Oridonin Attenuates TNBS-induced Post-inflammatory Irritable Bowel Syndrome via PXR/NF-κB Signaling

Shao, Yun-Yun; Guo, Yang; Feng, Xiaojuan; Liu, Junjin; Chang, Zhuang-Peng; Deng, Gui-Feng; Ding, Xu; Gao, Jianping; R, Hou

doi:10.1007/s10753-020-01364-0

Cited by 21 publications

(15 citation statements)

References 27 publications

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“…As we know, LCA is a secondary BA and can activate multiple transcription factors [such as farnesoid X receptor (FXR)] and BA receptors (such as Takeda G-protein coupled receptor 5 (TGR5)] ( Zhang et al, 2019a ; Hui et al, 2020 ; Liang et al, 2020 ). FXR can antagonize inflammation by negatively regulating the NF-κB signaling and reducing the expression of inflammatory cytokines ( Shao et al, 2020a ). These findings may well explain our results that the negative correlation between the abundance of Bacteroides and the levels of proinflammatory cytokines.…”

Section: Discussionmentioning

confidence: 99%

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Shaoyao-Gancao Decoction Ameliorates the Inflammation State in Polycystic Ovary Syndrome Rats via Remodeling Gut Microbiota and Suppressing the TLR4/NF-κB Pathway

et al. 2021

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Background: Emerging evidence suggests that gut microbiota plays a vital role in the occurrence of multiple endocrine disorders including polycystic ovary syndrome (PCOS). Shaoyao-Gancao Decoction (SGD), a classical Chinese prescription, has been widely used in the treatment of PCOS for decades. In previous studies, we found that SGD treatment could effectively reduce ovarian inflammation in PCOS rats. However, whether the anti-inflammation effect of SGD involves the regulation of the gut microbiota remains elusive.Methods: Letrozole-induced PCOS rat models were established, and the therapeutic effects of SGD were evaluated. Specifically, body weight, serum hormone concentrations, estrus phase and ovary histopathology were assessed. Then the structure of gut microbiota was determined by 16s rRNA sequencing. Additionally, the serum levels of pro-inflammatory cytokines and LPS were measured by ELISA kits. The key gene and protein expressions of TLR4/NF-κB signaling pathway were detected by quantitative real-time PCR and western blot.Results: SGD could effectively reduce body weight, regulate estrous cycles and ameliorate hyperandrogenism in PCOS rats. In addition, SGD treatment decreased releases of pro-inflammatory cytokines, enhanced the expressions of tight junction (occludin and claudin1), and then prevented a translocation of LPS into bloodstream. SGD could significantly reduce the ratio of Firmicutes to Bacteroidetes, decrease the abundance of LPS-producing pathogens Proteobateria and enrich the abundance of Butyricicoccus, Coprococcus, Akkermansia Blautia and Bacteroides in PCOS rats. Furthermore, SGD blunted the key gene and protein expressions of TLR4/NF-κB signaling pathway both in vivo and in LPS-induced RAW264.7 cells.Conclusion: SGD administration could ameliorate the inflammatory response in PCOS rats by remodeling gut microbiome structure, protecting gut barrier, and suppressing TLR4/NF-κB signaling pathway.

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Section: Discussionmentioning

confidence: 99%

“…The expression levels of related proteins were analyzed by western blot as described previously ( Shao et al, 2020a ). Briefly, protein samples were extracted using RIPA lysis buffer.…”

Section: Methodsmentioning

confidence: 99%

Shaoyao-Gancao Decoction Ameliorates the Inflammation State in Polycystic Ovary Syndrome Rats via Remodeling Gut Microbiota and Suppressing the TLR4/NF-κB Pathway

et al. 2021

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“…It is reported that PXR activation constrains the activity of NF-κB signaling that PXR competes with NF-κB for GRIP1 (NF-κB coactivator) interaction ( Okamura et al, 2019 ). Moreover, PXR could directly interact with NF-κB p65, which inhibited the translocation of NF-κB to the nuclear, thereby suppressing the downstream inflammatory response ( Wahli, 2008 ; Zhang et al, 2019 ; Shao et al, 2021 ). All these findings have suggested a potential role of PXR/NF-κB signaling in AKI.…”

Section: Discussionmentioning

confidence: 99%

Salvia miltiorrhiza Bunge (Danshen) and Bioactive Compound Tanshinone IIA Alleviates Cisplatin-Induced Acute Kidney Injury Through Regulating PXR/NF-κB Signaling

et al. 2022

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Objective: The present study aims to provide evidence on the potential protective role of Salvia miltiorrhiza Bunge (Danshen) and its bioactive compound Tanshinone IIA (TanIIA) in AKI and to reveal the specific regulatory function of PXR/NF-κB signaling in AKI-induced renal inflammation.Methods: A network pharmacological analysis was used to study target genes and regulatory networks in the treatment of Salvia miltiorrhiza on AKI. Further experiments with in vivo AKI mouse model and in vitro studies were applied to investigate the renal protective effect of TanIIA in AKI. The mechanisms of TanIIA regulating PXR/NF-κB signaling in renal inflammation were also studied.Results: Network pharmacology had suggested the nuclear receptor family as new therapeutic targets of Salvia miltiorrhiza in AKI treatment. The in vivo studies had demonstrated that TanIIA improved renal function and inflammation by reducing necrosis and promoting the proliferation of tubular epithelial cells. Improved renal arterial perfusion in AKI mice with TanIIA treatment was also recorded by ultrasonography. In vitro studies had shown that TanIIA ameliorated renal inflammation by activating the PXR while inhibiting PXR-mediated NF-κB signaling. The results had suggested a role of PXR activation against AKI-induced renal inflammation.Conclusion:Salvia miltiorrhiza Bunge (Danshen) may protect the kidneys against AKI by regulating nuclear receptors. TanIIA improved cell necrosis proliferation and reduced renal inflammation by upregulating the expression of the PXR and inhibiting NF-κB signaling in a PXR-dependent manner. The PXR may be a potential therapeutic target for AKI treatment.

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“…Although moledule docking indicates the original isomer of PA (CID: 10955174) earn an edge, the isomery of PA shows no significant difference as for its interaction with PXR. Interestingly, moledule docking was also applied to analyze the relationship between ligand and PXR (Shao et al, 2021), but compared with their study, we have take more nonbonding interactions into consideration, including Pi-Sigma, Pi-Alkyl, Van der Waals, which further indicating the high binding affinity of PA and PXR. Our results also showed that PAmediated inhibition of NF-κB nuclear translocation was reversed by PXR-siRNA transfection, which suggests that PXR is key to the effects of PA on the NF-κB signaling pathway in OCs.…”

Section: Discussionmentioning

confidence: 99%

“…PXR activation by chemical compounds involves the RANKL-induced signaling pathway and inhibits OC differentiation (Guo et al, 2017). Moreover, it's reported that PXR/NF-κB signaling is related to Post-inflammatory Irritable Bowel Syndrome, indicating their link to inflammatory pathways (Shao et al, 2021). Although PXR and NF-κB are the core elements of the inflammatory signaling pathway, the role of their interaction in the regulation of OCs has not been clarified (Zhou et al, 2016b;Li et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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The incidence of osteoporosis, which is primarily characterized by plethoric osteoclast (OC) formation and severe bone loss, has increased in recent years. Millions of people worldwide, especially postmenopausal women, suffer from osteoporosis. The drugs commonly used to treat osteoporosis still exist many disadvantages, but natural extracts provide options for the treatment of osteoporosis. Therefore, the identification of cost-effective natural compounds is important. Patchouli alcohol (PA), a natural compound extracted from Pogostemon cablin that exerts anti-inflammatory effects, is used as a treatment for gastroenteritis. However, no research on the use of Patchouli alcohol in osteoporosis has been reported. We found that PA dose-dependently inhibited the receptor activator of nuclear factor kappa-B ligand (RANKL)-induced formation and function of OCs without cytotoxicity. Furthermore, these inhibitory effects were reflected in the significant effect of PA on the NF-κB signaling pathway, as PA suppressed the transcription factors NFATc1 and c-Fos. We also determined that PA activated expression of the nuclear receptor pregnane X receptor (PXR) and promoted the PXR/Toll-like receptor 4 (TLR4) axis to inhibit the nuclear import of NF-κB (p50 and p65). Additionally, PA exerted therapeutic effects against osteoporosis in ovariectomized (OVX) mice, supporting the use of PA as a treatment for osteoporosis in the future.

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Oridonin Attenuates TNBS-induced Post-inflammatory Irritable Bowel Syndrome via PXR/NF-κB Signaling

Cited by 21 publications

References 27 publications

Shaoyao-Gancao Decoction Ameliorates the Inflammation State in Polycystic Ovary Syndrome Rats via Remodeling Gut Microbiota and Suppressing the TLR4/NF-κB Pathway

Shaoyao-Gancao Decoction Ameliorates the Inflammation State in Polycystic Ovary Syndrome Rats via Remodeling Gut Microbiota and Suppressing the TLR4/NF-κB Pathway

Salvia miltiorrhiza Bunge (Danshen) and Bioactive Compound Tanshinone IIA Alleviates Cisplatin-Induced Acute Kidney Injury Through Regulating PXR/NF-κB Signaling

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

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