Genotoxic and mutagenic properties of synthetic betulinic acid and betulonic acid

Фролова, Т. С.; Кукина, Т. П.; Синицына, О. И.

doi:10.1134/s1068162015040056

Cited by 7 publications

(4 citation statements)

References 34 publications

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“…Similar to our findings, Frolova et al. [48], demonstrated the absence of mutagenic and genotoxic activity of BA in the Ames test and SOS chromotest. A lack of genotoxicity of BA, a triterpenoid, has also been reported in normal human lymphocyte and fibroblast cells [19, 49, 50].…”

Section: Discussionsupporting

confidence: 93%

Potential antigenotoxicity assessment of Ziziphus jujuba fruit

Goswami¹,

Banerjee²,

Mukherjee

2019

Heliyon

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Ziziphus jujuba Mill. fruits are nutritionally rich and have a broad spectrum of health benefits. In this work we hypothesized that this natural product rich in polyphenols might protect humans against DNA damage and its consequences. This has led to our investigation to find out if the fruit extract showed an ability to decrease the frequency of DNA damage (antigenotoxicity) induced by two known genotoxins namely an alkylating agent methyl methane sulphonate (MMS) and a reactive oxygen species (ROS) inducer hydrogen peroxide (H 2 O 2 ). Human lymphocytes were incubated with the Ziziphus fruit ethanol extracts (ZFE) or betulinic acid (BA) followed by an exposure to either 50 μM of MMS or 250 μM of H 2 O 2 . Results suggest that ZFE (250, 500, 1000 μg/ml) and BA (10, 20, 40 μg/ml) were able to inhibit the DNA damaging effect caused by MMS and H 2 O 2 indicative of their protection against the genotoxin. This could be attributed to the interactions of the phenolics, flavonoid and BA present in the fruits. Additional in vivo experiments were carried since BA is an important phytochemical detected in ample amounts in the fruit extract. Mice were primed with BA (2.5, 5.0 and 10 mg/kg body weight) for a period of 6 days. The animals were injected with MMS (10 mg/kg body weight) 24 h later and sacrificed. The genotoxic activity of MMS was inhibited in a dose – related manner by BA. BA reduced the frequency of MMS – induced DNA damage in liver, kidney and bone marrow cells of mice thereby exhibiting its antigenotoxic properties. It could also reduce total glutathione level, lipid peroxidation and hydrogen peroxide content in liver cells of mice through the up-regulation of antioxidant enzymes. Therefore taking into account the antioxidant and antigenotoxic properties, the consumption of the Ziziphus fruit should be more popularized worldwide.

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Section: Discussionsupporting

confidence: 93%

Potential antigenotoxicity assessment of Ziziphus jujuba fruit

Goswami¹,

Banerjee²,

Mukherjee

2019

Heliyon

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“…According to Rundell et al (2003) , genotoxic damage is likely to undergo repair, whereas mutagenic damage is not, with changes becoming fixed in the genetic material as mutations. Such occurrence is not uncommon in preclinical chemoprevention experiments, both with natural products ( Synder and Gillies, 2002 ; Cunha et al , 2005 ; Rodeiro et al , 2006 ; Hoshina et al , 2013 ; Mendanha da Cunha et al , 2013 ; Luo et al , 2015 ) and with synthetic compounds ( Zhan et al , 2008 ; Cao et al , 2015 ; Frolova et al , 2015 ; de Araújo et al , 2017 ). Although there are significant differences in the frequency of micronuclei between the negative control group and the groups treated with IR-01, Vaz et al (2016) describes that this isolated fact does not necessarily imply in toxicogenetic damage.…”

Section: Discussionmentioning

confidence: 99%

Assessment of genetic integrity, splenic phagocytosis and cell death potential of (Z)-4-((1,5-dimethyl-3-oxo-2-phenyl-2,3dihydro-1H-pyrazol-4-yl) amino)-4-oxobut-2-enoic acid and its effect when combined with commercial chemotherapeutics

et al. 2018

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The increased incidence of cancer and its high treatment costs have encouraged the search for new compounds to be used in adjuvant therapies for this disease. This study discloses the synthesis of (Z)-4-((1,5-dimethyl-3-oxo-2-phenyl-2,3dihydro-1H-pyrazol-4-yl) amino)-4-oxobut-2-enoic acid (IR-01) and evaluates not only the action of this compound on genetic integrity, increase in splenic phagocytosis and induction of cell death but also its effects in combination with the commercial chemotherapeutic agents doxorubicin, cisplatin and cyclophosphamide. IR-01 was designed and synthesized based on two multifunctionalyzed structural fragments: 4-aminoantipyrine, an active dipyrone metabolite, described as an antioxidant and anti-inflammatory agent; and the pharmacophore fragment 1,4-dioxo-2-butenyl, a cytotoxic agent. The results indicated that IR-01 is an effective chemoprotector because it can prevent clastogenic and/or aneugenic damage, has good potential to prevent genomic damage, can increase splenic phagocytosis and lymphocyte frequency and induces cell death. However, its use as an adjuvant in combination with chemotherapy is discouraged since IR-01 interferes in the effectiveness of the tested chemotherapeutic agents. This is a pioneer study as it demonstrates the chemopreventive effects of IR-01, which may be associated with the higher antioxidant activity of the precursor structure of 4-aminoantipyrine over the effects of the 1,4-dioxo-2-butenyl fragment.

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“…The in vitro anthelmintic testing of UA and BA on Hymenolepis diminuta (Cestoda) has also revealed that both the compounds possess significant & Arun K. Yadav akynehu@hotmail.com anthelmintic effects (Vijaya and Yadav 2016). The genotoxic testing of BA, using Ames and SOS chromotests, did not revealed any genotoxic or mutagenic effects (Frolova et al 2015). Further, Mullauer et al (2010) have also reported a complete absence of systemic toxicity by BA treatment in rodents up to a dose of 500 mg/kg.…”

Section: Introductionmentioning

confidence: 99%

In vitro and in vivo anthelmintic efficacy of two pentacyclic triterpenoids, ursolic acid and betulinic acid against mice pinworm, Syphacia obvelata

2017

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Pinworm infections are one of the common problems in laboratory rodents and man. At present there are only few drugs against intestinal helminths, and new drugs are urgently needed to cope up any future risk of drug resistance. Interest in plant secondary metabolites (PSMs) has risen considerably in the recent years for the discovery and development of new drugs. In the present study, we explored the in vitro and in vivo anthelmintic potentials of two pentacyclic triterpenoids, ursolic acid (UA) and betulinic acid (BA), the important PSMs of many medicinal plants, against (Nematoda: Oxyuridae), a common pinworm of mice. The results of this study indicated that in both, in vitro and in vivo assays, BA showed comparatively better anthelmintic effects than UA. In the in vitro assay, 1.00 mg/ml concentration of BA showed paralysis and mortality of worms in 1.20 ± 0.04 and 2.30 ± 0.03 h, respectively. In the in vivo assay, a single 10.00 mg/kg dose of BA, administered for 5 days, revealed 68.78% reduction in egg counts and 84.08% reduction in worm counts of infected mice. The present study suggests that BA holds a great promise to be pursued further for detailed testing against some other representative group of helminth parasites.

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Genotoxic and mutagenic properties of synthetic betulinic acid and betulonic acid

Cited by 7 publications

References 34 publications

Potential antigenotoxicity assessment of Ziziphus jujuba fruit

Potential antigenotoxicity assessment of Ziziphus jujuba fruit

Assessment of genetic integrity, splenic phagocytosis and cell death potential of (Z)-4-((1,5-dimethyl-3-oxo-2-phenyl-2,3dihydro-1H-pyrazol-4-yl) amino)-4-oxobut-2-enoic acid and its effect when combined with commercial chemotherapeutics

In vitro and in vivo anthelmintic efficacy of two pentacyclic triterpenoids, ursolic acid and betulinic acid against mice pinworm, Syphacia obvelata

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