平、滑、弦脉的脉图分类参数范围研究

目的以单部脉脉图为依据,建立平、滑、弦三种脉象的特征参数及正常医学指标参考范围。方法分析447例非疾病人群的脉图,其中平脉脉图171例,弦脉脉图118例,滑脉脉图158例。对脉图幅值、时值等特征参数进行分析,探讨平、滑、弦脉特征参数指标与分布范围。结果平脉、弦脉、滑脉两两比较,h_1/t_1、h_3/h_1及h_4/h_1比值差异有统计学意义(P0.01)。平脉与滑脉比较,w/t比值差异无统计学意义(P0.05);弦脉与滑脉、平脉与弦脉比较,w/t比值差异有统计学意义(P0.01)。通过测量脉图特征参数的指标范围,建立了三种脉象特征参数的正常医学指标参考范围。结论基于以h_3/h_1、h_4/h_1、w/t和脉形为核心的指标参数,可以建立平脉、弦脉、滑脉脉图的判别标准。     

348例小儿反复呼吸道感染中医证型与脉图参数的相关研究

目的：探讨小儿反复呼吸道感染不同中医证型的脉图参数,为临床诊疗提供一定的客观依据及疗效评价指标。方法：348例反复呼吸道感染患儿分为肺气虚组、风热犯肺组、痰湿阻肺组、痰热壅肺组、风寒犯肺组共5组,65例健康幼儿作为对照组,应用Z-BOX脉象仪检测各受试者脉图参数,并进行统计分析。结果：与健康对照组比较：易感儿组h₁、h₃、h₄、h₅、t、h₄/h₁降低;小儿反复呼吸道感染肺气虚组h₁、h₃、h₄、h₅降低;风热犯肺组h₄、h₅、t、w、h₃/h₁、h₄/h₁、h₅/h₁降低;痰热壅肺组h₁、h₃、h₄、h₅、t、w、h₃/h₁、h₄/h₁降低;风寒犯肺组h₅、t、h₅/h₁降低。与肺气虚组比较：风热犯肺组h₁升高;风热犯肺组w、h₃/h₁、h₅/h₁、w/t降低;痰湿阻肺组h1升高;痰热壅肺组w、h₃/h₁降低;风寒犯肺组h₅/h₁降低。与风热犯肺组比较：痰湿阻肺组t、w、h₅/h₁升高;痰热壅肺组h₁、h₃降低。与痰湿阻肺组比较：痰热壅肺组h₃、h₄、t、w降低;风寒犯肺组t降低。结论：脉图参数可为小儿反复呼吸道感染辨证分型提供客观依据。     

159例原发性高血压病合并靶器官损害患者脉图参数分析

目的：本研究主要探讨原发性高血压病合并不同靶器官损害患者脉图时域参数的变化规律。方法：应用ZBOX-Ⅰ型中医脉象数字化分析仪记录159例原发性高血压病病患者和65例正常人的脉图,比较原发性高血压病合并心、肾、血管等不同靶器官损害患者以及原发性高血压病病合并单器官损害、两器官损害、三器官损害患者脉图时域参数的差异。结果：原发性高血压病病心脏损害组、肾脏损害组、血管损害组脉图参数h₃、h₄、h₃/h₁、w/t明显高于健康对照组（P<0.05）;原发性高血压病合并心脏损害组、肾脏损害组、血管损害组脉图参数h₅明显低于健康对照组（P<0.05）。原发性高血压病合并肾脏损害组、血管损害组脉图参数h₃/h₁、h₄/h₁、w/t明显高于心脏损害组（P<0.05）;原发性高血压病并肾脏损害组脉图参数h₁、h₃、h₅明显高于心脏损害组（P<0.05）;原发性高血压病并血管损害组脉图参数h₅明显低于心脏损害组（P<0.05）。原发性高血压病并两器官损害组脉图参数h₁、h₃、h₄明显低于单器官损害组（P<0.05）;原发性高血压病并三器官损害组脉图参数h₄/h₁、h₃/h₁明显低于单器官损害组（P<0.05）;原发性高血压病并两器官损害组脉图参数w/t明显高于单器官损害组（P<0.05）。结论：原发性高血压病患者不同靶器官损害患者脉图参数能反映其动脉粥样硬化、外周阻力增大的特点;原发性高血压病患者靶器官损害数量增加,脉图参数呈现相应变化。中医脉图参数可为原发性高血压病靶器官损害的诊断和防治提供参考。     

Aqueous extract of Astragali Radix ameliorates proteinuria in adriamycin nephropathy rats through inhibition of oxidative stress and endothelial nitric oxide synthase

Aim of the study

To investigate the effects of aqueous extract of Astragali Radix (ARE) on the oxidative stress status and endothelial nitric oxide synthase level in adriamycin (ADR) nephropathy rats.

Materials and methods

ADR nephropathy rats were randomly treated with ARE (2.5 g/kg/d, n = 6, ARE group), or benazepril (10 mg/kg/d, n = 6, angiotensin-converting enzyme inhibitor (ACEI) group) for ten weeks. Serum urea nitrogen, creatinine, albumin, total protein, cholesterol and 24-h urinary protein concentration were determined. Renal cortex catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), malondialdehyde (MDA) activities, and 24-h urinary NO₃⁻/NO₂⁻ excretion were determined by chromatometry. Renal cortex cyclic guanosine monophosphate (cGMP) level was measured by enzyme immunoassay and eNOS expression was determined by immunohistochemistry.

Results

ARE and ACEI treatments could remarkably reduce more 24 h urinary protein excretion than that in ADR group (88.32 ± 9.96 mg, 81.78 ± 16.28 mg vs. 153.91 ± 28.63 mg, P < 0.01), and there was no difference between ARE and ACEI group. Renal cortex CAT, GSH-Px activities in ARE and ACEI group were significantly higher than ADR group, and renal cortex SOD activity in ARE group was higher than ADR group. Renal cortex MDA activity, cGMP level, and glomerular and tubular eNOS expression in ARE and ACEI group were lower than that in ADR group, and 24-h urinary NO₃⁻/NO₂⁻ excretion in ARE group was lower than ADR group. Renal cortex MDA content (r = 0.895, P < 0.01), cGMP content (r = 0.666, P < 0.01) and eNOS expression in glomerulus (r = 0.910, P < 0.01) were strongly positively associated with 24 h urinary protein excretion. And renal cortex SOD content was negatively associated with 24 h urinary protein excretion (r = −0.861, P < 0.01).

Conclusions

ARE may ameliorate the proteinuria by suppressing the over expression of eNOS, and inhibiting the oxidative injury in ADR nephropathy rats.     

基于脉图参数的原发性高血压合并不同程度靶器官损害患者判别分析＊

目的 本研究旨在探讨脉图参数对于原发性高血压合并不同程度靶器官损害患者的判别分类价值。方法 采集原发性高血压患者458例，分为原发性高血压合并无靶器官损害组、单个靶器官损害组、多个靶器官损害组，分别取脉图参数h₃/h₁、h₄/h₁、w₁/t、w₂/t未分类情况下的连续变量和分级后的分类变量，应用Fisher判别分析法对三组进行分类，比较两种变量的判别分类结果。结果 基于脉图参数连续变量，对三组判别分类的正确率为88.2%，验证结果为87.3%，三组中无靶器官损害组的分类效果最好，为97.8%；从整体来看，脉图参数h₃/h₁、w₁/t判别函数系数较大，对分类结果的影响较大；脉图参数w₁/t、w₂/t对无靶器官损害组的分类结果影响较大，h₃/h₁、w₂/t对单个靶器官损害组的分类结果影响较大，h₃/h₁、h₄/h₁、w₁/t、w₂/t对多个靶器官损害组的分类结果影响均较大。基于脉图参数分类变量，对三组判别分类的正确率为99.1%，优于脉图参数连续变量的判别分类结果；脉图参数h₄/h₁、w₂/t对三组的分类结果影响均较大。结论 脉图参数分级变量对原发性高血压合并不同程度靶器官损害患者的分类效果优于连续变量；脉图参数连续变量h₃/h₁、w₁/t对原发性高血压合并不同程度靶器官损害组的判别分类结果影响较大，脉图参数分级变量h₄/h₁、w₂/t对原发性高血压合并不同程度靶器官损害组的判别分类结果影响较大，脉图参数对原发性高血压合并不同程度靶器官损害患者的分类识别有一定的参考价值。     

Effectiveness of external Sanjierupi Gao on mastalgia caused by mammary gland hyperplasia: a placebo controlled trial

Objective

To evaluate the curative effect of external application of the Chinese drug, Sanjierupi Gao, on mastalgia caused by mammary gland hyperplasia.

Methods

This randomized, double-blinded, and placebo controlled study enrolled 260 patients with mammary gland hyperplasia from five hospitals. Patients were randomly and equally divided into a Sanjierupi Gao treatment group and a placebo control group. An adhesive plaster was applied to the most painful area on either breast for 7 h a day. Treatment lasted for two menstrual cycles without application during menstruation. Mastalgia was used as the main index of curative effect. The change before and after treatment in days of mastalgia, the time to alleviate pain, pain extent, and severe pain scores were observed.

Results

Compared to the control group, the treatment group had significantly fewer days of mastalgia (P<0.01), a significantly lower severe pain score (P<0.01), and significantly less subjective pain and tenderness (P<0.05 and P<0.01, respectively). Three days before the follow-up visit, the pain score in the treatment group was significantly lower than that in the control group (P<0.05). A non-parametric test was used to compare the time to alleviate mastalgia between the two groups and found no statistical difference (Z=−0.313, P=0.754).

Conclusion

Application of Sanjierupi Gao can decrease mastalgia duration in patients with mammary gland hyperplasia during menstruation and alleviate the extent of mastalgia. The time to alleviate pain is psychologically influenced.     

The effects of Rhizoma Zingiberis on pharmacokinetics of six Aconitum alkaloids in herb couple of Radix Aconiti Lateralis−Rhizoma Zingiberis

Ethnopharmacological relevance

Radix Aconiti Lateralis (Fuzi in Chinese, derived from the lateral roots of Aconitum Carmichaeli Debx.) is widely used for the treatment of heart failure, internal cold, arthralgia, diarrhea and edema for thousands of years. It was usually prescribed in combination with Rhizoma Zingiberis (Ganjiang in Chinese, derived from the dry rhizome of Zingiber officinale Rosc.) to decrease toxicity and increase efficacy.

Aim of the study

In order to investigate the influence of Rhizoma Zingiberis on pharmacokinetics of six Aconitum alkaloids, i.e. aconitine (AC), hypaconitine (HA), mesaconitine (MA), benzoylaconine (BAC), benzoylhypaconine (BHA) and benzoylmesaconine (BMA), in Fuzi−Ganjiang herb couple, the comparative pharmacokinetics of six Aconitum alkaloids after oral administration of Fuzi and Fuzi−Ganjiang aqueous extract was carried out.

Materials and methods

A sensitive, specific and rapid LC−MS/MS method was developed to determine the six analytes in plasma. Then the rats were randomly divided into two groups and orally administered with Fuzi and Fuzi−Ganjiang aqueous extract. At designated time points after oral administration, the concentrations of the six Aconitum alkaloids in rat plasma were determined, and main pharmacokinetic parameters were investigated using 3P97 (Practical Pharmacokinetics Program Version 1.0).

Results

Comparing with Fuzi group, both T_1/2 and AUC_0−t of AC and HA decreased (P<0.05), while T_1/2, AUC_0−t and C_max of BAC, BHA increased (P<0.05) in Fuzi−Ganjiang group, which indicated that Ganjiang could promote the elimination of AC and HA and enhance the absorption of BAC, BHA and BMA.

Conclusion

The differences of pharmacokinetics of Aconitum alkaloids in rat plasma could support those of pharmacologics and toxicity in previous reports between Fuzi and Fuzi−Ganjiang herb couple. The results might be helpful in explaining the mechanism of combination of Fuzi−Ganjiang to decrease toxicity and increase efficacy.     

Spleen-Yang-deficiency patients with polycystic ovary syndrome have higher levels of visfatin

Objective

To study serum visfatin levels in women with polycystic ovary syndrome (PCOS) grouped by Traditional Chinese Medicine (TCM) patterns. To study the correlations of serum visfatin levels with homeostatic model assessment insulin resistance (HOMA-IR), fasting plasma glucose (FPG), fasting insulin (FINS), body mass index (BMI), testosterone (T), total cholesterol (TC), and triglycerides (TG).

Methods

Two hundred and twelve PCOS patients were placed into the following TCM pattern subgroups: Kidney-Yang deficiency (KYD) group, Spleen-Yang deficiency (SYD) group, stagnant Liver-Qi transforming into heat (SLQTH) group, and Kidney-Yin deficiency (KYIND) group. The correlations between serum visfatin levels and HOMA-IR, FPG, FINS, BMI, T, TC, and TG were analyzed.

Results

Of all patients with PCOS, there were 82 in the KYD group (38.6%), 67 in the SYD group (31.6%), 37 in the SLQTH group (17.5%), and 26 in the KYIND group (12.3%). Visfatin levels in all PCOS subgroups were higher than those in the control group (P<0.01 or P<0.05). Among these subgroups, the visfatin levels in the SYD group were significantly higher than those in the other three TCM pattern groups (P<0.05). There were no statistical differences among the remaining three pattern groups. The levels of BMI, FINS, HOMA-IR, T, and TG were significantly higher in all subgroups than those in the control group (P<0.05). There were no significant differences in FPG and TC between all PCOS subgroups and the control group (P>0.05). The SYD group had higher levels of FINS and HOMA-IR compared with the KYD, SLQTH, and KYIND groups (P<0.05). In all subgroups, after controlling for BMI, TG, TC, and age, visfatin was positively correlated with FINS (r= 0.197, P=0.015) and HOMA-IR (r=0.173, P=0.033), and was not correlated with T.

Conclusion

KYD and SYD patterns are most common in PCOS patients. Increased visfatin is a common pathophysiologic manifestation in PCOS patients. The SYD group had the highest levels of visfatin, and visfatin was positively correlated with FINS and HOMA-IR.     

Meta-analysis of the effect of herbal supplement on glycemic control in type 2 diabetes

Ethnopharmacological relevance

A variety of herbs has been used in traditional medicine for the treatment of diabetes. However, evidence is limited regarding the efficacy of individual herbs for glycemic control.We performed a systematic review and meta-analysis to evaluate the effect of herbal supplement on glycemic control in type 2 diabetes.

Materials and methods

Randomized controlled trials were identified through electronic searches (MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials) up until February 2011, historical searches of relevant articles and personal contact with experts in the area. Studies were included in the meta-analysis if they were (1) randomized placebo-controlled trial of single herb aimed at assessing glycemic control in type 2 diabetes, (2) of at least 8 weeks duration, and (3) reporting HbA_1c. Treatment effect was estimated with mean difference in the final value of HbA_1c and FBG between the treatment and the placebo groups.

Results

Nine randomized, placebo-controlled trials (n = 487 patients) were identified. Ipomoea batatas, Silybum marianum and Trigonella foenum-graecum significantly improved glycemic control, whereas Cinnamomum cassia did not. The pooled mean differences in HbA_1c were −0.30% (95% CI −0.04% to −0.57%; P = 0.02), −1.92% (95% CI −0.51% to −3.32%; P = 0.008), and −1.13% (95% CI −0.11% to −2.14%; P = 0.03), respectively, for Ipomoea batatas, Silybum marianum, and Trigonella foenum-graecum. The corresponding values for FBG were −10.20 mg/dL (95% CI −5.32 mg/dL to −15.08 mg/dL; P < 0.0001) and −38.05 mg/dL (95% CI −9.54 mg/dL to −66.57 mg/dL; P = 0.009), respectively, for Ipomoea batatas and Silybum marianum.

Conclusions

The current evidence suggests that supplementation with Ipomoea batatas, Silybum marianum, and Trigonella foenum-graecum may improve glycemic control in type 2 diabetes. Such effect was not observed with Cinnamomum cassia. Given the limitations of the available studies and high heterogeneity of the study results for milk thistle and fenugreek, further high quality, large controlled trials using standardized preparation are warranted to better elucidate the effects of these herbs on glycemic control in type 2 diabetes patients.     

A clinical trial of acupuncture about time-varying treatment and points selection in primary dysmenorrhea

Objective

To observe the clinical therapeutic effects of acupuncture at single point Shiqizhui (EX-B8) and multi-points in time-varying treatment for primary dysmenorrhea.

Methods

600 patients with primary dysmenorrhea were randomly assigned to the single point group (n=200) including group A (treating before the menstruation, n=100) and group B (immediately treating as soon as pain occurrence, n=100), the multi-points group (n=200) including group C (treating before the menstruation, n=100) and group D (immediately treating as soon as pain occurrence, n=100), or the control group, group E (n=200, no treatment). The therapeutic effects were analyzed after treatment for three menstrual cycles and interviewed for three follow-up periods.

Results

Acupuncture could effectively relieve menstrual pain for primary dysmenorrhea compared with the control group (P<0.05, P<0.01). Immediate pain relief occurred following acupuncture within 5 min in group B (P<0.01) and group D (P<0.01), and the two groups obviously relieved menstrual pain for VAS scores. Both group A and group C obviously relieved menstrual pain (P<0.01), and group C was better than group A (P<0.05). Compared with group D, Group C was much better for CMSS scores in cycle 1.

Conclusion

Treating before the menstruation is better than immediately treating as soon as pain occurrence at the improvement in symptoms of dysmenorrheal at multi-points. And single point is better than multi-points when immediately treating as soon as pain occurrence. The present trial suggest Shiqizhui (EX-B8) should be chosen as a convenient point.     

Qingkailing injection for the treatment of acute stroke: a systematic review and Meta-analysis

Objective

To evaluate systematically the clinical efficacy and safety of Qingkailing (QKL) injection in the treatment of acute stroke.

Methods

Searches for randomized controlled trials into acute stroke treated with QKL injection were performed in the China National Knowledge Infrastructure Database, China Science and Technology Journal Database, Wan fang Database, Chinese Biomedical Literature Database, PubMed and Cochrane Library, from January 1979 to March 2013. Two reviewers independently retrieved the RCTs and extracted the information. The Cochrane risk of bias method was used to assess the quality of the included studies, and a Meta-analysis was conducted with Review Manager 5.2 software.

Results

A total of 13 studies with 1110 participants were included. The quality of the studies was generally low. The Meta-analysis indicated that the combined use of QKL and Western Medicine was significantly superior to control group therapy in terms of the total effective rate. The relative risk (RR) in the acute cerebral hemorrhage (ACH) sub-group was 1.17 [95% confidence interval (CI) (1.08, 1.26), P=0.0001]. In the acute cerebral infarction (ACI) sub-group, RR was 1.27 [95% CI (1.14, 1.42), P<0.0001], and in the ACH and ACI mixed sub-group, RR was 1.34 [95% CI (1.20, 1.50), P<0.00001]. Additionally, QKL promoted the absorption of hematoma [mean difference (MD)= − 3.73, 95% CI (− 4.48, − 2.98), P<0.000 01], decreased neurological damage in ACI [MD= − 5.60, 95% CI (− 8.50, − 2.70), P=0.0002] and ACH [MD= − 4.08, 95% CI (− 8.00, − 0.16), P=0.04], promoted the recovery of awareness [RR=1.56, 95% CI (1.09, 2.21), P=0.01] and reduced the whole blood viscosity coefficient [MD= − 0.75, 95% CI (− 1.47, − 0.03), P=0.04]. There were no adverse drug reactions reported in the included studies.

Conclusion

Based on this systematic review, QKL combined with conventional therapy was effective compared with control treatment. However, because the articles used in the study were not of high quality, further studies should be conducted into the efficacy and safety of QKL in treating acute stroke.     

Combination use of ferulic acid,ligustrazine and tetrahydropalmatine inhibits the growth of ectopic endometrial tissue: A multi-target therapy for endometriosis rats

Ethnopharmacological relevance

Ferulic acid (FA), ligustrazine (LZ) and tetrahydropalmatine (THP) are separately isolated from Chinese Angelica, Szechwan Lovage Rhizome and Rhizoma in the Jiawei-Foshou-San formula, a popular traditional Chinese medicine for irregular menses. It has been reported that the combination use of FA+LZ+THP has similar effect on endometriosis, but the underlying mechanisms are unclear. This study was to investigate the combination effects and mechanisms of FA+LZ+THP on endometriosis rats.

Materials and methods

Fifty endometriosis rats were intragastricly treated with FA+LZ+THP for 4 wk. The volume of ectopic endometrial tissue was measured to evaluate the effects. Then the changes in hypothalamic–pituitary–ovarian axis and ERE pathway were indicated by the levels of E₂, GnRH, FSH and LH, and the expressions of ER, HSP90 and COX-2, respectively. In addition, peritoneal macrophages of each rat were cultured in vitro and treated with (FA+LZ+THP)-medicated serum for 24 h. The proliferation and phagocytosis abilities, the levels of IL-1β and TNF-α, and the expression of IκBα were then measured for the changes of peritoneal macrophage activities.

Results

Combination use of FA+LZ+THP diminished the volume of the ectopic endometrial tissues (P<0.05 or P<0.01). It also decreased the E₂ level, suppressed the expression of GnRH, FSH and LH, and decreased the protein expression of ER, HSP90 and COX-2 (all P<0.05 or P<0.01). The phagocytosis ability of peritoneal macrophage was enhanced by (FA+LZ+THP)-medicated serum (P<0.05) with no change of proliferation (P>0.05). Moreover, IL-1β and TNF-α were downregulated (both P<0.05 or P<0.01) and IκBα was upregulated by the (FA+LZ+THP)-medicated serum (P<0.01).

Conclusions

The combination use of FA, LZ and THP could inhibit the growth of ectopic endometrial tissue in endometriosis rats. It might be related to the down-regulation of hypothalamic–pituitary–ovarian axis, the amelioration in ERE pathway and the improvement of peritoneal macrophage activities.     

Effect of moxibustion on the expression levels of proteins of neuron and neuropeptide in the intestinal tract of rats with Crohn's disease

Objective

To explore the regulating effect of moxibustion on the enteric nervous system of rats with Crohn's disease.

Comparisons of pharmacokinetic and tissue distribution profile of four major bioactive components after oral administration of Xiang–Fu–Si–Wu Decoction effective fraction in normal and dysmenorrheal symptom rats

Ethnopharmacological relevance

Xiang–Fu–Si–Wu Decoction (XFSWD) has been widely used to treat primary dysmenorrhea in clinical practice for hundreds of years and shown great efficacy. One fraction of XFSWD, which was an elution product by macroporous adsorption resin from aqueous extract solution with 60% ethanol (XFSWE), showed great analgesic effect. The present study was conducted to investigate the possible pharmacokinetic and tissue distribution profiles of four major bioactive constituents (berberine, protopine, tetrahydrocoptisine and tetrahydropalmatine) after oral administration of XFSWE in dysmenorrheal symptom rats, and to compare the difference between normal and dysmenorrheal symptom rats.

Materials and methods

Estradiol benzoate and oxytocin were used to produce dysmenorrheal symptom rat model. The experimental period was seven days. At the final day of experimental period, both normal and dysmenorrheal symptom rats were orally administrated with XFSWE, and then the blood and tissues samples were collected at different time points. Berberine, protopine, tetrahydrocoptisine and tetrahydropalmatine in blood and tissue samples were determined by LC–MS/MS. Pharmacokinetic parameters were calculated from the plasma concentration–time data using non-compartmental methods. The differences of pharmacokinetic parameters among groups were tested by one-way analysis of variance (ANOVA).

Results

There were statistically significant differences (P<0.05) in C_max, T_max, AUC_0−t, AUC_0−∞, MRT_0−t, MRT_0−∞ and CL/F between normal and dysmenorrheal symptom rats that orally administered with same dosage of XFSWE. In tissue distribution study, the results showed that the overall trend was C_Spleen>C_Liver>C_Kidney>C_Uterus>C_Heart>C_Lung>C_Ovary>C_Brain>C_Thymus, C_M-60 min>C_M-120 min>C_M-30 min>C_C-60 min>C_C-120 min>C_C-30 min. The contents of protopine in liver, spleen and uterus were more than that in other tissues of dysmenorrheal symptom rats. Compared to normal rats, partial contents of the compounds in dysmenorrheal symptom rats? tissues at different time points had significant difference (P<0.05).

Conclusions

This study was the first report about pharmacokinetic and tissue distribution investigation in dysmenorrheal symptom animals. The results indicated that berberine, protopine, tetrahydrocoptisine and tetrahydropalmatine have higher uptake and slower elimination in the rats with dysmenorrheal syndrome, which suggests that the rate and extent of drug metabolism were altered in dysmenorrheal syndrome rats. And the results also demonstrated that berberine, protopine and tetrahydropalmatine in normal and dysmenorrheal symptom rats had obvious differences in some organs and time points, suggesting that the blood flow and perfusion rate of the organ were altered in dysmenorrheal symptom animals.     

Effects of moxibustion at different times on prostaglandin and vasopressin levels in uterine tissues of rats with dysmenorrhea due to cold-dampness retention

Objective

To observe the effects of moxibustion at different times on prostaglandin E₂ (PGE₂), prostaglandin F_2α (PGF_2α) and arginine vasopressin (AVP), in the uterine tissues of rats with dysmenorrhea due to cold-dampness retention, and to explore the differences and possible mechanisms of moxibustion at different times in easing pain in dysmenorrhea due to cold-dampness retention.

Methods

Forty-three female Wistar rats were randomly divided into a blank control group (n=7), a model group (n=9), a pre-moxibustion group (n=9), an immediate-moxibustion group (n=9) and a pre-moxibustion plus immediatemoxibustion group (n=9). Rat models of primary dysmenorrhea due to cold-dampness retention were established using (0±1) °C ice water immersion method combined with injection of estradiol benzoate for 10 d, followed by injection of oxytocin on the 11th day. Rats in the 3 intervention groups received moxibustion to Shenque (CV 8) and Guanyuan (CV 4), 10 min for each acupoint, once a day. Rats in pre-moxibustion group were given mild moxibustion, beginning on the 8th day during modeling, for 3 continuous days; rats in immediate-moxibustion group were given one time mild moxibustion, immediately after injection of oxytocin on the 11th day during modeling; rats in pre-moxibustion plus immediate-moxibustion group were given mild moxibustion, beginning on the 8th day during modeling till immediately after injection of oxytocin on the 11th day during modeling, for 4 continuous days. The level of PGF_2α in the rat uterine tissues was measured by enzyme-linked immunosorbent assay (ELISA), and the levels of PGE₂ and AVP in rat uterine tissues were measured by radioimmunoassay.

Results

Compared with the blank control group, the levels of PGF_2α and AVP, the PGF_2α/PGE₂ ratio in the model group were significantly increased (P<0.01), and the PGE₂ level was significantly decreased (P<0.01) in the rat uterine tissues in the model group. Compared with the model group, the writhing latency was significantly prolonged, the writhing number and the total writhing score were all decreased in the pre-moxibustion group, the immediate-moxibustion group and the pre-moxibustion plus immediate-moxibustion group (all P<0.01); the levels of PGF_2α and AVP, and the PGF_2α/PGE₂ ratio were all significantly decreased (P<0.05, P<0.01), and the PGE₂ level was significantly increased (P<0.01) in the rat uterine tissues of the 3 treatment groups. Compared with the pre-moxibustion group, the writhing number and the total writhing score were all decreased in the immediate-moxibustion group and the pre-moxibustion plus immediate-moxibustion group (all P<0.01), the writhing latency was significantly prolonged in the pre-moxibustion plus immediate-moxibustion group(P<0.01); the levels of PGF_2α and PGF_2α/PGE₂ ratio were significantly decreased (P<0.05, P<0.01), and the PGE₂ level was significantly increased (P<0.01) in rat uterine tissues in the immediate-moxibustion group and the pre-moxibustion plus immediate-moxibustion group. Compared with the immediate-moxibustion group, the writhing latency was significantly prolonged and the writhing number was decreased (all P<0.05), and the total writhing score was decreased (P<0.01) in the pre-moxibustion plus immediatemoxibustion group; the PGF_2α level and the PGF_2α/PGE₂ ratio were significantly decreased (P<0.01), and the PGE₂ level was significantly increased (P<0.01) in rat uterine tissues in the pre-moxibustion plus immediate-moxibustion group.

Conclusion

Moxibustion at different times all can produce obvious analgesic effects on dysmenorrhea due to cold-dampness retention in rats, and pre-moxibustion plus immediate-moxibustion ranks the top. The mechanism of this analgesic effect may be via the regulation of abnormal PGF_2α, PGE₂ and AVP levels, to effectively inhibit the spastic contraction of uterine smooth muscle in dysmenorrhea rat, thereby improving the ischemia and hypoxia in uterus.

     

Investigation on modulation of human P-gp by multiple doses of Radix Astragali extract granules using fexofenadine as a phenotyping probe

Ethnopharmacology

Herb–drug interactions may potentially affect drug efficacy and/or the likelihood of adverse drug reactions. Radix Astragali (RA) extract formulation is usually prescribed for long-term use for patients with immunodeficiency, diabetes, nephropathy or cardiovascular diseases. Its use in combination with P-glycoprotein (P-gp) substrates is possible in clinical practice. Currently there is little knowledge about whether concomitant use of RA extract has an influence on disposition of P-gp substrate.

Aim of the study

This study was to investigate whether continuous and multiple doses of RA extract granules had modulatory effects on human P-gp.

Material and methods

A randomised, placebo-controlled, two-period crossover pharmacokinetic drug interaction study was conducted in healthy Chinese volunteers. Fexofenadine was used as a P-gp phenotyping probe. Fourteen volunteers received RA extract granules or placebo (4 g bid) for 7 days and then received a single oral dose of 120 mg fexofenadine. Fexofenadine plasma concentrations were determined by HPLC. Pharmacokinetic parameters were calculated by non-compartmental method and bioequivalence evaluation was performed.

Results

Pharamcokinetic parameters in the placebo phase were as follows: T_1/2 (3.75±1.47 h), C_max (745.11±137.41 μg/L), T_max (2.25±0.47 h), AUC_(0−t) (3894.27±923.45 μg h/L), AUC_(0−∞) (3993.84±912.97 μg h/L). Pharamcokinetic parameters in the RA extract phase were as follows: T_1/2 (4.00±1.24 h), C_max (709.44±170.03 μg/L), T_max (2.21±0.51 h), AUC_(0−t) (3832.72±1077.60 μg h/L), AUC_(0−∞) (3983.53±1019.83 μg h/L). The influence of RA extract on fexofenadine C_max and AUC lacks statistical significance. Fexofenadine in the two phases were bioequivalent. In the placebo phase, T_1/2 of fexofenadine in ABCB1 3435T mutation allele carriers was longer compared to ABCB1 3435CC carriers (4.43±1.44 h vs. 2.54±0.21 h, p<0.05). However, RA extract pretreatment abolished such genotype-related difference due to the lengthened T_1/2 in ABCB1 3435CC carriers. There was no association of the C3435T polymorphism with C_max and AUC_(0−t) in subjects with two pretreatments.

Conclusion

One-week administration of RA extract granules did not have a statistically significant impact on systematic exposure to fexofenadine, suggesting that RA extract is not a potent modulator of P-gp in vivo. RA extract appears to have ABCB1 C3435T genotype-dependent inhibitory effect on elimination rather than absorption of a P-gp substrate. Further investigations are necessary in patients who receive long-term use of RA extract formulation and combined P-gp substrates, especially in those ABCB1 3435CC carriers.     

复方五仁醇胶囊对他克莫司大鼠体内药动学的影响

目的比较复方五仁醇胶囊(CWC)和五酯胶囊(WZC)及CWC单次和长期给药对他克莫司(FK506)在大鼠体内药动学的影响。方法 24只大鼠随机分成FK506组、CWC+FK506组、WZC+FK506组和CWC7d+FK506组,每组6只。FK506组、CWC+FK506组和WZC+FK506组分别一次性ig给予FK506、CWC+FK506、WZC+FK506,CWC7d+FK506组前6 d连续ig给予CWC,第7天ig给予CWC和FK506。各组大鼠于给药前和给药后不同时间点(CWC7d+FK506组为末次给药前后)眼眶取血,测定FK506血药浓度,计算FK506主要药动学参数。结果与FK506组比较,WZC+FK506组和CWC+FK506组大鼠FK506血药浓度峰值(Cmax)明显提高(P0.05、0.01),药-时曲线下面积(AUC0～t)显著增加(P0.01),体内滞留时间(MRT0～t)明显延长(P0.05、0.01),表观分布容积(V/F)及药物消除率(CL/F)显著减少(P0.01);与WZC+FK506组比较,CWC+FK506组大鼠FK506 AUC0～t显著增加(P0.01),CL/F明显减少(P0.05)。与CWC+FK506组比较,CWC7d+FK506组大鼠FK506Cmax显著提高(P0.01),血药浓度达峰时间(tmax)明显缩短(P0.05),AUC0～t明显增加(P0.05),CL/F明显减少(P0.05)。结论 CWC和WZC均可提高FK506Cmax,增加AUC0～t,延长MRT0～t,减小V/F和CL/F;在增加FK506 AUC0～t、减少CL/F方面,CWC优于WZC;在提高Cmax、增加AUC0～t、缩短tmax方面,CWC长期给药优于单次给药。     

Effects of HuangKui capsules on glibenclamide pharmacokinetics in rats

Ethnopharmacology

The main components of HuangKui capsules’ are the total flavonoids extracted from the flowers of Abelmoschus manihot L medic. They have been widely used to treat chronic glomerulonephritis, diabetic nephropathy and nephrotic syndrome. The combination of HuangKui capsules and glibenclamide is a possible therapy for patients with diabetes mellitus and diabetic nephropathy. However, there is no report about effects of HuangKui capsules on the glibenclamide pharmacokinetics till now.

Aim of the study

This study was aimed investigating the effect of HuangKui capsules on pharmacokinetics of glibenclamide in rats.

Material and methods

Eight rats were administered with an oral dose of HuangKui capsules (0.75 g kg⁻¹) once daily for 10 consecutive days. All the rats were administered orally with the glibenclamide (1 mg kg⁻¹) before the first time and after the last time given HuangKui capsules. LC-MS/MS was utilized to determine the concentration of glibenclamide in rat plasma and to calculate the corresponding pharmacokinetic parameters. The statistical differences of the two cycles were evaluated by paired-samples t-test.

Results

In the rats treated with HuangKui capsules and glibenclamide, the t_1/2, the time point of maximum plasma concentration (T_max) of glibenclamide increased obviously (p < 0.05) compared with the glibenclamide alone, while maximum plasma concentrations (C_max), area under the plasma concentration-time curve (AUC_(0−t)) decreased significantly (p < 0.05). There was no significant difference between other parameters.

Conclusion

HuangKui capsules can reduce the absorption of glibenclamide and accelerate the metabolism of glibenclamide.