Metformin is the first-line pharmacotherapy for treating type 2 diabetes mellitus (T2DM); however, its mechanism of modulating glucose metabolism is elusive. Recent advances have identified the gut as a potential target of metformin. As patients with metabolic disorders exhibit dysbiosis, the gut microbiome has garnered interest as a potential target for metabolic disease. Henceforth, studies have focused on unraveling the relationship of metabolic disorders with the human gut microbiome. According to various metagenome studies, gut dysbiosis is evident in T2DM patients. Besides this, alterations in the gut microbiome were also observed in the metformin-treated T2DM patients compared to the non-treated T2DM patients. Thus, several studies on rodents have suggested potential mechanisms interacting with the gut microbiome, including regulation of glucose metabolism, an increase in short-chain fatty acids, strengthening intestinal permeability against lipopolysaccharides, modulating the immune response, and interaction with bile acids. Furthermore, human studies have demonstrated evidence substantiating the hypotheses based on rodent studies. This review discusses the current knowledge of how metformin modulates T2DM with respect to the gut microbiome and discusses the prospect of harnessing this mechanism in treating T2DM.

The aim of this study was to systematically review data regarding pharmacokinetic (PK)-pharmacodynamic (PD) parameters from randomized controlled trials relating to interactions between herbal medicines and warfarin. Three electronic databases were searched to identify relevant trials. Two reviewers independently performed the study selection and data extraction. The risk of bias and reporting quality were also assessed independently by two reviewers using the Cochrane risk of bias tool and the consolidated standards of reporting trials (CONSORT). Outcomes were measured for all reported PK-PD parameters and adverse events. Nine randomized controlled trials met our inclusion criteria. Most of the included studies were unclear regarding the risk of bias and had a low quality of methodology. Using CONSORT, the reporting percentages for the articles ranged from 36.5% to 61.5% and the mean percentage for all articles was 45.6%. St John’s wort and echinacea affected the PK parameters of warfarin. Ginseng, ginger, garlic, and cranberry had no significant effect on the PK parameters. American ginseng altered the PD parameters of warfarin. St John’s wort, ginseng, Korea red ginseng, ginkgo, ginger, garlic, aged garlic, and echincea did not significantly alter the PD parameters. Studies of ginkgo and cranberry showed conflicting results on the PK parameters and PD parameters, respectively. The incidence of adverse events in all trials was low and no major adverse events were reported. It was difficult to determine whether ten herbal medicines had significant effects on the PK-PD parameters of warfarin. Low quality of evidence, different compounds within and different compositions of the herbs, and methodological limitations of the crossover study, which is a clinical study in which subjects receive a sequence of different interventions, made it difficult to form conclusions. Additional studies that remedy these vulnerabilities are necessary to verify these results.

Approximately 45-50% of the cases of infertility result from deficiencies associated with male factors, and 30-45% of these deficiencies are idiopathic. A standardized approach for the treatment of idiopathic male infertility remains elusive. In Korea, male infertility has been treated with either acupuncture, herbal remedies, or pharmacopuncture. We report a case of male idiopathic infertility in which the patient's semen quality improved through traditional Korean medicine (TKM) therapies, which was evaluated according to the 2010 World Health Organization (WHO) standards. A 35-year-old infertile man visited the Conmaul Hospital from August 2013 to December 2013. He was diagnosed with asthenoteratozoospermia. The patient received 3 TKM therapies-acupuncture, pharmacopuncture, and herbal remedies-for 3 months. After 3 months of treatment, a second semen analysis of the patient was conducted. The sperm motility increased by 13%, and the normal sperm morphology increased by 4% over 3 months. In addition, the total motile sperm count was 2.5 times higher than that before treatment. The results of the present study support the clinical potency of treatment with acupuncture, pharmacopuncture, and herbal remedies in idiopathic infertile men, especially for the improvement of sperm motility and morphology. Further large-scale randomized controlled trials with elaborate designs should be performed to verify the clinical effect of TKM therapies.

Choe S, et al. Exp Neurobiol. 2018 Feb;27(1):1-15. https://doi.org/10.5607/en.2018.27.1.1

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

Cognitive impairment is an age-dependent chronic disorder that exponentially worsens with age; however, its treatment is mostly symptomatic. Moxibustion is widely accepted in East Asia as a treatment for cognitive impairment. This systematic review aimed to verify the efficacy and underlying mechanism of moxibustion in treating cognitive impairment. Sixteen trials involving 324 animals obtained from MEDLINE (PubMed), EMBASE, the Cochrane library, the Chinese National Knowledge Infrastructure, Wan-Fang, Cqvip, the Korean Studies Information Service System, and the Oriental Medicine Advanced Searching Integrated System met the inclusion criteria. We extracted the results of behavioral tests and immunohistochemical biomarkers from the included articles and evaluated the risk of bias and reporting quality. The moxibustion group showed significantly decreased escape latency, increased crossing times, and prolonged dwelling times in the Morris water maze test. There was a significantly enhanced latency period and reduced error time in the step-down test and nerve behavior score. The effects of moxibustion were found to be mediated by suppression of oxidative stress and apoptosis, modulation of inflammation and Aβ genesis activation of vascular endothelial growth factor, and adjustment of metabolites in the tricarboxylic acid cycle and fatty acid metabolism. Our results demonstrated the therapeutic efficacy of moxibustion on cognitive impairment and suggested the putative mechanism. However, considering the small number of included studies, high bias risk, low reporting quality, and the limitations of animal experimentation, our results need to be confirmed by more detailed studies.