Simplified Practical Identification of Polyphenol Types in Natural Dietaries Based on 1D and 2D Nuclear Magnetic Resonance

Azis Saifudin^1, , Habibie Habibie², Muhammad Aswad², Yasuhiro Tezuka³ and Ken Tanaka⁴

¹Faculty of Pharmacy, Universitas Muhammadiyah Surakarta, Pabelan, KTS Solo, Jawa Tengah 57102, Indonesia

²Faculty of Pharmacy, Hasanuddin University, Tamalanrea, Makassar, South Sulawesi, Indonesia

³Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3, Kanagawa machi, Kanazawa 920-1181, Japan

⁴Department of Pharmacognosy, College of Pharmaceutical Science, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577, Japan

Cite this paper:
Azis Saifudin, Habibie Habibie, Muhammad Aswad, Yasuhiro Tezuka and Ken Tanaka. Simplified Practical Identification of Polyphenol Types in Natural Dietaries Based on 1D and 2D Nuclear Magnetic Resonance. Journal of Food and Nutrition Research. 2023; 11(12):742-751. doi: 10.12691/jfnr-11-12-6

Abstract

Polyphenol groups have gained great interest as health-promoting and ailment-preventing agents in food ingredients. Their large range of distribution in the plant kingdom offers prospective development for many kinds of food products. From the beginning of the development processes, polyphenol group identity must be confirmed in order to guarantee the quality of their bioactivity, concentration consistency from batch to batch, and molecular stability. 1D and 2D nuclear magnetic resonance (NMR) provide robust and efficient finger printing of each polyphenol type at the skeleton level. Therefore, understanding the molecular skeleton of polyphenol types and their corresponding NMR typical signal has clearly become a necessity. However, for those in the initial involvement stage of polyphenol studies who do not possess adequate fundamental concepts in organic molecule structure, this will be a burdensome task. The goal of this review is to facilitate understanding how to use ¹H and ¹³NMR spectra to figure out the type of polyphenol based on the type of skeleton derived from possible biosynthesis pathways. Since simple polyketide polyphenol groups are very rarely found in a settled group, shikimic acid-derived compounds such as hydroxy benzoic acid and ferulic acid become the entry point to insight into more complex groups: coumarin, lignan, diarylheptanoid, Anthraquinone, phloroglucinol, xanthonoid flavonoid, stilbenoid, glycosides, and combined polyphenols with terpenoids. 2D NMR methods, in particular COSY and HMBC spectra data, are highlighted for determining the attachment site of each skeleton identity. Flavonoid, lignan, and stilbenoid oligomer possibilities possessing spatial orientation are also featured.

Keywords:
polyphenols natural dietaries healthy food product ¹H ¹³C NMR HMBC

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

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References:

[1]	Hättenschwiler S, Vitousek PM (2000) The role of polyphenols in terrestrial ecosystem nutrient cycling. Trends in Ecology and Evolution 15 (6): 238-243.
[2]	Padhi EM, Liu R, Hernandez M, Tsao R, Ramdath DD (2017) Total polyphenol content, carotenoid, tocopherol and fatty acid composition of commonly consumed Canadian pulses and their contribution to antioxidant activity. Journal of Functional Foods, 38: 602-611.
[3]	Rajaram S, Jones J, Lee GJ (2019) Plant-based dietary patterns, plant foods, and age-related cognitive decline. Advances in Nutrition, 10(Supplement_4): S422-S436.
[4]	Bahramsoltani R, Ebrahimi F, Farzaei MH, Baratpourmoghaddam A, Ahmadi P, Rostamiasrabadi P, Amirabadi AHR, Rahimi R (2019) Dietary polyphenols for atherosclerosis: A comprehensive review and future perspectives. Critical Reviews in Food Science and Nutrition, 59(1): 114-132.
[5]	Medina‐Remón A, Casas R, Tressserra‐Rimbau A, Ros E, Martínez‐González MA, Fitó M, Corella D, Salas-Salvado J, Lamuela-Raventos RM, Estruch R (2017) Polyphenol intake from a Mediterranean diet decreases inflammatory biomarkers related to atherosclerosis: a substudy of the PREDIMED trial. British Journal of Clinical Pharmacology, 83(1): 114-128.
[6]	Oyenihi AB, Smith C (2019) Are polyphenol antioxidants at the root of medicinal plant anti-cancer success? Journal of Ethnopharmacology, 229: 54-72.
[7]	Sharma A, Kaur M, Katnoria JK, Nagpal AK (2018) Polyphenols in food: Cancer prevention and apoptosis induction. Current Medicinal Chemistry, 25(36): 4740-4757.
[8]	Zamora-Ros R, Knaze V, Rothwell JA, Hémon B, Moskal A, Overvad K, Tjønneland A, Kyrø C, Scalbert A (2016) Dietary polyphenol intake in Europe: the European Prospective Investigation into Cancer and Nutrition (EPIC) study. European Journal of Nutrition, 55: 1359-1375.
[9]	Bellavia D, Caradonna F, Dimarco E, Costa V, Carina V, De Luca A, Raimondi L, Milena F, Gentile C, Giavaresi G (2021) Non-flavonoid polyphenols in osteoporosis: Preclinical evidence. Trends in Endocrinology and Metabolism, 32(7): 515-529.
[10]	Chisari E, Shivappa N, Vyas S (2019) Polyphenol-rich foods and osteoporosis. Current Pharmaceutical Design, 25(22): 2459-2466.
[11]	Del Bo C, Bernardi S, Cherubini A, Porrini M, Gargari G, Hidalgo-Liberona N, González-Domínguez R, Zamora-Ros R, Peron G, Marino M, Gigliotti L, Winterbone MS, Kirkup, Kroon PA, Andreas-Lacueva C, Guglielmetti S, Riso P (2021) A polyphenol-rich dietary pattern improves intestinal permeability, evaluated as serum zonulin levels, in older subjects: The MaPLE randomised controlled trial. Clinical Nutrition, 40(5): 3006-3018.
[12]	Sun L, Miao M (2020) Dietary polyphenols modulate starch digestion and glycaemic level: A review. Critical Reviews in Food Science and Nutrition, 60(4): 541-555.
[13]	Wisnuwardani R W, De Henauw S, Forsner M, Gottrand F, Huybrechts I, Knaze V, Kersting M, Le Donne C, Manios Y, Marcos A, Molnar D, Rothwell JA, Scarlbert A, Sjöström M, Widhalm K, Moreno LA, Michels N (2020) Polyphenol intake and metabolic syndrome risk in European adolescents: the HELENA study. European Journal of Nutrition, 59: 801-812.
[14]	Dewick PM (2009) Medicinal Natural Products A Biosynthetic Approach 3rd Edition, John Wiley & Sons.
[15]	Holland HL, Weber HK (2000) Enzymatic hydroxylation reactions. Current Opinion in Biotechnology 11 (6): 547-553.
[16]	Laufs U, Parhofer KG, Ginsberg HN, Hegele RA (2020) Clinical review on triglycerides. European Heart Journal, 41(1): 99-109c.
[17]	Rawat G, Tripathi P, Saxena RK (2013). Expanding horizons of shikimic acid: Recent progresses in production and its endless frontiers in application and market trends. Applied Microbiology and Biotechnology, 97: 4277-4287.
[18]	Santos-Sánchez NF, Salas-Coronado R, Hernández-Carlos B, Villanueva-Cañongo C (2019) Shikimic Acid Pathway in Biosynthesis of Phenolic Compounds. In Plant Physiological Aspects of Phenolic Compounds (Marcos, S.-H. et al. eds), p. Ch. 3, IntechOpen.
[19]	El-Seedi HR, El-Barbary MA, El-Ghorab DMH, Bohlin L, Borg-Karlson AK, Goransson U, Verpoorte R (2010) Recent insights into the biosynthesis and biological activities of natural xanthones. Current Medicinal Chemistry, 17(9): 854-901.
[20]	Silverstein RM, Webster FX, Kiemle DJ (2005) Spectrometric Identification of Organic Compounds, Weiley, New York.
[21]	Metsämuuronen S, Sirén H (2019) Bioactive phenolic compounds, metabolism and properties: a review on valuable chemical compounds in Scots pine and Norway spruce. Phytochemistry Reviews 18 (3): 623-664.
[22]	Shahidi F, Varatharajan V, Oh WY, Peng H (2019) Phenolic compounds in agri-food by-products, their bioavailability and health effects. Food Bioact, 5(1): 57-119.
[23]	Takenaka M, Yan X, Ono H, Yoshida M, Nagata T, Nakanishi T (2003) Caffeic acid derivatives in the roots of yacon (Smallanthus sonchifolius). Journal of Agricultural and Food Chemistry, 51(3): 793-796.
[24]	Küpeli Akkol E, Genç Y, Karpuz B, Sobarzo-Sánchez E, Capasso R (2020) Coumarins and coumarin-related compounds in pharmacotherapy of cancer. Cancers, 12(7): 1959.
[25]	Sharifi-Rad J, Cruz-Martins N, López-Jornet P, Lopez EPF, Harun N, Yeskaliyeva B, Cho WC (2021). Natural coumarins: exploring the pharmacological complexity and underlying molecular mechanisms. Oxidative Medicine and Cellular Longevity, 2021.
[26]	Adfa M, Yoshimura T, Komura K, Koketsu M (2010) Antitermite activities of coumarin derivatives and scopoletin from Protium javanicum Burm. f. Journal of Chemical Ecology, 36, 720-726.
[27]	Carpinella MC, Ferrayoli CG, Palacios SM (2005) Antifungal synergistic effect of scopoletin, a hydroxycoumarin isolated from Melia azedarach L. fruits. Journal of Agricultural and Food Chemistry, 53(8): 2922-2927.
[28]	Sun DJ, Zhu LJ, Zhao YQ, Zhen YQ, Zhang L, Lin CC, Chen LX (2020) Diarylheptanoid: A privileged structure in drug discovery. Fitoterapia, 142: 104490.
[29]	Motiur Rahman AFM, Lu Y, Lee HJ, Jo H, Yin W, Alam MS, Jahng Y (2018) Linear diarylheptanoids as potential anticancer therapeutics: synthesis, biological evaluation, and structure–activity relationship studies. Archives of Pharmacal Research, 41, 1131-1148.
[30]	Sorng S, Balayssac S, Danoun S, Assemat G, Mirre A, Cristofoli V, Malet-Martino M (2022) Quality assessment of Curcuma dietary supplements: Complementary data from LC-MS and 1H NMR. Journal of Pharmaceutical and Biomedical Analysis, 212, 114631.
[31]	Singh J, Hussain Y, Luqman S, Meena A (2021) Purpurin: A natural anthraquinone with multifaceted pharmacological activities. Phytotherapy Research, 35(5), 2418-2428.
[32]	Siddamurthi S, Gutti G, Jana S, Kumar A, Singh SK (2020) Anthraquinone: a promising scaffold for the discovery and development of therapeutic agents in cancer therapy. Future Medicinal Chemistry, 12(11), 1037-1069.
[33]	Saifudin A, Tanaka K, Kadota S, Tezuka Y (2012) Protein tyrosine phosphatase 1B (PTP1B)-inhibiting constituents from the leaves of Syzygium polyanthum. Planta Medica, 78(12): 1378-1381.
[34]	Khan F, Tabassum N, Bamunuarachchi NI, Kim YM (2022) Phloroglucinol and its derivatives: Antimicrobial properties toward microbial pathogens. Journal of Agricultural and Food Chemistry, 70(16): 4817-4838.
[35]	Delfanian M, Sahari MA, Barzegar M, Ahmadi Gavlighi H (2021) Structure–antioxidant activity relationships of gallic acid and phloroglucinol. Journal of Food Measurement and Characterization, 15, 5036-5046.
[36]	Santos CM, Proença C, Freitas M, Araújo AN, Silva AM, Fernandes E (2022) Inhibition of the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase by hydroxylated xanthones. Food and Function, 13(14): 7930-7941.
[37]	Salman Z, Yu-Qing J, Bin L, Cai-Yun P, Iqbal CM, Atta-ur R, Wei W (2019) Antioxidant nature adds further therapeutic value: an updated review on natural xanthones and their glycosides. Digital Chinese Medicine, 2(3): 166-192.
[38]	Duangsrisai S, Choowongkomon K, Bessa LJ, Costa PM, Amat N, Kijjoa A (2014) Antibacterial and EGFR-tyrosine kinase inhibitory activities of polyhydroxylated xanthones from Garcinia succifolia. Molecules, 19(12): 19923-19934.
[39]	Panche AN, Diwan AD, Chandra SR (2016) Flavonoids: an overview. Journal of Nutritional Science, 5, e47.
[40]	Dalgaard F, Bondonno NP, Murray K, Bondonno CP, Lewis JR, Croft KD, Hodgson JM (2019) Associations between habitual flavonoid intake and hospital admissions for atherosclerotic cardiovascular disease: a prospective cohort study. The Lancet Planetary Health, 3(11): e450-e459.
[41]	Cassidy A, Franz M, Rimm EB (2016) Dietary flavonoid intake and incidence of erectile dysfunction. The American Journal of Clinical Nutrition, 103(2): 534-541.
[42]	Bondonno NP, Dalgaard F, Kyrø C, Murray K, Bondonno CP, Lewis JR, Hodgson JM (2019) Flavonoid intake is associated with lower mortality in the Danish Diet Cancer and Health Cohort. Nature Communications, 10(1): 3651.
[43]	Shishtar E, Rogers GT, Blumberg JB, Au R, Jacques PF (2020) Long-term dietary flavonoid intake and risk of Alzheimer disease and related dementias in the Framingham Offspring Cohort. The American Journal of Clinical Nutrition, 112(2): 343-353.
[44]	Lee DF, Swinny EE, Jones GP (2004) NMR identification of ethyl-linked anthocyanin–flavanol pigments formed in model wine ferments. Tetrahedron Letters, 45(8): 1671-1674.
[45]	Sun HY, Xiao CF, Cai YC, Chen Y, Wei W, Liu XK, Zou Y (2010) Efficient synthesis of natural polyphenolic stilbenes: resveratrol, piceatannol and oxyresveratrol. Chemical and Pharmaceutical Bulletin, 58(11): 1492-1496.
[46]	Balas L, Vercauteren J (1994) Extensive high‐resolution reverse 2D NMR analysis for the structural elucidation of procyanidin oligomers. Magnetic Resonance in Chemistry, 32(7): 386-393.
[47]	Wang CM, Hsu YM, Jhan YL, Tsai SJ, Lin SX, Su CH, Chou CH (2015) Structure elucidation of procyanidins isolated from Rhododendron formosanum and their anti-oxidative and anti-bacterial activities. Molecules, 20(7): 12787-12803.
[48]	Ji MS, Piao XL, Jin YL, Park RD (2005) Anticoagulant 1, 2, 3, 4, 6-pentagalloyl-β-d-glucopyranose isolated from geranium (Pelargonium inquinans Ait). Archives of Pharmacal Research, 28, 1037-1041.
[49]	Lavoie S, Ouellet M, Fleury PY, Gauthier C, Legault J, Pichette A (2016) Complete 1H and 13C NMR assignments of a series of pergalloylated tannins. Magnetic Resonance in Chemistry, 54(2): 168-174.
[50]	Oniki K, Kawakami T, Nakashima A, Miyata K, Watanabe T, Fujikawa H, Shuto T (2020) Melinjo seed extract increases adiponectin multimerization in physiological and pathological conditions. Scientific Reports, 10(1): 4313.
[51]	Yoneshiro T, Kaed R, Nagaya K, Saito M, Aoyama J, Elfeky M, Terao A (2018) Melinjo (Gnetum gnemon L.) seed extract induces uncoupling protein 1 expression in brown fat and protects mice against diet-induced obesity, inflammation, and insulin resistance. Nutrition Research, 58, 17-25.
[52]	Tse TJ, Guo Y, Shim YY, Purdy SK, Kim JH, Cho JY, Reaney MJ (2022) Availability of bioactive flax lignan from foods and supplements. Critical Reviews in Food Science and Nutrition, 1-16.
[53]	Suh WS, Subedi L, Kim SY, Choi SU, Lee KR (2016) Bioactive lignan constituents from the twigs of Sambucus williamsii. Bioorganic and Medicinal Chemistry Letters, 26(8): 1877-1880.
[54]	Meeprom S, Sathatip P, Leruksa C, Manosuthi N, Fakfare P (2023) Cannabis-infused food: Uncovering effective conditions for achieving well-being perception and choice behavior among young adult consumers. Food Quality and Preference, 104915.
[55]	Li Y, Shen Y, Yao CL, Guo DA (2020) Quality assessment of herbal medicines based on chemical fingerprints combined with chemometrics approach: A review. Journal of Pharmaceutical and Biomedical Analysis, 185, 113215.
[56]	Ludwig C, Viant MR (2010) Two‐dimensional J‐resolved NMR spectroscopy: review of a key methodology in the metabolomics toolbox. Phytochemical Analysis: An International Journal of Plant Chemical and Biochemical Techniques, 21(1): 22-32.
[57]	Monakhova YB, Kuballa T, Lachenmeier DW (2013) Chemometric methods in NMR spectroscopic analysis of food products. Journal of Analytical Chemistry, 68, 755-766.
[58]	Hatzakis E (2019) Nuclear magnetic resonance (NMR) spectroscopy in food science: A comprehensive review. Comprehensive Reviews in Food Science and Food Safety, 18(1): 189-220.
[59]	OIV Compendium of International Methods of Analysis: Determination of the Deuterium Distribution in Ethanol Derived from Fermentation of Grape Musts, Concentrated Grape Musts, Grape Sugar (Rectified Concentrated Grape Musts) and Wines by Application of Nuclea. , (accessed 7 December 2023).
[60]	Jamin E, Thomas F (2018) SNIF-NMR applications in an economic context: fraud detection in food products. Modern Magnetic Resonance; Springer: Berlin/Heidelberg, Germany, 1405-1416.