Table 4.
Anti-inflammatory activity and analgesic activity of SIN.
| Activity | Cell Type or Model In Vitro (Effective Concentrations or IC50 Values) | Mechanism of Action | In Vivo | Year | Ref. | |
|---|---|---|---|---|---|---|
| Dose (mg/kg) | Therapeutic Effect | |||||
| Anti-inflammatory | NR | 150 mg/kg | Joint swelling and ESR. | 1996 | [71] | |
| Anti-inflammatory | PMs and synoviocytes (91.1–364.3 μM for both cell lines) | ↑: IκBα. ↓: TNF-α, IL-1β, and NF-κB. |
NR | 2005 | [72] | |
| Anti-angiogenic | HUVEC (125–1000 μM) | NR | NR | 2005 | [73] | |
| Anti-inflammatory | PMs and synoviocytes (276.5–1105.9 μM for both cell lines) | ↑: IκBα. ↓: TNF-α, IL-1β, and NF-κB. |
NR | 2005 | [74] | |
| Anti-colitis | NR | ↓: TNF-α and IFN-γ. | 100, 200 mg/kg | ↑: Myeloperoxidase activity. ↓: Body weight, macroscopic score, and histological score. |
2007 | [77] |
| Inhibited activation of retinal microglia cells | Retinal microglia cells (0.1 mM and 1 mM y) | ↓: TNF-α, IL-1β, IL-6, ROS, and nuclear translocation of NF-κB p65. | NR | 2007 | [78] | |
| Analgesic | CHO cells (1 μM and 10 μM) | ↑: p-OMR. | 10, 20, 30 mg/kg | ↑: OMR activation. | 2008 | [79] |
| Anti-OA | NR | ↑: TIMP-1/-3. ↓: IL-1β, IL-6, and MMP-2/-9. |
100 mg/kg | ↓: Incidence and progression of CIA, foot swelling, ESR, and arthritis score. | 2008 | [80] |
| Anti-MSPGN | NR | ↓: T-bet, T-bet/GATA-3 ratio, and IFN-γ. | 240 mg/d | ↓: Albuminuria. ↑: Complement C3. |
2009 | [81] |
| Anti-OA | SW1353 and human osteoarthritic chondrocytes (1–5 mM for both cell lines) | ↓: MMP-1, MMP-3, MMP-9, and MMP-13, catabolism of IL-1β, and proteolytic enzymes. | NR | 2010 | [82] | |
| Anti-OA | Chondrocytes (10–250 mM) | ↑: TIMP-1. ↓: IL-1, β-induced GAG, and MMP-13. |
NR | 2010 | [83] | |
| Anti-inflammatory | FLS and THP-1 (0.01–1.00 mM for both cell lines) |
↓: Invasion and migration ability, CD147, and MMP-2/-9. | NR | 2011 | [84] | |
| Anti-inflammatory | RA-FLS (75.9–607.2 μM) | ↓: VCAM-1, IL-6, CCL 2, CXCL8, p-IκBα, and NF-κB. | NR | 2011 | [85] | |
| Anti-inflammatory | HMC-1 (IC50 = 52.73 μM) | ↓: TNF-α, IL-6, IL-8, COX-2, p-ERK1/2, p-p38 MAPK, p-κBα, and NF-κB. | NR | 2012 | [86] | |
| Anti-RA | RAW264.7 (0.0625–1 mM) | ↓: c-Src, MMP-9, TRACP, TRAF6, NF-κB, IκBα degradation and translocation of p65 to the nucleus, p-p38 and p-JNK, Ca2+ influx, NFATc1, AP-1, Fra-1, Fra-2, and c-Fos. | 80 mg/kg | ↑: Body weight. ↓: Hind paw swelling and bone loss. |
2013 | [87] |
| Anti-colitis | NR | ↓: MPO activity, miR-155, c-Maf, TNF-α, and IFN-c. | 100, 200 mg/kg) | ↑: Weight and survival rate, colon symptoms, and histological scores. ↓: Diarrhea score. |
2013 | [88] |
| Anti-RA | NR | ↓: TNF-α, IL-1β, and IL-6. | 100 mg/kg | ↓: Synovial hypertrophy, cartilage damage, joint space narrowing, osteoporosis, cartilage, and bone erosion. | 2013 | [89] |
| Analgesic | NR | GABAA | 10–40 mg/kg | ↑: Paw withdrawal threshold. ↓: Duration of immobile behavior, depression-like behavior, and chronic pain. |
2014 | [90] |
| Anti-macrophage activation | RAW264.7 (100 μM) | ↓: TNF-α, IL-6, α7nAChR, and NF-κB p65. ↑: Cytoplasmic IκBα. |
NR | 2015 | [91] | |
| Anti-arthritic | RA-FLS (0.125–1 mM) | ↓: ALP activity, MyD88, and TRAF-6. | NR | 2015 | [92] | |
| Analgesic | NR | GABAA. | 5–80 mg/kg | Analgesic effect on postoperative rats via GABAA receptor. | 2016 | [93] |
| Anti-inflammatory | NR | TGF-β1/CTGF pathway and oxidative stress. | 25, 50, 75 mg/kg | Asthmatic mice airway inflammation and remodeling alleviation | 2016 | [94] |
| Anti-arthritic | Treg cells (0.1–1 mM) | ↑: IL-10 level. ↓: Foxp3, IL-10, RoRγT, IL-17a, IL-17f, IL-21levels, Th17 cells, Treg cells, L–1β, TNF-α, IL-6, and IL-17. |
120 mg/kg | ↓: Arthritis index, inflammation and cartilage damage, and paw swelling. | 2016 | [95] |
| Anti-neuropathic pain | HEK293 (10 μM) | ↓: ATP activation, P2X3, p-P38MAPK, and pain behavior alleviation. | 40 mg/kg | MWT (about 50%) and TWL (about 80%) enhancement | 2017 | [96] |
| Anti-inflammatory bowel disease | NR | ↑: SIGIRR and IL-10. ↓: TLR/NF-κB, IFN-γ, IL-1β, TNF-α, IL-12p70, and IL-6. |
30, 90, 270 mg/kg of SIN; 180, 540, 1600 mg/kg of SIN microspheres | The colon length of SIN microspheres group was longer than SIN group; histological grade score of SIN microspheres group was lower than SIN group. | 2017 | [97] |
| Anti-endotoxin | Endothelial cells (3 mM) | ↓: Key control genes in the pathogenesis of LPS. | NR | 2018 | [98] | |
| Anti-microglial inflammatory response | BV-2 (25–100 μM) | ↑: IκB-α and miRNA-183-5p. ↓: SP1/miRNA-183-5p/IκB-α pathway, p-p65, p-p50, TNF-α, IL-1β, IL-6, and SP1. |
NR | 2018 | [99] | |
| Anti-RA | RAW264.7 (3–151.8 µM) | ↓: IL-6, GM-CSF, IL-12p40, IL-1α, TNF-α, IL-1β, KC (CXCL1), Eotaxin-2, IL-10, M-CSF, RANTES, and MCP-1. | 50, 100 mg/kg | ↓: Swollen paw score, inflammation score, and cartilage damage score of CIA mice, weight loss. | 2018 | [100] |
| Anti-arthritis | PC12 (0.03–0.3 mM) | ↑: α7nAChR-PI3K/Akt/mTO. | 120 mg/kg | VIP production promotion in the gut and neuronal cells. | 2018 | [101] |
| Anti-inflammatory pain | NR | ↓: P38MAPK, NF-κB, TNF-α, IL-1b, IL-6, p-p65, p-p3, COX-2, and PGE2. | 30 mg/kg | ↓: Inflammatory pain. | 2018 | [102] |
| Anti-inflammation of eye tissue | NR | ↓: NF-κB, TNF-α, PG-E2, and translocation of NF-κB p65 subunits to the nucleus. | 50, 100 mg/kg | ↓: Number of inflammatory cells, protein leakage. | 2018 | [103] |
| Anti-arthritis | NR | ↑: OD and MDA. ↓: NF-κB and MAPK, TNF-α, IL-6, IL-1β, IL-8, COX-2, iNOS, and MMP-2/-9. |
50 mg/kg | ↑: Total body weight of the rat. ↓: Paw volume and arthritis score. |
2018 | [104] |
| Anti-colitis | NR | ↑: Nrf2/NQO-1 and SOD activity. ↓: TNF-α, IL-6, and iNOS level. |
100 mg/kg | ↓: Body weight and DAI score, colon shortening, and colitis histological damage. | 2018 | [105] |
| Anti-inflammatory | MG63 (0.25–1 mM) |
↑: SOD, CAT, Nrf2, HO-1, NQO-1, and Nrf2. ↓: MAPKP38/NF-κB, IL-1β, IL-6, TNF-α, p-p38, p-NF-κB (P65), and MDA. |
NR | 2018 | [106] | |
| Analgesic | NR | ↓: JAK2/STAT3 and CAMKII/CREB. | 10, 20, 40 mg/kg | Mechanical hypersensitivity of pain in cancer bone algia rat alleviation, and microglia activation inhibition. | 2018 | [107] |
| Anti-RA | NR | ↑: IL-10. ↓: IL-1β, IL-6, and TNF-α. |
1.5 g/kg | The extract (4:1, 1.5 g/kg) and extract (3:1, 1.5 g/kg) groups were superior to SIN. | 2018 | [108] |
| Anti-OA | Mouse chondrocytes (6.25–25 μM) | ↑: Nrf2/HO-1. ↓: NF-κB, iNOS, COX-2, NO, PGE2, TNF-α, IL-6, P-NF-κB p65, p-IκBα, ADAMTS-5, and MMP. |
10 mg/kg | ↑: Thickness of articular cartilage. ↓: Degradation of ECM. |
2019 | [109] |
| Anti-OA | Mouse chondrocyte (30 μM) | ↓: IL-6, TNF-α, MiR-192, NF-κB, and MAPK. | NR | 2019 | [110] | |
| Anti-RA | NR | ↓: TNF-α, IL-6, ROS, and ESR. | 5 mg/kg (AS-TE) | ↓: Joint swelling, bone defects. | 2019 | [111] |
| Anti-inflammatory | HaCaT (1 μM) | ↓: IL-6, TNF-α, COX-2, iNOS, p-P65, p-IκBα, p-p38-MAPK, NF-κB, MAPK, and CAT1. | NR | 2019 | [112] | |
| Anti- inflammatory | NR | ↓: α7nAChR. | 120 mg/kg | ↓: Paw swelling, AI, TNF-α, and ESR. | 2019 | [113] |
| Anti-inflammatory | Raw264.7 (300 μM) | ↑: p-STAT3 and JAK2/STAT3. ↓: TNF-α, MCP-1, MIF, MMP-9, CD14, TLR4, intracellular Ca2+, and NF-κB. |
NR | 2019 | [114] | |
| Analgesic | NR | 0–80 mg/kg | Analgesic effect of older pups was better than that of younger pups. | 2020 | [115] | |
| Anti-inflammatory | Macrophage (303.6–3036 μM) | ↓: TNF-α, IL-1β, IL-6, TLR4, MyD 88, p-IκB, macrophage immune response, and TLR4/NF-κB. | NR | 2020 | [116] | |
| Anti-inflammatory | Raw264.7 (3–75.9 μM) | ↑: SOCS1. ↓: TNF-α, IL-1β, IL-6, inflammatory responses, miR-155, and NF-κB. |
NR | 2020 | [117] | |
| Anti-rheumatoid arthritis | NR | 2 mg/kg | Target RA site. The leakage of SIN prevention. |
2020 | [118] | |
| Promote MMP production | SW1353 (25–100 µM) | ↑: SOCS3. ↓: MMP, p-JAK2, and p-STAT3. |
NR | 2020 | [119] | |
| Anti-inflammatory | Raw264.7 (10–200 μM) | ↑: IL-6, TNF-α, and NF-κB nuclear translocation. ↓: ROS and LDH. |
NR | 2020 | [120] | |
| Anti-inflammation of dorsal root ganglion | DRG (800 μM) | ↓: P38MAPK, CREB, c-fos, p-CAMKII, NF-κB, COX2, TLR4, IL-1B, IL-17A, and p38MAPK/CREB. | 20 mg/kg | ↓: MWT and TWL. | 2021 | [121] |
| Anti-RA | PBMC (0.3–30 μM) | No direct effect on T cells. | NR | 2021 | [122] | |
| Anti-foodborne enteritis of fish | NR | ↓: TNF-α, IL-10, IL-22, and FOXP3a. | 35 ppm | ↑: Intestinal villus height ↓: Inflammation and dysregulation. |
2021 | [123] |
| Anti-neuropathic pain | NR | ↓: NF-α, IL-1β, IL-6; RIP3, p-JNK, c-Fos, and IP3/JNK. | 20, 40mg/kg | ↑: Survival neurons of spinal dorsal horn. | 2021 | [124] |
| Anti-migration and anti-inflammatory | RAW264.7 and BMDMs (160–640 μM for both cell lines) | ↓: RC/FAK/P130CAS, iNOS/NO, integrin αV, integrin β3, TNF-α, and IL-6. | 25, 50, 100 mg/kg | ↓: Migration of Mouse mononuclear macrophage leukemia cells Raw264.7 to the foot and swelling of the foot. | 2021 | [125] |
| Anti-arthritic | RASFs (12.5–100 μM) | ↑: Degradation of Keap1, HO-1, and p- p62 (Thr269/Ser272). ↓: IL-6, IL-33, ROS, Nrf2, and p-p62 (Ser35). |
25, 50, 100 mg/kg | ↓: Incidence rate of CIA mice and swelling of the hind paws. | 2021 | [126] |
| Anti-RA | FLSs (200 μM) | ↑: A2AR and cAMP. ↓: MCP-1, IL-6, vascular endothelial growth factor, and NF-κB pathway. |
120 mg/kg | ↓: Arthritis index, the hind paw volume, ESR, and TNF-α. | 2021 | [127] |
| Anti-RA | NR | ↑: Solubility. ↓: Drugs release. |
NR | 2021 | [10] | |
| Anti-colitis | NR | ↑: IL-10 and arginine 1. ↓: TNF-α, IL-6, inducable nitric oxide synthase, NOD-, LRR-, and NLRP3 inflammasome. |
100 mg/kg | Intestinal microbial composition alteration. | 2021 | [129] |
| Anti-pneumonia | WI-38 (5–20 μM) | ↓: TNF-α, IL-1β, MCP-1; IL-10, and GSTM 1. | NR | 2022 | [130] | |
| Anti-arthritis | RAW264.7 cell (50–400 µM) | ↓: TNF-α and inflammatory factors. | 25, 50, 100 mg/kg | ↓: Mean joint score and foot volume. | 2023 | [51] |
NR: None reported. ↓: Decrease or inhibition. ↑: Increase or induction. If IC50 values were reported, we displayed them in the second column. If IC50 values were not reported, we only displayed effective concentrations in the second column.