Combination of Luteolin and Solifenacin Improves Urinary Dysfunction Induced by Diabetic Cystopathy in Rats

Xu, Jing; Xu, Hong; Yu, Yang; He, Yi; Liu, Qi; Yang, Bo

doi:10.12659/msm.904534

Cited by 11 publications

(8 citation statements)

References 36 publications

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“…Similarly, bladder neuropathy caused by diabetes has been shown to increase the maximum bladder capacity and residual urine volume. LUT restores bladder function by inhibiting the activity of SCF and c-Kit [ 17 ]. In our study, LUT treatment significantly improved the pathological damage and urination abnormalities caused by CYP, proving the protective effect of LUT on the bladder.…”

Section: Discussionmentioning

confidence: 99%

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Luteolin Improves Cyclophosphamide-Induced Cystitis through TXNIP/NLRP3 and NF-κB Pathways

Zhang

Zhao

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Hemorrhagic cystitis is an important complication of cyclophosphamide chemotherapy, and current therapies for the disease are limited. The natural flavonoid luteolin (LUT) has significant anti-inflammatory and antioxidant properties, but its protective effect on cyclophosphamide (CYP)-induced bladder toxicity has yet to be evaluated. This study aims to explore the protective effect of LUT on CYP-induced acute cystitis in rats. Female Sprague-Dawley rats were randomly assigned to the control (CON) group, CON + LUT group, CYP group, and CYP + LUT group. A single intraperitoneal injection of CYP was administered to establish an acute hemorrhagic cystitis model. HE staining was performed to detect the degree of bladder tissue damage, and TUNEL staining was performed to count apoptotic cells. Oxidative stress indicators were measured using commercial kits, and bladder surgery was performed to assess urinary function. The levels of inflammatory cytokines, apoptosis-related indicators, TXNIP/NLRP3 pathway, and NF-κB pathway were detected by western blot. We found that LUT treatment reduced bladder bleeding, congestion, and edema caused by CYP. Compared with the CYP + LUT group, the level of apoptosis was more highly expressed in the CYP group. We also found that caspase-3, caspase-8, and Bax were significantly upregulated and Bcl-2 was downregulated after LUT treatment. In addition, LUT inhibited the activation of NF-κB signal pathway in the rat bladder tissue after CYP exposure. LUT treatment can also reduce the NLRP3 inflammasome (NLRP3, ASC, and caspase-1) and TXNIP in the bladder. Finally, LUT can reduce the increase in the urination frequency and maximum urination pressure caused by cystitis. These results indicate that LUT displays effective anti-inflammatory, antioxidant, and antiapoptotic properties in CYP-induced acute hemorrhagic cystitis rats by inhibiting the TXNIP/NLRP3 and NF-κB pathways. LUT may be a potent therapeutic agent for the prevention and treatment of hemorrhagic cystitis.

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Section: Discussionmentioning

confidence: 99%

“…In lower urinary tract diseases, LUT also shows a certain therapeutic effect. According to reports, luteolin can improve bladder dysfunction caused by diabetic bladder disease by downregulating SCF/c-kit and PI3K [ 17 ]. LUT can also protect the bladder epithelium from E. coli infection by inhibiting cAMP-phosphodiesterase [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Luteolin Improves Cyclophosphamide-Induced Cystitis through TXNIP/NLRP3 and NF-κB Pathways

Zhang

Zhao

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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“…Apigenin improves diabetic nephropathy by MAPK-NF-κB-TNF-α and TGF-β1-MAPK-fibronectin pathways (Malik et al, 2017). Isorhamnetin, genistein, oleanic acid, hyperoside, luteolin and formononetin have the effect of treating diabetes as well (Alkhalidy et al, 2018;Oza and Kulkarni, 2018;Wang et al, 2018;Xu et al, 2018;Wu et al, 2020;Matboli et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Hu-Zhang-Qing-Mai-Yin Inhibits Proliferation of Human Retinal Capillary Endothelial Cells Exposed to High Glucose

Liu

et al. 2021

Front. Pharmacol.

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Background: Diabetic retinopathy (DR) is one of the serious complications of diabetes and an important cause of blindness. Despite much research on the pathogenesis of DR, there is still a lack of safe and effective treatment methods. Hu-zhang-qing-mai-yin (HZQMY), a Chinese medicine formula, has been clinically used in the safe and effective treatment of DR for many years. However, the systematic pharmacological research is lacking. The aim of this study was to evaluate the anti-DR effects of HZQMY and explore the possible mechanism involved. Methods: The constituents of HZQMY were analyzed by LC-MS/MS. DR model was established by high glucose simulation on human retinal capillary endothelial cells (HRCECs) in vitro. The cell viability, cell proliferation, cell apoptosis, and tube formation were assessed. Subsequently the related mechanisms were analyzed by assays for JC-1 mitochondrial membrane potential (MMP), intracellular ROS, ATP, western blot and proteomics. Results: 27 main chemical components contained in HZQMY were identified. HZQMY significantly inhibited the viability and proliferation of HRCECs exposed to high glucose, and promoted the apoptosis. In addition, HZQMY also boosted the release of ROS and suppressed tube formation of HRCECs under high glucose exposure. Meanwhile, HRCECs treated with high glucose released more ROS than normal cells, which could be markedly inhibited by HZQMY in a dose-dependent manner. Additionally, western blot assay indicated that HZQMY increased the expression of proteins related to the P38 signaling pathway and inhibited nuclear factor kappa-B (NF-κB) pathway. Proteomic analysis predicted that HSPA4, MAPK3, ENO1, EEF2 and ERPS may be the candidate targets of HZQMY in HRCECs. Conclusions: HZQMY inhibited the proliferation and promoted the Mitochondria related apoptosis of HRCECs exposed to high glucose possibly through regulating P38 and NF-κB signaling pathway.

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“…In the treatment of diabetic OAB, traditional Chinese medicine and natural plant components have recently attracted increasing attention due to their safeness, few side effects, and excellent activity (Xu et al, 2018). SQW is a traditional Chinese herbal formula that was first recorded on Fu Ren Liang Fang in the Southern Song Dynasty (between 1127 and 1279 CE).…”

Section: Introductionmentioning

confidence: 99%

Suo Quan Wan Protects Mouse From Early Diabetic Bladder Dysfunction by Mediating Motor Protein Myosin Va and Transporter Protein SLC17A9

et al. 2019

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Objective: To investigate the effects of Suo Quan Wan (SQW), a traditional Chinese herbal formula, on the overactive bladder (OAB) of type 2 diabetes mellitus (T2DM) mouse models, particularly on its function of mediating the gene and protein expression levels of myosin Va and SLC17A9. Materials and Methods: After 4 weeks high-fat diet (HFD) feeding, C57BL/6J mice were injected with streptozotocin (100 mg/kg) for four times. After 3 weeks, the diabetic mice were treated with SQW for another 3 weeks. Voided stain on paper assay, fasting blood glucose (FBG) test, and oral glucose tolerance test (OGTT) were conducted. Urodynamic test, tension test [α,β-methylene ATP, electrical-field stimulation (EFS), KCl, and carbachol] and histomorphometry were also performed. Western blot analysis and qPCR assays were used to quantify the expression levels of myosin Va and SLC17A9. Results: The diabetic mice exhibited decreased weight but increased water intake, urine production, FBG, and OGTT. No significant changes were observed after 3 weeks SQW treatment. Urodynamic test indicated that the non-voiding contraction (NVC) frequency, maximum bladder capacity (MBC), residual volume (RV), and bladder compliance (BC) were remarkably increased in the diabetic mice, whereas the voided efficiency (VE) was decreased as a feature of overactivity. Compared with the model mice, SQW treatment significantly improved urodynamic urination with decreased NVC, MBC, RV, and BC, and increased VE. Histomorphometry results showed that the bladder wall of the diabetic mice thickened, and SQW effectively attenuated the pathological alterations. The contract responses of bladder strips to all stimulators were higher in the DSM strips of diabetic mice, whereas SQW treatment markedly decreased the contraction response for all stimuli. Moreover, the protein and gene expression levels of myosin Va and SLC17A9 were up-regulated in the bladders of diabetic mice, but SQW treatment restored such alterations. Conclusion: T2DM mice exhibited the early phase of diabetic bladder dysfunction (DBD) characterized by OAB and bladder dysfunction. SQW can improve the bladder storage and micturition of DBD mice by mediating the protein and gene expression levels of myosin Va and SLC17A9 in the bladder, instead of improving the blood glucose level.

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Combination of Luteolin and Solifenacin Improves Urinary Dysfunction Induced by Diabetic Cystopathy in Rats

Cited by 11 publications

References 36 publications

Luteolin Improves Cyclophosphamide-Induced Cystitis through TXNIP/NLRP3 and NF-κB Pathways

Luteolin Improves Cyclophosphamide-Induced Cystitis through TXNIP/NLRP3 and NF-κB Pathways

Hu-Zhang-Qing-Mai-Yin Inhibits Proliferation of Human Retinal Capillary Endothelial Cells Exposed to High Glucose

Suo Quan Wan Protects Mouse From Early Diabetic Bladder Dysfunction by Mediating Motor Protein Myosin Va and Transporter Protein SLC17A9

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