Hyperoside prevents high-fat diet-induced obesity by increasing white fat browning and lipophagy via CDK6-TFEB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Hypericum perforatum L. (genus Hypericum, family Hypericaceae) is a flowering plant native to Europe, North Africa and Asia, which can be used in the treatment of psychiatric disorder, cardiothoracic depression and diabetes. Crataegus pinnatifida Bunge (genus Crataegus pinnatifida Bunge, family Rosaceae) was another traditional Chinese medicine for treating hyperlipidemia. Hyperoside (Hype), a major flavonoid glycoside component of Hypericum perforatum L. and Crataegus pinnatifida Bunge, possesses multiple physiological activities, such as anti-inflammatory and antioxidant effects. However, the role of Hype on obesity and related metabolic diseases still needs to be further investigated. AIM OF THE STUDY: We explored the effect of Hype on high-fat diet (HFD)-induced obesity and its metabolic regulation on white fat tissues. MATERIALS AND METHODS: In vivo four-week-old male C57BL/6J mice were randomly assigned to vehicle (0.5% methycellulose) and Hype (80 mg/kg/day by gavage) group under a normal chow diet (NCD) or HFD for 8 weeks. In vitro, 3T3-L1 preadipocyte cell line and primary stromal vascular fraction (SVF) cells from inguinal white adipose tissue (iWAT) of mice were used to investigate the molecular mechanisms of Hype regulation on adipocyte energy metabolism. RESULTS: Hype treatment in vivo promotes UCP1-dependent white to beige fat transition, increases glucose and lipid metabolism, and resists HFD-induced obesity. Meanwhile, Hype induces lipophagy, a specific autophagy that facilitates the breakdown of lipid droplets, and blocking autophagy partially reduces UCP1 expression. Mechanistically, Hype inhibited CDK6, leading to the increased nuclear translocation of TFEB, while overexpression of CDK6 partially reversed the enhancement of UCP1 by Hype. CONCLUSIONS: Hype protects mice from HFD-induced obesity by increasing energy expenditure of white fat tissue via CDK6-TFEB pathway.

[Overview of research and development of polypeptide drugs and traditional Chinese medicine-peptides].

Peptide is a compound consisting of 2-50 amino acids, which is intermediate between small molecule and protein. It is characterized by a variety of biological activities, easy absorption, strong specific targeting, and few side effects and has become one of the hotspots in biomedical research in recent years. Chinese medicine contains a large number of peptides. The traditional processing methods such as decocting and boiling can effectively boost peptides to exert their due biological activities. At present, however, the research on Chinese medicinal components in laboratory generally employs high-concentration alcohol extraction method, which may cause the peptides to be ignored in many natural Chinese medicines. Substantial studies have revealed that the peptides in Chinese medicine are important material basis responsible for the traditional efficacy. Based on years of research and literature retrieval, this study put forward the concept of "traditional Chinese medicine(TCM)-peptides", referring to the components consisting of two or more amino acids with molecular weight between small molecules and proteins that can express the efficacy of Chinese medicine. Furthermore, this study also summarized the extraction and separation of TCM-peptides, and structure determination methods and routes, predicted the research prospect of modern research methods of TCM-peptides based on "holistic view" and big data. The artificial intelligence prediction was combined with high-throughput screening technology to improve the discovery efficiency and accuracy of TCM-peptides, and holographic images between TCM-peptides and biological targets were established to provide references for the innovative drug design and related health product development of TCM-peptides based on TCM theories.

Effects of Fish Oil Supplementation on Cardiometabolic Risk Factors in Overweight or Obese Children and Adolescents: A Meta-Analysis of Randomized Controlled Trials.

Background: Influences of fish oil supplementation on body weight and other cardiometabolic factors in overweight or obese children and adolescents remain not fully understood. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the role of fish oil for these children. Methods: Relevant studies were obtained by search of PubMed, Embase, and Cochrane's Library databases. A random-effect model, which incorporates the potential heterogeneity of the included studies, was used to pool the results. Results: Twelve RCTs including 1,028 overweight or obese children and adolescents were included. Compared to control, fish oil supplementation significantly reduced body mass index [BMI, mean difference (MD): -0.96 kg/m2, 95% confidence interval (CI): -1.69 to -0.23, P = 0.01] but did not significantly reduce body weight or waist circumference (P = 0.68 and 0.76). Moreover, fish oil supplementation significantly reduced serum triglyceride (MD: -0.24 mmol/L, 95% CI: -0.40 to -0.08, P = 0.004) but did not significantly affect serum total cholesterol and high-density or low-density lipoprotein cholesterol (P = 0.83, 0.42, and 0.31, respectively). Additionally, fish oil supplementation significantly lowered systolic blood pressure (SBP, MD: -2.46 mmHg, 95% CI: -4.93 to -0.01, P = 0.04) but did not significantly change diastolic blood pressure (P = 0.22). Supplementation with fish oil did not significantly affect fasting plasma glucose (P = 0.33). Conclusions: In overweight or obese children and adolescents, supplementation with fish oil could reduce BMI, decrease serum triglyceride, and lower SBP, while serum cholesterol and fasting glucose may not be significantly affected.

Chloroform extract from Sophora Tonkinensis Gagnep. inhibit proliferation, migration, invasion and promote apoptosis of nasopharyngeal carcinoma cells by silencing the PI3K/AKT/mTOR signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Sophora Tonkinensis Gagnep. (STG) has been used as a folk medicine for the treatment of different cancers, especially for nasopharyngeal carcinoma, cervical cancer, liver cancer, stomach cancer, lung cancer and leukemia in China. However, the main chemical composition and anticancer mechanism of chloroform extract of STG (CESTG) were still not very clear. AIM OF STUDY: This work was carried out to investigate the anticancer effects and mechanisms of chloroform extract of STG (CESTG) on NPC. METHODS: Cultured NPC CNE1, CNE2 and Np69 cells were treated with CESTG. Cells were subjected to cell proliferation, colony-forming, migration and invasion assays. Cell cycle and apoptosis were measured by flow cytometry. Western blotting and morphological analysis were also performed. Tumor xenografts and drug treatments were made in BALB/c nude mice. The main compounds of CESTG was separated by HPLC. RESULTS: CESTG inhibited cell viability, clonal growth and induced cell apoptosis in a dose-dependent manner by silencing the PI3K/AKT/mTOR signaling pathway, which is associated with upregulation of cleaved PARP, caspase 3/7/8/9, cleaved caspase 3/7/8/9, Bax and downregulation of PARP, P-PI3K, PI3K, P-AKT, AKT, P-mTOR, mTOR and Bcl-2. In addition, CESTG arrested cell cycle in the G1/S phase, correlating with decreased levels of cyclin D1/B1, CDK 4 and 6. CESTG decreased cell migration and invasion which correlated with decreased expression of ß-catenin, vimentin and snail. CESTG significantly inhibited the tumor growth without toxicity. CONCLUSION: The results presented here suggest that CESTG could be use as a potential source of NPC therapeutic drug.

Jieduquyuziyin Prescription-Treated Rat Serum Suppresses Activation of Peritoneal Macrophages in MRL/Lpr Lupus Mice by Inhibiting IRAK1 Signaling Pathway.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, and Jieduquyuziyin prescription (JP) is a traditional Chinese medicine (TCM) formula that has been testified to be effective for SLE treatment as an approved hospital prescription for many years in China. However, its mechanism of action in the treatment of this disease is largely unknown. The purpose of this study was to determine whether JP-treated rat serum can inhibit the activation of peritoneal macrophages in MRL/lpr mice by downregulating the IRAK1 signaling pathway, thereby achieving the effect of improving SLE. The JP-treated rat serum was prepared, and the peritoneal macrophages of MRL/lpr lupus mice were isolated in vitro, and the effect of JP on cell viability was detected by the CCK8 method. After LPS induction and shRNA lentiviral transfection, the effect of JP on the expression of IRAK1 in cells was detected by immunofluorescence staining. The content of TNF-α and IL-6 in the cell supernatant was determined by ELISA. The expression of IRAK1, NF-κB, TNF-α, and IL-6 mRNA was detected by RT-PCR, and the expression levels of IRAK1, p-IRAK1, TRAF6, IKBα, p-IKBα, IKK + IKK, NF-κB, and p-NF-κB proteins was detected by western blot method. We investigated the role of JP in peritoneal macrophages of the MRL/lpr mouse and identified the possible mechanisms of action. The results showed that JP could reduce the phosphorylation of IRAK1 and its downstream proteins induced by LPS and inhibit the expression of inflammatory cytokines, including TNF-α and IL-6. In addition, after the transfection of cells with shRNA lentiviral, the results of JP tended to be consistent. In conclusion, JP may inhibit the activation of peritoneal macrophages in MRL/lpr mice by downregulating the IRAK1-NF-κB signaling pathway, and IRAK1 may be a potential target for JP treatment of SLE.

Effect of Jieduquyuziyin prescription-treated rat serum on MeCP2 gene expression in Jurkat T cells.

How genomic DNA methylation and methyl CpG-binding protein 2 (MeCP2) gene expression affect the pathogenesis of systemic lupus erythematosus (SLE) remains poorly understood. Traditional Chinese medicine has a unique effect in the treatment of SLE patients. This study aimed to investigate the effect of Jieduquyuziyin prescription (JP)-treated rat serum on the gene expression of MeCP2 in Jurkat T cells and its role in the pathogenesis of SLE. Jurkat T cells were harvested, and drug-containing serum was prepared. The ferulic acid and paeoniflorin content in the drug-containing serum were determined by liquid chromatography-mass spectrometry (LC-MS/MS). 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assays were used to screen the optimal concentration of drug-containing serum. The DNA methylation level in Jurkat T cells was detected with a Methylamp™ Total DNA Methylation Kit. The methylation status of the MeCP2 promoter region was detected using bisulfite modification and methylation-specific PCR (MSP). Real-time PCR was used to measure MeCP2 mRNA expression. Western blotting and flow cytometry were done to detect MeCP2 protein expression in Jurkat cell nuclei. Paeoniflorin and ferulic acid were detected in the drug-containing serum of JP-treated rats. The results showed that cell growth was affected in the high serum-containing drug group. The experimental results showed that JP and prednisone acetate increased the level of genomic DNA methylation and MeCP2 gene promoter region methylation in Jurkat cells. MeCP2 mRNA and protein levels were also increased in the JP and prednisone acetate groups. Furthermore, flow cytometry revealed that the expression of MeCP2 protein in Jurkat T cell nuclei was higher in the drug group than the blank control group, and these results were consistent with the western blot analysis results. Our study found that there is a negative correlation between drug-containing serum and cell survival rate. JP upregulated the levels of DNA methylation, MeCP2 mRNA and protein as effectively as prednisone acetate and thus may activate the MeCP2 gene by increasing the methylation level, thereby inhibiting the pathogenesis of SLE. Therefore, JP may potentially be used to treat SLE patients. The Jurkat T lymphocyte in vitro experiments provided a foundation to study the effects of JP on the lupus mouse CD4+ T cell methylation mechanism and to further explore the pathogenesis of SLE.

Paeoniflorin inhibits activation of the IRAK1-NF-κB signaling pathway in peritoneal macrophages from lupus-prone MRL/lpr mice.

Systemic lupus erythematosus (SLE) is a chronic and multisystemic autoimmune disease. Interleukin-1 receptor-associated kinase 1 (IRAK1) is associated with the susceptibility of SLE in humans and paeoniflorin has recently been reported to exhibit immunosuppressive properties. The aim of this study was to determine the effect of paeoniflorin on lipopolysaccharide (LPS)-triggered macrophage activation and and its role in LPS-induced IRAK1-nuclear factor κB (NF-κB) signaling pathways. Peritoneal macrophages from lupus-prone MRL/lpr mice and ICR mice were isolated, prepared and cultured. Cells were treated with LPS alone or LPS with paeoniflorin, and macrophage proliferation was analyzed using the CCK8 assay. The expression of IRAK1 in cells was analyzed by immunofluorescence staining. The level of gene expression of IRAK1, NF-κB, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) was measured by RT-PCR, and TNF-α, IL-6 levels in the cell supernatant were determined by ELISA. The protein expression of IRAK1 and downstream molecules tumor necrosis factor receptor-associated factor 6 (TRAF6), inhibitor of nuclear factor kappa-B kinase (IKK), NF-kappa-B inhibitor alpha (IKBα), and NF-κB was detected by Western-blot analysis. Paeoniflorin was found to decrease the phosphorylation of IRAK1 and its downstream proteins induced by LPS and inhibit the expression of TNF-α and IL-6. Taken together, the data obtained indicate that paeoniflorin inhibits LPS-induced cell activation by inhibiting the IRAK1-NF-κB pathway in MRL/lpr mouse macrophages. Therefore, paeoniflorin may be a potential therapy for SLE.

Adjuvant Treatment with Yupingfeng Formula for Recurrent Respiratory Tract Infections in Children: A Meta-analysis of Randomized Controlled Trials.

This meta-analysis aimed to evaluate the immunomodulating function of Yupingfeng Formula (YPFF) in children with recurrent respiratory tract infections (RRTIs). The PubMed, EMBASE, Cochrane Library, CNKI and WanFang databases were searched for randomized controlled trials comparing with and without YPFF for RRTIs in children. Twelve trials with 1236 patients were identified. Adjuvant treatment with YPFF significantly increased serum levels of IgA (weighted mean difference [WMD] 0.33 mg/mL; 95% confidence interval [CI] 0.20 to 0.45), IgG (WMD 1.36 mg/mL; 95% CI 1.06 to 1.65), IgM (WMD 0.16 mg/mL; 95% CI 0.02 to 0.31), and CD3(+) T-lymphocytes (WMD 10.16%; 95% CI 4.62 to 15.69) but not CD4(+) T-lymphocytes (WMD 3.16%; 95% CI -0.27 to 6.59) and CD8(+) T-lymphocytes (WMD -0.84%; 95% CI -2.50 to 0.81). YPFF also reduced the frequency of RRTIs (WMD -3.80 times; 95% CI -4.86 to -2.74) and increased total effective rates of symptom improvement (risk ratio: 1.44; 95% CI 1.19 to 1.75). Adjuvant treatment with YPFF could improve total clinical effective rate and decrease the frequency of respiratory tract infections in children with RRTIs. The beneficial effects of YPFF may be correlated to its immunomodulating action. More well-designed trials with larger sample sizes are needed to evaluate its efficacy and safety. Copyright © 2016 John Wiley & Sons, Ltd.

The protective effects of Ribes diacanthum Pall on cisplatin-induced nephrotoxicity in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Ribes diacanthum Pall. (Saxifragaceae), a Mongolian folk medicinal plant, was used to treat urinary system diseases. The present work aims to investigate the protective effects of Ribes diacanthum Pall (RDP) against cisplatin-induced nephrotoxicity. METHODS: The renal injury was modeled by intraperitoneal injection of cisplatin for 5 consecutive days (5 mg/kg). Nephroprotection of RDP was investigated by oral administration of RDP aqueous extract at a daily dose of 40 mg/kg for 14 consecutive days, starting 7 days prior to cisplatin administration. RESULTS: We demonstrated that pretreatment with RDP aqueous extract protected the mice from death induced by cisplatin administration. RDP treatment also significantly reduced blood urea nitrogen (BUN) and serum creatinine (Cr) levels observed in cisplatin-administrated mice. Histopathological analysis demonstrated that RDP administration protected cisplatin-induced renal tubular cell apoptosis. Further western blotting analysis revealed that RDP significantly reversed cisplatin-increased expression levels of cleaved-Caspase-3, Bax and cisplatin-decreased expression level of Bcl-2 in renal tissue. Finally, RDP markedly enhanced enzyme activities of reduced superoxide dismutase (SOD), Heme oxygenase 1 (HO-1) and catalase (CAT), suppressed lipid peroxidation as well as reactive oxygen species (ROS) production. CONCLUSION: We concluded that RDP displayed nephroprotective effects against cisplatin-induced renal tubular cell apoptosis, possibly associated with both enhanced antioxidase activity and suppressed ROS generation. Given the major nephrotoxicity of cisplatin cancer chemotherapy, RDP might be a potential candidate for neoadjuvant chemotherapy.

Polydatin protects learning and memory impairments in a rat model of vascular dementia.

Polydatin is one of the most common encountered stilbenes of nature and a key component of the Chinese herb Polygonum cuspidatum. This study is to investigate the effects of polydatin on learning and memory impairments induced by chronic cerebral hypoperfusion in rats, as well as the potential mechanism. Both common carotid arteries and both vertebral arteries occlusion (four-vessel occlusion, 4-VO) induced severe cognitive deficits tested by water maze task, along with oxidative stress in hippocampus. Oral administration of polydatin for 30 days markedly attenuated cognitive deficits compared with the control (p < 0.05). Biochemical determination revealed that polydatin decreased the production of malondialdehyde (MDA) and significantly increased the activities of superoxide dismutase (SOD) and catalase (CAT). Additionally, polydatin effectively alleviated the injuries of cultured neurons induced by oxygen-glucose deprivation (OGD). These results suggest that polydatin exhibit therapeutic potential for vascular dementia, which is most likely related, at least in part, to its anti-oxidant activity and the direct protection of neurons.