Dissection of potential anti-osteoporosis mechanism of isopsoralen - a quality control marker in Psoraleae Fructus - by metabolite profiling and network pharmacology.

RATIONALE: Isopsoralen (ISO), a quality control marker (Q-marker) in Psoraleae Fructus, is proven to present an obvious anti-osteoporosis effect. Until now, the metabolism and anti-osteoporosis mechanisms of ISO have not been fully elucidated, greatly restricting its drug development. METHODS: The metabolites of ISO in rats were profiled by using ultrahigh-performance liquid chromatography coupled with time-of-flight mass spectrometry. The potential anti-osteoporosis mechanism of ISO in vivo was predicted by using network pharmacology. RESULTS: A total of 15 metabolites were characterized in rats after ingestion of ISO (20 mg/kg/day, by gavage), including 2 in plasma, 12 in urine, 6 in feces, 1 in heart, 3 in liver, 1 in spleen, 1 in lung, 3 in kidney, and 2 in brain. The pharmacology network results showed that ISO and its metabolites could regulate AKT1, SRC, NFKB1, EGFR, MAPK3, etc., involved in the prolactin signaling pathway, ErbB signaling pathway, thyroid hormone pathway, and PI3K-Akt signaling pathway. CONCLUSIONS: This is the first time for revealing the in vivo metabolism features and potential anti-osteoporosis mechanism of ISO by metabolite profiling and network pharmacology, providing data for further verification of pharmacological mechanism.

Characterization of metabolic features and potential anti-osteoporosis mechanism of pinoresinol diglucoside using metabolite profiling and network pharmacology.

RATIONALE: Eucommia cortex is the core herb in traditional Chinese medicine preparations for the treatment of osteoporosis. Pinoresinol diglucoside (PDG), the quality control marker and the key pharmacodynamic component in Eucommia cortex, has attracted global attention because of its definite effects on osteoporosis. However, the in vivo metabolic characteristics of PDG and its anti-osteoporotic mechanism are still unclear, restricting its development and application. METHODS: Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to analyze the metabolic characteristics of PDG in rats, and its anti-osteoporosis targets and mechanism were predicted using network pharmacology. RESULTS: A total of 51 metabolites were identified or tentatively characterized in rats after oral administration of PDG (10 mg/kg/day), including 9 in plasma, 28 in urine, 13 in feces, 10 in liver, 4 in heart, 3 in spleen, 11 in kidneys, and 5 in lungs. Furan-ring opening, dimethoxylation, glucuronidation, and sulfation were the main metabolic characteristics of PDG in vivo. The potential mechanism of PDG against osteoporosis was predicted using network pharmacology. PDG and its metabolites could regulate BCL2, MARK3, ALB, and IL6, involving PI3K-Akt signaling pathway, estrogen signaling pathway, and so on. CONCLUSIONS: This study was the first to demonstrate the metabolic characteristics of PDG in vivo and its potential anti-osteoporosis mechanism, providing the data for further pharmacological validation of PDG in the treatment of osteoporosis.

Osthole Activates the Cholinergic Anti-Inflammatory Pathway via α7nAChR Upregulation to Alleviate Inflammatory Responses.

Osthole (also known as Osthol) is the main anti-inflammatory coumarin found in Cnidium monnieri and severs as the exclusive quality-controlled component according the Chinese Pharmacopoeia. However, its underlying anti-inflammatory mechanism remains unknown. In this study, we demonstrated that Osthole treatment significantly inhibited the generation of TNF-α, but not IL-6 in the classical LPS-stimulated RAW264.7 macrophage model. In addition, LPS induced the activation of both MAPK and NF-κB signalling pathways, of which the former was dose-dependently restrained by Osthole via suppressing the phosphorylation of JNK and P38 proteins, while the phosphorylation of IκB and P65 proteins remained unaffected. Interestingly, Osthole dose-dependently up-regulated the expression of the key cholinergic anti-inflammatory pathway regulator α7nAChR, and the TNF-α inhibition effect of Osthole was also significantly alleviated by the treatment of α7nAChR antagonist methylbetaine. These results demonstrate that Osthole may regulate TNF-α by promoting the expression of α7nAChR, thereby activate the vagus nerve-dependent cholinergic anti-inflammatory pathway.

A Timing Estimation Method Based-on Skewness Analysis in Vehicular Wireless Networks.

Vehicle positioning technology has drawn more and more attention in vehicular wireless networks to reduce transportation time and traffic accidents. Nowadays, global navigation satellite systems (GNSS) are widely used in land vehicle positioning, but most of them are lack precision and reliability in situations where their signals are blocked. Positioning systems base-on short range wireless communication are another effective way that can be used in vehicle positioning or vehicle ranging. IEEE 802.11p is a new real-time short range wireless communication standard for vehicles, so a new method is proposed to estimate the time delay or ranges between vehicles based on the IEEE 802.11p standard which includes three main steps: cross-correlation between the received signal and the short preamble, summing up the correlated results in groups, and finding the maximum peak using a dynamic threshold based on the skewness analysis. With the range between each vehicle or road-side infrastructure, the position of neighboring vehicles can be estimated correctly. Simulation results were presented in the International Telecommunications Union (ITU) vehicular multipath channel, which show that the proposed method provides better precision than some well-known timing estimation techniques, especially in low signal to noise ratio (SNR) environments.

A population-based study of acquired bilateral nevus-of-Ota-like macules in Shanghai, China.

Acquired bilateral nevus-of-Ota-like macule (ABNOM) is a common skin dyspigmentation in Asian females. Although its clinical characteristics are well defined, its epidemiology and pathogenesis remain unclear. A large population-based cross-sectional study was conducted to determine the prevalence and risk factors of ABNOM. A total of 8,680 subjects (ages ranging from newborn to 99 years old; 54% female) were selected from urban areas in Shanghai, China, using a multistage sampling method. All participants (response rate=97%) were interviewed and examined for the presence of various pigmentary disorders by board-certified dermatologists. ABNOM was found in 2.5% of the study population (0.5% of males and 4.2% of females), and 90% of cases observed were female. In females, prevalence rose after the age of 15 years and sharply declined after the age of 50 years, with nearly half of the cases observed within ages 45-55 years (prevalence=8.5%). Age, contraceptive use, and sun exposure were independently associated with ABNOM. Women with ABNOM were less likely to have facial nevomelanocytic nevi and seborrheic keratoses. These findings indicate that sex hormone alteration and UV exposure may independently have an important role on the pathogenesis of ABNOM.