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. 2023 Sep 22;19(5):1045–1055. doi: 10.4103/1673-5374.385286

Figure 3.

Figure 3

Schematic of metformin’s effects on angiogenesis and anti-inflammation in the central nervous system.

Metformin treatment reduces inflammatory molecules by (1) lowering mononuclear cells entering the central nervous system through CAMs; (2) increasing production of Th1 and Th17 to reduce proinflammatory cytokines (interferon-γ, TNF-α, IL-6, IL-17, and inducible nitric oxide synthase) release; (3) inhibiting transcription of Mgll via the AMPK-aPKC-CBP pathway to reduce the conversion of 2-AG to inflammatory ARA; and (4) activating AMPK-P65 NF-κB pathway to suppress the transcription of proinflammatory cytokines (IL-1β and TNF-α). Metformin treatment also reduces glial activation through the AMPK-mTOR-S6K pathway. Finally, metformin can also restore autophagy via the AMPK-mTOR pathway. Created with BioRender.com. 2-AG: 2-Arachidonoylglycerol; AMPK: AMP-activated protein kinase; aPKC: atypical protein kinase C; ARA: arachidonic acid; CAM: cell adhesion molecule; CBP: CREB-binding protein; FFA: free fatty acid; IL-1β: interleukin-1 beta; Mgll: monoacylglycerol lipase; mTOR: mammalian target of rapamycin; p65-NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells subunit p65; Th1: T helper 1; Th17: T helper 17; TNF-α: tumor necrosis factor-alpha.