Cerebral ischemia reperfusion (IR) is associated with neuronal death, which leads to disability and cognitive decline. The pathomechanism occurs because ischemia is exacerbated during the reperfusion period. Neuronal damage susceptibility depends on the affected brain areas and the duration of ischemia. Prevention and supplementation to neurons may help them endure during IR and further benefit them in rehabilitation. We investigated the protective effect of p-coumaric acid (PC) on cerebral IR injuries in mice. We randomly divided 30 male ICR mice into 3 groups of Sham (received vehicle and not induced IR), Control-IR (received vehicle and induced IR) and PC-IR (received 100 mg/kg PC and induced IR). We orally administered vehicle or 100 mg/kg of p-coumaric acid for 2 weeks before inducing the cerebral IR injuries by using 30 min of a bilateral common carotid artery occlusion followed by a 45-min reperfusion. We induced the IR condition in the Control-IR and PC-IR groups but not the Sham group, and only the PC-IR group received p-coumaric acid. After IR induction, we sacrificed all the mice and collected their brain tissues to evaluate their oxidative statuses, whole brain infarctions and vulnerable neuronal deaths. We studied the whole-brain infarction volume by 2, 3, 5-triethyltetrazoliumchloride staining of sections. We performed a histological investigation of the vulnerable neuronal population in the dorsal hippocampus by staining brain sections with 0.1% cresyl violet. The results indicated that IR caused significant increases in calcium and malondialdehyde (MDA) levels, whole brain infarction volume and hippocampal neuronal death. Pretreatment with p-coumaric acid significantly reduced MDA levels, whole-brain infarction volume and hippocampal neuronal death together and increased catalase and superoxide dismutase activities. We conclude here that pretreating animals with p-coumaric acid can prevent IR-induced brain oxidative stress, infarction size and neuronal vulnerability to death in cerebral IR injuries.

Prediabetes is associated with sugar-sweetened beverages and sugar-rich processed foods. High sugar intake (HSI), which is represented as save dose, may silently alter the glycemic control. The present study investigated the effect of HSI and Tiliacora triandra (TT21) leaf extract on the glycemic control in mice. Eighteen male ICR mice were divided into three groups of Control-HSI, HSI-TT300 and HSI-TT600 that received 4 weeks of 30% glucose with a vehicle of T. triandra leaf extract 300 and 600 mg/kg, respectively. The blood glucose, serum insulin, glucose clearance, liver and muscle glycogen contents and tissue oxidative status were evaluated. The results showed that HSI increased the blood glucose (w2 and w3: p<0.05) and serum insulin levels (w3 and w4: p<0.05) with glucose intolerance (w4: 30, 60 and 90 min, p<0.05). T. triandra leaf extract reduced the blood glucose and serum insulin and increased the glycogen content in the liver and muscle tissues (p<0.05). We concluded that HSI silently induced an alteration of the glycemic control in the normal mice, and the T. triandra leaf extract nurtured the glycemic control in the HSI mice by lowering the blood glucose and serum insulin and increasing the liver and muscle glycogen contents, which indicated an involvement of peripheral insulin sensitivity.

Multiple pathomechanisms of cerebral ischemia reperfusion (I/R) injuries can be ameliorated by certain high-potential pharmaceutical substances. In the present study, we investigated the acute effect of p-hydroxycinnamic (pHCA) acid against cerebral I/R injury in mice. Thirty male ICR mice were divided into Sham, Control-I/R, and pHCA-I/R groups. The pHCA 100 mg/kg and the vehicle were given 30 min before I/R induction. Thirty-minute bilateral common carotid artery occlusion followed by 45-min reperfusion was performed on the Control-I/R and pHCA-I/R groups. Brains were collected for biochemical analysis, infarction and histological study of the cerebral cortex and corpus callosum (CC). The results showed that I/R induction significantly induced biochemical changes (p<0.05) along with the increase of brain infarction (p<0.05), percentage of degeneration in cerebral cortex (p<0.05) and decrease of CC white matter density (p<0.05). Pretreatment with pHCA significantly reduced MDA (p<0.05), brain infarction (p<0.05), cerebral cortex neuronal degeneration (p<0.05) and prevented the reduction of white matter density in the CC (p<0.05). The present study concluded that pretreatment with pHCA helps prevent cerebral I/R injury by amelioration of lipid peroxidation, white matter damage and neuronal degeneration. ABSTRAK Pelbagai patologi mekanisme kecederaan serebrum iskemia-reperfusi (I/R) boleh diperbaikkan oleh beberapa bahan farmaseutik berpotensi tinggi. Dalam penyelidikan ini, kami mengkaji kesan akut p-hidroksisinamik (pHCA) terhadap kecederaan I/R serebrum pada tikus. Tiga puluh tikus ICR jantan dibahagikan kepada Sham, kawalan-I/R, dan kumpulan pHCA-I/R. PHCA 100 mg/kg dan pembawa diberikan 30 min sebelum induksi I/R. Oklusi arteri karotid selama 12 min diikuti oleh reperfusi 45 min dilakukan pada kumpulan Kawalan-I/R dan pHCA-I/R. Tisu otak dikumpulkan untuk analisis biokimia, infarksi dan kajian histologi korteks serebrum dan korpus kalosum (CC). Keputusan menunjukkan bahawa induksi I/R menunjukkan perubahan biokimia yang ketara (p<0.05) dengan peningkatan infarksi otak (p<0.05), peratusan degenerasi dalam korteks serebrum (p<0.05). Pra-rawatan dengan pHCA mengurangkan MDA (p<0.05), infarksi otak (p<0.05), degenerasi neuron korteks serebrum (p<0.05) dan menghalang pengurangan kepadatan bahan putih otak di CC (p<0.05). Kajian ini menyimpulkan bahawa prarawatan dengan pHCA membantu mencegah kecederaan otak I/R dengan memperbaik peroksidasi lipid, kerosakan bahan putih otak dan degenerasi neuron. Kata kunci: Asid p-hidroksisinamik; bahan putih otak; infarksi; iskemia otak; tekanan oksidatif

Neurodegenerative disease, for instance, Parkinson's disease (PD), is associated with substantia nigra dopaminergic neuronal loss with subsequent striatal dopamine reduction, leading to motor de cits. Currently, there is no available effective therapy for PD; thus, novel therapeutic agents such as natural antioxidants with neuroprotective effects are emerging. Alpha-mangostin (αM) is a xanthone derivative compound from mangosteen peel with a cytoprotective effect depicted in neurodegenerative disease models. However, αM has low aqueous solubility and low biodistribution in the brain. Nanostructured lipid carriers (NLC) have been used to encapsulate bioactive compounds delivered to target organs to improve the oral bioavailability and effectiveness. This study aimed to investigate the effect of αM and αM encapsulated in NLC (αM-NLC) in mice with rotenone-induced PD-like neurodegeneration. Forty male ICR mice were divided into normal, PD, PD+αM, and PD+ αM-NLC groups. Vehicle, αM (25 mg/kg/48 h), and αM-NLC (25 mg/kg/48 h) were orally administered, along with PD induction by intraperitoneal injection of rotenone (2.5 mg/kg/48 h) for 4 consecutive weeks. Motor abilities were assessed once a week using rotarod and hanging wire tests. Biochemical analysis of brain oxidative status was conducted, and neuronal populations in substantia nigra par compacta (SNc), striatum, and motor cortex were evaluated using Nissl staining. Tyrosine hydroxylase (TH) immunostaining of SNc and striatum was also evaluated. Results showed that rotenone signi cantly induced motor de cits concurrent with signi cant SNc, striatum, and motor cortex neuronal reduction and signi cantly decreased TH intensity in SNc (p < 0.05).The signi cant reduction of brain superoxide dismutase activity (p < 0.05) was also detected.Administrations of αM and αM-NLC signi cantly reduced motor de cits, prevented the reduction of TH intensity in SNc and striatum, and prevented the reduction of neurons in SNc (p < 0.05). Only αM-NLC signi cantly prevented the reduction of neurons in both striatum and motor cortex (p < 0.05). These were found concurrent with signi cantly reduced malondialdehyde level and increased catalase and superoxide dismutase activities (p < 0.05). Therefore, this study depicted the neuroprotective effect of αM and αM-NLC against rotenone-induced PD-like neurodegeneration in mice. We indicated an involvement of NLC, emphasizing the protective effect of αM against oxidative stress. Moreover, αM-NLC exhibited broad protection against rotenone-induced neurodegeneration that was not limited to nigrostriatal structures and emphasized the bene t of NLC in enhancing αM neuroprotective effects.

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