Effects of Kv1.3 knockout on pyramidal neuron excitability and synaptic plasticity in piriform cortex of mice.

Kv1.3 belongs to the voltage-gated potassium (Kv) channel family, which is widely expressed in the central nervous system and associated with a variety of neuropsychiatric disorders. Kv1.3 is highly expressed in the olfactory bulb and piriform cortex and involved in the process of odor perception and nutrient metabolism in animals. Previous studies have explored the function of Kv1.3 in olfactory bulb, while the role of Kv1.3 in piriform cortex was less known. In this study, we investigated the neuronal changes of piriform cortex and feeding behavior after smell stimulation, thus revealing a link between the olfactory sensation and body weight in Kv1.3 KO mice. Coronal slices including the anterior piriform cortex were prepared, whole-cell recording and Ca2+ imaging of pyramidal neurons were conducted. We showed that the firing frequency evoked by depolarization pulses and Ca2+ influx evoked by high K+ solution were significantly increased in pyramidal neurons of Kv1.3 knockout (KO) mice compared to WT mice. Western blotting and immunofluorescence analyses revealed that the downstream signaling molecules CaMKII and PKCα were activated in piriform cortex of Kv1.3 KO mice. Pyramidal neurons in Kv1.3 KO mice exhibited significantly reduced paired-pulse ratio and increased presynaptic Cav2.1 expression, proving that the presynaptic vesicle release might be elevated by Ca2+ influx. Using Golgi staining, we found significantly increased dendritic spine density of pyramidal neurons in Kv1.3 KO mice, supporting the stronger postsynaptic responses in these neurons. In olfactory recognition and feeding behavior tests, we showed that Kv1.3 conditional knockout or cannula injection of 5-(4-phenoxybutoxy) psoralen, a Kv1.3 channel blocker, in piriform cortex both elevated the olfactory recognition index and altered the feeding behavior in mice. In summary, Kv1.3 is a key molecule in regulating neuronal activity of the piriform cortex, which may lay a foundation for the treatment of diseases related to piriform cortex and olfactory detection.

Hepatoprotection of Herpetospermum caudigerum Wall. against CCl4-induced liver fibrosis on rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Herpetospermum caudigerum Wall. (HCW) is a traditional Tibetan medicine, which has been used to ameliorate liver injuries in the folk. AIM OF THE STUDY: Liver fibrosis has been recognized as a major lesion of the liver that leads to liver cirrhosis/hepatocarcinoma and even to death in the end. This study aims to demonstrate the protective effect of HCW against CCl4-induced liver injury in rats and to explore the underlying mechanisms. MATERIALS AND METHODS: Hepatic fibrosis was induced by intraperitoneal injection of CCl4. Liver function markers, fibrosis markers, serum anti-oxidation enzymes as well as elements levels were determined. Serum and liver tissues were subjected to NMR-based metabolomics and multivariate statistical analysis. RESULTS: HCW could significantly reduce the elevated levels of fibrosis markers such as hyaluronidase, laminin, Type III procollagen and Type IV collagen in the serum, improve the activities of the antioxidant enzymes, and effectively reverse the abnormal levels of elements in liver fibrosis rats. Correlation network analysis revealed that HCW could treat liver fibrosis by ameliorating oxidative stress, repairing the impaired energy metabolisms and reversing the disturbed amino acids and nucleic acids metabolisms. CONCLUSION: This integrated metabolomics approach confirmed the validity of the traditional use of HCW in the treatment of liber fibrosis, providing new insights into the underlying mechanisms.

[Study on ursolic acid extraction rate by ultramicro smashing and conventional smashing from leaves of Paulownia fortunei].

OBJECTIVE: To study on ursolic acid extraction rate from leaves of Paulownia fortunei by conventional powder and ultramicro powder. METHODS: We spent different time extracting ursolic acid from coventional powder and ultramicro powder, then determined the content by HPLC and compared. RESULTS: In ultramicro powder the extraction of ursolic acid was nearly twice of conventional powder; The time reaching the maximum extraction of ultramicro powder was 5 minutes, but that of conventional powder was 20 minutes. CONCLUSIONS: The extraction of ursolic acid from leaves of Paulownia fortunei by ultramicro smashing is more efficient.

Anti-inflammatory and anticancer activities of ethanol extract of pendulous monkshood root in vitro.

AIM: Pendulous monkshood root is traditionally used for the treatment of several inflammatory pathologies such as rheumatisms, wounds, pain and tumors in China. In this study, the anti-inflammatory and anticancer activities and the mechanism of crude ethanol extract of pendulous monkshood root (EPMR) were evaluated and investigated in vitro. MATERIALS AND METHODS: The cytotoxic effects of EPMR on different tumor cell lines were determined by the MTT method. Cell apoptosis and cell nucleus morphology were assessed by Hoechst 33258 staining. Moreover, nitric oxide (NO) levels and intracellular oxidative stress in peritoneal macrophages were determined to further elucidate mechanisms of action. RESULTS: The data showed that EPMR could produce significant dose-dependent toxicity on three kinds of tumor cells. Furthermore, EPMR displayed obvious anti- inflammatory effects on LPS-induced mouse peritoneal macrophages at the dosage of 4 - 200 µg/mL. The results demonstrated the therapeutic potential of Pendulous Monkshood Root on cancer and inflammatory diseases. CONCLUSION: Our results indicate that EPMR has anti-inflammatory and anticancer properties, suggesting that pendulous monkshood root may be a useful anti-tumor and anti-inflammatory reagent in the clinic.