Chronic Gut Inflammation and Dysbiosis in IBS: Unraveling Their Contribution to Atopic Dermatitis Progression.

Emerging evidence suggests a link between atopic dermatitis (AD) and gastrointestinal disorders, particularly in relation to gut microbial dysbiosis. This study explored the potential exacerbation of AD by gut inflammation and microbial imbalances using an irritable bowel syndrome (IBS) mouse model. Chronic gut inflammation was induced in the model by intrarectal injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS), followed by a 4-week development period. We noted significant upregulation of proinflammatory cytokines in the colon and evident gut microbial dysbiosis in the IBS mice. Additionally, these mice exhibited impaired gut barrier function, increased permeability, and elevated systemic inflammation markers such as IL-6 and LPS. A subsequent MC903 challenge on the right cheek lasting for 7 days revealed more severe AD symptoms in IBS mice compared to controls. Further, fecal microbial transplantation (FMT) from IBS mice resulted in aggravated AD symptoms, a result similarly observed with FMT from an IBS patient. Notably, an increased abundance of Alistipes in the feces of IBS mice correlated with heightened systemic and localized inflammation in both the gut and skin. These findings collectively indicate that chronic gut inflammation and microbial dysbiosis in IBS are critical factors exacerbating AD, highlighting the integral relationship between gut and skin health.

Influence of Feeding Time on a Non-steroidal Anti-inflammatory Drug-induced Small Intestinal Injury Mouse Model.

BACKGROUND/AIM: Non-steroidal anti-inflammatory drugs (NSAIDs), the most widely used pharmaceuticals, induce various adverse effects, including gastrointestinal injuries, such as ulcers and bleeding. Animal models of NSAID-induced small intestinal injury (NSI) have been extensively employed for the development of preventive and therapeutic agents. However, some experimental variations related to feeding times have been observed following NSI induction. This study aimed to investigate the impact of feeding time on an NSI mouse model. MATERIALS AND METHODS: The mice were divided into eight groups: normal, sham, and model groups (with feeding times of 2 h, 6 h, 10 h, 14 h, 18 h, and 22 h; n=10 in each group). The mice were fasted for 18 h before the injection of indomethacin (15 mg/kg, subcutaneously), except for the normal group. Food supply was halted at specific time points (2 h, 6 h, 10 h, 14 h, 18 h, and 22 h); however, the normal and sham groups were continuously fed throughout the experiment. The length of the small intestine was measured, and histological analysis was performed 24 h after induction. RESULTS: Up to 14 h after induction, NSI, indicated by small intestine shortening, remained consistent, with a reduction in length of approximately 10-20%. However, feeding for more than 14 h significantly exacerbated NSI, both anatomically and histologically. CONCLUSION: The ulcerative changes observed in the small intestine 14 h after indomethacin injection may be closely associated with the influence of food on NSI.

Influence of patient-clinician relationship style on acupuncture outcomes in functional dyspepsia: A multi-site randomized controlled trial in Korea.

INTRODUCTION: Research suggests that a warm and empathic "patient-centered" patient-clinician relationship produces better clinical outcomes when compared with a more neutral "disease-centered" relationship. Acupuncturists performed both styles of therapy for patients with functional dyspepsia in Korea. METHODS: The present randomized controlled trial assigned patients (n = 73) to identical acupuncture treatment with either patient-centered augmented care or disease-centered limited care. The Korean version of the Nepean Dyspepsia Index (NDI-K) was the primary outcome measure. Secondary outcome measures included Consultation And Relational Empathy (CARE) scale. RESULTS: Both groups showed improvement in NDI-K. Patient-centered augmented acupuncture produced less effective symptom improvement compared to disease-centered limited acupuncture (NDI-K sum score and frequency; P = 0.008 and P = 0.037 respectively). CARE scores were higher for the augmented versus limited group (P = 0.001), supporting the fidelity of the experimentally controlled patient/clinician relationship. There were no significant differences between the groups in any of other secondary outcomes. CONCLUSION: Patients demonstrated greater improvement following acupuncture conducted with a more neutral, "disease-centered" style of relationship. This result is counter to similar research conducted in Western countries and suggests that cultural factors can significantly shape optimum styles of acupuncture therapy. PRACTICE IMPLICATIONS: Clinicians should consider cultural differences when applying acupuncture therapy.

A Study on the Effects of Muscarinic and Serotonergic Regulation by Bojanggunbi-tang on the Pacemaker Potential of the Interstitial Cells of Cajal in the Murine Small Intestine.

In traditional Korean medicine, the 16-herb concoction Bojanggunbi-tang (BGT) is used to treat various gastrointestinal (GI) diseases. In this study, we investigated the regulatory mechanism underlying the influence of BGT on the interstitial cells of Cajal (ICCs), pacemaker cells in the GI tract. Within 12 h of culturing ICCs in the small intestines of mice, the pacemaker potential of ICCs was recorded through an electrophysiological method. An increase in the BGT concentration induced depolarization and decreased firing frequency. This reaction was suppressed by cholinergic receptor muscarinic 3 (CHRM3) antagonists, as well as 5-hydroxytryptamine receptor (5HTR) 3 and 4 antagonists. Nonselective cation channel inhibitors, such as thapsigargin and flufenamic acid, along with protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) inhibitors, also suppressed the BGT reaction. Guanylate cyclase and protein kinase G (PKG) antagonists inhibited BGT, but adenylate cyclase and protein kinase A antagonists had no effect. In conclusion, we demonstrated that BGT acts through CHRM3, 5HTR3, and 5HTR4 to regulate intracellular Ca2+ concentrations and the PKC, MAPK, guanylate cycle, and PKG signaling pathways.

Herbal medicine, Banxia-xiexin tang, for functional dyspepsia: a systematic review and meta-analysis.

Background: The demand for complementary and alternative medicine for the management of functional dyspepsia (FD) is increasing due to the insufficient efficacy of conventional treatment options. In Asia, the Chinese herbal medicine formula Banxia-xiexin tang (BXT) has been used to treat FD. Methods: We searched 11 digital medical databases on 1 September 2021. Randomized controlled trials (RCTs) that investigated the efficacy of BXT or combination therapy (BXT plus Western medicines) for FD were selected. The outcome parameters were total clinical efficacy rate (TCE), motilin level, symptom checklist-90-revised (SCL-90-R), and visual analog scale (VAS) for dyspepsia and adverse events. Cochrane risk of bias tool 2.0 (RoB 2) was used for the quality assessment of included studies. Results: The meta-analysis comprised 57 RCTs with 5,525 participants. BXT was more efficacious, with a higher TCE than Western medicine. Combination therapy (BXT plus Western medicine) also resulted in a higher TCE than Western medicine. Combination therapy improved motilin levels and psychological symptoms to a greater extent than Western medicine, evidenced by a higher SCL-90-R score. However, no significant difference in VAS scores was observed between the BXT and placebo groups. BXT and combination therapy were associated with fewer adverse events than Western medicine or placebo. Conclusion: Our findings suggest that BXT and its combination therapy may be an effective and safe alternative treatment for FD. More RCTs with better methodologies are required to strengthen this evidence. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019123285], identifier [CRD42019123285].

Safety and effectiveness of traditional herbal medicine Siho-sogan-san in functional dyspepsia: A systematic review and meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Functional dyspepsia (FD), a chronic upper gastrointestinal syndrome, seriously affects the quality of life of patients and poses a significant economic burden. Since the pathological mechanisms of FD have not been fully elucidated, conventional therapies such as prokinetics, proton pump inhibitors, and antidepressants have some limitations. Siho-sogan-san (SHS) is commonly used as a therapeutic alternative in traditional medicine; however, scientific and clinical evidence supporting its application in FD remains insufficient. AIM OF THE STUDY: This review aimed to assess the safety and effectiveness of SHS and in combined with Western medicine (WM) for the treatment of FD. METHODS: Eleven databases, including EMBASE, Medline, and Cochrane Library, were searched for randomized controlled trials (RCTs) on FD published before December 31, 2022. After two independent reveiwers sceened and selected studies according to the inclusion and exclusion criteria, clinical data was pooled and synthesized via Review Manager software. The outcome parameters included total clinical effectiveness rate (TCE), time for symptom improvement, levels of motilin and corticotropin-releasing hormone (CRH), and adverse events. Cochrane's risk of bias tool was used for quality assessment. RESULTS: A total of 12 studies that included 867 participants comparing WM with SHS or combination therapy (SHS plus WM) were identified. Through a meta-analysis of five studies including 363 patients, SHS compared with WM showed a positive result in safely increasing TCE [risk ratio = 1.36, 95% confidence interval (CI) 1.22 to 1.51, P < 0.00001]. The time for symptom improvement, including abdominal pain, belching, nausea, vomiting, and abdominal distension, was significantly more shortened in the combination therapy than WM group. Furthermore, combination therapy resulted in greater secretion of motilin than WM alone [mean difference = 67.95, 95% CI 39.52 to 96.39, P < 0.00001]. No remarkable difference was observed in CRH levels between the combination therapy and WM groups. For a subgroup analysis, the administration of SHS based on the type of pattern identification (PI) showed larger effect size than in the group that do not consider PI. CONCLUSIONS: These results suggest that SHS and combination therapy can be considered effective and safe options for the treatment of FD. However, owing to the low quality of the included studies, more well-designed investigational studies and RCTs with longer treatment and follow-up period are needed.

Safety and efficacy of Xiaoyao-san for the treatment of functional dyspepsia: a systematic review and meta-analysis of randomized controlled trials.

Objective: Although Xiaoyao-san (XYS) is a popular herbal remedy for indigestion, there is insufficient evidence to recommend it as a treatment option for functional dyspepsia (FD). This review aimed to assess the safety and efficacy of XYS in patients with FD, compared to conventional Western medicine (WM). Methods: Two independent reviewers searched for randomized controlled trials (RCTs) using 11 electronic databases, including Medline and Embase, to evaluate therapeutic effects of XYS on FD up to 31 January 2023. The primary outcome was the total clinical efficacy rate (TCE), and secondary outcomes included scores of dyspepsia-related symptoms (DSS) and incidence of adverse events (AEs). The risk of bias was evaluated using the Cochrane collaboration tool, and data synthesis and subgroup analyses were performed using the Review Manager program. Results: Six studies involving 707 participants were included in the meta-analysis. XYS significantly improved TCE compared to WM (RR = 1.15, 95% CI: 1.05, 1.26, p = 0.002) with high heterogeneity (I 2 = 59%, p = 0.06). Combination therapy also showed higher TCE than WM alone (RR = 1.22, 95% CI: 1.05, 1.41, p = 0.008), and the heterogeneity was low (I 2 = 0%, p = 0.86). The results showed a greater reduction in DSS in the XYS and combination therapy groups than in the WM alone group (SMD = -0.72, 95% CI: -0.90, -0.53, p < 0.00001) with low heterogeneity (I 2 = 44%, p = 0.15), especially for abdominal distension and upper abdominal pain. AEs occurred less frequently in the XYS and combination therapy groups than in the WM alone group (RR = 0.20, 95% CI: 0.07, 0.63, p = 0.006), and the heterogeneity was low (I 2 = 45%, p = 0.18). The certainty of the evidence for each outcome was rated from "very low" to "high." Conclusion: This review suggests that XYS is effective and safe for reducing complaints in patients with FD. However, high-quality RCTs should be conducted to establish more convincing therapeutic evidence of XYS for the treatment of FD. Systematic Review Registration: https://www.crd.york.ac.uk/prospero, CRD42020178842.

Efficacy and safety of the herbal formula Naesohwajung-tang for functional dyspepsia: a randomized, double-blind, placebo-controlled, multi-center trial.

Background: Current treatment and management options for functional dyspepsia (FD) often fail to alleviate symptoms. Naesohwajung-tang (NHT) is a herbal formula frequently used to treat functional dyspepsia in traditional Korean medicine. However, few animal and case reports on the use of Naesohwajung-tang for functional dyspepsia treatment exist, and the clinical evidence remains deficient. Objectives: This study aimed to evaluate the efficacy of Naesohwajung-tang in patients with functional dyspepsia. Methods: We enrolled 116 patients with functional dyspepsia at two study sites in this 4 weeks, randomized, double-blind, placebo-controlled trial and randomly assigned them to either the Naesohwajung-tang or placebo group. To evaluate the efficacy of Naesohwajung-tang, the primary endpoint was a score on the total dyspepsia symptom (TDS) scale after treatment. The overall treatment effect (OTE), single dyspepsia symptom (SDS) scale, food retention questionnaire (FRQ), Damum questionnaire (DQ), functional dyspepsia-related quality of life (FD-QoL) questionnaire, and gastric myoelectrical activity measured using electrogastrography were evaluated as secondary outcomes. Laboratory tests were performed to confirm the safety of the intervention. Results: The 4 weeks administration of Naesohwajung-tang granules demonstrated a significantly higher reduction in the total dyspepsia symptom (p < 0.05) and a higher degree of improvement in the total dyspepsia symptom (p < 0.01) than the placebo group. Patients who underwent Naesohwajung-tang had a significantly higher overall treatment effect and a greater increase in the degree of improvement in scores such as epigastric burning, postprandial fullness, early satiation, functional dyspepsia-related quality of life, and Damum questionnaire (p < 0.05). Additionally, the Naesohwajung-tang group showed a greater effect in preventing a decrease in the percentage of normal gastric slow waves after meals than the placebo group. As a result of subgroup analyses using the degree of improvement in total dyspepsia symptom, Naesohwajung-tang was found to be more effective than placebo in female, younger patients (<65 years), with a high body-mass index (≥22), overlap type, food retention type, and Dampness and heat in the spleen and stomach systems pattern. There was no significant difference in the incidence of adverse events between the two groups. Conclusion: This is the first randomized clinical trial to verify that Naesohwajung-tang leads on symptom relief in patients with functional dyspepsia. Clinical Trial Registration: https://cris.nih.go.kr/cris/search/detailSearch.do/17613, identifier KCT0003405.

Network Pharmacological Analysis and Experimental Validation of the Effect of Smilacis Glabrae Rhixoma on Gastrointestinal Motility Disorder.

Gastrointestinal motility disorder (GMD) is a disease that causes digestive problems due to inhibition of the movement of the gastrointestinal tract and is one of the diseases that reduce the quality of life of modern people. Smilacis Glabrae Rhixoma (SGR) is a traditional herbal medicine for many diseases and is sometimes prescribed to improve digestion. As a network pharmacological approach, we searched the TCMSP database for SGR, reviewed its constituents and target genes, and analyzed its relevance to gastrointestinal motility disorder. The effects of the SGR extract on the pacemaker activity in interstitial cells of Cajal (ICC) and gastric emptying were investigated. In addition, using the GMD mouse model through acetic acid (AA), we investigated the locomotor effect of SGR on the intestinal transit rate (ITR). As a result of network pharmacology analysis, 56 compounds out of 74 candidate compounds of SGR have targets, the number of targets is 390 targets, and there are 904 combinations. Seventeen compounds of SGR were related to GMD, and as a result of comparing the related genes with the GMD-related genes, 17 genes (active only) corresponded to both. When looking at the relationship network between GMD and SGR, it was confirmed that quercetin, resveratrol, SCN5A, TNF, and FOS were most closely related to GMD. In addition, the SGR extract regulated the pacemaker activity in ICC and recovered the delayed gastric emptying. As a result of feeding the SGR extract to AA-induced GMD mice, it was confirmed that the ITR decreased by AA was restored by the SGR extract. Through network pharmacology, it was confirmed that quercetin, resveratrol, SCN5A, TNF, and FOS were related to GMD in SGR, and these were closely related to intestinal motility. Based on these results, it is suggested that SGR in GMD restores digestion through the recovery of intestinal motility.

Acupuncture and Acupoints for Low Back Pain: Systematic Review and Meta-Analysis.

Acupuncture has been used as a therapeutic intervention for the treatment of numerous diseases and symptoms for thousands of years, and low back pain has been studied and treated the most in acupuncture clinics. Traditional theory strongly suggests that the selection of acupoints will influence their clinical effects and combinations (e.g., the clinical effects of a particular acupoint or combination on reducing pain), but this idea was not considered in earlier systematic reviews and meta-analyses. We performed a systematic review, meta-analysis, and network analysis to evaluate the magnitude of the effects of acupoints used to treat low back pain in randomized controlled clinical trials. We found that acupuncture significantly reduced pain in patients with low back pain compared with the control group. The most frequently prescribed acupoints were BL23, GV3, BL20, BL40, and BL25, whereas the acupoints with the highest average effect size scores were BL20, GV3, GB30, GB34, and BL25. Further, the combinations of BL23-BL40, BL23-B25, and BL23-BL60 were the most frequently prescribed, while BL23-GV3, BL40-GV4, and BL23-BL25 showed the largest average effect size. By calculating clinical outcomes based on average effect sizes, we found that the most popular acupoints might not always be associated with the best results. Although a more thorough investigation is necessary to determine the clinical effects of each acupoint and combination on patients, we suggest that our approach may offer a fresh perspective that will be useful for future research.

The influence of herbal medicine on serum motilin and its effect on human and animal model: a systematic review.

Introduction: Motilin (MLN) is a gastrointestinal (GI) hormone produced in the upper small intestine. Its most well understood function is to participate in Phase III of the migrating myoelectric complex component of GI motility. Changes in MLN availability are associated with GI diseases such as gastroesophageal reflux disease and functional dyspepsia. Furthermore, herbal medicines have been used for several years to treat various GI disorders. We systematically reviewed clinical and animal studies on how herbal medicine affects the modulation of MLN and subsequently brings the therapeutic effects mainly focused on GI function. Methods: We searched the PubMed, Embase, Cochrane, and Web of Science databases to collect all articles published until 30 July 2023, that reported the measurement of plasma MLN levels in human randomized controlled trials and in vivo herbal medicine studies. The collected characteristics of the articles included the name and ingredients of the herbal medicine, physiological and symptomatic changes after administering the herbal medicine, changes in plasma MLN levels, key findings, and mechanisms of action. The frequency patterns (FPs) of botanical drug use and their correlations were investigated using an FP growth algorithm. Results: Nine clinical studies with 1,308 participants and 20 animal studies were included in the final analyses. Herbal medicines in clinical studies have shown therapeutic effects in association with increased levels of MLN, including GI motility regulation and symptom improvement. Herbal medicines have also shown anti-stress, anti-tumor, and anti-inflammatory effects in vivo. Various biochemical markers may correlate with MLN levels. Markers may have a positive correlation with plasma MLN levels included ghrelin, acetylcholine, and secretin, whereas a negative correlation included triglycerides and prostaglandin E2. Markers, such as gastrin and somatostatin, did not show any correlation with plasma MLN levels. Based on the FP growth algorithm, Glycyrrhiza uralensis and Paeonia japonica were the most frequently used species. Conclusion: Herbal medicine may have therapeutic effects mainly on GI symptoms with involvement of MLN regulation and may be considered as an alternative option for the treatment of GI diseases. Further studies with more solid evidence are needed to confirm the efficacy and mechanisms of action of herbal medicines. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=443244, identifier CRD42023443244.

Complementary and alternative medicine for functional dyspepsia: An Asian perspective.

A considerable number of Asian patients with functional dyspepsia (FD) are searching for complementary and alternative medicine (CAM) because they are unsatisfied with conventional medical treatment. However, no article has focused on CAM for FD from Asian perspective. In Asian countries, many traditional herbal formulas, including Banha-sasim-tang, Soyo-san, Sihosogan-san, Yukgunja-tang, and Pyeongwi-san, are used in patients with FD. In the few blinded and placebo-controlled studies conducted, the weak evidence regarding the effectiveness of herbal prescriptions in patients with FD did not allow any conclusions to be made. The clinical efficacy and safety of STW-5 were proven in several prospective randomized controlled trials and systematic reviews. Hence, it was recently approved as a therapeutic option for the treatment of FD. Peppermint and caraway, FDgard, black seed oil, and Jollab have been used in patients with FD, but there is limited evidence supporting their use. Reviews of acupuncture in patients with FD showed inconsistent results: a Cochrane review reported a negative result, while other meta-analyses reported positive results. Psychotherapy, including hypnotherapy, psychoanalytic psychotherapy, and cognitive behavioral therapy, may be used in patients with FD, although it is only supported by weak evidence. Therefore, well-planned, large-scale studies are necessary to evaluate the efficacy of CAM in treating FD, especially in Asian countries.

The Effect of Laminaria japonica on Metabolic Syndrome: A Systematic Review of Its Efficacy and Mechanism of Action.

Metabolic syndrome (MetS) is a medical condition characterized by abdominal obesity, insulin resistance, high blood pressure, and hyperlipidemia. An increase in the incidence of MetS provokes an escalation in health care costs and a downturn in quality of life. However, there is currently no cure for MetS, and the absence of immediate treatment for MetS has prompted the development of novel therapies. In accordance with recent studies, the brown seaweed Laminaria japonica (LJP) has anti-inflammatory and antioxidant properties, and so forth. LJP contains bioactive compounds used as food globally, and it has been used as a medicine in East Asian countries. We conducted a systematic review to examine whether LJP could potentially be a useful therapeutic drug for MetS. The following databases were searched from initiation to September 2021: PubMed, Web of Science, EMBASE, and Cochrane Central Register of Controlled Trials Library. Clinical trials and in vivo studies evaluating the effects of LJP on MetS were included. LJP reduces the oxidative stress-related lipid mechanisms, inflammatory cytokines and macrophage-related chemokines, muscle cell proliferation, and migration. Bioactive-glucosidase inhibitors reduce diabetic complications, a therapeutic target in obesity and type 2 diabetes. In obesity, LJP increases AMP-activated protein kinase and decreases acetyl-CoA carboxylase. Based on our findings, we suggest that LJP could treat MetS, as it has pharmacological effects on MetS.

An Overview of Systematic Reviews of Herbal Medicine for Irritable Bowel Syndrome.

Background: Irritable bowel syndrome (IBS) is a common disorder with abdominal pain and bowel habits changes. Herbal medicines (HMs) are frequently used in the treatment of IBS. Therefore, several systematic reviews (SRs) have been conducted to assess the efficacy and safety of HM in IBS patients. This study aimed to investigate the methodology and quality of evidence of SRs, and to describe the current state of research and evidence for the treatment of IBS with HM. Methods: SRs published up to January 2022 were searched using six electronic databases. SRs and/or meta-analyses on the use of HMs for IBS were included. The effects of placebo, conventional medicine (CM), and probiotics were compared with those of HMs. Two investigators independently extracted the data and assessed methodological quality using the Measure Tool to Assessment System Reviews 2 (AMSTAR 2). Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was used to evaluate the quality of evidence for each main finding. Results: Eighteen SRs were included in this overview. Among them, eight SRs reported only specific subtypes of IBS: six SRs reported patients with diarrhea-predominant IBS, and two SRs reported patients with constipation-predominant IBS. In terms of total efficacy, HM was more effective than placebo, CM, or probiotics. HM showed a more significant effect than CM in relieving independent IBS symptom score (abdominal pain score, diarrhea score, abdominal distension score, stool frequency score, etc.) and recurrence rate. The rate of adverse events was significantly lower with HM compared to CM, and no serious adverse events were reported with HM treatment. According to AMSTAR 2, the methodological quality of the included SRs was extremely low. Furthermore, the quality of evidence for total efficacy was considered low or very low according to the GRADE tool. Conclusion: HM can be considered as an effective and safe treatment for IBS. However, the methodological quality of the included SRs and the quality of evidence was generally low. Therefore, well-designed randomized controlled trials are needed in the future so that a high-quality SR can be used to better assess the safety and efficacy of HM in the treatment of IBS. Systematic Review Registration: https://osf.io/nt6wz, identifier 10.17605/OSF.IO/NT6WZ.

Prediction of the Medicinal Mechanisms of Pinellia ternata Breitenbach, a Traditional Medicine for Gastrointestinal Motility Disorders, through Network Pharmacology.

Pinellia ternata Breitenbach (PTB) is a widely used herbal medicine in China, Japan, and South Korea. It has antiemetic, anti-inflammatory, antitussive, and sedative properties. The raw material is toxic, but can be made safer using alum solution or by boiling it for a long time. In addition, PTB seems to be effective for gastrointestinal motility disorders (GMDs), but this is yet to be conclusively proven. Herein, PTB compounds, targets, and related diseases were investigated using the traditional Chinese medical systems pharmacology database and an analysis platform. Information on target genes was confirmed using the UniProt database. Using Cytoscape 3.8.2, a network was established and GMD-related genes were searched using the Cytoscape stringApp. The effects of the PTB extract on the pacemaker potential of interstitial cells of Cajal and GMD mouse models were investigated. In total, 12 compounds were found to target 13 GMD-related genes. In animal experiments, PTB was found to better regulate pacemaker potential in vitro and inhibit GMD signs compared to control groups in vivo. Animal studies showed that the mechanism underlying the effects of PTB is closely related to gastrointestinal motility. The results obtained demonstrated that PTB offers a potential means to treat GMDs, and we suggested that the medicinal mechanism of GMDs can be explained by the relationship between 12 major components of PTB, including oleic acid, and 13 GMD-related genes.

The efficacy and safety of Laminaria japonica for metabolic syndrome: A protocol for systematic review.

BACKGROUND: Metabolic syndrome is a pathological condition characterized by abdominal obesity, insulin resistance, hypertension, and hyperlipidemia. Conventional treatments for metabolic syndrome have limitations due to their nonselectivity, drug resistance, and low bioavailability. The brown seaweed Laminaria japonica (LJP) is a traditional medicine and food in Asia that has shown pharmacological and biochemical properties favorable to the prevention and treatment of lifestyle-related diseases. We will systematically review randomized controlled trials and in vivo preclinical studies evaluating the efficacy and safety of LJP as a useful treatment for metabolic syndrome. METHODS: The following databases will be searched from inception to September 2021: MEDLINE (via PubMed), EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science. Randomized controlled trials and in vivo preclinical studies that analyzed LJP for the prevention and treatment of metabolic syndromes will be included. The outcome measures will include body composition, dietary habit scores, serum lipid profiles, daily nutrient intake, quality of life, number of microbiomes, gastrointestinal symptoms, and bowel function. Studies comparing LJP with any type of control intervention will be included. Data extraction using Review Manager version 5.3 and risk of bias assessment using the Cochrane Collaboration's tool for assessing risk of bias will be performed by 2 independent assessors. RESULTS AND CONCLUSION: This systematic review will provide evidence confirming the efficacy and safety of LJP in the treatment of metabolic syndrome. ETHICS AND DISSEMINATION: Ethical approval was not required, as this study protocol does not include any personal information of the participants. TRIAL REGISTRATION NUMBER: DOI 10.17605/OSF.IO/G2BQK (https://osf.io/g2bqk).

Ginger (Zingiber officinale Roscoe), Lemon (Citrus limon L.) Juices as Preventive Agents from Chronic Liver Damage Induced by CCl4: A Biochemical and Histological Study.

Zingiber officinale Roscoe and Citrus limon L. are well known for their multi-use and for their pharmacological effect in the treatment of many illnesses. This study aims to investigate the chemical composition of the ginger and lemon juice extracts and in addition, to evaluate their antioxidant properties and their hepatoprotective effect against the liver damage of Wistar rats induced by the injection of CCl4 to treated animals. The obtained effects were completed by a histological study for better confirmation of the registered pharmacological effects. The ginger juice extract was found to be rich in 4-gingerol, 6-gingediol, and 6-gingerol, while the lemon juice extract chemical composition was highlighted by the presence of eriodyctiol, rutin, hesperidin, and isorhamnetin. Concerning the antioxidant activity, the ginger, lemon juice extracts, and their formulation showed an important antioxidant potential using TAC (total antioxidant capacity), an antiradical activity against the radical DPPH• (2,2-diphenyl-1-picrylhydrazil), and a ferric reducing power. Finally, the ginger, lemon, and their formulation at different doses were able to prevent CCl4 induced liver damage. Indeed, these different bioactive compounds could be used as alternative agents for the treatment of chronic liver diseases.

Acupuncture as an Add-On Treatment for Functional Dyspepsia: A Systematic Review and Meta-Analysis.

Background: We aimed to critically evaluate the effectiveness and safety of acupuncture as an add-on therapy to conventional Western medication (WM) and assess the quality of evidence (QoE) of these findings. Methods: A total of 12 English, Korean, and Chinese databases were searched on December 18, 2020. Randomized controlled trials (RCTs) assessing the effectiveness of acupuncture as an add-on therapy to conventional WM for functional dyspepsia (FD) were included. The primary outcome was the symptom score of FD. The risk of bias of the included studies and QoE were evaluated using the Cochrane Collaboration's risk of bias tool and Grading of Recommendations, Assessment, Development, and Evaluation method, respectively. Results: A total of 22 RCTs were included. The total and individual FD symptom scores were significantly improved in the acupuncture combined with WM groups compared with the WM alone groups, except for in one study. The Nepean dyspepsia index score and total effective rate mostly improved significantly in the acupuncture group, regardless of the WM used and acupuncture type. FD-related biomarkers, such as ghrelin and gastrin levels, showed mixed results. The acupuncture group showed a significantly lower recurrence rate after 3-6 months of follow-up than the WM alone group. There were no differences in the incidence of adverse events between the two groups. The included studies generally had low methodological quality. The QoE for the main findings was generally very low to moderate. Conclusion: Limited evidence suggests that acupuncture has the potential to improve FD treatment in combination with conventional WM. Furthermore, the methodological quality of the included studies and QoE of the main findings were generally low. Therefore, RCTs with a rigorous methodology, including sham acupuncture and multiethnic subjects, should be performed. Systematic Review Registration: OSF registries [https://osf.io/mxren], PROSPERO [CRD42021226608].

Gwakhyangjeonggi-san for irritable bowel syndrome: A protocol for systematic review and meta-analysis.

BACKGROUND: Irritable bowel syndrome (IBS) is a chronic functional bowel disorder characterized by abdominal pain or discomfort, stool irregularities, and bloating. Owing to its atypical symptoms and various mechanisms, there is no standard treatment for IBS. Gwakhyangjeonggi-san (GJS), a traditional Korean herbal medicine, has been used to treat lower intestinal abnormalities in Asia. We will systematically review randomized controlled trials (RCTs) to evaluate the efficacy and safety of GJS as a complementary treatment for IBS. METHODS AND ANALYSIS: Four English databases, namely, Medline (via PubMed), EMBASE, the Cochrane Central Register of Controlled Trials, and the Allied and Complementary Medicine Database, will be searched for entries up to May, 2021. Additional databases will include 5 Korean databases, 1 Chinese database, and 1 Japanese database. RCTs and quasi-RCTs will be searched for to assess the effectiveness and safety of GJS. The primary outcome measure will be the overall efficacy rate, and the secondary outcome will include data such as global symptom scores, IBS Quality of Life measurements, and adverse events. Data analysis will be performed using Review Manager Version 5.3, and the risk of bias will be assessed using the Cochrane Collaboration's risk-of-bias tool. The quality of the results will be evaluated using the Grading of Recommendations Assessment, Development, and Evaluation approach. CONCLUSION: This systematic review will provide evidence for the efficacy and safety of GJS for IBS. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/V93JN (https://osf.io/v93jn).

Development of a patient-report pressure algometer for the quantification of abdominal examination.

BACKGROUND: Abdominal examination (AE), one of the primary diagnostic tools used in traditional Korean medicine (TKM), has a limitation of being subjective due to depending on individual practitioner's experience. Therefore, we devised a novel patient-report pressure algometer (PA) and performed a clinical trial to investigate its validity. METHODS: In total, 44 participants with functional dyspepsia and 44 healthy participants completed the study. The participants were allocated into one of two groups according to the existence of abdominal stiffness at 5 acupoints or abdominal tenderness at 12 acupoints diagnosed by TKM doctors. The pressure depth and pressure pain threshold (PPT) were evaluated using the PA at the same acupoints. We assessed the validity (sensitivity and specificity) of PA and calculated the area under the curve (AUC) and optimal cutoff value of the test variables (pressure depth and PPT) to criterion standards (abdominal stiffness and tenderness). RESULTS: Pressure depth and PPT assessed by PA showed high sensitivity and specificity in diagnosing abdominal stiffness and tenderness. The validity at CV-14 of diagnosing abdominal tenderness with PPT by PA had a sensitivity of 73.1%, specificity of 77.8%, and an AUC of 0.807 with a P value of < 0.001. CONCLUSION: This study may provide evidence of standardization and quantification of AE through PA.