Oxidative stress is a key factor of comorbidities in obesity. A Mexican genotype of the medicinal mushroom Ganoderma lucidum (Gl) contains bioactive compounds showing antioxidant, hypocholesterolemic, anti-inflammatory, anticancer, and prebiotic properties. We assessed the effect of standardized Gl-1 and Gl-2 extracts (1%) consumed by obese C57BL/6 mice fed with a high-fat and sugar diet (HFSD), on weight increase, serum parameters, liver lipid accumulation, and the expression of antioxidant genes (glutathione peroxidase 1, catalase [CAT], superoxide dismutase [SOD] 1, SOD2) and proteins (CAT, SOD2, nuclear factor erythroid 2-related factor 2) in the liver. Fifty-six male C57BL/6 mice were randomized into seven groups involving the control and treatments during 17 weeks, as well as using metformin (Met, 250 mg/kg/day) as a reference drug. Serum lipids and glucose levels decreased in mice groups consuming Gl extracts and metformin, in comparison with the HFSD group, as follows: total cholesterol (−11.8% to −35.7%), triglycerides (−8.3% to −24.8%), low-density lipoprotein cholesterol (−19.6% to −51.6%), and glucose (−3.1% to −25.7%). Gl-1 and Gl-2 extracts showed antioxidant properties and prevented lipid accumulation in the liver. The expression of antioxidant genes and proteins was significantly higher (P < .001) in the mice groups consuming Gl extracts, as compared to the HFSD group. This evidence showed that Gl-1 and Gl-2 extracts prevented oxidative stress in the in vivo model of obesity induced by an HFSD.
NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: A pooled analysis of 2416 population-based measurement studies in 128.9 million children, adolescents, and adults. Lancet, 2017; 390(10113):2627–2642; doi: 10.1016/S0140-6736(17)32129-3
2.
De LorenzoA, GratteriS, GualtieriP, et al.Why primary obesity is a disease? J Transl Med, 2019; 17(1):169; doi: 10.1186/s12967-019-1919-y
3.
Dubois-DeruyE, PeugnetV, TurkiehA, et al.Oxidative stress in cardiovascular diseases. Antioxidants (Basel), 2020; 9(9):864; doi: 10.3390/antiox9090864
4.
Herranz-LópezM, Barrajón-CatalánE, Segura-CarreteroA, et al.Lemon verbena (Lippia citriodora) polyphenols alleviate obesity-related disturbances in hypertrophic adipocytes through AMPK-dependent mechanisms. Phytomedicine, 2015; 22(6):605–614; doi: 10.1016/j.phymed.2015.03.015
5.
LiangZ, YuanZ, LiG, et al.Hypolipidemic, antioxidant, and antiapoptotic effects of polysaccharides extracted from reishi mushroom, Gl (Leysser: Fr) Karst, in mice fed a high-fat diet. J Med Food, 2018; 21(12):1218–1227; doi: 10.1089/jmf.2018.4182
6.
SminaTP, MathewJ, JanardhananKK, et al.Antioxidant activity and toxicity profile of total triterpenes isolated from Gl (Fr.) P. Karst occurring in South India. Environ Toxicol Pharmacol, 2011; 32(3):438–446; doi: 10.1016/j.etap.2011.08.011
7.
ChangCJ, LinCS, LuCC, et al.Gl reduces obesity in mice by modulating the composition of the gut microbiota. Nat Commun, 2015; 6:7489; doi: 10.1038/ncomms8489
8.
XuF, LiX, LiQ, et al.Effect of Gl polysaccharide on antioxidative ability of rats with myocardial injury induced by doxorubicin. J Biosci Med, 2022; 10(4):14–19; doi: 10.4236/jbm.2022.104002
9.
SangT, GuoC, GuoD, et al.Suppression of obesity and inflammation by polysaccharide from sporoderm-broken spore of Gl via gut microbiota regulation. Carbohydr Polym, 2021; 256:117594; doi: 10.1016/j.carbpol.2020.117594
10.
CörD, KnezŽ, Knez HrnčičM. Antitumour, antimicrobial, antioxidant and antiacetylcholinesterase effect of Gl terpenoids and polysaccharides: A review. Molecules, 2018; 23(3):649; doi: 10.3390/molecules23030649
11.
MenesesME, Martínez-CarreraD, TorresN, et al.Hypocholesterolemic properties and prebiotic effects of Mexican Gl in C57BL/6 mice. PLoS One, 2016; 11(7):e0159631; doi: 10.1371/journal.pone.0159631
12.
Romero-CórdobaSL, Salido-GuadarramaI, MenesesME, et al.Mexican Gl extracts decrease lipogenesis modulating transcriptional metabolic networks and gut microbiota in C57BL/6 mice fed with a high-cholesterol diet. Nutrients, 2020; 13(1):38; doi: 10.3390/nu13010038
13.
Martínez-CarreraD, Larqué-SaavedraA, Tovar PalacioA, et al.Contribución de los hongos comestibles, funcionales y medicinales a la construcción de un paradigma sobre la producción, la dieta, la salud y la cultura en el sistema agroalimentario de México. In: Ciencia, Tecnología e Innovación en el Sistema Agroalimentario de México (Martínez-CarreraD, RamírezJuárezJ, eds.). Editorial del Colegio de Postgraduados-AMC-CONACYT-UPAEP-IMINAP: San Luis Huexotla: Texcoco, México; 2016; pp. 581–640.
14.
MenesesME, Martínez-CarreraD, González-IbáñezL, et al.Effects of Mexican Gl extracts on liver, kidney, and the gut microbiota of Wistar rats: A repeated dose oral toxicity study. PLoS One, 2023; 18(4):e0283605; doi: 10.1371/journal.pone.0283605
15.
AbenavoliL, GrecoM, MilicN, et al.Effect of Mediterranean diet and antioxidant formulation in non-alcoholic fatty liver disease: A randomized study. Nutrients, 2017; 9(8):870; doi: 10.3390/nu9080870
16.
Martínez-CarreraD, Pérez ArmendárizB, MayettY, et al.Propiedades funcionales agregadas al tequila, otros mezcales y destilados de Agave convencionales, derivadas del extracto de un hongo comestible de uso tradicional en México (Lentinula boryana). IMPI patent no. 322035, July 8, 2014, Mexico City; pp. 1–21.
17.
ReevesPG. Components of the AIN-93 diets as improvements in the AIN-76A diet. J Nutr, 1997; 127(5 Suppl):838S–841S; doi: 10.1093/jn/127.5.838S
18.
BowlingJL, KatayevA. An evaluation of the Roche Cobas c111. Lab Med, 2010; 41(7):398–402; doi: 10.1309/LM6T8D1LKQXVNCAC
19.
Coutiño-HernándezD, Sánchez-TapiaM, Leal-VegaF, et al.Modulation of gut microbiota by Mantequilla and Melipona honeys decrease low-grade inflammation caused by high fructose corn syrup or saccharose in rats. Food Res Int, 2022; 151:110856; doi: 10.1016/j.foodres.2021.110856
20.
LiY, LiN, YuX, et al.Hematoxylin and eosin staining of intact tissues via delipidation and ultrasound. Sci Rep, 2018; 8(1):12259; doi: 10.1038/s41598-018-30755-5
21.
Boon-Bee GohG, Qiang LeowW, LiangS, et al.Quantification of hepatic steatosis in chronic liver disease using novel automated method of second harmonic generation and two-photon excited fluorescence. Sci Rep, 2019; 9(1):2975; doi: 10.1038/s41598-019-39783-1
22.
DominguesCC, KunduN, KropotovaY, et al.Antioxidant-upregulated mesenchymal stem cells reduce inflammation and improve fatty liver disease in diet-induced obesity. Stem Cell Res Ther, 2019; 10(1):280; doi: 10.1186/s13287-019-1393-8
23.
BergerA, ReinD, KratkyE, et al.Cholesterol-lowering properties of Gl in vitro, ex vivo, and in hamsters and minipigs. Lipids Health Dis, 2004; 3:2; doi: 10.1186/1476-511X-3-2
24.
HajjajH, MacéC, RobertsM, et al.Effect of 26-oxygenosterols from Gl and their activity as cholesterol synthesis inhibitors. Appl Environ Microbiol, 2005; 71(7):3653–3658; doi: 10.1128/AEM.71.7.3653-3658.2005
25.
ChanSW, TomlinsonB, ChanP, et al.The beneficial effects of Gl on cardiovascular and metabolic disease risk. Pharm Biol, 2021; 59(1):1161–1171; doi: 10.1080/13880209.2021.1969413
26.
KluppNL, KiatH, BensoussanA, et al.A double-blind, randomised, placebo-controlled trial of Gl for the treatment of cardiovascular risk factors of metabolic syndrome. Sci Rep, 2016; 6:29540; doi: 10.1038/srep29540
27.
ChuT, BenzieI, LamC, et al.Study of potential cardioprotective effects of Ganoderma lucidum (Lingzhi): Results of a controlled human intervention trial. Br J Nutr, 2012; 107(7):1017–1027; doi: 10.1017/S0007114511003795
28.
HuD, GuoY, WuR, et al.New insight into metformin-induced cholesterol-lowering effect crosstalk between glucose and cholesterol homeostasis via ChREBP (carbohydrate-responsive element-binding protein)-mediated PCSK9 (proprotein convertase subtilisin/kexin type 9) regulation. Arterioscler Thromb Vasc Biol, 2021; 41(4):e208–e223; doi: 10.1161/ATVBAHA.120.315708
29.
HuangCH, LinWK, ChangS, et al.Evaluation of the hypoglycaemic and antioxidant effects of submerged Gl cultures in type 2 diabetic rats. Mycology, 2020; 12(2):82–93; doi: 10.1080/21501203.2020.1733119
30.
XiaoC, WuQP, CaiW, et al.Hypoglycemic effects of Gl polysaccharides in type 2 diabetic mice. Arch Pharm Res, 2012; 35(10):1793–1801; doi: 10.1007/s12272-012-1012-z
31.
WangF, ZhouZ, RenX, et al.Effect of Gl spores intervention on glucose and lipid metabolism gene expression profiles in type 2 diabetic rats. Lipids Health Dis, 2015; 14:49; doi: 10.1186/s12944-015-0045-y
32.
WangCD, TengBS, HeYM, et al.Effect of a novel proteoglycan PTP1B inhibitor from Gl on the amelioration of hyperglycaemia and dyslipidaemia in db/db mice. Br J Nutr, 2012; 108(11):2014–2025; doi: 10.1017/S0007114512000153
33.
JungOL, SooKL, JiHK, et al.Metformin regulates glucose transporter 4 (GLUT4) translocation through AMP-activated protein kinase (AMPK)-mediated Cbl/CAP signaling in 3T3-L1 preadipocyte cells. J Biol Chem, 2012; 287(53):44121–44129; doi: 10.1074/jbc.M112.361386
34.
SusiloRJK, WinarniD, HusenSA, et al.Hepatoprotective effect of crude polysaccharides extracted from Gl against carbon tetrachloride-induced liver injury in mice. Vet World, 2019; 12(12):1987–1991; doi: 10.14202/vetworld.2019.1987-1991
35.
PanR, LouJ, WeiL. Significant effects of Gl polysaccharide on lipid metabolism in diabetes may be associated with the activation of the FAM3C-HSF1-CAM signaling pathway. Exp Ther Med, 2021; 22(2):820–830; doi: 10.3892/etm.2021.10252
36.
KozarskiM, KlausA, JakovljevicD, et al.Antioxidants of edible mushrooms. Molecules, 2015; 20(10):19489–19525; doi: 10.3390/molecules201019489
37.
LiuW, WangH, PangX, et al.Characterization and antioxidant activity of two low-molecular-weight polysaccharides purified from the fruiting bodies of Gl. Int J Biol Macromol, 2010; 46(4):451–457; doi: 10.1016/j.ijbiomac.2010.02.006
38.
HapuarachchiK, WenT, JeewonR, et al.Ganoderma lucidum—Are the beneficial medical properties substantiated? Mycosphere Essays, 2016; 7(6):687–715; doi: 10.5943/mycosphere/7/6/1
39.
CaoYJ, HuangZR, YouSZ, et al.The protective effects of ganoderic acids from Gl fruiting body on alcoholic liver injury and intestinal microflora disturbance in mice with excessive alcohol intake. Foods, 2022; 11(7):949; doi: 10.3390/foods11070949
40.
ShiM, ZhangZ, YangY. Antioxidant and immunoregulatory activity of Gl polysaccharide (GLP). Carbohydr Polym, 2013; 95(1):200–206; doi: 10.1016/j.carbpol.2013.02.081
41.
WuS. Hypolipidaemic and anti-lipidperoxidant activities of Gl polysaccharide. Int J Biol Macromol, 2018; 118(Pt B):2001–2005; doi: 10.1016/j.ijbiomac.2018.07.082
42.
LiHN, ZhaoLL, ZhouDY, et al.Gl polysaccharides ameliorates hepatic steatosis and oxidative stress in db/db mice via targeting nuclear factor E2 (erythroid-derived 2)-related factor-2/heme oxygenase-1 (HO-1) pathway. Med Sci Monit, 2020; 26(26):e921905; doi: 10.12659/MSM.921905
43.
HeF, RuX, WenT. NRF2, a transcription factor for stress response and beyond. Int J Mol Sci, 2020; 21(13):4777; doi: 10.3390/ijms21134777
44.
PriorRL, WuX. Diet antioxidant capacity: Relationships to oxidative stress and health. Am J Biomed Sci, 2013; 5(2):126–139; doi: 10.5099/aj130200126
45.
Castañeda-AntonioMD, Martínez-CarreraDC, Rivera-TapiaJA, et al.Detection of polysaccharides in Gl extracts. Nova Sci, 2019; 10(21):247–257; doi: 10.21640/ns.v10i21.1538
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
