Synthesis of an environmentally friendly binding material using pyrolysis by-products and modified starch binder for slow-release fertilizers.

Biochar-based slow-release fertilizers (BSRFs) are vital for the development of eco-friendly and sustainable agriculture. Considerable attention has been given to enhancing the efficiency of fertilizers (EEFs) by appropriate modification or binding to reduce nutrient waste and improve the slow-release effect on the growth of plants. In this study, sustained binding materials were presented for BSRF synthesis, including pyroligneous acids (PA), bio-oil (BO), and modified starch binder (MSB). The results show that the release ratio of phosphorus from PA + BO+MSB was 4.7%, 15.2%, and 21.2% slower than that of PA, BO, and MSB alone, respectively. The BSRFs were characterized by SEM, XRD, FT-IR, XPS, and EDS, and the release kinetic outcome revealed that PA + BO+MSB contributed to the formation of a satisfactory structure in the BSRFs. The MSB viscosity significantly influences the slow-release performance and accumulation of N, P, and K nutrients. Moreover, economic assessments showed that PA + BO+MSB exhibited the lowest cost.

Study on the new anti-atherosclerosis activity of different Herba patriniae through down-regulating lysophosphatidylcholine of the glycerophospholipid metabolism pathway.

BACKGROUND: Atherosclerosis (AS) is a multifactor cardiovascular disease characterized by chronic inflammation. The safety of long-term medication is the focus of clinical treatment selection and application. It is urgent to develop more high-efficiency and low side effects drugs to treat AS. Therefore, the screening of anti-AS drugs with high efficiency and low toxicity from phytomedicine has attracted more and more attention. PURPOSE: The aim of this study was to explore the new pharmacological effect of Herba patriniae against AS, to find the best origin and extraction part of Herba patriniae, furthermore, to reveal its potential action mechanism. METHODS: Apolipoprotein E gene-knockout (ApoE-/-) mice were orally administered with different extracts of Patrinia villosa Juss (PVJ) and Patrinia scabiosaefolia Fisch (PSF). Their anti-AS effect was comprehensively evaluated by small animal ultrasound, HE staining, Oil-Red O staining, platelet aggregation rate and blood lipid level. Lipid metabolomics and network pharmacology were used to study the mechanism of drug action. Finally, the expression of related proteins were detected by western blots and immunofluorescence. RESULTS: PVJ EtOAc extract and PSF EtOAc extract could significantly reduce vascular plaque, liver inflammation, platelet aggregation and blood lipid levels in AS model. By comparison, the effect of PVJEE was better than that of PSFEE. Furthermore, the results of differential metabolites indicated that PVJEE may inhibit the apoptosis of vascular endothelial cells, proliferation and migration of smooth muscle cells by reversing lysophosphatidylcholine (LPC) in the glycerophospholipid metabolic pathway, so as to play an anti-AS role. This result was double verified by KEGG based metabolic pathway enrichment analysis and related protein expression study. CONCLUSION: By changing glycerophospholipid metabolism pathway, Herba patriniae can significantly regulate lipid metabolism and inflammatory level, showing the development potential of anti-AS, which provides new candidate drugs and good prospects for the safe treatment of AS. In addition, through comparison, this study also confirmed that PVJEE was the best origin and extraction part of anti-AS.

Pulchinenosides: Correlation of surface activity-cytotoxicity and hepatocyte apoptosis mechanism study.

Saponin is an active component of many phytomedicine, which has extensive pharmacology effects. Meanwhile, it is reported that cytotoxicity, especially hemolysis and hepatotoxicity, in pentacyclic triterpenoid saponin (PTS) hindered their further development and application. Surface activity, a unique physical property of saponins, is believed to be related to membrane toxicity. However, the correlation between the surface activity and cytotoxicity of saponins is still unexplained. In this paper, our aim was to explore the relationship between surface activity-cytotoxicity of pulchinenosides and the hepatotoxicity mechanism of PTS in vitro. The surface activity of different saponins was investigated by contact angle, surface free energy (SFE), and oil/water partition coefficient (log Papp). In the cytotoxicity study, the hemolysis and hepatotoxicity activity of different saponins was compared by HD50 of erythrocyte and MTT, flow cytometry and LDH assay in LO2 cells respectively. And in the hepatotoxicity mechanism study, western blot was used for observing the expression of proteins related to apoptosis and exploring the liver injury mechanism of PTS. The results suggested that the influences of surface activity on hepatocytes and erythrocytes were different, indicating that the correlation of surface activity-cytotoxicity could provide more information for development of PTS. And the result of hepatotoxicity mechanism study of saponins suggested that endogenous and exogenous apoptotic pathways could be the potential targets of PTS, which could not only provide basis for clinical monitoring and treatment of the toxicity in saponins, but also provide more reference for the clinical application of PTS and phytomedicine containing PTS.

Raw and wine processed Schisandra chinensis attenuate anxiety like behavior via modulating gut microbiota and lipid metabolism pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine, the fruit of Schisandra chinensis (Turcz.) Baill (SC) is used to treat various nervous system diseases, such as dysphoria, anxiety, insomnia and many dreams. It is worthy to be noted that wine processed Schisandra chinensis (WSC) has been applied in clinic for thousands of years. AIM OF STUDY: This study aimed to investigate the possible mechanism and related metabolism of SC and WSC ameliorating anxiety behavior through modulating gut microbiota. MATERIALS AND METHODS: The ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was used for the quality control of chemical components in SC and WSC. Chronic unpredictable stress procedure (CUSP)-induced anxiety rats were administrated with SC and WSC via gavage for five weeks. An untargeted UPLC/LTQ-Orbitrap MS metabolomic analysis of plasma was conducted to understand the effects of long-term intake of WSC and SC extracts on anxious rats. 16S rRNA microbial sequencing technology was applied to investigate gut microbiota structure. Expression of GPR81, TNF-α, S1PR2 as well as molecules in cAMP pathway was assayed by immunohistochemistry staining, RT-qPCR, or Western blot, respectively. RESULTS: 12 compounds were identified using UPLC-QTOF-MS technology, all of which are lignans. Results demonstrate that the amounts of 6-O-Benzoylgomisin O, Schisandrin, Gomisin D, Schizandrin A, Gomisin T, Schizandrin B, Schisandrin C were higher in wine-processed samples than in raw samples. Furthermore, both SC and WSC significantly ameliorated anxiety- and depression-like behavior and lipid metabolism dysfunction and attenuated hippocampal neuritis in anxiety rats. After WSC treatment, the structure and composition of gut microbiota in anxiety rats changed significantly, and gut microbiota derivatives lactate level was significantly lower in the plasma and feces. WSC treatment help restore gut microbial ecosystem dysbiosis and reverse the changes in Lachnospiraceae, Lactobacillus, Alloprevotella, and Bacteroidales in anxiety rat. In addition, the expression of liver GPR81 was decreased, and the molecules in cAMP pathway were increased in SC and WSC-treated anxiety rat. CONCLUSION: Raw and wine processed Schisandra chinensis treatment improved anxiety- and depression-like behavior through modulating gut microbiota derivatives in association with GPR81 receptor-mediated lipid metabolism pathway. And WSC has more exhibition than SC.

Pulsatilla chinensis saponins cause liver injury through interfering ceramide/sphingomyelin balance that promotes lipid metabolism dysregulation and apoptosis.

BACKGROUND: P. chinensis saponins (PRS) are pentacyclic triterpenoid bioactive constituents from Pulsatilla chinensis (Bunge) Regel. In our previous study, PRS caused chronic liver injury (CLI) with the significant changes of lipid metabolites including sphingomyelin (SM) in serum after long-term administration. The SM in the hepatocytes membrane plays an indispensable role in maintaining cell membrane stability and regulating the extracellular and intracellular signal transduction. However, it is still unknown the pathway related to SM and the mechanism of CLI on hepatocyte. PURPOSE: The purpose of this study was to explore the hepatotoxicity mechanism of PRS in vivo and in vitro, to reveal the action of mechanism of SM and the pathway related to liver injury. METHODS: SD rats were orally administered with PRS for 240 days and liver injury was evaluated by histological examinations. Metabolomics analysis was used to explore the liver metabolic pathway affected by PRS, and the expressions of related proteins were evaluated by western blots. To discover and elucidate the underlying mechanisms of metabolites changes induced by PRS at the cellular level, cellular morphology, MTT assays, western blots and cell membrane potential measurements were carried out using LO2 cells. Furthermore, the roles of SM and cholesterol (Chol) in hepatocyte injury were investigated individually in overload Chol and SM groups. Sphingolipid metabolic pathway related with ceramide/sphingomyelin (Cer/SM) balance was explored using cellular lipidomics and RT-PCR. RESULTS: PRS gradually damaged the rat's liver in a time-dependent manner. The analysis of liver metabolism profiles showed that lipids metabolites were changed, including sphingolipid, bile acid, linoleic acid and fatty acid. We found that PRS induced apoptosis by interfering with bile acid-mediated sphingolipid metabolic pathway and Cer/SM balance in CLI. In in vitro experiments, PRS led to the increase of LDH leakage, depolarized cell membrane potential and caused cell membrane toxicity. Furthermore, PRS inducedG0/G1 phase cell cycle arrest in LO2 cells, simultaneously activated cellular extrinsic and intrinsic apoptosis pathways. PRS acted on SM and interfered with Cer/SM balance, which promote lipid metabolism dysregulation and apoptosis. CONCLUSION: PRS acted on SM to interfere Cer/SM balance on LO2 cell. Both in vivo and in vitro, PRS induced Cer/SM imbalance which promoted lipid metabolism disorder and apoptosis. Apoptosis and lipids changes gradually damaged the rats liver, and ultimately developed into CLI.

Metabolite Profile Changes in Different Regions of Rat Brain Affected by Ephedra sinica.

Ephedra sinica Stapf (EP) has a long medication history dating back centuries in the world. There were some reports of adverse effects in the central nervous system (CNS) resulting from administration of a drug containing EP or ephedrine. Compared with alkaloid monomer compounds, the effects of EP on the CNS are usually neglected. It is necessary to explore CNS affection which is helpful to use EP rationally. However, the affection and the changes of substances by EP in the brain are still unknown because the effects of drug on the brain also exhibit different tendency and distribution and usually lead to diversity of metabolite alteration in different regions. In this study, metabolomics based on different brain regions was used to investigate the affection mechanism of EP in the CNS. The metabolites in 6 brain regions from a rat that underwent oral administration with EP for 14 days were determined by UPLC/Q-TOF-MS. Brain histological examinations showed that there were no obvious lesions in EP administration groups. Partial least square-discriminant analysis (PLS-DA) displayed that there were significant separations between control and EP administration groups. 7 CNS biomarkers were found and identified in different regions. 3 metabolic pathways were disturbed by EP, including amino acid metabolism, phospholipid metabolism, and amino sugar metabolism. Furthermore, all biomarkers were significantly changed in the cortex after administration. This study may be helpful to understand the affection mechanism of EP in the CNS and improve cognition of brain regional characteristics.

Safety investigation of Pulsatilla chinensis saponins from chronic metabonomic study of serum biomedical changes in oral treated rat.

ETHNOPHARMACOLOGICAL RELEVANCE: Pulsatilla chinensis (Bunge) Regel is a valuable traditional Chinese medicine (TCM) which is widely used for the treatment of schistosomiasis, inflammatory, bacterial infections. In recent years, P chinensis has been reported to exhibit antitumor activities. However, the mechanisms underlying its toxic effects remain largely unresolved. This paper is designed to investigate the damage of long-term oral P. chinensis saponins (PRS) and to explore its potential damage mechanisms by serum metabonomics approach. MATERIALS AND METHODS: The serum samples from control and PRS treated rats were analyzed by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) in positive ionization mode and negative ionization mode. Liver function index of ALT, AST and ALP, blood biochemistry and biomarkers were examined to identify specific changes of injury. Acquired data were subjected to principal component analysis (PCA) for differentiating the control and PRS treated groups. Then, serum metabolic profiling was analyzed and pathway analysis performed on the biomarkers reversed after PRS treated and further integration of metabolic networks. RESULTS: The results suggested that serum liver function indexes of ALT had significantly changed and stage increased. AST, ALP detection content show volatility changes. Changes in the 15 biomarkers found in the serum, such as acetaminophen glucuronide, 9 E, 11 E-linoleic acid, chenodeoxycholic acid, monoacylglycerides, sphingomyelin (SM), 7-ketodeoxycholic acid and 12-keto-deoxycholic acid, which were closely related to changes in liver injury. It could be seen clearly that with the change of the dosing time, the biomarkers in the serum have undergone obvious, regular and progressive changes through the score plot and corresponding loading plot. The underlying regulations of PRS-perturbed metabolic pathways were discussed according to the identified metabolites. CONCLUSION: The present study proves the potential of UPLC-QTOF-MS based metabonomics in mapping metabolic response. Long-term oral administration of P. chinensis saponins can cause chronic liver injury, and its safety needs further attention. It is of great significance in safeguarding human health to explore the damage mechanism of Pulsatilla chinensis saponins on liver by serum metabolomics.