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Meconopsis horridula is one of alpine plants belonging to family Papaveraceae, mainly distributed in Himalaya Range area. M. horridula is a rare alpine flower, and is a kind of traditional Tibetan medicine, which has been included in more than 40 compound formulae, having efficacies of clearing away heat and alleviating pain, activating blood circulation to remove stasis, traditionally used for the treatment of fractures, injuries, and chest and back pains. Modern research shows that the whole plant of M. horridula contains alkaloids, flavonoids, and terpenes, and its pharmacological activities including antitumor, antivirus and myocardial protection etc. However, due to various factors, the current research of M.horridula still faces many challenges. This paper summaries herein a progress of MH on its ecological resources, traditional uses, and studies on chemical constituents and pharmacological effects, hopefully to provide a useful reference for the ecological protection and applications.

Aim: To reinvestigate the chemical constituents of the ethanolic extract of Meconopsis quintuplinervia Regel which is a traditional Tibetan medicine used for treatments of hepatitis, tuberculosis etc..; Methods: The compounds were enriched by column chromatography techniques over silica gel, macro porous resin and Sephadex LH-20 absorbents, and finally purified by reverse phase preparative HPLC methods with isocratic mobile phase systems of methanol-H2O-acetic acid (500:500:1) and acetonitrile-H2O-acetic acid (200:800:1). Structural determination of the pure compounds were based on extensive analyses of modern spectroscopic methods including IR, MS, HRMS, 1D- and 2D-NMR spectra.; Results: Three alkaloids were obtained and their structures were elucidated as norsanguinarine (I), O-methylflavinantine (II) and 6-methoxy-17-methyl-2, 3-[methylenebis (oxy)]-morphin-5-en-7-one (III).; Conclusion: Norsanguinarine (I) was isolated from genus Meconopsis for the first time, and 6-methoxy-17-methyl-2,3-[methylenebis(oxy)]-morphin-5-en-7-one (III) is a new alkaloid named as meconoquintupline.;

<br>Display Omitted<br>• 4′-Carbonyl chloride rosamine was synthesized and used for NTs by UHPLC-MS/MS. • <b>In situ</b> UA-DDLLME was reported for the simultaneous determination of AANTs and MANTs. • The method was sensitive, selective, low matrix effect, speedy and eco-friendly. • A new analytical tool in diagnosis of AD-related disease.<br>Neurotransmitters (NTs) may play an important role in neurodegenerative disorders such as Alzheimer’s disease (AD). In order to investigate the potential links, a new simple, fast, accurate and sensitive analytical method, based on <b>in situ</b> ultrasound-assisted derivatization dispersive liquid-liquid microextraction (<b>in situ</b> UA-DDLLME) coupled with ultra high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS), has been developed and validated. The quantitation of amino acid neurotransmitters (AANTs) and monoamine neurotransmitters (MANTs) in urine of AD rats were performed in this work. The <b>in situ</b> UA-DDLLME procedure involved the rapid injection of the mixture of low toxic 4-bromoanisole (extractant) and acetonitrile (dispersant), which containing the new designed and synthesized 4′-carbonyl chloride rosamine (CCR) as derivatization reagent, into the aqueous phase of real sample and buffer. Under the selected conditions, the derivatization and microextraction of analytes were simultaneously completed within 1 min. Good linearity for each analyte (R > 0.992) was observed with low limit of detections (LODs, S/N > 3). Moreover, the proposed method was compared with direct detection or other reported methods, and the results showed that low matrix effects and good recoveries results were obtained in this work. Taken together, <b>in situ</b> UA-DDLLME coupled with UHPLC-MS/MS analysis was demonstrated to be a good method for sensitive, accurate and simultaneous monitoring of AANTs and MANTs. This method would be expected to be highly useful in AD diseases’ clinical diagnostics and may have potential value in monitoring the efficacy of treatment.

In this paper, the domestic varieties and quality standard of Leguminosae medicinal plants used in Tibetan medicine were analyzed. The results showed that there were 36 genera and 142 species (including varieties), as well as 64 medicinal materials varieties of Leguminosae plants were recorded in relevant literatures. In relevant Tibetan standards and literatures, there are great differences in varieties, sources, used parts, and efficacy of medicinal plants. Among them, about 38.0% (including 54 species) of the endemic plants, about 25.4% (including 36 species) of the original plants have medicinal standard legal records, except 9 kinds of traditional Chinese medicine general quality standard more fairly completed, the most varieties have only description about characters, identification, etc. Therefore it is necessary to reinforce study for the herbal textual, resources and the use present situation, chemical components and biological activity, quality standard, medicinal terms specification, to promote establishment of quality standard system for variety-terminologies-sources of Tibetan medicinal plants.

In this paper, the popular domestic varieties and quality standard of Scrophulariaceae plants used in Tibetan medicine were analyzed. The results showed that there were 11 genera and 99 species (including varieties), as well as 28 medicinal materials varieties of Scrophulariaceae plants were recorded in the relevant literatures. In relevant Tibetan standards arid literatures, there are great differences in varieties, sources, parts, and efficacies of medicinal plant. Among them, about 41.4% (including 41 species) of endemic plants, about 15.2% (including 15 species) of the original plants have medicinal standard legal records, except the medicinal materials of Scrophalaria ningpoensis, Lagotis brevituba, Picrorhiza scrophulariiflora, Veronica eriogyne general, most varieties have not completed quality standard. Consequently it is necessary to reinforce the herbal textual, resources and the use present situation investigation, the effects of the species resources material foundation and biological activity, quality standard, specification the medical terms of the plants, and promote Tibetan medicinal vareties-terminologies-sources such as the criterion and quality standard system for enriching the varieties of Tibetan medicinal materials and Chinese medicinal resources.

Dahuang Lidan Pian contains Rheum palmatum, Gymnadenia conopsea and Phyllanthus emblica, which has a significant effect in the treatment of alcoholic fatty liver, cholestasis and cholecystitis. The efficacy of the formula in traditional Chinese medicine was clearing heat and promoting diuresis, removing dampness, detoxifying and relieving jaundice. These three herbs are widely used in the traditional Chinese medicine, Mongolian medicine and Tibetan medicine. Therefore, the formula was a representative subject in the researches for ethno-drugs. In this research, computer aided drug design methods were used to predict the action targets of the formula. Protein interaction network (PIN) was then constructed, and molecular complex detection (MCODE) clustering algorithm was used to obtain the modules of the formula, so as to analyze the potential action mechanism. The results showed that Rh. palmatum and P. emblica may have a synergistic protective effect on liver function by acting on analogous targets and pathways. G. conopsea regulated metabolic balance of nutrients to strengthen physical fitness. The research explained the liver-protecting mechanism of Dahuang Lidan Pian based on the PIN analysis on molecular network, which provides an reference for the further study of Dahuang Lidan Pian.

The current study evaluated antioxidant activity of <i>Dracocephalum rupestre</i> Hance, characterized by the polyphenolic compounds in the ethyl acetate fraction (EAF) from <i>D. rupestre</i> and investigated the protective mechanisms of EAF in carbon tetrachloride (CCl₄)-induced hepatic injury. EAF showed the largest antioxidant capacity as demonstrated by DPPH, ABTS, OH, and FRAP assays (<i>p</i> ≤ .05). Using LC-MS, two polyphenolics, for example, rosmarinic acid, and eriodictyol were identified in EAF. Total phenol content of <i>D. rupestre</i> was correlated significantly with FRAP value (<i>r</i> = .999, <i>p</i> ≤ .001). The results also showed that EAF decreased serum ALT and AST activities compared with model group, as well as the histological findings. In addition, EAF remarkably decreased MDA and LDH levels in liver. This is the first time to reveal the hepatoprotective effect of EAF from <i>D. rupestre</i>, which may be developed as a new drug for treatment of liver injury in future.<br>Practical applications: <i>Dracocephalum rupestre</i> Hance is known as Chinese herbal medicine with pharmacological functions of antioxidant, anti-inflammatory and has been mainly used in the treatment of damp-heat, headache, fever, jaundice, hepatitis, liver toxicity, and other diseases. In order to detect the potential application of this plant, the antioxidant and hepatoprotective activities of <i>D. rupestre</i> were investigated. It was found that the ethyl acetate fraction (EAF) from <i>D. rupestre</i> displayed strong antioxidant activity. We also demonstrate that EAF could lessen CCl₄-induced acute liver injury in mice. Also, rosmarinic acid may play an important role in the antioxidant activity and hepatoprotective effect for EAF.

As important secondary plant metabolites, naphthoquinones exhibit a wide range of biological activities. However, their potential as sustainable alternatives to synthetic acaricides has not been studied. This study for the first time investigates the acaricidal activity of naphthoquinones against Psoroptes cuniculi in vitro. Furthermore, the in vivo activity, the skin irritation effects, the cytotoxicity and the inhibitory activities against mite acetylcholinesterase (AChE) and glutathione S-transferase (GST) of the two compounds that displayed the best insecticidal activity in vitro were evaluated. Among fourteen naphthoquinones and their analogs, juglone and plumbagin were observed to possess the strongest acaricidal activities against P. cuniculi with LC50 values of 20.53 ppm and 17.96 ppm, respectively, at 24 h. After three treatments, these two chemicals completely cured naturally infested rabbits in vivo within 15 days, and no skin irritation was found in any of the treated rabbits. Compared to plumbagin, juglone presented no or weak cytotoxicity against HL-7702 cells. Moreover, these two chemicals significantly inhibited AChE and GST activity. These results indicate that juglone has promising toxicity against P. cuniculi, is safe for both humans and animals at certain doses, and could be used as a potential alternative bio-acaricide for controlling the development of psoroptic mange in agricultural applications.

Studies have revealed that bullying victimization was a risk factor for symptoms of depression, however, less is known about the underlying processes that may mediate or moderate this relationship. This study examined the mediating effect of resilience and moderating effect of mindfulness in the relation between bullying victimization and symptoms of depression. 448 Chinese children in grade 3 to grade 6 were recruited to complete the revised Bully/Victim Questionnaire, the Chinese version of Center for Epidemiologic Studies Depression Scale for Children, the Child and Youth Resilience Measure, as well as the Child and Adolescent Mindfulness Measure. Results showed that resilience partially mediated the relation between bullying victimization and depressive symptoms. Besides, both the effect of bullying victimization on depressive symptoms and the mediating effect of resilience were moderated by mindfulness, and both of the two effects were stronger for children with low mindfulness. The present study can contribute to a better understanding of how and when bullying victimization increases the risk of depression. It suggests that early intervention concerning diminishing negative effects of bullying victimization may start with increasing individual resilience and mindfulness.

Zuota is regarded as the king of Tibetan medicine. However, due to the confidentiality of this precious medicine, the scientific characterization of Zuota is very scarce, which limits the pharmacology and biosafety studies of Zuota. Herein, we collected four different Zuota samples from Tibet, Qinghai, Gansu, and Sichuan and characterized them by multiple techniques. Our results showed that Zuota was mainly an inorganic mixture of HgS, sulfur, and graphite. Morphologically, Zuota samples were composed of nanoparticles, which further aggregated into microsized particles. Chemically, the majorities of Zuota were S and Hg (in the forms of HgS and pure sulfur). All samples contained pure sulfur with orthorhombic crystalline. Zuota from Qinghai province had different HgS crystalline, namely, hexagonal crystalline. The others were all face-centered cubic crystalline. Carbon in Zuota NPs was in the form of graphite. The implication to future studies of Zuota was discussed.

Zuota is regarded as the king of Tibetan medicine. However, due to the confidentiality of this precious medicine, the scientific characterization of Zuota is very scarce, which limits the pharmacology and biosafety studies of Zuota. Herein, we collected four different Zuota samples from Tibet, Qinghai, Gansu, and Sichuan and characterized them by multiple techniques. Our results showed that Zuota was mainly an inorganic mixture of HgS, sulfur, and graphite. Morphologically, Zuota samples were composed of nanoparticles, which further aggregated into microsized particles. Chemically, the majorities of Zuota were S and Hg (in the forms of HgS and pure sulfur). All samples contained pure sulfur with orthorhombic crystalline. Zuota from Qinghai province had different HgS crystalline, namely, hexagonal crystalline. The others were all face-centered cubic crystalline. Carbon in Zuota NPs was in the form of graphite. The implication to future studies of Zuota was discussed.

Six compounds were isolated from alcoholic extracts of Meconopsis quintuplinervia Regel.. On the basis of spectroscopic methods, their structures were identified as 8,9 -dihydroxy-1,5,6,10b-tetrahydro-2H-pyrrolo [ 2,1-a ] isoquinolin-3-one (1), o-methylflavinantine (2), amurine (3), tricin (4), luteolin (5) and β-sitosterol (6). Among them, compounds 1 and 4 were isolated from the plant for the first time.

Zuotai, a famous Tibetan medicinal mixture containing β-HgS, has been used to combine with herbal remedies for treating diseases for more than 1 300 years. The target organ for inorganic mercury toxicity is generally considered to be the kidney. Therefore, it is crucial to reveal the chemical speciation, spatial distribution and potential nephrotoxicity of mercury from Zuotai in kidney. To date, this remains poorly understood. We used X-ray absorption spectroscopy (XAS) and micro X-ray fluorescence (μ-XRF) imaging based on synchrotron radiation to study mercury chemical forms and mercury special distribution in kidney after mice were treated orally with Zuotai, β-HgS or HgCl2. Meanwhile, the histopathology of kidney was observed. Mice exposed with Zuotai showed kidney with significant proportion of mercury ions bound to sulfydryl biomolecules (e.g. Cys-S-Hg-S-Cys) plus some of unknown species, but without methylmercury cysteine, which is the same as β-HgS and HgCl2. The mercury is mainly deposited in renal cortex in mouse treated with Zuotai, β-HgS or HgCl2, but with a low level of mercury in medulla. The total mercury in kidney of mice treated with HgCl2 was much higher than that of β-HgS, and the later was higher than that of Zuotai. And, HgCl2 cause severe impairments in mouse kidney, but that was not observed in the Zuotai and β-HgS groups. Meanwhile, the bio-metals (Ca, Zn, Fe and Cu) micro-distributions in kidney were also revealed. These findings elucidated the chemical nature, spatial distribution and toxicity difference of mercury from Zuotai, β-HgS and HgCl2 in mouse kidney, and provide new insights into the appropriate methods for biological monitoring.

Zuotai (gTso thal) is one of the famous drugs containing mercury in Tibetan medicine. However, little is known about the chemical substance basis of its pharmacodynamics and the intrinsic link of different samples sources so far. Given this, energy dispersive spectrometry of X-ray (EDX), scanning electron microscopy (SEM), atomic force microscopy (AFM), and powder X-ray diffraction (XRD) were used to assay the elements, micromorphology, and phase composition of nine Zuotai samples from different regions, respectively; the XRD fingerprint features of Zuotai were analyzed by multivariate statistical analysis. EDX result shows that Zuotai contains Hg, S, O, Fe, Al, Cu, and other elements. SEM and AFM observations suggest that Zuotai is a kind of ancient nanodrug. Its particles are mainly in the range of 100–800 nm, which commonly further aggregate into 1–30 μm loosely amorphous particles. XRD test shows that β-HgS, S8, and α-HgS are its main phase compositions. XRD fingerprint analysis indicates that the similarity degrees of nine samples are very high, and the results of multivariate statistical analysis are broadly consistent with sample sources. The present research has revealed the physicochemical characteristics of Zuotai, and it would play a positive role in interpreting this mysterious Tibetan drug. [ABSTRACT FROM AUTHOR]

Four novel lactams, colletotrilactam A-D (1-4), along with six known compounds (5-10) were isolated from the culture broth of Colletotrichum gloeosporioides GT-7, a fungal endophyte of Uncaria rhynchophylla. The structures of these compounds were elucidated by comprehensive NMR spectroscopy. Isolates were tested for monoamine oxidase (MAO) inhibitory activity and compound 9 showed potent MAO inhibitory activity with IC50 value of 8.93±0.34μg/mL, when the IC50 value of iproniazid as a standard was 1.80±0.5μg/mL.

A quantitative analytical method of ultra-high performance liquid chromatography (UPLC) was developed for simultaneously determining twelve components in Tibetan medicine Zuozhu Daxi. SIMPCA 12.0 software was used a principal component analysis PCA) and partial small squares analysis (PLSD-DA) on the twelve components in 10 batches from four pharmaceutical factories. Acquity UPLC BEH C15 column (2.1 mm x 100 mm, 1.7 µm) was adopted at the column temperature of 35 °C and eluted with acetonitrile (A) -0.05% phosphate acid solution (B) as the mobile phase with a flow rate of 0. 3 mL · min(-1). The injection volume was 1 µL. The detection wavelengths were set at 210 nm for alantolactone, isoalantolactone and oleanolic; 260 nm for trychnine and brucine; 288 nm for protopine; 306 nm for protopine, resveratrol and piperine; 370 nm for quercetin and isorhamnetin. The results showed a good separation among index components, with a good linearity relationship (R2 = 0.999 6) within the selected concentration range. The average sample recovery rates ranged between 99.44%-101.8%, with RSD between 0.37%-1.7%, indicating the method is rapid and accurate with a good repeatability and stability. The PCA and PLSD-DA analysis on the sample determination results revealed a great difference among samples from different pharmaceutical factories. The twelve components included in this study contributed significantly to the quantitative determination of intrinsic quality of Zuozhu Daxi. The UPLC established for to the quantitative determination of the twelve components can provide scientific basis for the comprehensive quality evaluation of Zuozhu Daxi.

ETHNOPHARMACOLOGICAL RELEVANCE: Corydalis hendersonii Hemsl. (CH) with heat clearing and detoxifying effects are well described in Tibetan folk medicine. It has been used for centuries in China largely for the treatment of high altitude polycythemia, a pathophysiological condition referred to "plethora" in Tibetan medicine, hypertension, hepatitis, edema, gastritis, and other infectious diseases.AIM OF THE STUDY: To investigate the cardioprotective effects of Corydalis hendersonii extract in an ICR mouse model of myocardial ischemic injury. MATERIALS AND METHODS: Ethanol [85% (v/v)] extract of CH whole plant was prepared, and their chemical profile was analyzed with use of HPLC-DAD and IT-TOF-ESI-MS. A mouse model of AMI was established by ligation of the left ventricular dysfunction (LAD) coronary artery. Mice were randomly divided into six groups (n = 12 per group): sham group, model group, CH groups treated with three doses of CH (100, 200, and 400mg/kg, intragastric), and a positive control group (captopril, 16.67mg/kg, intragastric). Heart function was evaluated by measurement of ejection fraction (EF) and fractional shortening (FS) by echocardiography. Serum levels of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH), plasma levels of angiotensin II (AngII), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and expressions of matrix metalloproteinase-2 (MMP-2) and MMP-9 in the cardiac tissue homogenate, protein expressions of signal-transduction proteins, p65, IκBα, JAK2, and STAT3 in heart tissues were measured by ELISA and Western blot analyses. Inflammatory cell infiltration and changes in collagen deposition in the myocardial ischemic heart tissues were observed by histopathological examination. Platelet aggregation in vitro was also assessed. RESULTS: CH treatment showed a dose-dependent cardioprotective effect. It significantly reduced left ventricular end-diastolic diameter (LVEDd) and left ventricular end-diastolic diameter (LVEDs), improved EF and FS as compared to those in the model group; attenuated the increase levels of CK-MB and LDH in serum; reduced expressions of AngII, TNF-α, IL-6 and IL-1ß in plasma, MMP-2 and MMP-9 expressions in the cardiac tissue homogenate; and down-regulated myocardial expressions of p-p65, p-IκBα, p-JAK2, p-STAT3, MMP-2, and MMP-9 in AMI mice. Also, an obvious reduction in inflammatory cell infiltration in the myocardial infarct was found in all CH treated groups. Besides, CH also inhibited platelet aggregation induced by THR, ADP, and AA. CONCLUSION: CH extract exerted a protective effect against myocardial ischemic injury via inhibition of inflammation, myocardial fibrosis, and platelet aggregation. This study demonstrates such protection for the first time and provides a basis for development of CH-based drugs for treatment of ischemic heart disease in clinical settings.

Soil respiration (Rs) is an important source of atmospheric CO2 flux and is sensitive to changes in soil nutrient and water contents. Despite extensive studies on the effects of enhanced atmospheric nitrogen (N) deposition and changes in precipitation (P) on Rs, few studies have taken into account the effects of interactions between these factors on Rs of alpine grasslands. To address these questions, we investigated the effects of N addition (10 g N m-2 yr-1), changes in precipitation (±50% precipitation), and their interaction on soil respiration and its components, including heterotrophic respiration (Rh) and autotrophic respiration (Ra),in a Tibetan alpine steppe during three consecutive growing seasons. We found that Rs differed in its response to N addition and precipitation regimes. Specifically, decreased precipitation led to a significant reduction in Rs during the last two years, whereas N addition minimally impacted Rs. Another important finding was that soil respiration components differed in their response to N addition and precipitation regimes. Nitrogen addition significantly enhanced Ra, whereas Rh was not altered in response to N addition. By contrast, the precipitation regime led to marked changes in Rh, but exhibited marginally significant effects on Ra. Therefore, our findings highlighted that soil respiration differed in its response to N addition and precipitation regimes mainly due to the different responses of soil respiration components to these factors. Therefore, carbon dynamics should take soil respiration components into account under global change scenarios.

Zuotai, also named as "gTso thal", a known Tibetan medicinal mixture containing insoluble cubic crystal mercuric sulfide (β-HgS), has been used to treat diseases with long history. The mercury release ratio from Zuotai in gastrointestinal environment is one determinant factor for its bioavailability and biological effect. However, the information is still scarce now. Therefore, the study was designed to investigate the effect of sulfhydryl biomolecules [L-cysteine (Cys) and glutathione (GSH)] and pH on mercury dissociation from Zuotai, β-HgS, and hexagonal crystal mercuric sulfide (α-HgS) in artificial gastrointestinal juices or pure water with a 1:100 solid-liquid ratio. And, the digestion and peristalsis of gastrointestinal tract were simulated in vitro. The results showed the following trend for the mercury release ratio of Zuotai, artificial gastric juice > artificial intestinal juice > pure water, whereas the trend for β-HgS and α-HgS was as follows, artificial intestinal fluid > artificial gastric fluid > pure water. The mercury release ratios of Zuotai, β-HgS, and α-HgS significantly increased in artificial intestinal juice containing L-Cys or GSH compared to those without sulfhydryl biomolecules in the juice. However, in contrast to the results observed for β-HgS and α-HgS, the mercury release ratio of Zuotai was reduced remarkably in pure water and artificial gastric juice with Cys or GSH. And, we found that strong acidic or strong alkaline environments promoted the dissociation of mercury from Zuotai, β-HgS, and α-HgS. Taken together, current findings may contribute to other studies regarding clinical safety and bioavailability of the traditional drug Zuotai containing β-HgS.

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