Original research paper
Standardized Bacopa monnieri extract ameliorates acute paraquat-induced oxidative stress, and neurotoxicity in prepubertal mice brain
Pro of
Ravikumar Hosamani 1,2 , Gokul Krishna 1, Muralidhara 1 1
Biochemistry and Nutrition Department, CSIR-Central Food Technological Research Institute, Mysore, Karnataka, India, 2Space Bioscience Division, NASA Ames Research Center, Moffett Field, CA, USA
cor rec t
ed
Objectives: Bacopa monnieri (BM), an ayurvedic medicinal plant, has attracted considerable interest owing to its diverse neuropharmacological properties. Epidemiological studies have shown significant correlation between paraquat (PQ) exposure and increased risk for Parkinson’s disease in humans. In this study, we examined the propensity of standardized extract of BM to attenuate acute PQ-induced oxidative stress, mitochondrial dysfunctions, and neurotoxicity in the different brain regions of prepubertal mice. Methods: To test this hypothesis, prepubertal mice provided orally with standardized BM extract (200 mg/kg body weight/day for 4 weeks) were challenged with an acute dose (15 mg/kg body weight, intraperitoneally) of PQ after 3 hours of last dose of extract. Mice were sacrificed after 48 hours of PQ injection, and different brain regions were isolated and subjected to biochemical determinations/quantification of central monoamine (dopamine, DA) levels (by high-performance liquid chromatography). Results: Oral supplementation of BM for 4 weeks resulted in significant reduction in the basal levels of oxidative markers such as reactive oxygen species (ROS), malondialdehyde (MDA), and hydroperoxides (HP) in various brain regions. PQ at the administered dose elicited marked oxidative stress within 48 hours in various brain regions of mice. However, BM prophylaxis significantly improved oxidative homeostasis by restoring PQ-induced ROS, MDA, and HP levels and also by attenuating mitochondrial dysfunction. Interestingly, BM supplementation restored the activities of cholinergic enzymes along with the restoration of striatal DA levels among the PQ-treated mice. Discussion: Based on these findings, we infer that BM prophylaxis renders the brain resistant to PQ-mediated oxidative perturbations and thus may be better exploited as a preventive approach to protect against oxidative-mediated neuronal dysfunctions.
Introduction
Un
Keywords: Bacopa monnieri, Paraquat, Mice, Oxidative stress, Mitochondrial dysfunctions, Parkinson’s disease
Bacopa monnieri L. (Family: Scrophulariaceae), a well-known ayurvedic herbal medicine, is well known for its neuropharmacological effects.1 Bacopa monnieri (BM) formulations are available over the counter and recommended for the management of various mental illnesses such as poor cognition, anxiety, depression, epilepsy, and stress.2 In addition to this, numerous studies have ascribed antioxidant and anti-stress properties to BM. Its antioxidant properties are attributed to its ability to scavenge free radicals and modulate endogenous enzymic antioxidant defense systems in Correspondence to: Ravikumar Hosamani, Space Bioscience Division, NASA Ames Research Center, Moffett Field, CA 94035, USA. Email: [email protected]
© W. S. Maney & Son Ltd 2014 DOI 10.1179/1476830514Y.0000000149
vivo.2,3 Clinical trial data have reported Bacopa extract to be neurobeneficial in improving various neurocognitive aspects in children4 and to abrogate neurotoxic effects of metals such as aluminum.5 Parkinson’s disease (PD) is a neurodegenerative movement disorder characterized by profound and selective loss of nigrostriatal dopaminergic neurons in the substantia nigra pars compacta and consequent loss of dopamine (DA) in the striatum.6–8 Although genetic vulnerability plays an important role in disease progression, it is environmental toxicants, in particular pesticides and herbicides are implicated as an etiologic factor for PD.9 It has been suggested that exposure to Paraquat (1,1′ -dimethyl-4,4′ -bipyridium, PQ), a non-selective contact herbicide can
Nutritional Neuroscience
2014
VOL.
0
NO.
0
1
Bacopa monnieri protects paraquat-induced oxidative stress in mice brain
mitochondrial dysfunction, and neurotoxicity in selected brain regions (cortex, cerebellum, hippocampus, and striatum) of mice.
Materials and methods Chemicals PQ, 2′ -thiobarbituric acid (TBA), 5,5′ -dithio-bis-(2nitrobenzoic acid) (DTNB), 2,7,-dichlorofluorescein (DCF), acetylthiocholineiodide, DA, and other fine chemicals were purchased from Sigma-Aldrich (St Louis, MO, USA). All other chemicals were procured from commercial suppliers and of standard analytical grade.
Animals
Prepubertal male CFT-Swiss mice (4-week old, 22–26 g) were drawn from the stock colony of CSIRCFTRI ‘Institute animal house facility’ for the proposed study. The animals were housed in standard (27′′ long, 20′′ wide and 14′′ high; three per cage) polypropylene cages kept on racks built of slotted angles provided with dust-free paddy husk as bedding material. The animals were housed in a room maintained under controlled conditions of temperature (22 ± 5°C), humidity (50 ± 5%), and photoperiod 12hour light/dark cycle. All animals had ad libitum access to food and water at all times. The composition and nutrient levels of the basal diet (%, as-fed basis) according to the manufacturer is protein, 21; carbohydrates, 60; fat, 7; fiber, 6; mineral mix, 6; and moisture content,
Standardized Bacopa monnieri extract ameliorates acute paraquat-induced oxidative stress, and neurotoxicity in prepubertal mice brain
Pro of
Ravikumar Hosamani 1,2 , Gokul Krishna 1, Muralidhara 1 1
Biochemistry and Nutrition Department, CSIR-Central Food Technological Research Institute, Mysore, Karnataka, India, 2Space Bioscience Division, NASA Ames Research Center, Moffett Field, CA, USA
cor rec t
ed
Objectives: Bacopa monnieri (BM), an ayurvedic medicinal plant, has attracted considerable interest owing to its diverse neuropharmacological properties. Epidemiological studies have shown significant correlation between paraquat (PQ) exposure and increased risk for Parkinson’s disease in humans. In this study, we examined the propensity of standardized extract of BM to attenuate acute PQ-induced oxidative stress, mitochondrial dysfunctions, and neurotoxicity in the different brain regions of prepubertal mice. Methods: To test this hypothesis, prepubertal mice provided orally with standardized BM extract (200 mg/kg body weight/day for 4 weeks) were challenged with an acute dose (15 mg/kg body weight, intraperitoneally) of PQ after 3 hours of last dose of extract. Mice were sacrificed after 48 hours of PQ injection, and different brain regions were isolated and subjected to biochemical determinations/quantification of central monoamine (dopamine, DA) levels (by high-performance liquid chromatography). Results: Oral supplementation of BM for 4 weeks resulted in significant reduction in the basal levels of oxidative markers such as reactive oxygen species (ROS), malondialdehyde (MDA), and hydroperoxides (HP) in various brain regions. PQ at the administered dose elicited marked oxidative stress within 48 hours in various brain regions of mice. However, BM prophylaxis significantly improved oxidative homeostasis by restoring PQ-induced ROS, MDA, and HP levels and also by attenuating mitochondrial dysfunction. Interestingly, BM supplementation restored the activities of cholinergic enzymes along with the restoration of striatal DA levels among the PQ-treated mice. Discussion: Based on these findings, we infer that BM prophylaxis renders the brain resistant to PQ-mediated oxidative perturbations and thus may be better exploited as a preventive approach to protect against oxidative-mediated neuronal dysfunctions.
Introduction
Un
Keywords: Bacopa monnieri, Paraquat, Mice, Oxidative stress, Mitochondrial dysfunctions, Parkinson’s disease
Bacopa monnieri L. (Family: Scrophulariaceae), a well-known ayurvedic herbal medicine, is well known for its neuropharmacological effects.1 Bacopa monnieri (BM) formulations are available over the counter and recommended for the management of various mental illnesses such as poor cognition, anxiety, depression, epilepsy, and stress.2 In addition to this, numerous studies have ascribed antioxidant and anti-stress properties to BM. Its antioxidant properties are attributed to its ability to scavenge free radicals and modulate endogenous enzymic antioxidant defense systems in Correspondence to: Ravikumar Hosamani, Space Bioscience Division, NASA Ames Research Center, Moffett Field, CA 94035, USA. Email: [email protected]
© W. S. Maney & Son Ltd 2014 DOI 10.1179/1476830514Y.0000000149
vivo.2,3 Clinical trial data have reported Bacopa extract to be neurobeneficial in improving various neurocognitive aspects in children4 and to abrogate neurotoxic effects of metals such as aluminum.5 Parkinson’s disease (PD) is a neurodegenerative movement disorder characterized by profound and selective loss of nigrostriatal dopaminergic neurons in the substantia nigra pars compacta and consequent loss of dopamine (DA) in the striatum.6–8 Although genetic vulnerability plays an important role in disease progression, it is environmental toxicants, in particular pesticides and herbicides are implicated as an etiologic factor for PD.9 It has been suggested that exposure to Paraquat (1,1′ -dimethyl-4,4′ -bipyridium, PQ), a non-selective contact herbicide can
Nutritional Neuroscience
2014
VOL.
0
NO.
0
1
Bacopa monnieri protects paraquat-induced oxidative stress in mice brain
mitochondrial dysfunction, and neurotoxicity in selected brain regions (cortex, cerebellum, hippocampus, and striatum) of mice.
Materials and methods Chemicals PQ, 2′ -thiobarbituric acid (TBA), 5,5′ -dithio-bis-(2nitrobenzoic acid) (DTNB), 2,7,-dichlorofluorescein (DCF), acetylthiocholineiodide, DA, and other fine chemicals were purchased from Sigma-Aldrich (St Louis, MO, USA). All other chemicals were procured from commercial suppliers and of standard analytical grade.
Animals
Prepubertal male CFT-Swiss mice (4-week old, 22–26 g) were drawn from the stock colony of CSIRCFTRI ‘Institute animal house facility’ for the proposed study. The animals were housed in standard (27′′ long, 20′′ wide and 14′′ high; three per cage) polypropylene cages kept on racks built of slotted angles provided with dust-free paddy husk as bedding material. The animals were housed in a room maintained under controlled conditions of temperature (22 ± 5°C), humidity (50 ± 5%), and photoperiod 12hour light/dark cycle. All animals had ad libitum access to food and water at all times. The composition and nutrient levels of the basal diet (%, as-fed basis) according to the manufacturer is protein, 21; carbohydrates, 60; fat, 7; fiber, 6; mineral mix, 6; and moisture content,
