• Galina Krusir Odesa National University of Technology, 2Institute for Ecopreneurship, School of Life Sciences, University of Applied Sciences und Arts Northwestern Switzerland, Ukraine
  • Liudmyla Pylypenko Odesa National University of Technology, Ukraine
  • Elena Sevastyanova Odesa National University of Technology, Ukraine
  • Kseniia Mazurenko Odesa National University of Technology, Ukraine
  • Serhii Moshtakov Odessa Polytechnic National University, Ukraine
  • Hanna Shunko Odessa Polytechnic National University, Ukraine
  • Antonina Vitiuk Odesa National University of Technology, Ukraine
  • Tetyana Shpyrko Odesa National University of Technology, Ukraine
  • Oleksandr Zdoryk Institute for Pharma Technology, National University of Pharmacy, Ukraine



biotechnologie; pharmacology; pancreatic lipase inhibitor; rapeseed seeds; phenolic compounds; inhibitory activity; extraction and purification; composition and physico-chemical properties; pH-stability; temperature stable


Digestive enzymes and inhibitors of digestive enzymes are effective correctors of digestive processes in the body, the violation of which leads to various diseases (diabetes, hyperlipidemia, cardiovascular diseases, neoplasms and others). The present study identified the most promising plant objects characterized by the highest antilipolytic activity (ALA) in relation to pancreatic lipase. The experimental results indicate that the inhibitory activity (IA) of phenolic compounds of rapeseed is so much high and comparable to ALA "Orlistat", reaching 95.5 % of its activity. This determines the potential possibility of using the phenolic complex of rapeseed as an alternative to anti-lipolytic drugs of synthetic origin. The predominant component of the phenolic complex is low molecular weight phenolic compounds; polyphenolic compounds are almost equally represented by tannins – condensed and hydrolyzable. According to TLC data, the main components of low molecular weight phenols are glucopyranosylsinapate, sinapic acid and sinapin. Among the phenolic compounds of rapeseed seeds, sinapine and hydrolyzable tannins have the highest anti lipolytic activity against lipase. Significant ability to inhibit the action of pancreatic lipase is characterized by both low molecular weight and high molecular weight phenolic compounds of rapeseed.


Reshta S.P., Pylypenko L.M., Danilova O.I. (2021). Physiological aspects of food quality assessment, Kherson: OLDI-PLUS.

Cairns, E. (2005). Obesity: the fat lady sings? Drug Discov. Today, 10, 305–307. doi: 10.1016/S1359-6446(05)03375-1

Arbeeny, C.M. (2004). Addressing the unmet medical need for safe and effective weight loss therapies. Obes. Res. 12, 1191–1196 doi: 10.1038/oby.2004.150

Harrold, J., Williams G., Wong S. (2003). Neuroendocrine targets for the treatment of obesity: physiological roles and unrealized opportunities. Curr. Med. Chem. Central Nerv. Syst. Agents 3, 141–155. doi: 10.2174/1568015033477785

Foster-Schubert, K.E. and Cummings, D.E. (2006). Emerging therapeutic strategies for obesity. Endocr. Rev. 27, 779–793. doi: 10.1210/er.2006-0041

Halford, J., Cooper G., Dovey T., Ishii Y., Rodgers J., Blundell J. (2003) The psychopharmacology of appetite: targets for potential anti-obesity agents. Curr. Med. Chem. Central Nerv. Syst. Agents 3, 283–310. doi: 10.2174/1568015033477695

Cooke, D. and Bloom, S. (2006). The obesity pipeline: current strategies in the development of anti-obesity drugs. Nat. Rev. Drug Discov. 5, 919–931 doi: 10.1038/nrd2136

Ding Y., Wang L., Im S., Hwang O., Kim H.S., Kang M.C., Lee S.H. (2019). Anti-Obesity Effect of Diphlorethohydroxycarmalol Isolated from Brown Alga Ishige okamurae in High-Fat Diet-Induced Obese Mice. Mar. Drugs , 17(11), 637. doi: 10.3390/md17110637.

Moon J., Kim O.Y., Jo, G., Shin, M.J. (2017). Alterations in Circulating Amino Acid Metabolite Ratio Associated with Arginase Activity Are Potential Indicators of Metabolic Syndrome: The Korean Genome and Epidemiology Study. Nutrients, 9(7), 740. doi: 10.3390/nu9070740.

Hofbauer, K.G. (2002). Molecular pathways to obesity. Int. J. Obes. 26, 18–27.

Das, S. K., Chakrabarti, R. (2006). Antiobesity therapy: emerging drugs and targets. Curr. Med. Chem. 13, 1429–1460 doi: 10.2174/092986706776872880

Melnikova, I. and Wages, D. (2006). Antiobesity therapies. Nat. Rev. Drug Discov. 5, 369–370 doi: 10.1038/nrd2037

Shi, Y., Burn, P. (2004). Lipid metabolic enzymes: Emerging drug targets for the treatment of obesity. Nat. Rev. Drug Discov. 3, 695–710. doi: 10.1038/nrd1469

Mancini, M.C., Halpern, A. (2006). Investigational therapies in the treatment of obesity. Expert Opin. Investig. Drugs 15, 897–915. doi: 10.1517/13543784.15.8.897

Marcini, M.C., Halpern, A. (2006). Pharmacological treatment of obesity. Arq. Bras. Endocrinol. Metab., 50, 377–389

Szewczyk, J.R., Sternbach, D.D. (2005). Combating obesity by targeting nuclear receptors. Curr. Med. Chem. – Immun., Endoc. & Metab. Agents, 5, 73–84. doi: 10.2174/1568013053005427

Nisoli, E., Carruba, M.O. (2004). Emerging aspects of pharmacotherapy for obesity and metabolic syndrome. Pharmacol. Res., 50, 453–469. doi: 10.1016/j.phrs.2004.02.004

Srivastava, R.K., Srivastava, N. (2004). Search for obesity drugs: Targeting central and peripheral pathways. Curr. Med. Chem. – Immun., Endoc. & Metab. Agents, 4, 75–90 doi: 10.2174/1568013043357806

Weigle, D.S. (2003). Pharmacological therapy of obesity: Past, present, and future. J. Clin. Endocrinol. Metab. 88, 2462–2469.

Halpern, A., Mancini, M.C. (2003). Treatment of obesity: an update on antiobesity medications. Obes. Rev., 4, 25–42 doi: 10.1046/j.1467-789x.2003.00083.x

Ramesh S., Abraham R.A., Sarna A., Sachdev H.S., Porwal A., Khan N., Acharya R., Agrawal P.K., Ashraf S. (2022). Prevalence of metabolic syndrome among adolescents in India: a population-based study. BMC Endocr Disord., 22(1), 258. doi: 10.1186/s12902-022-01163-8.

Hauner, H. (2001) Current pharmacological approaches to the treatment of obesity. Int. J. Obes. 25, 102–106. doi: 10.1038/sj.ijo.0801711

Davidowa H., Li Y., Plagemann A. (2003). Altered responses to orexigenic (AGRP, MCH) and anorexigenic (alpha-MSH, CART) neuropeptides of paraventricular hypothalamic neurons in early postnatally overfed rats. Eur J Neurosci., 18(3), 13–21. doi: 10.1046/j.1460-9568.2003.02789.x

Bhutani, K.K., Birari R., Kapat K. (2007). Potential antiobesity and lipid lowering natural products: a review. Nat. Product Commun., 2, 331–348.


Srivastava, R.K., Srivastava, N. (2004) Search for obesity drugs: Targeting central and peripheral pathways. Curr. Med. Chem. – Immun., Endoc. & Metab. Agents 4, 75–90 doi: 10.2174/1568013043357806

Weigle, D.S. (2003) Pharmacological therapy of obesity: Past, present, and future. J. Clin. Endocrinol. Metab. 88, 2462–2469.

Mukherjee, M. (2003) Human digestive and metabolic lipases—a brief review. J. Mol. Catal., B Enzym. 22, 369–376. doi:10.1016/S1381-1177(03)00052-3

Ali-Shtayeh M.S., Abu-Zaitoun S.Y., Dudai N., Jamous R.M. (2020). Downy Lavender Oil: A Promising Source of Antimicrobial, Antiobesity, and Anti-Alzheimer's Disease Agents. Evid Based Complement Alternat Med. 5679408. doi: 10.1155/2020/5679408.

Heck A.M., Yanovski J.A., Calis K.A. (2000) Orlistat, a new lipase inhibitor for the management of obesity, Pharmacotherapy 20, 270–279.

Liu T.-T., Liu X.-T., Chen Q.-X., Shi Y. (2020) Lipase inhibitors for obesity: a review, Biomed. Pharmacother. 128, 110314.

Seyedan A., Alshawsh M.A., Alshagga M.A., Koosha S., Zahurin M (2015) Medicinal plants and their inhibitory activities against pancreatic lipase: a review, Alternat. Med., 973143

Singh G., Suresh S., V.K. Bayineni, R.K. Kadeppagari (2015) Lipase inhibitors from plants and their medical applications, Int J Pharm Pharm Sci 7 (Supple 1) 1–5., 4177.

Birari R.B., Bhutani K.K. (2007) Pancreatic lipase inhibitors from natural sources: unexplored potential, Drug Discov. Today 12 879–889.

Garza A.L., Milagro F.I., Boque N., Campion J., Martínez J.A. (2011) Natural inhibitors of pancreatic lipase as new players in obesity treatment, Planta Med. 77, 773–785. doi: 10.1055/s-0030-1270924

Buchholz T., Melzig M.F. (2015) Polyphenolic compounds as pancreatic lipase inhibitors, Planta Med. 81, 771–783. doi: 10.1055/s-0035-1546173

Lunagariya N.A., Patel N.K., Jagtap S.C., Bhutani K.K. (2014) Inhibitors of pancreatic lipase: state of the art and clinical perspectives, EXCLI J. 13, 897–921.

Almasri I.M. (2020) Computational approaches for the discovery of natural pancreatic lipase inhibitors as antiobesity agents, Future Med. Chem. 12, 741–757. doi: 10.4155/fmc-2019-0284

Weibel E.K., Hadvary P., Hochuli E., Kupfer E., Lengsfeld H. (1987) Lipstatin, an inhibitor of pancreatic lipase, produced by Streptomyces toxytricini. I. Producing organism, fermentation, isolation and biological activity, J. Antibiot. (Tokyo) 40, 1081–1085.

Híreš M., Rapavá N., Šimkovič M., Varečka Ľ., Berkeš D., Kryštofová S. (2018). Development and Optimization of a High-Throughput Screening Assay for Rapid Evaluation of Lipstatin Production by Streptomyces Strains. Curr Microbiol., 75(5), 580–587. doi: 10.1007/s00284-017-1420-x

Kim S., Lim S.D. Separation and Purification of Lipase Inhibitory Peptide from Fermented Milk by Lactobacillus plantarum Q180. Food Sci Anim Resour., 40(1), 87–95. doi: 10.5851/kosfa.2019.e87

Kamlesh K., Birari R., Kausik R. (2007) Potential antiobesity and lipid lowering natural products: a review. Nat. Product Commun. 2, 331–348. doi:10.1177/1934578X0700200316

Clapham, J.C., Arch, J.R.S., Tadayyon, M., (2001). Anti-obesity drugs: a critical review of current therapies and future opportunities. Pharmacol. Ther. 89(1), 81–121. doi: 10.1016/s0163-7258(00)00105-4

Kaila, B., Raman, M. (2008). Obesity: a review of pathogenesis and management strategies. Can. J. Gastroenterol. 22(1), 61–68. doi: 10.1155/2008/609039

Yun, J.W., 2010. Possible anti-obesity therapeutics from nature – a review. Phytochemistry 71(14-15), 1625–1641. doi: 10.1016/j.phytochem.2010.07.011

Zeng, S.L., Li, S.Z., Lai, C.J., Wei, M.Y., Chen, B.Z., Li, P., Zheng, G.D., Liu, E.H., (2018). Evaluation of anti-lipase activity and bioactive flavonoids in the Citri Reticulatae Pericarpium from different harvest time. Phytomedicine, 43, 103–109. doi: 10.1016/j.phymed.2018.04.008

Gondoin, A., Grussu, D., Stewart, D., McDougall, G. J. (2010). White and green tea polyphenols inhibit pancreatic lipase in vitro. Food Research International, 43(5), 1537–1544.

Rahim, A.T.M.A., Takahashi, Y., Yamaki, K. (2015). Mode of pancreatic lipase inhibition activity in vitro by some flavonoids and non-flavonoid polyphenols. Food Res. Int., 75, 289–294. doi: 10.1016/j.foodres.2015.05.017

Belfeki, H., Mejri, M., Hassouna, M. (2016). Antioxidant and anti-lipases activities in vitro of Mentha viridis and Eucalyptus globulus extracts. Ind. Crops Prod. 89, 514–521. doi:10.1016/j.indcrop.2016.06.002

Jeong, J.Y., Jo, Y.H., Kim, S.B., Liu, Q., Lee, J.W., Mo, E.J., Lee, K.Y., Hwang, B.Y., Lee, M.K. (2015). Pancreatic lipase inhibitory constituents from Morus alba leaves and optimization for extraction conditions. Bioorg. Med. Chem. Lett. 25(11), 2269–2274. doi: 10.1016/j.bmcl.2015.04.045

Dechakhamphu, A., Wongchum, N. (2015). Screening for anti-pancreatic lipase properties of 28 traditional Thai medicinal herbs. Asian Pac. J. Trop. Biomed. 5(12), 1042–1045.

Slanc, P., Doljak, B., Kreft, S., Lunder, M., Janes, D., Strukelj, B. (2009). Screening of selected food and medicinal plant extracts for pancreatic lipase inhibition. Phytother. Res. 23(6), 874–877. doi: 10.1002/ptr.2718

Wikiera A., Mika M., Zyla K., (2012) Methylxanthine drugs are human pancreatic lipase inhibitors, Pol. J. Food Nutr. Sci., 62 109–113.

Matsumoto M., Hosokawa M., Matsukawa N., Hagio M., Shinoki A., Nishimukai M. (2010) Suppressive effects of the marine carotenoids, fucoxanthin and fucoxanthinol on triglyceride absorption in lymph duct cannulated rats, Eur. J. Nutr. 49 243–249. doi: 10.1007/s00394-009-0078-y

Habtemariam S. (2013) Antihyperlipidemic components of Cassia auriculata aerial parts: identification through in vitro studies, Phytother. Res. 27, 152–155. doi: 10.1002/ptr.4711

Han L, Li W., Narimatsu S, Liu L., Fu H., Okuda H, (2007) Inhibitory effects of compounds isolated from fruit of Juglans mandshurica on pancreatic lipase, J. Nat. Med. 61, 184–186. doi:10.1007/s11418-006-0109-4

Lee E.M., Lee S.S., Chung B.Y., Cho J.Y., Lee I.C., Ahn S.R. (2010) Pancreatic lipase inhibition by C-glycosidic flavones isolated from Eremochloa ophiuroides, Mol 15, 8251–8259. doi: 10.3390/molecules15118251

Birari R.B., Gupta S, Mohan C.G., Bhutani K.K. (2011) Antiobesity and lipid lowering effects of Glycyrrhiza chalcones: experimental and computational studies, Phytomedicine 18, 795–801. doi: 10.1016/j.phymed.2011.01.002

Kumar S., Alagawadi K.R. (2013) Anti-obesity effects of galangin, a pancreatic lipase inhibitor in cafeteria diet fed female rats, Pharm. Biol. 51 607–613. doi: 10.3109/13880209.2012.757327

Kawaguchi K., Mizuno T., Aida K., Uchino K. (1997) Hesperidin as an inhibitor of lipases from porcine pancreas and Pseudomonas, Biosci. Biotechnol. Biochem. 61, 102–104. doi: 10.1271/bbb.61.102

Kato E., Yama M., Nakagomi R., Shibata T., Hosokawa K., Kawabata J. (2012) Substrate like water soluble lipase inhibitors from Filipendula kamtschatica, Bioorg. Med. Chem. Lett. 22 6410–6412. doi: 10.1016/j.bmcl.2012.08.055

Yamamoto M., Shimura S., Itoh Y., Ohsaka T., Egawa M., Inoue S. (2000) Anti-obesity effects of lipase inhibitor CT-II, an extract from edible herbs, Nomame herba, on rats fed a high-fat diet, Int. J. Obes. Relat. Metab. Disord. 24 758–764. doi: 10.1038/sj.ijo.0801222

Eom S.H., Lee M.S., Lee E.W., Kim Y.M., Kim T.H. (2013). Pancreatic lipase inhibitory activity of phlorotannins isolated from Eisenia bicyclis, Phytother. Res. 27 148–151. doi: 10.1002/ptr.4694

Moreno D.A., Ilic N., Poulev A., Raskin I. (2006). Effects of Arachis hypogaea nutshell extract on lipid metabolic enzymes and obesity parameters, Life Sci. 78 2797–2803. doi: 10.1016/j.lfs.2005.11.012

Alshehri M.M., Quispe C., Herrera-Bravo J., Sharifi-Rad J., Tutuncu S., Aydar E.F., Topkaya C., Mertdinc Z., Ozcelik B., Aital M., Kumar N.V.A., Lapava N., Rajkovic J., Ertani A., Nicola S., Semwal P., Painuli S., González-Contreras C., Martorell M., Butnariu M., Bagiu I.C., Bagiu R.V., Barbhai M.D., Kumar M., Daştan S.D., Calina D., Cho W.C. (2022). A Review of Recent Studies on the Antioxidant and Anti-Infectious Properties of Senna Plants. Oxid Med Cell Longev. 6025900. doi: 10.1155/2022/6025900.

Zheng Q., Li W., Han L., Koike K (2007). Pancreatic lipase-inhibiting triterpenoid saponins from Gypsophila oldhamiana. Chem Pharm Bull (Tokyo), 55(4), 646–650. doi: 10.1248/cpb.55.646

Nakai, M., Fukui Y., S., Toyoda-Ono Y., Iwashita T., Shibata H., Mitsunaga T., Hashimoto F., Kiso Y. (2005). Inhibitory effects of oolong tea polyphenols on pancreatic lipase in vitro. J. Agric. Food Chem., 53, 4593–4598.

Shin J.E., Han M.J., Kim D.H. (2003). 3-Methylethergalangin isolated from Alpinia officinarum inhibits pancreatic lipase, Biol. Pharm. Bull. 26 854–857. doi: 10.1248/bpb.26.854

Yoshikawa M., Shimoda H., Nishida N., Takada M., Matsuda H. (2002). Salacia reticulata and its polyphenolic constituents with lipase inhibitory and lipolytic activities have mild antiobesity effects in rats, J. Nutr. 132, 1819–1824. doi: 10.1093/jn/132.7.1819

Yoshizumi K., Hirano K., Ando H., Hirai Y., Ida Y., Tsuji T. (2006). Lupane type saponins from leaves of Acanthopanax sessiliflorus and their inhibitory activity on pancreatic lipase, J. Agric. Food Chem. 54 335–341. doi: 10.1021/jf052047f

Li F., Li W., Fu H., Zhang Q., Koike K. (2007). Pancreatic lipase-inhibiting triterpenoid saponins from fruits of Acanthopanax senticosus, Chem. Pharm. Bull. (Tokyo) 55, 1087–1089. doi: 10.1248/cpb.55.1087

Han L.K., Xu B.J., Kimura Y., Zheng Y., Okuda H. (2000). Platycodin radix affects lipid metabolism in mice with high fat diet-induced obesity, J. Nutr. 130, 2760–2764. doi: 10.1093/jn/130.11.2760

Han L.K., Zheng Y.N., Yoshikawa M., Okuda H., Kimura Y. (2005). Anti-obesity effects of chikusetsusaponins isolated from Panax japonicus rhizomes, BMC Complement. Altern. Med. 5, 09–18. doi: 10.1186/1472-6882-5-9

Liu W., Zheng Y., Han L., Wang H., Saito M., Ling M. (2008). Saponins (Ginsenosides) from stems and leaves of Panax quinquefolium prevented high-fat diet-induced obesity in mice, Phytomedicine 15, 1140–1145. doi: 10.1016/j.phymed.2008.07.002

Kimura H., Ogawa S., Jisaka M., Kimura Y., Katsube T., Yokota K. (2006). Identification of novel saponins from edible seeds of Japanese horse chestnut (Aesculus turbinate Blume) after treatment with wooden ashes and their nutraceutical activity, J. Pharm. Biomed. Anal. 41, 1657–1665. doi: 10.1016/j.jpba.2006.02.031

Zheng Q., Koike K., Han L.K., Okuda H., Nikaido T. (2004). New biologically active triterpenoid saponins from Scabiosa tschiliensis, J. Nat. Prod. 67, 604–613. doi: 10.1021/np0304722

Yoshikawa M., Sugimoto S., Kato Y., Nakamura S., Wang T., Yamashita C. (2009). Acylated oleanane-type triterpene saponins with acceleration of gastrointestinal transit and inhibitory effect on pancreatic lipase from flower buds of Chinese tea plant (Camellia sinensis), Chem. Biodivers. 6, 903–915. doi: 10.1002/cbdv.200800153

Kwon C.S., Sohn H.Y., Kim S.H., Kim J.H., Son K.H., Lee J.S. (2003). Anti-obesity effect of Dioscorea nipponicamakino with lipase-inhibitory activity in rodents, Biosci. Biotechnol. Biochem. 67, 1451–1456. doi: 10.1271/bbb.67.1451

Sugimoto S., Nakamura S., Yamamoto S., Yamashita C., Oda Y., Matsuda H. (2009). Structures of triterpene oligoglycosides and lipase inhibitors from mate, leaves of Ilex paraguariensis, Chem. Pharm. Bull 57, 257–261. doi: 10.1248/cpb.57.257

Zheng Q., Li W., Han L., Koike K., (2007). Pancreatic lipase inhibiting triterpenoid saponins from Gypsophila oldhamiana, Chem. Pharm. Bull., 55, 646–650. doi: 10.1248/cpb.55.646

Lee A., Lee J.H., Baek N.I., Kim D.H. (2005). Antihyperlipidemic effect of crocin isolated from the fructus of Gardenia jasminoides and its metabolite crocetin, Biol. Pharm. Bull. 28, 2106–2110. doi: 10.1248/bpb.28.2106

Jang D.S., Lee G.Y., Kim J., Lee Y.M., Kim J.M., Kim Y.S. (2008). A new pancreatic lipase inhibitor isolated from the roots of Actinidia arguta, Arch. Pharm. Res. 31, 666–670. doi: 10.1007/s12272-001-1210-9

Ninomiya, K., Matsuda, H., Shimoda, H., Nishida, N., Kasajima, N., Yoshino, T. (2004). Carnosic acid, a new class of lipid absorption inhibitor from sage, Bioorg. Med. Chem. Lett. 14, 1943–1946. doi: 10.1016/j.bmcl.2004.01.091

Yoshizumi K., Hirano K, Ando H., Hirai Y., Yoshiteru Ida Y., Tsuj T., Satouchi K., Terao J. (2006). Lupane type saponins from leaves of Acanthopanax sessiliflorus and their inhibitory activity on pancreatic lipase. J. Agric. Food Chem. 54, 335–341. doi: 10.1021/jf052047f

Masayuki Y., Shimoda H., Nishida N., Takada M., Matsuda H. (2002). Salacia reticulata and its polyphenolic constituents with lipase inhibitory and lypophilic activities have mild antiobesity effects in rats. J. Nutr. 132, 1819–1834 doi: 10.1093/jn/132.7.1819.

Yamamota M., Shimura S, Itoh Y., Ohsaka T., Egawa M., Inoue S. (2000). Anti-obesity effects of lipase inhibitor CT-II, an extract from edible herbs, Nomame Herba, on rats fed a high-fat diet. Int. J. Obes. 24, 758– 764 doi: 10.1038/sj.ijo.0801222.

Shin, J.E., Han M.J., Kim D.H. (2002). 3-Methylethergalangin isolated from Alpinia officinarum inhibits pancreatic lipase. Biol. Pharm. Bull. 25, 1442–1445 doi: 10.1248/bpb.26.854

Moreno, D.A. et al. (2003) Inhibitory effects of grape seed extract on lipases. Nutrition 19, 876–879. doi: 10.1016/s0899-9007(03)00167-9

Cherno N. K., Krusir G.V., Kovalenko O.V. (2010) Digestors of digestive processes. Kherson: OLDI-PLUS.