Table 1.

Skin culture studies included in the analysis.

Author	Year of Publication	Country	Type of Study	Mechanism and Effectiveness of Metformin Therapy in Psoriasis
Liu et al. [29]	2015	China	human keratinocytes HaCaT	- Metformin treatment significantly inhibited proliferation and proinflammatory responses (dose-dependently) in HaCaT cells, by a mechanism associated with inhibition of the mTOR signaling pathway. - Metformin inhibited the expression of IL-6, TNF-a, and VEGF proteins in HaCaT cells. - Metformin induced HaCaT cell apoptosis.
Wang et al. [30]	2018	China	human keratinocytes HaCaT	- Metformin could attenuate Raf-1-ERK1/2 signaling in HaCaT cells. - Metformin suppressed the expression and phosphorylation levels of Nrf2, which contributed to intracellular ROS generation and pro-apoptotic effects.
Wu et al. [31]	2017	China	Human HaCaT	- Metformin has antiproliferative and proapoptotic effects through the upregulation of ACAD10 expression, which is mediated by the negative regulation of mitochondria-mTORC1 signaling via the induction of cell-cycle arrest and apoptosis in human keratinocytes.
Ba et al. [35]	2018	China	Human cell culture	- Metformin significantly decreased the production of inflammatory cytokines and inhibited the nuclear localization of p65. - Metformin inhibits TNFα-induced inflammatory responses in HaCaT cells via nuclear factor kappa B (NF-κB) signaling.
				- Metformin suppresses the transcriptional activity of NF-κB by suppressing the degradation of IκBα. Furthermore, metformin’s inhibitory effect on NF-κB is comparable to that of the specific IKKβ inhibitor, BI605906.
Tsuji et al. [36]	2020	Japan	Animal tissue culture	- Metformin has immunomodulatory effects in an induced-psoriasis mouse model associated with type 2 diabetes mellitus. - TNF-α and IL-17A induce inflammatory responses by keratinocytes by blocking NLRP3 inflammasome activation in vitro. - Oral metformin treatment significantly attenuates IMQ-induced psoriasis-like inflammation in vivo. The therapeutic benefits can be partially attributed to its interference with mature IL-1β secretion by keratinocytes.