Effect of baicalin on ATPase and LDH and its regulatory effect on the AC/cAMP/PKA signaling pathway in rats with attention deficit hyperactivity disorder
ZHOU Rong-Yi, WANG Jiao-Jiao, YOU Yue, SUN Ji-Chao, SONG Yu-Chen, YUAN Hai-Xia, HAN Xin-Min
Institute of Pediatrics, Nanjing University of Chinese Medicine/Jiangsu Key Laboratory of Pediatric Respiratory Disease, Nanjing 210023, China
Abstract Objective To study the effect of baicalin on synaptosomal adenosine triphosphatase (ATPase) and lactate dehydrogenase (LDH) and its regulatory effect on the adenylate cyclase (AC) /cyclic adenosine monophosphate (cAMP) /protein kinase A (PKA) signaling pathway in rats with attention deficit hyperactivity disorder (ADHD). Methods A total of 40 SHR rats were randomly divided into five groups:ADHD model, methylphenidate hydrochloride treatment (0.07 mg/mL), and low-dose (3.33 mg/mL), medium-dose (6.67 mg/mL), and high-dose (10 mg/mL) baicalin treatment (n=8 each). Eight WKY rats were selected as normal control group. Percoll density gradient centrifugation was used to prepare brain synaptosomes and an electron microscope was used to observe their structure. Colorimetry was used to measure the activities of ATPase and LDH in synaptosomes. ELISA was used to measure the content of AC, cAMP, and PKA. Results Compared with the normal control group, the ADHD model group had a significant reduction in the ATPase activity, a significant increase in the LDH activity, and significant reductions in the content of AC, cAMP, and PKA (P P P P P P P P P Conclusions Both methylphenidate hydrochloride and baicalin can improve synaptosomal ATPase and LDH activities in rats with ADHD. The effect of baicalin is dose-dependent, and high-dose baicalin has a significantly greater effect than methylphenidate hydrochloride. Baicalin exerts its therapeutic effect possibly by upregulating the AC/cAMP/PKA signaling pathway.
ZHOU Rong-Yi,WANG Jiao-Jiao,YOU Yue et al. Effect of baicalin on ATPase and LDH and its regulatory effect on the AC/cAMP/PKA signaling pathway in rats with attention deficit hyperactivity disorder[J]. CJCP, 2017, 19(5): 576-582.
ZHOU Rong-Yi,WANG Jiao-Jiao,YOU Yue et al. Effect of baicalin on ATPase and LDH and its regulatory effect on the AC/cAMP/PKA signaling pathway in rats with attention deficit hyperactivity disorder[J]. CJCP, 2017, 19(5): 576-582.
Tsai CC, Lin MT, Wang JJ, et al. The antipyretic effects of baicalin in lipopolysaccharide-evoked fever in rabbits[J]. Neuropharmacology, 2006, 51(4):709-717.
[2]
Kang MJ, Ko GS, Oh DG, et al. Role of metabolism by intestinal microbiota in pharmacokinetics of oral baicalin[J]. Arch Pharm Res, 2014, 37(3):371-378.
[3]
Zeng L, Wang M, Yuan Y, et al. Simultaneous multi-component quantitation of Chinese herbal injection Yin-zhi-huang in rat plasma by using a single-tube extraction procedure for mass spectrometry-based pharmacokinetic measurement[J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2014, 967:245-254.
[4]
Polanczyk G, de Lima MS, Horta BL, et al. The worldwide prevalence of ADHD:a systematic review and metaregression analysis[J]. Am J Psychiatry, 2007, 164(6):942-948.
[5]
Swanson JM, Kinsbourne M, Nigg J, et al. Etiologic subtypes of attention deficit/hyperactivity disorder:brain imaging, molecular genetic and environmental factors and the dopamine hypothesis[J]. Neuropsychol Rev, 2007, 17(1):39-59.
[6]
Harvey RC, Sen S, Deaciuc A, et al. Methylphenidate treatment in adolescent rats with an attention deficit/hyperactivity disorder phenotype:cocaine addiction vulnerability and dopamine transporter function[J]. Neuropsychopharmacology, 2011, 36(4):837-847.
[7]
Napolitano F, Bonito-Oliva A, Federici M, et al. Role of aberrant striatal dopamine D1 receptor/cAMP/protein kinase A/DARPP32 signaling in the paradoxical calming effect of amphetamine[J]. J Neurosci, 2010, 30(33):11043-11056.
[8]
Kitagishi Y, Minami A, Nakanishi A, et al. Neuron membrane trafficking and protein kinases involved in autism and ADHD[J]. Int J Mol Sci, 2015, 16(2):3095-3115.
[9]
Baca M, Allan AM, Partridge LD, et al. Gene-environment interactions affect long-term depression (LTD) through changes in dopamine receptor affinity in Snap25 deficient mice[J]. Brain Res, 2013, 1532:85-98.
[10]
Zheng R, Yang L, Sikorski MA, et al. Deficiency of the RIIβ subunit of PKA affects locomotor activity and energy homeostasis in distinct neuronal populations[J]. Proc Natl Acad Sci U S A, 2013, 110(17):E1631-E1640.
[11]
Few WP, Scheuer T, Catterall WA. Dopamine modulation of neuronal Na(+) channels requires binding of A kinase-anchoring protein 15 and PKA by a modified leucine zipper motif[J]. Proc Natl Acad Sci U S A, 2007, 104(12):5187-5192.
Somkuwar SS, Darna M, Kantak KM, et al. Adolescence methylphenidate treatment in a rodent model of attention deficit/hyperactivity disorder:dopamine transporter function and cellular distribution in adulthood[J]. Biochem Pharmacol, 2013, 86(2):309-316.
[14]
Wang X, Zhang L, Hua L, et al. Effect of flavonoids in scutellariae radix on depression-like behavior and brain rewards:possible in dopamine system[J]. Tsinghua Sci Technol, 2010, 15(4):460-466.
[15]
Im HI, Joo WS, Nam E, et al. Baicalein prevents 6-hydroxydopamine-induced dopaminergic dysfunction and lipid peroxidation in mice[J]. J Pharmacol Sci, 2005, 98(2):185-189.
[16]
Mu X, He G, Cheng Y, et al. Baicalein exerts neuroprotective effects in 6-hydroxydopamine-induced experimental parkinsonism in vivo and in vitro[J]. Pharmacol Biochem Behav, 2009, 92(4):642-648.
[17]
Chen L, Zhang L, Wang X. Determination of dopamine and its relativity of baicalin in rat nuclei after intravenous administration of flavonoids from Scutellariae radix[J]. Biomed Chromatogr, 2007, 21(1):84-88.
[18]
Zhou R, Han X, Wang J, et al. Baicalin may have a therapeutic effect in attention deficit hyperactivity disorder[J]. Med Hypotheses, 2015, 85(6):761-764.
[19]
Sagvolden T, Johansen EB, Wøien G, et al. The spontaneously hypertensive rat model of ADHD-the importance of selecting the appropriate reference strain[J]. Neuropharmacology, 2009, 57(7-8):619-626.
[20]
Cao AH, Yu L, Wang YW, et al. Effects of methylphenidate on attentional set-shifting in a genetic model of attention-deficit/hyperactivity disorder[J]. Behav Brain Funct, 2012, 8(1):10.
[21]
Davids E, Zhang K, Tarazi FI, et al. Animal models of attention-deficit hyperactivity disorder[J]. Brain Res Rev, 2003, 42(1):1-21.
[22]
Okamoto K, Aoki K. Development of a strain of spontaneously hypertensive rats[J]. Jpn Circ J, 1963, 27:282-293.
Hugel S, Schlichter R. Presynaptic P2X receptors facilitate inhibitory GABAergic transmission between cultured rat spinal cord dorsal horn neurons[J]. J Neurosci, 2000, 20(6):2121-2130.
[31]
Pankratov Y, Lalo U, Krishtal O, et al. Ionotropic P2X purinoreceptors mediate synaptic transmission in rat pyramidal neurones of layer II/III of somato-sensory cortex[J]. J Physiol, 2002, 542(Pt 2):529-536.
Zhang DM, Liu HY, Xie L, et al. Effect of baicalin and berberine on transport of nimodipine on primary-cultured, rat brain microvascular endothelial cells[J]. Acta Pharmacol Sin, 2007, 28(4):573-578.
[37]
Kwak S, Ku SK, Han MS, et al. Vascular barrier protective effects of baicalin, baicalein and wogonin in vitro and in vivo[J]. Toxicol Appl Pharmacol, 2014, 281(1):30-38.
[38]
Liu XM, Feng Y, Li AM. Nerve protective effect of Baicalin on newborn HIBD rats[J]. Asia Pac J Trop Med, 2014, 7(10):806-810.
