TABLE 2.

Effect of antidepressant ingredient in single herbal.

Single herbal	Active ingredient	Subjects	Effects and mechanisms involved	References
Ligusticum Chuanxiong Hort	TMP	CUMS mice	Inhibiting the TLR4-NF-κB-NLRP3 signaling pathway, elevate the 5-HT and NE concentration in the serum and brain	Fu et al. (2019)
	TMP	CSDS mice	Increase the hippocampal BDNF/ERK expression	Jiang et al. (2015), Jiang et al. (2021)
	Ligustilide	CUMS rat	Increase levels of progesterone and allopregnanolone in the prefrontal cortex and hippocampus	Ma et al. (2021)
	Ligustilide	CUMS rat	Upregulate the hippocampal contents of tryptophan and 5-HT	Zhu et al. (2015)
	Ferulic acid	CORT mice	Repair stress caused by HPA axis dysfunction	Zeni et al. (2017)
	Ferulic acid	CUMS mice	Up-regulate BDNF expression, increase the levels of postsynaptic protein PSD95 and synapsin I	Liu et al. (2017a)
	Ferulic acid	CUMS mice	Inhibit the release of inflammatory factors and activation of microglia	Liu et al. (2017b)
	Ferulic acid	Stressed mice	Elevate serotonin and norepinephrine in mouse hippocampus and frontal cortex	Chen et al. (2015)
	Ferulic acid	Stressed mice	Increase catalase, superoxide dismutase and glutathione peroxidase in the blood, hippocampus and cerebral cortex, regulate antioxidant defense system	Lenzi et al. (2015)
	Ferulic acid	CUMS mice	Inhibit SIRT6 expression, and possibly suppress AKT/CRMP2 signaling	Li et al. (2020b)
Bupleurum Chinense DC	Total Saikosaponins	Stressed mice	Inhibit NE reuptake and increase serum NE level in mice	Liu et al. (2014)
	Saikosaponin D	CUMS rats	Inhibit the activation of the NF-κB signaling pathway, increase the expression of FGF2	Chao et al. (2020)
	Saikosaponin D	CUMS mice	Inhibit the expression of LPA protein in hippocampus, decreased the levels of P-P38, P-P65, P-ERK, RhoA and ROCK2	Xu et al. (2019)
	Saikosaponin D	CUMS rat	Enhance the HPA axis function	Li et al. (2017)
	Saikosaponin A	CUMS rats	Restore neuroendocrine, neuroinflammation and neurotrophic systems in the hippocampus	Chen et al. (2018)
	Saikosaponin A	CUMS rat	Up-regulate the expression level of PRRT2 and increase DA content in hippocampus	Guo et al. (2020)
Glycyrrhiza uralensis Fisch	Glycyrrhizic acid	Depressive patients	Inhibit extracellular cytokine activities of HMGB1 and inflammatory response	Cao et al. (2020)
	Glycyrrhizic acid	SH-SY5Y cells	Regulate autophagy, increase BDNF expression and modulate HPA activity	Yang et al. (2018)
Paeoniae Rubra Radix	Paeonol	LPS induced mice	Increase 5-HT and NE levels and inhibit inflammatory cytokines expression	Tao et al. (2016)
	Paeonol	CUMS mice	Promote the dendritic spines formation and regulate BDNF-Rac1/RhoA pathway	Zhu et al. (2018)
	Paeoniflorin	Reserpine-induced mice	Inhibiting inflammasome-induced pyroptosis and over-activated microglia in the depressive hippocampus	Tian et al. (2021)
	Paeoniflorin	CUMS rats	Modulate the ERK-CREB signaling pathway	Zhong et al. (2018)
	Paeoniflorin	Prenatal stress mice	Modulate the HPA axis	Li et al. (2020c)

CUMS, chronic unpredictable mild stress; CRS, chronic restraint stress; TMP, tetramethylpyrazine.