Guizhi Fuling Capsule inhibits uterine fibroids growth by modulating Med12-mediated Wnt/β-Catenin signaling pathway

Chen, Linwei; Chen, Honglin; Yang, Qiao-Wei; Jiang, Yong; Liu, Lunyuan; Yu, Hui; Chen, Yan; Li, Jindong; Chen, Nan; Wang, Hua; Wang, Qin

doi:10.1016/j.jep.2022.115115

Cited by 8 publications

(5 citation statements)

References 30 publications

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“…Cells were cultured in DMEM (Thermo Fisher Scientific, Waltham, MA, USA) containing 10% fetal bovine serum (FBS, Gibco, Waltham, MA, USA), 100 mg/ml streptomycin, and 100 U/ml penicillin at 37°C in a humidified atmosphere with 5% CO 2 . LX-2 cells were treated with acetaldehyde (400 μM; Macklin Inc., Shanghai, China) for 24 h, and then treated with colchicine (Sigma Aldrich, St. Louis, MO, USA) or GZFL (Chengdu Jiuzhitang Jinding Pharmaceutical Co., Ltd., Chengdu, China) for another 24 h. The procedure was performed in accordance with the previous reference[ 15 ].…”

Section: Methodsmentioning

confidence: 99%

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Guizhi Fuling pill attenuates liver fibrosisin vitroandin vivovia inhibiting TGF-β1/Smad2/3 and activating IFN-γ/Smad7 signaling pathways

Liu

Ding

et al. 2022

Bioengineered

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Liver fibrosis resulting from chronic liver injuries (CLI) is a common health problem globally. Guizhi Fuling pill (GZFL), a modern preparation from traditional Chinese medicine, exhibited anti-dysmenorrhea, anti-inflammatory, and immune-regulative effects. However, the effect of GZFL on liver fibrosis remains unknown. In this research, LX-2 cells were stimulated with acetaldehyde for mimicking liver fibrosis progression in vitro . In addition, carbon tetrachloride (CCl 4 )-induced mouse model of liver fibrosis was established as well. The data revealed GZFL obviously suppressed the proliferation and triggered the apoptosis of acetaldehyde-stimulated LX-2 cells. In addition, GZFL prevented acetaldehyde-induced activation of LX-2 cells via downregulation of TGF-β1, p-Smad2, p-Smad3, CUGBP1, and upregulation of p-STAT1 and Smad7. Meanwhile, GZFL significantly alleviated CCl 4 ‑induced liver fibrosis, as evidenced by the decrease of ALT and AST levels. Moreover, GZFL downregulated the expressions of TGF-β1, p-Smad2, p-Smad3, and CUGBP1 in CCl 4 -treated mice. Furthermore, GZFL remarkably elevated the levels of IFN-γ, p-STAT1, and Smad7 in CCl 4 -treated mice. To sum up, GZFL was able to inhibit liver fibrosis in vitro and in vivo through suppressing TGF-β1/Smad2/3-CUGBP1 signaling and activating IFN-γ/STAT1/Smad7 signaling. Thus, GZFL might have a potential to act as a therapeutic agent for anti-fibrotic therapy.

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Section: Methodsmentioning

confidence: 99%

“…It has been reported that Chinese herbal compounds exerted anti-fibrotic effects, including Guizhi Fuling pill (GZFL)[ 15 ]. GZFL is a Chinese herbal compound composed of five medicinal herbs, including Cinnamomi Ramulus, Poria, Moutan Cortex, Persicae Semen , and Paeoniae Radix Alba [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Guizhi Fuling pill attenuates liver fibrosisin vitroandin vivovia inhibiting TGF-β1/Smad2/3 and activating IFN-γ/Smad7 signaling pathways

Liu

Ding

et al. 2022

Bioengineered

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“…Results showed that GZFL drug serum possessed the potential to inhibit the proliferation and promote the apoptosis of leiomyoma cells by enhancing the expression of tuberous sclerosis 2 (TSC2) and forkhead box O (FOXO), which are associated with the 14-3-3c signal pathway [40]. However, one study on SD rats model of uterine fibroids and human uterine leiomyoma cells demonstrated that GZFL inhibited uterine fibroids growth by modulating Mediator complex subunit 12 (Med12)-mediated wingless-type (Wnt)/ β-Catenin signaling pathway [41]. Another research on estradiol-induced endometrial hyperplasia mice showed GZFL ameliorated endometrial hyperplasia through promoting p62-Keap1-NRF2-mediated ferroptosis [42].…”

Section: Uterinementioning

confidence: 99%

“…Estradiol benzoate-and progesterone-induced SD rats Human uterine leiomyoma cells [41] Ameliorates endometrial hyperplasia through promoting p62-Keap1-NRF2mediated ferroptosis…”

Section: Gynecologic Diseasesmentioning

confidence: 99%

The Multiple Pharmacologic Functions and Mechanisms of Action of Guizhi Fuling Formulation

Gao

Jin

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Objectives. Guizhi Fuling Formulation (GZFL), a traditional Chinese medical formulation, consists of Cinnamomi Ramulus, Paeoniae Radix Alba (or Paeoniae Radix Rubra), Moutan Cortex, Persicae Semen, and Poria, with multiple therapeutic functions such as sedation, antitumor activity, anti-inflammation, and neuroprotection. However, its clinical applications remain relatively fragmented, and the underlying mechanisms of GZFL in different diseases are still not very certain. Further research and summary in both application and mechanisms remain to be needed for human health and the best use of GZFL. Therefore, we summarized the multiple pharmacologic effects and possible mechanisms of action of GZFL according to recent 17 years of research. Methods. We retrieved four English and two Chinese databases using these keywords (the formulation name or its synonyms) and searched articles written in English from January 2006 up to February 2022. Key Findings. GZFL exhibits multiple pharmacologic advantages in gynecologic diseases and other expanding diseases such as cancer, blood, and vascular disease, renal failure, inflammation, and brain injury. Possibly due to its diverse bioactive components and pharmacologic activities, GZFL could target the multiple signaling pathways involved in regulating blood circulation, inflammatory and immune factors, proliferation, apoptosis, and so on. Conclusion. This review suggests that GZFL displays promising therapeutic effects for many kinds of diseases, which have been beyond the scope of the original prescription for gynecologic diseases. In this way, we wish to provide a reference and recommendation for further preclinic and clinic studies.

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“…Modern pharmacological experiments show that GZFL can inhibit the proliferation, migration, and invasion of UFs, and increase the levels of CD3 + , CD4 + /CD8 + . In addition, GZFL can induce the apoptosis of UFs and inhibit cell proliferation by down-regulating the expression of Wnt/β-Catenin signaling pathway-related proteins and mRNAs [ 29 , 30 ]. A randomized controlled trial showed that after a one-year follow-up of GZFL treatment, there was no recurrence in the GZFL group, and the incidence of adverse reactions was significantly lower than that in the control group.…”

Section: Introductionmentioning

confidence: 99%

The efficacy and safety of Chinese herbal medicine Guizhi Fuling capsule combined with low dose mifepristone in the treatment of uterine fibroids: a systematic review and meta-analysis of 28 randomized controlled trials

Lei

Yang

et al. 2023

BMC Complement Med Ther

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Objective Guizhi Fuling Capsule (GZFL), a classic traditional Chinese medicine prescription, is often recommended for the treatment of uterine fibroids (UFs). However, the efficacy and safety of GZFL in combination with low-dose mifepristone (MFP) remains controversial. Materials and methods We searched eight literature databases and two clinical trial registries for randomized controlled trials (RCTs) of the efficacy and safety of GZFL combined with low-dose MFP in the treatment of UFs from database inception to April 24, 2022. Data analysis was performed using the Meta package in RStudio and RevMan 5.4. GRADE pro3.6.1 software was used for the assessment of evidence quality. Results Twenty-eight RCTs were included in this study, including a total of 2813 patients. The meta-analysis showed that compared with low-dose MFP alone, GZFL combined with low-dose MFP significantly reduced follicle stimulating hormone (p < 0.001), estradiol (p < 0.001), progesterone (p < 0.001), luteinizing hormone (p < 0.001), uterine fibroids volume (p < 0.001), uterine volume (p < 0.001), menstrual flow (p < 0.001) and increased clinical efficiency rate (p < 0.001). Meanwhile, GZFL combined with low-dose MFP did not significantly increase the incidence of adverse drug reactions compared with low-dose MFP alone (p = 0.16). The quality of the evidence for the outcomes ranged from “very low” to “moderate.” Conclusion This study suggests that GZFL combined with low-dose MFP is more effective and safe in the treatment of UFs, and it is a potential treatment for UFs. However, due to the poor quality of the included RCTs formulations, we recommend a rigorous, high-quality, large-sample trial to confirm our findings.

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Guizhi Fuling Capsule inhibits uterine fibroids growth by modulating Med12-mediated Wnt/β-Catenin signaling pathway

Cited by 8 publications

References 30 publications

Guizhi Fuling pill attenuates liver fibrosisin vitroandin vivovia inhibiting TGF-β1/Smad2/3 and activating IFN-γ/Smad7 signaling pathways

Guizhi Fuling pill attenuates liver fibrosisin vitroandin vivovia inhibiting TGF-β1/Smad2/3 and activating IFN-γ/Smad7 signaling pathways

The Multiple Pharmacologic Functions and Mechanisms of Action of Guizhi Fuling Formulation

The efficacy and safety of Chinese herbal medicine Guizhi Fuling capsule combined with low dose mifepristone in the treatment of uterine fibroids: a systematic review and meta-analysis of 28 randomized controlled trials

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