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Review

Palmatine as an Agent Against Metabolic Syndrome and Its Related Complications: A Review

ORCID Icon, ORCID Icon & ORCID Icon
Pages 4963-4974 | Published online: 17 Nov 2020

References

  • ChanKL, CathomasF, RussoSJ. Central and peripheral inflammation link metabolic syndrome and major depressive disorder. Physiology (Bethesda). 2019;34(2):123–133.30724127
  • WangHH, LeeDK, LiuM, PortincasaP, WangDQ. Novel insights into the pathogenesis and management of the metabolic syndrome. Pediatr Gastroenterol Hepatol Nutr. 2020;23(3):189–230. doi:10.5223/pghn.2020.23.3.18932483543
  • ChinK-Y, WongSK, EkeukuSO, PangK-L. Relationship between metabolic syndrome and bone health – an evaluation of epidemiological studies and mechanisms involved. Diabetes Metab Syndr Obes. 2020;13:3667–3690.33116718
  • AlbertiKGMM, ZimmetP, ShawJ. Metabolic syndrome—a new world-wide definition. A consensus statement from the international diabetes federation. Diabet Med. 2006;23(5):469–480. doi:10.1111/j.1464-5491.2006.01858.x16681555
  • AguilarM, BhuketT, TorresS, LiuB, WongRJ. Prevalence of the metabolic syndrome in the United States, 2003–2012. JAMA. 2015;313(19):1973–1974. doi:10.1001/jama.2015.426025988468
  • RanasingheP, MathangasingheY, JayawardenaR, HillsAP, MisraA. Prevalence and trends of metabolic syndrome among adults in the asia-pacific region: a systematic review. BMC Public Health. 2017;17(1):101. doi:10.1186/s12889-017-4041-128109251
  • RobertsCK, SindhuKK. Oxidative stress and metabolic syndrome. Life Sci. 2009;84(21–22):705–712. doi:10.1016/j.lfs.2009.02.02619281826
  • VonaR, GambardellaL, CittadiniC, StrafaceE, PietraforteD. Biomarkers of oxidative stress in metabolic syndrome and associated diseases. Oxid Med Cell Longev. 2019;2019:8267234. doi:10.1155/2019/826723431191805
  • SpahisS, BorysJM, LevyE. Metabolic syndrome as a multifaceted risk factor for oxidative stress. Antioxid Redox Signal. 2017;26(9):445–461. doi:10.1089/ars.2016.675627302002
  • MannaP, JainSK. Obesity, oxidative stress, adipose tissue dysfunction, and the associated health risks: causes and therapeutic strategies. Metab Syndr Relat Disord. 2015;13(10):423–444. doi:10.1089/met.2015.009526569333
  • YeJ. Emerging role of adipose tissue hypoxia in obesity and insulin resistance. Int J Obes. 2009;33(1):54–66. doi:10.1038/ijo.2008.229
  • BhattacharyaI, DominguezAP, DragertK, HumarR, HaasE, BattegayEJ. Hypoxia potentiates tumor necrosis factor-alpha induced expression of inducible nitric oxide synthase and cyclooxygenase-2 in white and brown adipocytes. Biochem Biophys Res Commun. 2015;461(2):287–292. doi:10.1016/j.bbrc.2015.04.02025881506
  • KosackaJ, KernM, KlotingN, et al. Autophagy in adipose tissue of patients with obesity and type 2 diabetes. Mol Cell Endocrinol. 2015;409:21–32. doi:10.1016/j.mce.2015.03.01525818883
  • NetzerN, GattererH, FaulhaberM, BurtscherM, PramsohlerS, PestaD. Hypoxia, oxidative stress and fat. Biomolecules. 2015;5(2):1143–1150. doi:10.3390/biom502114326061760
  • MontezanoAC, Dulak-LisM, TsiropoulouS, HarveyA, BrionesAM, TouyzRM. Oxidative stress and human hypertension: vascular mechanisms, biomarkers, and novel therapies. Can J Cardiol. 2015;31(5):631–641. doi:10.1016/j.cjca.2015.02.00825936489
  • WongSK, ChinK-Y, SuhaimiFH, AhmadF, JamilNA, Ima-NirwanaS. Osteoporosis is associated with metabolic syndrome induced by high-carbohydrate high-fat diet in a rat model. Biomed Pharmacother. 2018;98:191–200. doi:10.1016/j.biopha.2017.12.04229257979
  • BennettJM, ReevesG, BillmanGE, SturmbergJP. Inflammation-nature’s way to efficiently respond to all types of challenges: implications for understanding and managing “the epidemic” of chronic diseases. Front Med (Lausanne). 2018;5:316.30538987
  • WongSK, ChinKY, SuhaimiFH, AhmadF, Ima-NirwanaS. Effects of metabolic syndrome on bone mineral density, histomorphometry and remodelling markers in male rats. PLoS One. 2018;13(2):e0192416. doi:10.1371/journal.pone.019241629420594
  • de la IglesiaR, Loria-KohenV, ZuletMA, MartinezJA, RegleroG, Ramirez de MolinaA. Dietary strategies implicated in the prevention and treatment of metabolic syndrome. Int J Mol Sci. 2016;17(11):1877. doi:10.3390/ijms17111877
  • WongSK, ChinKY, SuhaimiFH, AhmadF, Ima-NirwanaS. The effects of Vitamin E from Elaeis guineensis (Oil Palm) in a rat model of bone loss due to metabolic syndrome. Int J Environ Res Public Health. 2018;15(9):1828. doi:10.3390/ijerph15091828
  • PangKL, ChinKY. The role of tocotrienol in protecting against metabolic diseases. Molecules. 2019;24(5):923. doi:10.3390/molecules24050923
  • LongJ, SongJ, ZhongL, LiaoY, LiuL, LiX. Palmatine: a review of its pharmacology, toxicity and pharmacokinetics. Biochimie. 2019;162:176–184. doi:10.1016/j.biochi.2019.04.00831051209
  • VrbaJ, PapouskovaB, PyszkovaM, et al. Metabolism of palmatine by human hepatocytes and recombinant cytochromes P450. J Pharm Biomed Anal. 2015;102:193–198. doi:10.1016/j.jpba.2014.09.01525285405
  • TarabaszD, Kukula-KochW. Palmatine: a review of pharmacological properties and pharmacokinetics. Phytother Res. 2020;34(1):33–50. doi:10.1002/ptr.650431496018
  • MengFC, WuZF, YinZQ, LinLG, WangR, ZhangQW. Coptidis rhizoma and its main bioactive components: recent advances in chemical investigation, quality evaluation and pharmacological activity. Chin Med. 2018;13:13. doi:10.1186/s13020-018-0171-329541156
  • RiosJL, FranciniF, SchinellaGR. Natural products for the treatment of type 2 diabetes mellitus. Planta Med. 2015;81(12–13):975–994. doi:10.1055/s-0035-154613126132858
  • LeeJ-W, MaseN, YonezawaT, et al. Palmatine attenuates osteoclast differentiation and function through inhibition of receptor activator of nuclear factor-kB ligand expression in osteoblast cells. Biol Pharm Bull. 2010;33(10):1733–1739. doi:10.1248/bpb.33.173320930384
  • WangL, WangX, ZhangSL, et al. Gastroprotective effect of palmatine against acetic acid-induced gastric ulcers in rats. J Nat Med. 2017;71(1):257–264. doi:10.1007/s11418-016-1057-227858308
  • YanB, WangD, DongS, et al. Palmatine inhibits TRIF-dependent NF-kappaB pathway against inflammation induced by LPS in goat endometrial epithelial cells. Int Immunopharmacol. 2017;45:194–200. doi:10.1016/j.intimp.2017.02.00428236763
  • KhaksariM, EsmailiS, AbedlooR, KhastarH. Palmatine ameliorates nephrotoxicity and hepatotoxicity induced by gentamicin in rats. Arch Physiol Biochem. 2019:1–6.
  • KimYM, HaYM, JinYC, et al. Palmatine from Coptidis rhizoma reduces ischemia-reperfusion-mediated acute myocardial injury in the rat. Food Chem Toxicol. 2009;47(8):2097–2102. doi:10.1016/j.fct.2009.05.03119497345
  • PaksereshtZ, NorouziP, HojatiV, MoghaddamKH. Effect of palmatine hydrochloride on oxidative stress in streptozotocin -induced diabetic rats. J Adv Med Biomed Res. 2016;24(107):119–129.
  • RamliNZ, ChinKY, ZarkasiKA, AhmadF. The beneficial effects of stingless bee honey from Heterotrigona itama against metabolic changes in rats fed with high-carbohydrate and high-fat diet. Int J Environ Res Public Health. 2019;16(24).
  • LiY, LeeS, LangleiteT, et al. Subsarcolemmal lipid droplet responses to a combined endurance and strength exercise intervention. Physiol Rep. 2014;2(11):e12187. doi:10.14814/phy2.1218725413318
  • MisraA, GuptaA, TankN, KaklotarD, SinghS, SharmaP Pharmacotherapy in metabolic syndrome; 2017:3.
  • ChoiJS, KimJH, AliMY, MinBS, KimGD, JungHA. Coptis chinensis alkaloids exert anti-adipogenic activity on 3T3-L1 adipocytes by downregulating C/EBP-alpha and PPAR-gamma. Fitoterapia. 2014;98:199–208. doi:10.1016/j.fitote.2014.08.00625128422
  • NingN, HeK, WangY, et al. Hypolipidemic effect and mechanism of palmatine from coptis chinensis in hamsters fed high-fat diet. Phytother Res. 2015;29(5):668–673. doi:10.1002/ptr.529525586479
  • ChenHY, YeXL, CuiXL, et al. Cytotoxicity and antihyperglycemic effect of minor constituents from Rhizoma Coptis in HepG2 cells. Fitoterapia. 2012;83(1):67–73. doi:10.1016/j.fitote.2011.09.01421968062
  • ChiangJY. Bile acids: regulation of synthesis. J Lipid Res. 2009;50(10):1955–1966. doi:10.1194/jlr.R900010-JLR20019346330
  • HanH, XinP, ZhaoL, et al. Excess iodine and high-fat diet combination modulates lipid profile, thyroid hormone, and hepatic LDLr expression values in mice. Biol Trace Elem Res. 2012;147(1–3):233–239. doi:10.1007/s12011-011-9300-x22222482
  • ParkWH, PakYK. Insulin-dependent suppression of cholesterol 7alpha-hydroxylase is a possible link between glucose and cholesterol metabolisms. Exp Mol Med. 2011;43(10):571–579. doi:10.3858/emm.2011.43.10.06421817852
  • LanT, RaoA, HaywoodJ, KockND, DawsonPA. Mouse organic solute transporter alpha deficiency alters FGF15 expression and bile acid metabolism. J Hepatol. 2012;57(2):359–365. doi:10.1016/j.jhep.2012.03.02522542490
  • WaltersJR, TasleemAM, OmerOS, BrydonWG, DewT, le RouxCW. A new mechanism for bile acid diarrhea: defective feedback inhibition of bile acid biosynthesis. Clin Gastroenterol Hepatol. 2009;7(11):1189–1194. doi:10.1016/j.cgh.2009.04.02419426836
  • ChiangJYL, FerrellJM. Bile acid biology, pathophysiology, and therapeutics. Clin Liver Dis (Hoboken). 2020;15(3):91–94. doi:10.1002/cld.86132257118
  • HeK, KouS, ZouZ, et al. Hypolipidemic effects of alkaloids from rhizoma coptidis in diet-induced hyperlipidemic hamsters. Planta Med. 2016;82(8):690–697. doi:10.1055/s-0035-156826126848702
  • Wan HasanWN, ChinKY, Abd GhafarN, SoelaimanIN. Annatto-derived tocotrienol promotes mineralization of MC3T3-E1 cells by enhancing BMP-2 protein expression via inhibiting RhoA activation and HMG-CoA reductase gene expression. Drug Des Devel Ther. 2020;14:969–976. doi:10.2147/DDDT.S224941
  • HaererW, DelbaereK, BartlettH, LordSR, RowlandJ. Relationships between HMG-CoA reductase inhibitors (statin) use and strength, balance and falls in older people. Intern Med J. 2012;42(12):1329–1334. doi:10.1111/j.1445-5994.2011.02622.x22032261
  • NotarnicolaM, MessaC, RefoloMG, TutinoV, MiccolisA, CarusoMG. Synergic effect of eicosapentaenoic acid and lovastatin on gene expression of HMGCoA reductase and LDL receptor in cultured HepG2 cells. Lipids Health Dis. 2010;9:135. doi:10.1186/1476-511X-9-13521118482
  • BrondaniLA, AssmannTS, de SouzaBM, BoucasAP, CananiLH, CrispimD. Meta-analysis reveals the association of common variants in the uncoupling protein (UCP) 1-3 genes with body mass index variability. PLoS One. 2014;9(5):e96411. doi:10.1371/journal.pone.009641124804925
  • OhKS, KimM, LeeJ, et al. Liver PPARalpha and UCP2 are involved in the regulation of obesity and lipid metabolism by swim training in genetically obese db/db mice. Biochem Biophys Res Commun. 2006;345(3):1232–1239. doi:10.1016/j.bbrc.2006.04.18216716264
  • MaH, HuY, ZouZ, FengM, YeX, LiX. Antihyperglycemia and antihyperlipidemia effect of protoberberine alkaloids from rhizoma coptidis in HepG2 cell and diabetic KK-Ay mice. Drug Dev Res. 2016;77(4):163–170. doi:10.1002/ddr.2130227045983
  • SemwalDK, RawatU, SemwalR, SinghR, SinghGJ. Anti-hyperglycemic effect of 11-hydroxypalmatine, a palmatine derivative from Stephania glabra tubers. J Asian Nat Prod Res. 2010;12(2):99–105. doi:10.1080/1028602090311732520390750
  • KhademvatanK, AlinejadV, EghtedarS, RahbarN, AgakhaniN. Survey of the relationship between metabolic syndrome and myocardial infarction in hospitals of Urmia University of medical sciences. Glob J Health Sci. 2014;6(7 Spec No):58–65. doi:10.5539/gjhs.v6n7p5825363180
  • MaedaK, RuelM. Prevention of ischemia-reperfusion injury in cardiac surgery: therapeutic strategies targeting signaling pathways. J Thorac Cardiovasc Surg. 2015;149(3):910–911. doi:10.1016/j.jtcvs.2014.11.06725534485
  • Monserrat-MesquidaM, Quetglas-LlabresM, CapoX, et al. Metabolic syndrome is associated with oxidative stress and proinflammatory state. Antioxidants (Basel). 2020;9(3).
  • SchanzeN, BodeC, DuerschmiedD. Platelet contributions to myocardial ischemia/reperfusion injury. Front Immunol. 2019;10:1260. doi:10.3389/fimmu.2019.0126031244834
  • ParkJS, ArcaroliJ, YumHK, et al. Activation of gene expression in human neutrophils by high mobility group box 1 protein. Am J Physiol Cell Physiol. 2003;284(4):C870–C879. doi:10.1152/ajpcell.00322.200212620891
  • AmarasekaraDS, YunH, KimS, LeeN, KimH, RhoJ. Regulation of osteoclast differentiation by cytokine networks. Immune Netw. 2018;18(1):e8. doi:10.4110/in.2018.18.e829503739
  • LuoG, LiF, LiX, WangZG, ZhangB. TNFalpha and RANKL promote osteoclastogenesis by upregulating RANK via the NFkappaB pathway. Mol Med Rep. 2018;17(5):6605–6611.29512766
  • SoysaNS, AllesN. Positive and negative regulators of osteoclast apoptosis. Bone Rep. 2019;11:100225. doi:10.1016/j.bonr.2019.10022531720316
  • CallawayDA, JiangJX. Reactive oxygen species and oxidative stress in osteoclastogenesis, skeletal aging and bone diseases. J Bone Miner Metab. 2015;33(4):359–370. doi:10.1007/s00774-015-0656-425804315
  • FontaniF, MarcucciG, IantomasiT, BrandiML, VincenziniMT. Glutathione, N-acetylcysteine and lipoic acid down-regulate starvation-induced apoptosis, RANKL/OPG ratio and sclerostin in osteocytes: involvement of JNK and ERK1/2 signalling. Calcif Tissue Int. 2015;96(4):335–346. doi:10.1007/s00223-015-9961-025660312
  • MaratheN, RangaswamiH, ZhuangS, BossGR, PilzRB. Pro-survival effects of 17beta-estradiol on osteocytes are mediated by nitric oxide/cGMP via differential actions of cGMP-dependent protein kinases I and II. J Biol Chem. 2012;287(2):978–988. doi:10.1074/jbc.M111.29495922117068
  • HaladeGV, RahmanMM, WilliamsPJ, FernandesG. High fat diet-induced animal model of age-associated obesity and osteoporosis. J Nutr Biochem. 2010;21(12):1162–1169. doi:10.1016/j.jnutbio.2009.10.00220149618
  • CalderPC, AhluwaliaN, BrounsF, et al. Dietary factors and low-grade inflammation in relation to overweight and obesity. Br J Nutr. 2011;106(Suppl 3):S5–S78. doi:10.1017/S000711451100546022133051
  • CamposRM, de PianoA, da SilvaPL, et al. The role of pro/anti-inflammatory adipokines on bone metabolism in NAFLD obese adolescents: effects of long-term interdisciplinary therapy. Endocrine. 2012;42(1):146–156. doi:10.1007/s12020-012-9613-322315014
  • ChinKY, Ima-NirwanaS, MohamedIN, et al. Insulin-like growth factor-1 is a mediator of age-related decline of bone health status in men. Aging Male. 2014;17(2):102–106. doi:10.3109/13685538.2014.89689524593848
  • JackuliakP, PayerJ. Osteoporosis, fractures, and diabetes. Int J Endocrinol. 2014;2014:820615.25050121
  • IshikawaS, TamakiM, OgawaY, et al. Inductive effect of palmatine on apoptosis in RAW 264.7 cells. Evid Based Complement Alternat Med. 2016;2016:7262054. doi:10.1155/2016/726205427340419
  • IshikawaS, OgawaY, TamakiM, et al. Influence of palmatine on bone metabolism in ovariectomized mice and cytokine secretion of osteoblasts. In Vivo. 2015;29(6):671–677.26546523
  • LeeWC, KimJK, KangJW, et al. Palmatine attenuates D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure in mice. Food Chem Toxicol. 2010;48(1):222–228. doi:10.1016/j.fct.2009.10.00419818826
  • WangM, ShenJ, JinH, ImHJ, SandyJ, ChenD. Recent progress in understanding molecular mechanisms of cartilage degeneration during osteoarthritis. Ann N Y Acad Sci. 2011;1240:61–69. doi:10.1111/j.1749-6632.2011.06258.x22172041
  • World Health Organization. Chronic rheumatic conditions; 2020 Available from: https://www.who.int/chp/topics/rheumatic/en/. Accessed 820, 2020.
  • BucheleG, GuntherKP, BrennerH, et al. Osteoarthritis-patterns, cardio-metabolic risk factors and risk of all-cause mortality: 20 years follow-up in patients after hip or knee replacement. Sci Rep. 2018;8(1):5253. doi:10.1038/s41598-018-23573-229588472
  • OztasB, SahinD, KirH, et al. The effect of leptin, ghrelin, and neuropeptide-Y on serum Tnf-Alpha, Il-1beta, Il-6, Fgf-2, galanin levels and oxidative stress in an experimental generalized convulsive seizure model. Neuropeptides. 2017;61:31–37. doi:10.1016/j.npep.2016.08.00227522536
  • WilliamsRC, SkeltonAJ, TodrykSM, RowanAD, PreshawPM, TaylorJJ. Leptin and pro-inflammatory stimuli synergistically upregulate MMP-1 and MMP-3 secretion in human gingival fibroblasts. PLoS One. 2016;11(2):e0148024. doi:10.1371/journal.pone.014802426829555
  • BerenbaumF. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthritis Cartilage. 2013;21(1):16–21. doi:10.1016/j.joca.2012.11.01223194896
  • ZhouX, LinX, XiongY, et al. Chondroprotective effects of palmatine on osteoarthritis in vivo and in vitro: a possible mechanism of inhibiting the Wnt/beta-catenin and Hedgehog signaling pathways. Int Immunopharmacol. 2016;34:129–138. doi:10.1016/j.intimp.2016.02.02926945831
  • MiR, TuB, BaiXT, ChenJ, OuyangY, HuYJ. Binding properties of palmatine to DNA: spectroscopic and molecular modeling investigations. Luminescence. 2015;30(8):1344–1351. doi:10.1002/bio.290425829078
  • IslamMM, PandyaP, ChowdhurySR, KumarS, KumarGS. Binding of DNA-binding alkaloids berberine and palmatine to tRNA and comparison to ethidium: spectroscopic and molecular modeling studies. J Mol Struct. 2008;891(1):498–507. doi:10.1016/j.molstruc.2008.04.043
  • GiriP, HossainM, KumarGS. Molecular aspects on the specific interaction of cytotoxic plant alkaloid palmatine to poly(A). Int J Biol Macromol. 2006;39(4):210–221.16678250
  • BhadraK, MaitiM, KumarGS. Molecular recognition of DNA by small molecules: AT base pair specific intercalative binding of cytotoxic plant alkaloid palmatine. Biochim Biophys Acta. 2007;1770(7):1071–1080. doi:10.1016/j.bbagen.2007.03.00117434677
  • BhadraK, MaitiM, KumarGS. Interaction of isoquinoline alkaloid palmatine with deoxyribonucleic acids: binding heterogeneity, and conformational and thermodynamic aspects. Chem Biodivers. 2008;5(4):575–590.18421749
  • HirakawaK, KawanishiS, HiranoT. The mechanism of guanine specific photooxidation in the presence of berberine and palmatine: activation of photosensitized singlet oxygen generation through DNA-binding interaction. Chem Res Toxicol. 2005;18(10):1545–1552. doi:10.1021/tx050174016533018
  • AliD, AliH. Assessment of DNA damage and cytotoxicity of palmatine on human skin epithelial carcinoma cells. Toxicol Environ Chem. 2014;96(6):941–950. doi:10.1080/02772248.2014.987510
  • FungC, DinhP, Ardeshir-Rouhani-FardS, SchafferK, FossaSD, TravisLB. Toxicities associated with cisplatin-based chemotherapy and radiotherapy in long-term testicular cancer survivors. Adv Urol. 2018;2018:8671832. doi:10.1155/2018/867183229670654
  • YiJ, YeX, WangD, et al. Safety evaluation of main alkaloids from Rhizoma Coptidis. J Ethnopharmacol. 2013;145(1):303–310. doi:10.1016/j.jep.2012.10.06223159469
  • Reagan-ShawS, NihalM, AhmadN. Dose translation from animal to human studies revisited. FASEB J. 2008;22(3):659–661. doi:10.1096/fj.07-9574LSF17942826
  • WongSK, ChinK-Y, Ima-NirwanaS. Berberine and musculoskeletal disorders: the therapeutic potential and underlying molecular mechanisms. Phytomedicine. 2020;73:152892.30902523
  • CaoC, SuM. Effects of berberine on glucose-lipid metabolism, inflammatory factors and insulin resistance in patients with metabolic syndrome. Exp Ther Med. 2019;17(4):3009–3014.30936971
  • HuX, ZhangY, XueY, ZhangZ, WangJ. Berberine is a potential therapeutic agent for metabolic syndrome via brown adipose tissue activation and metabolism regulation. Am J Transl Res. 2018;10(11):3322–3329.30662589
  • SinghN, SharmaB. Toxicological effects of berberine and sanguinarine. Front Mol Biosci. 2018;5:21. doi:10.3389/fmolb.2018.0002129616225
  • MahmoudiM, Zamani Taghizadeh RabeS, Balali-MoodM, et al. Immunotoxicity induced in mice by subacute exposure to berberine. J Immunotoxicol. 2016;13(2):255–262. doi:10.3109/1547691X.2015.105830626100397
  • ZhangX, QiuF, JiangJ, GaoC, TanY. Intestinal absorption mechanisms of berberine, palmatine, jateorhizine, and coptisine: involvement of P-glycoprotein. Xenobiotica. 2011;41(4):290–296. doi:10.3109/00498254.2010.52918021319959
  • YuCP, HuangCY, LinSP, HouYC. Activation of P-glycoprotein and CYP 3A by coptidis rhizoma in vivo: using cyclosporine as a probe substrate in rats. J Food Drug Anal. 2018;26(2S):S125–S132. doi:10.1016/j.jfda.2017.11.00529703381
  • KoboriT, HaradaS, NakamotoK, TokuyamaS. Functional alterations of intestinal P-glycoprotein under diabetic conditions. Biol Pharm Bull. 2013;36(9):1381–1390. doi:10.1248/bpb.b13-0036923995645
  • NeeartiP, BarlaR, BedadaSK. Influence of diabetes mellitus on P-glycoprotein function in rat intestine. Pharmacologia. 2011;2:293–298. doi:10.5567/pharmacologia.2011.293.298