Saikosaponins A, C and D enhance liver-targeting effects of anticancer drugs by modulating drug transporters

Feng, Lili; Liu, Lijuan; Zhao, Yutong; Zhao, Ruo

doi:10.18632/oncotarget.22639

Cited by 17 publications

(10 citation statements)

References 26 publications

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“…The most popular source of it, B. chinense, is rich in triterpenoid saikosaponins (Wang et al 2018). Modern pharmacological research shows that saikosaponins isolated from B. chinense such as saikosaponin a (SSa), saikosaponin c (SSc), and saikosaponin d (SSd) have significant antiinflammatory (Chen et al 2018), antidepressant , antitumor (Feng et al 2017), hepatoprotective (Ashour and Wink 2011) and immunomodulatory (Yen et al 2010) effects, with a broad application foreground and high development potential.…”

Section: Introductionmentioning

confidence: 99%

Cloning and functional characterization of the β-amyrin synthase genefrom Bupleurum chinense

Li¹,

Wang²,

Qi³

et al. 2020

Biol. plant.

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Bupleurum chinense DC., a source of the traditional Chinese medicine Bupleuri Radix, is rich in triterpenoid saikosaponins with high pharmacological activities. The enzyme β-amyrin synthase (BAS), which converts the precursor 2,3-oxidosqualene to produce the triterpene skeleton, is crucial for the biosynthesis of triterpenoid saponins. In this study, we cloned the full-length sequence of the BAS gene from B. chinense, conducted a bioinformatics analysis, and expressed it in Saccharomyces cerevisiae to investigate its function. The cDNA of β-amyrin synthase (BcBAS, GenBank accession number: MN186093) cloned from aseptic seedlings of B. chinense was 2 307 bp with a 2 286 bp open reading frame coding for 761 amino acids. Phylogenetic analysis suggests that the BcBAS protein was closely related to the BAS proteins from Panax ginseng and Betula platyphylla as chromatography mass spectrometry analysis showed that the enzymatic product was indeed β-amyrin, the precursor of oleanane type triterpenes. Overall, our findings lay the foundation for in-depth analysis of the biosynthesis pathway of saikosaponins.

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Section: Introductionmentioning

confidence: 99%

Cloning and functional characterization of the β-amyrin synthase genefrom Bupleurum chinense

Li¹,

Wang²,

Qi³

et al. 2020

Biol. plant.

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“…Saikosaponins exert significant pharmacological activities, including antitumor, chemosensitizing, radiosensitizing, anti‐inflammatory, hepatoprotective, nephroprotective, anti‐Alzheimer, neuroprotective, immune‐modulatory, anti‐virus, and so on. Saikosaponins are considered to be the major bioactive ingredients and the key markers for quality control of Radix Bupleuri , which is a famous traditional Chinese medicine (TCM) that has been used for more than 1000 years.…”

Section: Introductionmentioning

confidence: 99%

Localization of malonyl and acetyl on substituted saikosaponins according to the full‐scan mass spectra and the fragmentation of sodium‐adduct ions in the positive mode

Liu

Zhang

et al. 2019

Rapid Comm Mass Spectrometry

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Rationale:Discriminating between aglycone-substituted and saccharide-substituted saikosaponins by liquid chromatography/tandem mass spectrometry (LC/MS n ) is a long-standing issue that is still to be resolved. It is necessary to characterize the two types of substituted saikosaponins taking into consideration the potential significant difference in their bioactivity. Methods:Taking the substituents malonyl and acetyl as examples, we developed a MS strategy to discriminate between the aglycone-substituted and saccharidesubstituted saikosaponins through comparing their Y 0 − nH 2 O (n = 1-2) ions from the protonated molecules in the full-scan mass spectra and their B ions in the MS 2 spectra of sodium-adduct molecules in the positive mode. Results:The deprotonated molecules of the aglycone-substituted saikosaponins presented similar fragmentation patterns to those of saccharide-substituted ones in the negative mode, which could not discriminate whether the substitutes were located on the aglycone or the saccharide. In contrast, the Y 0 − nH 2 O (n = 1-2) ions containing or no substituent were observed respectively in the mass fragmentation of the protonated molecules of aglycone-substituted or saccharide-substituted saikosaponins in the positive mode. In addition, the B ions containing or no substituent were observed respectively in the mass fragmentation of the sodiumadduct molecules of the saccharide-substituted or aglycone-substituted saikosaponins in the positive mode. Two aglycone-malonylated saikosaponins were reported for the first time. Conclusions:Whether the substituents were located on the aglycone or the saccharide could be determined according to the Y 0 − nH 2 O (n = 1-2) ions from the protonated molecules in the full-scan mass spectra and the B ions in the MS 2 spectra of sodium-adduct molecules in the positive mode. Our results have updated the mass fragmentation patterns of substituted saikosaponins, which is helpful for the quality control of pharmaceutical preparations containing saikosaponins. More importantly, this MS strategy should be able to be extended to characterize other substituted saponins of bioactive significance in future studies.

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“…In addition to our findings, there are still a lot interesting points worth further study. Previous studies in cancer treatment suggested that saikosaponins (SSa, SSb, SSc, SSd) be potent adjuvant that are able to override primary drug resistance [42][43][44], improve sensitivity to chemotherapy and radiotherapy [45][46][47], and enhance liver-targeting effects of anticancer drugs [48]. For chronic HBV therapy, various drug combination therapies have been tried.…”

Section: Discussionmentioning

confidence: 99%

Saikosaponin C exerts anti-HBV effects by attenuating HNF1α and HNF4α expression to suppress HBV pgRNA synthesis

Pan

et al. 2019

Inflamm. Res.

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Objective Saikosaponin c (SSc), a compound purified from the traditional Chinese herb of Radix Bupleuri was previously identified to exhibit anti-HBV replication activity. However, the mechanism through which SSc acts against HBV remains unknown. In this study, we investigated the mechanism of SSc mediated anti-HBV activity. Methods HepG2.2.15 cells were cultured at 37 ℃ in the presence of 1-40 μg/mL of SSc or DMSO as a control. The expression profile of HBV markers, cytokines, HNF1α and HNF4α were investigated by real-time quantitative PCR, Elisa, Western blot and Dot blotting. Knockdown of HNF1α or HNF4α in HepG2.2.15 cells was mediated by two small siRNAs specifically targeting HNF1α or HNF4α. Results We found that SSc stimulates IL-6 expression, leading to attenuated HNF1α and HNF4α expression, which further mediates suppression of HBV pgRNA synthesis. Knockdown of HNF1α or HNF4α in HepG2.2.15 cells by RNA interference abrogates SSc's anti-HBV role. Moreover, SSc is effective to both wild-type and drug-resistant HBV mutants. Conclusion SSc inhibits pgRNA synthesis by targeting HNF1α and HNF4α. These results indicate that SSc acts as a promising compound for modulating pgRNA transcription in the therapeutic strategies against HBV infection.

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Saikosaponins A, C and D enhance liver-targeting effects of anticancer drugs by modulating drug transporters

Cited by 17 publications

References 26 publications

Cloning and functional characterization of the β-amyrin synthase genefrom Bupleurum chinense

Cloning and functional characterization of the β-amyrin synthase genefrom Bupleurum chinense

Localization of malonyl and acetyl on substituted saikosaponins according to the full‐scan mass spectra and the fragmentation of sodium‐adduct ions in the positive mode

Saikosaponin C exerts anti-HBV effects by attenuating HNF1α and HNF4α expression to suppress HBV pgRNA synthesis

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