Quassinoids from Brucea javanica and attenuates lipopolysaccharide-induced acute lung injury by inhibiting PI3K/Akt/NF-κB pathways

He, Xueling; Wu, Jiahui; Tan, Ting; Guo, Wenjing; Xiong, Ziwei; Yang, Shilin; Feng, Yulin; Wen, Quan

doi:10.1016/j.fitote.2021.104980

Cited by 11 publications

(6 citation statements)

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“…Akt activation plays an important role in inflammation, apoptosis, and immunity [50,54]. The correlation between inflammatory response and PI3K/Akt signaling pathway had been reported in several other papers [37,55,56]. Therefore, to study the relationship between PI3K/Akt signaling pathways and ALI, we studied the PI3K/Akt signaling pathway and its downstream apoptosis-related pathways related to proteins via molecular biology experiments, such as PIP3, and p-PI3K, p-Akt, Bcl-2, Bax, etc.…”

Section: Discussionmentioning

confidence: 80%

Aqueous extract of Platycodon grandiflorus attenuates lipopolysaccharide-induced apoptosis and inflammatory cell infiltration in mouse lungs by inhibiting PI3K/Akt signaling

et al. 2023

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Background Acute lung injury (ALI), an acute inflammatory lung disease, can cause a rapid inflammatory response in clinic, which endangers the patient's life. The components of platycodon grandiflorum, such as platycodins have a wide range of pharmacological activities such as expectorant, anti-apoptotic, anti-inflammatory, anti-tumor and anti-oxidant properties, and can be used for improving human immunity. Previous studies have shown that aqueous extract of platycodon grandiflorum (PAE) has a certain protective effect on ALI, but the main pharmacodynamic components and the mechanism of action are not clear. Methods The anti-inflammatory properties of PAE were studied using the lipopolysaccharide (LPS)-induced ALI animal model. Hematoxylin and eosin stains were used to assess the degree of acute lung damage. Changes in RNA levels of pro-inflammatory cytokines in the lungs were measured using quantitative RT-qPCR. The potential molecular mechanism of PAE preventing ALI was predicted by lipidomics and network pharmacology. To examine the anti-apoptotic effects of PAE, TdT-mediated dUTP nick-end labelling (TUNEL) was employed to determine apoptosis-related variables. The amounts of critical pathway proteins and apoptosis-related proteins were measured using Western blotting. Results Twenty-six chemical components from the PAE were identified, and their related pathways were obtained by the network pharmacology. Combined with the analysis of network pharmacology and literature, it was found that the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signaling pathway is related to ALI. The results of lipidomics show that PAE alleviates ALI via regulating lung lipids especially phosphatidylinositol (PI). Finally, the methods of molecular biology were used to verify the mechanism of PAE. It can be found that PAE attenuates the inflammatory response to ALI by inhibiting apoptosis through PI3K/Akt signaling pathway. Conclusion The study revealed that the PAE attenuates lipopolysaccharide-induced apoptosis and inflammatory cell infiltration in mouse lungs by inhibiting PI3K/Akt signaling. Furthermore, our findings provide a novel strategy for the application of PAE as a potential agent for preventing patients with ALI.

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Section: Discussionmentioning

confidence: 80%

Aqueous extract of Platycodon grandiflorus attenuates lipopolysaccharide-induced apoptosis and inflammatory cell infiltration in mouse lungs by inhibiting PI3K/Akt signaling

et al. 2023

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“…Most of them were reported to have biological activities (Ye et al, 2015). Bruceine A-J, M (1-11) (Polonsky et al, 1967;Duncan and Henderson, 1968;Lee et al, 1979;Zhao et al, 2011;Chen et al, 2013;Su et al, 2013;Li et al, 2021), bruceanic acids E-F, bruceanic acids E methyl ester (12-14) , javanicolide A-E, and H (15-20) (Su et al, 2002;Kim et al, 2003;Kim et al, 2004b;, javanicoside B-G, I-L (21-30) (Kim et al, 2004a;Kim et al, 2004b;He et al, 2021), javanic acids A-B (31-32) , yadanzioside A-C, E-G, I,K,L-P (33-45) (Sakaki et al, 1985;Yoshimura et al, 1985;Sakaki et al, 1986;Kim et al, 2004b;Chen et al, 2011;Zhao et al, 2011;Su et al, 2013;Ye et al, 2015;He et al, 2021), yadanziolide C-S (46-47) (Su et al, 2013;He et al, 2021), yadanzigan (48) (Zhan et al, 2020), 20-hydroxyyadanzigan (49) (Zhan et al, 2020), brusatol (50) (Sim et al, 1968), bruceantin (51) (Su et al, 2013), bruceantinol (52) (Kupchan et al, 1975), bruceantinosides A (53) (Zhao et al, 2011), bruceoside A-F (54-59) (Ohnishi et al, 1995;Su et al, 2013;He et al, 2021), bruceene (60) (Su et al, 2013), bruceajavanin A-B (61-62) (Kitagawa et al, 1994), brujavanol A-D (63-66) ; Chumkaew and Srisawat, 2017), dihydrobruceajavanin A 67) (Kitagawa et al, 1994), demethyld...…”

Section: Quassinoidsmentioning

confidence: 99%

Major Constituents From Brucea javanica and Their Pharmacological Actions

Zhang

Dou

et al. 2022

Front. Pharmacol.

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Brucea javanica (Ya-dan-zi in Chinese) is a well-known Chinese herbal medicine, which is traditionally used in Chinese medicine for the treatment of intestinal inflammation, diarrhea, malaria, and cancer. The formulation of the oil (Brucea javanica oil) has been widely used to treat various types of cancer. It has also been found that B. javanica is rich in chemical constituents, including quassinoids, triterpenes, alkaloids and flavonoids. Pharmacological studies have revealed that chemical compounds derived from B. javanica exhibit multiple bioactivities, such as anti-cancer, anti-bacterial, anti-diabetic, and others. This review provides a comprehensive summary on the pharmacological properties of the main chemical constituents presented in B. javanica and their underlying molecular mechanisms. Moreover, the review will also provide scientific references for further research and development of B. javanica and its chemical constituents into novel pharmaceutical products for disease management.

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“…Bruceoside B, in particular, inhibited Akt and showed promise as a therapeutic lead structure for acute lung injury in an in vivo lipopolysaccharide (LPS) model. 9 Bruceantin (6), in contrast, was recently identified as a potent inhibitor of aberrant full-length androgen receptor (AR-FL) and its constitutively active variant 7 (AR-V7) in a cellbased castration-resistant prostate cancer (CRPC) reporter assay. In this case, mechanistic evidence pointed toward the quassinoid binding to heat shock protein 90 (HSP90) and disrupting the HSP90 complex with AR-FL/AR-V7.…”

Section: Selected Structure-activity Relationships and Investigations...mentioning

confidence: 99%

“…Bruceoside B, in particular, inhibited Akt and showed promise as a therapeutic lead structure for acute lung injury in an in vivo lipopolysaccharide (LPS) model. 9…”

Section: Selected Structure–activity Relationships and Investigations...mentioning

confidence: 99%

“…Since their isolation and structural elucidation, quassinoids such as quassin (5) and brusatol (7) have been the subject of intensive biological and synthetic studies attributable to their potent biological properties. [3][4][5][6][7][8][9][10][11][12] For example, the quassinoid bruceantin (6) has reached phase II clinical trials for the treatment of metastatic breast cancer and malignant melanoma in 1982 and 1983, respectively. 13,14 Although originally dismissed for its toxic side effects, bruceantin still appears to sustain potential as a viable drug candidate for several cancer types.…”

Section: Introductionmentioning

confidence: 99%

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