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BACKGROUND: Ginkgo Folium has a favorable effect on non-alcoholic fatty live disease (NAFLD), but its mechanism remains unclear. OBJECTIVE: The aim of this study is to reveal the underlying mechanism of Ginkgo Folium in the treatment of NAFLD. METHODS: Ingredients of Ginkgo Folium and ingredients-related genes were collected from TCMSP database and SwissTargetPrediction website, respectively. Genecards database was used to obtain NAFLD-related genes. Next, the protein-protein interaction network and key ingredients-genes network were constructed via Cytoscape3.7.0. Based on the Metascape website, gene ontology function analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were carried out for key genes. Finally, molecular docking was performed to present the interaction between components and genes using AutoDock Vina 1.1.2. RESULTS: Eighteen active ingredients and 10 target genes were screened from Ginkgo Folium. AKT1, TNF, EGFR, PTGS2, MAPK8, PPAγ, APP, ESR1, HIFα and PPAα were considered as potential therapeutic targets. These target genes were mainly enriched in insulin resistance, HIF-1, adipocytokine and AMPK signaling pathways. Molecular docking results suggested that Ginkgo Folium active ingredients including luteolin-4′-glucoside, sesamin, luteolin, chryseriol, isorhamnetin and laricitrin showed strong binding capacities with AKT1. CONCLUSION: The study showed that multi-components in Ginkgo Folium interacted with AKT1 and regulated AKT-AMPK/HIF pathway to alleviate NAFLD. Our findings provided an essential role and basis for new anti-NAFLD drug discovery and further research on Ginkgo Folium.

Supplementary figure legends

Inhibition of localized growth and dissemination to multiple organs of NAMALWA cells

Analysis of mitochondrial membrane potential and Lentivirus-encoded shRNA knockdown and NF-κB reporter assay

The cytotoxicity of JA on multiple tumor cells and normal cells (IC50).

JA selectively decreases cell growth and viability of various human cancer cells.

JA causes disruption of the mitochondrial membrane potential in Raji cells.

Purpose: NF-κB, a transcriptional regulator of diverse genes involved in cell survival, proliferation, adhesion, and apoptosis, has been implicated in various malignancies. We discovered a potent natural NF-κB inhibitor, Japonicone A, from the traditional herb Inula japonica Thunb, evaluated its preclinical pharmacology and therapeutic activity, and investigated the underlying mechanisms of action for its antitumor activity.Experimental Design: Various types of cancer and normal cells were exposed to Japonicone A for cytotoxicity screening, followed by determination of cell apoptosis and cell-cycle arrest. Western blotting, immunostaining, and gene reporter assay were used to analyze NF-κB activity. Two xenograft models were used for therapeutic efficacy evaluation.Results: Japonicone A killed cancer cells but had low cytotoxicity to normal cells. Burkitt lymphoma cells were particularly sensitive. Japonicone A inhibited the growth and proliferation of Raji, BJAB, and NAMALWA lymphoma cells and resulted in G2–M phase arrest and apoptosis. Furthermore, exposure of cells to Japonicone A caused inactivation of the TNF-α–TAK1–IKK-NF-κB axis and inhibition of TNF-α–stimulated NF-κB activity and nuclear translocation, followed by downregulation of NF-κB target genes involved in cell apoptosis (Bcl-2, Bcl-xL, XIAP, TRAF2) and in the cell cycle and growth (cyclin D, c-Myc). Moreover, Japonicone A inhibited local growth and dissemination of cancer cells to multiple organs in vivo.Conclusion: Japonicone A exerts significant anticancer effects on Burkitt lymphoma cells in vitro and in vivo through targeting of the NF-κB signaling cascade. These results highlight the potential of Japonicone A as a chemotherapeutic agent and warrant its development as a therapy for lymphomas. Clin Cancer Res; 19(11); 2917–28. ©2013 AACR.

Proliferative vitreoretinopathy (PVR) is an intractable condition after rhegmatogenous retinal detachment (RD), which is the primary cause of failure in retinal reattachment surgery. This study aimed to investigate the effects of chicken ovalbumin upstream promoter transcriptional factor 1 (COUP-TF1) in the development of proliferative vitreoretinopathy (PVR) both in vitro and in vivo. Adult retinal pigment epithelium cell line was used for in-vitro experiments. Immunocytochemistry assay, real-time quantitative polymerase chain reaction, and Western blot were used to measure the expression of COUP-TF1, alpha-smooth muscle actin (α-SMA), and E-cadherin. Epithelial-mesenchymal transition (EMT) was observed through cell counting kit-8 assay, wound healing tests, and the expression changes of related proteins. PVR rabbit models were established and evaluated by the images of fundus and vitreous cavity, pathological sections, and COUP-TF1 expression. As shown by our results, the proliferation and migration of the COUP-TF1 knockdown cells were reduced compared with the control cells with or without transforming growth factor-β1 (TGF-β1) treatment. After TGF-β1 treatment, α-SMA expression was upregulated in ARPE-19 cells but kept the same in COUP-TF1 knockdown cells. E-cadherin expression was down-regulated in all the groups but the extent of the decrease in COUP-TF1 knockdown cells was smaller. EMT was attenuated in ARPE-19 cells after COUP-TF1 was knocked down. In the in-vivo experiment, PVR severity was attenuated and the retinal detachment rate decreased on the 14th and 28th day in COUP-TF1 knockdown group. In conclusion, COUP-TF1 is related to the development of PVR, and COUP-TF1 knockdown attenuates the progression of PVR. This suggests that COUP-TF1 can be a promising candidate for the treatment of PVR.

Objective: Multiple myeloma (MM) remains incurable with high rates of relapse. New therapeutic drugs are therefore urgently needed to improve the prognosis. JaponiconeA (JA), a natural product isolated from Inula japonica Thunb, has shown good anti-MM potential. A comprehensive study should therefore be conducted to identify both the in vitro and in vivo mechanisms of the anti-MM effects of JA. Methods: CCK8 assays and flow cytometry were used to detect the proliferation, apoptosis, and cell cycle of MM cell lines when treated with JA. In vivo experiments were conducted using subcutaneous xenograft mouse models. We also identified possible targets and the mechanism of JA using RNA-seq and c-Map databases, and identified the specific targets of JA in bortezomib-sensitive and -resistant MM cell lines using CETSA, DARTS, and rescue experiments. Furthermore, JA and bortezomib were used separately or together to characterize their possible synergistic effects. Results: In vitro, JA inhibited proliferation, and induced apoptosis and G2/M phase arrest in MM cell lines, and selectively killed primary CD138+ MM cells. In vivo, JA also demonstrated a strong anti-tumor effect with no observable toxicity. In addition, JA showed synergetic effects in combination with bortezomib, and enhanced the anti-tumor effect of bortezomib in bortezomib-resistant cells. CETSA and DARTS confirmed direct binding of JA to NF-κB inhibitor kinase beta (IKKβ), and overexpression of IKKβ or knockdown of IκBα partially rescued the apoptosis induced by JA. Conclusions: JA exhibited strong anti-tumor effects in MM. It sensitized myeloma cells to bortezomib and overcame NF-κB-induced drug resistance by inhibiting IKKβ, providing a new treatment strategy for MM patients.

Aim. Chronic inflammation is crucial for age-related macular degeneration (AMD) pathogenesis. However, the mechanism involved in activating inflammation remains unclear. This study is aimed at investigating whether nuclear factor erythrocyte-associated factor 2 (Nrf2) negatively regulated the Nod-like receptor protein 3 (NLRP3) inflammasomes through the thioredoxin 1 (Trx1)/thioredoxin interaction protein (TXNIP) complex. Methods. We determined the optimal hydrogen peroxide (H2O2) concentration, time, and changes in reactive oxygen species (ROS) levels. We also constructed animal models using blue LED irradiation. Then, the expression of Nrf2, TXNIP, Trx1, NLRP3, and inflammation-related factors and proteins, along with the changes in retinal thickness and functional status, was analyzed. Results. The oxidative stress model was established after 1 h intervention with 100 μM H2O2. Nrf2 reduced ROS production, protected the ultrastructure of mitochondria, increased the thickness of the ONL layer, and increased the amplitude of a- and b-wave amplitudes in ERG. Trx1 knockdown increased the production of ROS, damaged the ultrastructure of mitochondria, reduced the thickness of the other ONL layer, and reduced the amplitudes of a- and b-waves in the electroretinogram (ERG). Thus, TXNIP in the cytoplasm activated the inflammasomes. Conclusions. Nrf2 showed antioxidant and anti-inflammatory activity in the H2O2-induced cell stress model and blue LED-induced retinal light damage model. TXNIP transferred from the nucleus to the cytoplasm, activated NLRP3, and aggravated the retinal injury in both the cell stress model and the animal blue LED model. In contrast, Trx1 knockout promoted this process. This study revealed the possible role of the thioredoxin system in developing AMD while also providing newer insights for the future treatment of AMD.

The crucial effect of vascular endothelial growth factor (VEGF)-induced vascular angiogenesis has been well known in corneal neovascularization (CNV). This research aimed to determine the underlying value and mechanism of Meg3 on CNV in vivo and in vitro. In an alkali-burned mouse model, length and area of new vessels were increased along with thinning of corneal epithelium, accompanied by the overexpression of Meg3. Notably, subconjunctival injection of shMeg3 suppressed the degree of injury in cornea, causing expression of the angiogenesis markers--VEGF-A and CD31 decreased. In VEGF-induced human umbilical vein endothelial cells (HUVECs), knockdown of Meg3 antagonized the enhancement of viability, proliferation, wound healing ability and angiogenesis by VEGF. The proteins expression of VEGF-A, CD31, SDF-1/CXCR4 as well as phosphoraylation-Smad2/3 pathways, which were related to angiogenesis, were reduced with Meg3 deficiency. Overall, knockdown of Meg3 alleviated formation of neovascularization in alkali-burned corneas and reduced VEGF-induced angiogenesis by inhibiting SDF-1/CXCR4 and Smad2/3 signaling in vitro.

Duhaldea pterocaula (Franch.) Anderb, also known as Inula pterocaula Franch (I. pterocaula), is a folk medicine of the Yi nationality in China. The Inula plants display various biological activities, including anti-nociceptive and anti-inflammatory properties. I. pterocaula has been traditionally used for the treatment of bronchitis, vasculitis, and dizziness. However, very few studies have been reported on the pharmacology of I. pterocaula. The present study aims to characterize the anti-nociceptive and anti-inflammatory properties of I. pterocaula and explore the underlying mechanism. I. pterocaula was extracted by 95% ethanol and further portioned with petroleum ether, ethyl acetate (EA) and n-butanol, sequentially, to obtain corresponding factions with different polarities. The EA fraction (IPEA) was found to be one of the most effective fractions. It demonstrated potent analgesic effects in both acute and inflammatory pain mouse models, and caused no anti-nociceptive tolerance. Furthermore, IPEA improved the tolerance of mice to morphine. IPEA also showed potent anti-inflammatory effects on LPS-induced septic mice. BIC, a GABAAR antagonist, reversed the effects of IPEA in pain and inflammation models. Collectively, GABAARs play a key role in the pharmacological effects of IPEA. I. pterocaula may be useful as a complementary or alternative therapeutic agent for the treatment of pain and inflammation.

Multiple myeloma (MM) remains incurable with high rates of relapse. New therapeutic drugs are therefore urgently needed to improve the prognosis. JaponiconeA (JA), a natural product isolated fromCCK8 assays and flow cytometry were used to detect the proliferation, apoptosis, and cell cycle of MM cell lines when treated with JA.JA exhibited strong anti-tumor effects in MM. It sensitized myeloma cells to bortezomib and overcame NF-κB-induced drug resistance by inhibiting IKKβ, providing a new treatment strategy for MM patients.

Hyperlipidemia refers to a chronic disease caused by systemic metabolic disorder, and its pathophysiology is very complex.

Non-cardiomyocytes (non-CMs) play an important role in the process of cardiac remodeling of chronic heart failure. The mechanism of non-CMs transit and interact with each other remains largely unknown. Here, we try to characterize the cellular landscape of non-CMs in mice with chronic heart failure by using single-cell RNA sequencing (scRNA-seq) and provide potential therapeutic hunts. Cellular and molecular analysis revealed that the most affected cellular types are mainly fibroblasts and endothelial cells. Specially, Fib_0 cluster, the most abundant cluster in fibroblasts, was the only increased one, enriched for collagen synthesis genes such as Adamts4 and Crem, which might be responsible for the fibrosis in cardiac remodeling. End_0 cluster in endothelial cells was also the most abundant and only increased one, which has an effect of blood vessel morphogenesis. Cell communication further confirmed that fibroblasts and endothelial cells are the driving hubs in chronic heart failure. Furthermore, using fibroblasts and endothelial cells as the entry point of CMap technology, histone deacetylation (HDAC) inhibitors and HSP inhibitors were identified as potential anti-heart failure new drugs, which should be evaluated in the future. The combined application of scRNA-seq and CMap might be an effective way to achieve drug repositioning.

Age-related macular degeneration (AMD) is a multifactor disease, which is primarily characterized by retinal pigment epithelium (RPE) cell loss. Since the retina is the most metabolically active tissue, RPE cells are exposed to consistent oxidative environment. So, oxidation-induced RPE cell death has long been considered a contributor to the onset of AMD. Here, we applied a retinal degeneration (RD) rat model induced by blue light-emitting diode (LED) and a cell model constructed by H2O2 stimulus to mimic the prooxidant environment of the retina. We detected that the expression of miR-27a was upregulated and the expression of FOXO1 was downregulated in both models. So, we furtherly investigated the role of miR-27a-FOXO1 axis in RPE in protesting against oxidants. Lentivirus-mediated RNA was injected intravitreally into rats to modulate the miR-27a-FOXO1 axis. Retinal function and histopathological changes were evaluated by electroretinography (ERG) analysis and hematoxylin and eosin (H&E) staining, respectively. Massive photoreceptor and RPE cell death were examined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The damage to the retina was aggravated in the FOXO1 gene-knockdown and miR-27a-overexpression groups after exposure to LED but was alleviated in the FOXO1 gene-overexpression or miR-27a-knockdown groups. Dual luciferase assay was used to detect the binding site of miR-27a and FOXO1. Upregulated miR-27a inhibited the expression of FOXO1 by directly binding to the FOXO1 mRNA 3 ′ UTR and decreased the autophagy activity of ARPE-19 cells, resulting in the accumulation of reactive oxygen species (ROS) and decrease of cell viability. The results suggest that miR-27a is a negative regulator of FOXO1. Also, our data emphasize the prominent role of miR-27a/FOXO1 axis in modulating ROS accumulation and cell death in RPE cell model under oxidative stress and influencing the retinal function in the LED-induced RD rat model.

Purpose. To determine the effectiveness and safety of trabeculectomy along with amniotic membrane transplantation (AMT) for glaucoma. Methods. This systematic review was performed using RevMan 5.3. We searched PubMed, EMBASE, and the Cochrane Library and included studies published until September 2019. The treatment group included patients with AMT and trabeculectomy (group A), and the control group had only trabeculectomy (group B). We only included randomized controlled trials. The outcomes were intraocular pressure (IOP), complete success rate, number of antiglaucoma medications, and complications. Results. Five studies, including 174 eyes (87 eyes in the AMT group and 87 eyes in the control group), were eligible in this review. The parameters had no significant difference in heterogeneity between the AMT and control groups preoperatively. In the AMT group, the mean IOP was significantly lower at 3 and 12 months after operation (P P = 0.02, respectively), while the number of complete successes in the AMT group was significantly higher at 6 and 12 months (P = 0.02 and P = 0.003, respectively) compared with the control group. Complications, including a flat anterior chamber and hyphema, appeared to be decreased in the AMT group compared to the control group (P = 0.02 and P = 0.02, respectively). No differences were observed in the number of antiglaucoma medications, hypotony, encapsulated bleb, or choroidal detachment. Conclusion. Compared with only trabeculectomy, it is more efficient and safer to add AMT to trabeculectomy during glaucoma filtering surgery.

Qingquan Wei,1,* Xiuwei Liang,2,* Ye Peng,3,* Donghui Yu,1 Ruiling Zhang,1 Huizi Jin,1 Jiaqi Fan,1 Wenting Cai,1 Chengda Ren,1 Jing Yu1,4 1Department of Ophthalmology, Shanghai Tenth People’s Hospital Affiliated with Tongji University, Shanghai, People’s Republic of China; 2Department of Ophthalmology, Nanchang University, Nanchang, People’s Republic of China; 3Department of Clinical Laboratory, Shanghai Tenth People’s Hospital Affiliated with Tongji University, Shanghai, People’s Republic of China; 4Department of Ophthalmology, Ninghai First Hospital, Zhejiang, People’s Republic of China *These authors contributed equally to this work Purpose: This study aimed to assess the effects of 17β-estradiol (βE2) on blue light-emitting diode (LED)-induced retinal degeneration (RD) in rats and hydrogen peroxide (H2O2)-induced retinal pigment epithelium cell injury in humans and elucidate the protective mechanism of βE2 underlying these processes.Methods: Female ovariectomized (OVX) rats were intravitreally injected with βE2 before blue LED exposure (3,000lux, 2hours). Retinal function and morphology were assayed via electroretinogram (ERG) and H&E, respectively. Cell viability was assayed using the Cell Counting Kit-8. Cell ROS were measured using dichlorofluorescein fluorescence. Apoptosis was evaluated by TUNEL and Annexin V/propidium iodide staining. Gene expression and protein expression were quantified using quantitative real-time RT-PCR, Western blotting, and immunohistochemistry. Autophagosomes were examined by electron microscopy.Results: Female OVX rats were exposed to blue LED, inducing RD. βE2 significantly prevented the reduction in the a- and b-wave ERG amplitudes and the disruption of retinal structure, the loss of photoreceptor cells, and the decrease in the thickness of the outer nuclear layer caused by blue LED exposure. βE2 also decreased cell apoptosis in the retina in blue LED-induced RD. Additionally, βE2 reduced ROS levels and apoptosis in H2O2-treated human retinal pigment epithelial (ARPE-19) cells. Furthermore, βE2 increased the protein expression of p-Akt and Bcl-2 and decreased the protein expression of cleaved caspase-3 and Bax during blue LED-induced retinal damage and in H2O2-treated ARPE-19 cells. βE2 also increased the number of autophagosomes and upregulated the expression of LC3-II/LC3-I and Beclin 1 in these processes.Conclusion: βE2 protects against blue LED-induced RD and H2O2-induced oxidative stress by acting as an antioxidant, and its protective mechanism might occur by reducing apoptosis and enhancing autophagy; βE2 may be a novel and effective therapy for age-related macular degeneration. Keywords: 17β-estradiol, hydrogen peroxide, retinal blue light-emitting diode degeneration, oxidative stress, apoptosis, autophagy

Aim: To improve the retention of fluorescein sodium (FS) as a kind of clinical contrast agent for fundus fluorescein angiography (FFA). Materials & methods: Polyethyleneimine (PEI) was designed to synthesize PEI–NHAc–FS nanoparticles (NPs), and the formed NPs were characterized by both physicochemical properties and their effects on FFA. Results: Compared with free FS, PEI–NHAc–FS NPs showed similar optical performance, and could obviously reduce cellular adsorption and uptake both in vitro and in vivo, which could promote the metabolism of NPs in ocular blood vessels. Conclusion: PEI–NHAc–FS NPs represent a smart nanosize fluorescence contrast agent, which hold promising potential for clinical FFA diagnosis, therapy and research work.

Two new lignans, named (7R, 8S)-balanophonin (1) and (7R, 8S)-tomentosanan A (2), together with eight known lignans, burselignan (3), (+)-isolariciresinol (4), (+)-lyoniresinol (5), 5-methoxy-(+)-isolariciresinol (6), (-)-syringaresinol (7), (+)-epipinoresinol (8), (-)-(7'S, 8S, 8'R)-4,4'-dihydroxy-3, 3', 5, 5'-. tetramethoxy-7', 9-epoxy-lignan-9'-ol-7-one (9), and (-)-(7R, 8S)-dihydrodehydrodiconiferyl alcohol (10) were isolated from the whole plants of Hedyotis uncinella Hook. et Am. Structures of these compounds were elucidated through 1H NMR, "C NMR, 2D NMR, ESI-MS and CD data.

Wenting Cai,1,* Donghui Yu,1,* Jiaqi Fan,2 Xiuwei Liang,3 Huizi Jin,1 Chang Liu,2 Meijiang Zhu,1 Tianyi Shen,1 Ruiling Zhang,1 Weinan Hu,4 Qingquan Wei,1 Jing Yu1,5 1Department of Ophthalmology, Shanghai Tenth People’s Hospital Affiliated with Tongji University, Shanghai, People’s Republic of China; 2Department of Ophthalmology, Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Ophthalmology, Nanchang University, Nanchang, People’s Republic of China; 4Department of Ophthalmology, Anhui University of Science and Technology, Huainan, People’s Republic of China; 5Department of Ophthalmology, Ninghai First Hospital, Zhejiang, People’s Republic of China *These authors contributed equally to this work Purpose: The purpose of this study was to evaluate the effect and mechanism of quercetin on TGF-β1-induced retinal pigment epithelial (RPE) cell proliferation, migration, and extracellular matrix secretion. Materials and methods: Cell counting kit-8, transwell, wound-healing assays, and ELISA were used to assess viability, migration, and collagen I secretion, respectively. Western blot analysis and qPCR were employed to detect mRNA and protein expression levels, respectively. Results: Quercetin suppressed TGF-β1-induced cell proliferation, migration, and collagen I secretion. The results also showed that mRNA and protein expression of epithelial–mesenchymal transition (EMT)-related markers such as alpha-smooth muscle actin and N-cadherin was downregulated by quercetin in TGF-β1-treated RPE cells; conversely, quercetin upregulated the expression of E-cadherin and tight junction protein 1 (ZO-1). In addition, quercetin could inhibit mRNA and protein expression of matrix metalloproteinases. Quercetin may reverse the progression of EMT via the Smad2/3 pathway. Conclusion: Our results demonstrate the protective effects of quercetin on RPE cell EMT, revealing a potential therapeutic agent for proliferative vitreoretinopathy treatment. Keywords: proliferative vitreoretinopathy, quercetin, epithelial–mesenchymal transition, transforming growth factor-β1

The aim of the present study was to investigate the effects of bradykinin (BK) on an epithelial-mesenchymal transition (EMT) model in retinal pigment epithelium (RPE) cells through exposure to transforming growth factor-β1 (TGF-β1). The aim was to improve the effect of BK on proliferative vitreoretinopathy (PVR) progression, and to find a novel method of clinical prevention and treatment for PVR. The morphology of ARPE-19 cells was observed using an inverted phase-contrast microscope. A Cell Counting Kit-8 was used to assess the effects of TGF-β1 on the proliferation of ARPE-19 cells. Western blotting and immunofluorescence were used to detect the expression levels of the epithelial marker E-cadherin, mesenchymal markers α-smooth muscle actin (SMA) and vimentin, and phosphorylated (p) mothers against decapentaplegic homolog (Smad)3 and Smad7 of the TGF/Smad signaling pathway. Wound healing tests and Transwell assays were performed to detect cell migration ability. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis was performed to detect the expression levels of pSmad3 and Smad7 in the TGF/Smad signaling pathway. The results revealed that the addition of 10 ng/ml TGF-β1 resulted in the expression of factors associated with EMT in ARPE-19 cells. BK decreased the expression levels of the mesenchymal markers α-SMA and vimentin, and increased the expression of the epithelial marker E-cadherin. BK decreased cell migration in TGF-β1-induced EMT. These effects were reversed by HOE-140, a specific BK 2 receptor antagonist. BK significantly downregulated the expression of pSmad3 and upregulated the expression of Smad7 in TGF-β1-treated ARPE-19 cells, and the protective alterations produced by BK were inhibited by HOE-140. In conclusion, 10 ng/ml TGF-β1 resulted in EMT in ARPE-19 cells and BK served a negative role in TGF-β1-induced EMT. BK had effects in TGF-β1-induced EMT by upregulating the expression of Smad7 and downregulating the expression of pSmad3 in TGF-β/Smad signaling pathway, indicating that BK may be a novel and effective therapy for PVR.

Shexiang Baoxin pills (SBP) are a traditional Chinese medicine that are used for treating coronary heart disease. Ginsenosides are the main effective components of SBP, but a comprehensive and deep pharmacokinetic study of ginsenosides in SBP, including multiple dosing and linear or nonlinear properties, is lacking. This study was designed to investigate and compare the pharmacokinetic characteristics of ginsenosides in SBP at a single dose and in multiple doses. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of the ginsenosides Rg1, Re, Rb3, Rc and Rb1 in rat plasma. Rats were randomly assigned to receive a single dose of 4, 8 or 12 g/kg and multiple doses (4 g/kg) of SBP for 8, 15 or 22 consecutive days. The results revealed that ginsenosides, following a single oral dose of 4 or 8 g/kg, were absorbed rapidly, with a Tmax ranging from 0.250 to 1.08 h. The AUC0-t and Cmax of the ppd-type ginsenosides Rb3, Rc and Rb1 were greater than those of the ppt-type ginsenosides Rg1 and Re. Nondose-dependent exposure was observed at doses of 4-12 g/kg for all of the ginsenosides. After multiple dosing, the plasma levels of the ppt-type ginsenosides decreased, whereas those of the ppd-type ginsenosides did not change significantly. In conclusion, the LC-MS/MS method was successfully applied to investigate the pharmacokinetics of ginsenosides after single and multiple oral administrations of SBP. The ginsenosides did not accumulate after multiple dosing. The ppd-type ginsenosides displayed more favorable pharmacokinetic properties compared with the ppt-type ginsenosides.

To investigate the sesquiterpene lactones of the aerial parts of Inula helianthus-aquatica.Compounds were isolated and purified by silica gel, Sephadex LH-20 and preparative HPLC. On the basis of physicochemical properties and spectroscopic data, their structures were identified.Seven sesquiterpene lactones and four other compounds were obtained and identified as 2-desoxy-4-epi-pulchellin (1), 6-acetoxy-4-hydroxy-1, 10H-pseudoguaia-11 (13)-en-12,8-olide (2), 4-acetoxy-6-hydroxy-1, 10H-pseudoguaia-11(13)-en-12,8-olide (3), 8-epi-inuviscolide (4), 2,3,11,13-tetrahydroaromaticin (5), 11,13-dihydro-ergolide (6), 4-epipulchellin-2-O-acetate (7), 7-epiloliolide (8), loliolide (9), beta-sitosterol (10) and daucosterol (11).All the compounds were isolated from this plant for the first time.

A liquid chromatography coupled with mass spectrometry based metabonomics approach was applied to investigate the protective effects of rosiglitazone (RGTZ) and caloric restriction (CR) for renal senescence in a rat model.Kidney tissues and serum samples were collected from four groups of rats, including 12- month and 24-month ad libitum fed rats, RGTZ and CR treated 24-month rats. Multivariate data analysis was performed on the mass data of metabonomic profiles to detect the differences among the groups.By metabolite profiling and partial least squares discriminate analysis, 23 renal senescence-related endogenous metabolites were discovered, including phospholipids, carnitine, acetylcarnitine, and creatinine, most of which were related to the oxidative stress and lipid metabolism.Renal senescence is characterized by oxidative stress and changes in lipid metabolism, and RGTZ administration and CR treatment may have similar protective effects for renal senescence via restraining oxidative stress and lipid metabolism.