Nonalcoholic fatty liver disease (NAFLD) is a major chronic liver disease that can lead to liver cirrhosis, liver cancer, and death. Artichoke leaf extract (ALE) is well known in folk medicine for its hepatoprotective effect. Till recent times, no sufficient data from randomized clinical trials (RCTs) exist to support such use. This meta-analysis summarizes evidence from recent RCTs that evaluated ALE in NAFLD patients. Electronic databases were searched for RCTs that used ALE in NAFLD patients. The random-effects model was used to pool effect sizes (standardized change score). Data synthesis from five RCTs (333 patients) showed that ALE resulted in a significant reduction in alanine aminotransferase (standardized mean difference [SMD]: 1.1; 95% confidence interval [CI], 0.79–1.73; P < .001) and aspartate aminotransferase levels (SMD: 1.01; 95% CI, 0.52–1.51; P < .001) compared with the control group. ALE also resulted in a significant reduction in total cholesterol (SMD: 0.98; 95% CI, 0.53–1.43; P = .004), low-density lipoprotein (SMD: 0.96; 95% CI, 0.3–1.62; P < .001) and triglycerides (SMD: 0.95; 95% CI, 0.58–1.32; P < .001). The current review provides evidence from RCTs to support the use of ALE as a hepatoprotective agent in NAFLD patients. The study was registered on the PROSPERO database with the Registration No. CRD42020182502 (https://www.crd.york.ac.uk/prospero).
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References
1.
BedogniG, MiglioliL, MasuttiF, TiribelliC, MarchesiniG, BellentaniS: Prevalence of and risk factors for nonalcoholic fatty liver disease: The Dionysos nutrition and liver study. Hepatology, 2005; 42:44–52.
2.
YounossiZ, AnsteeQM, MariettiM, et al.: Global burden of NAFLD and NASH: Trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol, 2018; 15:11–20.
3.
AdamsLA, AnsteeQM, TilgH, TargherG: Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases. Gut, 2017; 66:1138–1153.
4.
MachadoMV, Cortez-PintoH: Non-alcoholic fatty liver disease: What the clinician needs to know. World J Gastroenterol, 2014; 20:12956–12980.
5.
TargherG, ByrneCD, LonardoA, ZoppiniG, BarbuiC: Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: A meta-analysis. J Hepatol, 2016; 65:589–600.
6.
LonardoA, SookoianS, PirolaCJ, TargherG: Non-alcoholic fatty liver disease and risk of cardiovascular disease. Metabolism, 2016; 65:1136–1150.
7.
KäräjämäkiAJ, BloiguR, KaumaH, et al.: Non-alcoholic fatty liver disease with and without metabolic syndrome: Different long-term outcomes. Metabolism, 2017; 66:55–63.
8.
TripodiA, FracanzaniAL, PrimignaniM, et al.: Procoagulant imbalance in patients with non-alcoholic fatty liver disease. J Hepatol, 2014; 61:148–154.
9.
NeumanMG, CohenLB, NanauRM: Biomarkers in nonalcoholic fatty liver disease. Can J Gastroenterol Hepatol, 2014; 28:607–618.
10.
AsifM, FaridaA, NaveedaR, et al.: Carbon tetrachloride (CCl4)-induced hepatotoxicity in rats: Curative role of Solanum nigrum. J Med Plants Res, 2010; 4:2525–2532.
11.
LimaCF, Fernandes-FerreiraM, Pereira-WilsonC: Drinking of Salvia officinalis tea increases CCl4-induced hepatotoxicity in mice. Food Chem Toxicol, 2007; 45:456–464.
12.
GianniniEG, TestaR, SavarinoV: Liver enzyme alteration: A guide for clinicians. CMAJ, 2005; 172:367–379.
13.
LattanzioV, KroonPA, LinsalataV, CardinaliA: Globe artichoke: A functional food and source of nutraceutical ingredients. J Funct Foods, 2009; 1:131–144.
14.
RaccuiaSA, MainolfiA, MandolinoG, MelilliMG: Genetic diversity in Cynara cardunculus revealed by AFLP markers: Comparison between cultivars and wild types from Sicily. Plant Breed, 2004; 123:280–284.
15.
Salem MBen, AffesH, KsoudaK, et al.: Pharmacological studies of artichoke leaf extract and their health benefits. Plant Foods Hum Nutr, 2015; 70:441–453.
16.
GebhardtR: Choleretic and anticholestatic activities of flavonoids of artichoke (Cynara cardunculus L. subsp. scolymus (L.) Hayek). Acta Hortic, 2005; 681:429–436.
17.
FritscheJ, BeindorffCM, DachtlerM, ZhangH, LammersJG: Isolation, characterization and determination of minor artichoke (Cynara scolymus L.) leaf extract compounds. Eur Food Res Technol, 2002; 215:149–157.
18.
FaragMA, ElsebaiMF, KhattabAR: Metabolome based classification of artichoke leaf: A prospect for phyto-equivalency of its different leaf origins and commercial preparations. J Pharm Biomed Anal, 2018; 158:151–159.
19.
FaragMA, El-AhmadySH, ElianFS, WessjohannLA: Metabolomics driven analysis of artichoke leaf and its commercial products via UHPLC-q-TOF-MS and chemometrics. Phytochemistry, 2013; 95:177–187.
20.
Salem MBen, KsoudaK, DhouibiR, et al.: LC-MS/MS Analysis and Hepatoprotective activity of artichoke (Cynara scolymus L.) leaves extract against high fat diet-induced obesity in rats. Biomed Res Int, 2019; 2019:4851279.
21.
El SenousyAS, FaragMA, Al-MahdyDA, WessjohannLA: Developmental changes in leaf phenolics composition from three artichoke cvs. (Cynara scolymus) as determined via UHPLC-MS and chemometrics. Phytochemistry, 2014; 108:67–76.
22.
ZayedA, SeragA, FaragMA: Cynara cardunculus L.: Outgoing and potential trends of phytochemical, industrial, nutritive and medicinal merits. J Funct Foods, 2020; 69:103937.
23.
CiceroA, CollettiA, BellentaniS: Nutraceutical approach to non-alcoholic fatty liver disease (NAFLD): The available clinical evidence. Nutrients, 2018; 10:1153.
24.
ElsebaiMF, AbassK, HakkolaJ, AtawiaAR, FaragMA: The wild Egyptian artichoke as a promising functional food for the treatment of hepatitis C virus as revealed: Via UPLC-MS and clinical trials. Food Funct, 2016; 7:3006–3016.
25.
SperoniE, CervellatiR, GovoniP, GuizzardiS, RenzulliC, GuerraMC: Efficacy of different Cynara scolymus preparations on liver complaints. J Ethnopharmacol, 2003; 86:203–211.
26.
Ben SalemM, AffesH, DhouibiR, et al.: Effect of artichoke (Cynara scolymus) on cardiac markers, lipid profile and antioxidants levels in tissue of HFD-induced obesity. Arch Physiol Biochem, 2022; 128:184–194.
27.
AbdulkhaleqMM, AlnahdiHS, HusseinRH: The modulatory role of artichoke leaves water extract on lipid status on rats fed high fat diet. Int J Adv Res Biol Sci, 2018; 5:131–139.
28.
El SayedAM, HusseinR, MotaalAA, FouadMA, AzizMA, El-SayedA: Artichoke edible parts are hepatoprotective as commercial leaf preparation. Brazilian J Pharmacogn, 2018; 28:165–178.
29.
SahebkarA, PirroM, BanachM, MikhailidisDP, AtkinSL, CiceroAFGG: Lipid-lowering activity of artichoke extracts: A systematic review and meta-analysis. Crit Rev Food Sci Nutr, 2018; 58:2549–2556.
30.
LiberatiA, AltmanDG, TetzlaffJ, et al.: The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: Explanation and elaboration. PLoS Med, 2009; 6:e1000100.
31.
MethleyAM, CampbellS, Chew-GrahamC, McNallyR, Cheraghi-SohiS: PICO, PICOS and SPIDER: A comparison study of specificity and sensitivity in three search tools for qualitative systematic reviews. BMC Health Serv Res, 2014; 14:579.
32.
EggerM, SmithGD, SchneiderM, MinderC: Bias in meta-analysis detected by a simple, graphical test. Br Med J, 1997; 315:629–634.
33.
SterneJAC, SavovićJ, PageMJ, et al.: RoB 2: A revised tool for assessing risk of bias in randomised trials. BMJ, 2019; 366:1–8.
34.
DerSimonianR, LairdN: Meta-analysis in clinical trials. Control Clin Trials, 1986; 7:177–188.
35.
TakeshimaN, SozuT, TajikaA, OgawaY, HayasakaY, FurukawaTA: Which is more generalizable, powerful and interpretable in meta-analyses, mean difference or standardized mean difference?. BMC Med Res Methodol, 2014; 14:30.
36.
HernánMA, RobinsJM: Per-protocol analyses of pragmatic trials. N Engl J Med, 2017; 377:1391–1398.
37.
RanganathanP, PrameshC, AggarwalR: Common pitfalls in statistical analysis: Intention-to-treat versus per-protocol analysis. Perspect Clin Res, 2016; 7:144.
38.
CastellinoG, NikolicD, Magán-FernándezA, et al.: Altilix® supplement containing chlorogenic acid and luteolin improved hepatic and cardiometabolic parameters in subjects with metabolic syndrome: A 6 month randomized, double-blind, placebo-controlled study. Nutrients, 2019; 11:2580.
39.
RangbooV, NorooziM, ZavoshyR, et al.: The effect of artichoke leaf extract on alanine aminotransferase and aspartate aminotransferase in the patients with nonalcoholic steatohepatitis. Int J Hepatol, 2016; 2016:1–6.
40.
RadchenkoVG, SeliverstovPV, LedentsovaSS, ManyakovAV: Nonalcoholic steatohepatitis and biliary sludge in people with metabolic syndrome. Ter Arkh, 2016; 88:78–83.
41.
PanahiY, KianpourP, MohtashamiR, et al.: Efficacy of artichoke leaf extract in non-alcoholic fatty liver disease: A pilot double-blind randomized controlled trial. Phyther Res, 2018; 32:1382–1387.
42.
MusolinoV, GliozziM, BombardelliE, et al.: The synergistic effect of Citrus bergamia and Cynara cardunculus extracts on vascular inflammation and oxidative stress in non-alcoholic fatty liver disease. J Tradit Complement Med, 2020; 10:268–274.
El SohaimySA: Chemical composition, antioxidant and antimicrobial potential of artichoke. Open Nutraceuticals J, 2014; 7:15–20.
45.
GebhardtR: Antioxidative and protective properties of extracts from leaves of the artichoke (Cynara scolymus L.) against hydroperoxide-induced oxidative stress in cultured rat hepatocytes. Toxicol Appl Pharmacol, 1997; 144:279–286.
46.
AdzetTT, CamarasaJ, LagunaJC: Hepatoprotective activity of polyphenolic compounds from Cynara scolymus against CCl 4 toxicity in isolated rat hepatocytes. J Nat Prod, 1987; 50:612–617.
47.
ElsebaiMF, MocanA, AtanasovAG: Cynaropicrin: A comprehensive research review and therapeutic potential as an anti-hepatitis C virus agent. Front Pharmacol, 2016; 7:472.
48.
BerroukcheA, BoufadiYM, DellaouiH, LansariW, ZerarkiI: Study of Cynara cardunculus (Artichoke) stem and leave aqueous extract effects on biochemical parameters in rats fed with high-fat-diet and vitamin C-supplement. J Microbiol Biotechnol Food Sci, 2019; 8:1145–1149.
49.
KüçükgerginC, AydınAF, Özdemirler-ErataG, MehmetçikG, Koçak-TokerN, UysalM: Effect of artichoke leaf extract on hepatic and cardiac oxidative stress in rats fed on high cholesterol diet. Biol Trace Elem Res, 2010; 135:264–274.
50.
ShimodaH, NinomiyaK, NishidaN, et al.: Anti-hyperlipidemic sesquiterpenes and new sesquiterpene glycosides from the leaves of artichoke (Cynara scolymus L.): Structure requirement and mode of action. Bioorganic Med Chem Lett, 2003; 13:223–228.
51.
ChatrathH, VuppalanchiR, ChalasaniN: Dyslipidemia in patients with nonalcoholic fatty liver disease. Semin Liver Dis, 2012; 32:22–29.
52.
ClarkJM: Weight loss as a treatment for nonalcoholic fatty liver disease. J Clin Gastroenterol, 2006; 40(Suppl 1):S39–S43.
53.
FerenceBA, GinsbergHN, GrahamI, et al.: Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J, 2017; 38:2459–2472.
54.
OoiEMM, NgTWK, ChanDC, WattsGF: Plasma markers of cholesterol homeostasis in metabolic syndrome subjects with or without type-2 diabetes. Diabetes Res Clin Pract, 2009; 85:310–316.
55.
SimonenP, GyllingH, HowardAN, MiettinenTA: Introducing a new component of the metabolic syndrome: Low cholesterol absorption. Am J Clin Nutr, 2000; 72:82–88.
56.
Fallah HuseiniH, KianbakhtS, HeshmatR. Cynara scolymus L: in treatment of hypercholesterolemic type 2 diabetic patients: A randomized double-blind placebo-controlled clinical trial. J Med Plants, 2012; 11:58–65.
57.
RezazadehK, Rahmati-YamchiM, MohammadnejadL, Ebrahimi-MameghaniM, DelazarA: Effects of artichoke leaf extract supplementation on metabolic parameters in women with metabolic syndrome: Influence of TCF7L2-rs7903146 and FTO-rs9939609 polymorphisms. Phyther Res, 2018; 32:84–93.
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