*4.4. Paeoniflorin*

Paeoniflorin is a monoterpene glucoside extracted from the root of the *Paeonia Lactiflora*. Paeoniflorin shows anti-inflammatory properties and it is already used in traditional Chinese medicine for a wide range of pathologies [110,111]. Moreover, paeoniflorin shows immunomodulatory e ffects on microglial cells through the enhancement of the suppressor of cytokine signaling 3 (SOCS3) pathways [112]. Zhu et al. demonstrated, in an in vitro study on BV2 microglial cells exposed to high concentrations of glucose, that treatment with paeoniflorin reduces the expression of metalloproteinases-9 (MMP-9) through the inhibition of p38/NF-κB. In addition, paeoniflorin activates SOCS3, which blocks the TLR-4 pathway [112,113]. The repression of TLR-4 determines the reduction of HMGB1 mediated inflammation in retinal microglial cells [114].
