ABSTRACT
The quality markers(Q-markers) of Shujin Huoxue Capsules were comprehensively discriminated based on the five principles of transfer and traceability, specificity, compatibility, effectiveness and measurability. The compounds that could be transferred from the original medicinal materials to the preparation were selected with the principle of transfer and traceability. The specific components in the prescription were screened by reviewing literature with the principle of specificity. According to the principle of compatibility, the attributes of compounds were evaluated by the sovereign, minister, assistant and guide combination rules of the original medicinal materials in the prescription. According to the principle of measurability, the measurable components were summarized by reference to the pharmacopoeia and literature combined with the content. The mechanism of Shujin Huoxue Capsules in the treatment of osteoporosis was studied through network pharmacology based on the principle of effectiveness, which was the evaluation index of effectiveness. The chemical components screened out above were regarded as candidate Q-markers, and the cobweb model was plotted to obtain the comprehensive score of Q-markers. Hydroxysafflor yellow A, trachelosid, eleutheroside B, α-cyperone, protocatechuic acid, protocatechualdehyde and 4-methoxy salicylaldehyde were discriminated as the Q-markers of Shujin Huoxue Capsules based on the five principles combined with cobweb model.
Subject(s)
Drugs, Chinese Herbal , Biomarkers , Capsules , Drugs, Chinese Herbal/pharmacologyABSTRACT
As a new stage in the development of medicine and health, smart medicine has attracted attention from all parties in recent years. Especially, under the impetus of the Internet, due to the development of new technologies, smart medical care has made considerable progress, and it has also brought us new challenges. The concept, hypothesis, and design of intelligent medical care are analyzed, and the design objects and design principles of intelligent medical care are highlighted. In Africa, 79 patients with shoulder pain after stroke and hemiplegia in the recession period were disintegrated and divided into observation group (40 people) and control group (39 people). The observation group and the control group used two different treatment methods, acupuncture treatment and traditional western medicine treatment. Finally, the situation of the two groups is checked. From the results, the treatment effect of the control group was not as good as that of the observation group (P < 0.05). After treatment, the effects of capillary disease and patients' living conditions in the observation group were better than those in the control group (P < 0.05). It is concluded that the therapeutic effect of wisdom acupuncture treatment has a certain effect and can be used in medical treatment.
Subject(s)
Acupuncture Therapy , Stroke Rehabilitation , Hemiplegia/etiology , Hemiplegia/therapy , Humans , Shoulder Pain/etiology , Shoulder Pain/therapy , Treatment Outcome , Upper ExtremityABSTRACT
This research is focused on improving performance of chitosan based functional material by introducing active additive. A series of assays revealed incorporation with clove essential oil (CEO) significantly improved the physical, chemical and antimicrobial performance of chitosan. In this work, the prepared chitosan-CEO film (CH-CEO) showed varieties in color parameters, mechanical strength and water vapor permeability. Moreover, chitosan was endowed with significant antioxidant and antimicrobial activities, thereby it was used as protective coatings for fresh-cutting apple tubes at ~1 °C. Results demonstrated the treatment slowed down the quality deterioration process of preserved apple samples, especially for firmness and color. As well, CH-CEO coating reduced microbial counts in the preserved apple samples and inhibited the varieties in the chemical properties. The overall observations revealed that CH-CEO film has remarkable potential as an antioxidant and antimicrobial material, especially as an active coating for fresh-cutting foods during storage.
Subject(s)
Chitosan/chemistry , Clove Oil/chemistry , Coated Materials, Biocompatible/chemistry , Anti-Bacterial Agents/pharmacology , Antioxidants/pharmacology , Clove Oil/pharmacology , Color , Malus , Microbial Sensitivity Tests , Permeability , Porosity , SteamABSTRACT
It was recently disclosed that CYP3A is responsible for the tertiary stereoselective oxidations of deoxycholic acid (DCA), which becomes a continuum mechanism of the host-gut microbial cometabolism of bile acids (BAs) in humans. This work aims to investigate the species differences of BA redox metabolism and clarify whether the tertiary metabolism of DCA is a conserved pathway in preclinical animals. With quantitative determination of the total unconjugated BAs in urine and fecal samples of humans, dogs, rats, and mice, it was confirmed that the tertiary oxidized metabolites of DCA were found in all tested animals, whereas DCA and its oxidized metabolites disappeared in germ-free mice. The in vitro metabolism data of DCA and the other unconjugated BAs in liver microsomes of humans, monkeys, dogs, rats, and mice showed consistencies with the BA-profiling data, confirming that the tertiary oxidation of DCA is a conserved pathway. In liver microsomes of all tested animals, however, the oxidation activities toward DCA were far below the murine-specific 6ß-oxidation activities toward chenodeoxycholic acid (CDCA), ursodeoxycholic acid, and lithocholic acid (LCA), and 7-oxidation activities toward murideoxycholic acid and hyodeoxycholic acid came from the 6-hydroxylation of LCA. These findings provided further explanations for why murine animals have significantly enhanced downstream metabolism of CDCA compared with humans. In conclusion, the species differences of BA redox metabolism disclosed in this work will be useful for the interspecies extrapolation of BA biology and toxicology in translational researches. SIGNIFICANCE STATEMENT: It is important to understand the species differences of bile acid metabolism when deciphering biological and hepatotoxicology findings from preclinical studies. However, the species differences of tertiary bile acids are poorly understood compared with primary and secondary bile acids. This work confirms that the tertiary oxidation of deoxycholic acid is conserved among preclinical animals and provides deeper understanding of how and why the downstream metabolism of chenodeoxycholic acid dominates that of cholic acid in murine animals compared with humans.
Subject(s)
Bile Acids and Salts/metabolism , Cytochrome P-450 CYP3A/metabolism , Animals , Bile Acids and Salts/analysis , Bile Acids and Salts/chemistry , Dogs , Drug Evaluation, Preclinical , Feces/chemistry , Female , Germ-Free Life , Humans , Hydroxylation , Male , Mice , Microsomes, Liver , Oxidation-Reduction , Rats , Species Specificity , Stereoisomerism , Substrate Specificity , Tandem Mass Spectrometry , Urine/chemistryABSTRACT
Abscisic acid (ABA) has been advocated to play substantial role on ripening of non-climacteric fruit. Here we report that alginate oligosaccharide (AOS) postharvest treatments delayed the accumulation of ABA and ABA-conjugates and restrained the expression of ABA signaling genes, resulting enlarged storage life of strawberry. In addition, AOS postharvest treatments also increased the quality and reduced the degradation of cell wall components and repressed the expression of cell wall degradation genes. AOS treated fruits exhibited significant delays of hardness, decay percentage, titratable acidity, pH, total soluble solids and vitamin C content compared to untreated fruits. Moreover, AOS had a positive effect on retaining higher amount of anthocyanin, total phenol and flavonoids contents. The finding of this study suggests that AOS postharvest treatments are very useful for preserving fruit quality and enhancing shelf life by delayed ABA accretion, restrained the gene expression related to ABA signaling and cell wall degeneration.
Subject(s)
Abscisic Acid/metabolism , Alginates/chemistry , Fragaria/metabolism , Oligosaccharides/pharmacology , Abscisic Acid/analysis , Anthocyanins/analysis , Ascorbic Acid/analysis , Cell Wall/genetics , Cell Wall/metabolism , Chromatography, High Pressure Liquid , Food Storage , Fragaria/drug effects , Fragaria/genetics , Fruit/chemistry , Fruit/drug effects , Fruit/metabolism , Hardness , Oligosaccharides/chemistry , Phenols/analysis , Signal Transduction/drug effects , Spectrometry, Mass, Electrospray Ionization , SpectrophotometryABSTRACT
BACKGROUND: Zanthoxylum acanthopodium has insecticidal effect in Chinese traditional medicine. In this study, the essential oil from the dried Zanthoxylum plant was used as a larvicidal compound against the malaria mosquitoes, Anopheles anthropophagus and Anopheles sinensis. METHODS: Compounds in the Zanthoxylum essential oil were investigated by gas chromatography and mass spectroscopy (GC-MS). The larvicidal bioassays of the whole oil, as well as the main compounds in the oil (estragole and eucalyptol) were performed using WHO method. RESULTS: In total, 63 main compounds (99.32%) were found in the oils, including estragole (15.46%), eucalyptol (10.94%), ß-caryophyllene (5.52%), cis-linalool oxide (3.76%), cis-limonene oxide (3.06%). A dose-dependent effect on mortality was recorded with increasing concentrations of essential oil and compounds increasing mortality of the larvae. Larvicidal bioassays revealed that 24 h LC50 of the whole essential oil was 36.00 mg/L and LC90 was 101.49 mg/L against An. anthropophagus, while LC50 was 49.02 mg/L and LC90 was 125.18 mg/L against An. sinensis. Additionally, 24 h LC50 of estragole were 38.56 and 41.67 mg/L against An. anthropophagus and An. sinensis, respectively, while the related LC90 were 95.90 and 107.89 mg/L. LC50 of eucalyptol were 42.41 and 45.49 mg/L against An. anthropophagus and An. sinensis, while the related LC90 were 114.45 and 124.95 mg/L. CONCLUSION: The essential oil of Z. acanthopodium and its several major compounds may have potential for use in the control of malaria mosquitoes.
Subject(s)
Anopheles , Insecticides , Mosquito Vectors , Oils, Volatile , Zanthoxylum/chemistry , Animals , Anopheles/growth & development , Larva/growth & development , Malaria , Mosquito Vectors/growth & development , Species SpecificityABSTRACT
Selenite, one of the inorganic forms of selenium, is emerging as an attractive chemotherapeutic agent owing to its selectivity in eradicating cancer cells. Here we demonstrate a new formulation of nanomedicine based on selenous acid, which is mixed with lauric acid (a phase-change material with a melting point around 43⯰C) and then loaded into the cavities of Au nanocages. The Au nanocages can serve as a carrier during cell endocytosis and then as a photothermal agent to melt the lauric acid upon the irradiation with a near-infrared laser, triggering the swift release of selenous acid. The photothermal and chemo therapies can also work synergistically, leading to enhanced destruction of cancer cells relative to normal cells. Our systematic study suggests that the impaired mitochondrial function arising from the ROS generated through combination treatment is responsible for the cell death. This study offers an appealing candidate that holds great promise for synergistic cancer treatment.
Subject(s)
Gold/chemistry , Hyperthermia, Induced , Nanoparticles/chemistry , Neoplasms/therapy , Phototherapy , Selenious Acid/pharmacology , A549 Cells , Animals , Cell Death/drug effects , Combined Modality Therapy , Delayed-Action Preparations , Drug Liberation , Fluorescence , Humans , Intracellular Space/metabolism , Membrane Potential, Mitochondrial , Mice , NIH 3T3 Cells , Neoplasms/pathology , Reactive Oxygen Species/metabolism , Spectrophotometry, UltravioletABSTRACT
BACKGROUND: Persistent fibroblast activation initiated by transforming growth factor ß (TGF-ß) is a fundamental event in the pathogenesis of systemic sclerosis, and its pharmacological inhibition represents a potential therapeutic strategy. The nuclear receptor, peroxisome proliferator-activated receptor γ (PPAR-γ), exerts potent fibrotic activity. The synthetic oleanane triterpenoid, 2-cyano-3,12-dioxo-olean-1,9-dien-28-oic acid (CDDO), is a PPAR-γ agonist with potential effects on TGF-ß signalling and dermal fibrosis. OBJECTIVE: To examine the modulation of fibrogenesis by CDDO in explanted fibroblasts, skin organ cultures and murine models of scleroderma. MATERIAL AND METHODS: The effects of CDDO on experimental fibrosis induced by bleomycin injection or by overexpression of constitutively active type I TGF-ß receptor (TgfbR1ca) were evaluated. Modulation of fibrotic gene expression was examined in human skin organ cultures. To delineate the mechanisms underlying the antifibrotic effects of CDDO, explanted skin fibroblasts cultured in two-dimensional monolayers or in three-dimensional full-thickness human skin equivalents were studied. RESULTS: CDDO significantly ameliorated dermal fibrosis in two complementary mouse models of scleroderma, as well as in human skin organ cultures and in three-dimensional human skin equivalents. In two-dimensional monolayer cultures of explanted normal fibroblasts, CDDO abrogated fibrogenic responses induced by TGF-ß. These CDDO effects occurred via disruption of Smad-dependent transcription and were associated with inhibition of Akt activation. In scleroderma fibroblasts, CDDO attenuated the elevated synthesis of collagen. Remarkably, the in vitro antifibrotic effects of CDDO were independent of PPAR-γ. CONCLUSIONS: The PPAR-γ agonist triterpenoid CDDO attenuates fibrogenesis by antagonistically targeting canonical TGF-ß/Smad and Akt signalling in a PPAR-γ-independent manner. These findings identify this synthetic triterpenoid as a potential new therapy for the control of fibrosis.
Subject(s)
Oleanolic Acid/analogs & derivatives , PPAR gamma/agonists , Scleroderma, Systemic/drug therapy , Skin/pathology , Adipogenesis/drug effects , Adult , Animals , Biopsy , Cells, Cultured , Collagen/biosynthesis , Disease Models, Animal , Drug Evaluation, Preclinical/methods , Female , Fibroblasts/drug effects , Fibroblasts/metabolism , Fibrosis , Humans , Infant, Newborn , Mice , Mice, Inbred C57BL , Oleanolic Acid/pharmacology , Oleanolic Acid/therapeutic use , Organ Culture Techniques , PPAR gamma/metabolism , PPAR gamma/physiology , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , Proto-Oncogene Proteins c-akt/metabolism , Scleroderma, Systemic/metabolism , Scleroderma, Systemic/pathology , Signal Transduction/drug effects , Skin/drug effects , Transforming Growth Factor beta/antagonists & inhibitors , Transforming Growth Factor beta/pharmacologyABSTRACT
Many species from Senecio genus have been used in traditional medicine, and their pharmacological activities have been demonstrated. This study investigated the chemical composition and anti-inflammatory activities of essential oils from Senecio flammeus. A total of 48 components representing 98.41 % of the total oils were identified. The main compounds in the oils were α-farnesene (11.26 %), caryophyllene (8.69 %), n-hexadecanoic acid (7.23 %), and α-pinene (6.36 %). The anti-inflammatory activity of the essential oils was evaluated in rodents (10-90 mg/kg bw) in classical models of inflammation [carrageenan-induced paw edema, 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced ear edema, and cotton pellet-induced granuloma]. The essential oils at doses of 10, 30, and 90 mg/kg bw significantly reduced carrageenan-induced paw edema by 17.42 % (P < 0.05), 52.90 % (P < 0.05), and 66.45 % (P < 0.05) 4 h after carrageenan injection, respectively, and significantly reduced myeloperoxidase activity (P < 0.05). The essential oils (10, 30, and 90 mg/kg) also produced a significant dose-dependent response to reduce TPA-induced ear edema by 20.27 % (P < 0.05), 33.06 % (P < 0.05), and 53.90 % (P < 0.05), respectively. The essential oils produced significant dose-response anti-inflammatory activity against cotton pellet-induced granuloma that peaked at the highest dose of 90 mg/kg (49.08 % wet weight and 47.29 % dry weight). Results demonstrate that the essential oils of S. flammeus were effective in the treatment of both acute and chronic inflammatory conditions, thereby supporting the traditional use of this herb.
ABSTRACT
OBJECTIVE: To study whether Tongxinluo (TXL) can induce angiogenesis in bone marrow mesenchymal stem cells (MSCs), and to investigate the underlying mechanism. METHODS: Bone marrow MSCs were obtained from male Sprague-Dawley rats. We established an angiogenesis model in vitro via matrigel experiment. MSCs were seeded on matrigel coated 24-well plates, and treated by TXL 50 and 100 mg/L. After 24 h, we observed the tube formations of MSCs in the matrigel. Cell migration ability was examined by wound scratch test and transwell assay. Expressions of vascular endothelial growth factor (VEGF), fetal liver kinase-1 (Flk-1), matrix metalloproteinase-2 (MMP-2), MMP-9, and tissue inhibitor of metalloproteinase-2 (TIMP-2) were analyzed at the protein level by Western blot. Gelatin zymography assay was applied to investigating the MSC paracrine abilities of pro-MMP-2 and activated MMP-2. RESULTS: TXL promoted MSC tube formation in matrigel. The ratio of TXL 100 mg/L treated-MSC tubular length was increased 3.04-fold compared to the control group (P<0.05). Scratch test and transwell assay showed that TXL could improve the cell migration ability of MSCs. Western blot experiments showed that TXL promoted MSC synthesis of MMP-2, but it had no influence on the expressions of MMP-9 and TIMP-2. This effect was confirmed by gelatin zymography assay, which showed that TXL increased MSC secretion of pro-MMP-2 and activated MMP-2. VEGF expression of TXL treated-MSCs was increased compared to the control group. The expression of Flk-1 was not different among the groups. CONCLUSIONS: This study demonstrates that TXL can promote the tube formation of MSCs, and the underlying mechanisms are associated with increased migration ability of MSCs and the up-regulation of MMP-2 and VEGF expressions.
Subject(s)
Drugs, Chinese Herbal/pharmacology , Gene Expression Regulation , Mesenchymal Stem Cells/cytology , Animals , Cell Movement , Collagen/chemistry , Drug Combinations , In Vitro Techniques , Laminin/chemistry , Male , Matrix Metalloproteinase 2/metabolism , Mesenchymal Stem Cells/drug effects , Neovascularization, Pathologic , Neovascularization, Physiologic , Proteoglycans/chemistry , Rats , Rats, Sprague-Dawley , Vascular Endothelial Growth Factor A/metabolism , Wound HealingABSTRACT
Intracellular application of certain charged methanethiosulfonate (MTS) reagents modified and irreversibly inhibited Kir6.2 channels when cysteine substitutions were introduced at positions Ile-210, Ile-211, or Ser-212 within the putative cytoplasmic region. Inhibition depends on the spatial dimensions of the MTS reagents. Reaction of MTS reagents, having head diameters of 7.6-8.2 A, with cysteines introduced at position Ser-212 must occur in more than two subunits of the tetrameric Kir6.2 complex to inhibit channel activity. MTS reagents with head diameters less than 6.6 A modified cysteines without causing channel inhibition. An MTS reagent with a head diameter of approximately 10 A could neither modify nor inhibit the channels. Channel inhibition is interpreted as blockage of the intracellular vestibule by MTS reagents that enter the channel vestibule and react with the cysteine residues at vestibule-lining positions. Data are consistent with the hypothesis that residues Ile-210-Ser-212 line a funnel-shaped vestibule of 20-25 A in diameter, which remains unchanged during channel gating.