The targets of β-sitosterol as a novel therapeutic against cardio-renal complications in acute renal ischemia/reperfusion damage

Koç, Kübra; Geyikoğlu, Fatime; Cakmak, Özge; Koca, Aynur; Kutlu, Zerrin; Aysin, Ferhunde; Yilmaz, Aslı; Aşkın, Hakan

doi:10.1007/s00210-020-01984-1

Cited by 27 publications

(14 citation statements)

References 39 publications

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“…It has been reported that beta-sitosterol plays a protective role in the chemical-induced injury of tissues, organs and apoptosis. 33 , 34 It enters the cell membrane via a ESR1 mediated PI3K/GSK3 beta signal transduction pathway to enhance the resistance to oxidative stress and lipid peroxidation to slow the aging process. 35 …”

Section: Discussionmentioning

confidence: 99%

Mechanism of Ba Zhen Tang Delaying Skin Photoaging Based on Network Pharmacology and Molecular Docking

Han¹,

Li²,

Ke³

et al. 2022

CCID

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Purpose To study the efficacy of Ba Zhen Tang in delaying skin photoaging and its potential mechanism based on network pharmacology and molecular docking. Methods First, we screened the active components and targets of Ba Zhen Tang by Traditional Chinese Medicine Database and Analysis Platform (TCMSP) and The Universal Protein Resource (UniProt). The target genes of skin photoaging were obtained from GeneCards and GeneMap database. Then, we analyzed the protein–protein interaction (PPI) by STRING database. The network map was constructed by Cytoscape. Finally, we performed Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis by Metascape database. The molecular docking via Autodock Vina and Pymol. Furthermore, skin photoaging cellular models were established, and the effects of Ba Zhen Tang on ameliorating skin photoaging were investigated. Results A total of 160 active ingredients in Ba Zhen Tang and 60 targets of Ba Zhen Tang for delaying skin photoaging were identified. By GO enrichment analysis, 1153 biological process entries, 45 cellular component entries and 89 molecular functional entries were obtained. A total of 155 signal pathways were obtained by KEGG analysis. Ba Zhen Tang is related to MAPK signaling pathway, TNF signaling pathway and AGE-RAGE signaling pathway in diabetic complications, etc., which directly affect the key nodes of photoaging. The molecular docking results showed that there was a certain affinity between the main compounds (kaempferol, quercetin, β-sitosterol, naringenin) and core target genes (PTGS2, CASP3, MAPK1, MAPK3, TP53). Ba Zhen Tang-treated mouse serum inhibited the senescence and p16 INK4a expression of human immortalized keratinocyte (HaCaT) cells irradiated by ultraviolet-B (UVB). Conclusion Our study elucidated the potential pharmacological mechanism of Ba Zhen Tang in the treatment of photoaging through multiple targets and pathways. The therapeutic effects of Ba Zhen Tang on skin photoaging were validated in cellular models.

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Section: Discussionmentioning

confidence: 99%

Mechanism of Ba Zhen Tang Delaying Skin Photoaging Based on Network Pharmacology and Molecular Docking

Han¹,

Li²,

Ke³

et al. 2022

CCID

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“…β -Sitosterol has anti-inflammatory effects. Sitosterol may inhibit renal and cardiac necrosis and apoptosis by limiting inflammatory response and oxidative stress [ 25 ]. Isorhamnetin has a protective effect on ischemia–reperfusion injury of isolated rat hearts [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Mechanisms of Tinglizi against Chronic Heart Failure Determined by Network Pharmacology and Molecular Docking

Luo

Wang

Huang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Objective. Tinglizi has been extensively used to treat chronic heart failure (CHF) in modern times, but the material basis and pharmacological mechanisms are still unclear. To explore the material basis and corresponding potential targets and to elucidate the mechanism of Tinglizi, network pharmacology and molecular docking methods were utilized. Methods. The main chemical compounds and potential targets of Tinglizi were collected from the pharmacological database analysis platform (TCMSP). The corresponding genes of related action targets were queried through gene cards and UniProt database. The corresponding genes of CHF-related targets were searched through Disgenet database, and the intersection targets were obtained by drawing Venn map with the target genes related to pharmacodynamic components. Then, drug targets and disease targets were intersected and put into STRING database to establish a protein interaction network. The “active ingredient-CHF target” network was constructed with Cytoscape 3.8.2. Finally, Gene Ontology (GO) Enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of intersection targets were analyzed using metascape. With the aid of SYBYL software, the key active ingredients and core targets were docked at molecular level, and the results were visualized by PyMOL software. Molecular docking was carried out to investigate interactions between active compounds and potential targets. Results. A total of 12 active components in Tinglizi were chosen from the TCMSP database, and 193 corresponding targets were predicted. Twenty-nine potential targets of Tinglizi on CHF were obtained, of which nine were the core targets of this study. Twenty GO items were obtained by GO function enrichment analysis ( P < 0.05 ), and 10 signal pathways were screened by KEGG pathway enrichment analysis ( P < 0.05 ), which is closely related to the treatment of CHF by Tinglizi. The constructed drug compound composition action target disease network shows that quercetin, kaempferol, and other active compounds play a key role in the whole network. The results of molecular docking showed that all the key active ingredients, such as quercetin and isorhamnetin, were able to successfully dock with ADRB2 and HMOX1 with a total score above 5.0, suggesting that these key components have a strong binding force with the targets. Conclusion. Through network pharmacology and molecular docking technology, we found that the main components of Tinglizi in the treatment of CHF are quercetin, kaempferol, β-sitosterol, isorhamnetin, and so on. The action targets are beta 2-adrenergic receptor (ADRB2), heme oxygenase 1 (HMOX1), and so on. The main pathways are advanced glycation end products/receptor for advanced glycation end products (AGE-RAGE) signaling pathway in diabetic complications, hypoxia-inducible factor (HIF-1) signaling pathway, estrogen signaling pathway, and so on. They play an integrated role in the treatment of CHF.

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“…Cao et al reported that oleanolic acid and ursolic acid, as the active components of FLL, had a beneficial effect on calcium balance and calcium stimulating hormone circulation level, so it is expected to become a candidate drug for the prevention and treatment of osteoporosis [ 78 ]. Acacetin, beta-sitosterol, apigenin, and kaempferol, as active components of Chinese medicine, have been screened and reported for many times in the treatment of many diseases [ 79 , 80 ]. In addition, EZF was quantitatively analyzed by HPLC, and the contents of active components such as specnuezhenide and wedelolactone were detected.…”

Section: Discussionmentioning

confidence: 99%

Elaborate the Mechanism of Ancient Classic Prescriptions (Erzhi Formula) in Reversing GIOP by Network Pharmacology Coupled with Zebrafish Verification

Cai

Wang

Jiang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Osteoporosis is a degenerative disease that endangers human health. At present, chemical drugs used for osteoporosis have serious side effects. Therefore, it is valuable to search herbs with high safety and good curative effect in antiosteoporosis. Erzhi formula (EZF), an ancient classic compound, has been reported to have a beneficial effect in antiosteoporosis, but its mechanism is unclear. In this paper, the active compounds of EZF were found in Systems Pharmacology Database, and gene targets related to osteoporosis were obtained in GeneCards. The GO functional and KEGG pathway enrichment analysis were performed by Metascape. The network of “components-targets-signal pathway” was constructed by Cytoscape. Next, molecular docking between the active components and hub genes related to the PI3K-Akt signaling pathway was conducted by Autodock. In the verification experiment, the zebrafish induced by prednisolone (PNSL) was used to reproduce glucocorticoid-induced osteoporosis (GIOP) model, and then the reversal effects of EZF were systematically evaluated according to the behavior, skull staining area, bone mineralization area (BMA), average optical density (AOD), and cumulative optical density (COD). Finally, it was shown that 24 components in EZF could regulate 39 common gene targets to exert antiosteoporosis effect. Besides, the main regulatory mechanisms of EZF were 4 signaling pathways: PI3K-Akt, JAK-STAT, AGE-RAGE, and cancer pathway. In PI3K-Akt signaling pathway, wedelolactone, dimethyl wedelolactone, specnuezhenide, ursolic acid, acacetin, beta-sitosterol, apigenin, and kaempferol can bind tightly with EGF, IL-2, and IL-4 genes. Compared with the model group, the moving distance, swimming speed, and cumulative swimming time of zebrafish in EZF group were significantly increased ( P < 0.05 ). Meanwhile, the BMA and COD of zebrafish were significantly improved after the intervention of EZF ( P < 0.05 ). In summary, the 24 components of EZF exert their antiosteoporosis effects by regulating 39 related gene targets, among which the PI3K signaling pathway is crucial. EZF can promote bone formation and reversed GIOP through “multicomponent/multitarget/multipathway” and the medium dose of EZF may be the most suitable concentration for the treatment of GIOP in zebrafish model.

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The targets of β-sitosterol as a novel therapeutic against cardio-renal complications in acute renal ischemia/reperfusion damage

Cited by 27 publications

References 39 publications

Mechanism of Ba Zhen Tang Delaying Skin Photoaging Based on Network Pharmacology and Molecular Docking

Mechanism of Ba Zhen Tang Delaying Skin Photoaging Based on Network Pharmacology and Molecular Docking

Pharmacological Mechanisms of Tinglizi against Chronic Heart Failure Determined by Network Pharmacology and Molecular Docking

Elaborate the Mechanism of Ancient Classic Prescriptions (Erzhi Formula) in Reversing GIOP by Network Pharmacology Coupled with Zebrafish Verification

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