Neuroprotective effect of Liuwei Dihuang decoction on cognition deficits of diabetic encephalopathy in streptozotocin-induced diabetic rat
Authors: Liang Feng
Ji-ping Liu
Junfei Gu
Qiang Fu
Dong-ying Ma
Ming-hua Zhang
Shi-ping Ma
Shu-yuan Wang
Rong Qu
Journal: Journal of Ethnopharmacology (2013)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: AChE; AD; ANOVA; Alzheimer's disease; Anti-apoptosis
Affiliations: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Jiangsu, Nanjing 210009, PR China; Department of Pharmacology, Shaanxi University of Chinese Medicine, Xianyang 712046, PR China.

Abstract:  Ethnopharmacological relevance: Liuwei Dihuang decoction (LWDHD) is a well-known prescription of traditional Chinese medicine (TCM) and consists of six crude drugs including Rehmannia glutinosa Libosch. (family: Scrophulariaceae), Cornus officinalis Sieb. (family: Cornaceae), Dioscorea oppositifolia L. (family: Dioscoreaceae), Paoenia ostii (family: Paeoniaceae), Alisma orientale (G. Samuelsson) Juz (family: Alismataceae) and Poria cocos (Schw.) Wolf (family: Polyporaceae). It has been used for the treatment of "Kidney-Yin" deficiency syndrome in clinic in China for a long time. Recent studies found that LWDHD had a potential benefit for the treatment of diabetic complications. The aim of the present study is to investigate the neuroprotective effect of LWDHD on memory and cognition deficits in streptozotocin (STZ)-induced diabetic encephalopathy (DE) rats. Materials and methods: Adult male Sprague Dawley (SD) rats were fed with high-glucose-fat diet for 50 days and then received an intraperitoneal injection of STZ (40 mg/kg) to induce DE model. Morris water maze test was used to evaluate the memory and cognition capability of DE rats. Choline acetyltransferase (ChAT), acetylcholinesterase (AChE), Na(+)-K(+)-ATP enzyme, iNOS and GSH kits were used to determine their activities or content in hippocampus. TUNEL staining, immunohistochemistry and Congo red staining were conducted to evaluate the apoptosis, caspase-3 protein expression, insulin-like growth factors 1 (IGF-1) and brain derived neurophic factor (BDNF) expressions, as well as Aβ deposition. Results: The treatment with LWDHD (1 and 2g/kg, p.o., once daily, 30 days) could significantly reduce the escape latency time and path length, and obviously enhance the spent time in the target quadrant and platform crossings in Morris water maze test compared with model group (P&lt;0.05, P&lt;0.01). LWDHD could also significantly decrease the level of fasting blood glucose, increase Na(+)-K(+)-ATP enzyme and ChAT activities, enhance remarkedly GSH level while decrease significantly AChE and iNOS activities in hippocampus (P&lt;0.05, P&lt;0.01). Furthermore, TUNEL staining, Congo red staining and immunohistochemistry showed that LWDHD significantly improved the expressions of IGF-1 and BDNF, attenuated the neural apoptosis, overexpression of caspase-3 and Aβ deposition in the hippocampus and cerebral cortex of STZ-induced DE rats (P&lt;0.01). Conclusion: Our findings suggested that LWDHD had a neuroprotective effect on DE rats. LWDHD may be of benefit in the treatment of DE. 

Retracted: Yes

PubPeer comments:
 Fig 3  Effect of LWDHD on the TUNEL apoptosis staining (A) and caspase-3 expression (B) in the hippocampus and cerebral cortex in DE rats . ![file] Fig 2 from [Liu et al (2013a)] .  Effect of paeonol on the apoptosis and caspase-3 expression in the hippocampus and 12 cerebral cortex in DE rats. (A) apoptosis by Tunel staining; (B) caspase-3 expression . ![file] Panels in blue rectangles are labeled consistently across the two papers. Red boxes: Donepezil or Paeonil? , 
 *[above]* Fig. 5.  Effect of LWDHD on Au03b2 deposition in the hippocampus (A) and cerebral cortex (B) in DE rats by Congo red staining . *[below]* Fig 1B from [Liu et al (2013a)] .  Effect of paeonol on STZ-induced memory impairment and Au03b2 deposition in the hippocampus and cerebral cortex in rats. ... (B) Au03b2 deposition. ![] Panels in blue rectangles are labeled consistently between papers. Green rectangles: Donepezil or paeonol? , 
 Dear Dr. Hoya Camphorifolia, Thank you for raising this concern, which we have very carefully checked and discussed. As we all know, Reduction, Refinement, and Replacement are referred to as 3R in laboratory animals. Specifically,  Reduction  is to reduce the number of animals used in the experiment as much as possible, to improve the utilization of experimental animals and the accuracy of the experiment. The research objects of these two papers are compound Liuwei Dihuang Decoction and its main ingredient paeonol. Taking into account the principle of  3R in experimental animals, in order to minimize the use of experimental animals, and to explore and compare the role of paeonol in this compound. Liuwei Dihuang Decoction and its main ingredient paeonol were investigated simultaneously in the animal experiments. Therefore, the normal group, the model group and positive control groups (donepezil and rosiglitazone) were used together in these two papers, respectively. The result is objective rather than deliberate use of repeated pictures. Therefore, the panels in blue rectangles are labeled consistently between Fig 1B and Fig. 5 in these two papers. As for green rectangles in Fig 1B and Fig. 5, we regret that two of the images (Fig 5., Cerebral cortex, panel 6 and Fig1B, Cerebral cortex (Au03b2), panel 5) were misincorporated during figure assembly when we were preparing for manuscript submission. After revisiting all the raw data of these experiments, we could show the original images for those images presented in Fig 1B and Fig. 5. We also regret that we didn t catch this error during subsequent revisions and examinations when the manuscript underwent the review and publication processes. We are preparing a correction request which we will submit to the two journals as soon as possible. We apologize to our readers for any confusion caused by this unintentional error. Thank you for your attentions. Yours, Jiping Liu , 
 Retracted, [13 March 2022] . ---------------------- This article has been retracted at the request of the Editor-in-Chief. The authors have plagiarized duplicated part of a paper that appeared in Neurosci Lett, 549 (2013) 63u201368, . Several images in the Journal of Ethnopharmacology paper; 3A, 3B, 4A, 4B correspond to figures; 2A, 2B, 3A and 3B respectively as published in Neuroscience Letters. One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original and has not appeared in a publication elsewhere. Re-use of any data should be appropriately cited. As such this article represents a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process. ,