Cyclo(his-pro) TFA, an orally active cyclic dipeptide structurally related to tyreotropin-releasing hormone, has shown inhibitory effects on NF-κB nuclear accumulation. Additionally, it possesses the ability to cross the blood-brain barrier and impact various inflammatory and stress responses [1, 2].

Cyclo(his-pro) TFA (Cyclo(histidyl-proline) TFA; 50 μM; 1-48 hours) increases the nuclear level of Nrf2 and inhibits NF-κB nuclear translocation. Cyclo(His-Pro) alone has no effect on nuclear translocation of these transcription factors [2]. Cyclo(his-pro) TFA (50 μM; prior to PQ exposure for 48 hours) abolishes protein nitration that followed paraquat (PQ) exposure and lessenes its functional consequences, as shown by decrease in cell apoptosis, detected by caspase 3 activity and by cytochrome c release [2]. Cyclo(his-pro) TFA inhibits NF-κB nuclear accumulation induced by paraquat in rat pheochromocytoma PC12 cells via the Nrf2/heme oxygenase-1 pathway [2]. Western Blot Analysis [1] Cell Line: PC12 cells Concentration: 50 μM Incubation Time: 1, 2, 4, 8, 24, 48 hours Result: Increased the nuclear level of Nrf2 and inhibited NF-κB nuclear translocation.

Cyclo(his-pro) TFA (Cyclo(histidyl-proline) TFA; 1.8 mg/ear; topical application on the right ear; 30 min prior to TPA) reduces TPA-induced ear oedema confirming that it can exert anti-inflammatory effect [2]. Cyclo(his-pro) TFA exerts in vivo anti-inflammatory effects in the central nervous system by down-regulating hepatic and cerebral TNFα expression thereby counteracting LPS-induced gliosis. Moreover, by up-regulating Bip, Cyclo(his-pro) increases the ER stress sensitivity andtriggers the unfolded protein response to alleviate the ER stress [3]. Animal Model: Sixty two/three month-old male C57BL/6 mice (25-30 g) [2] Dosage: 1.8 mg/ear Administration: Topical application on the right ear; 30 min prior to TPA Result: Reduced TPA-induced ear oedema.