Table 3.

Anti-AD mechanism of catalpol.

Category	Possible mechanisms (signaling pathway)	References
Inhibits excessive production of reactive oxygen species	(1) Increase cell survival and reduce intracellular ROS level	[24]
Improve the activity of antioxidant enzymes	(1) Improve the activities of SOD and GSH-Px	[32]
	(2) Improve the level of GSH and the activities of SOD and GSH-Px	[32]
	(3) Increase antioxidant enzyme activity	[18, 39]
Inhibition of NO production	(1) Negative effects on LPS + IFN-γ stimulation, NO and ROS formation, and iNOS activity	[16]
	(2) Inhibition of NO formation and improvement of neurodegenerative conditions	[18]
	(3) To prevent neuronal apoptosis by regulating the increase of NO and iNOS	[44]
Inhibits mitochondrial dysfunction	(1) Prevention of apoptosis induced by fiber Aβ1-42 through mitochondrial-dependent and death receptor pathways	[36]
	(2) Protecting brain mitochondrial function by decreasing MMP opening	[46]
	(3) Inhibition of mitochondrial dysfunction	[34, 47]
Inhibition of apoptosis	Attenuated mitochondria-dependent caspase cascade; inhibits the leakage of cytochrome C from mitochondria to the cytoplasm, and weakens the activation of caspase-3 and cleavage of polyADP ribose polymerase	[27, 39]
Regulation of NF-κB pathway	(1) Inhibition of NF-κB activation and LPS-induced acute inflammatory response	[43]
	(2) Inhibition of NF-κB activation and protection of mitochondrial function	[46]
	(3) Reducing microglia-mediated neuroinflammatory response by inhibiting NF-κB signaling pathway	[15, 16]
Regulation of neurotrophic factors	(1) Hippocampus BDNF was significantly increased, which was positively correlated with synaptophysin expression; “Normalize” presynaptic proteins and their associated signaling pathways	[35]
	(2) Enhance the expression of BDNF	[58, 60]
Increase the density of muscarinic receptors in the brain	(1) Protective effect on cholinergic	[49]
	(2) Improve learning ability and increase the density of muscarinic receptors in the brain	[62]
	(3) Regulating cholinergic nervous system function through the influence on ChAT	[64]
The expression levels of Bcl-2 and Bax were regulated	(1) Stimulate Bcl-2 expression and inhibit Bax expression	[67]
	(2) Inhibition of the increase of Bax expression and decrease of Bcl-2 expression induced by Aβ25-35	[68]