Top

BMC Complementary Medicine and Therapies

Published in:

Open Access 01-12-2021 | Research

Metagenomic and phytochemical analyses of kefir water and its subchronic toxicity study in BALB/c mice

Authors: Muganti Rajah Kumar, Swee Keong Yeap, Nurul Elyani Mohamad, Janna Ong Abdullah, Mas Jaffri Masarudin, Melati Khalid, Adam Thean Chor Leow, Noorjahan Banu Alitheen

Published in: BMC Complementary Medicine and Therapies | Issue 1/2021

Abstract

Background

In recent years, researchers are interested in the discovery of active compounds from traditional remedies and natural sources, as they reveal higher therapeutic efficacies and improved toxicological profiles. Among the various traditional treatments that have been widely studied and explored for their potential therapeutic benefits, kefir, a fermented beverage, demonstrates a broad spectrum of pharmacological properties, including antioxidant, anti-inflammation, and healing activities. These health-promoting properties of kefir vary among the kefir cultures found at the different part of the world as different media and culture conditions are used for kefir maintenance and fermentation.

Methods

This study investigated the microbial composition and readily found bioactive compounds in water kefir fermented in Malaysia using 16S rRNA microbiome and UHPLC sequencing approaches. The toxicity effects of the kefir water administration in BALB/c mice were analysed based on the mice survival, body weight index, biochemistry profile, and histopathological changes. The antioxidant activities were evaluated using SOD, FRAP, and NO assays.

Results

The 16S rRNA amplicon sequencing revealed the most abundant species found in the water kefir was Lactobacillus hilgardii followed by Lactobacillus harbinensis, Acetobacter lovaniensis, Lactobacillus satsumensis, Acetobacter tropicalis, Lactobacillus zeae, and Oenococcus oeni. The UHPLC screening showed flavonoid and phenolic acid derivatives as the most important bioactive compounds present in kefir water which has been responsible for its antioxidant activities. Subchronic toxicity study showed no toxicological signs, behavioural changes, or adverse effects by administrating 10 mL/kg/day and 2.5 mL/kg/day kefir water to the mice. Antioxidants assays demonstrated enhanced SOD and FRAP activities and reduced NO level, especially in the brain and kidney samples.

Conclusions

This study will help to intensify the knowledge on the water kefir microbial composition, available phytochemicals and its toxicological and antioxidant effects on BALB/c mice since there are very limited studies on the water kefir grain fermented in Malaysia.

Bourrie BCT, Willing BP, Cotter PD. The Microbiota and Health Promoting Characteristics of the Fermented Beverage Kefir. Front Microbiol [Internet]. 2016 May 4 [cited 2020 Mar 24];7. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854945/

de Oliveira Leite AM, Miguel MAL, Peixoto RS, Rosado AS, Silva JT, Paschoalin VMF. Microbiological, technological and therapeutic properties of kefir: a natural probiotic beverage. Braz J Microbiol Publ Braz Soc Microbiol. 2013;44(2):341–9. https://doi.org/10.1590/S1517-83822013000200001.CrossRef

Tamang JP, Watanabe K, Holzapfel WH. Review: Diversity of Microorganisms in Global Fermented Foods and Beverages. Front Microbiol. 2016;7. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4805592/. [cited 2020 Mar 24].

Prado MR, Blandón LM, Vandenberghe LPS, Rodrigues C, Castro GR, Thomaz-Soccol V, et al. Milk kefir: composition, microbial cultures, biological activities, and related products. Front Microbiol. 2015;6 Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626640/. [cited 2018 Feb 24].

Tamime AY. Fermented milks: a historical food with modern applications--a review. Eur J Clin Nutr. 2002;56(Suppl 4):S2–15. https://doi.org/10.1038/sj.ejcn.1601657.CrossRefPubMed

Verce M, De Vuyst L, Weckx S. Shotgun Metagenomics of a Water Kefir Fermentation Ecosystem Reveals a Novel Oenococcus Species. Front Microbiol [Internet]. 2019 [cited 2019 Dec 8];10. Available from: https://www.frontiersin.org/articles/10.3389/fmicb.2019.00479/full.

Marsh AJ, O’Sullivan O, Hill C, Ross RP, Cotter PD. Sequence-based analysis of the microbial composition of water kefir from multiple sources. FEMS Microbiol Lett. 2013;348(1):79–85. https://doi.org/10.1111/1574-6968.12248.CrossRefPubMed

Gulitz A, Stadie J, Wenning M, Ehrmann MA, Vogel RF. The microbial diversity of water kefir. Int J Food Microbiol. 2011;151(3):284–8. https://doi.org/10.1016/j.ijfoodmicro.2011.09.016.CrossRefPubMed

Zamberi NR, Abu N, Mohamed NE, Nordin N, Keong YS, Beh BK, et al. The Antimetastatic and Antiangiogenesis effects of kefir water on murine breast Cancer cells. Integr Cancer Ther. 2016;15(4):NP53–66. https://doi.org/10.1177/1534735416642862.CrossRefPubMedPubMedCentral

10.

Miao J, Guo H, Chen F, Zhao L, He L, Ou Y, et al. Antibacterial effects of a cell-penetrating peptide isolated from kefir. J Agric Food Chem. 2016;64(16):3234–42. https://doi.org/10.1021/acs.jafc.6b00730.CrossRefPubMed

11.

Chen Z, Shi J, Yang X, Nan B, Liu Y, Wang Z. Chemical and physical characteristics and antioxidant activities of the exopolysaccharide produced by Tibetan kefir grains during milk fermentation. Int Dairy J. 2015;43:15–21. https://doi.org/10.1016/j.idairyj.2014.10.004.CrossRef

12.

Kim D-H, Chon J-W, Kim H, Seo K-H. Modulation of intestinal microbiota in mice by kefir administration. Food Sci Biotechnol. 2015;24(4):1397–403. https://doi.org/10.1007/s10068-015-0179-8.CrossRef

13.

Khoury N, El-Hayek S, Tarras O, El-Sabban M, El-Sibai M, Rizk S. Kefir exhibits anti-proliferative and pro-apoptotic effects on colon adenocarcinoma cells with no significant effects on cell migration and invasion. Int J Oncol. 2014;45(5):2117–27. https://doi.org/10.3892/ijo.2014.2635.CrossRefPubMed

14.

Adiloğlu AK, Gönülateş N, Işler M, Senol A. The effect of kefir consumption on human immune system: a cytokine study. Mikrobiyol Bul. 2013;47(2):273–81. https://doi.org/10.5578/mb.4709.CrossRefPubMed

15.

Topuz E, Derin D, Can G, Kürklü E, Cinar S, Aykan F, et al. Effect of oral administration of kefir on serum proinflammatory cytokines on 5-FU induced oral mucositis in patients with colorectal cancer. Invest New Drugs. 2008;26(6):567–72. https://doi.org/10.1007/s10637-008-9171-y.CrossRefPubMed

16.

Liu J-R, Chen M-J, Lin C-W. Antimutagenic and antioxidant properties of milk-kefir and soymilk-kefir. J Agric Food Chem. 2005;53(7):2467–74. https://doi.org/10.1021/jf048934k.CrossRefPubMed

17.

Liu J-R, Lin Y-Y, Chen M-J, Chen L-J, Lin C-W. Antioxidative activities of kefir. Asian-Australas J Anim Sci. 2005;18(4):567–73. https://doi.org/10.5713/ajas.2005.567.CrossRef

18.

Cevikbas A, Yemni E, Ezzedenn FW, Yardimici T, Cevikbas U, Stohs SJ. Antitumoural antibacterial and antifungal activities of kefir and kefir grain. Phytother Res. 1994;8(2):78–82. https://doi.org/10.1002/ptr.2650080205.CrossRef

19.

Verce M, De Vuyst L, Weckx S. Shotgun Metagenomics of a Water Kefir Fermentation Ecosystem Reveals a Novel Oenococcus Species. Front Microbiol [Internet]. 2019 [cited 2020 Mar 24];10. Available from: https://www.frontiersin.org/articles/10.3389/fmicb.2019.00479/full.

20.

Lee M, Song JH, Jung MY, Lee SH, Chang JY. Large-scale targeted metagenomics analysis of bacterial ecological changes in 88 kimchi samples during fermentation. Food Microbiol. 2017;66:173–83. https://doi.org/10.1016/j.fm.2017.05.002.CrossRefPubMed

21.

Ceugniez A, Taminiau B, Coucheney F, Jacques P, Delcenserie V, Daube G, et al. Use of a metagenetic approach to monitor the bacterial microbiota of ‘Tomme d’Orchies’ cheese during the ripening process. Int J Food Microbiol. 2017;247:65–9. https://doi.org/10.1016/j.ijfoodmicro.2016.10.034.CrossRefPubMed

22.

Escobar-Zepeda A, Sanchez-Flores A, Quirasco BM. Metagenomic analysis of a Mexican ripened cheese reveals a unique complex microbiota. Food Microbiol. 2016;57:116–27. https://doi.org/10.1016/j.fm.2016.02.004.CrossRefPubMed

23.

Lusk TS, Ottesen AR, White JR, Allard MW, Brown EW, Kase JA. Characterization of microflora in Latin-style cheeses by next-generation sequencing technology. BMC Microbiol. 2012;12(1):254. https://doi.org/10.1186/1471-2180-12-254.CrossRefPubMedPubMedCentral

24.

Paramithiotis S, Patra JK. Food Molecular Microbiology. CRC Press; 2019. p. 263.

25.

Oulas A, Pavloudi C, Polymenakou P, Pavlopoulos GA, Papanikolaou N, Kotoulas G, et al. Metagenomics: tools and insights for analyzing next-generation sequencing data derived from biodiversity studies. Bioinforma Biol Insights. 2015;9:75–88.CrossRef

26.

Wang Z-M, Lu Z-M, Shi J-S, Xu Z-H. Exploring flavour-producing core microbiota in multispecies solid-state fermentation of traditional Chinese vinegar. Sci Rep [Internet]. 2016 May 31 [cited 2020 Mar 24];6. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4886211/.

27.

Wang Z-M, Lu Z-M, Yu Y-J, Li G-Q, Shi J, Xu Z. Batch-to-batch uniformity of bacterial community succession and flavor formation in the fermentation of Zhenjiang aromatic vinegar. Food Microbiol [Internet]. 2015 Sep 1 [cited 2020 Mar 24]; Available from: https://scinapse.io/papers/1997389326.

28.

Ayed L, M’hir S, Hamdi M. Microbiological, biochemical, and functional aspects of fermented vegetable and fruit beverages. J Chem. 2020;2020:e5790432.CrossRef

29.

Velu G, Palanichamy V, Rajan AP. Phytochemical and pharmacological importance of plant secondary metabolites in modern medicine. In: Roopan SM, Madhumitha G, editors. Bioorganic phase in natural food: an overview [internet]. Cham: Springer international publishing; 2018. p. 135–56. https://doi.org/10.1007/978-3-319-74210-6_8. [cited 2021 May 14].CrossRef

30.

Lampe JW, Chang J-L. Interindividual differences in phytochemical metabolism and disposition. Semin Cancer Biol. 2007;17(5):347–53. https://doi.org/10.1016/j.semcancer.2007.05.003.CrossRefPubMedPubMedCentral

31.

Gowda G, Djukovic D. Overview of mass spectrometry-based metabolomics: opportunities and challenges. - PubMed - NCBI [Internet]. 2014 [Cited 2020 mar 25]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25270919.

32.

Swartz ME. UPLC™: An Introduction and Review: Journal of Liquid Chromatography & Related Technologies: Vol 28, No 7–8 [Internet]. 2007 [cited 2020 Mar 25]. Available from: https://www.tandfonline.com/doi/abs/10.1081/JLC-200053046.

33.

Guan H, Luo X, Chang X, Su M, Li Z, Li P, et al. Identification of the chemical constituents of an anti-arthritic Chinese medicine wen Luo yin by liquid chromatography coupled with mass spectrometry. Molecules. 2019;24(2):233. https://doi.org/10.3390/molecules24020233.CrossRefPubMedCentral

34.

Blazenovic I, Kind T, Ji J, Fiehn O. Software Tools and Approaches for Compound Identification of LC-MS/MS Data in Metabolomics. - PubMed - NCBI [Internet]. 2018 [cited 2020 Mar 25]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/29748461.

35.

Kind T, Fiehn O. Advances in structure elucidation of small molecules using mass spectrometry [Internet]. 2010 [cited 2020 Mar 25]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3015162/.

36.

Walsh AM, Crispie F, Kilcawley K, O’Sullivan O, O’Sullivan MG, Claesson MJ, et al. Microbial Succession and Flavor Production in the Fermented Dairy Beverage Kefir. mSystems. 2016;1(5) Available from: https://msystems.asm.org/content/1/5/e00052-16. [cited 2020 Mar 26].

37.

Zamberi NR, Mohamad NE, Yeap SK, Ky H, Beh BK, Liew WC, et al. 16S metagenomic microbial composition analysis of kefir grain using MEGAN and BaseSpace. Food Biotechnol. 2016;30(3):219–30. https://doi.org/10.1080/08905436.2016.1200987.CrossRef

38.

Zanirati DF, Abatemarco M, Sandes SH de C, Nicoli JR, Nunes ÁC, Neumann E. Selection of lactic acid bacteria from Brazilian kefir grains for potential use as starter or probiotic cultures. Anaerobe. 2015;32:70–6. https://doi.org/10.1016/j.anaerobe.2014.12.007.CrossRefPubMed

39.

Koh WY, Uthumporn U, Rosma A, Effarizah ME, Wan Rosli WI. Assessment of yeast, acetic and lactic acid bacteria isolated from water kefir grains and their application as starter culture in the production of fermented pumpkin-based water kefir beverages in improving gastrointestinal tract digestive tolerance and inhibition against α-glucosidase. Int Food Res J. 2019;26(2):429–39.

40.

Laureys D, Van Jean A, Dumont J, De Vuyst L. Investigation of the instability and low water kefir grain growth during an industrial water kefir fermentation process. Appl Microbiol Biotechnol. 2017;101(7):2811–9. https://doi.org/10.1007/s00253-016-8084-5.CrossRefPubMed

41.

Plessas S, Nouska C, Mantzourani I, Kourkoutas Y, Alexopoulos A, Bezirtzoglou E. Microbiological exploration of different types of kefir grains. Fermentation. 2017;3(1):1.CrossRef

42.

Korsak N, Taminiau B, Leclercq M, Nezer C, Crevecoeur S, Ferauche C, et al. Short communication: evaluation of the microbiota of kefir samples using metagenetic analysis targeting the 16S and 26S ribosomal DNA fragments. J Dairy Sci. 2015;98(6):3684–9. https://doi.org/10.3168/jds.2014-9065.CrossRefPubMed

43.

Garofalo C, Osimani A, Milanović V, Aquilanti L, De Filippis F, Stellato G, et al. Bacteria and yeast microbiota in milk kefir grains from different Italian regions. Food Microbiol. 2015;49:123–33. https://doi.org/10.1016/j.fm.2015.01.017.CrossRefPubMed

44.

Li L, Wieme A, Spitaels F, Balzarini T, Nunes OC, Manaia CM, et al. Acetobacter sicerae sp. nov., isolated from cider and kefir, and identification of species of the genus Acetobacter by dnaK, groEL and rpoB sequence analysis. Int J Syst Evol Microbiol. 2014;64(Pt 7):2407–15. https://doi.org/10.1099/ijs.0.058354-0.CrossRefPubMed

45.

Laureys D, Vuyst LD. The water kefir grain inoculum determines the characteristics of the resulting water kefir fermentation process. J Appl Microbiol. 2017;122(3):719–32. https://doi.org/10.1111/jam.13370.CrossRefPubMed

46.

Laureys D, De Vuyst L. Microbial species diversity, community dynamics, and metabolite kinetics of water kefir fermentation. Appl Environ Microbiol. 2014;80(8):2564–72. https://doi.org/10.1128/AEM.03978-13.CrossRefPubMedPubMedCentral

47.

Leroi F, Pidoux M. Characterization of interactions between Lactobacillus hilgardii and Saccharomyces florentinus isolated from sugary kefir grains. J Appl Bacteriol. 1993;74(1):54–60. https://doi.org/10.1111/j.1365-2672.1993.tb02996.x.CrossRef

48.

Ardhana MM, Fleet GH. The microbial ecology of cocoa bean fermentations in Indonesia. Int J Food Microbiol. 2003;86(1–2):87–99. https://doi.org/10.1016/S0168-1605(03)00081-3.CrossRefPubMed

49.

Rodriguez AV, de Nadra MCM. Mixed culture of Lactobacillus hilgardii and Leuconostoc oenos isolated from argentine wine. J Appl Bacteriol. 1995;78(5):521–5. https://doi.org/10.1111/j.1365-2672.1995.tb03094.x.CrossRef

50.

Pidoux M. The microbial flora of sugary kefir grain (the gingerbeer plant): biosynthesis of the grain from Lactobacillus hilgardii producing a polysaccharide gel. MIRCEN J Appl Microbiol Biotechnol. 1989;5(2):223–38. https://doi.org/10.1007/BF01741847.CrossRef

51.

Pidoux M, De Ruiter GA, Brooker BE, Colquhoun IJ, Morris VJ. Microscopic and chemical studies of a gelling polysaccharide from Lactobacillus hilgardii. Carbohydr Polym. 1990;13(4):351–62. https://doi.org/10.1016/0144-8617(90)90035-Q.CrossRef

52.

Waldherr FW, Doll VM, Meissner D, Vogel RF. Identification and characterization of a glucan-producing enzyme from Lactobacillus hilgardii TMW 1.828 involved in granule formation of water kefir. Food Microbiol. 2010;27(5):672–8. https://doi.org/10.1016/j.fm.2010.03.013.CrossRefPubMed

53.

Pidoux M, Brillouet JM, Quemener B. Characterization of the polysaccharides from aLactobacillus brevis and from sugary kefir grains. Biotechnol Lett. 1988;10(6):415–20. https://doi.org/10.1007/BF01087442.CrossRef

54.

Miyamoto M, Seto Y, Hao DH, Teshima T, Sun YB, Kabuki T, et al. Lactobacillus harbinensis sp. nov., consisted of strains isolated from traditional fermented vegetables ‘Suan cai’ in Harbin, northeastern China and Lactobacillus perolens DSM 12745. Syst Appl Microbiol. 2005;28(8):688–94. https://doi.org/10.1016/j.syapm.2005.04.001.CrossRefPubMed

55.

Lönnermark E, Nowrouzinan F, Adlerberth I, Ahrné S, Wold A, Friman V. Oral and faecal lactobacilli and their expression of mannose-specific adhesins in individuals with and without IgA deficiency. Int J Med Microbiol IJMM. 2012;302(1):53–60. https://doi.org/10.1016/j.ijmm.2011.08.004.CrossRefPubMed

56.

Sekwati-Monang B, Valcheva R, Gänzle MG. Microbial ecology of sorghum sourdoughs: effect of substrate supply and phenolic compounds on composition of fermentation microbiota. Int J Food Microbiol. 2012;159(3):240–6. https://doi.org/10.1016/j.ijfoodmicro.2012.09.013.CrossRefPubMed

57.

Solieri L, Bianchi A, Giudici P. Inventory of non starter lactic acid bacteria from ripened Parmigiano Reggiano cheese as assessed by a culture dependent multiphasic approach. Syst Appl Microbiol. 2012;35(4):270–7. https://doi.org/10.1016/j.syapm.2012.04.002.CrossRefPubMed

58.

Delavenne E, Ismail R, Pawtowski A, Mounier J, Barbier G, Le Blay G. Assessment of lactobacilli strains as yogurt bioprotective cultures. Food Control. 2013;30(1):206–13. https://doi.org/10.1016/j.foodcont.2012.06.043.CrossRef

59.

Talib N, Mohamad NE, Yeap SK, Hussin Y, Aziz MNM, Masarudin MJ, et al. Isolation and Characterization of Lactobacillus spp. from Kefir Samples in Malaysia. Molecules. 2019;24(14). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6680525/. [cited 2019 Dec 8].

60.

Bhanja Dey T, Chakraborty S, Jain KK, Sharma A, Kuhad RC. Antioxidant phenolics and their microbial production by submerged and solid state fermentation process: A review. Trends Food Sci Technol. 2016;53:60–74.CrossRef

61.

Filannino P, Bai Y, Di Cagno R, Gobbetti M, Gänzle MG. Metabolism of phenolic compounds by Lactobacillus spp. during fermentation of cherry juice and broccoli puree. Food Microbiol. 2015;46:272–9. https://doi.org/10.1016/j.fm.2014.08.018.CrossRefPubMed

62.

Svensson L, Sekwati-Monang B, Lutz DL, Schieber A, Gänzle MG. Phenolic acids and flavonoids in nonfermented and fermented red Sorghum (Sorghum bicolor (L.) Moench). J Agric Food Chem. 2010;58(16):9214–20. https://doi.org/10.1021/jf101504v.CrossRefPubMed

63.

Zhou Y, Wang R, Zhang Y, Yang Y, Sun X, Zhang Q, et al. Biotransformation of phenolics and metabolites and the change in antioxidant activity in kiwifruit induced by Lactobacillus plantarum fermentation. J Sci Food Agric. 2020;100(8):3283–90.

64.

Zulkawi N, Ng KH, Zamberi R, Yeap SK, Satharasinghe D, Jaganath IB, et al. In vitro characterization and in vivo toxicity, antioxidant and immunomodulatory effect of fermented foods; Xeniji™. BMC Complement Altern Med. 2017;17(1):344. https://doi.org/10.1186/s12906-017-1845-6.CrossRefPubMedPubMedCentral

65.

Chen B, Peng Y, Wang X, Li Z, Sun Y. Preparative separation and purification of four glycosides from Gentianae radix by high-speed counter-current chromatography and comparison of their anti-NO production effects. Molecules. 2017;22(11):2002. https://doi.org/10.3390/molecules22112002.CrossRefPubMedCentral

66.

Wang S, Xu Y, Jiang W, Zhang Y. Isolation and identification of constituents with activity of inhibiting nitric oxide production in RAW 264.7 macrophages from Gentiana triflora. Planta Med. 2013;79(8):680–6. https://doi.org/10.1055/s-0032-1328460.CrossRefPubMed

67.

Yang E-J, Lee J-G, Song K-S. The glycosidase treatment of Gentianae Scabrae Radix converts Trifloroside into Deglucosyltrifloroside with an enhancement of Antioxidative effects. J Med Food. 2017;20(10):951–8. https://doi.org/10.1089/jmf.2017.3938.CrossRefPubMed

68.

Olennikov DN, Gadimli AI, Isaev JI, Kashchenko NI, Prokopyev AS, Kataeva TN, et al. Caucasian Gentiana Species: Untargeted LC-MS Metabolic Profiling, Antioxidant and Digestive Enzyme Inhibiting Activity of Six Plants. Metabolites. 2019;9(11). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918269/. [cited 2021 May 18].

69.

Suh H-W, Lee K-B, Kim K-S, Yang HJ, Choi E-K, Shin MH, et al. A bitter herbal medicine Gentiana scabra root extract stimulates glucagon-like peptide-1 secretion and regulates blood glucose in db/db mouse. J Ethnopharmacol. 2015;172:219–26. https://doi.org/10.1016/j.jep.2015.06.042.CrossRefPubMed

70.

Chen J-W, Zhu Z-Q, Hu T-X, Zhu D-Y. Structure-activity relationship of natural flavonoids in hydroxyl radical-scavenging effects. Acta Pharmacol Sin. 2002;23(7):667–72.PubMed

71.

Suksamrarn A, Poomsing P, Aroonrerk N, Punjanon T, Suksamrarn S, Kongkun S. Antimycobacterial and antioxidant flavones from Limnophila geoffrayi. Arch Pharmacal Res. 2003;26(10):816–20. https://doi.org/10.1007/BF02980026.CrossRef

72.

Alhusainy W, Williams GM, Jeffrey AM, Iatropoulos MJ, Taylor S, Adams TB, et al. The natural basil flavonoid nevadensin protects against a methyleugenol-induced marker of hepatocarcinogenicity in male F344 rat. Food Chem Toxicol Int J Publ Br Ind Biol Res Assoc. 2014;74:28–34. https://doi.org/10.1016/j.fct.2014.08.016.CrossRef

73.

Jung IH, Lee HE, Park SJ, Ahn YJ, Kwon G, Woo H, et al. Ameliorating effect of spinosin, a C-glycoside flavonoid, on scopolamine-induced memory impairment in mice. Pharmacol, Biochem Behav. 2014;120:88–94. https://doi.org/10.1016/j.pbb.2014.02.015.CrossRef

74.

Liu J, Zhai W-M, Yang Y-X, Shi J-L, Liu Q-T, Liu G-L, et al. GABA and 5-HT systems are implicated in the anxiolytic-like effect of spinosin in mice. Pharmacol, Biochem Behav. 2015;128:41–9. https://doi.org/10.1016/j.pbb.2014.11.003.CrossRef

75.

Ko SY, Lee HE, Park SJ, Jeon SJ, Kim B, Gao Q, et al. Spinosin, a C-Glucosylflavone, from Zizyphus jujuba var. spinosa ameliorates Aβ1-42 oligomer-induced memory impairment in mice. Biomol Ther. 2015;23(2):156–64. https://doi.org/10.4062/biomolther.2014.110.CrossRef

76.

Diniz Rosa D, do Carmo Gouveia Peluzio M, Pérez Bueno T, Vega Cañizares E, Sánchez Miranda L, Mancebo Dorbignyi B, et al. Evaluation of the subchronic toxicity of kefir by oral administration in Wistar rats. Nutr Hosp. 2014;29(6):1352–9. https://doi.org/10.3305/nh.2014.29.6.7390.CrossRefPubMed

77.

Verhaegen AA, Gaal LFV. Drugs That Affect Body Weight, Body Fat Distribution, and Metabolism - Endotext - NCBI Bookshelf [Internet]. 2019 [cited 2020 Mar 30]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537590/.

78.

Pijl H, Meinders A. Bodyweight change as an adverse effect of drug treatment. Mechanisms and management. - PubMed - NCBI [Internet]. 1996 [Cited 2020 mar 30]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/8800628.

79.

Gowda S, Desai PB, Hull VV, AAK M, Vernekar SN, Kulkarni SS. A review on laboratory liver function tests. Pan Afr Med J. 2009;3. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2984286/. [cited 2018 May 4].

80.

Giannini EG, Testa R, Savarino V. Liver enzyme alteration: a guide for clinicians [Internet]. 2005 [cited 2020 Mar 30]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC545762/.

81.

Mercado MG, Smith DK, Guard EL. Acute Kidney Injury: Diagnosis and Management - American Family Physician [Internet]. 2019 [cited 2020 Mar 30]. Available from: https://www.aafp.org/afp/2019/1201/p687.html.

82.

Waikar SS, Bonventre JV. Creatinine Kinetics and the Definition of Acute Kidney Injury | American Society of Nephrology [Internet]. 2009 [cited 2020 Mar 30]. Available from: https://jasn.asnjournals.org/content/20/3/672.

Title: Metagenomic and phytochemical analyses of kefir water and its subchronic toxicity study in BALB/c mice
Authors: Muganti Rajah Kumar
Swee Keong Yeap
Nurul Elyani Mohamad
Janna Ong Abdullah
Mas Jaffri Masarudin
Melati Khalid
Adam Thean Chor Leow
Noorjahan Banu Alitheen
Publication date: 01-12-2021
Publisher: BioMed Central
Published in: BMC Complementary Medicine and Therapies / Issue 1/2021
Electronic ISSN: 2662-7671
DOI: https://doi.org/10.1186/s12906-021-03358-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Metagenomic and phytochemical analyses of kefir water and its subchronic toxicity study in BALB/c mice

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2021

Bioactive fractions and compound of Ardisia crispa roots exhibit anti-arthritic properties mediated via angiogenesis inhibition in vitro

Effect of the standard herbal preparation, STW5, treatment on dysbiosis induced by dextran sodium sulfate in experimental colitis

Efficacy and safety of Si-Jun-Zi-Tang-based therapies for functional (non-ulcer) dyspepsia: a meta-analysis of randomized controlled trials

A standardized polyherbal preparation POL-6 diminishes alcohol withdrawal anxiety by regulating Gabra1, Gabra2, Gabra3, Gabra4, Gabra5 gene expression of GABAA receptor signaling pathway in rats

Complementary medicine in Germany: a multi-centre cross-sectional survey on the usage by and the needs of patients hospitalized in university medical centers

Lippia javanica (Zumbani) herbal tea infusion attenuates allergic airway inflammation via inhibition of Th2 cell activation and suppression of oxidative stress