Synthetic flavokawain analog (E)-1-(2'-hydroxy-4',6'-dimethoxyphenyl)-3-(3-methoxy-4-(3-morpholinopropoxy)phenyl)prop-2-en-1-one (FK-morph) effectively regresses endometriotic implants in rats. 2022

Jing Chen, and Zhenghuan Rao, and Qinqin Li, and Tao Jiang, and Yuan Chen, and Xia Gu, and Mengyue Miao, and Daifeng Hu, and Hui Zhou, and Alexander Tobias Teichmann, and Youzhe Yang
Sichuan Provincial Center for Gynaecology and Breast Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, PR China; Academician (Expert) Workstation of Sichuan Province, Luzhou, 646000, PR China.

Endometriosis is an estrogen-dependent inflammatory gynecological disorder that is pathologically defined as the growth of endometrial glands and stroma outside of the uterine cavity. It is estimated that more than 15% of women of reproductive age are affected by endometriosis. Immunological and inflammatory responses, anti-apoptotic effects and angiogenesis processes have been reported to be involved in endometriosis. Surgery and pharmacotherapy are applied in the treatment of this disease. Frustratingly, a high recurrence rate and/or side effects are observed during and after the treatments. In our previous study, we designed and synthesized serial analogs of naturally occurring flavokawain chalcones. Among these molecules, FK-morph exhibited excellent anti-inflammatory activity and showed therapeutic potential in vitro and in vivo. In the current study, we demonstrate the beneficial effects of FK-morph on a surgically induced endometriosis rat model. After treatment with FK-morph, the volumes and adhesion scores of implants in rats were effectively reduced and the levels of inflammatory cytokines and related chemokines in peritoneal fluid and blood were significantly downregulated. FK-morph also mediated cell apoptosis of endometriosis foci. In addition, the angiogenesis process was attenuated by decreasing the expression of VEGF. Meanwhile, the underlying mechanism was further explored. FK-morph effectively reduced the expression of Akt, p-Akt, PI3K, p-PI3K and NF-κB in endometriosis lesions. Overall, the results revealed the efficacy of FK-morph against endometriosis by reducing the levels of inflammatory factors, accelerating apoptosis and attenuating angiogenesis, which may be associated with blocking the activation of the PI3K/Akt and NF-κB signaling pathways.

UI MeSH Term Description Entries
D004715 Endometriosis A condition in which functional endometrial tissue is present outside the UTERUS. It is often confined to the PELVIS involving the OVARY, the ligaments, cul-de-sac, and the uterovesical peritoneum. Endometrioma,Endometriomas,Endometrioses
D004717 Endometrium The mucous membrane lining of the uterine cavity that is hormonally responsive during the MENSTRUAL CYCLE and PREGNANCY. The endometrium undergoes cyclic changes that characterize MENSTRUATION. After successful FERTILIZATION, it serves to sustain the developing embryo. Endometria
D004967 Estrogens Compounds that interact with ESTROGEN RECEPTORS in target tissues to bring about the effects similar to those of ESTRADIOL. Estrogens stimulate the female reproductive organs, and the development of secondary female SEX CHARACTERISTICS. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Estrogen,Estrogen Effect,Estrogen Effects,Estrogen Receptor Agonists,Estrogenic Agents,Estrogenic Compounds,Estrogenic Effect,Estrogenic Effects,Agents, Estrogenic,Agonists, Estrogen Receptor,Compounds, Estrogenic,Effects, Estrogen,Effects, Estrogenic,Receptor Agonists, Estrogen
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000893 Anti-Inflammatory Agents Substances that reduce or suppress INFLAMMATION. Anti-Inflammatory Agent,Antiinflammatory Agent,Agents, Anti-Inflammatory,Agents, Antiinflammatory,Anti-Inflammatories,Antiinflammatories,Antiinflammatory Agents,Agent, Anti-Inflammatory,Agent, Antiinflammatory,Agents, Anti Inflammatory,Anti Inflammatories,Anti Inflammatory Agent,Anti Inflammatory Agents
D016207 Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Cytokine
D016328 NF-kappa B Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA. Immunoglobulin Enhancer-Binding Protein,NF-kappa B Complex,Nuclear Factor kappa B,Transcription Factor NF-kB,kappa B Enhancer Binding Protein,Ig-EBP-1,NF-kB,NF-kappaB,Nuclear Factor-Kappab,Complex, NF-kappa B,Enhancer-Binding Protein, Immunoglobulin,Factor NF-kB, Transcription,Factor-Kappab, Nuclear,Ig EBP 1,Immunoglobulin Enhancer Binding Protein,NF kB,NF kappa B Complex,NF kappaB,NF-kB, Transcription Factor,Nuclear Factor Kappab,Transcription Factor NF kB
D042461 Vascular Endothelial Growth Factor A The original member of the family of endothelial cell growth factors referred to as VASCULAR ENDOTHELIAL GROWTH FACTORS. Vascular endothelial growth factor-A was originally isolated from tumor cells and referred to as "tumor angiogenesis factor" and "vascular permeability factor". Although expressed at high levels in certain tumor-derived cells it is produced by a wide variety of cell types. In addition to stimulating vascular growth and vascular permeability it may play a role in stimulating VASODILATION via NITRIC OXIDE-dependent pathways. Alternative splicing of the mRNA for vascular endothelial growth factor A results in several isoforms of the protein being produced. Vascular Endothelial Growth Factor,Vascular Endothelial Growth Factor-A,GD-VEGF,Glioma-Derived Vascular Endothelial Cell Growth Factor,VEGF,VEGF-A,Vascular Permeability Factor,Vasculotropin,Glioma Derived Vascular Endothelial Cell Growth Factor,Permeability Factor, Vascular

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