Flaxseed extract reduces tissue accumulation and enhances urinary excretion of chondroitin sulphate in the rat: a possible new path in substrate reduction therapy for mucopolysaccharidosis.

CONTEXT: Chondroitin 6 sulphate (C6S) is a glycosaminoglycan (GAG) whose accumulation is notable in mucopolysaccharidosis type IVA and VII. Flaxseed, Linum usitatissimum L. (Linaceae) (FS), is reported to have comparable properties to those of soybean, a source of genistein, a potential new treatment for MPSs. OBJECTIVE: We assess the effect of total ethanol flaxseed extract (EFSE) in an animal model of C6S accumulation. MATERIALS AND METHODS: The study was performed in adult male Wistar rats (n = 24) for 15 successive days. The animals were divided into four groups: (1) control injected with physiological saline buffer, (2) intoxicated rats injected intraperitoneally with C6S, (3) intoxicated with C6S and treated with EFSE, and (4) treated with EFSE. All groups were subjected to histopathological and biochemical studies. The antioxidant and phytochemical properties of EFSE were examined. RESULTS: Dry EFSE contains total phenols (6.28 mg EAG/g), condensed tannins (2.98 mg ECAT/g) and flavonoids (0.44 mg ECAT/g) with high antioxidant potential [RPE (IC50 = 8.37 ± 0.176), DPPH (IC50 = 12.79 ± 0.273)]. The LD50 is higher than 5000 mg/kg. The histopathological examination showed an accumulation of C6S in the C6S intoxicated group, which disappeared in the C6S-EFSE treated group. GAGs assays showed an increased excretion in the C6S intoxicated group and increased excretion of 14% in the C6S-EFSE group compared to the C6S group. DISCUSSION AND CONCLUSIONS: EFSE showed significant potential for chelation. Its use for the treatment of GAG accumulation could be suggested and generalized to a larger study population.

Study of the neurochemical alterations produced by acute and subchronic Pb-exposure in Meriones shawi: Immunohistochemical study of Reissner's fiber secretion by the subcommissural organ after curcumin-III treatment.

BACKGROUND: Lead neurotoxicity is associated with numerous alterations including behavioral and neurochemical disruptions. This study evaluates the possible neurochemical disruption in the subcommissural organ (SCO) after acute (three days) and subchronic (six weeks) Pb-exposure inMeriones shawi, and the possible effect of the third active compound, curcumin-III, in mitigating the neurological alterations caused by lead exposure. METHODS: Using immunohistochemical stainings, we evaluated the Reissner's fiber (RF) secretion utilizing RF-antibody in the SCO. We compared both acute (25 mg/kg bw of Pb i.p. for 3 days) and subchronic (3 g/l of Pb in drinking water for six weeks) Pb-treatedMeriones shawi. RESULTS: The two models of lead exposure showed a significant increase in RF level in the SCO. Conversely, co-treatment with Curcumin-III at a dose of 30 mg/kg bw significantly ameliorate SCO secretory activity, as revealed by decreased RF-immunoreactivity. CONCLUSION: Together, our findings suggest the protective effects of Curcumin-III in regulating the secretory activity of the SCO after Pb-induced neuroanatomical disruptions of the SCO in Meriones.

Aluminum induced oxidative stress, astrogliosis and cell death in rat astrocytes, is prevented by curcumin.

Aluminum (Al) is recognized potent neurotoxic metal, which causes oxidative stress leading to intracellular accumulation of reactive oxygen species (ROS) and neuronal cell death in various neurodegenerative diseases. Among several medicinal plants with beneficial effects on health, curcumin acts as a multi-functional drug with antioxidant activity. Thus, the purpose of the present study was to evaluate the protective effect of curcumin against aluminum induced-oxidative stress and astrocytes death, in vitro ad in vivo. Incubation of cultured rat astrocytes with two concentrations of Al (37 µM and 150 µM) for 1 h provoked a dose-dependent reduction of the number of living cells as evaluated by Fluorescein diacetate and lactate dehydrogenase assay. Al-treated cells exhibited a reduction of both superoxide dismutase (SOD) and catalase activities. Pretreatment of astrocytes with curcumin (81 µM) prevented Al-induced cell death. Regarding in vivo study, rats were exposed acutely during three consecutive days to three different doses of Al (25 mg/kg, 50 mg/kg and 100 mg/kg, i.p injection), together with curcumin treatment (30 mg/kg). For the chronic model, animals were exposed to Al (3 g/l) in drinking water from intrauterine age to 4 months ages, plus curcumin treatment (175 mg/kg). Data showed that both acute and chronic Al intoxication induced an obvious astrogliosis within motor cortex and hippocampus, while, such effects were restored by curcumin. We showed herein that Al was highly toxic, induced astrocytes death. Then, curcumin protected astrocytes against Al-toxicity. The cytoprotective potential of curcumin is initiated by stimulation of endogenous antioxidant system.

Altered nigrostriatal dopaminergic and noradrenergic system prompted by systemic lead toxicity versus a treatment by curcumin-III in the desert rodent Meriones shawi.

Exposure to lead is a threat factor for neurodegenerative disorders progress as it could trigger dopaminergic deficiency. We aimed herein to assess the effect of acute lead exposure (25mg/kg B.W i.p.) during three continuous days on the dopaminergic and noradrenergic systems together with locomotor performance in Meriones shawi (M. shawi), then the neuroprotective potential of curcumin-III (30mg/kg B.W) by oral gavage. Pb-exposed M. shawi exhibited increased tyrosine hydroxylase (TH) immunoreactivity in substantia nigra compacta (SNc), ventral tegmental area (VTA), locus coeruleus (LC), and dorsal striatum (DS), unlike the controls. This was correlated with decreased locomotor performance. A noticeable protective effect by co-treatment with curcumin-III was observed; in consequence, TH-immunoreactivity and locomotor disturbance were restored in Pb-treated Meriones. Our data results proved, on the one hand, an evident neurotoxic effect of acute Pb exposure and, on the other hand, a potent therapeutic effect of curcumin-III. Thereby, this compound may be recommended as a neuroprotective molecule for neurodegenerative disorders involving catecholaminergic impairment initiated by metallic elements.

Curcumin prevents the midbrain dopaminergic innervations and locomotor performance deficiencies resulting from chronic aluminum exposure in rat.

Aluminum (Al) among the abundant metals on the earth crust, is able to cross the biological barriers via the gastrointestinal and lung tissues. Once in the body, this heavy metal accumulates in different organs, especially the central nervous system. Though its influence is evidently shown in the substantia nigra of Parkinson's disease patients and other brain areas in other neurodegenerative diseases, few studies have demonstrated that Al could trigger profound changes in neurotransmission systems including the dopaminergic (DAergic) system. A variety of medicinal plants may be prescribed in such contamination, including some culinary spices such as Curcumin (Cur). Several studies have proven Cur to exhibit a wide variety of biological and pharmacological activities, especially its antioxidant potential. Using the immunohistochemistry, of tyrosine hydroxylase (TH), in the midbrain substantia nigra pars compact (SNc) and the ventral tegmental area (VTA) and the open field test, we examined the DAergic system together with the locomotor behavior respectively in rats exposed chronically to Al (0,3%) in drinking water during 4 months since the intra-uterine age, as well as the neuroprotective effect of the concomitant administration of Cur I (30 mg/kg B.W) of chronic Al exposed rats. Our results have shown a significant decrease of TH immureactivity in both SNc and VTA associated to a loss of the number of crossed boxes, leading to a difficient locomotor performance in the Al group while Cur I prevents such TH immunoreactivity impairment and maintains a higher locomotor activity in the Al-CurI group. Our findings lead to suppose a powerful and obvious neuroprotective potential of CurI against Al-induced neurotoxicity of the DAergic system involved in the control of the locomotor behavior.

Neuroprotective effect of curcumin-I in copper-induced dopaminergic neurotoxicity in rats: A possible link with Parkinson's disease.

Numerous findings indicate an involvement of heavy metals in the neuropathology of several neurodegenerative disorders, especially Parkinson's disease (PD). Previous studies have demonstrated that Copper (Cu) exhibits a potent neurotoxic effect on dopaminergic neurons and triggers profound neurobehavioral alterations. Curcumin is a major component of Curcuma longa rhizomes and a powerful medicinal plant that exerts many pharmacological effects. However, the neuroprotective action of curcumin on Cu-induced dopaminergic neurotoxicity is yet to be investigated. The aim of the present study was to evaluate the impact of acute Cu-intoxication (10mg/kg B.W. i.p) for 3days on the dopaminergic system and locomotor performance as well as the possible therapeutic efficacy of curcumin I (30mg/kg B.W.). Intoxicated rats showed a significant loss of Tyrosine Hydroxylase (TH) expression within substantia nigra pars compacta (SNc), ventral tegmental area (VTA) and the striatal outputs. This was correlated with a clear decrease in locomotor performance. Critically, curcumin-I co-treatment reversed these changes and showed a noticeable protective effect; both TH expression and locomotor performance was reinstated in intoxicated rats. These results demonstrate altered dopaminergic innervations following Cu intoxication and a new therapeutic potential of curcumin against Cu-induced dopaminergic neurotransmission failure. Curcumin may therefore prevent heavy metal related Parkinsonism.

Neuroprotective potential of Aloe arborescens against copper induced neurobehavioral features of Parkinson's disease in rat.

Copper (Cu) is an important trace element for the organism survival, which ensures the normal functioning of different biosystems. However, excessive levels of this heavy metal are responsible for profound physiological alterations including the central nervous system. Numerous findings sustain the involvement of heavy metals, as an environmental risk factor such as copper (Cu), in the neuropathology of Parkinson's disease (PD) which is a chronic neurodegenerative disorder that principally affects the motor system. The classic and evident symptoms of PD namely rigidity, tardiness of movement, and difficulty with walking, result from progressive dopaminergic neurons death within substantia nigra. Whereas, few pharmacological trials have shown a beneficial role against Cu neurotoxicity, Aloe arborescens is one of the powerful medicinal plants with an array of therapeutic effects. Thus, we aimed through the present study, to evaluate the impact of acute Cu intoxication (10µg/g B.W. i.p) for 3days on the dopaminergic system and locomotor performance, together with the possible restorative effect of oral administration of aqueous extract of Aloe arborescens gel (AEAAG) (200mg/kg B.W.). By means of immunohistochemistry, we noted, in the Cu intoxicated rats, a significant loss of TH (tyrosine hydroxylase) expression within substantia nigra compacta (SNc), ventral tegmental area (VTA) and the subsequent striatal outputs, those alterations were correlated to behavioral abnormalities such as a severe drop of locomotor performance. While AEAAG administration to Cu intoxicated rats showed a noticeable beneficial effect; this potential was featured by a complete recovery of the TH expression and locomotor behavior deficiencies in the intoxicated rats. The present investigation have brought, on the one hand, an experimental evidence of an altered dopaminergic innervations following Cu intoxication and on the other hand, a new pharmacological property of Aloe arborescens that may be used as a neuroprotective plant for neurodegenerative disorders, such as PD, touching the dopaminergic system trigged by heavy metals.

A blunted anxiolytic like effect of curcumin against acute lead induced anxiety in rat: involvement of serotonin.

Anxiety is one of the most common mental disorders sharing extreme or pathological anxiety states as the primary disturbance in mood or emotional tone, with increased fear and exaggerated acute stress responses. Medicinal plants are very variable, but some of them are used as a spice such as curcumin (Curcuma longa). Curcumin shows a wide range of pharmacological potentialities, however, little is known about its anxiolytic properties. The aim of our study was to assess the anti-anxiety potential of curcumin extract against experimental lead induced-anxiety in rats. Experiments were carried out on male Wistar rats intoxicated acutely with an intraperitoneal injection of Pb (25mg/kg B.W.) and/or concomitantly with administration of curcumin (30 mg/kg B.W.) for 3 days. Using immunohistochemistry and anxiety assessment tests (dark light box and elevated plus maze), we evaluated, respectively, the expression of serotonin (5HT) in the dorsal raphe nucleus (DRN) and the anxiety state in our animals. Our results showed, for the first time, a noticeable anxiolytic effect of curcumin against lead induced anxiety in rats and this may possibly result from modulation of central neuronal monoaminergic neurotransmission, especially serotonin, which has shown a significant reduction of the immunoreactivity within the DRN.