Stigmasterol alleviates cerebral ischemia/reperfusion injury by attenuating inflammation and improving antioxidant defenses in rats

Liang, Qilong; Yang, Jun Young; He, Jia-ji; Chen, Xiaoling; Zhang, Hong; Jia, Maolin; Li, Kai; Jia, Chuangchuang; Pan, Yan-Hong; JinWang, Wei

doi:10.1042/bsr20192133

Cited by 60 publications

(34 citation statements)

References 32 publications

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“…Beta-sitosterol was predicted to mediate NF-κB signaling pathway ( Kasirzadeh et al, 2021 ) and was found to significantly reduce the pro-inflammatory cytokines in the sera of cecal ligation and puncture-induced septic rats, such as TNF-α and NF-κB mRNA expressions. In addition, stigmasterol was proved to decrease the levels of cyclooxygenase-2 (Cox-2) and NF-κB (p65) in the brain of rats, thereby attenuating inflammation and improving antioxidant defenses ( Liang et al, 2020 ). Caffeic acid could reduce pro-inflammatory cytokines IL-1β, IL-6, and TNF-α and attenuate iNOS and COX-2 in LPS-stimulated macrophages ( Chen et al, 2019 ).…”

Section: Resultsmentioning

confidence: 99%

Detecting Critical Functional Ingredients Group and Mechanism of Xuebijing Injection in Treating Sepsis

Yin

et al. 2021

Front. Pharmacol.

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Sepsis is a systemic inflammatory reaction caused by various infectious or noninfectious factors, which can lead to shock, multiple organ dysfunction syndrome, and death. It is one of the common complications and a main cause of death in critically ill patients. At present, the treatments of sepsis are mainly focused on the controlling of inflammatory response and reduction of various organ function damage, including anti-infection, hormones, mechanical ventilation, nutritional support, and traditional Chinese medicine (TCM). Among them, Xuebijing injection (XBJI) is an important derivative of TCM, which is widely used in clinical research. However, the molecular mechanism of XBJI on sepsis is still not clear. The mechanism of treatment of “bacteria, poison and inflammation” and the effects of multi-ingredient, multi-target, and multi-pathway have still not been clarified. For solving this issue, we designed a new systems pharmacology strategy which combines target genes of XBJI and the pathogenetic genes of sepsis to construct functional response space (FRS). The key response proteins in the FRS were determined by using a novel node importance calculation method and were condensed by a dynamic programming strategy to conduct the critical functional ingredients group (CFIG). The results showed that enriched pathways of key response proteins selected from FRS could cover 95.83% of the enriched pathways of reference targets, which were defined as the intersections of ingredient targets and pathogenetic genes. The targets of the optimized CFIG with 60 ingredients could be enriched into 182 pathways which covered 81.58% of 152 pathways of 1,606 pathogenetic genes. The prediction of CFIG targets showed that the CFIG of XBJI could affect sepsis synergistically through genes such as TAK1, TNF-α, IL-1β, and MEK1 in the pathways of MAPK, NF-κB, PI3K-AKT, Toll-like receptor, and tumor necrosis factor signaling. Finally, the effects of apigenin, baicalein, and luteolin were evaluated by in vitro experiments and were proved to be effective in reducing the production of intracellular reactive oxygen species in lipopolysaccharide-stimulated RAW264.7 cells, significantly. These results indicate that the novel integrative model can promote reliability and accuracy on depicting the CFIGs in XBJI and figure out a methodological coordinate for simplicity, mechanism analysis, and secondary development of formulas in TCM.

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Section: Resultsmentioning

confidence: 99%

Detecting Critical Functional Ingredients Group and Mechanism of Xuebijing Injection in Treating Sepsis

Yin

et al. 2021

Front. Pharmacol.

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“…Stigmasterol (3.09%) exerts antitumor [ 58 , 72 , 73 , 74 ], hypolipidemic [ 75 , 76 , 77 , 78 , 79 , 80 ], antidiabetic [ 81 , 82 ], antimutagenic [ 83 ], antiparasitic [ 84 ], and antinociceptive [ 85 ] effects. It can also alleviate manifestations of osteoarthritis [ 86 , 87 ], inflammation and autoimmune diseases [ 88 , 89 , 90 , 91 ], and mitigate central nerve system injuries and disorders in both neuroprotective and function-improving manner [ 92 , 93 , 94 , 95 , 96 , 97 , 98 ]. In several studies its antioxidant activity was also demonstrated [ 79 , 81 , 89 , 92 , 93 , 94 ].…”

Section: Discussionmentioning

confidence: 99%

“…It can also alleviate manifestations of osteoarthritis [ 86 , 87 ], inflammation and autoimmune diseases [ 88 , 89 , 90 , 91 ], and mitigate central nerve system injuries and disorders in both neuroprotective and function-improving manner [ 92 , 93 , 94 , 95 , 96 , 97 , 98 ]. In several studies its antioxidant activity was also demonstrated [ 79 , 81 , 89 , 92 , 93 , 94 ]. Stigmasterol accumulation, however, can cause cardiac injury [ 99 ].…”

Section: Discussionmentioning

confidence: 99%

Phytochemical Characterization, Antioxidant Activity, and Cytotoxicity of Methanolic Leaf Extract of Chlorophytum Comosum (Green Type) (Thunb.) Jacq

et al. 2022

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Chlorophytum genus has been extensively studied due to its diverse biological activities. We evaluated the methanolic extract of leaves of Chlorophytum comosum (Green type) (Thunb.) Jacques, the species that is less studied compared to C. borivilianum. The aim was to identify phytoconstituents of the methanolic extract of leaves of C. comosum and biological properties of its different fractions. Water fraction was analyzed with matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Nineteen compounds belonging to different chemical classes were identified in the methanolic extract of leaves of C. comosum (Green type) (Thunb.) Jacques. In addition to several fatty acids, isoprenoid and steroid compounds were found among the most abundant constituents. One of the identified compounds, 4′-methylphenyl-1C-sulfonyl-β-d-galactoside, was not detected earlier in Chlorophytum extracts. The water fraction was toxic to HeLa cells but not to Vero cells. Our data demonstrate that methanolic extract of leaves of C. comosum can be a valuable source of bioactive constituents. The water fraction of the extract exhibited promising antitumor potential based on a high ratio of HeLa vs. Vero cytotoxicity.

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“…In the past, many studies have reported the therapeutic effects of stigmasterol in antioxidative activities, anti-inflammatory activities, regulation of lipid metabolism, and antitumour activities. Studies have shown that stigmasterol improves rat brain damage caused by ischaemia-reperfusion by reducing oxidative stress and inflammation [ 62 ]. Stigmasterol relieves collagen-induced arthritis in rats by inhibiting proinflammatory cytokines [ 63 ].…”

Section: Discussionmentioning

confidence: 99%

A Network Pharmacology Study on the Active Components and Targets of the Radix Ginseng and Radix Bupleuri Herb Pair for Treating Nonalcoholic Fatty Liver Disease

Zhang

Liu

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Objective. To explore the potential active components and corresponding target herb pairs of Radix Ginseng (Renshen) and Radix Bupleuri (Chaihu) in the treatment of nonalcoholic fatty liver disease (NAFLD) through network pharmacology and in vitro experiments. Methods. The active components and potential targets of the herb pair of Renshen and Chaihu were screened through a network database system, and Venn analysis was performed with the obtained NAFLD targets. The intersecting targets were analysed for gene ontology (GO) functions and Kyoto Encyclopedia of Genes and Genome (KEGG) pathways, and a protein-protein interaction (PPI) network was generated. Cytoscape software was used to construct active component-target networks of the Renshen and Chaihu herb pair. Free fatty acids were added to the HepG2 cell line to create high-fat models that were treated with different concentrations of stigmasterol. The effect of stigmasterol on the lipid metabolism in HepG2 cells and PPARγ-knockdown cells was determined by oil red O staining, Nile red staining, and TG level. PPARγ and UCP-1 mRNA, and protein expression levels were detected by qRT-PCR and Western blot analyses, respectively. Results. Twenty active components obtained from the Renshen and Chaihu herb pair were identified. The herb pair active component-target network showed that both Renshen and Chaihu contained stigmasterol and kaempferol as active components. The PPI network comprised 63 protein nodes. GO enrichment analysis and KEGG pathway enrichment analysis showed that the targets were mainly involved in lipid metabolism. Eight core targets were identified: AKT1, PPARG, MAPK3, TNF, TP53, SIRT1, STAT3, and PPARA. In vitro experiments demonstrated that stigmasterol reduced lipid accumulation and TG levels in HepG2 cells, and the mechanism may have been related to the activation of the PPARγ-UCP-1 signalling pathway. Conclusion. This study preliminarily illustrated the potential components and corresponding core targets of the Renshen and Chaihu herb pair in treating NAFLD. The effect of stigmasterol on the PPARγ-UCP-1 signalling pathway in enhancing lipid metabolism may represent one of the mechanisms of the Renshen and Chaihu herb pair in the treatment of NAFLD. The results provide new evidence and research insights to reveal the roles of Renshen and Chaihu in the management of NAFLD.

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Stigmasterol alleviates cerebral ischemia/reperfusion injury by attenuating inflammation and improving antioxidant defenses in rats

Cited by 60 publications

References 32 publications

Detecting Critical Functional Ingredients Group and Mechanism of Xuebijing Injection in Treating Sepsis

Detecting Critical Functional Ingredients Group and Mechanism of Xuebijing Injection in Treating Sepsis

Phytochemical Characterization, Antioxidant Activity, and Cytotoxicity of Methanolic Leaf Extract of Chlorophytum Comosum (Green Type) (Thunb.) Jacq

A Network Pharmacology Study on the Active Components and Targets of the Radix Ginseng and Radix Bupleuri Herb Pair for Treating Nonalcoholic Fatty Liver Disease

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