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1.
Acta Pharmaceutica Sinica B ; (6): 2869-2886, 2022.
Article in English | WPRIM | ID: wpr-939926

ABSTRACT

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis and insulin resistance and there are currently no approved drugs for its treatment. Hyperactivation of mTOR complex 1 (mTORC1) and subsequent impairment of the transcription factor EB (TFEB)-mediated autophagy-lysosomal pathway (ALP) are implicated in the development of NAFLD. Accordingly, agents that augment hepatic TFEB transcriptional activity may have therapeutic potential against NAFLD. The objective of this study was to investigate the effects of nuciferine, a major active component from lotus leaf, on NAFLD and its underlying mechanism of action. Here we show that nuciferine activated ALP and alleviated steatosis, insulin resistance in the livers of NAFLD mice and palmitic acid-challenged hepatocytes in a TFEB-dependent manner. Mechanistic investigation revealed that nuciferine interacts with the Ragulator subunit hepatitis B X-interacting protein and impairs the interaction of the Ragulator complex with Rag GTPases, thereby suppressing lysosomal localization and activity of mTORC1, which activates TFEB-mediated ALP and further ameliorates hepatic steatosis and insulin resistance. Our present results indicate that nuciferine may be a potential agent for treating NAFLD and that regulation of the mTORC1-TFEB-ALP axis could represent a novel pharmacological strategy to combat NAFLD.

2.
Article in Chinese | WPRIM | ID: wpr-872738

ABSTRACT

Objective:To elucidate the key medicinal substances that cause the difference of efficacy between lotus leaf and lotus plumule, and to analyze their material basis of "homologous and different effect". Method:UPLC-Q-TOF-MS/MS technique was used to identify the main alkaloids in lotus leaf, lotus latex (juice in lotus petiole) and lotus plumule, chromatographic separation was achieved on a Waters XBridge C18 column (4.6 mm×150 mm, 5 μm), and gradient elution was performed with 0.1% ammonia aqueous solution (A)-acetonitrile (B) as mobile phase (0-13 min, 35%-60%B; 13-20 min, 60%-80%B; 20-20.1 min, 80%-95%B; 20.1-25 min, 95%B; 25-25.1min, 95%-35%B; 25.1-40 min, 35%B). Data acquisition was carried out in electrospray ionization (ESI) under the positive ion mode, the scanning range was m/z 100-1 000. Besides, the metabolic network of the main alkaloids was constructed. Result:A total of 5 alkaloids (N-nornuciferine, O-nornuciferine, anonaine, nuciferine and roemerine) were identified from lotus leaf, 6 alkaloids (nuciferine, norisoliensinine, 6-hydroxynorisoliensinine, liensinine, isoliensinine and neferine) in lotus latex, and 8 alkaloids (lotusine, norcoclaurine, N-methylcoclaurine, pronuciferine, armepavine, liensinine, isoliensinine and neferine) in lotus plumule. Also, the biosynthetic pathways of the terminal alkaloids of bisbenzylisoquinoline alkaloids (liensinine, isoliensinine and neferine) and aporphine alkaloids (N-nornuciferine, O-nornuciferine, anonaine, nuciferine and roemerine) was conducted. Conclusion:Five aporphine alkaloids in lotus leaf and three bisbenzylisoquinoline alkaloids in lotus plumule are the material basis for "homologous and different effect" of lotus leaf and lotus plumule. The metabolism of alkaloids in lotus leaf and lotus plumule is derived from the same compound of (S)-N-methylcoclaurine, and two types of alkaloids are synthesized through the action of two different enzymes. The synthetic alkaloids have different structures, resulting in different chemical composition between different tissues, thus producing different efficacy between lotus leaf and lotus plumule.

3.
Article in Chinese | WPRIM | ID: wpr-350153

ABSTRACT

To investigate the overall intestinal permeability of multiple components in lotus leaves and make clear the interaction in composition absorption process. Rat single-pass intestinal perfusion technique was used, and the results showed that the Peff values of nuciferine, demethylanuciferine, rutin, quercetin, kaempferol from lotus leaf were greater than 0.5×10⁻⁴ cm•s⁻¹. In the biopharmaceutics classification system (BCS) intestinal permeability property, these ingredients were high permeable components, while the hyperin was low permeable component. However, in the multi-component environment of the lotus leaf extract, component permeation was changed. Semi quantitative analysis of the unclear components showed that under the multi-component environment, four in seven components with relatively high contents had a Peff value less than 0.5×10⁻⁴ cm•s⁻¹, indicating these 4 components were of low permeability, while other 3 components were of high permeability. The results could be valuable to make clear the overall intestinal permeability of multiple components in lotus leaf, and lay a foundation for studying the mechanism of the lipid-lowering effect of lotus leaf.

4.
Article in Chinese | WPRIM | ID: wpr-307145

ABSTRACT

Lotus leaf (LL) is one of the traditional Chinese herbs which can be used for both pharmaceutical and food application, and it posses lipid regulating efficacy. To observe the effect of LL on experimental nonalcoholic fatty liver disease (NAFLD) and its potential mechanism, a NAFLD model was established by feeding SD rat with high-fat and high-glucose diet. LL was administrated to rats in experiment group at the same time. AST,ALT,Cr,BUN,GLU levels in serum were determined by automatic biochemical analyser and TNF-α,IL-6,INS,ADPN,LEP and liver NF-κB,TGF-β1 levels were determined by ELISA according to the specification of the kits. HE staining was applied for histopathological examination and RT-PCR,Western blot was applied for AdipoR2 mRNA and protein expression.Results have shown that LL could significantly decrease ALT,AST,IL-6 level in serum and NF-κB,TGF-β1 level in liver,promote adiponectin content in serum and AdipoR2 protein expression in liver and could alleviate hepatocyte lipid degeneration. These results indicating that LL has protective effect for NAFLD induced by high-fat and high-glucose diet via promoting AdipoR2 expression, improving insulin resistance and inhibiting inflammatory reaction.

5.
Article in Chinese | WPRIM | ID: wpr-320881

ABSTRACT

In the study of biopharmaceutics classification system of Chinese materia medica (CMMBCS), the interactions of multiple components in the absorption should be taken into consideration in simultaneous multi-component determination. To investigate the absorption of multiple components, the in vitro everted gut sac model was used in this study, wtih lotus leaves as the research object. Aquantitative analysis was also carried out for the known components in this study. Totally 19 components in lotus extracts were absorbed by the intestinal tract, the Papp levels of the known components were nuciferine (1×10⁻⁵-1×10⁻⁶ cm•s⁻¹), rutin (1×10⁻⁶-1×10⁻⁷ cm•s⁻¹), hyperoside (1×10⁻⁶ cm•s⁻¹), isoquercitrin (1×10⁻⁶-1×10⁻⁷ cm•s⁻¹) and astragalin (1×10⁻⁶-1×10⁻⁷ cm•s⁻¹), respectively. These components showed a low permeability under a multi-component environment. This study was carried out to lay a foundation for further relevant target studies for different categories of components.

6.
Article in English | WPRIM | ID: wpr-156148

ABSTRACT

The purpose of this study was to investigate the effects of lotus leaf on hyperglycemia and dyslipidemia in animal model of diabetes. Inhibitory activity of ethanol extract of lotus leaf against yeast alpha-glucosidase was measured in vitro. The effect of lotus leaf on the postprandial increase in blood glucose levels was assessed in streptozotocin-induced diabetic rats. A starch solution (1 g/kg) with and without lotus leaf extract (500 mg/kg) was administered to the rats after an overnight fast, and postprandial plasma glucose levels were monitored. Four-week-old db/db mice were fed a basal diet or a diet containing 1% lotus leaf extract for 7 weeks after 1 week of acclimation to study the chronic effect of lotus leaf. After sacrifice, plasma glucose, insulin, triglycerides (TG), total cholesterol (CHOL), high-density lipoprotein (HDL)-CHOL, and blood glycated hemoglobin levels were measured. Lotus leaf extract inhibited alpha-glucosidase activity by 37.9%, which was 1.3 times stronger than inhibition by acarbose at a concentration of 0.5 mg/mL in vitro. Oral administration of lotus leaf extract significantly decreased the area under the glucose response curve by 35.1% compared with that in the control group (P < 0.01). Chronic feeding of lotus leaf extract significantly lowered plasma glucose and blood glycated hemoglobin compared with those in the control group. Lotus leaf extract significantly reduced plasma TG and total CHOL and elevated HDL-CHOL levels compared with those in the control group. Therefore, we conclude that lotus leaf is effective for controlling hyperglycemia and dyslipidemia in an animal model of diabetes mellitus.


Subject(s)
Acarbose , Acclimatization , Administration, Oral , alpha-Glucosidases , Animals , Blood Glucose , Cholesterol , Diabetes Mellitus , Diet , Dyslipidemias , Ethanol , Glucose , Hemoglobins , Hyperglycemia , Insulin , Lipoproteins , Lotus , Mice , Models, Animal , Plasma , Rats , Starch , Triglycerides , Yeasts
7.
Article in Chinese | WPRIM | ID: wpr-681244

ABSTRACT

Object To study the action of lotus leaf extract (LLE) in scavengings hydroxyl and superoxide anion radical Methods By spin trapping with electron spin resonance Results 26 94 ug/mL LLE can scavenge 65 60% superoxide anion radical (O ? 2) produced by Hypoxanthine Xanthine oxidase system, while at concentrations over 8 98 mg/mL a complete eradication of hydroxyl radical (?OH) produced from Fenten reaction system was achieved Conclusion LLE is highly effective in scavenging ?OH and O ? 2 free radicals

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