New Cytotoxic Cyclobutanoid Amides, a New Furanoid Lignan and Anti-Platelet Aggregation Constituents from<i>Piper arborescens</i>

Tsai, Ian‐Lih; Lee, Fan Pin; Wu, Chin Chung; Duh, Chang‐Yih; Ishikawa, Tsutomu; Chen, Jih Jung; Chen, Yu Chang; Seki, Hiroko; Chen, Ih Sheng

doi:10.1055/s-2005-864155

Cited by 124 publications

(88 citation statements)

References 11 publications

(17 reference statements)

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“…Several of them have been reported to show cytotoxic activity towards tumor cell lines (5). Piperine has been reported to display central nervous system depressant, antipyretic, analgesic, and anti-inflammatory activities (3).…”

Section: Introductionmentioning

confidence: 99%

In vivo growth-inhibition of Sarcoma 180 by piplartine and piperine, two alkaloid amides from Piper

Bezerra

Castro

Alves

et al. 2006

Braz J Med Biol Res

171

103

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Piplartine {5,6-dihydro-1-[1-oxo-3-(3,4,5-trimethoxyphenyl)-2-propenyl]-2(1H)pyridinone} and piperine {1-5-(1,3)-benzodioxol-5-yl)-1-oxo-2,4-pentadienyl]piperidine} are alkaloid amides isolated from Piper. Both have been reported to show cytotoxic activity towards several tumor cell lines. In the present study, the in vivo antitumor activity of these compounds was evaluated in 60 female Swiss mice (N = 10 per group) transplanted with Sarcoma 180. Histopathological and morphological analyses of the tumor and the organs, including liver, spleen, and kidney, were performed in order to evaluate the toxicological aspects of the treatment with these amides. Administration of piplartine or piperine (50 or 100 mg kg -1 day -1 intraperitoneally for 7 days starting 1 day after inoculation) inhibited solid tumor development in mice transplanted with Sarcoma 180 cells. The inhibition rates were 28.7 and 52.3% for piplartine and 55.1 and 56.8% for piperine, after 7 days of treatment, at the lower and higher doses, respectively. The antitumor activity of piplartine was related to inhibition of the tumor proliferation rate, as observed by reduction of Ki67 staining, a nuclear antigen associated with G1, S, G2, and M cell cycle phases, in tumors from treated animals. However, piperine did not inhibit cell proliferation as observed in Ki67 immunohistochemical analysis. Histopathological analysis of liver and kidney showed that both organs were reversibly affected by piplartine and piperine treatment, but in a different way. Piperine was more toxic to the liver, leading to ballooning degeneration of hepatocytes, accompanied by microvesicular steatosis in some areas, than piplartine which, in turn, was more toxic to the kidney, leading to discrete hydropic changes of the proximal tubular and glomerular epithelium and tubular hemorrhage in treated animals.

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Section: Introductionmentioning

confidence: 99%

In vivo growth-inhibition of Sarcoma 180 by piplartine and piperine, two alkaloid amides from Piper

Bezerra

Castro

Alves

et al. 2006

Braz J Med Biol Res

171

103

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“…Piplartine has shown significant cytotoxicity against cell tumor lines, as well as antifungal, antimitotic and anti-platelet aggregation compound. [9][10][11][12][13] Piplartine anticancer potential has been highlighted by the undergoing preclinical evaluation. In vivo studies using murine tumors demonstrated that in spite of a moderate anticancer activity, piplartine has weak toxicological side effects.…”

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confidence: 99%

Biomimetic Oxidation of Piperine and Piplartine Catalyzed by Iron(III) and Manganese(III) Porphyrins

Schaab

Crotti

Iamamoto

et al. 2010

Biological & Pharmaceutical Bulletin

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Piperine and piplartine ( Fig. 1) are naturally occurring amides from Piper species (Piperaceae), which have been used in folk medicine of tropical and subtropical countries for treatment of asma, bronchitis, fever, hemorrhoidal afflictions, gastrointestinal diseases, rheumatism, and as food additive.1-3) The amide piperine is the pungent principle of black pepper (P. nigrum) and can be extracted from dried fruits with a yield of 3-7%.4) Several biological activities have been associated to piperine, including inhibition of liver metabolism, antioxidant, central nervous system depressant and antitumoral activities. [4][5][6][7][8][9] Piplartine is one of the major amide isolated from the roots of P. tuberculatum (popularly known as "long pepper"), which has been largely used in the folk medicine as a sedative and antidote for snake bite. Piplartine has shown significant cytotoxicity against cell tumor lines, as well as antifungal, antimitotic and anti-platelet aggregation compound.9-13) Piplartine anticancer potential has been highlighted by the undergoing preclinical evaluation. In vivo studies using murine tumors demonstrated that in spite of a moderate anticancer activity, piplartine has weak toxicological side effects. 3,14) Additionally, it increases 5-fluorouracil anticancer efficacy, while reduces chemotherapeutical side effects, as evidenced by the prevention of 5-FUinduced leucopenia.15) These data suggests that piplartine is a promising anticancer compound to be used in combination of already known antineoplastic agents.The study of the oxidative metabolism on promising natural products is of major importance before they become medicines, since their oxidations can affect the drug's safety and efficacy, due to the formation of therapeutically active or toxic metabolites. 16) Thus, efforts have been addressed to describe the metabolic pathways of drug candidate compounds.The cytochrome P450 (CYP) enzymes are catalytic hemoproteins known for their role in the metabolism of non-polar comounds, present in all forms of life (plants, bacteria, mammals). They have played a key role in the oxidative transformation of endogenous and exogenous molecules. 17,18) The cytochrome P450 enzymes catalyze the hydroxylation of saturated carbon-hydrogen bonds, epoxidation of double bounds, oxidation of heteroatoms, dealkylation reactions, and oxidations of aromatic carbons, etc.17) The oxidative metabolism of drugs by cytochrome P450 monooxygenases has been extensively studied through biological models, such as direct experiments on animals, the use of perfused organs or isolated cells. However, there are several ethical restrictions using animals and also experimental drawnbacks associated with the isolation of some hydrophilic and reactive metabolites that could bind to biological macromolecules, preparation of liver and cells (microsomes, hepatocytes) are of variable quality with low yields. [18][19][20] Thus, alternative model systems of cytocrome P450 have been employed in studies of P450 functions, as well as in syn...

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“…Several of them have been reported to be cytotoxic activity towards tumor cell lines [2]. Piperine has been reported to display central nervous system depressant, antipyretic, analgesic, and anti-inflammatory activities.…”

Section: Introductionmentioning

confidence: 99%

“…It is metabolized in the liver by hepatic CYP3A4 activity. Piperine, a major plant alkaloid, has been shown to inhibit the CYP3A [2], enzymatic activity in a cell-free system. In a study, it was observed piperine and docetaxel could increase docetaxel's pharmacokinetic activity in vitro and in vivo.Docetaxel is one of the most commonly used cytotoxic chemotherapeutic agents.…”

Section: Introductionmentioning

confidence: 99%

A study on piperine, active compound of black pepper

Gökalp¹

2016

APJES

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Piperine, the most important compound of black pepper, is used for treating several diseases such as breast, colon, rectal, and stomach cancer. In this study, the thermodynamical properties of this molecule in blood were obtained by using DFT and HF at the level of B3LYP/6-31+g(d,p). The results of calculations are supported with the experimental literatüre knowledges. DFT and HF basis set calculations support to the each other as comparing theoretical calculations of the interactions taking place within the molecular species Keywords: Piperine, DFT and HF Abbreviations DFTdensity functional theory HF hartree-fock HOMO highest occupied molecular orbital LUMO lowest unoccupied molecular orbital FDA the food and drug administration CYP3A4 Cytochrome P450 3A4

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New Cytotoxic Cyclobutanoid Amides, a New Furanoid Lignan and Anti-Platelet Aggregation Constituents fromPiper arborescens

Cited by 124 publications

References 11 publications

In vivo growth-inhibition of Sarcoma 180 by piplartine and piperine, two alkaloid amides from Piper

In vivo growth-inhibition of Sarcoma 180 by piplartine and piperine, two alkaloid amides from Piper

Biomimetic Oxidation of Piperine and Piplartine Catalyzed by Iron(III) and Manganese(III) Porphyrins

A study on piperine, active compound of black pepper

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