SYNERGISM BETWEEN PROBIOTICS AND HERBS TO MANAGE TYPE 2 DIABETES IN RATS
Keywords:Type 2 diabetes, Probiotics, Saffron, Cardamom, Ginger, Cinnamon, Synergistic relationship
Objective: This study aims to explore the adjuvant effect of multi-strain probiotics with either saffron, cardamom, ginger, or cinnamon herbs to achieve synergistic management for controlling type 2 diabetes (T2D).
Methods: Eighty-eight adult male, Wistar rats were used. Eight rats were kept as healthy control. Eighty rats were used to induce type 2 diabetic rats (T2DR) and were randomly assigned to ten groups. One group was an offer to 0.2 ml multi-strain probiotics orally. The rest of T2DR were gavage with 100 mg/kg aqueous extract of saffron, cardamom, ginger, or cinnamon without or with 0.2 ml multi-strain probiotics orally. Bodyweight gain (BWG), and feed efficiency ratio (FER) were recorded. Determination of oral glucose tolerance test (OGTT), serum insulin, C-peptide, HDL, LDL, HDL/total cholesterol ratio were performed. Serum antioxidant activity, Th1and Th2 cytokines and histopathology of the pancreas were done.
Results: Comparable with T2DR, solely multi-strain probiotics or with herbs caused a significant reduction in BWG (P<0.05). Groups fed saffron, cardamom, and ginger and enriched with multi-strain probiotic showed significant improvement in OGTT, serum insulin, C-peptide and lipid abnormalities (P<0.05) compared to T2DR. Besides, they had antioxidant and anti-inflammatory effects. The group received ginger alone exerted anti-hyperglycemia and anti-inflammatory effects. However, cinnamon had a moderate anti-diabetic effect and solely probiotics did not show a significant benefit for all parameters except BWG.
Conclusion: Cardamom, saffron, and ginger enriched with multi-strain probiotics achieve a synergistic relationship for managing T2D. This finding exhibits a possible new hypothesis to manage diabetes that needs further study.
Musaiger AO, Takruri HR, Hassan AS, Abu Tarboush H. Food-based dietary guidelines for the Arab Gulf countries. J Nutr Metab 2012;11:1-10.
Whiting DR, Guariguata L, Weil C, Shaw J. IDF. Diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract 2011;94:311-21.
World Health Organization. Global Health Observatory (GHO); 2013. Available from: http://www.who.int/gho/en. [Last accessed on 25 Dec 2019].
International Diabetes Federation (IDF) Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Pract 2017;128:40-50.
Alotaibi A, Perry L, Gholizadeh L, Ali Al-Ganmi. Incidence and prevalence rates of diabetes mellitus in Saudi Arabia: an overview. J Epidemiol Glob Health 2017;7:211-8.
Garcia Perez LE, Alvarez M, Dilla T, Gil-Guillen V, Orozco Beltran D. Adherence to therapies in patients with type 2 diabetes. Diabetes Ther 2013;4:175–94.
Milajerdi A, Jazayeri S, Bitarafan V, Hashemzadeh N, Shirzadi E, Derakhshan Z, et al. The effect of saffron (Crocus sativus L.) hydro-alcoholic extract on liver and renal functions in type 2 diabetic patients: a double-blinded randomized and placebo control trial. J Nutr Intermed Metab 2017;9:6-11.
Samarghandian S, Azimi Nezhad M, Farkhondeh T. Immunomodulatory and antioxidant effects of aqueous saffron extract (Crocus sativus L.) on streptozotocin-induced diabetes in rats. Indian Heart J 2017;69:151-9.
Sharma BR, Kim HJ, Rhyu DY. Caulerpa lentillifera extract ameliorates insulin resistance and regulates glucose metabolism in C57BL/KsJ-db/db mice via PI3K/AKT signaling pathway in myocytes. J Transl Med 2015;13:62.
Shoaib A, Salem Bekhit MM, Siddiqui HH, Dixit RK, Bayomi M, Khalid M, et al. Antidiabetic activity of standardized dried tubers extract of Aconitum napellus in streptozotocin-induced diabetic rats. 3 Biotech 2020;10:56.
Singh U, Singh S, Kochhar A. Therapeutic potential of antidiabetic neutraceuticals. J Phytopharmacol 2012;2:144-69.
Farahmand SK, Samini F, Samini M, Samarghandian S. Safranal ameliorates antioxidant enzymes and suppresses lipid peroxidation and nitric oxide formation in aged male rat liver. Biogerontology 2013;14:63–71.
Hemmati M, Asghari S, Zohoori E, Karamian M. Hypoglycemic effects of three Iranian edible plants; jujube, barberry and saffron: correlation with serum adiponectin level. Pak J Pharm Sci 2015;28:2095-9.
Samarghandian S, Azimi Nezhad M, Samini F. Ameliorative effect of the aqueous saffron extract on hyperglycemia, hyperlipidemia, and oxidative stress on diabetic encephalopathy in streptozotocin-induced experimental diabetes mellitus. Biomed Res Int 2014;2014:1-12.
Razavi BM, Hosseinzadeh H. Saffron: a promising natural medicine in the treatment of the metabolic syndrome. J Sci Food Agric 2017;97:1679-85.
Aghasi M, Ghazi Zahedi S, Koohdani F, Siassi F, Nasli Esfahani E, Keshavarz A, et al. The effects of green cardamom supplementation on blood glucose, lipids profile, oxidative stress, sirtuin-1 and irisin in type 2 diabetic patients: a study protocol for a randomized placebo-controlled clinical trial. BMC Complem Altern Med 2018;18:1-6.
kazemi S, Yaghooblou F, Siassi F, Rahimi A, Ghavipour M, Koohdani F, et al. Cardamom supplementation improves inflammatory and oxidative stress biomarkers in hyperlipidemic, overweight, and obese prediabetic women: a randomized double-blind clinical trial. J Sci Food Agric 2017;97:5296-301.
Son MJ, Miura Y, Yagasaki K. Mechanisms for antidiabetic effect of gingerol in cultured cells and obese diabetic model mice. Cytotechnology 2015;67:641–52.
Wei CK, Tsai YH, Korinek M, Hung PH, El-Shazly M, Cheng YB, et al. 6-Paradol and 6-shogaol, the pungent compounds of ginger, promote glucose utilization in adipocytes and myotubes, and 6-paradol reduces blood glucose in high-fat diet-fed mice. Int J Mol Sci 2017;18:168.
Semwal RB, Semwal DK, Combrinck S, Viljoen AM. Gingerols and shogaols: Important nutraceutical principles from ginger. Phytochemistry 2015;117:554-68.
Danwilai K, Konmun J, Sripanidkulchai BO, Subongkot S. Antioxidant activity of ginger extract as a daily supplement in cancer patients receiving adjuvant chemotherapy: a pilot study. Cancer Manag Res 2017;9:11.
Forouhar E, Sack P. Non-traditional therapies for diabetes: fact or fiction. J Community Hosp Intern Med Perspect 2012;2:18447.
Khan A, Safdar M, Ali Khan MM, Khattak KN, Anderson RA. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care 2003;26:3215–8.
Yilmaz Z, BCPS, Fawad Piracha, Leeann Anderson, Nissa Mazzola. CDE supplements for diabetes mellitus a review. Literature J Pharm Pract 2017;30:631-8.
Azimi P, Ghiasvand R, Feizi A, Hariri M, Abbasi B. Effects of cinnamon, cardamom, saffron and ginger consumption on markers on glycemic control, lipid profile, oxidative stress and Inflammation in type 2 diabetes patients. Rev Diabet Stud 2014;11:258–66.
Akhani SP, Vishwakarma SL, Goyal RK. Anti‐diabetic activity of Zingiber officinale in streptozotocin‐induced type I diabetic rats. J Pharm Pharmacol 2004;56:101-5.
Weidner MS, Sigwart K. The safety of a ginger extract in the rat. J Ethnopharmacol 2000;73:513-20.
Daneshi Maskooni M, Keshavarz SA, Mansouri S, Qorbani M, Alavian SM, Badri-Fariman M, et al. The effects of green cardamom on blood glucose indices, lipids, inflammatory factors, paraxonase-1, sirtuin-1, and irisin in patients with nonalcoholic fatty liver disease and obesity: study protocol for a randomized controlled trial. Trials 2017;18:260.
Ranasinghe P, Galappaththy P, Constantine GR, Jayawardena R, Weeratunga HD, Premakumara S, et al. Cinnamomum zeylanicum (Ceylon cinnamon) as a potential pharmaceutical agent for type-2 diabetes mellitus: study protocol for a randomized controlled trial. Trials 2017;18:446.
Kübeck R, Bonet Ripoll C, Hoffmann C, Walker A, Müller VM, Schuppel VL, et al. Dietary fat and gut microbiota interactions determine diet-induced obesity in mice. Mol Metab 2016;5:1162-74.
McCabe LR, Parameswaran N. Advances in probiotic regulation of bone and mineral metabolism. Calcified Tissue Int 2018;102:480-8.
Naito E, Yoshida Y, Kunihiro S, Makino K, Kasahara K, Kounoshi Y, et al. Effect of Lactobacillus casei strain Shirota-fermented milk on metabolic abnormalities in obese prediabetic Japanese men: a randomised, double-blind, placebo-controlled trial. Biosci Microb Food H 2018;37:9-18.
Wang G, Li X, Zhao J, Zhang H, Chen W. Lactobacillus casei CCFM419 attenuates type 2 diabetes via a gut microbiota dependent mechanism. Food Funct 2017;8:3155-64.
Firouzi S, Majid HA, Ismail A, Kamaruddin NA, Barakatun-Nisak MY. Effect of multi-strain probiotics (multi-strain microbial cell preparation) on glycemic control and other diabetes-related outcomes in people with type 2 diabetes: a randomized controlled trial. Eur J Nutr 2017;56:1535-50.
Samah S, Ramasamy K, Lim SM, Neoh CF. Probiotics for the management of type 2 diabetes mellitus: a systematic review and meta-analysis. Diabetes Res Clin Pract 2016;118:172-82.
NRC (National Research Council). Guide for the care and use of laboratory animals. Rev National Institutes of Health, Bethesda, MD; 1985.
Research Diets. Inc. Obesity. Open formula purified diets for lab animals; 2009. p. 3000-2-09. Available from: www.researchdiets.com [Last accessed on 25 Dec 2019]
Skovsø Søs. Modeling type 2 diabetes in rats using high fat diet and streptozotocin. J Diabetes Invest 2014;5:349–58.
Soumya V, Muzib YI, Venkatesh P, Hariprasath K. GC-MS analysis of cocus nucifera flower extract and its effects on heterogeneous symptoms of polycystic ovarian disease in female wistar rats. Chin J Nat Med 2014;12:677-84.
Musa KH, Abdullah A, Jusoh K, Subramaniam V. Antioxidant activity of pink-flesh guava (Psidium guajava L.): effect of extraction techniques and solvents. Food Anal Methods 2011;4:100-7.
Slinkard K, Singleton VL. Total phenol analysis: automation and comparison with manual methods. Am J Enol Viticult 1977;28:49-55.
Brand Williams W, Cuvelier ME, Berset CL. Use of a free radical method to evaluate antioxidant activity. LWT-Food Sci Technol 1995;28:25-30.
Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice Evans C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radical Bio Med 1999;26:1231-7.
Aboubakr M, Abdelazem MA. Hepatoprotective effect of aqueous extract of cardamom against gentamicin induced hepatic damage in rats. Int J Basic Appl Sci 2016;5:1-4.
Park KY, Kim B, Hyun CK. Lactobacillus rhamnosus GG improves glucose tolerance through alleviating ER stress and suppressing macrophage activation in db/db mice. J Clin Biochem Nutr 2015;56:240-6.
Kim SH, Choung SY. Antihyperglycemic and antihyperlipidemic action of Cinnamomi Cassiae (Cinnamon bark) extract in C57BL/Ks db/db mice. Arch Pharm Res 2010;33:325-33.
Day CE. Histopathology; methods and protocols. Springer New York Heidelberg Dordrecht London. Human Press; 2014. p. 3-31.
Yamamoto N, Kanemoto Y, Ueda M, Kawasaki K, Fukuda I, Ashida H. Anti-obesity and anti-diabetic effects of ethanol extract of Artemisia princeps in C57BL/6 mice fed a high-fat diet. Food Funct 2011;2:45-52.
Tremaroli V, Backhed F. Functional interactions between the gut microbiota and host metabolism. Nature 2012;489:242-9.
Ziętak M, Kovatcheva Datchary P, Markiewicz LH, Stahlman M, Kozak LP, Bäckhed F. Altered microbiota contributes to reduced diet-induced obesity upon cold exposure. Cell Metab 2016;23:1216-23.
Jayaswal RP, Vijayasimha M, Prabhakar PK. Gut microbiota and diabetes mellitus-an interlinkage. Asian J Pharm Clin Res 2018;11:13-6.
Balakumar M, Prabhu D, Sathishkumar C, Prabu P, Rokana N, Kumar R, et al. Improvement in glucose tolerance and insulin sensitivity by probiotic strains of Indian gut origin in high-fat diet-fed C57BL/6J mice. Eur J Nutr 2018;57:279-95.
Lee E, Jung SR, Lee SY, Lee NK, Paik HD, Lim SI. Lactobacillus plantarum strain ln4 attenuates diet-induced obesity, insulin resistance, and changes in hepatic mRNA levels associated with glucose and lipid metabolism. Nutrients 2018;10:643.
Kim SH, Hyun SH, Choung SY. Anti-diabetic effect of cinnamon extract on blood glucose in db/db mice. J Ethnopharmacol 2006;104:119-23.
Leach MJ, Kumar S. Cinnamon for diabetes mellitus. The Cochrane Database of Syst Rev. Published by John Wiley and Sons, Ltd; 2012. p. 1-41.
Costello RB, Dwyer JT, Saldanha L, Bailey RL, Merkel J, Wambogo E. Do cinnamon supplements have a role in glycemic control in type 2 diabetes? A narrative review. J Acad Nutr Diet 2016;116:1794-802.
Couturier K, Qin B, Batandier C, Awada M, Hininger Favier I, Canini F, et al. Cinnamon increases liver glycogen in an animal model of insulin resistance. Metab 2011;60:1590-7.
Li J, Liu T, Wang L, Guo X, Xu T, Wu L, et al. Antihyperglycemic and antihyperlipidemic action of cinnamaldehyde in C57BLKS/J db/db mice. J Tradit Chin Med 2012;32:446-52.
Ahmed AS, Ahmed Q, Saxena AK, Jamal P. Evaluation of in vitro antidiabetic and antioxidant characterizations of Elettaria cardamomum (L.) Maton (Zingiberaceae), Piper cubeba L. f. (Piperaceae), and Plumeria rubra L. (Apocynaceae). Pak J Pharm Sci 2017;30:113–26.
Jackson MB, Ahima RS. Neuroendocrine and metabolic effects of adipocyte-derived hormones. Clin Sci (Lond) 2006;110:143–52.
Chen G, Xueping Yang, Xiaoyu Yang, Lingli Li, Jinlong Luo, Hui Dong, et al. ameliorates type 2 diabetes by improving β cell function and reducing insulin resistance in diabetic rats. BMC Complem Altern Med 2017;17:507.
Shen J, Obin MS, Zhao L. The gut microbiota, obesity and insulin resistance. Mol Aspects Med 2013;34:39–58.
Hulston CJ, Churnside AA, Venables MC. Probiotic supplementation prevents high-fat, overfeeding-induced insulin resistance in human subjects. Br J Nutr 2015;113:596-602.
Kvit KV. Kharchenko role of gut microbiota in lipid metabolism. Asian J Pharm Clin Res 2018;11:4-8.
Andallu B, Radhika B, Suryakantham V. Effect of aswagandha, ginger and mulberry on hyperglycemia and hyperlipidemia. Plant Foods Hum Nutr 2003;58:1–7.
Baker W, Gutierrez Williams G, White M, Kluger J, Coleman C. Effect of cinnamon on glucose control and lipid parameters. Diabetes Care 2008;31:41–3.
Joshi SC, PK Jain, P Sharma. Antiatherosclerotic and lipid lowering effects of Cinnamomum verum in cholesterol-fed rabbits. Int J Curr Pharm Res 2017;9:75-80.
Madawala SR, Andersson RE, Jastrebova JA, Almeida M, Dutta PC. Novel conjugates of 1, 3-diacylglycerol and lipoic acid: synthesis, DPPH assay, and RP-LC-MS-APCI analysis. J Lipids 2011:1-10. DOI:10.1155/2011/419809
Salar Amoli J, Hejazy M, Esfahani TA. Comparison between some oxidative Stress Biomarkers values in serum and plasma of clinically healthy adult camels (Camelus dromedarius) in Iran. Vet Res Commun 2009;33:849-54.
Saleh MA, Mahran OM, Al-Salahy MB. Circulating oxidative stress status in dromedary camels infested with sarcoptic mange. Vet Res Commun 2011;35:35-45.
Kandikattu HK, Rachitha P, Jayashree GV, Krupashree K, Sukhith M, Majid A, et al. Anti-inflammatory and anti-oxidant effects of Cardamom (Elettaria repens (Sonn.) Baill) and its phytochemical analysis by 4D GCXGC TOF-MS. Biomed Pharmacother 2017;91:191–201.
Kumari JA, Venkateshwarlu G, Choukse MK, Anandan R. Effect of essential oil and aqueous extract of ginger (Zingiber Officinale) on oxidative stability of fish oil-in-water emulsion. J Food Process Technol 2014;6:412-6.
Kale MA, Bindu SMP. Khadkikar role of antioxidants and nutrition in oxidative stress: a review. Int J Appl Pharm 2015;7:1-4.
Gong F, Fung YS, Liang YZ. Determination of volatile components in ginger using gas chromatography-mass spectrometry with resolution improved by data processing techniques. J Agric Food Chem 2004;52:6378–83.
Galassetti PR, Rosa JS, Heydari S, Oliver SR, Flores RL, Pontello AM, et al. Inflammatory cytokine profiles during exercise in obese, diabetic, and healthy children. J Clin Res Pediatr E 2011;3:115.
Winarsi H, Sasongko ND, Purwanto A, Nuraeni I. Cardamom leave extract lowers atherogenic index of diabetic rats alloxan-induced. Agritech 2013;33:273-80.
Winarsi H, Yuniaty A, Nuraeni I. Improvement of antioxidant and immune status of atherosclerotic rats adrenaline and egg-yolks-induced using cardamom-rhizome-ethanolic-extract: an initial study of functional food. Agric Agric Sci Procedia 2016;9:264-70.
Cheng N, Luo L, Jiang KO. Inventors; beijing tang an nutrition, healthcare products co ltd, assignee. Process for preparing water extract of cinnamon. United States patent US 8,329,232; 2012.
Rychlik M. Quantification of free coumarin and its liberation from glucosylated precursors by stable isotope dilution assays based on liquid chromatography-tandem mass spectrometric detection. J Agric Food Chem 2008;56:796–801.