The discovery of bioisoster compound for plumbagin using the knowledge-based rational method

Jeong, Seo Hee; Choi, Jung Sup; Ko, Yongmin; Kang, Nam Sook

doi:10.1016/j.molstruc.2014.12.025

Cited by 6 publications

(5 citation statements)

References 20 publications

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“…PI is extensively used in Ayurvedic and Thai traditional remedies, especially as a hematinic agent and for post-partum women [ 2 ]. Besides, the numerous pharmacological properties, the active constituent of PI, plumbagin, have been reported to possess many undesirable effects [ 25 ] principally due to its capability to generate ROS, leading to an imbalance of the oxidant-antioxidant system [ 26 , 27 ]. The accumulation of ROS induces excessive lipid oxidation, further along with oxidative attack to lipids, proteins, and DNA materials.…”

Section: Discussionmentioning

confidence: 99%

“…Plumbagin has been reported to exhibit several side effects including diarrhea, skin rashes, leukocytosis, and increased serum phosphatase levels [ 25 ]. In addition, there are reports of plumbagin-induced hepatotoxicity [ 3 , 25 , 26 ], cardiotoxicity [ 27 ], cytotoxicity toward human keratinocytes [ 26 ], and radiomimetic nucleotoxic and cytotoxic effects [ 3 ]. These effects are possibly due to the activity of plumbagin as a strong inducer of reactive oxygen species (ROS) and a depleting agent of cellular glutathione (GSH) [ 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

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Imbalance of the antioxidative system by plumbagin and Plumbago indica L. extract induces hepatotoxicity in mice

Sukkasem¹,

Chatuphonprasert²,

Tatiya-aphiradee³

et al. 2016

J Intercult Ethnopharmacol

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Background/Aim:Plumbago indica (PI) L. and its active constituent, plumbagin, has been traditionally claimed for several pharmacological activities; however, there is little information regarding their toxicity. The present study aims to examine the effects of plumbagin and PI extract (PI) on hepatic histomorphology and antioxidative system in mice.Materials and Methods:Adult male intelligent character recognition mice were intragastrically administered plumbagin (1, 5, and 15 mg/kg/day) or PI (20, 200, and 1,000 mg/kg/day) consecutively for 14 days. Hepatic histomorphology was examined. Plasma alanine transaminase (ALT) and aspartate transaminase (AST) levels, hepatic lipid peroxidation, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, and the ratio of reduced to oxidized glutathione (GSH/GSSG) were determined.Results:Plumbagin and PI concentration-dependently induced hepatic injury based on histopathological changes via imbalance of antioxidative system. Plumbagin and PI significantly increased plasma ALT and AST levels, hepatic lipid peroxidation, and GPx activity but significantly decreased hepatic SOD and CAT activities. The GSH/GSSG ratio was significantly reduced by plumbagin.Conclusion:Plumbagin and PI caused hepatotoxic effects in the mice by unbalancing of the redox defense system. Therefore, plumbagin and PI-containing supplements should be used cautiously, especially when consumed in high quantities or for long periods.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Imbalance of the antioxidative system by plumbagin and Plumbago indica L. extract induces hepatotoxicity in mice

Sukkasem¹,

Chatuphonprasert²,

Tatiya-aphiradee³

et al. 2016

J Intercult Ethnopharmacol

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show abstract

“…In previous studies in mice however, various types of toxicity of plumbagin were reported. These included diarrhea, skin rashes, leukocytosis, increased serum phosphatase levels [20], hepatotoxicity [21, 22], and cardiotoxicity [23]. In a more recent study in mice [24], hepatotoxicity of plumbagin through unbalancing of the anti-oxidative system was observed, i.e., marked increased plasma ALT and AST levels, hepatic lipid peroxidation, and glutathione peroxidase activity; but decreased superoxide dismutase and catalase activities.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics, toxicity, and cytochrome P450 modulatory activity of plumbagin

Sumsakul

Plengsuriyakarn

Na‐Bangchang

2016

BMC Pharmacol Toxicol

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BackgroundThe antimalarial activity of plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone), a naturally occurring naphthoquinone widely distributed in the Plumbaginaceae family has previously been demonstrated in vitro (good activity) and in vivo (weak activity). The aim of the study was to investigate the pharmacokinetic profile following a single oral dosing to explain inconsistency of results of the in vitro and in vivo antimalarial activities. In addition, toxicity profiles and potential of modulation of cytochrome P450 enzymes (CYP1A2 and CYP3A11) were also investigated.MethodsThe pharmacokinetics and toxicity of plumbagin were investigated in rats. The propensity of plumbagin to modulate the mRNA expression and activities of the two inducible forms of hepatic drug metabolizing enzyme cytochrome P450 (CYP450), i.e., CYP1A2 and CYP3A11, was investigated using microsomes prepared from mouse livers.ResultsAcute and subacute toxicity tests indicate low toxicity of plumbagin with maximum tolerated doses of 150 (single oral dose) and 25 (daily doses for 28 days) mg/kg body weight, respectively. The pharmacokinetic profile of plumbagin following a single oral dose of 100 mg/kg body weight suggests that delayed absorption and short residence time (median values of time to maximal concentration and elimination half-life = 9.63 and 5.0 h, respectively) in plasma. Plumbagin did not modulate mRNA expression and activities of CYP1A2 and CYP3A11.ConclusionsPlumbagin was well tolerated following oral dose administration in rats. Pharmacokinetic property of this compound may be a limiting factor that explains the weak antimalarial activity of plumbagin observed in animal models. Potential metabolic interaction with co-administered drugs that are metabolized by CYP1A2 or CYP3A11 are unlikely.

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“…Other toxic effects of PLB include diarrhea, skin rashes, leukocytosis, neutrophilia, increase in serum phosphatase and acid phosphatase levels, hepatic toxicity, and cardiotoxicity. 106…”

Section: Fe W Limitati On S a Sso Ciated With Plumbag Inmentioning

confidence: 99%

Unmasking the potential role of plant‐based medicine “Plumbagin” in oral cancer—A Novel Paradigm

Taneja

Alam

Patnaik

et al. 2021

Oral Science International

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Cancer is one of the foremost dangerous diseases of the 20th century which is spreading further with the continuance and increasing incidence in the 21st century and certainly a significant reason for morbidity and mortality. A report by GLOBOCAN 2018 has provided estimates of incidence and mortality for 36 types of cancer and all cancer sites in 185 countries. 1 It estimated that cancer burden rises to 18.1 million new cancer cases and 9.6 million cancer deaths worldwide in 2018, which includes 354 864 and 92 887 cases of the lip

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The discovery of bioisoster compound for plumbagin using the knowledge-based rational method

Cited by 6 publications

References 20 publications

Imbalance of the antioxidative system by plumbagin and Plumbago indica L. extract induces hepatotoxicity in mice

Imbalance of the antioxidative system by plumbagin and Plumbago indica L. extract induces hepatotoxicity in mice

Pharmacokinetics, toxicity, and cytochrome P450 modulatory activity of plumbagin

Unmasking the potential role of plant‐based medicine “Plumbagin” in oral cancer—A Novel Paradigm

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