Abstract
Blumea lacera (Burm. f.) DC. is an aromatic annual herb that has traditionally been used to treat or protect against diabetes. Although it has infallible uses, its supply is limited due to its short lifespan. In this study, we aim to investigate the anti-diabetic potential of its micropropagated plants in type 2 diabetic mammalian (mouse) model and further expand the molecular mechanistic understanding of its activity. The water extract of the micropropagated plants was tested in mice with streptozotocin-induced diabetes. The extract effectively suppressed glucose levels prevented weight loss, and improved dyslipidemia in mice. Additionally, it improved liver injury as well as all investigated toxicity indicators, including serum glutamate-pyruvate transaminase, serum glutamic oxaloacetic transaminase, and serum anti-inflammatory marker C-reactive protein. The intramolecular interaction study revealed that the innate polyphenolic constituents of this plant more profoundly inhibited α-amylase, α-glucosidase, and lipase compared to the standard. The prolific bioactive compounds of the micropropagated plant could be attributed to these superior anti-diabetic effects, presumably via an elaborate inhibition of carbohydrate and lipid hydrolyzing enzymes. Thus, the obtained results provide solid experimental proof of the year-round utility of micropropagated plants as a standard source plant material of Blumea lacera (Burm. f.) DC. for drug research and therapeutic production.
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References
Akintola AA, van Heemst D (2015) Insulin, aging, and the brain: mechanisms and implications. Front Endocrinol 6:1–13. https://doi.org/10.3389/fendo.2015.00013
Akter R, Uddin SJ, Tiralongo J, Grice ID, Tiralongo E (2016) A new cytotoxic diterpenoid glycoside from the leaves of Blumea lacera and its effects on apoptosis and cell cycle. Nat Prod Res 30:2688–2693. https://doi.org/10.1080/14786419.2016.1146887
Asmat U, Abad K, Ismail K (2016) Diabetes mellitus and oxidative stress—a concise review. Saudi Pharm J 24:547–553. https://doi.org/10.1016/j.jsps.2015.03.013
Assadi S, Shafiee SM, Erfani M, Akmali M (2021) Antioxidative and antidiabetic effects of Capparis spinosa fruit extract on high-fat diet and low-dose streptozotocin-induced type 2 diabetic rats. Biomed Pharmacother 138:111391. https://doi.org/10.1016/j.biopha.2021.111391
Beckman JA, Creager MA, Libby P (2002) Diabetes and atherosclerosis. JAMA 287:2570. https://doi.org/10.1001/jama.287.19.2570
Chen ZC, Zhang SL, Yan L, Wu MC, Chen LH, Ji LN (2011) Association between side effects of oral anti-diabetic drugs and self-reported mental health and quality of life among patients with type 2 diabetes. Zhonghua Yi Xue Za Zhi 91:229–233. https://doi.org/10.3760/cma.j.issn.0376-2491.2011.04.004
Cho NH, Shaw JE, Karuranga S, Huang Y, da Rocha Fernandes JD, Ohlrogge AW, Malanda B (2018) IDF Diabetes Atlas: global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract 138:271–281. https://doi.org/10.1016/j.diabres.2018.02.023
DeFronzo RA (2009) From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes 58:773–795. https://doi.org/10.2337/db09-9028
DeFronzo RA, Ferrannini E, Groop L, Henry RR, Herman WH, Holst JJ, Hu FB, Kahn CR, Raz I, Shulman GI, Simonson DC (2015) Type 2 diabetes mellitus. Nat Rev Dis Primers 1:15019. https://doi.org/10.1038/nrdp.2015.19
Diabetes DOF (2010) Diagnosis and classification of diabetes mellitus. Diabetes Care 33:S62–S69. https://doi.org/10.2337/dc10-S062
Ekor M (2014) The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety. Front Neurol 4(Jan):1–10. https://doi.org/10.3389/fphar.2013.00177
Ezzat SM, Abdallah HM, Yassen NN, Radwan RA, Mostafa ES, Salama MM, Salem MA (2021) Phenolics from Physalis peruviana fruits ameliorate streptozotocin-induced diabetes and diabetic nephropathy in rats via induction of autophagy and apoptosis regression. Biomed Pharmacother 142:111948. https://doi.org/10.1016/j.biopha.2021.111948
Feng H, Chen G, Zhang Y, Guo M (2022) Potential multiple bioactive components from Sinopodophyllum hexandrum explored by affinity ultrafiltration with four drug targets. Phytomed plus 2:100219. https://doi.org/10.1016/j.phyplu.2022.100219
Giacco F, Brownlee M (2010) Oxidative stress and diabetic complications. Circ Res 107:1058–1070. https://doi.org/10.1161/CIRCRESAHA.110.223545
Goyal A, Singh NP (2007) Consumer perception about fast food in India: an exploratory study. Br Food J 109:182–195. https://doi.org/10.1108/00070700710725536
Harley BK, Dickson RA, Amponsah IK, Ben IO, Adongo DW, Fleischer TC, Habtemariam S (2020) Flavanols and triterpenoids from Myrianthus arboreus ameliorate hyperglycaemia in streptozotocin-induced diabetic rats possibly via glucose uptake enhancement and α-amylase inhibition. Biomed Pharmacother 132:110847. https://doi.org/10.1016/j.biopha.2020.110847
Hiriart M, Velasco M, Larqué C, Diaz-Garcia CM (2014) Metabolic syndrome and ionic channels in pancreatic beta cells. Vitam Horm 95:87–114. https://doi.org/10.1016/B978-0-12-800174-5.00004-1
Imran M, Saeed F, Hussain G et al (2021) Myricetin: a comprehensive review on its biological potentials. Food Sci Nutr 9:5854–5868. https://doi.org/10.1002/fsn3.2513
Kan J, Velliquette RA, Grann K, Burns CR, Scholten J, Tian F, Zhang Q, Gui M (2017) A novel botanical formula prevents diabetes by improving insulin resistance. BMC Complement Altern Med 17:352. https://doi.org/10.1186/s12906-017-1848-3
Kim DY, Kim SR, Jung UJ (2020) Myricitrin ameliorates hyperglycemia, glucose intolerance, hepatic steatosis, and inflammation in high-fat diet/streptozotocin-induced diabetic mice. Int J Mol Sci 21:1870. https://doi.org/10.3390/ijms21051870
Krauss RM (2004) Lipids and lipoproteins in patients with type 2 diabetes. Diabetes Care 27:1496–1504. https://doi.org/10.2337/diacare.27.6.1496
Lenzen S (2008) The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia 51:216–226. https://doi.org/10.1007/s00125-007-0886-7
Li W, Yuan G, Pan Y, Wang C, Chen H (2017) Network pharmacology studies on the bioactive compounds and action mechanisms of natural products for the treatment of diabetes mellitus: a review. Front Pharmacol 08:1–10. https://doi.org/10.3389/fphar.2017.00074
Liu M, Liu SW, Wang LJ, Bai YM, Zeng XY, Guo HB, Liu YN, Jiang YY, Dong WL, He GX, Zhou MG (2019) Burden of diabetes, hyperglycaemia in China from to 2016: findings from the 1990 to 2016, global burden of disease study. Diabetes Metab 45:286–293. https://doi.org/10.1016/j.diabet.2018.08.008
Loizzo MR, Marrelli M, Pugliese A, Conforti F, Nadjafi F, Menichini F, Tundis R (2016) Crocus cancellatus subsp. damascenus stigmas: chemical profile, and inhibition of amylase, glucosidase and lipase, key enzymes related to type 2 diabetes and obesity. J Enzyme Inhib Med Chem 31:212–218. https://doi.org/10.3109/14756366.2015.1016510
Mechchate H, Es-Safi I, Haddad H, Bekkari H, Grafov A, Bousta D (2021) Combination of catechin, epicatechin, and rutin: optimization of a novel complete antidiabetic formulation using a mixture design approach. J Nutr Biochem 88:108520. https://doi.org/10.1016/j.jnutbio.2020.108520
Murashige T, Skoog F (1962) A revised medium for rapid growth and bio assays with tobacco tissue cultures. Physiol Plant 15:473–497. https://doi.org/10.1111/j.1399-3054.1962.tb08052.x
Nathan DM, Bayless M, Cleary P, Genuth S, Gubitosi-Klug R, Lachin JM, Lorenzi G, Zinman B, DCCT/EDIC Research Group (2013) Diabetes control and complications trial/epidemiology of diabetes interventions and complications study at 30 years: advances and contributions. Diabetes 62:3976–3986. https://doi.org/10.2337/db13-1093
Negahdari R, Bohlouli S, Sharifi S, Maleki Dizaj S, Rahbar Saadat Y, Khezri K, Jafari S, Ahmadian E, Gorbani Jahandizi N, Raeesi S (2021) Therapeutic benefits of rutin and its nanoformulations. Phytother Res 35:1719–1738. https://doi.org/10.1002/ptr.6904
Nyambe-Silavwe H, Villa-Rodriguez JA, Ifie I, Holmes M, Aydin E, Jensen JM, Williamson G (2015) Inhibition of human α-amylase by dietary polyphenols. J Funct Foods 19:723–732. https://doi.org/10.1016/j.jff.2015.10.003
Okoye TC, Uzor PF, Onyeto CA, Okereke EK (2014) Safe African medicinal plants for clinical studies. In: Kuete V (ed) Toxicological survey of African medicinal plants. Elsevier, Amsterdam, pp 535–555. https://doi.org/10.1016/B978-0-12-800018-2.00018-2
Penman AD, Kaufman GE, Daniels KK (2014) MicroRNA expression as an indicator of tissue toxicity. In: Gupta RC (ed) Biomarkers in toxicology. Academic Press/Elsevier, Amsterdam, pp 1003–1018. https://doi.org/10.1016/B978-0-12-404630-6.00060-9
Petersen MC, Shulman GI (2018) Mechanisms of insulin action and insulin resistance. Physiol Rev 98:2133–2223. https://doi.org/10.1152/physrev.00063.2017
Petrie JR, Guzik TJ, Touyz RM (2018) Diabetes, hypertension, and cardiovascular disease: clinical insights and vascular mechanisms. Can J Cardiol 34:575–584. https://doi.org/10.1016/j.cjca.2017.12.005
Prakash M, Basavaraj BV, Chidambara Murthy KN (2019) Biological functions of epicatechin: plant cell to human cell health. J Funct Foods 52:14–24. https://doi.org/10.1016/j.jff.2018.10.021
Qu Z, Liu A, Li P, Liu C, Xiao W, Huang J, Liu Z, Zhang S (2021) Advances in physiological functions and mechanisms of (-)-epicatechin. Crit Rev Food Sci Nutr 61:211–233. https://doi.org/10.1080/10408398.2020.1723057
Rahman HMM, Islam KMR, Rahman MM (2013) An anatomical investigation on asteraceae family at Rajshahi division, Bangladesh. Int J Biosci 3:13–23
Rahman S, Jan G, Jan FG, Rahim HU (2021) Phytochemical screening and antidiabetic, antihyperlipidemic, and antioxidant effects of Leptopus Cordifolius Decne. in diabetic mice. Front Pharmacol 12:1–11. https://doi.org/10.3389/fphar.2021.643242
Saltiel AR, Kahn CR (2001) Insulin signalling and the regulation of glucose and lipid metabolism. Nature 414:799–806. https://doi.org/10.1038/414799a
Samarghandian S, Azimi-Nezhad M, Farkhondeh T (2017) Catechin treatment ameliorates diabetes and its complications in streptozotocin-induced diabetic rats. Dose Response 15:1–7. https://doi.org/10.1177/1559325817691158
Saravanakumar K, Park S, Mariadoss AV, Sathiyaseelan A, Veeraraghavan VP, Kim S, Wang MH (2021) Chemical composition, antioxidant, and anti-diabetic activities of ethyl acetate fraction of Stachys riederi var. japonica (Miq.) in streptozotocin-induced type 2 diabetic mice. Food Chem Toxicol 155:112374. https://doi.org/10.1016/j.fct.2021.112374
Shahwar D, Ullah S, Ahmad M, Ullah S, Ahmad N (2011) Anti-diabetic activity of the methanolic extract of Blumea lacera DC (Asteraceae) in alloxan-induced diabetic rats. Asian J Chem 23:5403–5406
Su H, Ruan YT, Li Y, Chen JG, Yin ZP, Zhang QF (2020) In vitro and in vivo inhibitory activity of taxifolin on three digestive enzymes. Int J Biol Macromol 150:31–37. https://doi.org/10.1016/j.ijbiomac.2020.02.027
Swaraz AM, Sumi SK, Sultana F, Hasan M, Islam MM, Bari MW, Islam MA, Satter MA, Ahmed KS, Hossain MH (2020) Bioactive compound and bioactivity fidelitous micropropagation method of Blumea lacera (Burm. f.) DC.: a large scale production potential. Ind Crops Prod 151:112370. https://doi.org/10.1016/j.indcrop.2020.112370
Swaraz AM, Sultana F, Bari MW, Ahmed KS, Hasan M, Islam MM, Islam MA, Satter MA, Hossain MH, Islam MS, Khan MI (2021) Phytochemical profiling of Blumea laciniata (Roxb.) DC and its phytopharmaceutical potential against diabetic, obesity, and Alzheimer’s. Biomed Pharmacother 141:111859. https://doi.org/10.1016/j.biopha.2021.111859
Swaraz AM, Sultana F, Shahin Ahmed K et al (2022) Polyphenols profile and enzyme inhibitory properties of Blumea lacera (Burm. f.) DC.: a potential candidate against obesity, aging, and skin disorder. Chem Biodivers. https://doi.org/10.1002/cbdv.202200282
Taheri Y, Suleria HA, Martins N, Sytar O, Beyatli A, Yeskaliyeva B, Seitimova G, Salehi B, Semwal P, Painuli S, Kumar A (2020) Myricetin bioactive effects: moving from preclinical evidence to potential clinical applications. BMC Complementary Med Ther 20:1–14. https://doi.org/10.1186/s12906-020-03033-z
Tutuncu Y, Satman I, Celik S, Dinccag N, Karsidag K, Telci A, Genc S, Issever H, Tuomilehto J, Omer B (2016) A comparison of hs-CRP levels in new diabetes groups diagnosed based on FPG, 2-hPG, or HbA1c criteria. J Diabetes Res 2016:1–9. https://doi.org/10.1155/2016/5827041
Uddin SJ, Grice ID, Tiralongo E (2011) Cytotoxic effects of Bangladeshi medicinal plant extracts. Evid Based Complementary Altern Med 2011:1–7. https://doi.org/10.1093/ecam/nep111
Udler MS, Kim J, von Grotthuss M, Bonàs-Guarch S, Cole JB, Chiou J, Christopher D (2018) Type 2 diabetes genetic loci informed by multi-trait associations point to disease mechanisms and subtypes: a soft clustering analysis. PLoS Med 15:e1002654. https://doi.org/10.1371/journal.pmed.1002654
UKPDS Group (1998) Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 352:837–853. https://doi.org/10.1016/S0140-6736(98)07019-6
Ushakova NA, Brodsky ES, Tikhonova OV, Dontsov AE, Marsova MV, Shelepchikov AA, Bastrakov AI (2021) Novel extract from beetle Ulomoides dermestoides: a study of composition and antioxidant activity. Antioxidants 10:1055. https://doi.org/10.3390/antiox10071055
Wang X, Bao W, Liu J, OuYang YY, Wang D, Rong S, Xiao X, Shan ZL, Zhang Y, Yao P, Liu LG (2013) Inflammatory markers and risk of type 2 diabetes: a systematic review and meta-analysis. Diabetes Care 36:166–175. https://doi.org/10.2337/dc12-0702
Wang Q, Wu X, Shi F, Liu Y (2019) Comparison of antidiabetic effects of saponins and polysaccharides from Momordica charantia L. in STZ-induced type 2 diabetic mice. Biomed Pharmacother 109:744–750. https://doi.org/10.1016/j.biopha.2018.09.098
Washabau RJ (2013) Liver. In: Washabau RJ, Day MJ (eds) Canine and feline gastroenterology. Saunders/Elsevier, Amsterdam, pp 849–957. https://doi.org/10.1016/B978-1-4160-3661-6.00061-4
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The authors are also thankful to all chemical suppliers for delivering quality chemicals and reagents in time. This research did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors.
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Hasan, M., Islam, M.M., Raihan, M.O. et al. Clonal Blumea lacera (Burm. f.) DC. ameliorates diabetic conditions by modulating carbohydrate and lipid hydrolases: a combine in vivo experimental and chemico-biological interaction study. 3 Biotech 13, 152 (2023). https://doi.org/10.1007/s13205-023-03575-2
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DOI: https://doi.org/10.1007/s13205-023-03575-2