Caraway (Carum carvi L.) Agro-industrial Waste; Anti-obesity Effect and Chemical Characterization
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Abstract
Roots and aerial parts are the agricultural by-products of caraway (Carum carvi L.) fruit production. Hereto, the anti-obesity and hypolipidemic effects of caraway waste were assessed using different in vitro and in vivo tests performed on total ethanol extract (TEE), as well as its fractions. The ethyl acetate fraction (EtOAc fr.) exhibited the highest inhibitory activity on pancreatic lipase (PL), α-amylase and DPPH free radical. Accordingly, it showed the highest ameliorative activity against dyslipidaemia among other fractions and the total extract when tested on a high fat diet-fed mice model. It attenuated hepatic steatosis, reduced adipocyte size, ameliorated the lipid profile, and suppressed leptin concentrations as revealed by the histopathological and biochemical examinations. Umbelliferone, p-coumaric acid and isoquercitrin were isolated from the bioactive EtOAc fr. and quantified in both, the EtOAc fr. and TEE, using HPLC. Isoquercitrin displayed the highest inhibitory activity towards DPPH and PL (IC50: 10 ± 2.50 and 93.54± 2.62 µg/mL, respectively), whereas umbelliferone was the most active against α-amylase (IC50: 50.70 ± 2.83 µg/mL). Molecular docking was carried out to uncover the binding affinities to the enzymes’ active sites. Isoquercitrin demonstrated strong interaction in the binding site of lipase (-130.87 kcal·mol-1), via H-bonding with Asp79, Ile78, Arg256, Ser152 and Tyr114, whereas, umbelliferone formed H-bonding with Tyr59 and Leu142 and H-Pi interaction with Gln63 in the amylase enzyme’s active site (-65.99 kcal·mol-1). The current research highlights the great potential for caraway waste as a multitarget remedy against obesity, which incites further molecular and clinical studies.
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Jin, X., Qiu, T., Li, L., Yu, R., Chen, X., Li, C., Proud, C.G. and Jiang, T., 2023. Pathophysiology of obesity and its associated diseases. Acta Pharm Sin. B. 2023; 13(6): 2403-2424.
WHO. World Health Organization. Obesity and overweight. [Online]. 2024 [cited 2024 July 28] Available from: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight.
World Obesity Federation. Obesity Atlas. [Online]. 2024 [cited 2024 October 20]. Available from: https://data.worldobesity.org/publications/?cat=22.
Okunogbe, A., Nugent, R., Spencer, G., Ralston, J. and Wilding, J. Economic impacts of overweight and obesity: current and future estimates for eight countries. BMJ Glob. Health. 2021; 6(10): p.e006351.
Jackson SE, Llewellyn CH, Smith L. The obesity epidemic–Nature via nurture: A narrative review of high-income countries. SAGE open medicine. 2020; 8: 2050312120918265.
Aboulghate M, Elaghoury A, Elebrashy I, Elkafrawy N, Elshishiney G, Abul-Magd E. The burden of obesity in Egypt. Front. Public Health. 2021; 9: 718978
Moradi, M., Mozaffari, H., Askari, M. and Azadbakht, L. Association between overweight/obesity with depression, anxiety, low self-esteem, and body dissatisfaction in children and adolescents: a systematic review and meta-analysis of observational studies. Crit. Rev. Food Sci. Nutr. 2021; 62(2): 555-570.
Kwok S, Adam S, Ho JH, Iqbal Z, Turkington P, Razvi S, Le Roux CW, Soran H, Syed AA. Obesity: a critical risk factor in the COVID‐19 pandemic. Clinical obesity. 2020; 10(6): e12403.
Hancková M, Betakova T. Pandemics of the 21st century: the risk factor for obese people. Viruses. 2021; 14(1): 25-41.
Kazemipoor M, Cordell, GA. Clinical effects of caraway, a traditional medicine for weight loss. In: Mukherjee, P.K. (Ed.), Evidence-Based Validation of Herbal Medicine. Elsevier; 2015. 339-362 p.
Karri S, Sharma S, Hatware K, Patil K. Natural anti-obesity agents and their therapeutic role in management of obesity: A future trend perspective. Biomed Pharmacother. 2019; 110: 224-228.
Vasudeva N, Yadav N, Sharma SK. Natural products: a safest approach for obesity. Chin J. Integr Med. 2012; 18(6): 473-480.
Muhammed, M.T. and Aki-Yalcin, E., 2024. Molecular docking: principles, advances, and its applications in drug discovery. Lett Drug Des Discov. 2024; 21(3): 480-495.
Khalil, M.N., Choucry, M.A., El Senousy, A.S., Hassan, A., El-Marasy, S.A., El Awdan, S.A. and Omar, F.A. Ambrosin, a potent NF-κβ inhibitor, ameliorates lipopolysaccharide induced memory impairment, comparison to curcumin. PLOS One. 2019; 14(7): p.e0219378.
Hussein, M.E., Mohamed, O.G., El-Fishawy, A.M., El-Askary, H.I., Hamed, A.A., Abdel-Aziz, M.M., Alnajjar, R., Belal, A., Naglah, A.M., Almehizia, A.A. and Al-Karmalawy, A.A.& El Senousy, A. S. Anticholinesterase activity of budmunchiamine alkaloids revealed by comparative chemical profiling of two Albizia spp., molecular docking and dynamic studies. Plants. 2022; 11(23): 3286.
Primiani, C.N., Sari, D.R., Krisnamurti, G.C., Pujiati, P. and Setiawan, M.A. Anti-Inflammatory Potentials of Elaeocarpus sphaericus Schum Fruit Compounds by Molecular Docking Approach. Trop J Nat Prod. 2022; 6(10):1663–1669.
Seida AA, El Tanbouly ND, Islam WT, Eid HH, El Maraghy SA, El Senousy AS. Bioassay-guided fractionation of a hepatoprotective and antioxidant extract of pea by-product. Nat Prod Res. 2015; 29(16):1578-1583.
Javed R, Hanif MA, Rehman R, Hanif M, Tung BT. Chapter 7—Caraway. In: Hanif MA, Nawaz H, Khan MM, Byrne HJ, (Eds.) Medicinal Plants of South Asia. Amsterdam: Elsevier; 2020. 87–100 p.
Lemhadri A, Hajji L, Michel JB, Eddouks M. Cholesterol and triglycerides lowering activities of caraway fruits in normal and streptozotocin diabetic rats. J Ethnopharmacol. 2006; 106(3): 321-326.
Begum S, Aslama M. Lipid lowering activity of fruits of Carum carvi Linn in cholesterol and triton fed hyperlipidemic rats. Int PharmSci. 2012; 2(2) :103-107.
Saghir MR, Sadiq S, Nayak S, Tahir MU. Hypolipidemic effect of aqueous extract of Carum carvi (black Zeera) seeds in diet induced hyperlipidemic rats. Pak J Pharm Sci. 2012; 25(2): 333-337.
Kazemipoor M, Radzi CW, Hajifaraji M, Haerian BS, Mosaddegh MH, Cordell GA. Antiobesity effect of caraway extract on overweight and obese women: a randomized, triple‐blind, placebo‐controlled clinical trial. Evid Based Complement Alternat Med. 2013; 2013(1): 928582.
Kazemipoor M, Hamzah S, Hajifaraji M, Radzi CW, Cordell GA. Slimming and Appetite‐Suppressing Effects of Caraway Aqueous Extract as a Natural Therapy in Physically Active Women. Phytother Res. 2016; 30(6): 981-987.
Cho S, Choi Y, Park S, Park T. Carvacrol prevents diet-induced obesity by modulating gene expressions involved in adipogenesis and inflammation in mice fed with high-fat diet. J Nutr Biochem. 2012; 23(2): 192-201.
Taga MS, Miller EE, Pratt DE. Chia seeds as a source of natural lipid antioxidants. J Am Oil Chem Soc. 1984; 61: 928-931.
Yadav RN, Agarwala M. Phytochemical analysis of some medicinal plants. J. Phytol. 2011; 3(12): 10-14
Bustanji Y, Al-Masri IM, Mohammad M, Hudaib M, Tawaha K, Tarazi H, AlKhatib HS. Pancreatic lipase inhibition activity of trilactone terpenes of Ginkgo biloba. J Enzym Inhib Med Ch. 2011; 26(4): 453-459.
Miller GL. Use of dinitrosalicylic acid reagent for determination of reducing sugar. Anal Chem. 1959; 31(3): 426-428.
Ijoma, K.I., Ajiwe, V.I.E. and Odinma, S.C. The organic extracts from the leaves of Ficus thonningii Blume, Jatropha tanjorensis JL Ellis and Saroja and Justicia carnea Lindley as potential nutraceutical antioxidants and functional foods. Trends Phytochem. Res. 2023; 7(1): 76-85.
Kim TR, Kim YJ, Woo CH. Anti-obesity effects of Banggihwnggi-tang-hap-yeonggyechulgam-tang in high fat diet induced obese mice model. J. Korean Med. Rehabil. 2019; 29(4): 29-45.
Kazempor SF, Hosseini M, Shafei MN, Ghorbani A, Pourganji M. The analgesic effects of different extracts of aerial parts of Coriandrum Sativum in mice. Int J Biomed Sci. 2015; 11(1): 23-28.
Showraki A, Emamghoreishi M, Oftadegan S. Anticonvulsant effect of the aqueous extract and essential oil of Carum carvi L. seeds in a pentylenetetrazol model of seizure in mice. Iran J Med Sci. 2016; 41(3): 200-208.
Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972; 18(6): 499-502.
Rylander L, Nilsson-Ehle P, Hagmar L. A simplified precise method for adjusting serum levels of persistent organohalogen pollutants to total serum lipids. Chemosphere. 2006; 62(3): 333-336.
Jeong EJ, Jegal J, Ahn J, Kim J, Yang MH. Anti-obesity effect of Dioscorea oppositifolia extract in high-fat diet-induced obese mice and its chemical characterization. Biol Pharm Bull. 2016; 39(3): 409-414.
Lei F, Zhang XN, Wang W, Xing DM, Xie WD, Su H, Du LJ. Evidence of anti-obesity effects of the pomegranate leaf extract in high-fat diet induced obese mice. Int J Obesity. 2007; 31(6): 1023-1029.
Hsu, K.C., Chen, Y.F., Lin, S.R. and Yang, J.M. iGEMDOCK: a graphical environment of enhancing GEMDOCK using pharmacological interactions and post-screening analysis. BMC Bioinformatics. 2011; 12(1): 1-11.
Devi, M., Kumar, P., Singh, R., Sindhu, J. and Kataria, R. Design, synthesis, spectroscopic characterization, single crystal X-ray analysis, in vitro α-amylase inhibition assay, DPPH free radical evaluation and computational studies of naphtho [2, 3-d] imidazole-4, 9-dione appended 1, 2, 3-triazoles. Eur J Med Chem. 2023; 250: 115230.
Kumar, S., Saroha, B., Lathwal, E., Kumar, G., Kumar, S., Kumar, R., Arya, P. and Raghav, N. An Ultrasound-assisted Three Component Protocol for the Regio and Stereo-selective Synthesis of Some Novel Dispiroheterocycles and Their Biological Evaluation as Anti-inflammatory, Anti-obesity Agents. Lett Drug Des Discov. 2024; 21(1): 133-142.
Vallverdú-Queralt A, Regueiro J, Alvarenga JF, Martinez-Huelamo M, Leal LN, Lamuela-Raventos RM. Characterization of the phenolic and antioxidant profiles of selected culinary herbs and spices: caraway, turmeric, dill, marjoram and nutmeg. Food Sci Technol. 2015; 35(1): 189-195.
Trifan A, Bostănaru AC, Luca SV, Grădinaru AC, Jităreanu A, Aprotosoaie AC, Miron A, Cioancă A, Hăncianu M, Ochiuz L, Bujor A. Antifungal potential of Pimpinella anisum, Carum carvi and Coriandrum sativum extracts. A comparative study with focus on the phenolic composition. Farmacia. 2020; 68(1): 22-27
De La Garza AL, Milagro FI, Boque N, Campión J, Martínez JA. Natural inhibitors of pancreatic lipase as new players in obesity treatment. Planta Med. 2011; 77(08): 773-785.
Yun JW. Possible anti-obesity therapeutics from nature–A review. Phytochemistry. 2010; 71(14-15): 1625-1641.
Mahmood N. A review of α-amylase inhibitors on weight loss and glycemic control in pathological state such as obesity and diabetes. Comp Clin Pathol. 2016; 25(6): 1253-1264.
Wajidi M, Vaid FH, Rizwani GH, Faiyaz A, Shareef H, Akram A, Ahmed A. Anti-Oxidant and digestive enzymes inhibitory based anti-diabetic activity of crude and fractions of Carum carvi L. extracts. Pak J Pharm Sci. 2019; 32(6): 2687-2695
Fernández-Sánchez A, Madrigal-Santillán E, Bautista M, Esquivel-Soto J, Morales-González Á, Esquivel-Chirino C, Durante-Montiel I, Sánchez-Rivera G, Valadez-Vega C, Morales-González JA. Inflammation, oxidative stress, and obesity. Int J Mol Sci. 2011; 12(5): 3117-3132.
Agbor, C.A., Fischer, C.E., Agaba, E.A. and Nnenna, W.A. Neuroprotective Effect of Beta-D-glucan Polysaccharide Fractionate of Auricularia Polytrichaon on Hyperglycaemia-Induced Cerebral Injury in Diabetic Animal Model. Trop J Nat Prod Res. 2021; 5(12): 2182-2186.
Taherkhani S, Suzuki K, Ruhee RT. A brief overview of oxidative stress in adipose tissue with a therapeutic approach to taking antioxidant supplements. Antioxidants. 2021; 10(4): 594.
Vermaak I, Viljoen AM, Hamman JH. Natural products in anti-obesity therapy. Nat Prod Rep. 2011; 28(9): 1493-533.
Abdel-Raziq MS, Bar FM, Ashamallah SA, Barakat N, Gohar AA. Anti-Obesity and Antihyperlipidemic Effects of Musa cavendishii. Rec Nat Prod. 2022; 16(3): 212-224.
Obradovic, M., Sudar-Milovanovic, E., Soskic, S., Essack, M., Arya, S., Stewart, A.J., Gojobori, T. and Isenovic, E.R. Leptin and obesity: Role and clinical implication. Front Endocrinol. 2021; 12: 585887.
Grisotto, C., Taïlé, J., Planesse, C., Diotel, N., Gonthier, M.P., Meilhac, O. and Couret, D. High-fat diet aggravates cerebral infarct, hemorrhagic transformation and neuroinflammation in a mouse stroke model. Int J Mol Sci. 2021; 22(9): 4571.
Lyu, X., Yan, K., Wang, X., Xu, H., Guo, X., Zhu, H., Pan, H., Wang, L., Yang, H. and Gong, F. A novel anti-obesity mechanism for liraglutide by improving adipose tissue leptin resistance in high-fat diet-fed obese mice. Endocr J. 2022; 69(10): 1233-1244.
Vekic, J., Stefanovic, A. and Zeljkovic, A. Obesity and dyslipidemia: a review of current evidence. Curr Obes Rep. 2023; 12(3): 207-222.
Li, Y., Feng, Y., Li, S., Ma, Y., Lin, J., Wan, J. and Zhao, M. The atherogenic index of plasma (AIP) is a predictor for the severity of coronary artery disease. Front Cardiovasc Med. 2023; 10: 1140215.
Kong LY, Li Y, Min ZD, Li X, Zhu TR. Coumarins from Peucedanum praeruptorum. Phytochemistry. 1996; 41(5): 1423-1426.
Shui G, Peng LL. An improved method for the analysis of major antioxidants of Hibiscus esculentus Linn. J Chromatogr A. 2004; 1048(1): 17-24.
Eldahshan OA. Isolation and structure elucidation of phenolic compounds of carob leaves grown in Egypt. Curr Res J Biol Sci. 2011; 3(1): 52-55.
Liao CR, Kuo YH, Ho YL, Wang CY, Yang CS, Lin CW, Chang YS. Studies on cytotoxic constituents from the leaves of Elaeagnus oldhamii Maxim. in non-small cell lung cancer A549 cells. Molecules. 2014; 19(7): 9515-9534.
Shimura S, Itoh Y, Yamashita A, Kitano A, Hatano T, Yoshida T, Okuda T. Inhibitory effects of flavonoids on lipase. Nippon Shokuhin Kogyo Gakkaishi. 1994; 41(11): 847-8450.
Sergent T, Vanderstraeten J, Winand J, Beguin P, Schneider YJ. Phenolic compounds and plant extracts as potential natural anti-obesity substances. Food Chem. 2012; 135(1): 68-73.
Hou XD, Guan XQ, Cao YF, Weng ZM, Hu Q, Liu HB, Jia SN, Zang SZ, Zhou Q, Yang L, Ge GB. Inhibition of pancreatic lipase by the constituents in St. John's Wort: In vitro and in silico investigations. Int J Biol Macromol. 2020; 145: 620-633.
Yadav N, Auti P, George G, Paul AT. Design, synthesis and biological evaluation of O-alkyl umbelliferone derivatives as pancreatic lipase inhibitors. J. Indian Chem Soc. 2020; 97: 1265-1271.
Martinez-Gonzalez AI, Alvarez-Parrilla E, Díaz-Sánchez ÁG, Rosa LD, Núñez-Gastélum JA, Vazquez-Flores AA, Gonzalez-Aguilar GA. In vitro inhibition of pancreatic lipase by polyphenols: A kinetic, Fluorescence spectroscopy and molecular docking study. Food Technol Biotechnol. 2017; 55(4): 519-530.
Rayar A, Manivannan R. In-vitro alpha-amylase and alpha-glucosidase inhibition activity of umbelliferone and beta-ionone isolated from Coriandrum sativum Linn. World J. Pharm. Pharm. Sci. 2016; 5(1): 1280-1289.
Salau VF, Erukainure OL, Ibeji CU, Koorbanally NA, Islam MS. Umbelliferone stimulates glucose uptake; modulates gluconeogenic and nucleotide-hydrolyzing enzymes activities, and dysregulated lipid metabolic pathways in isolated psoas muscle. J Funct Foods. 2020; 67: 103847.
Karakaya S, Gözcü S, Güvenalp Z, Özbek H, Yuca H, Dursunoğlu B, Kazaz C, Kılıç CS. The α-amylase and α-glucosidase inhibitory activities of the dichloromethane extracts and constituents of Ferulago bracteata roots. Pharm Biol. 2018; 56(1): 18-24.
Pollini L, Riccio A, Juan C, Tringaniello C, Ianni F, Blasi F, Mañes J, Macchiarulo A, Cossignani L. Phenolic acids from Lycium barbarum leaves: In vitro and in silico studies of the inhibitory activity against porcine pancreatic α-amylase. Processes. 2020; 8(11): 1388.
Kiliç I, Yeşiloğlu Y. Spectroscopic studies on the antioxidant activity of p-coumaric acid. Spectrochim. Acta - A: Mol. Biomol. Spectrosc. 2013; 115: 719-724.
Li X, Jiang Q, Wang T, Liu J, Chen D. Comparison of the antioxidant effects of quercitrin and isoquercitrin: Understanding the role of the 6 ″-OH group. Molecules. 2016; 21(9): 1246.
Mazimba O. Umbelliferone: Sources, chemistry and bioactivities review. Bull Fac Pharm (Cairo Univ). 2017; 55(2): 223-232.
Nguyen PT, Huynh HA, Truong DV, Tran TD, Vo CV. Exploring aurone derivatives as potential human pancreatic lipase inhibitors through molecular docking and molecular dynamics simulations. Molecules. 2020; 25(20): 4657.
Kim HM, Kim JK, Kang LW, Jeong KJ, Jung SH. Docking and scoring of quercetin and quercetin glycosides against α-amylase receptor. B Korean Chem Soc. 2010;31(2):461-463.
Luo S, Lenon GB, Gill H, Hung A, Dias DA, Li M, Nguyen LT. Inhibitory effect of a weight-loss Chinese herbal formula RCM-107 on pancreatic α-amylase activity: Enzymatic and in silico approaches. PLOS One. 2020; 15(4): e0231815.
Altuner EM. In silico proof of the effect of quercetin and umbelliferone as alpha-amylase inhibitors, which can be used in the treatment of diabetes. Kastamonu Univ J For. 2022; 22(3): 202-216.
Rasouli H, Hosseini-Ghazvini SM, Adibi H, Khodarahmi R. Differential α-amylase/α-glucosidase inhibitory activities of plant-derived phenolic compounds: A virtual screening perspective for the treatment of obesity and diabetes. Food Funct. 2017; 8(5): 1942-1954.
Sim MO, Ham JR, Lee HI, Seo KI, Lee MK. Long-term supplementation of umbelliferone and 4-methylumbelliferone alleviates high-fat diet induced hypertriglyceridemia and hyperglycemia in mice. Chem Biol Interact. 2014; 216: 9-16.
Naowaboot J, Somparn N, Saentaweesuk S, Pannangpetch P. Umbelliferone improves an impaired glucose and lipid metabolism in high‐fat diet/streptozotocin‐induced type 2 diabetic rats. Phytother Res. 2015; 29(9): 1388-95.
Park NW, Lee ES, Ha KB, Jo SH, Kim HM, Kwon MH, Chung CH. Umbelliferone Ameliorates Hepatic Steatosis and Lipid-Induced ER Stress in High-Fat Diet-Induced Obese Mice. Yonsei Med J. 2023; 64(4): 243-250.
Shen Y, Song X, Li L, Sun J, Jaiswal Y, Huang J, Liu C, Yang W, Williams L, Zhang H, Guan Y. Protective effects of p-coumaric acid against oxidant and hyperlipidemia-an in vitro and in vivo evaluation. Biomed Pharmacother. 2019; 111: 579-587.
Yoon DS, Cho SY, Yoon HJ, Kim SR, Jung UJ. Protective effects of p-coumaric acid against high-fat diet-induced metabolic dysregulation in mice. Biomed Pharmacother. 2021; 142: 111969.
Liu Z, Liu J, Tang R, Zhang Z, Tian S. Procyanidin B1 and Coumaric Acid from Highland Barley Alleviated High-Fat-Diet-Induced Hyperlipidemia by Regulating PPARα-Mediated Hepatic Lipid Metabolism and Gut Microbiota in Diabetic C57BL/6J Mice. Foods. 2024; 13(12): 1843.
Seo SH, Jo SM, Truong TT, Zhang G, Kim DS, Lee M, Lee Y, Kang I. Peanut sprout rich in p-coumaric acid ameliorates obesity and lipopolysaccharide-induced inflammation and the inhibition of browning in adipocytes via mitochondrial activation. Food Funct. 2021; 12(12): 5361-5374.
Hassan W, Rongyin G, Daoud A, Ding L, Wang L, Liu J, Shang J. Reduced oxidative stress contributes to the lipid lowering effects of isoquercitrin in free fatty acids induced hepatocytes. Oxid Med Cell Longev. 2014; 2014(1): 313602.
Lee CW, Seo JY, Lee J, Choi JW, Cho S, Bae JY, Sohng JK, Kim SO, Kim J, Park YI. 3-O-Glucosylation of quercetin enhances inhibitory effects on the adipocyte differentiation and lipogenesis. Biomed Pharmacother. 2017; 95: 589-598.
Kim JH, Lee S, Cho EJ. The protective effects of acer okamotoanum and Isoquercitrin on obesity and amyloidosis in a mouse model. Nutrients. 2020; 12(5):1353.