Xiaoyao Pill Research Articles

Characterization and In vitro Release & In vivo Behavior Study of Self-Assembled Nano-Emulsion in XiaoYao Pill for Enhanced Drug Delivery.

Traditional Chinese medicine formulations often contain hydrophobic components with limited solubility and stability, leading to low oral bioavailability. Self-assembled nanoparticles (SANs) have shown promise in enhancing oral bioavailability of these components. However, whether un-decocted Chinese herbal pellets can generate SANs and the impact of SANs formed by multiple components on pharmacokinetic parameters remains unexplored. In this study, single-factor approach was employed to determine the optimal separation method of nano-emulsion phase of XiaoYao pill (N-XY). Morphological and particle size analyses confirmed the nanoscale nature of N-XY. High-performance liquid chromatography (HPLC) fingerprint analysis was conducted to compare the distribution of active ingredients among three different phases of XiaoYao pill (XY pill). In vitro release studies were performed to evaluate the release mechanism of four ingredients from N-XY. Additionally, in vivo pharmacokinetics and tissue distribution behaviors were investigated in rats. N-XY exhibited uniform and stable characteristics as a water-in-oil (O/W) nano-emulsion. Fingerprint analysis identified 25 characteristic peaks and 8 key ingredients in N-XY, with the highest peak areas. In vitro release studies showed a sustained release behavior of N-XY. The pharmacokinetics study showed that the ferulic acid of N-XY had a 1.37-fold higher AUC, 1.44-fold lower Vd/F, 1.39-fold lower CL/F, and a prolonged t1/2 than A-XY, indicating enhanced bioavailability due to reduced elimination. Furthermore, the tissue distribution revealed that the levels of paeoniflorin and ferulic acid from N-XY significantly increased in liver, spleen, lungs, uterus and ovaries, exhibiting targeting characteristics. This study comprehensively explored the formation, characterization, and pharmacokinetics of nano-emulsion in XY pill, introducing novel perspectives and initiating preliminary research on potential SANs in un-decocted traditional Chinese medicine formulations. It also emphasized the importance of enhancing pharmacokinetics of hydrophobic components in Chinese herbal formulations and laid the foundation for future nano-formulation research for XY pill.

A refined formula derived from Jiawei-Xiaoyao pill exerts rapid antidepressant-like effects in LPS-induced depression by reducing neuroinflammation and restoring neuroplasticity signaling

Ethnopharmacological relevanceJiawei-Xiaoyao Pill (JWX), a classic formula in traditional Chinese medicine, is derived from Xiaoyao Pill by adding significant amounts of Gardeniae Fructus (GF) and Moutan Cortex (MC). It is frequently used for the treatment of depression. JWX has been demonstrated to uniquely elicit rapid antidepressant-like effects within the prescribed dosage range. To date, GF has been shown to have rapid antidepressant-like effects, but a much higher dose is required than its proportion in JWX. It is assumed that the synergism of GF with a minimum number of other herbs in JWX serves as a refined formula that exerts these rapid antidepressant-like effects. Identification of a refined formula is important for prioritizing the herbs and ingredients to optimize the quality control of JWX. However, such a refined formula for JWX has not been identified yet. Aim of the studyHere we aimed to identify a refined formula derived from JWX for optimized rapid antidepressant-like effects. Since the neuroinflammation mechanism involving in depression treatment has not been previously investigated for JWX, we tested the mechanism for both JWX and the refined formula. Materials and methodsIndividual herbs (MC; ASR, Angelica Sinensis Radix; Bupleuri Radix; Paeonia Radix Alba) that show antidepressant-like responses were mixed with GF at the proportional dosage in JWX to identify the refined formula. Rapid antidepressant-like effects were assessed by using NSF (Novelty Suppressed Feeding Test) and other behavioral tests following a single administration. The identified formula was further tested in a lipopolysaccharide (LPS)-induced depressive model, and the molecular signaling mechanisms were investigated using Western blot analysis, immunofluorescence, and pharmacological inhibition of mTOR signaling. Scopolamine (Scop) was used as a positive control for induction of rapid antidepressant effects. ResultsA combination of GF, MC and ASR (GMA) at their dosages proportional to JWX induced behavioral signs of rapid antidepressant-like responses in both normal and LPS-treated mice, with the antidepressant-like effects sustained for 5 d. Similar to JWX or Scop, GMA rapidly reduced the neuroinflammation signaling of Iba-1-NF-кB, enhanced neuroplasticity signaling of CaMKII-mTOR-BDNF, and attenuated the upregulated expressions of the NMDAR sub-units GluN1 and GluN2B in the hippocampus of LPS-treated mice. GMA, JWX and Scop rapidly restored the number of BDNF-positive cells reduced by LPS treatment in the CA3 region of the hippocampus. Furthermore, rapamycin, a selective inhibitor of mTOR, blunted the rapid antidepressant-like effects and hippocampal BDNF signaling upregulation by GMA. ConclusionGMA may serve as a refined formula from JWX, capable of inducing rapid antidepressant-like effects. In the LPS-induced depression model, the effects of GMA were mediated via rapidly alleviating neuroinflammation and enhancing neuroplasticity.

Xiaoyao Pills, a Chinese patent medicine, treats mild and moderate depression: A randomized clinical trial combined with DNA methylation analysis

BackgroundXiaoyao pills (XYP) is a commercial Chinese patent medicine used in the treatment of depression. However, the mechanisms underlying its therapeutic effects, as well as the patients who can benefit from XYP, have not been evaluated so far. ObjectivesTo this end, we conducted a double-blinded, random, and placebo-controlled clinical trial of orally administered XYP in patients with depression. MethodsThe 17-item Hamilton Depression Rating Scale (HAMD-17) scores were recorded at baseline, and every 2 weeks after the start of treatment. To further elucidate the epigenetic mechanism of XYP, we performed mRNA sequencing and genome-wide DNA methylation sequencing using peripheral blood leukocytes of patients and healthy. ResultsXYP effectively alleviated the symptoms in patients with mild or moderate depressive disorders, particularly that of psychomotor retardation. XYP restored aberrant gene expression and DNA methylation patterns associated with depression, and the normalization of DNA methylation correlated with downregulation of several genes. In addition, altered DNA methylation levels in the XYP-treated samples were attributed to increased expression of the DNA methyltransferase DNMT1. ConclusionsOur study provides new insights into the epigenetic mechanism underlying depression and the therapeutic effects of XYP, along with an experimental basis for using XYP in the treatment of depression. Trial Registration InformationThe name of the registry and number: U.S. Clinical Trials Registry. The link to the registration: ClinicalTrials.gov ISRCTN12746343 (https://www.isrctn.com/ISRCTN12746343). The name of the trial register is “Efficacy and safety of the Xiaoyao pill for improving the clinical symptoms of stagnation of liver qi (chi) and spleen deficiency”. The clinical trial registration number is ISRCTN12746343.

Efficacy and safety of Xiaoyao Pill combined with Western medicine in the treatment of schizophrenia: A Meta-analysis and Systematic review.

The efficacy and safety of Xiaoyao Pill combined with Western medicine in the treatment of schizophrenia are still inconclusive. This meta-analysis summarized relevant studies to compare the efficacy and safety of Xiaoyao Pill combined with Western medicine and Western medicine alone in the treatment of schizophrenia, aiming to provide guidance for clinical treatment. In this meta-analysis, we searched PubMed, Embase, Cochrane Library, CNKI, Wanfang, CQVIP, and CBM databases from the establishment of the databases to August 2023. The study proposed to include studies that reported combination of Xiaoyao Pill with Western medicine and Western medicine alone in the treatment of schizophrenia, excluding published literature, unpublished literature, literature with incomplete or inadequate information, animal experiments, literature reviews and systematic studies. Data were analyzed using Review manager 5.3. About 9 studies (6 RCTs and 3 case-control studies) were included in this meta-analysis. The sample size ranged from 60 to 128, with a total of 779 patients, including 395 in the combined treatment group and 384 in the control group. Pooled results showed that the total effective rate of combined treatment group was significantly higher than that of Western medicine alone (OR = 4.21, 95% CI: 1.50-11.83, P = .006). Positive and Negative Syndrome Scale (PANSS) (-) (MD = -2.30, 95% CI: -3.72 ~ -0.89, P = .001) and PANSS (+) (MD = -2.60, 95% CI: -3.34 ~ -1.86, P < .00001) of combined treatment group were all significantly lower than that of Western medicine alone. Additionally, PRL levels of combined treatment group was significantly lower than that of Western medicine alone (MD = -28.78, 95% CI: -42.20 ~ -15.35, P < .0001). However, there was no significant difference in BPRS and total PANSS between combined treatment group and Western medicine alone group. Notably, pooled results showed that there was no significant difference in incidence of adverse events between combined treatment group and Western medicine alone group. The effective rate of Xiaoyao Pill combined with Western medicine in the treatment of schizophrenia is higher than that of Western medicine alone, which can effectively relieve the positive and negative symptoms of schizophrenia, and can significantly reduce the level of PRL. In the treatment of schizophrenia, clinicians can give priority to Xiaoyao Pill combined with Western medicine therapy.

Comparative efficacy of tonifying kidney on treatment of mammary gland hyperplasia: Systematic review with network meta-analysis

BackgroundNetwork meta-analysis is used as a data synthesizer, incorporating direct and indirect evidence about treatments in a series of randomized control trials. ObjectiveTo evaluate the comparative efficacy of various Kidney nourishments for treating mammary gland hyperplasia (HMG). MethodsWe performed a network meta-analysis to combine direct and indirect data to investigate the efficiency of drug therapies, which were evaluated in relevant randomized control trials for HMG. ResultsThirty-seven eligible studies were included in this meta-analysis. A total of 4002 patients were included, in whom 21 therapeutic interventions were used. BieJiaJain Pill showed the highest efficacy in total efficiency, whereas Tamoxifen was the least effective. YanLuRuKang Capsule/Pill, AnRu Decoction showed higher efficacy in modulating Estradiol, whereas Tamoxifen and RuPiSanJie Capsule were lower effective. YanLuRuKang Capsule/Pill, RuKangShu Capsule, AnRu Decoction showed higher efficacy in narrowing lump, whereas RuKang Pill/Capsule, RuPiXiao Granules/Pill, RuPiSanJie Capsule were lower effective. YiShenShuGan Capsule/Decoction, WenYangXiaoPi Compound, TiaoChongGuBen Decoctiom showed higher efficacy in reducing painscore, whereas Tamoxifen, RuPiXiao Granules/Pill, RuPiSanJie Capsule were lower effective. XiaoYao Pill, RuPiSanJie Capsule showed higher efficacy in modulating progesterone, whereas WenYangXiaoPi Compound, TiaoChongGuBen Decoctiom were poorly effective. YiShenShuGan Capsule/Decoction, WenYangXiaoPi Compound, AnRu Decoction showed higher efficacy in modulating prolactin, whereas Tamoxifen, RuPiXiao Granules/Pill, RuPiSanJie Capsule were lower effective. ConclusionIn this study, the efficacy of oral Chinese herbal compounds in treating mammary glands hyperplasia was analyzed systematically and objectively, which provided a theoretical basis for clinical medication and was helpful for clinicians to make the best choice of medication. Due to the limitations of the selected literature, the conclusions of this study still need to be validated by high-quality clinical trial studies.

Efficacy, safety and mechanism of Honghua Xiaoyao Pill in the treatment of peri-menopausal syndrome: A study protocol for a randomized controlled trial.

Background: Peri-menopausal syndrome (PMPS) has a high incidence rate and seriously affects the physical and mental health of women. Honghua Xiaoyao Pill (HHXYP) is a Chinese patent medicine, which has been reported to be used to treat PMPS. However, there is still a lack of randomized clinical trial to evaluate the efficacy and safety of HHXYP on life quality, mood and vasomotor symptoms for PMPS women. This study aims to investigate whether HHXYP is effective and safe in treating PMPS and the possible mechanism. Methods: A multicenter, randomized, controlled clinical trial will be conducted in China to evaluate the efficacy and safety of HHXYP. Sixty women with peri-menopausal syndrome will be recruited at three centers and randomly in a 1:1 ratio to a treatment group using HHXYP (HHXYP group) and a control group using oryzanol (OC group). Participants will be treated with HHXYP or oryzanol for 12 weeks and followed up for 4 weeks. The primary outcome is the modified Kupperman Index (KI), which will be measured at baseline and 4, 8, 12, 16 weeks after randomization. The secondary outcomes include Hot flash scale (HFs), Menopause-Specific Quality of Life Scale (MENQOL) and Hamilton Depression/Anxiety Scale (HAMD/HAMA). The HFs are measured at the same point as the KI, other secondary outcomes are measured at baseline and 12, 16 weeks after randomization. The other outcomes are the levels of serum sex hormone, monoamine neurotransmitter, vascular vasomotor factor and the expression of phosphatidylinositol 3-active enzyme (PI3K)/protein activator enzyme B (Akt), which will be measured at baseline and 12 weeks after randomization. Adverse events will also be reported. Discussion: HHXYP is a potential alternative Chinese patent medicine for PMPS. This trial will provide evidence for HHXYP on improving the quality of life, mood and vasomotor symptoms, and sex hormone levels of PMPS patients.

Xiaoyao Pill Improves the Affective Dysregulation of Sleep-deprived Female Mice by Inhibiting Brain Injury and Regulating the Content of Monoamine Neurotransmitter.

Sleep curtailment is a serious problem in many societies. Clinical evidence has shown that sleep deprivation is associated with mood dysregulation, formation of false memory, cardio-metabolic risk factors and outcomes, inflammatory disease risk, and all-cause mortality. The affective disorder dysregulation caused by insufficient sleep has become an increasingly serious health problem. However, to date, not much attention has been paid to the mild affective dysregulation caused by insufficient sleep, and there is no clear and standard therapeutic method to treat it. The Xiaoyao Pill is a classic Chinese medicinal formula, with the effect of dispersing stagnated hepatoqi, invigorating the spleen, and nourishing the blood. Therefore, it is most commonly used to treat gynecological diseases in China. In the present study, the effects of the Xiaoyao Pill on affective dysregulation of sleep-deprived mice and its underlying molecular mechanisms were investigated. Forty adult female mice were used in the present study. The sleep deprivation model was established by improving the multi-platform water environment method. After 7 consecutive days of sleep deprivation, the mice were administrated low (LXYP, 0.32mg/kg) and high (HXYP, 0.64 mg/kg) doses of the Xiaoyao Pill for two weeks. Then, the body weight, behavioral deficits, and histopathology were evaluated. Meanwhile, the expression of c-fos protein and the concentrations of monoamine neurotransmitters in the hippocampus and prefrontal cortex were determined after two weeks of treatment. Xiaoyao Pill treatment significantly increased body weight and sucrose consumption and decreased the irritability scores of the sleep-deprived mice. Meanwhile, Xiaoyao Pill treatment prevented brain injury and inhibited the expression of c-fos protein in the hippocampus and prefrontal cortex. In addition, HXYP treatment significantly upregulated the levels of NE in the hippocampus and prefrontal cortex (p < 0.01). LXYP treatment significantly up-regulated the levels of 5-HT in the prefrontal cortex. Meanwhile, both HXYP and LXYP treatment significantly upregulated the levels of DA in the prefrontal cortex (p < 0.05 or p < 0.01) of sleep-deprived mice. The present study demonstrates that Xiaoyao Pill treatment prevented the behavioral deficits of mice induced by sleep deprivation by promoting the recovery of brain tissue injury and up-regulating the levels of NE, 5-HT, and DA in the brain tissue.

Xiaoyao Pills Attenuate Inflammation and Nerve Injury Induced by Lipopolysaccharide in Hippocampal Neurons In Vitro.

Lipopolysaccharides (LPS) are proinflammation mediators that can induce the inflammatory model of the hippocampal neuron, and neuroinflammation participates in the pathophysiology of depression. Xiaoyao Pill is a classical Chinese medicine formula that has been used for the treatment of mental disorders such as depression in China since the Song dynasty. We established a hippocampal neuronal cell inflammation model by LPS and investigate the intervention effect and mechanism of Xiaoyao Pills. The expression levels of IL-6, TNF-α, IDO, 5-HT, brain-derived neurotrophic factor, and β-nerve growth factor were detected by enzyme-linked immunosorbent assay. mRNA levels of IL-6, TNF-α, 5-HT1A, IDO-1, brain-derived neurotrophic factor, nerve growth factor, tropomyosin receptor kinase B, tropomyosin receptor kinase A, and cAMP response element-binding protein were detected by reverse transcription-polymerase chain reaction. To further validate, protein expression was determined by western blot and immunofluorescence. Lipopolysaccharide-induced neuroinflammatory state resulted in the release of IL-6, TNF-α, and IDO and a decrease of BDNF, NGF, TrkB, TrkA, CREB, p-CREB, p-CREB/CREB, and SYP and inhibited hippocampal neurogenesis in the hippocampal neuron. Xiaoyao Pills significantly decreased the levels of IL-6, TNF-α, and IDO in cell supernatant and increased the expression of BDNF, NGF, TrkB, TrkA, CREB, p-CREB, p-CREB/CREB, and SYP as well as the average optical density of BrdU/NeuN double-labelled positive cells. Our study shows that lipopolysaccharides induce inflammation and nerve damage in hippocampal neurons, which are closely related to the pathological mechanism of depression. Xiaoyao Pills (XYW) play an important neuroprotective effect, which is related to its inhibition of neuronal inflammation and promoting the recovery of nerve injury. These results provide a pharmacologic basis for the treatment of depression of XYW in clinical application.

The study on the effect of depression on breast cancer incidence through IDO/kynurenine pathway.

e13569 Background: Psychosocial factors have been considered as the most common causes for women with breast cancer. However, it remains unclear whether mental stress can influence cancer incidence and progression. This study aims to investigate the relationship between them and the potential molecular mechanism. Methods: Depression model was established by restricting MMTV-PyMT mice in a 50ml-fixator for 4 h per day for 21 consecutive days. Behavioral tests including light-dark box test, open-field test and force swimming test were performed. Then blood, brain and mammary samples were collected at the indicated time points. ELISA was used to detect the concentration of neurotransmitters serotonin, epinephrine and norepinephrine and inflammatory factors IL-6, TNF-a and IL-1β in brain tissue and serum. Real-time quantitative qPCR and western blot were used to detect indoleamine 2, 3-dioxygenase (IDO) expression. The level of tryptophan was measured by high performance liquid chromatography(HPLC). Flow cytometry was used to evaluate the exhaustion of CD8+ T cells. Besides, the correlation between IDO expression detected by immunohistochemistry and the severity of mammary tumors was analyzed in the tumor specimens. Results: We observed that chronic stress caused depression-like behaviors, abnormal secretion of neurotransmitters serotonin, epinephrine and norepinephrine and promoted the development of breast cancer in MMTV-PyMT mice. Depression elevated the secretion of inflammatory factors IL-6, TNF-a and IL-1β in brain tissue and serum, which upregulated the expression of IDO and decreased the level of tryptophan in mice. Furthermore, T cells are sensitive to low tryptophan concentration, so elevated IDO expression suppressed and exhausted CD8+ T cells, ultimately promoting cancer incidence. Administration of xiaoyao pill (a well-known Chinese herbal formula for treating depression) or IDO inhibitor reversed the depression-like behaviors in mice and slowed the development of breast cancer. At the same time, the analysis of clinical samples showed that depression identified by Hamilton Depression Scale(HAMD) and IDO expression in mammary tumor tissues were positively correlated with the severity of mammary tumors. Conclusions: Altogether, our results suggest that depression can promote tumor immune privilege and cancer occurrence through inducing upregulated IDO expression.

Simultaneous determination of six components of Danzhi Xiaoyao Pill in beagle plasma by HPLC-MS/MS and a study of pharmacokinetic of paeoniflorin and geniposide after single-dose administration

This study was to develop a reliable and simple high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to detect paeoniflorin, geniposide, saikosaponin b2, liquiritin, paeonol and atractylenolide Ⅲ in beagle plasma and to study pharmacokinetic of paeoniflorin and geniposide after single-dose administration of Danzhi Xiaoyao Pill (DZXY). Chromatographic separation was performed using an Agilent C18 column, and multiple reaction monitoring (MRM) mode was used. A gradient elution procedure was used with solvent A (acetonitrile) and solvent B (0.1 % formic acid-water) as mobile phases. The elution procedure was as follows: 85 % B-30 % B (0−7 min) and 30 % B-30 % B (7.1−8 min). The flow rate was 0.3 mL/min. The column temperature was 40 ℃, and the injection volume was 10 μL. The main analytical parameters of paeoniflorin, geniposide, saikosaponin b2, liquiritin, paeonol and atractylenolide Ⅲ were m/z 525→449, m/z 433→224, m/z 780→617, m/z 417→254, m/z 167→43 and m/z 249→231, respectively. Ethyl acetate was used to extract the analytes in the plasma. Standard calibration curves of six analytes showed satisfactory linearity (r2≥0.99 2) within the determined ranges. The lower limits of quantification were 0.5 ng/mL for paeoniflorin and liquiritin, 2.5 ng/mL for geniposide and saikosaponin b2 and 1.0 ng/mL for atractylenolide Ⅲ and paeonol, respectively. The intra-day and inter-day precision (RSD %) were all below 6.94 %, and the intra-day and inter-day accuracy (RE %) were within ± 6.10 %. The recovery and ME of six analytes were 85.99 %–98.10 % and 95.78%–108.06%, respectively. Additionally, the method we established in this experiment can be successfully used to study the pharmacokinetics of paeoniflorin and geniposide in beagle plasma.

Clinical evaluation of modified Xiaoyao pill on the treatment of oral lichen planus patients with anxiety or depression

To investigate the clinical effect and safety of modified Xiaoyao pill on the treatment of oral lichen planus (OLP) patients with anxiety or depression. Sixty OLP patients with anxiety and depression were randomly divided into 2 groups, treated separately with hydroxychloroquine(HCQ, control group) and HCQ+modified Xiaoyao pill(experimental group). The results were measured with semi quantitative reticular erosive and ulcerative lesion (REU) and visual analogue scale（VAS） scoring system at the first visit, the second week, the fourth week and the eighth week, respectively. Data analysis was performed using SPSS 18.0 software package. The clinical effect of HCQ+modified Xiaoyao pill was better than that of the HCQ. The REU, VAS scores were lower after treatment in both groups (P<0.05), but the effect of the experimental group was more remarkable in reducing the pain indexes, accelerating the healing of erosive lesion and preventing recurrence than the control group. There was no significant difference in the overall effective rate between the two groups (P>0.05). Modified Xiaoyao pill was effective and safe in the treatment of OLP patients with anxiety or depression, especially for EOLP.

Clinical effect of large speckle modulated Q1064nm laser combined with Xiaoyao pills in treatment of chloasma

Objective To investigate the clinical efficacy of large spot modulated Q 1064 nm laser combined with Xiaoyao pills in the treatment of chloasma. Methods 90 patients with chloasma were treated in the hospital. The patients were randomly divided into 3 groups: treatment group were treated with Q 1064 nm laser combined with large spot Xiao Yao pill; the control group 1 was treated with large spot Q 1064 nm laser only, and control group 2 was treated with Xiaoyao Pill only. Results After 8 weeks of treatment, the effective rate was higher in the treatment group than the control group 2 (P<0.05); after 16 weeks of treatment, the efficacy was better in the treatment group than the control group 1 and control group 2 (P<0.05). The combination of the two methods can improve the curative effect and inhibit the recurrence. Conclusions The treatment of chloasma with large speckle modulated Q 1064 nm laser combined with Xiaoyao pills is effective and worthy of clinical promotion. Key words: Large aperture modulation Q 1064 nm laser; Xiaoyao pills; Chloasma

Research on rat models of acute liver injury with syndrome of liver depression and spleen deficiency

This paper aimed to establish animal models which are suitable for the activity found, efficacy evaluation of herbs resistant to acute liver injury with syndrome of liver depression and spleen deficiency and new drug research and development based on corresponding of formula and syndrome. The symptoms that are suitable for evaluating the rat models of acute liver injury with syndrome of liver depression and spleen deficiency were extracted according to the evolution rule of the etiology and pathogenesis in traditional Chinese medicine and the modern pathological mechanism. Xiaoyao pill and silibin meglumine tablets were used as drug counter evidence for models in accordence with the principle of consistence of prescription and syndrome. Rats model were fed with high-lipid and low-protein fodder of different proportion and induced by intraperitoneal injection with pig serum, intragastric administration with edible alcohol once a day for 7 days. Daily record of body weight, daily food intake and daily water intake were conducted day after day in experimental session. Symptoms were also observed and evaluated by score at the same time. The contents of ALT, AST, PA, TBIL and TBA in serum were detected and histopathological changes of liver were checked at the ending of experiment. Obvious acute liver injury occurred to all rats in model groups at 1 week following model induction. Both main symptoms and secondary symptoms were consistent with syndrome manifestation of liver depression and spleen deficiency. Compared with normal control group, the activity of ALT,AST and contents of TBIL,TBA in serum increased and the content of PA decreased. Liver tissue pathological morphology showed inflammatory cells infiltration, eosinophilic or eosinophilic adipose change in hepatocytes of rats in model groups. All the above lesions manifestation could be improved by drug counterevidence. By the disproof of medicine, rat models of acute liver injury with syndrome of liver depression and spleen deficiency could be induced by fed with high-lipid and low-protein fodder which contained 89.5% cornstarch, 10% lard and 0.5% cholesterol, intraperitoneal injected with pig serum, intragastric administrated with edible alcohol for 7 days. The rat models with a low mortality could be induced in a short time and animal status were similar to syndrome performance of patients. So the rats models are suitable for the activity found, efficacy evaluation and drug discovery of herbs resistant to acute liver injury with syndrome of liver depression and spleen deficiency, and also can be used in the research of correlation between prescription and syndrome and its mechanism.

Efficacy of Psychological Interventions for Patients with Breast Hyperplasia.

To explore the efficacy of psychological interventions (PI) in patients with breast hyperplasia (BH). In total 120 BH patients who were treated in the Third Affiliated Hospital of the Third Military Medical University were randomly divided into PI group (n = 40; treated with oral XiaoYao Pill and psychological interventions), anti-anxiety/depression medication (AADM) group (n = 40; treated with oral XiaoYao Pill and paroxetine), and control group (n = 40; treated with oral XiaoYao Pill) and the treatment lasted for 1 year. Before the treatment and 4, 8, and 12 months after the initiation of treatment, the changes in the psychological indicators were measured using Toronto Alexithymia Scale (TAS), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), and Ways of Coping Questionnaire (WCQ), as well as the physiological indicators including estradiol, prolactin, and progesterone were determined. The overall response rates were evaluated at the end of the treatment, and the relapse rates were calculated during the 1-year follow-up. The HAMD and HAMA scores were declined in all three groups. The scores of TAS and WCQ negative coping subscales showed a declining trend after treatment for the AADM and PI groups. Compared to the control and PI groups, the HAMA and HAMD scores were significantly lower in the AADM group 4, 8, and 12 months after the initiation of treatment (P < 0.05). The scores of TAS and WCQ negative coping subscales were significantly lower in AADM group but were significantly higher than those in PI group and lower than the control group 4, 8, and 12 months after the initiation of treatment (P < 0.05). The HAMA and HAMD scores were significantly lower in PI group than in control group 4, 8, and 12 months after the initiation of treatment (P < 0.05). After the initiation of treatment, the estradiol and prolactin levels decreased while the progesterone levels increased in all three groups. Compared with the control group and AADM group, the PI group had significantly higher estradiol and prolactin levels and higher progesterone levels 4, 8, and 12 months after the initiation of treatment (P < 0.05). Compared with the control group, the AADM group had significantly lower levels of estradiol and prolactin and higher progesterone levels 4, 8, and 12 months after the initiation of treatment (P < 0.05). The overall response rate was not significantly different for both PI group and AADM group (P > 0.05), while the relapse rate was significantly lower in the PI group than the control and AADM groups (P < 0.05). However, the relapse rate did not significantly differ between the control group and AADM group (P > 0.05). PI can effectively improve the psychological status of BH patients and restore the disordered endocrine system. The efficacy lasts for long and the relapse rate is lower. Therefore, it could be an effective method for treating BH.

Xiaoyao pill for treatment of functional dyspepsia in perimenopausal women with depression.

To evaluate the efficacy and safety of the Xiaoyao pill for treatment of functional dyspepsia (FD) associated with perimenopausal depression. This was a double-blind, randomized, controlled trial including 180 patients with FD accompanied by depression that were divided into two groups of 90. Patients in the treatment group received oral administration of the Xiaoyao pill for soothing the liver and activating the spleen, and patients in the control group received a placebo. This trial included an 8-wk therapy period with a follow-up period of 6 mo. The total efficacy and degree of depression, as assessed by the Hamilton Rating Scale for Depression (HRSD), were evaluated. Plasma levels of motilin and gastrin were measured and a gastric emptying test was conducted in each participant. The Xiaoyao pill had a good therapeutic effect and improved the symptoms in patients with perimenopausal FD as assessed by the HRSD score, motilin and gastrin levels, and rate of gastric emptying. The total effective rate of the Xiaoyao pill in the treatment group was significantly superior to that of the placebo in the control group. In the control group, the initial HRSD score was 12.12 ± 2.29 and decreased to 7.14 ± 1.67 after therapy (P < 0.01). In the treatment group, the initial HRSD score was 11.44 ± 2.15, which significantly decreased to 6.20 ± 2.08 after therapy (P < 0.01). Moreover, the HRSD score in the treatment group was significantly lower than in control group after 8 wk (P < 0.01). Motilin and gastrin levels in both groups were significantly increased after the 8-wk therapy (P < 0.05). The gastric emptying rate was also improved in both groups after therapy (P < 0.05), and the improvement was significantly better in the treatment group compared to the controls (P < 0.05). These results confirm the therapeutic effects of the Xiaoyao pill in perimenopausal FD patients and indicate that it is worthy of clinical promotion. The Xiaoyao pill is effective and safe for the treatment of perimenopausal women with FD associated with depression.

Comparative study on effect of three preparations of Xiaoyao formula on soothing liver and strengthening spleen

To compare the effect of three preparations of xiaoyao formula (xiaoyao capsule, xiaoyao pill and Xiaoyao decoction) on soothing liver and strengthening spleen. The liver depression and spleen deficiency rat model were established by forcing swimming, confining movement test and feeding on alternate days. The rats were randomly divided into eight groups, namely the blank group, the model group, the Cisapride group (2.7 mg x kg(-1)), the xiaoyao decoction group (1.62 g x kg(-1)), the xiaoyao pill group (1.62 g x kg(-1)) and the Xiaoyao capsule groups of high dose (3.24 g x kg(-1)), medium dose (1.62 g x kg(-1)) and low dose (0.81 g x kg(-1)), with intragastric administration for 3 weeks. The contents of NE, DA, 5-HT in serum were measured by HPLC-electrochemical detection method. The contents of motilin (MTL) and somatostation (SS) in plasma was determined by radioimmunassay. The expressions of MTL and SS in tissue were determined by immunohistochemical method. The contents of NE and MTL in the xiaoyao decoction group was significantly higher than that in the model group, while the content of 5-HT and SS was significantly lower than that in the model group (P < 0.01). The expression of MTL in the xiaoyao capsule group (1.62 g x kg(-1)) was significantly higher than that in the model group and the contents of 5-HT and SS was significantly lower than that in the model group (P < 0.05). The mean optical density of MTL in gastrointestinal tissue of rats in the xiaoyao decoction group and the xiaoyao capsule group (1.62 g x kg(-1)) was remarkably higher than that in the model group, while the expression of SS was notably lower than that in the model group (P < 0.05). All of the three preparations of Xiaoyao formula have the effect on soothing liver and strengthening spleen. Xiaoyao decoction shows better effect than xiaoyao capsule with same dosage, while xiaoyao capsule shows better effect than xiaoyao pill with same dosage.

The influences of paroxetine modified Xiaoyao pill therapy on subjective well-beingfor type 2 diabetes patients with anxiety

Objective To explore the influence of integrated Chinese and western medicine therapy on anxiety,sugar metabolism and subjective well-being for type 2 diabetes Patients associated with anxiety.Methods Use glycated hemoglobin (HbAlc),trait anxiety inventory(TAI),and Memorial University of Newfoundland Scale of Happiness (MUNSH) to evaluate the condition of 60 patients with type 2 diabetes associated with anxiety.The patients participated in the study were randomly divided into Western medicine therapy group(control group)and integrated traditional Chinese and Western medicine therapy group (experimental group),with 30 cases in each group.The control group was treated with paroxetine while the experimental group was treated with paroxetine plus Jiawei-Xiaoyaowan.6 weeks after treatment,we tested the HbAlc level.TAI score and MUNSH score of those patients.Results After 6 weeks,the TAI score of patients in both experimental group and control group have obviously decreased (before treatment:54.07±6.41 and 56.33 ±6.01,respectively; after treatment:38.89±6.70 and 45.29±6.55,respectively) and the difference was statistically significant (P＜0.05).And the TAI score of the two groups after treatment was significantly different (P＜0.05).For both experimental and control groups,the HbA1e level were not obviously changed before and after the study with P＞0.05 (before treatment:8.14±2.69 and 8.07±2.11,respectively; after treatment:8.21±2.07 and 7.92± 1.90,respectively).Comparison between groups also showed no significant difference.MUNSH score have obviously increased in experimental group (before treatment:40.49±5.22; after treatment:44.53 ± 6.28,P＜0.05).The result of comparison between the two groups after treatment shows that MUNSH score of patients in the experimental group were obviously improved compared with patients in the control group (57.56 ±6.39),and the difference was statistically significant (P＜0.05).Conclusion The integrated traditional Chinese and western medicine therapy can obviously release anxiety and enhance subjective well-being in patients with cerebral infarction associated with anxiety. Key words: Type 2 diabetes; Anxiety; Glycated hemoglobin; Subjective well-being

Assessment of the clinical effect of Chinese medicine therapy combined with psychological intervention for treatment of patients of peri-menopausal syndrome complicated with hyperlipidemia

To observe the effect of Chinese medicine therapy combined with psychological intervention (combined therapy) on the clinical symptoms and levels of blood lipids and sex hormones of patients of peri-menopausal syndrome complicated with hyperlipidemia. With the use of a randomizing digital table method, 185 patients that fit the registration standard were randomly assigned to three groups. The 59 cases in Group A were treated with two Chinese patents, Kunbao Pill and Modified Xiaoyao Pill; the 63 in Group B received psychological intervention alone; and the 63 in Group C were treated with both (the combined therapy), with the treatment course for all six months. The items of observation included: (1) scoring by SCL-90 on eight factors and seven symptoms; (2) scoring on Chinese medicine symptoms by Kupermann scale, including anxiety and bad temper, scorching sense action with sweating, dizziness, tinnitus, soreness and weakness of the loin and knees, palpitation, insomnia, lassitude, weakness, and hyposexuality; (3) blood contents of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apoprotein AI (ApoAI) and B (ApoB); (4) levels of sex hormones, including estradiol (E(2)), progesterone (P), pituitary prolactin (PRL), follicular stimulating hormone (FSH), and), luteinzing hormone (LH) in some randomly selected patients; (5) adverse reaction; and (6) one-year follow-up study on long-term effect. A total of 21 patients (6, 8, and 7 cases in Groups A, B, and C, respectively) dropped out; the drop-out rate was insignificant among groups. (1) The markedly effective rates in Group A, B, and C were 26.42% (14/53), 18.18% (10/55), and 53.57% (30/56), respectively, and the total effective rates in them were 64.15% (34/53), 50.91% (28/55), and 87.50% (49/56), respectively, suggesting the therapeutic efficacy in Group C was significantly better than that in Groups A and B (P<0.01). (2) SCL-90 scoring showed that the total scores decreased significantly after treatment in Group C (P<0.01), but remained unchanged in Groups A and B (P>0.05). (3) Scoring on Chinese medicine symptoms showed the same results as shown by SCL-90 scoring in terms of total scores and individual symptoms, except that menstrual disorder and amenorrhea were unchanged in all three groups (P>0.05). (4) Levels of HDL-C, ApoAI, and E(2) increased and those of TG, TC, LDL-C, ApoB, FSH, and LH decreased after treatment in Group C, reaching near normal levels; similar trends of blood lipids were shown in Group A, but the level of sex hormones was unchanged. In Group B all the above-mentioned indices were unchanged (P>0.05). (5) A one-year follow-up study showed the markedly effective rate and the total effective rate in Group C were higher than those in the other two groups respectively (P<0.01). (6) No adverse reaction was found. Chinese medicine therapy combined with psychological intervention could not only improve the nervous symptoms, but also regulate the blood levels of lipids and sex hormones in patients of peri-menopausal syndrome complicated with hyperlipidemia.

Effects and potential mechanisms of Danzhi Xiaoyao Pill (丹栀逍遥丸) on proliferation of MCF-7 human breast cancer cells in vitro

To investigate the effects of 50% ethyl alcohol (EtOH) extracts from Danzhi Xiaoyao Pill (, DXP) on the proliferation of MCF-7 human breast cancer cells and potential mechanisms. ATP-Lite assay was performed to test the proliferation of the MCF-7 breast cancer cell line; and antioxidant activity was measured by the oxygen radical absorbance capacity (ORAC). The effects of DXP on nitric oxide (NO) production were tested by lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophages using the Griess reaction. The 50% EtOH DXP extracts displayed a cytotoxic response on MCF-7 cells at 0.10, 0.25 and 0.50 mg/mL dose-dependently with the proliferation inhibited by more than 85%. The ORAC value of the DXP was 820 micro moL Trolox equivalent/g, about 40% of the vitamin C value. DXP extracts had significant inhibitory effect on NO production at the concentration from 0.0625 mg/mL to 0.5 mg/mL (P<0.05, P<0.01). The extracts of DXP could significantly inhibit the proliferation of MCF-7 cells, with the effect possibly related to its antioxidant activity and the inhibition of NO production.

Clinical observation on treatment of mammary gland hyperplasia by acupoint injection combined with ion-introduction of Chinese herbal medicine

Objective: To observe the effect of combined therapy of acupoint injection and Chinese herbal medicine ion-introduction in treating mammary gland hyperplasia (MGH).Methods: Eighty-six patients of MGH were treated with the combined therapy and compared with a control group treated with other Chinese or western drugs.Results: Therapeutic effect evaluated after 3 courses of treatment showed that the effect of combined therapy was superior to that of the control groups treated by Xiaoyao Pill, Rupixiao tablet, Asparagine tablet and combined therapy of vitamin E+oryzanol+vitamin B6.Conclusion: Combined treatment of acupoint injection and ion-introduction of Chinese herbal medicine is an effective treatment for mammary gland hypertrophy.