. 2023 Jan 5;13:1035220. doi: 10.3389/fphar.2022.1035220

TABLE 1.

Phytochemicals identified in M. oleifera with neuropharmacological effects and their mechanisms of action.

Compound	Bioassay methods	Mechanisms of action	References
Phenolic acids
Gallic acid	Deoxyribose and hydrogen peroxidase assay	Enhanced deoxyribose oxidation and neutralizes free radicals.	Yen et al. (2002)
	In vitro assay using glioma cell	Dowregulated the PI3K/Akt and rat sarcoma virus (Ras)/MAPK signaling pathways by suppressing coding gene (ADAM17), p-Akt, and p- extracellular signal-regulated kinase (Erk) expression.	Lu et al. (2010)
	In vitro using primary rat cortex neuronal culture	Provide anti-oxidative activities and suppressed regulation of proinflammatory cytokines.	Maya et al. (2018)
	*Glutamate-induced neurotoxicity		Maya et al. (2018)
	In vivo male Sprague-Dawley	Mediated with biomarkers of activated astrocytes and microglia, proinflammatory enzymes and cytokines, apoptotic cells.	Liu et al. (2020a)
	*LPS-induced neuroinflammation		Liu et al. (2020a)
Chlorogenic acid	In vitro assay using primary cortical neurons	Mediation Nrf2-NF-κB pathways by the activation of Sirt1 and further reduce the apoptosis of brain neurons.	Zheng et al. (2022)
	In vivo male Sprague Dawley rats	Suppressed hypoxia ischemia-induced proliferation of glia to alleviate the brain injury.
	*Hypoxia-ischemia brain injury
	*Hypoxia-ischemia brain injury	Inhibited the expression of TNF-α, IL-1β, and nitric oxide synthase (iNOS) in the brain tissue.
Ferulic acid	In vitro assay using SH-SY5Y neuroblastoma cells	Activated HO-1/Nrf2 system through carbon monoxide and bilirubin production.	Catino et al. (2016)
Ferulic acid	In vitro assay using SH-SY5Y neuroblastoma cells	Prevented disruption of cell lines by up-regulating the HO-1/Nrf2 system.	Catino et al. (2016)
Caffeic acid	In vivo male Swiss albino mice	Supressed production of LPS-induced TNF-α and IL-6.	Mallik et al. (2016)
	In vivo male Swiss albino mice	Reducing the levels of malondialdehyde and GSH as well as inhibiting the c-Src/ERK pathway of MAPK activation to alleviate oxidative stress.
	*LPS-induced neuroinflammation	Facilitated downregulation of NF-κB-dependent pro-inflammatory genes.
Flavonoids
Kaempferol	In vitro assay using murine microglial BV2 cells	Alleviated LPS-induced TNF-a, IL-1b, NO, ROS production, prostaglandin E2 (PGE2), and phagocytosis.	Park et al. (2011)
	In vitro assay using murine microglial BV2 cells	Facilitate the downregulation of TLR4, NF-kB, p38 MAPK, c-Jun N-terminal kinase (JNK), and protein kinase B (AKT) phosphorylation.	Park et al. (2011)
	In vivo rat model of neuropathic pain	Inhibited microglial activation, reduced cytokine production and alleviate pain	Chang et al. (2022)
	Chronic constriction injury (CCI)-induced injury		Chang et al. (2022)
Myricetin	In vitro assay using mouse macrophage RAW 264.7	Inhibited NO and pro-inflammatory cytokines.	Kim et al. (2013)
	*LPS-stimulated cells	Inhibited NO and pro-inflammatory cytokines.
	*LPS-stimulated cells	Reduce expression of cyclooxygenase-2 (COX-2) and iNOS.
(−)− Epicatechin	In vivo male C57BL/6 mice (wild type) and Nrf2 gene knockout (KO) mice	Reduced neutrophil infiltration and oxidative stress.	Cheng et al. (2016)
		Facilitate activation of Nrf2 pathway, averted expression of heme oxygenase-1 protein, and reduced iron deposition.
	*Traumatic brain injury (TBI)-induced
Quercetin	In vitro assay using SK-N-MC human neuroblastoma cell line In vivo male Sprague-Dawley (SD) rat	Alleviated oxidative stress and inhibited cell apoptosis.	Bahar et al. (2017)
		Exhibited antioxidant activity by apoptosis regulation, iNOS/NF-κB, and HO-1/Nrf2 related pathways.
	*Manganese (Mn)-induced neurotoxicity
Isoquercitrin	In vitro assay using mesenchymal stem cells	Exhibited ROS scavenging activities.	Li et al. (2016)
	*ROS-Induced Damage	Exhibited ROS scavenging activities.	Li et al. (2016)
	In vivo male C57BL/6J mice	Attenuated impaired behaviors and loss of dopamine neurons, elevated expression of dopamine transporter and tyrosine hydroxylase.	Liu et al. (2021)
	*1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced acute mouse model of PD
		Reduced the expression of pro-apoptotic signaling molecule Bax and supressing MPTP-triggered oxidative stress.
	In vivo male C57BL mice	Suppressed inflammatory responses and inhibited TLR4 and C5aR1 expression, as well as down-regulated MAPK signaling pathways.	Kim et al. (2022b)
	*LPS-induced neuroinflammation
	*LPS-induced neuroinflammation	Inhibited ROS generation.
	In vitro assay using mesenchymal stem cells	Exhibited ROS scavenging activities.	Li et al. (2016)
	*ROS-Induced Damage	Exhibited ROS scavenging activities.	Li et al. (2016)
Astragalin	In vivo female C57BL/6 mice	Modulated inflammatory cascade; decreased release of INF-γ and IL-17 (pro-inflammatory cytokines) and increased for IL-10 (anti-inflammatory cytokine).	Liu et al. (2021)
	*Neuropathy model
	*Neuropathy model	Inhibited inflammatory pathway and impeded voltage-gated ion channels.
Isothiocyanates (ITCs)
Moringin	In vivo female C57BL/6 mice	Modulated inflammatory cascade; reduced production of INF-γ and IL-17 (pro-inflammatory cytokines) and increased IL-10 (anti-inflammatory cytokine).	Giacoppo et al. (2017)
	In vivo female C57BL/6 mice	Inhibited inflammatory pathway and impeded voltage-gated ion channels.
	*Neuropathy model
Allyl isothiocyanates (AITC)	In vitro assay using C6 glioma, BV2 murine microglia, and N2a mouse neuroblastoma cells	Impeded with TNF-α formation in LPS-activated microglia and activation of JNK, NF-κB.	Subedi et al. (2017)
Allyl isothiocyanates (AITC)		Alleviated inducing anti-apoptotic proteins and pro-apoptotic proteins to avert neuronal death.	Subedi et al. (2017)