Study on the potential mechanism of Qingxin Lianzi Yin Decoction on renoprotection in db/db mice via network pharmacology and metabolomics.

BACKGROUND: Diabetic nephropathy (DN) was one of the most popular and most significant microvascular complications of diabetes mellitus. Qingxin Lianzi Yin Decoction (QXLZY) was a traditional Chinese classical formula, suitable for chronic urinary system diseases. QXLZY had good clinical efficacy in early DN, but the underlying molecular mechanism remained unrevealed. PURPOSE: This study aimed to establish the content determination method of QXLZY index components and explore the mechanism of QXLZY on DN by network pharmacology and metabolomics studies. METHODS: Firstly, the content determination methods of QXLZY were established with calycosin-7-O-ß-d-glucoside, acteoside, baicalin and glycyrrhizic acid as index components. Secondly, pharmacological experiments of QXLZY were evaluated using db/db mice. UHPLC-LTQ-Orbitrap MS was used to carry out untargeted urine metabolomics, serum metabolomics, and kidney metabolomics studies. Thirdly, employing network pharmacology, key components and targets were analyzed. Finally, targeted metabolomics studies were performed on the endogenous constituents in biological samples for validation based on untargeted metabolomics results. RESULTS: A method for the simultaneous determination of multiple index components in QXLZY was established, which passed the comprehensive methodological verification. It was simple, feasible, and scientific. The QXLZY treatment alleviated kidney injury of db/db mice, included the degree of histopathological damage and the level of urinary microalbumin/creatinine ratio. Untargeted metabolomics studies had identified metabolic dysfunction in pathways associated with amino acid metabolism in db/db mice. Treatment with QXLZY could reverse metabolite abnormalities and influence the pathways related to energy metabolism and amino acid metabolism. It had been found that pathways with a high degree were involved in signal transduction, prominently on amino acids metabolism and lipid metabolism, analyzed by network pharmacology. Disorders of amino acid metabolism did occur in db/db mice. QXLZY could revert the levels of metabolites, such as quinolinic acid, arginine, and asparagine. CONCLUSION: This study was the first time to demonstrate that QXLZY alleviated diabetes-induced pathological changes in the kidneys of db/db mice by correcting disturbances in amino acid metabolism. This work could provide a new experimental basis and theoretical guidance for the rational application of QXLZY on DN, exploring the new pharmacological effect of traditional Chinese medicine, and promoting in-depth research and development.

[Systematic comparison of two kinds of Bufonis Venenum derived from different Bufo gargarizans subspecies based on metabolomics and antitumor activity].

This paper compared the differences between two kinds of Bufonis Venenum produced by Bufo gargarizans gargarizans and B. gararizans andrewsi, and verified the rationality of the market value orientation of Bufonis Venenum based on the zebrafish mo-del. Twenty batches of Bufonis Venenum from Jiangsu province, Hebei province, Liaoning province, Jilin province, and Liangshan, Sichuan province, including B. gargarizans gargarizans and B. gararizans andrewsi, were collected. The UHPLC-LTQ-Orbitrap-MS combined with principal component analysis was used to compare the differences between two kinds of Bufonis Venenum. According to the limiting conditions of VIP>1, FC<0.5 or FC>2.0, and peak total area ratio>1%, 9 differential markers were determined, which were cinobufagin, cinobufotalin, arenobufagin, resibufogenin, scillaredin A, resibufagin, 3-(N-suberoylargininyl)-arenobufagin, 3-(N-suberoylargininyl)-marinobufagin, and 3-(N-suberoylargininyl)-resibufogenin. The content of 20 batches of Bufonis Venenum was determined according to the Chinese Pharmacopoeia(2020 edition) by high-performance liquid chromatography, and the 2 batches of Bufonis Venenum, CS7(8.99% of total content) and CS9(5.03% of total content), with the largest difference in the total content of the three quality control indexes of the Chinese Pharmacopoeia(bufalin, cinobufagin, and resibufogenin) were selected to evaluate their anti-liver tumor activity based on the zebrafish model. The tumor inhibition rates of the 2 batches were 38.06% and 45.29%, respectively, proving that only using the quality control indexes of the Chinese Pharmacopoeia as the value orientation of Bufonis Venenum market circulation was unreasonable. This research provides data support for the effective utilization of Bufonis Venenum resources and the establishment of a rational quality evaluation system of Bufonis Venenum.

Tea consumption and cancer: a Mendelian randomization study / 中华流行病学杂志

Objective: A Mendelian randomization (MR) analysis was performed to assess the relationship between tea consumption and cancer. Methods: There were 100 639 participants with the information of gene sequencing of whole genome in the China Kadoorie Biobank. After excluding those with cancer at baseline survey, a total of 100 218 participants were included in this study. The baseline information about tea consumption were analyzed, including daily tea consumption or not, cups of daily tea consumption, and grams of daily tea consumption. We used the two-stage least square method to evaluate the associations between three tea consumption variables and incidence of cancer and some subtypes, including stomach cancer, liver and intrahepatic bile ducts cancer, colorectal cancer, tracheobronchial and lung cancer, and female breast cancer. Multivariable MR and analysis only among nondrinkers were used to control the impact of alcohol consumption. Sensitivity analyses were also performed, including inverse variance weighting, weighted median, and MR-Egger. Results: We used 54, 42, and 28 SNPs to construct non-weighted genetic risk scores as instrumental variables for daily tea consumption or not, cups of daily tea consumption, and grams of daily tea consumption, respectively. During an average of (11.4±3.0) years of follow-up, 6 886 cases of cancer were recorded. After adjusting for age, age2, sex, region, array type, and the first 12 genetic principal components, there were no significant associations of three tea consumption variables with the incidence of cancer and cancer subtypes. Compared with non-daily tea drinkers, the HR (95%CI) of daily tea drinkers for cancer and some subtypes, including stomach cancer, liver and intrahepatic bile ducts cancer, colorectal cancer, tracheobronchial and lung cancer, and female breast cancer, are respectively 0.99 (0.78-1.26), 1.17 (0.58-2.36), 0.86 (0.40-1.84), 0.85 (0.42-1.73), 1.39 (0.85-2.26) and 0.63 (0.28-1.38). After controlling the impact of alcohol consumption and performing multiple sensitivity analyses, the results were similar. Conclusion: There is no causal relationship between tea consumption and risk of cancer in population in China.

[Determination of neohesperidin and naringin in Qingfei Paidu Granules by RP-HPLC and their transfer rates in preparation process].

The present study established an RP-HPLC method for simultaneous determination of two active components in Qingfei Paidu Granules and investigated the transfer rates of neohesperidin and naringin in the preparation process to provide references for improving the quality control standard and production of Qingfei Paidu Granules.RP-HPLC was performed on a YMC Triart C_(18) column(4.6 mm×150 mm, 5 µm)with column temperature of 30 ℃, acetonitrile(A) and 0.2% phosphoric acid solution(B) as mobile phases for gradient elution at a flow rate of 1.0 mL·min~(-1) and detection wavelength of 284 nm.Good linearity was observed for naringin at 0.10-1.0 µg(R~2=0.999 9) and neohesperidin at 0.12-1.2 µg(R~2=0.999 9).The average recovery of naringin was 99.52% with an RSD of 1.2%, and that of neohesperidin was 100.8% with an RSD of 1.2%.The transfer rates of naringin and neohesperidin between medicinal materials, extracts, concentrates, and granules were measured by this method.The average transfer rate of naringin from medicinal materials to granules was 54.89%±4.38%, and that of neohesperidin was 57.63%±5.88%.The process from medicinal materials to extracts was presumedly the key link affecting the whole preparation process.The established method is simple and sensitive and can be adopted for the quality control of Qingfei Paidu Granules.Meanwhile, it can be used to investigate the transfer rate of neohesperidin and naringin in the preparation of Qingfei Paidu Granules, and further improve the quality control standard of Aurantii Fructus Immaturus in Qingfei Paidu Granules.

[Comprehensive evaluation system for quality of Chinese medicinal decoction pieces based on "experience-ingredients-activity-electronic sensing"].

Quality evaluation of Chinese medicinal decoction pieces is vital for the development of the downstream industries, and is an important channel for implementing the strategy of "higher quality, higher price, and priority for the high quality" for traditional Chinese medicine. At the moment, the quality of Chinese medicinal decoction pieces is mainly evaluated based on chemical component examination. Considering the weak preliminary research foundation and poor research conditions, traditional experience-based evaluation is undervalued in the quality rating of Chinese medicinal decoction pieces. However, traditional experience is a summary of the quality of Chinese medicinal materials based on clinical experience, which thus can be a potential basis for the quality evaluation of the decoction pieces. It is a challenge in the evaluation of Chinese medicinal decoction pieces to objectify the traditional experience-based evaluation from multiple aspects such as chemistry, effect, and characterization via modern techniques. Therefore, this study developed the "experience-ingredients-activity-electronic sensing" evaluation system for Chinese medicinal decoction pieces on the basis of experience-based assessment, chemical ingredients that can truly reflect the traditional experience, biological effect assessment, and electronic sensory evaluation, which is expected to quantify the traditional experience of quality evaluation of Chinese medicinal decoction pieces via chemistry, biology, and sensory simulation. The evaluation system can serve as a reference for clinical experience-based quality evaluation of Chinese medicinal decoction pieces.

[Determination and comparison of 10 active components in different parts of Loropetalum chinensis based on ultra-high performance liquid chromatography-tandem mass spectrometry].

To establish a method for the simultaneous determination of ellagic acid, quercetin, gallic acid, kaempferol, myricetin, tiliroside, salidroside, isoquercetin, chlorogenic acid, and quinic acid in the leaves, flowers, fruits, and roots of Loropetalum chinensis by ultra-performance liquid chromatography-tandem mass spectrometry, and provide references for the development and utilization of L. chinensis resources. The analysis was performed on the chromatographic column ACQUITY UPLC HSS T3(2.1 mm×100 mm, 1.8 µm) with a gradient mobile phase of acetonitrile-0.2% formic solution at the flow rate of 0.3 mL·min~(-1). Column temperature was 30 ℃ and injection volume was 2 µL. Multiple reactive ion monitoring mode(MRM) was used in the negative ion ionization mode of electrospray ion source. The 10 active components had a good linear relationship, and the established method was stable, simple, and accurate. The 10 active components existed in different parts of L. chinensis, with significant different content. The main components in different parts of L. chinensis were polyphenols, with the highest content, followed by flavonoids. The content of 10 active components was generally high in flowers. Among them, the content of quinic acid was the highest, reaching 22.539 1 mg·g~(-1). This study elucidates the differences of active components in the same part and the different parts of L. chinensis, thereby providing basis for the research on the pharmacodynamic substances of L. chinensis and references for the comprehensive development and utilization of L. chinensis resources.

Association between tea consumption and all-cause mortality in Chinese adults / 中华流行病学杂志

Objective: To investigate the association between tea consumption and the risk of all-cause and cause-specific mortality among Chinese adults. Methods: This study was based on China Kadoorie Biobank (CKB). Tea consumption information was self-reported by participants at baseline. Death was mainly identified by linkage to the death registry system. Cox proportional hazard regression models estimated HR and 95%CI. Results: With a median follow-up of 11.1 years, there were 34 661 deaths in 438 443 participants. Compared with those who never drink tea, all-cause mortality HR(95%CI) were 0.89(0.86-0.91) and 0.92(0.88-0.95) for non-daily tea drinkers and daily tea drinkers, respectively. A statistically significant difference was found in the association of tea consumption and the risk of all-cause mortality between men and women(interaction P<0.05). The protective effect was mainly seen in men. Compared with those who never drink tea, daily tea drinkers had a reduced risk of death from ischemic heart disease, ischemic stroke, hemorrhagic stroke, cancer, respiration diseases and other causes of death, and the corresponding HR(95%CI) were 0.83(0.76-0.92), 0.82(0.69-0.97), 0.86(0.78-0.94), 1.03(0.97-1.09), 1.00(0.87-1.16), 0.84(0.78-0.90). Among never smokers and non-excessive drinkers, there was no statistically significant association between daily tea drinking and the risk of death from cancer. While smokers and excessive drinkers had an increased risk of death from cancer (interaction P<0.001). Conclusions: Tea consumers had reduced risks of all-cause mortality and partial cause-specific mortality, but not for the risk of death from cancer. On the contrary, daily tea drinkers with smoking habits and excessive alcohol drinking had an increased risk of death from cancer.

The integrated study on the chemical profiling and in vivo course to explore the bioactive constituents and potential targets of Chinese classical formula Qingxin Lianzi Yin Decoction by UHPLC-MS and network pharmacology approaches.

ETHNOPHARMACOLOGICAL RELEVANCE: Qingxin Lianzi Yin Decoction (QXLZY), a Chinese classical formula, has been widely used in the treatment of various chronic kidney diseases over 1,000 years. However, the current studies on QXLZY were mostly focused on its clinical efficacy, lacking systematic material basis research on constituents. AIM OF THE STUDY: This work aims to elucidate and quantify the chemical constituents, clarify the blood-absorbed components and excretion pathways, predict major bioactive constituents and discover potential therapeutic targets. MATERIALS AND METHODS: UHPLC-LTQ-Orbitrap HRMS was employed to clarify the chemical constituents and metabolites of QXLZY. The extraction of diagnostic ion and neutral loss fragment was aimed for searching specific type of constituents. The plasma, urine, bile and feces samples of rats after oral administration of QXLZY were systematically studied. UHPLC-QQQ-MS/MS was employed to simultaneously detect different types of constitutes. Based on the analysis of ingredients in vivo, the bioactive constituents and potential therapeutic targets in the treatment of diabetic nephropathy (DN) was investigated by using network pharmacological analysis. RESULTS: Totally, 220 compounds were identified or tentatively characterized by UHPLC-LTQ-Orbitrap HRMS. Among them, 59 compounds were confirmed by reference standards. Meanwhile, 21 representative components were simultaneously determined within 15 min by UHPLC-QQQ-MS/MS. 123 components (74 prototypes as well as 49 metabolites) were identified or tentatively characterized. By using network pharmacological analysis, baicalein, liquiritigenin, succinic acid, formononetin, wogonin might be the major effective constituents in QXLZY during the treatment of DN. CONCLUSIONS: Flavonoids, saponins and organic acids were the major chemical ingredients of QXLZY. Flavonoids were the main components absorbed into blood, followed by organic acids. Phase II conjugation reaction was the major metabolic type. The pathways that QXLZY in the treatment of DN were probably related to glucose and lipid metabolism, oxidative stress and inflammation.

[Application of MALDI-mass spectrometry imaging in spatial distribution of secondary metabolites in medicinal plants -- a case study of Lepdium meyenii root].

Matrix-assisted laser desorption/ionization mass spectrometry imaging(MALDI-MSI) is a novel technique for in-situ distribution of various substances in tissue without labeling. This technique is increasingly applied to the study of medicinal plants owing to its high spatial resolution and its potential of in-situ analysis in small molecules. In this study, the structural information and their fragmentation patterns of the midazole alkaloids(1,3-dibenzyl-4,5-dimethylimidazolium chloride and 1,3-dibenzyl-2,4,5-trimethylimi-dazolium chloride) and benzylglucosinolate in the medicinal plant Maca(Lepdium meyeni) root were analyzed by ultra-high-performance liquid phase combined with LTQ-Orbitrap mass spectrometry(UHPLC-HR-MS). The localization of these active ingredients in the cross-sections of Maca root was performed by MALDI-MSI. These results demonstrated that the two types of imidazole alkaloids had a similar distributed pattern. They were located more in the cortex and the periderm than those in the medulla of a lateral root, while the localization of benzylglucosinolate was concentrated in the center of the root rather than in the cortex and the periderm. The precise spatial distribution of various secondary metabolites in tissue provides an important scientific basis for the accumulation of medicinal plant active ingredients in tissues. In addition, this imaging method is a promising technique for the rapid evaluation and identification of the active ingredients of traditional Chinese medicine in plant tissues, as well as assisting the research on the processing of medicinal plants.

Application of RBL-2H3 cells on allergenicity assessment of Qing kailing and Tanreqing Injections / 中草药

Objective: To explore the allergenicity of two kinds of Chinese materia medica (CMM) injections, Qingkailing (QKL) and Tanreqing (TRQ) Injections, with serum antibody sensitized RBL-2H3 cells. Methods: The antiserum was prepared by sc injection of allergen composed of ovalbumin (OVA), QKL, or TRQ combined with aluminum hydroxide adjuvant respectively in Wistar rats. The total IgE level in serum antibody was determined by radioimmunoassay. The RBL-2H3 cells were sensitized with serum antibodies, then stimulated by OVA, QKL, or TRQ after 48 h. The release rate of β-hexosaminidase in the supernatant was determined after the degranulation of sensitized RBL-2H3 cells. Passive cutaneous anaphylaxis (PCA) test was performed with rats, and the positive reaction rate with blue plaque in animal skin was observed. Results: Compared with the control group, the total IgE level in serum antibody was increased significantly in OVA, TRQ, and QKL groups (P < 0.05). The degranulation test revealed that the release rate of β-hexosaminidase was significantly increased in the supernatant when the cells were incubated with the antiserum and then stimulated with OVA, QKL, and TRQ. Compared with the control group, the largest relative times of release were 3.7, 1.53, and 1.98, respectively. The results of PCA test showed that the highest percentage rates of positive reaction of blue plaque were 100%, 100%, and 86% respectively. The results of RBL-2H3 cell test and PCA test have good consistency. Conclusion: The serum antibody sensitized RBL-2H3 cell model can be used for screening or assessing allergenicity of CMM injection.

Relations between attitude and practice of smoking and the training program regarding tobacco control among community medical staff members in Hangzhou, Zhejiang province / 中华流行病学杂志

Objective To investigate the relations between training and both the attitude and practice on smoking control among community medical staff members in Hangzhou,Zhejiang province.Methods Three representative districts including Xiacheng,Gongshu and Westlake were chosen from Hangzhou city.Questionnaire survey was applied to collect information from the related community medical staff members.The survey mainly contained three aspects:knowledge,attitude and practice regarding smoking control involved in the community medical activities.Availability and application of the resources on smoking cessation were also studied.Logistic regression analysis was applied to explore the factors associated with the smoking control training programs.Differences of rates between groups were assessed with chi-square statistics.Wilcoxon rank sum test was used to study the relationships among knowledge,attitude and practice related to smoking control programs,targeted to the community medical staff members.Results Eight hundred forty-six community medical workers were involved.Sixty-five percent of the community medical staff members had learned related knowledge on smoking control.Proportion of the community medical staff who had taken lessons on smoking control with 3-10 working years was 1.77 times more than the ones with experience less than two years (OR=1.77,95％CI:1.25-2.51).Eighty-eight point seven percent of the medical staff who had received smoking control training programs were identified with the consciousness that they should advise the patients to quit smoking,comparing to the proportion 81.60％ (Z=-2.87,P=0.00) in the control group.In terms of the practice regarding smoking control,data showed that 21.62％ of the medical staff who had received smoking control training programs would provide ‘how to quit smoking' to more than 90％ of the smoking patients,while the proportion in the control group was 10.65％ (Z=-5.68,P=0.00).The use of drugs,traditional Chinese medicine therapy and the smoking cessation hotline rate were all less than 30％.Conclusion The training programs being used on smoking control seemed useful in improving the consciousness and practice towards the smoking control programs during their medical activities among the community medical staff members.

Detection of metabolites in the white matter of frontal lobes and hippocampus with proton in first-episode treatment-naïve schizophrenia patients.

AIM: This study aimed to investigate the changes of the metabolites in the white matter of frontal lobes and hippocampus in schizophrenia by using proton magnetic resonance spectroscopy ((1) H-MRS). METHODS: Sixty-three first-episode treatment-naïve schizophrenia (FES) patients and 63 age-, gender- and education level-matched healthy controls were recruited. The relative levels of metabolites including N-acetylaspartate (NAA), choline-containing compounds (Cho), (Cr) and myo-inositol (MI) were detected with (1) H-MRS, and the laterality index (Li) was calculated. The severity of symptoms was assessed using the Positive and Negative Syndrome Scale. RESULTS: Compared with controls, FES patients did not show significant differences in all metabolites. The severity of positive symptoms was negatively correlated with the NAA/Cho in the white matter of the left frontal lobe and positively correlated with the Cho/Cr in the right white matter of frontal lobes. A negative correlation was observed between the severity of negative symptoms and the NAA/Cr in the white matter of bilateral frontal lobes. No difference was shown in the Li of metabolites between FES patients and controls. CONCLUSIONS: The metabolites such as NAA, Cho and MI in white matter of frontal lobes and hippocampus were not significantly altered in FES patients. The lower axonal integrity/number (NAA concentration) may be associated with more severe negative symptoms, and dysmetabolism in process of myelination in the white matter of frontal lobes associated with more severe positive symptoms.

Steady-state pharmacokinetics and tissue distribution of anthraquinones of Rhei Rhizoma in rats.

AIM OF THE STUDY: Rhei Rhizoma, the rhizome of Rheum palmatum L. (RP), is a popular herb in clinical Chinese medicine. RP is abundant in polyphenolic anthraquinones, which have been reported to show various beneficial bioactivities. This study investigated the pharmacokinetics and tissue distribution of anthraquinones following seven-dose administration of RP decoction to rats. MATERIALS AND METHODS: Six Sprague-Dawley rats were given 2.0 g/kg of RP twice daily for seven doses and blood samples were collected at designated time after the 7th dose. Another six rats were sacrificed at 30 min after the 7th dose and organs including liver, kidney, lung and brain were collected. Serum and tissue specimens were assayed by HPLC before and after hydrolysis with ß-glucuronidase and sulfatase, respectively. RESULTS: Pharmacokinetic analysis indicated that the anthraquinones in serum mainly presented as glucuronides/sulfates and contained higher ratio of sulfates when compared with single-dose administration of RP. Contrary to the finding in serum, tissue analysis discovered mainly free form of anthraquinone in most organs assayed, such as aloe-emodin and rhein in kidney, liver, lung; emodin in liver, lung; trace of chrysophanol in kidney and liver. In all brains, neither free forms nor their glucuronides/sulfates have been detected. CONCLUSIONS: The glucuronides/sulfates of anthraquinones were the major forms in bloodstream, whereas the free forms of most anthraquinones were predominant in kidney and liver.

Evidence of the effectiveness on tobacco control programs: a systematic review on the intervention studies in China / 中华流行病学杂志

To systematically summarize the evidence on the effectiveness of measures regarding tobacco control in China. Papers on several databases published between 1990 and 2009were systematically searched. Methods in American Guide to Community Preventive Services were used to evaluate the quality and strength of evidence on the effectiveness of tobacco control programs.Overall, 282 studies were included in this paper, but only 75 (26.41%) studies had acceptable execution quality. Items as pharmaceutical therapy and behavior intervention in the smoking population that would show sufficient evidence on the effectiveness of the programs. In general population, multi-component intervention programs appeared to be effective. However, the effectiveness regarding items as clinical consultation, therapy with traditional Chinese medicine,education programs alone, non-smoking related laws and regulations etc. were of insufficient evidence. The overall execution quality of intervention studies on tobacco control in China was considered to be poor and few of them would show the evidence on the effectiveness of the programs. Only few studies on non-smoking related laws and regulations touched upon the positive effectiveness on this issue. We suggested that the execution and evaluation on non-smoking related laws and regulations be strengthened.

Anti-diabetic effects of cinnamaldehyde and berberine and their impacts on retinol-binding protein 4 expression in rats with type 2 diabetes mellitus.

BACKGROUND: Retinol binding protein 4 (RBP4), as an adipocyte secreted cytokine, was recently found to be inversely correlated with expression of glucose transporter 4 (GLUT4) in insulin resistance (IR) state and to have an intimate relationship with IR and type 2 diabetes mellitus (T2DM). The present study aimed to evaluate the anti-diabetic efficacy of cinnamaldehyde (Cin), berberine (Ber), and metformin (Met) as well as their impacts on the RBP4-GLUT4 system. METHODS: Rat models of T2DM were established by combination of intraperitoneal injection of low-dose streptozotocin and high fat diet induction. Rats were divided into five groups: the control group, the diabetes group, the diabetes + Ber group, the diabetes + Cin group, and the diabetes + Met group. Western blotting was used to detect the serum or tissue RBP4 and GLUT4 protein levels. RESULTS: After treatment for four weeks, both Cin and Ber displayed significant hypolipidemic, hypoglycemic, and insulin sensitizing functions (P < 0.01) compared with the control group. Their effects on lowering fasting plasma glucose (FPG), low density lipoprotein-cholesterol (LDL-C) and homeostasis model assessment of insulin resistance (HOMA-IR) seem even better than that of Met. Cin and Ber markedly lowered serum RBP4 levels and up-regulated the expression of tissue GLUT4 protein, and Cin seemed more notable in affecting these two proteins. CONCLUSIONS: Both Cin and Ber display an exciting anti-diabetic efficacy in this study and may be of great value for the treatment of type 2 diabetes. Their mechanisms involve the RBP4-GLUT4 system, during which the serum RBP4 levels are lowered and the expression of tissue GLUT4 protein is up-regulated.