To investigate effects of α-asarone and β-asarone on induced PC12 cell injury and related mechanisms. Aβ toxic injury cell model was induced by Aβ in PC12 cells. PC12 cells were divided into blank control group, model control group, α-asarone group (0.5, 1.0, β-asarone group (6.3, 12.5, vasoactive intestinal peptide (VIP) group, and VIP antagonist control group. Cell survival rate was detected by CCK-8 kit; cell apoptosis rate was detected by flow cytometry. The levels of inflammatory cytokines interleukin (IL)-1, , tumor necrosis factor (TNF)-α, oxidation-related inducible nitric oxide synthase (iNOS), nitric oxide (NO), apoptosis factors caspase-3 and p53 were detected by ELISA method. The expressions of C-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK) were detected by Western blotting. Compared with model control group, cell survival rates of group, β-asarone group and VIP group increased; the cell apoptosis rate decreased; levels of apoptosis-related factors caspase-3, p53, inflammatory factors IL-1, TNF-α decreased; IL-10 level increased; levels of oxidization-related factors iNOS and NO decreased; the expression of JNK and p38MAPK protein decreased (all <0.05). After VIP antagonist intervention, the survival rate of β-asarone group decreased; apoptosis rate increased; apoptosis related factors caspase-3, p53, inflammatory factors IL-1, TNF-α increased; IL-10 decreased; oxidation related factors iNOS and NO increased; the expression of JNK and p38MAPK protein increased (all <0.05); while there were no significant changes in these indicators of α-asarone group (all >0.05). α-asarone and β-asarone have protective effects on PC12 cell injury induced by Aβ. β-asarone may inhibit inflammatory factors and oxidation-related factors through promoting VIP secretion, regulating JNK/MAPK pathway, and reducing PC12 cell apoptosis; however, the effect of α-asarone may be not related to VIP secretion.
Allylbenzene Derivatives ; Animals ; Anisoles/pharmacology* ; Apoptosis ; PC12 Cells ; Rats

To prepare and optimize the self-microemulsion co-loaded with tenuifolin and β-asarone(TF/ASA-SMEDDS) and evaluate its quality. The prescription compositions of TF/ASA-SMEDDS were screened by solubility test, single factor test and pseudo-tern-ary phase diagram, and the prescriptions were further optimized by Box-Behnken response surface method, with the drug loading and particle size as the evaluation indexes. Then the optimized TF/ASA-SMEDDS was evaluated for emulsified appearance, particle size, morphology and drug release in vitro. The optimized prescription for TF/ASA-SMEDDS was as follows: caprylic citrate triglyceride polyoxyethylene castor oil-glycerol(10.8∶39.2∶50), drug loading of(5.563±0.065) mg·g~(-1) for tenuifolin and(5.526±0.022) mg·g~(-1) for β-asarone; uniform and transparent pan-blue nanoemulsion can be formed after emulsification, with particle size of(28.84±0.44) nm. TEM showed that TF/ASA-SMEDDS can form spherical droplets with a uniform particle size after emulsification; In vitro release test results showed that the drug release rate and cumulative release of tenuifolin and β-asarone were significantly improved. The preparation process of TF/ASA-SMEDDS was simple and can effectively improve in vitro release of tenuifolin and β-asarone.
Anisoles ; Biological Availability ; Diterpenes, Kaurane ; Drug Delivery Systems ; Emulsions ; Particle Size ; Solubility ; Surface-Active Agents

PURPOSE: This study was performed to analyze the potential impact of cement use and favorable pre-injury activity on clinical outcomes of bipolar hemiarthroplasty (BHA) compared with total hip arthroplasty (THA) in elderly patients with femoral neck fractures. MATERIALS AND METHODS: Systematic review and meta-analysis of 12 clinical studies (5 randomized controlled trials and 7 comparative studies). Subgroup analysis was performed based on type of fixation method (cemented vs. cementless) and in the patient with independent ambulation, respectively. RESULTS: A significantly higher dislocation rate was observed in patients treated with THA compared with those treated with BHA in individuals capable of independent ambulation before injury (odds ratio [OR], 0.17; 95% confidence interval [CI], 0.05–0.62; P=0.05, Z=1.98). Also, the dislocation rate was significantly higher in patients treated with cemented THA compared with those treated with cemented BHA (OR, 0.18; 95% CI, 0.05–0.62; P=0.006, Z=2.73). EQ-5D was significantly higher in those treated with cemented THA compared with patients treated with cemented BHA. Lastly, HHS was significantly higher in patients treated with cementless THA compared with those treated with cementless BHA. CONCLUSION: An increase in the dislocation rate was observed when THA was performed in elderly patients with femoral neck fracture and who were pre-injury independent walkers. In addition, cemented THA was associated with a higher dislocation rate compared with cemented BHA. However, the dislocation rate in those treated with cementless THA were similar to patients treated with cementless BHA. With regards to functional score, THA was superior to BHA in both cementless and cemented fixation.
Aged ; Arthroplasty ; Arthroplasty, Replacement, Hip ; Butylated Hydroxyanisole ; Dislocations ; Femoral Neck Fractures ; Femur Neck ; Hemiarthroplasty ; Humans ; Methods ; Walkers ; Walking

PURPOSE: The aim of the current study is to report the advantage and disadvantage of total hip arthroplasty performed in direct anterior approach (DAA) by comparing it to the posterolateral approach (PLA). MATERIALS AND METHODS: Twenty-five hip arthroplasty done in DAA (12 total hip arthroplasty [THA] and 13 bipolar hemiarthroplasty [BHA]) were compared with the same number done in PLA (13 THA and 12 BHA). Intraoperative assessments including operation time, anesthetic time, bleeding amount were recorded with intraoperative complications. Immediate postoperatively, position of the prosthesis and leg length discrepancy were measured and were compared between the two approaches. RESULTS: The operation time was 22 minutes and 19 minutes longer in DAA for THA and BHA respectively while the anesthetic time difference was 26 and 10 respectively. However, these parameters showed no statistical difference. No significance was found when bleeding amount was compared. For DAA, cup alignment was within safe zone in 100% both for inclination and for anteversion while this was 83.3% and 75.0% respectively in PLA. Leg length difference was 3 mm in DAA and 5 mm in PLA but had no significant difference. Tensor fascia lata tear was the most common complication occurring in 9 patients. CONCLUSION: Although significant was not reached there was trend toward more operation time and anesthetic time when DAA was used. However, the trend also showed that cup and stem were likely to be in more accurate position and in adequate size which is likely due to the accurate use of fluoroscopy.
Arthroplasty* ; Arthroplasty, Replacement, Hip ; Bleeding Time ; Butylated Hydroxyanisole ; Fascia Lata ; Fluoroscopy ; Hemiarthroplasty ; Hemorrhage ; Hip* ; Humans ; Intraoperative Complications ; Leg ; Prostheses and Implants ; Tears

OBJECTIVETo detect the embryo toxicity and the teratogenicity of DNAN in rats and provide basic data to occupational protection.

METHODS120 adult female SD rats and 60 male rats are mating for 1: 1, and the pregnant rats were randomly divided into five groups by the pregnant time. The negative control group are gavaged with 4% starch, and the three experiment groups are gavaged with DNAN suspension with the dose of 5 mg/kg, 15 mg/kg and 45 mg/kg respectively, while the positive control give aspirin of 280 mg/kg. All rats of the five groups are administrated gavage from gestation day 5 (GD5) to GD19 continuously. The rats are dislocated in GD20, and the toxicity of embryo and toetus are detected.

RESULTSThe net weight growth in all three dose group are less than that of negative group, while the dead foetus in high dose group is more than negative group. Moreover, the body weight, body lenghth, tail lenghth and the anal genital distance of foetus rats in high dose group are all less than that of negative group. The foetus external malformations of three dose groups appear no significant compared with negative group.However, the prevalences of skeleton malformation in high dose group and the internal organs malformation in the median and high dose group appear significant higher than that of negative group. There are significantly maternal reproductive toxicity, embryo toxicity and toetus toxicity in positive group.

CONCLUSIONDNAN can induced maternal reproductive toxicity, embryo toxicity and the teratogenicity to rats.

Animals ; Anisoles ; toxicity ; Female ; Male ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; Teratogens ; toxicity ; Toxicity Tests

PURPOSE: To compare the clinical and radiological results between internal fixation using the proximal femoral nail system and bipolar hemiarthroplasty (BHA) in reverse oblique intertrochanteric hip fractures in elderly patients. MATERIALS AND METHODS: From January 2005 to July 2012, we reviewed the medical records of 53 patients who had been treated surgically for reverse oblique intertrochanteric fracture and had been followed-up on for a minimum of two years. All patients were > or =70 years of age, and divided into two groups for retrospective evaluation. One group was treated with internal fixation using the proximal femoral nail system (31 cases), and the other group was treated with BHA (22 cases). RESULTS: Early ambulation postoperatively and less pain at postoperative three month were significantly superior in the BHA group. However, by 24 months postoperatively, the internal fixation group exhibited higher Harris scores and correspondingly less pain than the BHA group. There were no significant differences in union rate, duration of hospitalization or lateral wall fracture healing between the two groups. Four patients in the internal fixation group underwent reoperation. CONCLUSION: In the treatment of intertrochanteric fracture of the reverse oblique type, open reduction and internal fixation should be considered to be the better choice for patients with good health and bone quality. However, in cases of severe comminition of fracture and poor bone quality, BHA is an alternative offering advantages including early ambulation, less pain at early stages, and a lower risk of reoperation.
Aged* ; Butylated Hydroxyanisole ; Early Ambulation ; Femoral Fractures* ; Femur ; Fracture Fixation, Intramedullary ; Fracture Healing ; Hemiarthroplasty* ; Hip Fractures ; Hospitalization ; Humans ; Medical Records ; Reoperation ; Retrospective Studies

Taking α-asarone as model drug, mono methoxy polyethylene glycol-polylactic acid copolymer (mPEG-PLA) as the drug carrier material to prepare drug-loading nanoparticles by premix membrane emulsification for nasal administration. The prepared nanoparticles were spherical with smooth surface and average particle size of 360 nm. Polydispersity index (PDI) was 0. 030, average drug loading of (11.5 ± 0.045) % (n = 3), and the encapsulation efficiency of (86.34 ± 0.11) % (n = 3). X-ray diffraction and differential scanning calorimetry results showed that, α-asarone existed in mPEG-PLA carrier in amorphous or molecular state, different from simple physical mixture. In the in vitro release test in simulated human nasal cavity, α-asarone apis can be released quickly at close to 94% at 102 h, in line with the first-order kinetics (R² = 0.981 9). mPEG-PLA drug-loading nanoparticles release only 54%, with slow release effect, in line with Riger-Peppas model (R² = 0.967 9, n = 0.630 2), for non-fick diffusion, released by the spread of drugs and skeleton dissolution dual control. This provided the foundation for nasal drug delivery in vivo pharmacokinetic study.
Administration, Intranasal ; Anisoles ; chemistry ; Calorimetry, Differential Scanning ; Nanoparticles ; chemistry ; Polyesters ; chemistry ; Polyethylene Glycols ; chemistry ; Solubility ; X-Ray Diffraction

In order to clarify material basis of effective parts of liangxue tongyu prescription, blood-heat and blood-stasis rat model induced by dry yeast was established. The changes of rectal temperature, blood viscosity and plasma viscosity were used to evaluate the cooling-blood and activating-blood effects of liangxue tongyu prescription and its parts. Compared with the model group, the extract from liangxue tongyu prescription, its volatile oil and n-butanol part could significantly reduce rectal temperature (P<0.01), and also reduce blood viscosity and plasma viscosity to various degrees (P<0.01 or P<0.05). So volatile oil and n-butanol part were primarily identified as effective parts of liangxue tongyu prescription. By using GC-MS with normalization method of area to analyze volatile oil of liangxue tongyu prescription, 70 compounds were identified, accounting for about 92.54%, mainly as β-asarone, paeonol, α-asarone and shyobunone. 42 compounds such as peony glycosides, tannins, and iridoid glycosides were identified by HPLC-MS techniques and standard comparison. The study determined the effective parts of liangxue tongyu prescription and clarified the chemical composition providing the foundation for further studies on material basis of liangxue tongyu prescription.
Acetophenones ; chemistry ; Animals ; Anisoles ; chemistry ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; chemistry ; Gas Chromatography-Mass Spectrometry ; Oils, Volatile ; chemistry ; Rats ; Tannins ; chemistry

Butylated hydroxyanisole (BHA) is a synthetic phenolic compound consisting of a mixture of two isomeric organic compounds: 2-tert-butyl-4-hydroxyanisole and 3-tert-butyl-4-hydroxyanisole. We examined the effect of BHA against hydrogen peroxide (H2O2)-induced apoptosis in primary cultured mouse hepatocytes. Cell viability was significantly decreased by H2O2 in a dose-dependent manner. Additionally, H2O2 treatment increased Bax, decreased Bcl-2, and promoted PARP-1 cleavage in a dose-dependent manner. Pretreatment with BHA before exposure to H2O2 significantly attenuated the H2O2-induced decrease of cell viability. H2O2 exposure resulted in an increase of intracellular reactive oxygen species (ROS) generation that was significantly inhibited by pretreatment with BHA or N-acetyl-cysteine (NAC, an ROS scavenger). H2O2-induced decrease of cell viability was also attenuated by pretreatment with BHA and NAC. Furthermore, H2O2-induced increase of Bax, decrease of Bcl-2, and PARP-1 cleavage was also inhibited by BHA. Taken together, results of this investigation demonstrated that BHA protects primary cultured mouse hepatocytes against H2O2-induced apoptosis by inhibiting ROS generation.
Animals ; Apoptosis/*drug effects ; Butylated Hydroxyanisole/chemistry/*pharmacology ; Cell Survival/drug effects ; Cells, Cultured ; Hepatocytes/*drug effects ; Hydrogen Peroxide/*toxicity ; Male ; Mice ; Mice, Inbred ICR ; Molecular Structure

To study the pharmacokinetic characteristics and absolute bioavailability of α-asarone through dry powder inhalation in rats, and compare with that through oral administration and intravenous injection. A HPLC method was established for the determination of α-asarone in rat plasma to detect the changes in plasma concentrations of α-asarone through dry powder inhalation (20 mg · kg(-1)), oral administration (80 mg · kg(-1)) and intravenous injection (20 mg · kg(-1)) in rats. DAS 2.0 software was used to calculate the pharmacokinetic parameters. The absolute bioavailability of α-asarone was calculated according to AUC(0-t)) of administration routes and administration doses. According to the results, α-asarone showed good linear relations (r = 0. 999 4) at concentrations between 0.282-14.1 mg · L(-1), with the limit of detection (LOD) at 0.212 mg · L(-1). Through dry powder inhalation, oral administration and intravenous injection of α-asarone, the metabolic processes of α-asarone in rats conformed to one, two and three compartment models respectively, with the elimination half-life of (95.48 ± 48.28), (64.34 ± 27.59), (66.99 ± 29.76) min. According to the bioavailability formula, the absolute bioavailability of α-asarone through dry powder inhalation and oral administration were 78.32% and 33. 60%, respectively. This study showed that significant increase in elimination half-life and absolute bioavailability of α-asarone through dry powder inhalation, which lays a theoretical foundation for preparing α-asarone dry powder inhalers.
Administration, Inhalation ; Animals ; Anisoles ; administration & dosage ; blood ; pharmacokinetics ; Biological Availability ; Drugs, Chinese Herbal ; administration & dosage ; analysis ; pharmacokinetics ; Half-Life ; Male ; Rats ; Rats, Sprague-Dawley