The effect of genistein on TGF-β signal, dysregulation of apoptosis, cyclooxygenase-2 pathway, and NF-kB pathway in mice peritoneum of endometriosis model

Sutrisno, Sutrisno; Sulistyorini, Chandra; Manungkalit, Eviyani Margaretha; Winarsih, Lilik; Noorhamdani, Noorhamdani; Winarsih, Sri

doi:10.1016/j.mefs.2017.05.002

Cited by 14 publications

(14 citation statements)

References 47 publications

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“…Expression of Bcl‐2 was suppressed, whereas that of Bax was enriched. It also reduced COX‐2 and PGE 2 expression to levels comparable to those in the control group 85 . Curcumin inhibited MMP‐3 and increased the Bax/Bcl‐2 ratio by upregulating tumor protein p53 (p53) 81 .…”

Section: Potential New Pharmaceuticals and Their Target‐signaling Pathwaysmentioning

confidence: 94%

“…The activity of Bay11‐7085 has been shown in in vitro studies, but there has been no clinical study of its therapeutic potential. Ginsenoside Rg3, genistein, and curcumin are found in natural products, and they enhanced apoptosis via regulation of the NF‐κB pathway 79,85 . In addition, ginsenoside Rg3 neutralized the effect of TNF‐α to regulate proliferation 79 .…”

Section: Potential New Pharmaceuticals and Their Target‐signaling Pathwaysmentioning

confidence: 99%

“…In EM animal models, genistein downregulated MMP‐2/‐9 and regulated cell invasion and migration by targeting NF‐κB 311 . It also regulated NF‐κB by inhibiting TGF‐β 85 . Long‐term treatment with genistein lower the incidence of endometrial hyperplasia and provided support for bone formation in postmenopausal women 83,312 .…”

Section: Potential Pharmaceuticals With Multiple Targetsmentioning

confidence: 99%

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Pharmaceuticals targeting signaling pathways of endometriosis as potential new medical treatment: A review

Hung

Zhang

Tan

et al. 2021

Medicinal Research Reviews

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Endometriosis (EM) is defined as endometrial tissues found outside the uterus. Growth and development of endometriotic cells in ectopic sites can be promoted via multiple pathways, including MAPK/MEK/ERK, PI3K/Akt/mTOR, NF‐κB, Rho/ROCK, reactive oxidative stress, tumor necrosis factor, transforming growth factor‐β, Wnt/β‐catenin, vascular endothelial growth factor, estrogen, and cytokines. The underlying pathophysiological mechanisms include proliferation, apoptosis, autophagy, migration, invasion, fibrosis, angiogenesis, oxidative stress, inflammation, and immune escape. Current medical treatments for EM are mainly hormonal and symptomatic, and thus the development of new, effective, and safe pharmaceuticals targeting specific molecular and signaling pathways is needed. Here, we systematically reviewed the literature focused on pharmaceuticals that specifically target the molecular and signaling pathways involved in the pathophysiology of EM. Potential drug targets, their upstream and downstream molecules with key aberrant signaling, and the regulatory mechanisms promoting the growth and development of endometriotic cells and tissues were discussed. Hormonal pharmaceuticals, including melatonin, exerts proapoptotic via regulating matrix metallopeptidase activity while nonhormonal pharmaceutical sorafenib exerts antiproliferative effect via MAPK/ERK pathway and antiangiogenesis activity via VEGF/VEGFR pathway. N‐acetyl cysteine, curcumin, and ginsenoside exert antioxidant and anti‐inflammatory effects via radical scavenging activity. Natural products have high efficacy with minimal side effects; for example, resveratrol and epigallocatechin gallate have multiple targets and provide synergistic efficacy to resolve the complexity of the pathophysiology of EM, showing promising efficacy in treating EM. Although new medical treatments are currently being developed, more detailed pharmacological studies and large sample size clinical trials are needed to confirm the efficacy and safety of these treatments in the near future.

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Section: Potential New Pharmaceuticals and Their Target‐signaling Pathwaysmentioning

confidence: 94%

Section: Potential New Pharmaceuticals and Their Target‐signaling Pathwaysmentioning

confidence: 99%

Section: Potential Pharmaceuticals With Multiple Targetsmentioning

confidence: 99%

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Pharmaceuticals targeting signaling pathways of endometriosis as potential new medical treatment: A review

Hung

Zhang

Tan

et al. 2021

Medicinal Research Reviews

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“…Modeling of endometriosis mice was carried out according to previous study [ 30 ]. Characterization and diagnosis of endometriosis mice were made by examining the expression of estrogen receptors a and b in the peritoneal tissues [ 31 ].…”

Section: Methodsmentioning

confidence: 99%

“…Peritoneal isolation was performed according to the procedure in a previous study [ 30 ]. Peritoneal samples were stored at −80 °C before biomarker analysis was made.…”

Section: Methodsmentioning

confidence: 99%

Phytochemical characteristics from Phaleria macrocarpa and its inhibitory activity on the peritoneal damage of endometriosis

Maharani

Lajuna²,

Yuniwati³

et al. 2021

Journal of Ayurveda and Integrative Medicine

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Background Endometriois represents a gynecological disease that still becomes an issue in community. Phaleria macrocarpa is a plant native to Indonesia that contains an antioxidant substance, which may serve as apoptotic modulator and useful for angiogenesis. Objective This study aims to evaluate the effects of flavonoid isolates from P. macrocarpa (PM) on the development of granulomas, apoptosis, proliferation, and angiogenesis of the disease. Material and methods Total thirty mice ( Mus musculus ) were categorized into six groups, including the normal group (without any treatment), EMT (endometriosis) group, and EMT group treated with PM flavonoid isolates. Identification of the active compounds of P. macrocarpa was done using LC-HRMS. Measurement of granuloma scores and vascular density was done histologically. Apoptosis and proliferation analysis was performed by immunohistochemical techniques. Results There was an increase in granulomas, proliferation, and apoptosis in the peritoneal tissues of the endometriosis model. This change can be normalized by extract of P. macrocarpa . Conclusion We concluded that the flavonoid isolates from P. macrocarpa can suppress the growth of endometriosis lesions through normalization of proliferation and apoptosis. Thus, the P. macrocarpa flavonoid can be used as an alternative to inhibit the development of endometriosis.

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Therapeutic Potential of Genistein and its Derivatives as a Target for Anticancer Agents

Gupta

Kumar³

et al. 2023

ChemistrySelect

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Genistein is a natural isoflavone and a phytoestrogen known to possess broad range of pharmacological properties specifically explored for anticancer effects. The compound is under clinical trials for different types of cancer treatment. Structural modification of genistein has been done to prepare analogs with improved anticancer potential and pharmaceutical properties. Also, novel formulations of genistein have been developed to further improve water solubility and bioavailability for better clinical effectiveness. In the present review, we have summarized the recent available literature on genistein anticancer effects along with mechanism of action and clinical trial studies, reported analogs and novel formulations developed for improving the anticancer efficacy of genistein during the period 2013–2022. Also, the structure activity relationship (SAR) study of reported genistein analogs is described. Further, articles published in this period showed that both genistein and its various derivatives exhibit promising potential for the development of effective chemotherapeutic agents against different types of cancer. Further, the present review will help the researchers in design and development of genistein formulation with desired drug profile.

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The effect of genistein on TGF-β signal, dysregulation of apoptosis, cyclooxygenase-2 pathway, and NF-kB pathway in mice peritoneum of endometriosis model

Cited by 14 publications

References 47 publications

Pharmaceuticals targeting signaling pathways of endometriosis as potential new medical treatment: A review

Pharmaceuticals targeting signaling pathways of endometriosis as potential new medical treatment: A review

Phytochemical characteristics from Phaleria macrocarpa and its inhibitory activity on the peritoneal damage of endometriosis

Therapeutic Potential of Genistein and its Derivatives as a Target for Anticancer Agents

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