[Pharmacokinetics, pharmacodynamics, and tissue distribution of oral co-loaded puerarin/daidzein mixed micelles in rats].

This study investigated the drug delivery performance of oral co-loaded puerarin(PUE) and daidzein(DAZ) mixed micelles(PUE/DAZ-FS/PMMs) from the perspectives of pharmacokinetics, pharmacodynamics, and tissue distribution. The changes in PUE plasma concentration in rats were evaluated based on PUE suspension, single drug-loaded micelles(PUE-FS/PMMs), and co-loaded micelles(PUE/DAZ-FS/PMMs). Spontaneously hypertensive rats(SHR) were used to monitor systolic blood pressure, diastolic blood pressure, and mean arterial pressure for 10 weeks after administration by tail volume manometry. The content of PUE in the heart, liver, spleen, lung, kidney, brain, and testes was determined using LC-MS/MS. The results showed that compared with PUE suspension and PUE-FS/PMMs, PUE/DAZ-FS/PMMs significantly increased C_(max) in rats(P<0.01) and had a relative bioavailability of 122%. The C_(max), AUC_(0-t), AUC_(0-∞), t_(1/2), and MRT of PUE/DAZ-FS/PMMs were 1.77, 1.22, 1.22, 1.17, and 1.13 times higher than those of PUE suspension, and 1.76, 1.16, 1.08, 0.84, and 0.78 times higher than those of PUE-FS/PMMs, respectively. Compared with the model control group, PUE/DAZ-FS/PMMs significantly reduced systolic blood pressure, diastolic blood pressure, and mean arterial pressure in SHR rats(P<0.05). The antihypertensive effect of PUE/DAZ-FS/PMMs was greater than that of PUE suspension, and even greater than that of PUE-FS/PMMs at high doses. Additionally, the distribution of PMMs in various tissues showed dose dependency. The distribution of PMMs in the kidney and liver, which are metabolically related tissues, was lower than that in the suspension group, while the distribution in the brain was higher than that in the conventional dose group. In conclusion, PUE/DAZ-FS/PMMs not only improved the bioavailability of PUE and synergistically enhanced its therapeutic effect but also prolonged the elimination of the drug to some extent. Furthermore, the micelles facilitated drug penetration through the blood-brain barrier. This study provides a foundation for the development of co-loaded mixed micelles containing homologous components.

[Pharmaceutics research advances in oral administration of puerarin].

Puerarin is a naturally occurring isoflavone C-glycoside,isolated from the root of Pueraria lobata,which has attracted extensive attention in the medical circles because of its various pharmacological effects,such as vasodilation,cardioprotection,neuroprotection,antioxidant,anticancer,anti-inflammation,alleviating pain,promoting bone formation,inhibiting alcohol intake,and attenuating insulin resistance. However,its low oral bioavailability has limited its clinical application. This review gives a comprehensive summary of the researches on physicochemical properties,pharmacokinetics( absorption,distribution,metabolism and excretion,pharmacokinetic parameters) in oral administration,and pharmaceutics research strategies of puerarin in recent years,and the in vivo behavior difference between multicomponent and single component environment was also summarized. The reasons( low water solubility,poor membrane permeability,short half-life,inhibition of P-gp efflux and first-pass metabolic effects of intestinal enzymes,etc.) for low bioavailability were concluded and the idea that multicomponent enviroment would affect the bioavailability was clarified. The aim of this review is to provide literature basis for the development of new dosage forms and new technologies for multivariate compound drug delivery system to improve the bioavailability of oral puerarin,and to propose ways to improve the bioavailability of BCS Ⅳ drugs derived from traditional Chinese medicine by fully enlarging the synergistic effect of multi-components or reasonably using the inhibitory effect between components.

[The molecular identification of licorice species and the quality evaluation of licorice slices].

Licorice is one of the most common herbs in traditional Chinese medicine, and classified as top grade in Shen Nong Ben Cao Jing. There are three different original plants of licorice stipulated in Chinese Pharmacopeia, Glycyrrhiza uralensis Fisch., Glycyrrhiza glabra L., and Glycyrrhiza inflata Bat. However, previous investigation showed that the pharmacodynamic effects of the three licorices were quite different. It is very difficult to identify them by the classical identification methods. In order to establish a fast and effective identification method, we collected 240 licorice plants from 21 populations of 7 provinces, and amplified their ITS and psbA-trnH sequences. ITS sequences with a full length of 616 bp and psbA-trnH sequences with a full length of 389 bp were obtained separately. Using DNAMAN to analyze these sequences, 4 variable sites were found in ITS sequences and 2 ITS haplotypes were determined, and 3 variable sites were found in psbA-trnH sequences and 4 psbA-trnH haplotypes were determined. With the combination analysis of ITS and psbA-trnH sequences, the molecular identification method of original licorice was established. Using this method, 40 samples of licorice slices collected from 4 main herbal material markets in China were identified successfully. Furthermore, the contents of 2 triterpenes, 18α-glycyrrhizic acid and 18ß-glycyrrhizic acid, and 4 flavonoids, liquiritin, isoliquiritin, liquiritigenin, and isoliquiritigenin in these licorice pieces were examined by HPLC and the results were analyzed using SPSS 21.0. This study provides a new method in identification of licorice, which may serve as a guideline for quality control of licorice slices.

[The molecular identification of Bupleurum medicinal species and the quality investigation of Bupleuri Radix].

Bupleuri Radix is one of the most frequently used herbal medicines in China with a 2 000-year medicinal history. However, the use of Bupleuri Radix is very confused. Twenty-five species and eight varieties of Bupleurum have been used as Bupleuri Radix in different regions of China. It is very difficult to identify these Bupleurum species using traditional morphological method. In order to establish a fast and effective method to identify these Bupleurum species, we collected 168 Bupleurum medicinal plants from 14 populations of 9 provinces, and amplified their ITS sequences. 168 ITS sequences with a full length of 600-606 bp were obtained. DNAMAN analyzing results showed that 86 variable sites were present in these sequences and 19 haplotypes (TH1-TH19) were determined. After calculating K2P distance and analyzing an NJ tree, we established a molecular identification method based on ITS sequence. Using this method, 52 samples of Bupleuri Radix were identified successfully. Furthermore, we tested saikosaponin a, c, d content in these Bupleuri Radix by HPLC and analyzed the results by ANOVA and LSD T test to evaluate the quality of Bupleuri Radix. This method is significant for effective identification of Bupleurum medicinal plants, and quality control of Bupleuri Radix in the market.

Enhancing ergosterol production in Pichia pastoris GS115 by overexpressing squalene synthase gene from Glycyrrhiza uralensis.

The present study was designed to determine the effects of copy number variations (CNVs) of squalene synthase 1(SQS1) gene on the mevalonate (MVA) pathway. SQS1 gene from G. uralensis (GuSQS1) was cloned and over-expressed in Pichia pastoris GS115. Six recombinant P. pastoris strains containing different copy number of GuSQS1 were constructed. HPLC was used to assay the level of ergosterol in all transgenic P. pastoris strains containing GuSQS1. HPLC analysis showed that the contents of ergosterol in all of the transgenic P. pastoris containing GuSQS1 were higher than that in the negative control. And with the increase of copy number of GuSQS1, the content of ergosterol showed an increasing-decreasing-increasing pattern. The contents of ergosterol in 10-copy-GuSQS1 P. pastoris and 47-copy-GuSQS1 P. pastoris were significantly higher than that in the rest recombinant P. pastoris strains. In conclusion, the CNVs of GuSQS1 influence the content of secondary metabolites in the MVA pathway. The present study provides a basis for over-expressing GuSQS1 and increasing the content of glycyrrhizin in G. uralensis cultivars.

Effect of Yiqi Bufei recipe see text on patients with pulmonary incompetence after pneumonectomy / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the effect of Yiqi Bufei Recipe ([see text], YBR) on surgical tolerability, pulmonary compensatory function and post-operation rehabilitation in patients with pulmonary incompetence (PI) after pneumonectomy.</p><p><b>METHODS</b>YBR intervention was applied to 60 patients with PI after pneumonectomy (as test group), the pulmonary and cardiac functions changes before and after operation, occurrence of postoperative complications, mortality, and the number of hospitalization days and intensive care unit (ICU) confinement period were observed. Meantime, for the negative and positive controls, the same parameters were observed comparatively in 60 patients with normal lung function, and in 60 patients with PI undergoing a similar operation but untreated with Chinese herbs.</p><p><b>RESULTS</b>Lung function in the test group showed insignificant change before and after operation (P >0.05), while significant decrease was seen in the two control groups (P<0.05). Furthermore, the incidences of post-operation complications and mortality as well as the number of hospitalization days and the ICU confinement period in the test group were significantly lower than those in the positive control group respectively (P <0.05).</p><p><b>CONCLUSION</b>YBR could relieve lung injury after pneumonectomy, improve surgical tolerability, reduce the length of postoperative hospitalization days and ICU confinement period, and lower the incidence of postoperative complications and mortality in patients with PI after pneumonectomy.</p>

Rule of Chinese medicine syndrome differentiation in the patients with thoracic diseases at perioperation stage / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the rule of syndrome differentiation in the patients with thoracic diseases at perioperation stage.</p><p><b>METHODS</b>A standard was created referring to the related literature, and it was applied to differentiate the Chinese medicine syndrome in 150 patients before and three days after thoracic operation.</p><p><b>RESULTS</b>Before operation, Chinese medicine syndromes were as differentiated as phlegm type in 45.3%, blood stasis type in 17.3%, and qi-stagnancy type in 16.0%. The patients with asthenia syndrome markedly increased after operation, accounting for 34.0% (51 patients, including qi-, yin-, and blood-deficiency syndromes). The most frequently seen intermixed syndromes were qi-deficiency with phlegm-stasis syndrome and Pi ()-deficiency with phlegm-dampness syndrome. The intermixed syndromes revealed in 37.5% and 42.0% of the patients before and after operation, respectively.</p><p><b>CONCLUSIONS</b>The syndrome in the patients with thoracic disease before operation was mostly the excessive syndrome, mainly the phlegm syndrome type; at postoperation stage, Chinese medicine syndrome in patients become asthenia in essence with excessive superficiality, which is mostly revealed as Pi-deficiency with phlegm-dampness.</p>

[Protective mechanism on the vascular pathological process in diabetes mellitus rats by Rheum officeinale].

OBJECTIVE: To explore the protective mechanism of officeihale on the vascular pathological process in diabetes mellitus (DM) rats. METHOD: After the DM rat model was established, 24 DM rats were randomly divided into model group (12 DM rats) and Rheum officeinale group (12 DM rats). Rheum officeinale was orally given in 10 g kg(-1) per day, and the other two groups were given equal pure water. 8 weeks later, blood samples were collected to determine the level of nitric oxide (NO) and endothelin-1 (ET-1). Thoracic aortic rings was prepared to observe the inhibiting effect of Ach with different concentration on contraction caused by NE. Another part of aorta was made to observe the expression of ICAM-1 and VCAM-1 by method of SP immunohistochemistry staining, RESULT: Rheum officeinale group obviously decreased the level of ET-1 and increased the NO compared with model group (P <0.05). The expression of ICAM-1 and VCAM-1 could be obviously inhibited in Rheum officeinale group compared with model group. (P <0.05). CONCLUSION: Rheum officeinale could decrease the level of ET-1 with increased the NO in diabetes rats, and inhibit the expression of ICAM-1 and VCAM-1, which may be mechanisms of protecting the endothelium of vessel in diabetes rats.

[Randomized controlled study on acupuncture for treatment of diabetic paralytic squint].

OBJECTIVE: To observe clinical therapeutic effect of acupuncture on diabetic paralytic squint. METHODS: Seventy-two cases of diabetic paralytic squint were randomly divided into a medication group, an acupuncture group and an acupuncture and medication group. The medication group were treated with intramuscular injection of Methyl vitamin B12 250 microg, once daily; the acupuncture group were treated by acupuncture at different acupoints according to different paralytic muscles of eyes with adjuvant acupoints selected according to symptoms; the acupuncture and medication group were treated with the routine medicine and acupuncture. The treatment was given for 28 days. RESULTS: The total effective rate of 87. 5% in the acupuncture group and 95.7% in the acupuncture and medication group were higher than 54.5% in the medication group (P < 0.05, P < 0.01), with no significant difference between the acupuncture group and the acupuncture and medication group (P > 0.05). CONCLUSION: Acupuncture has a definite therapeutic effect on diabetic paralytic squint, which is better than that of routine medication.

[Study on acupuncture treatment of diabetic neurogenic bladder].

OBJECTIVE: To probe into a better therapy for diabetic neurogenic bladder. METHODS: The patients were randomly divided into a treatment group and a control group, 35 cases in each group. The control group were treated with intramuscular injection of Methycobal 250 microg, once every other day; the treatment group were treated with intramuscular injection of Methycobal 250 microg, once every other day, and acupuncture at Guanyuan (CV 4), Shenshu (BL 23), Ciliao (BL 32), Huiyang (BL 35), once every day. The residual urine were compared before and after treatment in the two groups; the effective rate for improvement of symptoms were compared between the two groups. The mental and healthy nursing were conducted for the patients. RESULTS: After treatment, the improving rate for the urgency of urination, frequency of micturition, dribbling urination, urinary incontinence and dysuria in the treatment group was significantly better than that in the control group, but with no significant difference between the two groups in prolongation of urination time. After treatment, the residual urine in the bladder significantly improved in the two groups with more significantly improved in the treatment group than in the control group. CONCLUSION: Methycobal plus acupuncture has a better result than the simple Methyeobal for treatment of diabetic neurogenic bladder, and strengthening nursing care in the treatment can significantly enhance life quality of the patient.

Clinical observation on intervention of Yiqi Bufei Recipe in patients with severe pulmonary function incompetence after lung resection / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of Yiqi Bufei Recipe (YBR) on clinical symptoms, pulmonary function and recovery in patients with severe pulmonary function incompetence (PFI) after lung resection (LR).</p><p><b>METHODS</b>The clinical symptoms were observed, the pulmonary function examined and blood-gas analysis conducted in 30 patients with PFI after LR (the treatment group) and in 30 cases with normal pulmonary function after LR (the control group).</p><p><b>RESULTS</b>In the treatment group, clinical manifestations including cough, dyspnea, frequency of oxygen inhalation, and mobility, as well as the results of blood-gas analysis were improved after operation, while pulmonary function changed insignificantly. There was no significant difference in occurrence of postoperative complications and in-hospital mortality between the two groups (P > 0.05).</p><p><b>CONCLUSION</b>YBR can relieve acute lung injury caused by LR and improve the tolerance of patients with PFI for operation, which is benificial for postoperative recovery.</p>

Tissue distribution of Aconitum alkaloids extracted from Radix aconiti preparata after oral administration to rats.

AIM: To develop an HPLC method for the determination of Aconitum alkaloids extracted from Radix aconiti preparata in rats. METHODS: Waters 2690@996 PAD system was used. The analytical column was a Halsil 100 C18 column (250 mm x 4.6 mm ID, 5 microm). The mobile phase was water, methanol and diethyl amine at the ratio of 75:25:0.1. The flow rate was 0.9 mL.min(-1). The wavelength of the detector was 240 nm. RESULTS: The linear ranges of aconitine in the heart, spleen, lung and kidney were 0.4-100 microg.mL(-1), the correlation coefficients were 0.9972, 0.9986, 0.9993 and 0.9994, respectively. The linear range of aconitine in liver was 2-200 microg.mL(-1) and the correlation coefficient was 0.9990. The linear ranges of hypaconitine in heart, liver, spleen, lung, kidney, brain and spinal cord were 5-100 microg.mL(-1), the correlation coefficients were 0.9994, 0.9997, 0.9998, 0.9984, 0.9998, 0.9998 and 0.9997, respectively. Detection limits (S/N = 3) of aconitine and hypaconitine were 0.4 microg.mL(-1). The recoveries of aconitine and hypaconitine ranged from 88.7% to 102.2% and 86.5% to 101.3%, respectively, and the RSD of precision of aconitine and hypaconitine was 10%. CONCLUSION: It appears to be an accurate and effective method that can offer reference basis for in toxication of Radix aconiti preparata clinically.