Mechanism of Erzhiwan in treating osteoporosis based on molecular docking technology and molecular dynamics simulation.

This experiment was a network pharmacology research based on the theoretical system of traditional Chinese medicine. TCMSP database, PubChem database, RCSB database, and SwissTargetPrediction database were used to study the effective chemical constituents of Ligustri lucidi Fructus and Ecliptae Herba in Erzhiwan, a traditional prescription for nourishing the liver and kidney. Then Genecards database, OMIM database, OMIM Gene Map, and Metascape database were used to study the therapeutic targets of osteoporosis. At last, Cytoscape 3.6.0 software, its built-in Bisogenet and CytoNCA, AutoDockTools-1.5.6 software, PYMOL-2.2.0 software, and Gromacs software, by drawing the relationship diagram between chemical components and disease targets, PPI network of disease, semi-flexible molecular docking technology, evaluation and analysis of enrichment pathway, and molecular dynamics simulation, were used to study the therapeutic mechanism of Erzhiwan on osteoporosis. It is found that the intervention and regulation of Erzhiwan on osteoporosis were mainly realized through multiple targets of active ingredients and multiple pathways, which provided support for the continued development of Erzhiwan.

Effects of Different Chemicals on Sexual Regulation in Persimmon (Diospyros kaki Thunb.) Flowers.

Research on crop sexuality is important for establishing systems for germplasm innovation and cultivating improved varieties. In this study, androecious persimmon trees were treated with various concentrations of ethrel (100, 500, and 1,000 mg/L) and zeatin (1, 5, and 10 mg/L) to investigate the morphological, physiological, and molecular characteristics of persimmon. Ethrel at 1,000 mg/L and zeatin at 10 mg/L both significantly reduced the stamen length and pollen grain diameter in androecious trees. Ethrel treatment also led to reduced stamen development with degenerated cellular contents; zeatin treatment promoted the development of arrested pistils via maintaining relatively normal mitochondrial morphology. Both treatments altered carbohydrate, amino acid, and endogenous phytohormone contents, as well as genes associated with hormone production and floral organ development. Thereafter, we explored the combined effects of four chemicals, including ethrel and zeatin, as well as zebularine and 5-azacytidine, both of which are DNA methylation inhibitors, on androecious persimmon flower development. Morphological comparisons showed that stamen length, pollen viability, and pollen grain diameter were significantly inhibited after combined treatment. Large numbers of genes involving in carbohydrate metabolic, mitogen-activated protein kinase (MAPK) signaling, and ribosome pathways, and metabolites including uridine monophosphate (UMP) and cyclamic acid were identified in response to the treatment, indicating complex regulatory mechanisms. An association analysis of transcriptomic and metabolomic data indicated that ribosomal genes have distinct effects on UMP and cyclamic acid metabolites, explaining how male floral buds of androecious persimmon trees respond to these exogenous chemicals. These findings extend the knowledge concerning sexual differentiation in persimmon; they also provide a theoretical basis for molecular breeding, high-yield cultivation, and quality improvement in persimmon.

Faster Lumbar Spine Bone Loss in Midlife Predicts Subsequent Fracture Independent of Starting Bone Mineral Density.

CONTEXT: Bone mineral density (BMD) decreases rapidly during menopause transition (MT), and continues to decline in postmenopause. OBJECTIVE: This work aims to examine whether faster BMD loss during the combined MT and early postmenopause is associated with incident fracture, independent of starting BMD, before the MT. METHODS: The Study of Women's Health Across the Nation, a longitudinal cohort study, included 451 women, initially premenopausal or early perimenopausal, and those transitioned to postmenopause. Main outcome measures included time to first fracture after early postmenopause. RESULTS: In Cox proportional hazards regression, adjusted for age, body mass index, race/ethnicity, study site, use of vitamin D and calcium supplements, and use of bone-detrimental or -beneficial medications, each SD decrement in lumbar spine (LS) BMD before MT was associated with a 78% increment in fracture hazard (P = .007). Each 1% per year faster decline in LS BMD was related to a 56% greater fracture hazard (P = .04). Rate of LS BMD decline predicted future fracture, independent of starting BMD. Women with a starting LS BMD below the sample median, and an LS BMD decline rate faster than the sample median had a 2.7-fold greater fracture hazard (P = .03). At the femoral neck, neither starting BMD nor rate of BMD decline was associated with fracture. CONCLUSION: At the LS, starting BMD before the MT and rate of decline during the combined MT and early postmenopause are independent risk factors for fracture. Women with a below-median starting LS BMD and a faster-than-median LS BMD decline have the greatest fracture risk.

Antioxidant ability and mechanism of rhizoma Atractylodes macrocephala.

Rhizoma Atractylodes macrocephala (AM) has been used in Traditional Chinese Medicine (TCM) for about 2,000 years. In the study, we firstly determined the antioxidant levels of five AM extracts by •OH-scavenging, •O2−-scavenging, Fe2+-chelating, Cu2+-chelating, DPPH·-scavenging, and ABTS+·-scavenging assays. After measurement of the chemical contents in five AM extracts, we quantitatively analyzed the correlations between antioxidant levels and chemical contents. It was observed that total phenolics and total flavonoids had significant positive correlations with antioxidant levels (R = 0.685 and 0.479, respectively). In contrast, total sugars and total saponins presented lower correlations with antioxidant levels (R=−0.272 and 0.244, respectively). It means that antioxidant activity of AM should be attributed to total phenolics (including phenolic acids and flavonoids), and not total sugars and total saponins. Further analysis indicated that phenolic acids exhibited higher R values with radical-scavenging assays (R=0.32­1.00), while flavonoids showed higher R values with metal-chelating assays (R=0.86 and 0.90). In conclusion, AM exerts its antioxidant effect through metal-chelating, and radical-scavenging which is via donating hydrogen atom and donating electron. Its metal-chelating may result from flavonoids, while its radical-scavenging can be attributed to phenolic acids, especially caffeic acid, ferulic acid, and protocatechuic acid.

Antioxidant activity and mechanism of Rhizoma Cimicifugae.

BACKGROUND: As a typical Chinese herbal medicine, rhizoma Cimicifugae (RC, in Chinese) possesses various pharmacological effects involved in antioxidant activity. However, its antioxidant activity has not been reported so far. The aim of the present study was to systematically evaluate the antioxidant ability of RC in vitro, then discuss the mechanism. METHODS: Firstly, five RC extracts (i.e. petroleum ether extract PERC, ethyl acetate extract EARC, absolute ethanol extract AERC, 95% ethanol extract 95ERC, and water extract WRC) were prepared and determined by various antioxidant methods, including anti-lipidperoxidation, protection against DNA damage, ·OH scavenging, ·O2- scavenging, DPPH· (1,1-diphenyl-2-picryl-hydrazl radical) scavenging, ABTS+· (2,2'-azino-bis (3-ethylbenzo- thiazoline-6-sulfonic acid radical ion) scavenging, Cu2+-chelating, and Fe3+ reducing assays. Subsequently, we measured the chemical contents of five RC extracts, including total phenolics, total saponins, total sugars, caffeic acid, ferulic acid and isoferulic acid. Finally, we quantitatively analyzed the correlations between antioxidant levels (1/IC50 values) and chemical contents. RESULTS: In the study, the antioxidant levels and chemical contents (including total phenolics, total saponins, total sugars, caffeic acid, ferulic acid and isoferulic acid) of five RC extracts were determined by various methods. In all antioxidant assays, five RC extracts increased the antioxidant levels in a dose-dependent manner. However, their antioxidant levels (IC50 values) and chemical contents significantly differed from each other. Quantitative analysis of the correlation showed that total phenolic was of significant positive correlations (average R value was 0.56) with antioxidant levels; In contrast, total sugars and total saponins had no positive correlation with antioxidant (the average R values were -0.20 and -0.26, for total sugars and total saponins, respectively); Among total phenolics, three phenolic acids (caffeic acid, ferulic acid and isoferulic acid) also displayed positive correlations (the average R values were 0.51, 0.50, and 0.51, for caffeic acid, ferulic acid and isoferulic acid, respectively). CONCLUSIONS: As an effective antioxidant, Rhizoma Cimicifugae can protect DNA and lipids against oxidative damage. Its antioxidant ability can be responsible for its various pharmacological effects and may be mainly attributed to the existence of total phenolics, among which caffeic acid, ferulic acid and isoferulic acid are regarded as main bioactive components. Rhizoma Cimicifugae exerts its antioxidant effect through metal-chelating, and radical-scavenging which is via donating hydrogen atom (H·) and donating electron (e).

Development of an updated phytoestrogen database for use with the SWAN food frequency questionnaire: intakes and food sources in a community-based, multiethnic cohort study.

Phytoestrogens, heterocyclic phenols found in plants, may benefit several health outcomes. However, epidemiologic studies of the health effects of dietary phytoestrogens have yielded mixed results, in part due to challenges inherent in estimating dietary intakes. The goal of this study was to improve the estimates of dietary phytoestrogen consumption using a modified Block Food Frequency Questionnaire (FFQ), a 137-item FFQ created for the Study of Women's Health Across the Nation (SWAN) in 1994. To expand the database of sources from which phytonutrient intakes were computed, we conducted a comprehensive PubMed/Medline search covering January 1994 through September 2008. The expanded database included 4 isoflavones, coumestrol, and 4 lignans. The new database estimated isoflavone content of 105 food items (76.6%) vs. 14 (10.2%) in the 1994 version and computed coumestrol content of 52 food items (38.0%), compared to 1 (0.7%) in the original version. Newly added were lignans; values for 104 FFQ food items (75.9%) were calculated. In addition, we report here the phytonutrient intakes for each racial and language group in the SWAN sample and present major food sources from which the phytonutrients came. This enhanced ascertainment of phytoestrogens will permit improved studies of their health effects.