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Hypoglycemic potential of Pycnogenol and extract of black pine Pinus nigra on the experimental model of diabetic rats

dc.contributor.advisorRašković, Aleksandar
dc.contributor.advisorMilić, Nataša
dc.contributor.otherGoločorbin-Kon, Svetlana
dc.contributor.otherMikov, Momir
dc.contributor.otherDobrić, Silva
dc.contributor.otherRašković, Aleksandar
dc.contributor.otherMilić, Nataša
dc.creatorBukumirović, Nina
dc.date.accessioned2019-07-18T12:48:01Z
dc.date.available2019-07-18T12:48:01Z
dc.date.issued2019-06-12
dc.identifier.urihttps://www.cris.uns.ac.rs/DownloadFileServlet/Disertacija155135897129466.pdf?controlNumber=(BISIS)110269&fileName=155135897129466.pdf&id=12662&source=NaRDuS&language=srsr
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dc.identifier.urihttps://www.cris.uns.ac.rs/DownloadFileServlet/IzvestajKomisije155135898036310.pdf?controlNumber=(BISIS)110269&fileName=155135898036310.pdf&id=12663&source=NaRDuS&language=srsr
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dc.identifier.urihttp://nardus.mpn.gov.rs/123456789/11235
dc.description.abstractBor je bilo koji četinar roda Pinus koji pripada porodici Pinaceae. U Republici Srbiji nalaze se prirodne i veštačke šume crnog bora Pinus nigra Arnold. Kora bora se vekovima koristila u tradicionalnoj medicini, međutim tek u novije vreme su otkriveni i potvrđeni njeni pozitivni biološki efekti u medicini. Najpoznatiji komercijalni preparat kore bora je piknogenol, standardizovani ekstrakt kore francuskog primorskog bora Pinus pinaster Aiton, koji raste duţ obale jugozapadne Francuske. Pozitivni efekti koje ispoljava piknogenol, kao što su antioksidativno, hipoglikemijsko, hipolipidemijsko delovanje, zasnovani su na njegovom visokom sadržaju fenolnih jedinjenja. Danas, i pored saznanja da je kora bora bogata sekundarnim metabolitima ona najčešće završava kao nusproizvod drvne industrije. Ciljevi ovog rada bili su ispitivanje kvalitativnih i kvantitativnih karakteristika i biohemijskih aktivnosti ekstrakata kore crnog bora Pinus nigra sa Mokre gore i Tare, dobijenih različitim rastvaračima; upoređivanje glikemijskog i lipidnog delovanja ekstrakta kore bora Pinus nigra sa komercijalnim preparatom piknogenol; uticaj ekstrakta kore bora Pinus nigra i piknogenola na delovanje standardnih antidijabetika metformina i gliklazida; kao i uticaj na parametre oksidativnog stresa nakon izlaganja životinja toksičnoj dozi paracetamola. In vitro ispitivanja su uključivala analizu ekstrakata dobijenih različitim rastvaračima. Ukupni sadržaj fenola, tanina, flavonoida i proantocijanidna, kao i ispitivanje antioksidativne aktivnosti kroz pet različitih metoda, određivani su spektrofotometrijski. Vršena je analiza ekstrakata kore bora visokoefikasnom tečnom hromatografijom (HPLC). In vivo ispitivanje je rađeno na 156 albino laboratorijska pacova soja Wistar. Eksperimentalne ţivotinje su tokom 7 dana per os primale ekstrakt kore crnog bora poreklom sa Mokre gore 100 mg/kg, koji je pokazao najbolju aktivnost, piknogenol 50 mg/kg, metformin 100 mg/kg, gliklazid 10 mg/kg, kao i njihove kombinacije. Za ispitivanje uticaja primenjivanih supstanci na glikemiju ţivotinja korišćeni su test oralnog podnošenja glukoze i indukcija trajne hiperglikemije aloksanom. Od biohemijskih parametara u serumu je određivana koncentracija lipida, kao i parametric pokazatelji funkcije bubrega i jetre. Ex vivo ispitivanja uključivala su određivanje intenzitet lipidne peroksidacije i anktivnosti enzima antioksidativne zaštite u homogenatu jetre ispitivanih ţivotinja, nakon primene toksične doze paracetamola. HPLC analizom ekstrakata kore crnog bora utvrđeno je da ekstrakti poreklom sa Mokre gore i Tare u najvećoj meri sadrţe taksifolin, a zatim katehin, njegove derivate, kafenu kiselinu i epikatehin. PotvrĎen je visok antioksidativni kapacitet piknogenola, ali takođe i značajan antioksidativni kapacitet ekstrakata kore crnog bora, sa najboljim rezultatima kod ekstrakta poreklom sa Mokre gore. Sedmodnevni tretman ekstraktom kore bora 100 mg/kg, metforminom 100 mg/kg, gliklazidom 10 mg/kg i piknogenolom 50 mg/kg, kod ţivotinja sa aloksanski izazvanim dijabetesom, doveo je do sniženja glikemije u krvi. Uočeno je povećanje konentracije HDL holesterola i značajno sniženje serumskih triglicerida kod dijabetičnih i normoglikemičnih ţivotinja koje su primale piknogenol, ekstrakta kore bora, gliklazid i metformin u poređenju sa kontrolnom grupom ţivotinja. Zajednička primena ekstrakta kore bora i standardnih antidijabetika značajno je snizila vrednosti AST, ALP i direktni bilirubin u grupi dijabetičnih i normoglikemičnih ţivotinja u odnosu na kontrolnu grupu, čime se ukazuje na potencijalno hepatoprotektivno delovanje ekstrakta kore crnog bora. Oštećenje jetre izazvano toksičnom dozom paracetamola je potvrđeno ispitivanim parametrima, uključujući oksidativni status u homogenatu jetre i histološka ispitivanja. Rezultati našeg istraživanja su pokazali da piknogenol 50 mg/kg, kao i ekstrakt kore crnog bora 100 mg/kg značajno smanjuju nivo MDA u poređenju sa kontrolnom grupom i grupom koja je primala paracetamol. Na osnovu rezultata istraţivanja može se zaključiti da primena piknogenola i ekstrakta kore crnog bora: ublaţava poremećaj homeostaze glukoze, utiče povoljno na lipidni status, značajno potencira antihiperglikemijsko delovanje metformina i hipoglikemijski efekat gliklazida, sprečava poremećaj biohemijskih parametara pokazatelja funkcije jetre i bubrega u serumu ispitivanih životinja i ispoljava značajno in vitro antioksidativno delovanje i sprečava oštećenje jetre laboratorijskih životinja izazvano toksičnom dozom paracetamola.sr
dc.description.abstractA pine is any conifer in the genus Pinus of the family Pinaceae. In the Republic of Serbia there are natural and artificial forests of black pine Pinus nigra Arnold. Pine bark has been used for centuries in traditional medicine, but only recently its positive biological effects has been revealed and confirmed in medicine. The most famous commercial pine bark product is Pycnogenol, a standardized extract of the French maritime pine bark (Pinus pinaster Aiton), which grows along the coast of southwestern France. The positive effects of Pycnogenol, such as antioxidant, hypoglycemic, hypolipidemic, are based on its high content of phenolic compounds. Nowdays, despite the knowledge that the pine bark is rich in secondary metabolites, it usually ends up as a by-product of the wood industry. The objectives of this dissertation were to investigate the qualitative and quantitative characteristics and biochemical activities of the black pine (Pinus nigra) extracts from Mokra gora and Tara, obtained by different solvents; comparison of glycemic and lipid action of Pinus nigra bark extract with commercial product Pycnogenol; the influence of black pine bark extract and Pycnogenol on the action of standard antidiabetics metformin and gliclazide; as well as the influence on the parameters of oxidative stress in animals exposed to the toxic dose of paracetamol. In vitro analyses included the analysis of extracts obtained with different solvents. The total phenolic, tannin, flavonoid and proanthocyanidin content, as well as the antioxidant activity tests, were determined spectrophotometrically. High-efficiency liquid chromatography (HPLC) was performed in order to determine black pine bark extract content. In vivo analyses was performed on 156 albino Wistar laboratory rats. Experimental animals received for 7 days per os: black pine bark extract obtained from Mokra gora 100 mg/kg, which showed the best activity; Pycnogenol 50 mg/kg; metformin 100 mg/kg; gliclazide 10 mg/kg; and their combinations. An oral glucose tolerance test and the aloxan-induced hyperglycaemia were used to examined the effects of the substances on experimental animals. Biochemical parameters, the lipids concentration and parameters of the kidney and liver function, were determined in animal serum. Ex vivo analyses included determination of lipid peroxidation activity and the activity of antioxidant protection enzymes in liver homogenates of the test animals, after administration of a toxic dose of paracetamol. HPLC analysis of black pine bark extracts obtained from Mokra gora and Tara showed the greatest content of taxifolin, then catechin, and its derivatives, caffeic acid and epicatechin. A high antioxidative capacity of Pycnogenol was confirmed, but also a significant antioxidant capacity of black pine bark extract, with the best results in the extract obtained from Mokra gora. Seven-day treatment in aloxan-induced diabetes animals with 100 mg/kg black pine bark extract, metformin 100 mg/kg, gliclazide 10 mg/kg and Pycnogenol 50 mg/kg led to a decrease of serum glycemic index. There was an increase in the HDL cholesterol concentration and a significant reduction in serum triglycerides in diabetic and normoglycemic animals which received Pycnogenol, black pine bark extract, gliclazide and metformin compared to the control group. Concomitant usage of the black pine bark extract and standard antidiabetics significantly reduced the levels of AST, ALP and direct bilirubin in the group of diabetic and normoglycemic animals compared to the control group, indicating the potential hepatoprotective action of the black pine bark extract. Damage to the liver caused by the toxic dose of paracetamol was confirmed by the liver homogenate oxidative status and histological examination. The results of our study have shown that Pycnogenol 50 mg/kg, as well as 100 mg/kg black pine bark extract significantly reduce the level of MDA in comparison with the control and the paracetamol treated group. Based on the results of the dissertation, it can be concluded that the use of Pycnogenol and black pine bark extract alleviate glucose homeostasis disorder; positively affects the lipid status; significantly increases the antihyperglycemic effect of metformin and the hypoglycemic effect of gliclazide; prevents impairment biochemical parameters of the liver and kidney function in the serum of the experimental animals; significantly exhibits in vitro antioxidant activity and prevents liver damage caused by toxic dose of paracetamol in experimental animals.en
dc.languagesr (latin script)
dc.publisherУниверзитет у Новом Саду, Медицински факултетsr
dc.rightsAttribution-NonCommercial-NoDerivs
dc.sourceУниверзитет у Новом Садуsr
dc.subjectpinus; kora biljaka; eksperimentalni dijabetes melitus; antioksidansi; oksidativni stres; hipoglikemijski agensi; fitoterapijasr
dc.subjectPinus; Plant Bark; Diabetes Mellitus, Experimental; Antioxidants; Oxidative Stress; Hypoglycemic Agents; Phytotherapyen
dc.titleHipoglikemijsko delovanje piknogenola i ekstrakta crnog bora Pinus nigra na eksperimentalnom modelu dijabetičnih pacovasr
dc.title.alternativeHypoglycemic potential of Pycnogenol and extract of black pine Pinus nigra on the experimental model of diabetic ratsen
dc.typeDoktorska disertacijasr


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