Tetrahydropiperine

Tetrahydropiperine is an orally effective, selective inhibitor of NF-κB and MAPKs<、b>, and an activator of the PI3K/Akt/mTOR<、b> pathway. Tetrahydropiperine reduces the production of pro-inflammatory cytokines such as TNF-α, IL-6, and nitric oxide (NO) by inhibiting the nuclear translocation of NF-κB and the phosphorylation of MAPKs such as ERK, JNK, and p38. At the same time, Tetrahydropiperine inhibits excessive autophagy by activating the PI3K/Akt/mTOR pathway, protecting neurons from oxidative damage. Tetrahydropiperine has anti-inflammatory, anti-apoptotic, and neuroprotective effects, and is mainly used in the study of inflammatory diseases (such as endotoxemia, arthritis) and neurological diseases such as ischemic stroke^[1][2][3]. In Vitro:Tetrahydropiperine (1, 5, 10 μM; pretreatment for 1 h + LPS stimulation for 24 h) can significantly inhibit the production of NO, TNF-α, IL-6 and IL-1β induced by 1 μg/mL LPS in RAW 264.7 cells, and down-regulate the expression of COX-2 and i-NOS^[1].
Tetrahydropiperine (10, 20, 40 μg/mL; 24 h) can improve the survival rate of PC-12 cells in the oxygen glucose deprivation (OGD) model, reduce cell morphological damage, and up-regulate the expression of proteins related to the PI3K/Akt/mTOR pathway^[2]. In Vivo:Tetrahydropiperine (10, 20 mg/kg; oral; single dose; 1 hour before administration) significantly improves the survival rate of mice, reduced the thickness of paw edema, and decreases the serum levels of TNF-α, IL-6, and IL-1β in the endotoxemia and carrageenan-induced paw edema models in mice^[1][2]. Tetrahydropiperine (10, 20, 30 mg/kg; oral; once daily; for 14 days) improves neurobehavioral damage, reduces cerebral infarction area, and regulates the expression of proteins related to the PI3K/Akt/mTOR pathway in the permanent middle cerebral artery occlusion model in Sprague-Dawley rats^[2].