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Table 3 Studies of Epimedium and its active ingredients in improving OA synovial inflammation

From: Effects of genus Epimedium in the treatment of osteoarthritis and relevant signaling pathways

References

Assay type

Component of Epimedium

Concentration/dosage

Cells/model

Effects

Mechanisms

Pan [114]

In vitro

Icariin

0.1, 0.5 and 1 μM

Fibroblast-like synovial cells in OA patients

Proliferation and migration of OA-fibroblast-like synovial cells↓

Matrix degradation: IL-1β↓, MMP14↓

ER stress-related protein: BIP↓

Regulating cellular functions and gene expression of Fibroblast-like synovial cells in OA patients

Jin [115]

In vivo

Total flavonoids of Epimedium

150, 300 and 600 mg/kg

OA rat model established by the transection of anterior cruciate ligament

Pain related indices: PWT↑

Knee joint diameter↓

Inflammatory factors: IL-6↓, IL-1β↓, TNF-α↓

Histopathology: inflammatory cell infiltration in synovial tissue↓, Synovial hyperplasia↓

Signal pathway: p-IκB-α/IκB-α↓, p-p65/p65↓

Relieving synovial inflammation by inhibiting NF-κB signal pathway in rat OA

Hu [116]

In vitro

Quercetin

2, 4 and 8 μM

IL-1β treated chondrocytes in the knee joint of SD rats

Chondrocyte proliferation↑

Matrix formation: aggrecan↑, Col2α↑, GAG↑

Inflammatory factors: PGE2↓, NO↓, iNOS↓, COX-2↓

Matrix degradation: MMP13↓, ADAMTS-4↓

Signal pathway: IκBα↑, p-AKT/AKT↓, p-P65/P65↓, nuclear P65↓

1. Anti-inflammation by inhibiting the Akt/NF-κB signaling pathway

2. Promoting the polarization of synovial macrophages to M2 macrophages, to create a microenvironment for chondrogenesis

In vitro

Quercetin

8 μM

RAW 264.7 cells

M2 macrophage-related genes: Arg1↑, MR↑, Ym1↑

Pro-chondrogenic cytokines: TGF-β1↑, TGF-β2↑, TGF-β3↑, IGF-1↑, IGF-2↑

Signal pathway: pSTAT6↑, p-AKT↑

In vivo

Quercetin

8 μM, 0.1 mL

OA rat model established by removing the medial meniscus and transecting the anterior meniscotibial ligament

Histopathology: structural integrity of cartilage↑, OARSI score↓

Matrix formation: GAG↑, aggrecan↑, Col2α↑

Matrix degradation: MMP13↓

Cell apoptosis: chondrocyte apoptosis↓

M2 macrophage marker (synovial tissues): MR↑

Pro-chondrogenic cytokines (synovial fluid): TGF-β1↑, TGF-β2↑

Luo [117]

In vitro

Icariin

2, 5 and 10 µM

LPS-induced human synovial cells (HUM-CELL-0060)

Synovial cell mortality↓, cell viability↑

Ferroptosis-related factors: iron content↓, MDA↓, TFR1↓, NCOA4↓

Antioxidant-related factors: GPX4↑, Nrf2↑

Signal pathway: SLC7A11↑, GPX4↑, SLC3A2L↑

Treating synovitis by activating the Xc−/GPX4 axis to inhibit ferroptosis