Thymoquinone and Curcumin Defeat Aging-Associated Oxidative Alterations Induced by D-Galactose in Rats’ Brain and Heart
Authors: Yaser H A Elewa
Shaker A Mousa
Mustafa S Atta
Soad K Al Jaouni
Ahmed E Noreldin
Elsayeda-Zeinab A Abdelfattah
Khalid M Abou-Zeid
Ali H El-Far
Abdel-Wahab A Alsenosy
Journal: International Journal of Molecular Sciences (2021)
Discipline: CHEMISTRY
Keywords: D-galactose; anti-aging; curcumin; oxidative stress; thymoquinone.
Affiliations: Department of Biochemistry, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, Egypt., Department of Histology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, Egypt., Animal Care Unit, Medical Research Institute, Alexandria University, Alexandria 21544, Egypt., Department of Physiology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh 33516, Egypt., Department of Hematology/Pediatric Oncology, Yousef Abdulatif Jameel Scientific Chair of Prophetic Medicine Application, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia., Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA., Histology and Cytology Department, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, Egypt.

Abstract:  D-galactose (D-gal) administration causes oxidative disorder and is widely utilized in aging animal models. Therefore, we subcutaneously injected D-gal at 200 mg/kg BW dose to assess the potential preventive effect of thymoquinone (TQ) and curcumin (Cur) against the oxidative alterations induced by D-gal. Other than the control, vehicle, and D-gal groups, the TQ and Cur treated groups were orally supplemented at 20 mg/kg BW of each alone or combined. TQ and Cur effectively suppressed the oxidative alterations induced by D-gal in brain and heart tissues. The TQ and Cur combination significantly decreased the elevated necrosis in the brain and heart by D-gal. It significantly reduced brain caspase 3, calbindin, and calcium-binding adapter molecule 1 (IBA1), heart caspase 3, and BCL2. Expression of mRNA of the brain and heart TP53, p21, Bax, and CASP-3 were significantly downregulated in the TQ and Cur combination group along with upregulation of BCL2 in comparison with the D-gal group. Data suggested that the TQ and Cur combination is a promising approach in aging prevention. 

Retracted: No

PubPeer comments:
 Some images in this paper seem to have been edited as they show repeated regions. See Figures 7A and 7C as an example. Could the authors please post the unedited images? *** ![file] , 
 #1 Dear Actinopolyspora biskrensis, Please, increase the zoom and see the differences in the area you determined. Also, what is the scientific value to repeat these areas for the results of our article? Thanks , 
 #2 Thank you for your reply. Do the authors still have the original images? , 
 #3 Dear Actinopolyspora biskrensis, Greetings! Thank you for your comment. We will send the original images of Figure 7 after holiday vacation. Thanks , 
 The drugs used in this study are extremely reactive substances that suffer from poor bio-availability https: pubs.rsc.org en content articlelanding 2016 md c5md00481k https: pubs.acs.org doi 10.1021 acs.jmedchem.6b00975 , 
 #5 Dear Parabagrotis sulinaris,realistic Greetings! Thank you for your efforts. It is true that curcumin and thymoquinone have poor solubility in aqueous solutions. Therefore, we dissolved it in oil to form emulsion enhancing its bioavailability. In the PubMed database, the following studies the authors dissolved curcumin in oil: https: pubmed.ncbi.nlm.nih.gov 22509079 https: pubmed.ncbi.nlm.nih.gov 21450899 https: pubmed.ncbi.nlm.nih.gov 22005253 https: pubmed.ncbi.nlm.nih.gov 30255470 https: pubmed.ncbi.nlm.nih.gov 29177247 https: pubmed.ncbi.nlm.nih.gov 26098480 https: pubmed.ncbi.nlm.nih.gov 25869755 https: pubmed.ncbi.nlm.nih.gov 23796760 https: pubmed.ncbi.nlm.nih.gov 32719085 https: pubmed.ncbi.nlm.nih.gov 32696423 https: pubmed.ncbi.nlm.nih.gov 32602579 https: pubmed.ncbi.nlm.nih.gov 24364912 https: pubmed.ncbi.nlm.nih.gov 31854220 https: pubmed.ncbi.nlm.nih.gov 31127514 https: pubmed.ncbi.nlm.nih.gov 21245202 https: pubmed.ncbi.nlm.nih.gov 19788403 https: pubmed.ncbi.nlm.nih.gov 19821784 https: pubmed.ncbi.nlm.nih.gov 24020431 (important). https: pubmed.ncbi.nlm.nih.gov 30252460 (important). https: pubmed.ncbi.nlm.nih.gov 28410669 (important). Also, please, find some studies using oils for thymoquinone administration supplementation: https: pubmed.ncbi.nlm.nih.gov 28078054 https: pubmed.ncbi.nlm.nih.gov 28480357 https: pubmed.ncbi.nlm.nih.gov 30821514 https: pubmed.ncbi.nlm.nih.gov 31136753 , 
 #6 My major concern was about how these molecules act non specifically on various targets via covalent means There have been several articles published on why curcumin-type-polyphenolic compounds are unusable as human pharmaceuticals: https: www.science.org content blog-post curcumin-waste-your-time https: pubs.acs.org doi 10.1021 acs.jmedchem.6b00975 https: www.nature.com articles 513481a I however, wish you the best on your research , 
 #7 Dear Parabagrotis sulinaris, Greetings! Thank you for your comment. As I found in my field of interest, using natural bioactive compounds is significant for the protection or treatment of numerous diseases, especially when it is used in nanoformulations. Many Thanks for you , 
 #6 Perhaps coincidentally, the third of the three  important papers you reference in #6 seems to have some data problems of its own. I have posted that paper [here] with my concerns, and notified the journal and people at the author s institution. For convenience, here s what I saw: ![file] , 
 #9 Dear Actinopolyspora biskrensis, Greetings! I just mention in comment #6 the studies in which authors use oil to increase the bioavailability of curcumin or thymoquinone. Thanks , 
 #10 So, you are saying the effect of different oil on the bioavailability of curcumin was evaluated via using different area of an image? , 
 #11 Dear Oeneis buddha, Greetings! I never said that. I wrote in my comments #6 different published studies, the authors used oils to increase curcumin bioavailability. The authors of each article are responsible for their data. Thanks , 
 #10 Yes, I understand. That might be an important paper to curcumin proponents, but as I pointed out in #9, and another commenter noted in #11, the data in that paper does not appear to support the paperu2019s conclusion. The authors there seem to have used one sample to demonstrate results of 3 different experiments. , 
 #13 Dear Actinopolyspora biskrensis Thanks for your comments. I advise waiting until you receive their reply. Thanks , 
 The images in Figure 6D and 6F appear to overlap (or are strikingly similar), after rotation, but are described as coming from two different treatment groups. *** ![file] *** ![file] , 
 The image in Figure 9B appears to have at least one repeated region. Are high resolution images available for review? *** ![file] ,