Table 2.

The specific function of TCM formulas used to treat insomnia.

Pharmaceutical name	Composition (Medicinal materials belonging to MFH)	Experimental model, object	Dosage	Biological sample collection	Pharmacological effects	Refs.
Nyctinastic herbs decoction	Albizia julibrissin Durazz. Polygonum multiflorum Thunb Lilium brownie F. E. Brown var.viridulum Baker Nelumbo nucifera Gaertn	PCPA, male Wistar rats	3,6,12 g/kg	Hypothalamus	Nyctinastic herbs decoction reduced the proportions of NE, DA and ACh in PCPA induced insomnia rats, suggesting that it could effectively inhibit the excitability of the central nervous system.	[136]
Zhumian Granules	ZiziphiSpinosaeSemen SchisandraeChinensisFructus CaulisPolygoniMultiflori AngelicaeSinensisRadix Corydalis Rhizoma AnemarrhenaeRhizoma	PCPA, male KM mice	1.8,3.6,7.2 g/kg	Brain	Zhumian Granules maintain the production of 5-HT,5-HTIAA, NE, DA, GABA and decrease the cell death of nerve	[137]
HuoxueAnshen Recipe	SalviamiltiorrhizaBunge PanaxpseudoginsengWall. AstragalusmongholicusBunge Ziziphusjujubavar.spinosa(Bunge) Hu ex H. F. Chow	the modified multiple platform method, male Wistar rats	1.4 g/kg	Heart	HuoxueAnshen Recipe could not only improve hormone disorders, inflammation, endothelial dysfunction, and mental state after SD, but also ameliorate SD-induced myocardial apoptosis and I/R injury.	[134]
Heweianshen Decoction	Pinellia ternate (Thunb.) Breit Coixlacryma-jobiL.var.mayuen(Roman.) Stapf CitrusreticulataBlanco Poriacocos(Schw.) Wolf Acorus gramineus Cortex albiziae CaulisPolygoniMultiflori	PCPA, male Wistar rats	5.25,10.5,21 g/kg	Hypothalamus	Heweianshen Decoction decreased orexin A content and increased CCK-8 content in hypothalamus of insomnia rats in a dose-dependent manner	[135]
Shuangxia decoction	Pinellia ternate (Thunb.) Breit Prunella vulgaris L.	PCPA, male Wistar rats	2.5,5and10 g/kg	Cerebral cortex, hypothalamus	Shuangxia decoction alleviate PCPA induced insomnia by increasing the content of 5-HT in cortex, decreasing the content of DA and NE, enhanced the expression of 5-HT1A and 5-HT2A receptors in hypothalamic and reduced serum levels of IL-1, TNF-α	[131]
Chaihu-Longgu-Muli Decoction	Bupleurum chinense DC. Fossilia Ossia Mastodi Scutellaria baicalensis Georgi ZingiberofficinaleRoscoe PanaxginsengC. A. Mey. Cinnamomumcassia(L.) J.Presl Poriacocos(Schw.) Wolf Pinellia ternata (Thunb.) Makino Rheum palmatum L. OstreagigasThunberg ZiziphusjujubaMill.	PCPA, male ICR mice	5,10 mg/kg	Brain, Hypothalamus	Chaihu-Longgu-Muli Decoction has regulatory effect on DA, 5-HT, NE, and 5-HTR1A, can ameliorate the histopathological changes in the hypothalamic of sleepless mice and deactivation the NLRP3 inflammasome.	[129]
		a 0.2 % adenine diet, C57/BL6 mice	2.36,4.725and9.45 g/kg	Hypothalamus, hippocampus	Chaihu-Longgu-Muli Decoction can improve sleep disturbances and reduce neuron loss in CKD mice. The mechanism may be related to the up-regulation of orexin-A and increases in the phosphorylation level of CaMKK2/AMPK, which further inhibit NF-κB downstream signaling pathways without affecting renal function.	[130]
Jiaotai pill	Rhizome Coptidis Cinnamomumcassia(L.) J.Presl	PCPA, male SD rats	2.2 mg/kg	Brain stem, hippocampus, prefrontallobe and hypothalamus, r serum	Jiaotai pill increased the level of GABA in brain stem, prefrontal lobe and serum	[123]
		PCPA, male SD rats	6 ml/kg	Brain, heart, liver, kidneys, adrenal gland, serum, urine	The levels of 5-HT, epinephrine, DA, Glu, ACH, NE, GABA, 5-HIAA and vanillaldehyde (HVA) in the blood and tissues of insomnia rats were all changed. Jiaotai Pill reduced the levels of neurotransmitters in different tissues, especially in brain and adrenal gland. It is suggested that one of the mechanisms of Jiaotai pill in treating cardio-renal incompatibility insomnia may be through regulating the content of neurotransmitters in blood and tissue, thereby connecting the heart and kidneys and restoring the relationship between normal information exchange and physiological function of the body.	[124]
		PCPA, male SD rats		Hypothalamus, blood, heart, liver, kidneys	It can down-regulate the activity of organic cation transporters and norepinephrine in peripheral organs by down-regulating the activity of serotonin transporter and dopamine transporter in hypothalamus and various organs transporter expression is upregulated in the hypothalamus. The underlying molecular mechanism involves the regulation of monoamine transporters and organic cation transporters.	[125]
		Exposed to 80–100 dB of noise, obesity-resistant rats	1.1,2.2 g/kg	Blood, intestine and brain tissues	Jiaotai pill can reduce the increased levels of Aβ42, caspase3, IL-6 and TNF-α in rat brain tissue caused by sleep deprivation, improve the activation of intestinal TLR4/NF-κB pathway, and reduce the expression of IL-6 and TNF-α. It also has beneficial effects on tight junction protein and intestinal permeability in intestinal tissue. The possible underlying mechanism is by preventing an inflammation trigger being transferred through the gut-brain-axis.	[126]
Suanzaoren decoction	ZiziphiSpinosaeSemen Poriacocos(Schw.) Wolf AnemarrhenaasphodeloidesBunge. LigusticumchuanxiongHort. GlycyrrhizauralensisFisch	PCPA, Male Wistar rats	31.2 g/kg	serum and brain	Suanzaoren decoction can regulate various phenotypes of host metabolism in insomnia rats, so as to play an anti-insomnia role.	[115]
		PCPA, male SD rats	8.0 g/kg	Serum, hippocampus, liver, brain	It can improve the liver and brain lesions caused by insomnia, and regulate the levels of neurotransmitters in the hippocampus (5-HT, DA, Glu, GABA, NE) and inflammatory cytokines in the serum (PGD2, TNF-α, IL-1β, IL-6). This therapeutic effect is closely related to amino acid metabolism and other pathways	[116]
		A sleep deprivation device, Male kunming mice	13 g/kg	Serum, liver, ileum	With the determination of AST, ALT, TBA in serum and liver index, Suanzaoren Decoction was proved had liver protection effect on insomnia mice. It can also improve the pathological changes of liver tissue and ileum tissue and restore bile acid levels in each tissue, which shows that Suanzaoren Decoction can repair the disorder of bile acid hepatoenteric circulatory system caused by insomnia.	[118]
		PCPA, male SD rats	8.0 g/kg	Hippocampus, intestinal contents	Suanzaoren Decoction regulates the structure of intestinal flora and promotes the production of short-chain fatty acids by influencing metabolic pathways such as amino acids, thus indirectly playing a role in improving sleep.	[119]
Modified Suanzaoren decoction	Ziziphus jujuba Mill.var.spinosa (Bunge) Hu ex H.F.Chou Dendrobium officinale Kimura et Migo Ligusticum chuanxiong Hort. Poria cocos (Schw.) Wolf Glycyrrhiza uralensis Fisch	chronic unpredictable mild stress combined with PCPA, ICR male mice	3.6,7.2,14.4 g/kg	Serum、hypothalamus、hippocampus	Three doses of modified Suanzoren decoction can increase the production of 5-HT in hypothalamus, and affect the content of NE and DA. GABA and Glu in the blood of the insomniac mice were also affected. The modified Suanzoren decoction significantly improved the pathological damage of the hippocampus of mice, regulated the amount of CRH, ACTH, COTR, and decreased the expression of OX2R protein. Therefore, it is concluded that the hypnotic effect of this innovative health food is related to the regulation of neurotransmitter levels to restore the homeostasis of the HPA axis.	[120]
		Modified water-filled multiple platforms, Male SD rats	1.55,3.72,7.44 g/kg	Serum, brain, stomach	By regulating CCK-8 and orexin A, modified Suanzoren decoction increased the expression of GABA and decreased the secretion of GAS, MTL, gastric acid and pepsin, thus producing hypnotic and gastric protective effects on insomnia rats with gastrointestinal discomfort.	[121]
Shumian Capsule	ZiziphiSpinosaeSemen Bupleuri Radix PaeoniaeRadixAlba Albiziae Flos Albiziae Cortex Bombyx batryticatus Cicadae Periostracu JunciMedulla.	sleep deprivation box, Male C57BL/6 mice	0.25,0.5,1 g/kg	Hypothalamus	Shumian Capsule treatment restored the alterations in the expression levels of OX1R and OX2R. Meanwhile, the results indicated that the regulation of OX1R by Shumian Capsule treatment is through MT receptors,	[138]
Songyu Anshen Fang	Nardostachys chinensis Batal Curcumapetiolate Rosarugosa Fossilia Ossis Mastodi Concha Margaritifera Usta CaulsPolugoniMultiflori SalviaeMiltiorrhizae SemenZiziphiSpinosae Cortex Albiziae	PCPA, male SD rats	8.5and17 g/kg	Hypothalamus	Songyu Anshen Fang can significantly normalized the level of GABA, Glu and adjusted the expression of GABA(B) mRNA and GABA(B) protein of PCPA-induced insomnia rats. The mechanism may be related to the modulation of neurotransmitter levels and the expression of GABA(B) receptor in the hypothalamus	[139]
Foshouningshen decoction	Citrus medica ‘Fingered' Liliumbrowniivar.viridulumBaker SemenZiziphiSpinosae Poriacocos(Schw.) Wolf NelumbonuciferaGaertn	PCPA, male SD rats	6,12,24 g/kg	Hippocampus	Foshouningshen decoction can up-regulate the content of 5-HT in hippocampus and increase the expression level of 5-HT1AR protein and mRNA in hippocampus.	[140]
Banxia Houpo decoction	Pinellia ternate (Thunb.) Breit. MagnoliaofficinalisRehd.etWils. Poriacocos(Schw.) Wolf Perillafrutescens(L.) Britt. ZingiberofficinaleRoscoe	Pentobarbital sodium induces sleep,male SD rats	500 mg/kg	Serum and urine	Banxia Houpu Decoction can induce sleep in rats by regulating the content of glutamine, creatine phosphate and 2-ketoglutaric acid to reduce nerve excitability in brain.	[141]
Polygala tenuifolia granule	Polygalatenuifolia	PCPA + D-gal, male SD rats	0.0875,0.175,0.35 g/kg	Hippocampus	The level of 5-HT and GABA are upregulated in Aged Insomnia Rats, while the level of Glu is downregulated. The sedative effect of the granule in aged insomnia rats may be related to neuro, metabolism pathways, especially GABAergic signaling pathway.	[51]
Ciwujia Tablets	Eleutherococcussenticosus	PCPA, male SD rats	600,300,150 mg/kg	Brain	The treatment of insomnia by Ciwujia Tablets is involved in the regulation of 5-HT, GABA, DA, NE and several pathways discovered by network pharmacology	[64]