Banxia-houpu decoction is a safe and effective traditional Chinese medicinal formula used in the treatment of mild and manic-depressive disorders for centuries. There has been increasing interest in its therapeutic application in depression. However, the mechanisms behind behavioural changes are still poorly understood. Chronic mild stress (CMS)-induced preference behaviour change has been used as a model to predict the clinical efficacy of many types of antidepressant treatment. Both EtOH and water extracts (AE and WE) of Banxia-houpu decoction exhibited a significantly increased sucrose intake in the CMS model in rats, but there was no effect in unstressed animals. In the present study, it was found that the c-fos expression in cerebral cortex, hippocampus and striatum corpora were very high in the CMS model in rats. WE and AE at a dose of 130mg/kg exhibited a significantly decreased c-fos expression in the cerebral regions in CMS model in rats, respectively. The former was more potent than the latter. However, no significant changes in the c-fos expression were observed in unstressed rats treated with the decoction. Fluoxetine not only significantly reduced cfos expression in all regions in the CMS model in rats, but only showed a marked decrease in c-fos expression in the hippocampus in unstressed animals. A different molecular mechanism of Banxia-houpu decoction and fluoxetine may be implied. The cerebral cortex, hippocampus and striatum conpora might be important structural substrates in the central nervous system mediating the section of the Banxia-houpu decoction on preference behaviour in CMS-induced rats, and fos protein might be the common substrate of the signal transduction process of the decoction. Copyright.

A total of seventeen phytochemicals including seven alkaloids (piperine, strychnine, brucine, stachydrine, tetrandrine, frangchinoline and sinomenine), four phenols (paeonol, honokiol, magnolol and eugenol) and six anthraquinones (emodin, rhein, chrysorphanol, aloe-emodin, physcion and 1,8-dihydroxyanthraquinone) was examined for inhibitory activity of monoamine oxidase (MAO) A and B from rat brain mitochondrial. Among these compounds, piperine and paeonol were found to be inhibitory against MAO A in a dose-dependent manner with IC50 values of 49.3 and 54.6μM, respectively. Piperine, paeonol and emodin were shown to inhibit MAO B in a dose-dependent manner with the IC50 data of 91.3, 42.5 and 35.4μM, respectively. Lineweaver-Burk transformation of the inhibition data indicated that the inhibitory action of piperine onMAO A was of mixed type, and that of paeonol on the same type of the enzyme was of non-competitive type. For piperine, the Ki and KI were determined to be 35.8 and 25.7μM, respectively. For paeonol, the Ki was estimated to be 51.1μM. The inhibition of piperine and paeonol on MAO B was of competitive type with Ki values of 79.9 and 38.2μM, respectively. The inhibition of emodin on MAO B was of mixed type with the Ki and KI data of 15.1 and 22.9μM, respectively. The present investigation showed that the phytochemicals piperine, paeonol and emodin are potent MAO inhibitors whereas other compounds were inactive against any type of MAO at 100μM in the present assay.

In this study we have investigated the effects of administration of procyanidins from grape seeds on serum uric acid levels in a model of hyperuricaemia in mice pretreated with oxonate, as well as the xanthine dehydrogenase and xanthine oxidase activities in mouse liver in vivo. The procyanidins, when orally administered to the oxonate-pretreated hyperuricaemic mice, were able to elicit a dose-dependent hypouricaemic effect. At a dose of 400mg/kg for 3 days, the serum urate levels of the oxonate-pretreated mice were not different from the normal mice. In addition, the hepatic activities of xanthine dehydrogenase and xanthine oxidase in the procyanidins-treated mice were found to decrease significantly. However, the hypouricaemic effects observed in the experimental animals did not seem to parallel the changes in xanthine dehydrogenase and xanthine oxidase activities, implying that the procyanidins might be acting via other mechanisms apart from simple inhibition of enzyme activities. Furthermore, the procyanidin-treated animals exhibited normal growth while the allopurinol-treated animals exhibited some retarded growth. These results demonstrated for the first time that the procyanidins from grape seeds possess in vivo urate-lowering activities. The potential application of these natural compounds in the treatment of hyperuricaemia is discussed.

The hypouricemic actions of Biota orientalis (BO) extract and its flavonoid constituents quercetin and rutin, were in vivo examined using oxonate-induced hyperuricemic mice. Quercetin and rutin, when administered three times orally to the oxonate-induced hyperuricemic mice, were able to elicit dose-dependent hypouricemic effects. The effects of quercetin and rutin were more potent than that of Biota orientalis extract at the same dose of 100mg/kg. At doses of 50mg/kg of quercetin or above, or at doses of 100mg/kg of rutin or above, the serum urate levels of the oxonate-pretreated mice were not different from normal mice. In addition, Biota orientalis extract, quercetin and rutin, when tested in vivo on mouse liver homogenates, elicited significant inhibitory actions on the xanthine dehydrogenase/xanthine oxidase (XDH/XO) activities. The effects of quercetin and rutin resulted less potent than that of allopurinol. However, intraperitoneal administration at the same scheme did not produce any observable hypouricemic effect. These hypouricemic effects are partly due to the inhibition of XDH/XO activities in mouse liver. The pharmacological profile of the flavonoids is partly different from that of allopurinol. Such hypouricemic action and inhibition of the enzyme activity of quercetin and rutin may be responsible for a part of the beneficial effects of Biota orientalis extract on hyperuricemia and gout. The effects of quercetin and rutin on serum urate levels in hyperuricemic mice induced by oxonate and the inhibition of enzyme activities in mouse liver are discussed in relation to their absorption and metabolism, and their potential application to treat gout and hyperuricemia.

Ermiao wan, which is composed of phellodendri cortex and atractylodis rhizome, is described as eliminating heat, excreting dampness and anti-edema prescription in traditional Chinese medical literatures including Danxi's Experiences in Medicine and State Pharmacopoeia of People's Republic of China. So it is being used clinically in the treatment of gout and hyperuricemia in China. In the present study, the water extracts of Ermiao wan and phellodendri cortex at 840 and 480mg/kg/day orally for 7 days were demonstrated to possess in vivo potent hypouricemic effects both in hyperuricemic mice pretreated with oxonate and in normal mice, respectively. In the hyperuricemic animals, the effect of Ermiao wan was equal to that of the reference drug allopurinol (at 10mg/kg/day orally for 7 days), but in the normal mice, the former was weaker than latter. In addition, both Ermiao wan and phellodendri cortex were found to have in vivo relatively inhibitory effects on mouse liver xanthine dehydrogenase (XDH) and xanthine oxidase (XO) activities at the same dose described above. These inhibitory effects were weaker than that observed for allopurinol. Atractylodis rhizome at 340mg/kg/day orally for 7 days did not show any effects on the above experiments. These results suggested that atractylodis rhizomes assisted and enhanced the effect of phellodendri cortex on reduction of serum uric acid level in hyperuricemic mice, and hypouricemic effects of Ermiao wan and phellodendri cortex may be achieved by other mechanism partly instead of the XDH and XO inhibition.