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Article: Microbial biotransformation to obtain stilbene methylglucoside with GPR119 agonistic activity.

Peng, Yu / Huan, Yi / Chen, Jing-Jing / Chen, Tian-Jiao / Lei, Lei / Yang, Jin-Ling / Shen, Zhu-Fang / Gong, Ting / Zhu, Ping

Frontiers in microbiology

2023 Volume 14, Page(s) 1148513

Abstract: Introduction: Limitation of pharmaceutical application of resveratrol (RSV) and piceatannol (PIC) continue to exist, there is a need to obtain the superior analogs of two stilbenes with promoted activity, stability, and bioavailability. Microbial ... ...

Abstract	Introduction: Limitation of pharmaceutical application of resveratrol (RSV) and piceatannol (PIC) continue to exist, there is a need to obtain the superior analogs of two stilbenes with promoted activity, stability, and bioavailability. Microbial transformation has been suggested as a common and efficient strategy to solve the above problems. Methods: In this study, Results: Three new methylglucosylated derivatives of PIC ( Discussion: Our work presents that 3-
Language	English
Publishing date	2023-03-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2023.1148513
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: [Determination of serum acetaminophen based on the diazo reaction and its application in the evaluation of gastric emptying].

Li, Cai-na / Sun, Su-juan / Shen, Zhu-fang

Yao xue xue bao = Acta pharmaceutica Sinica

2015 Volume 50, Issue 5, Page(s) 560–564

Abstract: This study aims to establish a method to determine the serum acetaminophen concentration based on diazo reaction, and apply it in the gastric emptying evaluation. Theoretically, acetaminophen could take hydrolysis reaction in hydrochloric acid solution ... ...

Abstract	This study aims to establish a method to determine the serum acetaminophen concentration based on diazo reaction, and apply it in the gastric emptying evaluation. Theoretically, acetaminophen could take hydrolysis reaction in hydrochloric acid solution to produce p-aminophenol, which could then take diazo reaction resulting in a product with special absorption peak at 312 nm. Then the serum acetaminophen concentration and recovery rate were calculated according to the standard curve drawn with absorbance at 312 nm. ICR mice were given a dose of acetaminophen (500 mg x kg(-1)) by gavage and the serum acetaminophen was dynamically measured through the diazo reaction. Besides, ICR mice were subcutaneously injected with the long-acting GLP-1 analog GW002 before the gavage of acetaminophen, and serum acetaminophen concentration was measured as above to study how GW002 could influence the gastric emptying. The data showed acetaminophen ranging from 0 to 160 μg x mL(-1) could take diazo reaction with excellent linear relationship, and the regression equation was y = 0.0181 x +0.0104, R2 = 0.9997. The serum acetaminophen was also measured with good linear relationship (y = 0.0045 x + 0.0462, R = 0.9982) and the recovery rate was 97.4%-116.7%. The serum concentration of acetaminophen reached peak at about 0.5 h after gavage, and then gradually decreased. GW002 could significantly lower the serum acetaminophen concentration and make the area under the concentration-time curve (AUC) decrease by 28.4%. In conclusion, a method for the determination of serum acetaminophen based on the diazo reaction was established with good accuracy and could be used in the evaluation of gastric emptying.
MeSH term(s)	Acetaminophen/blood ; Acetaminophen/pharmacokinetics ; Aminophenols ; Animals ; Gastric Emptying ; Mice ; Mice, Inbred ICR
Chemical Substances	Aminophenols ; Acetaminophen (362O9ITL9D) ; 4-aminophenol (R7P8FRP05V)
Language	Chinese
Publishing date	2015-05
Publishing country	China
Document type	English Abstract ; Journal Article
ZDB-ID	788758-9
ISSN	0513-4870
ISSN	0513-4870
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Article: Ramulus Mori

Chen, Yan-Min / Lian, Chun-Fang / Sun, Qian-Wen / Wang, Ting-Ting / Liu, Yuan-Yuan / Ye, Jun / Gao, Li-Li / Yang, Yan-Fang / Liu, Shuai-Nan / Shen, Zhu-Fang / Liu, Yu-Ling

Antioxidants (Basel, Switzerland)

2022 Volume 11, Issue 5

Abstract: Nonalcoholic fatty liver disease (NAFLD), obesity, and type 2 diabetes mellitus (T2DM) have highly related mechanisms. ...

Abstract	Nonalcoholic fatty liver disease (NAFLD), obesity, and type 2 diabetes mellitus (T2DM) have highly related mechanisms.
Language	English
Publishing date	2022-05-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox11050905
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Article ; Online: The Chinese patent medicine, Jin-tang-ning, ameliorates hyperglycemia through improving β cell function in pre-diabetic KKAy mice.

Liu, Shuai-Nan / Liu, Quan / Lei, Lei / Sun, Su-Juan / Li, Cai-Na / Huan, Yi / Hou, Shao-Cong / Shen, Zhu-Fang

Chinese journal of natural medicines

2020 Volume 18, Issue 11, Page(s) 827–836

Abstract: Jin-tang-ning (JTN), a Chinese patent medicine, mainly comprised of Bombyx moriL., has been proved to show α-glucosidase inhibitory efficacy and clinically effective for the treatment of type 2 diabetes (T2DM). Recently, we have reported that JTN could ... ...

Abstract	Jin-tang-ning (JTN), a Chinese patent medicine, mainly comprised of Bombyx moriL., has been proved to show α-glucosidase inhibitory efficacy and clinically effective for the treatment of type 2 diabetes (T2DM). Recently, we have reported that JTN could ameliorate postprandial hyperglycemia and improved β cell function in monosodium glutamate (MSG)-induced obese mice, suggesting that JTN might play a potential role in preventing the conversion of impaired glucose tolerance (IGT) to T2DM. In this study, we evaluated the effect of JTN on the progression of T2DM in the pre-diabetic KKAy mice. During the 10 weeks of treatment, blood biochemical analysis and oral glucose tolerance tests were performed to evaluate glucose and lipid profiles. The β cell function was quantified using hyperglycemic clamp at the end of the study. JTN-treated groups exhibited slowly raised fasting and postprandial blood glucose levels, and also ameliorated lipid profile. JTN improved glucose intolerance after 8 weeks of treatment. Meanwhile, JTN restored glucose-stimulated first-phase of insulin secretion and induced higher maximum insulin levels in the hyperglycemic clamp. Thus, to investigate the underlying mechanisms of JTN in protecting β cell function, the morphologic changes of the pancreatic islets were observed by optical microscope and immunofluorescence of hormones (insulin and glucagon). Pancreatic protein expression levels of key factors involving in insulin secretion-related pathway and ER stress were also detected by Western blot. Pre-diabetic KKAy mice exhibited a compensatory augment in β cell mass and abnormal α cell distribution. Long-term treatment of JTN recovered islet morphology accompanied by reducing α cell area in KKAy mice. JTN upregulated expression levels of glucokinase (GCK), pyruvate carboxylase (PCB) and pancreas duodenum homeobox-1 (PDX-1), while down-regulating C/EBP homologous protein (Chop) expression in pancreas of the hyperglycemic clamp, which indicated the improvement of mitochondrial metabolism and relief of endoplasmic reticulum (ER) stress of β cells after JTN treatment. These results will provide a new insight into exploring a novel strategy of JTN for protecting β cell function and preventing the onset of pre-diabetes to T2DM.
MeSH term(s)	Animals ; Biological Products/pharmacology ; Bombyx ; Endoplasmic Reticulum Stress ; Female ; Glucokinase ; Glucose Tolerance Test ; Homeodomain Proteins ; Hyperglycemia/drug therapy ; Insulin Secretion ; Insulin-Secreting Cells/drug effects ; Islets of Langerhans/drug effects ; Medicine, Chinese Traditional ; Mice ; Mice, Inbred C57BL ; Nonprescription Drugs/pharmacology ; Prediabetic State ; Pyruvate Carboxylase ; Trans-Activators ; Transcription Factor CHOP
Chemical Substances	Biological Products ; Ddit3 protein, mouse ; Homeodomain Proteins ; Nonprescription Drugs ; Trans-Activators ; pancreatic and duodenal homeobox 1 protein ; Transcription Factor CHOP (147336-12-7) ; Glucokinase (EC 2.7.1.2) ; Pyruvate Carboxylase (EC 6.4.1.1)
Language	English
Publishing date	2020-12-11
Publishing country	China
Document type	Journal Article
ZDB-ID	2192577-X
ISSN	1875-5364 ; 2095-6975 ; 1672-3651
ISSN (online)	1875-5364
ISSN	2095-6975 ; 1672-3651
DOI	10.1016/S1875-5364(20)60023-1
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Article: The Chinese patent medicine, Jin-tang-ning, ameliorates hyperglycemia through improving β cell function in pre-diabetic KKAy mice

LIU, Shuai-Nan / LIU, Quan / LEI, Lei / SUN, Su-Juan / LI, Cai-Na / HUAN, Yi / HOU, Shao-Cong / SHEN, Zhu-Fang

Chinese journal of natural medicines. 2020 Nov., v. 18, no. 11

2020

Abstract	Jin-tang-ning (JTN), a Chinese patent medicine, mainly comprised of Bombyx moriL., has been proved to show α-glucosidase inhibitory efficacy and clinically effective for the treatment of type 2 diabetes (T2DM). Recently, we have reported that JTN could ameliorate postprandial hyperglycemia and improved β cell function in monosodium glutamate (MSG)-induced obese mice, suggesting that JTN might play a potential role in preventing the conversion of impaired glucose tolerance (IGT) to T2DM. In this study, we evaluated the effect of JTN on the progression of T2DM in the pre-diabetic KKAy mice. During the 10 weeks of treatment, blood biochemical analysis and oral glucose tolerance tests were performed to evaluate glucose and lipid profiles. The β cell function was quantified using hyperglycemic clamp at the end of the study. JTN-treated groups exhibited slowly raised fasting and postprandial blood glucose levels, and also ameliorated lipid profile. JTN improved glucose intolerance after 8 weeks of treatment. Meanwhile, JTN restored glucose-stimulated first-phase of insulin secretion and induced higher maximum insulin levels in the hyperglycemic clamp. Thus, to investigate the underlying mechanisms of JTN in protecting β cell function, the morphologic changes of the pancreatic islets were observed by optical microscope and immunofluorescence of hormones (insulin and glucagon). Pancreatic protein expression levels of key factors involving in insulin secretion-related pathway and ER stress were also detected by Western blot. Pre-diabetic KKAy mice exhibited a compensatory augment in β cell mass and abnormal α cell distribution. Long-term treatment of JTN recovered islet morphology accompanied by reducing α cell area in KKAy mice. JTN upregulated expression levels of glucokinase (GCK), pyruvate carboxylase (PCB) and pancreas duodenum homeobox-1 (PDX-1), while down-regulating C/EBP homologous protein (Chop) expression in pancreas of the hyperglycemic clamp, which indicated the improvement of mitochondrial metabolism and relief of endoplasmic reticulum (ER) stress of β cells after JTN treatment. These results will provide a new insight into exploring a novel strategy of JTN for protecting β cell function and preventing the onset of pre-diabetes to T2DM.
Keywords	Bombyx ; Western blotting ; area ; blood ; blood glucose ; duodenum ; endoplasmic reticulum ; fluorescent antibody technique ; glucagon ; glucokinase ; glucose ; glucose tolerance ; hyperglycemia ; insulin ; insulin secretion ; islets of Langerhans ; lipid composition ; mass ; medicine ; mice ; mitochondria ; monosodium glutamate ; noninsulin-dependent diabetes mellitus ; protein synthesis ; pyruvate carboxylase
Language	English
Dates of publication	2020-11
Size	p. 827-836.
Publishing place	Elsevier B.V.
Document type	Article
Note	NAL-light
ZDB-ID	2192577-X
ISSN	1875-5364 ; 2095-6975 ; 1672-3651
ISSN (online)	1875-5364
ISSN	2095-6975 ; 1672-3651
DOI	10.1016/S1875-5364(20)60023-1
Database	NAL-Catalogue (AGRICOLA)

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Article: [Farnesoid X receptor regulates glucose and lipid metabolisms].

Jiang, Qian / Peng, Jun / Liu, Shuai-nan / Shen, Zhu-fang

Yao xue xue bao = Acta pharmaceutica Sinica

2015 Volume 50, Issue 3, Page(s) 245–251

Abstract: As a member of nuclear receptor superfamily, farnesoid X receptor (FXR) has been shown to regulate numerous metabolic pathways, which include playing an important role in bile acid metabolism, maintaining lipid and glucose homeostasis when FXR is ... ...

Abstract	As a member of nuclear receptor superfamily, farnesoid X receptor (FXR) has been shown to regulate numerous metabolic pathways, which include playing an important role in bile acid metabolism, maintaining lipid and glucose homeostasis when FXR is activated. With the prevalence of the glucose and lipids disorder, FXR attracts increasing attention. It may be a potential target for the treatment of type 2 diabetes mellitus and lipid disorders.
MeSH term(s)	Bile Acids and Salts ; Diabetes Mellitus, Type 2 ; Glucose/metabolism ; Homeostasis ; Humans ; Lipid Metabolism ; Receptors, Cytoplasmic and Nuclear/metabolism
Chemical Substances	Bile Acids and Salts ; Receptors, Cytoplasmic and Nuclear ; farnesoid X-activated receptor (0C5V0MRU6P) ; Glucose (IY9XDZ35W2)
Language	Chinese
Publishing date	2015-06-09
Publishing country	China
Document type	Journal Article
ZDB-ID	788758-9
ISSN	0513-4870
ISSN	0513-4870
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Article: [Advances in diabetic animal models and its application in the traditional Chinese medicine research].

Cheng, Long / Shen, Zhu-fang / Sun, Gui-bo / Sun, Xiao-bo

Yao xue xue bao = Acta pharmaceutica Sinica

2015 Volume 50, Issue 8, Page(s) 951–958

Abstract: The high and continuing soaring incidence of diabetes may become a huge obstacle to China's development. The antidiabetic drug development is one way to solve the problem. Animal model is a powerful tool for drug development. This paper compares and ... ...

Abstract	The high and continuing soaring incidence of diabetes may become a huge obstacle to China's development. The antidiabetic drug development is one way to solve the problem. Animal model is a powerful tool for drug development. This paper compares and analyzes the three kinds of animal models for antidiabetic drug development in replicating principle, methods and characteristic, then summarized the application in the research of traditional Chinese medicine. At the same time, the analysis of the market, application and clinical advantages of hypoglycemic medicine from traditional Chinese medicine, is given in this paper, based on the literature analysis. From the point of the clinic advantage embodiment and new drug development, this paper will provide advisory and assistance support for the anti-diabetic fighting with traditional Chinese medicine.
MeSH term(s)	Animals ; China ; Diabetes Mellitus/drug therapy ; Disease Models, Animal ; Drug Discovery ; Humans ; Hypoglycemic Agents ; Medicine, Chinese Traditional
Chemical Substances	Hypoglycemic Agents
Language	Chinese
Publishing date	2015-08
Publishing country	China
Document type	English Abstract ; Journal Article
ZDB-ID	788758-9
ISSN	0513-4870
ISSN	0513-4870
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Article: Efficacy and Safety of Mulberry Twig Alkaloids Tablet for Treatment of Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Multicenter Clinical Study.

Qu, Ling / Liang, Xiao-Chun / Tian, Guo-Qing / Zhang, Gai-Li / Wu, Qun-Li / Huang, Xiu-Mei / Cui, Ya-Zhong / Liu, Yu-Ling / Shen, Zhu-Fang / Ma, Guo-Qing / Lu, Hao / Li, Yi / Jiang, Hong / Yang, Xi-Yan / Zhang, Guang-de / Yang, Chen-Hua

Chinese journal of integrative medicine

2022 Volume 28, Issue 4, Page(s) 304–311

Abstract: Objective: To assess the efficacy and safety of mulberry twig alkaloids (Sangzhi alkaloids, SZ-A) for treatment of type 2 diabetes in a randomized, double-blind, placebo-controlled multicenter clinical trial.: Methods: A total of 200 patients were ... ...

Abstract	Objective: To assess the efficacy and safety of mulberry twig alkaloids (Sangzhi alkaloids, SZ-A) for treatment of type 2 diabetes in a randomized, double-blind, placebo-controlled multicenter clinical trial. Methods: A total of 200 patients were randomized to receive SZ-A (n=100) or placebo (n=100) for 16 weeks. The data analysis system for electronic data capture clinical trial central randomization system was used for randomization and dispensing of drugs. The primary outcome was the change in glycosylated hemoglobin (HbA1c) level. The secondary outcome included the proportions of cases with HbA1c <7.0% and HbA1c <6.5%, fasting blood glucose (FBG), postprandial blood glucose (PBG), area under curve for the PBG (AUC Results: Compared with baseline, the change of HbA1c at week 16 was -0.80% (95% CI: -0.98% to -0.62%) and -0.09% (95% CI: -0.27% to 0.09%) in SZ-A group and placebo group, respectively. The proportion of patients with HbA1c <7% and <6.5% was higher in the SZ-A group than in the placebo group (46.8% vs. 21.6% and 29.9% vs. 10.8%). The observed values and changes in FBG, 1 h-PBG, 2 h-PBG, and AUC Conclusion: SZ-A are effective and safe for treatment of type 2 diabetes. The protocol was registered in http://www.chictr.org.cn/showproj.aspx?proj=60117 (ChiCTR2000038550).
MeSH term(s)	Alkaloids ; Blood Glucose ; Diabetes Mellitus, Type 2/drug therapy ; Double-Blind Method ; Glycated Hemoglobin A ; Humans ; Hypoglycemic Agents/therapeutic use ; Morus ; Tablets/therapeutic use ; Treatment Outcome
Chemical Substances	Alkaloids ; Blood Glucose ; Glycated Hemoglobin A ; Hypoglycemic Agents ; Tablets
Language	English
Publishing date	2022-01-19
Publishing country	China
Document type	Journal Article ; Multicenter Study ; Randomized Controlled Trial
ZDB-ID	2171254-2
ISSN	1993-0402 ; 1672-0415
ISSN (online)	1993-0402
ISSN	1672-0415
DOI	10.1007/s11655-021-2885-9
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Zs.A 5823: Show issues

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Article ; Online: Establishment of a dipeptidyl peptidases (DPP) 8/9 expressing cell model for evaluating the selectivity of DPP4 inhibitors.

Huan, Yi / Jiang, Qian / Liu, Jing-long / Shen, Zhu-fang

Journal of pharmacological and toxicological methods

2015 Volume 71, Page(s) 8–12

Abstract: Introduction: Dipeptidyl peptidases (DPPs) 8 and 9 are homologous, cytoplasmic postproline-cutting enzymes, which have similar enzymatic activity and preferred substrates as DPP4. DPP4 is a well-known target for treating diabetes mellitus. With the ... ...

Abstract	Introduction: Dipeptidyl peptidases (DPPs) 8 and 9 are homologous, cytoplasmic postproline-cutting enzymes, which have similar enzymatic activity and preferred substrates as DPP4. DPP4 is a well-known target for treating diabetes mellitus. With the increased concern of non-selectivity and toxicities caused by DPP4 inhibitors, it is essential to establish new ex vivo system to investigate DPP4 inhibitors' effect on DPP8 and DPP9. Method: Here we reported a newly established cell model system by cloning and transfecting human DPP8/9 genes into HEK 293 cells. We then used this model to evaluate the clinically applied DPP4 inhibitors' effect on DPP8/9, by direct enzymatic activity assay. Given the difference of cellular locations between DPP4 and DPP8/9, we also evaluated the influence of these drugs on intracellular DPP8/9 activity and cell viability by extracellular treatment with different inhibitors. Results: Direct enzymatic activity assay revealed significant and concentration-dependent inhibition effect of vildagliptin, saxagliptin on DPP8/9. Extracellular incubation of DPP8/9 over expressed cells with sitagliptin, vildagliptin, saxagliptin, alogliptin and linagliptin, showed only mild inhibition on DPP8/9. Moreover, all of these drugs showed no significant influence on cell viability. Discussion: Our results demonstrated that the DPP8/9 over-expressing cell model system is a very useful and promising system for investigating the selectivity and associated toxicity of DPP4 inhibitors on DPP8/9.
MeSH term(s)	Adamantane/analogs & derivatives ; Adamantane/chemistry ; Adamantane/pharmacology ; Cell Survival/drug effects ; Dipeptidases/genetics ; Dipeptidases/metabolism ; Dipeptides/chemistry ; Dipeptides/pharmacology ; Dipeptidyl Peptidase 4/metabolism ; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/genetics ; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/metabolism ; Dose-Response Relationship, Drug ; Enzyme Inhibitors/chemistry ; Enzyme Inhibitors/pharmacology ; HEK293 Cells ; Humans ; Models, Biological ; Nitriles/chemistry ; Nitriles/pharmacology ; Pyrrolidines/chemistry ; Pyrrolidines/pharmacology ; Recombinant Proteins/genetics ; Recombinant Proteins/metabolism ; Structure-Activity Relationship
Chemical Substances	Dipeptides ; Enzyme Inhibitors ; Nitriles ; Pyrrolidines ; Recombinant Proteins ; saxagliptin (9GB927LAJW) ; Dipeptidases (EC 3.4.13.-) ; DPP9 protein, human (EC 3.4.14.-) ; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases (EC 3.4.14.-) ; DPP4 protein, human (EC 3.4.14.5) ; DPP8 protein, human (EC 3.4.14.5) ; Dipeptidyl Peptidase 4 (EC 3.4.14.5) ; vildagliptin (I6B4B2U96P) ; Adamantane (PJY633525U)
Language	English
Publishing date	2015-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1105919-9
ISSN	1873-488X ; 1056-8719
ISSN (online)	1873-488X
ISSN	1056-8719
DOI	10.1016/j.vascn.2014.11.002
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Article: The Traditional Chinese Medicine Fuyou Formula Alleviates Precocious Puberty by Inhibiting GPR54/GnRH in the Hypothalamus.

Bai, Guo-Liang / Hu, Kai-Li / Huan, Yi / Wang, Xing / Lei, Lei / Zhang, Meng / Guo, Chun-Yan / Chang, Hong-Sheng / Zhao, Li-Bo / Liu, Jing / Shen, Zhu-Fang / Wang, Xiao-Ling / Ni, Xin

Frontiers in pharmacology

2021 Volume 11, Page(s) 596525

Abstract: The purpose of this study was to explore the effect of the traditional Chinese medicine Fuyou formula on precocious puberty (PP). The Fy formula may exert an effect in female rats with PP and GT-7 cells through the GPR54/GnRH signaling pathway. To ... ...

Abstract	The purpose of this study was to explore the effect of the traditional Chinese medicine Fuyou formula on precocious puberty (PP). The Fy formula may exert an effect in female rats with PP and GT-7 cells through the GPR54/GnRH signaling pathway. To confirm the effect of the Fy formula on PP through the GPR54/GnRH signaling pathway, we first treated GT1-7 cells with the Fy formula and observed changes in the expression of related genes and proteins and in GnRH secretion. Then, we randomly divided young female Sprague-Dawley rats into the control group, model group, leuprorelin group and the Fy formula group. A PP model was established by injection of danazol on postnatal day 5, and the Fy formula was administered on PND15. The time of vaginal opening, the wet weights of the ovary and uterus, serum hormone levels and the expression of hypothalamic-related genes were observed. We found that the Fy formula delayed vaginal opening, decreased the wet weights and coefficients of the ovary and uterus, decreased the levels of serum hormones (E2, follicle-stimulating hormone and luteinizing hormone) and the cellular GnRH level, and downregulated the gene expression of Kiss1, GPR54 and GnRH in the hypothalamus and the gene and protein expression of GPR54 and GnRH in GT1-7 cells. In conclusion, the Fy formula may alleviate PP via the GPR54/GnRH signaling pathway.
Language	English
Publishing date	2021-01-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2020.596525
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