Clinical Efficacy of the Chinese Herbal Medicine Shumian Capsule for Insomnia: A Randomized, Double-Blind, Placebo-Controlled Trial.

Purpose: Shumian capsule (SMC) is a patent Chinese herbal medicine that can soothe the liver and relieves depression, quiet the spirit. Here, we aimed to investigate the efficacy of SMC for treating insomnia using both scales and polysomnography (PSG). Patients and Methods: A randomized, double-blind, placebo-controlled trial was performed. Twenty-six insomnia patients randomly received SMC (n = 11) or placebo (n = 15) for four weeks. Pittsburgh Sleep Quality Inventory (PSQI), Insomnia Severity Index (ISI), 9-items Patient Health Questionnaire (PHQ-9), 7-items Generalized Anxiety Disorder (GAD-7), 17-item Hamilton Depression Rating Scale (HAMD-17), and Hamilton Anxiety Rating Scale (HAMA) were applied at the baseline and the 2nd, 4th week after treatment. Treatment Emergent Symptom Scale was used to assess adverse reactions. We used PSG to record and analyze sleep features at baseline and after four weeks. Results: PSQI, ISI, PHQ-9, HAMD-17, and HAMA scores decreased significantly after SMC treatment. Also, the total sleep time, rapid-eye-movement (REM) sleep latency, stage 2 sleep, deep sleep, REM sleep, and sleep efficiency improved significantly after SMC treatment. In the placebo group, the only significant change was the decrease of PHQ-9 at week-2. Furthermore, both SMC and placebo reported no adverse events. Conclusion: SMC could safely improve sleep quality with depression and anxiety remission in insomnia patients.

The phytochemical hyperforin triggers thermogenesis in adipose tissue via a Dlat-AMPK signaling axis to curb obesity.

Stimulation of adipose tissue thermogenesis is regarded as a promising avenue in the treatment of obesity. However, pharmacologic engagement of this process has proven difficult. Using the Connectivity Map (CMap) approach, we identified the phytochemical hyperforin (HPF) as an anti-obesity agent. We found that HPF efficiently promoted thermogenesis by stimulating AMPK and PGC-1α via a Ucp1-dependent pathway. Using LiP-SMap (limited proteolysis-mass spectrometry) combined with a microscale thermophoresis assay and molecular docking analysis, we confirmed dihydrolipoamide S-acetyltransferase (Dlat) as a direct molecular target of HPF. Ablation of Dlat significantly attenuated HPF-mediated adipose tissue browning both in vitro and in vivo. Furthermore, genome-wide association study analysis indicated that a variation in DLAT is significantly associated with obesity in humans. These findings suggest that HPF is a promising lead compound in the pursuit of a pharmacological approach to promote energy expenditure in the treatment of obesity.

Yin Yang 1 protein ameliorates diabetic nephropathy pathology through transcriptional repression of TGFß1.

Transforming growth factor-ß1 (TGFß1) has been identified as a major pathogenic factor underlying the development of diabetic nephropathy (DN). However, the current strategy of antagonizing TGFß1 has failed to demonstrate favorable outcomes in clinical trials. To identify a different therapeutic approach, we designed a mass spectrometry-based DNA-protein interaction screen to find transcriptional repressors that bind to the TGFB1 promoter and identified Yin Yang 1 (YY1) as a potent repressor of TGFB1. YY1 bound directly to TGFB1 promoter regions and repressed TGFB1 transcription in human renal mesangial cells. In mouse models, YY1 was elevated in mesangial cells during early diabetic renal lesions and decreased in later stages, and knockdown of renal YY1 aggravated, whereas overexpression of YY1 attenuated glomerulosclerosis. In addition, although their duration of diabetic course was comparable, patients with higher YY1 expression developed diabetic nephropathy more slowly compared to those who presented with lower YY1 expression. We found that a small molecule, eudesmin, suppressed TGFß1 and other profibrotic factors by increasing YY1 expression in human renal mesangial cells and attenuated diabetic renal lesions in DN mouse models by increasing YY1 expression. These results suggest that YY1 is a potent transcriptional repressor of TGFB1 during the development of DN in diabetic mice and that small molecules targeting YY1 may serve as promising therapies for treating DN.

Effects of matrine and oxymatrine on catalytic activity of cytochrome p450s in rats.

Matrine and oxymatrine are the major bioactive compounds extracted from the root of Sophora flavescens Ait, which have been widely used in traditional Chinese medicines. The objective of the study was to investigate the effects of matrine or oxymatrine on hepatic cytochrome P450 (CYP450) and the underlying molecular mechanisms. Matrine (15, 75 and 150 mg/kg) or oxymatrine (36, 180 and 360 mg/kg) was administered to rats for 14 days and the activities of CYP450 were measured by the quantification of the metabolites from multiple CYP450 probe substrates, using validated liquid chromatography coupled with liquid chromatography-tandem mass spectrometry detection (LC-MS/MS) and high-performance liquid chromatography methods. The mRNA and protein expression levels of CYPs were determined by quantitative real-time reverse-transcription polymerase chain reaction and Western blotting analysis respectively. Interactions between matrine or oxymatrine and human constitutive androstane (CAR), pregnane X receptor were evaluated by means of the reporter gene assay in CV-1 cells. Our study showed that matrine and oxymatrine significantly induced the activity and gene expression of CYP2B1 in a dose-dependent manner; matrine (150 mg/kg) slightly induced the mRNA and protein expression of CYP2E1 and mildly inhibited the mRNA and protein expression of CYP3A1 in rats. Matrine or oxymatrine could activate human CAR and induce the CYP2B reporter construct in CV-1 cells. These results reveal that matrine and oxymatrine can induce the activity and expression of CYP2B1/2 in rats, and the underlying mechanism may be related to the activation of CAR.