The natural compound rutaecarpine promotes white adipocyte browning through activation of the AMPK-PRDM16 axis.

The prevalence of obesity is increasing globally and is associated with many metabolic disorders, such as type 2 diabetes and cardiovascular diseases. In recent years, a number of studies suggest that promotion of white adipose browning represents a promising strategy to combat obesity and its related metabolic disorders. The aim of this study was to identify compounds that induce adipocyte browning and elucidate their mechanism of action. Among the 500 natural compounds screened, a small molecule named Rutaecarpine, was identified as a positive regulator of adipocyte browning both in vitro and in vivo. KEGG pathway analysis from RNA-seq data suggested that the AMPK signaling pathway was regulated by Rutaecarpine, which was validated by Western blot analysis. Furthermore, inhibition of AMPK signaling mitigated the browning effect of Rutaecaripine. The effect of Rutaecaripine on adipocyte browning was also abolished upon deletion of Prdm16, a downstream target of AMPK pathway. In collusion, Rutaecarpine is a potent chemical agent to induce adipocyte browning and may serve as a potential drug candidate to treat obesity.

[Screening of 10 types of Chinese herbal compounds inhibiting Abeta and their possible related mechanism in vitro].

This study is to screen the Chinese herbal compounds which could inhibit the production of Abeta and investigate the underlying mechanism. Ten types of compounds which have potential value in the treatment of AD were selected as initial screening trial. The cell models which used could overexpress Abeta and beta-secretases or Abeta and gamma-secretases. Extracellular Abeta was determined by ELISA after the cell models treated with different concentrations of compounds (0.5-100 micromol x L(-1)), separately. Then the compounds were selected which could inhibit extracellular Abeta and their best concentration ranges were decided, too. Furthermore, the cell viability and apoptosis rate, the level of intracellular Abeta, beta and gamma-secretases were determined after the cell models treated with different concentrations of selected compounds. The results showed that 4 of the 10 compounds could reduce the level of extracellular Abeta; they were cryptotanshinone, astragalosides, gastrodin and paeoniflorin, and their best concentration ranges were 0.5-5.0, 0.5-5.0, 5.0-50, 1.0-25 micromol x L(-1), respectively. Further study indicated that the 4 selected compounds were nontoxic to the cellular models and lowering intracellular Abeta were more effective compared with extracellular; of which astragalosides and gastrodin showed dose-dependent inhibition to the activities of beta and gamma-secretases, with the maximum inhibiting rates of 78.2% and 80.3%, respectively. In conclusion, cryptotanshinone, astragalosides, gastrodin and paeoniflorin could inhibit the expression and secretion of Abeta, and the underlying inhibiting mechanism of astragalosides and gastrodin were related with the reduction of the beta and gamma-secretase activities, respectively.

Two new lignans from Celastrus flagellaris Rupr.

Two new lignans (R-biar)-12-angeloyloxy-6,7,8,9-tetrahydro-1,2,3,13,14-pentamethoxy-7,8-dimethyl-7-dibenzo[a,c]cyclooctenol (1) and (R-biar)-12-benzoyloxy-6,7,8,9-tetrahydro-1,2,3,13,14-pentamethoxy-7,8-dimethyl-7-dibenzo[a,c]cyclooctenol (2) were isolated from the stems of Celastrus flagellaris Rupr. Their structures were elucidated on the basis of spectroscopic methods including HR-EI-MS, 1D and 2D NMR, HMQC, NOESY, and CD.

Hydroxysafflor yellow A protects against chronic carbon tetrachloride-induced liver fibrosis.

Hydroxysafflor yellow A (HSYA) was isolated from the dried flower of Carthamus tinctorius L. which was extensively used in traditional Chinese medicine to treat cirrhosis. However, the potential protective effect of HSYA in liver fibrosis is still unknown. In the present study, we investigated the effects of HSYA in rats with carbon tetrachloride (CCl4)-induced liver fibrosis. Sprague-Dawley (SD) rats were subjected to biweekly CCl4 injections over 12 weeks, while controls were given isovolumetric injections of olive oil. HSYA was given in a daily dose of 5 mg/kg by means of intraperitoneal concurrent with CCl4. Hepatic fibrosis was quantified by digital analysis of Masson's trichrome stained slides and hydroxyproline content. mRNA expression was quantified by real-time polymerase chain reaction (PCR), and protein was quantified by western blot or enzyme-linked immunosorbent assay (ELISA). CCl4 treatment induced micronodular liver fibrosis with a pronounced deposition of collagen fibers. HSYA significantly reduced liver fibrosis. HSYA down regulates α-smooth muscle actin (SMA), collagen α type I, matrix metalloproteinases (MMP)-9, and tissue inhibitors of metalloproteinases (TIMP)-1 gene expression. This was accompanied by a decreased expression of transforming growth factor (TGF)-ß1 and phosphorylation of Smad4. These results indicate that HSYA might be a promising antifibrotic agent in chronic liver disease.

A low molecular weight polysaccharide isolated from Agaricus blazei Murill (LMPAB) exhibits its anti-metastatic effect by down-regulating metalloproteinase-9 and up-regulating Nm23-H1.

The components of Agaricus blazei Murill (AbM) have been shown to possess antitumor potentials. Herein, we attempted to explore the anti-metastatic effect and underlying mechanism of a low molecular weight polysaccharide isolated from AbM (LMPAB). Matrigel invasion assay was applied to evaluate the effect of LMPAB on migration of BEL-7402 hepatic cancer cells in vitro. In vivo, the anti-metastatic effect of LMPAB was investigated in mouse B16 melanoma and a double-grafted SW180 tumor models. mRNA and protein levels of metalloproteinase-9 (MMP-9) or nm23-H1 upon LMPAB treatment were detected by real-time PCR and immunohistochemistry assays. LMPAB significantly reduced the invasion of BEL-7402 cells. In vivo, LMPAB was revealed to decrease lung metastatic foci in mouse B16 melanoma model. In the double-grafted SW180 mouse tumor model, we further demonstrated that intratumoral treatment of LMPAB inhibited the growth of tumor on treated side but also suppresses the regression of metastatic tumors on the non-treated side. Moreover, LMPAB reduced MMP-9 but enhanced nm23-H1 mRNA and protein expression. LMPAB displays anti-metastatic activities, indicating the potential of its clinical application for the prevention and treatment of cancer metastasis. Its anti-metastatic effect may relate to the modulation on MMP-9 and nm23-H1.

A novel compound isolated from the peels of Citrus changshan-huyou.

Five compounds, huyouyisu (1), vomifoliol (2), isoferulic acid (3), 1,2,3-trihydroxyphenol (4) and p-hydroxy-phenol (5), were isolated from the peels of Citrus changshan-huyou Y. B. Chang for the first time by utilizing repeated column chromatography on silica gel. Among them, huyouyisu (1) is a new compound. The structure was elucidated by using 1D and 2D spectra.

[Experimental studies on compound Duzhong Jiangya prescription by semi-bionic extraction].

OBJECTIVE: Optimize the technic condition of Duzhong Jiangya prescription with Semi-bionic Extraction. METHOD: Using homogeneous design, under the same materials granularity, decoction temperature, consumption of water, filtration, concentration, and taking aucubin, hydrochloric acid stachydrine, maloicacid, baicalin, ethanol extract, dry extract as the indexes, the results were comprehensive considered to optimize the semi-bionic extraction condtions. RESULT: The optimized SBE extraction conditions are the following: pH values of the water for the thrice extraction is 5.845 3, 7.496 1, 8.011 7, and the total extraction time is 3.418 0 h. CONCLUSION: Considering the fact of manufacture, the SBE extraction conditions are the following: pH values of the water for the thrice extraction is 6.0, 7.5, 8.0, and the thrice extraction time is 1.5, 1.0, 1.0 h.

[Study on correlativity of different syndrome types with acupoint resistance in the patient of epigastralgia].

OBJECTIVE: To study on correlativity of different syndrome types with acupoint resistance in the patient of epigastric pain. METHODS: Changes of electric resistance of acupoints in 60 cases of epigastric pain with different syndrome types were detected by TZ-01 model acupoint resistance determination instrument, and the correlativity was analyzed. RESULTS: Imbalance of resistance occurred at special acupoints of the spleen and stomach channels in all of the 60 patients of epigastric pain. The imbalance of resistance at Zusanli (ST 36) was the most obvious, and the response of the imbalance of resistance of acupoints was different among different syndrome types. CONCLUSION: There is correlativity of different syndrome types with changes of acupoint resistance in the patient of epigastric pain.

[Studies on chemical constituents in the peels of Citrus changshan-huyou (I)].

OBJECTIVE: To reveal the pharmacological activities of the components for their further utilization and development by studying the chemical constituents of Citrus changshan-huyou. METHOD: The structures were determined by repeated silica gel chromatographic separation and spectral analysis. RESULT: Five compounds were obtained, and identified as 3-oxo friedelin (I), limonin (II), beta-sitosterol (III), 8-(2',3'-dihydroxy-4'-methylbutane)-7-methoxycoumarin (IV), sucrose (V). CONCLUSION: The five compounds were obtained from this plant for the first time.