Research progress in pharmacotherapy of insomnia / 中国中药杂志

Insomnia is extremely common and is a risk factor for a variety of physical and psychological disorders in addition to contributing to the reduced quality of life of patients and the burden of healthcare costs. Although cognitive behavioral therapy is the first-line treatment for insomnia, its difficulty of access and high cost have hindered its application. Therefore, pharmacotherapy remains the common treatment choice for patients and clinicians. Existing chemical drugs including benzodiazepine receptor agonists, dual orexin receptor antagonists, melatonin and its receptor agonists, histamine antagonists, antidepressants, and antipsychotics are able to induce and/or maintain sleep and have good therapeutic effects on acute insomnia, but their efficacy on chronic insomnia is indefinite. Furthermore, they have several side effects and affect sleep structure and physiological function. Under the guiding principle of holistic view and treatment based on syndrome differentiation, traditional Chinese medicine(TCM) has shown a good effect in clinical practice, but with little high-grade clinical evidence. The mechanism, dose, half-life period, adjustment of sleep structure, and side effects of hypnotic drugs are key factors to be considered for clinical use. This paper analyzed and summarized the drugs for insomnia from the above aspects, and is expected to provide references for the application and development of sedative and hypnotic drugs.

Metabolomic characteristics of spontaneously hypertensive rats under chronic stress and the treatment effect of Danzhi Xiaoyao Powder, a traditional Chinese medicine formula / 中西医结合学报

OBJECTIVE@#Numerous studies have demonstrated the close relationship between chronic stress and blood pressure (BP). Hypertensive subjects exhibit exaggerated reactions to stress, especially higher BP. The mechanisms by which stress affects pre-existing hypertension still need to be explored. Danzhi Xiaoyao Powder (DP), a historical traditional Chinese medicine formula, is a promising treatment for BP control in hypertensive patients under stress. The present study investigated the metabolomic disruption caused by chronic stress and the treatment effect and mechanism of DP.@*METHODS@#Spontaneously hypertensive rats (SHRs) were subjected to chronic restraint stress (CRS) for 4 weeks. BP was measured via the tail-cuff method, and anxiety-like behavior was quantified using the elevated-plus-maze test. Meanwhile, DP was administered intragastrically, and its effects were observed. Global metabolomic analysis was performed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, followed by multivariate statistical analysis to detect differential metabolites and pathways.@*RESULTS@#DP alleviated the CRS-induced increase in BP and anxiety-like behavior. Systematic metabolic differences were found among the three study groups. A total of 29 differential plasma metabolites were identified in both positive- and negative-ion modes. These metabolites were involved in triglyceride metabolism, amino acid (phenylalanine, tryptophan, and glycine) metabolism, and steroid hormone pathways.@*CONCLUSION@#These findings expose the metabolomic disturbances induced by chronic stress in SHRs and suggest an innovative treatment for this disorder.

Overview of Metabolomics in Research of Hypertension / 中国实验方剂学杂志

Hypertension is one of the most common chronic diseases, also an important risk factor for a series of cardio-and cerebra-vascular diseases. Due to its polygenic, multi-factorial nature and heterogeneity, the underlying cause has not been fully elucidated, satisfied therapeutic effect hasn't been totally achieved either. Metabolomics is used to evaluate metabolic changes of organisms from a holistic perspective, associating with biological processes to reveal the whole situation of the body. In recent years, researchers have used metabolomics to study the pathogenesis of hypertension, potential biomarkers, effects of lifestyle interventions, and mechanisms of antihypertensive drugs. Targeted or untargeted ways are applied to study metabolites form blood, urine, or tissues of human or animals. Metabolic pathways of gut microflora, oxidative stress, fatty acids, and amino acids have drawn more attention, and the discovered metabolites may become potential biomarkers, further the diagnostic biomarkers and treatment targets. In addition, traditional Chinese medicine (TCM) is an integrated complex system in syndrome diagnosis and treatment, and metabolomics coincides well with the concepts of it. TCM researchers also use this method to study the biological basis of syndromes in hypertension and the mechanism of antihypertensive Chinese medicine. There are significant differences in the metabolites between different syndromes. TCM treatments can restore the metabolite disturbance caused by high pressure, which is probably one of the pharmacological pathways of antihypertensive Chinese medicine. Metabolomic studies in hypertension have achieved great progress, but there're still challenges in data analysis, integration with other metabolomic studies and other omic studies and causal relationship in further study.

Withaminimas A-F, six withanolides with potential anti-inflammatory activity from Physalis minima / 中国天然药物

Withaminimas A-F (1-6), six new withaphysalin-type withanolides were isolated from the aerial parts of Physalis minima L.. The structures of these compounds were elucidated through a variety of spectroscopic techniques including HR-MS, NMR, and ECD. Compound 1 belongs to rare 18-norwithanolides, and 2-3 were 13/14-secowithanolides. According to the traditional usage of P. minima, inhibitory effects on nitric oxide (NO) production in lipopolysaccaride-activated RAW264.7 macrophages were evaluated, and compounds 1-4 exhibited significant inhibitory effects with IC values among 3.91-18.46 μmol·L.

Decitabine Enhances the Sensitivity of Leukemia Stem Cell to Allo-NK Cell-Mediated Killing / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the allo-NK cell-mediated killing effect enhanced by decitabine on leukemia stem cells(LSC) and the underlying mechanisms.</p><p><b>METHODS</b>LSC were separated from KG1a cells by using immunomagnetic beads. Allo-NK cells were isolated and purified from PBMC of healthy donors. Cytotoxicity of allo-NK cells against LSC were measured by LDH releasing assay. The apoptosis induced by allo-NK cells in LSC and the expressions of NKG2D ligands including MICA/B and ULBP1-3 on LSC were detected by flow cytometry.</p><p><b>RESULTS</b>The killing rate of allo-NK cells to LSC treated with 10 µmol/L decitabine for 24 hours was significant higher than that to LSC without treatment(60.52%±3.52% vs 22.08%±2.07%, 73.93%±2.33% vs 28. 99%±3.13%, 83.08%±1.32% vs 36.44%±2.40%, respectively)at the effector-target ratios of 5:1, 10:1, 20:1 (P<0.05). At the effector-target ratio of 10:1, decitabine significantly enhanced the apoptosis of LSC induced by allo-NK cells (7.84%±0.34% vs 3.33%±0.64%)(P<0.05). The expressions of NKG2D ligands(MICA/B,ULBP1,ULBP2,ULBP3) on LSC treated with decitabine 10 µmol/L for 24 hours were significantly increased (P<0.05).</p><p><b>CONCLUSION</b>Decitabine may enhance the allo-NK cell-mediated killing effects on LSC by up-regulation of the expressions of NKG2D ligands on LSC.</p>

Traditional herbal formula Sini Powder extract produces antidepressant-like effects through stress-related mechanisms in rats / 中国天然药物

Sini Powder (SP), a traditional Chinese herbal formula, has long been used to treat depression in patients, although the underlying mechanisms remain to be elucidated. In the present study, we found that rats treated with SP extract for 7 days showed a significant increase in swimming time and reduction in immobility time in forced swimming test in a dose-dependent manner, without changes in locomotion. These effects could be attributed to SP's modulation of the hypothalamus-pituitary-adrenal axis, because a single pretreatment of SP extract could rescue increased serum corticosterone and plasma adrenocorticotropin levels induced by acute elevated platform stress. A single pretreatment of SP extract could also elevate the mRNA expression of hippocampal glucocorticoid receptors. In conclusion, our results suggest that SP extract may act as an anti-stress medication to produce antidepressant-like effects.

Distribution of podophyllotoxin-loaded nanostructured lipid carriers after topical application on cervical mucosa in Tibet minipigs / 南方医科大学学报

<p><b>OBJECTIVE</b>To assess the distribution and systemic toxicity of podophyllotoxin-loaded nanostructured lipid carriers (POD-NLC) after topical application on the cervical mucosa in Tibet minipigs.</p><p><b>METHODS</b>Twelve Tibet mini-pigs were randomized into test group and control group to receive topical application of 0.5% POD-NLC and 0.5% POD tincture, respectively, on the cervical mucosa. Cervical mucosal irritation, targeted distribution and systemic absorption of POD were observed at different time points within 24 h after the drug application.</p><p><b>RESULTS</b>No local inflammation reaction was observed in the test group, while serious local irritations (swelling, blisters, blood blisters, erosion and ulceration) occurred in the control group. The fluorescence intensity of POD in the mucosal tissue reached the peak level at 4 h after drug application in the control group, while the POD fluorescence intensity increased slowly and reached the peak level at 16 h in the test group. The peak blood POD concentration occurred at 6 h after POD-NLC application in the test group (14.28∓0.33 ng/mL), as compared to 4 h in the control group (42.46∓0.32 ng/mL). At all the time points within 24 h, blood POD concentration remained significantly lower in the test group than in the control group (P<0.05), and the area under curve of blood POD concentration in the control group was 1.38-fold greater than that in the test group.</p><p><b>CONCLUSION</b>POD-NLC allows sustained release of POD and achieves a higher POD concentration in the mucosal tissue without causing local irritation or obvious systemic toxicity in Tibet minipigs.</p>

Simultaneous determination and assignment of 13 major flavonoids and glycyrrhizic acid in licorices by HPLC-DAD and Orbirap mass spectrometry analyses / 中国天然药物

To determine 13 flavonoids and glycyrrhizic acid in licorice (Glycyrrhiza spp.), several samples from different areas were examined by HPLC-DAD analysis. The analysis was performed on a Zorbax Extend-C18 (250 mm × 4.6 mm, 5 μm) column connected with a Zorbax Extend guard column (20 mm × 4.6 mm, 5 μm). The mobile phase consisted of (A) acetonitrile and (B) 0.026% aqueous H3PO4 (VV) using a gradient elution of 20%-25% A at 0-20 min, 25%-33% A at 20-30 min, 33%-50% A at 30-55 min, 50%-60% A at 55-65 min, and 60% A between 65 min and 80 min, and peaks were detected at 280 nm. The fourteen compounds were assigned by HPLC-Orbitrap MS methods. The regression coefficient for the linear equations for the 14 compounds ranged between 0.9998 and 1. The limits of detection and quantification lay in the range of 0.032-2.461 and 0.154-8.202 μg·mL(1), respectively. The relative recovery rates for the 14 compounds were in the range of 93.90%-106.73% with RSDs being less than 5%. Coefficient variations for intra-day and inter-day precisions were in the range of 0.27%-2.38% and 0.31%-3.51%, respectively. In summary, the validated method was applied to the simultaneous determination of the 14 components in 29 different licorice samples and was proven to be suitable for quality evaluation of licorices and their active fractions.

Treatment of osteochondritis lesion in the knee with reduction and fixation under arthroscopy / 中国骨伤

<p><b>OBJECTIVE</b>To study clinical results of reduction and fixation under arthroscopy for the treatment of osteochondrotical lesion in the knee.</p><p><b>METHODS</b>From December 2012 to December 2013, 4 patients with the knee joint osteochondritis lesion and free bone fragments were treated with arthroscopy to detect the stripped cartilage, and then the cartilages were reduced with small incision and fixed by cartilage nail. There were 3 males and 1 female, with age of 15, 15, 20 and 27 years old. The durations of the disease were 1 d, 5 d, 1 month and 1 year. All the patients had swelling and effusion in the knee joint, and the floating patellar test was positive. CT examination showed bone defects and loose bodies. The Lysholm, VAS, and Tegner scale were used to evaluate the knee joint functions before and after operation.</p><p><b>RESULTS</b>All the patients underwent successful surgery. Postoperative CT showed good location of the cartilage without loss of reduced bone and cartilage. All the patients were followed up, and the duration ranged from 10 to 13 months, with a mean of 12 months. In one patient, arthroscopy examination was conducted for a second time to examine the connection of the fracture part to the surrounding cartilage, and it showed that the internal fixator was not absorbed. The Lysholm, VAS and Tegner scale of all patients were better than those before operation.</p><p><b>CONCLUSION</b>Treatment of osteochondritis lesion with the fixation of absorbable cartilage nails may reconstruct the integrity of articular surface and recover the stability of joints, and it is an effective treatment method.</p>

The effect of exercises on TNF-alpha, IL-6 and adiponectin in different fat diet rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To evaluate the role of serum tumor necrosis factor-alpha (TNF-alpha) and adiponectin on insulin resistance in different fat diet rats.</p><p><b>METHODS</b>Thirty weanling female rats were randomly divided into 3 group (n = 10): a low-fat soybean oil (LFS; 22% of total energy fed as fat), high-fat soybean oil (HFS; 40% of total energy fed as fat), or high-fat soybean oil and swimming training at the same time (HFS + T). After fed for 10 weeks, the level of TNF-alpha, adiponectin in serum of rats were observed.</p><p><b>RESULTS</b>(1) The body weight, percentage of body fat of HFS group increased compared with that of LFS group (P < 0.05), however those of HFS + T group were decreased (P < 0.05). (2) The level of serum insulin and ISI in HFS group were increased by LFS group (P < 0.05), in HFS+ T group the levels decreased. (3) And the serum level of TNF-alpha and IL-6 in HFS group were higher than those in LFS group (P < 0.05), the serum levels of adiponectin in HFS group were lower than those in LFS rats, and in HFS+ T group the levels of TNF-alpha and IL-6 were lower than those in HFS group (P < 0.05), the adiponectin level was higher than that in HFS group, and there were no significant difference between LFS group and HFS + T group.</p><p><b>CONCLUSION</b>Exercises training could improve sugar and fat metabolism disorders, which also contributes to improving insulin resistance caused by high-fat diet.</p>

Construction of the safety evaluation platform related to formula-medicine dose in TCM / 中国药学杂志

OBJECTIVE: To put forward a method of construction of the safety evaluation platform related to formula-medicine dose of TCM because of the lack of the dose-effect relationship research and the insufficient of safety monitoring in Chinese medicine. METHODS: Under the guidance of Chinese medicine theory, an ADR (adverse drug reaction)/ADE (adverse drug event) monitoring scale with TCM characteristics was developed based on patients reporting, thus to promote positive and prospective evaluation researches related to formula-medicine dose. On the basis of the ADR/ADE data base, the safety monitoring module will be formed then. RESULTS AND CONCLUSION: The safety evaluation platform related to formula-medicine dose is supposed to be structured.

Nicotine enhances insulin sensitivity in rats / 第二军医大学学报

Objective: To investigate the effect of nicotine on insulin sensitivity in rats and its relationship with PPAR-γ. Methods: Male Sprague-Dawley rats (10-11 weeks old) were randomly divided into saline group and nicotine group, and the two groups were further divided into 3 subgroups: 1 week, 3 weeks, and 6 weeks subgroups according to the time they were treated by different agents. Rats were subcutaneously injected with saline (saline group) daily or nicotine (3 mg·kg-1·d-1, nicotine group) for 1 week, 3 weeks, and 6 weeks. The body weights of animals were recorded on a weekly basis. Insulin tolerance tests were performed at 3 weeks and 6 weeks after treatment, and the serum parameters were determined at 1 week, 3 weeks, and 6 weeks after drug administration. At the end of the experiment, fat tissue weights of different body parts were weighed, and PPAR-γ expression in the subcutaneous fat and visceral fat was detected by Western blotting analysis. Results: The body weight increase of rats was inhibited after nicotine treatment. Insulin sensitivity of rats was significantly enhanced 3 weeks and 6 weeks after nicotine treatment (P<0.05), serum triglyceride level was decreased significantly at 3 weeks after nicotine treatment (P<0.01), insulin sensitivity indices were increased after 6 weeks (P<0.05), and both the weight and relative weight of subcutaneous and visceral fat tissues were significantly decreased 6 weeks after nicotine treatment (P<0.01), with the visceral fat decreased more severely than that of the subcutaneous fat. PPAR-γ expressions in the subcutaneous fat and visceral fat tissues were not significantly different between saline and nicotine treated groups. Conclusion: Nicotine can improve insulin sensitivity in rats, which is partly due to the fact that nicotine can decrease the serum triglyceride levels and fat tissue, especially the visceral fat tissue, but has no relation with PPAR-γ protein expression in fat tissue.