Effects of Herb-Partitioned Moxibustion on the miRNA Expression Profiles in Colon from Rats with DSS-Induced Ulcerative Colitis.

Objective. This study explored the mechanism of herb-partitioned moxibustion (HM) on dextran sulfate sodium- (DSS-) induced ulcerative colitis (UC) from the miRNA perspective. Methods. Rats were randomly divided into 3 groups [normal control (NC) group, UC model (UC) group, and herb-partitioned moxibustion (UCHM) group]. The UC and UCHM groups were administered 4% DSS for 7 days. The UCHM group received HM at the Tianshu (bilateral, ST25). The effect of HM on UC was observed and the miRNA expression profile in the colon tissues was analyzed. Results. Compared with the UC group, the body weights were significantly higher in the UCHM group on day 14 (P < 0.001); the macroscopic colon injury scores and microscopic histopathology scores in the UCHM group decreased (P < 0.05); and there were 15 differentially expressed miRNAs in the UCHM group. The changes in miR-184 and miR-490-5p expression levels on the UC were reversed by HM intervention. Validation using qRT-PCR showed that two miRNAs expression trend was consistent with the sequencing results. Conclusion. HM at ST25 might regulate miR-184 and miR-490-5p expression, act on the transcription of their target genes to regulate inflammatory signaling pathways, and attenuate inflammation and tissue injury in the colons of rats with DSS-induced UC.

Research Advance in Intestinal Mucosal Barrier and Pathogenesis of Crohn's Disease.

To date, the etiology and pathogenesis of Crohn's disease (CD) have not been fully elucidated. It is widely accepted that genetic, immune, and environment factors are closely related to the development of CD. As an important defensive line for human body against the environment, intestinal mucosa is able to protect the homeostasis of gut bacteria and alleviate the intestinal inflammatory and immune response. It is evident that the dysfunction of intestinal mucosa barriers plays a crucial role in CD initiation and development. Yet researches are insufficient on intestinal mucosal barrier's action in the prevention of CD onset. This article summarizes the research advances about the correlations between the disorders of intestinal mucosal barriers and CD.

[Effect of Electroacupuncture and Moxibustion on Visceral Pain and Expression of VR 1 and HSP 70 of "Tianshu" (ST 25) Region in Colorectal Distension-induced Visceral Hypersensitivity Rats].

OBJECTIVE: To compare the effects of electroacupuncture (EA) and moxibustion (Moxi) on visceral pain and expression of vanilloid receptor subtype 1 (VR 1) and heat shock protein (HSP)70 in "Tianshu" (ST 25) region in colorectal distension (CRD)-induced visceral hypersensitivity (VHS) rats. METHODS: Fifty male SD rats were randomly divided into normal control, VHS model, 43℃-moxi, 46℃-moxi, 1 mA-EA and 3 mA-EA groups (n=10 in each group). The VSH model was established by CRD once daily for 14 days. EA or Moxi stimulation was applied to bilateral "Tianshu" (ST 25) for 10 min, once daily for consecutive 10 days. The abdominal withdrawal reflex (AWR) scores (0-4 points) were rated according to Al-Chaer's and coworkers' standards (2000) and the expression levels of VR 1 and HSP 70 in bilateral ST 25 area tissues detected by immunohistochemistry. RESULTS: The AWR scores for 20, 40, 60 and 80 mmHg CRD pressures were significantly increased compared to the normal control group (P<0.01) and notably decreased after 43℃- and 46℃-moxi, and 1 mA- and 3 mA-EA stimulation of bila-teral ST 25 in comparison with the model group (P<0.05, P<0.01), and the effect of 46℃-moxi was apparently superior to those of 1 mA-EA at 40 and 80 mmHg, and 3 mA-EA at 40 mmHg (P<0.05). After modeling, the expression of both VR 1 and HSP 70 (percentages of area of positive-cells) in ST 25 region had no significant changes (P>0.05). Compared to the model group, the expression levels of VR 1 in the 43℃-moxi and 46℃-moxi groups, and HSP 70 in the 43℃-moxi and 46℃-moxi, 1 mA-EA and 3 mA-EA groups were significantly up-regulated (P<0.01), but without obvious changes in the expression of VR 1 in the 1 mA-EA and 3 mA-EA groups (P>0.05). The effects of 46℃-moxi were considerably better than those of 43℃-moxi, 1 mA-EA and 3 mA-EA in up-regulating VR 1 and HSP 70 expression (P<0.05, P<0.01). No significant differences were found among the 43℃-moxi, 1 mA-EA and 3 mA-EA groups in the expression of VR 1 and HSP 70 (P>0.05). CONCLUSIONS: Moxibustion at 43℃ and 46℃ and EA at 1 mA and 3 mA, especially the 46℃-moxi, can relieve visceral pain in visceral hypersensitivity rats, which may be related to their effects in up-regulating expression of VR 1 and HSP 70 in "Tianshu" (ST 25) area.

Comparison of Electroacupuncture and Moxibustion for Relieving Visceral Hypersensitivity in Rats with Constipation-Predominant Irritable Bowel Syndrome.

Aim. To compare whether there is different effect between electroacupuncture (EA) and moxibustion (Mox) on visceral hypersensitivity (their analgesic effects) in constipation-predominant irritable bowel syndrome (C-IBS). Methods. EA at 1 mA and 3 mA and Mox at 43°C and 46°C were applied to the Shangjuxu (ST37, bilateral) acupoint in rats with C-IBS and normal rats. An abdominal withdrawal reflex (AWR) score was used to assess visceral hypersensitivity. Toluidine blue staining was used to assess mast cell (MC) activity in colon of rats. Immunochemistry was used to measure 5-HT and 5-HT4 receptor expression in the colon. Results. AWR scores in all EA (1 mA and 3 mA) and Mox (43°C and 46°C) treatment groups after colorectal distention (CRD) stimulation pressure of 20, 40, 60, and 80 mmHg were significantly lower than those of the model (MC) group (P all < 0.01). The MC counts and degranulation rates in the colon of all EA and Mox treatment groups and the MC group were significantly higher than those of the NC group (P all < 0.01). MC degranulation rates in the colon of all EA and Mox treatment groups were lower than those of the MC group (P all < 0.05). 5-HT expression in colon of all EA and Mox treatment groups was significantly lower than that of the MC group (P all < 0.01), and 5-HT4R expression in colon of both EA groups was significantly higher than that of the MC group (P both < 0.01). Conclusion. EA and Mox treatments may both ameliorate visceral hypersensitivity at different degree in rats with C-IBS, and EA treatment was better than Mox.

Moxibustion and Acupuncture Ameliorate Crohn's Disease by Regulating the Balance between Th17 and Treg Cells in the Intestinal Mucosa.

Previous studies have demonstrated that acupuncture is beneficial to patients with Crohn's disease (CD), but the mechanism underlying its therapeutic effects remains unclear. To identify the mechanism by which acupuncture treats CD, the balance between Th17 and Treg cells was assessed in CD patients. In this study, Ninety-two CD patients were randomly and equally assigned to a treatment group that were treated with herb-partitioned moxibustion and acupuncture or a control group with wheat bran-partitioned moxibustion and superficial acupuncture. The effect of these treatments on Th17 and Treg cells and their related molecular markers in the intestinal mucosa were detected before (week 0) and after (week 12) treatment. The results suggested that the ratio of Th17 and Treg cells was significantly decreased after treatment and that the levels of IL-17 and RORγt in the intestinal mucosa were obviously reduced, while the expression of FOXP3 was increased after treatment in both groups. In the treatment group, the expression of these molecules was more markedly regulated than the control group. In conclusion, moxibustion and acupuncture have been shown to regulate the ratio of Th17 and Treg cells in the intestinal mucosa of CD patients and restore the balance between these immune cell subsets.

Mechanisms underlying the analgesic effect of moxibustion on visceral pain in irritable bowel syndrome: a review.

Irritable bowel syndrome (IBS) is a functional bowel disorder that causes recurrent abdominal (visceral) pain. Epidemiological data show that the incidence rate of IBS is as high as 25%. Most of the medications may lead to tolerance, addiction and toxic side effects. Moxibustion is an important component of traditional Chinese medicine and has been used to treat IBS-like abdominal pain for several thousand years in China. As a mild treatment, moxibustion has been widely applied in clinical treatment of visceral pain in IBS. In recent years, it has played an irreplaceable role in alternative medicine. Extensive clinical studies have demonstrated that moxibustion for treatment of visceral pain is simple, convenient, and inexpensive, and it is being accepted by an increasing number of patients. There have not been many studies investigating the analgesic mechanisms of moxibustion. Studies exploring the analgesic mechanisms have mainly focused on visceral hypersensitivity, brain-gut axis neuroendocrine system, and immune system. This paper reviews the latest developments in moxibustion use for treatment of visceral pain in IBS from these perspectives. It also evaluates potential problems in relevant studies on the mechanisms of moxibustion therapy to promote the application of moxibustion in the treatment of IBS.

Randomized controlled trial: moxibustion and acupuncture for the treatment of Crohn's disease.

AIM: To evaluate the clinical efficacy and safety of acupuncture and moxibustion for the treatment of active Crohn's disease (CD). METHODS: Ninety-two patients were equally and randomly divided into the treatment group and received herb-partitioned moxibustion combined with acupuncture, and the control group received wheat bran-partitioned moxibustion combined with superficial acupuncture. The patients received three treatment sessions per week for 12 wk and were followed up for 24 wk. The main outcome was evaluated using the CD Activity Index (CDAI) score, and the secondary outcomes were evaluated using laboratory indicators such as hemoglobin (HGB), C-reactive protein (CRP), erythrocyte sedimentation rate, quality-of-life, endoscopic ratings, and intestinal histology scores. RESULTS: The CDAI scores of both the treatment and control groups were significantly reduced after treatment compared with those measured before treatment. However, the degree of improvement in the treatment group was significantly greater than that of the control group. The improvement in symptoms in patients of the treatment group was sustained at follow-up, whereas that of the control group was not. The overall efficacy of the treatment was significantly greater than that of the control. Both groups demonstrated significant improvements in quality-of-life ratings after treatment, but the improvement was significantly greater in the treatment group than in the control group. In addition, the patients in the treatment group showed significantly increased HGB and significantly decreased CRP levels and histopathological scores at the end of treatment, whereas the control group did not exhibit significant changes. CONCLUSION: Moxibustion with acupuncture provided significant therapeutic benefits in patients with active CD beyond the placebo effect and is therefore an effective and safe treatment for active CD.

Moxibustion Inhibits the ERK Signaling Pathway and Intestinal Fibrosis in Rats with Crohn's Disease.

Intestinal fibrosis is the main pathological process in Crohn's disease (CD); acupuncture and moxibustion can inhibit the process of fibrosis in CD rats, but the regulatory mechanism remains unknown. The present study observed the effect of moxibustion on the extracellular signal-regulated kinase (ERK) signaling pathway in the CD rat. The result shows that the phosphorylation of the Ras, Raf-1, MEK-1, and ERK-1/2 proteins and the expression of the corresponding mRNAs in the colon tissue of CD rat were significantly higher than the normal control group. Both treatments with mild moxibustion and with herb-separated moxibustion significantly reduced the expression of the Ras, Raf-1, MEK-1, and ERK-1/2 proteins and Ras and Raf-1 mRNA. MEK-1 and ERK-1/2 mRNA expression in each treatment group showed a downward trend, and the ERK-1/2 mRNA levels were significantly lower in the mild moxibustion group. It indicates that Ras, Raf-1, MEK-1, and ERK-1/2 are involved in the process of intestinal fibrosis in CD rats. Moxibustion can downregulate the abnormal expression of colonic Ras, Raf-1, MEK-1, and ERK-1/2 protein and mRNA levels in CD intestinal fibrosis in rats. Moxibustion may play a role in the treatment of CD intestinal fibrosis by regulating ERK signaling pathway.