基于1H-NMR代谢组学探讨柴胡-白芍药对“疏肝解郁”的代谢调控途径

目的:利用核磁共振氢谱(~1H-NMR)代谢组学技术,分析慢性不可预知温和应激(CUMS)抑郁模型大鼠肝脏内源性代谢物的变化,观察柴胡-白芍药对对此的调节作用,分析柴胡-白芍药对疏肝解郁相关的代谢通路。方法:将SD大鼠随机分为对照组、CUMS模型组、阳性药文拉法辛组和柴胡-白芍药对高(CBH)、低(CBL)剂量组。通过抑郁症的传统药效学指标(大鼠体质量、旷场测试、糖水偏爱实验及强迫游泳实验)评价柴胡-白芍药对的药效。采用~1H-NMR代谢组学技术结合多元统计分析方法,分析CBH、CBL组大鼠肝脏代谢物的变化,鉴定可靠的生物标志物并进行代谢通路分析。结果:与对照组比较,模型组大鼠药效学指标均有显著变化,即体质量,旷场穿越格数、直立次数,糖水偏爱率降低(P0.001)及强迫游泳不动时间增加(P0.001);柴胡-白芍药对能显著改善模型组大鼠的抑郁样行为。~1H-NMR代谢组学分析显示,CUMS会使大鼠体内24个代谢物和10条代谢通路紊乱,柴胡-白芍药对能显著回调其中的21个差异代谢物,对其中7条代谢通路产生影响。结论:柴胡-白芍药对能够改善CUMS抑郁模型大鼠的抑郁样症状,可能是通过调节大鼠体内氨基酸代谢和能量代谢等通路实现的。     

左归降糖解郁方对糖尿病并发抑郁症大鼠海马胰岛素抵抗的影响

目的研究左归降糖解郁方对糖尿病并发抑郁症大鼠海马胰岛素抵抗的调节作用。方法建立糖尿病并发抑郁症大鼠模型,并随机分为4组,模型组,阳性药组(二甲双胍0.18 g/kg+氟西汀1.8 mg/kg),左归降糖解郁方高、低剂量组(20.52、10.26g/kg),另设健康大鼠为对照组。各组大鼠ig给药28 d后,采用血糖仪及ELISA法检测空腹血糖及外周胰岛素抵抗程度。采用旷野实验和强迫游泳实验检测大鼠抑郁样行为。采用免疫荧光法和Western blotting法检测大鼠海马胰岛素受体磷酸化蛋白(p-IR)、磷酸化的胰岛素受体底物-1(p-IRS-1)的表达,采用Westernblotting法检测海马磷酸化的磷脂酰肌醇3-激酶(p-PI3K)、磷酸化蛋白激酶B(p-Akt)蛋白的表达。结果与对照组比较,模型组大鼠血糖显著升高并伴随明显的外周胰岛素抵抗,其在旷野实验中的活动次数显著降低、在强迫游泳实验中的不动时间显著延长;蛋白检测结果表明大鼠脑内p-IR、p-IRS-1、p-PI3K、p-Akt表达水平均显著降低。与模型组比较,左归降糖解郁方高剂量组大鼠血糖水平显著降低,外周胰岛素抵抗水平减轻,其在旷野实验中的活动次数显著增加、在强迫游泳实验中的不动时间显著缩短,而海马内p-IR、p-IRS-1、p-PI3K、p-Akt表达显著升高。结论左归降糖解郁方可有效调节糖尿病并发抑郁症大鼠海马胰岛素信号通路,从而改善动物脑内的胰岛素抵抗状态。     

黄芪葛根配伍对糖尿病大鼠脂肪组织AMPK信号通路的影响

目的探讨黄芪与葛根配伍对糖尿病脂肪中腺苷酸活化蛋白激酶(AMPK)信号通路的作用,明确其调控血糖血脂机制。方法将86只SPF级SD雄性大鼠按照随机数字表分成6组:正常组、模型组、金芪降糖组、黄芪组、葛根组、黄芪葛根配伍组,正常组11只,其余各组15只大鼠。一次性腹腔注射2%STZ(46 mg/kg)造模,同日各组分别予金芪降糖混悬液1.47 g/kg、黄芪2.7 g/kg、葛根1.35 g/kg、黄芪葛根汤4.05 g/kg灌胃,给药30 d。酶联免疫吸附测定(ELISA)检测脂联素(APN)、葡萄糖转运体4(GLUT-4),实时荧光定量聚合酶链式反应法(Real-time PCR)检测脂联素受体1(AdipoR1)、脂联素受体2(AdipoR2)、AMPK、GLUT-4、过氧化物酶增殖体激活受体-α(PPARα)、PPARγmRNA。结果与正常组比较,模型组大鼠APN、GLUT-4水平降低,AdipoR1、AdipoR2、AMPK、GLUT-4、PPARα、PPARγmRNA表达减少(P<0.05)。黄芪、黄芪与葛根配伍能升高模型大鼠APN、GLUT-4水平(P<0.05);黄芪、葛根及两药配伍能增加AdipoR1(葛根、黄芪与葛根配伍除外)、AdipoR2、AMPK、PPARα(葛根除外)、PPARγ、GLUT-4mRNA表达(P<0.05),黄芪促进AdipoR2、PPARαmRNA表达的作用优于两药合用,黄芪与葛根配伍调节AMPK、PPARγ、GLUT-4mRNA表达的作用优于单一用药(P<0.05)。结论黄芪、葛根及其配伍调节血糖血脂与调控糖尿病大鼠脂肪组织AMPK信号通路有关,黄芪葛根配伍调控血糖、血脂作用优于单一用药,可能与其促进APN、AMPK、GLUT-4、PPARγmRNA表达有关。     

Ginsenoside Rc,an active component of Panax ginseng, stimulates glucose uptake in C2C12 myotubes through an AMPK-dependent mechanism

Ethnopharmacological relevance

Panax ginseng and its major component, ginsenosides, are widely used for the prevention of various disorders in oriental medicine.

Aim of the study

To evaluate the effect of ginsenoside Rc (Rc), one of the active constituents in Panax ginseng, on glucose uptake in C2C12 myotubes.

Results

Treatment of the C2C12 myotubes with Rc significantly increased glucose uptake. To determine the mechanism of Rc-induced glucose uptake, either insulin-dependent signaling or insulin-independent signaling pathway activities were measured using western blot analysis. We showed that Rc significantly activated an insulin-independent AMPK signaling pathway. However, Rc had no effect on the components of the insulin-dependent signaling pathway, such as receptor substrates (IRS)-1 and protein kinase B or Akt (PKB/Akt). Moreover, we found that treatment with an AMPK inhibitor abolished both glucose uptake and p38 MAPK phosphorylation. This result implies that AMPK activity is critical for the Rc-induced glucose uptake and that AMPK is situated upstream of p38 MAPK. In addition, we also showed that the activation of AMPK and p38 induced by ginsenoside Rc is mediated by reactive oxygen species (ROS) production, suggesting that upstream regulators of AMPK- and p38 MAPK-mediated glucose uptake.

Conclusion

Ginsenoside Rc significantly enhances glucose uptake by inducing ROS generation, which leads to AMPK and p38 MAPK activation. Consequently, ginsenoside Rc can be used as a potent natural anti-diabetic agent.     

女贞苷通过激活AMPK促进脂联素的组装

目的:检测女贞苷对AMPK[一磷酸腺苷激活的蛋白激酶,adenosine 5'-monophosphate(AMP)-activated protein kinase]的激活作用,探究其激活机制以及对脂联素高聚体组装的影响。方法:用一定浓度的女贞苷处理人胚肾细胞衍生株293T细胞,通过蛋白质印迹法检测AMPK磷酸化水平,通过HPLC检测细胞中AMP和ATP(三磷酸腺苷,Adenosine 5'-triphosphate)的含量。用女贞苷处理3T3-L1脂肪细胞,检测其对脂联素组装的影响。结果:女贞苷能够使293T细胞中AMPK磷酸化水平升高。经过女贞苷处理后,细胞中AMP与ATP浓度的比值(AMP/ATP比值)升高。当AMPK表达被沉默后,女贞苷对脂联素高聚体组装的促进作用被解除。结论:女贞苷能够通过提高细胞中AMP/ATP比值来激活AMPK,进而促进脂联素高聚体的组装。     

补肾降压方对糖脂代谢异常的自发性高血压大鼠脂联素通路的影响

目的:观察补肾降压方对糖脂代谢异常的自发性高血压大鼠(spontaneous hypertensive rat,SHR)的影响及其对脂联素通路的影响。方法:选用清洁级5周龄SHR 40只,随机分为正常组和高糖高脂组。8周造模后将高糖高脂组大鼠分为模型组(空白SHR伴糖脂代谢异常),卡托组(卡托普利)和补肾组(补肾降压方)。连续用药8周。检测血压,血糖,血脂,胰岛素。心肌组织切片行HE染色观察心脏组织病理形态学改变。Elisa法检测血清中ADP的含量。实时定量PCR检测心脏组织和肝脏组织PPARα的表达。Western blot检测心脏AdipoR1、AdipoR2的蛋白表达。结果:与SHR组比较,模型组血压明显升高,卡托组和补肾组有明显降低;与模型组相比,卡托组和补肾组都有明显降低;与卡托组比较,补肾组有升高的趋势。与SHR组相比,模型组,卡托组,补肾组胰岛素均有降低;与模型组相比,卡托组和补肾组皆有降低的趋势。与SHR组相比,模型组,卡托组,补肾组脂联素均有降低趋势;与模型组相比,卡托组与补肾组有升高趋势。心脏PPAR-αmRNA表达中,模型组,卡托组和补肾组较SHR组有所升高;与模型组比较,卡托组和补肾组皆有所降低。在AdipoR1蛋白表达的比较中,模型组,卡托组,补肾组较SHR组均有升高;与模型组相比,卡托组与补肾组有降低趋势。在AdipoR2蛋白表达的比较中,模型组,卡托组,补肾组较SHR组均有升高,其中模型组和卡托组有显著性差异(P0.05);与模型组和卡托组相比,补肾组有降低趋势。结论:补肾降压方对SHR伴糖脂代谢异常具有调节作用,对心脏具有一定保护作用,其作用很有可能通过调节脂联素通路实现。     

Electroacupuncture Promotes Neural Proliferation in Hippocampus of Perimenopausal Depression Rats via Wnt/β-Catenin Signaling Pathway

Background and ObjectivePerimenopausal depression is caused by the impaired function of the ovarium before menopause and with a series of symptoms. Electroacupuncture (EA) therapy has been demonstrated to improve clinically depression. However, the mechanism underlying its therapeutic activity remains unknown. This study aimed to investigat the effects of EA treatment on the hippocampal neural proliferation through Wnt signaling pathway.MethodsChronic unpredictable mild stress (CUMS) combined with bilateral ovariectomy (OVX) were used to establish a rat model of perimenopausal depression. The open field test (OFT) and sucrose preference test (SPT) were used to assess depression-like behaviors in rats. ELISAs were used to measure estrogen (E2), luteinizing hormone (LH) and gonadotropin-releasing hormone (GnRH) levels in the serum. RT-PCR and Western blot assay were utilized for measuring the mRNA expressions and protein expressions of GSK-3β/β-catenin.ResultsFour-week EA treatment at three points including “Shenshu” (BL23), “Baihui” (GV20) and “Sanyinjiao” (SP6) simultaneously ameliorated depression-like behaviors in rats with CUMS and OVX, whereas rescued the decreased serum level of E2 and prevented the increased serum levels of GnRH and LH. EA treatment ameliorated CUMS and OVX-induced alterations of glycogen synthase kinase-3β (GSK-3β) and β-catenin mRNA levels, β-catenin and phosphorylated β-catenin (p-β-catenin) protein levels.ConclusionsThe results showed that EA treatment promoted hippocampal neural proliferation in perimenopausal depression rats via activating the Wnt/β-catenin signaling pathway, indicating that EA may represent an efficacious therapy for perimenopausal depression.     

Hypoglycaemic activity and molecular mechanisms of Caesalpinia ferrea Martius bark extract on streptozotocin-induced diabetes in Wistar rats

Ethnopharmacological relevance

The tea from the stem bark of Caesalpinia ferrea Martius (Leguminosae) has been popularly used in the treatment of diabetes in Brazil.

Aim of the study

To investigate the hypoglycaemic properties and to elucidate the mechanisms by which the aqueous extract of the stem bark of Caesalpinia ferrea reduces blood glucose levels in streptozotocin-induced diabetic rats via the enzymatic pathways of protein kinase B (PKB/Akt), AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC).

Materials and methods

The aqueous extract of the stem bark of Caesalpinia ferrea (300 and 450 mg/kg/day), vehicle and metformin (500 mg/kg/day) were administered orally to STZ-diabetic rats (n = 7/group) for 4 weeks. Changes in body weight, food and water intake, fasting glucose levels and oral glucose tolerance were evaluated. Phosphorylation (P) and the expression of Akt, AMPK and ACC in the liver and skeletal muscle were determined using Western blot.

Results

The aqueous extract of the stem bark of Caesalpinia ferrea reduced blood glucose levels and improved the metabolic state of the animals. P-Akt was increased in the liver and skeletal muscle of the treated animals, P-AMPK was reduced only in the skeletal muscle of these animals and P-ACC was reduced in both when compared with untreated rats.

Conclusion

The results indicate that the aqueous extract of the stem bark of Caesalpinia ferrea has hypoglycaemic properties and possibly acts to regulate glucose uptake in liver and muscles by way of Akt activation, restoring the intracellular energy balance confirmed by inhibition of AMPK activation.     

补阳还五汤对慢性不可预知性温和应激抑郁模型小鼠行为及脑海马CA3区病理形态学影响

目的:探讨补阳还五汤神经保护作用及抗抑郁机制。方法:清洁级昆明小鼠随机分为正常组,模型组,氟西汀组(3.0 mg·kg-1,ig),补阳还五汤低、中、高剂量组(9.0,18.0,27.0 g·kg-1,ig),每组10只。各给药组于每日应激前1 h ig给药,其余各组给予等体积生理盐水,共计21 d。采用慢性不可预知性温和应激法(CUMS)建立小鼠抑郁症模型,采用旷场实验(OFT),悬尾实验(TST)及体重测试(BWM)观察动物抑郁样行为;采用尼氏体染色检测海马CA3区神经元形态学变化;采用透射电镜观察海马区超微结构变化;采用TUNEL法检测海马CA3区神经元凋亡情况。结果:与正常组比较,模型组小鼠出现抑郁样行为,表现为体重减少,OFT水平及垂直运动得分减少及TST不动时间延长(P0.05,P0.01);尼氏染色及透射电镜显示海马CA3区神经元损伤及早期凋亡变化;TUNEL法显示海马CA3区神经元凋亡数量增加(P0.01)。与模型组比较,氟西汀组及补阳还五汤各剂量组小鼠抑郁样行为均有改善,表现为体重增加,OFT水平及垂直运动得分增加,TST不动时间减少(P0.05,P0.01);尼氏染色及透射电镜显示海马CA3区神经元细胞损伤减轻;TUNEL法显示海马CA3区神经元凋亡数量减少,差异有统计学意义(P0.01)。结论:补阳还五汤可能通过减轻海马CA3区神经元损伤及抑制神经元凋亡而改善小鼠抑郁样行为,具有神经保护及抗抑郁症作用。     

Selected compounds derived from Moutan Cortex stimulated glucose uptake and glycogen synthesis via AMPK activation in human HepG2 cells

Aim of the study

To evaluate the effect of selected compounds derived from Moutan Cortex on glucose uptake and glycogen synthesis associated with AMPK activation in insulin-resistant human HepG2 cell.

Materials and methods

The effect of isolated compounds (1-16) on glucose uptake and glycogen synthesis was performed using HepG2 cells. The western blot was used to determine the expression of AMPK and its downstream substrates, ACC, p-ACC, and p-GSK-3β.

Results

The effects of the 16 compounds from Moutan Cortex on glucose metabolism in HepG2 cells under high glucose conditions were evaluated. Compounds 2, 3, and 6 displayed highly potent effects on the stimulation of glucose uptake and glycogen synthesis in human HepG2 cells under high glucose conditions. Compounds 2, 3, and 6 phosphorylate AMPK (AMP-activated protein kinase), and resulted in increased phosphorylation of GSK-3β and suppression of lipogenic expression (ACC and FAS) in a dose-dependent manner. Compounds 2, 3, and 6 also demonstrated interesting, strong eNOS phosphorylation in human umbilical vein endothelial cells (HUVECs). Compounds 1, 4, 5-12, and 14 displayed considerable effects on hepatic glucose production, AMPK activation, and phosphorylation of GSK-3β in HepG2 cells under high glucose conditions.

Conclusions

These effects may indicate that the activation of AMPK by the active compounds from Moutan Cortex has considerable potential for reversing the metabolic abnormalities associated with type-2 diabetes.     

逍遥散及其功效拆方对CUMS抑郁模型大鼠行为学的影响

目的: 探讨逍遥散及其功效拆方水煎液对慢性不可预见性轻度应激(CUMS)抑郁模型大鼠行为活动和学习记忆能力的影响,初步揭示方中体现不同治法的功效药组的作用特点。 方法: 采用慢性不可预知温和应激+孤养方法制备CUMS大鼠抑郁模型,观察逍遥散(30 g·kg^-1)、疏肝药(即柴胡+薄荷,5.25 g·kg^-1)、养血药(即当归+白芍,9 g·kg^-1)、疏肝药+健脾药(即柴胡+薄荷+白术+茯苓+生姜+炙甘草,21 g·kg^-1)、养血药+健脾药(即当归+白芍+白术+茯苓+生姜+炙甘草,24.75 g·kg^-1)、阿米替林(10 mg·kg^-1)连续ig给药4周,观察对模型大鼠体重、糖水偏爱程度、自主活动和Morris水迷宫指标的影响,并设空白和模型对照组。 结果: 与模型组比较,逍遥散组、疏肝药组、养血药组、疏肝药+健脾药组、养血药+健脾药组均能显著提高模型大鼠的体重增长度、糖水偏爱百分比及自主活动量,缩短Morris水迷宫测试中定位航行的潜伏期,增加空间搜索时目标象限运动百分比与有效区域进入次数。各药物组之间比较,逍遥散组、疏肝药组、疏肝药+健脾药组的改善作用优于养血药组和养血药+健脾药组,其中疏肝药组在连续给药2周时,其对模型动物行为学的改善作用甚至优于逍遥散全方与疏肝药+健脾药组。 结论: 逍遥散对CUMS抑郁模型大鼠表现出良好的抗抑郁作用。在其功效拆方中,柴胡+薄荷药组所代表的疏肝治法是体现逍遥散抗抑郁效应的主要治法,当归+白芍药组所代表的养血治法则发挥重要的辅助作用。     

四逆散对抑郁模型大鼠HPA轴、海马BDNF及其受体TrKB的影响

目的：探讨四逆散的高、低剂量组对抑郁模型大鼠下丘脑-垂体-肾上腺轴（HPA轴）、海马脑源性神经营养因子（BDNF）及其受体型酪氨酸激酶B（TrKB）表达的影响。方法：SD雄性大鼠50只,随机分为正常对照组、模型组、盐酸文拉法辛组（12.5 mg·kg^-1）、四逆散高、低剂量组（10,5 g·kg^-1）。采用慢性轻度不可预见性刺激造模,同时ig给药21 d后分别取血、下丘脑和海马。采用放射免疫分析法检测大鼠血浆皮质醇（CORT）、促肾上腺皮质激素（ACTH）及下丘脑中促肾上腺皮质激素释放激素（CRH）的含量变化,采用免疫组化分析法检测海马BDNF及其TrKB阳性神经元面密度值的变化。结果：与正常组相比,模型组大鼠血浆中CORT,ACTH及下丘脑CRH的含量明显升高,海马中BDNF和TrKB的神经面密度值明显降低。与模型组相比,四逆散高、低剂量组可以显著降低抑郁症模型大鼠血浆CORT,ACTH、下丘脑CRH的含量;增加大鼠海马BDNF及其TrKB阳性神经元面密度值。结论：四逆散可明显改善抑郁模型大鼠的抑郁状态,其机制可能是通过HPA轴增加海马BDNF,TrKB的表达。     

Loganin regulates glycolipid metabolism by influencing intestinal microbiota and AMPK signaling in obese mice

ObjectiveWe aimed to observe the effects of loganin (Log) on serum glycolipid levels and probe the mechanisms focusing on intestinal flora and AMP-activated protein kinase (AMPK) signaling in obese mice.MethodsA high-fat diet was given for 12 consecutive weeks to generate the obesity model in institute of cancer research (ICR) mice. Body weight was measured weekly and fasting blood glucose (FBG) was determined every 2 weeks. Both the oral glucose tolerance test and the intraperitoneal insulin tolerance test were performed. The serum levels of total cholesterol (TC), triglyceride, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol (LDL-C), and free fatty acids (FFA) were measured. The expression of key proteins in the AMPK signaling pathway in skeletal muscle tissue was detected by immunoblotting, and gut microbiota were characterized using 16S rDNA sequencing.ResultsLog significantly decreased the body weight and the FBG in obese mice (P < .05), and it could restore FBG to normal levels. The total cholesterol, LDL-C, and FFA levels were significantly reduced by Log compared with the obese controls (TC: P = .0020; LDL-C: P = .0233; FFA: P = .0127), and the glucose tolerance of animals was significantly improved (P = .0477). The western blot results showed that Log could upregulate the protein expression of Adenosine 5‘-monophosphate (AMP)-activated protein kinase (AMPKα), Sirtuin 1 (SIRT1), and peroxisome proliferator-activated receptor-gamma coactivator -1alpha (PGC1α) in skeletal muscle tissue of obese mice. 16S rDNA sequencing indicated that Log reduced the diversity of the gut flora in feces and altered the floral composition of obese mice.ConclusionsLog was effective in reducing body weight and improving glucolipid metabolism in obese mice, probably through activating AMPK signaling and regulating intestinal microbial diversity.     

Effects of Fuhe decoction on behaviors and monoamine neurotransmitters in different brain regions of CUMS combined with social isolation depression model rats

ObjectiveTo investigate the effect of Fuhe decoction on the behavior and levels of monoamine neurotransmitters in different brain regions in a depression rat model induced by chronic unpredictable mild stimulation (CUMS) combined with social isolation.MethodsFifty male SD rats were randomly divided into a blank group, model group, fluoxetine group, Chaiqinwendan decoction group, and Fuhe decoction group. Chronic unpredictable mild stimulation combined with a social isolation method was used to replicate the depression rat model. After 42 days of administration, a tail suspension test and high-performance liquid electrochemical detection (HPLC-ECD) were used to detect the behavioral changes and changes in the content of monoamine neurotransmitters norepinephrine (NE), dopamine (DA), 5-hydroxytrytamine (5-HT), and metabolites in different brain regions of rats in each group before and after treatment.ResultsCompared with the model group, the epinephrine (E) content in the Fuhe decoction group was highly significantly increased (P < .01). Compared with the model group, the 5-HT content of the prefrontal cortex in rats in the Fuhe decoction group was highly significantly increased (P < .01). Furthermore, compared with the model group, the 5-HT content in the hippocampus of rats in the Fuhe decoction group was significantly increased (P < .05).ConclusionFuhe decoction can improve the depression-like behaviors of model rats, and its antidepressant effect may be related to the increase in 5-HT content in the prefrontal cortex and hippocampus of rats.     

A refined-JinQi-JiangTang tablet ameliorates prediabetes by reducing insulin resistance and improving beta cell function in mice

Ethnopharmacological relevance

Refined-JQ (JQ-R) is a mixture of refined extracts from three major herbal components of JinQi-JiangTang tablet: Coptis chinensis (Ranunculaceae), Astragalus membranaceus (Leguminosae), and Lonicera japonica (Caprifoliaceae). Our previous studies have indicated that JQ-R could decrease fasting blood glucose levels in diabetic mice and insulin resistance mice. Investigating the hypoglycemic effect of JQ-R on prediabetes has practical application value for preventing or delaying insulin resistance, impaired glucose tolerance and possibly the development of clinical diabetes.

Materials and methods

The anti-diabetic potential of JQ-R was investigated using a high fat-diet (HFD)-induced obesity mouse model. C57BL/6J mice (HFD-C57 mice) were fed with high-fat diet for 4 months. HFD-C57 mice were treated with either JQ-R (administered intragastrically once daily for 4 weeks) or metformin (as positive control), and the effects of JQ-R on body weight, blood lipids, glucose metabolism, insulin sensitivity, and beta cell function were monitored.

Results

The body weight, serum cholesterol, and the Homeostasis Model Assessment ratio (insulin resistance index) were significantly reduced in JQ-R or metformin-treated mice, and the glucose tolerance was enhanced and insulin response was improved simultaneously. Moreover, both JQ-R and metformin could activate liver glycogen syntheses even under a relatively high glucose loading. Although glyconeogenesis was inhibited in the metformin treated mice, it was not observed in JQ-R treated mice. Similar to metformin, JQ-R could also improve the glucose infusion rate (GIR) in hyperglycemic clamp test. JQ-R was also shown to increase the levels of phosphorylated AMPKα and phosphorylated acetyl CoA carboxylase (ACC), similar to metformin.

Conclusion

JQ-R could reduce HFD-induced insulin resistance by regulating glucose and lipid metabolism, increasing insulin sensitivity through activating the AMPK signaling pathway, and subsequently improving β cell function. Therefore, JQ-R may offer an alternative in treating disorders associated with insulin resistance, such as prediabetes and T2DM.