Objective: This study aimed to investigate the therapeutic effects of Xiaoyao San（XYS）, a herbal medicine formula, on exercise capacity and liver mitochondrial metabolomics in a rat model of depression induced by chronic unpredictable mild stress（CUMS）.Methods: A total of 24 male SD rats were randomly divided into four groups: control group（C）, CUMS control group（M）, Venlafaxine positive treatment group（V）, and XYS treatment group（X）. Depressive behaviour and exercise capacity of rats were assessed by body weight, sugar-water preference test, open field test, pole test, and rotarod test. The liver mitochondria metabolomics were analyzed by using liquid chromatography-mass spectrometry（LC-MS） method. TCMSP database and Gene Cards database were used to screen XYS for potential targets for depression, and GO and KEGG enrichment analyses were performed.Results: Compared with C group, rats in M group showed significantly lower body weight, sugar water preference rate, number of crossing and rearing in the open field test, climbing down time in the pole test,and retention time on the rotarod test（P ＜ 0.01）. The above behaviors and exercise capacity indices were significantly modulated in rats in V and X groups compared with M group（P ＜ 0.05, 0.01）. Compared with C group, a total of 18 different metabolites were changed in the liver mitochondria of rats in M group.Nine different metabolites and six metabolic pathways were regulated in the liver mitochondria of rats in X group compared with M group. The results of network pharmacology showed that 88 intersecting targets for depression and XYS were obtained, among which 15 key targets such as IL-1β, IL-6, and TNF were predicted to be the main differential targets for the treatment of depression. Additionally, a total of 1 553 GO signaling pathways and 181 KEGG signaling pathways were identified, and the main biological pathways were AGE-RAGE signaling pathway, HIF-1 signaling pathway, and calcium signaling pathway.Conclusion: XYS treatment could improve depressive symptoms, enhance exercise capacity, positively regulate the changes of mitochondrial metabolites and improve energy metabolism in the liver of depressed rats. These findings suggest that XYS exerts antidepressant effects through multi-target and multi-pathway.
目的 初步明确秋菊丸化学成分,研究秋菊丸对慢性高尿酸血症(HUA)模型大鼠尿酸(UA)升高及肾脏损伤的治疗作用及机制.方法 借助超高效液相色谱串联四极杆静电场轨道阱质谱(UPLC-Q-Exactive Orbitrap MS)技术,初步鉴定秋菊丸的化学成分.48只雄性SD大鼠随机分成对照组、模型组、苯溴马隆(5.45 mg·kg-1,阳性药)组和秋菊丸低、中、高剂量(1.31、2.62、5.24g·kg-1)组,除对照组外,通过ig腺嘌呤和乙胺丁醇制备大鼠慢性HUA模型,造模同时每天ig给药1次,连续28d.使用全自动生化仪测定大鼠血清UA、肌酐(CRE)、尿素氮(BUN)水平;HE及Masson染色观察肾脏组织病理学变化;实时荧光定量PCR(qRT-PCR)法检测肾脏组织中葡萄糖转运蛋白9(GLUT9)、有机阴离子转运体家族蛋白3(OAT3)、ATP结合盒亚家族G成员2(ABCG2)、转化生长因子-β(TGF-β1)、SMAD蛋白3(Smad3)、a-平滑肌肌动蛋白(a-SMA)的mRNA水平.结果 秋菊丸中共鉴定出41个成分,包括黄酮类(9个)、有机酸类(5个)、生物碱类(3个)、苯丙素类(7个)、香豆素类(1个)、酚类(3个)、呋喃类(2个)、脂肪酰类(6个)、醌类(2个)、萜类(1个)、内酯类(1个)、脂肪酸类(1个).给药28d后,HE染色结果表明,与模型组比较,各给药组肾损伤的病理学改变明显恢复,减轻了肾小球萎缩、肾小管扩张、肾纤维化及肾间质炎性细胞浸润等病理改变,其中秋菊丸高剂量组及苯溴马隆组肾脏损伤最轻.与模型组比较,秋菊丸高剂量组的CRE、UA水平均显著降低(P＜0.01),各剂量组BUN水平有降低趋势,但无显著性差异;高、中剂量组肾组织中肾小管上皮细胞中胶原蛋白的含量显著降低(P＜0.05、0.01);高剂量组GLUT9 mRNA表达量显著减少(P＜0.05、0.01),各剂量组OAT3、ABCG2的mRNA表达量均显著增加(P＜0.05、0.01);中、高剂量a-SMAmRNA表达量显著减少(P＜0.05、0.01),高剂量组TGF-β1 mRNA表达量显著减少(P＜0.01),各给药组Smad3的mRNA表达量有减少趋势,但无显著性差异.结论 初步明确秋菊丸化成成分,秋菊丸具有增强UA代谢、减轻HUA所致肾脏损伤及肾纤维化的作用,其机制可能与调控GLUT9-OAT3尿酸转运体相关.
Objective To evaluate the efficacy and safety of coenzyme Q10 in the adjuvant treatment of heart failure.Methods Databases such as PubMed,The Cochrane Library,Embase,Web of science,CNKI,SinoMed,VIP and Wanfang Data were consulted to obtain randomized controlled trials(RCTs)concerning the use of coenzyme Q10 in treating heart failure from the beginning to February 2023.After literature screening,relevant effective information extraction and deviation risk included in the evaluation study,the two researchers used RevMan 5.4.1 analysis tool for meta-analysis.Results A total of 27 RCTs were collected,and the total number of patients was 3 222.Meta-analysis results revealed that:The mortality rate of coenzyme Q10 adjuvant treatment group was lower than that of the control group[RR=0.62,95％CI(0.47,0.82),P=0.000 6],and the ejection fraction was higher than that of the control group[MD=3.62,95％CI(2.53,4.71),P＜0.000 01],NYHA cardiac function grade was lower than control group[MD=-0.31,95％CI(-0.40,-0.22),P＜0.000 01],and 6-minute walking test(6MWT)was superior to the control group[MD=35.36,95％CI(23.00,47.72),P＜0.000 01],adverse reactions were lower than those in control group[RR=0.73,95％CI(0.50,1.06),P=0.10].Conclusion The evidence currently available suggests that coenzyme Q10 has the potential to reduce mortality,NYHA cardiac function grade,and increase ejection fraction and 6-minute walking test in those with heart failure,without any major adverse effects.Nevertheless,due to the limited number of studies included,these conclusions must be further corroborated by more high-quality studies.
Objective To investigate the therapeutic effect of Xiaozhi Pills(XZP)on constipation induced by diphenoxylate in mice and its mechanism.Methods ICR mice were randomly divided into control group,model group,methylnaltrexone bromide group(positive control,58.5 mg·kg-1)and XZP low,medium,and high doses group(1.17,2.34,and 4.68 g·kg1).Each group was administered by gavage of the corresponding drug once a day for seven days.Except for the control group,the other groups were given diphenoxylate suspension at 7.5 mg·kg-1 body weight by gavage on the same day.Observe the general situation of mice.After the end of the last administration,each experimental group fasted for 16 hours and couldn't help but water.The model group and each administration group were given compound diphenoxylate by ig.After 30 minutes,the administration group ig contained activated carbon suspension of the corresponding test drug,while the control group and model group ig contained activated carbon suspension.The first batch of mice were observed for the first time of black stools,the number of stools within six hours,the quality of stools within 6 and 24 hours,and the fecal moisture content.The second batch of mice were tested for intestinal propulsion rate,enzyme-linked immunosorbent assay(ELISA)was used to detect changes in levels of serotonin(5-HT),substance P(SP),and vasoactive intestinal polypeptide(VIP)in colon tissue and serum,real-time fluorescence quantitative PCR(qRT-PCR)was used to detect levels of aquaporin 3(AQP3)and AQP9 mRNA in colon tissue,and Western blotting was used to detect protein expression levels of AQP3 and AQP9.Results Compared with the model group,the fecal dryness of mice in each treatment group improved,with varying degrees of increase in fecal volume,increased body mass,and gradually improved mental state.Compared with the model group,each medication group significantly shortened the first black stool discharge time,improved the number of fecal particles and fecal moisture content at six hours,and improved the quality of feces at 6 and 24 hours(P＜0.05,0.01,0.001);Except for the low-dose group of XZP,the 24-hour fecal moisture content of mice in all other treatment groups significantly increased(P＜0.01,0.001).The distance and rate of small intestine charcoal powder propulsion in each administration group were significantly increased(P＜0.05,0.01,0.001).All treatment groups were able to significantly reduce VIP levels in colon tissue(P＜0.01,0.001).Except for the low-dose group of XZW,all other treatment groups were able to significantly increase the levels of 5-HT and SP in colon tissue(P＜0.01,0.001).Each administration group significantly increased the levels of 5-HT and SP in serum and decreased the expression level of VIP(P＜0.05,0.01,0.001).The expression of AQP3 protein significantly decreased in each treatment group(P＜0.01,0.001),while the expression of AQP9 protein significantly increased(P＜0.05,0.01,0.001).The levels of AQP3 mRNA was significantly decreased in each treatment group(P＜0.01,0.001),while the levels of AQP9 mRNA was significantly increased(P＜0.05,0.01,0.001).Conclusion XZP had a significant therapeutic effect on the constipation model induced by compound diphenoxylate in mice.It can significantly shorten the first black stool time,increase the number of stool particles and increase the fecal water content,and significantly promote small intestine propulsion.The mechanism of action is related to regulating the release of intestinal secretion related factors such as 5-HT,SP,VIP,and the expression of AQP3 and AQP9.
Objective To establish an quantitative analysis method and QAMS by UPLC for ganoderol A,ganoderal A,ganodermanontriol and ergosterol from Ganoderma Lucidum extract.Methods The UPLC content determination was performed on a Phenomenex Luna Omega PS C18 chromatographic column(150 mm × 2.1 mm,1.6 μm),with acetonitrile-0.04％formic acid as the mobile phase,the detection wave was set at 254 nm,the column temperature was 30 ℃.QAMS used ganoderal A as the internal reference material to calculate the relative correction factors of ganoderal A,ganodermanontriol and ergosterol.Precisely aspirate 10 batches of Ganoderma lucidum test solution for injection testing,and compare the results of the established external standard method and QAMS for consistency.Result The results showed that the 4 components established a good linear relationship(r ≥0.998 8),and the relative standard deviations(RSD)of precision,stability,and repeatability were all less than 2.13％,and the recovery rate was 92％-105％,RSD was less than 1.99％,the accuracy of this method was good.The relative correction factors for ganoderal A,ganodermanontriol and ergosterol were 1.02,0.99,and 1.80,respectively.There was no significant difference in the results between the one test multiple evaluation method and the external standard method.Conclusion The UPLC determination method and QAMS of neutral triterpenoids and ergosterol in this study is specific,simple,efficient and accurate,which is suitable for the quantitative analysis of Ganoderma neutral triterpenoids and ergosterol.
