DOCSLIB.ORG

Activation of TRPV1 and TRPA1 by Black Pepper Components

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Activation of TRPV1 and TRPA1 by Black Pepper Components 90964 (178) Biosci. Biotechnol. Biochem., 74 (5), 90964-1–5, 2010 Activation of TRPV1 and TRPA1 by Black Pepper Components Yukiko OKUMURA,1 Masataka NARUKAWA,1;2;3 Yusaku IWASAKI,1;2 Aiko ISHIKAWA,3 y Hisashi MATSUDA,4 Masayuki YOSHIKAWA,4 and Tatsuo WATANABE1;2;3; 1Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan 2Global COE Program, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan 3School of Food and Nutritional Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan 4Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan Received December 25, 2009; Accepted January 26, 2010; Online Publication, May 7, 2010 [doi:10.1271/bbb.90964] We searched in this study for novel agonists of V, member 1 (TRPV1).4,5) TRPV1 is also activated by transient receptor potential cation channel, subfamily capsaicin (CAP), a pungent component of hot pepper. It V, member 1 (TRPV1) and transient receptor potential is known that TRPV1 activation enhances the energy cation channel, subfamily A, member 1 (TRPA1) in metabolism.6) It is therefore possible that, like CAP, pepper, focusing attention on 19 compounds contained piperine can also enhance the energy metabolism via in black pepper. Almost all the compounds in HEK cells TRPV1, although the detailed mechanism for this is heterogeneously expressed TRPV1 or TRPA1, increas- unknown. Various piperine analogs have also been ingAdvance the intracellular Ca2þ concentration ([Ca2 Viewþ] )ina 7,8) i identified in pepper. Since it has been reported that concentration-dependent manner. Among these, piper- CAP analogs activated TRPV1 as well as CAP,9,10) it is ine, isopiperine, isochavicine, piperanine, pipernonaline, also possible that piperine analogs could activate dehydropipernonaline, retrofractamide C, piperolein A, TRPV1. and piperolein B relatively strongly activated TRPV1. Many thermosensitive TRP receptors have recently The EC50 values of these compounds for TRPV1 were been cloned as TRPV1 homologs. Among these, the 0.6–128 M. Piperine, isopiperine, isochavicine, pipera- transient receptor potential cation channel, subfamily A, nine, piperolein A, piperolein B, and N-isobutyl- member 1 (TRPA1) is similar to TRPV1 in several (2E,4E)-tetradeca-2,4-diamide also relatively strongly respects: TRPA1 is coexpressed in TRPV1-expressing 11) activated TRPA1, the EC50 values of these compounds somatosensory neurons, and TRPA1 induces sensory for TRPA1 were 7.8–148 M. The Ca2þ responses of stimuli such as painProofs and pungency like TRPV1.12) Many these compounds for TRPV1 and TRPA1 were signifi- pungent components such as allyl isothiocyanate (AITC; cantly suppressed by co-applying each antagonist. We wasabi),13) cinnamaldehyde (cinnamon),14) hydroxy - identified in this study new transient receptor potential sanshool (zanthoxylum fruit),15) and miogadial and (TRP) agonists present in black pepper and found that miogatrial (myoga)16) have been reported to be TRPA1 piperine, isopiperine, isochavicine, piperanine, pipero- agonists. We therefore hypothesized that the pungent lein A, and piperolein B activated both TRPV1 and compounds contained in pepper could also activate TRPA1. TRPA1. We investigated in this study the activation of TRPV1 and TRPA1 by 19 components of pepper. Key words: pepper; piperine; transient receptor potential cation channel, subfamily V, member 1 Materials and Methods (TRPV1); transient receptor potential cation channel, subfamily A, member 1 (TRPA1); Materials. CAP, piperine, and capsazepine (CPZ) were purchased intracellular calcium concentration from Sigma (St. Luis, MO, USA). Allyl isothiocyanate (AITC) was obtained from Wako Pure Chem. Ind. (Osaka, Japan), and HC030031 was purchased from ChemBridge (San Diego, CA, USA). All other Pepper, Peperineer nigrum Linne, grows on a climb- chemicals were of guaranteed reagent grade. ing plant belonging to the Piperineerales family. The dried fruit of pepper is used as a spice throughout the Purification of the pepper components. We studied 19 components world. Traditional Chinese medicine classifies pepper of black pepper: piperine, isopiperine, isochavicine, piperanine, as a food that generates body heat. Pepper has such piperonal, methylpiperate, fragaramide, pipernonaline, dehydropiper- pharmacological effects as anti-oxidative,1) anti-proto- nonaline, piperlonguminine, retrofractamide A (retro A), retrofracta- zoan,2) and prokinetic.3) mide B (retro B), retrofractamide C (retro C), guineensine, brachystamide B, N-isobutyl-(2E,4E)-tetradeca-2,4-diamide (N-tetra), Piperine is a pungent component of pepper and has N-isobutyl-(2E,4E)-octadeca-2,4-diamide (N-octa), piperolein A, and been reported as acting on the capsaicin receptor, piperolein B. The structural formulae of the black pepper components transient receptor potential cation channel, subfamily are shown in Fig. 1. With the exception of piperine, these components y To whom correspondence should be addressed. Fax: +81-54-264-5550; E-mail: [email protected] 2þ 2þ Abbreviations: AITC, allyl isothiocyanate; [Ca ]i, intracellular Ca concentration; CAP, capsaicin; CPZ, capsazepine; retro A, retrofractamide A; retro B, retrofractamide B; retro C, retrofractamide C; N-octa, N-isobutyl-(2E,4E)-octadeca-2,4-diamide; N-tetra, N-isobutyl-(2E,4E)-tetradeca- 2,4-diamide; TRP, transient receptor potential; TRPA1, transient receptor potential cation channel, subfamily A, member 1; TRPV1, transient receptor potential cation channel, subfamily V, member 1 90964-2 Y. OKUMURA et al. Piperine Retrofractamide A (retro A) Piperanine Piperolein A Retrofractamide B (retro B) Pipernonailne Piperolein B Retrofractamide C (retro C) Piperonal Dehydro pipernonailne Guineensine Methyl piperate Brachystamide B Fragaramide Isopiperine N-Isobutyl-(2E,4E)-tetradeca-2,4-diamide (N-Tetra) AdvanceIsochavicine Piperlonguminine ViewN-Isobutyl-(2E,4E)-octadeca-2,4-diamide (N-Octa) Fig. 1. Chemical Structures of the 19 Pepper Components. were isolated and purified from black pepper (Gaban Co., Tokyo, inhibitory activity of the antagonists, 30 mM CPZ for TRPV1 or Japan) and the fruits of Piper chaba Hunter purchased in Thailand. HC030031 for TRPA1 was added to 100 mM of each pepper compound, Piperolein A and B were extracted with hexane from black pepper and except for N-isobutyl-(2E,4E)-octadeca-2,4-diamide; we used 30 mM of purified by silica gel and reversed-phase chromatography. The other this compound in DMSO since it did not dissolve in 100 mM. We used compounds were obtained from P. chaba. The dried fruits of P. chaba 0.01–100 mM piperine, isopiperine, isochavicine, piperanine and piper- were extracted with 80% aqueous acetone and partitioned between nonaline, 0.1–100 mM dehydropipernonaline, retro C, piperolein A and ethyl acetate and water, before the ethyl acetate fraction was purified piperolein B, and 0.1 nM–10 mM CAP to obtain the dose-response by silica gel and reversed-phase chromatography.8) curves for TRPV1. We used 0.03–100 mM piperine, isopiperine, isochavicine and piperanine,Proofs 0.1–100 mM piperolein A, piperolein B Cloning and expression of human TRPV1 and human TRPA1. and N-tetra, and 0.01–100 mM AITC for TRPA1. In some experiments, Human TRPV1 and TRPA1 cDNA were amplified by RT-PCR, using TRPV1 antagonist CPZ (30 mM) or TRPA1 antagonist HC030031 mRNA respectively obtained from human brain first-strand cDNA (30 mM) were added together with these compounds. Each test (Agilent Technologies, Santa Clara, CA, USA) and human WI38 cells. compound was prepared in DMSO and added to the loading solution Human TRPV1 cDNA was subcloned into pcDNA3 (Invitrogen, to a final DMSO concentration of 0.1% or 0.2%. A 5 mM amount of Carlsbad, CA, USA) and then transfected into HEK293T cells by using ionomycin was added to each well to elicit maximum fluorescence the SuperFect transfection reagent (Qiagen, Hilden, Germany). After intensity. The data values for the test compounds are expressed as the culturing in the presence of 750 mg/ml of G418, we obtained a stable percentage response to 5 mM ionomycin. Curves were fitted and HEK293T cell line that expressed human TRPV1. parameters estimated by using Prism 4.0a software (Graph Pad The expression of full-length human TRPA1 in stable HEK cells Software, San Diego, CA, USA). was induced by the tetracycline-inducible T-RExÔ expression system from Invitrogen. The hTRPA1 cDNA was subcloned into pcDNA4/TO Results (Invitrogen) and then transfected into HEK T-RExÔ cells by using the Lipofectamine 2000 reagent (Invitrogen). HEK T-RExÔ cells that stably maintained the hTRPA1 gene were selected by using 500 mg/ml The activity of TRPV1 and TRPA1 by the 19 pepper of zeocin and 10 mg/ml of blasticidin, and were grown according to the components was compared to that by TRPV1 agonist manufacturer’s instructions. The following primers were used for CAP or TRPA1 agonist AITC. cloning: human TRPV1 forward primer, 50-GCAAGGATGAAGAA- GAAATGGA-30 and reverse primer, 50-TCACTTCTCCCCGGAAG- 0 0 Effect of the 19 pepper components on human TRPV1 CGC-3 ; human TRPA1 forward primer, 5 -TGGGTCAATGAAGTG- Figure 2A shows the calcium response induced by CAG-30 and reverse primer, 50-GAAGGTCTGAGGAGCTAAGGC-30. each of the 19 pepper components in TRPV1-expressing Measurement of the intracellular Ca2þ concentration. The intra- cells. Among these components, piperine, isopiperine, 2þ 2þ cellular Ca concentration ([Ca ]i) was measured by FlexStationÔ isochavicine,
Load more

Recommended publications
  • Technical Developments in the Use of Spices Dr David Baines Baines Food Consultancy Ltd
    EUROPEAN SPICE ASSOCIATION GENERAL ASSEMBLY 2013 Technical Developments in the Use of Spices Dr David Baines Baines Food Consultancy Ltd Co-editor: Flavour Horizons TECHNICAL DEVELOPMENTS IN THE USE OF SPICES TOPICS: Recent health claims submitted to the EU for the use of spices Compounds in selected spices that have beneficial effects on health The use of spices to inhibit of carcinogen formation in cooked meats The growing use of spices in animal feeds Salt reduction using spices Interesting culinary herbs from Vietnam Recent Health Claims Submitted to the EU EU REGULATION OF HEALTH CLAIMS • The Nutrition and Health Claims Regulation, 1924/2006/EC is designed to ensure a high level of protection for consumers and legal clarity and fair competition for food business operators. • Claims must not mislead consumers; they must be, accurate, truthful, understandable and substantiated by science. • Implementation of this Regulation requires the adoption of a list of permitted health claims, based on an assessment by the European Food Safety Authority (EFSA) of the science substantiating the claimed effect and compliance with the other general and specific requirements of the Regulation. • This list of permitted health claims was adopted in May 2012 by the Commission and became binding on 14th December 2012. Food companies must comply from this date or face prosecution for misleading marketing. APPROVAL OF CLAIMS EU REGULATION OF HEALTH CLAIMS CLAIMS BY COMPONENT CLAIMS BY FUNCTION CLAIMS FOR SPICES – NOT APPROVED/ON HOLD SPICE CLAIM(S) Anise / Star Anise Respiratory Health, Digestive Health, Immune Health, Lactation Caraway Digestive Health, Immune Health, Lactation Cardamon Respiratory Health, Digestive Health, Immune Health, Kidney Health, Nervous System Health, Cardiovascular Health, Capsicum Thermogenesis, Increasing Energy Expenditure, Enhancing Loss of Calories, Body Weight Loss, Stomach Health, Reduction of Oxidative Stress, promotion of Hair Growth.
    [Show full text]
  • Piperine-Pro-Nanolipospheres As a Novel Oral Delivery System of Ca
    Piperine-pro-nanolipospheres as a novel oral delivery system of ca... https://www.ncbi.nlm.nih.gov/pubmed/28890215 PubMed Format: Abstract Full text links J Control Release. 2017 Nov 28;266:1-7. doi: 10.1016/j.jconrel.2017.09.011. Epub 2017 Sep 8. Piperine-pro-nanolipospheres as a novel oral delivery system of cannabinoids: Pharmacokinetic evaluation in healthy volunteers in comparison to buccal spray administration. Cherniakov I1, Izgelov D1, Barasch D1, Davidson E2, Domb AJ1, Hoffman A3. Author information Abstract Nowadays, therapeutic indications for cannabinoids, specifically Δ9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) are widening. However, the oral consumption of the molecules is very limited due to their highly lipophilic nature that leads to poor solubility at the aqueous environment. Additionally, THC and CBD are prone to extensive first pass mechanisms. These absorption obstacles render the molecules with low and variable oral bioavailability. To overcome these limitations we designed and developed the advanced pro-nanolipospheres (PNL) formulation. The PNL delivery system is comprised of a medium chain triglyceride, surfactants, a co-solvent and the unique addition of a natural absorption enhancer: piperine. Piperine was selected due to its distinctive inhibitory properties affecting both Phase I and Phase II metabolism. This constellation self emulsifies into nano particles that entrap the cannabinoids and the piperine in their core and thus improve their solubility while piperine and the other PNL excipients inhibit their intestinal metabolism. Another clear advantage of the formulation is that its composition of materials is approved for human consumption. The safe nature of the excipients enabled their direct evaluation in humans.
    [Show full text]
  • Technical Document for Piperine Also Referred to As a BRAD
    BIOPESTICIDES REGISTRATION ACTION DOCUMENT PIPERINE (PC Code 043501) U.S. Environmental Protection Agency Office of Pesticide Programs Biopesticides and Pollution Prevention Division Piperine Biopesticides Registration Action Document Piperine (PC Code 043501) TABLE OF CONTENTS I. Executive Summary.........................................................5 II. Overview .................................................................6 A. ACTIVE INGREDIENT OVERVIEW .......................................6 B. USE PROFILE .........................................................6 C. ESTIMATED USAGE ...................................................7 D. DATA REQUIREMENTS.................................................7 E. REGULATORY HISTORY ...............................................7 F. CLASSIFICATION ....................................................8 G. FOOD CLEARANCES/TOLERANCES .....................................8 III. Science Assessment .........................................................8 A. PHYSICAL/CHEMICAL PROPERTIES ASSESSMENT .......................8 1. Product Identity and Mode of Action .....................................8 a. Product Identity: ..................................................8 b. Mode of Action:...................................................8 2. Physical And Chemical Properties Assessment .............................8 B. HUMAN HEALTH ASSESSMENT........................................10 1. Toxicology Assessment ...............................................10 a. Acute Toxicity ...................................................11
    [Show full text]
  • TRP Mediation
    molecules Review Remedia Sternutatoria over the Centuries: TRP Mediation Lujain Aloum 1 , Eman Alefishat 1,2,3 , Janah Shaya 4 and Georg A. Petroianu 1,* 1 Department of Pharmacology, College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi 127788, United Arab Emirates; [email protected] (L.A.); Eman.alefi[email protected] (E.A.) 2 Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi 127788, United Arab Emirates 3 Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, The University of Jordan, Amman 11941, Jordan 4 Pre-Medicine Bridge Program, College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi 127788, United Arab Emirates; [email protected] * Correspondence: [email protected]; Tel.: +971-50-413-4525 Abstract: Sneezing (sternutatio) is a poorly understood polysynaptic physiologic reflex phenomenon. Sneezing has exerted a strange fascination on humans throughout history, and induced sneezing was widely used by physicians for therapeutic purposes, on the assumption that sneezing eliminates noxious factors from the body, mainly from the head. The present contribution examines the various mixtures used for inducing sneezes (remedia sternutatoria) over the centuries. The majority of the constituents of the sneeze-inducing remedies are modulators of transient receptor potential (TRP) channels. The TRP channel superfamily consists of large heterogeneous groups of channels that play numerous physiological roles such as thermosensation, chemosensation, osmosensation and mechanosensation. Sneezing is associated with the activation of the wasabi receptor, (TRPA1), typical ligand is allyl isothiocyanate and the hot chili pepper receptor, (TRPV1), typical agonist is capsaicin, in the vagal sensory nerve terminals, activated by noxious stimulants.
    [Show full text]
  • Targeting Angiogenesis by Phytochemicals
    Arom & at al ic in P l ic a n d t Kadioglu et al., Med Aromat Plants 2013, 2:5 e s M Medicinal & Aromatic Plants DOI: 10.4172/2167-0412.1000134 ISSN: 2167-0412 ResearchReview Article Article OpenOpen Access Access Targeting Angiogenesis By Phytochemicals Onat Kadioglu, Ean Jeong Seo and Thomas Efferth* Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany Abstract Cancer is a major cause of death worldwide and angiogenesis is critical in cancer progression. Development of new blood vessels and nutrition of tumor cells are heavily dependent on angiogenesis. Thus, angiogenesis inhibition might be a promising approach for anticancer therapy. Anti-angiogenic small molecule and phytochemicals as a cancer treatment approach are focused in these main points; modes of action, adverse effects, mechanisms of resistance and new developments. Treatment with anti-angiogenic compounds might be advantageous over conventional chemotherapy due to the fact that those compounds mainly act on endothelial cells, which are genetically more stable and homogenous compared to tumor cells and they show lower susceptibility to acquired drug resistance (ADR). Targeting the VEGF (vascular endothelial growth factor) signalling pathway with synthetic small molecules inhibiting Receptor Tyrosine Kinases (RTKs) in addition to antagonizing VEGF might be a promising approach. Moreover, beneficial effect of phytochemicals were proven on cancer-related pathways especially concerning anti-angiogenesis. Plant phenolics being an important category of prominent phytochemicals affect different pathways of angiogenesis. Green tea polyphenols (epigallocatechin gallate) and soy bean isoflavones (genistein) are two examples involving an anti-angiogenic effect.
    [Show full text]
  • Transient Receptor Potential (TRP) Channels in Haematological Malignancies: an Update
    biomolecules Review Transient Receptor Potential (TRP) Channels in Haematological Malignancies: An Update Federica Maggi 1,2 , Maria Beatrice Morelli 2 , Massimo Nabissi 2 , Oliviero Marinelli 2 , Laura Zeppa 2, Cristina Aguzzi 2, Giorgio Santoni 2 and Consuelo Amantini 3,* 1 Department of Molecular Medicine, Sapienza University, 00185 Rome, Italy; [email protected] 2 Immunopathology Laboratory, School of Pharmacy, University of Camerino, 62032 Camerino, Italy; [email protected] (M.B.M.); [email protected] (M.N.); [email protected] (O.M.); [email protected] (L.Z.); [email protected] (C.A.); [email protected] (G.S.) 3 Immunopathology Laboratory, School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino, Italy * Correspondence: [email protected]; Tel.: +30-0737403312 Abstract: Transient receptor potential (TRP) channels are improving their importance in differ- ent cancers, becoming suitable as promising candidates for precision medicine. Their important contribution in calcium trafficking inside and outside cells is coming to light from many papers published so far. Encouraging results on the correlation between TRP and overall survival (OS) and progression-free survival (PFS) in cancer patients are available, and there are as many promising data from in vitro studies. For what concerns haematological malignancy, the role of TRPs is still not elucidated, and data regarding TRP channel expression have demonstrated great variability throughout blood cancer so far. Thus, the aim of this review is to highlight the most recent findings Citation: Maggi, F.; Morelli, M.B.; on TRP channels in leukaemia and lymphoma, demonstrating their important contribution in the Nabissi, M.; Marinelli, O.; Zeppa, L.; perspective of personalised therapies.
    [Show full text]
  • Chemoprevention of Prostate Cancer by Natural Agents: Evidence from Molecular and Epidemiological Studies KEFAH MOKBEL, UMAR WAZIR and KINAN MOKBEL
    ANTICANCER RESEARCH 39 : 5231-5259 (2019) doi:10.21873/anticanres.13720 Review Chemoprevention of Prostate Cancer by Natural Agents: Evidence from Molecular and Epidemiological Studies KEFAH MOKBEL, UMAR WAZIR and KINAN MOKBEL The London Breast Institute, Princess Grace Hospital, London, U.K. Abstract. Background/Aim: Prostate cancer is one of the Prostate cancer is the second cause of cancer death in men most common cancers in men which remains a global public accounting for an estimated 1.28 million deaths in 2018 (1, 2). health issue. Treatment of prostate cancer is becoming The incidence of prostate cancer has been increasing globally increasingly intensive and aggressive, with a corresponding with 1.3 million new cases reported in 2018 (3, 4). Prostate increase in resistance, toxicity and side effects. This has cancer is still considered the most common life-threatening revived an interest in nontoxic and cost-effective preventive malignancy affecting the male population in most European strategies including dietary compounds due to the multiple countries. In the UK, prostate cancer is the most common effects they have been shown to have in various oncogenic cancer among men accounting for 13% of all cancer deaths in signalling pathways, with relatively few significant adverse males. Furthermore, the incidence of prostate cancer in British effects. Materials and Methods: To identify such dietary men has increased by more than two-fifths (44%) since the components and micronutrients and define their prostate early 1990s (5). cancer-specific actions, we systematically reviewed the current Based on clinical stage, histological grade and serum levels literature for the pertinent mechanisms of action and effects of prostate-specific antigen (PSA), current treatment options on the modulation of prostate carcinogenesis, along with for prostate cancer include surgery, radiotherapy and/or relevant updates from epidemiological and clinical studies.
    [Show full text]
  • Snapshot: Mammalian TRP Channels David E
    SnapShot: Mammalian TRP Channels David E. Clapham HHMI, Children’s Hospital, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA TRP Activators Inhibitors Putative Interacting Proteins Proposed Functions Activation potentiated by PLC pathways Gd, La TRPC4, TRPC5, calmodulin, TRPC3, Homodimer is a purported stretch-sensitive ion channel; form C1 TRPP1, IP3Rs, caveolin-1, PMCA heteromeric ion channels with TRPC4 or TRPC5 in neurons -/- Pheromone receptor mechanism? Calmodulin, IP3R3, Enkurin, TRPC6 TRPC2 mice respond abnormally to urine-based olfactory C2 cues; pheromone sensing 2+ Diacylglycerol, [Ca ]I, activation potentiated BTP2, flufenamate, Gd, La TRPC1, calmodulin, PLCβ, PLCγ, IP3R, Potential role in vasoregulation and airway regulation C3 by PLC pathways RyR, SERCA, caveolin-1, αSNAP, NCX1 La (100 µM), calmidazolium, activation [Ca2+] , 2-APB, niflumic acid, TRPC1, TRPC5, calmodulin, PLCβ, TRPC4-/- mice have abnormalities in endothelial-based vessel C4 i potentiated by PLC pathways DIDS, La (mM) NHERF1, IP3R permeability La (100 µM), activation potentiated by PLC 2-APB, flufenamate, La (mM) TRPC1, TRPC4, calmodulin, PLCβ, No phenotype yet reported in TRPC5-/- mice; potentially C5 pathways, nitric oxide NHERF1/2, ZO-1, IP3R regulates growth cones and neurite extension 2+ Diacylglycerol, [Ca ]I, 20-HETE, activation 2-APB, amiloride, Cd, La, Gd Calmodulin, TRPC3, TRPC7, FKBP12 Missense mutation in human focal segmental glomerulo- C6 potentiated by PLC pathways sclerosis (FSGS); abnormal vasoregulation in TRPC6-/-
    [Show full text]
  • Dietary Compounds for Targeting Prostate Cancer
    Review Dietary Compounds for Targeting Prostate Cancer Seungjin Noh 1, Eunseok Choi 1, Cho-Hyun Hwang 1, Ji Hoon Jung 2, Sung-Hoon Kim 2 and Bonglee Kim 1,2,* 1 College of Korean Medicine, Kyung Hee University, Seoul 02453, Korea; [email protected] (S.N.); [email protected] (E.C.); [email protected] (C.-H.H.) 2 Department of Pathology, College of Korean Medicine, Graduate School, Kyung Hee University, Seoul 02453, Korea; [email protected] (J.H.J.); [email protected] (S.-H.K.) * Correspondence: [email protected]; Tel.: +82-2-961-9217 Received: 10 August 2019; Accepted: 17 September 2019; Published: 8 October 2019 Abstract: Prostate cancer is the third most common cancer worldwide, and the burden of the disease is increased. Although several chemotherapies have been used, concerns about the side effects have been raised, and development of alternative therapy is inevitable. The purpose of this study is to prove the efficacy of dietary substances as a source of anti-tumor drugs by identifying their carcinostatic activities in specific pathological mechanisms. According to numerous studies, dietary substances were effective through following five mechanisms; apoptosis, anti-angiogenesis, anti- metastasis, microRNA (miRNA) regulation, and anti-multi-drug-resistance (MDR). About seventy dietary substances showed the anti-prostate cancer activities. Most of the substances induced the apoptosis, especially acting on the mechanism of caspase and poly adenosine diphosphate ribose polymerase (PARP) cleavage. These findings support that dietary compounds have potential to be used as anticancer agents as both food supplements and direct clinical drugs.
    [Show full text]
  • Formulation of Piperine–Chitosan-Coated Liposomes: Characterization and in Vitro Cytotoxic Evaluation
    molecules Article Formulation of Piperine–Chitosan-Coated Liposomes: Characterization and In Vitro Cytotoxic Evaluation Syed Sarim Imam 1 , Sultan Alshehri 1,* , Mohammad A. Altamimi 1, Afzal Hussain 1, Wajhul Qamar 2, Sadaf Jamal Gilani 3, Ameeduzzafar Zafar 4, Nabil K. Alruwaili 4, Saleh Alanazi 1 and Bjad K. Almutairy 5 1 Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; [email protected] (S.S.I.); [email protected] (M.A.A.); [email protected] (A.H.); [email protected] (S.A.) 2 Central Laboratory, Research Center, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; [email protected] 3 Department of Basic Health Sciences, Preparatory Year, Princess Nourahbint Adbulrahman University, Riyadh 11671, Saudi Arabia; [email protected] 4 Department of Pharmaceutics, College of Pharmacy, Jouf University, Aljouf Region, Sakaka 72341, Saudi Arabia; [email protected] (A.Z.); [email protected] (N.K.A.) 5 Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj 11942, Saudi Arabia; [email protected] * Correspondence: [email protected] Abstract: The present research work is designed to prepare and evaluate piperine liposomes and piperine–chitosan-coated liposomes for oral delivery. Piperine (PPN) is a water-insoluble bioactive compound used for different diseases. The prepared formulations were evaluated for physicochem- ical study, mucoadhesive study, permeation study and in vitro cytotoxic study using the MCF7 Citation: Imam, S.S.; Alshehri, S.; breast cancer cell line. Piperine-loaded liposomes (PLF) were prepared by the thin-film evaporation Altamimi, M.A.; Hussain, A.; Qamar, method.
    [Show full text]
  • Sulforaphene Isolated from Radish (Raphanus
    Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 3 July 2018 doi:10.20944/preprints201807.0060.v1 Article Sulforaphene Isolated from Radish (Raphanus Sativus L.) Seeds Inhibits Growth of Six Cancer Cell Lines and Induces Apoptosis of A549 Cells Sooyeon Lim 1, 4, Jin-Chul Ahn 2, Eun Jin Lee 3, *, and Jongkee Kim 1, * 1 Department of Integrative Plant Science, Chung-Ang University, Anseong 456-756, Republic of Korea; [email protected] (S.L.); [email protected] (J.K.) 2 Department of Biomedical Engineering, College of Medicine, Dankook University, Cheonan 31116, Republic of Korea; [email protected] 3 Department of Plant Science, Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea; [email protected] 4 Seed Viability Research Team, Department of Seed Vault, Baekdudaegan National Arboretum, Bonghwa, 36209, Republic of Korea; [email protected] *Co-correspondence (E.J.L): [email protected]; Tel. +82-2-880-4565; Fax +82-2-880-2056 *Co-correspondence (J.K): [email protected]; Tel. +82-31-670-3042; Fax +82-31-670-3042 Abstract: Sulforaphene (SFE), a major isothiocyanate in radish seeds, is a close chemical relative of sulforaphane (SFA) isolated from broccoli seeds and florets. The anti-proliferative mechanisms of SFA against cancer cells have been well investigated, but little is known about the potential anti- proliferative effects of SFE. In this study, we showed that SFE purified from radish seeds inhibited the growth of six cancer cell lines (A549, CHO, HeLa, Hepa1c1c7, HT-29, and LnCaP), with relative © 2018 by the author(s).
    [Show full text]
  • A Novel Self-Emulsifying Drug Delivery System (SEDDS) Based on Vesisorb® Formulation Technology Improving the Oral Bioavailability of Cannabidiol in Healthy Subjects
    molecules Article A Novel Self-Emulsifying Drug Delivery System (SEDDS) Based on VESIsorb® Formulation Technology Improving the Oral Bioavailability of Cannabidiol in Healthy Subjects Katharina Knaub 1, Tina Sartorius 1,* , Tanita Dharsono 1, Roland Wacker 1, Manfred Wilhelm 2 and Christiane Schön 1 1 BioTeSys GmbH, Schelztorstr. 54-56, 73728 Esslingen, Germany 2 Natural and Economic Sciences, Department of Mathematics, Ulm University of Applied Sciences, Albert-Einstein-Allee 55, 89081 Ulm, Germany * Correspondence: [email protected]; Tel.: +49-711-3105-7138 Received: 18 July 2019; Accepted: 13 August 2019; Published: 16 August 2019 Abstract: Cannabidiol (CBD), a phytocannabinoid compound of Cannabis sativa, shows limited oral bioavailability due to its lipophilicity and extensive first-pass metabolism. CBD is also known for its high intra- and inter-subject absorption variability in humans. To overcome these limitations a novel self-emulsifying drug delivery system (SEDDS) based on VESIsorb® formulation technology incorporating CBD, as Hemp-Extract, was developed (SEDDS-CBD). The study objective was to evaluate the pharmacokinetic profile of SEDDS-CBD in a randomized, double-blind, cross-over design in 16 healthy volunteers under fasted conditions. As reference formulation, the same Hemp-Extract diluted with medium-chain triglycerides (MCT-CBD) was used. CBD dose was standardized to 25 mg. Pharmacokinetic parameters were analyzed from individual concentration-time curves. Single oral administration of SEDDS-CBD led to a 4.4-fold higher Cmax and a 2.85-/1.70-fold higher AUC0–8h/AUC0–24h compared to the reference formulation. Tmax was substantially shorter for SEDDS-CBD (1.0 h) compared to MCT-CBD (3.0 h).
    [Show full text]