Potent effects of alkaloid-rich extract from Huperzia selago against sodium nitroprusside-evoked PC12 cells damage via attenuation of oxidative stress and apoptosis

Lenkiewicz, Anna; Czapski, Grzegorz A.; Jęśko, Henryk; Wilkaniec, Anna; Szypuła, Wojciech J.; Pietrosiuk, Agnieszka; Uszyńska, Aneta Marta; Adamczyk, Agata

doi:10.5114/fn.2016.60361

Cited by 12 publications

(7 citation statements)

References 36 publications

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“…Table 2 shows that SNP-induced nitrosative stress caused severe damage to the mitochondria of hepatic and neuronal cells and significantly reduced MMP. Since it has been shown that higher concentrations of RNS can inhibit not only complex IV of the respiratory chain but also complexes I and III [26, 40], these results were expected. Further, these changes led to a decreased production of ATP at complex V. We used hepatic HepG2 cells due to their low expression of Cyp450 enzymes and thus their low metabolism of xenobiotics [41] to gain better insight into the effect of SIL A on the cells.…”

Section: Discussionmentioning

confidence: 93%

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Differential Effects of Silibinin A on Mitochondrial Function in Neuronal PC12 and HepG2 Liver Cells

Esselun

Bruns

Hagl

et al. 2019

Oxidative Medicine and Cellular Longevity

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The Mediterranean plant Silybum marianum L., commonly known as milk thistle, has been used for centuries to treat liver disorders. The flavonolignan silibinin represents a natural antioxidant and the main bioactive ingredient of silymarin (silybin), a standard extract of its seeds. Mitochondrial dysfunction and the associated generation of reactive oxygen/nitrogen species (ROS/RNS) are involved in the development of chronic liver and age-related neurodegenerative diseases. Silibinin A (SIL A) is one of two diastereomers found in silymarin and was used to evaluate the effects of silymarin on mitochondrial parameters including mitochondrial membrane potential and ATP production with and without sodium nitroprusside- (SNP-) induced nitrosative stress, oxidative phosphorylation, and citrate synthase activity in HepG2 and PC12 cells. Both cell lines were influenced by SIL A, but at different concentrations. SIL A significantly weakened nitrosative stress in both cell lines. Low concentrations not only maintained protective properties but also increased basal mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP) levels. However, these effects could not be associated with oxidative phosphorylation. On the other side, high concentrations of SIL A significantly decreased MMP and ATP levels. Although SIL A did not provide a general improvement of the mitochondrial function, our findings show that SIL A protects against SNP-induced nitrosative stress at the level of mitochondria making it potentially beneficial against neurological disorders.

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Section: Discussionmentioning

confidence: 93%

“…Nitrosative stress in the form of nitric oxide radicals plays a role in the aging process and in neurodegenerative diseases by contributing to inflammation, neuronal loss, and oxidative stress [24, 25]. SNP is a source widely used to introduce nitrosative stress into cellular models [15, 26].…”

Section: Introductionmentioning

confidence: 99%

Differential Effects of Silibinin A on Mitochondrial Function in Neuronal PC12 and HepG2 Liver Cells

Esselun

Bruns

Hagl

et al. 2019

Oxidative Medicine and Cellular Longevity

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“…The major therapeutic interest described for HupA is as treatment for acetylcholine-deficit dementia, including Alzheimer's disease [6]. Our previous results [31,32] demonstrated for the first time that alkaloids from H. selago possess antioxidative properties and scavenge free radicals as well as prevent lipid and protein oxidation, presenting the desired mechanism of action in neurodegenerative disorders. These alkaloids might be a promising source of active constituents of novel treatments for Alzheimer's and Parkinson's diseases [6,8].…”

Section: Discussionmentioning

confidence: 95%

“…(=Lycopodium selago L., fir club moss, Huperziaceae Rothm) gametophytes (prothallus), which is the best available and rich source of huperzine A (HupA, selagine) and other alkaloids. These compounds have a considerable therapeutic potential and are being extensively investigated for uses as treatments for a number of diseases [5,6,11,31,32]. The major therapeutic interest described for HupA is as treatment for acetylcholine-deficit dementia, including Alzheimer's disease [6].…”

Section: Discussionmentioning

confidence: 99%

Huperzine A and Huperzine B Production by Prothallus Cultures of Huperzia selago (L.) Bernh. ex Schrank et Mart

et al. 2020

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This is the first report of an efficient and effective procedure to optimize the biosynthesis of huperzine A (HupA) and huperzine B (HupB) in vitro from Huperzia selago gametophytes. Axenic tissue cultures were established using spores collected from the sporophytes growing in the wild. The prothalia were obtained after 7–18 months. Approximately 90 up to 100% of the gametophytes were viable and grew rapidly after each transfer on to a fresh medium every 3 months. The best biomass growth index for prothallus calculated on a fresh (FW) and dry weight (DW) basis, at 24 weeks of culture, was 2500% (FW) and 2200% (DW), respectively. The huperzine A content in the gametophytes was very high and ranged from 0.74 mg/g to 4.73 mg/g DW. The highest yield HupA biosynthesis at >4 mg/g DW was observed on W/S medium without growth regulators at 8 to 24 weeks of culture. The highest HupB content ranged from 0.10 mg/g to 0.52 mg/g DW and was obtained on the same medium. The results demonstrate the superiority of H. selago gametophyte cultures, with the level of HupA biosynthesis approximately 42% higher compared to sporophyte cultures and 35-fold higher than when the alkaloid was isolated from H. serrata, its current source for the pharmaceutical industry. Moreover, the biosynthesis of HupB was several-fold more efficient than in H. selago sporophytes growing in the wild. HPLC-HR-MS analyses of the extracts identified eight new alkaloids previously unreported in H. selago: deacetylfawcettine, fawcettimine, 16-hydroxyhuperzine B, deacetyllycoclavine, annopodine, lycopecurine, des-N-methylfastigiatine and flabelline.

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“…That is consistent with previous studies that direct production of nitric oxide (NO) via addition of the NO donor sodium nitroprusside (SNP) to cells caused oxidative stress damage and apoptosis. 26,27 The results showed that the viability of HUVECs was decreased in a concentration-dependent manner by SNP ( Figure 1B), When DMY was added, the apoptosis of cells were attenuated ( Figure 1C). SNP decreased the FoxO3a and Akt phosphorylation, in a concentration and time-dependent manner (Figure 4).…”

Section: Discussionmentioning

confidence: 98%

Dihydromyricetin protects HUVECs of oxidative damage induced by sodium nitroprusside through activating PI3K/Akt/FoxO3a signalling pathway

Zhang

Wang

et al. 2019

J Cellular Molecular Medi

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The damage of vascular endothelial cells induced by oxidative stress plays an important role in the pathogenesis of atherosclerosis. Dihydromyricetin (DMY) is considered as a natural antioxidant. However, the mechanism of DMY on endothelial cell injury induced by oxidative stress remains unclear. In this study, we found that DMY could reduce the oxidative damage of HUVECs induced by sodium nitroprusside (SNP), HUVECs pre‐treated with DMY suppressed SNP‐induced apoptosis by reduced ROS overproduction of intracellular, decreased MDA level and elevated the superoxide dismutase activity. Meanwhile, we found that DMY could promote the expression of phosphorylated FoxO3a and Akt, and affect the nuclear localization of FoxO3a, when treated with the PI3K inhibitor LY294002, the effect of DMY was blocked. These data suggest that DMY protects HUVECs from oxidative stress by activating PI3K/Akt/FoxO3a signalling pathway. Therefore, DMY may have great therapeutic potential as a new drug for atherosclerosis.

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Potent effects of alkaloid-rich extract from Huperzia selago against sodium nitroprusside-evoked PC12 cells damage via attenuation of oxidative stress and apoptosis

Abstract: A b s t r a c t Imbalance between production and scavenging of free radicals and other reactive oxygen species (ROS) is a component of many diseases, but it is especially important in aging-

Cited by 12 publications

References 36 publications

Differential Effects of Silibinin A on Mitochondrial Function in Neuronal PC12 and HepG2 Liver Cells

Differential Effects of Silibinin A on Mitochondrial Function in Neuronal PC12 and HepG2 Liver Cells

Huperzine A and Huperzine B Production by Prothallus Cultures of Huperzia selago (L.) Bernh. ex Schrank et Mart

Dihydromyricetin protects HUVECs of oxidative damage induced by sodium nitroprusside through activating PI3K/Akt/FoxO3a signalling pathway

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