Amelioration of Aluminum Maltolate-Induced Inflammation and Endoplasmic Reticulum Stress-Mediated Apoptosis by Tannoid Principles of Emblica officinalis in Neuronal Cellular Model
Authors: Thamilarasan Manivasagam
Chidambaram Saravana Babu
Musthafa Mohamed Essa
Gilles J Guillemin
Mathiyazahan Dhivya Bharathi
Mashoque Ahmad Rather
Arokiasamy Justin-Thenmozhi
Journal: Neurotoxicity research (2019)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Aluminum maltolate; Endoplasmic reticulum stress; Inflammation; Neurotoxicity; Tannoids principles of Emblica officinalis.
Affiliations: Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalai Nagar, Tamil Nadu, 608002, India., Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalai Nagar, Tamil Nadu, 608002, India. ., Department of Pharmacology, JSS College of Pharmacy, JSS University, SS Nagar, Mysore, Karnataka, 570015, India., Department of Food Science and Nutrition, CAMS, Sultan Qaboos University, Muscat, Oman., Ageing and Dementia Research Group, Sultan Qaboos University, Muscat, Oman., Food and Brain Research Foundation, Chennai, Tamil Nadu, 600094, India., Neuroinflammation group, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia.

Abstract:  The neuroprotective role of tannoid principles of Emblica officinalis (EoT), an Indian and Chinese traditional medicinal plant against memory loss in aluminum chloride-induced in vivo model of Alzheimer's disease through attenuating AChE activity, oxidative stress, amyloid and tau toxicity, and apoptosis, was recently reported in our lab. However, to further elucidate the mechanism of neuroprotective effect of EoT, the current study was designed to evaluate endoplasmic reticulum stress-suppressing and anti-inflammatory role of EoT in PC 12 and SH-SY 5Y cells. These cells were divided into four groups: control (aluminum maltolate (Al(mal)3), EoT + Al(mal)3, and EoT alone based on 3-(4, 5-dimethyl 2-yl)-2, and 5-diphenyltetrazolium bromide (MTT) assay. EoT significantly reduced Al(mal)3-induced cell death and attenuated ROS, mitochondrial membrane dysfunction, and apoptosis (protein expressions of Bax; Bcl-2; cleaved caspases 3, 6, 9, 12; and cytochrome c) by regulating endoplasmic reticulum stress (PKR-like ER kinase (PERK), α subunit of eukaryotic initiation factor 2 (EIF2-α), C/EBP-homologous protein (CHOP), and high-mobility group box 1 protein (HMGB1)). Moreover, inflammatory response (NF-κB, IL-1β, IL-6, and TNF-α) and Aβ toxicity (Aβ1-42) triggered by Al(mal)3 was significantly normalized by EoT. Our results suggested that EoT could be a possible/promising and novel therapeutic lead against Al-induced neurotoxicity. However, further extensive research is needed to prove its efficacy in clinical studies. 

Retracted: No

PubPeer comments:
 Concern about Figures 2C (MMP expression) and 4C (Apoptosis). * Fig. 2C s EoT panel looks very similar to Fig. 4C s control panel. Shown with thick red boxes. * Then, certain cells from Figure 2C panels appear to be visible in panels in Figure 4C. I highlighted several of these with rounded boxes of the same color. * Some cells appear to be change color (from green to red) in Figure 4C panels, where the red color indicates apoptosis. Could the authors please clarify what happened here? ![file] , 
 #1  Then, certain cells from Figure 2C panels appear to be visible in panels in Figure 4C. And in Fig 3C - here at right. ![file] , 
 More fun with Fig 3c. ![file] , 
 Hoya beat me to it. I was going to update with this compilation, in which Figure 2C, 3C, and 4C are all combined. ![file] , 
 Dear Elisabeth and Hoya Thank you so much for reporting this issue. Immediately I have contacted Dr. Justin-Thenmozhi (senior author), to clarify this with the research scholar (1st author) who performed this work. As a collaborator, I do all the time offering support for the structure of the project and editing revising the manuscript, not the data or laboratory works. The senior author will address this important issue asap and will follow with that. Regards Essa , 
 We thank you for pointing out these issues. These issues have brought our attention we will seriously check all of the raw data related to this article and response as soon as possible. We will try to fix this problem by contacting the publishers as well. I apologies if it takes some time to find the original images because research scholar who did the experiment has left. Regards A. Justin Thenmozhi , 
 Dear authors, it has been two years since we last spoke. Would any of you have any update to share, please? Did you contact the journal and publisher? Did you find the original images? Looking forward to your reply. ,