Central and peripheral analgesic active components of triterpenoid saponins from Stauntonia chinensis and their action mechanism.

Triterpenoid saponins from Stauntonia chinensis have been proven to be a potential candidate for inflammatory pain relief. Our pharmacological studies confirmed that the analgesic role of triterpenoid saponins from S. chinensis occurred via a particular increase in the inhibitory synaptic response in the cortex at resting state and the modulation of the capsaicin receptor. However, its analgesic active components and whether its analgesic mechanism are limited to this are not clear. In order to further determine its active components and analgesic mechanism, we used the patch clamp technique to screen the chemical components that can increase inhibitory synaptic response and antagonize transient receptor potential vanilloid 1, and then used in vivo animal experiments to evaluate the analgesic effect of the selected chemical components. Finally, we used the patch clamp technique and molecular biology technology to study the analgesic mechanism of the selected chemical components. The results showed that triterpenoid saponins from S. chinensis could enhance the inhibitory synaptic effect and antagonize the transient receptor potential vanilloid 1 through different chemical components, and produce central and peripheral analgesic effects. The above results fully reflect that "traditional Chinese medicine has multi-component, multi-target, and multi-channel synergistic regulation".

Systems pharmacology-based dissection of mechanisms of Tibetan medicinal compound Ruteng as an effective treatment for collagen-induced arthritis rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Compound Ruteng (CRT) is a prescribed formulation based on the theory of Tibetan medicine for the treatment of yellow-water-disease. It is consisted with 7 medicinal material include Boswellia carterii Birdw (named "Ruxiang" in Chinese); Tinospora sinensis (Lour.) Merr. (named "Kuan-Jin-Teng" in Chinese), Cassia obtusifolia L (named "Jue-Ming-Zi" in Chinese); Abelmoschus manihot (L.) Medic (named "Huang-Kui-Zi" in Chinese); Terminalia chebula Retz. (named "He-Zi" in Chinese); Lamiophlomis rotata (Benth.) Kudo (named "Du-Yi-Wei" in Chinese) and Pyrethrum tatsienense (Bur. et Franch.) Ling (named "Da-Jian-Ju" in Chinese). They are widely distributed in Tibet area of China and have been used to treat rheumatism, jaundice, and skin diseases for centuries. AIM OF THE STUDY: The present study was conducted to investigate the anti-arthritis effect of CRT and to disclose the systems pharmacology-based dissection of mechanisms. MATERIALS AND METHODS: The chemical constituents in CRT were identified using HPLC method, and CRT candidate targets against RA were screened by network pharmacology-based analysis and further experimentally validated based on collagen-induced arthritis (CIA) rat model. Furthermore, therapeutic mechanisms and pathways of CRT were investigated. RESULTS: 391 potential targets (protein) were predicted against 92 active ingredients of 7 medicinal materials in CRT. Enrichment analysis and molecular docking studies also enforced the practiced results. X-ray based physiological imaging showed the attenuated effect of CRT on paw swelling, synovial joints and cartilage with improved inflammation in CIA rats. Moreover, the expression of biomarkers associated with RA such as MMP1, MMP3 and MMP13 and TNF-a, COX2 and iNOS are down-regulated in ankle joints, serum, or liver. CONCLUSION: In conclusion, CRT compound could attenuate RA symptoms and active ingredients of this compound could be considered for drug designing to treat RA.

Veratrilla baillonii Franch Could Alleviate Lipid Accumulation in LO2 Cells by Regulating Oxidative, Inflammatory, and Lipid Metabolic Signaling Pathways.

Based on the pathological theory of lipid metabolism and using network pharmacology, this study was designed to investigate the protective effect of water extract of Veratrilla baillonii (WVBF) on non-alcoholic fatty liver disease (NAFLD) model using LO2 cells and to identify the potential mechanism underlying the effect. The components of V. baillonii were identified from the public database of traditional Chinese medicine systems pharmacology database (TCMSP). Cytoscape software was used to construct the related composite target network. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were carried out for critical nodes. The BioGPS database was used to determine the distribution of the target in tissues and organs. Moreover, the inhibitory effect of V. baillonii was further investigated using an in vitro hepatocyte NAFLD model. Fourteen active components were then selected from the 27 known compounds of V. baillonii. The targets of gene enrichment analysis were mainly distributed in the lipid catabolism-related signaling pathway. Network analysis revealed that five target genes of TNF, MAPK8, mTOR, NF-ĸB, and SREBP-1c were key nodes and played important roles in this process. Organ localization analysis indicated that one of the core target site of V. baillonii was liver tissue. The results of the in vitro study revealed that WVBF can alleviate the inflammatory response and lipid accumulation in LO2 hepatocytes by inhibiting oxidative stress and the adipocytokine signaling pathway. Genes and proteins related to the lipid synthesis, such as SREBP-1C, acetyl-CoA carboxylase (ACC), and fatty acid synthase (FASN), were significantly decreased, and PPARα expression is significantly increased with WVBF administration. In conclusion, V. baillonii may regulate local lipid metabolism and attenuate oxidative stress and inflammatory factors through the PPARα/SREBP-1c signaling pathway. The present study also indicates that multiple components of V. baillonii regulate multiple targets and pathways in NAFLD. The findings highlight the potential of V. baillonii as a promising treatment strategy for nonalcoholic fatty liver injury.

Isolation, Structural Elucidation of Three New Triterpenoids from the Stems and Leaves of Schisandra chinensis (Turcz) Baill.

Schisandra chinensis (Turcz) Baill. is sufficiently well known as a medicinal plant worldwide, which modern research shows has many pharmacological activities such as hepatoprotective, anti-inflammatory effect, potent anti-HIV-1 activity, anti-tumor effect, and activity on the central nervous system. With considerable chemical investigation, three new triterpenoids (1⁻3), together with four known triterpenoids were isolated from the S. chinensis (Turcz) Baill. Their structures were elucidated by 1D- and 2D-NMR spectroscopic analyses, single-crystal X-ray diffraction and high-resolution mass spectroscopy, which were identified as Schisanlactone I (1), Schinalactone D, (2), Schisanlactone J, (3) Kadsuphilactone B (4), Schisanlactone C (5), Schisphendilactone B (6), and Schinchinenlactone A (7). The cytotoxicity of those compounds (1⁻7) was tested against Hep-G2 cell lines, but no apparent antitumor activity was observed at 50 µg/mL using MTT method.

Hepatoprotective activity of iridoids, seco-iridoids and analog glycosides from Gentianaceae on HepG2 cells via CYP3A4 induction and mitochondrial pathway.

Gentianaceae herb extracts have been widely used as food additives, teas or medicinal remedies for various diseases and disorders of the human body. Herein, the potential effects of iridoids, seco-iridoids and analog glycosides from gentian on acontine-induced hepatotoxicity were investigated in HepG2 cells to obtain metabolic data of drug-biotarget interactions. Molecular docking analysis was performed to assess the binding efficiencies of 53 iridoids, seco-iridoids and analog compounds obtained from 50 gentian species to the active sites of human CYP3A4 enzyme. The docking scores of 29 iridoids, seco-iridoids and 24 analog glycosides were calculated from the free energy of ligand-protein complexes using a computer-assisted docking simulation. After comprehensive evaluation, 6 of these compounds, i.e., gentiopicroside, sweroside, swertiamarin, loganic acid, 6-O-ß-d-glucosyl-gentiopicroside and amarogentin were selected to evaluate their hepatoprotective effects. Quantitative real-time PCR was used to measure the expression levels of CYP3A4 mRNA in HepG2 cells. Amarogentin displayed the most clear inductive effect on CYP3A4 mRNA levels in the HepG2 cells. Moreover, amarogentin was further studied for acontine-induced toxicity in the HepG2 cells to determine the potential mechanisms. Amarogentin displayed obvious inductive effect on CYP3A4 mRNA levels in the HepG2 cells. These results elucidated that the hepatoprotective effects were caused by the facilitation of drug metabolism, amelioration of mitochondrial dysfunction and reduction of oxidative stress. Our data demonstrated that the naturally found iridoids, seco-iridoids and analog glycosides in gentian may be responsible for the hepatoprotective effects of gentian-extracted compounds and thus, this study may be useful in the food industry or in clinical practice.

Trends in the diffusion of robotic surgery: A retrospective observational study.

BACKGROUND: Recent studies have suggested that the use of robotic surgery for prostatectomy has been increasing, but characterization of the diffusion of robotic surgery in other procedures has not been available. METHODS: Data were analysed for the years 2006-2014 using hospital episode statistics (HES), a database of all admissions to National Health Service (NHS) hospitals in England. OPCS codes were used to determine the annual number of prostatectomy, partial nephrectomy, and total abdominal hysterectomy procedures. Concurrent OPCS codes were then used to identify whether these procedures were robotic, conventional laparoscopic or open surgery. RESULTS: The proportion of robotic cases varied depending on the surgical procedure. Diffusion of robotic surgery was relatively rapid in prostatectomy, moderate in partial nephrectomy, and slow in total abdominal hysterectomy. CONCLUSIONS: Although high institutional cost might explain the earliest delays in diffusion, this barrier does not fully account for the different rates of diffusion among surgical procedures.

Garcinia xanthochymus extract protects PC12 cells from H2O2-induced apoptosis through modulation of PI3K/AKT and NRF2/HO-1 pathways.

The aim of the present study was to investigate the protective effects and underlying mechanisms of Garcinia xanthochymus, a perennial medicinal plant native to Yunnan, China, against H2O2-induced oxidative damage in rat pheochromacytoma PC12 cells. Preincubation of PC12 cells with fruit EtOAc fraction (fruit-EFr., 12.5-50 µmol·L-1) of G. xanthochymus for 24 h prior to H2O2 exposure markedly improved cell viability and increased the activities of antioxidant enzymes (superoxide dismutase, catalase, and heme oxygenase-1 [HO-1]), prevented lactate dehydrogenase release and lipid peroxidation malondialdehyde production, attenuated the decrease of matrix metalloproteinases (MMP), and scavenged reactive oxygen species (ROS). Fruit-EFr. also reduced BAX and cytochrome C expression and improved BCL-2 expression, thereby decreasing the ratio of BAX to BCL-2. Fruit-EFr. activated the nuclear translocation of NRF2 to increase HO-1 and induced the phosphorylation of AKT. Its cytoprotective effect was abolished by LY294002, a specific inhibitor of PI3K. Taken together, the above findings suggested that fruit-EFr.of G. xanthochymus could enhance cellular antioxidant defense capacity, at least in part, through upregulating HO-1 expression and activating the PI3K/AKT pathway and that it could suppress H2O2-induced oxidative damage via PI3K/AKT and NRF2/HO-1 signaling pathways.

The water extract of Veratrilla baillonii could attenuate the subacute toxicity induced by Aconitum brachypodum.

BACKGROUND: Aconitum brachypodum Diels (Family Ranunculaceae) is a Chinese ethnodrug and is well known for both its therapeutic application and high toxicity. However, no detoxication strategy is available for the complete elimination of the toxicity of Aconitum plants. Veratrilla baillonii Franch is believed to possess antitoxic effects on the toxicity induced by Aconitum plants and has been clinically used for hundreds of time by Naxi and Lisu nationalities in Yunnan Province of China. To further address the mechanism of the detoxication of Veratrilla baillonii, the effect of water decoction of Veratrilla baillonii (WVBF) on subacute toxicology of SD rats induced by Aconitum brachypodum (CFA), a genus Aconitum, was determined and studied in the present work. METHODS: The clinical behavior and number of survivors for different dosage of WVBF (25, 50, 100mg/kg) on CFA (4mg/kg) induced rats were observed until day 28. Histological changes and haematological parameters were evaluated. Moreover, Na+-K+-ATPase pathway in heart as well as key enzymes in liver were determined to further discuss the mechanism. RESULTS: The results showed that the exposure of CFA led to some subacute toxicity to rats, especially male ones, accompanied with abnormality of serum biochemical index in rats' serum. The toxicological target organs of CFA may be the heart, liver, kidney and brain. It is demonstrated that WVBF could attenuate the toxicity induced by Aconitum brachypodum via promoting the metabolic enzymes CYP3A1 and CYP3A2 in liver, downregulating the expression of Sodium/Calcium exchanger 1 (NCX1) and SCN5A sodium channal mRNA, and inducing Na+/K+-ATPase activity in heart. This study provides insights into detoxifying measures of Aconitum plants. CONCLUSIONS: Aconitum brachypodum may lead to subacute toxicity of rats after long term of administration, and the toxicity could be attenuated by Veratrilla baillonii via promoting the metabolic enzymes in liver, downregulating the expression of NCX1 and SCN5A mRNA, and inducing Na+/K+-ATPase activity in heart.

[Chemical constituents from leaves of Garcinia xanthochymus].

The constituents were isolated and purified by the silica gel and semi-preparative HPLC, and their structures were elucidated by NMR spectral and MS data. Fifteen compounds were isolated from the ethyl acetate fraction of 95% ethanol extract from the leaves of Garcinia xanthochymus, and identified as 5, 7, 4'-trihydroxy-6-(3-hydroxy-3-methylbutyl)-flavone(1), 1,5-dihydroxy-3-methoxyxanthone(2), 1, 3-dimethoxy-5-hydroxy xanthone(3), kaempferol(4),(2S,3S)-trans-dihydrokaempferol(5), 3, 24, 25-trihydroxytirucall-7-ene(6), 4-hydroxycinnamic acid(7), isovanillic acid(8),(Z)-2-(2,4-dihydroxy-2, 6, 6-trimethylcyclohexylidene)acetic acid(9), volkensiflavone(10), morelloflavone(11), 3, 8″-biapigenin(12), bilobetin(13), fukugiside(14), GB2a glucoside(15). Compound 1 is a new compound, compounds 5, 6, 9 and 13 are isolated from the genus Garcinia for the first time, and compounds 4, 7-8, 10-12, 14 and 15 are firstly found from this plant. α-Amylase inhibitory activities of 10 compounds were determined using starch azure as the substrate, and the results show that compound 13 has the inhibitory activities against α-amylase, IC50 values of compound 13 and acarbose are 8.12, 4.32 µmol•L⁻¹ respectively.

Development and Characterization of Polymorphic Microsatellite Markers for Sedum sarmentosum (Crassulaceae) and Their Cross-Species Transferability.

Sedum sarmentosum is an important Chinese medicinal herb that exhibits anti-inflammatory, anti-angiogenic and anti-nociceptive properties. However, little is known about its genetic background. The first set of 14 microsatellite markers were isolated and characterized for S. sarmentosum using an SSR-enriched library. Fourteen polymorphic microsatellite markers were acquired with satisfactory amplifications and a polymorphic pattern in 48 S. sarmentosum individuals. The number of alleles ranged from 3 to 15. The observed and expected heterozygosities varied from 0.0833 to 0.8750 and 0.2168 to 0.9063, respectively. Two loci showed significant departure from the Hardy-Weinberg equilibrium. Cross-species amplification was carried out in other Sedum species. High rates of cross-species amplification were observed. The transferability value ranged from 85.7% in S. lineare to 64.3% in S. ellacombianum. These markers will be valuable for studying the genetic variation, population structure and germplasm characterization of S. sarmentosum and related Sedum species.

From Wearable Sensors to Smart Implants--Toward Pervasive and Personalized Healthcare.

OBJECTIVE: This paper discusses the evolution of pervasive healthcare from its inception for activity recognition using wearable sensors to the future of sensing implant deployment and data processing. METHODS: We provide an overview of some of the past milestones and recent developments, categorized into different generations of pervasive sensing applications for health monitoring. This is followed by a review on recent technological advances that have allowed unobtrusive continuous sensing combined with diverse technologies to reshape the clinical workflow for both acute and chronic disease management. We discuss the opportunities of pervasive health monitoring through data linkages with other health informatics systems including the mining of health records, clinical trial databases, multiomics data integration, and social media. CONCLUSION: Technical advances have supported the evolution of the pervasive health paradigm toward preventative, predictive, personalized, and participatory medicine. SIGNIFICANCE: The sensing technologies discussed in this paper and their future evolution will play a key role in realizing the goal of sustainable healthcare systems.

Phenolic glycosides from Glycosmis pentaphylla.

Three new phenolic glycosides, named as glycopentosides A-C (1-3), along with nine known compounds were isolated from the n-BuOH extract of stems of Glycosmis pentaphylla. Their structures were determined by using spectroscopic and chemical methods. Bioassay showed that compound 10 (tachioside) could inhibit nitric oxide production in lipopolysaccharides-stimulated RAW 264.7 cells with IC50 value of 12.14 µM.

Triterpene saponins from the stems of Entada phaseoloides.

Ten new triterpene saponins (1-10) have been isolated from the stems of Entada phaseoloides. Their structures were elucidated by spectroscopic analysis and chemical methods. Among these compounds, the aglycons of 6-10 are being reported for the first time, in this study, including 3ß,15α,16α-trihydroxy-11α,12α-epoxy olean-28,13ß-olide (6), 3ß,15α,16α-trihydroxy-11-oxo-olean-12-en-28-oic acids (7 and 8), and 3ß,15α,16α-trihydroxy-oleana-11,13(18)-dien-28-oic acids (9 and 10). The cytotoxic activities of all of these compounds were evaluated against HepG-2, A549, and Ec-1 cell lines.

Lycojaponicuminol A-F: cytotoxic serratene triterpenoids from Lycopodium japonicum.

Six new serratene triterpenoids (1-6), together with nine known triterpenoid compounds were isolated from the extract of club moss Lycopodium japonicum. The structures of isolated compounds were established by spectroscopic methods. The cytotoxic activities of all compounds were evaluated against three human cancer cell lines in vitro by MTT assay. Compounds 2, 6-8 and 11 exhibited moderate activities against all three cell lines with IC50 values of 2.28-11.81 µg/mL.

Color reflectance fiber bundle endomicroscopy without back-reflections.

Coherent fiber imaging bundles can be used as passive probes for reflectance-mode endomicroscopy providing that the back-reflections from the fiber ends are efficiently rejected. We describe an approach specific to widefield endomicroscopy in which light is injected into a leached fiber bundle near the distal end, thereby avoiding reflections from the proximal face. We use this method to demonstrate the color widefield reflectance endomicroscopy of ex vivo animal tissue.

Two new flavonol glycosides from the leaves of Elaeagnus pungens.

The leaves of Elaeagnus pungens were extracted with 70% ethanol and successively purified by column chromatography. Seven constituents were obtained and characterized, all of which belong to the class of flavonol glycosides. Their structures were elucidated on the basis of spectroscopic methods including 1D/2D NMR and MS analysis techniques. The seven flavonol glycosides were determined as kaempferol 3-O-ß-d-glucopyranosyl-(1 â†’ 3)-α-l-rhamnopyranosyl-(1 â†’ 6)-[α-l-rhamnopyranosyl(1 â†’ 2)]-ß-d-galactopyranoside (1), isorhamnetin 3-O-ß-d-glucopyranosyl-(1 â†’ 3)-α-l-rhamnopyranosyl-(1 â†’ 6)-ß-d-galactopyranoside (2), together with five known compounds, respectively. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliu-m bromide assay in vitro showed that the isolated flavonol glycosides showed no proliferation activity in the asthma airway smooth muscle cells, comparing with solvent as the control group.

Chemical constituents with free-radical-scavenging activities from the stem of Fissistigma polyanthum.

BACKGROUND: Fissistigma polyanthum is a liane belonging to the Annonaceae family and it is one of the most important crude drugs in traditional Chinese medicine. OBJECTIVE: The objective was to describe the structural elucidation and the free-radical-scavenging activities of the isolated compounds from Fissistigma polyanthum. MATERIAL AND METHODS: The chemical constituents were isolated and purified by normal, reverse column chromatography and HPLC. Their structures were identified by spectroscopic methods ((1)H NMR and (13)C NMR) and by comparison with literature values, and the free-radical-scavenging activities of these two compounds were also evaluated through three in vitro model systems (DPPH, trolox equivalent antioxidant capacity (TEAC) and Co (II) EDTA-induced luminol chemiluminescence by flow injection). RESULTS: Two known compounds, named kanakugiol (1) and teutenone A (2), were isolated from the stem of Fissistigma polyanthum for the first time, and compound 1 exhibited moderate free-radical-scavenging activity. CONCLUSION: Fissistigma polyanthum, which has traditionally been used as an important Chinese medicine, showed a certain free-radical-scavenging activity.

Two new flavanols from Glycosmis pentaphylla.

Two new flavanols, glycoflavanones A (1) and B (2), which were found to possess α-pyrone moiety, together with five known compounds 4'-O-methylgallocatechine (3), ß-sitosterol (4), alphitol (5), 3,4-dimethoxy-5-hydroxy-trans-cinnamyl alcohol (6), and oxyresveratrol (7), were isolated from the stems of Glycosmis pentaphylla by normal-phase and reverse-phase silica gel column chromatography. Their structures were determined on the basis of chemical and spectroscopic analyses.

Photo-activated DNA binding and antimicrobial activities of alkaloids from Glycosmis pentaphylla.

In our screening for photosensitizers from natural resources, four alkaloids were isolated from Glycosmis pentaphylla by various chromatography techniques. Their structures were identified as glycoborinine (1), glybomine B (2), carbalexin A (3) and N-p-coumaroyltyramine (4) by spectral analysis. Their photoactivated antimicrobial activities were evaluated by thin-layer chromatography (TLC) agar overlay assay against Staphylococcus aureus and Bacillus subtilis. It was found that compounds 1 and 4 showed photo-activated antimicrobial activities. Meantime, photo-activated DNA binding activities of these compounds were also assessed by using a specially prepared 1.8 kb DNA fragment and restriction enzymes. Under UVA irradiation, compound 1 showed moderate inhibition on Nde I, Xba I, Nco I and Bcl I which have either 5'-TpA or 5'-ApT and trace or no inhibition on other restriction enzymes. It showed a similar inhibition pattern with the reference 8-methoxypsoralen. However, compounds 2-4 showed no inhibition against any of the restriction enzymes.