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Effects of aged garlic extract on aging‑related changes in gastrointestinal function and enteric nervous system cells

  • Authors:
    • Kensuke Ohishi
    • Ahmed A. Rahman
    • Takahiro Ohkura
    • Alan J. Burns
    • Allan M. Goldstein
    • Ryo Hotta
  • View Affiliations / Copyright

    Affiliations: Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    Copyright: © Ohishi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 103
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    Published online on: March 26, 2025
       https://doi.org/10.3892/etm.2025.12853
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Abstract

Dysmotility of the gastrointestinal (GI) tract is commonly seen in elderly individuals, where it causes significant morbidity and can lead to more severe conditions, including sarcopenia and frailty. Although the precise mechanisms underlying aging‑related GI dysmotility are not fully understood, neuronal loss or degeneration in the enteric nervous system (ENS) may be involved. Aged garlic extract (AGE) has been shown to have several beneficial effects in the GI tract; however, it is not known whether AGE can improve GI motility in older animals. The aim of the present study was to examine the effects of AGE on the ENS and gut motility in older mice and elucidate potential mechanisms of action. An AGE‑formulated diet was given to 18‑month‑old female mice for 2 weeks. Organ bath studies and cell culture demonstrated that AGE: i) Altered gut contractile activity; ii) enhanced viability of ENS cells; and iii) exhibited neuroprotective effects on the ENS via reduction in oxidative stress. These findings suggest that AGE could be used to develop novel dietary therapeutics for aging‑related GI dysmotility by targeting the associated loss and damage of the ENS.
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1 

Kennedy BK, Berger SL, Brunet A, Campisi J, Cuervo AM, Epel ES, Franceschi C, Lithgow GJ, Morimoto RI, Pessin JE, et al: Geroscience: Linking aging to chronic disease. Cell. 159:709–713. 2014.PubMed/NCBI View Article : Google Scholar

2 

Campisi J: Aging, cellular senescence, and cancer. Annu Rev Physiol. 75:685–705. 2013.PubMed/NCBI View Article : Google Scholar

3 

Saffrey MJ: Aging of the mammalian gastrointestinal tract: A complex organ system. Age (Dordr). 36(9603)2014.PubMed/NCBI View Article : Google Scholar

4 

Cox NJ, Ibrahim K, Sayer AA, Robinson SM and Roberts HC: Assessment and treatment of the anorexia of aging: A systematic review. Nutrients. 11(144)2019.PubMed/NCBI View Article : Google Scholar

5 

Parker BA and Chapman IM: Food intake and ageing-the role of the gut. Mech Ageing Dev. 125:859–866. 2004.PubMed/NCBI View Article : Google Scholar

6 

Siddappa PK and Birk JW: Gastrointestinal health and healthy aging. In: Healthy Aging: A Complete Guide to Clinical Management. Coll PP (ed). Springer International Publishing, Cham, pp67-79, 2019.

7 

Doan TN, Ho WC, Wang LH, Chang FC, Nhu NT and Chou LW: Prevalence and methods for assessment of oropharyngeal dysphagia in older adults: A systematic review and meta-analysis. J Clin Med. 11(2605)2022.PubMed/NCBI View Article : Google Scholar

8 

Mounsey A, Raleigh M and Wilson A: Management of constipation in older adults. Am Fam Physician. 92:500–504. 2015.PubMed/NCBI

9 

Chang L, Toner BB, Fukudo S, Guthrie E, Locke GR, Norton NJ and Sperber AD: Gender, age, society, culture, and the patient's perspective in the functional gastrointestinal disorders. Gastroenterology. 130:1435–1446. 2006.PubMed/NCBI View Article : Google Scholar

10 

Kim YS and Kim N: Sex-gender differences in irritable bowel syndrome. J Neurogastroenterol Motil. 24:544–558. 2018.PubMed/NCBI View Article : Google Scholar

11 

Alqudah M, Al-Shboul O, Al Dwairi A, Al-U´Datt DG and Alqudah A: Progesterone inhibitory role on gastrointestinal motility. Physiol Res. 71:193–198. 2022.PubMed/NCBI View Article : Google Scholar

12 

Oh JE, Kim YW, Park SY and Kim JY: Estrogen rather than progesterone cause constipation in both female and male mice. Korean J Physiol Pharmacol. 17:423–426. 2013.PubMed/NCBI View Article : Google Scholar

13 

Shah E, Rezaie A, Riddle M and Pimentel M: Psychological disorders in gastrointestinal disease: Epiphenomenon, cause or consequence? Ann Gastroenterol. 27:224–230. 2014.PubMed/NCBI

14 

Haug TT, Mykletun A and Dahl AA: Are anxiety and depression related to gastrointestinal symptoms in the general population? Scand J Gastroenterol. 37:294–298. 2002.PubMed/NCBI View Article : Google Scholar

15 

Salk RH, Hyde JS and Abramson LY: Gender differences in depression in representative national samples: Meta-analyses of diagnoses and symptoms. Psychol Bull. 143:783–822. 2017.PubMed/NCBI View Article : Google Scholar

16 

Furness JB: The enteric nervous system and neurogastroenterology. Nat Rev Gastroenterol Hepatol. 9:286–294. 2012.PubMed/NCBI View Article : Google Scholar

17 

Rao M and Gershon MD: Enteric nervous system development: What could possibly go wrong? Nat Rev Neurosci. 19:552–565. 2018.PubMed/NCBI View Article : Google Scholar

18 

Camilleri M, Cowen T and Koch TR: Enteric neurodegeneration in ageing. Neurogastroenterol Motil. 20:418–429. 2008.PubMed/NCBI View Article : Google Scholar

19 

Saffrey MJ: Cellular changes in the enteric nervous system during ageing. Dev Biol. 382:344–355. 2013.PubMed/NCBI View Article : Google Scholar

20 

El-Salhy M, Sandström O and Holmlund F: Age-induced changes in the enteric nervous system in the mouse. Mech Ageing Dev. 107:93–103. 1999.PubMed/NCBI View Article : Google Scholar

21 

Bernard CE, Gibbons SJ, Gomez-Pinilla PJ, Lurken MS, Schmalz PF, Roeder JL, Linden D, Cima RR, Dozois EJ, Larson DW, et al: Effect of age on the enteric nervous system of the human colon. Neurogastroenterol Motil. 21:746–e46. 2009.PubMed/NCBI View Article : Google Scholar

22 

Colín-González AL, Santana RA, Silva-Islas CA, Chánez-Cárdenas ME, Santamaría A and Maldonado PD: The antioxidant mechanisms underlying the aged garlic extract- and S-allylcysteine-induced protection. Oxid Med Cell Longev. 2012(907162)2012.PubMed/NCBI View Article : Google Scholar

23 

Matsutomo T and Kodera Y: Development of an analytic method for sulfur compounds in aged garlic extract with the use of a postcolumn high performance liquid chromatography method with sulfur-specific detection. J Nutr. 146:450S–455S. 2016.PubMed/NCBI View Article : Google Scholar

24 

Ried K, Frank OR and Stocks NP: Aged garlic extract lowers blood pressure in patients with treated but uncontrolled hypertension: A randomised controlled trial. Maturitas. 67:144–150. 2010.PubMed/NCBI View Article : Google Scholar

25 

Ried K, Frank OR and Stocks NP: Aged garlic extract reduces blood pressure in hypertensives: A dose-response trial. Eur J Clin Nutr. 67:64–70. 2013.PubMed/NCBI View Article : Google Scholar

26 

Ried K, Travica N and Sali A: The effect of aged garlic extract on blood pressure and other cardiovascular risk factors in uncontrolled hypertensives: The AGE at Heart trial. Integr Blood Press Control. 9:9–21. 2016.PubMed/NCBI View Article : Google Scholar

27 

Ried K, Travica N and Sali A: The effect of kyolic aged garlic extract on gut microbiota, inflammation, and cardiovascular markers in hypertensives: The GarGIC trial. Front Nutr. 5(122)2018.PubMed/NCBI View Article : Google Scholar

28 

Zini A, Mann J, Mazor S and Vered Y: The efficacy of aged garlic extract on gingivitis-A randomized clinical trial. J Clin Dent. 29:52–56. 2018.PubMed/NCBI

29 

Takahashi K, Nango H, Ushijima M, Takashima M, Nakamoto M, Matsutomo T, Jikihara H, Arakawa N, Maki S, Yabuki A, et al: Therapeutic effect of aged garlic extract on gingivitis in dogs. Front Vet Sci. 10(1277272)2023.PubMed/NCBI View Article : Google Scholar

30 

Harauma A and Moriguchi T: Aged garlic extract improves blood pressure in spontaneously hypertensive rats more safely than raw garlic. J Nutr. 136 (3 Suppl):769S–773S. 2006.PubMed/NCBI View Article : Google Scholar

31 

Matsutomo T, Ushijima M, Kodera Y, Nakamoto M, Takashima M, Morihara N and Tamura K: Metabolomic study on the antihypertensive effect of S-1-propenylcysteine in spontaneously hypertensive rats using liquid chromatography coupled with quadrupole-Orbitrap mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 1046:147–155. 2017.PubMed/NCBI View Article : Google Scholar

32 

Matsutomo T, Ushijima M, Kunimura K and Ohtani M: Metabolomic study reveals the acute hypotensive effect of S-1-propenylcysteine accompanied by alteration of the plasma histidine level in spontaneously hypertensive rats. J Pharm Biomed Anal. 168:148–154. 2019.PubMed/NCBI View Article : Google Scholar

33 

Ushijima M, Takashima M, Kunimura K, Kodera Y, Morihara N and Tamura K: Effects of S-1-propenylcysteine, a sulfur compound in aged garlic extract, on blood pressure and peripheral circulation in spontaneously hypertensive rats. J Pharm Pharmacol. 70:559–565. 2018.PubMed/NCBI View Article : Google Scholar

34 

Matsutomo T: Potential benefits of garlic and other dietary supplements for the management of hypertension. Exp Ther Med. 19:1479–1484. 2020.PubMed/NCBI View Article : Google Scholar

35 

Borek C: Antioxidant health effects of aged garlic extract. J Nutr. 131 (3S):1010S–1015S. 2001.PubMed/NCBI View Article : Google Scholar

36 

Yamato O, Tsuneyoshi T, Ushijima M, Jikihara H and Yabuki A: Safety and efficacy of aged garlic extract in dogs: Upregulation of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway and Nrf2-regulated phase II antioxidant enzymes. BMC Vet Res. 14(373)2018.PubMed/NCBI View Article : Google Scholar

37 

Tsuneyoshi T: BACH1 mediates the antioxidant properties of aged garlic extract. Exp Ther Med. 19:1500–1503. 2020.PubMed/NCBI View Article : Google Scholar

38 

Moriguchi T, Saito H and Nishiyama N: Aged garlic extract prolongs longevity and improves spatial memory deficit in senescence-accelerated mouse. Biol Pharm Bull. 19:305–307. 1996.PubMed/NCBI View Article : Google Scholar

39 

Ogawa T, Kodera Y, Hirata D, Blackwell TK and Mizunuma M: Natural thioallyl compounds increase oxidative stress resistance and lifespan in Caenorhabditis elegans by modulating SKN-1/Nrf. Sci Rep. 6(21611)2016.PubMed/NCBI View Article : Google Scholar

40 

Morihara N, Hino A, Miki S, Takashima M and Suzuki JI: Aged garlic extract suppresses inflammation in apolipoprotein E-knockout mice. Mol Nutr Food Res. 61:2017.PubMed/NCBI View Article : Google Scholar

41 

Suzuki JI, Kodera Y, Miki S, Ushijima M, Takashima M, Matsutomo T and Morihara N: Anti-inflammatory action of cysteine derivative S-1-propenylcysteine by inducing MyD88 degradation. Sci Rep. 8(14148)2018.PubMed/NCBI View Article : Google Scholar

42 

Ohtani M and Nishimura T: Sulfur-containing amino acids in aged garlic extract inhibit inflammation in human gingival epithelial cells by suppressing intercellular adhesion molecule-1 expression and IL-6 secretion. Biomed Rep. 12:99–108. 2020.PubMed/NCBI View Article : Google Scholar

43 

Miki S, Suzuki JI, Kunimura K and Morihara N: Mechanisms underlying the attenuation of chronic inflammatory diseases by aged garlic extract: Involvement of the activation of AMP-activated protein kinase. Exp Ther Med. 19:1462–1467. 2020.PubMed/NCBI View Article : Google Scholar

44 

Liu J: Aged garlic therapeutic intervention targeting inflammatory pathways in pathogenesis of bowel disorders. Heliyon. 10(e33986)2024.PubMed/NCBI View Article : Google Scholar

45 

Maeda T, Miki S, Morihara N and Kagawa Y: Aged garlic extract ameliorates fatty liver and insulin resistance and improves the gut microbiota profile in a mouse model of insulin resistance. Exp Ther Med. 18:857–866. 2019.PubMed/NCBI View Article : Google Scholar

46 

Ried K: Garlic lowers blood pressure in hypertensive subjects, improves arterial stiffness and gut microbiota: A review and meta-analysis. Exp Ther Med. 19:1472–1478. 2020.PubMed/NCBI View Article : Google Scholar

47 

Horie T, Li T, Ito K, Sumi S and Fuwa T: Aged garlic extract protects against methotrexate-induced apoptotic cell injury of IEC-6 cells. J Nutr. 136 (3 Suppl):861S–863S. 2006.PubMed/NCBI View Article : Google Scholar

48 

Kang YK, Min B, Eom J and Park JS: Different phases of aging in mouse old skeletal muscle. Aging (Albany NY). 14:143–160. 2022.PubMed/NCBI View Article : Google Scholar

49 

Jackson SJ, Andrews N, Ball D, Bellantuono I, Gray J, Hachoumi L, Holmes A, Latcham J, Petrie A, Potter P, et al: Does age matter? The impact of rodent age on study outcomes. Lab Anim. 51:160–169. 2017.PubMed/NCBI View Article : Google Scholar

50 

Mallon BS and Macklin WB: Overexpression of the 3'-untranslated region of myelin proteolipid protein mRNA leads to reduced expression of endogenous proteolipid mRNA. Neurochem Res. 27:1349–1360. 2002.PubMed/NCBI View Article : Google Scholar

51 

Guyer RA, Stavely R, Robertson K, Bhave S, Mueller JL, Picard NM, Hotta R, Kaltschmidt JA and Goldstein AM: Single-cell multiome sequencing clarifies enteric glial diversity and identifies an intraganglionic population poised for neurogenesis. Cell Rep. 42(112194)2023.PubMed/NCBI View Article : Google Scholar

52 

Kodera Y, Kurita M, Nakamoto M and Matsutomo T: Chemistry of aged garlic: Diversity of constituents in aged garlic extract and their production mechanisms via the combination of chemical and enzymatic reactions. Exp Ther Med. 19:1574–1584. 2020.PubMed/NCBI View Article : Google Scholar

53 

Bradham KD, Scheckel KG, Nelson CM, Seales PE, Lee GE, Hughes MF, Miller BW, Yeow A, Gilmore T, Serda SM, et al: Relative bioavailability and bioaccessibility and speciation of arsenic in contaminated soils. Environ Health Perspect. 119:1629–1634. 2011.PubMed/NCBI View Article : Google Scholar

54 

Sasselli V, Boesmans W, Vanden Berghe P, Tissir F, Goffinet AM and Pachnis V: Planar cell polarity genes control the connectivity of enteric neurons. J Clin Invest. 123:1763–1772. 2013.PubMed/NCBI View Article : Google Scholar

55 

Natale G, Kastsiushenka O, Fulceri F, Ruggieri S, Paparelli A and Fornai F: MPTP-induced parkinsonism extends to a subclass of TH-positive neurons in the gut. Brain Res. 1355:195–206. 2010.PubMed/NCBI View Article : Google Scholar

56 

Patel BA, Patel N, Fidalgo S, Wang C, Ranson RN, Saffrey MJ and Yeoman MS: Impaired colonic motility and reduction in tachykinin signalling in the aged mouse. Exp Gerontol. 53:24–30. 2014.PubMed/NCBI View Article : Google Scholar

57 

Jeong D, Kim DH, Kang IB, Kim H, Song KY, Kim HS and Seo KH: Modulation of gut microbiota and increase in fecal water content in mice induced by administration of Lactobacillus kefiranofaciens DN1. Food Funct. 8:680–686. 2017.PubMed/NCBI View Article : Google Scholar

58 

Rahman AA, Ohkura T, Bhave S, Pan W, Ohishi K, Ott L, Han C, Leavitt A, Stavely R, Burns AJ, et al: Enteric neural stem cell transplant restores gut motility in mice with Hirschsprung disease. JCI Insight. 9(e179755)2024.PubMed/NCBI View Article : Google Scholar

59 

Rahman AA, Stavely R, Pan W, Ott L, Ohishi K, Ohkura T, Han C, Hotta R and Goldstein AM: Optogenetic activation of cholinergic enteric neurons reduces inflammation in experimental colitis. Cell Mol Gastroenterol Hepatol. 17:907–921. 2024.PubMed/NCBI View Article : Google Scholar

60 

McCann CJ, Cooper JE, Natarajan D, Jevans B, Burnett LE, Burns AJ and Thapar N: Transplantation of enteric nervous system stem cells rescues nitric oxide synthase deficient mouse colon. Nat Commun. 8(15937)2017.PubMed/NCBI View Article : Google Scholar

61 

Fried DE, Watson RE, Robson SC and Gulbransen BD: Ammonia modifies enteric neuromuscular transmission through glial γ-aminobutyric acid signaling. Am J Physiol Gastrointest Liver Physiol. 313:G570–G580. 2017.PubMed/NCBI View Article : Google Scholar

62 

Stavely R, Bhave S, Ho WLN, Ahmed M, Pan W, Rahman AA, Ulloa J, Bousquet N, Omer M, Guyer R, et al: Enteric mesenchymal cells support the growth of postnatal enteric neural stem cells. Stem Cells. 39:1236–1252. 2021.PubMed/NCBI View Article : Google Scholar

63 

Bhave S, Arciero E, Baker C, Ho WL, Stavely R, Goldstein AM and Hotta R: Enteric neuronal cell therapy reverses architectural changes in a novel diphtheria toxin-mediated model of colonic aganglionosis. Sci Rep. 9(18756)2019.PubMed/NCBI View Article : Google Scholar

64 

Hotta R, Rahman A, Bhave S, Stavely R, Pan W, Srinivasan S, de Couto G, Rodriguez-Borlado L, Myers R, Burns AJ and Goldstein AM: Transplanted ENSCs form functional connections with intestinal smooth muscle and restore colonic motility in nNOS-deficient mice. Stem Cell Res Ther. 14(232)2023.PubMed/NCBI View Article : Google Scholar

65 

Sahakian L, Filippone RT, Stavely R, Robinson AM, Yan XS, Abalo R, Eri R, Bornstein JC, Kelley MR and Nurgali K: Inhibition of APE1/Ref-1 redox signaling alleviates intestinal dysfunction and damage to myenteric neurons in a mouse model of spontaneous chronic colitis. Inflamm Bowel Dis. 27:388–406. 2021.PubMed/NCBI View Article : Google Scholar

66 

Mueller JL, Leavitt AR, Rahman AA, Han CY, Ott LC, Mahdavian NS, Carbone SE, King SK, Burns AJ, Poole DP, et al: Highly neurogenic glia from human and mouse myenteric ganglia generate functional neurons following culture and transplantation into the gut. Cell Rep. 43(114919)2024.PubMed/NCBI View Article : Google Scholar

67 

Jonscher R and Belkind-Gerson J: Concise review: Cellular and molecular mechanisms of postnatal injury-induced enteric neurogenesis. Stem Cells. 37:1136–1143. 2019.PubMed/NCBI View Article : Google Scholar

68 

Sohal RS and Weindruch R: Oxidative stress, caloric restriction, and aging. Science. 273:59–63. 1996.PubMed/NCBI View Article : Google Scholar

69 

Thrasivoulou C, Soubeyre V, Ridha H, Giuliani D, Giaroni C, Michael GJ, Saffrey MJ and Cowen T: Reactive oxygen species, dietary restriction and neurotrophic factors in age-related loss of myenteric neurons. Aging Cell. 5:247–257. 2006.PubMed/NCBI View Article : Google Scholar

70 

Li J, O W, Li W, Jiang ZG and Ghanbari HA: Oxidative stress and neurodegenerative disorders. Int J Mol Sci. 14:24438–24475. 2013.PubMed/NCBI View Article : Google Scholar

71 

Liu Z, Zhou T, Ziegler AC, Dimitrion P and Zuo L: Oxidative stress in neurodegenerative diseases: From molecular mechanisms to clinical applications. Oxid Med Cell Longev. 2017(2525967)2017.PubMed/NCBI View Article : Google Scholar

72 

Morén C, deSouza RM, Giraldo DM and Uff C: Antioxidant therapeutic strategies in neurodegenerative diseases. Int J Mol Sci. 23(9328)2022.PubMed/NCBI View Article : Google Scholar

73 

Fukui K: Reactive oxygen species induce neurite degeneration before induction of cell death. J Clin Biochem Nutr. 59:155–159. 2016.PubMed/NCBI View Article : Google Scholar

74 

Zhao X, Fang J, Li S, Gaur U, Xing X, Wang H and Zheng W: Artemisinin attenuated hydrogen peroxide (H2O2)-induced oxidative injury in sh-sy5y and hippocampal neurons via the activation of AMPK pathway. Int J Mol Sci. 20(2680)2019.PubMed/NCBI View Article : Google Scholar

75 

Becker L, Nguyen L, Gill J, Kulkarni S, Pasricha PJ and Habtezion A: Age-dependent shift in macrophage polarisation causes inflammation-mediated degeneration of enteric nervous system. Gut. 67:827–836. 2018.PubMed/NCBI View Article : Google Scholar

76 

Sun T, Li D, Hu S, Huang L, Sun H, Yang S, Wu B, Ji F and Zhou D: Aging-dependent decrease in the numbers of enteric neurons, interstitial cells of Cajal and expression of connexin43 in various regions of gastrointestinal tract. Aging (Albany NY). 10:3851–3865. 2018.PubMed/NCBI View Article : Google Scholar

77 

Kruger GM, Mosher JT, Bixby S, Joseph N, Iwashita T and Morrison SJ: Neural crest stem cells persist in the adult gut but undergo changes in self-renewal, neuronal subtype potential, and factor responsiveness. Neuron. 35:657–669. 2002.PubMed/NCBI View Article : Google Scholar

78 

Laszczyk AM, Fox-Quick S, Vo HT, Nettles D, Pugh PC, Overstreet-Wadiche L and King GD: Klotho regulates postnatal neurogenesis and protects against age-related spatial memory loss. Neurobiol Aging. 59:41–54. 2017.PubMed/NCBI View Article : Google Scholar

79 

Song H, Lu Y, Qu Z, Mossine VV, Martin MB, Hou J, Cui J, Peculis BA, Mawhinney TP, Cheng J, et al: Effects of aged garlic extract and FruArg on gene expression and signaling pathways in lipopolysaccharide-activated microglial cells. Sci Rep. 6(35323)2016.PubMed/NCBI View Article : Google Scholar

80 

Wlosinska M, Nilsson AC, Hlebowicz J, Hauggaard A, Kjellin M, Fakhro M and Lindstedt S: The effect of aged garlic extract on the atherosclerotic process-a randomized double-blind placebo-controlled trial. BMC Complement Med Ther. 20(132)2020.PubMed/NCBI View Article : Google Scholar

81 

Lindstedt S, Wlosinska M, Nilsson AC, Hlebowicz J, Fakhro M and Sheikh R: Successful improved peripheral tissue perfusion was seen in patients with atherosclerosis after 12 months of treatment with aged garlic extract. Int Wound J. 18:681–691. 2021.PubMed/NCBI View Article : Google Scholar

82 

Yang J, Luo J, Tian X, Zhao Y, Li Y and Wu X: Progress in understanding oxidative stress, aging, and aging-related diseases. Antioxidants (Basel). 13(394)2024.PubMed/NCBI View Article : Google Scholar

83 

Chen X, Guo C and Kong J: Oxidative stress in neurodegenerative diseases. Neural Regen Res. 7:376–385. 2012.PubMed/NCBI View Article : Google Scholar

84 

Sienes Bailo P, Llorente Martín E, Calmarza P, Montolio Breva S, Bravo Gómez A, Pozo Giráldez A, Sánchez-Pascuala Callau JJ, Vaquer Santamaría JM, Dayaldasani Khialani A, Cerdá Micó C, et al: The role of oxidative stress in neurodegenerative diseases and potential antioxidant therapies. Adv Lab Med. 3:342–360. 2022.PubMed/NCBI View Article : Google Scholar : (In English, Spanish).

85 

Smith AN, Shaughness M, Collier S, Hopkins D and Byrnes KR: Therapeutic targeting of microglia mediated oxidative stress after neurotrauma. Front Med (Lausanne). 9(1034692)2022.PubMed/NCBI View Article : Google Scholar

86 

Pan W, Rahman AA, Ohkura T, Stavely R, Ohishi K, Han CY, Leavitt A, Kashiwagi A, Burns AJ, Goldstein AM and Hotta R: Autologous cell transplantation for treatment of colorectal aganglionosis in mice. Nat Commun. 15(2479)2024.PubMed/NCBI View Article : Google Scholar

87 

Imai J, Ide N, Nagae S, Moriguchi T, Matsuura H and Itakura Y: Antioxidant and radical scavenging effects of aged garlic extract and its constituents. Planta Med. 60:417–420. 1994.PubMed/NCBI View Article : Google Scholar

88 

Shi H, Jing X, Wei X, Perez RG, Ren M, Zhang X and Lou H: S-allyl cysteine activates the Nrf2-dependent antioxidant response and protects neurons against ischemic injury in vitro and in vivo. J Neurochem. 133:298–308. 2015.PubMed/NCBI View Article : Google Scholar

89 

Wu W, Liu BH, Xie CL, Xia XD and Zhang YM: Neuroprotective effects of N-acetyl cysteine on primary hippocampus neurons against hydrogen peroxide-induced injury are mediated via inhibition of mitogen-activated protein kinases signal transduction and antioxidative action. Mol Med Rep. 17:6647–6654. 2018.PubMed/NCBI View Article : Google Scholar

90 

Shah SA, Yoon GH, Kim HO and Kim MO: Vitamin C neuroprotection against dose-dependent glutamate-induced neurodegeneration in the postnatal brain. Neurochem Res. 40:875–884. 2015.PubMed/NCBI View Article : Google Scholar

91 

Hui Y, Chengyong T, Cheng L, Haixia H, Yuanda Z and Weihua Y: Resveratrol attenuates the cytotoxicity induced by amyloid-β1-42 in PC12 cells by upregulating heme oxygenase-1 via the PI3K/Akt/Nrf2 pathway. Neurochem Res. 43:297–305. 2018.PubMed/NCBI View Article : Google Scholar

92 

Tonelli C, Chio IIC and Tuveson DA: Transcriptional regulation by Nrf2. Antioxid Redox Signal. 29:1727–1745. 2018.PubMed/NCBI View Article : Google Scholar

93 

Moratilla-Rivera I, Sánchez M, Valdés-González JA and Gómez-Serranillos MP: Natural products as modulators of Nrf2 signaling pathway in neuroprotection. Int J Mol Sci. 24(3748)2023.PubMed/NCBI View Article : Google Scholar

94 

Nagy N and Goldstein AM: Enteric nervous system development: A crest cell's journey from neural tube to colon. Semin Cell Dev Biol. 66:94–106. 2017.PubMed/NCBI View Article : Google Scholar

95 

Belkind-Gerson J, Graham HK, Reynolds J, Hotta R, Nagy N, Cheng L, Kamionek M, Shi HN, Aherne CM and Goldstein AM: Colitis promotes neuronal differentiation of Sox2+ and PLP1+ enteric cells. Sci Rep. 7(2525)2017.PubMed/NCBI View Article : Google Scholar

96 

Hotta R, Stamp LA, Foong JP, McConnell SN, Bergner AJ, Anderson RB, Enomoto H, Newgreen DF, Obermayr F, Furness JB and Young HM: Transplanted progenitors generate functional enteric neurons in the postnatal colon. J Clin Invest. 123:1182–1191. 2013.PubMed/NCBI View Article : Google Scholar

97 

Stamp LA, Gwynne RM, Foong JPP, Lomax AE, Hao MM, Kaplan DI, Reid CA, Petrou S, Allen AM, Bornstein JC and Young HM: Optogenetic demonstration of functional innervation of mouse colon by neurons derived from transplanted neural cells. Gastroenterology. 152:1407–1418. 2017.PubMed/NCBI View Article : Google Scholar

98 

Hotta R, Pan W, Bhave S, Nagy N, Stavely R, Ohkura T, Krishnan K, de Couto G, Myers R, Rodriguez-Borlado L, et al: Isolation, expansion, and endoscopic delivery of autologous enteric neuronal stem cells in swine. Cell Transplant. 32(9636897231215233)2023.PubMed/NCBI View Article : Google Scholar

99 

Lindley RM, Hawcutt DB, Connell MG, Almond SL, Vannucchi MG, Faussone-Pellegrini MS, Edgar DH and Kenny SE: Human and mouse enteric nervous system neurosphere transplants regulate the function of aganglionic embryonic distal colon. Gastroenterology. 135:205–216.e6. 2008.PubMed/NCBI View Article : Google Scholar

100 

Cheng LS, Hotta R, Graham HK, Belkind-Gerson J, Nagy N and Goldstein AM: Postnatal human enteric neuronal progenitors can migrate, differentiate, and proliferate in embryonic and postnatal aganglionic gut environments. Pediatr Res. 81:838–846. 2017.PubMed/NCBI View Article : Google Scholar

101 

Metzger M, Bareiss PM, Danker T, Wagner S, Hennenlotter J, Guenther E, Obermayr F, Stenzl A, Koenigsrainer A, Skutella T and Just L: Expansion and differentiation of neural progenitors derived from the human adult enteric nervous system. Gastroenterology. 137:2063–2073.e4. 2009.PubMed/NCBI View Article : Google Scholar

102 

Rollo BN, Zhang D, Stamp LA, Menheniott TR, Stathopoulos L, Denham M, Dottori M, King SK, Hutson JM and Newgreen DF: Enteric neural cells from hirschsprung disease patients form ganglia in autologous aneuronal colon. Cell Mol Gastroenterol Hepatol. 2:92–109. 2015.PubMed/NCBI View Article : Google Scholar

103 

Lin L, Wu Q, Lu F, Lei J, Zhou Y, Liu Y, Zhu N, Yu Y, Ning Z, She T and Hu M: Nrf2 signaling pathway: Current status and potential therapeutic targetable role in human cancers. Front Oncol. 13(1184079)2023.PubMed/NCBI View Article : Google Scholar

104 

Kärkkäinen V, Pomeshchik Y, Savchenko E, Dhungana H, Kurronen A, Lehtonen S, Naumenko N, Tavi P, Levonen AL, Yamamoto M, et al: Nrf2 regulates neurogenesis and protects neural progenitor cells against Aβ toxicity. Stem Cells. 32:1904–1916. 2014.PubMed/NCBI View Article : Google Scholar

105 

Mittal RK: Integrated Systems Physiology: From Molecule to Function to Disease. In: Motor Function of the Pharynx, Esophagus, and its Sphincters. Morgan & Claypool Life Sciences. Copyright © 2011 by Morgan & Claypool Life Sciences, San Rafael (CA), 2011.

106 

Takashima M, Kanamori Y, Kodera Y, Morihara N and Tamura K: Aged garlic extract exerts endothelium-dependent vasorelaxant effect on rat aorta by increasing nitric oxide production. Phytomedicine. 24:56–61. 2017.PubMed/NCBI View Article : Google Scholar

107 

Sanders KM: Regulation of smooth muscle excitation and contraction. Neurogastroenterol Motil. 20 (Suppl 1):S39–S53. 2008.PubMed/NCBI View Article : Google Scholar

108 

Sarna SK: Integrated Systems Physiology: From Molecule to Function to Disease. In: Colonic Motility: From Bench Side to Bedside. Morgan & Claypool Life Sciences. Copyright © 2010 by Morgan & Claypool Life Sciences, San Rafael (CA), 2010.

109 

Mori M and Gotoh T: Regulation of nitric oxide production by arginine metabolic enzymes. Biochem Biophys Res Commun. 275:715–719. 2000.PubMed/NCBI View Article : Google Scholar

110 

Bayer S, Jellali A, Crenner F, Aunis D and Angel F: Functional evidence for a role of GABA receptors in modulating nerve activities of circular smooth muscle from rat colon in vitro. Life Sci. 72:1481–1493. 2003.PubMed/NCBI View Article : Google Scholar

111 

Ghia JE, Pradaud I, Crenner F, Metz-Boutigue MH, Aunis D and Angel F: Effect of acetic acid or trypsin application on rat colonic motility in vitro and modulation by two synthetic fragments of chromogranin A. Regul Pept. 124:27–35. 2005.PubMed/NCBI View Article : Google Scholar

112 

Tepavcević SN, Isenović ER, Varagić VM and Milovanović SR: Sodium nitroprusside regulates the relaxation of the longitudinal muscle in the gut. Pharmazie. 63:151–155. 2008.PubMed/NCBI

113 

Shah V, Lyford G, Gores G and Farrugia G: Nitric oxide in gastrointestinal health and disease. Gastroenterology. 126:903–913. 2004.PubMed/NCBI View Article : Google Scholar

114 

Dunn WR, Alexander SP, Ralevic V and Roberts RE: Effects of hydrogen sulphide in smooth muscle. Pharmacol Ther. 158:101–113. 2016.PubMed/NCBI View Article : Google Scholar

115 

Rose P, Moore PK and Zhu YZ: Garlic and gaseous mediators. Trends Pharmacol Sci. 39:624–634. 2018.PubMed/NCBI View Article : Google Scholar

116 

Benavides GA, Squadrito GL, Mills RW, Patel HD, Isbell TS, Patel RP, Darley-Usmar VM, Doeller JE and Kraus DW: Hydrogen sulfide mediates the vasoactivity of garlic. Proc Natl Acad Sci USA. 104:17977–17982. 2007.PubMed/NCBI View Article : Google Scholar

117 

Abe K, Hori Y and Myoda T: Volatile compounds of fresh and processed garlic. Exp Ther Med. 19:1585–1593. 2020.PubMed/NCBI View Article : Google Scholar

118 

Gallego D, Clavé P, Donovan J, Rahmati R, Grundy D, Jiménez M and Beyak MJ: The gaseous mediator, hydrogen sulphide, inhibits in vitro motor patterns in the human, rat and mouse colon and jejunum. Neurogastroenterol Motil. 20:1306–1316. 2008.PubMed/NCBI View Article : Google Scholar

119 

Gil V, Parsons S, Gallego D, Huizinga J and Jimenez M: Effects of hydrogen sulphide on motility patterns in the rat colon. Br J Pharmacol. 169:34–50. 2013.PubMed/NCBI View Article : Google Scholar

120 

Kerfoot WW, Park HY, Schwartz LB, Hagen PO and Carson CC III: Characterization of calcium channel blocker induced smooth muscle relaxation using a model of isolated corpus cavernosum. J Urol. 150:249–252. 1993.PubMed/NCBI View Article : Google Scholar

121 

Zheng Z, Tang J, Hu Y and Zhang W: Role of gut microbiota-derived signals in the regulation of gastrointestinal motility. Front Med (Lausanne). 9(961703)2022.PubMed/NCBI View Article : Google Scholar

122 

Carabotti M, Scirocco A, Maselli MA and Severi C: The gut-brain axis: Interactions between enteric microbiota, central and enteric nervous systems. Ann Gastroenterol. 28:203–209. 2015.PubMed/NCBI

123 

Panyod S, Wu WK, Chen PC, Chong KV, Yang YT, Chuang HL, Chen CC, Chen RA, Liu PY, Chung CH, et al: Atherosclerosis amelioration by allicin in raw garlic through gut microbiota and trimethylamine-N-oxide modulation. NPJ Biofilms Microbiomes. 8(4)2022.PubMed/NCBI View Article : Google Scholar

124 

Li M, Yun W, Wang G, Li A, Gao J and He Q: Roles and mechanisms of garlic and its extracts on atherosclerosis: A review. Front Pharmacol. 13(954938)2022.PubMed/NCBI View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Ohishi K, Rahman AA, Ohkura T, Burns AJ, Goldstein AM and Hotta R: Effects of aged garlic extract on aging‑related changes in gastrointestinal function and enteric nervous system cells. Exp Ther Med 29: 103, 2025.
APA
Ohishi, K., Rahman, A.A., Ohkura, T., Burns, A.J., Goldstein, A.M., & Hotta, R. (2025). Effects of aged garlic extract on aging‑related changes in gastrointestinal function and enteric nervous system cells. Experimental and Therapeutic Medicine, 29, 103. https://doi.org/10.3892/etm.2025.12853
MLA
Ohishi, K., Rahman, A. A., Ohkura, T., Burns, A. J., Goldstein, A. M., Hotta, R."Effects of aged garlic extract on aging‑related changes in gastrointestinal function and enteric nervous system cells". Experimental and Therapeutic Medicine 29.5 (2025): 103.
Chicago
Ohishi, K., Rahman, A. A., Ohkura, T., Burns, A. J., Goldstein, A. M., Hotta, R."Effects of aged garlic extract on aging‑related changes in gastrointestinal function and enteric nervous system cells". Experimental and Therapeutic Medicine 29, no. 5 (2025): 103. https://doi.org/10.3892/etm.2025.12853
Copy and paste a formatted citation
x
Spandidos Publications style
Ohishi K, Rahman AA, Ohkura T, Burns AJ, Goldstein AM and Hotta R: Effects of aged garlic extract on aging‑related changes in gastrointestinal function and enteric nervous system cells. Exp Ther Med 29: 103, 2025.
APA
Ohishi, K., Rahman, A.A., Ohkura, T., Burns, A.J., Goldstein, A.M., & Hotta, R. (2025). Effects of aged garlic extract on aging‑related changes in gastrointestinal function and enteric nervous system cells. Experimental and Therapeutic Medicine, 29, 103. https://doi.org/10.3892/etm.2025.12853
MLA
Ohishi, K., Rahman, A. A., Ohkura, T., Burns, A. J., Goldstein, A. M., Hotta, R."Effects of aged garlic extract on aging‑related changes in gastrointestinal function and enteric nervous system cells". Experimental and Therapeutic Medicine 29.5 (2025): 103.
Chicago
Ohishi, K., Rahman, A. A., Ohkura, T., Burns, A. J., Goldstein, A. M., Hotta, R."Effects of aged garlic extract on aging‑related changes in gastrointestinal function and enteric nervous system cells". Experimental and Therapeutic Medicine 29, no. 5 (2025): 103. https://doi.org/10.3892/etm.2025.12853
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