Aqueous extract of Epimedium sagittatum (Sieb. et Zucc.) Maxim. induces liver injury in mice via pyroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Epimedium sagittatum (Sieb. et Zucc.) Maxim. has been used traditionally in Asia. It can dispel wind and cold, tonify the kidney, and strengthen bones and tendons. However, adverse effects of E. sagittatum have been reported, and the underlying mechanisms remain unclear. AIM OF THE STUDY: This study aimed to investigate liver injury caused by an aqueous extract of E. sagittatum in Institute of Cancer Research (ICR) mice and explore its potential mechanisms. MATERIALS AND METHODS: Dried E. sagittatum leaves were decocted in water to prepare aqueous extracts for ultra-high performance liquid chromatography analysis. Mice were administered an aqueous extract of E. sagittatum equivalent to either 3 g raw E. sagittatum/kg or 10 g raw E. sagittatum/kg once daily via intragastric injection for three months. The liver weights and levels of the serum biochemical parameters including alanine transaminase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), total bilirubin (TBIL), and alkaline phosphatase were measured. Hematoxylin-eosin staining was performed for histopathology. Apoptosis was detected using the TUNEL apoptosis assay kit. IL-1ß was detected using ELISA kits. Proteomics was used to identify the differentially expressed proteins. Western blot analysis was performed to determine the levels of proteins significantly affected by the aqueous extract of E. sagittatum. RESULTS: E. sagittatum treatment increased the liver weights and liver coefficients, and ALT and AST levels significantly increased (p < 0.05). A high dose of E. sagittatum significantly increased LDH and TBIL levels (p < 0.05). Ruptured cell membranes and multiple sites of inflammatory cell infiltration were also observed. No evidence of apoptosis was observed. IL-1ß levels were significantly increased (p < 0.05). The expressions of PIK3R1, p-MAP2K4, p-Jun N-terminal kinase (JNK)/JNK, p-c-Jun, VDAC2, Bax, and CYC were upregulated, whereas that of Bcl-2 was inhibited by E. sagittatum. The expression of cleaved caspase-1 was significantly increased; however, its effects on GSDMD and GSDMD-N were significantly decreased. The expression levels of cleaved caspase-3 and its effector proteins GSDME and GSDME-N significantly increased. CONCLUSIONS: Our results suggest that the aqueous extract of E. sagittatum induces liver injury in ICR mice after three months of intragastric injection via inflammatory pyroptosis.

Gypenoside XVII attenuates renal ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress and NLRP3 inflammasome-triggered pyroptosis.

BACKGROUND: Renal ischemia-reperfusion (I/R) is one of the main causes of acute kidney injury (AKI), for which there is currently no effective treatment. Recently, the interaction between endoplasmic reticulum (ER) stress and pyroptosis during AKI has been investigated. AIM: The purpose of this study was to investigate the protective effects of Gypenoside XVII (GP-17) against I/R-induced renal injury. METHODS: In this study, mice were divided into 6 groups, sham group, I/R group, GP-17 low-, medium-, high-dose group, and positive control 4-PBA group. The renal I/R was performed in mice by clamping the bilateral renal pedicles for 40 min, and then reperfusing for 24 h. Blood and kidney samples were collected for analysis. RESULTS: The results showed that GP-17 improved renal function and alleviated renal histopathological abnormalities caused by I/R. In addition, GP-17 pretreatment significantly decreased the expression or phosphorylation of ER stress response proteins including BIP, p-PERK, and CHOP. Besides, GP-17 inhibited the expression of pyroptosis proteins including caspase-1, GSDMD, and apoptotic protein BAX. The inflammatory factor IL-1ß in these GP-17 pretreatment groups was also significantly reduced. CONCLUSION: GP-17 blocked NLRP3 inflammasome activation by inhibiting ERS, thereby inhibiting renal tubular cell pyroptosis and apoptosis, and prevented renal I/R injury.

Untargeted metabolomics analysis of Gannan navel orange at different storage periods under room temperature using HS-SPME-GC-MS and UPLC-Q-TOF/MS.

Navel orange remains metabolized continuously during postharvest storage, but few studies have monitored the changes of these metabolites. Therefore, HS-SPME-GC-MS and UPLC-Q-TOF/MS were used to comprehensively investigate the dynamic changes of the components of Gannan navel orange during storage at room temperature. A total of 62 volatile components and 68 non-volatile components were identified. Principal Component Analysis and Partial Least Squares Discriminant Analysis showed that navel orange under different storage periods were clearly distinguished. Combined with VIP > 1 and p < 0.05, 19 volatile and 27 non-volatile differential metabolites were obtained. KEGG enrichment analysis revealed that flavonoid biosynthesis (map00941) was the primary metabolic pathway. The middle storage period had a higher antioxidant enzyme activity, but the malondialdehyde content was the opposite. These results reveal the changes of postharvest components of Gannan navel orange, providing a theoretical basis for the storage and product development of navel orange.

Exploring Effects and Mechanism of Ingredients of Herba Epimedii on Osteogenesis and Osteoclastogenesis In Vitro.

BACKGROUND: Herba Epimedii, a commonly used traditional herb, has been proven effective in ameliorating osteoporosis. However, the active ingredients and potential mechanism need further exploration. OBJECTIVE: To screen active ingredients of Herba Epimedii with the effect of ameliorating osteoporosis and to explore their potential mechanisms. METHODS: TCMSP and Swiss Target Prediction were applied to collect the ingredients of Herba Epimedii and their targets. UniProt, GeneCards, TTD, DisGeNET, and OMIM were adopted to search osteoporosis-related genes. STRING and DAVID were used to perform enrichment analysis. Effects of screened ingredients were evaluated on MC3T3-E1 cells and RAW264.7 cells, respectively. RESULTS: Eleven ingredients were screened by Network Pharmacology. They exerted a promoting effect on MC3T3-E1 cells (10-9-10-5 M). The ingredients didn't significantly affect ALP activity and osteoblastogenesis-related genes. Baohuoside 1, Sagittatoside B, Chlorogenic acid, Cryptochlorogenic acid, and Neochlorogenic acid significantly increased calcium depositions. The ingredients didn't exhibit a dose-dependent inhibition or promotion on RAW264.7 cells. Baohuoside 1, Sagittatoside B, Neochlorogenic acid, Cryptochlorogenic acid, Icariin, Epimedin A, Chlorogenic acid, Sagittatoside A, and Epimedin C suppressed the level of TRACP. Baohuoside 1, Sagittatoside B, Cryptochlorogenic acid, Neochlorogenic acid, Chlorogenic acid, Sagittatoside A, and Icariin decreased the number of multinucleated osteoclastic cells. Baohuoside 1, Sagittatoside B, and Cryptochlorogenic acid could significantly inhibit MMP-9 expression. CONCLUSION: Neochlorogenic acid, Sagittatoside B, Chlorogenic acid, and Cryptochlorogenic acid promoted MC3T3-E1 differentiation, among which Neochlorogenic acid showed significant promotion in viability, mineralization, and OPN expression. Baohuoside 1, Sagittatoside B, Cryptochlorogenic acid, Neochlorogenic acid, Chlorogenic acid, and Icariin inhibited RAW264.7 differentiation, among which Baohuoside 1 showed significant inhibition on TRACP, multinucleated osteoclastic cells number and MPP-9 expression. The mechanism might relate to the FoxO signaling pathway, MAPK signaling pathway, and TNF signaling pathway.

Global research hotspots and trends in exercise interventions for rheumatoid arthritis over the past two decades: A bibliometric and visualization study.

Rheumatoid arthritis (RA) is a prolonged multifactorial autoimmune disease of unknown etiology. With the global population aging, the incidence of RA is increasing, highlighting the need for more effective treatments. Exercise interventions have been recognized as safe and effective for managing pain, improving function, and reducing fatigue in RA patients. However, the existing literature in this field lacks a thorough, organized, and clear line of analysis. In this study, we conducted a comprehensive analysis of the 20-year literature on exercise interventions for RA, aiming to identify hotspots and cutting-edge trends. Our objective is to provide subsequent researchers with valuable ideas and references. Using Cite Space, VOS viewer, and R-bibliometrix software for visualization and analysis, we compiled the main dataset from the web of science database, consisting of 1790 articles on exercise interventions in RA published between 2000 and 2023. Among these articles, the United States contributed the highest number of papers (433), while Karolinska Institutet ranked first institutionally with 90 papers. The study focused on the keyword's quality of life, cardiovascular disease, aerobic exercise, social support, psychology, and multidisciplinary care. The research highlighted the importance of clinical efficacy studies that investigate different types of exercise modalities (cardiorespiratory aerobic, resistance, aquatic, and neurological) either alone or in combination, to improve pain and function and reduce cardiovascular disease risk in patients with RA. Additionally, sedentary behavior, fatigue, and multidisciplinary care were identified as potential areas for further research. Overall, this study provides a scientific perspective on exercise interventions for RA and offers valuable insights for academics, funding organizations, and policymakers.

Effects of lumbar-pelvic training combined with electroacupuncture on chronic nonspecific low back pain.

This observational study was conducted to investigate the effect of lumbar-pelvic training (LP) combined with electroacupuncture (EA) in the treatment of chronic nonspecific low back pain. One hundred and twenty patients diagnosed with chronic nonspecific low back pain were evenly randomized to receive the following 4 treatments for 2 weeks: LP combined with EA (Group A), EA (Group B), LP (Group C) or no intervention (Group D). The LP was a self-developed training program containing 5 movements and was conducted three times a week to build up the strength of abdomen muscle groups. Four acupoints along the foot-taiyang bladder meridian and the governor vessel were chosen for EA five times a week based on the theory of Traditional Chinese Medicine. The Visual Analog Scale and Oswestry Disability Index were measured before and after treatment to assess the reduction of pain intensity and functional disability, respectively. Following the treatments, Visual Analog Scale and Oswestry Disability Index scores in all 3 intervention groups were significantly lower than those in the Group D without intervention (P < .01). Among the intervention groups, Group A's scores were lower than those of Group B or Group C (P < .01). The overall efficacy of Group A was 93.33%, which was higher than that of Group B (76.67%) and Group C (70.00%) (P < .01). In conclusion, this study suggest that our self-developed lumbar-pelvic training combined with electroacupuncture is effective for chronic nonspecific low back pain in terms of pain and disability reduction.

Celastrol assuages oxygen-glucose deprivation and reoxygenation-induced damage in human brain microvascular endothelial cells through the circDLGAP4/miR-6085/GDF11 pathway.

The effect of Celastrol on cerebral ischemia-reperfusion remains unknown. The study aims to explore the role of circular RNA DLGAP4 (circDLGAP4) in cerebral ischemia-reperfusion and the underlying mechanism. Ischemia-reperfusion (I/R) injury of human brain microvascular endothelial cells (HBMECs) was induced by oxygen-glucose deprivation and reoxygenation (OGD/R). Reverse transcription quantitative real-time PCR (RT-qPCR) and western blotting analysis were performed to detect the expression of circDLGAP4, microRNA-6085 (miR-6085), growth differentiation factor 11 (GDF11), B-cell lymphoma-2 (BCL2) and BCL2-associated x protein (BAX). Cell viability, proliferation, and apoptosis were analyzed by cell counting kit-8, 5-Ethynyl-2'-deoxyuridine and flow cytometry analysis. Oxidative stress was analyzed by evaluating the levels of Malondialdehyde (MDA) and Reactive Oxygen Species (ROS) and the activity of Superoxide Dismutase (SOD). The associations among circDLGAP4, miR-6085 and GDF11 were identified by dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays. Celastrol reduced OGD/R-induced inhibition of circDLGAP4 expression in HBMECs. Celastrol treatment protected HBMECs from OGD/R-induced cell proliferation inhibition and apoptosis and oxidative stress promotion; however, circDLGAP4 depletion attenuated these effects. CircDLGAP4 acted as a sponge for miR-6085, and miR-6085 mimics restored circDLGAP4-mediated effects in OGD/R-stimulated HBMECs. In addition, GDF11 was identified as a targte of miR-6085, and participated in the regulation of miR-6085 to OGD/R-induced HBMEC damage. Further, circDLGAP4 absence inhibited GDF11 expression by interacting with miR-6085 under Celastrol treatment. Celastrol ameliorated OGD/R-induced HBMEC apoptosis and oxidative stress by circDLGAP4/miR-6085/GDF11 pathway, supporting the use of Celastrol as a therapeutic agent for cerebral infarction.

Sub-chronic toxicity of an aqueous extract of Epimedium sagittatum (Sieb. Et Zucc.) Maxim. in rats.

Epimedium sagittatum (Sieb. et Zucc.) Maxim., a traditional medicinal plant in Asia, is widely used in clinical settings but its safety in vivo is unclear. This study investigated the sub-chronic toxicity of E. sagittatum aqueous extract to rats with a 13-week daily intragastric administration of 7.5, 15, or 30 g/kg. Nine constituents of the aqueous extract were identified by ultra-performance liquid chromatography (UPLC). Organ weights, organ coefficients, serum biochemistry parameters, histopathology, and metabolomic analysis were performed. In female rats, treatment increased the liver, thymus, and adrenal gland coefficients (p < 0.05). Liver, pancreas, and adrenal gland injury were observed. The levels of six metabolites were altered by the treatment (p < 0.05). In male rats, treatment altered liver, heart, and thymus coefficients (p < 0.05) and liver, adrenal gland, and heart injury were observed. The levels of 11 metabolites were altered (p < 0.05). The no-observed-adverse-effect level was not determined but would be below 7.5 g/kg in rats treated for 13 weeks. In female rats, E. sagittatum may injure the liver and pancreas and dysregulate the biosynthesis of phenylalanine, tyrosine, tryptophan, valine, leucine, and isoleucine and the metabolism of phenylalanine. In male rats, the extract may injure the liver and adrenal gland and dysregulate the biosynthesis of valine, leucine, and isoleucine and the metabolism of pyruvate.

Isobavachalcone disrupts mitochondrial respiration and induces cytotoxicity through ROS accumulation and Akt suppression.

Isobavachalcone (IBC) is one of the flavonoid components in Fructus Psoraleae, and has been found multiple pharmacological effects. However, the hepatotoxicity of IBC has been overlooked and not been carefully studied. We aim to find out the cytotoxicity of IBC on HepG2 cells, and explore the underlying mechanisms. HepG2 cells were treated with IBC for 24 h, then MTT assay and LDH assay were used to detect the cell viability. The apoptosis and reactive oxygen species (ROS) production were reflected by the flow cytometry. Using Seahorse Analyzer, we measured the mitochondrial respiratory capacity. The expression of oxidative stress and mitochondrial apoptosis-related proteins were determined by Western blot. The results showed that IBC induced the cell death and apoptosis of HepG2 cells. IBC initiated the accumulation of ROS in cells and impaired the mitochondrial function, triggered apoptosis and suppressed the phosphorylation of Akt. Additionally, scavenging ROS by the antioxidant N-acetyl-l-cysteine (NAC) reduced IBC-induced mitochondria damage and increased Akt phosphorylation. Taken together, IBC caused mitochondrial damage and induced hepatotoxicity by ROS accumulation and Akt suppression. Targeting oxidative stress and depressing mitochondrial damage may provide a theoretical basis for the treatment and prevention of IBC-induced hepatotoxicity in clinic.

Cardioprotective effects of gypenoside XVII against ischemia/reperfusion injury: Role of endoplasmic reticulum stress, autophagy, and mitochondrial fusion fission balance.

Gypenoside XVII (GP-17), a tetracyclic triterpene saponin isolated from the functional food Gynostemma pentaphyllum, has been demonstrated protective effects against cerebrovascular and cardiovascular diseases on multiple disease models. In this study, we established a myocardial infarction (MI) model by ligating the left anterior descending coronary artery, and explored whether GP-17 prevent myocardial ischemia/reperfusion (I/R) injuries in mice. Compared with the I/R group, GP-17 significantly improved the cardiac function, reduced the MI, decreased myocardial pathology, activated superoxide dismutase and catalase, and reduced the content of lactate dehydrogenase, creatine kinase, malondialdehyde, and inflammatory factor. The proteomic analysis showed multiple differential proteins between the GP-17 and I/R groups enriched in endoplasmic reticulum and mitochondria. Western-Blot showed that GP-17 significantly decreased the expression of GRP78, ATF6, CHOP, and phosphorylation of PERK, indicating the inhibition of ERS. GP-17 inhibited the expression of ATG5, LC3A/B, and BAX, illustrating the suppression of autophagy and apoptosis. Moreover, both GP-17 and 4-PBA could improve the downregulated Mfn2, meaning that inhibition of ERS regulated the mitochondrial fusion fission balance, thus protected the function of mitochondria. In conclusion, we found that GP-17 prevented against myocardial I/R injury by inhibit ERS-induced cell apoptosis, autophagy, oxidative stress, and mitochondrial division.

Rapid and One-Step Screening of Taxane Compounds by a Two-Dimensional Carbon Microfiber Fractionation System Combined with Tandem Mass Spectrometry.

Taxane compounds have attracted wide attention due to the basic chemical structure of taxol as an alternative anticancer drug. The full-scan tandem mass spectrometry (MS/MS) fragmentation behaviors of seven taxane compounds were studied. For taxanes of Sc-T and Sc-T-Xyl types, diagnostic product ions are originated from a cleavage in the ester bond of the C13 position and the C-O bond of the C7 position, and the subsequent fragmentation pattern is similar to those of M-type taxanes with the loss of different numbers of acetic acid moieties (AcOH), benzoic acid moieties (BzOH), and H2O molecules. A rapid (7 min) and one-step screening method of two-dimensional microscale carbon fiber and active carbon fiber columns combined with tandem mass spectrometry (2DµCFs-MS/MS) was developed for the screening of taxane compounds from Taxus cuspidata samples. Before MS/MS analysis, the 2DµCFs system can group the sample extract without any pretreatment into three chromatographic-type fractions of strong, medium, and weak polarity to avoid matrix interference, such as lipids and pigments. The 2DµCFs-MS/MS can also conduct qualitative and quantitative analysis of taxane compounds, which is evaluated by limits of detection ranging from 3 to 50 ng mL-1, limits of quantitation ranging from 10 to 150 ng mL-1, satisfactory recoveries from 75.2 to 112.2%, and reproducibilities with relative standard deviations from 1.4 to 11.7%.

Psoralen induces liver injuries through endoplasmic reticulum stress signaling in female mice.

Psoralen is the main coumarin component of Fructus psoraleae. Previously, we have found that psoralen induced hepatocytes apoptosis via PERK and ATF6 related ER stress pathways in vitro. In this study, we investigated the toxicity and ER stress induced by psoralen in female C57 mice. Mice were fed with 80 mg/kg of psoralen intra-gastrically for either 3, 7, or 21 days. Liver and kidney were weighed and their coefficients were calculated. The serum was isolated to examine the biochemical parameters including alanine aminotransferase (ALT) activity, aspartate aminotransferase (AST) activity, alkaline phosphatase (ALP) activity, blood urea nitrogen (BUN), total bile acid (TBA), total bilirubin (TBIL), and creatinine (CRE). The transcription and expression of ER stress-related markers were determined by Wes-automated Protein Simple system, Western blot and RT-PCR. Psoralen administration for 3 days significantly increased liver coefficients but decreased kidney coefficients of mice. Histopathological examination showed minimal inflammatory cell foci and vacuolar degeneration in the liver. Besides, serum levels of ALT, TBA, BUN, and CRE were markedly altered by psoralen. Moreover, psoralen significantly increased expression and transcription levels of ER stress related markers, including Grp78, PERK, eIF2α, ATF4, IRE1α, ATF6, and XBP1. These results illustrated that psoralen induced liver injuries through ER stress signaling in female mice.

Gypenoside XVII protects against myocardial ischemia and reperfusion injury by inhibiting ER stress-induced mitochondrial injury.

BACKGROUND: Effective strategies are dramatically needed to prevent and improve the recovery from myocardial ischemia and reperfusion (I/R) injury. Direct interactions between the mitochondria and endoplasmic reticulum (ER) during heart diseases have been recently investigated. This study was designed to explore the cardioprotective effects of gypenoside XVII (GP-17) against I/R injury. The roles of ER stress, mitochondrial injury, and their crosstalk within I/R injury and in GP-17-induced cardioprotection are also explored. METHODS: Cardiac contractility function was recorded in Langendorff-perfused rat hearts. The effects of GP-17 on mitochondrial function including mitochondrial permeability transition pore opening, reactive oxygen species production, and respiratory function were determined using fluorescence detection kits on mitochondria isolated from the rat hearts. H9c2 cardiomyocytes were used to explore the effects of GP-17 on hypoxia/reoxygenation. RESULTS: We found that GP-17 inhibits myocardial apoptosis, reduces cardiac dysfunction, and improves contractile recovery in rat hearts. Our results also demonstrate that apoptosis induced by I/R is predominantly mediated by ER stress and associated with mitochondrial injury. Moreover, the cardioprotective effects of GP-17 are controlled by the PI3K/AKT and P38 signaling pathways. CONCLUSION: GP-17 inhibits I/R-induced mitochondrial injury by delaying the onset of ER stress through the PI3K/AKT and P38 signaling pathways.

Human epididymis protein 4: a novel predictor of ischemic cardiomyopathy.

BACKGROUND: The prognostic value of human epididymis protein 4 (HE4) in patients with ischemic cardiomyopathy (ICM) is unknown. METHODS: A total of 103 patients with ICM were prospectively enrolled in this study from Hunan Provincial People's Hospital between February 2019 and June 2019. All patients were tested for HE4 levels at baseline and follow-up. Endpoints of the study included cardiovascular death and heart failure-related hospitalization. RESULTS: A total of 96 patients with ICM were included for analysis. After a mean follow-up period of 263 (153-313) days, cardiovascular events were observed in 45 patients. Serum HE4 levels in patients with events were significantly higher than those in patients without events [188.70 (113.35-326.82) pmol/L versus 92.90 (61.50-123.20) pmol/L, P < 0.001]. Multivariate Cox regression analysis revealed that HE4 [χ2: 9.602, hazard ratio (HR): 1.003, 95% confidence interval (CI): 1.001-1.005, P = 0.002] and age [χ2: 4.55, HR: 1.044, 95% CI: 1.003-1.085, P = 0.033] were independent predictors of events. After adjusting for age and sex, the risk of events in patients with HE4 > 100.2 pmol/L was higher than that in patients with HE4 ≤ 100.2 pmol/L [HR: 3.372, 95% CI: 1.409-8.065, P < 0.001]. CONCLUSION: HE4 is an independent predictor of cardiovascular death and heart failure-related rehospitalization in patients with ICM.

Development and validation of a sensitive UHPLC-MS/MS method for the measurement of ß-elemonic acid in rat plasma and tissues and its application to pharmacokinetics and tissue distribution study.

ß-Elemonic acid is one of the main active ingredients isolated from Boswellia carterii Birdw. which has been reported to exhibit potential anti-inflammatory and anti-cancer activities. There is few information about pharmacokinetics and tissue distribution of ß-elemonic acid by now. In this study, an ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC-MS/MS) method has been developed and validated to determine ß-elemonic acid in rat plasma and various tissues after intragastric administration. Oleanolic acid was chosen as an internal standard (IS) and the plasma/tissue samples were pretreated with one-step liquid-liquid extraction. Chromatographic separation was accomplished on Eclipse Plus C18 analytical column (2.1 × 50 mm, 1.8 µm) utilizing a gradient mobile phase system consisting of water (with 0.1% ammonia-solution) and acetonitrile. ß-Elemonic acid and IS were detected and quantified using negative electrospray ionization in multiple reaction monitoring (MRM) mode with transitions of m/z 453.3 â†’ 423.5 for ß-elemonic acid and m/z 455.3 â†’ 407.6 for IS. ß-Elemonic acid showed good linearity over the investigated concentration range (r > 0.9934) in rat plasma and tissue sample. The method was successfully applied for determination of ß-elemonic acid in bio-samples. A bimodal phenomenon appeared in the plasma concentration-time curve of the ß-elemonic acid. The highest tissue concentrations were found in the intestine including jejunum, ileum and colon.

Simultaneous characterization of multiple Psoraleae Fructus bioactive compounds in rat plasma by ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry for application in sex-related differences in pharmacokinetics.

A method for the simultaneous quantification of 13 bioactive compounds (psoralen, isopsoralen, isobavachin, bakuchalcone, neobabaisoflavone, bavachin, corylin, psoralidin, isobavachalcone, bavachinin, corylifol A, bavachalcone, and bakuchiol) by ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry has been developed and validated in rat plasma. Osthol was used as an internal standard and plasma samples were pretreated with one-step liquid-liquid extraction. These analytes were separated using a gradient mobile phase system of water and acetonitrile at a flow rate of 0.2 mL/min on a reverse-phase C18 column and analyzed in the selected multiple reactions monitoring mode. All calibration curves were linear (r > 0.9952) over the tested ranges. The intra- and interday accuracy and precisions of these analytes at three different concentration levels were within the acceptable limits of <15% at all concentrations. The mean recoveries of these analytes at three concentrations were more than 60.2% and the matrix effects were in the range of 85-115%. Stability studies proved that the analytes were stable under the tested conditions. The developed method was applied to evaluating the pharmacokinetic study of 13 bioactive compounds after oral administration of Psoraleae Fructus in rat of different genders. Some active compounds in Psoraleae Fructus had sex-related pharmacokinetics.

The Accumulation of Psoralen Contributes to Its Hepatotoxicity Revealed by Pharmacokinetic and Toxicokinetic Study after Repeated Administration.

Psoralen is a furanocoumarin compound found in many herb medicines and is claimed to contribute to the hepatotoxicity caused by lots of traditional Chinese medicine. So far, there has been no research on the differences in pharmacokinetics of single and repeated dosing of psoralen. Moreover, the research on the cumulative toxicity of low concentration and long-term administration on cells has not been reported. Therefore, this study investigated the pharmacokinetic differences and the accumulated cytotoxicity of psoralen from repeated administration. The study found that after single or repeated administration of psoralen for 3 months at various dosages (14, 28, and 56 mg/kg), the pharmacokinetic parameters of female rats between single dose and repeated dose administration are totally different. Compared with a single administration, multiple administrations increased psoralen's in vivo exposure, prolonged the peak time, prolonged the half-life of the drug, reduced the drug clearance rate, and prolonged the drug's stay in the body. HepG2 cells were exposed to low doses (5, 10, 20, or 40 µM) of psoralen for 1, 2, 3, or 4 days. A 20 and 40 µM dose of psoralen did not induced cell death in the 1st day but significantly decreased the cell viability at the 3rd and 4th day of repeated administration, respectively. In addition, multiple administrations of psoralen decreased cell viability due to G2 arrest.

Profiling Aerosol Liquid Water Content Using a Polarization Lidar.

Aerosol liquid water content (ALWC) plays fundamental roles in atmospheric radiation and chemical processes. However, there is little information about ALWC vertical distribution due to the lack of sufficient measurement. In this study, a novel method to retrieve ALWC using a polarization lidar is proposed. By analyzing lidar measurement combined with in situ chemical composition measurements at the surface, the particle linear depolarization ratio δp is found to be well correlated with the liquid water mass fraction. The method is built upon a valid relationship between δp and the ratio of ALWC to the particle backscatter coefficient. ALWC can be retrieved with a relative error of 30% with this method. A case study shows that the ALWC in upper levels of the boundary layer may be different from that at the ground, suggesting the importance of measuring ALWC vertical profiles during haze episodes. The study proves that polarization lidars have the potential to retrieve vertical distributions of ALWC which will benefit studies on haze formation.

Psoralen induces hepatic toxicity through PERK and ATF6 related ER stress pathways in HepG2 cells.

Psoralen has potential hepatotoxicity and has a certain promoting effect on the clinical liver injury of Psoralea corylifolia L (Fructus Psoraleae). This study investigated the underlying mechanisms of psoralen-induced hepatotoxicity in vitro. HepG2 cells were treated with psoralen for 6, 12, 24, or 48 h, and an endoplasmic reticulum (ER) stress-specific inhibitor, 4-PBA, was employed to investigate the mechanism of psoralen on ER stress and unfolded protein response (UPR). Cell viability was tested by MTT assay, ATP assay, and cell death by LDH. The apoptosis was reflected by the flow cytometry, caspase-8, and caspase-3 activates. The expression of ER stress-related markers was determined by RT-PCR and western blot. We found that psoralen significantly decreased cell viability, increased activities of caspase-8 and caspase-3, and upregulated expression of CHOP and BAX in a time- and dose-dependent manner. Moreover, psoralen significantly increased the expression and transcription levels of ER stress-related markers, including Grp78, PERK, eIF2α, ATF4, and ATF6, while IRE1α was not significantly affected. And 4-PBA could effectively inhibit psoralen-induced cell death and apoptosis along with the inhibition of ER stress responses. These results suggested that psoralen causes liver injury due to the induction of the ER stress-mediated apoptosis via PERK-eIF2α-ATF4-CHOP and ATF6-CHOP related pathways.

Anti-inflammatory effects of Rhodiola rosea L.: A review.

Rhodiola rosea L., a worldwide botanical adaptogen, has been confirmed to possess protective effects of inflammatory injury for many diseases, including cardiovascular diseases, neurodegenerative diseases, diabetes, sepsis, and cancer. This paper is to review the recent clinical and experimental researches about the anti-inflammatory effects and the related mechanisms of Rhodiola rosea L. extracts, preparations, and the active compounds. From the collected information reviewed, this paper will provide the theoretical basis for its clinical application, and provide the evidences or guidance for future studies and medicinal exploitations of Rhodiola rosea L.