The American Journal of Chinese Medicine

This study is a double-blind randomized controlled trial on the effect of intradermal acupuncture on insomnia after stroke. Hospitalized stroke patients with insomnia were enrolled in the study and were randomly assigned to either a real intradermal acupuncture group (RA group) or a sham acupuncture group (SA group). The RA group received intradermal acupuncture on Shen-Men (He-7) and Nei-Kuan (EH-6) for three days, and the SA group received sham acupuncture on the same points. The effect of acupuncture on insomnia was measured using Insomnia Severity Index (ISI) and Athens Insomnia Scale (AIS) at baseline and three days after treatment. To assess the effect of acupuncture on the autonomic nervous function, the subjects' blood pressure and heart rate variability were monitored. Fifty-two subjects (27 in the RA group and 25 in the SA group) were included in the final analysis. The insomnia-related scales ISI and AIS showed greater improvement of insomnia in the RA group than in the SA group. Moreover, there is a greater reduction of the number of non-dippers and a greater decrease of the LF/HF ratio (heart rate variability) in the RA group than in the SA group. These results indicate that sympathetic hyperactivities were stabilized in the RA group. It can thus be concluded that intradermal acupuncture on Shen-Men and Nei-Kuan is a useful therapeutic method for post stroke-onset insomnia as it reduces sympathetic hyperactivities.

Ear acupuncture stimulation has been used for body weight reduction as early as the 1970s. Several hypotheses have been proposed in literature regarding its mechanism of action, among which are the effects of the stimulation of the hypothalamic satiety center on decreased neuropeptide Y production. Here, we present another possible mechanism to account for the temporary and short-term effects of ear acupuncture stimulation in the treatment of obesity, the sympathetic effects of the autonomic nervous system. 14 female volunteers underwent a randomized clinical trial of the ear acupuncture stimulation. A prospective, sham-point control, crossover study was performed with two sequential four-week stimulation periods separated by a two-week washout interval. The clinical features of and effects on the autonomic nervous system were recorded and analyzed. Decreased body weight was observed in both the experimental and the control groups in the first 4 weeks of stimulation. Sympathomimetic effects were also noted in both groups. Whereas the sympathomimetic effects and body weight reduction were sustained in the experimental group in the second 4 weeks of stimulation, such effects were not observed in the control group. Some sympathomimetic effects were noted in both the experimental and the control groups initially. This effect remained apparent in the experimental group in sequential stimulation but was lost in the control group. Consequently, we believe that sympathomimetic effects may account for the reduction in body weight by temporarily increasing basal metabolic rate and decreasing appetite, but the body may regain weight after the termination of such effects. Accordingly, the combination of an optimal exercise and diet program with repeated acupoint therapy may be necessary to maintain a healthy body weight.

This was the first study to determine the effect of tanshinone IIA (an active ingredient in herb Danshen) on fetuses in utero under unstressed condition. Tanshinone IIA or 0.9% NaCl as control was intravenously (i.v.) administrated into pregnant ewes. Both maternal and fetal blood were analyzed for PO₂, PCO₂, SO₂%, hemoglobin, hemotecrit, glucose, lactic acid, Na⁺, K⁺, and Cl^- concentrations. Maternal and fetal heart functions were assessed by examining cardiac enzymes and cardiovascular responses. The results showed that tanshinone IIA did not alter the blood values in ewes and fetuses. Cardiac enzyme activities related to the heart remained unchanged. In cardiovascular experiments, no alternation in maternal blood pressure by tanshinone IIA was observed. However, fetal systolic pressure was slightly and significantly increased following i.v. tanshinone IIA into the mothers, while fetal diastolic pressure, mean arterial pressure, and heart rate were not changed. The results demonstrated that tanshinone IIA used during the last third of gestation did not cause the biochemical changes related to cardiac functions in both maternal and fetal sheep. Fetal oxygen metabolism remained stable in utero, providing new information for clinical use of the herb in pregnancy. That tanshinone IIA increased fetal systolic pressure may open new opportunities to study the herb in fetal medicine.

We previously reported that the leaf extract of Muntingia calabura L. (Tiliaceae) exerts a potent hypotensive effect in the normotensive rats. The antihypertensive activity of this plant extract, however, is currently unknown. In the present study, we investigated the antihypertensive effects of the n-butanol soluble fraction (BSF) from methanol leaf extract of M. calabura in spontaneously hypertensive rats (SHR), and delineated is underlying mechanisms. The intravenous bolus administration of the BSF (10–100 mg/kg) of M. calabura produced biphasic dose-related antihypertensive and bradycardiac effects in SHR. The BSF-induced initial cardiovascular depressive effects lasted for 10 min, and the delayed effects commenced 40 min and lasted for at least 120 min postinjection. These cardiovascular depressive effects of BSF treatments were greater in SHR than in normotensive Wistar-Kyoto (WKY) rats. Both the initial and delayed antihypertensive and bradycardiac effects of BSF (25 mg/kg, i.v.) in SHR, were significantly blocked by pretreatment with a nonselective nitric oxide (NO) synthase (NOS) inhibitor, a soluble guanylyl cyclase (sGC) inhibitor, or a protein kinase G (PKG) inhibitor. Moreover, the initial effects of BSF in SHR were inhibited by pretreatment with a selective endothelial NOS (eNOS) inhibitor; whereas the delayed effects were attenuated by a selective inducible NOS (iNOS) inhibitor. These results indicate that the BSF from the leaf of M. calabura elicited both transient and delayed antihypertensive and bradycardiac actions in SHR, which might be mediated through NO generated respectively by eNOS and iNOS. Furthermore, activation of sGC/cGMP/PKG signaling pathway may participate in the M. calabura-induced biphasic cardiovascular effects.

The relationship between changes of cardiac function and the gene expressions of two major myocardial skeleton proteins, titin and nebulin, and the effect of gypenosides on these gene expressions in diabetic cardiomyopathy rat were explored in the present study. Forty Sprague-Dawley rats were randomly divided into three groups: control group, diabetic cardiomyopathy group and gypenosides-treated diabetic cardiomyopathy group. The diabetic cardiomyopathy was induced in rats by injecting streptozotocin (STZ, 55 mg/kg) intraperitoneally. Seven weeks after the rats suffered from diabetes, the rats were treated with gypenosides 100 mg/kg per day orally for six weeks in gypenosides-treated group. In the meanwhile, the pure water was given to diabetic cardiomyopathy and the control groups. Subsequently, the cardiac functions, including left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), ± dP/dt_max and t–dP/d_maxt, as well as the mRNA content and proteins of titin and nebulin in myocardium were determined. The results indicated that (1) the diabetic cardiomyopathy rats had decreased LVSP and ± dP/dt_max, increased LVEDP, and prolonged t–dP/dt_max than normal rats; (2) LVSP and ± dP/dt_max in diabetic cardiomyopathy rats treated with gypenosides were significantly higher and LVEDP and t–dP/dt_max were significantly lower than those without giving gypenosides; (3) the mRNA contents and proteins of titin and nebulin in diabetic cardiomyopathy rats were remarkably lower than those in the control rats and gypenosides had no effect on mRNA and protein expression levels of titin and nebulin in diabetic cardiomyopathy rats. We conclude that (1) the cardiac function as well as the mRNA expressions of titin and nebulin decreased in diabetic cardiomyopathy rats; (2) gypenosides secure cardiac muscles and their function from diabetic impairment and these beneficial effects of gypenosides are not by changing the expressions of titin and nebulin.

It was reported that Dipsaci radix (DR) has a reinforcement effect on the bone-muscle dysfunction in the oriental medical classics and the experimental animal studies. The muscle atrophy was induced by unilateral transection of the sciatic nerve of the rats. Water-extract of DR was used as treatment once a day for 12 days. The muscle weights of the hind limb, atrophic changes, glycogen contents, compositions and cross-section areas of muscle fiber types in soleus and medial gastrocnemius were investigated. Muscle fiber type was classified to type-I and type-II with MHCf immunohistochemistry. Furthermore, Bax and Bcl-2 expressions were observed with immunohistochemiatry. DR treatment significantly increased muscle weights of soleus, medial gastrocnemius, lateral gastrocnemius, and posterior tibialis of the damaged hind limb. DR treatment reduced apoptotic muscle nuclei and hyaline-degenerated muscle fibers in soleus and medial gastrocnemius of the damaged hind limb. DR treatment also significantly increased glycogen contents in medial gastrocnemius of the damaged hind limb. DR treatment significantly attenuated the slow-to-fast shift in soleus of the damaged hind limb but not in medial gastrocnemius. DR treatment significantly increased cross-section areas of type-I and type-II fibers in soleus and medial gastrocnemius of the damaged hind limb. In soleus and medial gastrocnemius, DR treatment significantly reduced Bax positive muscle nuclei in the damaged hind limb. These results suggest that DR treatment has an anti-atrophic effect and an anti-apoptotic effect against myonuclear apoptosis induced by the peripheral nerve damage.

This study investigates the hepatoprotective activity of ethanol extract from Shidagonglao roots (SDGL_EtOH). The hepatoprotective effect of SDGL_EtOH (20, 100 and 500 mg/kg) was analyzed on carbon tetrachloride (CCl₄)-induced acute liver injury. Rats pretreated orally with SDGL_EtOH (100 and 500 mg/kg) and silymarin (200 mg/kg) for 3 consecutive days prior to the administration of a single dose of 50% CCl₄ (0.10 ml/100 g of bw, ip) significantly prevented the increases in the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in CCl₄-treated rats. Histological analysis also showed that SDGL_EtOH (100 and 500 mg/kg) and silymarin reduced the incidence of liver lesions including vacuole formation, neutrophil infiltration and necrosis of hepatocytes induced by CCl₄ in rats. Moreover, the SDGL_EtOH (100 and 500 mg/kg) increased the activities of anti-oxidative enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRd) and decreased malondialdehyde (MDA) level in liver, as compared to those in the CCl₄-treated group. Furthermore, SDGL_EtOH (100 and 500 mg/kg) and silymarin attenuated the increased levels of tumor necrosis factor-α (TNF-α) in serum and nitric oxide (NO) in liver as compared to the CCl₄-treated group. The hepatoprotective mechanisms of SDGL_EtOH are likely related to inhibition of TNF-α, MDA and NO productions via increasing the activities of antioxidant enzymes (SOD, GPx and GRd). These experimental results suggest that SDGL_EtOH can attenuate CCl₄-induced acute liver injury in rats.

The goal of this study was to investigate the possible therapy mechanism of triterpene acids of Eriobotrya japonica (Thunb.) Lindl. Leaf (TAL) in alveolar macrophage (AM) of chronic bronchitis (CB) rats. CB model was established by injection of bacillus calmette guein (BCG) plus lipopolisacharide (LPS) in rats. TAL significantly inhibited the increased NO concentration, iNOS expression and phosphorylation of p38 MAPK in alveolar macrophages (AMs) of CB rats. Using in vivo test, we found that SB203580, a p38 MAPK inhibitor, (10 μM) significantly inhibited inducible nitric oxide synthase (iNOS) mRNA expression in AM. This data indicate that TAL highly decreases excessive iNOS expression and NO induction, and p38 MAPK signal transduction participates in iNOS expression and NO induction in AM of CB rats. The effect of TAL on iNOS expression in AM may be related to its inhibition of p38 MAPK signal transduction.

Depression is one of the most common psychiatric disorders that affects over 10% of individuals. However there is no desirable therapeutic approach nowadays. Thus, looking for an alternative treatment is important. The objectives of this study are to investigate the antidepressant effects of the rhizomes of Gastradia elata B_L, a traditional Chinese medicine, in the animal model forced-swimming test (FST), and to analyze the monoamine content in the rats' brain regions in order to better understand the possible mechanisms of the water extract of the rhizomes of Gastrodia elata B_L (WGE). Subchronic administration of 0.5 or 1.0 mg/kg bw WGE by gavage for 21 consecutive days significantly reduced the immobility duration of rats in the test session of FST as compared to the control group (p < 0.05), with the equivalent effects as the antidepressant drug fluoxetine. The concentration of serotonin (5-HT) in the frontal cortex and dopamine (DA) in striatum were significantly increased after WGE administration (p < 0.05). The ratio of 5-HIAA/5-HT and (DOPAC + HVA)/DA, i.e. the turnover of 5-HT and DA respectively, were also significantly lowered in WGE groups (p < 0.05). In summary, the present study showed that the WGE possesses antidepressant-like effect on rats in the animal model FST, and the possible mechanism may be via regulating both the serotonergic and dopaminergic systems.

The roots of Cistanche (C.) tubulosa (Orobanchaceae), a parasitic plant that grows in the Taklamakan desert, are traditionally used as medicines and foods in China. We prepared aqueous ethanol extract (CTE) from the roots of C. tubulosa and its hypocholesterolemic effect was evaluated. Using gene chip and RT-PCR analysis of the livers of mice given CTE (400 mg/kg) for 14 days, we found mRNA expression of molecules related to cholesterol transport [apolipoprotein B and very low density lipoprotein (VLDL) receptor] and metabolism [cytochrome P450 side chain cleave (SCC) and steroid 5α-reductase 2] were up-regulated. The administration of CTE (400 mg/kg) for 14 days significantly suppressed serum cholesterol elevation in high cholesterol diet-fed mice. The mRNA expressions of VLDL receptor and cytochrome P450 SCC were significantly enhanced. In addition, acteoside, a major constituent of CTE, was found to enhance the mRNA expressions of apolipoprotein B, VLDL receptor, and cytochrome P450 SCC in HepG2 hepatocytes. These results suggest that CTE affects the mRNA expressions of molecules related to cholesterol transport and metabolism and exhibits hypocholesterolemic activity in diet-induced hypercholesterolemia mice. Acteoside was involved in the hypocholesterolemic activity of CTE.

Panax ginseng C A Meyer (PG) is one of the most popular qi-invigorating herbal medicine and has been used to promote health, vitality, and longevity in China. Although PG has been used in traditional Chinese medicine for millennia, its qi-invigorating activities still lack convincing evidence. We investigated the effects of Panax ginseng polysaccharide (PGP) on energy metabolism and mitochondrial protection. The chronic hypoxia model was set up. Lipid peroxidation product malondialdehyde (MDA) was assayed by thiobarbituric acid (TBA) colorimetry. Mice liver mitochondria were isolated by differential centrifugation. The spectrophotometric method was used to measure the swelling of mitochondria. The levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate (AMP) in liver cells were determined by reversed-phase high performance liquid chromatography (RP-HPLC), adenylate energy charge (AEC), total adenylate pool (TAP), ATP/ADP and ATP/AMP ratio were calculated. The creatine kinase (CK) activities in mice skeletal muscle were determined by a commercial monitoring kit. The result showed that PGP could inhibit mitochondrial injury and swelling induced by Fe²⁺-L-Cys in a concentration-dependent manner. PGP which was administered by oral gavage daily for 10 days could inhibit the formation of MDA in mice brain, increase levels of ATP, ADP, TAP and AEC, ratio of ATP/ADP and ATP/AMP in liver cells, increase CK activities in mice skeletal muscle under chronic hypoxia condition. These results indicate that PGP protect mitochondria by inhibiting mitochondrial swelling, and improving energy metabolism. PGP functions as a preventive antioxidant by increasing CK activities. Therefore, PGP had the pharmaceutical activities of antihypoxia, antioxidation and improving energy status.

The aim of the present work was to explore the anti-hepatoma effects of icariin both in vitro and in vivo and to elucidate its potential mechanism of action. The MTT assay was applied to test the anti-proliferative effects of icariin in vitro. HepG2 bearing NMRI nu/nu mice were used to test the anticancer effects of icariin in vivo. Immunohistochemical assay and flow cytometry assay (FACS) were applied to detect the possible mechanisms of action of icariin. MTT assay illustrated that icariin inhibited the proliferation of HepG2 cells in a concentration dependent manner; meanwhile, icariin inhibited the tumor growth in HepG2 bearing NMRI nu/nu mice. The tumor weight was inhibited by 55.6% and tumor volume was inhibited by 47.2%. Icariin did not influence the spleen and body weights or blood parameters. Immunohistochemical analysis indicated that the expressions of both CD31 and Ki67 in the icariin treated group were significantly lower than those in the control group (p < 0.01). FACS assay showed that icariin dramatically decreased the percentage of CD4+ and CD8+ cells in bone marrow and CD19+ cells in blood on day 8. On day 17, the percentage of CD8+ cells in blood was lower than those in the control group. CD4/CD8 ratio in icariin group was significantly elevated in bone marrow on day 17. Icariin showed anticancer efficacy both in vitro and in vivo. The possible mechanism of action could be related to its anti-angiogenesis and anti-proliferative effects in tumors.

To study the oxidative stress level of the influenza virus A FM1 subset-infected mouse in intranasal inhalation as a model, we employ an ascorbyl radical's ESR (electron spin resonance) spectrum as an oxidative stress biomarker. These infected mice were pretreated with Ribavirin, ascorbic acid, superoxide dismutase (SOD) or Kegan Liyan oral prescription (KGLY, proprietary Chinese medicine for influenza and common cold) in the stomach tube for 3 days, and then followed by the virus-infecting for 4 days. On the 4th day, samples were collected. It is recognized the strength of ascorbyl radical's ESR signal (A^-.) (a_{H4 = 0.177} Gauss, g = 2.00517) denotes oxidative stress level in vivo and in vitro. The magnitude of ESR spectrum (28.65 ± 10.71 AU) in mice infected with influenza virus was significantly higher than those of healthy control mice (19.10 ± 3.61 AU). Serum A^-. in mice treated with Ribavirin, ascorbic acid, SOD and KGLY declined to 19.70 ± 6.05, 18.50 ± 2.93 and 16.25 ± 3.59, 18.40 ± 2.14 AU respectively. It is close to A^-. signal height in healthy controls via down-regulation of the influenza virus-caused oxidative stress level getting decline in the lung index of pneumonia as compare to those of untreated healthy and the influenza virus infected mice pneumonia. It is well known that SOD can prevent the influenza virus pneumonia enhancing mouse survival rate; Ribavirin can treat viral diseases. Data from this study suggested that KGLY may indirectly relieve influenza virus-infected pneumonia via down- regulation of virus caused oxidative stress coupled with a redox reaction cascade as ribavirin, ascorbic acid and SOD.

This study was carried out to determine the effect of saponins of Panax notoginseng (SPN), a naturally occurring cardiovascular agent, on: (1) glucose uptake, (2) GLUT4 translocation and (3) glycogen synthesis in 3T3-L1 adipocytes. Electrospray ionization-Mass spectrometry (ESI-MS) was used to determine the structural characterization of the major active components of SPN. 3T3-L1 adipocytes were cultured and treated with 100 nM insulin alone or with 10, 50 and 100 μg/ml of SPN. [³H]2-deoxyglucose glucose uptake, GLUT4 immunofluorescence imaging and glycogen synthesis assay were carried out to determine the effects of SPN on glucose metabolism. Under insulin stimulation, SPN significantly increased glucose uptake in a dose-dependent manner; 50 μg/ml of SPN increased glucose uptake by 64% (p < 0.001). Immunofluorescence imaging and analysis have revealed that 50 and 100 μg/ml of SPN increased GLUT4 in the plasma membrane by 3-fold and 6-fold respectively (p < 0.001). Furthermore, the incorporation of D-[U-¹⁴C] glucose into glycogen was enhanced by 53% in 3T3-L1 cells treated with 100 μg/ml of SPN (p < 0.01 vs. insulin stimulation alone). SPN, a naturally occurring agent used to treat ischemic cardio-cerebral vascular disease in China, enhanced insulin-stimulated glucose uptake and glycogen synthesis in adipocytes. The results of this study indicate that SPN may have a therapeutic potential for hyperglycaemia in type 2 diabetes.

This study evaluated the proliferative effects of chishao on RSC96, Schwann cells. A dose-dependent proliferative effect of chishao was obtained by methylthiazol tetrazolium (MTT), proliferating cell nuclear antigen (PCNA) Western blotting, and wound healing assays in Schwann cells administered with chishao (0–500 mg/ml), except at 500 mg/ml concentration. The chishao-treated cells also showed a dose-dependent activated fibroblast growth factor-2 (FGF-2) signaling with increased urokinase plasminogen activator (uPA) and decreased plasminogen activator inhibitor-1 (PAI-1), enhanced proliferative proteins, extracellular signal regulated kinase (ERK) and c-Jun N-terminal kinase (JNK)-signaling. Using mitogen-actvated protein kinase (MAPK)-signaling chemical inhibitors, U0126, SB203580, and SP600125, the proliferative effects of chishao on RSC cells were identified to be ERK- and JNK- signaling dependent. Based on the results, applying appropriate doses of chishao to Schwann cells would be a potential approach for enhancing neuron regeneration.

Resveratrol is a polyphenol compound and prominent anti-inflammatory agent found in plants, including the fruits of Morus alba. However, the therapeutic mechanisms of resveratrol remain largely unclear. To gain insight into the biological effects of resveratrol, we examined its influence on LPS-induced IL-8 production in the human monocytic cell line, THP-1. In inflammatory diseases, IL-8 plays a central role in the initiation and maintenance of inflammatory response. In the present study, IL-8 production was measured by ELISA and RT-PCR, while MAPK activation, IκBα degradation, nuclear factor (NF)-κB activation and cyclooxygenase (COX)-2 expression were determined by Western blot analysis. Resveratrol inhibited LPS-induced IL-8 production in a dose-dependent manner. Furthermore, resveratrol inhibited extracellular signal-regulated kinase (ERK) and p38 MAPK phosphorylation, IκBα degradation, NF-κB activation and cyclooxygenase (COX)-2 expression, which suggest that resveratrol inhibits IL-8 secretion by blocking MAPK phosphorylation and NF-κB activation. Taken together, these findings may help elucidate the mechanism by which resveratrol modulates THP-1 cell activation under inflammatory conditions.