Increased protein expression of ABCA1, HMG-CoA reductase, and CYP46A1 induced by garlic and allicin in the brain mouse and astrocytes-isolated from C57BL/6J

Document Type : Original Research Article


1 Department of Biochemistry, Medical School, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

2 Department of Biochemistry, Medical School, Cellular & Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran


Objective: Regulation of cholesterol level is essential for the brain optimal function. The beneficial effect of garlic consumption on cholesterol homeostasis is well known; however, the molecular mechanism to support its properties is unclear. Here, we investigated the beneficial effect of aqueous extract of garlic and allicin on lipid profile and the main players involved in brain cholesterol homeostasis including ABCA1, HMG-CoA reductase, and CYP46A1 in both C57BL/6J mice brain and astrocytes. 
Materials and Methods: Thirty mice were divided into control and garlic groups. Garlic group was fed with the aqueous extract of garlic. Serum lipids were measured and brain protein levels of ABCA1, HMGCR, and CYP46A1 were determined by western blotting. Changes in these proteins expression were also studied in the presence of allicin in cultured astrocytes.
Results: A moderate decrease in serum total cholesterol and a significant increase in plasma HDL-C levels (p <0.05) were detected. A significant increase in ABCA1, HMGCR, and CYP46A1 protein levels was observed in the garlic group and in the cultured astrocytes treated with allicin by western blotting (p <0.05).
Conclusion: Our findings indicated that the main players involved in cholesterol turnover including HMGCR that is involved in cholesterol synthesis, ABCA1 that is important in cholesterol efflux, and CYP46A1 that is necessary in cholesterol degradation, were up regulated by garlic/allicin in both animal and cell culture model. We concluded that increasing cholesterol turnover is a possible mechanism for the beneficial effects of garlic in cholesterol homeostasis.


Adler AJ, Holub BJ. 1997. Effect of garlic and
fish-oil supplementation on serum lipid and
lipoprotein concentrations in
hypercholesterolemic men. Am J Clin Nutr,
65: 445-450.
Azizidoost S, Nazeri Z, Mohammadi A,
Mohammadzadeh G, Cheraghzadeh M,
Jafari A, Kheirollah A. 2019. Effect of
hydroalcoholic ginger extract on brain
HMG-CoA reductase and CYP46A1 levels
in streptozotocin-induced diabetic rats.
Avicenna J Med Biotechnol, 11: 234-238.
Bayan L, Koulivand PH, Gorji A. 2014. Garlic:
a review of potential therapeutic effects.
Avicenna J Phytomed, 4: 1-14.
Björkhem I, Meaney S. 2004. Brain cholesterol:
long secret life behind a barrier. ATVB, 24:
Chen J, Zhang X, Kusumo H, Costa LG,
Guizzetti M. 2013. Cholesterol efflux is
differentially regulated in neurons and
astrocytes: implications for brain cholesterol
homeostasis. Biochim Biophys Acta, 1831:
Cui X, Chopp M, Zhang Z, Li R, Zacharek A,
Landschoot-Ward J, Venkat P, Chen J.
2017. ABCA1/ApoE/HDL pathway
mediates GW3965-induced
neurorestoration after stroke. Stroke, 48:
De Martino A, Filomeni G, Aquilano K, Ciriolo
MR, Rotilio G. 2006. Effects of water garlic
extracts on cell cycle and viability of HepG2
hepatoma cells. J Nutr Biochem, 17: 742-
Djelti F, Braudeau J, Hudry E, Dhenain M,
Varin J, Bièche I, Marquer C, Chali F,
Ayciriex S, Auzeil N, Alves S, Langui D,
Potier MC, Laprevote O, Vidaud M,
Duyckaerts C, Miles R, Aubourg P, Cartier
N. 2015. CYP46A1 inhibition, brain
cholesterol accumulation and
neurodegeneration pave the way for
Alzheimer’s disease. Brain, 138: 2383-
Hajhashemi V, Dashti G, Saberi S,
Malekjamshidi P. 2014. The effect of
hydroalcoholic extract and essential oil of
Heracleum persicum on lipid profile in
cholesterol-fed rabbits. Avicenna J
Phytomed, 4: 144-150.
Han M, Wang S, Yang N, Wang X, Zhao W,
Saed HS, Daubon T, Huang B, Chen A, Li
G, Miletic H, Thorsen F, Bjerkvig R, Li X,
Wang J. 2020. Therapeutic implications of
altered cholesterol homeostasis mediated by
loss of CYP46A1 in human glioblastoma.
EMBO Mol Med, 12: e10924.
Hashemi SA, Bathaie Sz, Mohagheghi MA.
2020. Crocetin and crocin decreased
cholesterol and triglyceride content of both
breast cancer tumors and cell lines.
Avicenna J Phytomed, 10: 384-397.
Ito J, Nagayasu Y, Kheirollah A, Abe-Dohmae
S, Yokoyama S. 2011. ApoA-I enhances
generation of HDL-like lipoproteins through
interaction between ABCA1 and
phospholipase Cgamma in rat astrocytes.
Biochim Biophys Acta, 1811: 1062-1069.
Kennedy MA, Barrera GC, Nakamura K,
Baldán A, Tarr P, Fishbein MC, Frank J,
Francone OL, Edwards PA. 2005. ABCG1
has a critical role in mediating cholesterol
efflux to HDL and preventing cellular lipid
accumulation. Cell Metab, 1: 121-131.
Kheirollah A, Ito J-i, Nagayasu Y, Lu R,
Yokoyama S. 2006. Cyclosporin A inhibits
apolipoprotein AI-induced early events in
cellular cholesterol homeostasis in rat
astrocytes. Neuropharmacology, 51: 693-
Kheirollah A, Nagayasu Y, Ueda H, Yokoyama
S, Michikawa M, Ito J. 2014. Involvement
of cdc42/Rho kinase in apoA-I-mediated
cholesterol efflux through interaction
between cytosolic lipid-protein particles and
microtubules in rat astrocytes. J Neurosci
Res, 92: 455-463.
Kotti TJ, Ramirez DM, Pfeiffer BE, Huber KM,
Russell DW. 2006. Brain cholesterol
turnover required for geranylgeraniol
production and learning in mice. Proc Natl
Acad Sci U S A,
 103: 3869-3874.
Kudinov VA, Alekseeva OY, Torkhovskaya TI,
Baskaev KK, Artyushev RI, Saburina IN,
Markin SS.
 2020. High-density lipoproteins as
homeostatic nanoparticles of blood plasma.
Int J Mol Sci, 21: 8737.
Nazeri et al.
AJP, Vol. 11, No. 5, Sep-Oct 2021 482
Lin XL, Hu HJ, Liu YB, Hu XM, Fan XJ, Zou
WW, Pan YQ, Zhou WQ, Peng MW, Gu
CH. 2017. Allicin induces the upregulation
of ABCA1 expression via
PPARgamma/LXRalpha signaling in THP1 macrophage-derived foam cells. Int J Mol
Med, 39: 1452-1460.
Liu L, Yeh Y-Y 2002. S-alk (en) yl cysteines of
garlic inhibit cholesterol synthesis by
deactivating HMG-CoA reductase in
cultured rat hepatocytes. J nutr, 132: 1129-
Liu L, Yeh YY. 2001. Water‐ soluble
organosulfur compounds of garlic inhibit
fatty acid and triglyceride syntheses in
cultured rat hepatocytes. Lipids, 36: 395-
Lowry OH, Rosebrough NJ, Farr AL, Randall
RJ. 1951. Protein measurement with the
Folin phenol reagent. JBC, 193: 265-275.
Lu F, Fan S, Romo AR, Xu D, Ferriero DM,
Jiang X. 2020. Serum 24Shydroxycholesterol predicts long-term brain
structural and functional outcomes after
hypoxia-ischemia in neonatal mice. J Cereb
Blood Flow Metab, 41: 312-323.
Madkor HR, Mansour SW, Ramadan G. 2011.
Modulatory effects of garlic, ginger,
turmeric and their mixture on
hyperglycaemia, dyslipidaemia and
oxidative stress in streptozotocin–
nicotinamide diabetic rats. Br J Nutr, 105:
Malekpour-Dehkordi Z, Javadi E, Doosti M,
Paknejad M, Nourbakhsh M, Yassa N,
Gerayesh-Nejad S, Heshmat R. 2013. S‐
Allylcysteine, a garlic compound, increases
ABCA1 expression in human THP‐ 1
macrophages. Phytother Res, 27: 357-361.
Mohammadi A, Oshaghi EA. 2014. Effect of
garlic on lipid profile and expression of
LXR alpha in intestine and liver of
hypercholesterolemic mice. J Diabetes
Metab Disord, 13: 20.
Morze J, Koch M, Aroner SA, Budoff M,
McClelland RL, Mukamal KJ, Jensen MK.
2020. Associations of HDL subspecies
defined by ApoC3 with non-alcoholic fatty
liver disease: The multi-ethnic study of
atherosclerosis. J Clin Med, 9: 3522.
Moutinho M, Nunes MJ, Rodrigues E. 2017.
The mevalonate pathway in neurons: It's not
just about cholesterol. Exp Cell Res, 360:
Perovic M, Mladenovic Djordjevic A,
Smiljanic K, Tanic N, Rakic L, Ruzdijic S,
Kanazir S. 2009. Expression of cholesterol
homeostasis genes in the brain of the male
rat is affected by age and dietary restriction.
Biogerontology, 10: 735.
Repa JJ, Berge KE, Pomajzl C, Richardson JA,
Hobbs HH, Mangelsdorf DJ. 2002.
Regulation of ATP-binding cassette sterol
transporters, ABCG5 and ABCG8, by the
oxysterol receptors, LXRα and β. JBC, 277:
Rothblat GH, de la Llera-Moya M, Atger V,
Kellner-Weibel G, Williams DL, Phillips
MC. 1999. Cell cholesterol efflux:
integration of old and new observations
provides new insights. JLR, 40: 781-796
Rouhi-Boroujeni H, Rouhi-Boroujeni H,
Heidarian E, Mohammadizadeh F, RafieianKopaei M. 2015. Herbs with anti-lipid
effects and their interactions with statins as
a chemical anti-hyperlipidemia group drugs:
A systematic review. ARYA
atherosclerosis, 11: 244.
Saadane A, Mast N, Trichonas G, Chakraborty
D, Hammer S, Busik JV, Grant MB,
Pikuleva IA. 2019. Retinal vascular
abnormalities and microglia activation in
mice with deficiency in cytochrome P450
46A1-mediated cholesterol removal. Am J
Pathol, 189: 405-425.
Sangouni AA, Mohammad Hosseini Azar MR,
Alizadeh M. 2020. Effect of garlic powder
supplementation on hepatic steatosis, liver
enzymes and lipid profile in patients with
non-alcoholic fatty liver disease: a doubleblind randomised controlled clinical trial. Br
J Nutr, 124: 450-456.
Sarkaki A, Valipour Chehardacheric S,
Farbood Y, Mansouri SMT, Naghizadeh B,
Basirian E. 2012. Effects of fresh, aged and
cooked garlic extracts on short- and longterm memory in diabetic rats. Avicenna J
Phytomed, 3: 45-55.
Shabani E, Sayemiri K, Mohammadpour M.
2019. The effect of garlic on lipid profile
and glucose parameters in diabetic patients:
A systematic review and meta-analysis.
Prim Care Diabetes, 13: 28-42.
Vitali C, Wellington CL, Calabresi L. 2014.
HDL and cholesterol handling in the brain.
Cardiovasc Res, 103: 405-413.
Garlic and the brain cholesterol homeostasis
AJP, Vol. 11, No. 5, Sep-Oct 2021 483
Wang YL, Guo XY, He W, Chen RJ, Zhuang
R. 2017. Effects of alliin on LPS-induced
acute lung injury by activating
PPARgamma. Microb Pathog, 110: 375-
Yang R, Zhao Y, Gu Y, Yang Y, Gao X, Yuan
Y, Xiao L, Zhang J, Sun C, Yang H, Qin J,
Li J, Zhang F, Zhang L, Ye J. 2020.
Isocitrate dehydrogenase 1 mutation
enhances 24(S)-hydroxycholesterol
production and alters cholesterol
homeostasis in glioma. Oncogene, 39: 6340-
Zeb F, Safdar M, Fatima S, Khan S, Alam S,
Muhammad M, Syed A, Habib F, Shakoor
H. 2018. Supplementation of garlic and
coriander seed powder: Impact on body
mass index, lipid profile and blood pressure
of hyperlipidemic patients. Pak J Pharm Sci,
31: 1935-1941.
Zhang J, Liu Q. 2015. Cholesterol metabolism
and homeostasis in the brain. Protein & cell,
6: 254-264.