Beneficial effects of Cuscuta chinensis extract on glucocorticoid-induced osteoporosis through modulation of RANKL/OPG signals

Cuscuta chinensis Lam. (Convolvulaceae) is an important herbal medicine widely used to improve sexual function, treat osteoporosis, and prevent aging, and has been reported to exhibit anti-osteoporotic effects in vitro. However, the activity of Cuscuta chinensis Lam. on glucocorticoid-induced osteoporosis still remains unclear. The present study aimed to assess the protective effect and the underlying mechanism of action of Cuscuta chinensis extract (CCE) against glucocorticoid-induced osteoporosis in vivo. Sprague-Dawley rats were randomly divided into four groups as follows: control group, osteoporosis group, and 2 CCE-treated osteoporosis groups (100 mg·kg-1·day-1). Blood samples and femur bones were collected for immunohistochemistry, biochemical, mRNA expression, and western blot analysis. HPLC analysis revealed that chlorogenic acid, quercetin, and hyperin were the major constituents of CCE. The results indicated that CCE increased bone length, bone weight, and bone mineral density and suppressed dexamethasone (DEX)-induced reduction in body weight. In addition, TRAP staining indicated that CCE reduced osteoclasts in DEX-induced osteoporosis rats. Mechanistically, CCE treatment alleviated the increase of bone resorption markers and the decline of osteogenic markers, which might be partially mediated by regulation of RANKL/OPG and RunX2 pathways. These results suggest that CCE showed promising effects in the protection against glucocorticoid-induced osteoporosis through protecting osteoblasts and suppressing osteoclastogenesis.

Synergistic suppression of pre-perfusion of donor livers with recipient serum and cobra venom factor treatment on hyperacute rejection following liver xenotransplantation / Supressão sinérgica da rejeição hiperaguda no xenotransplante hepático com uso da pre-perfusão dos fígados doadores tratados com soro do receptor e com fator veneno de cobra

PURPOSE: To investigate synergistic suppression of donor liver pre-perfusion with recipient serum (RS) and cobra venom factor (CVF) treatment on hyperacute rejection (HAR) following liver xenotransplantation. METHODS: Guinea-pigs (GP, n=24) and Sprague-Dawley rats (SD, n=24) were recruited. Before transplantation, serum was collected from SD rats and used for preparation of inactivated complements. GP and SD rats were randomly assigned into four groups (n=6), respectively: RS group, CVF group, RS+CVF group and control group. Orthotopic liver xenotransplantation was performed with modified two-cuff technique. The survival time and liver function of recipients, morphological and pathological changes in rat livers were investigated. RESULTS: There was no piebald like change in the recipient livers in all experiment groups. The survival time of recipients in all experiment groups was longer than that in control group (p<0.05). Moreover, the survival time in the RS+CVF group was markedly longer than that in the RS group (p<0.01) and CVF group (p<0.05). The serum ALT level in all experiment groups were lower than that in the control group (p<0.05). Furthermore, the ALT level in the RS+CVF group was significantly lower than that in the CVF group (p<0.05) and RS group (p<0.01). The histological damages were significantly improved when compared with the control group, and the histological damages in the RS+CVF group were milder than those in the remaining groups (p<0.05) CONCLUSION: Pre-perfusion of donor liver with recipient serum and cobra venom factor treatment can exert synergistic suppressive effects on the hyperacute rejection following liver xenotransplantation.

OBJETIVO: Investigar a supressão sinérgica da pré-perfusão do doador de fígado com soro do receptor (SR) e tratamento com fator veneno de cobra (FVC) na rejeição hiperaguda (RHA) após o xenotransplante de fígado. MÉTODOS: Foram utilizados Cobaias (GP, n=24) e ratos Sprague-Dawley (SD, n=24). Antes do transplante foram coletadas amostras de soro dos ratos SD e usados para a preparação dos complementos inativados. Cobaias GP e ratos SD foram randomicamente distribuídos em quatro grupos (n=6), respectivamente: grupo RS, grupo FVC, grupo SR+FVC e grupo controle. Xenotransplante ortotópico do fígado foi realizado com a técnica de dois cuffs modificados. Foram investigados o de tempo de sobrevida, a função hepática dos receptores e alterações morfopatológicas em fígados de ratos. RESULTADOS: Não houve alteração na coloração do parênquima dos fígados nos receptores. O tempo de sobrevida dos receptores em todos os grupos experimentais foi mais longo do que o grupo controle (p<0,05). Além disso, o tempo de sobrevida do grupo SR+ FVC foi marcadamente maior do que o grupo SR (p<0,01) e o grupo FVC (p<0,05). O nível sérico ALT foi menor em todos os grupos experimentais do que o grupo controle (p<0,05). O nível de ALT no grupo SR+ FVC foi significantemente menor do que no grupo FVC (p<0,05) e o grupo SR (p<0,01). As alterações histológicas foram significantemente melhoradas quando comparado com o grupo controle, e os danos histológicos no grupo SR+ FVC foram mais moderados do que nos grupos restantes (p<0,05). CONCLUSÃO: Pré-perfusão do fígado doador com soro do receptor e fator veneno de cobra pode exercer efeito supressor sinérgico da rejeição hiperaguda após xenotransplante de fígado.

Advances in novel anti-HIV-1 drugs and drug candidates: 2005-2008 / 药学学报

HIV and AIDS remain as the crucial global health concern, therefore, research and development of novel anti-HIV-1 chemical therapeutics is still of paramount significance, which may be illuminated by cases of successful marketed drugs. Herein, we document the discovery and biological profile of new anti-HIV-1 drugs approved by FDA between 2005 and 2008 and some drug candidates are also discussed.