ABSTRACT
Based our previous work, twelve purine derivatives were designed and synthesized as dual modulators of GPR119 and DPP-4by conjugating the GPR119 activating and DPP-4 inhibiting fragments with the position 6 and 9 of purine core via an approach of merged pharmacophores. Compound 11, bearing 2-fluoro-4-methylsulphonyl anilide and cyanopyrrolidine moieties, exhibited the most potent GPR119 agonistic activities (EC50 = 0.33 μmol·L-1, IA = 71.1%) and DPP-4 inhibitory (58.4% inhibition at 10 μmol·L-1, 21.2% inhibition at 1 μmol·L-1) activities in the in vitro antidiabetic study. Subsequently, we performed studies on structure activity relationships and molecular docking to guide the further drug design.
ABSTRACT
Objective:To investigate the effect of Wendantang on cyclic adenosine monophosphate （cAMP）-response element binding protein（CREB） gene silencing hippocampal cell activity， apoptosis and signal pathway of brain-derived neurotrophic factor/protomyosin related receptor kinase B/adenosine cyclophosphate effector binding protein （BDNF/TrkB/CREB）. Method:Wendantang-containing serum was prepared. Animal grouping： SD male rats were randomly divided into high， medium， low-dose groups， clozapine group and normal saline group， with 10 rats in each group， while 15 rats for the normal group. Dosage： 20 mL·kg-1 normal saline was given to normal group N， clozapine 0.02 g·kg-1 was given to dozapine group X， while high， medium and low-dose Wendantang groups were respectively given the same amount of Wendantang concentrated crude drug， with concentrations of 2， 1 and 0.5 g·mL-1 respectively once a day for 8 days continuously， and then blood was taken from femoral artery， and centrifuged for 15 min at 5 000 r·min-1. Supernatant was taken， inactivated， stored at -80 ℃ for standby. The CREB gene silenced hippocampal neuron cell line was constructed through transfection of liposomes into hippocampal cells， and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to verify the effect of small interfering RNA （siRNA） transcription. The mRNA expressions of BDNF， TrkB， CREB and CaMKⅡ in normal hippocampal cells and CREB gene silenced hippocampal cells were measured. Result:Compared with normal group， the apoptosis of the normal gene silencing group was significantly increased （P<0.01）， compared with the normal gene silencing group， the apoptosis of each group was significantly reduced （P<0.01）. As for the mRNA expressions of BDNF， TrkB， CREB and CaMKⅡ， compared with the normal group， the mRNA expression of CREB， BDNF in the normal gene silencing group was significantly decreased （P<0.01）. Compared with the normal gene silencing group， the mRNA expression of BDNF in each administration group was highly increased （P<0.01）， but with no statistically significant difference between TrkB and CaMKⅡ groups. Conclusion:The Wendantang-containing serum could improve the mRNA expression of BDNF， protect hippocampal neurons and prevent cognitive impairment of schizophrenia by regulating BDNF/TrkB/CREB signal pathway.
ABSTRACT
Polygalae Radix， a traditional Chinese medicine， has the functions of improving intelligence， calming nerves， relieving cough and eliminating phlegm. Its processing methods are various， but the purpose of processing is to reduce toxicity and increase efficiency. In this paper， the methods of ancient processing， such as cleansing， cutting， processing with excipient and processing without excipient， were summarized， the processing methods of Polygalae Radix in the different versions of Chinese Pharmacopoeia and the local processing specifications were summarized， in order to compare the differences and research progress of different processing methods. On this basis， taking the modern research of processed products of Polygalae Radix as the breakthrough point， this paper reviewed the modern research on processed products of Polygalae Radix from the aspects of processing technology， chemical composition changes and pharmacodynamics changes before and after processing， and the mechanism of reducing toxicity and increasing efficiency. Based on the research status of processing of Polygalae Radix， some existing problems were analyzed in this paper， including not many ancient processing methods used in modern times， lack of standardized research on processing technology， few studies on the ingredients introduced by excipients， etc. The author thinks that it is necessary to strengthen the research on the ancient processing of Polygalae Radix combined with processing methods with local characteristics. While discussing the processing technology， combining with the composition and efficacy， we should carry out in-depth research on the processing mechanism of different processing products of Polygalae Radix， so as to provide scientific basis for the rationality of processing of Polygalae Radix and ensure the clinical safety of medication.
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The processing of Aurantii Fructus has a long history and many methods. In addition to the current mainstream varieties of raw products and stir-fried products with bran of Aurantii Fructus, other 17 processing methods, such as stir-fried with rice, processed with salt, honey and medicinal juice, are recorded in the literature of past dynasties. Through a comprehensive review and sorting out of ancient and modern literature, this paper clarifies the historical evolution of the processing of Aurantii Fructus, through clarifying the historical evolution of processing and analyzing the present situation of modern research on Aurantii Fructus, summarizes the modern research progress on processing in production place, processing technology, chemical compositions and pharmacological effects before and after being processed, and puts forward some ideas for the follow-up research on processing of Aurantii Fructus, in order to provide reference for screening the dominant varieties, standardizing the processing technology, explaining the scientific connotation of processing, and improving the utilization ratio of medicinal resources of Aurantii Fructus.
ABSTRACT
Objective: To analyze the effect of honey bran stir-frying method in Zhang faction and honey chaff stir-frying method in Jianchang faction on the composition and relative content of volatile components in Cimicifugae Rhizoma. Method: The volatile oil in different processed products of Cimicifugae Rhizoma was extracted by steam distillation and analyzed by gas chromatography-mass spectrometry (GC-MS). The inlet temperature was 260℃, the transmission line temperature was 250℃, the carrier gas was helium, the flow rate was 1.0 mL·min-1, the split ratio was 10:1, the injection volume was 1 μL. The column temperature was set at 70℃ by programmed heating, rising to 150℃ by 2℃·min-1 and keeping it there for 2 min, rising to 240℃ by 6℃·min-1 and keeping it there for 3 min, rising to 300℃ by 25℃·min-1 and keeping it there for 2 min. The relative content of each component in volatile oil was calculated by peak area normalization method. Result: A total of 73 components were identified from raw products of Cimicifugae Rhizoma, 37 components were identified from honey bran stir-frying products, 93 components were identified from honey chaff stir-frying products, and 71 components were identified from honey stir-frying products. The relative content of n-hexadecanoic acid was the highest among all components in different processed products, accounting for 30.38%-46.47% of the total volatile components. In addition to fatty acids, volatile oils also contained alkanes, esters, alcohols, etc. There were 8 common components with relative content ≥ 1.0% in raw and processed products of Cimicifugae Rhizoma, after stir-frying with honey bran, the relative contents of these 8 components showed an upward trend, but showed a decreasing trend after stir-frying with honey chaff. Conclusion: After processing with Zhang faction method or Jianchang faction method, the composition and relative content of volatile components in Cimicifugae Rhizoma were significantly changed. This study can provide a scientific basis for explaining the processing mechanism of Jiangxi characteristic Cimicifugae Rhizoma decoction pieces.