Dataset Information

Therapeutic approach of natural products that treat osteoporosis by targeting epigenetic modulation.

ABSTRACT: Osteoporosis (OP) is a metabolic disease that affects bone, resulting in a progressive decrease in bone mass, quality, and micro-architectural degeneration. Natural products have become popular for managing OP in recent years due to their minimal adverse side effects and suitability for prolonged use compared to chemically synthesized products. These natural products are known to modulate multiple OP-related gene expressions, making epigenetics an important tool for optimal therapeutic development. In this study, we investigated the role of epigenetics in OP and reviewed existing research on using natural products for OP management. Our analysis identified around twenty natural products involved in epigenetics-based OP modulation, and we discussed potential mechanisms. These findings highlight the clinical significance of natural products and their potential as novel anti-OP therapeutics.

SUBMITTER: Zhang G

PROVIDER: S-EPMC10242146 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Therapeutic approach of natural products that treat osteoporosis by targeting epigenetic modulation.

Zhang Guokai G Liu Zhenying Z Li Zihan Z Zhang Bing B Yao Pengyu P Qiao Yun Y

Frontiers in genetics 20230523

Osteoporosis (OP) is a metabolic disease that affects bone, resulting in a progressive decrease in bone mass, quality, and micro-architectural degeneration. Natural products have become popular for managing OP in recent years due to their minimal adverse side effects and suitability for prolonged use compared to chemically synthesized products. These natural products are known to modulate multiple OP-related gene expressions, making epigenetics an important tool for optimal therapeutic developme ...[more]

PMID: 37287533

Similar Datasets

Project description:BackgroundImmune checkpoint inhibitors (ICIs) are successful in treating many cancers but may cause immune-related adverse events. ICI-mediated myocarditis has a high fatality rate with severe cardiovascular consequences. Targeted therapies for ICI myocarditis are currently limited.MethodsWe used a genetic mouse model of PD1 deletion (MRL/Pdcd1-/-) along with a novel drug-treated ICI myocarditis mouse model to recapitulate the disease phenotype. We performed single-cell RNA-sequencing, single-cell T-cell receptor sequencing, and cellular indexing of transcriptomes and epitopes on immune cells isolated from MRL and MRL/Pdcd1-/- mice at serial time points. We assessed the impact of macrophage deletion in MRL/Pdcd1-/- mice, then inhibited CXCR3 (C-X-C motif chemokine receptor 3) in ICI-treated mice to assess the therapeutic effect on myocarditis phenotype. Furthermore, we delineated the functional and mechanistic effects of CXCR3 blockade on T-cell and macrophage interactions. We then correlated the results in human single-cell multiomics data from blood and heart biopsy data from patients with ICI myocarditis.ResultsSingle-cell multiomics demonstrated expansion of CXCL (C-X-C motif chemokine ligand) 9/10+CCR2+ macrophages and CXCR3hi (C-X-C motif chemokine receptor 3 high-expressing) CD8+ (cluster of differentiation) effector T lymphocytes in the hearts of MRL/Pdcd1-/- mice correlating with onset of myocarditis development. Both depletion of CXCL9/10+CCR2+ (C-C motif chemokine receptor) macrophages and CXCR3 blockade, respectively, led to decreased CXCR3hi CD8+ T-cell infiltration into the heart and significantly improved survival. Transwell migration assays demonstrated that the selective blockade of CXCR3 and its ligand, CXCL10, reduced CXCR3+CD8+ T-cell migration toward macrophages, implicating this interaction in T-cell cardiotropism toward cardiac macrophages. Furthermore, cardiomyocyte apoptosis was induced by CXCR3hi CD8+ T cells. Cardiac biopsies from patients with confirmed ICI myocarditis demonstrated infiltrating CXCR3+ T cells and CXCL9+/CXCL10+ macrophages. Both mouse cardiac immune cells and patient peripheral blood immune cells revealed expanded TCRs (T-cell receptors) correlating with CXCR3hi CD8+ T cells in ICI myocarditis samples.ConclusionsThese findings bring forth the CXCR3-CXCL9/10 axis as an attractive therapeutic target for ICI myocarditis treatment, and more broadly as a druggable pathway in cardiac inflammation.

Project description:Misfolded proteins are the main common feature of neurodegenerative diseases, thereby, normal proteostasis is an important mechanism to regulate the neural survival and the central nervous system functionality. The ubiquitin-proteasome system (UPS) is a non-lysosomal proteolytic pathway involved in numerous normal functions of the nervous system, modulation of neurotransmitter release, synaptic plasticity, and recycling of membrane receptors or degradation of damaged and regulatory intracellular proteins. Aberrant accumulation of intracellular ubiquitin-positive inclusions has been implicated to a variety of neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington disease (HD), Amyotrophic Lateral Sclerosis (ALS), and Multiple Myeloma (MM). Genetic mutation in deubiquitinating enzyme could disrupt UPS and results in destructive effects on neuron survival. To date, various agents were characterized with proteasome-inhibitory potential. Proteins of the ubiquitin-proteasome system, and in particular, E3 ubiquitin ligases, may be promising molecular targets for neurodegenerative drug discovery. Phytochemicals, specifically polyphenols (PPs), were reported to act as proteasome-inhibitors or may modulate the proteasome activity. PPs modify the UPS by means of accumulation of ubiquitinated proteins, suppression of neuronal apoptosis, reduction of neurotoxicity, and improvement of synaptic plasticity and transmission. This is the first comprehensive review on the effect of PPs on UPS. Here, we review the recent findings describing various aspects of UPS dysregulation in neurodegenerative disorders. This review attempts to summarize the latest reports on the neuroprotective properties involved in the proper functioning of natural polyphenolic compounds with implication for targeting ubiquitin-proteasome pathway in the neurodegenerative diseases. We highlight the evidence suggesting that polyphenolic compounds have a dose and disorder dependent effects in improving neurological dysfunctions, and so their mechanism of action could stimulate the UPS, induce the protein degradation or inhibit UPS and reduce protein degradation. Future studies should focus on molecular mechanisms by which PPs can interfere this complex regulatory system at specific stages of the disease development and progression.

Dataset Information

Therapeutic approach of natural products that treat osteoporosis by targeting epigenetic modulation.

Publications

Therapeutic approach of natural products that treat osteoporosis by targeting epigenetic modulation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets