Abstract

Mucuna pruriens has been used in the treatment of numerous diseases in India. Ayurvedic medicine is mainly for treating Parkinson’s disease. The seeds of the plant have a potent medicinal valve & its extract has been tested in different models of neurodegenerative disease and has as its main component levodopa. The main aim of this work is to systematically review the effects of Mucuna pruriens supplementation on experimental of Parkinson's disease due to its Neuroprotective & Anti-oxidants properties. Apart from Parkinson’s disease Mucuna pruriens is also used to treat male infertility for ages & the immune mechanism of Mucuna pruriens Activity. Apart from Parkinson's disease & male fertility of ages, the MP is now being studied in models of other Nervous system disorders such as Alzheimer's disease, and stroke because of its Neuroprotective properties.

Keywords

Mucuna Pruriens, neurological disorder, neuroprotection, Parkinson’s disease

Introduction

Neuroprotection is defined as relative preservation of neuronal structure and/or function OR a process, which promotes salvaging, recovering, and preserving the integrity of neurons and neurovascular unit (NVU) for performing their physiological functions. .It can be an approach before the onset of the disease so that neurons cannot be affected by any risk factors. It can also be an approach during the progression of the disease to prevent spreading of injury from one neuron to neighboring neurons. Therefore, neuroprotection can also be one approach as “disease-modifying agent” to delay and even stop progressive neurodegeneration. It includes neuroprotective agents that protect against neuronal injury. It refers to a disease-modifying event, one that protects cells from pathological insult-for example, toxic insult or genetic mutation. It is a widely explored treatment option for many central nervous system disorders including neurodegenerative diseases, stroke, traumatic brain injury, spinal cord injury, and acute management of neurotoxin consumption (i.e. methamphetamine overdoses). Neuroprotection aims to prevent or slow disease progression and secondary injuries by halting or at least slowing the loss of neurons. The mechanism of neuroprotection is commonly protecting degeneration of the CNS resulting acute ailments. There have been countless pharmaceutical and herbal agents, together with some surgical methods, shown to be neuroprotective in animal models of Parkinson’s disease; and another neurodegenerative disease.

Neurological Disorder –

A neurological disorder is any disorder of the nervous system. Structural, biochemical or electrical abnormalities in the brain, spinal cord or other nerves can result in a range of symptoms The specific causes of neurological problems vary, but can include genetic disorders, congenital abnormalities or disorders, infections, lifestyle or environmental health problems including malnutrition, and brain injury, spinal cord injury or nerve injury. Neurological disease such as,  some of the most common are epilepsy, Alzheimer’s and other dementias, strokes, migraine and other headaches, multiple sclerosis, Parkinson’s disease, neurological infections, brain tumors, traumatic conditions of the nervous system such as head injuries and disorders caused by malnutrition.  Alzheimer’s disease and Parkinson’s disease are the most common neurodegenerative diseases. It can prevent by healthy lifestyle will help you reduce the risk of suffering from one of these diseases, eating healthy, avoiding cigarettes, and leading an active life with frequent physical activity can work as preventive measures. It treated by although some of these diseases have no cure, some others can be controlled or, in their case, they can mitigate the symptoms with a timely diagnosis and adequate treatment.  There are some herbal plant are help to reduce neurological disorder such Parkinson and Alzheimer’s, Huntington’s disease. Many plants and natural compounds have been used to help with neurological disorders, including, Mucuna pruriens, Ashwagandha, Curcumin, Snowdrop, Other plants that may help with neurological disorders include: Ginkgo biloba, Bacopa monnieri, Withania somnifera, Hypericum perforatum, Glycine max, Allium sativum, Piper methysticum, and Acterasemosa.

Plant profile:-

       
           
       
(Mucuna Pruriens)

Morphology:- 

Kingdom: Plantae

Family: Fabaceae

Subfamily: Faboideae

Genus: Mucuna

Species’. pruriens

Appearance: A long, slender, climbing shrub with tripinnate leaves, and white, lavender, or purple flowers

• Size: Vines can grow over 15 meters (50 feet) long

• Leaves: Young plants are covered in fuzzy hairs, but older plants are almost hairless. Leaves are trip innate, ovate, reverse ovate, rhombus-shaped, or widely ovate.

• Flowers: Pea-like but larger, with curved petals, and arranged in axillary arrayed panicles

• Pods: About 10-20 cm long, covered with loose white to creamish hairs that can cause severe itching if they touch the skin

• Seeds: Shiny black, brown, or spotted white.

. Weight: - 55-85 grams.

Phytochemical constitution:-

According to the review of literature, the Mucuna Pruriens contains this phytochemical.

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Sr no	Chemical Name	Observation/Inference Present/ Absent
1.	Alkaloids	Present
2.	Flavonoids	Present
3.	Saponins	Present
4.	Steroid	Present
5.	Tannins	Absent
6.	Terpenoid	Present
7.	Glycoside	Present
8.	Phenolic	Present

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Application:-

?Dopamine restoration: - Mucuna pruriens can restore dopamine levels in animal models           of Parkinson’s disease.

? Neuroprotective effects:-Mucuna pruriens has been shown to have neuroprotective effects, which may be due to its antioxidant activity.

? Comparable effectiveness to L-DOPA:-Some clinical trials suggest that Mucuna pruriens is comparable to L-DOPA in treating Parkinson’s disease symptoms.

?Improved motor responses:-One study found that Mucuna pruriens improved motor symptoms in Parkinson’s disease patients.

?Reduced climbing distance in flies:-One study found that Mucuna pruriens reduced the negative effects of neurotoxins on climbing behavior in fruit flies.

Side effects:-

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Common side effects	Severe side effects
Nausea.	Confusion
Vomiting	Hallucinations
Dizziness	Agitation
Headache	Psychosis
Behavioral	Movement problems
emotional changes

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Traditional use:-

As a nervine tonic, and as an aphrodisiac for male virility. It has been used in Ayurveda to treat arthritis and neurological disorders. In homeopathic Materia Medica, Mucuna Pruriens is recognized for its potential to manage various neurological and reproductive conditions.

Medicinal uses:-

Management of male infertility, nervous disorders, and also as an aphrodisiac. In males helps to improve sperm concentration, count, and motility and increase testosterone levels. In females medical use of MP is to support reproductive health, hormonal balance, and neurological function.

Geographical distribution:-

Mucuna pruriens is extensively distributed in Southeast Asia and it is largely found in Bangladesh, India, Sri Lanka, and Malaysia. It is also found in Asia, America, and Africa. It is found in indigenous tropical regions. Mucuna pruriens is extensively spread over most of the subcontinent as well as is found in bushes, hedges, plus dry-deciduous, low forests throughout the plains of India. 14 species of Mucuna are found in India, especially in the foothills of the Himalayas, the plains of West Bengal, Madhya Pradesh, Karnataka, Kerala, Andhra Pradesh, Uttar Pradesh, the Andaman and Nicobar Islands as well as Srilanka.

Neurodegenerative Disease:-

1. Parkinson’s disease
2. Alzheimer’s disease
3. Huntington’s disease
4. Ataxia
5. Motor neuron disease
6. Multiple system atrophy

Cause:-

 Neurodegenerative diseases are caused by a combination of genetic and environmental factors, as well as age, medical history, and lifestyle choices:  Genetics- Many neurodegenerative diseases are linked to family history and specific inherited mutations.  Environment-Exposure to toxins, chemicals, pesticides, and other pollutants can increase the risk of developing a neurodegenerative disease.

The older you are, the greater your chances of developing a neurodegenerative disease.  Medical history medical events can cause or worsen neurodegenerative diseases. Lifestyle choices-Alcohol consumption, tobacco use, diet, and activity level can all play a role. Viruses viral infections, such as influenza, have been linked to an increased risk of developing neurodegenerative diseases.

Symptoms: -

-Weakness or paralysis.

-Abnormal movement, such as tremors or difficulty walking.

-Loss of balance.

-Difficulty swallowing or feeling “a lump in the throat”

-Seizures or episodes of shaking and apparent loss of consciousness (no epileptic seizures)

-Episodes of unresponsiveness.

-Confusion.

Diagnosis: -

To diagnose a nervous system disorder, a healthcare provider starts with a complete medical history and physical exam. They may also use one or more of these tests:

1. -CT scan. This imaging test uses a combination of X-rays and computer technology to create detailed images of any part of the body, including bones, muscles, fat, and organs. CT scans are more detailed than general X-rays. They are used to diagnose disorders of the brain, spine, or other parts of the nervous system.
2. -Electroencephalogram (EEG). This test records the brain’s continuous electrical activity through electrodes attached to the scalp.
3. -MRI. This test uses a combination of large magnets, radio waves, and a computer to make detailed images of organs and structures within the body. MRI creates images with much more detail than CT scans without radiation.
4. -Electrodiagnostic tests, such as electromyography (EMG) and nerve conduction velocity (NCV). These tests evaluate and diagnose disorders of the muscles and motor neurons. Electrodes are inserted into the muscle or placed on the skin overlying a muscle or muscle group. Electrical activity and muscle response are recorded.
5. -Positron emission tomography (PET). This test uses a small amount of radioactive material, a camera, and a computer to see how well organs and tissues are working. This test may see the early onset of disease before imaging tests can.
6. -Arteriogram (angiogram). This X-ray of the arteries and veins detects blockage or narrowing of the blood vessels.

Current treatment:-

Unfortunately, all neurodegenerative diseases are incurable. They are typically treated with a combination of medication and psychotherapy. Mesenchymal stem cell (MSC) therapies it is new treatment for neurodegenerative Disease.

Role Of Mucuna Pruriens In Neurodegenerative Disorders:-

The medicinal plant Mucuna pruriens (Fabaceae) is widely known for its anti-oxidative and anti-inflammatory properties. It is a well-established drug in Ayurveda and has been widely used for the Treatment of neurological disorders and male infertility for ages. The seeds of the plant have potent medicinal Value and its extract has been tested in different models of neurodegenerative diseases, especially Parkinson’s disease (PD). Apart from PD, Mucuna pruriens is now being studied in models of other nervous system disorders such as Alzheimer’s disease (AD), Amyotrophic lateral sclerosis (ALS), and stroke because of Its neuroprotective importance. This review briefly discusses the pathogenesis of PD, AD, ALS, and stroke. It aims to summarize the medicinal importance of Mucuna pruriens in the treatment of these diseases and put Forward the potential targets where Mucuna pruriens can act for therapeutic interventions. In this review, the Effect of Mucuna pruriens on ameliorating the neurodegeneration evident in PD, AD, ALS, and stroke is briefly discussed. The potential targets for neuroprotection by the plant are delineated, which can be studied further. To validate the hypothesis regarding the use of Mucuna pruriens for the treatment of these diseases.

Pharmacology Use of Mucuna Pruriens:-

Parkinson’s disease:-

Parkinsonism is treated by the administration of powdered seed of M. pruriens containing 4 to 6% of levodopa. 19.29 For the dose, M. pruriens showed twice the anti-Parkinsonian activity of synthetic L-DOPA. 19.30 Clinical study revealed the contribution of L-DOPA in the recovery of PD followed by Ayurveda medication. 19. 31 30 g Mucuna seed powder preparation has considerable faster action in treating PD patients than conventional standard drugs, namely, Levodopa or Carbidopa and suggested that natural source of L-DOPA might possess advantages over conventional drugs in long term management of PD. 19.31 M. pruriens cotyledon powder significantly increased the brain mitochondrial complex-I activity but did not affect the total monoamine oxidase activity (in vitro) as having Nicotine adenine dinucleotide (NADH) and coenzyme Q-10 in the cotyledon powder which are shown to have a therapeutic benefit in Parkinson’s disease. Unlike syntheticlevodopa treatment, M. pruriens cotyledon powder treatment significantly restored the endogenous levodopa, dopamine, norepinephrine and serotonin content in the substantianigra.Clinical study confirmed the efficacy of the M. pruriens seeds in the management of Parkinson’s disease by virtue of their L-DOPA content. M. pruriens has been shown to increase testosterone levels Seeds of M. pruriens contain high levels (1-6%) of L Dopa (L-3,4-dihydroxyphenylalanine ; a precursor of dopamine used in the treatment of Parkinson’s disease.

Clinical Studies & Human Trails:-

Recently. Cilia et al. (2017) have performed the clinical trial of Mp in PD patients. They have suggested that Mp might provide an excellent option for PD patients who belong to low-income countries in the place of marketed standard L-DOPA as it can be tolerated for the long term without causing severe dyskinesia. As compared to dispersible levodopa/benserazide treatment, a single dose of Mp from roasted seeds shows potent anti-Parkinsonian activity in 18 advanced PD patients. A large sample size is needed to validate the findings regarding the anti-PD potential of Mp (Cilia et al. 2017).Another study done by Johnson et al. has suggested that Mp extract with reduced L-DOPA exhibits prominent neuroprotective activity in the PD model of Murine Microglia, Human Neuroblastoma Cells, Caenorhabditis elegans, and Drosophila melanogaster. Thus, L-DOPA is not only the main bioactive component in Mp which is responsible for its neuroprotective activity; but there might be some other key components that contribute to the activity in a synergistic way as well. Thus, Mp extract which contains reduced L-DOPA prevents the death of dopaminergic neurons in four different model system and clinical trial for the same is needed to justify this interesting finding (Johnson et al. 2018).Cilia et al. have further performed the clinical trial in 2018 to show the effect of Mp in PD patients and have shown that its daily intake for 16 days has significantly more beneficial effects with minimal side effects. In this study, quality of life along with the motor and non-motor symptoms was compared between standard L-DOPA and Mp treatment for 16 weeks in 14 PD patients. Similar to previous clinical trials performed by Cilia et al., this clinical trial also has a very low number of PD patients, and a large sample size needed to again justify the same (Cilia et al. 2018). Recently, a short communication demonstrated the combined potential of Mp and carbidopa in PD. This finding has shown that by adding a DDCI in Mp might result in a strong personalized alternative for PD patients who are Unwilling to start L-DOPA treatment (Radder et al. 2019).Major limitations in the above-discussed clinical trial regarding the anti- Parkinsonian activity of Mp are the sample size which was very small to apply for the general population. PD patients affected in different geographical region should be checked to prove the efficacy of Mp. Furthermore, the efficacy of Mp Should also be compared in different large-sized populations.

Safety, Toxicity And Side Effects Of Mucuna Pruriens In Neurodegenerative Disease Patient:-

Safety for certain conditions people with certain conditions may need to avoid Mucuna pruriens.

Safety during pregnancy and breastfeeding RIVM advises against using Mucuna Pruriens during pregnancy and breastfeeding. Safety for liver and kidney problems RIVM advises against using Mucuna pruriens supplements if you have liver or kidney problems. Safety when taking other medications -Mucuna pruriens can interact with certain medications, including those for depression, methyldopa, and levodopa. There is a risk of toxicity when using M. pruriens due to its L-dopa Content. In rare cases, toxicity may be Possible if you take too much M.Pruriens, use it for too long, or consume its raw seeds. The hairs on the seeds contain a compound called Mucunain, which may cause skin Irritation or tingling. Ingesting raw seeds may also lead to nausea, vomiting, diarrhea, and even amnesia. Although, this has only been reported in very rare cases.

Future prospects:-

Mucuna Pruriens   possesses strong anti-PD potential in toxin-induced PD models and also shows significant improvement in the clinical trial. Mp shows this potent anti-PD activity due to the high percentage of L-DOPA. Different parts of the Mp have been explored in different diseased conditions with significant outcomes. The major question toward the efficacy of different parts of Mp is the pharmacokinetic effects on different organs. Another advancement that is required is the complete identification of various bioactive components in different vital parts of Mp. A large sample size will be needed to justify and validate the anti-PD potential of Mp in clinical trials. Different community-wise studies are needed to compare the efficacy of different parts of Mp in PD along with in some other diseases. In addition, the anti-PD potential of various bioactive components of Mp’s also needed to demonstrate any mechanism of action behind it. Furthermore, the potential of Mp should be explored in various brain regions to see any side effects associated with the plant. Strong in vitro activity in different cell lines should be required to compare Mp’s potential with in vivo models. Nanomaterials should be made of different bioactive components of Mp and should be tested in various disease conditions. The half-life of different parts of Mp should be checked in the brain to demonstrate its efficacy and sustainability. Finally, Mp might be a novel and potential drug in the near future when the above-mentioned necessary formalities are conducted in different disease conditions and compared with positive controls and find any positive outcomes in long-term clinical trials with a large sample size. There is also a need to compare the neuroprotective activity of different extract of Mp as aqueous, ethanolic, methanolic, etc. in PD and some other neurodegenerative diseases. Also, the neuroprotective activity of Mp should also be compared to another herbal plant extracts like Ws and Bm, etc. This might surely help in the development of the novel drug from Mp. Besides, Mp also shows vital medicinal properties in some other diseases like ischemia, diabetes, cancers and also shows potent aphrodisiac activity. Thus, Mp might be a potent and magical compound which might be used in the future to treat multiple disease condition. There will be a strong need to explore the neuroprotective potential of Mp in other neurodegenerative diseases like Alzheimer’s and Huntington’s disease. Mp might offer strong herbal drug that can be used for the treatment of neurodegenerative diseases.

CONCLUSION:-

Thus the review of scientific data clearly indicates that Mucuna pruriens seeds contain various substances that possess antioxidant and neuroprotective activities that support the antiparkinsonian activity of levodopa. The review also emphasizes the importance of the holistic approach of Ayurveda in using the Mucuna pruriens in the treatment of PD. Further studies on these phytoconstituents to reveal their mode of action will help in understanding the treatment of PD.

ACKNOWLEDGMENT:

We are thankful to Arihant College of Pharmacy, Ahilyanagar. For providing us with the platform and infrastructure for preparing this article also thanks to our Principal Dr. Yogesh Bafana sir, and Assistant professor Mr. Swapnil Kale for their support and expert opinion during the writing process.

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