Various herbal remedies for the management of Parkinson’s disease: A Review

 

Mohammed Nazish Quasmi, Pooja, Sumit Kumar*

Department of Pharmaceutical Sciences, Central University of Haryana Mahendarghar -123031, Haryana, India.

 

ABSTRACT:

Parkinson's disease (PD) is a condition of neurodegeneration characterised by the decreased levels of dopaminergic neurons. Some of the physical issues with PD include resting tremors, stiffness, bradykinesia or akinesia, instability, and freezing. Damage to the brain's SN and other regions is present in PD. Reactive oxygen species are important and oxidative stress may be related to the disorder (ROS). There are active components in many herbal treatments that have been found to have antioxidant benefits. Therefore, the importance of herbal remedies in the management of PD cannot be undermind. The major goal of the current review is to examining the Parkinson’s disease pathogenesis (PD) and describes function of several potential herbal extracts on its pathogenesis, which may serve as the foundation for treatment. We also go into the chemical components that are present in each herb and useful in treating Parkinson's disease. These herbs are Mucuna pruriens (MP, kapikacchu), Centella asiatica (CA, Mandookaparni), Bacopa monnieri (BM, Brahmi), Cinnamomum verum (CV, cinnamon), Sida cordifolia (SC, bala), Juglandis semen (JS, walnut), Camellia sinens (CS, green tea), Curcuma longa (CL, turmeric), Withania somnifera (PL, kudzu). Future drug development for the successful treatment of PD may benefit from the findings of the current review.

 

 

 

INTRODUCTION: 

One percent of people over age 60 have Parkinson's disease (PD), the IInd most common neurodegenerative disorder¹. According to estimates, there were around one million cases of PD in the US in year 2017 with a $51.9 billion economic toll. In the report, Medicare programme bears the major portion of medical costs because most PD patients are over 65 and because it is predicted that more than 1.6 million people will have the disease and that the overall financial burden will reach more than $79 billion by year 2037². Parkinson’s disease is characterised by the symptoms like tremor, muscular rigidity, less movement of body, difficulty in balancing and walking, mental depression and dementia. It is brought on by the steady loss of nigrostriatal dopaminergic neurons and the reduction of dopamine in stratum³.

 

The origin and pathogenesis of Parkinson’s disease have not yet been completely understood. As of now no preclinical model for Parkinson’s disease has been able to reproduce all of the pathogenic aspects of the disease to far, but some models have greatly advanced our understanding of PD in humans. The dopamine transporter absorbs 6-OHDA and releases free radicals. Monoamine oxidase B (MAO B ) transforms MPTP into 1-Methyl-4-phenylpyridinium (MPP+), which is then taken by the dopaminegic transporter and build up in the mitochondria, inhibiting complex I and causing free radicals production⁴. Complex I direct inhibition by rotenone prevents the production of free radicals⁵. The evaluation of the effectiveness and adverse effects of drug therapies for Parkinson's disease In-vivo or In-vitro, may be done using C57/BL6 mice, SH-SY5Y cells, PC12 cells and C57/BL6 cells⁶. These models have been extensively studied and is used to induce cell death by causing nitric oxide, excitotoxicity, neuroinflammation and mitochondrial dysfunction have all been discovered⁷. The most neurotoxins to mimic Parkinson are: Rotenone, (MPTP) and (6-OHDA). Drugs can controls majority of symptoms; however no single medication is 100% efficient. The best PD treatments involve the usage of the dopamine precursor i.e. levodopa alone or with carbidopa or benserazide additional medications such agonists of dopamine, anticholinergic drugs or amantadine all of these medications can be found in synthetic form. It costs large amount of money to make these medications switching towards the herbal management may be more cost effective⁸. Ayurveda, which is a traditional Indian system of medicine, has a very unique approach to prevent, treat and management of various neurodegenerative diseases. According to Ayurveda, illnesses with symptoms similar to Parkinson's disease are known as "Vatavyadhi" includes Kampavata, which has temblors as its primary manifestation⁹. Whole systems approach, that is aspecialised, multidimensional therapy plan comprising different exterior therapies, internal drugs, and behavioural changes, is what Ayurveda recommends for PD. According to clinical research, Ayurvedic treatments can help people with Parkinson's disease¹⁰. The main herbal medication fot the  managment of Parkinson’s disease are Centella asiatica, Mucuna pruriens (MP, kapikacchu) (CA, Mandookaparni), Bacopa monnieri (BM, Brahmi), Cinnamomum Verum (CV, Cinnamon) Sida cordifolia (SC, Bala), Juglandis Semen (JS, Walnut), Camellia Sinenis (CS, Green tea), Curcuma longa (CL, Turmeric), Withania somnifera (WS, Ashwagandha) and Pueraria lobata ( PL, kudzu). The nootropic effect of these herbs has been shown in numerous independent clinical trials, as well as in vitro and in vivo research. These plants are also said to lessen the phenotype of neurological illness¹¹. Some cells line, small insects such as Drosophila melanogaster, Caenorhabditis elegans and some rodents are just a few of the model systems that are used to mimic PD biology and find possible therapeutics. Neurotoxins like 6-OHDA, aluminium, (MPP) iodide and paraquat are used to cause Parkinson like conditions. Other methods include modifying the utterance of proteins like LRRK2, PINK1and alpha synuclein¹².

 

Pathophysiology of parkinson’s disease:

There are two principal exit points from the striatum:

First one is indirect and is caused by inhibition of DA effect on D2 Dopamine receptors of striatal. The striatum in this pathway sends GABA-mediated signals to lateral GPe neurons that communicate with the STN, which in turn communicates glutamate-based excitatory impulses to the interior portion of the GPi and SN pars reticulata. GPi and SNr than inhibits the thalamocortical-spinal pathway and cause symtoms include stiffness and bradykinesia. The second pathway is the direct pathway, which is mediated by DA's excitatory action on striatal D1 Dopamine receptors. Deficiency of DA reduces the striatum's capacity to inhibit GPi and SNr¹³. Although the precise cause and mechanism of Parkinson's disease is unknown till date, but there has been considerable progress in knowing the disease's basic mechanisms¹⁴. This was achieved through genetics research and experimental methods of Parkinson’s disease. The pathophysiology of Parkinson's disease, the use of numerous herbal supplements, and their primary chemical components, structures, and mechanisms of action will all be discussed in this paper.

 

Pathogenisis of Parkinson’s disease:

Neurodegeneration linked to PD is already been started years before motor symptoms appear. The neuropathology of Lewy body formation and the loss of dopamine neurons in the SNpars compacta are the markers of Parkinson's disease (PD), which also affects many other CNS structures and peripheral tissues¹⁵. PD neuropathology is linked with various Toxins, medicines, pesticides, brain microtrauma, localised cerebrovascular injury, and gene abnormalities are examples of potentially pathogenic risk factors. In the midbrain, Lewy bodies are deposited. in a form of multisystemic alpha synucleinopathy causing Parkinson's disease¹⁶. In the midbrain, Lewy bodies are deposited in a form of multisystemic synucleinopathy causing Parkinson's disease. This neuropathological phenotype can be partially explained by the following descriptive phenomena: 1.genomic factors 2.toxic factors 3.epigenetic changes, 4. anomalies, 5.neuroinflammatory reactions 6.oxidative stress  7.hypoxic-ischemic conditions and 8.dysfunction of the ubiquitin-proteasome system, all of which result in protein misfolding and aggregation as well as early neuronal death^17,18. SNCA makes the protein alpha-synuclein

 

Figure 1: Parkinson’s disease Pathogenesis Current available drugs for PD

 

Table 1: Merits And Demerits of Drugs

Sr. No.	DRUG (s)	Merits	Demerits
1	decarboxylase inhibitor + dopa decarboxylase	·    The dopaminergic drug that may be most successful at relieving symptoms. ·    They are tolerated well	·     Motor Difficulties can occur
2	Ergot dopaminergic agonists eg. Bromocriptine and ropinirole.	·    Efficacy is good ·    Onset of   motor difficulties is delayed ·    Tolerated well	·     Can cause risks likes confusion, hallucinations, andbehavioural changes ·     It can cause cardiac valve fibrosis
3	Anticholinergics	·    Have low Parkinson inhibitory effect	·     Lesser side effects
4	MAO B inhibitor; selegiline, rasagiline	·    It improve motor activity in early and late disease ·    Easy to use ·    It’s Tolerated well	·     Low efficacy ·     Metabolized to amphetamine is the metabolites product of  Selegiline which can cause cognitive effects
5	Catechol-O-methyltransferase inhibitors eg. Entacapone,	·    It inc. half-life of  levodopa ·    Off time is reduced	·     It can damage liver ·     Diarrhoea can be caused
6	Amantadine	·    Low Anti Parkinsonian effect ·    Results in the Improvement dyskinesias	·     Results in Cognitive disturbances, peripheral oedema, livedo reticularis
7	Surgical Treatments	·    Might have high effectiveness with long time results	·     Some methods have side effects and are irreversible

 

Although the actual pathogensis of parkinson’s disease is not know till date but the advancements in treatmenting PD has made. Treatments aim to lower the symptoms instead of stop or sloweing disease's development because there is no known cure for the illness. Treatments can as medication, surgery, therapy or a combination of them are just a few examples of possible treatments shown in. Additionally, they shall be modified because some common medications, like Levo-DOPA, eventually lowers their efficacy after some period of time¹⁹. The use of currently available medications to treat Positive clinical effects are seen with PD, but there are no known disease modifying or neuroprotective treatments. are available to slow the disease's progression²⁰. Multiple neural pathways in the brain are impacted by PD. L-DOPA may be able to treat dopamine deficiency-related motor issues, but it cannot address acetylcholine deficiency-related issues in other pathways²¹. Although these drugs have some advantages but they also some disadvantages as shown in Table 1.

 

Herbal medicine and Parkinson’s Disease:

Many researchers in recent years has explored the use of various herbal treatments and natural items in the treatment of PD. Some herbal remedies has shown to be more reliable and effective than the typical synthetic medications²². We highlighted some of the natural herbs in this review, along with their main phytochemicals and structural components in Table 2, that may be useful in the management of PD symptoms.

 

1. Mucuna pruriens:

Mucuna pruriens belonging to the family Leguminosae has been the primary medicinal plant in India for three thousand years. More than 200 traditional medicinal preparations use all plant parts. Levodopa, used to treat Parkinson's disease, can be found in the seeds in concentrations of up to 7%. Studies have shown that taking velvet bean, which is recommended as an aphrodisiac in Ayurvedia increases testosterone levels, increases muscle mass and strength, and also enhances coordination and attention²³. Levodopa is present in significant amounts in Mucuna pruriens seeds. Mucuna pruriens has an endocarp that is 2-3 times more potent than synthetic levodopa and is non-toxic. By increasing the activity of the brain mitochondrial complex I and substantially reversing the levels of dopamine and nor-epinephrine in an animal model of Parkinsonism, Mucuna pruriens has also demonstrated to have neuroprotective effects²⁴.

 

Table 2: Phytochemicals And Structural Components Of Herbs

S. No	Herbal medicine	Chief Phytochemicals
1	Mucuna pruriens	Levodopa
2	Centella asiatica	Asiatic acid and Madecassic acid
3	Bacopa monnieri	bacosideA3
4	Cinnamomum Verum	cinnamaldehyde
5	Sida cordifolia	Phenylethanolamineand ephedrine
6	Juglandis Semen	Quercetin
7	Camellia Sinenis	Catechin
8	Curcuma longa	Curcumin
9	Withania somnifera	Withaferin
10	Pueraria lobata	Daidzein

 

2. Centella asiatica:

Centella asiatica of the apiaceae family is widely distributed throughout the globe. This plant's extract has been used in Indian medicine for a variety of ailments including ulcers, body aches, wound healing, skin disorders, and asthma. Additionally, the plant extract exhibited central nervous system depressant properties and fibroblast biosynthetic activity inhibition²⁵. Recent studies have established the anti-lipid peroxidative and free radical scavenging properties of Centella asiatica. Triterpenes and polyphenols make up the majority of the extract of Centella asiatica's active ingredients. According to reports, triterpenes like asiatic acid and high polyphe- nolic contents help this plant extract's antioxida-tive properties²⁶. Earlier clinical studies have demonstrated the extensive therapeutic benefits of Centella asiatica and its triterpenoids in treating neurological and skin conditions. They showed anti-inflammatory, anti-oxidative stress, anti-apoptotic, and mitochondrial function improvement effects²⁷. Kainic acid induced toxicity in rats seizures has been shown to be prevented by the Centella asiatica extract, asiatic acid, which also increased synaptic activity, and reduced cognitive limitations²⁸. Asiaticoside, a Centella asiatica chemical components, was discovered to prevent, A-beta caused neuronal apoptosis by restoring and sustaining mitochondrial membrane potential²⁹. Additionally, it has been discovered that Centella asiatica extract protection against locomotor impairment, dopaminergic neuronal death and lipid peroxidation in rats with parkinsonism brought on by rotenone. The neuroprotective effects were associated with increased production of anti-oxidant enzymes and preservation of mitochondrial complex-I activity, which controls the rate-limiting phase in oxidative phosphorylation³⁰.

 

3. Bacopa monnieri:

Bacopa monnieri, a member of the Plantaginaceae family, has been known as Brahmi since ancient times and is more widely known as Water hyssop. From ages Assamese locals have utilised brahmi to alleviate memory loss²³. Bacosides A and B are present in Bacopa monnieri in active fractions, with other chemicals components like  glycosides, saponins, flavonoids, alkaloids and others³¹. Evidence from recent studies on BM suggests that the potential neuroprotective lead exhibits Neuroprotection by antioxidants via redox and enzyme activation, reduction, and free radical removal, metal ions and lipid peroxidation inhibitory activities; acetylcholinesterase inhibition and/or choline acetyltransferase activation, reduction of beta amyloid, improved Modulation of neurotransmitters and cerebral blood flow^32,33. The triterpenoid saponins and related bacosides in Bacopa are responsible for its ability to increase nerve impulse transmission.. By promoting kinase activity, neuronal formation, the recovering activity of synapse, and eventually transmission of nerve impulse, the bacosides help restore injured neuron³⁴.

 

 

bacosideA3

  

             Madecassic_acid                                   Catechin

 

    

          Cinnamaldehyde                               cinnamaldehyde

 

      

                 Quercetin                                            Levodopa

 

  

                     Daidzein                                         Phenylethanolamine

 

 

                                                           Withaferin

 

4. Cinnamomum verum:

With about 250 species, cinnamon is one of the oldest genera of tropical plants belonging to the  family Lauraceae³⁵. Cinnamomum has two primary species: Cinnamomum verum and Cinnamomum cassia⁴. Various cinnamon tree parts, including the leaves, barks, roots, flowers, and fruits, have been used traditionally as medicines³⁶. One of the primary species of the Cinnamomum genus that is frequently utilised as a medicinal plant is Cinnamomum verum³⁷. Different elements of this plant have amazing pharmacological effects on human health as well as historical uses as traditional medicines³⁸ One of the main constituents of Cinnamomum verum and its essential oil is Cinnamaldehyde. That has been found to have potent anti-oxidant properties. In addition, a recent study using the SH-SY5Y cellular model of oxidative stress demonstrated that cinnamaldehyde has neuroprotective effects against H2O2-induced cell death³⁹. In MPTP model of  mice, Cinnamomum possesses antiparkinsonian effects. 100µl of cinnamon powder dissolved in 0.5 percent methylcellulose (MC) was administered to mice. The results suggest that cinnamon can be used in the managment of PD⁴⁰.

 

5. Sida cordifolia:

Sida cordifolia, a member of the Malvaceae family, is a significant Rasayana herb in the Ayurvedic medical system. Vasicine, vasicinol, Asparagin, hypaphorine, ephedrine, vasicinone and as well as The chemical components of the plant are  Mucin,phytosterols, potassium nitrate and gelatin⁴¹. Aa per⁴² study this plant exhibits strong antioxidant activity in  In-vitro and In-vivo. Anti-peroxidative and Anti-inflammatory activity of Sida cordifolia on neurotoxicity caused by quinolinic acid has been documented by⁴³. Additionally, it is stated in the  ayurvedia this plant may be used to treat nerve illnesses like hemiplegia, facial paralysis, and Parkinson's disease⁴⁴.

 

6. Juglandis semen:

The Juglans regia’s seed  which belongs to the family Juglandaceae is known as Juglandis Semen(JS), and it’s both popular food as well as useful herb⁴⁵. A polyphenol-rich extract of JS was found to reduce oxidation by low density lipoproteins and to increase osteoblast activity in the human cells of aortic endothelial, according to earlier research⁴⁶. Additionally, JS prevented the metabolic damage that cyclophosphamide-induced in the mouse liver and kidney⁴⁷. The Monoamine oxidase-B functioning in C6 astrocyte cells from rats was dramatically reduced by the JS-rich caffeine, along with this derivatives of phenethyl ester prevented 6-hydroxydopamine from inducing degeneration of neurons⁴⁸. Levels of Nitric oxide, tumour, inducible nitric oxide synthase and necrosis factor in lipopolysaccharide stimulated mice cells of microglial were found to be reduced in earlier research on the neuroprotective effects of Juglandis Semen⁴⁹. In seizures induced by pentylenetetrazol, JS displayed anticonvulsant and neuroprotective properties⁵⁰. Additionally, in a transgenic model of mouse Alzheimer's disease (AD), Juglandis semen and 3 fatty acids reduced memory deficits induced by Amyloid beta fibrils and prevented hippocampus cell necrosis through Calcium dysregulation caused by LPS^51,52.

 

7. Camellia sinenis:

Camellia sinenis belong to family Theaceae commonly known as green tea. Green tea has several health advantages for a wide range of conditions, including cancer and weight loss, have garnered substantial attention worldwide⁵³. Green tea contains a number of polyphenolic catechins, epigallocatechin-3-gallate is the most prevalent, making up 65% of the beverage's total catechin content⁵⁴. It is most likely the source of green tea's medical effects. Camellia sinenis along with its chief components are recognised for strong anti-oxidant qualities, which have led to clinical investigations in diseases like cancer or cardiovascular and neurological diseases that are linked to reactive oxygen species⁵⁵. Epigallocatechin gallate and other polyphenols have been shown to have neuroprotective characteristics as a result of their anti-inflammatory and antioxidant actions, which may account for their advantages in treating neurodegenerative illnesses⁵⁶. There is limited information on green tea's polyphenols and their effects on Parkinson's disease in the literature of⁵⁷ the most of studies use in vitro models or focus on the positive effects of green tea consumption on Parkinson's disease patients⁵⁸

 

8. Curcuma longa:

Curcuma longa belongs to  Zingiberaceae family. From centuries in India it is used as a traditional medicine as well as for flavouring and food processing⁵⁹. Rheumatism, eye infections, and liver issues have all been treated for a very long time using turmeric⁶⁰. The active component of turmeric, curcumin, possesses anti-inflammatory, antioxidant, and anti-apoptotic characteristics that it protect tissues by damaging effects of reactive oxygen species⁶¹. The antioxidant effects of curcumin are assumed to be caused by the moiety of phenol, that transfers  proton to reactive oxygen species⁶⁰. Additionally, curcumin inhibits monoamine oxidase B and A53T-synuclein aggregation, making it a substance of interest for the managment of Parkinson's^62,63. Animal models have shown that curcumin can prevent damage to nigrostriatal dopaminergic neurons. Following the injection of (6-OHDA) to rats or mice, curcumin at 200 mg/kg dose demonstrated alpha7 nicotinic acetylcholine receptor protection⁶⁴.

 

9. Withania somnifera:

Withania somnifera commonly known as Aswaghanda of family Solanaceae is a plant-derived neuroprotective agent. It is thought to promote better sleep by lowering stress. Withaferin-A and withanolide-A, its two main biologically active components, have demonstrated pro-dopaminergic and neuroprotective effects in PD⁶⁵. It is used to treat a variety of clinical conditions, including improving cognitive function, lowering level of blood sugar, managing depression, lowering stress, and improving energy levels. This medicinal plant has been touted as being helpful against epilepsy, inflammation, arthritis, depression, coagulation problems, free radicals, diabetes, and pyrexia in addition to benefits, such as its analgesic, rejuvenating, and growth-promoting characteristics. Withania somnifera has the ability to reduce ROS, reduce inflammation, increase mitochondrial activity, control apoptosis, and enhance endothelial function by boosting the immune system, which contributes to these therapeutic actions⁶⁶.

 

10. Pueraria lobata:

Pueraria lobata belongs to the family Leguminosae. Daidzein is its main phytochemical. It has been used extensively in clinical practise for years in china as a antioxidant to lessen neuronal damage and in the treatment of cerebrovascular illnesses and cardiovascular disorders⁶⁷. Free radicals play a role in cell death in cardiovascular and cerebrovascular disorders. Similar to Parkinson's disease, oxidative stress is linked to the production of intracellular stressors that may facilitate the processes leading to the death of dopaminergic cells. These results imply that puerarin possess the ability to defend dopamine neurons and slowers process of neurodegenerative in Parkinson's disease via antioxidative mechanisms⁶⁸. Puerarin reduces the ratio of caspase-3 to bcl-2/bax activity. Puerarin may boost the protein expression of DJ-1 and superoxide dismutase-2, according to results of another investigation. Tyrosine hydroxylase (TH)-positive neurons are not damaged by 6-OHDA, and the contents of DA and its metabolites are restored by puerarin²².

 

CONCLUSION:

For the complex disorder like Parkinson's disease (PD), there are numerous targets. In general, a single component only affects one or a small number of targets, making it challenging to permanently and consistently regulate a complex disease. By using herbal formulations work can be done on several targets and control can be achieved on a complex disorder i.e. PD. Well since herbal medications are less costly than synthetic and standard medication for the treatment of Parkinson also these herbal medications have less toxicity than standard medications so switching toward herbal remedies can be beneficial for the patients. In this review we have summarized 10 different herbal remedies that are promising in the management of PD. Future clinical research will be conducted to treat PD, one of the most serious neurodegenerative disorders.

 

CONFLICT OF INTEREST:

The authors have no conflicts of interest regarding the investigation.

 

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Accepted on 27.12.2023           © RJPT All right reserved

Research J. Pharm. and Tech 2024; 17(2):963-970.