The present study aimed at investigating the possible effects of β-elemene on the progression of atherosclerosis in a rabbit model. The rabbit atherosclerosis model was established by the combination of balloon angioplasty-induced endothelial injury and an atherogenic diet fed to the rabbits. New Zealand White rabbits were randomly divided into four groups (8/group): the normal control group (fed with normal chow diet), and three experimental groups, placebo group, atorvastatin group, and β-elemene group (received the atherogenic diet). After two weeks on the diet, the three experimental groups underwent balloon injury at right common carotid artery and were treated with drugs or placebo for five weeks. Serum lipids were measured. Carotid artery lesions were isolated for histological and immunohistochemical analysis. In vitro, RAW264.7 macrophages were pretreated with β-elemene and ox-LDL for 24 h and the viability of macrophages was assayed using the MTT method. TNF-α and IL-6 were also determined. Compared with the control group, the thickness of the atherosclerosis lesion in the placebo group was significantly increased; The thickness the drug treatment groups were significantly decreased, compared with that of the placebo group. The infiltration of macrophage was markedly reduced in the β-elemene group compared with that of the placebo group. β-elemene treatment also reduced the levels of TC, TG, and LDL-C, compared with the placebo group. β-elemene decreased the TNF-α and IL-6 levels in vitro. In conclusion, our results demonstrated that β-elemene retarded the progression of atherosclerosis in vivo and in vitro, which may be related to the capacity of β-elemene to reduce the infiltration of macrophages and suppress inflammatory factors.
Pterocephalus hookeri (C. B. Clarke) Höeck, recorded in the Chinese Pharmacopoeia (2015 version) as a Tibetan medicine for the treatment of various diseases, especially rheumatoid arthritis, was believed to possess a slight toxicity. However, hardly any research has been carried out about it. The present study aimed to evaluate the toxicity in vivo and in vitro. Toxicity was observed by the evaluation of mice weight loss and histopathological changes in the liver. Then, the comparison research between ethyl acetate extract (EAE) and n-butanol extract (BUE) suggested that liver toxicity was mainly induced by BUE. The mechanical study suggested that BUE-induced liver toxicity was closely associated with necrosis detected by MTT and propidium iodide (PI) staining, via releasing lactate dehydrogenase (LDH), reducing the fluidity, and increasing the permeability of the cell membrane. Western blot analysis confirmed that the necrosis occurred molecularly by the up-regulation of receptor-interacting protein kinase 1 (RIP1) and receptor-interacting protein kinase 3 (RIP3), as well as the activation of the nuclear factor-kappa-gene binding (NF-κB) signaling pathway in vivo and in vitro. This finding indicated that the liver toxicity induced by BUE from P. hookeri was mainly caused by necrosis, which provides an important theoretical support for further evaluation of the safety of this folk medicine.
Pterocephalus hookeri (C. B. Clarke) Höeck, recorded in the Chinese Pharmacopoeia (2015 version) as a Tibetan medicine for the treatment of various diseases, especially rheumatoid arthritis, was believed to possess a slight toxicity. However, hardly any research has been carried out about it. The present study aimed to evaluate the toxicity in vivo and in vitro. Toxicity was observed by the evaluation of mice weight loss and histopathological changes in the liver. Then, the comparison research between ethyl acetate extract (EAE) and n-butanol extract (BUE) suggested that liver toxicity was mainly induced by BUE. The mechanical study suggested that BUE-induced liver toxicity was closely associated with necrosis detected by MTT and propidium iodide (PI) staining, via releasing lactate dehydrogenase (LDH), reducing the fluidity, and increasing the permeability of the cell membrane. Western blot analysis confirmed that the necrosis occurred molecularly by the up-regulation of receptor-interacting protein kinase 1 (RIP1) and receptor-interacting protein kinase 3 (RIP3), as well as the activation of the nuclear factor-kappa-gene binding (NF-κB) signaling pathway in vivo and in vitro. This finding indicated that the liver toxicity induced by BUE from P. hookeri was mainly caused by necrosis, which provides an important theoretical support for further evaluation of the safety of this folk medicine.
OBJECTIVE: To evaluate the medicinal reasonableness and resource utilization of Dida from different species.METHOD: With common characteristic absorption peaks of HPLC fingerprints and SPSS cluster, the composition similarity of Dida from different species was evaluated.
RESULT: The composition similarity of HPLC fingerprints of 33 Dida samples from 15 species and 1 variety originated from Swertia, Halenia, Gentianopsis, Lomatogonium was difference. The original species can be clustered into four groups by the relative area of 10 common characteristic peaks of HPLC fingerprints. The compositions of four different genera are quite different.
CONCLUSION: Because of containing iridoids, xanthones, and triterpenes which have liver protection and cholagogue functions, all of species from Swertia, Halenia, Gentianopsis and Lomatogonium in Gentianaceae are classified as Dida in Tibetan medicine. According to the composition difference among different species, the HPLC fingerprints established for Dida from different source are an effective means to identify nd control the quality of Dida.
Context: Tsothel, a traditional Tibetan medicine, is regarded as 'the king of essences'. Nevertheless, tsothel has aroused serious concern regarding its biosafety because its main component is HgS. Unfortunately, toxicological studies on tsothel are scarce. Objective: As inorganic mercury has high affinity for the kidney, the present investigation was designed to determine the potential nephrotoxicity and mechanism of tsothel. Materials and methods: Sprague-Dawley rats were orally administered different doses of tsothel (0, 66.70, 33.35 and 16.68 mg/kg) daily for 180 days, followed by the withdrawal of tsothel for 120 days. Then, the related nephrotoxicity was examined by the ICP-MS, ELISA, colorimetric, RT-PCR, HE staining, immunohistochemical staining and flow cytometry methods. Results: Although tsothel administration led to a large accumulation of Hg (794.25 ± 464.30 ng/g in the 66.70 mg/kg group, 775.75 ± 307.89 ng/g in the 33.35 mg/kg group and 532.60 ± 356.77 ng/g in the 16.68 mg/kg group) in the kidney after 120 days of tsothel withdrawal, the blood CREA and BUN, urinary Kim-1, NAG, RBP and β2-MG, renal SOD, MDA, pathology, proliferation, apoptosis and cell cycle had no significant changes compared with the control group. Additionally, the high GSH content (318.87 ± 44.19 nmol/mL in the 33.35 mg/kg group) and the relative expression levels of Kim-1 (1.08 ± 0.11 in the 33.35 mg/kg group), MT-1 (1.46 ± 0.10 in the 66.70 mg/kg group, 1.61 ± 0.19 in the 33.35 mg/kg group and 1.57 ± 0.14 in the 16.68 mg/kg group) and GST-Pi (1.76 ± 0.89 in the 33.35 mg/kg group) mRNA recovered to normal after tsothel withdrawal. Interestingly, the change trend of GST-Pi gene expression was consistent with the change trend of GSH activity. Conclusions: Overall, our study shows that tsothel administration did not induce overt nephrotoxicity but did have reversible stress-related effects. These results suggest that tsothel affects stress response mechanisms with the involvement of detoxifying enzyme systems. The formulation method and chemotype could play a role in the reduced toxicity potential of tsothel compared to common mercurials. [ABSTRACT FROM AUTHOR]
CONTEXT: Tsothel, a traditional Tibetan medicine, is regarded as 'the king of essences'. Nevertheless, tsothel has aroused serious concern regarding its biosafety because its main component is HgS. Unfortunately, toxicological studies on tsothel are scarce. OBJECTIVE: As inorganic mercury has high affinity for the kidney, the present investigation was designed to determine the potential nephrotoxicity and mechanism of tsothel. MATERIALS AND METHODS: Sprague-Dawley rats were orally administered different doses of tsothel (0, 66.70, 33.35 and 16.68 mg/kg) daily for 180 days, followed by the withdrawal of tsothel for 120 days. Then, the related nephrotoxicity was examined by the ICP-MS, ELISA, colorimetric, RT-PCR, HE staining, immunohistochemical staining and flow cytometry methods. RESULTS: Although tsothel administration led to a large accumulation of Hg (794.25 ± 464.30 ng/g in the 66.70 mg/kg group, 775.75 ± 307.89 ng/g in the 33.35 mg/kg group and 532.60 ± 356.77 ng/g in the 16.68 mg/kg group) in the kidney after 120 days of tsothel withdrawal, the blood CREA and BUN, urinary Kim-1, NAG, RBP and β2-MG, renal SOD, MDA, pathology, proliferation, apoptosis and cell cycle had no significant changes compared with the control group. Additionally, the high GSH content (318.87 ± 44.19 nmol/mL in the 33.35 mg/kg group) and the relative expression levels of Kim-1 (1.08 ± 0.11 in the 33.35 mg/kg group), MT-1 (1.46 ± 0.10 in the 66.70 mg/kg group, 1.61 ± 0.19 in the 33.35 mg/kg group and 1.57 ± 0.14 in the 16.68 mg/kg group) and GST-Pi (1.76 ± 0.89 in the 33.35 mg/kg group) mRNA recovered to normal after tsothel withdrawal. Interestingly, the change trend of GST-Pi gene expression was consistent with the change trend of GSH activity. CONCLUSIONS: Overall, our study shows that tsothel administration did not induce overt nephrotoxicity but did have reversible stress-related effects. These results suggest that tsothel affects stress response mechanisms with the involvement of detoxifying enzyme systems. The formulation method and chemotype could play a role in the reduced toxicity potential of tsothel compared to common mercurials.
Present views of several experts on Tibetan medicine. Benefits of the medicine, according to Vincanne Adams of the University of California; Comment of professor Cai Jingfeng on the presence of heavy metal ingredients in the medicine; Impression of doctor Eliot Tokar on the importance of a conference on Tibetan medicine.
Tibetan Herbal medicine has its own complete theory based on five sources doctrine. And the theories of "Liuwei", "Baxing" and "Shiqi Gongxiao" formed the basic core components of the property theory of Tibetan medicine. However, books and literature of Tibetan medicine have never been systematically expounded and discussed about it specially which thus will limit the further development of Tibetan medicine theory. In this thesis, we firstly introduced three basic core components of the property theory-the "Liu Wei", "Baxing", and "Shiqi Gongxiao" and their interactions as well. At the same time, the links and similarities between the theory of Tibetan medicine and Chinese medicine theory were compared. The job of the thesis done above is to lay the foundation for further systematic reveal and development of Tibetan medicine theory.
BACKGROUND: Sleep is a natural part of every individual's life. Delta sleep-inducing peptide (DSIP) is a nonapeptide that could promote sleep through the induction of slow wave sleep. However, little is known about the pharmacological effect of DSIP on insomnia. OBJECTIVES: The main objective of this study was to analyze the pharmacological effect of DSIP on insomnia. METHODS: We designed a fusion protein containing N-terminal TAT-based transduction domain followed by human serum albumin and DSIP and designated this protein as PHD fusion protein. The PHD fusion protein were expressed in Pichia pastoris and purified. Mice were administered single subcutaneous injections three concentrations of PHD fusion protein (0.5, 1, 2 mg/kg), and the pharmacological activity of PHD fusion protein was studied using classic pentobarbitalinduced sleep test. RESULTS: We expressed the PHD fusion protein in P. pastoris; furthermore, the PHD fused protein was purified to near homogeneity by DEAE Sepharose FF, Phenyl Sepharose HP and Blue Sepharose 6 FF. Our result showed that the increase of pentobarbital-induced hypnotic effect characterized by reducing sleep latency and prolonged sleep duration was observed for increasing concentrations of PHD fusion protein (P<0.05); moreover, different dose of PHD fusion protein could induce the mice to re-sleep in a dose-dependent manner, whereas higher doses of PHD fusion protein (1.0, 2.0 mg/kg) significantly increased the rate of sleep re-onset compared with the vehicle group of mice (P<0.05). CONCLUSION: PHD fusion protein increased the hypnotic effects of pentobarbital by reducing sleep latency and prolonged sleep duration. The present study suggested PHD fusion protein could be a new drug candidate for insomnia.
Naturally occurring oligostilbenes are receiving more attention because they exhibit several beneficial effects for health, including hepatoprotective, antitumor, anti-adipogenic, antioxidant, antiaging, anti-inflammatory, anti-microbial, antiviral, immunosuppressive and neuroprotective activities. Thus, they could be of some potentially therapeutic values for several diseases. In this study, we adopted the alkaline extraction-acid precipitation (AEAP) method for extraction of oligostilbenes from the seed kernel of Iris lactea Then, the high-speed counter-current chromatography (HSCCC) was used for preparative isolation and purification of oligostilbenes from the AEAP extracts. Finally, three oligostilbenes, namely vitisin D (73 mg), ampelopsin B (25 mg) and cis-vitisin A (16 mg), were successfully fractionated by HSCCC with a two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (2:5:3:6, v/v/v/v) from 300 mg of the AEAP extracts in ∼ 190 min. The purities of the three isolated oligostilbenes were all over 95.0% as analyzed by high performance liquid chromatography. They all were isolated from I. lacteal for the first time.The method of AEAP for the preparation of the oligostilbene-enriched crude sample was simple, and the HSCCC technique for the isolation and purification of oligostilbenes was efficient.
Naturally occurring oligostilbenes are receiving more attention because they exhibit several beneficial effects for health, including hepatoprotective, antitumor, anti-adipogenic, antioxidant, antiaging, anti-inflammatory, anti-microbial, antiviral, immunosuppressive and neuroprotective activities. Thus, they could be of some potentially therapeutic values for several diseases. In this study, we adopted the alkaline extraction-acid precipitation (AEAP) method for extraction of oligostilbenes from the seed kernel of Iris lactea Then, the high-speed counter-current chromatography (HSCCC) was used for preparative isolation and purification of oligostilbenes from the AEAP extracts. Finally, three oligostilbenes, namely vitisin D (73 mg), ampelopsin B (25 mg) and cis-vitisin A (16 mg), were successfully fractionated by HSCCC with a two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (2:5:3:6, v/v/v/v) from 300 mg of the AEAP extracts in ∼ 190 min. The purities of the three isolated oligostilbenes were all over 95.0% as analyzed by high performance liquid chromatography. They all were isolated from I. lacteal for the first time.The method of AEAP for the preparation of the oligostilbene-enriched crude sample was simple, and the HSCCC technique for the isolation and purification of oligostilbenes was efficient.
OBJECTIVE: The purpose of this pilot study was to test the feasibility of delivering the mobile mindfulness-based stress reduction for breast cancer (mMBSR(BC)) program using an iPad and to evaluate its impact on symptom improvement. METHODS: A single group, pre-posttest design was implemented among female stages 0-III breast cancer survivors (BCS) who completed treatment. Data were collected at baseline and week 6 on measures of psychological and physical symptoms and quality of life. The mMBSR(BC) program is a standardized, stress-reducing intervention that combines sitting and walking meditation, body scan, and yoga and is designed to deliver weekly 2-hour sessions for 6 weeks using an iPad. RESULTS: The mean age of the 15 enrolled BCS was 57 years; one participant was non-Hispanic black, and 14 were non-Hispanic white. Of the 13 who completed the study, there were significant improvements from baseline to 6 weeks post-mMBSR(BC) in psychological and physical symptoms of depression, state anxiety, stress, fear of recurrence, sleep quality, fatigue, and quality of life (P's < .05). Effect sizes for improvements of multiple symptoms ranged from medium to large. CONCLUSIONS: These results provide preliminary support that the mMBSR(BC) program may be feasible and acceptable, showing a clinical impact on decreasing psychological and physical symptoms. This mobile-based program offers a delivery of a standardized MBSR(BC) intervention to BCS that is convenient for their own schedule while decreasing symptom burden in the survivorship phase after treatment for breast cancer.
In this paper, we report an efficient method by high-speed counter-current chromatography for the first separation of four aromatic acids and two analogs with similar structures and polarities from Clematis akebioides. First, the ethyl acetate extract was treated by silica gel column chromatography to enrich the target compounds. And then the fraction with target compounds were purified by high-speed counter-counter chromatography using a two-phase solvent system consisting of chloroform/acetonitrile/water (10:6:4, v/v). The results showed high-speed counter-current chromatography could be a powerful technology for the separation of compounds with similar structures and polarities. Besides, it was found acetonitrile could be a good methanol substitute when a chloroform/methanol/water system could not provide a good separation factor. This study provides a reference for the separation of compounds from Clematis akebioides.
Glucose carbon with uniform diameter was successfully anchored by TiO<sub>2</sub> nanoparticles via a facile low-temperature hydrothermal process independent of surfactants or external forces. The resultant TiO<sub>2</sub>@glucose carbon composite (TiO<sub>2</sub>@GCs) was characterized by scanning electron microscopy (SEM) and energy dispersive spectrometry (EDS). The elimination of direct deep blue (DDB) from aqueous solution by adsorption onto TiO<sub>2</sub>@GCs was investigated in the up-flow fixed-bed columns. The effects of the influent concentration (10-30 mg L<sup>−1</sup>), flow rate (3-5 mL min<sup>−1</sup>), bed depth (1.0-2.0 cm) and pH (1.0-9.0) were investigated. Breakthrough time and adsorption capacity of the fixed-bed increased with increasing bed depth, whereas decreased with the increase in initial concentration, bed depth and solution pH values. The experimental data was in good agreement with both Thomas model and Yoon-Nelson model. The employed bed saturated with DDB was readily regenerated through a simple regeneration process with UV irradiation for 1 h. Furthermore, the adsorption-regeneration process was conducted for six cycles and no major decrease of regeneration efficiency was observed for the first three cycles. One possible mechanism for regenerating dye-loaded TiO<sub>2</sub>@GCs was proposed. The verifying experiment found that hydroxyl radicals and superoxide ions significantly affected the regeneration of employed TiO<sub>2</sub>@GCs bed.
Fenugreek is a well known annual herb widely used in both medicine and food. Four flavonoid glycosides have been separated from fenugreek seeds in our previous study. In this study, the effects of the four flavonoid glycosides on regulating glycolipid metabolism and improving mitochondrial function were investigated. Isoorientin showed a very significant activity among these flavonoid glycosides. First, isoorientin decreased the accumulation of lipid droplets in 3T3-L1 preadipocytes by reducing the expression of adipokines including PPARγ, C/EBPα, and FAS. Second, isoorientin restored insulin-stimulated glucose uptake in dexamethasone-induced insulin-resistant 3T3-L1 adipocytes by reactivating Akt and AMPK. Finally, isoorientin improved mitochondrial dysfunction induced by dexamethasone in 3T3-L1 adipocytes. Isoorientin also reversed dexamethasone-induced decrease in mitochondrial membrane potential (MMP) and intracellular ATP production, reduced accumulation of intracellular reactive oxygen species (ROS), and protected mitochondrial DNA (mtDNA) from oxidative damage. At the same time, mitochondrial biogenesis is promoted. Therefore, isoorientin may be an attractive candidate as a glucose-lowering and insulin-resistance-improving agent for the treatment of diabetes.
Fenugreek is a well known annual herb widely used in both medicine and food. Four flavonoid glycosides have been separated from fenugreek seeds in our previous study. In this study, the effects of the four flavonoid glycosides on regulating glycolipid metabolism and improving mitochondrial function were investigated. Isoorientin showed a very significant activity among these flavonoid glycosides. First, isoorientin decreased the accumulation of lipid droplets in 3T3-L1 preadipocytes by reducing the expression of adipokines including PPARγ, C/EBPα, and FAS. Second, isoorientin restored insulin-stimulated glucose uptake in dexamethasone-induced insulin-resistant 3T3-L1 adipocytes by reactivating Akt and AMPK. Finally, isoorientin improved mitochondrial dysfunction induced by dexamethasone in 3T3-L1 adipocytes. Isoorientin also reversed dexamethasone-induced decrease in mitochondrial membrane potential (MMP) and intracellular ATP production, reduced accumulation of intracellular reactive oxygen species (ROS), and protected mitochondrial DNA (mtDNA) from oxidative damage. At the same time, mitochondrial biogenesis is promoted. Therefore, isoorientin may be an attractive candidate as a glucose-lowering and insulin-resistance-improving agent for the treatment of diabetes.
<i>Potentilla parvifolia </i>Fisch. (Rosaceae) is a traditional medicinal plant in P. R. China. In this study, seven flavonoids, ayanin (<b>1</b>), tricin (<b>2</b>), quercetin (<b>3</b>), tiliroside (<b>4</b>), miquelianin (<b>5</b>), isoquercitrin (<b>6</b>), and astragalin (<b>7</b>), were separated and purified from ethyl acetate extractive fractions from ethanol extracts of <i>P. parvifolia</i> using a combination of sevaral chromatographic methods. The human neuroblastoma SH-SY5Y cells were differentiated with all trans-retinoic acid and treated with okadaic acid to induce tau protein phosphorylation and synaptic atrophy, which could establish an Alzheimer's disease cell model. The neuroprotective effects of these flavonoids in cellular were evaluated <i>in vitro</i> by this cell model. Results from the Western blot and morphology analysis suggested that compounds <b>3</b> and <b>4</b> had the better neuroprotective effects.
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