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@#Two Hofmann-Martius-like rearrangement products generated in the production of duloxetine hydrochloride were studied. The structures and generation mechanism of the two Hofmann-Martius rearrangement products were analyzed by LC-MS and NMR. The results showed that under the acidic conditions, the naphthol ether bond of duloxetine would break down and the intermediates of naphthol and the alkyl thiophene cation was generated; the two Hofmann-Martius-like rearrangement products were proven to be a pair of isomers produced by nucleophilic substitution between the naphthol intermediate state and the alkyl thiophene cation intermediate state at the ortho or the para position, respectively. The production of two isomers was related to the strong acidic and protic solvent environment. Therefore, in the salting process of duloxetine hydrochloride, the pH value should be controlled in the range of 3-7 and temperature should be maintained below 50 °C, as well as the nonprotic solvent acetone is chosen to avoid generation of the two isomers.
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Hexane is a widely used organic solvent in industry, and chronic hexane poisoning is the main occupational toxic lesion in China. In particular, axonal and myelin lesions in the distal thick fibers of the peripheral nervous system may be caused by 2, 5-hexanedione (2, 5-HD), an intermediate metabolite of n-hexane in humans. Hexane has toxic effects not only on the nervous system but also on the liver, kidneys, and reproductive organs. In this paper, we review the progress of research on the mechanism of n-hexane toxic neuropathy.
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Humans , Hexanes/toxicity , Hexanones , Industry , SolventsABSTRACT
Objective:To explore the effect of Chaihu Jia Longgu Muli Tang on the hippocampus of rats with chronic stress depression based on the brain-derived neurotrophic factor (BDNF)/tyrosine kinase B (TrkB)/cyclic adenosine phosphate response element-binding protein (CREB) pathway. Method:Sixty SD rats were divided into a blank group (<italic>n</italic>=10) and an experimental group (<italic>n</italic>=50) for the induction of the chronic stress depression model. The rats in the experimental group were further divided into the following five groups: a model group， a fluoxetine hydrochloride group (0.003 g·kg<sup>-1</sup>), and low-(1.625 g·kg<sup>-1</sup>), medium-(3.25 g·kg<sup>-1</sup>), and high-dose (6.5 g·kg<sup>-1</sup>) Chaihu Jia Longgu Muli Tang groups. The rats were administered correspondingly by gavage once a day for eight weeks. Behavioral tests were performed to evaluate the depression state of the rats before modeling， after modeling， and after drug administration. Hematoxylin-eosin (HE) staining was used to observe the morphological changes in the hippocampus of rats. The immunohistochemical (IHC) staining was used to quantitatively detect BDNF protein expression in the rat hippocampus. The mRNA and protein expression of BDNF， TrkB， and CREB in the rat hippocampus was detected by the real-time fluorescence-based quantitative PCR (Real-time PCR) and Western blot， respectively. Result:Compared with the blank group， the model group showed decreased sucrose preference rate (<italic>P</italic><0.05)， declining horizontal and vertical scores (<italic>P</italic><0.05)， and prolonged immobility time and floating time (<italic>P</italic><0.05). Additionally， HE staining results revealed that hippocampal neuron structure was damaged. IHC staining showed that the mRNA and protein expression of BDNF， TrkB， and CREB was significantly decreased (<italic>P</italic><0.05). Compared with the model group， the fluoxetine hydrochloride group and the Chaihu Jia Longgu Muli Tang groups displayed elevated sucrose preference rate (<italic>P</italic><0.05)， increased horizontal and vertical scores (<italic>P</italic><0.05)， and shortened immobility time and floating time (<italic>P</italic><0.05). Furthermore, the hippocampal neuron structure was significantly repaired. IHC staining showed that the mRNA and protein expression of BDNF， TrkB， and CREB was significantly increased (<italic>P</italic><0.05). Conclusion:Chaihu Jia Longgu Muli Tang can significantly improve the depression-like behaviors of rats after chronic stress stimulation and enhance the regeneration and repair of neurons in the hippocampus. The underlying mechanism may be related to the up-regulation of the BDNF/TrkB/CREB signaling pathway in the hippocampus of rats.
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In this study, Andrographis paniculata seedlings were used as experimental materials to study the effects of salicylic acid(SA) on the growth and effective component accumulation of A. paniculata under NaCl stress. The results showed that with the increase of NaCl concentration, the growth of A. paniculata seedlings was significantly inhibited, and the content of carotene and carotenoid decreased. The activity of antioxidant enzyme was enhanced. At the same time, the contents of proline, proline and soluble protein were on the rise. The contents of andrographolide, new andrographolide and deoxyandrographolide showed an upward trend, while deoxyandrographolide showed a downward trend. Treatment with 100 mmol·L~(-1) NaCl+5 mg·L~(-1) SA showed a significant increase in antioxidant enzyme activity in A. paniculata leaves. Treatment with 100 mmol·L~(-1) NaCl+10 mg·L~(-1) SA showed significant changes in soluble protein and proline content in A. paniculata leaves, while MDA content in A. paniculata leaves significantly decreased. 10 mg·L~(-1) SA had the best effect on the growth of A. paniculata seedlings under salt stress. Under the treatment of 50 mmol·L~(-1) NaCl+10 mg·L~(-1) SA, fresh weight, dry weight and leaf dry weight of A. paniculata seedlings reached the highest level, which were 1.02, 1.09 and 1.11 times of those in the control group, respectively. The concentrations of NaCl and 10 mg·L~(-1) SA were significantly higher than those of the control group. Four key enzyme genes of A. paniculata diterpene lactone synthesis pathway were selected to explore the molecular mechanism of salicylic acid to alleviate salt stress. With the increase of salt stress, the relative expressions of HMGR, GGPS and ApCPS were up-regulated, indicating that salt stress may enhance the synthesis of A. paniculata diterpene lactone through MVA pathway. SA can effectively promote the growth and development of A. paniculata under salt stress, improve its osmotic regulation and antioxidant capacity, improve its salt tolerance, and alleviate the effects of salt stress on A. paniculata.
Subject(s)
Andrographis , Plant Leaves , Salicylic Acid , Salt Tolerance , Seedlings/geneticsABSTRACT
Polysaccharides from Chinese medicines are attracting increasing attention to their wide range of valuable biological activities. As these polysaccharides are mostly from edible materials, their safety can be greatly ensured. Therefore, the Chinese medicine polysaccharides have been the focus of research and development of new drugs and health products. However, there are rarely successful cases. Here, based on the authors' own research experience, the difficulties and challenges in chemical analysis and mechanism study of Chinese medicine polysaccharides are discussed, in the hope of eliciting more innovative ideas and solutions.
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To investigate the preventive effect and possible mechanism of puerarin(Pur) in rat model of disuse osteoporosis(DOP),thirty healthy Wistar female rats of 2 months old were randomly divided into control group(Control), hindlimb suspension group(HLS), and puerarin group(HLS+Pur) in hindlimb suspension, with 10 rats in each group. A disuse osteoporosis model was established by tail suspension method, and 15.4 mg·kg~(-1) puerarin suspension was administered to HLS+Pur group every day, and the same volume of distilled water was administered to Control group and HLS group respectively. After 28 days, the rats were sacrificed by abdominal aorta blood collection, the main organs of the rats were removed, and the bone tissues of the rats were dissected. The organ index of the rats was calculated and the histopathology of the organs was observed under microscope. Bone mineral density test and bone biomechanical experiment were performed. Bone histomorphometry results were observed after bone tissue sectioning, and serum biochemical markers of bone metabolism were determined. There was no significant difference in organ index between the groups. There was no obvious abnormality in the pathological examination of the organs. The results of bone mineral density showed that puerarin could significantly increase the bone density of the tibia and vertebrae caused by hindlimb suspension. The mechanical parameters experiments showed that puerarin could effectively increase the maximum load and elastic modulus of the tibia and vertebrae. Fluorescence labeling showed that the fluorosis interval increased and the bone formation increased during puerarin treatment. The VG staining results showed that compared with the HLS group, in the puerarin group, the number of trabecular bone increased, the thickness of the trabecular bone became thicker, and the bone separation became smaller, which greatly improved the bone microstructure after hindlinb suspension. In addition, serum biochemical indicators showed that puerarin could promote bone formation index bone calcium. The content of osteocalcin(OC) increased and inhibited the formation of tartrate-resistant acid phosphatase 5 b(TRACP 5 b). Puerarin has a preventive effect in the rat model of disuse osteoporosis and its effect is good, and its mechanism may be related to promoting bone formation and inhibiting bone resorption.
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Animals , Female , Rats , Bone Density , Isoflavones , Pharmacology , Osteocalcin , Metabolism , Osteoporosis , Drug Therapy , Rats, Wistar , Tartrate-Resistant Acid Phosphatase , MetabolismABSTRACT
The decreased efficacy and severe side effects of antibiotics, as well the increase of multidrug resistant pathogens are seriously threatening human health. It has become an urgent task for the whole world to actively respond to threats and establish effective prevention and control plans. Traditional Chinese medicine (TCM) has a long history with exact curative effect in the treatment of infectious diseases. It not only inhibits pathogens and eliminates endotoxin, but also has therapeutic effect on inflammation, immune abnormality and overall disorder caused by infection. Antibiotics mainly inhibit the pathogen itself, while the combination of TCM and antibiotics is complementary with each other and is considered as a feasible solution to the challenges. Some clinical observations have shown that TCM has potentiality of enhancing antibiotics efficiency and reducing toxicity. Exploring its mechanism is the necessary measure to optimize and popularize treatment regimen. Firstly, multi-level and multi-dimensional systematic pharmacology network analysis methods are used to predict the mechanism of TCM combined with antibiotics in the treatment of infectious diseases, so as to provide the evidence for further empirical research and selection of test indicators. Then by following the principle of corresponding drug use in specific TCM syndromes, the antibiotics and TCM are individually and jointly applied to treat patients with specific syndrome conditions of infectious diseases. Besides routine and comprehensive evaluation of synergistic and attenuated effect of the combined drug use, multi-omics technique is also used to find the subtle effects of these two drugs at a molecular level. The sensitive and stable clinical biomarkers of synergism and attenuation of combined drug use are determined by using biomolecular network analysis technology. Finally, taking these biomarkers as clues, the biotransformation process and regulation mechanism of the biomarkers are traced back in animal models of infectious diseases and cell level, and all of these are clinically verified. As a result, the mechanism of efficacy enhancing and toxicity reducing of combined drug use can be revealed, providing basis for the promotion and application of such combined drug use.
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Objective@#To investigate the possible mechanism of doxycycline inhibiting paraquat-induced pulmonary fibrosis and provide a theoretical basis for its clinical application.@*Methods@#Human lung fibroblast HFL1 cells were selected as the research object in the cell group. Divided into blank group, paraquat group, paraquat+doxycycline group. The expression of TGF-β1, a-SMA, Smad3 and Smad2 protein was detected by ELISA using 40 ml of paraquat 40 umol/L and 3 mg/L of oleic acid 10 mg/L. In the animal group, 120 healthy and clean SD rats were randomly divided into three groups: blank group, paraquat group, paraquat+doxycycline group. The expression of TGF-β1, a-SMA, Smad3 and Smad2 protein in lung tissue of mice at 1 day, 3 days, 7 days, 14 days and 21 days was detected by Elisa method. The expression of TGF-β1, a-SMA, Smad3 and Smad2 protein in lung tissue of 21-day mice was detected by Western Blotting. The pathological changes of lung tissue were observed by HE staining for 1 day, 3 days, 7 days, 14 days and 21 days.@*Results@#In the cell group experiment, the expression of TGF-β1, a-SMA, Smad3 and Smad2 protein increased gradually with paraquat in the paraquat group, and the expression of TGF-β1, a-SMA, Smad3 and Smad2 protein was significantly higher than that in the blank group. The difference was statistically significant (P<0.05) . The expressions of TGF-β1, a-SMA, Smad3 and Smad2 in the paraquat+doxycycline group were significantly lower than those in the paraquat group, but still higher than the blank group, the difference was statistically significant (P<0.05) .@*Conclusion@#Doxycycline inhibits paraquat-induced pulmonary fibrosis by inhibiting the expression of TGF-β1, a-SMA and Smad3, Smad2 proteins.
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This review discusses the mutual regulative effects of Wnt/β-catenin signaling pathway, tissue renin-angiotensin system (RAS) and vitamin D receptor (VDR) pathway in chronic non-infectious diseases (abbr. chronic diseases). The interaction between RAS and Wnt/β-catenin might induce the occurrence of multiple chronic diseases. The activation of VDR inhibits Wnt signaling transduction through blocking the action of β-catenin on down-stream genes via various pathways. Moreover, the agonists on VDR suppress the biological actions of RAS in whole circulation and local tissues. Thus, Wnt/β-catenin signaling pathway, RAS and VDR synergistically exert vital biological modulations on the pathophysiological process of chronic diseases.
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Objective: To explore the anti-inflammatory immune mechanism in moxibustion treatment of Crohn.s disease (CD) from the perspective of c-Jun N-terminal kinase (JNK) signaling pathway, through observing the regulatory effect ofmoxibustion on colonic JNK, c-Jun, monocyte chemoattractant protein 1 (MCP-1) and cyclooxygenase 2 (COX2) in CDmodel rats. Method: Male Sprague-Dawley rats of clean grade were randomized into a normal group, a model group, amoxibustion group and a sham moxibustion group. CD model was developed by the mixture of 2, 4, 6 Trinitro-benzene-sulfonic acid (TNBS) and ethanol via enema. Hematoxylin-eosin (HE) staining was used to observe the morphologicalchanges in rat.s colon tissues for pathological scoring; enzyme-linked immunosorbent assay (ELISA) was used to detectthe contents of MCP-1, COX2, JNK, and c-Jun in colon tissues; real-time fluorescence quantitative PCR was adopted toexamine the mRNA expressions of JNK and c-Jun in rat.s colon. Result: Compared with the normal group, the modelgroup showed more significant colonic damage and thus had a higher colonic damage score (P ＜ 0.01), manifested astopical inflammation which involved the submucosa, fissuring ulcers and granuloma; the model group also showedincreased contents of protein MCP-1 and COX2, and elevated contents of JNK protein and mRNA in colon (all P ＜ 0.05), while the change in the content of c-Jun was insignificant (all P＞ 0.05) . Compared with the model group and shammoxibustion group, the colonic damage score was lower in the moxibustion group (P ＜ 0.01, P ＜ 0.05), with improvementin colonic structure and inflammation; the contents of MCP-1 and COX2 in colon tissues declined, so did the proteincontent and mRNA expression of JNK (all P ＜ 0.05), while the change in the content of c-Jun was insignificant (all P＞0.05) . There were no significant differences between the model group and sham moxibustion group comparing all theindexes (all P＞ 0.05) . Conclusion: Moxibustion down-regulates the expressions of JNK protein and mRNA in CD rat.scolon, as well as the contents of MCP-1 and COX2 in colon tissues, which is possibly one significant mechanism formoxibustion to ease intestinal inflammation and promote the repair of colon tissues in CD.
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Endemic arsenicosis is a disease with complex systemic damage,but the mechanism and its control strategy are mostly focused on a single organ or system damage caused by arsenic,and the systemic damage of arsenic exposure remains not fully understood.In recent years,considerable progress has been made in the field of immunology,which made an important contribution for the pathogenic mechanism of various complex diseases,and also brings a new dawn for its prevention and treatment.In consequence,a breakthrough progress is expected to make in aspects of the mechanism and its control strategy of arsenic caused systemic damage from the perspective of immunology.
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OBJECTIVE:To provide theoretical reference for clinical research and application of TCM Mahuang decoction.METHODS:TCM components of Mahuang decoction were analyzed by literature searching and data analysis,and TCM component database was established.The active compounds were selected through computer simulation prediction,and the related targets were predicted.Molecular pharmacology mechanism of TCM Mahuang decoction in the treatment of typhoid syndrome was investigated.RESULTS:Mahuang decoction contained about 723 compounds,among which E.sinica contained 236 compounds,Cinnamomum cassia contained 115 compounds,Glycyrrhiza uralensis contained 287 compounds,and Amygdalus Communis contained 85 compounds.43 active compounds were screened through computer simulation prediction,and 18 related targets were mainly related to vasodilation effect,adrenergic action and the effect of promoting smooth muscle contraction.CONCLUSIONS:By combining oral bioavailability prediction by computer,drug-like analysis and target prediction,the study determines the effect of active compounds in Mahuang decoction on typhoid syndrome by the means of vasodilation,adrenergic action and promoting smooth muscle contraction.
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This study was aimed to observe the protective effect of extract from Rhizoma A nemones Raddeanae (RAR) on hepatic fibrosis induced by porcine serum in rats. A total of 68 SD rats were randomly divided into 5 groups, which were the normal group, model group, RAR group, extraction of RAR (EXRAR) group, Fu-Zheng Hua-Y u(FZHY) group. Each rat was intraperitoneally injected with 0.5~0.6 ml of porcine serum twice a week for 15 suc-cessive weeks to establish liver fibrosis model. Intragastric administration was given after the model was successfully established. The FZHY group was given FZHY capsule (0.525 g·kg-1). The RAR group was given RAR decoction (0.7 g·kg-1). The EXRAR group was given EXRAR (0.071 g·kg-1). The model group and normal group were given e-qual amount of physiological saline. The medication was given once a day. And the treatment course was 8 weeks. At the end of the 23th week, rats were sacrificed. Contents of SOD and MDA in blood serum were assayed. The protein expressions of α-SMA and TGF-β1 in liver tissues were detected by SABC. The results showed that compared with the model group, content of MDA decreased in the EXRAR group, RAR group and FZHY group (P<0.05), and content of SOD increased obviously (P<0.05). In the model group, expression of α-SMA and TGF-β1 increased, with dark brown dyeing and diffusion area. Expression area and strength of the FZHY group, RAR group, and EXRAR group were ob-viously weak with tasteless interval dyeing and no formation of typical pseudolobule in comparison with the model group. The color rendering index showed that compared with the model group, the protein expression of α-SMA and TGF-β1 decreased obviously in liver tissues of the FZHY group, EXRAR group, and RAR group (P< 0.05). It was concluded that RAR and its extract had a good antifibrosis effect. And the EXRAR had basically the same antifibrosis effect as RAR. It was assumed that the possible mechanism was related with the inhibiting of hepatic stellate cell (HSC) activation and the expression of TGF-β1 as well as the resisting of lipid peroxidation.
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Objective To investigate the mechanism of anticancer activities of the extracts of prescription 921. Methods The inhibitory effects of the extracts of prescription 921 on DNA and RNA biosyntheses in cultured prostate PC-3M were investigated with 3H-TdR or 3H-UR incorporation. Flowcytometry was applied to analyze the regulating cell cycle of the extracts of prescription 921. The expression of cell cycle related factors CyclinA, CyclinB, p21 and p27 were detected by Western-blot. Results The extracts of prescription 921 showed inhibitory effect on DNA biosyntheses. The cells of PC-3M were arrested in S-phage when treated with the extracts for 72 h. The expression level of CyclinA was down-regulated while expression of CyclinB, p21 and p27 was not altered. Conclusion The extracts of prescription of 921 play its anticancer activities by inhibiting DNA biosyntheses and arresting the cells in S-phage by down-regulating the expression of Cyclin A.