In this study, the active components and potential molecular .mechanism of Guizhi Fuling formula in treatment on dysmenorrhea, pelvic inflammation, and hysteromyoma were investigated using network pharmacological methods. Sterols and pentacyclic triterpenes, with high moleculal network degree, revealed promising effects on anti-inflammatory, analgesic, anti-tumor, and immune-regulation, according to D-T network analysis. On the other hand, the targets with high degree were involved in inflammatory, coagulation, angiopoiesis, smooth muscle contraction, and cell reproduction, which showed the novel function in anti-dysmenorrhea, pelvic inflammation, and hysteromyoma. Furthermore, the formula was indicated to play a key role in smooth muscle proliferation, inhibition of new vessels, circulation improvement, reduction of hormone secretion, alleviation of smooth muscle, block of arachidonic acid metabolism, and inflammation in uterus. Thus, the main mechanism of Guizhi Fuling formula was summarized. In conclusion, Guizhi Fuling formula was proven to alleviated dysmenorrhea, pelvic inflammation, and hysteromyoma by acting on multiple targets through several bioactive compounds, regulating 21 biological pathways.
Drugs, Chinese Herbal ; therapeutic use ; Dysmenorrhea ; drug therapy ; genetics ; metabolism ; Female ; Gene Regulatory Networks ; drug effects ; Humans ; Leiomyoma ; drug therapy ; genetics ; metabolism ; Pelvic Inflammatory Disease ; drug therapy ; genetics ; metabolism

Actins ; metabolism ; Calcium-Binding Proteins ; metabolism ; Calmodulin-Binding Proteins ; metabolism ; Desmin ; metabolism ; Diagnosis, Differential ; Female ; Humans ; Hysterectomy ; Leiomyoma, Epithelioid ; metabolism ; pathology ; Leiomyomatosis ; metabolism ; pathology ; surgery ; Leiomyosarcoma ; pathology ; Microfilament Proteins ; metabolism ; Middle Aged ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Rhabdoid Tumor ; metabolism ; pathology ; surgery ; Sarcoma, Endometrial Stromal ; metabolism ; pathology ; Uterine Neoplasms ; metabolism ; pathology ; surgery ; Vascular Neoplasms ; metabolism ; pathology ; surgery ; Veins ; pathology ; Vimentin ; metabolism

Aged ; Angiomyolipoma ; metabolism ; pathology ; Diagnosis, Differential ; Humans ; Kidney Neoplasms ; metabolism ; pathology ; surgery ; Leiomyoma ; metabolism ; pathology ; Lymphocytes ; pathology ; Male ; Nephrectomy ; Neurilemmoma ; metabolism ; pathology ; surgery ; S100 Proteins ; metabolism

Adult ; Calmodulin-Binding Proteins ; metabolism ; Desmin ; metabolism ; Diagnosis, Differential ; Female ; Humans ; Leiomyoma ; metabolism ; pathology ; surgery ; Leiomyosarcoma ; pathology ; Spinal Canal ; Spinal Neoplasms ; metabolism ; pathology ; surgery ; Young Adult

Actins ; metabolism ; Adult ; Diagnosis, Differential ; Endometrial Neoplasms ; metabolism ; pathology ; surgery ; Endometrial Stromal Tumors ; metabolism ; pathology ; surgery ; Female ; Humans ; Hysterectomy ; Leiomyoma, Epithelioid ; metabolism ; pathology ; Melanoma-Specific Antigens ; metabolism ; Perivascular Epithelioid Cell Neoplasms ; metabolism ; pathology ; surgery ; Receptors, Progesterone ; metabolism ; Sarcoma, Clear Cell ; metabolism ; pathology ; Uterine Neoplasms ; metabolism ; pathology ; surgery

Adenocarcinoma ; pathology ; Adenomatoid Tumor ; metabolism ; pathology ; surgery ; Adenomyoma ; pathology ; Adult ; Antibodies, Monoclonal, Murine-Derived ; metabolism ; Biomarkers, Tumor ; metabolism ; Calbindin 2 ; metabolism ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Keratins ; metabolism ; Leiomyoma ; pathology ; Lymphatic Vessel Tumors ; metabolism ; pathology ; Middle Aged ; Uterine Neoplasms ; metabolism ; pathology ; surgery ; Young Adult

The Mediator Complex plays key roles in activating gene transcription in eukaryotes. Mediator of RNA polymerase II transcription subunit 12 homolog (MED12) is a subunit of the Mediator Complex and regulates the activity of the complex. MED12 is involved in a variety of cellular activities, and mutations in MED12 gene impair MED12 activities and are associated with several diseases, including Opitz-Kaveggia syndrome, Lujan syndrome, uterine leiomyomas and prostate cancer. This review will discuss the biological function of MED12 and the relationship between MED12 mutations and diseases.
Agenesis of Corpus Callosum ; genetics ; Anus, Imperforate ; genetics ; Constipation ; genetics ; Craniofacial Abnormalities ; genetics ; Female ; Genetic Predisposition to Disease ; Humans ; Leiomyoma ; genetics ; Male ; Marfan Syndrome ; genetics ; Mediator Complex ; genetics ; metabolism ; Mental Retardation, X-Linked ; genetics ; Muscle Hypotonia ; congenital ; genetics ; Mutation ; Prostatic Neoplasms ; genetics ; Transcription, Genetic ; Uterine Neoplasms ; genetics

Previously, we found that high doses of genistein show an inhibitory effect on uterine leiomyoma (UtLM) cell proliferation. In this study, using microarray analysis and Ingenuity Pathways Analysis(TM), we identified genes (up- or down-regulated, > or = 1.5 fold, P < or = 0.001), functions and signaling pathways that were altered following treatment with an inhibitory concentration of genistein (50 microg/ml) in UtLM cells. Downregulation of TGF-beta signaling pathway genes, activin A, activin B, Smad3, TGF-beta2 and genes related to cell cycle regulation, with the exception of the upregulation of the CDK inhibitor P15, were identified and validated by real-time RT-PCR studies. Western blot analysis further demonstrated decreased protein expression of activin A and Smad3 in genistein-treated UtLM cells. Moreover, we found that activin A stimulated the growth of UtLM cells, and the inhibitory effect of genistein was partially abrogated in the presence of activin A. Overexpression of activin A and Smad3 were found in tissue samples of leiomyoma compared to matched myometrium, supporting the contribution of activin A and Smad3 in promoting the growth of UtLM cells. Taken together, these results suggest that down-regulation of activin A and Smad3, both members of the TGF-beta pathway, may offer a mechanistic explanation for the inhibitory effect of a high-dose of genistein on UtLM cells, and might be potential therapeutic targets for treatment of clinical cases of uterine leiomyomas.
Activins/*genetics/metabolism/pharmacology ; Anticarcinogenic Agents/*pharmacology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cyclin-Dependent Kinase Inhibitor p15/genetics/metabolism ; Down-Regulation ; Female ; Genistein/*pharmacology ; Humans ; Leiomyoma/*metabolism ; Oligonucleotide Array Sequence Analysis ; Signal Transduction/drug effects ; Smad3 Protein/*genetics/metabolism ; Transforming Growth Factor beta/*genetics/metabolism ; Up-Regulation ; Uterine Neoplasms/*metabolism

Actins ; metabolism ; Adenocarcinoma, Clear Cell ; metabolism ; pathology ; Adult ; Carcinoma, Renal Cell ; metabolism ; pathology ; Desmin ; metabolism ; Diagnosis, Differential ; Endometrial Stromal Tumors ; metabolism ; pathology ; Female ; Follow-Up Studies ; Humans ; Hysterectomy ; Leiomyoma, Epithelioid ; metabolism ; pathology ; Melanoma ; metabolism ; pathology ; Melanoma-Specific Antigens ; metabolism ; Perivascular Epithelioid Cell Neoplasms ; metabolism ; pathology ; surgery ; Receptors, Progesterone ; metabolism ; Uterine Neoplasms ; metabolism ; pathology ; surgery ; Vimentin ; metabolism

Actins ; metabolism ; Calcium-Binding Proteins ; metabolism ; Desmin ; metabolism ; Female ; Humans ; Leiomyoma ; metabolism ; pathology ; Microfilament Proteins ; metabolism ; Middle Aged ; Sex Cord-Gonadal Stromal Tumors ; metabolism ; pathology ; Uterine Neoplasms ; metabolism ; pathology