Table 1.
Other Natural medicines of targeted RA and their mechanism of action.
| Natural medicines | Model/Cell | Dosage | Mechanism of action | Ref. |
|---|---|---|---|---|
| Curcumin | CIA rats FLSs |
200 mg/kg 5, 10, 20 ng/ml |
MAPK, ERK1/2, AP-1, mTOR and NF-kB↓ | (147–149) |
| Chlorogenic acid | FLSs CFA rats |
50, 100 mmol/L 5, 25, 50, 100 mg/kg | activation of JAK/STAT and NF-κB pathway↓. IL‐17/IL‐17RA/STAT‐3 cascade pathway↓, TLR‐3, IL‐23, GM‐CSF, Cyr61, RANKL↓ | (150–152) |
| Hesperidin | AIA mice | 20 mg/kg | PI3K/AKT signaling pathway↓, levels of MMP3, MMP9, and MMP13 in FLSs↓, the polarization of macrophages to M1↓ | (153) |
| 7,3 ′-dimethoxyhesperidin | AIA rats | 20,40, 80 mg/kg | activation of JAK2/STAT3 pathway↓, regulate the expression of Bcl-2/Bax | (154, 155) |
| Kaempferol | CIA mice FLSs | 100, 200 mg/kg 2, 5, 10, 20, 40 μM |
activation of NF-κB and MAPK pathway↓, AKT/mTOR pathways↓, bFGF-induced FGFR3-RSK2 signaling pathway↓ | (156, 157) |
| Matrine | CIA rats CIA FLSs |
100 mg/kg 0.75 mg/ml |
NF-κB pathway↓, regulate the imbalance of Th1/Th2 cytokine response, activation of JAK/STAT pathway↓ | (158, 159) |
| Berberine | CIA rats | 75, 150 mg/kg | regulate the PI3K/Akt, Wnt1/β-catenin, AMPK/lipogenesis and LPA/LPA1/ERK/p38 MAPK pathways, regulate the balance between Treg/Th17 cells, DC activation↓ | (160, 161) |
| Pentaacetyl geniposide | AIA FLSs MH7A | 50, 100, 200 μM 12.5, 25, 50 μM |
activation of NF-κB and Wnt/β-catenin pathway↓ | (162, 163) |
| Gentiopicrin | HFLS AIA rats RA-FLS |
5-25 μM 100, 200 mg/kg 50, 100 μM |
p38 MAPK/NF-κB pathway and the ROS-NF-κB-NLRP3 axis↓ | (164, 165) |
| Betulinic acid | AIA rats RA-FLS CIA mice |
20, 40 mg/kg 2.5, 5, 10, 20 μM 20 mg/kg |
Rho/ROCK signaling pathway↓, block the activation of AKT/NF-κB pathway and NF-κB nuclear accumulation↓ | (166–168) |
| Emodin | CIA mice AIA mice |
10 mg/kg 30 μg/kg |
NF-κB pathway↓, neutrophil apoptosis↑, neutrophil autophagy and NETosis↓ | (169, 170) |
| α-mangiferin | AIA rats RA‐FLS |
40 mg/kg 10, 50, 100 μM |
the polarization of M1 macrophages↓, activate CAP, SIRT1↑, PPAR-γ↑, ROS production and ERK1/2 phosphorylation↑ | (171, 172) |
| Cinnamaldehyde | MH7A CFA rats CFA FLSs |
40, 60, 80 nM 20 mg/kg, 20 μM |
JAK/STAT and PI3K/AKT pathway↓ | (173, 174) |
| Thymoquinone | RAW 264.7 RA-FLS |
2.5, 5, 7.5, 10 μM 1, 5 μM |
RANKL-induced activation of NF-KB and MAPKs signals and ROS production↓, ASK1-p38/JNK pathway↓ | (175, 176) |
| Cyanidin-3-O-Glucoside | CIA mice FLS, RASF, MNCs |
25, 50 mg/kg 10, 20, 40 μM |
activation of NF-κB and MAPK signaling pathways↓, relieve inhibition of CD38+ NK cells on Treg cell differentiation | (177, 178) |
| Genistein | MH7A RA-FLS |
15, 20, 25 μmol/L 37 μM |
JAK2/STAT3/VEGF pathway↓, Erk1/2-mediated RA-FLS proliferation and EGF-induced MMP-9↓ | (179, 180) |
| Punicalagin | RA-FLS, CIA mice |
12.5, 25, 50 μM 10, 20, 50 mg/kg |
block the activation of NF-κB↓, M1 phenotypic polarization and focal ptosis↓ | (181, 182) |
| Periplocin | AIA rats RA-FLSs |
50 mg/kg 10, 20, 30 μM |
T-bet, GATA3, and C-Jun genes↓, cleaved caspase-3 and caspase-9↑, regulate the expression of Bcl-2/Bax, NF-κB pathway↓ | (183, 184) |
↑, increase, up-regulate, promote or improve; ↓, suppress, down-regulate, reduce, or inhibit; bFGF, basic fibroblast growth factor; RSK2, p90 ribosomal S6 kinase 2; LPA, lysophosphatidic acid; CAP, Cholinergic anti-inflammatory pathway; ASK1, apoptosis-regulated signaling kinase 1; RA-FLS, fibroblast-like synoviocytes from human RA patients; CIA FLSs, FLSs from CIA rats; MNCs, mononuclear cells; RASFs, RA synovial fibroblasts; GM‐CSF, granulocyte-macrophage colony stimulating factor; Cyr61, Cysteine-rich angiogenesis inducer 61; T-bet, T-box transcription factor; GATA3, GATA binding protein 3.