Prophylactic effects of Lonicera japonica extract on dextran sulphate sodium-induced colitis in a mouse model by the inhibition of the Th1/Th17 response.

Inflammatory bowel diseases (IBD) are chronically relapsing inflammatory disorders of the intestine. Although some therapeutic agents, including steroids, are available for the treatment of IBD, these agents have limited use. Therefore, dietary supplements have emerged as possible interventions for IBD. Japanese honeysuckle flower, the flower of Lonicera japonica, is a well-known dietary supplement and has been used to prevent or treat various inflammatory diseases. In the present study, we investigated the effects of L. japonica on experimental murine colitis. Colitis was induced by 5 % dextran sulphate sodium (DSS) in Balb/c mice. The water extract of L. japonica (LJE) at doses of 20, 100 or 500 mg/kg was orally administered to mice twice per day for 7 d. Body weight, colon length and a histological damage score were assessed to determine the effects on colitis. Cytokine profiles were assessed to examine the effects on helper T (Th) cell-related immunological responses. In addition, CD4⁺CD25⁺Foxp3⁺T cells were analysed in vivo and in vitro for investigating the effects on regulatory T (Treg) cells. LJE showed dose-dependent inhibitory effects against colon shortening, weight loss and histological damage. LJE down-regulated IL-1ß, TNF-α, interferon-γ, IL-6, IL-12 and IL-17. However, LJE did not show any significant effects on IL-10, IL-23, transforming growth factor-ß1 and Treg cell populations. In conclusion, LJE showed protective effects against DSS-induced colitis via the Th1/Th17 pathway and not via Treg cell-related mechanisms.

Effects of multiple herb formula SEC-22 supplementation on dietary intake, picky eating behaviors, and growth indices in thin preschool children.

BACKGROUND/OBJECTIVES: Thin children may have insufficient intake of energy and nutrients, resulting in reduced immune function and growth. This study aimed to identify the effects of multiple herb formula SEC-22 supplementation on growth, dietary changes, and picky eating behaviors in thin children. SUBJECTS/METHODS: A double-blind, randomized clinical trial was conducted on 79 children aged 2-5 years with poor appetites, BMI percentile < 25, and without any illness. Subjects were given either SEC-22 (n = 35) or placebo (n = 44) for 2 months and followed for an additional 2 months. Three-day dietary records, questionnaires on picky eating behaviors, and anthropometric measures were collected. RESULTS: Energy, carbohydrate intake, and feeding difficulty improved in both groups during the intervention period. However, changes were maintained only in the SEC-22 group after 2 months of follow-up post-supplementation. 'Frequency of trying to feed' was improved in the SEC-22 group compared to the placebo group after the first month of follow-up (P < 0.05). Intakes of potassium and thiamine were improved in the SEC-22 group compared to the placebo group after the first month of intervention (P < 0.05). 'Frequency of food reward', eating amount, and intakes of carbohydrate, potassium, and vitamin C showed significant improvement compared to the placebo group after the second month of follow-up (P < 0.05). CONCLUSIONS: These results suggest that SEC-22 supplementation can improve parental feeding difficulty resulting from insufficient eating amount or picky eating as well as increase nutrient intake in thin children. Although these improvements were observable at least 2 months after supplementation, effects beyond this time frame need to be confirmed.

Laminaria japonica combined with probiotics improves intestinal microbiota: a randomized clinical trial.

UNLABELLED: Laminaria japonica--a widely used ingredient in seaweed kimchi--and lactic acid bacteria (LAB)--a main component of traditional fermented Korean food--may alter human intestinal microbiota composition and have a positive effect on various digestive problems. However, few clinical trials have investigated the potential benefits of L. japonica when combined with LAB for human intestinal microbiota. Therefore, this study was designed to evaluate the effects of L. japonica and representative LAB on the human intestine. Forty participants with no known digestive diseases were randomly assigned to one of the two combination groups: (1) L. japonica with LAB and (2) L. japonica with placebo LAB. The study agents were administered for 4 weeks with a 2-week follow-up period. The primary outcome measure was the number of each of the seven LAB species in the human intestine, and the secondary outcome measures included the Korean version of the Gastrointestinal Symptom Rating Scale, the World Health Organization Quality of Life, and bowel functions. The primary outcome was evaluated before and after administration of the study agents (0 and 4 weeks), and the secondary outcomes were evaluated at 0, 4, and 6 weeks. Four of the seven LAB species were found to be significantly increased in the L. japonica with the LAB group and five species were significantly different from those of the placebo group. The secondary outcome measures did not change significantly. In conclusion, L. japonica with LAB facilitated the proliferation of beneficial human intestinal microbiota. ( TRIAL NUMBER: ClinicalTrials.gov NCT01651741).

Tongue diagnosis system for quantitative assessment of tongue coating in patients with functional dyspepsia: a clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Tongue diagnosis is a significant procedure to examine the physiological and pathological changes of the human body in oriental medicine. However, the conventional method of tongue diagnosis including direct observation of tongue has limitations because of various external factors and subjective factors. Therefore, the current study investigated the usefulness of the tongue diagnosis system (TDS) as a diagnostic tool for evaluating tongue coating thickness (TCT) by assessing the agreement between the TDS and a gold standard established by assessors using the conventional method. MATERIALS AND METHODS: The present study was designed as a prospective clinical trial including 60 patients with functional dyspepsia. The TDS was used to capture tongue images twice within a 30-min interval to assess its reproducibility. Tongue coating percentage was measured by the TDS, and TCT was classified as either no coating, thin coating, or thick coating according to the existing diagnostic criteria. After both TDS examinations, the weight of tongue coating was quantitatively measured, and the correlation between the actual quantity of tongue coating and the percentage of the coating measured by the TDS was analyzed using Pearson׳s correlation. After collecting tongue images in all 60 patients, tongue coating was evaluated using a conventional method by 5 well-trained assessors to establish the gold standard for evaluating TCT, which allowed us to assess the diagnostic agreement between the TDS and the gold standard. After 2 weeks, TCT evaluation was repeated by the same assessors using the same images but in a random order. RESULTS: The agreement between the TDS and the gold standard for evaluating TCT was almost perfect (weighted kappa, 0.840), as was the reproducibility of the TDS (weighted kappa, 0.851). The percentage of tongue coating measured by the TDS was significantly correlated with the weight of tongue coating (r=0.442, p <0.001). The levels of intra-rater reliability ranged from substantial to almost perfect (range of weighted kappa, 0.777-0.923). The inter-rater reliability of 5 assessors was moderate (weighted kappa, 0.563). CONCLUSIONS: The present study demonstrated that the TDS can be used as a diagnostic tool for the objective and standardized evaluation of TCT in actual clinical practice.

The Effects of Banha-sasim-tang on Dyspeptic Symptoms and Gastric Motility in Cases of Functional Dyspepsia: A Randomized, Double-Blind, Placebo-Controlled, and Two-Center Trial.

Introduction. Functional dyspepsia (FD) is highly prevalent, and no standard treatments exist for this condition. Herbal prescriptions are widely used to treat FD. In traditional Korean medicine, Banha-sasim-tang (BST) is a famous herbal prescription for dyspepsia. This study aimed to evaluate the efficacy of BST and to examine the relationship between gastric slow waves and dyspeptic symptoms. Materials and Methods. In total, 100 FD patients were recruited; BST or placebo was administered for 6 weeks. The gastrointestinal symptom scale, FD-related quality of life scale, and frequency or power variables regarding gastric slow waves were measured at 0, 6, and 14 weeks. Results. There were no significant differences in the overall dyspeptic symptoms or quality of life between the BST and placebo groups. However, early satiety was significantly improved in the BST group (P = 0.009, at 6 weeks by intention-to-treat analysis). Abnormal gastric dysrhythmias and power ratios were also significantly improved by BST. Conclusion. BST had no significant effects on FD. However, early satiety appeared to improve after BST administration. Electrogastrography may be a useful technique for assessing changes in gastric motility dysfunction after interventions for FD. Further investigation focused on specific symptoms or subtypes of FD is required.

Effects of low level laser therapy on ovalbumin-induced mouse model of allergic rhinitis.

Introduction. This study was designed to investigate the effects of low level laser therapy (LLLT) on experimental allergic rhinitis (AR) models induced by ovalbumin. Materials and Methods. AR was induced by 1% ovalbumin in mice. Twenty-four mice were divided into 4 groups: normal, control, low, and high dose irradiation. Low and high dose LLLT were irradiated once a day for 7 days. Total IgE, cytokines concentrations (IL-4 and IFN- γ ), and thymus and activation regulated chemokine (TARC) were measured. Histological changes in the nasal mucosal tissue by laser irradiation were examined. Results. LLLT significantly inhibited total IgE, IL-4, and TARC expression in ovalbumin-induced mice at low dose irradiation. The protein expression level of IL-4 in spleen was inhibited in low dose irradiation significantly. IL-4 expression in EL-4 cells was inhibited in a dose dependent manner. Histological damages of the epithelium in the nasal septum were improved by laser irradiation with marked improvement at low dose irradiation. Conclusion. These results suggest that LLLT might serve as a new therapeutic tool in the treatment of AR with more effectiveness at low dose irradiation. To determine the optimal dose of laser irradiation and action mechanisms of laser therapy, further studies will be needed.

Yukmijihwang-tang for the treatment of xerostomia in the elderly: study protocol for a randomized, double-blind, placebo-controlled, two-center trial.

BACKGROUND: Xerostomia, a subjective sense of dry mouth, is not generally regarded a disease despite its high prevalence among the elderly, and therefore continues to impair affected patients' quality of life. In traditional Korean medicine, 'Yin-Deficiency' has been implicated in the pathogenesis of xerostomia among the elderly. Yukmijihwang-tang is a famous herbal prescription used to relieve 'Yin-Deficiency', and reportedly has antioxidant effects; therefore, it is postulated that Yukmijihwang-tang can be used to treat xerostomia in the elderly. However, to our knowledge, no clinical trial has been conducted on the effects of Yukmijihwang-tang on xerostomia. Thus, we designed a randomized clinical trial to investigate the effects and safety of Yukmijihwang-tang on xerostomia in the elderly. In addition, we will clarify the aforementioned assumption that 'Yin-Deficiency' is the major cause of xerostomia in the elderly by identifying a correlation between xerostomia and 'Yin-Deficiency'. METHODS/DESIGN: This randomized, double-blind, placebo-controlled trial will be carried out at two centers: Kyung Hee University Korean Medicine Hospital and Kyung Hee University Hospital at Gangdong. We will recruit 96 subjects aged 60-80 years who have experienced xerostomia for 3 months prior to participation. Subjects who present with score >40 on the visual analogue scale for xerostomia and unstimulated salivary flow rate under 0.3mL/min will be included and the randomization will be carried out by an independent statistician by using a random number creation program. The subjects and all researchers except the statistician will be blinded to the group assignment. Yukmijihwang-tang or placebo will be administered to each group for 8 weeks. The primary outcome is change in the scores for the visual analogue scale for xerostomia and the dry mouth symptom questionnaire from 0 to 8 weeks. DISCUSSION: It will be assessed whether Yukmijihwang-tang can be used as a new herbal treatment for xerostomia in the elderly by demonstrating its therapeutic effects in a well-designed clinical trial. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01579877.

Availability of tongue diagnosis system for assessing tongue coating thickness in patients with functional dyspepsia.

Tongue diagnosis is an important procedure in traditional Korean medicine (TKM). In particular, tongue coating thickness (TCT) is deemed to show the progression of the disease. However, conventional tongue diagnosis has limitations because of various external factors. Therefore, it is necessary to investigate the availability of tongue diagnosis system (TDS) in the assessment of TCT. This study has been designed as a prospective clinical trial involving 60 patients with functional dyspepsia. Tongue images will be obtained by TDS twice with a 30 min interval. The system will measure the percentage of TCT and classify it as either no coating, thin coating, or thick coating according to the existing diagnostic criteria. After finishing the collection of 60 patients' tongue images, TCT on the images will be simultaneously evaluated by the conventional method to establish the gold standard for assessing TCT by 5 well-trained clinicians. The evaluation will be repeated by the same clinicians after 2 weeks, but the order of the images will be changed. This trial is expected to provide clinical evidence for the availability of TDS as a diagnostic tool and to contribute to the standardization of the diagnosis system used in TKM. This trial is registered with ClinicalTrials.gov NCT01864837.

Effect of korean herbal medicine combined with a probiotic mixture on diarrhea-dominant irritable bowel syndrome: a double-blind, randomized, placebo-controlled trial.

Introduction. Although combination therapy with herbal medicine and probiotics is gaining popularity for controlling diarrhea-dominant irritable bowel syndrome (D-IBS) symptoms, few studies have investigated its clinical effects. Materials and Methods. Fifty-three patients with D-IBS were randomly allocated into 1 of the following 4 groups: herbal medicine (Gwakhyangjeonggisan; GJS) plus probiotics (Duolac7S; DUO), GJS plus placebo DUO, placebo GJS plus DUO, and placebo GJS plus placebo DUO. The study period consisted of a 2-week run-in, 8 weeks of administration, and 2 weeks of follow-up. The primary outcomes were weekly adequate relief (AR) of overall IBS symptoms and the proportion of responders (PR) during the administration period. The secondary outcomes included individual IBS symptoms, stool assessment, and quality of life. Changes of intestinal microbiota and intestinal permeability were also analyzed. Results and Discussion. Weekly AR was not different among the 4 groups throughout the treatment period. However, the 3 treatment groups exhibited significant improvements in PR compared to the findings in the placebo group. In the intestinal microbiota assessment, herbal medicine and probiotics synergistically increased beneficial bacteria counts. Conclusion. Combination therapy with herbal medicine and probiotics appears to relieve overall IBS symptoms by synergistically increasing beneficial intestinal microbe counts.

Myristica fragrans seed extract protects against dextran sulfate sodium-induced colitis in mice.

Nutmeg (seed of Myristica fragrans [MF]) is one of the most commonly used spices in the world and also a well-known herb for the treatment of various intestinal diseases, including colitis in traditional Korean medicine. The purpose of the current study was to investigate whether water extract of MF (MFE) can protect against dextran sulfate sodium (DSS) induced colitis in a mouse model. Colitis was induced by 5% DSS in balb/c mice. MFE (100, 300 or 1000 mg/kg) was orally administered to the mice twice a day for 7 days. Body weight, colon length, clinical score, and histological score were assessed to determine the effects on colitis. Proinflammatory cytokines (interferon-γ, tumor necrosis factor-α, interleukin [IL]-1ß, and IL-6) were measured to investigate the mechanisms of action. MFE dose dependently inhibited the colon shortening and histological damage to the colon. However, it did not prevent weight loss. MFE also inhibited proinflammatory cytokines. The current results suggest that MFE ameliorates DSS-induced colitis in mice by inhibiting inflammatory cytokines. Further investigation, including the exact mechanisms is needed.

Development of differential criteria on tongue coating thickness in tongue diagnosis.

OBJECTIVE: To develop differential criteria on the tongue coating thickness (TCT), and especially propose the standard for judgment on thin and thick coating in tongue diagnosis. METHODS: Sixty oriental medical doctors evaluated the TCT (none, thin, and thick coating) in 50 realistic tongue photographs revealing from tip-to-root. The photographs were obtained with a digital tongue imaging system (DTIS) which measured the percentages of tongue coating on the tongue surface. We calculated the match rate which is the ratio in which the assessor's judgment is consistent with the decision standard on the tongue coating, and then 24 assessors (≥80% match rate) were selected to improve the reliability of the decision. The agreement level among 24 assessors was examined to assess the inter-rater reliability. The correlation between TCT judgments and DTIS-measured values was examined to ascertain the reliability of DTIS measurements. Finally, the assumption probability for the analysis of quantified characteristics of the tongue coating was calculated with a proportional odds model. RESULTS: The inter-rater reliability was assessed as moderate (κ=0.56) among 24 assessors, the level of correlation between TCT judgments and DTIS measurements in 24 assessors was relatively high (0.76, p<0.01). As the analysis of the proportional odds model, 29.06% was a cut-off point to separate no coating and thin coating, 63.51% was a cut-off point to separate thin and thick coating. CONCLUSIONS: The differential criteria for TCT in tongue diagnosis were suggested, and particularly thick coating is defined as one that tongue coating which tongue body is invisible, occupy approximately more than two third areas on the tongue surface.

Effect of herbal extract granules combined with probiotic mixture on irritable bowel syndrome with diarrhea: study protocol for a randomized controlled trial.

BACKGROUND: Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder characterized by abdominal pain and change of bowel habits without organic disease. Many patients seek alternative IBS treatments because of the limitations of conventional treatments. Gwakhyangjeonggisan (GJS), a herbal formula, has long been used for alleviating diarrhea-predominant IBS (D-IBS) in traditional medicine. Duolac7S, which comprises 7 bacterial species as probiotics, has been frequently used for D-IBS. Although GJS and Duolac7S have been administered simultaneously in many D-IBS patients, no study has investigated the effects of GJS and Duolac7S combination therapy on D-IBS. METHODS/DESIGN: The current trial is a randomized, double-blinded, placebo-controlled, 4-arm study. After a 2-week run-in period, 60 patients with D-IBS will be randomly assigned to one of the 4 combination groups consisting of GJS (water extract granules, 3 g/pack, 3 times a day) with Duolac7S (powder form, 1 capsule, 2 times a day) or their placebos and followed up for 2 weeks. The assigned treatments will last for 8 weeks. The primary outcomes are adequate relief of IBS pain and discomfort and the proportion of responders (on a weekly basis). The secondary outcomes are visual analog scale for IBS symptoms (on a daily basis), quality of life (at 0, 8, and 10 weeks), intestinal permeability, and composition of intestinal microbiota (at 0 and 8 weeks). DISCUSSION: The present study is designed to examine the safety and efficacy of GJS and Duolac7S combination therapy on D-IBS. Our study provides the clinical evidence of a new therapeutic strategy for D-IBS.

Bojanggunbi-tang, a traditional Korean herbal prescription, ameliorates colonic inflammation induced by dextran sulfate sodium and 2,4,6-trinitrobenzene sulfonic acid in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Korean medicine, Bojanggunbi-tang (BGT), which consists of 16 herbs, is one of the most frequently used herbal prescriptions in South Korea for treating intestinal disorders such as colitis. AIM OF THE STUDY: This study investigated whether BGT could show a protective action on 2 different mice models of experimental colitis induced by dextran sulfate sodium (DSS) and 2,4,6-trinitrobenzene sulfonic acid (TNBS), which have been popularly used as inflammatory bowel disease models. MATERIALS AND METHODS: Colitis was induced by DSS and TNBS in institute of cancer research mice. BGT at doses of 50, 150, or 450 mg/kg were orally administered twice a day for 7d in the DSS model and for 3d in the TNBS model. The body weight of the mice was measured daily. Colon length and histological damages were assessed on day 7 in the DSS model and on day 3 in the TNBS model. RESULTS: BGT showed protective effects in both types of experimental colitis. In the DSS model, BGT dose dependently inhibited weight loss, shortening of colon length, and histological damages of the colon. In the TNBS model, BGT inhibited shortening of colon length and improved the survival rate of mice; however, it did not inhibit weight loss. CONCLUSION: The current results indicate that BGT ameliorates both DSS- and TNBS-induced colitis in mice. Further investigations to unveil the exact mechanisms are needed.

Banha-sasim-tang as an herbal formula for the treatment of functional dyspepsia: a randomized, double-blind, placebo-controlled, two-center trial.

BACKGROUND: Functional dyspepsia (FD) is characterized by a high prevalence rate and no standard conventional treatments. Alternative therapies, such as herbal formulas, are widely used to treat FD. However, there are inadequate evidences regarding the safety and efficacy of these formulas. Moreover, the mechanisms by which herbal formulas act in the gastrointestinal tract are controversial. In traditional Korean medicine, Banha-sasim-tang has long been one of the most frequently prescribed herbal formulas for treating dyspepsia. The current study is designed to evaluate the efficacy and safety of Banha-sasim-tang for FD patients and to examine whether there will be a significant correlation between cutaneous electrogastrography recordings and dyspeptic symptoms in FD patients, and between changes in gastric myoelectrical activity and improvement in dyspeptic symptoms during Banha-sasim-tang administration. METHODS: This randomized, double-blind, placebo-controlled trial will be performed at two centers and will include a Banha-sasim-tang group and placebo group. Each group will consist of 50 FD patients. Six weeks of administration of Banha-sasim-tang or placebo will be conducted. During the subsequent 2 months, follow-up observations of primary and secondary outcomes will be performed. The primary outcomes are differences as measured on the gastrointestinal symptom scale, and the secondary outcomes are differences as measured on the visual analogue scale for dyspepsia and on the questionnaire for FD-related quality of life. All outcomes will be measured at baseline, at 2, 4, and 6 weeks of treatment, and at the 1 and 2 month follow-up. Cutaneous electrogastrography will be performed and assessed at baseline and at 6 weeks. DISCUSSION: This trial will provide evidence of the safety and efficacy of Banha-sasim-tang for the treatment for FD. Furthermore, based on the assessment of the relationship between cutaneous electrogastrography recordings and dyspeptic symptoms in this trial, the possibility of clinical applications of cutaneous electrogastrography in the treatment of FD will be elucidated. TRIAL REGISTRATION: Current Controlled Trials (ISRCTN 51910678); Clinical Trials.gov Identifier: NCT00987805.