Neuroprotective and anti‐inflammatory effects of morin in a murine model of Parkinson's disease

Abstract

Parkinson's disease (PD) is one of the most common neurodegenerative disorders and is characterized by loss of dopaminergic neurons in the substantia nigra (SN). Although the causes of PD are not understood, evidence suggests that oxidative stress, mitochondrial dysfunction, and inflammation are associated with its pathogenesis. Morin (3,5,7,2',4'-pentahydroxyflavone) is a flavonol found in wine and many herbs and fruits. Previous studies have suggested that morin prevents oxidative damage and inflammation and ameliorates mitochondrial dysfunction. The present study describes the neuroprotective effects of morin in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD, and we report the results of our investigation into its neuroprotective mechanism in primary neurons and astrocytes. In the mouse model, morin pretreatment ameliorated motor dysfunction, protected against dopaminergic neuronal losses in SN and striatum, and alleviated MPTP-induced astrocyte activation. In vitro studies revealed that morin protected primary cultured neurons against 1-methyl-4-phenylpyridine (MPP(+) )-mediated reactive oxygen species production and mitochondrial membrane potential (MMP) disruption. In addition, morin effectively reduced MPP(+) -induced astroglial activation and nuclear translocation of nuclear factor-κB in primary cultured astrocytes. These results indicate that morin acts via multiple neuroprotective mechanisms in our mouse model and suggest that morin be viewed as a potential treatment and preventative for PD. © 2016 Wiley Periodicals, Inc.

Neuroimmunomodulatory properties of DPSCs in an in vitro model of Parkinson's disease

“…The decrement in proliferative behavior as noted in this study could be reflecting the inhibitory effect elicited on microglia as DPSCs has immunomodulatory properties as we have previously reported . The secretory factors by DPSCs have contributed to the reversal of inflammatory processes that both LPS and MPTP had initiated . We believe that the anti‐inflammatory factors which were observed in this study were originated mainly by DPSCs since their release was much elevated as compared to their basal level .…”

“…This neurotoxin has been reported to have activated nucleotide-binding domain, leucine-rich repeat containing proteins (also known as NOD-like receptors, NLRs), especially NLRP3 to augment the expression of proinflammatory mediators and induce mitochondrial dysfunction as well as pyroptosis, an inflammatory form of cell death (35,36). Moreover, studies have indicated presence of nuclear-factor-E2-related factor 2 (Nrf2) activation in response to MPTP, leading to depletion of glutathione, decreased cell viability, and inhibition of mitochondrial oxygen consumption as well as glycolysis rates in a dose-dependent manner (37,38). In this study, the presence of both toxins had inhibited the proliferation rate of neurons and these phenomena could be highly attributed to the activation of apoptosis and pyroptosis, as suggested by previous studies (39,40).…”

Morin exerts neuroprotection via attenuation of ROS induced oxidative damage and neuroinflammation in experimental diabetic neuropathy

“…Besides to its antioxidant property, morin administration also proved to show anti-inflammatory properties in several animal models [41][42][43]. Emerging evidence have shown that antiinflammatory properties of morin are mediated through attenuation of ROS mediate NF-jB activation and amelioration of mitochondrial dysfunction [21,44,45].…”

“…Morin has been well studied for its antioxidant and mitochondrial protective effects. Lee et al proved that morin administration ameliorated oxidative stress, inflammation, and mitochondrial dysfunction in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice model of Parkinson's disease (PD) [21]. Moreover through our previous studies, we have observed that morin exhibits potent anti oxidative and anti inflammatory effects against experimental chronic constriction injury (CCI)-Induced peripheral neuropathy by reducing ROS [22].…”

Morin, a novel liver X receptor α/β dual antagonist, has potent therapeutic efficacy for nonalcoholic fatty liver diseases

“…Morin has been considered as a promising natural drug (Caselli et al , ; Sinha et al , ) because of its wide spectrum of biological effects, which include antioxidant (Subash and Subramanian, ; Rizvi et al , ), anti‐inflammatory (Wang et al , ; Dhanasekar and Rasool, ), anti‐cancer (Park et al , ), anti‐ageing and cardiovascular protective. These may have beneficial actions in cancer (Nandhakumar et al , ), liver fibrosis (Heeba and Mahmoud, ; MadanKumar et al , ), Alzheimer's disease (Noor et al , ), Parkson's disease (Lee et al , ), and many other chronic diseases. Recently, morin was shown to reduce blood pressure (Prahalathan et al , ), improve endothelial dysfunction in diabetic animals (Taguchi et al , ), ameliorate blood glucose, serum lipid and liver TG levels (Vanitha et al , ; Naowaboot et al , ), mimic the effects of insulin (Paoli et al , ) and inhibit fatty acid synthase (FAS) (Tian, ).…”