Patchouli Alcohol Modulates the Pregnancy X Receptor/Toll-like Receptor 4/Nuclear Factor Kappa B Axis to Suppress Osteoclastogenesis

Lü, Qian; Jiang, Chao; Hou, Jialong; Qian, Haoliang; Chu, Feifan; Zhang, Weiqi; Ye, Mengke; Chen, Ziyi; Liu, Jian; Yao, Han-Bing; Zhang, Jianfeng; Xu, Jiake; Wang, Te; Fan, Shunwu; Wang, Qingqing

doi:10.3389/fphar.2021.684976

Cited by 8 publications

(9 citation statements)

References 54 publications

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“…Since the publication of our original paper on microbial metabolites and PXR (Venkatesh, Mukherjee et al 2014), several groups have independently replicated our findings concerning IPA (indole propionic acid) and its effects on mouse intestinal barrier function (Dodd, Spitzer et al 2017); IPA abrogates intestinal inflammation (Konopelski and Mogilnicka 2022); IPA action partly depends on PXR (Pulakazhi Venu, Saifeddine et al 2019, Xiao, Cui et al 2020, Du, Qi et al 2021; PXR inversely regulates TLR4 (Esposito, Nobile et al 2016, Huang, Mukherjee et al 2018, Erickson, Alston et al 2020, Lu, Jiang et al 2021, Su, Zhang et al 2022, Yuan, Lv et al 2022; epithelial TLR4 regulates inflammation and tumors (Fukata, Shang et al 2011, Sodhi, Neal et al 2012, Burgueño, Fritsch et al 2021; discovery of additional indole microbial metabolites (e.g., indole acetamide) with weak effects on PXR (Illés, Krasulová et al 2020). Two reports from the same investigators challenge the notion that epithelial TLR4 is functional (Crame, Bowen et al 2021, Tam, Coller et al 2022; however, further work is needed to clarify this discrepancy as these observations are likely to be context-and model-specific (Gribar, Anand et al 2008, Takahashi, Sugi et al 2009, Soliman, Michelsen et al 2010, Nanthakumar, Meng et al 2011, Sodhi, Neal et al 2012, Li, Teo et al 2014, Belmonte, Achamrah et al 2016, Dheer, Santaolalla et al 2016, Kim, Li et al 2016, Coleman and Haller 2017, Inoue, Yajima et al 2017, Hu, Tan et al 2018, Latorre, ...…”

Section: Brief Historical Perspectivementioning

confidence: 57%

Microbial Metabolites as Ligands to Xenobiotic Receptors: Chemical Mimicry as Potential Drugs of the Future

Dvořák

Mani

2022

Drug Metab Dispos

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Xenobiotic receptors, for example like the pregnane X receptor, regulate multiple host physiological pathways including xenobiotic metabolism, certain aspects of cellular metabolism, and innate immunity. These ligand-dependent nuclear factors regulate gene expression via genomic recognition of specific promoters and transcriptional activation of the gene. Natural or endogenous ligands are not commonly associated with this class of receptors; however, since these receptors are expressed in a cell-type specific manner in the liver and intestines, there has been significant recent effort to characterize microbially derived metabolites as ligands for these receptors. In general, these metabolites are thought to be weak micromolar affinity ligands. This journal anniversary minireview will focus on recent efforts to derive potentially non-toxic microbial metabolite chemical mimics that could one day be developed as drugs combating xenobiotic-receptor modifying pathophysiology. The review will include our perspective of the field and recommend certain directions for future research. SIGNIFICANCE STATEMENTThe xenobiotic receptors (XR) regulate host drug metabolism, cellular metabolism, and immunity. Their presence in host intestines allows them to function not only as xenosensors, but also to respond to the complex metabolic environment present in the intestines. Specifically, this review focuses on describing microbial metabolite-XR interactions and the translation of these findings towards discovery of novel chemical mimics as potential drugs of the future for diseases such as inflammatory bowel disease.

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Section: Brief Historical Perspectivementioning

confidence: 57%

Microbial Metabolites as Ligands to Xenobiotic Receptors: Chemical Mimicry as Potential Drugs of the Future

Dvořák

Mani

2022

Drug Metab Dispos

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“…Lu et al. ( 64 ) demonstrated that PA suppressed osteoclastogenesis by downregulating TLR4/Myd88/TRAF6 via pregnane X receptor (PXR) and inhibited NF-κB signaling. Bacteroides vulgatus is identified to be a probiotic microbiota.…”

Section: Current Treatments For Osteoporosis By Targeting Tlr4mentioning

confidence: 99%

“…TLR4, one of the receptors of LPS, increases in both osteoclast differentiation and survival. Within the topic of this review, three included studies ( 60 , 62 , 64 ) reported the roles of TLR4/TRAF6 in osteoporosis development. He et al.…”

Section: Current Treatments For Osteoporosis By Targeting Tlr4mentioning

confidence: 99%

The critical role of toll-like receptor 4 in bone remodeling of osteoporosis: from inflammation recognition to immunity

Zhu,

Du,

Zhang

et al. 2024

Front. Immunol.

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Osteoporosis is a common chronic metabolic bone disorder. Recently, increasing numbers of studies have demonstrated that Toll-like receptor 4 (TLR4, a receptor located on the surface of osteoclasts and osteoblasts) plays a pivotal role in the development of osteoporosis. Herein, we performed a comprehensive review to summarize the findings from the relevant studies within this topic. Clinical data showed that TLR4 polymorphisms and aberrant TLR4 expression have been associated with the clinical significance of osteoporosis. Mechanistically, dysregulation of osteoblasts and osteoclasts induced by abnormal expression of TLR4 is the main molecular mechanism underlying the pathological processes of osteoporosis, which may be associated with the interactions between TLR4 and NF-κB pathway, proinflammatory effects, ncRNAs, and RUNX2. In vivo and in vitro studies demonstrate that many promising substances or agents (i.e., methionine, dioscin, miR-1906 mimic, artesunate, AEG-1 deletion, patchouli alcohol, and Bacteroides vulgatus) have been able to improve bone metabolism (i.e., inhibits bone resorption and promotes bone formation), which may partially attribute to the inhibition of TLR4 expression. The present review highlights the important role of TLR4 in the clinical significance and the pathogenesis of osteoporosis from the aspects of inflammation and immunity. Future therapeutic strategies targeting TLR4 may provide a new insight for osteoporosis treatment.

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“…It is suggested that these two TLR play an important role in OC genesis. Lu et al (30) have shown that patchoulol can inhibit OC activity and bone resorption by regulating the expression of TLR4.…”

Section: Toll-like Receptorsmentioning

confidence: 99%

Regulation of differentiation and generation of osteoclasts in rheumatoid arthritis

et al. 2022

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IntroductionRheumatoid arthritis (RA), which affects nearly 1% of the world’s population, is a debilitating autoimmune disease. Bone erosion caused by periarticular osteopenia and synovial pannus formation is the most destructive pathological changes of RA, also leads to joint deformity and loss of function,and ultimately affects the quality of life of patients. Osteoclasts (OCs) are the only known bone resorption cells and their abnormal differentiation and production play an important role in the occurrence and development of RA bone destruction; this remains the main culprit behind RA.MethodBased on the latest published literature and research progress at home and abroad, this paper reviews the abnormal regulation mechanism of OC generation and differentiation in RA and the possible targeted therapy.ResultOC-mediated bone destruction is achieved through the regulation of a variety of cytokines and cell-to-cell interactions, including gene transcription, epigenetics and environmental factors. At present, most methods for the treatment of RA are based on the regulation of inflammation, the inhibition of bone injury and joint deformities remains unexplored.DiscussionThis article will review the mechanism of abnormal differentiation of OC in RA, and summarise the current treatment oftargeting cytokines in the process of OC generation and differentiation to reduce bone destruction in patients with RA, which isexpected to become a valuable treatment choice to inhibit bone destruction in RA.

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Patchouli Alcohol Modulates the Pregnancy X Receptor/Toll-like Receptor 4/Nuclear Factor Kappa B Axis to Suppress Osteoclastogenesis

Cited by 8 publications

References 54 publications

Microbial Metabolites as Ligands to Xenobiotic Receptors: Chemical Mimicry as Potential Drugs of the Future

Microbial Metabolites as Ligands to Xenobiotic Receptors: Chemical Mimicry as Potential Drugs of the Future

The critical role of toll-like receptor 4 in bone remodeling of osteoporosis: from inflammation recognition to immunity

Regulation of differentiation and generation of osteoclasts in rheumatoid arthritis

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