Inhibition on acid-sensing ion channels and analgesic activities of flavonoids isolated from dragon's blood resin.

Acid-sensing ion channel (ASIC) serves important roles in the transmission of nociceptive information. To confirm the analgesic mechanism of dragon's blood resin, patch-clamp technique, in vivo animal experiments, and immunohistochemical staining were used to observe the effects of the three flavonoids (loureirin B, cochinchinemin A, and cochinchinemin B) isolated from dragon's blood resin on ASIC. Results showed that the three flavonoids exerted various inhibitory effects on ASIC currents in rat dorsal root ganglion (DRG) neurons. The combination of the three flavonoids with total concentration of 6.5 µM could decrease (53.8 ± 4.3%) of the peak amplitude and (45.8 ± 4.5%) of the sustained portion of ASIC currents. The combination of the three flavonoids was fully efficacious on complete Freud's adjuvant (CFA)-induced inflammatory thermal hyperalgesia at a dose of 6.5 mM similar with amiloride at 10 mM. The analgesic effects of the combination could be weakened by an ASIC activator 2-guanidine-4-methylquinazoline. CFA-induced hyperalgesia was accompanied by c-Fos up-regulation in DRG neurons, and the combination rescued thermal hyperalgesia through down-regulation of c-Fos and ASIC3 expression in CFA-induced inflammation. These collective results suggested that the flavonoids isolated from dragon's blood resin could be considered as the chemical compounds that exert analgesic effects on inflammatory thermal pain due to action on ASIC.

Total saponins from the leaves of Panax notoginseng inhibit depression on mouse chronic unpredictable mild stress model by regulating circRNA expression.

OBJECTIVES: Total saponins from the leaves of Panax notoginseng saponins (SLPN) could inhibit development of depression, but the underlying mechanisms remains unclear. This study aimed to address the roles of circular RNAs in depression inhibition by SLPN. METHODS: The mouse chronic unpredictable mild stress (CUMS) model was established, which were confirmed by mouse weight, forced swimming test (FST) and tail suspension test (TST). Effects of SLPN on depression were evaluated in CUMS through these same assays. Circular RNA profiles in mouse ventral medial prefrontal cortex (VMPC) and hippocampus of CUMS mice were determined by high-through sequencing, followed by confirmation via qRT-PCR. Overexpression of mmu_circ_0001223 was done by transfection of PC12 cell through lentiviral system. Protein abundances of cAMP response element binding protein 1(CREB1) and brain-derived neurotrophic factor (BDNF) were evaluated by western blotting. RESULTS: Mouse body weight, immobility time in FST and immobility time in TST of CUMS mice were significantly recovered by SLPN treatment. A large number of circular RNAs were differentially expressed in the ventral medial prefrontal cortex (VMPC) and hippocampus tissues of CUMS mice. Among them, mmu_circ_0001223 expression was greatly decreased in CUMS mice, but significantly elevated by SLPN treatment. The protein levels of CREB1 and BDNF were also remarkably promoted in CUMS mice by treatment of SLPN. Overexpression of mmu_circ_0001223 enhanced CREB1 and BDNF protein levels in PC12 cells. CONCLUSION: SLPN regulate the expression of large number circular RNAs in CUMS mice, which might be important mediators of SLPN's anti-depression effects.