Heat stress can stimulate an increase in body temperature,which is correlated with increased expression of heat shock protein 70(HSP70) and tumor necrosis factor α(TNFα).The exact mechanism underlying the HSP70 and TNFα induction is unclear.Berberine(BBR) can significantly inhibit the temperature rise caused by heat stress,but the mechanism responsible for the BBR effect on HSP70 and TNFα signaling has not been investigated.The aim of the present study was to explore the relationship between the expression of HSP70 and TNFα and the effects of BBR under heat conditions,using in vivo and in vitro models.The expression levels of HSP70 and TNFα were determined using RT-PCR and Western blotting analyses.The results showed that the levels of HSP70 and TNFα were up-regulated under heat conditions(40 °C).HSP70 acted as a chaperone to maintain TNFα homeostasis with rising the temperature,but knockdown of HSP70 could not down-regulate the level of TNFα.Furthermore,TNFα could not influence the expression of HSP70 under normal and heat conditions.BBR targeted both HSP70 and TNFα by suppressing their gene transcription,thereby decreasing body temperature under heat conditions.In conclusion,BBR has a potential to be developed as a therapeutic strategy for suppressing the thermal effects in hot environments.
A simple, reliable, economical method was developed using HPLC with a diode-array detector for determination of total flavonoids in plasma after introvenous administration of ginkgo biloba extract. The method simultaneously detects quercetin, kaempferol, and isorhamnetin after acid hydrolysis and recalcula-tion. The hydrolysis and extraction conditions were optimized in an orthogonal test. The specificity was tested by comparing the retention time, UV spectra, and peak purity indices with standards. The detection limits were 20 ng/mL for quercetin, 20 ng/mL for kaempferol, and 50 ng/mL for isorhamnetin. The calibration curve ranges were 75-2400, 71-2280, and 70-2240 ng/mL. The pharmacokinetic characteristics of ginkgo biloba flavonoids after venous administration of 50 mg/kg ginkgo biloba extract to rats were analyzed using a two-compartment model. The initial plasma concentration was 171.22 μg/mL. The half-life of flavonoids in the first compartment (distribution) was 0.07 h and at the second compartment (elimination) was 4.51 h, while the AUC(0-∞) was 1711.06 μg·min/mL. The apparent volume of distribution was 0.11 L/kg. The total body clearance is 10.52 mL/(min·kg). The result shows the method is suitable for pharmacokinetic studies.
Corticosterone, a principal glucocorticoid synthesized in the rodent adrenal cortex, can be cumulatively toxic to hippocampal neurons, the cause of which is not known. The present study determined whether the cytosol adenylate kinase (AK) system was involved in the neuronal damage induced by long-term exposure to high corticosterone levels. We investigated the effects of long-term exposure to high corticosterone levels on AK1 activity, AK1 mRNA expression, and energy levels in cultured hippocampal neurons. The results show that long-term exposure to high corticosterone levels induces a reduction of the cultured hippocampal neuron viability, significantly reduces energy levels, and causes a time-dependant reduction of the AK1 activity. These findings indicate that changes in the AK system might be the mechanism underlying neuronal damage induced by long-term exposure to high corticosterone levels.
