Gut Microbiota and Bile Acids Mediate the Clinical Benefits of YH1 in Male Patients with Type 2 Diabetes Mellitus: A Pilot Observational Study.

Our previous clinical trial showed that a novel concentrated herbal extract formula, YH1 (Rhizoma coptidis and Shen-Ling-Bai-Zhu-San), improved blood glucose and lipid control. This pilot observational study investigated whether YH1 affects microbiota, plasma, and fecal bile acid (BA) compositions in ten untreated male patients with type 2 diabetes (T2D), hyperlipidemia, and a body mass index ≥ 23 kg/m2. Stool and plasma samples were collected for microbiome, BA, and biochemical analyses before and after 4 weeks of YH1 therapy. As previous studies found, the glycated albumin, 2-h postprandial glucose, triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels were significantly improved after YH1 treatment. Gut microbiota revealed an increased abundance of the short-chain fatty acid-producing bacteria Anaerostipes and Escherichia/Shigella. Furthermore, YH1 inhibited specific phylotypes of bile salt hydrolase-expressing bacteria, including Parabacteroides, Bifidobacterium, and Bacteroides caccae. Stool tauro-conjugated BA levels increased after YH1 treatment. Plasma total BAs and 7α-hydroxy-4-cholesten-3-one (C4), a BA synthesis indicator, were elevated. The reduced deconjugation of BAs and increased plasma conjugated BAs, especially tauro-conjugated BAs, led to a decreased glyco- to tauro-conjugated BA ratio and reduced unconjugated secondary BAs. These results suggest that YH1 ameliorates T2D and hyperlipidemia by modulating microbiota constituents that alter fecal and plasma BA compositions and promote liver cholesterol-to-BA conversion and glucose homeostasis.

Activation of IGF-1 pathway and suppression of atrophy related genes are involved in Epimedium extract (icariin) promoted C2C12 myotube hypertrophy.

The regenerative effect of Epimedium and its major bioactive flavonoid icariin (ICA) have been documented in traditional medicine, but their effect on sarcopenia has not been evaluated. The aim of this study was to investigate the effects of Epimedium extract (EE) on skeletal muscle as represented by differentiated C2C12 cells. Here we demonstrated that EE and ICA stimulated C2C12 myotube hypertrophy by activating several, including IGF-1 signal pathways. C2C12 myotube hypertrophy was demonstrated by enlarged myotube and increased myosin heavy chains (MyHCs). In similar to IGF-1, EE/ICA activated key components of the IGF-1 signal pathway, including IGF-1 receptor. Pre-treatment with IGF-1 signal pathway specific inhibitors such as picropodophyllin, LY294002, and rapamycin attenuated EE induced myotube hypertrophy and MyHC isoform overexpression. In a different way, EE induced MHyC-S overexpression can be blocked by AMPK, but not by mTOR inhibitor. On the level of transcription, EE suppressed myostatin and MRF4 expression, but did not suppress atrogenes MAFbx and MuRF1 like IGF-1 did. Differential regulation of MyHC isoform and atrogenes is probably due to inequivalent AKT and AMPK phosphorylation induced by EE and IGF-1. These findings suggest that EE/ICA stimulates pathways partially overlapping with IGF-1 signaling pathway to promote myotube hypertrophy.

The efficacy and safety of concentrated herbal extract granules, YH1, as an add-on medication in poorly controlled type 2 diabetes: A randomized, double-blind, placebo-controlled pilot trial.

BACKGROUND: In Asian countries, many patients with type 2 diabetes fail to achieve controlled glycated hemoglobin (HbA1c) levels while taking several classes of oral hypoglycemic agents (OHAs). Traditional Chinese medicine could be an alternative therapeutic option for poorly controlled type 2 diabetes. YH1 is a concentrated Chinese herbal extract formula that combines Rhizoma Coptidis and Shen-Ling-Bai-Zhu-San. This randomized, double-blind, placebo-controlled pilot study evaluated YH1 as an add-on medication for poorly controlled type 2 diabetes. METHODS: Forty-six patients with poorly controlled type 2 diabetes were randomly assigned 1:1 to the YH1 or placebo group. Before the trial, all subjects had received three or more classes of OHAs with HbA1c > 7.0% (53 mmol/mol) and a body mass index ≥ 23 kg/m2. During the 12-week trial, participants continued to take OHAs without any dose or medication changes. The primary endpoint was the percentage change in HbA1c level. Per-protocol analysis was applied to the final evaluation. RESULTS: At week 12, there was an 11.1% reduction in HbA1c from baseline and a 68.9% increase in homeostatic model assessment (HOMA) of ß cell function in the YH1 group, which also exhibited significant reductions in two-hour postprandial glucose (-26.2%), triglycerides (-29.5%), total cholesterol (-21.6%), low-density lipoprotein cholesterol (-17.4%), body weight (-0.5%), and waist circumference (-1.1%). The changes in fasting plasma glucose, HOMA insulin resistance and symptom scores were not significantly different between the YH1 and placebo groups. No serious adverse events occurred during this clinical trial. CONCLUSIONS: This pilot study indicates that YH1 together with OHAs can improve hypoglycemic action and ß-cell function in overweight/obese patients with poorly controlled type 2 diabetes. YH1 is a safe add-on medication for OHAs and has beneficial effects on weight control and lipid metabolism. A larger study population with longer treatment and follow-up periods is required for further verification.

Inhibitory effect of berberine on interleukin-2 secretion from PHA-treated lymphocytic Jurkat cells.

Berberine is an isoquinoline alkaloid isolated from herb plants, such as Cortex phellodendri (Huangbai) and Rhizoma coptidis (Huanglian). Huanglian and Huangbai have been used as "heat-removing" agents. In addition, berberine has been reported to exert anti-inflammatory effect both in vivo and in vitro, where mitogen-activated protein kinase (MAPK) and cyclooxygenase-2 (COX-2) expressions are critically implicated. We herein tested the hypothesis that berberine exerts an anti-inflammatory effect through MAPK and COX-2 signaling pathway in T-cell acute lymphoblastic leukemia (T-ALL). In Jurkat cells, we found that PHA exposure caused elevation on interleukin-2 (IL-2) production in a time-dependent manner. PHA-stimulated reactions were steeply suppressed by berberine, such as IL-2 mRNA expression and protein secretion. However, berberine did not exert any cytotoxic effect at doses of 40 µg/ml. In addition, the possible molecular mechanism of anti-inflammation effect of berberine could be the inhibition of PHA-evoked phosphorylation of p38, since c-Jun N-terminal kinases (JNK) and extracellular signal-regulated kinase (ERK) expressions did not alter. Consistent with above results, berberine inhibition on PHA-induced IL-2 secretion could be reversed by treatment of SB203580, a specific inhibitor of p38-MAPK. Interestingly, upregulation of PHA-induced COX-2 expression was also observed following berberine treatment of Jurkat cells. Furthermore, flow cytometry analysis showed berberine-induced cell cycle arrest at G1 phase after PHA stimulation and decreased percentage of G2/M phase. In conclusion, our study demonstrated that the anti-inflammatory effect of berberine largely potentially results from its ability to attenuate p38 MAPK expression, and does not exclude a positive action of berberine on cell cycle arrest. These results provide an innovative medicine strategy to against or treat T-ALL patients.

A comparison of different definitions of metabolic syndrome for the risks of atherosclerosis and diabetes.

BACKGROUND: The reported outcomes of the metabolic syndrome (MetS), containing atherosclerotic cardiovascular disease and diabetes, vary according to the definitions used. This study was designed to compare the performance of the Adult Treatment Panel III/American Heart Association/National Heart, Lung, and Blood Institute (ATP III/AHA/NHLBI) and International Diabetes Federation (IDF) criteria for the risks of atherosclerosis and diabetes. METHODS: We sifted subjects from a self-paid Health examination program from 1999 to 2015 in this cross-sectional population-based study. On the basis of the ATP III/AHA/NHLBI and IDF criteria, the MetS diagnosis and scores were concluded. A brachial-ankle pulse wave velocity (baPWV) more than or equal to 1400 cm/s indicated more severe arterial stiffness, and a high fasting glucose level more than or equal to 6.99 mmol/L or postprandial glucose level more than or equal to 11.10 mmol/L indicated diabetic-level hyperglycemia. Comparisons of the areas under receiver operating characteristic curves (AUC-ROC) for both MetS scores to correlate with a higher baPWV and diabetic-level hyperglycemia were evaluated. RESULTS: In the 26,735 enrolled subjects with an average age of 55 (± 12) years, 6633 and 7388 (24.8% vs. 27.6%, p < 0.001) were classified as having MetS on the basis of the ATP III/AHA/NHLBI and IDF criteria, respectively. The AUC-ROC for the ATP III/AHA/NHLBI-MetS score were higher than those for the IDF-MetS score (0.685 vs. 0.595 to correlate with a higher baPWV, p < 0.001; 0.791 vs. 0.665 to correlate with diabetic-level hyperglycemia, p < 0.001). CONCLUSIONS: To the best of our knowledge, this is the first study to demonstrate that through a holistic approach, the performance of the ATP III/AHA/NHLBI-MetS score for the risks of atherosclerosis and diabetes was superior to the IDF-MetS score for Asians.

Metabolic syndrome positively correlates with the risks of atherosclerosis and diabetes in a Chinese population.

BACKGROUND: Published studies seldom tested the weight of different waist circumference (WC) cut-off values for the diagnosis of metabolic syndrome (MetS) in predicting clinical outcomes, including cardiovascular disease and diabetes. METHODS: This is a Chinese population-based cross-sectional study screening subjects from a Health Examination Program since 1999 to 2015. The MetS identification and scores were determined either according to the Adult Treatment Panel III/American Heart Association/National Heart, Lung, and Blood Institute (ATP III/AHA/NHLBI)- or Asian-WC cut-off points. The developments of a higher brachial-ankle pulse wave velocity (baPWV), defined as ≥1400 cm/s, and diabetic-level hyperglycemia, defined as a high fasting glucose level ≥6.99 mmol/L or postprandial glucose level ≧11.10 mmol/L, were surveyed by comparing the areas under receiver operating characteristic curves (AUC-ROC) for both MetS scores. RESULTS: According to the ATP III/AHA/NHLBI- vs Asian-MetS criteria, 6633 vs 9133 (24.8% vs 34.2%, p < 0.001) subjects were diagnosed as the MetS among 26,735 study subjects with a mean age of 55 ±â€¯12 years. The stepwise increases in baPWV and prevalence of diabetic-level hyperglycemia were associated with both MetS scores after adjusting for age and sex. Both MetS scores yielded similar results for correlation with a higher baPWV (AUC-ROC = 0.685 for ATP III/AHA/HLBI- vs 0.680 for Asian-MetS, p = 0.271) and diabetic-level hyperglycemia (AUC-ROC = 0.791 for ATP III/AHA/HLBI- vs 0.784 for Asian-MetS, p = 0.546). CONCLUSIONS: In a stepwise manner, both ATP III/AHA/NHLBI- or Asian-MetS scores were strong risk factors for arterial stiffness and diabetes. Through a novel and holistic approach, the performance of the ATP III/AHA/NHLBI-MetS score for the risks of arterial stiffness and diabetes was comparable to the Asian-MetS score among a Chinese population.

Operative strategy for follicular thyroid cancer in risk groups stratified by pTNM staging.

This study determined cancer survival rates and follow-up status at different pTNM stages to stratify risk groups in follicular thyroid carcinoma. Two hundred and fourteen follicular thyroid cancer patients (167 females, 47 males) who underwent surgery and followed-up treatment at a single medical center were enrolled in this retrospective study. Tumors were staged by UICC-TNM criteria (6th edition). Low risk for follicular thyroid cancer was defined as pT1N0M0. (Moderate-risk group) was defined as all other patients in pTNM stage I, and high risk as patients in stages II-IV. After mean follow-up of 9.6+/-0.3 years, 1.6% (2/120), 21.9% (7/32), 5.6% (1/18) and 52.3% (23/44) of patients in pTNM stages I-IV, respectively, died of thyroid cancer. Of 214 follicular thyroid cancer patients, 35 (16.4%), 85 (39.7%) and 94 (43.9%) were defined as low-, moderate- and high-risk groups at the time of surgery. None of the low-risk patients died, and all achieved disease-free status. In the moderate- and high-risk groups, 2.4% (2/85) and 27.7% (26/94) died of thyroid cancer. The moderate- and high-risk groups underwent near-total thyroidectomy and (131)I therapies, and 15 of 107 (14.9%) died of thyroid cancer while 18 (16.8%) had persistent disease at the end of the study period. Multiple regression analysis demonstrated that tumor size, radioactive iodide therapy and post-operative thyroglobulin level significantly differ between the mortality and survival groups. In conclusion, the low-risk follicular thyroid cancer group as defined by pTNM staging had excellent prognosis. Total thyroidectomy and post-operative radioactive iodide therapy are mandatory in moderate- and high-risk groups. Over one-fourth of the follicular thyroid cancer patients in the high-risk group died of thyroid cancer despite aggressive treatment.