Table 1.
Constituents of CHM that modulate the release of HPA axis hormones and exhibit anti-inflammatory and antidepressant-like activities in animal models of depression.
| Herb | Herbal Constituent | Animal Model | Behavioral Test | Administration Dose/Time/Route of Treatment | Effects on Mediators of Inflammation | Effects on Hormones of the HPA Axis | Reference |
|---|---|---|---|---|---|---|---|
| Fallopia multiflora (Thunb.) Harald. | 2, 3, 5, 4′-Tetrahydroxystilbene-2-O-β-D-glucoside | LPS-induced depressive mice | TPT, FST, SPT | 30, 60 mg/kg, 7 days, i.p. | ↓ IL-6, TNF-α, IL-1β in hippocampus and PFC | ND | [84] |
| Acanthopanax sessiliflorus (Rupr. et Maxim.) Seem. | Chiisanoside | LPS-induced depressive mice | TST, FST | 2.5, 5.0 mg/kg, 7 days, i.p. | ↓ IL-6, TNF-α in serum ↓ NF-κB in hippocampus |
ND | [85] |
| Polygala tenuifolia Willd. | Senegenin | CUMS mice | TST, FST, SPT | 4, 8 mg/kg, 21 days, i.g. | ↓ NF-κB/NLRP3 signal pathway in hippocampus | ND | [86] |
| Gastrodia elata Bl. | Gastrodin | CUS rats | SPT, FST, Morris water test | 50, 100, 200 mg/kg, 14 days, i.p. | ↓ NF-κB and IL-1β expression in hippocampus | ND | [87] |
| Cinnamomum cassia Presl | Trans-Cinnamaldehyde | CUMS rats | Sucrose consumptions, FST | 10 mg/kg, 3 weeks, p.o. | ↓ IL-1β, IL-18, TNF-α in serum ↓ NF-κB/NLRP3 in PFC and hippocampus |
ND | [28] |
| Lonicera japonica Thunb. | Lonicera japonicapolysaccharide | CUMS mice | OFT, EPM, TST, FST | 30, 100 mg/kg, 21 days, i.g. | ↓ NLRP3, IL-1β, caspase-1 in hippocampus | ND | [88] |
| Andrographis paniculata (Burm. f.) Nees | Andrographolide | CUMS mice | FST, SPT, TST, Y maze | 2.5, 5 mg/kg, 14 days, p.o. | ↓ IL-1β, IL-6, TNF-α, NF-κB signaling, NLRP3 in PFC | ND | [89] |
| Houpoea officinalis (Rehder and E. H. Wilson) N. H. Xia and C. Y. Wu | Honokiol | LPS-induced depressive mice | FST, TST, | 2.5, 5 10 mg/kg, 11 days, p.o. | ↓ NF-κB activation in hippocampus ↓ IL-1β, TNF-α, IFN-γ in serum |
ND | [90] |
| Gardenia jasminoides Ellis /Crocus sativus L. | Crocin | LPS-induced depressive mice | SPT, FST, TST, OFT | 20, 40 mg/kg, 7 days, i.p. | ↓ TNF-α, IL-1β, IL-18 in BV-2 microglial cells and hippocampus ↓ NF-κB and NLRP3 in hippocampus |
ND | [91] |
| Perilla frutescens (Linn.) Britt. | Perilla aldehyde | CUMS rats | SPT, FST, OFT | 20, 40 mg/kg, 3 weeks, i.g. | ↓ TNF-α, IL-1β in hippocampus ↓ NLRP3 in hippocampus |
ND | [92] |
| LPS-induced depressive mice | TST, FST | 60, 120 mg/kg, 7 days, i.g. | ↓ TNF-α, IL-6 in serum and PFC | ND | [93] | ||
| Essential oil of Perilla frutescens | CUMS mice | OFT, TST, FST, SPT | 3, 6, 9 mg/kg, 3 weeks, g.i. | ↓ TNF-α, IL-6, IL-1 in plasma | ND | [94] | |
| Polygonum aviculare L. | Polygonum aviculare L. extract | Restraint-stressed mice | FST, SPT, OFT | 100, 200 mg/kg, 15 days, p.o. | ↓ TNF-α, IL-6, IL-1β in the brain | ND | [95] |
| Hemerocallis fulva (L.) L. | Ethanol extracts | LPS-induced depressive mice | SPT | 180 mg/kg, 7 days, p.o. | ↓ NF-κB signaling pathway in PFC | ND | [96] |
| Angelica sinensis (Oliv.) Diels | Ferulic Acid | CUMS mice | SPT | 20, 40, 80 mg/kg, 4 weeks, p.o. | ↓ TNF-α, IL-6, IL-1β, microglial activation, NF-κB and NLRP3 in PFC | ND | [97] |
| Paeonialactiflora Pall | Paeoniflorin | IFN-α-induced depressive mice | SPT, OFT, TST, FST | 10, 20, 40 mg/kg, 4 weeks, i.g. | ↓ TNF-α, IL-6, IL-1β, IL-9, IL-10, IL-12, MCP-1 in serum, mPFC, vHi and amygdala | ND | [98] |
| Xiaobuxin-Tang | Total flavonoid extract | LPS-induced depressive mice | TST, FST | 25, 50, 100 mg/kg, 1 h, i.p. | ↓ TNF-α, IL-1β in the barin | ND | [99] |
| Ginkgo biloba L. | EGb761 | LPS-induced depressive mice | FST, TST, SPT | 50, 100, 150 mg/kg, 10 days, p.o. | ↓ IL-6, TNF-α, IL-1β, IL-17A in hippocampus ↑ IL-10 in hippocampus |
ND | [100] |
| Pueraria lobate (Willd.) Ohwi | Puerarin | CUS rats | SPT, NSFT, FST | 30, 60, 120 mg/kg, 20 days, i.g. | ND | ↓ CRH, CORT, ACTH in serum | [101] |
| Tribulus terrestris Linnaeus | Tribulus Terrestris Saponins | CMS rats | OFT, SPT | 0.375, 0.75, 2.25 g/kg, 4 weeks, i.g. | ND | ↓ CRH, CORT in serum | [102] |
| Rehmannia glutinosa (Gaert.) Libosch. ex Fisch. et Mey. | Ethanol extracts | CUMS rats | SPT | 150, 300, 600 mg/kg, 3 weeks, p.o. | ND | ↓ CORT in serum | [103] |
| Panax ginseng C.A. Meyer | Ginseng total saponins | LPS-induced depressive mice/RAW264.7 cells; CUMS rats | FST, TST, SPT | 200 mg/kg, 7 days, i.g.; 12.5, 25, 50 mg/kg, 6 weeks, i.g. | ↓ IL-1β, IL-6, TNF-α, IDO mRNA in hippocampus | ↓ CORT in serum ↑ GR mRNA in hippocampus |
[104,105] |
| Ginsenoside Rg1 | CSDS mice; CUMS rats | Social interaction test, SPT, FST, TST | 20, 40 mg/kg, 34 days, i.g.; 5, 10, 20 mg/kg, 28 days, i.g. | ↓ IL-6, TNF-α, IL-1β, microglial activation, p-NF-κB in hippocampus | ↓ CORT level in serum ↑ GR protein in PFC and hippocampus |
[72,106] | |
| Ginsenoside Rg3 | LPS-induced depressive mice; CUS rats | TPT, FST, EPMT, NSFT, OFT | 20, 40 mg/kg, 3 days, i.g.; 10, 20, 40 mg/kg, 14 days, i.g. | ↓ IL-6, TNF-α in plasma ↓ IL-6, IL-1β, IDO, microglial activation, NF-κB pathway in brain |
↓ CRH, CORT, ACTH in serum | [107,108] | |
| Salvia miltiorrhiza Bunge | Salvianolic acid B | CMS mice | SPT, FST, TST | 20 mg/kg, 3 weeks, i.p. | ↓ IL-1β, TNF-α in hippocampus and cortex ↑ IL-10, TGF-β in hippocampus and cortex |
↓ CORT in plasma | [109] |
| Aquilaria spp. | Agarwood Essential Oil |
Restraint stress-induced mice | TST, FST | 10, 20, 40 mg/kg, 10 days, i.p. | ↓ IL-1β, IL-1α, IL-6 in serum | ↓ CRF, CRF receptor in cortex ↓ CORT, ACTH in serum |
[110] |
| Chaihu-Shugan-San | Saikosaponin A | CUMS rats | SPT, NPFT, FST | 25, 50 or 100 mg/kg, 4 weeks, p.o. | ↓ IL-1β, IL-6, TNF-α in hippocampus | ↓ CRH in hypothalamus ↓ GR mRNA in hippocampus |
[53] |
| Rhodiola rosea L. | Salidroside | OBX rats | TST, FST, SPT | 20, 40 mg/kg, 2 weeks, p.o.; 20, 40 mg/kg, 2 weeks, i.g. | ↓ TNF-α, IL-1β in hippocampus ↓ IL-1β, IL-6, TNF-α, NF-κB activation in PFC |
↑ GR in hippocampus ↓ CRH in hypothalamus |
[111,112] |
| Epimedium brevicornu Maxim. | Icariin | CMS rats; CSD mice | SPT, FST, social avoidance evaluations | 20, 40 mg/kg, 35 days, p.o.; 25, 50 mg/kg, 28 days, i.g. | ↓ IL-1β, TNF-α, NF-κB signaling pathway, NLRP3/caspase-1/IL-1β axis activation in hippocampus | ↓ CORT, IL-6 in serum ↑ GR in livers |
[83,113] |
| Curcuma longa L. | Curcumin | CUMS rats; CUS rats | SPT, FST, EPM, Shuttle-box testing | 40 mg/kg, 5 weeks, i.p.; 100 mg/kg, 4 weeks, i.g.; 2.5, 5, 10 mg/kg, 21 days, p.o. | ↓ TNF-α, IL-1β, IL-6, NF-κB in mPFC ↓ TNF-α, IL-1β, IL-6 mRNA, NLRP3 in hippocampus |
↓ CORT in serum ↑ GR mRNA in serum |
[114,115,116] |
| Polygonum cuspidatum Siebold et Zucc. | Resveratrol | Ouabain-induced depressive mice; Hippocampal neuron cells; CUMS rats | OFT, EPM, Barnes maze performance, object recognition, passive avoidance experiments, SPT, FST | 10 mg/kg, 10 weeks, p.o.; 15 mg/kg, 21 days, i.g. | ↓ IL-1β, IL-17A, IL-8, TNF-α in serum and hippocampal neuron cells | ↓ CORT in serum ↓ CRF mRNA in hypothalamus |
[117,118] |
| Bupleurum chinense DC. | Saikosaponin D | LPS-induced depressive mice; UCMS rats | SPT, TST, FST, OFT | 1 mg/kg, 7 days, i.g.; 0.75, 1.5 mg/kg, 21 days, i.g. | ↓ microglia activation in hippocampus ↓ IL-6, TNF-α, IL-1β in vivo and vitro ↓ TLR4/NF-κB signaling pathway in hippocampus |
↓ CORT in serum ↑ GR in hippocampus |
[52,119] |
| Scutellaria baicalensis Georgi | Baicalin | CUMS mice; CUMS rats; CORT-induced depressive-like mice | SPT, OFT, TST FST | 60 mg/kg, 14 days, i.g.; 20, 40 mg/kg, i.g., 3 weeks; 10, 20 mg/kg, 21 days, i.g. | ↓ IL-1β, TNF-α, IL-6, TLR4 in the hippocampus ↓ GSK3β/NF-κB/NLRP3 signal pathway in hippocampus |
↓ GR mRNA, GRα in hippocampus | [120,121,122] |