ETHNOPHARMACOLOGICAL RELEVANCE:For centuries, Paeonia lactiflora Pall. (Baishao) has been used to treat liver disorders. Paeoniae Radix Alba Polysaccharide (PRP), the main active ingredient of Baishao, has definite hepatoprotective properties. The exact mechanism by which PRP protects against liver fibrosis remains unknown. AIM OF THE STUDY:This study was to explore anti-hepatic fibrosis effect and underlying mechanisms of PRP. MATERIALS AND METHODS:40 % carbon tetrachloride (CCl4) olive oil solution induced hepatic fibrosis in rats. Therapeutic effect of PRP in mitigating liver fibrosis was assessed by detecting liver function, liver pathological changes, oxidative stress, inflammatory reaction, ferroptosis, and liver fibrosis indicators. Network pharmacology and transcriptomics identified PRP's anti-hepatic fibrosis targets and pathways. Subsequently, validation was performed employing. RESULTS:PRP reduced liver function, inhibited fibrotic tissue proliferation and extracellular matrix (ECM) deposition, modulated inflammation, slowed oxidative stress, inhibited ferroptosis of model rats. In vitro, PRP also suppressed HSCs proliferation, activation, ECM deposition, and enhanced mitochondrial membrane potential, exerting antifibrotic effects. Meanwhile, PRP inhibited PI3K/AKT/mTOR pathway and activated SLC7A11/GPX4 pathway-related protein expression. More importantly, PI3K inhibitor (LY294002) experiments confirmed PI3K/AKT/mTOR pathway's importance in inhibiting ferroptosis by PRP. CONCLUSION:These findings reveal PRP attenuates ferroptosis and liver fibrosis through inhibiting PI3K/AKT/mTOR and activating SLC7A11/GPX4 pathway.

Background: Diabetic liver injury (DLI) is a common complication of diabetes mellitus (DM), which seriously endangers the health of diabetic patients. Puerarin, the main active component of Pueraria lobata, has shown positive effects in lowering blood glucose and lipids, resisting oxidative stress, and protecting the liver. However, the mechanism of protective effect of Puerarin on DLI remains unclear. Methods: Various databases were used to screen for targets of Puerarin, ferroptosis and DLI. Protein-protein interaction (PPI) network and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used to predict key targets and pathways. Molecular docking was used to predict the interactions between Puerarin and core targets. KK/Upj-Ay/J (KKAy) mice and high glucose (HG)-induced AML12 cells were used to study the protective effect of Puerarin on DLI. The molecular mechanisms by which Puerarin acts were further verified by in vivo and in vitro experiments. Results: KEGG analysis indicated that the JAK/STAT pathway might be related to the anti-DLI effect of Puerarin. Molecular docking revealed that Puerarin has good affinity for JAK2 and STAT3. In vivo, Puerarin (80 mg/kg) reduced body weight, blood glucose, blood lipids and liver function in KKAy mice fed a high-sugar, high-fat diet. Puerarin also ameliorated hepatic pathological changes and inflammatory responses, and attenuated oxidative stress and iron overload in KKAy mice. Western blotting results showed that Puerarin could regulate the expression of proteins related to JAK2/STAT3 pathway and ferroptosis pathway. In vitro, Puerarin (25, 50, 100 mu M) increased cell viability and decreased steatosis and liver function indexes in AML12 cells induced by HG (30 mm) to varying degrees. More importantly, AG490 blocker experiments showed that the regulation of ferroptosis process by Puerarin was dependent on the JAK2/STAT3 pathway. Conclusion: In conclusion, this study revealed Puerarin may regulate the ferroptosis process by inhibiting the JAK2/STAT3 pathway for the treatment of DLI.

Objective: To investigate the protective effect and mechanism of Qiyu Granules in alleviating insulin resistance in KKAy mice. Methods: The chemical ingredients of Qiyu Granules were analyzed using ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Network pharmacology and animal experiments were used to verify the pharmacological effects of Qiyu Granules in alleviating insulin resistance in diabetic KKAy mice and to explore its mechanism of action. High-sugar, high-fat chow was fed to KKAy mice for modeling. After 12 weeks, indicators of glucose metabolism (FBG, AUC), lipid metabolism (TC, TG, LDL, HDL, FFA), liver function (ALT, AST) and insulin resistance (FINS, HOMA-IR, HOMA-beta, ISI) were detected. Pathological changes in pancreatic and liver tissues were observed by hematoxylin-eosin (H&E) and Oil Red O staining. Hepatic glycogen levels were analyzed using enzyme-linked immunosorbent assay (ELISA) method and periodic acid-Schiff (PAS) staining. Western blot was used to detect the protein expression levels of InsR, p-PI3 K, p-AKT, FoxO1, PEPCK, G6pase, p-AMPK, p-GSK-3 beta, GLUT2, PPAR gamma and PPAR alpha. Results: FBG, AUC, HOMA-IR, TC, TG, LDL, FFA, ALT, AST and hepatic index were decreased in mice treated with Qiyu Granules; while FINS, HOMA-beta, ISI, HDL and hepatic glycogen content were increased. Qiyu Granules also improved histopathological changes in the pancreas and liver of KKAy mice. Besides, Qiyu Granules up-regulated the expression levels of InsR, p-PI3 K, p-AKT, p-AMPK, GLUT2 and PPAR alpha proteins in the livers of mice in the model group. However, Qiyu Granules down-regulated the expression levels of FoxO1, PEPCK, G6Pase, p-GSK-3 beta and PPAR gamma proteins. Conclusion: Qiyu Granules may regulate the InsR/PI3K/AKT/FoxO1 pathway, AMPK pathway, and PPAR gamma/PPAR alpha pathway to ameliorate insulin resistance. Therefore, Qiyu Granules is a promising hypoglycaemic agent for the treatment of DM.

Nonalcoholic fatty liver disease (NAFLD) and hyperlipidemia belong to the metabolic disorder syndromes of metabolic syndrome. They share a common pathological basis and are often complicated. Complanatoside A (CA), a flavonoid abundant in Astragali complanati semen, helps to prevent NAFLD and hyperlipidemia. However, the exact molecular mechanism is uncertain. Therefore, this study aims to explore the core mechanism. Network pharmacology was used to analyze the preventive mechanism of CA against NAFLD and hyperlipidemia. The efficacy of CA was proven in a high-fat diet-fed mouse model and a steatogenic hepatocyte model. Transcriptomic analysis, Western blot validation, and molecular docking methods were used to explore the common mechanism of CA in preventing NAFLD and hyperlipidemia. Network pharmacology revealed that the AMP-activated protein kinase (AMPK) pathway is a common mechanism leading to NAFLD and hyperlipidemia. It is also a potential pathway by which CA exerts its protective effect, which was confirmed in transcriptomics in vivo. Both in vitro and in vivo experiments showed that CA could inhibit lipid synthesis and promote fatty acid oxidation by activating the AMPK, alleviating lipid accumulation, and lipotoxic liver injury. This was demonstrated by the use of an AMPK inhibitor in vitro. Furthermore, molecular docking results showed that CA could directly interact with AMPK to regulate downstream lipid-related proteins. In conclusion, the AMPK pathway is key in developing NAFLD and hyperlipidemia. CA plays a dual preventive role in NAFLD and hyperlipidemia by activating AMPK to regulate lipid metabolism.

BACKGROUND:Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) significantly contributes to the high mortality rate associated with chronic obstructive pulmonary disease (COPD). It leads to a decline in health status, increased rates of readmission, and accelerated disease progression. LouDan LiFei granule (LDLF), a Traditional Chinese Medicine (TCM) granule, has demonstrated efficacy in treating AECOPD patients. However, its underlying regulatory mechanisms remain to be fully elucidated. PURPOSE:To investigate the pharmacodynamic components and regulatory mechanisms of LDLF in the treatment of AECOPD, and to provide a scientific basis for the further clinical application of subsequent drugs. METHODS:This study focused on identifying the pharmacodynamic components and regulatory mechanisms of LDLF. In vivo experiments, we established a rat model of AECOPD and systematically evaluated the therapeutic effect by monitoring the body weight, lung function and pathological changes in lung tissue. UPLC-MS/MS was employed to detect the components of LDLF medicated serum. Network pharmacology and molecular docking were utilized to determine the therapeutic targets and pathways of LDLF in AECOPD treatment. Finally, we further verified the research results by establishing AECOPD moded in rat and BEAS-2B. RESULTS:Our study revealed that LDLF significantly reduced inflammation and pathological damage in lung tissue of AECOPD model rats and improved pulmonary function. UPLC-MS/MS analysis identified 1502 compounds in LDLF medicated serum, primarily comprising flavonoids, terpenoids, alkaloids, ketones, and aldehydes acids. Network pharmacology results suggested that LDLF may treat AECOPD by modulating Th17 cell differentiation and signaling pathways related to IL-17, T cell receptor, and NOD-like receptor. Molecular docking confirmed stable interactions between core compounds and their targets. In vivo validation showed that LDLF redused the proportion of Th17 cells and increased Treg cells proportion in peripheral blood of rat model. Protein expression levels of FOXP3 were elevated, and RORγ and STAT3 were reduced in lung tissue. Inflammatory markers (IL-6, IL-1β, IL-8, IL-17, TNF-α, IL-10, and TGF-β1) in serum and balf were improved after LDLF treatment. Additionally, LDLF significantly inhibited the NLRP3 inflammasome pathway at protein and mRNA levels in lung. In vitro experiments demonstrated that LDLF enhanced the BEAS-2B cells viability and inhibited inflammatory markers IL-6 and TNF-α as well as key targets of NLRP3, STAT3, CASP3, and AKT1. CONCLUSIONS:This research highlights the potential for LDLF in the treatment of AECOPD and enhances our understanding of its pathogenic and therapeutic mechanisms.

Objective Major depressive disorder (MDD) is a severe psychiatric symptom worldwide, and the coexistence of MDD with metabolic syndrome (MetS) is common in clinical practice. However, gender differences in comorbid MetS in first-episode and drug-naive (FEDN) MDD patients have not been reported. Here, we explored potential gender differences in the prevalence and clinical correlates of comorbid MetS in FEDN MDD patients. Methods A cross-sectional study of 1718 FEDN MDD patients was conducted. Demographic and clinical data were collected. The Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale, and Positive and Negative Syndrome Scale positive subscale were used to evaluate depression, anxiety, and psychotic symptoms, respectively. Results The prevalence of MetS was 1.645-fold higher in female MDD patients (38.50%) than in male patients (26.53%). Patients with MetS had higher HAMD score, Hamilton Anxiety Scale score, and Positive and Negative Syndrome Scale positive subscale score than patients without MetS (p values < .001). Furthermore, suicide attempts (male: odds ratio [OR] = 1.706, p = .034; female: OR = 1.639, p = .004) and HAMD score (male: OR = 1.251, p < .001; female: OR = 1.148, p < .001) were independently associated with MetS in male and female patients, whereas age of onset was independently associated with MetS only in female patients (OR = 1.744, p = .047). Conclusions Our findings suggest significant gender differences in the prevalence and clinical correlates of comorbid MetS in FEDN MDD patients. Clinical variables (suicide attempts and HAMD scores) may be independently associated with MetS in MDD patients.

Objective To evaluate the antioxidant effect of American ginseng Rhodiola formula on ethanol-induced oxidative damage in model mice, and to explore its mechanism of action, providing a scientific basis for the development of healthy food. Methods Mice were randomly divided into blank control group, acute oxidative injury model group, low dose (330 mg/kg), medium dose (660 mg/kg) and high dose (990 mg/kg) groups according to body weight, 10 mice in each group. Each dose group was given test samples by oral gavage. Blank control group and model group were given equal volume of distilled water. After continuous gavage for 30 days, 50% ethanol was intragastrically administered at 12 mL/kg after fasting for 16 h in each group except blank control group. Blood and liver were collected from mice 6 h later. Malondialdehyde (MDA), 8-epoxyisoprostane (8-Isoprostane), protein carbonyl (PCO), glutathione (GSH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin- 6 (IL- 6) content and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activity in mouse serum, MDA, PCO, GSH content and SOD activity in liver tissue were measured, and the protein expression of p-p38, p-ERK and p-JNK was detected by Western blotting.. Results Compared with the model group, the MDA content in the serum of mice in the low-dose group of American ginseng Rhodiola formula decreased (P<0.05), the 8-Isoprostane and PCO contents in each dose group decreased (P<0.05), the GSH content and GSH-Px and SOD activities in each dose group increased (P<0.05), the TNF-α, IL-1β, and IL- 6 levels in each dose group decreased (P<0.05), and the ALT and AST activities in each dose group decreased (P<0.05). The MDA content in the liver of mice in the low and medium dose groups decreased (P<0.05), the PCO and TG contents in each dose group decreased (P<0.05), and the SOD activity in the low and medium dose groups and the GSH content in the low dose group increased (P<0.05). The low dose group could inhibit the expression of p-p38 and p-JNK (P<0.05), and the medium and high dose groups could inhibit the expression of p-p38, p-ERK and p-JNK (P<0.05). Conclusion Rhodiola rosea, American ginseng, acerola cherry powder and grape seed extract composition of medicinal food homologous complex formula has a strong antioxidant health care effect.

Objective: To explore and validate the potential targets of Paeoniae Radix Alba (P. Radix, Bai Shao) in protecting against chemical liver injury through network pharmacology, molecular docking technology, and in vitro cell experiments. Methods: Network pharmacology was used to identify the common potential targets of P. Radix and chemical liver injury. Molecular docking was used to fit the components, which were subsequently verified in vitro. A cell model of hepatic fibrosis was established by activating hepatic stellate cell (HSC)-LX2 cells with 10 ng/mL transforming growth factor-β1. The cells were exposed to different concentrations of total glucosides of paeony (TGP), the active substance of P. Radix, and then evaluated using the cell counting kit-8 assay, enzyme-linked immunosorbent assay, and western blot. Results: Analysis through network pharmacology revealed 13 key compounds of P. Radix, and the potential targets for preventing chemical liver injury were IL-6, AKT serine/threonine kinase 1, jun proto-oncogene, heat shock protein 90 alpha family class A member 1 (HSP90AA1), peroxisome proliferator activated receptor gamma (PPARG), PTGS2, and CASP3. Gene Ontology (GO) enrichment analysis indicated the involvement of response to drugs, membrane rafts, and peptide binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the main pathways involved lipid and atherosclerosis and chemical carcinogenesis-receptor activation. Paeoniflorin and albiflorin exhibited strong affinity for HSP90AA1, PTGS2, PPARG, and CASP3. Different concentrations of TGP can inhibit the expression of COL-Ⅰ, COL-Ⅲ, IL-6, TNF-α, IL-1β, HSP-90α, and PTGS2 while increasing the expression of PPAR-γ and CASP3 in activated HSC-LX2 cells. Conclusion: P. Radix primarily can regulate targets such as HSP90AA1, PTGS2, PPARG, CASP3. TGP, the main active compound of P. Radix, protects against chemical liver injury by reducing the inflammatory response, activating apoptotic proteins, and promoting the apoptosis of activated HSCs.

Objective: To explore the neuroprotective effects of the Shaoyao Gancao decoction (SGD) against excitatory damage in PC12 cells and the role of the Src-NR2-nNOS pathway mediation by SGD in regulating γ-aminobutyric acid (GABA)-glutamate (Glu) homeostasis. Methods: N-Methyl-d-aspartic acid (NMDA) was used to establish a PC12 cell excitability injury model. To investigate the neuroprotective effect of SGD, a cell counting kit-8 (CCK-8) assay was used to determine PC12 cell viability, Annexin V/Propidium Iodide (Annexin V/PI) double staining was used to determine PC12 cell apoptosis, and Ca2+ concentration was observed using laser confocal microscopy. GABA receptor agonists and antagonists were used to analyze the neuroprotective interactions between γ-aminobutyric acid (GABA) and NMDA receptors. Additionally, molecular biology techniques were used to determine mRNA and protein expression in the Src-NR2-nNOS pathway. We analyzed the correlations between the regulatory sites of GABA and NMDA interactions, excitatory neurotoxicity, and brain damage at the molecular level. Results: NMDA excitotoxic injury manifested as a significant decrease in cell activity, increased apoptosis and caspase-3 protein expression, and a significant increase in intracellular Ca2+ concentration. Administration of SGD, a GABAA receptor agonist (muscimol), or a GABAB receptor agonist (baclofen) decreased intracellular Ca2+ concentrations, attenuated apoptosis, and reversed NMDA-induced upregulation of caspase-3, Src, NMDAR2A, NMDAR2B, and nNOS. Unexpectedly, a GABAA receptor antagonist (bicuculline) and a GABAB receptor antagonist (saclofen) failed to significantly increase excitatory neurotoxicity. Conclusions: Taken together, these results not only provide an experimental basis for SGD administration in the clinical treatment of central nervous system injury diseases, but also suggest that the Src-NR2A-nNOS pathway may be a valuable target in excitotoxicity treatment.

Introduction: The rising prevalence and severe consequences of nonalcoholic fatty liver disease (NAFLD) have driven the quest for preventive medications. Complanatoside A (CA) is the marked flavonoid of Astragali complanati semen, a traditional Chinese herb that acts on the liver meridian and is widely used to treat liver problems. CA has been proven to have considerable lipid-lowering and liver-protective effects in vitro. However, the efficacy of CA in preventing NAFLD has yet to be shown in vivo. Methods: First, the effectiveness of CA against NAFLD was assessed using a high-fat diet (HFD) mouse model. Second, the CA protective mechanism against NAFLD was investigated using a combined metabolomics and network pharmacology strategy. Differential metabolites were identified by metabolomics-based analyses, and metabolic pathway analysis was accomplished by MetaboAnalyst. Potential therapeutic targets were obtained through network pharmacology. Finally, key targets were identified via compound-target networks and validated by molecular docking and western blotting. Results: CA prevented NAFLD mainly by reducing liver lipid accumulation in HFD mice. Metabolomics identified 22 potential biomarkers for CA treatment of NAFLD, primarily involving glycerophospholipid and arachidonic acid metabolism. Fifty-one potential targets were determined by network pharmacology. Co-analysis revealed that albumin, peroxisome proliferator-activated receptor-alpha, retinoid X receptor alpha, interleukin-6, and tumor necrosis factor alpha were key targets. Conclusion: This experiment revealed that CA has a preventive effect on NAFLD, primarily by regulating the peroxisome proliferator-activated receptor-alpha/retinoid X receptor alpha pathway. Furthermore, it provides evidence supporting the potential use of CA in the long-term prevention of NAFLD.

目的 系统评价藤黄健骨片治疗膝骨关节炎的临床疗效和安全性,为临床用药提供循证参考.方法 计算机检索中国知识资源总库(CNKI)、中国学术期刊数据库(万方数据)、中文科技期刊数据库(VIP)、中国生物医学文献数据库(CBM)、PubMed、Cochrane Library、Embase建库至2022年7月29日藤黄健骨片单独服用或联合常规疗法治疗膝骨关节炎随机对照试验(RCT).采用Cochrane系统评价员手册5.1.0进行文献质量评价,采用RevMan5.4进行Meta分析.结果 共纳入9项RCT,涉及1 029例患者.Meta分析结果显示:试验组总有效率[OR=4.26,95%CI(2.59,7.02),P<0.000 01]、VAS评分[MD=-1.32,95%CI(-2.31,-0.33),P<0.01]、WOMAC评分[MD=-12.98,95%CI(-24.65,-1.31),P<0.05]均优于对照组.单独服用藤黄健骨片试验组不良反应发生率低于对照组[OR=0.19,95%CI(0.05,0.69),P<0.05].结论 采用藤黄健骨片单用或者联合常规疗法治疗膝骨关节炎疗效确切,安全性好.但纳入研究质量偏低,尚需开展更多大样本、高质量的RCT验证.

Objective:To summarize the medication rules of Chinese patent medicines in the treatment of type 2 diabetes and analyze the distribution rules of the targets of the medicines for lowering blood glucose via TCM inheritance assistance system（V2.5）,hence providing guidance for the development and clinical application of new drugs.Methods:The Chinese patent medicines for treating type 2 diabetes were collected from the Pharnexcloud, and the medication rules were analyzed via the data mining method in the TCM inheritance assistance platform.The relevant articles were retrieved from China National Knowledge Infrastructure（CNKI） and China Science Periodical Database（CSPD） for revealing the blood glucose-lowering mechanisms and targets of high-frequency Chinese medicines.Results:The main syndromes treated by the 138 retrieved prescriptions, as well as the frequency of use, core drug combinations, and new drug combinations of 220 Chinese medicines, were summarized via data analysis.The glucose-lowering targets of high-frequency Chinese medicines were summarized.The main syndromes of type 2 diabetes treated by Chinese patent medicines were qi-yin deficiency and yin deficiency with internal heat.The high-frequency Chinese medicines for the disease were mainly qi-tonifying, yin-tonifying, and heat-clearing ones.Sweet Chinese medicines（frequency of 80） and bitter（frequency of 69） Chinese medicines in the prescriptions had higher frequency.Cold Chinese medicines had the highest frequency（97） and hot ones had the lowest（2）.In addition, most of the Chinese medicines used had the tropism to the liver meridian（frequency of 94）.Arctii Fructus for dispersing wind and discharging heat, Celosiae Semen for clearing liver and draining fire, and Hirudo for activating blood and resolving stasis appeared in the new drug combinations obtained by the entropy-based hierarchical cluster analysis.The drug targets of the Chinese patent medicines were mainly molecules involved in inhibiting gluconeogenesis and promoting glycogen synthesis, promoting insulin secretion, and preventing islet cell apoptosis.Conclusion:The dominant syndromes of type 2 diabetes include qi-yin deficiency and yin deficiency with internal heat.Sweet, bitter, and cold Chinese medicines and those with tropism to the liver meridian are mainly used to treat the disease.The Chinese medicines most frequently used are qi-tonifying, yin-tonifying, and heat-clearing ones.In the clinical diagnosis and treatment, the Chinese medicines for dispersing wind and dissipating cold, clearing liver and reducing fire, and activating blood and resolving stasis can be appropriately used to enhance the efficacy.The drug targets are mainly molecules involved in the inhibition of gluconeogenesis, the promotion of glycogen synthesis and insulin secretion, and the prevention of islet cell apoptosis.

目的 观察黄芪石斛方对正常小鼠免疫功能的影响.方法 80 只昆明小鼠均分为A、B两批,共设置7 个试验,每批试验将40 只昆明小鼠随机分为空白对照组和黄芪石斛方低(1.833 g/kg)、中(3.667 g/kg)、高(5.5 g/kg)剂量组,每组10 只,每天灌胃给药1 次,持续30 天.检测黄芪石斛方对小鼠免疫器官指数、迟发型变态反应(delayed type hypersensitivity,DTH)、抗体生成细胞数、脾淋巴细胞转化能力、血清溶血素水平(serum hemolysin level,HC50)及自然杀伤细胞(natural killer cell,NK细胞)活性等指标的影响.并采用比色法检测血清中免疫球蛋白IgG、IgM、IgA含量,免疫比浊法检测血清中补体C3、C4 含量.结果 与空白对照组相比,黄芪石斛方对胸腺指数、脾脏指数均没有影响,各剂量组攻击前后足跖厚度差值、溶血空斑数、HC50、脾淋巴细胞转化值与NK细胞活性水平显著升高(P<0.05,P<0.01),血清中 IgG、IgM、IgA、补体 C3、补体 C4 含量显著升高(P<0.05,P<0.01).结论 黄芪石斛方可通过健脾补肾、益气养阴增强机体免疫功能,适用于中医脾肾不足、气阴两虚证候的亚健康人群.

目的 研究黄芪桑叶玉竹颗粒对气阴两虚型高血糖大鼠肾脏氧化应激及TGFβ1/P-Smad3/P-Smad7信号通路的影响.方法 雄性SD大鼠48只,根据基础血糖水平分为空白组、模型组、十味消渴胶囊阳性药组、黄芪桑叶玉竹颗粒低、中、高剂量组.采用甲状腺素皮下注射、连续高脂饲料喂养合并链脲佐菌素注射复合因素造模.空白组大鼠不予给药,模型组大鼠给予0.9%氯化钠溶液,十味消渴胶囊阳性药组灌胃剂量为1.32 g/kg、黄芪桑叶玉竹颗粒低、中、高剂量组灌胃剂量分别为1.25、2.5、7.5 g/kg,连续给药30 d.检测大鼠空腹血糖(FBG)、血清糖化血红蛋白(GHbA1c)、白蛋白(ALB)、总蛋白(TP)、血尿素氮(BUN)、肌酐(Scr)、尿酸(UA)水平,肾脏活性氧(ROS)、过氧化氢酶(CAT)含量,HE染色观察胰腺组织病理变化,Western Blot法检测肾脏组织转化生长因子β1(TGF-β1)、P-Smad3、P-Smad7表达水平.结果 与空白组相比,模型组大鼠FBG、GHbA1c、ALB、TP、UA、BUN、Scr、ROS、TGF-β1、P-Smad3显著升高(P＜0.05),CAT、P-Smad7显著降低(P＜0.05).与模型组相比,黄芪桑叶玉竹颗粒低、中、高剂量组大鼠FBG、GHbA1c、ALB、BUN、Scr、ROS、TGF-β1、P-Smad3显著降低(P＜0.05),CAT、P-Smad7显著升高(P＜0.05),受损胰腺组织改善.黄芪桑叶玉竹颗粒低、中剂量组大鼠TP显著降低(P＜0.05),黄芪桑叶玉竹颗粒低剂量组大鼠UA显著降低(P＜0.05).结论 黄芪桑叶玉竹颗粒可改善高血糖诱导的肾脏氧化应激反应,抑制肾脏纤维化,延缓肾功能损害,其作用机制可能与调节TGF-β1/P-Smad3/P-Smad7通路有关.

目的 研究桑芪益气养阴方对胰岛素抵抗大鼠肝脏组织乙酰辅酶 A 羧化酶 1(Acetyl-coa carboxylase 1,ACC1)/脂肪酸合成酶(fatty acid synthase,FASN)/硬脂酰-辅酶A去饱和酶1(stearoyl-CoA desaturase 1,SCD1)通路及葡萄糖转运蛋白 2(glucose transporter2,GLUT2)的影响.方法 雄性SD大鼠48 只,根据基础血糖水平分为空白组、模型组、阳性药组、桑芪益气养阴方低、中、高剂量组.采用甲状腺素皮下注射、连续高脂饲料喂养合并链脲佐菌素注射复合因素造模.空白组大鼠不予给药,模型组大鼠给予给予 0.9%氯化钠溶液,阳性药组十味消渴胶囊灌胃剂量为1.32 g/kg、桑芪益气养阴方低、中、高剂量组灌胃剂量分别为1.25、2.5、7.5 g/kg.连续给药 30 天,比色法检测大鼠外周血谷丙转氨酶(Alanine aminotransferase,ALT)、谷草转氨酶(Aspartate aminotransferase,AST)和肝脏肝糖原、游离脂肪酸(free fat acid,FFA)、丙二醛(malondi-aldehyde,MDA)、超氧化物歧化酶(Superoxide dismutase,SOD)、谷胱甘肽过氧化物酶(Glutathione peroxidase,GSH-Px)含量,使用 RT-PCR及 Western blot分别检测大鼠 ACC1、FASN、SCD1、GLUT2的mRNA和蛋白表达.结果 与空白组相比,模型组大鼠 ALT、AST、MDA显著升高,SOD、肝糖原、GSH-PX显著降低(P<0.05,P<0.01),ACC1、FASN、SCD1 的 mRNA和蛋白表达水平显著升高,GLUT2 的mRNA和蛋白表达水平显著降低(P<0.01);与模型组比较,各干预组大鼠 ALT、AST、MDA显著降低,SOD、肝糖原、GSH-PX显著升高(P<0.05,P<0.01),桑芪益气养阴方中、高剂量组FFA含量显著降低(P<0.05,P<0.01),桑芪益气养阴方中、高剂量组ACC1、FASN、SCD1的mRNA和蛋白表达水平显著降低(P<0.01),GLUT2 的 mRNA 和蛋白表达水平显著升高(P<0.01).结论 桑芪益气养阴方可调节大鼠肝脏糖脂代谢紊乱,缓解氧化应激,预防肝损伤,其机制可能与抑制ACC1/FASN/SCD1 和上调GLUT2 基因和蛋白表达相关.

目的 探讨脂质代谢过程中沙苑子苷A对脂肪变性L02细胞肝细胞核因子4α(HNF4α)调控甘油三酯(TG)转运通路的影响.方法 体外培养L02细胞,以油酸钠:棕榈酸钠=2:1的比例配制1 mmol/L的游离脂肪酸(FFA),干预L02细胞24 h后建立细胞脂肪变性模型.将L02细胞分为空白组、模型组、沙苑子苷A低浓度组(25μmol/L)、沙苑子苷A中浓度组(50μmol/L)和沙苑子苷A高浓度组(100μmol/L).细胞贴壁培养24 h后,空白组给予含有10％胎牛血清(FBS)的高糖DMEM培养基(即完全培养基)培养48 h;模型组给予完全培养基培养24 h后,再使用含有1 mmol/L FFA的完全培养基培养24 h;沙苑子苷A各浓度组给予相应浓度的沙苑子苷A预处理24 h后,再使用含有1 mmol/L FFA和不同浓度沙苑子苷A的完全培养基共同培养L02细胞24 h.采用微板法检测各组TG、总胆固醇(TC)、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)含量,酶联免疫吸附(ELISA)法检测各组瘦素(LEP)、脂联素(ADPN)、抵抗素(Retn)、白细胞介素-2(IL-2)、白细胞介素-10(IL-10)、载脂蛋白B100(ApoB100)含量,Western blotting法检测各组HNF4α、核因子κB(NF-κB)/p65蛋白的表达.结果 与模型组相比,沙苑子苷A低浓度组TC、Retn含量降低(P<0.05),IL-10含量升高(P<0.05);沙苑子苷A中浓度组TC、ALT、Retn含量降低(P<0.05),ADPN、IL-10含量升高(P<0.05);沙苑子苷A高浓度组TG、TC、ALT、AST、Retn、ApoB100含量降低(P<0.05),ADPN、IL-10含量升高(P<0.05);沙苑子苷A低、中、高浓度组LEP、IL-2含量降低,但差异无统计学意义(P>0.05).与模型组相比,沙苑子苷A高浓度组HNF4α蛋白表达上调(P<0.05),NF-κB/p65蛋白表达下调(P<0.05).结论 沙苑子苷A对TG转运通路的影响可能是通过刺激HNF4α转录调控ApoB100的装配和分泌,激活脂肪因子促进脂肪酸氧化,以此加速脂质转运和抑制脂质生成,从而发挥沙苑子维持脂质代谢稳态和减轻肝细胞炎症损伤的作用.

目的 观察参竹降糖方对糖尿病气阴两虚证大鼠模型血糖、血脂及神经内分泌免疫功能的影响.方法 将60只SD大鼠随机分为空白组、复合模型组、十味消渴组及参竹降糖低、中、高剂量组共6组,每组10只.采用高热量饲料喂养3周,强迫大鼠进行负重力竭游泳2周,模拟劳倦伤脾所致气虚,甲状腺素注射1周造成甲亢型阴虚,同时一次性腹腔注射2％链脲佐菌素溶液(30 mg/kg),造模周期维持33天,建立多因素复合的病证结合的气阴两虚型高血糖动物模型.观察各组大鼠证候表征的变化,包括大鼠毛色、饮食量、饮水量、排尿量、排便量.测量大鼠体质量、肛温、空腹血糖值(fasting blood glucos,FBG)、血清胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、低密度脂蛋白(low-density lipoprotein,LDL)、高密度脂蛋白(high-density lipoprotein,HDL)含量.Elisa试剂盒测定空腹胰岛素(fasting insulin,FINS)、三碘甲状腺原氨酸(triiodothyronine,T3)、甲状腺素(thyroxine,T4)、环磷酸腺苷(cyclic adenosine monophosphate,cAMP)和环磷酸鸟苷(cyclic guanosinc monophosphate,cGMP)含量.称重胸腺和脾脏并据公式计算胸腺、脾脏指数.根据公式计算胰岛素抵抗指数(homeostasismodel assessment-insulin resistance,HOMA-IR)、胰岛β细胞功能指数(homeosta-sismodel assessment-β,HOMA-β)、胰岛素敏感指数(insulin sensitivity index,ISI)和cAMP/cGMP,记录负重游泳力竭运动时间.结果(1)与空白组相比,模型组大鼠饮水量、进食量、排尿量、排便量、肛温、FBG、HOMA-IR、TC、TG、LDL、T3、T4、cAMP、cAMP/cGMP显著升高,体质量、HOMA-β、ISI、FINS、HDL、cGMP、胸腺指数、脾脏指数、力竭游泳时间显著降低,差异均有统计学意义(P<0.01,P<0.05).(2)与模型组相比,十味消渴胶囊组和参竹降糖各剂量组均能减少气阴两虚型高血糖大鼠的饮食量、饮水量、排尿量,降低肛温及FBG、HOMA-IR、TC、TG、LDL、T3、T4、cAMP、cAMP/cGMP水平,升高体质量、FINS、HOMA-β、ISI、HDL、cGMP、胸腺指数、脾脏指数、力竭游泳时间,差异均有统计学意义(P<0.01,P<0.05).结论 参竹降糖方能够调节糖脂代谢紊乱,缓解胰岛素抵抗,同时能够改善气阴两虚证候表征和相关指标.

目的:全面了解鸿茅药酒服用人群的基本特征、服用后的有效性和安全性,为安全规范指导鸿茅药酒的临床应用提供科学的依据.方法:采用横断面研究抽样调查设计,从鸿茅药酒公司信息数据库中随机抽取900人进行电话访问.应用EpiData3.1软件建立数据库和数据录入控制程序;对所提取的资料进行双份录入,逻辑检查及手工核查后,锁定数据库,导出到SPSS统计学软件,对性别、文化程度、职业、地区、服用鸿茅药酒的频次和时间、服用鸿茅药酒的自我判断疗效、安全性评价等进行汇总、分析.结果:本研究共调查900人,应答858人,应答率95.3％.排除鸿茅药酒服用量超过药品说明书的调查对象187人,有效问卷671份,有效率78.2％.鸿茅药酒的服用者以老年人居多,平均年龄64岁,多为男性,占58.9％,文化程度普遍较低,多为小学、初中文化水平,主要以从事农林牧渔的劳动者居多,其次是离退休人员,事业单位人员;分布地区以二、三线城市最多,其次是城镇、农村,而一线城市最少.70.4％ 的研究对象报告自己很少或不经常饮酒,4.3％ 的研究对象已戒酒.治疗疾病以风湿性关节炎、腰椎间盘突出、骨性关节炎为主,分别占57.2％、26.8％、23.0％,均属于中医"痹症".研究对象服用鸿茅药酒治疗各种疾病的自我判断疗效中位数均≥85分.绝大部分的研究对象认为服用鸿茅药酒是安全的,6.4％ 认为相对安全,没有研究对象认为服用鸿茅药酒不安全的.绝大部分的研究对象服用鸿茅药酒后没有不适症状,偶发皮疹瘙痒.结论:服用鸿茅药酒的研究对象有较为清楚的认知,以治疗疾病为目的,主要用于"风湿痹痛、筋骨疼痛";不良反应发生率低,较为安全,服用者自我判断疗效较好.

目的:研究沙苑子苷A对脂肪变L02细胞的降脂效果和作用机制.方法:采用游离脂肪酸(FFA)诱导肝L02细胞脂肪变性,分为对照组、模型组、沙苑子苷A低剂量、中剂量、高剂量组(1μmol/L、10μmol/L、50μmol/L),流式细胞仪检测细胞凋亡和脂肪堆积,按照试剂盒检测三酰甘油(TG)、胆固醇(TC)、丙二醛(MDA)、超氧化物歧化酶(SOD)的水平,实时荧光定量PCR(qPCR)检测三酰甘油水解酶(ATGL)、过氧化物酶体增殖物激活受体α(PPAR-α)、过氧化物酶体增殖物激活受体γ(PPARγ)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)mRNA的表达,蛋白质印迹法(Western Blotting)检测ATGL、PPAR-α、PPARγ、TNF-α、IL-6蛋白的表达.结果:沙苑子苷A能显著减少脂肪堆积,降低TG、TC、MDA含量,增加SOD活性,降低细胞凋亡率,减轻脂毒性造成的肝细胞损伤,与模型组比较差异有统计学意义(P<0.05,P<0.01);沙苑子苷A能升高ATGL、PPAR-α、PPARγmRNA和蛋白的表达,同时降低TNF-α、IL-6 mRNA和蛋白的表达,与模型组比较差异有统计学意义(P<0.01).结论:沙苑子苷A可能通过上调PPARα、PPARγ的表达,使ATGL表达增加,促进肝脏TG的水解,减少肝脏脂肪的沉积,缓解氧化应激,抑制TNF-α和IL-6的分泌,减轻炎症反应,从而恢复肝细胞的正常功能.

目的:通过建立"气阴两虚型胰岛素抵抗糖脂代谢紊乱动物模型",探索符合中医辨证特点且适用于保健食品功能评价的证候模型,以期为研发辅助降血糖辨证保健产品提供方法学参考.方法:选取45只雄性SD大鼠,根据基础血糖值分为空白组、模型组、阳性组[十味消渴胶囊1.32 g(kg·d),相当于人7.92 g/d].采用力竭游泳、甲状腺素(T4)皮下注射、连续高脂饲料合并链脲佐菌素(STZ)注射复合因素造模.实验第一天开始给药,连续灌胃33 d.结果:模型组大鼠出现懒动无力、毛发枯黄、情绪躁动等气阴两虚的证候表证;饮水量、进食量、排尿量显著增加、体质量显著降低;空腹血糖(FBG)、血糖曲线下面积(AUC)、胰岛素抵抗指数(HOMA-IR)显著升高,HOMA-β、胰岛素敏感指数(Insulin Sensitivity In-dex,ISI)显著降低,血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL)显著升高,高密度脂蛋白(HDL)显著降低,三碘甲状腺原氨酸(T3)、T4显著升高,环磷酸腺苷(cAMP)显著升高、环磷酸鸟苷(cGMP)显著降低、cAMP/cGMP显著升高,力竭游泳时间显著降低,脾脏指数、胸腺指数显著降低.十味消渴胶囊能显著增加模型大鼠体质量,降低空腹血糖,改善糖耐量,延长力竭游泳时间,降低T3、T4的水平,降低cAMP/cGMP比值,改善胰岛素抵抗.结论:采用力竭游泳、T4注射、高脂喂养结合STZ注射复合因素建立"气阴两虚型胰岛素抵抗糖脂代谢紊乱动物模型",造模设计在思路和方法上符合中医基本理论,可以用于益气养阴类中药保健食品降血糖功能的评价.