Antioxidant, Antimicrobial and Cytotoxic Activities of Amides and Aristolactams from Piper wallichii (Miq.) Hand.-Mazz. Stems

Abstract Four amides, namely, piperine (1), pellitorine (2), piperiline (5) and N-trans-p-coumaroyltyramine (7), and three aristolactams, i.e., piperolactams D (3), B (4) and A (6), were isolated from the methanol extract of Piper wallichii stems. Piperiline, piperolactams B and D were obtained from this plant for the first time. Compounds 1, 3, 5, 6 and 7 were evaluated for their antioxidant, antimicrobial and cytotoxic activities. Piperine (1) displayed the highest antioxidant activity in scavenging DPPH radicals with an IC50 value of 94.51 ± 11.91 μM. Piperolactams D (3) and A (6) showed antibacterial activity against Gram-positive bacteria (B. subtilis and S. aureus) with MICs of between 500-1000 μM. All test compounds were cytotoxic to breast cancer (MCF-7) cells, while the aristolactams were more toxic to colon cancer (Caco-2) cells than the amides. Compounds 1, 3, 6 and 7 were moderately cytotoxic to the doxorubicin-resistant MCF-7 subline (MCF-7/DOX). All compounds were non-toxic to normal human fibroblast (NIH/3T3) cells. GRAPHICAL ABSTRACT

[1]  S. Jianmongkol,et al.  N-Trans-p-Coumaroyltyramine Enhances Indomethacin- and Diclofenac-induced Apoptosis Through Endoplasmic Reticulum Stress-dependent Mechanism in MCF-7 Cells , 2022, AntiCancer Research.

[2]  A. Phrutivorapongkul,et al.  Conventional and molecular pharmacognostic characters integrated with chemical profiles of five Piper plants in the Thai herbal pharmacopoeia and their admixture/adulteration/substitution situations in Thailand , 2022, Journal of Natural Medicines.

[3]  A. Das,et al.  Antimicrobial activities of extract, fractions and isolated compounds from the fruits of Elaeocarpus floribundus growing in North-East India , 2021, Journal of Herbal Medicine.

[4]  K. Kanokmedhakul,et al.  Chemical constituents and antibacterial activity from the stems and leaves of Piper wallichii , 2021, Journal of Asian natural products research.

[5]  M. Benkhaled,et al.  Phytochemicals, Antihemolytic, Anti-inflammatory, Antioxidant, and Antibacterial Activities from Thymus Algeriensis , 2021 .

[6]  N. Davies,et al.  The effects of Benjakul extract and its isolated compounds on cell cycle arrest and apoptosis in human non-small cell lung cancer cell line NCI-H226 , 2021, Research in pharmaceutical sciences.

[7]  Duangjai Tungmunnithum,et al.  Plant Polyphenols, More than Just Simple Natural Antioxidants: Oxidative Stress, Aging and Age-Related Diseases , 2020, Medicines.

[8]  K. V. Bhat,et al.  ‘Choijwal’ (Piper wallichii (Miq.) Hand.-Mazz.): a wild pepper used as spice and medicine in Andaman Islands of India , 2019, Genetic Resources and Crop Evolution.

[9]  A. Szumny,et al.  Essential Oils as Antimicrobial Agents—Myth or Real Alternative? , 2019, Molecules.

[10]  B. Salehi,et al.  Piper Species: A Comprehensive Review on Their Phytochemistry, Biological Activities and Applications , 2019, Molecules.

[11]  P. Abete,et al.  Oxidative stress, aging, and diseases , 2018, Clinical interventions in aging.

[12]  S. Jianmongkol,et al.  Rhinacanthin‐C enhances doxorubicin cytotoxicity via inhibiting the functions of P‐glycoprotein and MRP2 in breast cancer cells , 2017, European journal of pharmacology.

[13]  Ying-Jun Zhang,et al.  A Survey of the Chemical Compounds of Piper spp. (Piperaceae) and Their Biological Activities , 2016, Natural product communications.

[14]  S. Basak,et al.  In Vitro susceptibilities of wild and drug resistant Leishmania donovani amastigotes to piperolactam A loaded hydroxypropyl-β-cyclodextrin nanoparticles. , 2016, Acta tropica.

[15]  D. Woyessa,et al.  In vitro antibacterial activities of compounds isolated from roots of Caylusea abyssinica , 2015, Annals of Clinical Microbiology and Antimicrobials.

[16]  Xing-Cong Li,et al.  Lignans and aromatic glycosides from Piper wallichii and their antithrombotic activities. , 2015, Journal of ethnopharmacology.

[17]  Xing-Cong Li,et al.  Chemical constituents from Piper wallichii , 2015, Natural product research.

[18]  Guowei Zhao,et al.  A new flavonol C-glycoside and a rare bioactive lignanamide from Piper wallichii Miq. Hand.-Mazz. , 2014, Chinese journal of natural medicines.

[19]  Jayanta J Bora,et al.  Antioxidant Activities and Phenolic Content of Piper wallichii (Miq.) Hand.-Mazz. , 2014 .

[20]  K. Lee,et al.  Anticancer Principles from Medicinal Piper (胡椒 Hú Jiāo) Plants , 2014, Journal of traditional and complementary medicine.

[21]  T. K. Goswami,et al.  Piper nigrum and Piperine: An Update , 2013, Phytotherapy research : PTR.

[22]  Chwan-Fwu Lin,et al.  A New Hydroxychavicol Dimer from the Roots of Piper betle , 2013, Molecules.

[23]  R. Gutierrez,et al.  Alkaloids from piper: a review of its phytochemistry and pharmacology. , 2013, Mini reviews in medicinal chemistry.

[24]  Joa Kyum Kim,et al.  Synthesis of aristolactam analogues and evaluation of their antitumor activity. , 2009, Bioorganic & medicinal chemistry letters.

[25]  A. Chaveerach,et al.  Ethnobotany of the Genus Piper (Piperaceae) in Thailand , 2006 .

[26]  C. Liaw,et al.  Potential Anti-Inflammatory Activities of Bractelactone and other Compounds Isolated from Fissistigma bracteolatum , 2005 .

[27]  Shihua Wu,et al.  Preparative isolation and purification of amides from the fruits of Piper longum L. by upright counter-current chromatography and reversed-phase liquid chromatography. , 2004, Journal of chromatography. A.

[28]  R. Hider,et al.  Effects of piperine analogues on stimulation of melanocyte proliferation and melanocyte differentiation. , 2004, Bioorganic & medicinal chemistry.

[29]  N. Nalini,et al.  Antioxidant efficacy of black pepper (Piper nigrum L.) and piperine in rats with high fat diet induced oxidative stress , 2004, Redox report : communications in free radical research.

[30]  Chin‐Chung Wu,et al.  A new aristolactam alkaloid and anti-platelet aggregation constituents from Piper taiwanense. , 2004, Planta medica.

[31]  Poonam,et al.  Naturally occurring aristolactams, aristolochic acids and dioxoaporphines and their biological activities. , 2003, Natural product reports.

[32]  H. Glaeser,et al.  Piperine, a Major Constituent of Black Pepper, Inhibits Human P-glycoprotein and CYP3A4 , 2002, Journal of Pharmacology and Experimental Therapeutics.

[33]  R. D. Mittal,et al.  In vitro antioxidant activity of piperine. , 2000, Methods and findings in experimental and clinical pharmacology.

[34]  A. I. Gray,et al.  Piperdardine, a piperidine alkaloid from Piper tuberculatum☆ , 1997 .

[35]  C. Olsen,et al.  An aristolactam from Piper acutisleginum and revision of the structures of piperolactam B and D , 1993 .

[36]  M. Luscombe,et al.  A study of some variables in a tetrazolium dye (MTT) based assay for cell growth and chemosensitivity. , 1987, British Journal of Cancer.

[37]  Ruihua Tang,et al.  Chemical constituents of Piper wallichii (Miq.) Hand.-Mazz. and inhibitory effects on Tca83 cells. , 2016 .

[38]  T. Tanee,et al.  Betel-like-scented Piper Plants as Diverse Sources of Industrial and Medicinal Aromatic Chemicals , 2014 .

[39]  M. Bordoloi,et al.  In vitro study on antioxidant activity and phenolic content of three Piper species from North East India , 2013, Journal of Food Science and Technology.

[40]  Wu Lian-hua.  Analysis of Volatile Oil of Piper wallichii from 2 Producing Areas of Guizhou Province by GC-MS , 2013 .

[41]  Guowei Zhao,et al.  [Study on the bioactive constituents of Piper wallichii]. , 2012, Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials.

[42]  P. Yu,et al.  [Neolignans and lignan from Piper wallichii]. , 2010, Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica.

[43]  D. Kim,et al.  Inhibitory effect of trans-N-p-coumaroyl tryamine from the twigs of Celtis chinensis on the acetylcholinesterase. , 2003, Archives of pharmacal research.