PMID- 28840511 OWN - NLM STAT- MEDLINE DCOM- 20180727 LR - 20231230 IS - 1573-9546 (Electronic) IS - 1573-9538 (Print) IS - 1573-9538 (Linking) VI - 13 IP - 4 DP - 2017 Dec TI - Nanoparticle-encapsulated emodin decreases diabetic neuropathic pain probably via a mechanism involving P2X3 receptor in the dorsal root ganglia. PG - 559-568 LID - 10.1007/s11302-017-9583-2 [doi] AB - Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes mellitus (DM). More than 90% of all cases of DM belong to type 2 diabetes mellitus (T2DM). Emodin is the main active component of Radix et rhizoma rhei and has anti-bacterial, anti-viral, anti-ulcerogenic, anti-inflammatory, and anti-cancer effects. Nanoparticle encapsulation of drugs is beneficial for drug targeting and bioavailability as well as for lowering drug toxicity side effects. The aim of this study was to investigate the effects of nanoparticle-encapsulated emodin (nano emodin) on diabetic neuropathic pain (DNP) mediated by the Purin 2X3 (P2X3) receptor in the dorsal root ganglia (DRG). Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) values in T2DM rats were lower than those of control rats. MWT and TWL in T2DM rats treated with nano emodin were higher compared with those in T2DM rats. Expression levels of P2X3 protein and messenger RNA (mRNA) in the DRG of T2DM rats were higher than those of controls, while levels in T2DM rats treated with nano emodin were significantly lower than those of the T2DM rats. Phosphorylation and activation of ERK1/2 in the T2DM DRG were decreased by nano emodin treatment. Nano emodin significantly inhibited currents activated by the P2X3 agonist alpha,beta-meATP in HEK293 cells transfected with the P2X3 receptor. Therefore, nano emodin treatment may relieve DNP by decreasing excitatory transmission mediated by the DRG P2X3 receptor in T2DM rats. FAU - Li, Lin AU - Li L AD - Department of Physiology, Medical School of Nanchang University, Nanchang, 330006, Jiangxi, People's Republic of China. AD - Jiangxi Provincial Key Laboratory of autonomic nervous function and disease, Nanchang, 330006, Jiangxi, People's Republic of China. FAU - Sheng, Xuan AU - Sheng X AD - Department of Physiology, Medical School of Nanchang University, Nanchang, 330006, Jiangxi, People's Republic of China. AD - Jiangxi Provincial Key Laboratory of autonomic nervous function and disease, Nanchang, 330006, Jiangxi, People's Republic of China. FAU - Zhao, Shanhong AU - Zhao S AD - Department of Physiology, Medical School of Nanchang University, Nanchang, 330006, Jiangxi, People's Republic of China. AD - Jiangxi Provincial Key Laboratory of autonomic nervous function and disease, Nanchang, 330006, Jiangxi, People's Republic of China. FAU - Zou, Lifang AU - Zou L AD - Department of Physiology, Medical School of Nanchang University, Nanchang, 330006, Jiangxi, People's Republic of China. AD - Jiangxi Provincial Key Laboratory of autonomic nervous function and disease, Nanchang, 330006, Jiangxi, People's Republic of China. FAU - Han, Xinyao AU - Han X AD - First Clinical Department, Medical School of Nanchang University, Nanchang, 330006, Jiangxi, People's Republic of China. FAU - Gong, Yingxin AU - Gong Y AD - First Clinical Department, Medical School of Nanchang University, Nanchang, 330006, Jiangxi, People's Republic of China. FAU - Yuan, Huilong AU - Yuan H AD - Department of Physiology, Medical School of Nanchang University, Nanchang, 330006, Jiangxi, People's Republic of China. AD - Jiangxi Provincial Key Laboratory of autonomic nervous function and disease, Nanchang, 330006, Jiangxi, People's Republic of China. FAU - Shi, Liran AU - Shi L AD - Department of Physiology, Medical School of Nanchang University, Nanchang, 330006, Jiangxi, People's Republic of China. AD - Jiangxi Provincial Key Laboratory of autonomic nervous function and disease, Nanchang, 330006, Jiangxi, People's Republic of China. FAU - Guo, Lili AU - Guo L AD - Department of Physiology, Medical School of Nanchang University, Nanchang, 330006, Jiangxi, People's Republic of China. AD - Jiangxi Provincial Key Laboratory of autonomic nervous function and disease, Nanchang, 330006, Jiangxi, People's Republic of China. FAU - Jia, Tianyu AU - Jia T AD - Department of Physiology, Medical School of Nanchang University, Nanchang, 330006, Jiangxi, People's Republic of China. AD - Jiangxi Provincial Key Laboratory of autonomic nervous function and disease, Nanchang, 330006, Jiangxi, People's Republic of China. FAU - Liu, Shuangmei AU - Liu S AD - Department of Physiology, Medical School of Nanchang University, Nanchang, 330006, Jiangxi, People's Republic of China. AD - Jiangxi Provincial Key Laboratory of autonomic nervous function and disease, Nanchang, 330006, Jiangxi, People's Republic of China. FAU - Wu, Bing AU - Wu B AD - Department of Physiology, Medical School of Nanchang University, Nanchang, 330006, Jiangxi, People's Republic of China. AD - Jiangxi Provincial Key Laboratory of autonomic nervous function and disease, Nanchang, 330006, Jiangxi, People's Republic of China. FAU - Yi, Zhihua AU - Yi Z AD - Department of Physiology, Medical School of Nanchang University, Nanchang, 330006, Jiangxi, People's Republic of China. AD - Jiangxi Provincial Key Laboratory of autonomic nervous function and disease, Nanchang, 330006, Jiangxi, People's Republic of China. FAU - Liu, Hui AU - Liu H AD - Department of Physiology, Medical School of Nanchang University, Nanchang, 330006, Jiangxi, People's Republic of China. AD - Jiangxi Provincial Key Laboratory of autonomic nervous function and disease, Nanchang, 330006, Jiangxi, People's Republic of China. FAU - Gao, Yun AU - Gao Y AD - Department of Physiology, Medical School of Nanchang University, Nanchang, 330006, Jiangxi, People's Republic of China. AD - Jiangxi Provincial Key Laboratory of autonomic nervous function and disease, Nanchang, 330006, Jiangxi, People's Republic of China. FAU - Li, Guilin AU - Li G AD - Department of Physiology, Medical School of Nanchang University, Nanchang, 330006, Jiangxi, People's Republic of China. AD - Jiangxi Provincial Key Laboratory of autonomic nervous function and disease, Nanchang, 330006, Jiangxi, People's Republic of China. FAU - Li, Guodong AU - Li G AD - Department of Physiology, Medical School of Nanchang University, Nanchang, 330006, Jiangxi, People's Republic of China. AD - Department of Clinical Translational Research, Singapore General Hospital, Singapore, Singapore. FAU - Zhang, Chunping AU - Zhang C AD - Jiangxi Provincial Key Laboratory of autonomic nervous function and disease, Nanchang, 330006, Jiangxi, People's Republic of China. AD - Department of Cell Biology, Medical School of Nanchang University, Nanchang, 330006, Jiangxi, People's Republic of China. FAU - Xu, Hong AU - Xu H AD - Department of Physiology, Medical School of Nanchang University, Nanchang, 330006, Jiangxi, People's Republic of China. AD - Jiangxi Provincial Key Laboratory of autonomic nervous function and disease, Nanchang, 330006, Jiangxi, People's Republic of China. FAU - Liang, Shangdong AU - Liang S AD - Department of Physiology, Medical School of Nanchang University, Nanchang, 330006, Jiangxi, People's Republic of China. liangsd@hotmail.com. AD - Jiangxi Provincial Key Laboratory of autonomic nervous function and disease, Nanchang, 330006, Jiangxi, People's Republic of China. liangsd@hotmail.com. LA - eng GR - 81570735, 31560276/National Natural Science Foundation of China/ PT - Journal Article DEP - 20170824 PL - Netherlands TA - Purinergic Signal JT - Purinergic signalling JID - 101250499 RN - 0 (Nanoconjugates) RN - 0 (Receptors, Purinergic P2X3) RN - KA46RNI6HN (Emodin) SB - IM MH - Animals MH - Diabetes Mellitus, Experimental MH - Diabetes Mellitus, Type 2 MH - Diabetic Neuropathies/*metabolism MH - Emodin/*administration & dosage MH - Ganglia, Spinal/*drug effects/metabolism MH - HEK293 Cells MH - Humans MH - Male MH - *Nanoconjugates MH - Random Allocation MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Purinergic P2X3/*metabolism PMC - PMC5714846 OTO - NOTNLM OT - Diabetic peripheral neuropathy OT - Dorsal root ganglia OT - Nanoparticle-encapsulated emodin OT - P2X3 receptor COIS- The procedures were approved by the Animal Care and Use Committee of Nanchang University Medical School. CONFLICT OF INTEREST: The authors declare that they have no conflicts of interest. EDAT- 2017/08/26 06:00 MHDA- 2018/07/28 06:00 PMCR- 2018/02/24 CRDT- 2017/08/26 06:00 PHST- 2017/05/20 00:00 [received] PHST- 2017/08/10 00:00 [accepted] PHST- 2017/08/26 06:00 [pubmed] PHST- 2018/07/28 06:00 [medline] PHST- 2017/08/26 06:00 [entrez] PHST- 2018/02/24 00:00 [pmc-release] AID - 10.1007/s11302-017-9583-2 [pii] AID - 9583 [pii] AID - 10.1007/s11302-017-9583-2 [doi] PST - ppublish SO - Purinergic Signal. 2017 Dec;13(4):559-568. doi: 10.1007/s11302-017-9583-2. Epub 2017 Aug 24.