This study aimed to explore the mechanisms and molecular targets of total flavones of Abelmoschus manihot(TFA) plus empagliflozin(EM) in attenuating diabetic tubulopathy(DT) by targeting mitochondrial homeostasis and pyroptosis-apoptosis-necroptosis(PANoptosis). In the in vivo study, the authors established the DT rat models through a combination of uninephrectomy, administration of streptozotocin via intraperitoneal injections, and exposure to a high-fat diet. Following modeling successfully, the DT rat models received either TFA, EM, TFA+EM, or saline(as a vehicle) by gavage for eight weeks, respectively. In the in vitro study, the authors subjected the NRK52E cells with or without knock-down Z-DNA binding protein 1(ZBP1) to a high-glucose(HG) environment and various treatments including TFA, EM, and TFA+EM. In the in vivo and in vitro studies, The authors investigated the relative characteristics of renal tubular injury and renal tubular epithelial cells damage induced by reactive oxygen species(ROS), analyzed the relative characteristics of renal tubular PANoptosis and ZBP1-mediatted PANoptosis in renal tubular epithelial cells, and compared the relative characteristics of the protein expression levels of marked molecules of mitochondrial fission in the kidneys and mitochondrial homeostasis in renal tubular epithelial cells, respectively. Furthermore, in the network pharmacology study, the authors predicted and screened targets of TFA and EM using HERB and SwissTargetPrediction databases; The screened chemical constituents and targets of TFA and EM were constructed the relative network using Cytoscape 3.7.2 network graphics software; The relative targets of DT were integrated using OMIM and GeneCards databases; The intersecting targets of TFA, EM, and DT were enriched and analyzed signaling pathways by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG) software using DAVID database. In vivo study results showed that TFA+EM could improve renal tubular injury, the protein expression levels and characteristics of key signaling molecules in PANoptosis pathway in the kidneys, and the protein expression levels of marked molecules of mitochondrial fission in the kidneys. And that, the ameliorative effects in vivo of TFA+EM were both superior to TFA or EM. Network pharmacology study results showed that TFA+EM treated DT by regulating the PANoptosis signaling pathway. In vitro study results showed that TFA+EM could improve ROS-induced cell injury, ZBP1-mediatted PANoptosis, and mitochondrial homeostasis in renal tubular epithelial cells under a state of HG, including the protein expression levels of marked molecules of mitochondrial fission, mitochondrial ultrastructure, and membrane potential level. And that, the ameliorative effects in vitro of TFA+EM were both superior to TFA or EM. More importantly, using the NRK52E cells with knock-down ZBP1, the authors found that, indeed, ZBP1 was mediated PANoptosis in renal tubular epithelial cells as an upstream factor. In addition, TFA+EM could regulate the protein expression levels of marked signaling molecules of PANoptosis by targeting ZBP1. In summary, this study clarified that TFA+EM, different from TFA or EM, could attenuate DT with multiple targets by ameliorating mitochondrial homeostasis and inhibiting ZBP1-mediated PANoptosis. These findings provide the clear pharmacological evidence for the clinical treatment of DT with a novel strategy of TFA+EM, which is named "coordinated traditional Chinese and western medicine".
Animals ; Rats ; Mitochondria/metabolism* ; Benzhydryl Compounds/administration & dosage* ; Glucosides/administration & dosage* ; Abelmoschus/chemistry* ; Male ; Homeostasis/drug effects* ; Flavones/administration & dosage* ; Rats, Sprague-Dawley ; Diabetic Nephropathies/physiopathology* ; Drugs, Chinese Herbal/administration & dosage* ; DNA-Binding Proteins/genetics* ; Humans ; Apoptosis/drug effects*

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

OBJECTIVE: EPF3 is a fibrinolysin monomer isolated and purified from Pheretima vulgaris Chen, an earthworm used in traditional Chinese medicine as Dilong for treating blood stasis syndrome. Its composition, anticoagulant and fibrinolytic activities, and relevant mechanisms have been confirmed through in vitro experiments. However, whether it has antithrombotic effects in vivo and can be absorbed by the gastrointestinal tract is unknown. This study evaluates the antithrombotic effect in zebrafish and investigates the gastrointestinal stability and intestinal absorption mechanism of this protein in vitro. METHODS: The antithrombotic effect of EPF3 in vivo was verified using the zebrafish thrombus model induced by arachidonic acid and FeCl₃. Then, the protein bands of EPF3 incubated with simulated gastric fluid (SGF), simulated intestinal fluid (SIF), and homogenate of Caco-2 cells (HC2C) were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to evaluate its gastrointestinal stability. Finally, the transport behavior and absorption mechanism of EPF3 were studied using Caco-2 cell monolayer. RESULTS: EPF3 could significantly enhance the returned blood volume and blood flow velocity in zebrafish with platelet aggregation thrombus induced by arachidonic acid. It could also prolong the formation time of tail artery thrombus and increase the blood flow velocity in zebrafish with vessel injury thrombus induced by FeCl₃. EPF3 was stable in SIF and HC2C and unstable in SGF. The permeability of EPF3 in Caco-2 monolayer was time-dependent and concentration-dependent. The efflux ratio was less than 1.2 during transport, and the transport behavior was not affected by inhibitors. EPF3 could reversibly reduce the expression of tight junction-related proteins, including zonula occludens-1, occludin, and claudin-1 in Caco-2 cells. CONCLUSION EPF3 could play a thrombolytic and antithrombotic role in zebrafish. It could be transported and absorbed into the intestine through cellular bypass pathway by opening the intestinal epithelium tight junction. This study provides a scientific explanation for the antithrombotic effect of earthworm and provides a basis for the feasibility of subsequent development of EPF3 as an antithrombotic enteric-soluble preparation. Please cite this article as: Zhong WL, Yang JQ, Liu H, Wu YL, Shen HJ, Li PY, Du SY. Antithrombotic effect in zebrafish of a fibrinolytic protein EPF3 from Dilong (Pheretima vulgaris Chen) and its transport mechanism in Caco-2 monolayer through cell bypass pathway. J Integr Med. 2025; 23(4): 415-428.
Animals ; Zebrafish ; Humans ; Caco-2 Cells ; Fibrinolytic Agents/pharmacology* ; Thrombosis/drug therapy* ; Intestinal Absorption

AIM To investigate the mechanism of triterpenoids quillaic acid and gypsogenin-3-O-glucuronide from Psammosilene tunicoides on tunicamycin-induced rheumatoid arthritis fibroblasts-like synoviocytes(RA-FLS)via the endoplasmic reticulum pathway.METHODS The research objects of tunicamycin-induced RA-FLS intervened with quillaic acid and gypsogenin-3-O-glucuronide had their cell proliferation activity detected;their level of tumor nerosis factor-α(TNF-α)detected by ELISA;their apoptosis detected by flow cytometry;their cell migration ability detected by Transwell experiment;their expressions of transcription activator 6(ATF-6),glucose regulatory protein 78(GRP78),C/EBP homologous protein(CHOP),cysteine protease protein-12(caspase-12)and anti-apoptosis Bcl-2 protein detected by Western blot;and their mRNA expressions of ATF-6,GRP78 and CHOP detected by RT-qPCR.RESULTS Compared with the model group,each group intervened with quillaic acid or gypsogenin-3-O-glucuronide displayed decreased levels of TNF-α(P＜0.01);weakened cell proliferation and migration ability(P＜0.01);increased apoptosis rate(P＜0.01);decreased protein expressions of ATF-6 and Bcl-2(P＜0.05,P＜0.01);and increased protein expressions of CHOP and caspase-12(P＜0.05,P＜0.01).In addition,decreased GRP78 protein expression in the low and medium dose groups(P＜0.05,P＜0.01);decreased mRNA expression of ATF-6,GRP78(P＜0.01)and increased CHOP mRNA expression(P＜0.01)in the medium dose groups of quillaic acid and gypsogenin-3-O-glucuronide were observed as well.CONCLUSION Quillaic acid and gypsogenin-3-O-glucuronide may play a protective role in rheumatoid arthritis by inhibiting the proliferation and migration of RA-FLS,inducing apoptosis and reducing the secretion of related inflammatory factors via endoplasmic reticulum signal pathway.

Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH＞3 after 20 mg qd and 10 mg bid were 82.64％and 61.92％,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.

Objective To explore the effect of phillyrin(KD-1)on lung injury in rats with influenza virus pneumonia and its regulatory mechanism on the sphingosine kinases 1(SphK1)/sphingosine 1-phosphate(S1P)/S1P receptors 1(S1PR1)signal pathway.Methods Wistar male rats were divided into control group(gavage with equal amount of 0.9％NaCl),model group(gavage with equal amount of 0.9％NaCl),positive drug group(gavage with 0.02 g·kg-1 ribaverin),PF-543 group(gavage with 10 mg·kg-1 SphK1 inhibitor PF-543 Citrate)and experimental-L,-H groups(gavage with 6.5,13 mg·kg-1 KD-1,respectively).Except the control group,the other rats were treated with influenza virus nasal drip to establish influenza virus infection pneumonia model.The lung index of rats was measured;Hematoxylin-eosin(HE)staining was applied to observe the pathological damage of lung tissue in rats;the contents of interleukin 1β(IL-1β),tumor necrosis factor α(TNF-α)and IL-6 in bronchoalveolar lavage fluid(BALF)were detected by enzyme linked immunosorbent assay(ELISA);Western blot was applied to detect the expression levels of SphK1,S1P and S1PR1 proteins in rat lung tissue.Results The lung indices of experimental-L,-H groups,PF-543 group,positive drug group,model group and control group were(7.62±0.51),(5.34±0.46),(6.53±0.52),(5.48±0.43),(12.46±0.87)and(4.41±0.32)mg·g-1;IL-1β content were(47.26±2.05),(25.18±1.58),(35.75±1.50),(27.31±1.67),(62.37±2.51)and(13.28±1.04)ng·L-1;the contents of TNF-α were(76.58±4.73),(51.82±3.90),(64.81±4.15),(53.06±3.86),(98.47±4.92)and(42.71±3.52)ng·L-1;IL-6 content were(57.62±4.29),(39.06±3.86),(48.75±3.83),(41.23±3.61),(76.92±5.24)and(28.56±3.17)ng·L-1;SphK1 protein expression were 1.07±0.08,0.51±0.04,0.65±0.05,0.53±0.04,1.28±0.09 and 0.36±0.03;S1P protein expression were 1.21±0.10,0.57±0.05,0.73±0.06,0.58±0.05,1.39±0.11 and 0.39±0.03;S1PR1 protein expression were 0.45±0.03,0.83±0.07,0.64±0.05,0.81±0.07,0.28±0.02 and 1.03±0.07,respectively.Compared with the control group,the above indexes in the model group had statistical significance(all P＜0.05);compared with the model group,the above indexes in experimental-L,-H groups,PF-543 group and positive drug group had statistical significance(all P＜0.05).Conclusion KD-1 may alleviate lung injury in rats with influenza virus pneumonia by inhibiting the SphK1/S1 P/S1 PR1 signal pathway.

Objective: To investigate the clinical features and long-term prognostic factors of diabetic patients with low or intermediate complexity coronary artery disease (CAD) post percutaneous coronary intervention (PCI). Methods: This was a prospective, single-centre observational study. Consecutive diabetic patients with SYNTAX score (SS)≤32 undergoing PCI between January and December 2013 in Fuwai hospital were included in this analysis. The patients were divided into two groups based on SS, namely SS≤22 group and SS 23-32 group. Multivariate Cox regression analysis was performed to identify independent factors related to poor 5-year prognosis. The primary outcomes were cardiac death and recurrent myocardial infarction, the secondary outcomes were all cause death and revascularization. Results: Of the 3 899 patients included in the study, 2 888 were men (74.1%); mean age was 59.4±9.8 years. There were 3 450 patients in the SS≤22 group and 449 patients in the SS 23-32 group. Compared with SS≤22 group, the incidence of revascularization was higher in SS 23-32 group (18.9% (85/449) vs. 15.2% (524/3450), log-rank P=0.019). There was no significant difference in all-cause death, cardiac death and recurrent myocardial infarction between the two groups (log-rank P>0.05). Multivariate Cox regression analysis showed that age (HR=1.05, 95%CI 1.02-1.08, P<0.001), chronic obstructive pulmonary disease (HR=3.12, 95%CI 1.37-7.07, P=0.007) and creatinine clearance rate (CCr)<60 ml/min (HR=3.67, 95%CI 2.05-6.58, P<0.001) were independent risk factors for 5-year cardiac death, while left ventricular ejection fraction (HR=0.94, 95%CI 0.91-0.96, P<0.001) was a protective factor. Previous PCI (HR=2.04, 95%CI 1.38-3.00, P<0.001), blood glucose level≥11.1 mmol/L on admission (HR=2.49, 95%CI 1.32-4.70, P=0.005) and CCr<60 ml/min (HR=1.85, 95%CI 1.14-2.99, P=0.012) were independent risk factors for 5-year recurrent myocardial infarction. The SS of 23-32 was independently associated with risk of revascularization (HR=1.54, 95%CI 1.09-2.16, P=0.014), after adjusting for residual SS. Residual SS was not a risk factor for 5-year prognosis. Conclusions: In diabetic patients with low-or intermediate complexity CAD, SS 23-32 is associated with increased risk of 5-year revascularization; the clinical characteristics of the patients are associated with the long-term mortality and recurrent myocardial infarction, but not related to revascularization.
Male ; Humans ; Middle Aged ; Aged ; Female ; Coronary Artery Disease/surgery* ; Stroke Volume ; Percutaneous Coronary Intervention ; Prospective Studies ; Treatment Outcome ; Ventricular Function, Left ; Prognosis ; Risk Factors ; Myocardial Infarction/etiology* ; Diabetes Mellitus

This study investigated the effect and mechanism of morin in inducing autophagy and apoptosis in hepatocellular carcinoma cells through the protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/signal transducer and activator of transcription protein 3(STAT3) pathway. Human hepatocellular carcinoma SK-HEP-1 cells were stimulated with different concentrations of morin(0, 50, 100, 125, 200, and 250 μmol·L~(-1)). The effect of morin on the viability of SK-HEP-1 cells was detected by Cell Counting Kit-8(CCK-8). The effect of morin on the proliferation and apoptosis of SK-HEP-1 cells was investigated using colony formation assay, flow cytometry, and BeyoClick~(TM) EdU-488 with different concentrations of morin(0, 125, and 250 μmol·L~(-1)). The changes in the autophagy level of cells treated with morin were examined by transmission electron microscopy and autophagy inhibitors. The impact of morin on the expression levels of proteins related to the Akt/mTOR/STAT3 pathway was verified by Western blot. Compared with the control group, the morin groups showed decreased viability of SK-HEP-1 cells in a time-and concentration-dependent manner, increased number of apoptotic cells, up-regulated expression level of apoptosis marker PARP, up-regulated phosphorylation level of apoptosis-regulating protein H2AX, decreased number of positive cells and the colony formation rate, an upward trend of expression levels of autophagy-related proteins LC3-Ⅱ, Atg5, and Atg7, and decreased phosphorylation levels of Akt, mTOR, and STAT3. These results suggest that morin can promote apoptosis, inhibit proliferation, and induce autophagy in hepatocellular carcinoma cells, and its mechanism of action may be related to the Akt/mTOR/STAT3 pathway.
Humans ; Proto-Oncogene Proteins c-akt/metabolism* ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; TOR Serine-Threonine Kinases/metabolism* ; Apoptosis ; Autophagy ; Cell Proliferation ; Cell Line, Tumor ; STAT3 Transcription Factor/metabolism*

This study aims to investigate the therapeutic effects and potential mechanisms of resveratrol(Res) on poor ovarian response(POR) in mice. The common target genes shared by Res and POR were predicted by network pharmacology, used for Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment, and then validated by animal experiments. The mice with regular estrous cycle after screening were randomized into normal, POR, and low-and high-dose(20 and 40 mg·kg~(-1), respectively) Res groups. The normal group was administrated with an equal volume of 0.9% sodium chloride solution by gavage, and the mice in other groups with tripterygium glycosides suspension(50 mg·kg~(-1)) by gavage for 2 weeks. After the modeling, the mice in low-and high-dose Res groups were treated with Res by gavage for 2 weeks, and the mice in normal and POR groups with an equal volume of 0.9% sodium chloride solution by gavage. Ovulation induction and sample collection were carried out on the day following the end of treatment. Vaginal smears were collected for observation of the changes in the estrous cycle, the counting of retrieved oocytes, and the measurement of ovarian wet weight and ovarian index. The enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of anti-mullerian hormone(AMH), follicle-stimulating hormone(FSH), estradiol(E_2), and luteinizing hormone(LH) in the serum. The ovarian tissue morphology and granulosa cell apoptosis were observed by hematoxylin-eosin(HE) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL), respectively. Western blot was employed to determine the protein levels of phosphatidylinositol 3-kinase(PI3K), protein kinase B(AKT), forkhead box O(FOXO) 3a, hypoxia-inducible factor(HIF)-1α, B-cell lymphoma-2(Bcl-2), and Bcl-2-associated X protein(Bax). A total of 222 common targets shared by Res and POR were collected. GO annotation indicated that these targets were mainly involved in oxidative stress response. KEGG enrichment analysis revealed that Res can intervene in POR via PI3K/AKT, HIF-1, and FOXO signaling pathways. Animal experiments showed that the model group had higher rate of estrous cycle disorders, lower number and poorer morphology of normally developed follicles at all levels, more atretic follicles, higher apoptosis of ovarian granulosa cells, lower number of retrieved oocytes, lower ovarian wet weight and ovarian index, higher serum levels of FSH and LH, lower levels of AMH and E_2, higher expression levels of HIF-1α, FOXO3a and Bax, and lower expression levels of PI3K, AKT, and Bcl-2 in the ovarian tissue than the normal group. Compared with the POR group, low-and high-dose Res decreased the rate of estrous cycle disorders, improved the follicle number and morphology, reduced atretic follicles, promoted the apoptosis of ovarian granulosa cells, increased retrieved oocytes, ovarian wet weight and ovarian index, and lowered serum FSH and LH levels. Moreover, Res down-regulated the expression levels of HIF-1α, FOXO3a and Bax, and up-regulated the expression levels of PI3K, AKT and Bcl-2 in the ovarian tissue. In summary, Res can inhibit apoptosis and mitigate poor ovarian response in mice by regulating the PI3K/AKT/FOXO3a and HIF-1α pathways.
Female ; Mice ; Animals ; Proto-Oncogene Proteins c-akt/metabolism* ; Resveratrol/pharmacology* ; bcl-2-Associated X Protein ; Phosphatidylinositol 3-Kinases/metabolism* ; Sodium Chloride ; Follicle Stimulating Hormone ; Proto-Oncogene Proteins c-bcl-2