The American Journal of Chinese Medicine

Despite the recent technological advances in in vitro fertilization and embryo transfer (IVF-ET), a significant proportion of women still do not become pregnant after long-term infertility, whether it is originally due to older age or other undetermined factors. In the present study, macrophage activating Chinese herbs (MACH) were evaluated for their effects on embryo qualities in women who were undergoing repeated IVF-ET because of long-term infertility. Thirty women, who had significantly low rates of developing good quality cleaved embryos and did not become pregnant after three or more cycles of Assisted Reproductive Technology (ART) procedure, were included in the study. Oral administration of MACH significantly increased the percentage of good quality early stage blastocysts (the number of grade 1 or grade 2 cleaved embryos/the number of retrieved oocytes) from 18.7 ± 16.2% to 36.1 ± 27.1% (1.9-fold increase, p < 0.01). The rate of good quality early stage blastocysts increased in all patients. In 19 patients who desired embryo transfer using late stage blastocysts, MACH significantly increased the percentage of late stage blastocysts from the initial value of 14.8 ± 11.2% to 21.1 ± 23.1% (1.4-fold increase, p < 0.05). The rate of embryonic progress into late stage blastocyst increased in 52.6% (10/19) of the patients. Furthermore, treatment with MACH significantly decreased the plasma follicle stimulating hormone (FSH) concentration on the day of oocyte retrieval from 14.4 ± 3.2 to 10.5 ± 2.4 mIU/ml (p < 0.05). No adverse events were observed with MACH supplementation, and there was no patient dropout. Administration of MACH resulted in improved embryo quality in the difficult cases. The present study demonstrates a new benefit of this herbal blend in women with refractory infertility of unknown etiology.

Sleep-Disordered Breathing (SDB) is a prevalent affliction, which can range from simple snoring to severely obstructive sleep apnea. Compared to current treatment options of SDB, traditional Chinese medicine (TCM) provides a noninvasive way to relieve SDB-related symptoms and deaths. The purpose of this retrospective study was to observe the progression of adult SDB patients who had taken compound formula SZ + NUH (concentrated herbal granules) for four weeks. Depending on subjects’ individual needs, minor additions of formulas or single herbs were allowed. We found a significant amount of relief from snoring among the 118 enrolled subjects, according to before-after scores observed through the Snore Outcome Survey (SOS). Furthermore, as projected from the moderate linear correlation in before-after scores, we inferred that those cases with more severe snoring at baseline had greater improvement after treatment. Excessive daytime sleepiness was also significantly improved according to the results of the Epworth Sleepiness Scale (ESS). Assessment, using the SF-36 (Taiwanese version) revealed possible benefits of SZ + NUH in improving multiple facets of subjects’ quality of life. During treatment, no significant side effects occurred. In conclusion, the TCM compound formula based on SZ + NUH could be a safe and effective option for SDB treatment.

Ligustrazine, a bioactive component contained in Chuanxiong (Ligusticum chuanxiong Hort), is widely applied in the treatment of vascular diseases in China, e.g. myocardial and cerebral infarction. The aim of this study was to perform a meta-analysis of randomized controlled trials (RCTs) to evaluate the clinical effect of Ligustrazine on diabetic nephropathy (DN). PUBMED, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Chinese Biological Medicine Database (CBM), China National Knowledge Infrastructure (CNKI) Database, etc. were searched by computer and manual methods to identify RCTs that were used to evaluate the clinical effect of Ligustrazine on DN patients. Twenty five studies comprising 25 RCTs were involved including 1645 patients (858 in the treatment group and 787 in the control group). The meta-analysis suggests that compared with the control group, Ligustrazine injection has a significant therapeutic effect on improving renal function (blood urea nitrogen [BUN] and serum creatinine [SCr]) and reducing in urine protein (24 h urine protein, urine micro albumin and urinary albumin excretion rate [UAER]) in DN patients.

A twelve-week pilot study was conducted on 11 male children, aged five to 19 years, who had ASD (autistic symptom disorder) of varying degrees of severity. These eleven subjects were each examined three times in the 12-week period: at the first week, 6th week, and 12th week. During each examination, two sets of full-body thermographs were taken of each child, before and fifteen minutes after drinking a solution of stable water clusters with a double helix configuration. This solution of stable water clusters is called double helix water (DHW). In the before thermographs, a consistent thermal pattern of six hot regions of body surface temperature were identified. They are: left and right upper forehead region of the face; left and right area in front of the center of the ear; left and right area of the inner extreme point of the eye; left and right collarbone region; left and right side neck region; and left and right armpit region. These areas may be interpreted as regions surrounding various acupoints along the GB, BL, ST, SI, SJ meridians. These meridians are yang meridians that on one end reach the head, and hence have branches reaching into the brain, and on the other end reach to the gastrointestinal tract and urinary bladder system. Thus, they can be considered to explain the major clinical symptoms of ASD. These thermal patterns, if confirmed in a larger clinical study, may lead to a new way to diagnose ASD, and to test the effectiveness of any treatment. When such a thermal pattern is discovered early, say around the age of 18 months, preventive action can be initiated before observation of any behavior disorder. We simultaneously studied the healing effect of stable water clusters with double helix configuration (DHW) on these subjects. The quantitative reduction of maximum temperature at these six regions was calculated. A consistent reduction was noted and suggests a positive healing effect taking place within a very short time period (fifteen minutes), and lasting over a long time period (12 weeks). Quantitative evaluation by the parents over the 12-week period showed that eight out of 11 children had physiological and behavioral improvement. Our findings with these small numbers suggest a reliable method of early diagnosis/detection and also an effective treatment of ASD. We therefore conclude that a study of larger numbers of children with ASD should be conducted.

The purpose of this study is to evaluate the effects of Chinese herbal medicines on the enzymatic activity of CYP3A4 and the possible metabolism-based herb-drug interactions in human liver microsomes and in rats. Fifty single-herbal preparations were screened for the activity of CYP3A4 using human liver microsomes for an in vitro probe reaction study. The enzymatic activity of CYP3A4 was estimated by determing the 6β-hydroxytestosterone metabolized from testosterone performed on a liquid chromatography-tandem mass spectrometry (LC-MS/MS). Huang Qin (Scutellaria baicalensis Geprgi), Mu Dan Pi (Paeonia suffruticosa Andr.), Ji Shiee Terng (Spatholobus suberectus Dunn.) and Huang Qi (Astragalus membranaceus [Fisch] Bge) have been demonstrated to have remarkable inhibiting effects on the metabolism of CYP3A4, whereas Xi Yi Hua (Magnolia biondii Pamp.) exhibited a moderate inhibition. These five single herbs were further investigated in an animal study using midazolam. Mu Dan Pi, Ji Shiee Terng and Huang Qi were observed to have greatly increased in the C_max and AUC of midazolam. This study provides evidence of possible herb-drug interactions involved with certain single herbs.

According to the principles of traditional Chinese medicine, channels and collaterals within the body provide pathways through which qi and blood travel, and each channel or collateral is linked with a specific organ. The Yinlingquan (spleen 9, SP9) and Ququan (liver 8, LR8) acupoints represent the sea points of the spleen and liver meridians, respectively, from which qi and blood flow into their specific visceral organs. The purpose of this study was to investigate the changes in blood flow/perfusion in the liver and spleen resulting from the application of 2 Hz electro-acupuncture (EA) to the Yinlingquan (SP9) or Ququan (LR8) acupoints. A total of 18 Spragrue-Dawley rats were randomly divided into three groups of six rats each as follows: sham group receiving sham EA; Yinlingquan (SP9) group receiving 2 Hz EA, applied at bilateral Yinlingquan (SP9) acupoints; and Ququan (LR8) groups receiving 2 Hz EA, applied at bilateral Ququan (LR8) acupoints. The mean blood flow/perfusion of the spleen and liver was recorded using a laser Doppler blood flow monitor prior to EA (representing the baseline), during EA, and post-EA. Each measurement period lasted ten minutes. Nitric oxide levels were also measured from the right femoral arterial blood, following the conclusion of each series of blood flow/perfusion recordings. The results indicate that the sham EA did not increase the mean blood flow/perfusion in the liver or spleen; 2 Hz EA at bilateral Yinlingquan (SP9) acupoints increased the mean blood flow/perfusion in the spleen, but not in the liver. In contrast, 2 Hz EA at bilateral Ququan (LR8) acupoints increased the mean blood flow/perfusion in the liver, but not in the spleen. Nitric oxide levels showed no significant difference between any of the groups at any stage of the measurements. According to the results, we conclude that EA at the Yinlingquan (SP9) and Ququan (LR8) acupoints can increase the blood flow in the spleen and liver, respectively.

Disruption of the blood-brain barrier (BBB) contributes to the inflammatory response and edema formation in the brain, exacerbating brain damage. The present study evaluated the effects of Scutellaria baicalensis (SR) water extracts on BBB disruption after intracerebral hemorrhage (ICH) in rats. ICH was induced by stereotaxic intrastriatal injection of bacterial type VII collagenase, and SR was administrated orally three times (50 mg/ml/kg) during the 48 h after ICH onset. SR treatment significantly reduced the degree of (1) hemorrhage volume and edema percentage of the ipsilateral hemisphere, (2) brain water content, (3) MPO-positive neutrophil infiltration in the peri-hematoma, and (4) BBB permeability measured by Evans blue leakage. In addition, expression of matrix metalloproteinase (MMP)-9, MMP-12, and tissue inhibitor of MMPs (TIMP)-1 were investigated with immunohistochemistry. SR treatment reduced MMP-9 and MMP-12 expression in the peri-hematoma after ICH. These results indicate that SR attenuates the BBB disruption through anti-inflammatory effects and suppression of MMP expression. These findings provide a pharmacological basis for the use of SR in the treatment of the BBB disruption following stroke and trauma.

Type 2 diabetes is characterized by oxidative stress and a chronic low-grade inflammatory state, which also play roles in the pathogenesis of this disease and the accompanying vascular complications by increasing the production of free radicals and pro-inflammatory cytokines. Cucurbita ficifolia Bouché (C. ficifolia) is an edible Mexican plant whose hypoglycemic activity has been demonstrated in several experimental and clinical conditions. Recently, D-chiro-inositol has been proposed as the compound responsible for the hypoglycemic effects; however, the antioxidant and anti-inflammatory potential of this plant has not yet been explored. The aim of this research is to study the influence of a hypoglycemic, D-chiro-inositol-containing fraction from the C. ficifolia fruit (AP-Fraction) on biomarkers of oxidative stress, as well as on the inflammatory cytokines in streptozotocin-induced diabetes. The AP-Fraction obtained from the mature fruit of C. ficifolia contained 3.31 mg of D-chiro-inositol/g of AP-Fraction. The AP-Fraction was administrated daily by gavage to normal mice for 15 days as a preventive treatment. Then these animals were given streptozotocin, and the treatments were continued for an additional 33 days. Pioglitazone was used as a hypoglycemic drug for comparison. Administration of the AP-Fraction significantly increased glutathione (GSH) and decreased malondialdehyde (MDA) in the liver without significantly affecting the levels in other tissues. The AP-Fraction reduced TNF-α and increased IL-6 and IFN-γ in serum. Interestingly, the AP-Fraction also increased IL-10, an anti-inflammatory cytokine. These results suggest that C. ficifolia might be used as an alternative medication for the control of diabetes mellitus and that it has antioxidant and anti-inflammatory properties in addition to its hypoglycemic activity.

The purpose of the present study was to investigate the anti-fatigue effect of Zizania caudiflora (Turczaninow) Nakai (ZC) and hydrolyzed ZC by malted barley (HZC) through a forced swimming test (FST) in mice. After the first measurement of immobility times, the mice were divided into control, fluoxetine, ZC, and HZC groups to match the swimming times in each group. The immobility times in the FST of the control as well as the fluoxetine, ZC, and HZC-administered groups after administration for three days were 135.3 ± 3.3,66.8 ± 3.9,120.2 ± 2.7, and 123.2 ± 2.9 sec, respectively. The immobility times in the FST of the ZC and HZC-administered groups for 14 days were significantly decreased in comparison with the control group (p < 0.01). In addition, the immobility times of ZC and HZC-administered groups for 14 days in the tail-suspension test were also significantly decreased in comparison with the control group (p < 0.05). The plasma levels of albumin, glucose, and total protein were significantly increased and creatine phosphokinase was significantly decreased in the ZC and HZC-administered groups compared to the control group. However, the levels of lactate dehydrogenase and blood urea nitrogen in the ZC and HZC-administered groups did not represent a significant difference compared to the control group. In summary, these results suggest that ZC or HZC might be a candidate for an anti-fatigue agent.

Rhizoma Dioscoreae Nipponicae (RDN) is an herbal medicine. In the theories of Traditional Chinese Medicine (TCM), the function of RDN is to expel wind and remove dampness. Inflammatory mechanisms play an important role in the pathological process and prognosis of acute gouty arthritis (AGA). The aim of this study was to determine the specially expressed proteins through testing the proteins of the synovium in rats with AGA. The animal model of AGA was set up by Monosodium urate crystal (MSU) combined with hypoxanthine (HX), which was ameliorated in our previous experiment. Blood samples for measurement of serum uric acid were collected prior to sacrifice. Outcomes were assessed (two days after injection) by histological stain and protein quantitation. Three chips of RayBio^Ⓡ Human Label-based Antibody Array I were applied to detect 90 proteins in the synovium tissue of AGA rats. 14 differently expressed proteins were found in the synovium of AGA rats, and nine of them were first found in this model. There were seven up-regulated and seven down-regulated proteins, both TRAIL and Neuropilin-2 could be identified as key contributors to the pathomechanism of AGA.

Eucommiae cortex (EC) is used in various traditional Korean medicines in the form of tonics, analgesics, and sedatives. However, the underlying mechanism of its anti-inflammatory effect remains unclear. This study attempts to determine the effects of EC on lipopolysaccharide (LPS)-induced inflammatory responses in mouse peritoneal macrophages. The findings of the study show that EC inhibits the LPS-induced production of tumor necrosis factor-alpha and interleukin-6. Exposure to EC also reduces an inflammation-induced increase in the levels of cyclooxigenase-2 and the production of prostaglandin E₂ and nitric oxide in mouse peritoneal macrophages. Furthermore, EC suppresses the activation of nuclear factor-kappa B and caspase-1. These results provide novel insights into the pharmacological action of EC and indicate that EC has a potential in the treatment of inflammatory diseases.

Human respiratory syncytial virus (HRSV) causes serious pediatric infection of the lower respiratory tract without effective therapeutic modality. Sheng-Ma-Ge-Gen-Tang (SMGGT; Shoma-kakkon-to) has been proven to be effective at inhibiting HRSV-induced plaque formation, and Cimicifuga foetida is the major constituent of SMGGT. We tested the hypothesis that C. foetida effectively inhibited the cytopathic effects of HRSV by a plaque reduction assay in both human upper (HEp2) and lower (A549) respiratory tract cell lines. Its ability to stimulate anti-viral cytokines was evaluated by an enzyme-linked immunosorbent assay (ELISA). C. foetida dose-dependently inhibited HRSV-induced plaque formation (p < 0.0001) before and after viral inoculation, especially in A549 cells (p < 0.0001). C. foetida dose-dependently inhibited viral attachment (p < 0.0001) and could increase heparins effect on viral attachment. In addition, C. foetida time-dependently and dose-dependently (p < 0.0001) inhibited HRSV internalization. C. foetida could stimulate epithelial cells to secrete IFN-β to counteract viral infection. However, C. foetida did not stimulate TNF-α secretion. Therefore, C. foetida could be useful in managing HRSV infection. This is the first evidence to support that C. foetida possesses antiviral activity.

Mulberry (Morus alba L.) leaf tea is promoted for its health benefits and the control of diabetes in Asian nations. The blood glucose lowering activity of mulberry leaf extract (MA) has been proven; however, the molecular basis underlying this effect remains unclear. The aim of the present work is to elucidate its mechanism of the antihyperglycemic action, by examining the effect of MA on glucose uptake and the translocation of glucose transporter 4 protein (GLUT4) to the plasma membrane of adipocytes isolated from diabetic rats. The incubation of adipocytes with 5–45 μg/ml MA resulted in 31–54% increase of glucose uptake in a dose-dependent manner. This glucose uptake enhancing effect was inhibited by the phosphoinositol 3-kinase (PI3-K) inhibitor, wortmannin (100 nM). The GLUT4 protein on the plasma membrane fraction of adipocytes was markedly increased after treatment with 15 μg/ml MA extract. Interestingly, gallic acid, one of the phenolic compounds found in MA extract, increased glucose uptake and enhanced the translocation of GLUT4 at concentrations comparable to the amount of gallic acid in the effective concentration ranges of MA. Thus, it is likely that gallic acid contributes, at least in part, to its antihyperglycemic activity. The present results suggest that the antihyperglycemic action of MA is mediated by increasing glucose uptake via the activation of PI3-K signaling pathway and translocation of GLUT4 to the plasma membrane. These findings are the first molecular evidence supporting the mulberry tea as herbal medicine for diabetic patients.

Dehydrocorydaline is an alkaloid isolated from traditional Chinese herb Corydalis yanhusuo W.T. Wang. We discovered that it possessed anti-tumor potential during screening of anti-tumor natural products from Chinese medicine. In this study, its anti-tumor potential was investigated with breast cancer line cells MCF-7 in vitro. The anti-proliferative effect of dehydrocorydaline was determined by MTT assay and the mitochondrial membrane potential (Δ Ψ m) was monitored by JC-1 staining. DNA fragments were visualized by Hoechst 33342 staining and DNA ladder assay. Apoptotic related protein expressions were measured by Western blotting. Dehydrocorydaline significantly inhibited MCF-7 cell proliferation in a dose- dependent manner, which could be reversed by a caspase-8 inhibitor, Z-IETD-FMK. Dehydrocorydaline increased DNA fragments without affecting ΔΨm. Western blotting assay showed that dehydrocorydaline dose-dependently increased Bax protein expression and decreased Bcl-2 protein expression. Furthermore, dehydrocorydaline induced activation of caspase-7,-8 and the cleavage of PARP without affecting caspase-9. These results showed that dehydrocorydaline inhibits MCF-7 cell proliferation by inducing apoptosis mediated by regulating Bax/Bcl-2, activating caspases as well as cleaving PARP.

Administration of mountain ginseng (MG) extract can restore advanced cancer to a normal state. To elucidate the mechanism by which MG extract prevents the progression of lung cancer, the processes of proliferation and death of lung cancer cells (A549) were examined after treatment with MG extract. Butanol-extracted MG (BX-MG) showed a high inhibitory effect (IC₅₀ = 2 mg/ml) by attenuating proliferation and inducing apoptosis in lung cancer cells. By HPLC-UV analysis of BX-MG, ginsenosides, Rb1 was identified as the most abundant ginsenoside, followed by Rg1, Re, Rc and Rb2. BX-MG induced caspase-3 dependent apoptosis by inhibiting NF-κB. In addition, BX-MG activated p53 and p21, resulting in the attenuated proliferation of A549 cells. Reduced activity of the NF-κB promoter and increased activity of the p53 promoter indicate that BX-MG regulates apoptosis at the level of transcription in lung cancer cells. Furthermore, BX-MG blocked the nuclear translocation of RelA and the associated reduction in surviving. These results suggest that BX-MG inhibits lung cancer cell growth by activating tumor suppressors and inhibiting nuclear translocation of NF-κB.

Ginsenosides and withanolides are the secondary metabolites from Panax ginseng and Withania somnifera, respectively. These compounds have similar biological properties. Two-dimensional electrophoresis (2-DE) analysis was utilized to reveal the protein profile in the roots of both plants, with the aim of clarifying similarly- and differentially-expressed proteins. Total proteins of Korea ginseng (P. ginseng) and Indian ginseng (W. somnifera) roots were separated by 2-DE using a pH 4–7 immobilized pH gradient strip in the first dimension and 12% sodium dodecyl sulfate polyacrylamide gel electrophoresis in the second dimension. The protein spots were visualized by silver staining. Twenty-one P. ginseng proteins and 35 W. somnifera proteins were chosen for identification by matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry; of these, functions were ascribed to 14 and 22 of the P. ginseng and W. somnifera proteins, respectively. Functions mainly included general cell metabolism, defense and secondary metabolism. ATPase and alcohol dehydrogenase proteins were expressed in both plants. The results of this study, to our knowledge, are the first to provide a reference 2-DE map for the W. somnifera root proteome, and will aid in the understanding of the expression and functions of proteins in the roots of Korean ginseng and Indian ginseng.