamate from hippocampal nerve terminals, which might be useful in treating epilepsy [30]. The role of apigenin (**16**) in the treatment of cognition was demonstrated by attenuating the Aβ-induced cytotoxicity in rat cortical neurons but having no intervention with oxidative stress. The biological activities of the flavonoids might be due to hydroxyl groups at R2 and R3 position influencing various cellular events eventually leading to apoptosis [27–30]. Other phenolics such as ferulic acid (**17**) exert neuroprotective effect through middle cerebral artery occlusion [31] and by decreasing the number of microglia/macrophages after cerebral ischemia/reperfusion injury in rats [32]. Chlorogenic acid (**18**) present in honey exerts a neuroprotective effect against methyl mercury-induced apoptosis in pheochromocytoma-12 (PC12) cell lines. It prevents the generation of reactive-oxygen species (ROS), suppressing the decreasing action of glutathione peroxidase (GPx) and GSH and attenuating apoptosis by the activation of caspase-3 [33] and also inhibits the activity of acetylcholine esterase and MDA in the hippocampus as well as in the frontal cortex in mice [34]. Honey as such has also shown to be neuroprotective in male Sprague-Dawley rats, and there was a decrease in the thiobarbituric acid reactive substance levels in the rats, which were pretreated with honey [35]. Chrysin (**19**) improved the morphological integrity of nigrostriatal neurons and increased the endogenous levels of BDNF, S100B, NGF, and GDNF in mice striatum improving behavioral and better muscular coordination [36]. Its lipophilic nature and bioflavonoid nucleus confers an added advantage to grow as a compelling therapeutic agent for neurological disorders. Pinocembrin

**Figure 3.** *Structures of compounds present in* Jaggery *and honey.*

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

(**20**) elevated glutamate level, which was an important excitatory neurotransmitter produced by global cerebral I/R [37].

*Jaggery* is used in most of the ayurvedic formulations [4]. Traditionally, it is indicated for treating neurodegenerative disorders. The chemistry of sugar cane reveals that it is rich in phenolics and their glycosides [38], flavonoid glycosides, and flavones [39]. Tricin-7-glucoside **(21)** was reported to possess neuroprotective activity against cerebral ischemia via reduced expression of NF-κB and HMGB1. SH-SY5Y cells, which were pretreated with tricin **(21a**), reduced the apoptosis induced by OGD. Attenuation of histopathological damage reduced brain edema was reported in animal models of ischemia along with reduced NF-κB and HMGB1 expression [40]. It also has potential for Alzheimer's disease [41] (**Figure 3**).
