[Effect of moxibustion on plaque psoriasis complicated with obesity].

OBJECTIVE: To observe the clinical efficacy of moxibustion combined with coptis chinensis ointment sealing on plaque psoriasis complicated with obesity. METHODS: A total of 52 patients of plaque psoriasis complicated with obesity were randomized into an observation group (26 cases) and a control group (26 cases, 2 cases dropped off). Coptis chinensis ointment sealing was adopted in the control group. On the basis of the treatment in the control group, moxibustion was applied at ashi point (area of local target lesions), Zhongwan (CV 12) and bilateral Zusanli (ST 36), Fenglong (ST 40), Quchi (LI 11), Tianshu (ST 25), Shangjuxu (ST 37) in the observation group. The treatment was given 30 min each time, once a day for 4 weeks in both groups. The psoriasis area and severity index (PASI) score, obesity related indexes (body mass, waist circumference, body mass index [BMI]), triglyceride, cholesterol, uric acid and plasma glucose were compared before and after treatment, and the clinical efficacy was evaluated in the two groups. RESULTS: After treatment, the PASI scores were decreased compared with those before treatment in the two groups (P<0.01), and the PASI score in the observation group was lower than that in the control group (P<0.05); the body mass, waist circumference, BMI, triglyceride, cholesterol, uric acid and plasma glucose were decreased compared with those before treatment in the observation group (P<0.01, P<0.05), the triglyceride and cholesterol in the observation group were lower than those in the control group (P<0.05). The total effective rate was 53.8% (14/26) in the observation group, which was superior to 20.8% (5/24) in the control group (P<0.05). CONCLUSION: Moxibustion combined with coptis chinensis ointment sealing can effectively improve the clinical symptoms in patients of plaque psoriasis complicated with obesity.

A Luminol-Based Self-Illuminating Nanocage as a Reactive Oxygen Species Amplifier to Enhance Deep Tumor Penetration and Synergistic Therapy.

The dense extracellular matrix (ECM) in tumor tissues resists drug diffusion into tumors and leads to a poor prognosis. To address this problem, glucose oxidase (GOx)-modified ferritin loaded with luminol-curcumin was fabricated. Once delivered to the tumor, this luminol-based self-illuminating nanocage could actively convert glucose to reactive oxygen species (ROS) to achieve starvation therapy. Then, excessive ROS were transmitted to luminol, thereby emitting 425 nm blue-violet light. Momentarily, light was further absorbed by curcumin and ROS production was amplified. Abundant ROS helps break down the ECM network to penetrate deep into tumors. In addition, ROS produced after cell internalization can induce apoptosis of tumor cells by decreasing the mitochondrial membrane potential and can promote ferroptosis by consuming reduced glutathione. Effective penetration and multiple pathways inducing tumor cell death contributed to the efficient antitumor effect (tumor inhibition rate of GOx-modified ferritin loaded with luminol-curcumin: 71.73%). This study developed a glucose-driven self-illuminating nanocage for active tumor penetration via ROS-mediated destruction of the ECM and provided the synergetic mechanism of apoptosis and ferroptosis.

Salvianolic Acids for Injection alleviates cerebral ischemia/reperfusion injury by switching M1/M2 phenotypes and inhibiting NLRP3 inflammasome/pyroptosis axis in microglia in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: After cerebral ischemia/reperfusion injury, pro-inflammatory M1 and anti-inflammatory M2 phenotypes of microglia are involved in neuroinflammation, in which activation of NLRP3 inflammasome and subsequent pyroptosis play essential roles. Salvianolic Acids for Injection (SAFI) is Chinese medicine injection which composed of multiple phenolic acids extracted from Radix Salviae Miltiorrhizae, and has been reported to generate neuroprotective effects after cerebral ischemic insult in clinical and animal studies. AIM OF THE STUDY: The present study was designed to investigate whether SAFI exerts neuroprotective effects by switching microglial phenotype and inhibiting NLRP3 inflammasome/pyroptosis axis in microglia. MATERIALS AND METHODS: The middle cerebral artery occlusion/reperfusion (MCAO/R) model in rats and oxygen-glucose deprivation/reoxygenation (OGD/R) model in co-cultured primary neurons and primary microglia were utilized. The neuroprotective effect of SAFI was evaluated through measuring neurological deficit scores, neuropathological changes, inflammatory factors, cell phenotype markers, and related proteins of NLRP3 inflammasome/pyroptosis axis. RESULTS: The results showed that SAFI treatment was able to: (1) produce a significant increase in neurological deficit scores and decrease in infarct volumes, and alleviate histological injury and neuronal apoptosis in cerebral cortex in MCAO/R model; (2) increase neuronal viability and reduce neuronal apoptosis in the OGD model; (3) reshape microglial polarization patterns from M1-like phenotype to M2-like phenotype; (4) inhibit the activation of the NLRP3 inflammasome and the expression of proteins related to NLRP3 inflammasome/pyroptosis axis in vivo and in vitro. CONCLUSION: These findings indicate that SAFI exert neuroprotective effect, probably via reducing neuronal apoptosis, switching microglial phenotype from M1 towards M2, and inhibiting NLRP3 inflammasome/pyroptosis axis in microglia.

Pancreas protective effects of Urolithin A on type 2 diabetic mice induced by high fat and streptozotocin via regulating autophagy and AKT/mTOR signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Urolithin A (UroA), the main intestinal microflora metabolite of ellagic acid of berries, pomegranate,and some other traditional chinese herbals such as emblica officinalis,etc,has been reported to exhibit anti-inflammatory, anti-oxidative, anti-tumor and pro-autophagy effects. AIM OF THE STUDY: This study evaluated the anti-diabetic and pancreas-protective effects of UroA using a mice model of type 2 diabetes and preliminarily explored its effect on autophagy as well as the mechanism involved. MATERIALS AND METHODS: Type 2 diabetes model was induced by high-fat diet (HFD; 60% energy as fat) and low-dose streptozotocin (85 mg/kg) injection. Mice were administered with UroA (50 mg/kg/d) alone or UroA-chloroquine (autophagy inhibitor) combination for 8 weeks. RESULTS: UroA improved symptoms of diabetic mice such as high water intake volume, high urine volume, significantly decreased fasting blood glucose (FBG), after-glucose-loading glucose, glycated hemoglobin (GHb) levels, plasma C-peptide, malondialdehyde (MDA) and interleukin-1 ß level, increased reduced glutathione (GSH), interleukin-10 content, and glucose tolerance. UroA also improved pancreatic function indexes such as HOMA-ß as evidenced by improved pathological and ultrastructural features of the pancreas assessed by light microscopy and transmission electron microscopy (TEM). Accordingly, UroA decreased mitochondrial swelling and myelin-like cytoplasmic inclusions. UroA significantly upregulated the protein levels of microtubule-associated protein 1 light chain 3-II (LC3II) and beclin1, downregulated sequestosome 1 (p62) accompanied by decreased expression of apoptotic protein cleaved caspase3 in pancreas of diabetic mice. In addition, it increased the phosphorylation level of protein kinase B (p-Akt) and mammalian target of rapamycin (p-mTOR). Most of these effects of UroA were reversed by treatment with autophagy inhibitor chloroquine. CONCLUSIONS: Our findings reveal that the pancreas protective effects of UroA against diabetes were partially mediated by its regulation of autophagy and AKT/mTOR signal pathway.

1H Nuclear Magnetic Resonance Based Metabolomics Approach Reveals the Metabolic Mechanism of (-)-5-Hydroxy-equol against Hepatocellular Carcinoma Cells in Vitro.

1H nuclear magnetic resonance (NMR)-based metabolomics can rapidly detect metabolic shift under various stimulus; thus, it facilitated the dissection of the therapeutic mechanisms of compounds. (-)-5-Hydroxy-equol is an isoflavone metabolite that be obtained by microbial biotransformation. In the current work, the effect of (-)-5-hydroxy-equol on hepatocellular carcinoma (HCC) cells and its mechanism have been explored based on 1H NMR-based metabolomics approach. Our results revealed that (-)-5-hydroxy-equol can significantly inhibit the proliferation, migration, and invasion of SMMC-7721 cells and inhibit the proliferation of HepG2 cells. Metabolomics revealed that 17 differential metabolites involving in amino acid metabolism and energy metabolism were significantly changed inside and outside of the cells after treatment of (-)-5-hydroxy-equol. Specifically, (-)-5-hydroxy-equol at a concentration of 30 µM significantly decreased the concentrations of pyruvate, glutamate, and glucose. Because glycometabolism is a crucial feature of cancer-specific metabolism, we further verified enzymes and proteins that are closely relevant to glycometabolism. Our results indicated that (-)-5-hydroxy-equol-modulated glycolysis in HCC through the inhibition of activities of hexokinase, phosphofructokinase, and pyruvate kinase, and the expression of pyruvate kinase M2. This study revealed that metabolomic analysis integrating with further verifications at the biochemical level can facilitate understanding the anti-HCC mechanisms of (-)-5-hydroxy-equol.

Beneficial effects of Fu-Zheng-Qu-Zhuo oral liquid combined with standard integrated therapy in patients with chronic kidney disease (stage 3-4): A randomized placebo-controlled clinical trial.

BACKGROUND: The high worldwide prevalence of chronic kidney disease (CKD) is a critical health problem and the development of more effective therapies is urgently needed. We conducted a randomized, double-blinded, placebo-controlled clinical trial from October 2010 to December 2012 to assess whether Fu-Zheng-Qu-Zhuo oral liquid (FZQZ) has a beneficial effect in preventing CKD progression when added to standard integrated therapies. METHODS: Patients with CKD stage 3 to 4 from 3 hospitals in Beijing, China were enrolled. Patients were randomly assigned to the FZQZ or placebo groups and were treated with standard integrated therapy plus FZQZ or placebo (20 mL each time, 3 times/d) for 12 months. Patients received post-trial follow-up until October 2014. The primary outcome was the estimated glomerular filtration rate (eGFR)-Slope (mL/min per 1.73 m2 per month) during the in-trial time, which was calculated by the eGFR regression curve estimated from each serum creatinine measurement during the in-trial period. Secondary outcomes were changes in 24-h urine protein excretion (24-h UP) and albumin and hemoglobin levels from baseline during the in-trial period. Time to composite endpoint events (initiation of long-term dialysis, doubling of serum creatinine, or CKD-related death during the in-trial and post-trial phases) was assessed as a secondary outcome. RESULTS: A total of 68 patients (43 in the FZQZ group and 25 in the placebo group) completed the in-trial and post-trial phases, with an average follow-up time of 31.6 ±â€Š9.6months. The FZQZ group had amean eGFR-Slope of 0.25 ±â€Š1.44 as compared with -0.72 ±â€Š1.46 (mL/min per 1.73m2 per month) in the placebo group during the in-trial period (P = .003). The FZQZ group showed decreased 24-h UP, with a change from baseline of -0.08 (interquartile range [IQR], -0.33 to 0.01) versus 0.01 (IQR, -0.19 to 0.33) g/24h in the placebo group (P = .049). Decreased risk of composite endpoint events was observed only in the post-trial phase (hazard ratio = 0.42, 95% confidence interval: 0.16-1.11, P = .038). No significant differences in albumin and hemoglobin level changes were observed. CONCLUSION: Adding FZQZ oral liquid to standard integrated therapies may aid in attenuating CKD progression.

Effect of Huanshuai Recipe Oral Liquid ([characters: see text]) on renal dysfunction progression in patients with atherosclerotic renal artery stenosis.

OBJECTIVE: To investigate the effect of Huanshuai Recipe Oral Liquid ([characters: see text], HSR) on retarding the progression of renal dysfunction in patients with atherosclerotic renal artery stenosis (ARAS). METHODS: A total of 52 ARAS patients with the Chinese medicine (CM) syndrome of qi deficiency and blood stasis, phlegm and dampness retention were recruited and randomly assigned into the treatment group (36 cases) and the control group (16 cases). Both groups received a basic treatment (high-quality low-protein diet, blood pressure control, lipid-lowering, correcting the acidosis, etc.). In addition, the treatment group received 20 mL HSR and the control group received placebo, 3 times a day for 6 months. Renal function (serum creatinine, blood urea nitrogen and uric acid) and blood lipids (cholesterol, triglycerides and low density lipoprotein) were examined monthly. The estimated glomerular filtration rate (eGFR) and CM syndrome score were compared between groups. RESULTS: After treatment, compared with the control group, the serum creatinine level, uric acid level and CM syndrome score of the treatment group were significantly decreased (P<0.05 or P<0.01), and the eGFR in the treatment group were significantly increased (P<0.05). CONCLUSION: HSR can effectively improve the renal function and clinical symptoms of ARAS patients.

Hair growth-promoting activity of hot water extract of Thuja orientalis.

BACKGROUND: Thuja orientalis has been traditionally used to treat patients who suffer from baldness and hair loss in East Asia. The present study sought to investigate the hair growth-promoting activity of T. orientalis hot water extract and the underlying mechanism of action. METHODS: After T. orientalis extract was topically applied to the shaved dorsal skin of telogenic C57BL/6 N mice, the histomorphometric analysis was employed to study induction of the hair follicle cycle. To determine the effect of T. orientalis extract on the telogen to anagen transition, the protein expression levels of ß-catenin and Sonic hedgehog (Shh) in hair follicles were determined by immunohistochemistry. RESULTS: We observed that T. orientalis extract promoted hair growth by inducing the anagen phase in telogenic C57BL/6 N mice. Specifically, the histomorphometric analysis data indicates that topical application of T. orientalis extract induced an earlier anagen phase and prolonged the mature anagen phase, in contrast to either the control or 1% minoxidil-treated group. We also observed increases in both the number and size of hair follicles of the T. orientalis extract-treated group. Moreover, the immunohistochemical analysis reveals earlier induction of ß-catenin and Shh proteins in hair follicles of the T. orientalis extract-treated group, compared to the control or 1% minoxidil-treated group. CONCLUSION: These results suggest that T. orientalis extract promotes hair growth by inducing the anagen phase in resting hair follicles and might therefore be a potential hair growth-promoting agent.

The inhibitory activity of atractylenolide Ш, a sesquiterpenoid, on IgE-mediated mast cell activation and passive cutaneous anaphylaxis (PCA).

ETHNOPHARMACOLOGICAL RELEVANCE: AT Ш, a sesquiterpenoid, is the major component of Atractylodes japonica Koidz that has been used as a traditional oriental medicine. AIM OF THE STUDY: We investigated the anti-allergic activity of AT Ш and its mechanism of action. MATERIALS AND METHODS: The released amount of ß-hexosaminidase in mast cells, a key parameter of degranulation, was measured. Anti-allergic potential of AT Ш was evaluated using passive cutaneous anaphylaxis in vivo. The anti-allergic mechanism of AT Ш was investigated by immunoblotting analysis, RT-PCR and measurement of [Ca(2+)]i in mast cells. RESULTS: AT Ш significantly inhibited IgE/Ag-mediated degranulation with an IC(50) value (36 ± 4 µM) in RBL-2H3 cells without affecting cell viability. It also suppressed IgE/Ag-mediated passive cutaneous anaphylaxis (PCA) response with an ED(50) value (65 ± 41 mg/kg) in vivo. AT Ш suppressed the production of interleukin (IL-4) and tumor necrosis factor (TNF)-alpha mRNAs more potent than the Src-family kinase inhibitor PP2 in RBL-2H3 cells at all concentrations. In order to elucidate the anti-allergic mechanisms of AT Ш in mast cells, we examined the activated levels of signaling molecules. AT Ш inhibited the phosphorylation of Lyn, Fyn, Syk, LAT, PLCγ, Gab2, Akt, p38, and JNK kinases expression. IgE/Ag-mediated [Ca(2+)]i elevation was significantly inhibited by AT Ш. CONCLUSIONS: Our study suggests that AT Ш might be used as a therapeutic agent for allergic diseases.

[Active ingredients in rhubarb with anti-proliferative effects on scar fibroblasts].

This study is to explore the active ingredients of traditional Chinese medicine rhubarb with antiproliferative activity on hypertrophic scar fibroblasts (HSF). Rhubarb was extracted with Soxhlet extraction method by different polar solvents. MTS method was used to screen rhubarb solvent extracts (25 microg x mL(-1)) with anti-proliferative activity on HSF, and flow cytometry was used to detect their influences on cell cycle. Then, the active ingredients were analyzed by HPLC. The components with high activity were identified by UPLC-Q/TOF and verified by HE staining. The results showed that the ethyl acetate extract of rhubarb had higher anti-proliferative activity (P < 0.01), increased significantly the proportion of cells in G0/G1 phase (P < 0.01), and reduced the proliferation index (PI) (P < 0.01). The main active ingredients were anthraquinones. The results of confirming experiment showed that emodin, rhein and gallic acid could inhibit cell proliferation in a dose-dependent manner. In conclusion, the ethyl acetate extract of rhubarb showed anti-proliferative activity on HSF, and the anti-proliferative ingredients might be anthraquinones.

[Study on the chemical changes of whole constituents in the preparing process of kansui root].

OBJECTIVE: To study the chemical changes of whole constituents in the preparing process of kansui root in order to uncover the mechanism of detoxication in preparing process. METHODS: The raw and prepared kansui were extracted with water and methanol and analyzed with HPLC respectively. RESULTS: Seven constituents disappeared in the prepared kansui and four new consitituents were produced in the water extracts. The concentration of four other constituents decreased. In the methoanol extract, two constituents disappeared and one constituent produced during preparing process. The concentration of six other constituents increased in the methanol extracts. CONCLUSION: The mechanism of detoxication of kansui root preparing process is may be that the toxic constituents decomposing or water solubility reducing.