Ursolic Acid Prevents Retinoic Acid-Induced Bone Loss in Rats / 中国结合医学杂志

OBJECTIVE@#To examine the effects of ursolic acid (UA) on mitigating retinoic acid (RA)-induced osteoporosis in rats.@*METHODS@#Fifty female Sprague-Dawley rats were randomly divided into the control group (n=10) and the osteoporosis group (n=40). The 40 osteoporosis rats were induced by 75 mg/(kg•d) RA once daily for 2 weeks, and then were randomly assigned to vehicle control (model), low-, middle-, and high-dose UA [(UA-L, UA-M, UA-H; 30, 60, 120 mg/(kg•d), respectively] groups (10 rats each). UA were administered once daily to the rats from the 3rd weeks for up to 4 weeks by gavage. Bone turnover markers [serum alkaline phosphatase (ALP), osteocalcin (OCN), urine deoxypyridinoline (DPD)] and other parameters, including serum calcium (S-Ca), serum phosphorus (S-P), urine calcium (U-Ca), urine phosphorus (U-P), and bone mineral density (BMD) of the femur, 4th lumbar vertebra and tibia, bone biomechanical properties and trabecular microarchitecture, were measured.@*RESULTS@#The osteoporosis in rats was successfully induced by RA. Compared with the model group, UA-M and UA-H significantly reversed the RA-induced changes in S-P, U-Ca, U-P, ALP, OCN and urine DPD ratio and markedly enhanced the BMD of right femur, 4th lumbar vertebra and tibia (Plt;0.05 or Plt;0.01). Further, biomechanical test and microcomputed tomography evaluation also showed that UA-H drastically improved biomechanical properties and trabecular microarchitecture (Plt;0.05 or Plt;0.01).@*CONCLUSION@#UA could promote bone formation, increase osteoblastic activity and reduce osteoclastic activity in rats, indicating that UA might be a potential therapeutic of RA-induced acute osteoporosis.

Interaction between a novel folate receptor targeted rhaponticin conjugate and human serum albumin by molecular spectroscopy / 国际药学研究杂志

Objective To investigate the affinity and inteaction of a folate receptor targeted rhapontion (RHA) conjugate (FRHA) with human serum albumins(HSA). Method The interaction between FRHA and HSA under physiological conditions was investigated by fluorescence spectroscopy, UV- visual (vis) spectroscopy and circular dichroism (CD) spectroscopy. Great attempts were made to investigate their interaction mechanism regarding the quenching mechanism, the specific binding site, the type of interaction force, and the effect of FRHA on the micro-environmental and conformational changes in HSA molecules. Results The formation of the complex of FRHA-HSA would lead to fluorescence quenching. The corresponding values of Ka were 1.4322×105, 1.1793× 105, 0.9334×105 and 0.7896×105 L/mol when the temperature were 298, 302, 306, and 310 K, respectively. The enthalpy change (ΔH) and entropy change (ΔS) were calculated to be -38.772 kJ/mol and -31.39 J/(mol·K), indicating that van der Waals force and hydrogen bonds played major roles in stabilizing the complex. Conclusion The interaction process of the formation of FRHA-HSA is spontaneous. The negative values of enthalpy change (ΔH) and entropy change (ΔS) indicate that van der Waals force and hydrogen bonds play major roles in stabilizing the complex. The conformational investigation reveals the α·-helical structure is decreased and the microenvironment of HSA is changed upon the addition of FRHA. The fluorescence quenching of HSA caused by FRHA is static quenching. Furthermore, the results of site marker competitive experiment suggest that FRHA binds to the sub-domain II A of HSA.

Process optimization and component analysis of extracting seed oil from Schisandra sphenanthera by supercritical CO2 / 国际药学研究杂志

Objective To optimize the extraction conditions of Schisandra sphenanthera(SS)seed oil by supercritical CO2ex?traction and identify its components by GC-MS.Methods SS seed oil was used as tested material,response surface methodology was used to optimize the process of supercritical CO2extraction,and GS-MS method was used to analyse SS seed oil composition.Results A model of an equation was established,which could be used to optimize the process parameters of supercritical CO2extraction of SS seed oil. The optimum extraction parameters were as follows:the extraction pressure was 33 MPa,the extraction temperature was 53℃,the extraction time was 90 min,the CO2flow rate was 21.40 ml/min.In this condition,the extraction rate of SS seed oil was 7.97%.The SS seed oil was analyzed by GC-MS,and 23 compounds were identified.In these compounds,(1α,4a.β,8a.α)-1,2,3, 4,4a,5,6,8a-octahydro-7-methyl-4-methylene-1-(1-methylethenyl)-naphthalene,(-)-1,7-dimethyl-7-(4-methyl-3-pentenyl)-tricyc?lo[2.2.1.0(2,6)]heptane and(R)-2,4a,5,6,7,8-octahydro-3,5,5,9-tetramethyl-1H-(σ-phenyl)cycloheptene had the content of more than 10% and the contents were 27.78%,14.77% and 13.12% respectively.Conclusion This process has high extraction rate, fast speed and simple operation,and can be used for the extraction of SS seed oil.

Preparation of folate-targeted Ergosta-4,6,8(14),22-tetraen-3-one liposomes and its evaluation in vitro and pharmacokinetic studies / 中国药学杂志

OBJECTIVE: To prepare folate-conjugated ergosta-4,6,8,22-tetraen-3-one liposomes(FLE). Then to study the release feature of FLE in vitro and the eytotoxieity and targeting ability of it via folate receptor-mediated endocytosis on tumor cells in vitro. Pharmacokinetic characterization was also studied in rats. METHODS The characteristics were measured by transmission electron microscope(TEM), laser light scattering granularity equipment and HPLC. Dialytic method was used to determine ergone release rate of FLE in vitro. The cytotoxicity and targeting ability of FLE on HeLa in vitro was measured by MTT assay. The concentrations of ergone in plasma of rats and their pharmacokinetic behaviors after oral administration were studied by HPLC. The pharmacokinetic parameters were computed by software DAS2.0. RESULTS: The prepared FLE was round and uniform, and the mean particle size was 112 nm. The encapsulating efficiency of it reached 73%. The experiment of drug release in vitro follows Higuchi releasing process and showed significant sustained-release feature. The IC50 of ergone, LE and FLE was 10, 14, 5 μg · mL-1, respectively. Compared with ergone solution, AUC in FLE had increased significantly. And the residence time of ergone was prolonged. CONCLUSION: The FLE were characterized by sustained-release performance, target recognition, and low toxic and side effect and did improve the bioavailability of ergone significantly. It can also be expected to be used for tumor by targeting therapy.