Mitragynine is a major bioactive compound of Kratom, which is derived from the leave extracts of Mitragyna speciosa Korth or Mitragyna speciosa (M. speciosa), a medicinal plant from South East Asia used legally in many countries as stimulant with opioid-like effects for the treatment of chronic pain and opioid-withdrawal symptoms. Fatal incidents with Mitragynine have been associated with cardiac arrest. In this study, we determined the cardiotoxicity of Mitragynine and other chemical constituents isolated using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs).
Methods and Results
The rapid delayed rectifier potassium current (IKr), L-type Ca2+ current (ICa,L) and action potential duration (APD) were measured by whole cell patch-clamp. The expression of KCNH2 and cytotoxicity was determined by real-time PCR and Caspase activity measurements. After significant IKr suppression by Mitragynine (10 µM) was confirmed in hERG-HEK cells, we systematically examined the effects of Mitragynine and other chemical constituents in hiPSC-CMs. Mitragynine, Paynantheine, Speciogynine and Speciociliatine, dosage-dependently (0.1∼100 µM) suppressed IKr in hiPSC-CMs by 67% ∼84% with IC50 ranged from 0.91 to 2.47 µM. Moreover, Mitragynine (10 µM) significantly prolonged APD at 50 and 90% repolarization (APD50 and APD90) (439.0±11.6 vs. 585.2±45.5 ms and 536.0±22.6 vs. 705.9±46.1 ms, respectively) and induced arrhythmia, without altering the L-type Ca2+ current. Neither the expression,and intracellular distribution of KCNH2/Kv11.1, nor the Caspase 3 activity were significantly affected by Mitragynine.
Conclusions
Our study indicates that Mitragynine and its analogues may potentiate Torsade de Pointes through inhibition of IKr in human cardiomyocytes. 相似文献
Phenylalanine ammonia lyase (PAL) plays a major role in plant growth, development and adaptation. In Arabidopsis thaliana, the enzyme is encoded by four genes, namely PAL1, PAL2, PAL3, and PAL4 with PAL1 and PAL2 being closely related phylogenetically and functionally. PAL1 promoter activities are associated with plant development and are inducible by various stress agents. However, PAL2 promoter activities have not been functionally analysed. Here, we show that the PAL2 promoter activities are associated with the structural development of a plant and its organs. This function was inducible
in an organ-specific manner by the avirulent strain of Pseudomonas syringae pv. tomato (JL1065). The PAL2 promoter was active throughout the course of the plant development particularly in the root, rosette leaf, and inflorescence
stem that provide the plant with structural support. In aerial organs, the levels of PAL2 promoter activities were negatively correlated with relative positions of the organs to the rosette leaves. The promoter
was inducible in the root following an inoculation by JL1065 in the leaf suggesting PAL2 to be part of an induced defence system. Our results demonstrate how the PAL2 promoter activities are being coordinated and synchronised for the structural development of the plant and its organs based
on the developmental programme. Under certain stress conditions the activity may be induced in favour of certain organs. 相似文献
Background: Alcohol drinking is an oral cancer (OC) risk factor; tobacco smoking (TS) and betel quid chewing (BQC) are oral carcinogens and effect modifiers of drinking. Although the assessment of the independent effect of drinking on OC must necessarily account for effect modifiers, no observational study has included interaction terms between drinking, TS, BQC in regression analyses. In order to assess the independent association between drinking and OC, this pooled analysis focused on subjects who were not exposed to such effect modifiers. Methods: Case-control studies on OC, which discriminated non TS/non BQC drinkers from multiexposed drinkers were searched. Exposed subjects (≥1 drink daily, ≥10 years) were compared to unexposed subjects (non/occasional drinkers). Unadjusted odds ratios (ORs) were extracted/calculated. Pooled ORs were assessed with the random-effect method, which assumed high between-study heterogeneity (assessed with Cochran's Q). Robustness of estimates was investigated through use of adjusted ORs, correction for publication bias, sensitivity analysis to inclusion criteria. The drinking–TS interaction was assessed with the Interaction Contrast Ratio (ICR) and the Attributable Proportion due to Interaction (AP). Results: Sixteen studies were used, with substantially high heterogeneity. The pooled OR was 0.787 (95CI, 0.677–0.914). Use of adjusted ORs, correction for publication bias, sensitivity analysis corroborated these results. ICR and AP were 2.444 and 54.6%. Conclusions: Consistent with stratified analyses reporting non significant/negative associations between alcohol drinking and OC in non multiexposed subjects, an OC preventive activity of drinking is inferable. However, given the high prevalence and the oral carcinogenicity of concomitant drinking and smoking, drinking control policies remain essential. 相似文献
Irradiated carrageenan (IC) could elicit plant growth promoting activities in plants. The effect of foliar spray of five concentrations of IC (20, 40, 60, 80 and 100 mg L−1) was studied on Mentha arvensis L. in terms of plant growth, physiological attributes, herbage yield and the content and yield of essential oil and its components. Un-irradiated carrageenan and deionized water had no effect on the attributes studied. GPC study revealed formation of low molecular weight fractions in irradiated samples containing less than 20,000 molecular weight oligomers which are responsible for plant growth promotion in this study. 80 mg L−1 of IC was the most effective concentration which resulted in the highest values of growth attributes, herbage yield and the content and yield of essential oil and menthol content of the oil. It also improved the leaf-nutrient contents, photosynthetic rate and other physiological parameters. 100 mg L−1 of IC did not further improve the attributes studied, but it was always better than the control. 相似文献
The fungal species Trichoderma is reported to have a significant impact on the growth and physiological performance of rice plants. However, the molecular mechanisms that induce these effects remain unspecified. Using next-generation sequencing technology, this study compared the differential expression of genes in rice seedlings that had been inoculated with Trichoderma asperellum SL2 with the gene expression in seedlings that had no such inoculation. The study showed that many genes related to plant growth enhancement and physiological functioning are differentially expressed in seedlings which have been symbiotically colonized by T. asperellum SL2. In these seedlings, specific genes related to photosynthesis, RNA activity, stomatal activity, and root development were found to be up-regulated as others were down-regulated. Although the exact causal mechanisms at the molecular level remain to be identified, the presence of Trichoderma versus its absence was associated with almost ten times more significant up-regulations than down-regulations for specific genes that have been identified from previous genomic mapping. Such analysis at the molecular level can help to explain observed phenotypic effects at the organismic level, and it begins to illuminate the observed beneficial relationships expressed phenotypically between crop plants and certain symbiotic microbes.
Journal of Plant Research - Carnivorous plants capture and digest insects for nutrients, allowing them to survive in soil deprived of nitrogenous nutrients. Plants from the genus Nepenthes produce... 相似文献
The internal transcribed spacer (ITS) region of nuclear ribosomal DNA, trnL and trnL-F genes of Cardamine glechomifolia Levl. (family Brassicaceae) were sequenced and analyzed with the sequence of related Cardamine species retrieved from NCBI GenBank to detect pattern of evolutionary differentiation. All trees resulting from combined sequence analyses data of ITS, trnL and trnL-F gene resolve that C. glechomifolia – an endemic species to South Korea clade with Cardamine microzyga (100% bootstrap support). The evolutionary history was inferred using the Maximum Parsimony method. The consistency index is (0.588235), the retention index is (0.687500), and the composite index is 0.519622 (0.404412) for all sites and parsimony-informative sites (in parentheses). The result of the analysis using Maximum Parsimony was found congruence with Maximum Likelihood method and in Baseyan analysis. 相似文献
Wheat germ lipase is a cereal lipase which is a monomeric protein. In the present study we sought to structurally characterize this protein along with equilibrium unfolding in solution. Conformational changes occurring in the protein with varying pH, were monitored by circular dichroism (CD) spectroscopy, fluorescence emission spectroscopy, binding of hydrophobic dye, 1-anilino 8-naphthalenesulfonic acid (ANS) and dynamic light scattering (DLS). Our study showed that acid denaturation of lipase lead to characterization of multiple monomeric intermediates. Native protein at pH 7.0 showed far-UV spectrum indicating mixed structure with both alpha and beta-type of characteristics. Activity of lipase was found to fall on either sides of pH 7.0–8.0. Acid-unfolded state was characterized at pH 4.0 with residual secondary structure, disrupted tertiary spectrum and red-shifted fluorescence spectrum with decreased intensity. Further decrease in pH lead to formation of secondary structure and acid-induced molten globule state was found to be stabilized at pH 1.4, with exposed tryptophan residues and hydrophobic patches. Notably, interesting finding of this study was characterization of acid-induced state at pH 0.8 with higher secondary structure content than native lipase, regain in tertiary spectrum and induction of compact conformation. Although enzymatically inactive, acid-induced state at pH 0.8 was found to be structurally more stable than native lipase, as shown by chemical and thermal denaturation profiles. 相似文献