Pre-clinical Aspects and Contemporary Treatments of Parkinson's Disease.

BACKGROUND: After Alzheimer's disease, the second slot for the most common neurodegenerative disease, is occupied by Parkinson's disease. The symptoms of Parkinson's are classified as motor symptoms and non-motor symptoms. Motor symptoms involve rigidity, tremors, bradykinesia, and postural instability. Non-motor symptoms consist of cognitive dysfunction, salivation, lacrimation, etc. Objectives: The objectives of this study are to find out the most recent treatment options for Parkinson's disease. METHODS: Research and review papers are collected from different databases like Google Scholar, PubMed, Mendeley, Scopus, Science Open, and the Directory of Open Access Journals using different keywords such as "Parkinson's disease, biomarkers, animal models". RESULTS: Currently, various novel therapeutics have been emerging for PD. These may include treatments that may control the symptoms without causing any other severe side effects with already available treatments. Better therapies such as gene therapies, cell-based treatments, and regenerative therapies, which may evolve over time, can be a better therapeutic option. CONCLUSION: There is a need for the development of novel and potential therapeutic strategies that offer fewer side effects to patients. Several clinical, biochemical, and imaging markers that are noteworthy in Parkinson's disease examination have been discussed here. Current work in the field of Parkinson's disease has developed a variety of significant small animal models, such as viral vector models and seeding models, including the insertion of preformed fibrils of alpha-synuclein. The brief concepts regarding risk factors, pathogenesis, clinical diagnosis, and emerging treatments of PD are discussed in this review article.

Oxidative Stress and Male Infertility: Role of Herbal Drugs.

Infertility is a universal health problem affecting 15% of couples, out of which 20-30% cases are due to male infertility. The leading causes of male infertility include hormonal defects, physical reasons, sexual problems, hazardous environment, stressful lifestyle, genetic factors, epigenetic factors, and oxidative stress. Various physiological functions involve reactive oxygen species (ROS) and nitrogen species at appropriate levels for proper smooth functioning. ROS control critical reproductive processes such as capacitation, acrosomal reaction, hyperactivation, egg penetration, and sperm head decondensation. The excessive free radicals or imbalance between ROS and endogenous antioxidant enzymes damages sperm membrane by inducing lipid peroxidation causing mitochondrial dysfunction and DNA damage that eventually lead to male infertility. Numerous synthetic products are available in the market to treat infertility problems, largely ending in side effects and repressing symptoms. Ayurveda contains a particular group of Rasayana herbs, called vajikarana, that deals with nourishment and stimulation of sexual tissues, improves male reproductive vitality, and deals with oxidative stress via antioxidant mechanism. The present study aims to describe oxidative stress and the role of herbal drugs in treating male infertility.

Neuroprotective effect of standardized extracts of three Lactuca sativa Linn. varieties against 3-NP induced Huntington's disease like symptoms in rats.

OBJECTIVES: The study was aimed to evaluate the efficacy of three commonly consumed Lactuca sativa (LS) Linn. varieties viz., Grand rapid, Lollo rosso and Iceberg (Asteraceae) against 3-NP induced HD like symptoms in rats. METHODS: Ethanol extracts of leaves of three LS varieties were prepared, and standardized on the basis of quercetin content using HPLC. These extracts (100 and 200 mg kg, p.o. for 20 days) were evaluated for their neuroprotective effect against 3-NP (10 mg/kg, i.p. for 14 days) induced neurotoxicity in male Wistar rats. The extract that exhibited maximum activity was successively fractionated using hexane, ethyl acetate, n-butanol and aqueous in increasing order of polarity. These fractions were also evaluated (dose equivalent to the dose of the extract of LS variety exhibiting maximum activity) for their neuroprotective effect. The protective effect of extracts and fractions was evaluated using different behavioral (rota rod, actophotometer, beam walk and Morris water maze) and biochemical (malondialdehyde, nitrite, superoxide dismutase, catalase and reduced glutathione) parameters. RESULTS: 3-NP elicit marked deterioration in motor coordination, locomotor activity and memory in comparison to control group. Standardized ethanol extract of grand rapid (200 mg/kg) exhibited maximum activity amongst the three tested varieties. Therefore, its fractions were also evaluated, and n-butanol fraction (40 mg/kg) exhibited maximum attenuation of 3-NP induced HD like symptoms which was evident from improved behavioral and biochemical parameters. DISCUSSION: The results exhibit that LS (Grand rapid variety) prophylaxis mitigated 3-NP induced neurotoxicity and HD like symptoms in rats due to its potent antioxidant potential.

Development and Validation of a Novel, Rapid Gradient HPLC Method for Simultaneous Estimation of Bioactive Marker Compounds in a Mixture of Convolvulus pluricaulis, Withania somnifera and Bacopa monnieri Extracts.

The use of herbs as medicine is an ancient form of healthcare known to mankind. Standardization of herbal medicines is however a challenging task and is the major bottleneck in their acceptance as the primary therapeutic option. The aim of this study was to develop and validate a simple, rapid HPLC method for standardizing the mixture of extracts of three Medhya Rasayanas (neurotonic), Convolvulus pluricaulis, Withania somnifera and Bacopa monnieri. Simultaneous estimation of the respective bioactive markers of these plants viz., scopoletin, withaferin A, bacoside A 3, bacopaside II, jujubogenin and bacosaponin C has been reported for the first time. The method was developed using Waters Hybrid X-Bridge shield with BEH technology 2.5 µm, 4.6 × 75 mm column and validated according to ICH guidelines. The 20 minutes run time makes the method eco-friendly. The method was linear over a range of 12.5-400 ng/10 µL for scopoletin and 62.5-2,000 ng/10 µL for withaferin A, bacoside A 3, bacopaside II, jujubogenin and bacosaponin C with detection limits of 8.0, 48.3, 30.4, 40.7, 15.6 and 18.9 ng/10 µL and quantification limits of 24.5, 146.5, 92.2, 123.4, 47.4 and 57.4 ng/10 µL, respectively. The correlation coefficient for each analyte was >0.999. The intra-day and inter-day precision was <2%. These results confirmed the precision, accuracy and robustness of the proposed method.

Standardized extract of Lactuca sativa Linn. and its fractions abrogates scopolamine-induced amnesia in mice: A possible cholinergic and antioxidant mechanism.

OBJECTIVES: The present study was designed to evaluate the efficacy of Lactuca sativa (LS) Linn. (Asteraceae) against scopolamine-induced amnesia and to validate its traditional claim as memory enhancer. METHODS: Ethanol extract of fresh LS leaves (LSEE), standardized on the basis of quercetin content, was successively partitioned using various solvents viz., hexane, ethyl acetate, and n-butanol in increasing order of polarity. LSEE (50, 100, and 200 mg/kg) and its various fractions (at a dose equivalent to dose of LSEE exhibiting maximum activity), administered orally for 14 days, were evaluated for their memory enhancing effect against scopolamine-induced (1 mg/kg, i.p.) amnesia in 3-4 months old male Laca mice (n = 6 in each group). The memory enhancing effect was evaluated using behavioural (elevated plus maze, novel object recognition and Morris water maze tests) and biochemical parameters (acetylcholinesterase activity, malonaldehyde, superoxide dismutase, nitrite, catalase, and reduced gultathione content). The results of the test substances were compared with both scopolamine and donepezil that was used as a standard memory enhancer and acetylcholinesterase inhibitor. RESULTS: Scopolamine elicit marked deterioration of memory and alteration in biochemical parameters in comparison to the control group. LSEE and its n-butanol and aqueous fractions significantly (P < 0.05) attenuated the scopolamine-induced amnesia that was evident in all the behavioural and biochemical test parameters. LSEE (200 mg/kg) and n-butanol fraction (15 mg/kg) exhibited maximum anti-amnesic effect among various tested dose levels. DISCUSSION: The results exhibited that LS prophylaxis attenuated scopolamine-induced memory impairment through its acetylcholinesterase inhibitory and antioxidant activity validating its traditional claim.

Protective effect of Convolvulus pluricaulis standardized extract and its fractions against 3-nitropropionic acid-induced neurotoxicity in rats.

CONTEXT: Convolvulus pluricaulis Chois. (Convolvulaceae), a well-known Ayurvedic "Medhya Rasayana" (nervine tonic), is extensively used for different central nervous system (CNS) disorders. OBJECTIVE: The objective of this study was to evaluate the protective effect of standardized hydro-methanol extract of C. pluricaulis (CPE) and its fractions, namely ethyl acetate (EAE), butanol (BE), and aqueous (AE), against 3-nitropropionic acid (3-NP) induced neurotoxicity in rats. MATERIALS AND METHODS: The extract of the whole plant was standardized on the basis of scopoletin content (0.014%) using thin layer chromatography densitometric analysis. CPE (100 and 200 mg/kg) and its fractions, namely EAE (15 and 30 mg/kg), BE (25 and 50 mg/kg), and AE (50 and 100 mg/kg) were administered orally for 20 d. Their protective effect against 3-NP (10 mg/kg, i.p. for 14 d) was assessed by the effect on various behavioral parameters, namely body weight, locomotor activity, grip strength, gait pattern, and the effect on cognitive dysfunction. Biochemical parameters for oxidative damage were also assessed in the striatum and cortex regions of the brain. RESULTS: Administration of 3-NP induced HD-like symptoms that were indicated by reduced body weight, locomotor activity, memory, grip strength, and oxidative defense. CPE (200 mg/kg), EAE (30 mg/kg), and BE (50 mg/kg) significantly (p < 0.001) attenuated 3-NP induced reduction in locomotor activity, grip strength, memory, body weight, and oxidative defense in comparison with 3-NP-treated animals on 10 and 15 d. CONCLUSION: The present study suggested that CPE has a protective action against 3-NP-induced neurotoxicity and can be further explored for its efficacy against Huntington's disease.

Plants and phytochemicals for Huntington's disease.

Huntington's disease (HD) is a neurodegenerative disorder characterized by progressive motor dysfunction, including chorea and dystonia, emotional disturbances, memory, and weight loss. The medium spiny neurons of striatum and cortex are mainly effected in HD. Various hypotheses, including molecular genetics, oxidative stress, excitotoxicity, metabolic dysfunction, and mitochondrial impairment have been proposed to explain the pathogenesis of neuronal dysfunction and cell death. Despite no treatment is available to fully stop the progression of the disease, there are treatments available to help control the chorea. The present review deals with brief pathophysiology of the disease, plants and phytochemicals that have shown beneficial effects against HD like symptoms. The literature for the current review was collected using various databases such as Science direct, Pubmed, Scopus, Sci-finder, Google Scholar, and Cochrane database with a defined search strategy.