RESUMO
Angelica sinensis, commonly known as Dong Quai in Europe and America and as Dang-gui in China, is a medicinal plant widely utilized for the prevention and treatment of osteoporosis. In this study, we report the discovery of a new category of phthalide from Angelica sinensis, namely falcarinphthalides A and B (1 and 2), which contains two fragments, (3R,8S)-falcarindiol (3) and (Z)-ligustilide (4). Falcarinphthalides A and B (1 and 2) represent two unprecedented carbon skeletons of phthalide in natural products, and their antiosteoporotic activities were evaluated. The structures of 1 and 2, including their absolute configurations, were established using extensive analysis of NMR spectra, chemical derivatization, and ECD/VCD calculations. Based on LC-HR-ESI-MS analysis and DFT calculations, a production mechanism for 1 and 2 involving enzyme-catalyzed Diels-Alder/retro-Diels-Alder reactions was proposed. Falcarinphthalide A (1), the most promising lead compound, exhibits potent in vitro antiosteoporotic activity by inhibiting NF-κB and c-Fos signaling-mediated osteoclastogenesis. Moreover, the bioinspired gram-scale total synthesis of 1, guided by intensive DFT study, has paved the way for further biological investigation. The discovery and gram-scale total synthesis of falcarinphthalide A (1) provide a compelling lead compound and a novel molecular scaffold for treating osteoporosis and other metabolic bone diseases.
RESUMO
Digested piggery wastewater(DPW) contains high concentrations of nitrogen and phosphorus which could be used as a cost-effective culture medium for Spirulina platensis. However, Spirulina platensis would be limited by many factors in the complex composition of DPW, especially the high concentration of ammonium. In this paper, a traditional sequencing batch reactor(SBR) was used to remove these inhibitors in DPW. The retention of nitrate and nitrite in the effluent, which was used as nitrogen source for cultivating Spirulina platensis, was studied at different ratios of chemical oxygen demand(COD) to total nitrogen(TN) in the influent. By comparing the growth of Spirulina platensis in the related effluents, the operation condition of SBR was optimized. The lab-scale cultivation results showed that Spirulina platensis possessed a high biomass yield of 0.084 g·(L·d)-1 in the effluent when the COD/TN ratio of SBR influent was 3.0. In particular, the concentrations of ammonium, nitrate and nitrite in the effluent were 51.2 mg·L-1, 91.6 mg·L-1and 213.1 mg·L-1, respectively. Furthermore, the aforementioned effluent was also used to culture Spirulina platensis in a 120 L outdoor raceway pond, and the growth rate of Spirulina platensis reached(0.075±0.003)g·(L·d)-1 after 10-day culture. The protein content of Spirulina platensis was approximately 60% and the removal efficiency of ammonium was 99%. This study provides an alternative method for the utilization of DPW.
