Stigmasterol

Stigmasterol is an orally acitve, immunomodulatory agent with anti-inflammatory and neuroprotective effect, as well as able to cross the blood-brain barrier. Stigmasterol activates AMPK, which in turn inhibits NF-κB and NLRP3 signaling pathways, reduces microglia-mediated neuroinflammation, and alleviates cognitive impairment and Alzheimer's disease. Stigmasterol regulates M1/M2 polarization of microglia through the TLR4/ NF-κB pathway, thereby reducing neuropathic pain. Stigmasterol can be used for neurodegenerative diseases, inflammatory diseases, and pain management, among others^{[1][2][3][4][5]}. IC50 & Target:MMP^[1] In Vitro:Preincubation of Stigmasterol to IL-1beta-treated cells shows signi cant reduction of MMP-3 mRNA in human and mouse, MMP-3 protein in mouse, MMP-13 mRNA in mouse and human, ADAMTS-4 mRNA in human, PGE2 protein in human and mouse. Stigmasterol is also capable of counteracting the IL-1beta-induced NF-κB pathway^[1]. In Vivo:Stigmasterol (50 mg/kg; gavage; once a day; one month) alleviates cognitive deficits in mice, reduced Aβ42 concentrations in the cerebral cortex and hippocampus, and inhibits neuroinflammation by reducing proinflammatory cytokine levels and microglial activation^[1].
Stigmasterol (40 mg/kg; gavage; twice a day; 21 days) reduces thermal and mechanical hyperalgesia, serum IL-1β and IL-8 levels, and increased serum IL-4 and TGF-β levels in rats with chronic constriction injury (CCI). Stigmasterol also reduces the expression of IL-1β, COX-2, and TLR4 in the right sciatic nerve and IL-1β in the spinal cord, and promoted the transformation of M1 microglia to M2 microglia in the spinal cord^[2].
Stigmasterol (50-100 mg/kg; intraperitoneal injection; injected before LPS treatment, single dose) can reduce the total febrile response induced by LPS in rats and mice, inhibit the proliferation of neutrophils in the blood and peritoneal fluid of mice, control lung and liver damage, and inhibit the lethal effect of LPS^[3].
Stigmasterol (20-80 mg/kg; intraperitoneal injection; injected 2 hours after ischemia, single dose) can effectively reduce neurological deficits and infarct damage, improve tissue pathological changes, restore the level of endogenous antioxidant defense system, reduce the expression level of beclin1 and the conversion of LC3 I to LC3 II, promote the phosphorylation of mTOR, and inhibit the phosphorylation of AMPK and JNK and the expression of JNK induced by 24 hours of reperfusion in the rat cerebral ischemia-reperfusion injury model^[4].
Stigmasterol (10 mg/kg; oral; single dose) significantly alleviates scopolamine-induced memory impairment in the passive avoidance and Morris water maze tasks, and increases the phosphorylation levels of ERK and CREB in the hippocampus in the scopolamine-induced memory impairment model in mice. This improvement can be blocked by dizocilpine (HY-15084B) and tamoxifen (HY-13757A)^[5].