Systems pharmacology approach uncovers Ligustilide attenuates experimental colitis in mice by inhibiting PPARγ-mediated inflammation pathways

Huang, Yujie; Zhang, Yifan; Wan, Ting; Mei, Yu; Wang, Zihao; Xue, Jincheng; Luo, Yi; Li, Min; Fang, Shuhuan; Pan, Huafeng; Wang, Qi; Fang, Jiansong

doi:10.1007/s10565-020-09563-z

Cited by 14 publications

(6 citation statements)

References 55 publications

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“…Huang et al [ 76 ] conducted an in vivo study to investigate the actions of ligustilide, a bioactive compound richly found in Angelica acutiloba and Cnidium officinale , in activating NF-kB in a DSS-induced C57BL/6 mice model of colitis. The controls exhibited decreased body weight and colon length and increased diarrhea, rectal bleeding, ulceration, and inflammatory cell infiltration.…”

Section: Discussionmentioning

confidence: 99%

Phytochemicals and Regulation of NF-kB in Inflammatory Bowel Diseases: An Overview of In Vitro and In Vivo Effects

et al. 2023

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Inflammatory bowel diseases (IBD) are chronic relapsing idiopathic inflammatory conditions affecting the gastrointestinal tract. They are mainly represented by two forms, ulcerative colitis (UC) and Crohn’s disease (CD). IBD can be associated with the activation of nuclear factors, such as nuclear factor-kB (NF-kB), leading to increased transcription of pro-inflammatory mediators that result in diarrhea, abdominal pain, bleeding, and many extra-intestinal manifestations. Phytochemicals can interfere with many inflammation targets, including NF-κB pathways. Thus, this review aimed to investigate the effects of different phytochemicals in the NF-KB pathways in vitro and in vivo models of IBD. Fifty-six phytochemicals were included in this study, such as curcumin, resveratrol, kaempferol, sesamol, pinocembrin, astragalin, oxyberberine, berberine hydrochloride, botulin, taxifolin, naringin, thymol, isobavachalcone, lancemaside A, aesculin, tetrandrine, Ginsenoside Rk3, mangiferin, diosgenin, theanine, tryptanthrin, lycopene, gyngerol, alantolactone, mangostin, ophiopogonin D, fisetin, sinomenine, piperine, oxymatrine, euphol, artesunate, galangin, and nobiletin. The main observed effects related to NF-kB pathways were reductions in tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, interferon-gamma (IFN-γ), and cyclooxygenase-2 (COX-2), and augmented occludin, claudin-1, zonula occludens-1, and IL-10 expression levels. Moreover, phytochemicals can improve weight loss, stool consistency, and rectal bleeding in IBD. Therefore, phytochemicals can constitute a powerful treatment option for IBD in humans.

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Section: Discussionmentioning

confidence: 99%

Phytochemicals and Regulation of NF-kB in Inflammatory Bowel Diseases: An Overview of In Vitro and In Vivo Effects

et al. 2023

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“…In this study, we use the chromogenic assay, Q-PCR, Western blot and flow cytometry assays to verify whether the active ingredients of CX could affect the TF in human endothelial cells. As the representative active ingredient of CX, LIG has a high content and abundant activity, such as anti-inflammatory activity [ 31 , 32 ], vasodilative activity [ 33 ], anti-apoptotic activity [ 34 ], neuroprotective activity [ 35 , 36 ] and anti-myocardial ischemia [ 37 ]. Therefore, we chose LIG as the representative component to explore whether CX could inhibit TF so as to suppress thrombosis.…”

Section: Discussionmentioning

confidence: 99%

Exploring the Mechanism of Chuanxiong Rhizoma against Thrombosis Based on Network Pharmacology, Molecular Docking and Experimental Verification

He,

Pan

et al. 2023

Molecules

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Chuanxiong rhizoma (CX) has been utilized for centuries as a traditional herb to treat blood stasis syndromes. However, the pharmacological mechanisms are still not completely revealed. This research was aimed at exploring the molecular mechanisms of CX treatment for thrombosis. Network pharmacology was used to predict the potential anti-thrombosis mechanism after correlating the targets of active components with targets of thrombosis. Furthermore, we verified the mechanism of using CX to treat thrombosis via molecular docking and in vitro experiments. Network pharmacology results showed that a total of 18 active ingredients and 65 targets of CX treatment for thrombosis were collected, including 8 core compounds and 6 core targets. We revealed for the first time that tissue factor (TF) had a close relationship with most core targets of CX in the treatment of thrombosis. TF is a primary coagulation factor in physiological hemostasis and pathological thrombosis. Furthermore, core components of CX have strong affinity for core targets and TF according to molecular docking analysis. The in vitro experiments indicated that Ligustilide (LIG), the representative component of CX, could inhibit TF procoagulant activity, TF mRNA and protein over-expression in a dose-dependent manner in EA.hy926 cells through the PI3K/Akt/NF-κB signaling pathway. This work demonstrated that hemostasis or blood coagulation was one of the important biological processes in the treatment of thrombosis with CX, and TF also might be a central target of CX when used for treating thrombosis. The inhibition of TF might be a novel mechanism of CX in the treatment of thrombosis.

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“…5 Peroxisome proliferator-activated receptor-gamma (PPARγ), a subtype of the nuclear receptor superfamily, is involved in immune response, lipid metabolism, glucose homeostasis, inflammation, and apoptosis .6 PPAR-γ can regulate the transcription of inflammation-related genes by interacting with transcription factors, such as nuclear factor-kappa B (NF-κB), activating protein-1, and transcriptional coactivator-1. [7][8][9] Previous studies have indicated that the activation of the PPAR-γ pathway can mitigate neuroinflammation in conditions, such as brain injury, neurodegenerative disorders, and psychiatric diseases. [10][11][12][13] Although the PPAR-γ signaling pathway has anti-inflammatory and neuroprotective effects, [14][15][16] its involvement in SAE regulation remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective effects of annexin A1 tripeptide in rats with sepsis‐associated encephalopathy

Cui,

Qin,

Zhang

et al. 2024

Biotech and App Biochem

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Sepsis‐associated encephalopathy (SAE) is characterized by high incidence and mortality rates, with limited treatment options available. The underlying mechanisms and pathogenesis of SAE remain unclear. Annexin A1 (ANXA1), a membrane‐associated protein, is involved in various in vivo pathophysiological processes. This study aimed to explore the neuroprotective effects and mechanisms of a novel bioactive ANXA1 tripeptide (ANXA1sp) in SAE. Forty Sprague–Dawley rats were randomly divided into four groups (n = 10 each): control, SAE (intraperitoneal injection of lipopolysaccharide), vehicle (SAE + normal saline), and ANXA1sp (SAE + ANXA1sp) groups. Changes in serum inflammatory factors (interleukin‐6 [IL‐6], tumor necrosis factor‐α [TNF‐α]), hippocampal reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and adenosine triphosphate (ATP) levels were measured. The Morris water maze and Y maze tests were used to assess learning and memory capabilities in the rats. Further, changes in peroxisome proliferator–activated receptor‐gamma (PPAR‐γ) and apoptosis‐related protein expression were detected using western blot. The IL‐6, TNF‐α, and ROS levels were significantly increased in the SAE group compared with the levels in the control group. Intraperitoneal administration of ANXA1sp led to a significant decrease in the IL‐6, TNF‐α, and ROS levels (p < 0.05). Compared with the SAE group, the ANXA1sp group exhibited reduced escape latency on day 5, a significant increase in the number of platform crossings and the percent spontaneous alternation, and significantly higher hippocampal MMP and ATP levels (p < 0.05). Meanwhile, the expression level of PPAR‐γ protein in the ANXA1sp group was significantly increased compared with that in the other groups (p < 0.05). The expressions of apoptosis‐related proteins (nuclear factor‐kappa B [NF‐κB], Bax, and Caspase‐3) in the SAE and vehicle groups were significantly increased, with a noticeable decrease in Bcl‐2 expression, compared with that noted in the control group. Moreover, the expressions of NF‐κB, Bax, and Caspase‐3 were significantly decreased in the ANXA1sp group, and the expression of Bcl‐2 was markedly increased (p < 0.05). ANXA1sp can effectively reverse cognitive impairment in rats with SAE. The neuroprotective effect of ANXA1sp may be attributed to the activation of the PPAR‐γ pathway, resulting in reduced neuroinflammatory response and inhibition of apoptosis.

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Systems pharmacology approach uncovers Ligustilide attenuates experimental colitis in mice by inhibiting PPARγ-mediated inflammation pathways

Cited by 14 publications

References 55 publications

Phytochemicals and Regulation of NF-kB in Inflammatory Bowel Diseases: An Overview of In Vitro and In Vivo Effects

Phytochemicals and Regulation of NF-kB in Inflammatory Bowel Diseases: An Overview of In Vitro and In Vivo Effects

Exploring the Mechanism of Chuanxiong Rhizoma against Thrombosis Based on Network Pharmacology, Molecular Docking and Experimental Verification

Neuroprotective effects of annexin A1 tripeptide in rats with sepsis‐associated encephalopathy

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