In Vitro and in Vivo Evaluation of Scutellarin-phospholipid Complex Nanoemulsion and Analysis of Its Activity in Ameliorating LPS-induced Vascular Endothelial Injury / 中国实验方剂学杂志

ObjectiveTo evaluate some properties of scutellarin-phospholipid complex nanoemulsion（SCU-PC-NE）， such as release， cell uptake and tissue distribution， and to investigate its effect on ameliorating lipopolysaccharide（LPS）-induced vascular endothelial injury. MethodSCU-PC-NE was prepared by weighting SCU-PC， ethyl oleate， Kolliphor HS15， 1，2-propylene glycol（50， 400， 514.3， 85.7 mg）， respectively. And the appearance of SCU-PC-NE was observed by transmission electron microscope， the average paticle size and Zeta potential were measured by nanopotential particle size analyzer. The cumulative release of SCU-PC-NE in vitro was measured by dynamic dialysis， thiazolyl blue（MTT） colorimetric assay was used to investigate the effect of SCU-PC-NE on the viability of human umbilical vein endothelial cells（HUVECs）， the inverted fluorescence microscope and flow cytometry were used to investigate cell uptake of HUVECs by SCU-PC-NE in vitro using coumarin 6 as a fluorescent probe， the tissue distribution of DiR/SCU-PC-NE labeled by near infrared fluorescent dyes was obeserved by small animal in vivo imaging system. The inflammation injury model was established by co-incubation with LPS（1 mg·L-1） and HUVECs， the effect of SCU-PC-NE on the levels of interleukin（IL）-1β and IL-6 were determined by enzyme-linked immunosorbent assay（ELISA）， 18 Kunming male mice were randomly divided into blank group， model group， blank preparation group（equivalent to high dose group）， SCU group and SCU-PC-NE low and high dose groups（5， 10 mg·kg-1）， 3 mice in each group， and the drug administration groups were administered once in the tail vein at the corresponding dose every 48 h， equal volume of normal saline was given to the blank group and the model group， and the drug was administered for 4 consecutive times. Except for the blank group， the endothelial inflammatory injury was induced by intraperitoneal injection of LPS（10 mg·kg-1） at 12 h before the last administration in each group. Hematoxylin-eosin（HE） staining was used to investigate the effect of SCU-PC-NE on the histopathological changes in the thoracic aorta of mice. ResultThe appearance of SCU-PC-NE displayed pale yellow milky light， mostly spherical with rounded appearance and relatively uniform particle size distribution， with the average particle size of 35.31 nm， Zeta potential of 7.23 mV， and the encapsulation efficiency of 75.24%. The cumulative release in vitro showed that SCU-PC-NE exhibited sustained release properties compared with SCU. The cell viability of SCU-PC-NE was >90% at a concentration range of 1.05-8.4 mg·L-1. The results of cellular uptake experiments showed that the cellular uptake ability of SCU-PC-NE was significantly enhanced when compared with the SCU group（P<0.01）. Compared with normal mice， the results of tissue distribution showed that the fluorescence intensity of DiR/SCU-PC-NE was significantly enhanced in the spleen， kidney， brain and thoracic aorta of mice at different time points after intraperitoneal injection of LPS（P<0.05， P<0.01）， especially in thoracic aorta. ELISA results showed that the levels of IL-1β and IL-6 in the model group were significantly increased when compared with the blank group（P<0.05， P<0.01）， and compare with the model group， all administration groups significantly down-regulated IL-1β level， with the strongest effect in the SCU-PC-NE high-dose group（P<0.01）， and all administration groups significantly down-regulated IL-6 level， with the strongest effect in the SCU-PC-NE low-dose group（P<0.05）. Compare with the blank group， the results of HE staining showed that the endothelial cells were damaged， the elastic fibers were broken and arranged loosely in the model group， although similar vascular injury could be observed in the blank preparation group， SCU group and SCU-PC-NE low-dose group， the vascular endothelial damage was significantly reduced in the high-dose group of SCU-PC-NE， which had a better effect than that in the SCU group. ConclusionSCU-PC-NE can promote the uptake of drugs by endothelial cells and effectively enriched in the site of vascular endothelial injury caused by LPS， suggesting that it has a protective effect on vascular endothelial injury and is a good carrier of SCU.

Preparation and in vitro dissolution behaviors evaluation of silymarin phospholipid complex / 药学实践杂志

Objective To prepare silymarin phospholipids complex（SM-PC） and investigate its physicochemical properties. Methods On the basis of single-factor tests, the drug-lipid ratio, drug concentration and reaction temperature were selected as the factors of the central composite design and response surface methodology in the preparation of SM-PC by solvent volatilization, and the best process was optimized with the compound rate as the index. And its in vitro dissolution was measured. Results The optimum preparation technology of SM-PC was as follows: acetone was used as compound solvent, the concentration of SM was 8.0 mg/ml, the mass ratio of SM to phospholipid was 1∶1.8, the reaction temperature was 56 ℃ and the recombination rate was（95.15±1.55）% with deviation of less than 3%. The in vitro dissolution test showed that the dissolution of SM-PC was close to 90% in 60 min. The dissolution behavior of main component of silybin was similar to that of silymarin capsules（Legalon ®）, which was higher than SM-API. Conclusion SM-PC was successfully prepared by central composite design response surface method, which significantly improved the dissolution and laid a foundation for the study of subsequent preparations.

Evaluation of core decompression outcome in systemic lupus erythematosus with hip osteonecrosis: a retrospective cohort study

Abstract Background Osteonecrosis is a major cause of morbidity for patients with systemic lupus erythematosus (SLE). Although core decompression is an approved and trusted technique to prevent further joint deterioration, this surgical method seems to be less beneficial for SLE patients. We aimed to evaluate the outcomes of core decompression in SLE patients with primary stages of femoral head osteonecrosis. Methods In this study, 23 patients (39 affected hip joints) with osteonecrosis of the femoral head with stage II of the disease, based on the Ficat-Arlet classification system, underwent core decompression. Also, patients demographic characteristics, clinical data, medication history, comorbidities, immunological findings, hip plain radiographs, history of total hip arthroplasty after core decompression, and patients satisfaction with joint function according to the Oxford hip score questionnaire were obtained. Results In the study, 53.8% of affected joints showed signs of radiographic deterioration in follow-up imaging. Sixty-one and a half percent (61.5%) of patients had unsatisfactory joint performance. A third (33.3%) of affected hip joints underwent total hip arthroplasty up to 5 years from core decompression. SLE patients with a history of receiving bisphosphonate were 83.2% less dissatisfied with their joint function than patients without a history of bisphospho-nate use (P < 0.02). Of the 23 studied cases, the mean cumulative dose of prednisolone before and after core decompression surgery was 46.41 mg and 14.74 mg respectively. Besides, one case (2.6%) that had a high anti-phospholipid antibodies level during follow-up did not have any radiographic deterioration, and 9 cases (23.1%) had some degrees of radiographic deterioration. Conclusions The patients group that used bis-phosphonate, had a higher level of satisfaction with joint function after core decompression. Patients with high-level anti-phospholipid antibodies are related to a poor prognosis after core decompression.

In vivo pharmacokinetics and in vitro-in vivo correlation of silymarin phospholipid complex microporous osmotic pump controlled-release tablets in beagle dogs / 药学实践杂志

Objective To evaluate the release characteristics in vitro, pharmacokinetics in rabbits and in vivo-in vitro correlation of silymarin phospholipid complex microporous osmotic pump controlled release tablets（SM-PC MPOP）. Methods The release characteristics of SM-PC MPOP in vitro were detected by HPLC in the artificial gastric fluid. Six beagle dogs were subjected to double cycle cross control, which were given SM-PC MPOP and Legalon（30 mg/kg）. The concentration of silybin in plasma was determined by HPLC and the data were processed by software. Results The cumulative release rate of SM-PC MPOP in vitro was over 85% in 12 h. The pharmacokinetics in beagle dogs showed that SM-PC MPOP and legalon conformed to double compartment first-order absorption model and the pharmacokinetic parameters were obtained: tmax:（3.2±0.4）and（0.9±0.1）h, Cmax:（0.298 6±0.068 9）and（0.629 9±0.076 5）μg/ml, AUC0→24:（2.996 8±0.583 3）and（2.268 9±0.432 8）h·μg /ml. The relative bioavailability of SM-PC MPOP was（162.21 ± 30.82）%. Conclusion SM-PC MPOP could release slowly, which could increase the relative bioavailability significantly. The correlation between the absorption in vivo and release in vitro was fine（r = 0.839 0）.

Hepatopancreatic contributions of lipids and carotenoids to vitellogenesis in the intertidal anomuran crab, Emerita asiatica (Milne Edwards)

In decapod crustaceans, lipids and the associated carotenoid pigments form an integral part of yolk to serve as nutrientsduring embryogenesis. This study reports on the analysis of different lipid classes and the major carotenoids in the ovary,hepatopancreas and hemolymph and their fluctuation during different phases of ovarian maturation in an anomuran crab, Emerita asiatica. Neutral lipids including triglycerides (TG) and free fatty acids (FFA) formed the bulk of ovarian lipids. Important fatty acids are Saturated fatty acids (SFA) 16:0 and 18:0, Monounsaturated fatty acids (MUFA) 16:1n7 and18:1n9, and Polyunsaturated fatty acids (PUFA) 20:5n3 and 22:6n3. While phospholipids increased during maturation, glycolipids decreased. Cholesterol level in ovary increased initially, but declined during later stages. Dominant pigments, ?-carotene and astaxanthin, steadily increased during ovarian maturation within the ovary, although canthaxanthin declineddrastically towards last stage. In hepatopancreas, however, TG and FFA showed gradual decrease during maturation. Palmitic acid, palmitoleic acid and eicosapentaenoic acid are the predominant fatty acids in hepatopancreas, showing asteady decline during ovarian maturation. Other lipid classes such as glycolipids also showed a decline in hepatopancreas. Both ?-carotene and astaxanthin in hepatopancreas declined from the first stage of ovarian development, suggestingtranslocation to ovary. The overall metabolic changes of lipids and carotenoids in hepatopancreas, hemolymph and ovary areindicative of their accumulation within developing eggs to provide metabolic energy and substrates for membrane formation, and to serve as precursors for pigment formation respectively, during embryogenesis.

Folic acid-modified phospholipid-encapsulated paclitaxel nanocrystals for preoperative chemotherapy of gastric cancer / 药学学报

This paper aims to develop folic acid-modified paclitaxel nanocrystals (PTX NC@FA) with good stability, high drug loading and tumor cell targeting for endoscopic injection for preoperative local chemotherapy of gastric cancer. PTX NC@FA was prepared by the "bottom-up" followed by ultrasonic to study its morphology, particle size, ζ-potential, drug loading, folic acid-modified phospholipid (FA-DSPE-PEG2000) content, crystalline characteristics, stability, in vitro release, cytotoxicity against human gastric cancer cell line SGC-7901, and anti-tumor effect in two different tumor sizes (tumor volume 100 mm3 or 300 mm3) after single peri-tumor injection in a murine subcutaneous SGC-7901 tumor model. Animal experiments were approved by the Experimental Animal Ethics Committee of the School of Pharmacy, Fudan University. The resulting PTX NC@FA was of short rod-like shape, average particle size 175.3 ± 2.5 nm (PDI 0.17 ± 0.02), ζ- potential -2.5 ± 0.2 mV, PTX loading (28.23 ± 0.74) % (w/w) and FA-DSPE-PEG2000 content (4.40 ± 0.60) % (w/w). The size of the PTX NC@FA remained unchanged for 4 days in phosphate buffer with or without serum. Cellular growth inhibition effect on SGC-7901 showed the superiority of PTX NC@FA over nanocrystals without FA modification. PTX NC@FA inhibited tumor growth more efficiently than both nanocrystals without FA modification and commercially available paclitaxel injection (Taxol) 12 days after peri-tumor injection. For model tumor with the volume of 100 mm3, tumors of all animals in the PTX NC@FA group disappeared completely. For model tumor with the volume of 300 mm3, tumors of 3 animals in the PTX NC@FA group completely disappeared and tumors of the rest 4 animals also became significantly smaller with a tumor volume inhibition rate of 90%. PTX NC@FA showed good potential for preoperative chemotherapy of increase the chances of function preserving gastrectomy and improve the quality of life of patients.

Research advances of phospholipid peroxidation in pathogenesis of coronary heart disease / 中国药理学通报

Coronary heart disease (CHI)) is a kind of coronary atheroselerotie cardiovascular disease that seriously endangers human health and needs to he solved urgently in the world.Epidemiological

Phospholipid remodeling and Parkinson's disease / 药学学报

The remodeling of phospholipid includes two processes: deacylation and reacylation. It realizes the conversion of nascent phospholipids to mature phospholipids by changing the length and types of fatty acids at specific sites of phospholipids, which is a key step in phospholipid metabolism. Phospholipids are not only the basic components of biological membranes, but also participate in the transduction of many molecular signals in cells. Therefore, phospholipid remodeling disorders can affect the structure and function of cell membranes, as well as the activity of membrane proteins, causing a series of intricate signaling cascades, and finally lead to many pathological changes including neurodegeneration. This paper reviews the basic process of phospholipid remodeling and the involvement of its key enzymes, calcium independent group VIA phospholipase A2 (iPLA2β), peroxiredoxin 6 (PRDX6), calcium independent group VIB phospholipase A2 (iPLA2γ) as well as acyl-CoA lysocardiolipin acyltransferase 1 (ALCAT1) in the pathology of Parkinson's disease. The mutations in the gene encoding iPLA2β, PLA2G6, have been widely reported to be directly related to hereditary Parkinson disease-14 (PARK14). Here we focus on the molecular mechanism of iPLA2β in the development of Parkinson's disease, mainly involving phospholipid fatty acid metabolism disorders, mitochondrial physiology abnormalities and α-synuclein aggregate formation and other aspects, which will help to understand the role of phospholipid remodeling in Parkinson's disease, and provide new clues for the development of new Parkinson's disease diagnosis and treatment strategies.

Effect of Qinggan Xiefei Fang on increasing susceptibility of influenza virus caused by "liver fire invading lung" / 药学学报

In this study, chronic emotional stress-induced H1N1 influenza susceptibility model was employed to simulate the states of "emotional stagnation" and "liver fire invading lung", and the protective effect of Qinggan Xiefei Fang on viral pneumonia was investigated. Survival rate and morbidity rate of mice were observed within 21 days after H1N1 infection, the symptoms of viral pneumonia and the level of phospholipid peroxidation were detected in lungs of mice after 6-day infection. The experimental results showed that Qinggan Xiefei Fang could alleviate the decline of survival rate and morbidity rate of mice caused by chronic constraint stress loaded with H1N1, inhibit the replication of H1N1 and the production of inflammatory factors, reduce the level of phospholipid peroxidation, and improve the symptoms of pneumonia in mice. The results also showed that compound-target network of Qinggan Xiefei Fang contained 171 compounds and 260 corresponding targets involved in the signaling pathway of oxidative stress, inflammation and immunity. All the above results indicate that Qinggan Xiefei Fang protecting influenza virus pneumonia was related to the regulation of oxidative stress. The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Jinan University, in compliance with the Institutional Animal Care Guidelines.

Research progress on the role of bile salts in ischemic-type biliary lesion after liver transplantation / 器官移植

Ischemic-type biliary lesion (ITBL) refers to biliary tract injury caused by insufficient blood supply of hepatic artery, which is one of the main factors affecting the long-term survival and quality of life of liver transplant recipients. The incidence of ITBL is associated with cold and warm ischemia, acute and chronic rejection, cytomegalovirus infection and the bile effect, etc. The occurrence of ITBL is a complicated process involving with multiple factors and steps. The therapeutic option of ITBL is extremely limited. A large proportion of ITBL patients should undergo repeated liver transplantation. ITBL has become one of the most critical factors preventing further advancement of liver transplantation. Hence, it is of significance to strengthen prevention and explore more effective modalities. Recent studies have found that toxic injury of bile salts plays a central role in ITBL. Active regulation of bile components, regulation of bile acid-related receptor expression and blockage or activation of bile acid-related signaling pathways probably have potentials in the prevention and treatment of ITBL. In this article, the cytotoxicity of bile salts and the mechanism of bicarbonate umbrella in the incidence and progression of ITBL after liver transplantation were reviewed, aiming to provide reference for the diagnosis and treatment of ITBL.

Reasearch on lipid metabolism of Plasmodium and antimalarial mechanism of artemisinin / 中国中药杂志

As a unicellular organism, Plasmodium displays a panoply of lipid metabolism pathways that are seldom found together in a unicellular organism. These pathways mostly involve the Plasmodium-encoded enzymatic machinery and meet the requirements of membrane synthesis during the rapid cell growth and division throughout the life cycle. Different lipids have varied synthesis and meta-bolism pathways. For example, the major phospholipids are synthesized via CDP-diacylglycerol-dependent pathway in prokaryotes and de novo pathway in eukaryotes, and fatty acids are synthesized mainly via type Ⅱ fatty acid synthesis pathway. The available studies have demonstrated the impacts of artemisinin and its derivatives, the front-line compounds against malaria, on the lipid metabolism of Plasmodium. Therefore, this article reviewed the known lipid metabolism pathways and the effects of artemisinin and its derivatives on these pathways, aiming to deepen the understanding of lipid synthesis and metabolism in Plasmodium and provide a theoretical basis for the research on the mechanisms and drug resistance of artemisinin and other anti-malarial drugs.

Phospholipid peroxidation: a key factor in "susceptibility" to neurodegenerative diseases / 药学学报

The biochemical integrity of the brain is necessary to maintain normal function. Oxidative damage is one of the mortal important reasons leading to the destruction of this integrity. The nervous system is enriched in phospholipid and polyunsaturated fatty acids (PUFAs). Due to the nature of high oxygen-consumption and rich lipids, brain is particularly vulnerable to oxidative damages. Phospholipid peroxidation is one of the results of imbalance in oxidation-antioxidant system. Once the antioxidant system is insufficient to resist oxidative damage, membrane phospholipids will be prone to free radical attack. Phospholipid peroxidation leads to a variety of toxic oxidation products, including membrane damage, mitochondrial dysfunction, rapid accumulation of amyloid, etc. Multiple proteins and nucleic acids can be covalently modified by peroxidation products, resulting in the loss of the protein functions, which eventually triggers programmed cell death and general neuroinflammation in brain, and ends up with an increased susceptibility to neurodegenerative diseases. Based on the knowledge of mechanisms of phospholipid peroxidation, this review focuses on the characteristics of phospholipid peroxidation as a key factor in the development of neurodegenerative diseases, in order to provide theoretical basis for targeted intervention of phospholipid peroxidation as a potential strategy to prevent neurodegenerative diseases.

Approach to the primary adrenal insufficiency caused by anti-phospholipid syndrome / 中华内分泌代谢杂志

The causes of primary adrenal insufficiency(PAI) are varying, however, anti-phospholipid syndrome (APS) is a relatively rare one. PAI lacks unique clinical manifestations, so the confirmation of PAI was easily to be neglected by physicians. We report a case with abdominal pain as the first complaint, followed by multiple infections, thrombotic events, and aggravating fatigue. Through a series of the laboratory examination, medical imaging, and pathology examination, this patient was diagnosed as PAI caused by APS. Combining this report with literature review, we aim to raise awareness of the disease and avoid misdiagnosis and missed diagnosis.

Osthole attenuates pulmonary arterial hypertension by modulation of phospholipid metabolism / 中国药理学与毒理学杂志

OBJECTIVE Pulmonary arterial hypertension (PAH) is a malignant pulmonary vascular disease lacking efficacy therapeutics. Therefore, it urgently needs to develop safe and effective drugs for PAH treatment. Osthole derived from Cnidium monnieri (L.) Cusson (Shechuangzi) or Angelica pubescens Maxim (Duhuo) has the capacity to alleviate PAH by decreasing pulmonary arterial pressure and alleviating pulmonary vascular remodeling in rats, which is a candi?date drug for the prevention of PAH, but the underlying modulatory mechanism is still unclear. Our study aims at investi?gating the metabolic modulatory mechanism of osthole against PAH employing functional metabolomics strategy. METH?ODS PAH model rats were successfully established with MCT, following osthole administration, then functional metabo?lomics based on untargeted metabolomics assay, targeted lipidomics analysis, qRT-PCR, Western blotting and ELISA were performed to investigate the modulatory mechanism of osthole against pulmonary arterial pressure and pulmonary vascular remodeling in PAH. RESULTS Untargeted metabolomics results found that sphingosine 1-phosphate (S1P) was the differential metabolites characterized PAH and reversed by osthole treatment. S1P is a crucial sphingolipid metabolite catalyzed by sphingosine kinases1 (Sphk1) and functions as promoting PASMCs proliferation contributing to pulmonary vascular remodeling and pulmonary arterial pressure increase. We revealed that osthole reversed high level of S1P by modulating metabolic enzyme Sphk1 via inactivating microRNA-21-PI3K/Akt/mTOR signal pathway to decrease pulmonary arterial pressure in rats with PAH. Then, targeted phospholipid metabolomics results uncovered that decadienyl-L-carnitine (C10:2) was the differential metabolite characterized PAH and corrected by osthole treatment in rat with PAH. C10:2 is the intermediate metabolite of fatty acid oxidation (FAO), and C10:2 accumulation indicated mitochondrial dysfunction and FAO increase. CONCLUSION Osthole could block lipid metabolic reprogramming through functional modulating the expression of fatty acid translocase, fatty acid synthase, phospholipase A2, carnitine palmitoyltransferase 1A to inhibit C10:2, thus to improve mitochondrial dysfunction and inhibit utilizing lipid to biosyn?thesize necessary essence for pulmonary artery smooth muscle cells (PASMCs) proliferation. Moreover, we delineated that C10:2 and metabolic reprogramming enzymes were modulated by miRNA-22-3p which was involved in PASMCs proliferation and pulmonary vascular remodeling. Therefore, osthole inhibited miRNA-22-3p mediated lipid metabolic reprogramming to ameliorate pulmonary vascular remodeling.

Identification of phosphatidic acid interacting proteins in Ganoderma lingzhi / 生物工程学报

Ganoderma lingzhi is widely recognized as a medicinal basidiomycetes. Triterpene acids (TAs) are the key bioactive medicinal components of G. lingzhi. Our previous studies have shown that phospholipid acid (PA) produced by phospholipase D (PLD) plays a regulatory role in TA synthesis. In order to further elucidate the molecular mechanism how PA regulates TA synthesis in G. lingzhi, PA beads enrichment combined with LC-MS/MS technology was used to identify PA interacting proteins in G. lingzhi. A total of 19 PA interacting proteins were identified, including cytochrome P450 monooxygenase (GL22084), specific protein kinase MAPK (GL23765), catalase and cell surface hydrophobicity-associated protein. GST tagged GL22084 and GL23765 proteins were obtained through gene cloning, heterologous expression, and purification. The interactions between GL22084/GL23765 and PA were verified by GST pull down assay. The identification of PA interacting proteins provides a basis for further understanding the molecular mechanism how PLD-mediated PA signaling molecules regulates the TA synthesis in G. lingzhi. Moreover, the PA interacting proteins identified in this study can also provide clues for the research of PLD/PA signaling pathway in other species.

Protective effects of naringin phospholipid complex on oxidative injury in ARPE-19 cells associated with activation of Nrf2 pathway / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To investigate the protective effects of naringin(Nar)phospholipid complex(NPC)on oxidative injury in retinal pigment epithelium cells(ARPE-19 cells)induced by tert-butyl hydroperoxide(t-BHP)and elucidate the underlying mechanism.<p>METHODS:The NPC was prepared by solvent method. Experimental cells are divided into seven groups: control group \〖cultured with dimethylsulfoxide(DMSO)\〗, model group(intervention with 200μmol/L t-BHP), nuclear factor erythroid 2-related factor 2(Nrf2)-siRNA group(cell transfection for Nrf2 gene), naringin group(add 200μmol/L t-BHP after pretreatment with 200μmol/L naringin medium), NPC group(add 200μmol/L t-BHP after pretreatment with 200μmol/L NPC medium), Nrf2-siRNA+ naringin group(after 200μmol/L naringin pretreatment, Nrf2 gene interference, then add 200μmol/L t-BHP)and Nrf2-siRNA+ NPC group(after 200μmol/L NPC pretreatment, Nrf2 gene interference, then add 200μmol/L t-BHP). The intracellular levels of superoxide dismutase(SOD), malondialdehyde(MDA)and total antioxidant capacity(T-AOC)were detected, intracellular level of reactive oxygen species(ROS)was detected by DCFH-DA staining method. The mRNA and protein expressions of HO-1, NQO-1, GCL and Nrf2 were detected by real-time PCR and western blot, respectively. <p>RESULTS:NPC more significantly increased the levels of SOD and T-AOC, reduced the contents of ROS and MDA than naringin in t-BHP-treated ARPE-19 cells. After naringin and NPC pre-protected ARPE-19 cells, the relative expression and protein expression of Nrf2, HO-1, NQO-1 and GCL mRNA were higher than those of the model group and Nrf2-siRNA group. There were statistically significant differences in the relative expression of 4 genes and the expression levels of 4 proteins in the naringin group and the NPC group, the Nrf2-siRNA+naringin group and the Nrf2-siRNA+NPC group. The expression of Nrf2, HO-1 and NQO-1 protein in the Nrf2-siRNA+naringin group was not significantly different than that in the Nrf2-siRNA group. Compared with the Nrf2-siRNA group, the expression of 4 proteins in the Nrf2-siRNA+NPC group was statistically significant, and the effect of NPC was significantly stronger than that of naringin.<p>CONCLUSION: After naringin forms a phospholipid complex, it can significantly increase the antioxidant capacity in cells and reduce the oxidation level. It up-regulates the expression of Nrf2 and its downstream antioxidant enzymes and phase Ⅱ detoxification enzymes by activating the Nrf2/ARE antioxidative stress pathway to better protect ARPE-19 cells from oxidative damage.

Manifestaciones relacionadas con alteraciones en la coagulación en lupus eritematoso sistémico de inicio juvenil. Reporte de casos y revisión de la literatura / Manifestations related to alterations in coagulation in systemic lupus erythematosus of juvenile onset. Case report and literature review

RESUMEN Las alteraciones hematológicas son comunes en los pacientes con lupus eritematoso sistémico (LES). Pueden expresarse relacionadas con el compromiso de las líneas celulares y con la presencia de alteraciones de la coagulación. El compromiso en la coagulación se asocia con manifestaciones trombóticas. Se han descrito factores de riesgo asociados a trombosis, como la presencia de niveles elevados de homocisteína, déficit adquirido de la proteína S, proteína C y antitrombina. Sin embargo, la diátesis hemorrágica también se ha descrito con menor frecuencia y relacionada con el déficit de factores de la coagulación, secundaria a la presencia de inhibidores. Presentamos 3 pacientes con LES juvenil con manifestaciones hematológicas poco usuales y revisión de la literatura relacionada. Se concluye que las manifestaciones hematológicas en LES juvenil no solo se relacionan con alteraciones en las líneas celulares. Trombosis vasculares y trastornos hemorrágicos deben sospecharse. El diagnóstico precoz y el tratamiento temprano disminuyen la morbimortalidad relacionada con este tipo de manifestaciones.

ABSTRACT Haematological alterations are common in patients with systemic lupus erythematosus (SLE). These haematological manifestations may be expressed related to the involvement of cells affected and coagulation changes. The compromise in coagulation is associated with thrombotic manifestations. Risk factors associated with thrombosis have been described, such as the presence of elevated levels of homocysteine, acquired deficit of protein S, protein C, and antithrombin. However, the haemorrhagic diathesis has also been described at a lower frequency and related to the acquired deficiency of coagulation factors caused by the development of autoantibodies directed against coagulation factors. The cases are presented of 3 patients with juvenile SLE with unusual haematological manifestations, as well as a review of the literature in relation to them. The haematological manifestations in juvenile SLE are not only related to alterations in cell lines, vascular thrombosis and bleeding disorders should also be suspected. Early diagnosis and treatment reduces morbidity and mortality related to this type of manifestations.

Effect of Phospholipid Composition on Intradermal Delivery of Fluorescent Modified Cyclodextrin Liposomes / 中国药学杂志

OBJECTIVE: To compare the intradermal delivery effects of composite phospholipid liposomes composed of different proportions of soy phospholipids (SPC) and hydrogenated soy phospholipids (HSPC) on the fluorescent modified hydroxypropyl-β-cyclodextrin(HP-β-CD), and to optimize the phospholipid composition with the best skin retention. METHODS: The fluorescent probe, fluorescein isothiocyanate (FITC), was combined with HP-β-CD to prepare fluorescent modified cyclodextrin FITC-HP-β-CD. FITC-HP-β-CD was encapsulated in different composite phospholipid liposomes. The amount of the permeation in the receiving solution and skin retention of the cyclodextrin after 10 h were determined in the in vitro intradermal delivery experiment. RESULTS: The order of cyclodextrin permeation of liposomes in the receiving solution was SPC > S/H (3:1) > S/H (1:1) > S/H (1:3) > HSPC >FITC-HP-β-CD, while the order of cyclodextrin intradermal retention was S/H (1:1) > S/H (1:3) > HSPC > S/H (3:1) > SPC > FITC-HP-β-CD. CONCLUSION: Using SPC to prepare liposomes is more beneficial to promote the permeation of FITC-HP-β-CD into the skin than HSPC, but the addition of HSPC can increase the skin retention of FITC-HP-β-CD. The S/H(1:1) liposomes have the better intradermal delivery effect on the fluorescent modified cyclodextrin, of which the skin retention effect is the best.

Development of liquiritigenin-phospholipid complex with the enhanced oral bioavailability / 中国天然药物

In the present study, liquiritigenin-phospholipid complex (LPC) was developed and evaluated to increase the oral bioavailability of liquiritigenin. A single-factor test methodology was applied to optimize the formulation and process for preparing LPC. The effects of solvent, drug concentration, reaction time, temperature and drug-to-phospholipid ratio on encapsulation efficiency were investigated. LPCs were characterized by UV-visible spectroscopy, differential scanning calorimetry (DSC), fourier transform infrared spectroscopy (FTIR), and powder X-ray diffractometry (PXRD). The apparent solubility and n-octanol/water partition coefficient were tested. The pharmacokinetic characteristics and bioavailability of the LPC were investigated after oral administration in rats in comparison with liquiritigenin alone. An LPC was successfully prepared. The optimum level of various parameters for liquiritigenin-phospholipid complex was obtained at the drug concentration of 8 mg·mL

Effects of salidroside on structure and function of erythrocyte membrane in high altitude polycythemia rats / 中草药

Objective: To investigate the effects of salidroside on the structure and function of erythrocyte membrane in rats with high altitude polycythemia (HAPC), and to provide the scientific basis for the mechanism of salidroside preventing and treating HAPC. Methods: A total of 40 Wistar rats were randomly divided into five groups, control group, HAPC model group, salidroside high-dose (200 mg/kg), medium-dose (100 mg/kg), and low-dose (50 mg/kg) groups, four female and four male rats in each group. In addition to the control group, the remaining four groups established the HAPC model. The rats in the control group and model group were ig administered with saline, and rats in salidroside group were treated with different doses of salidroside at the same time. The dosage volume was 10 mL/kg, and once a day for 40 d. After the administration, blood was collected from femoral artery of the rats. Biochemical and enzyme-linked immunoassay were used to determine the lipid fluidity of erythrocyte membrane, total cholesterol content, total phospholipids content, the content of phospholipid components including phosphatidic acid (PA), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), the activity of Na+, K+-ATPase and Ca2+, Mg2+-ATPase on erythrocyte membrane, and the concentrations of Na+ and Ca2+ in erythrocyte. Results: Salidroside can significantly improve the lipid fluidity, total phospholipids, PA, PC, PE, and PS content of erythrocyte membrane, and improve the activity of Na+, K+-ATPase and Ca2+, Mg2+-ATPase of erythrocyte membrane in HAPC rats. Total cholesterol content on erythrocyte membrane, and the concentrations of sodium and calcium in erythrocyte were significantly reduced. Conclusion: These findings suggested that salidroside can improve the function of erythrocyte membrane and cell metabolic activities by regulating the lipid composition of erythrocyte membrane, thereby alleviating the symptoms associated with high altitude polycythemia.