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Cyclo(his-pro) is a naturally occurring cyclic dipeptide formed from the condensation of L-histidine and L-proline. It is a metabolite of thyrotropin-releasing hormone (TRH) and is found in various tissues including blood serum, brain, cerebrospinal fluid, and the prostate gland[6][7]. Cyclo(his-pro) acts as an endogenous neuroprotective agent and has demonstrated anti-inflammatory properties by inhibiting NF-κB nuclear accumulation through activation of the Nrf2/heme oxygenase-1 pathway[5][10]. It can cross the blood-brain barrier and modulate inflammatory responses in the central nervous system by down-regulating TNFα expression. Cyclo(his-pro) also plays a role in glucose metabolism regulation and has been studied for its potential to improve blood sugar control in type 2 diabetes[7]. Its mechanism involves modulation of oxidative stress pathways via Nrf2 signaling.
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