Fatma PEHLİVAN KARAKAS, Hamit COSKUN, Hayriye SOYTURK, Bihter Gokce BOZAT

Anxiolytic, antioxidant, and neuroprotective effects of goji berry polysaccharides in ovariectomized rats: experimental evidence from behavioral, biochemical, and immunohistochemical analyses

Recent studies have indicated that polysaccharides, the main component of the Lycium barbarum L. fruit, have beneficial effects (e.g., anxiolytic, antioxidant, and neuroprotective) on humans and rodents. However, the effects of different dosages of such polysaccharides on ovariectomized rats and their underlying mechanisms in the brain have not been evaluated in the literature. Here, we aimed to evaluate the effects of the high and low doses of polysaccharides obtained from Lycium barbarum fruits (HD-LBP and LD-LBP, respectively) on anxious behaviors via behavioral (using the OFT and EPM), biochemical (using ELISA), and immunohistochemical (using immunohistochemical staining) measures in detail. Two weeks after ovariectomy, the rats were randomly assigned to either the treatment conditions [control (DW, 3 mL/kg, p.o., per day), LD-LBP (20 mg/kg, 3 mL/kg, p.o., per day), HD-LBP (200 mg/kg, 3 mL/kg, p.o., per day), 17 beta-ES (1 mg/kg, 3 mL/kg, p.o., per day), DZ(1 mg/kg, 3 mL/kg, p.o., per day)] or operation type [SHAM (pseudo-ovariectomized) and OVX (ovariectomized)]. The treatments were applied for 30 consecutive days, and then serum and brain tissue samples of all rats were collected. Biochemical (SOD, CAT, GPX, MDA, and 17 beta-ES) and immunohistochemical (BDNF, SER, and apoptosis) analyses of the samples were performed as well. The rats administered HD-LBP and LD-LBP were less anxious than the control groups. The HD-LBP-treated rats had high levels of SOD and low levels of MDA in their serum samples. Moreover, HD-LBP and drug-treated groups had a high number of SER receptors and BDNF-positive cells and a low number of TUNEL-positive cells in their hippocampal brain tissues. The HD-LBP treatments decrease anxious behavior by increasing antioxidant enzyme activities, hippocampal SER and BDNF neurotransmitter levels and decreasing the TUNEL-positive cell count of ovariectomized rats. Given these findings, we suggest that menopause-induced symptoms of anxiety can be reduced by polysaccharides obtained from goji berry fruits, and that these findings will be beneficial for the production studies of natural herbal-origin antianxiety (anxiolytic) drugs in the future.

Keywords:

Lycium barbarum L., pharmacological activity, antioxidant enzymes, neurotransmitters serotonin, BDNF, ELISA, menopause,

PDF

___

Amagase H, 2011, FOOD RES INT, V44, P1702, DOI 10.1016/j.foodres.2011.03.027
Banerjee S, 2016, NEUROSCIENCE, V319, P79, DOI 10.1016/j.neuroscience.2016.01.032
Belviranli M, 2013, BIOGERONTOLOGY, V14, P187, DOI 10.1007/s10522-013-9422-y
Benabid N, 2008, BRAIN RES BULL, V75, P53, DOI 10.1016/j.brainresbull.2007.07.016
Berent-Spillson A, 2017, PSYCHONEUROENDOCRINO, V76, P218, DOI 10.1016/j.psyneuen.2016.08.026
Bilgic Y, 2015, EUR J INFLAMM, V13, P154, DOI 10.1177/1721727X15618413
Bozdogan O, 2018, MOJ ANATOMY PHYSL, V5, P362
Bradley BF, 2011, BEHAV BRAIN RES, V216, P285, DOI 10.1016/j.bbr.2010.08.006
Brinton RD, 2015, NAT REV ENDOCRINOL, V11, P393, DOI 10.1038/nrendo.2015.82
Cai Y, 2017, BIOMED RES-INDIA, V28, P5874
Cevik O, 2015, MOL BIOL REP, V42, P167, DOI 10.1007/s11033-014-3756-7
Chang RCC, 2008, CELL MOL NEUROBIOL, V28, P643, DOI 10.1007/s10571-007-9181-x
Chen L, 2015, DEV PSYCHOPATHOL, V27, P137, DOI 10.1017/S0954579414001357
Chen P, 2018, SCI REP-UK, V8, DOI 10.1038/s41598-018-19732-0
Chen R, 2012, J MOL HISTOL, V43, P535, DOI 10.1007/s10735-012-9420-4
Cheng D, 2011, MOLECULES, V16, P2542, DOI 10.3390/molecules16032542
Citraro R, 2015, PHARMACOL BIOCHEM BE, V129, P65, DOI 10.1016/j.pbb.2014.12.006
Cui J, 2013, TRENDS MOL MED, V19, P197, DOI 10.1016/j.molmed.2012.12.007
Cui JJ, 2010, J ETHNOPHARMACOL, V132, P512, DOI 10.1016/j.jep.2010.08.052
da Silva CC, 2014, BEHAV PROCESS, V103, P327, DOI 10.1016/j.beproc.2014.01.022
Devi SA, 2011, EXP GERONTOL, V46, P958, DOI 10.1016/j.exger.2011.08.006
Dornellas APS, 2018, FRONT NEUROSCI-SWITZ, V12, DOI 10.3389/fnins.2018.00557
Duan CB, 2012, AFR J PHARM PHARMACO, V6, P643, DOI 10.5897/AJPP11.863
Duman RS, 2006, BIOL PSYCHIAT, V59, P1116, DOI 10.1016/j.biopsych.2006.02.013
Fatemi I, 2019, NEUROSCI LETT, V690, P95, DOI 10.1016/j.neulet.2018.10.024
Gao J, 2015, LIFE SCI, V121, P124, DOI 10.1016/j.lfs.2014.11.026
Gao YJ, 2017, AGING DIS, V8, P778, DOI 10.14336/AD.2017.0725
Guimaraes RAM, 2015, PHYSIOL BEHAV, V147, P319, DOI 10.1016/j.physbeh.2015.05.009
HALLIWELL B, 1985, MOL ASPECTS MED, V8, P89, DOI 10.1016/0098-2997(85)90001-9
Han NR, 2018, BIOMED PHARMACOTHER, V103, P524, DOI 10.1016/j.biopha.2018.04.070
Han NR, 2015, REPRODUCTION, V150, P173, DOI 10.1530/REP-15-0157
Karakas FP, 2020, PLANT PHYSIOL BIOCH, V146, P384, DOI 10.1016/j.plaphy.2019.11.009
Kroeze Wesley K., 2002, Current Topics in Medicinal Chemistry, V2, P507, DOI 10.2174/1568026023393796
Li W, 2020, FOOD FUNCT, V11, P3741, DOI [10.1039/D0FO00030B, 10.1039/d0fo00030b]
Li YJ, 2018, BEHAV BRAIN RES, V348, P184, DOI 10.1016/j.bbr.2018.04.025
Liu Y, 2015, MOL NUTR FOOD RES, V59, P1130, DOI 10.1002/mnfr.201400753
Miranda M, 2019, FRONT CELL NEUROSCI, V13, DOI 10.3389/fncel.2019.00363
Musumeci G, 2015, EXP CELL RES, V339, P407, DOI 10.1016/j.yexcr.2015.09.007
Patki G, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0074522
Pehlivan K, 2016, TURK J BIOL, V40, P762
Pic-Taylor A, 2015, BEHAV PROCESS, V118, P102, DOI 10.1016/j.beproc.2015.05.004
Pithia NK, 2016, BIOORG MED CHEM LETT, V26, P1919, DOI 10.1016/j.bmcl.2016.03.018
Potterat O, 2010, PLANTA MED, V76, P7, DOI 10.1055/s-0029-1186218
Ren-Patterson RF, 2006, CELL MOL NEUROBIOL, V26, P755, DOI 10.1007/s10571-006-9048-6
Rettberg JR, 2014, FRONT NEUROENDOCRIN, V35, P8, DOI 10.1016/j.yfrne.2013.08.001
Rosa E, 2016, NEUROBIOL AGING, V48, P135, DOI 10.1016/j.neurobiolaging.2016.08.020
Russo E, 2013, NEUROPHARMACOLOGY, V64, P371, DOI 10.1016/j.neuropharm.2012.06.039
Selli J, 2016, GYNECOL ENDOCRINOL, V32, P234, DOI 10.3109/09513590.2015.1110139
Shaif NA, 2018, BIOMEDICINES, V6, DOI 10.3390/biomedicines6040108
Shin SK, 2019, NUTR NEUROSCI, DOI 10.1080/1028415X.2019.1696613
Teng P, 2013, MOL MED REP, V7, P1977, DOI 10.3892/mmr.2013.1442
Valvassori SS, 2015, MOL NEUROBIOL, V52, P353, DOI 10.1007/s12035-014-8873-8
Walf AA, 2007, NAT PROTOC, V2, P322, DOI 10.1038/nprot.2007.44
Wang TF, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0090780
Wang YG, 2016, FOOD ANAL METHOD, V9, P131, DOI 10.1007/s12161-015-0178-7
Wu HT, 2010, INT J BIOL MACROMOL, V46, P540, DOI 10.1016/j.ijbiomac.2010.02.010
Yang L, 2018, CRYOBIOLOGY, V85, P7, DOI 10.1016/j.cryobiol.2018.10.265
[于宁 Yu Ning], 2016, [中国病理生理杂志, Chinese Journal of Pathophysiology], V32, P1370
Zhang ED, 2012, CELL TRANSPLANT, V21, P2635, DOI 10.3727/096368912X655181
Zhang Q, 2015, FOOD NUTR RES, V11, P286 .
Zhang SS, 2019, PSYCHOPHARMACOLOGY, V236, P3301, DOI 10.1007/s00213-019-05287-z
Zhao P, 2017, CELL TISSUE RES, V369, P455, DOI 10.1007/s00441-017-2648-2
Zhao R, 2015, IRAN J BASIC MED SCI, V18, P1245