Integrated UHPLC-QE/MS, transcriptomics and network pharmacology reveal the mechanisms via which Liang-Yan-Yi-Zhen-San promotes the browning of white adipose tissue.

We have previously shown that Liang-Yan-Yi-Zhen-San (LYYZS), an ancient Chinese herbal formula, can promote the browning of white adipose tissue. In this study, we sought to determine which active ingredients of LYYZS mediated its effects on the browning of white adipose tissue. Employing ultra-high performance liquid chromatography-Q-Exactive HF mass spectrometry, a total of 52 LYYZS ingredients were identified. On this basis, 1,560 ingredient-related targets of LYYZS were screened using the HERB databases. Meanwhile, RNA sequencing analysis of the inguinal white adipose tissue of mice produced a total of 3148 genes that were significantly differentially expressed following LYYZS treatment and differentially expressed genes regarded as browning-related targets. Through the network pharmacological analysis, a total of 136 intersection targets were obtained and an ingredient-target-pathway network was established. According to network pharmacology analysis, 10 ingredients containing trans-cinnamaldehyde, genistein, daidzein, calycosin, arginine, coumarin, oleic acid, isoleucine, palmitic acid and tyrosine were regarded as active ingredients of browning of white adipose tissue. Integrated evaluation using chemical analysis, transcriptomics and network pharmacology provides an efficient strategy for discovering the active ingredients involved in how LYYZS promotes the browning of white adipose tissue.

Atractylenolide III from Atractylodes macrocephala Koidz promotes the activation of brown and white adipose tissue through SIRT1/PGC-1α signaling pathway.

BACKGROUND: Hypothermia is a complex pathophysiological response that can be life-threatening in low-temperature environment because of impaired thermoregulation. However, there is currently no clinically effective drugs that can prevent or treat this disease. Brown adipose tissue (BAT) activation or browning of white adipose tissue (WAT) is a promising therapeutic strategy to prevent or treat hypothermia. Atractylodes macrocephala Koidz extract (AE) and its active compound Atractylenolide III (AIII) has been reported to regulate glycolipid metabolism, which might be relevant to BAT activation. However, the thermogenic effect and mechanism of AE and AIII on adipose tissues have not been explored yet. Therefore, this study firstly investigated the role of AE and AIII on hypothermia by promoting heat production of BAT and WAT. PURPOSE: To explore the anti-cold effect of AE and AIII in cold exposure model and explore their biological function and mechanism underlying thermogenesis. METHODS: The effect of thermogenesis and anti-hypothermia of AE and AIII on C57BL/6J mice were evaluated with several experiment in cold environment, such as toxicity test, cold exposure test, metabolism estimation, histology and immunohistochemistry, and protein expression. Additionally, BAT, inguinal WAT (iWAT) and brown adipocytes were utilized to explore the mechanism of AE and AIII on thermogenesis in vivo and in vitro. Finally, SIRT1 agonist and inhibitor in brown adipocytes to verify that AIII activated BAT through SIRT1/PGC-1α pathway. RESULTS: Both AE and AⅢ could significantly maintain the core body temperature and body surface temperature of mice during cold exposure. Besides, AE and AⅢ could significantly improve the capacity of total antioxidant and glucose, lipid metabolism of mice. In addition, AE and AIII reduced mitochondrial membrane potential and ATP content both in BAT and brown adipocytes, and decreased the size of lipid droplets. Moreover, AE and AⅢ promoted the expression of proteins related to heat production in BAT and iWAT. And AIII might activate BAT via SIRT1/PGC-1α pathway. CONCLUSION: AE and AⅢ were potential candidate drugs that treated hypothermia by improving the heat production capacity of the mice. Mechanistically, they may activate SIRT1/PGC-1α pathway, thus enhancing the function of BAT, and promoting the browning of iWAT, to act as anti-hypothermia candidate medicine.

[Establishment of spectrum-effect relationship network model of qizhiweitong granules promoting gastrointestinal motility].

OBJECTIVE: To establish the spectrum-effect relationship network model of Qizhiweitong granules promoting gastrointestinal motility for providing scientific basis for its quality control and efficacy evaluation. METHODS: The Latin hypercube sampling was used to establish full-time multi-wavelength fusion fingerprints of different compatibility groups of Qizhiweitong granules. At the same time, the appreciation rate, the contents of cGMP and NO in small intestine smooth muscle cells after administrated drugs were determined. Then the spectrum-effect relationship of different compatibility groups were correlated, and the network model was established with gray correlation method and BP neural network. RESULTS: 20 compounds with correlation index more than 0.9 were found from 36 constituents in Qizhiweitong granules. The spectrum-effect relationship network model of Qizhiweitong granules promoting gastrointestinal motility was successfully established. And through this model to forecast the result of the test, the absolute value of the relative error was less than 6.83%. CONCLUSION: In this study, a spectrum-effect relationship network model of Qizhiweitong granules promoting gastrointestinal motility is established successfully, which provides a new method for its reasonable quality control and efficacy evaluation, lays the experiment basis for component-effect study, and provides reference for other TCM's study.

[Immediately effects of inhaled aerosolised iloprost in adult patients with severe pulmonary hypertension secondary to congenital heart diseases].

OBJECTIVE: To investigate the immediately effects of inhaled aerosolized iloprost in adult patients with severe pulmonary arterial hypertension (PAH) secondary to congenital heart diseases (CHD). METHODS: Adult patients with severe PAH secondary to CHD (n = 165) were included in this study. Right heart catheterization was performed, Pulmonary and systemic blood flow, the oxygen consumption VO(2) (ml/min) were calculated using Fick's principle. Pulmonary vascular resistances (PVR) were calculated with standard formulas and indexed to body surface area. Hemodynamic parameters were measured before and after iloprost inhalation (20 µg). RESULTS: Post iloprost inhalation, heart rate, mean aortic pressure, pulmonary systolic pressure to aortic systolic pressure ratio all remained un changed (P > 0.05), while pulmonary artery pressure (PAP) were significantly reduced and Qp significantly increased from (7.2 ± 4.8) L/min to (9.9 ± 7.2) L/min (P < 0.01), PVR was also significantly reduced from (13.4 ± 8.7) Wood units to (9.5 ± 6.6) Wood units (P < 0.01), and left-to-right shunt volume increased from (3.2 ± 4.4) L/min to (5.5 ± 7.0) L/min (P < 0.01) and right-to-left shunt volume decreased from (1.0 ± 1.0) L/min to (0.7 ± 0.7) L/min (P < 0.01). Subgroup analysis showed that adult patients with patent ductus arteriosus and/or ventricular septal defects are more likely to develop severe pulmonary arterial hypertension or Eisenmenger syndrome than patients with atrial septal defects. CONCLUSIONS: Inhaled Aerosolised iloprost use is effective and safe for adult patients with severe pulmonary arterial hypertension secondary to congenital heart diseases.

[The trend of cancer mortality from 1988 to 2005 in Kaifeng county, China].

OBJECTIVE: To investigate the time trends of cancer mortality among residents in Kaifeng county, Henan province. METHODS: Data on cancer mortality from the vital registration system in Kaifeng county from 1988 to 2005 was analyzed. A total of 9543 death records (5974 males and 3567 females) due to malignant tumors were studied. A two-year-period age-specified standardized mortality rates were directly adjusted by the world standard population, and the annual percentage change (APC) of mortality were estimated by a linear logarithm regression. RESULTS: The crude cancer death rate for male was 95.09/100,000 and its age-standardized death rate was 117.41/100,000. While, the crude cancer death rate for female was 59.13/100,000 and the age-standardized death rate was 57.15/100,000. There was a significant growth tread for lung cancer (APC: 6.54%), liver cancer (5.07%) in males and breast cancer (7.04%) in females in the groups aged over 18. On the contrary, the decreasing treads for esophageal cancer in both of sexes (-7.09%, -13.53%) were also observed in this study. Meanwhile, there was no other significant changes in the trend, either in the tumor sites or mortality, was observed. CONCLUSION: In the past two decades, there has been a significant increasing trend for cancer mortality in Kaifeng county, of Henan Province. Hence, it is necessary to enhance epidemiological survey to identify risk factors at the earlier stages.