The Major Cholesterol Metabolite Cholestane-3β,5α,6β-Triol Functions as an Endogenous Neuroprotectant

Abstract

Overstimulation of NMDA-type glutamate receptors is believed to be responsible for neuronal death of the CNS in various disorders, including cerebral and spinal cord ischemia. However, the intrinsic and physiological mechanisms of modulation of these receptors are essentially unknown. Here we report that cholestane-3␤,5␣,6␤-triol (triol), a major metabolite of cholesterol, is an endogenous neuroprotectant and protects against neuronal injury both in vitro and in vivo via negative modulation of NMDA receptors. Treatment of cultured neurons with triol protects against glutamate-induced neurotoxicity, and administration of triol significantly decreases neuronal injury after spinal cord ischemia in rabbits and transient focal cerebral ischemia in rats. An inducible elevation of triol is associated with ischemic preconditioning and subsequent neuroprotection in the spinal cord of rabbits. This neuroprotection is effectively abolished by preadministration of a specific inhibitor of triol synthesis. Physiological concentrations of triol attenuate [Ca

Determination of neuroprotective oxysterols in Calculus bovis, human gallstones, and traditional Chinese medicine preparations by liquid chromatography with mass spectrometry

“…Studies suggest that these four oxysterols show direct and indirect neuroprotective bioactivity [20][21][22][23][24]. It has been proved that cholestane-3␤,5␣,6␤-triol (Triol) could functions as a neuroprotectant as well in our previous research [25]. So, we surmise that in Calculus bovis there might be oxysterols conferring Calculus bovis the neuroprotective effects.…”

“…Another aim was to minimize the oxidation of oxysterols themselves. These amounts of EDTA and BHT were added by reference to our previous study on the endogenous oxysterols, especially Triol [25]. According to the previous research [33], a series of comparison tests with the same sample preparation protocol were conducted to verify the effect of EDTA and BHT (Supporting Information S1) using a standard of cholesterol.…”

Hexokinase 2‐dependent hyperglycolysis driving microglial activation contributes to ischemic brain injury

“…Every five rats were kept in a cage and given ad libitum access to food and water. MCAo surgery was performed on male as previously reported (Hu et al 2014). From our previous experiments, SDs are about 15-20% of the mean infract volume in the model we are using in our laboratory.…”

Exploring the potential of natural and synthetic neuroprotective steroids against neurodegenerative disorders: A literature review

“…Haiyan Hu and his co‐workers reported the cholestane‐3,5,6‐triol (Triol) (40) , a major metabolite of cholesterol as an endogenous neuroprotectant . Treatment of cultured neurons with Triol 40 protects the neuronal cells from injury in both in vitro and in vivo animal models via negative modulation of NMDA receptors.…”

“…Haiyan Hu and his co-workers reported the cholestane-3,5,6-triol (Triol) (40), a major metabolite of cholesterol as an endogenous neuroprotectant. 203 effects of the marine steroid Tetrol. 205 The structures of prominent neuroprotective cholestane derivatives have been given in Figure 13.…”