Hepatoprotective effect of anemoside B4 against sepsis-induced acute liver injury through modulating the mTOR/p70S6K-mediated autophagy

Liang, Pei; He, Li-Xian

doi:10.1016/j.cbi.2021.109534

Cited by 14 publications

(6 citation statements)

References 47 publications

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“…As reported, AB4 can effectively reduce in ammatory responses, such as klebsiella pneumoniae, bacterial and viral pneumonia, as well as acute lung injury caused by sepsis [13,14]. In addition, it also reduced acute hepatitis associated with sepsis [15], renal injury [16], ulcerative colitis, endometritis induced by phenol [17], chemotactic aggregation of neutrophils and other in ammatory reactions [18]. Recent studies provide evidence that AB4 has surprising anti-in ammatory and analgesic effects in in ammatory pain, but the underlying mechanisms remain unclear [19].…”

Section: Introductionmentioning

confidence: 76%

Anemoside B4 alleviates neuropathic pain through inhibiting inflammation

Zhao,

Li,

Yang

et al. 2022

Preprint

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Research background: Neuropathic pain (NP), which is caused by nerve injury or other diseases damages patients’ life quality seriously. Anemoside B4 (AB4) is the active component of triterpenoid saponins in traditional Chinese medicine Pulsatilla, with prominent effects of anti-inflammation and analgesia. However, its pharmacological mechanisms acting on NP remains unclear.Methods: The analgesia effects of AB4 against NP were investigated on the basis of the spinal nerve ligation (SNL) rat model by detecting the thresholds of mechanical pain and response times to cold stimulate. The key targets of AB4 acting on NP is selected based on the transcriptomic analysis, and their relative expression level was further verified by RT-qPCR. The binding sites of AB4 to the targets were searched by molecular docking. The regulation effects of AB4 on cytokines including IL-1β, IL-6 and TNF-α in the serum of SNL rats were tested by ELISA.Results: In contrast with normal rats, the thresholds of mechanical pain was decreased, whereas the response times to cold stimulate was increased in SNL rats, and the above phenomenon was reversed by AB4 treatment. The transcriptome sequencing results revealed that AB4 mainly regulated the serotonergic synapse, glutamatergic synapse, GABAergic synapse, dopaminergic synapse and cholinergic synapse pathways which was closely related to neuroinflammation and central pain sensitization. Further overlap analysis selected five genes in the pathway, named Alox15, Gngt1, Gngt2, Gnb3 and Tph1 respectively. Further RT-qPCR confirmed that the gene expression of them was down-regulated in the hippocampus of SNL rats, and up-regulated by AB4 administration. According to the molecular docking results, Anemoside B4 forms tightly bonded hydrogen bonding forces with key target molecules of the synaptic pathway, including Alox15, Gngt1, Gngt2, Gnb3 and Tph1. In addition, AB4 treatment also decreased the contents of inflammatory cytokines IL-1β, IL-6 and TNF-α in the serum of SNL rats.Conclusion: Our findings suggested the possibility of AB4 as a promising candidate for NP treatment by inhibiting inflammation.

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Section: Introductionmentioning

confidence: 76%

Anemoside B4 alleviates neuropathic pain through inhibiting inflammation

Zhao,

Li,

Yang

et al. 2022

Preprint

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“…Pei and He ( 2021 ) reported that anemoside B4 improves sepsis by alleviating the inflammatory reaction, apoptosis, and oxidative stress. Ma et al ( 2020 ) showed that the therapeutic effect of B4 for ulcerative colitis involved inflammatory pathways; indeed, B4 improves macrophage activity in rats induced by lipopolysaccharide (LPS).…”

Section: Discussionmentioning

confidence: 99%

Pulchinenoside B4 ameliorates oral ulcers in rats by modulating gut microbiota and metabolites

Luo,

Yan,

Wang

et al. 2024

Appl Microbiol Biotechnol

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Pulchinenoside B4, a natural saponin monomer from the Pulsatilla plant, plays an important role as an immunomodulator in the treatment of acute inflammation. Oral ulcer (OU) is a common ulcerative injury disease that occurs in the oral mucosa, including mucosal ulceration and abnormalities of lips and tongue. A close correlation exists between gut microbiota and circulating metabolites in patients with OU. However, the correlation between gut microbiota and serum metabolomics is not clear. Therefore, this study aimed to explore the changes in gut microbiota and metabolites in OU. The 16S ribosomal RNA (16S rRNA) gene sequencing was used to detect the changes in the composition of gut microbiota in OU rat model. Moreover, the endogenous small metabolites were explored by collecting the non-targeted serum metabolomics data. A total of 34 OU-related biomarkers were identified, mainly related to fatty acid metabolism and inflammatory pathways. The administration of B4 effectively reduced the occurrence of OU and restored the levels of multiple endogenous biomarkers and key gut microbial species to the normal level. This study demonstrated that the gut microbiota and metabolites were altered in the OU rat model, which were significantly restored to the normal level by B4, thereby showing good application prospects in the treatment of OU. Key points • The first investigating the correlation between OU and gut microbiota. • A close correlation between metabolites and gut microbiota in OU disease was successfully identified. • Pulchinenoside B4 ameliorates oral ulcers in rats by modulating gut microbiota and metabolites.

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“…Its outstanding anti-inflammatory effect was used to suppress the inflammatory reaction of acute and chronic kidney injury, chronic obstructive pulmonary disease (COPD), lung injury, and colitis diseases [ 7 , 8 , 9 , 10 , 11 , 12 ]. It also has an antiliver cancer effect by inhibiting PI3K/AKT/mTOR pathway and plays a protective role in liver injury by regulating the mTOR/p70S6K-mediated autophagy [ 13 , 14 ]. In addition, B4 could inhibit the proliferation of neointima by inhibiting the PI3K/AKT and P38MAPK signaling pathways, which has the potential to treat occlusive vascular disease [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Anemoside B4 Exerts Hypoglycemic Effect by Regulating the Expression of GLUT4 in HFD/STZ Rats

Gong

Yin²,

Wang³

et al. 2023

Molecules

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Anemoside B4 (B4) is a saponin that is extracted from Pulsatilla chinensis (Bge.), and Regel exhibited anti-inflammatory, antioxidant, antiviral, and immunomodulatory activities. However, its hypoglycemic activity in diabetes mellitus has not been evaluated. Here, we explored the effect of B4 on hyperglycemia and studied its underlying mechanism of lowering blood glucose based on hyperglycemic rats in vivo and L6 skeletal muscle cells (L6) in vitro. The rats were fed a high-fat diet (HFD) for one month, combined with an intraperitoneal injection of 60 mg/kg streptozotocin (STZ) to construct the animal model, and the drug was administrated for two weeks. Blood glucose was detected and the proteins and mRNA were expressed. Our study showed that B4 significantly diminished fasting blood glucose (FBG) and improved glucose metabolism. In addition, B4 facilitated glucose utilization in L6 cells. B4 could enhance the expression of glucose transporter 4 (GLUT4) in rat skeletal muscle and L6 cells. Mechanistically, B4 elevated the inhibition of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathways. Furthermore, we confirmed the effect of B4 on glucose uptake involved in the enhancement of GLUT4 expression in part due to PI3K/AKT signaling by using a small molecule inhibitor assay and constructing a GLUT4 promoter plasmid. Taken together, our study found that B4 ameliorates hyperglycemia through the PI3K/AKT pathway and promotes GLUT4 initiation, showing a new perspective of B4 as a potential agent against diabetes.

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Hepatoprotective effect of anemoside B4 against sepsis-induced acute liver injury through modulating the mTOR/p70S6K-mediated autophagy

Cited by 14 publications

References 47 publications

Anemoside B4 alleviates neuropathic pain through inhibiting inflammation

Anemoside B4 alleviates neuropathic pain through inhibiting inflammation

Pulchinenoside B4 ameliorates oral ulcers in rats by modulating gut microbiota and metabolites

Anemoside B4 Exerts Hypoglycemic Effect by Regulating the Expression of GLUT4 in HFD/STZ Rats

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