Yu-Chen Lee

Acute effect of electroacupuncture at the Zusanli acupoints on decreasing insulin resistance as shown by lowering plasma free fatty acid levels in steroid-background male rats

BackgroundInsulin sensitivity has been enhanced by electroacupuncture (EA) in rats, but the EA phenomenon in an insulin resistant state is still unclear. This study reports the use of a large dose of prednisolone to evaluate the effects of EA in a state of insulin resistance.MethodsThe plasma levels of free fatty acids (FFAs) were estimated in steroid-background rats (SBRs) and compared with those in healthy rats treated with normal saline. In addition, plasma glucose and endogenous insulin levels were assayed to calculate the homeostasis model assessment (HOMA) index. Intravenous glucose tolerance test (IVGTT) was carried out to compare glucose tolerance. The SBRs were randomly divided into EA-treatment and non-EA treatment groups and 15-Hz EA was applied to the bilateral Zusanli acupoints to investigate its effects on insulin resistance. In addition to an insulin challenge test (ICT) and IVGTT, the plasma levels of FFAs were measured and western blot was performed to help determine the effects of EA on the insulin resistant state.ResultsThe plasma levels of FFAs increased markedly in SBRs, the HOMA index was markedly higher, and glucose tolerance was impaired. EA improved glucose tolerance and insulin sensitivity by decreasing the plasma levels of FFAs. Further, the insulin signaling proteins (IRS1) and glucose transporter isoform protein (GLUT4) in skeletal muscle inhibited by prednisolone recovered after EA.ConclusionInsulin resistance was successfully induced by a large dose of prednisolone in male rats. This insulin resistance can be improved by 15 Hz EA at the bilateral Zusanli acupoints, as shown by decreased plasma levels of FFAs.

Electroacupuncture at the Zusanli (ST-36) Acupoint Induces a Hypoglycemic Effect by Stimulating the Cholinergic Nerve in a Rat Model of Streptozotocine-Induced Insulin-Dependent Diabetes Mellitus

Animal studies have shown that electroacupuncture (EA) at Zusanli (ST-36) and Zhongwan (CV-12) acupoints reduces plasma glucose concentrations in rats with type II diabetes. However, whether EA reduces plasma glucose levels in type I diabetes is still unknown. In this study, we explore the various non-insulin-dependent pathways involved in EA-induced lowering of plasma glucose. Streptozotocin (STZ) (60 mg kg−1, i.v.) was administered via the femoral vein to induce insulin-dependent diabetes in non-adrenalectomized and in adrenalectomomized rats. EA (15 Hz) was applied for 30 min to bilateral ST-36 acupoints after administration of Atropine (0.1 mg kg−1 i.p.), Eserine (0.01 mg kg−1 i.p.), or Hemicholinium-3 (5 μg kg−1 i.p.) in non-adrenalectomized rats. Rats administered acetylcholine (0.01 mg kg−1 i.v.) did not undergo EA. Adrenalectomized rats underwent EA at bilateral ST-36 acupoints without further treatment. Blood samples were drawn from all rats before and after EA to measure changes in plasma glucose levels. Expression of insulin signaling proteins (IRS1, AKT2) in atropine-exposed rats before and after EA was measured by western blot. Atropine and hemicholinium-3 completely blocked the plasma glucose lowering effects of EA, whereas eserine led to a significant hypoglycemic response. In addition, plasma glucose levels after administration of acetylcholine were significantly lower than the fasting glucose levels. In STZ-adrenalectomized rats, EA did not induce a hypoglycemic response. EA stimulated the expression of IRS1 and AKT2 and atropine treatment blocked the EA-induced expression of those insulin signaling proteins. Taken together, EA at the ST-36 acupoint reduces plasma glucose concentrations by stimulating the cholinergic nerves.

Characteristics of traditional Chinese medicine usage in patients with stroke in Taiwan: A nationwide population-based study.

ETHNOPHARMACOLOGICAL RELEVANCE Stroke has been the leading causes of death worldwide. Traditional Chinese medicine (TCM) has been used for stoke patients for thousands of years. This study aimed to investigate TCM usage and prescription patterns in stroke patients in Taiwan. MATERIALS AND METHODS We analyzed a random sample of one million individuals representing the 23 million enrollees selected from the National Health Insurance Research Database in Taiwan. Demographic characteristics, TCM usage, prescription patterns and mortality rate among stroke patients were analyzed. RESULTS We identified 23,816 patients who were newly diagnosed with stroke between 2001 and 2009 by their diagnostic codes (ICD-9-CM 430-438). Among them, 4302 patients had hemorrhagic stroke while 19,514 patients had ischemic stroke. Overall, 12% of the stroke patients (n=2862) were TCM users. The median interval between stroke onset to the first TCM consultation is 12.2 months. Among the TCM users, more than half (52.7%) of the patients received both Chinese herbal remedies and acupuncture/traumatology treatment. Bu-yang-huan-wu-tang and Dan-shen (Radix Salviae Miltiorrhizae; Salvia miltiorrhiza Bunge) was the most commonly prescribed Chinese herbal formula and single herb, respectively. TCM users had a higher incidence rate ratio in myalgia, myositis, fasciitis and insomnia than non-TCM users. Mental disorders such as anxiety and depression are common in both TCM and non-TCM users. Comparing with the non-TCM users, the TCM users had a lower mortality rate (adjusted hazard ratios were 0.44 in overall stroke, 0.50 in ischemic stroke and 0.25 in hemorrhagic stroke). CONCLUSION Adjunctive TCM use may reduce the risk of mortality rate among stroke patients. Bu-yang-huan-wu-tang and Dan-shen are the most common prescribed Chinese herbal formula and single herb for stroke patients, respectively. Future study investigating the anti-inflammatory and neuroprotective efficacy of Bu-yang-huan-wu-tang and Dan-shen in stroke is warranted.

A combined therapy using stimulating auricular acupoints enhances lower-level atropine eyedrops when used for myopia control in school-aged children evaluated by a pilot randomized controlled clinical trial

OBJECTIVE This study was designed to compare the reduction in myopia progression in patients treated with atropine eyedrops alone with patients treated with a combined treatment of atropine and stimulation of the auricular acupoints. METHODS This study was a randomized single-blind clinical controlled trial. A total of 71 school-aged children with myopia, who fulfilled the eligibility criteria, were recruited. They were randomly assigned into three groups. These were 22 treated with the 0.25% atropine (0.25A) only, 23 treated with the 0.5% atropine (0.5A) only and 26 treated with 0.25% atropine together with stimulation of the auricular acupoints (0.25A+E). The differences in the post-treatment effects among these three groups were statistically assessed. The primary outcome parameter was myopia progression, which was defined as diopter change per year (D/Y) after cycloplegic refraction measurement. RESULTS The mean myopia progression of the 0.25A group was 0.38+/-0.32 D/Y. No significant difference in mean myopia progression was found between the 0.5A (0.15+/-0.15 D/Y) and 0.25A+E (0.21+/-0.23 D/Y) groups. However, there was a markedly reduced myopia progression in the 0.25A+E group compared to the 0.25A group (p<0.05). Furthermore, there was no statistical difference among these three groups in axial length elongation (ALE) of eye during this stage of the investigation. CONCLUSIONS This study demonstrates that there was efficacy in stimulating the auricular acupoints and this enhanced the action of 0.25% atropine as a means of myopia control. The result was an effect almost equal to that of 0.5% atropine alone. There is also a need that the ALE of the eye should be further investigated over a longer period using the combined therapy.

Electroacupuncture improves glucose tolerance through cholinergic nerve and nitric oxide synthase effects in rats

The purpose of this investigation was to evaluate the effect and mechanisms of electroacupuncture (EA) at the bilateral Zusanli acupoints (ST-36) on glucose tolerance in normal rats. Intravenous glucose tolerance test (IVGTT) was performed to examine the effects of electroacupuncture (EA) on glucose tolerance in rats. The EA group underwent EA at the ST-36, with settings of 15 Hz, 10 mA, and 60 min; the control group underwent the same treatments, but without EA. Atropine, hemicholinium-3 (HC-3) or NG-nitro-L-arginine methyl ester (L-NAME) were injected into the rats alone or simultaneously and EA was performed to investigate differences in plasma glucose levels compared to the control group. Plasma samples were obtained for assaying plasma glucose and free fatty acid (FFA) levels. Western blot was done to determine the insulin signal protein and nNOS to exam the correlation between EA and improvement in glucose tolerance. The EA group had significantly lower plasma glucose levels compared to the control group. Plasma glucose levels differed significantly between the EA and control groups after the administration of L-NAME, atropine, or HC-3 treatments alone, but there were no significant differences in plasma glucose with combined treatment of L-NAME and atropine or L-NAME and HC-3. EA decreased FFA levels and enhanced insulin signal protein (IRS1) and nNOS activities in skeletal muscle during IVGTT. In summary, EA stimulated cholinergic nerves and nitric oxide synthase for lowering plasma FFA levels to improve glucose tolerance.

Ginger and Zingerone Ameliorate Lipopolysaccharide-Induced Acute Systemic Inflammation in Mice, Assessed by Nuclear Factor-κB Bioluminescent Imaging

Ginger is a commonly used spice in cooking. In this study, we comprehensively evaluated the anti-inflammatory activities of ginger and its component zingerone in lipopolysaccharide (LPS)-induced acute systemic inflammation in mice via nuclear factor-κB (NF-κB) bioluminescent imaging. Ginger and zingerone significantly suppressed LPS-induced NF-κB activities in cells in a dose-dependent manner, and the maximal inhibition (84.5% ± 3.5% and 96.2% ± 0.6%) was observed at 100 μg/mL ginger and zingerone, respectively. Moreover, dietary ginger and zingerone significantly reduced LPS-induced proinflammatory cytokine production in sera by 62.9% ± 18.2% and 81.3% ± 6.2%, respectively, and NF-κB bioluminescent signals in whole body by 26.9% ± 14.3% and 38.5% ± 6.2%, respectively. In addition, ginger and zingerone suppressed LPS-induced NF-κB-driven luminescent intensities in most organs, and the maximal inhibition by ginger and zingerone was observed in small intestine. Immunohistochemical staining further showed that ginger and zingerone decreased interleukin-1β (IL-1β)-, CD11b-, and p65-positive areas in jejunum. In conclusion, our findings suggested that ginger and zingerone were likely to be broad-spectrum anti-inflammatory agents in most organs that suppressed the activation of NF-κB, the production of IL-1β, and the infiltration of inflammatory cells in mice.

Increase in Plasma Glucose Lowering Action of Rosiglitazone by Electroacupuncture at Bilateral Zusanli Acupoints (ST.36) in Rats

OBJECTIVES Hypoglycemia induced by electroacupuncture (EA) is due to an increase of insulin secretion and/or mediation of beta-endorphin. We applied EA at the Zusanli (ST.36) acupuncture point (acupoint) in combination with rosiglitazone (TZD) administration to evaluate their effect on plasma glucose and to explore possible mechanisms of action. METHODS Thirty six normal adult Wistar rats were randomly divided into four groups: the 0.1 mg/kg TZD group (0.1TZD), 0.1 mg/kg TZD and EA group (0.1TZD + EA), EA group, and control group. In other experiments, streptozotocin was used to induce type 2 diabetes mellitus in neonatal rats; these were then randomly divided into a 0.1TZD group, 0.1TZD + EA group, and EA group and changes in plasma glucose and insulin concentrations evaluated. RESULTS A marked hypoglycemic response was observed in the normal rat 0.1TZD, 0.1TZD + EA and EA groups, with the response more significant in the 0.1TZD + EA group than in the 0.1TZD group. Among the diabetic animals, the hypoglycemic responses in the 0.1TZD + EA and EA groups were greater than in the 0.1TZD group. In both the normal and diabetic rats, insulin secretion was increased by EA or 0.1TZD + EA treatment, but not by 0.1TZD. CONCLUSIONS The plasma glucose lowering action of rosiglitazone was increased by EA in both normal and diabetic rats, indicating that the application of EA may enhance the hypoglycemic action of this insulin sensitizer.

Extracts of Cordyceps militaris Lower Blood Glucose via the Stimulation of Cholinergic Activation and Insulin Secretion in Normal Rats

Previous studies have shown that Cordyceps militaris (CM) has a hypoglycemic effect, but the actual mechanism remains unclear. This study explored the hypoglycemic mechanism of aqueous extracts of CM in normal Wistar rats. First, the optimal dose of CM for lowering plasma glucose and insulin secretion was tested. Further, atropine and hemicholinium‐3 (HC‐3) were injected and a western blot was used to investigate insulin signaling. It was found that 10 mg/kg CM extracts had a stronger hypoglycemic effect than a higher dose (100 mg/kg); therefore, a dose of 10 mg/kg was used in subsequent experiments. In normal rats, CM extracts decreased plasma glucose by 21.0% and induced additional insulin secretion by 54.5% after 30 min. When atropine or HC‐3 was injected, CM induced a hypoglycemic effect, but the enhancement of insulin secretion was blocked. By western blotting, significant increases in the insulin receptor substrate 1 (IRS‐1) and glucose transporter 4 (GLUT‐4) were observed after CM feeding. However, the elevation of these signaling proteins was abolished by atropine or HC‐3. Taken together, these findings indicate that CM can lower plasma glucose via the stimulation of insulin secretion and cholinergic activation involved in the hypoglycemic mechanism of normal Wistar rats. Copyright

Electroacupuncture plus metformin lowers glucose levels and facilitates insulin sensitivity by activating MAPK in steroid-induced insulin-resistant rats

Background Type 2 diabetes mellitus is the predominant form of diabetes. Although metformin is the preferred first-line drug for treatment of the disease, it is associated with a risk of secondary failure. Electroacupuncture (EA) can enhance insulin sensitivity and reduce blood glucose levels. Objectives To examine, in an animal study, whether EA combined with metformin (EA–metformin) results in a better glucose-lowering effect and greater insulin sensitivity than metformin alone in steroid-induced insulin-resistant rats. Methods Adult Wistar rats were injected with dexamethasone to induce diabetes and subsequently treated with EA plus metformin or metformin alone. Variations in plasma glucose, plasma insulin, and plasma free fatty acid levels were studied at the midpoint and end of the experimental course. Insulin receptor substrate 1 (IRS-1) and peroxisome proliferator-activated receptor γ (PPAR-γ), which are associated with glucose transporter type 4 (GLUT4) translocation, and mitogen-activated protein kinase (MAPK), which is related to GLUT4 activation, were measured after EA treatment. Results We found that EA–metformin resulted in a better glucose-lowering effect, greater insulin sensitivity, lower plasma free fatty acid levels and higher levels of MAPK than metformin alone (p<0.05). There were no significant differences between treatment groups in expression of IRS-1 or PPAR-γ. Conclusions The glucose-lowering effect and increased insulin sensitivity associated with EA–metformin administration is governed, at least in part, by its ability to stimulate the activation of GLUT4 via upregulation of MAPK expression.

Electroacupuncture-Induced Cholinergic Nerve Activation Enhances the Hypoglycemic Effect of Exogenous Insulin in a Rat Model of Streptozotocin-Induced Diabetes

The aim of this study is to explore the mechanisms by which electroacupuncture (EA) enhances the hypoglycemic effect of exogenous insulin in a streptozotocin- (STZ-) diabetic rats. Animals in the EA group were anesthetized and subjected to the insulin challenge test (ICT) and EA for 60 minutes. In the control group, rats were subjected to the same treatment with the exception of EA stimulation. Blood samples were drawn to measure changes in plasma glucose, free fatty acids (FFA), and insulin levels. Western blot was used to assay proteins involved in insulin signaling. Furthermore, atropine, hemicholinium-3 (HC-3), and Eserine were used to explore the relationship between EA and cholinergic nerve activation during ICT. EA augmented the blood glucose-lowering effects of EA by activating the cholinergic nerves in STZ rats that had been exposed to exogenous insulin. This phenomenon may be related to enhancement of insulin signaling rather than to changes in FFA concentration.