scholarly journals Natural Products Targeting Liver X Receptors or Farnesoid X Receptor

2022 ◽  
Vol 12 ◽  
Author(s):  
Jianglian She ◽  
Tanwei Gu ◽  
Xiaoyan Pang ◽  
Yonghong Liu ◽  
Lan Tang ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Natural Products ◽  
Nuclear Receptors ◽  
Farnesoid X Receptor ◽  
Liver X Receptors ◽  
Terrestrial Plants ◽  
Comprehensive Overview ◽  
Chemical Structures ◽  
Bioactive Properties ◽  
X Receptors

Nuclear receptors (NRs) are a superfamily of transcription factors induced by ligands and also function as integrators of hormonal and nutritional signals. Among NRs, the liver X receptors (LXRs) and farnesoid X receptor (FXR) have been of significance as targets for the treatment of metabolic syndrome-related diseases. In recent years, natural products targeting LXRs and FXR have received remarkable interests as a valuable source of novel ligands encompassing diverse chemical structures and bioactive properties. This review aims to survey natural products, originating from terrestrial plants and microorganisms, marine organisms, and marine-derived microorganisms, which could influence LXRs and FXR. In the recent two decades (2000–2020), 261 natural products were discovered from natural resources such as LXRs/FXR modulators, 109 agonists and 38 antagonists targeting LXRs, and 72 agonists and 55 antagonists targeting FXR. The docking evaluation of desired natural products targeted LXRs/FXR is finally discussed. This comprehensive overview will provide a reference for future study of novel LXRs and FXR agonists and antagonists to target human diseases, and attract an increasing number of professional scholars majoring in pharmacy and biology with more in-depth discussion.

scholarly journals LXRs, SHP, and FXR in Prostate Cancer: Enemies or Ménage à Quatre With AR?

2018 ◽  
Vol 15 ◽  
pp. 155076291880107 ◽  
Author(s):  
Marica Cariello ◽  
Simon Ducheix ◽  
Salwan Maqdasy ◽  
Silvère Baron ◽  
Antonio Moschetta ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Nuclear Receptors ◽  
Cancer Progression ◽  
Prostate Cancer Cell ◽  
Farnesoid X Receptor ◽  
New Drugs ◽  
Liver X Receptors ◽  
Castration Resistance ◽  
Orphan Nuclear Receptors ◽  
X Receptors

Androgens and androgen receptor (AR, NR3C4) clearly play a crucial role in prostate cancer progression. Besides, the link between metabolic disorders and the risk of developing a prostate cancer has been emerging these last years. Interestingly, “lipid” nuclear receptors such as LXRα/NR1H3 and LXRβ/NR1H2 (as well as FXRα/NR1H4 and SHP/NR0B2) have been described to decrease the lipid metabolism, while AR increases it. Moreover, these former orphan nuclear receptors can regulate androgen levels and modulate AR activity. Thus, it is not surprising to find such receptors involved in the physiology of prostate. This review is focused on the roles of liver X receptors (LXRs), farnesoid X receptor (FXR), and small heterodimeric partner (SHP) in prostate physiology and their capabilities to interfere with the androgen-regulated pathways by modulating the levels of active androgen within the prostate. By the use of prostate cancer cell lines, mice deficient for these nuclear receptors and human tissue libraries, several authors have pointed out the putative possibility to pharmacologically target these receptors. These data open a new field of research for the development of new drugs that could overcome the castration resistance in prostate cancer, a usual phenomenon in patients.

scholarly journals Absence of nuclear receptors LXRs impairs immune response to androgen deprivation and leads to prostate neoplasia

PLoS Biology ◽  
2020 ◽  
Vol 18 (12) ◽  
pp. e3000948
Author(s):  
Laura Bousset ◽  
Amandine Septier ◽  
Julio Bunay ◽  
Allison Voisin ◽  
Rachel Guiton ◽  
...  
Keyword(s):  
Chronic Inflammation ◽  
Nuclear Receptors ◽  
Metabolic Disorders ◽  
Androgen Deprivation ◽  
Liver X Receptors ◽  
Phenotypic Alteration ◽  
Prostate Cells ◽  
Common Causes ◽  
X Receptors

Chronic inflammation is now a well-known precursor for cancer development. Infectious prostatitis are the most common causes of prostate inflammation, but emerging evidence points the role of metabolic disorders as a potential source of cancer-related inflammation. Although the widely used treatment for prostate cancer based on androgen deprivation therapy (ADT) effectively decreases tumor size, it also causes profound alterations in immune tumor microenvironment within the prostate. Here, we demonstrate that prostates of a mouse model invalidated for nuclear receptors liver X receptors (LXRs), crucial lipid metabolism and inflammation integrators, respond in an unexpected way to androgen deprivation. Indeed, we observed profound alterations in immune cells composition, which was associated with chronic inflammation of the prostate. This was explained by the recruitment of phagocytosis-deficient macrophages leading to aberrant hyporesponse to castration. This phenotypic alteration was sufficient to allow prostatic neoplasia. Altogether, these data suggest that ADT and inflammation resulting from metabolic alterations interact to promote aberrant proliferation of epithelial prostate cells and development of neoplasia. This raises the question of the benefit of ADT for patients with metabolic disorders.

Origins, Structures, and Bioactivities of Secondary Metabolites from Marine-derived Penicillium Fungi

2021 ◽  
Vol 21 ◽  
Author(s):  
Xiliang Yang ◽  
Jinping Liu ◽  
Jiahui Mei ◽  
Rui Jiang ◽  
Shizheng Tu ◽  
...  
Keyword(s):  
Natural Products ◽  
Secondary Metabolites ◽  
Drug Development ◽  
Valuable Source ◽  
Chemical Structures ◽  
New Drug ◽  
Bioactive Properties ◽  
Potential Applications ◽  
New Drug Development ◽  
Anti Inflammatory

: In recent years, marine-derived Penicillium fungi have received remarkable interest as a valuable source of novel natural products encompassing diverse chemical structures and bioactive properties. Mangroves, sediments, algae, and sponges are the four main sources of marine-derived Penicillium fungi. As of 2014, more than 390 novel natural products have been isolated from the marine-derived Penicillium fungi, mainly including polyketides, alkaloids, terpenoids, and macrolides. Biological investigations have shown that these compounds possess antimicrobial, anti-inflammatory, cytotoxic, and other activities with potential applications in new drug development. To provide an updated catalog of this field, our mini-review summarized the origins, structures, and bioactivities of 188 secondary metabolites from marine-derived Penicillium fungi based on bioactivities classification published from 2015 to 2020.

Diterpenoid, Steroid, and Triterpenoid Agonists of Liver X Receptors from Diversified Terrestrial Plants and Marine Sources

2005 ◽  
Vol 68 (8) ◽  
pp. 1247-1252 ◽  
Author(s):  
Hiranthi Jayasuriya ◽  
Kithsiri B. Herath ◽  
John G. Ondeyka ◽  
Ziqiang Guan ◽  
Robert P. Borris ◽  
...  
Keyword(s):  
Liver X Receptors ◽  
Terrestrial Plants ◽  
X Receptors

scholarly journals The versatility of liver X receptors in T cell homeostasis: Location, location, location!

2021 ◽  
Vol 218 (4) ◽  
Author(s):  
Truong San Phan ◽  
Thomas Brunner
Keyword(s):  
T Cell ◽  
Nuclear Receptors ◽  
Target Cells ◽  
Liver X Receptors ◽  
T Cell Homeostasis ◽  
Specific Expression ◽  
Cell Homeostasis ◽  
Cell Type Specific Expression ◽  
X Receptors ◽  
And Function

Nuclear receptors control the transcriptional program of target cells and thereby their phenotype and activities. Two complementary studies by Micheals et al. (https://doi.org/10.1084/jem.20201311) and Chan et al. (https://doi.org/10.1084/jem.20200318) published in JEM uncover the cell type–specific expression and role of the nuclear receptors liver X receptors in the regulation of T cell homeostasis and function.

scholarly journals New Insights in Prostate Cancer Development and Tumor Therapy: Modulation of Nuclear Receptors and the Specific Role of Liver X Receptors

2018 ◽  
Vol 19 (9) ◽  
pp. 2545 ◽  
Author(s):  
Laura Bousset ◽  
Amandine Rambur ◽  
Allan Fouache ◽  
Julio Bunay ◽  
Laurent Morel ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Nuclear Receptors ◽  
Molecular Mechanisms ◽  
Tumor Therapy ◽  
Locally Advanced ◽  
Complementary Therapy ◽  
Liver X Receptors ◽  
Castration Resistant ◽  
Prostate Cancer Development ◽  
X Receptors

Prostate cancer (PCa) incidence has been dramatically increasing these last years in westernized countries. Though localized PCa is usually treated by radical prostatectomy, androgen deprivation therapy is preferred in locally advanced disease in combination with chemotherapy. Unfortunately, PCa goes into a castration-resistant state in the vast majority of the cases, leading to questions about the molecular mechanisms involving the steroids and their respective nuclear receptors in this relapse. Interestingly, liver X receptors (LXRα/NR1H3 and LXRβ/NR1H2) have emerged as new actors in prostate physiology, beyond their historical roles of cholesterol sensors. More importantly LXRs have been proposed to be good pharmacological targets in PCa. This rational has been based on numerous experiments performed in PCa cell lines and genetic animal models pointing out that using selective liver X receptor modulators (SLiMs) could actually be a good complementary therapy in patients with a castration resistant PCa. Hence, this review is focused on the interaction among the androgen receptors (AR/NR3C4), estrogen receptors (ERα/NR3A1 and ERβ/NR3A2), and LXRs in prostate homeostasis and their putative pharmacological modulations in parallel to the patients’ support.

Using integrative lipid systems biology to understand the role of Liver X receptors (LXRs) in male reproduction

2018 ◽  
Author(s):  
Sheba Jarvis ◽  
Lee Gethings ◽  
Raffaella Gadeleta ◽  
Emmanuelle Claude ◽  
Robert Winston ◽  
...  
Keyword(s):  
Systems Biology ◽  
Male Reproduction ◽  
Liver X Receptors ◽  
X Receptors

Unzipping Natural Products: Improved Natural Product Structure Predictions by Ensemble Modeling and Fingerprint Matching

2018 ◽  
Author(s):  
William A. Shirley ◽  
Brian P. Kelley ◽  
Yohann Potier ◽  
John H. Koschwanez ◽  
Robert Bruccoleri ◽  
...  
Keyword(s):  
Natural Products ◽  
Open Source ◽  
Natural Product ◽  
Gene Cluster ◽  
Public Domain ◽  
Product Structure ◽  
Fingerprint Matching ◽  
Ensemble Modeling ◽  
Chemical Structures ◽  
Source Gene

This pre-print explores ensemble modeling of natural product targets to match chemical structures to precursors found in large open-source gene cluster repository antiSMASH. Commentary on method, effectiveness, and limitations are enclosed. All structures are public domain molecules and have been reviewed for release.

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