Ameliorative Effect of Imperatorin on Dermatophagoides pteronyssinus-Induced Allergic Asthma by Suppressing the Th2 Response in Mice.

Imperatorin is a furanocoumarin derivative and an effective ingredient in several Chinese medicinal herbs. It has favorable expectorant, analgesic, and anti-inflammatory effects. In this study, we investigated whether imperatorin has protective effects against Dermatophagoides pteronyssinus (Der p)-induced asthma in mice. Lung and bronchial tissues were histopathologically examined through hematoxylin-eosin staining. The concentrations of immunoglobin E (IgE), IgG1, IgG2a in serum and those of T helper 1 (Th1) and two cytokines and eosinophil-activated chemokines in bronchoalveolar lavage fluid (BALF) were detected using an enzyme immunoassay. Histological examination revealed that imperatorin reduced inflammatory cell infiltration, mucus hypersecretion, and endothelial cell hyperplasia. The examination also indicated that imperatorin could reduce the inflammatory cell count in BALF as well as IgE and IgG1 expression in serum, but IgG2a expression was significantly increased. Imperatorin reduced the production of interleukin (IL)-4, IL-5, and IL-13 by Th2, promoted the production of interferon-γ and IL-12 by Th1, and increased the production of IL-10 in bronchoalveolar lavage fluid. These findings suggest that imperatorin has a considerable anti-inflammatory effect on Der p-induced allergic asthma in mice.

Electroacupuncture combined with acarbose improves insulin sensitivity via peroxisome proliferator-activated receptor γ activation and produces a stronger glucose-lowering effect than acarbose alone in a rat model of steroid-induced insulin resistance.

BACKGROUND: Previous studies have reported that electroacupuncture (EA) induces a glucose-lowering effect by improving insulin resistance (IR) and reduces plasma free fatty acid (FFA) levels in rats with steroid-induced insulin resistance (SIIR). In addition, EA can activate cholinergic nerves and stimulate endogenous opioid peptides to lower plasma glucose in streptozotocin-induced hyperglycemic rats. The aim of this study was to investigate the glucose-lowering effects of 15 Hz EA at bilateral ST36 in combination with acarbose (ACA). We hypothesized that EA combined with ACA would produce a stronger glucose-lowering effect than ACA alone. METHODS: In this study, normal Wistar rats and SIIR rats were randomly divided into two groups: ACA and ACA + EA. To explore the potential mechanisms underlying the glucose-lowering effect, plasma FFA/insulin and insulin transduction signal pathway proteins were assayed. RESULTS: Combined ACA + EA treatment had a greater glucose-lowering effect than ACA alone in normal Wistar rats (-45% ± 3% vs -19% ± 3%, p < 0.001) and SIIR model rats (-43% ± 2% vs -16% ± 6%, p < 0.001). A significant reduction in plasma FFA levels, improvement in homeostatic model assessment of IR (HOMA-IR) index (-48.9% ± 4.0%, p < 0.001) and insulin sensitivity index (102% ± 16.9%, p < 0.001), and significant increases in insulin receptor substrate 1, glucose transporter 4, and peroxisome proliferator-activated receptor γ protein expressions in skeletal muscle, were also observed in the ACA + EA group of SIIR rats. CONCLUSION: Combined EA and ACA therapy had a greater glucose-lowering effect than ACA monotherapy; this combined therapy could be more effective at improving IR in SIIR rats, which may be related to a reduction in plasma FFA levels and an elevation of insulin signaling proteins. Whether this combined therapy has an effect in type 2 diabetes mellitus (T2DM) patients still needs to be explored.

15†Hz electroacupuncture at ST36 improves insulin sensitivity and reduces free fatty acid levels in rats with chronic dexamethasone-induced insulin resistance.

OBJECTIVE: To evaluate the effect of electroacupuncture (EA) in a rat model of chronic steroid-induced insulin resistance (SIIR). METHODS: An SIIR rat model was created using daily intraperitoneal injections of clinically relevant doses of dexamethasone (1 mg/kg) for 5 days to induce chronic insulin resistance. Thirty-six SIIR rats were randomly divided into the SIIR+EA group (n=18), which received 15 Hz EA at ST36 for 60 min, and the SIIR group (n=18), which remained untreated. Plasma glucose and free fatty acid (FFA) levels were measured in serial blood samples taken without further manipulation (n=6 per group) and during insulin challenge test (ICT, n=6 per group) and intravenous glucose tolerance test (ivGTT, n=6 per group). Insulin receptor substrate (IRS)-1 and glucose transporter (GLUT)-4 were measured using Western blotting and expressed relative to ß-actin. RESULTS: Following EA, area-under-the-curve (AUC) for glucose was reduced (7340±291 vs 10 705±1474 mg/dL/min, p=0.049) and FFA levels significantly lower at 30/60 min in the SIIR+EA versus SIIR groups. Similar effects on glucose AUC were seen during the ICT (5568±275 vs 7136±594 mg/dL/min, p<0.05) and igVTT (11 498±1398 vs 16 652±1217 mg/dL/min, p<0.01). FFA levels were lower at 30 and/or 60 min in SIIR+EA versus SIIR groups (p<0.01). Relative expression of IRS-1 and GLUT4 were significantly increased by EA (p<0.01). CONCLUSIONS: EA decreased the FFA level and increased insulin sensitivity in SIIR rats. Further clinical studies are needed to determine whether EA is an effective alternative treatment for the reduction of insulin resistance in patients requiring chronic use of dexamethasone.

Intracellular signalling pathways associated with the glucose-lowering effect of ST36 electroacupuncture in streptozotocin-induced diabetic rats.

BACKGROUND AND AIM: Previous animal studies have reported a glucose-lowering effect of electroacupuncture (EA) and suggested that the mechanisms are closely related to intracellular signalling pathways. The aim of this study was to screen for potential intracellular signalling pathways that are upregulated by EA at ST36 bilaterally in rats with diabetes mellitus (DM) using microarray analysis. METHODS: Streptozotocin (STZ)-induced diabetic rats were randomly assigned to experimental (EA, n=8) or control (non-EA, n=8) groups. Plasma glucose levels were measured at baseline and after 30 and 60 min, and microarray analysis was performed on samples of gastrocnemius muscle. RESULTS: Relative to baseline values, EA significantly reduced plasma levels of glucose at 30 and 60 min. The microarray pathway analysis showed that cell adhesion molecules and type 1 DM gene sets were both upregulated in EA versus non-EA groups (p<0.05). CONCLUSIONS: Cell adhesion molecules might be related to the glucose-lowering effect induced by EA in rats with STZ-induced type 1 diabetes. Further research will be required to examine the involvement of related intracellular signalling pathways.

Single-blinded, randomised preliminary study evaluating the effects of 2†Hz electroacupuncture for postoperative pain in patients with total knee arthroplasty.

OBJECTIVE: To explore the point-specific clinical effect of 2 Hz electroacupuncture (EA) in treating postoperative pain in patients undergoing total knee arthroplasty (TKA), METHODS: In a randomised, partially single-blinded preliminary study, 47patients with TKA were randomly divided into three groups: control group (CG, n=17) using only patient-controlled analgesia (PCA); EA group (EAG, n=16) with 2 Hz EA applied at ST36 (Zusanli) and GB34 (Yanglingquan) contralateral to the operated leg for 30 min on the first two postoperative days, also receiving PCA; and non-point group (NPG, n=14), with EA identical to the EAG except given 1 cm lateral to both ST36 and GB34. The Mann-Whitney test was used to show the difference between two groups and the Kruskal-Wallis test to show the difference between the three groups. RESULTS: The time until patients first required PCA in the CG was 34.1±22.0 min, which was significantly shorter than the 92.0±82.7 min in the EAG (p<0.001) and 90.7±94.8 min in the NPG (p<0.001); there was no difference between the EAG and NPG groups (p>0.05). The total dosage of PCA solution given was 4.6±0.9 mL/kg body weight in the CG, 4.2±1.0 mL/kg in the EAG and 4.5±1.0 mL/kg in the NPG; there were no significant differences (p>0.05) among the three groups. CONCLUSIONS: In this small preliminary study, EA retarded the first demand for PCA in comparison with no EA. No effect was seen on the total dosage of PCA required and no point-specific effect was seen.

The Involvement of Serotonin in the Hypoglycemic Effects Produced by Administration of the Aqueous Extract of Xylaria nigripes with Steroid-Induced Insulin-Resistant Rats.

Xylaria nigripes (XN) is a medicinal fungus with a high-economic value. The aim of this study was to explore the hypoglycemic effects and mechanisms of the XN aqueous extract in steroid-induced insulin-resistant (SIIR) rats. Significant hypoglycemic effects were observed 60 min after administration of XN aqueous extract. In normal Wistar, hypoglycemic effects were 21% (the plasma glucose level decreased from 128.6 ± 12.5 to 100.9 ± 10.7 mg/dL). In SIIR, hypoglycemic effects were 26% (the plasma glucose level decreased from 177.6 ± 12.5 to 133.3 ± 29.7 mg/dL) rats refer to their baseline. The signaling proteins for insulin-receptor substrate-1 and glucose transporter-4 increased 0.51-fold and 1.12-fold, respectively, as determined by Western blotting; the increase in the proteins was 13% and 9%, respectively, as determined by immunohistochemistry. The serotonin antagonist, α-p-chlorophenylalanine, effectively blocked the hypoglycemic effects and increased the signaling protein levels. After XN administration, none of the animals showed significant changes in plasma-free fatty acids in 60 min. In summary, the XN extract may have hypoglycemic effects in normal Wistar and SIIR rats that may have a serotonin-related hypoglycemic effect and enhance insulin sensitivity in the SIIR rats.

Acupoint-specific, frequency-dependent, and improved insulin sensitivity hypoglycemic effect of electroacupuncture applied to drug-combined therapy studied by a randomized control clinical trial.

The application of electroacupuncture (EA) to specific acupoints can induce a hypoglycemic effect in streptozotocin-induced rats, normal rats, and rats with steroid-induced insulin resistance. EA combined with the oral insulin sensitizer rosiglitazone improved insulin sensitivity in rats and humans with type II diabetes mellitus (DM). There are different hypoglycemic mechanisms between Zhongwan and Zusanli acupoints by EA stimulation. On low-frequency (2 Hz) stimulation at bilateral Zusanli acupoints, serotonin was involved in the hypoglycemic effect in normal rats. Moreover, after 15 Hz EA stimulation at the bilateral Zusanli acupoints, although enhanced insulin activity mainly acts on the insulin-sensitive target organs, the muscles must be considered. In addition, 15 Hz EA stimulation at the bilateral Zusanli acupoints has the combined effect of enhancing cholinergic nerve activity and increasing nitric oxide synthase (NOS) activity to enhance insulin activity. Despite the well-documented effect of pain control by EA in many systemic diseases, there are few high-quality long-term clinical trials on the hypoglycemic effect of EA in DM. Combination treatment with EA and other medications seems to be an alternative treatment to achieve better therapeutic goals that merit future investigation.

Peroxisome proliferator-activated receptor activating hypoglycemic effect of Gardenia jasminoides Ellis aqueous extract and improvement of insulin sensitivity in steroid induced insulin resistant rats.

BACKGROUND: The active components of Gardenia (Gardenia jasminoides Ellis, GJ) exhibit a hypoglycemic effect by improving insulin secretion and lowering plasma lipids. In the present study, we fed a water extract of gardenia to steroid-induced insulin-resistant (SIIR) rats and observed changes in signaling proteins in order to elucidate the mechanisms of the insulin-sensitizing effect of GJ and evaluate its possibility as an insulin-sensitizing agent. METHODS: Normal Wistar rats were randomly divided into a control group (i.e., saline) and experimental groups (GJ 100 and 200 mg/kg). Blood samples were taken at 0, 30, and 60 min for plasma glucose assay in order to determine the optimal dose to induce the hypoglycemic effect. SIIR rats were then randomly divided into a control group (i.e., saline) and an experimental group (optimal dose of gardenia extract) to observe the insulin-sensitizing effect of the extract. Finally, western blot analysis was performed to detect intracellular signaling proteins to elucidate the mechanisms of the insulin-sensitization effect of GJ. RESULTS: The normal Wistar rats in the GJ 200 mg/kg group exhibited significant hypoglycemic activity. Meanwhile, the SIIR rats had higher plasma glucose levels than normal rats. There was no obvious change in insulin level, but the insulin sensitivity index and homeostasis model assessment index were significantly elevated. Meanwhile, a significant hypoglycemic effect was observed with GJ 200 mg/kg. In addition, intracellular signaling proteins including insulin receptor substrate-1 (IRS-1) and peroxisome proliferator-activated receptor (PPARγ) were elevated in muscle cells. CONCLUSIONS: The optimal dose of GJ aqueous extract of 200 mg/kg exerts a PPARγ-activating hypoglycemic effect and improves insulin resistance in SIIR rats. Therefore, it is a potential insulin-sensitizing agent in type 2 diabetes mellitus with insulin resistance.

Electroacupuncture and rosiglitazone combined therapy as a means of treating insulin resistance and type 2 diabetes mellitus: a randomized controlled trial.

Aims. To evaluate the efficacy of rosiglitazone (TZD) and electroacupuncture (EA) combined therapy as a treatment for type 2 diabetes mellitus (T2DM) patients by randomized single-blind placebo controlled clinical trial. Methods. A total of 31 newly diagnostic T2DM patients, who fulfilled the study's eligibility criteria, were recruited. The individuals were randomly assigned into two groups, the control group (TZD, N = 15) and the experimental group (TZD + EA, N = 16). Changes in their plasma free fatty acid (FFA), glucose, and insulin levels, together with their homeostasis model assessment (HOMA) indices, were statistically compared before and after treatment. Hypoglycemic activity (%) was also compared between these two groups. Results. There was no significant difference in hypoglycemic activity between the TZD and TZD + EA group. The effectiveness of the combined therapy seems to derive from an improvement in insulin resistance and a significant lowering of the secreted insulin rather than the effect of TZD alone on T2DM. The combined treatment had no significant adverse effects. A lower plasma FFA concentration is likely to be the mechanism that causes this effect. Conclusion. This combined therapy seems to suppress endogenous insulin secretion by improving insulin resistance via a mechanism involving a reduction in plasma FFA. This trial is registered with ClinicalTrials.gov NCT01577095.

Aqueous extracts of Cordyceps militaris (Ascomycetes) lower the levels of plasma glucose by activating the cholinergic nerve in streptozotocin-induced diabetic rats.

In our previous research, Cordyceps militaris (CM) had a hypoglycemic effect in normal rats. In this study we wanted to elucidate whether CM also had an effect on diabetic rats. Twelve rats with streptozotocin-induced diabetes were separated randomly into 2 groups. First, aqueous extracts of CM 10 mg/kg (CM group) or saline (control group) was fed to the rats; then the plasma glucose levels were assayed. Second, the signaling proteins IRS-1 and GLUT-4 collected from the muscle were detected. Finally, another 2 groups of rats were injected with atropine 0.1 mg/kg intraperitoneally just before the CM/saline feeding, and the assays mentioned above were repeated. Blood glucose decreased 7.2% in the CM group but only 1.5% in the control group (P < 0.05). The IRS-1 signal was 2.9-fold higher than actin in the CM group but only 0.8-fold higher in the control group (P < 0.005). In GLUT-4 signal, the difference was 1.7- vs. 0.6-fold, respectively, compared with actin (P < 0.05). However, atropine injection made CM-induced hypoglycemia or elevation of IRS-1 and GLUT-4 not significant. In conclusion, CM had a hypoglycemic effect in diabetic rats and atropine blocked it. Therefore, the cholinergic activation also was considered to be involved in the hypoglycemic effect of CM in rats with streptozotocin-induced diabetes.

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.

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.

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.

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.

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.

BACKGROUND: Insulin 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. METHODS: The 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. RESULTS: The 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. CONCLUSION: Insulin 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.

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.

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.