Induction of oxidative stress, apoptosis and DNA damage by koumine in Tetrahymena thermophila

Ye, Qiao; Wang, Qiujie; Wang, Zhenlü; Yuan, Feng; Zhou, Aiguo; Xie, Shaolin; Xiang, Qiong; Song, Enfeng

doi:10.1371/journal.pone.0212231

Cited by 14 publications

(5 citation statements)

References 54 publications

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“…The first total syntheses of (±)-gelsemine were disclosed in 1994 by the groups of Johnson. Gelsemine and koumine of G. elegans inhibited Tetrahymena thermophila cells’ growth in a dose-dependent manner [14,15]. In the present study, two optical isomers, +/− gelsemine (1, 2), together with one known compound, koumine, were isolated from the whole plant of G. elegans (Figure 1).…”

Section: Introductionmentioning

confidence: 58%

The Difference in Cytotoxic Activity between Two Optical Isomers of Gelsemine from Gelsemium elegans Benth. on PC12 Cells

Lin

Liu

2019

Molecules

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Two optical isomers, +/− gelsemine (1, 2), together with one known compound were isolated from the whole plant of G. elegans. The structures of the separated constituents were elucidated on 1D and 2D (1H-1H COSY, HMBC, HSQC) NMR spectroscopy and high-resolution mass spectrometry (HRMS). The isolated alkaloids were tested in vitro for cytotoxic potential against PC12 cells by the MTT assay. As a result, (+) gelsemine (compound 1) exhibited cytotoxic activity against PC12 cells with an IC50 value of 31.59 μM, while (−) gelsemine (compound 2) was not cytotoxic.

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Section: Introductionmentioning

confidence: 58%

The Difference in Cytotoxic Activity between Two Optical Isomers of Gelsemine from Gelsemium elegans Benth. on PC12 Cells

Lin

Liu

2019

Molecules

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“…In studies conducted in China, GEB research has focused on its structural composition, pharmacological effects and its growth-promoting effects on poultry and livestock [ 4 , 7 , 29 ]. In aquaculture, the growth-promoting effects of GEB on aquatic animals have not been systematically studied, and the current work intends to fill this knowledge gap using the guidance of previous studies [ 1 , 12 , 30 ]. As a major component of GEB, KM improved the growth and intestinal health of C. carpio.…”

Section: Discussionmentioning

confidence: 99%

“…It possesses analgesic, anti-cancer, neuroprotective, immunomodulatory, and anti-inflammatory effects [ 9 , 10 , 11 ]. KM demonstrated a a dose-dependent inhibition of Tetrahymena thermophila proliferation, accompanied by the significant ( p < 0.05) elevation of antioxidant enzyme activity and apoptosis, but induced DNA damage at high concentrations in one study [ 12 ]. Overall, KM has rapid pharmacokinetic characteristics and concentration dependence compared to other alkaloids [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of Dietary Koumine on Growth Performance, Intestinal Morphology, Microbiota, and Intestinal Transcriptional Responses of Cyprinus carpio

Wang

Zuo

et al. 2022

IJMS

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Gelsemium elegans Benth. (GEB) is a traditional medicinal plant in China, and acts as a growth promoter in pigs and goats. Koumine (KM) is the most abundant alkaloid in GEB and produces analgesic, anti-cancer, and immunomodulatory effects. KM can be used as an aquatic immune stimulant, but its growth-promoting effects and transcriptional mechanisms have not been investigated. Diets containing KM at 0, 0.2, 2, and 20 mg/kg were fed to Cyprinus carpio for 71 days to investigate its effects on growth performance, intestinal morphology, microflora, biochemical indicators, and transcriptional mechanisms. Cyprinus carpio fed with KM as the growth promoter, and the number of intestinal crypts and intestinal microbial populations were influenced by KM concentration. KM increased the abundance of colonies of Afipia, Phyllobacterium, Mesorhizobium, and Labrys, which were associated with compound decomposition and proliferation, and decreased the abundance of colonies of pathogenic bacteria Methylobacterium-Methylorubrum. A total of 376 differentially-expressed genes (DEGs) among the four experimental groups were enriched for transforming growth factor-β1 and small mother against decapentaplegic (TGF-β1/Smad), mitogen-activated protein kinase (MAPK), and janus kinases and signal transducers and activators of transcription (Jak/Stat) signaling pathways. In particular, tgfbr1, acvr1l, rreb-1, stat5b, smad4, cbp, and c-fos were up-regulated and positively correlated with KM dose. KM had a growth-promoting effect that was related to cell proliferation driven by the TGF-β1/Smad, MAPK, and Jak/Stat signaling pathways. KM at 0.2 mg/kg optimized the growth performance of C. carpio, while higher concentrations of KM (2 and 20 mg/kg) may induce apoptosis without significantly damaging the fish intestinal structure. Therefore, KM at low concentration has great potential for development as an aquatic growth promotion additive.

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“…Following a 4 h co-incubation with wild-type V. cholerae , Triton-X (1% final concentration) was added to the protozoan cells and the sample was centrifuged at 20,598 × g for 2 min to collect the supernatant containing the oxidative radicals. Oxidative radicals were measured using the dye 2′,7′-dichlorofluorescin diacetate (DCF-DA) as previously described [ 25 ]. Briefly, 10 µM DCF-DA (Sigma, USA) was added and the supernatant incubated at 37 °C for 30 min.…”

Section: Methodsmentioning

confidence: 99%

Protozoal food vacuoles enhance transformation in Vibrio cholerae through SOS-regulated DNA integration

et al. 2022

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Vibrio cholerae, the bacterial pathogen responsible for the diarrheal disease cholera, resides in the aquatic environment between outbreaks. For bacteria, genetic variation by lateral gene transfer (LGT) is important for survival and adaptation. In the aquatic environment, V. cholerae is predominantly found in biofilms associated with chitinous organisms or with chitin “rain”. Chitin induces competency in V. cholerae, which can lead to LGT. In the environment, V. cholerae is also subjected to predation pressure by protist. Here we investigated whether protozoal predation affected LGT using the integron as a model. Integrons facilitate the integration of mobile DNA (gene cassettes) into the bacterial chromosome. We report that protozoal predation enhances transformation of a gene cassette by as much as 405-fold. We show that oxidative radicals produced in the protozoal phagosome induces the universal SOS response, which in turn upregulates the integron-integrase, the recombinase that facilitates cassette integration. Additionally, we show that during predation, V. cholerae requires the type VI secretion system to acquire the gene cassette from Escherichia coli. These results show that protozoal predation enhances LGT thus producing genetic variants that may have increased capacity to survive grazing. Additionally, the conditions in the food vacuole may make it a “hot spot” for LGT by accumulating diverse bacteria and inducing the SOS response helping drive genetic diversification and evolution.

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Induction of oxidative stress, apoptosis and DNA damage by koumine in Tetrahymena thermophila

Cited by 14 publications

References 54 publications

The Difference in Cytotoxic Activity between Two Optical Isomers of Gelsemine from Gelsemium elegans Benth. on PC12 Cells

The Difference in Cytotoxic Activity between Two Optical Isomers of Gelsemine from Gelsemium elegans Benth. on PC12 Cells

Effects of Dietary Koumine on Growth Performance, Intestinal Morphology, Microbiota, and Intestinal Transcriptional Responses of Cyprinus carpio

Protozoal food vacuoles enhance transformation in Vibrio cholerae through SOS-regulated DNA integration

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