Anti-inflammatory effects of vinpocetine in LPS-stimulated microglia via activation of AMPK

Abstract

Microglia are the resident immune cells in the central nervous system (CNS), which play important roles in the repair of neuroinfl ammatory injury. The present study investigated the anti-neuroinfl ammatory effects of vinpocetine induced by lipopolysaccharide (LPS) in BV2 microglia. BV2 microglia were pretreated with vinpocetine, and then stimulated with LPS (100 ng/mL). The cytotoxicity of BV2 microglia was assessed by MTT assay. The expression levels of nitrite oxide were measured by Griess assay. Proinfl ammatory cytokines and mediators were determined by Western blot, ELISA, or quantitative real-time PCR. Vinpocetine signifi cantly decreased the generation of nitric oxide-inducible nitric oxide synthase (iNOS), cyclooxygenase-(COX-) 2 in a dose-dependent manner. In addition, vinpocetine decreased the production of pro-infl ammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin (IL)-6 and IL-1β. Furthermore, it was observed that phosphorylation levels of AMPK (Thr-172) decreased in LPS-stimulated BV2 microglia. Vinpocetine treatment increased AMPK phosphorylation in LPS-stimulated BV2 microglia. AMPK inhibition by siRNA blocked the anti-infl ammatory effects of vinpocetine induced by LPS in BV2 microglia. The overall results demonstrate that vinpocetine has anti-infl ammatory effects on LPS-stimulated BV2 microglia via inducing phosphorylation of AMPK, suggesting that vinpocetine is a potential therapeutic agent in neuroinfl ammatory injury.

Vinpocetine attenuates diabetic cardiomyopathy by downregulating transforming growth factor-1 and phosphodiesterase-1 expression in rats

“…Signi cant increase in cytokines has been reported in streptozotocin-induced diabetes mellitus in rodents [26]. It has been reported that vinpocetine has an anti-in ammatory effect and inhibit the release the cytokines [27]. In the present study, the levels of TNF-α and IL-6 was signi cantly increased in diabetic control group.…”

Unauthorized ingredients in “nootropic” dietary supplements: A review of the history, pharmacology, prevalence, international regulations, and potential as doping agents

“…However, it has exhibited potential as an AMPK activator. Research from 2020 demonstrated that “vinpocetine treatment can inhibit microglia‐mediated inflammation, and the anti‐inflammatory mechanism is associated with activation of the AMPK signaling pathway.” The WADA Prohibited List includes “Activators of the AMP‐activated protein kinase (AMPK)” under Section S4 Hormone and Metabolic Modulators in section 4.1, and based on this activity, vinpocetine could be considered as a doping agent in the future 25,26,128 . Vinpocetine is on the OPSS US DOD Prohibited Dietary Supplement Ingredients List 129…”

“…List includes "Activators of the AMP-activated protein kinase (AMPK)" under Section S4 Hormone and Metabolic Modulators in section 4.1, and based on this activity, vinpocetine could be considered as a doping agent in the future. 25,26,128 Vinpocetine is on the OPSS US DOD Prohibited Dietary Supplement Ingredients List. 129 3.8 | Adrenergic substances including indole alkaloids in Rauwolfia spp.…”

Attenuated effects of topical vinpocetine in an imiquimod-induced mouse model of psoriasis

“… 128 Likewise, Zhou and colleagues have found that VNP decreases levels of TNF-α and IL-6 cytokine peptides in murine microgliocytes challenged by LPS. 129 Notably, the medication suppresses the mRNA levels of TLR4 and TLR2 and their key signalling molecules, including the mitogen-activated protein kinase (MAPK) cascade and MYD88. 130 Moreover, VNP has been found to prevent SARS infection and COVID-19 via modulating IL1β, IL-8, IL-12, and TNF-α/MAPK/NF-κB transcription pathways.…”