Pomegranate-derived anthocyanin regulates MORs-cAMP/CREB-BDNF pathways in opioid-dependent models and improves cognitive impairments

Abstract

Background Pomegranate ( Punica granatum ) is one of the oldest known edible fruit. Recently, there has been an increased interest in this fruit as a functional food for health benefits due to its use in disease prevention and promotion of overall health wellness. Objective This study aims to investigate the effects of pomegranate extract for the development of non-opioid substitution therapy for in-vitro and in-vivo studies. Materials and methods Anthocyanin contents consisting of cyanidin 3-glucoside, diglucoside, and pelargonidin 3-glucoside, diglucoside were detected and quantified in pomegranate extract using high-performance liquid chromatography. The optimum dosage of the extract was determined based on the regulation of MORs and cAMP proteins in U-87 cells. Co-treatment of the extract with morphine was performed to evaluate its potency in reducing the concentration levels of MORs and cAMP. For animal studies, rats were divided into two major groups representing both acute and chronic morphine-induced treatments and the Morris water maze (MWM) study was employed after treatment for each rat. The rats were sacrificed after the treatments and serum samples were collected to evaluate the levels of CREB and BDNF. Results The results indicated that each of the anthocyanin content tested in the study was present in the pomegranate extract. Additionally, in-vitro studies using pomegranate extract treatment showed that the extract was effective in decreasing the MORs and cAMP protein levels in U-87 cells at a concentration of 0.125 mg/mL. The memory impairment based on the MWM study in rats was also subsequently improved after treatment with pomegranate extract as compared to treatment with morphine. The blood serum derived from the rats treated with pomegranate extract also showed a significant decrease in CREB level and an increase in BDNF as compared to rats treated with morphine. Conclusion In conclusion, this study substantiates the potency of pomegranate extract as a non-opioid substitution therapy for in-vitro and in-vivo studies.

Walnut polyphenols and the active metabolite urolithin A improve oxidative damage in SH-SY5Y cells by up-regulating PKA/CREB/BDNF signaling

“…elderly people) to produce sufficient or required health benefits. 52 Recently, it has been reported that administration of ET-rich pomegranate extract and EA improved cognitive impairments and brain dysfunction by up-regulating CREB/BDNF signaling in rodents, 53,54 which is in line with our results. It seems that CREB signaling may be a common target of both UroA and its precursors.…”

Blueberry Anthocyanins Extract Attenuates Acrylamide-Induced Oxidative Stress and Neuroinflammation in Rats

“…In this study, BAE significantly ameliorated the ERK/CREB/BDNF signaling suppressed by AA in the hippocampus ( Figure 7 ), suggesting that the BDNF pathway may be a potential molecular target for dietary anthocyanin. Consistent with our findings, supplementation of pomegranate-derived anthocyanins can improve the CREB/BDNF pathways and alleviate cognitive impairments in an opioid-dependent rat model [ 36 ]. As previously reported, GSH deficiency and IL-1 β administration can impair the expressions of BDNF in the hippocampus of rats [ 37 , 38 ].…”

Pomegranate juice consumption by patients under medication for addiction treatment as regulator of craving and blood redox status: The study protocol of a randomized control trial (the NUTRIDOPE study)

“…In addition, DeltaFosB has been linked to drug-related behaviors through affecting the overexpression of dopamine receptor-1 in the NAc inducing reward sensitization (Nestler, 2008;Russo et al, 2009) leading to organic and behavioral changes (Ruffle, 2014). Recent evidence in morphine-administered mice has pointed out the positive effects of anthocyanins present in pomegranate by reducing MORs and cyclic AMP (Ridzwan et al, 2020). This molecular pathway is crucial in opioid dependence and withdrawal (Browne et al, 2020).…”

“…craving of patients under MAT towards their trajectory to successful rehabilitation. Concerning psychosocial parameters, it appears to be beneficial against impaired cognitive function inopioid-dependent in vitro and in vivo models (Cambay et al, 2011; Hajipour et al, 2014;Ridzwan et al, 2020). Moreover, pomegranate seems to be effective on depression and anxiety of OUDs patients (Abu Taweel and Al Mutary, 2021) as well as on the improvement of impaired behavioral aspects ameliorating aggressiveness through the inactivation of ROS, whose enhanced levels have been associated with aggressive behavior(Felippe et al., 2021).…”