Selective estrogen receptor modulators against Gram-positive and Gram-negative bacteria: an experimental study

In Vivo Studies ◽

Synergistic Activity ◽

Antibacterial Mechanism ◽

Receptor Modulators ◽

Antibacterial Potential

Aim: This study was conducted to explore the antibacterial potential of selective estrogen receptor modulators (SERMs). Materials & methods: The percentage growth retardation, bacterial growth kinetics, biofilm, checkerboard and bacterial burden assays were conducted to check antibacterial potential of SERMs. Finally, docking study was also conducted to predict possible antibacterial mechanism of SERMs. Results: In vitro and in vivo studies have shown the antibacterial activity of SERMs against different tested strains of bacteria. The synergistic activity of SERMs in combination with standard antibacterial agents was also observed and tested further under in vivo conditions. In vivo results have shown decreased bacterial bioburden. Docking studies have predicted the multimodal antibacterial mechanism of SERMs. Conclusion: SERMs can be considered as promising broad-spectrum antibacterial agents.

Drug-Herb Interaction Between Selective Estrogen Receptor Modulators and Estrogenic Herbal Medicine Er-Xian Decoction in Bone in Vivo and in Vitro

10.21203/rs.3.rs-101206/v1 ◽

2020 ◽

Author(s):

Ka-Ying Wong ◽

Liping Zhou ◽

Wenxuan Yu ◽

Christina Chui Wa Poon ◽

Man-Sau Wong

Keyword(s):

Estrogen Receptor ◽

Serum Estradiol ◽

Mineral Density ◽

Alp Activity ◽

Combined Use ◽

Abstract Background: Er-Xian decoction (EXD), a traditional Chinese Medicine for managing menopausal syndrome and osteoporosis in China, could exert osteoprotective action via activation of estrogen receptor (ERs) and regulation of serum estradiol without causing severe side effects. However, no fundamental studies have explored its potential interaction in the combined use of prescription drugs, Selective Estrogen Receptor Modulators (SERMs), regarding the osteogenic and uterotrophic effects. The present study evaluated the estrogenic effects of EXD and its potential interactions with tamoxifen and raloxifene in bone and uterus using a mature ovariectomized (OVX) Sprague-Dawley (SD) rat model and human osteoblastic MG-63 cells. Methods: Six-month-old female SD rats were randomly assigned to Sham-operated group or seven OVX groups: vehicle, 17ß-estradiol (E2, 1.0 mg/kg.day), Tamoxifen (Tamo, 1.0 mg/kg.day), Raloxifene (Ralo, 3.0 mg/kg.day), EXD (EXD, 1.6 g/kg.day), EXD+Tamoxifen (EXD+Tamo) and EXD+Raloxifene (EXD+Ralo). The effect of EXD on bodyweight, bone mineral density (BMD), bone microarchitecture, biochemical analysis of serum and urine, and uterus were evaluated. In addition, Alkaline phosphatase assay and activation of estrogen-responsive element mediated by EXD and in its combination with SERMs were investigated in MG-63 cells. Results: In vivo, EXD could interact with SERMs to modulate the serum estradiol, follicle-stimulating hormone, osteocalcin level as well as BMD and bone properties in OVX rats. Moreover, EXD could relieve the uterotrophic effect of SERMs. In vitro, EXD crude extract and EXD-treated serum could promote ALP activity. In particular, EXD-treated serum could interact with SERMs on regulating ALP activity in MG-63 cells. Conclusion: Our study demonstrated that EXD in vivo and EXD-treated serum in vitro did not weaken the osteogenic effect of SERMs. Interestingly, EXD seems to ameliorate the uterotrophic effects of SERMs. Therefore, the combined use of EXD and SERMs may be considered safe and effective in managing postmenopausal osteoporosis.

Genistein derivatives as selective estrogen receptor modulators: Sonochemical synthesis and in vivo anti-osteoporotic action

Bioorganic & Medicinal Chemistry ◽

10.1016/j.bmc.2005.04.082 ◽

2005 ◽

Vol 13 (16) ◽

pp. 4880-4890 ◽

Cited By ~ 32

Author(s):

Shi F. Wang ◽

Qing Jiang ◽

Yong H. Ye ◽

Yang Li ◽

Ren X. Tan

Keyword(s):

Estrogen Receptor ◽

Sonochemical Synthesis ◽

Responsiveness of endometrial genes Connexin26, Connexin43, C3 and clusterin to primary estrogen, selective estrogen receptor modulators, phyto- and xenoestrogens

Journal of Molecular Endocrinology ◽

10.1677/jme.0.0290239 ◽

2002 ◽

Vol 29 (2) ◽

pp. 239-249 ◽

Cited By ~ 33

Author(s):

S Heikaus ◽

E Winterhager ◽

O Traub ◽

R Grummer

Keyword(s):

Estrogen Receptor ◽

Reproductive Tract ◽

Polychlorinated Biphenyl ◽

Estrogenic Activity ◽

Complement C3 ◽

Industrial Compounds ◽

Phytohormones and chemical compounds revealing estrogenic effects are of increasing interest for their possible influence on the physiology of the reproductive tract. The gap junction connexin (Cx) genes Cx26 and Cx43, the plasma glycoprotein clusterin gene and the complement C3 gene are highly regulated by estrogen in rat endometrium. To test the value of these genes as markers for estrogenic responsiveness we analyzed the effects of estradiol, diethylstilbestrol, the selective estrogen receptor modulators (SERMs) raloxifene and tamoxifen, the phytoestrogens genistein and daidzein, and the industrial compounds DDT (1,1,1-trichloro-2-(2-chlorophenyl)-2-(4-chlorophenyl) ethane) and polychlorinated biphenyl (PCB) on the transcription of these genes in rat endometrium in vivo. Enhancement of Cx26 and decrease of clusterin transcripts expression by estradiol was observed at 0.03 micro g/250 g body weight (BW), and induction of C3 expression was observed at 0.05 micro g/250 g BW. A comparable effect was obtained by a tenfold higher concentration of diethylstilbestrol. Tamoxifen had a regulatory effect on this set of genes at about a 300-fold higher concentration, while raloxifen revealed much weaker estrogenic activity. No effect on Cx43 transcripts was observed with any of the compounds at the concentrations used. An effect of genistein was observed only on Cx26 expression, while PCB decreased clusterin transcripts. These results show that Cx26, C3 and clusterin reveal a comparable sensitivity to estrogens and SERMs. With respect to the phytoestrogen genistein, however, Cx26 seems to be the most sensitive gene. The analysis of clusters of estrogen-sensitive endometrial genes could help to identify estrogenic substances, assess their potency, and elucidate their mechanism of action.

Selective estrogen receptor modulators limit alphavirus infection by targeting the viral capping enzyme nsP1

10.1101/2021.08.19.457046 ◽

2021 ◽

Author(s):

Rajat Mudgal ◽

Chandrima Bharadwaj ◽

Aakriti Dubey ◽

Shweta Choudhary ◽

Perumal Nagarajan ◽

...

Keyword(s):

Cell Culture ◽

Estrogen Receptor ◽

Febrile Illness ◽

Tamoxifen Treatment ◽

Structural Protein ◽

Capping Enzyme ◽

Alphaviruses cause animal or human diseases that are characterized by febrile illness, debilitating arthralgia, or encephalitis. Selective estrogen receptor modulators (SERMs), a class of FDA-approved drugs, have been shown to possess antiviral activities against multiple viruses, including Hepatitis C virus, Ebola virus, dengue virus, and vesicular stomatitis virus. Here, we evaluated three SERM compounds, namely 4-hydroxytamoxifen, tamoxifen, and clomifene, for plausible antiviral properties against two important alphaviruses, chikungunya virus (CHIKV) and Sindbis virus (SINV). In cell culture settings, these SERMs displayed potent activity against CHIKV and SINV at non-toxic concentrations with EC50 values ranging between 400 nM and 3.9 μM. Further studies indicated that these compounds inhibit a post-entry step of the alphavirus life cycle, while enzymatic assays involving purified recombinant proteins confirmed that these SERMs target the enzymatic activity of non-structural protein 1 (nsP1), the capping enzyme of alphaviruses. Finally, tamoxifen treatment restrained CHIKV growth in the infected mice and diminished musculoskeletal pathologies. Combining biochemical, cell culture-based studies, and in vivo analyses, we strongly argue that SERM compounds, or their derivatives, may provide for attractive therapeutic options against alphaviruses.