The mercury in Tibetan medicine has become important focus in the research on medicine safety evaluation. The total mercury and the ionic mercury in artificial gastric juice of Tibetan medicine Dangzuo were detected by Gold Amalgam Enrichment-Atomic Fluorescence Spectrometry (GAE-AFS). In the present study, Tibetan medicine Dangzuo was prepared by H2SO4-KNO3 digestion system and artificial gastric juice. The established method and condition of instrument were investigated. Under the optimum experimental conditions and instrumental operation parameters, the recovery (n=6) of HgS is 99.56$ (RSD = 1.94%), the limit of detection for mercury is 0.2 ng x L(-1), the linear range is 0-500 ng x L(-1), and r = 0.9999. Then, the total mercury and the ionic mercury in artificial gastric juice in Dangzuo samples from different Tibetan regions were assayed. The result showed that the ranges of total mercury and ionic mercury in artificial gastric juice were 3.9980-16.7358 x mg x g(-1) and 45.5377-1033.9850 ng x g(-1), respectively. The analytical method mentioned above is rapid and accurate for determining the amount of mercury in Tibetan medicine Dangzuo.
OBJECTIVE: It has been speculated that cancer survivors in Asia may have lower quality of life (QOL) compared with their Western counterparts. However, no studies have made international comparisons in QOL using a comprehensive measure. This study aimed to compare Chinese breast cancer survivors' QOL with US counterparts and examine if demographic and medical factors were associated with QOL across groups. METHOD: The sample consisted of 159 breast cancer patients (97 Chinese and 62 American) who completed the Functional Assessment for Cancer Therapy Breast Cancer (FACT-B) scale before the start of radiotherapy in Shanghai, China and Houston, USA. RESULTS: Higher income was associated with higher QOL total scores in both Chinese and American cancer patients, but QOL was not significantly associated with other factors including age, education, disease stage, mastectomy, and chemotherapy. Consistent with hypotheses, compared to their US counterparts, Chinese breast cancer survivors reported lower QOL and all four subdimensions including functional well-being (FWB), physical well-being (PWB), emotional well-being (EWB), and social well-being (SWB); they also reported more breast cancer-specific concerns (BCS). Differences were also clinically significant for Functional Assessment for Cancer Therapy General (FACT-G) scale total scores and the FWB subscale. After controlling for demographic and medical covariates, these differences remained except for the SWB and BCS. Furthermore, Chinese breast cancer survivors receiving chemotherapy reported significantly lower FACT-G scores than those who did not, but this difference did not emerge among US breast cancer survivors. DISCUSSION: Chinese breast cancer survivors reported poorer QOL on multiple domains compared to US women. Findings indicate that better strategies are needed to help improve the QOL of Chinese breast cancer survivors, especially those who underwent chemotherapy.
ETHNOPHARMACOLOGICAL RELEVANCE: Dioscorea zingiberensis C. H. Wright (D. zingiberensis), Dioscoreaceae, is used extensively in traditional Chinese medicines. The aim of the current review paper is to give a comprehensive overview of the traditional usage and phytochemistry of the plant. Clinical studies performed and products prepared from the plant and active principles will be mentioned. In addition a review of the taxonomy of the genus Dioscorea is given.MATERIALS AND METHODS: A systematic search on literature has been performed in databases like Google Scholar, Science Direct, Scifinder, Web of Science, and in Chinese databases (China Knowledge Resource Integrated, i.e., CNKI and Wanfang) including Ph.D. and M.Sc. dissertations. These from the period 1983-2016 have been searched.
RESULTS: D. zingiberensis is an endemic plant in China widely distributed in some provinces, especially Hubei and Shaanxi. The rhizomes are the medicinal part in Dun-Ye-Guan-Xin-Ning tablets and are used for isolation of diosgenin. Steroidal saponins are believed to be the active principles. More than 70 compounds have been identified. Several of these have been tested in preclinical assays and clinical trials. A wide spectrum of biological effects including cardiovascular, anti-thrombosis, hyperlipidemia, neuroprotection, anti-inflammatory, and anthelmintic effect has been verified.
CONCLUSIONS: Because of the promising results from the investigations on the plant material of D. zingiberensis, further in depth analyses ought to be performed to evaluate its potential as either a traditional drug or a source of bioactive principle. The presently performed studies do not explain mechanism of action, pharmacokinetics (ADME properties), or toxicity. All of these topics need more elaborate investigations.
ETHNOPHARMACOLOGICAL RELEVANCE: In Chinese folk medicine, the flower of Edgeworthia gardneri (Wall.) Meisn. is used to treat various metabolic diseases, such as hyperglycemia, hypertension, and hyperlipidemia. AIM OF THE STUDY: This study aimed to explore the antidiabetes potential of the flower of E. gardneri and investigate whether it can benefit the entire gut bacteria community. MATERIALS AND METHODS: Chemical constituents of the extract were analyzed by UHPLC-Q Exactive Mass Spectrometer (UHPLC-QE-MS). The antidiabetes effect of the water extract (WAE) of the flower of E. gardneri was evaluated in diabetic mice induced by high-fat diet (HFD) and streptozotocin (STZ) (six groups, n = 8) daily at doses of 1, 2, and 3 g/kg for 4 weeks. The gut microbiota was analyzed using high-throughput 16S rRNA gene sequencing. Short-chain fatty acids (SCFAs) in the fecal were also investigated. RESULTS: UHPLC-QE-MS analysis identified 29 compounds, including five alkaloids, six coumarins, four flavonoids, 11 organic acids, and three additional compounds, in the WAE. Results showed that the high dose of WAE considerably decreased the blood glucose level by 30.0%. Furthermore, E. gardneri significantly ameliorated insulin resistance and lipid metabolism dysfunction and repaired islet, hepatic, and white fat and colon histology in diabetic mice. Diabetic mice treated with WAE showed apparent changes in the structure and composition of the gut microbiota. WAE reversed the changes in Clostridiales, Lachnospiraceae, S24-7, Rikenellaceae, and Dorea in diabetic mice. The correlation analysis indicated that key OTUs were related to diabetes indices. The amounts of SCFAs, including acetic, propionic, and valeric acids, were significantly high in WAE-treated diabetic groups. CONCLUSIONS: E. gardneri treatment improved the glucose metabolism and reshaped the unbalanced gut microbiota of diabetic mice. Our study provides evidence for application of E. gardneri to treatment of diabetes mellitus.
Total ash clearance rates and saponins' loss rates of <i>Panax notoginseng</i> rhizome, root tuber, and rootlet all increased with a prolonged washing time and the rising of water temperature. Under the same conditions, the total ash clearance rates of fresh <i>P. notoginseng</i> were significantly higher than those dried. Meanwhile, the saponins' loss rates were opposite. The highest daily intake of bioavailability heavy metals was rootlet. However, all of that was significantly lower than the recommended daily intake, and both the target hazard quotients and hazard index values were lower than 1. Conclusion, it is effective to decrease washing time and water temperature in order to reduce the loss of saponins of <i>P. notoginseng</i> on the premise that ash content of Notoginseng conforms to standard of Chinese Pharmacopeias. Safety risk assessments of heavy metals based on bioavailability can further reduce the health risk of the heavy metal exposure of Notoginseng.<br>Practical applications: Notoginseng possesses the functions of hemostatic and promoting blood circulation. Clay on the surface of Notoginseng contains high content of heavy metal and induces the exceeding of standard. Washing is the most effective way to clean heavy metal attached on Notoginseng. However, research about the washing technology of <i>Panax notoginseng</i> is still blank. Heavy metals in Notoginseng that are taken orally are much higher than the amount actually absorbed by humans. In such a condition, the risk of heavy metals in Notoginseng will be overestimated, which may bring unnecessary loss to the development of Notoginseng industry. Therefore, this experiment researches the remaining of heavy metal under different washing water temperature and washing time. Also, we evaluate the bioavailability and risk of heavy metals in Notoginseng that are washed in an optimum condition. In this way, we provide technological parameters for the washing operation in processing <i>P. notoginseng</i> and referential data to set the quantity standard of heavy metal in Notoginseng.
This study is aimed to explore the effect of nitrogen, phosphorus and potassium combined application on the active components of Rhodiola crenulata. R. crenulata was used as the research object, "3414" fertilization experiment were conducted with regular fertilization of NPK(N 60 kg·hm⁻², P₂O₅ 100 kg·hm⁻²,KCl 160 kg·hm⁻²) to study the effect of different rates of NPK fertilization on the total amount of 4 phenolic constituents of gallic acid, salidroside, tyrol and ethyl gallate through field test. The results show that the content of salidroside was higher in the treatment of N₁P₂K₁ and N₁P₂K₂, andthe total amount of four phenols was higher in the treatment of N₁P₂K₂ and N₂P₂K₂. The suitable level of nitrogen, phosphorus and potassium promoted the accumulation of the 4 kinds of phenols.The amount of fertilizer recommended by the three factor fertilizer effect equation,(N 0 kg·hm⁻²,P₂O₅ 150 kg·hm⁻²,KCl 31.71 kg·hm⁻²) obtained the highest content of salidroside, and it was 1.54%.（N 35.54 kg·hm⁻²,P₂O₅ 150 kg·hm⁻²,KCl 237.73 kg·hm⁻²）obtained the highest content of 4 kinds of phenolic compounds, and it was 1.93%. This study provides a reference for the standardization of artificial planting of endangered Tibetan medicine.
ObjectiveTo investigate the effects of short-term forest bathing on human health.
Methods
Twenty healthy male university students participated as subjects and were randomly divided into two groups of 10. One group was sent on a two-night trip to a broad-leaved evergreen forest, and the other was sent to a city area. Serum cytokine levels reflecting inflammatory and stress response, indicators reflecting oxidative stress, the distribution of leukocyte subsets, and plasma endothelin-1 (ET-1) concentrations were measured before and after the experiment to evaluate the positive health effects of forest environments. A profile of mood states (POMS) evaluation was used to assess changes in mood states.
Results
No significant differences in the baseline values of the indicators were observed between the two groups before the experiment. Subjects exposed to the forest environment showed reduced oxidative stress and pro-inflammatory level, as evidenced by decreased malondialdehyde, interleukin-6, and tumor necrosis factor a levels compared with the urban group. Serum cortisol levels were also lower than in the urban group. Notably, the concentration of plasma ET-1 was much lower in subjects exposed to the forest environment. The POMS evaluation showed that after exposure to the forest environment, subjects had lower scores in the negative subscales, and the score for vigor was increased.
Conclusion
Forest bathing is beneficial to human health, perhaps through preventive effects related to several pathological factors.
Fourteen self-reported insomniacs (SRI) and 14 good sleepers (GS) had their cardiac neuronal activity assessed by heart rate variability (HRV) under controlled respiration at a slow frequency rate of 0.1 Hz, and a forced rate of 0.2 Hz during daytime rest. Nighttime sleep was measured by polysomnography. The SRI showed depressed high frequency power of HRV compared to the GS. An increased total power of HRV was observed among the SRI during slow, paced breathing compared with spontaneous breathing and 0.2 Hz. Sleep onset latency, number of awakenings, and awakening time during sleep were decreased and sleep efficiency was increased if SRI practiced slow, paced breathing exercises for 20 min before going to sleep. Our results indicate that there is autonomic dysfunction among insomniacs, especially in relation to vagal activity; however, this decreased vagal activity can be facilitated by practicing slow, paced breathing, thereby improving sleep quality.
Artemisia vestita Wall., a traditional Tibetan medicine, has wide clinical application for inflammatory diseases. However, its molecular mechanism of anti-inflammatory effect is poorly understood. In the present study, we investigated the anti-inflammatory activity and underlying mechanism of the ethanol extract from Artemisia vestita (AV-ext) on lipopolysaccharide (LPS)-induced sepsis. Pretreatment with AV-ext significantly decreased the levels of tumor necrosis factor-alpha (TNF-alpha) in serum and liver and lung tissues, and improved the survival of mice with experimental sepsis. AV-ext also remarkably reduced the expression levels of TNF-alpha, interleukin-1beta and cyclooxygenase-2 in LPS-stimulated RAW 264.7 macrophages and dose dependently suppressed the activation of mitogen-activated protein kinases (MAPKs), such as p38, extracellular signal-regulated kinase (ERK1/2) and c-Jun NH2-terminal kinase (JNK). Furthermore, pretreatment with AV-ext dose dependently inhibited the activation of nuclear factor-kappaB (NF-kappaB), as well as the degradation and phosphorylation of inhibitory kappaB (IkappaB) in LPS-activated RAW 264.7 macrophages. These results collectively reveal that AV-ext inhibits TNF-alpha release from macrophages by suppressing MAPK and NF-kappaB signaling pathways and suggest that AV-ext may be beneficial for the treatment of endotoxin shock or sepsis.
Artemisia vestita Wall., a traditional Tibetan medicine, has wide clinical application for inflammatory diseases. However, its molecular mechanism of anti-inflammatory effect is poorly understood. In the present study, we investigated the anti-inflammatory activity and underlying mechanism of the ethanol extract from Artemisia vestita (AV-ext) on lipopolysaccharide (LPS)-induced sepsis. Pretreatment with AV-ext significantly decreased the levels of tumor necrosis factor-alpha (TNF-alpha) in serum and liver and lung tissues, and improved the survival of mice with experimental sepsis. AV-ext also remarkably reduced the expression levels of TNF-alpha, interleukin-1beta and cyclooxygenase-2 in LPS-stimulated RAW 264.7 macrophages and dose dependently suppressed the activation of mitogen-activated protein kinases (MAPKs), such as p38, extracellular signal-regulated kinase (ERK1/2) and c-Jun NH2-terminal kinase (JNK). Furthermore, pretreatment with AV-ext dose dependently inhibited the activation of nuclear factor-kappaB (NF-kappaB), as well as the degradation and phosphorylation of inhibitory kappaB (IkappaB) in LPS-activated RAW 264.7 macrophages. These results collectively reveal that AV-ext inhibits TNF-alpha release from macrophages by suppressing MAPK and NF-kappaB signaling pathways and suggest that AV-ext may be beneficial for the treatment of endotoxin shock or sepsis.
Artemisia vestita Wall., a traditional Tibetan medicine, has wide clinical application for inflammatory diseases. However, its molecular mechanism of anti-inflammatory effect is poorly understood. In the present study, we investigated the anti-inflammatory activity and under-lying mechanism of the ethanol extract from Artemisia vestita (AV-ext) on lipopolysaccharide (LPS)-induced sepsis. Pretreatment with AV-ext significantly decreased the levels of tumor necrosis factor-α (TNF-α) in serum and liver and lung tissues, and improved the survival of mice with experimental sepsis. AV-ext also remarkably reduced the expression levels of TNF-α, interleukin-1β and cyclooxygenase-2 in LPS-stimulated RAW 264.7 macrophages and dose dependently suppressed the activation of mitogen-activated protein kinases (MAPKs), such as p38, extracellular signal-regulated kinase (ERK1/2) and c-Jun NH2-terminal kinase (JNK). Furthermore, pretreatment with AV-ext dose dependently inhibited the activation of nuclear factor-κB (NF-κB), as well as the degradation and phosphorylation of inhibitory κB (IκB) in LPS-activated RAW 264.7 macrophages. These results collectively reveal that AV-ext inhibits TNF-α release from macrophages by suppressing MAPK and NF-κB signaling pathways and suggest that AV-ext may be beneficial for the treatment of endotoxin shock or sepsis.
The Meconopsis plants (Chinese: ), belonging to the family Papaveraceae, have been used as traditional Tibetan medicine (TTM) for thousands of years. Meconopsis has the effects of clearing heat, reducing swelling, and easing pain, and is mainly prescribed for heat syndromes, hepatitis, pneumonia, and pain in joints. Phytochemical studies have revealed the presence of major isoquinoline alkaloids and flavonoids. Modern pharmacological research has demonstrated its antitumor, hepatoprotective, analgestic, antimicrobial, anti-oxidant, antitussive, and anti-inflammatory activities. However, resource availability, in-depth in vivo pharmacological study and qualitative and quantitative analysis are still insufficient and deserve further efforts. This paper provides a comprehensive advance on the ethnopharmacological, phytochemical, and pharmacological studies of the genus, in hopes of promoting a better understanding of their medicinal values.
The Meconopsis plants (Chinese: ), belonging to the family Papaveraceae, have been used as traditional Tibetan medicine (TTM) for thousands of years. Meconopsis has the effects of clearing heat, reducing swelling, and easing pain, and is mainly prescribed for heat syndromes, hepatitis, pneumonia, and pain in joints. Phytochemical studies have revealed the presence of major isoquinoline alkaloids and flavonoids. Modern pharmacological research has demonstrated its antitumor, hepatoprotective, analgestic, antimicrobial, anti-oxidant, antitussive, and anti-inflammatory activities. However, resource availability, in-depth in vivo pharmacological study and qualitative and quantitative analysis are still insufficient and deserve further efforts. This paper provides a comprehensive advance on the ethnopharmacological, phytochemical, and pharmacological studies of the genus, in hopes of promoting a better understanding of their medicinal values.
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.
The genus Adonis L. (Ranunculaceae), native to Europe and Asia, comprises 32 annual or perennial herbaceous species. Due to their cardiac-enhancing effects, Adonis spp. have long been used in European and Chinese folk medicine. These plants have been widely investigated since the late 19th century, when the cardiovascular activity of Adonis vernalis L. was noted in Europe. The present paper provides a review of the phytochemistry, biological activities and toxicology in order to highlight the future prospects of the genus. More than 120 chemical compounds have been isolated, with the most important components being cardiac glycosides as well as flavones, carotenoids, coumarins and other structural types. Plants of the genus, especially A. vernalis L. and A. amurensis Regel & Radde, their extracts and their active constituents possess broad pharmacological properties, including cardiovascular, antiangiogenic, antibacterial, antioxidant, anti-inflammatory and acaricidal activities, and exhibit both diuretic effects and effects on the central nervous system. However, most plants within the 32 species have not been comprehensively studied, and further clinical evaluation of their cardiovascular activity and toxicity should be conducted after addressing the problem of the rapidly decreasing resources. This review provides new insight into the genus and lays a solid foundation for further development of Adonis.
<br>Display Omitted<br>• The effect of organic sample solvents in SCX mode were systematically studied. • Organic sample solvents affect the separation efficiency in SCX mode seriously. • Elution strength of organic solvents affect efficiency of later-eluted analyte. • Retention of organic solvents affected efficiency of earlier-eluted analyte. • The results can be used for the optimization of SCX methods.<br>This study investigated the influence of organic sample solvents on separation efficiency of basic compounds under strong cation exchange (SCX) mode. The mixtures of acidic aqueous solution and organic solvent such as acetonitrile, ethanol, methanol and dimethyl sulfoxide (DMSO) were tested as sample solvents. For later-eluting analytes, the increase of sample solvent elution strength was responsible for the decrease of separation efficiency. Thus, sample solvents with weak elution strength could provide high separation efficiencies. For earlier-eluting analytes, the retention of organic sample solvents was the main factor affecting separation efficiency. Weakly retained solvents could provide high separation efficiency. In addition, an optimized approach was proposed to reduce the effect of organic sample solvent, in which low ionic solvent was employed as initial mobile phase in the gradient. At last, the analysis of impurities in hydrophobic drug berberine was performed. The results showed that using acidic aqueous methanol as sample solvents could provide high separation efficiency and good resolution (<b>R</b> > 1.5).
OBJECTIVE: To investigate the role of Tibetan medicine-Twenty Wei Chenxiang Pill interfering with serum ET-1 level, in order to confirm that ET-1 is involved to the pathogenesis of hypoxic pulmonary hypertension.METHODS: 165 Wistar rats were randomly divided into high altitude control group,Tibetan medicine-Twenty Wei Chenxiang Pill group and plain control group. The physiological signal acquisition system was used to record pulmonary arterial pressure, and RV/(LV + S) ratio were caculated. Serum HIF-1alpha and ET-1 protein levels were determined by the method of ELISA, and ETA protein levels in lung tissue were determined by Western Blot method.
RESULTS: Compared with the high altitude group,in the rats of Tibetan medicine-Twenty Wei Chenxiang Pill group,the pulmonary arterial pressure decreased significantly from the seventh day and the seventh day (P < 0.01), the RV/(LV + S) ratio and serum HIF-1alpha levels decreased significantly from the third day (P < 0.05 or P < 0.01), the serum ET-1 levels decreased significantly from the third day (P < 0.05 or P < 0.01), and the expression of ETA protein decreased significantly from the beginning (P < 0.01 or P < 0.001).
CONCLUSION: ET-1 is one of the important factors causing pulmonary artery pressure increasing and right ventricular wall thickening, which plays a role in hypoxic pulmonary artery only involved in the early period hypoxia, but not in the later period. Tibetan medicine--twenty Wei Chenxiang Pill can prevent the pulmonary artery hypertension and the right ventricular wall thickening in rats, and its mechanism may be related to the direct inhibition of ET-1 and protein levels of ETA or the indirect downregulation of ET-1 level and ETA through inhibition of HIF-la level.
Based on literature data, related specimens, commercial samples and field investigation, botanical origin of "bolingguazi" was clarified. Boling guazi was found to be used as a Tibetan medicine in China from 8th century, it was derived from Herpetospermum pedunculosum of cucurbitaceae, and main species of bolingguazi used in most areas of China were H. pednculosura, while seeds of Momordica charantia, Thladiantha setispina and M. cohinchinensis were also available in some areas of China.
Diosgenin wastewater produced from <b>Dioscorea zingiberensis</b> C. H. Wright in diosgenin enterprise is the by-product of numerous operations chiefly including washing raw materials, acid hydrolysis, and cleaning the apparatus with water. It requires the removal of high concentrations of various organic and inorganic contaminants from this wastewater in order to avoid pollution to the environment and fresh water system. Currently, several different methods such as chemical, physicochemical, biological recovery resource, constructed wetland, and integrated methods of these processes are being applied for treating diosgenin wastewater. Aiming to get a comprehensive overview, available reports from experimental scale to industry scale about the treatment of this wastewater were collected and summarized. Therefore, this review paper will provide appropriate choice for the efficient treatment of diosgenin wastewater and supportive information for the other scientists who want to continue this valuable research in the future.<br><br>Display Omitted<br>• Studies of diosgenin wastewater treatment between 2003 and 2016 are reviewed. • Characteristics of diosgenin wastewater are presented. • These methods used for diosgenin wastewater are compared. • Merits and demerits of each approach to cope with diosgenin wastewater are stated. • Future promising ways should be updated based on currently available ones.
In this study, a computer-based network pharmacology approach was applied to investigate the potential mechanism and important components of Rhodiola crenulata in the protection of H9c2 cells against hydrogen peroxide (H₂O₂)-induced oxidative stress. The intestinal absorption liquid of R. crenulata enhanced the cell viability, maintained cell morphology and inhibited cell apoptosis in the H₂O₂-induced oxidative stress in H9c2. Then, computer-based network pharmacology was used to analyze the relevant mechanism. A total of 133 oxidative stress-related compounds were screened out; and 26 of them occupied the top 20%, and all of the compounds enriched in 43 oxidative stress-related key targets. Finally, a "compound-target-pathway-function" network was constructed. Based on the analysis of the network pharmacology, R. crenulata protected H9c2 cells against H₂O₂-induced oxidative stress probably by affecting apoptosis-related processes, such as cell death, nitric oxide metabolism, oxidative stress, mitochondrial mechanism, redox process, redox-related enzyme activty and other oxidative stress-related process. And salidroside, ethyl gallate and catechins, which were the main components of R. crenulata, played an important role in this process. Therefore, the potential mechanism and important components of R. crenulata revealed the protective effect on oxidative stress. This study shows a multi-component, multi-target and overall regulation effect of R. crenulata on the oxidative stress, and provides a reliable reference for subsequent systematic experimental studies for the pharmacodynamic material foundation and mechanism of action R. crenulata.
DMNG-3(3β-Methyl-[2-(4-nitrophenoxy)ethyl]-amino]con-5-enine), is a new and the potentially most potent acetylcholinesterase inhibitor recently obtained from conessine by N-demethylation and nucleophilic substitution reaction. In the present study, a step-down passive avoidance test was used to investigate whether DMNG-3 could modulate impairment of learning and memory induced by scopolamine, and a high performance liquid chromatography(HPLC) method for the determination of DMNG-3 in biological samples was applied to study its pharmacokinetics and tissues distribution. Separation was achieved on C18 column using a mobile phase consisting methanol-water (70:30, v/v) at a flow rate of 1.0ml/min. The intra- and inter-day precisions were good and the RSD was all lower than 1.30%. The mean absolute recovery of DMNG-3 in plasma ranged from 88.55 to 96.45 %. Our results showed oral administration of DMNG-3(10,25,50 mg/kg/day) can significantly improve the latency and number of errors and had a positive effect of improvement of learning and memory in mice in passive avoidance tests. The elimination half-life (T1/2) was 14.07±1.29, 15.87±1.03h, and the total clearance (CL) values were 0.70±0.11, 0.78±0.13 L/h/kg, respectively. The pharmacokinetic studies showed that DMNG-3 has a slowly clearance and large distribution volume in experimental animals, and its disposition is linear over the range of doses tested. The liver, small intestine, stomach, and large intestine were the major distribution tissues of DMNG-3 in mice. It was found that DMNG-3 could be detected in brain, suggesting that DMNG-3 can cross the blood-brain barrier. The present study shows that DMNG-3 can be possible developed as a new drug for the treatment of Alzheimer's disease in the future.
DMNG-3(3β-Methyl-[2-(4-nitrophenoxy)ethyl]-amino]con-5-enine), is a new and the potentially most potent acetylcholinesterase inhibitor recently obtained from conessine by N-demethylation and nucleophilic substitution reaction. In the present study, a step-down passive avoidance test was used to investigate whether DMNG-3 could modulate impairment of learning and memory induced by scopolamine, and a high performance liquid chromatography(HPLC) method for the determination of DMNG-3 in biological samples was applied to study its pharmacokinetics and tissues distribution. Separation was achieved on C18 column using a mobile phase consisting methanol-water (70:30, v/v) at a flow rate of 1.0ml/min. The intra- and inter-day precisions were good and the RSD was all lower than 1.30%. The mean absolute recovery of DMNG-3 in plasma ranged from 88.55 to 96.45 %. Our results showed oral administration of DMNG-3(10,25,50 mg/kg/day) can significantly improve the latency and number of errors and had a positive effect of improvement of learning and memory in mice in passive avoidance tests. The elimination half-life (T1/2) was 14.07±1.29, 15.87±1.03h, and the total clearance (CL) values were 0.70±0.11, 0.78±0.13 L/h/kg, respectively. The pharmacokinetic studies showed that DMNG-3 has a slowly clearance and large distribution volume in experimental animals, and its disposition is linear over the range of doses tested. The liver, small intestine, stomach, and large intestine were the major distribution tissues of DMNG-3 in mice. It was found that DMNG-3 could be detected in brain, suggesting that DMNG-3 can cross the blood-brain barrier. The present study shows that DMNG-3 can be possible developed as a new drug for the treatment of Alzheimer's disease in the future.
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