INTRODUCTION:

Neurodegenerative conditions include Alzheimer's Disease, Parkinson's Disease, Multiplie Sclerosis lead to gradual neuronal death, including memory loss and sensory impairment. Alzheimer's disease is thought to be caused by the classic triad of senile plaques, neurofibrillary tangles, and granulovascular degeneration. Memory loss, difficulties understanding and remembering new knowledge, depression symptoms, aggression, anxiety, and vision disturbances are also the diagnostic traits.¹

Neuroprotection extends to both acute and progressive neurodegenerative diseases e.g., Alzheimer's and Parkinson's disease, relative processes able to support the central nervous system (CPS) from neural damage. Herbal medicine, along with balanced lifestyles including proper eating patterns and moderate physical activities, can be a beneficial resource in prevention rather than occurrence of diseases. Herbal treatment or simply plant therapy refers to the use of plant organs for their health purposes as a supplementary and alternative remedy (leafs, branches, roots, bulbs, fruits and seeds).^1-3

In light of the above, a thorough review of the herbal ingredients recommended in Ayurvedic text in the treatment of nervous system disorders related to above diseases has been mentioned.

METHODOLOGY

The information for this study was gathered from ancient ayurvedic classical text and also databases such as PubMed, Web of Science, Google Scholar and Scopus were thoroughly scrutinized. A meticulous data was evaluated related to herbal plants having neuroprotective behaviour and behavrioul changes, oxidant/anti-oxidant parameters, and pro-inflammatory cytokines, in vitro studies, animal studies, review papers, and clinical studies related to them were included.

NEURO PROTECTIVE HERBAL PLANTS

Ayurveda is a diverse and ancient knowledge structure that incorporates philosophy, theology, and science (medicine) into everyday life. It is based on three basic concepts, or doshas, vata, pitta, and kapha, which regulate all cellular processes that are necessary for living a healthy life. Vata is in charge of activity and events, pitta of health and resources, and kapha of development and systemic modification. When these values are disrupted, such as by a poor diet or an unfavourable climate, the person develops diseases.³

Guduchi (Tinospora cordifolia)

In certain people, sleep deficiency (SD) causes a variety of mood disturbances such as anxiety, cognitive dysfunctions, and muscle control disability. In one of thestudy it was seen that whether a 50% ethanolic extract of Tinospora cordifolia (TCE) could reduce the negative consequences of SD. Adult Wistar female rats were evaluated behaviorally for cognitive abilities, anxiety, and motor control in three groups: (1) vehicle treated-sleep undisturbed (VUD), (2) vehicle treated-sleep deprived (VSD), and (3) TCE treated-sleep deprived (TSD). When compared to VSD animals, TSD animals displayed better behavioural response in the EPM and NOR tests for fear and cognitive functions, respectively. Stress-induced proliferation of plasticity markers PSA-NCAM, NCAM, and GAP-43, as well as proteins are involved in LTP maintenance, is modulated by TCE retherapy. TCE, alone or in collaboration with other cognition strengthening agents, can aid in the management of sleep deprivation-related stress and the improvement of cognitive abilities, according to this research.⁴

Ayurvedic formulations are said to have life-enhancing properties that improve the body's ability to resist stress and cope with adversity. Ayurvedic formulations such as Guduchi (Tinospora cordifolia) and Madhuyashti (Glycirrhiza glabra) are believed to have immunomodulatory, intellect-enhancing, and adaptogenic properties, encouraging good health and safe ageing. Using a Drosophila model the effectiveness of Guduchi and Madhuyashti in providing stress resistance and the underlying mechanisms was evaluated.⁵

One research reports that in primary cerebellar neurons, the monosodium salt of glutamate was used to cause neurotoxic damage. From fractionation of a previously published aqueous ethanolic extract of T. cordifolia, four extracts were obtained and tested for neuroprotective activity: hexane extract, chloroform extract, ethyl acetate, and butanol extract. Butanol extract of T. cordifolia (B-TCE) was shown to be the most neuroprotective of the four fractions, avoiding glutamate-induced neurodegeneration. Immunohistochemistry and Western blotting were used to look at the expression of various synaptic, apoptotic, inflammatory, cell cycle regulatory, and plasticity markers. Main explant cultures, wound scrape, and the gelatin zymogram assay were also used to investigate neurite outgrowth and migration. B-TCE pretreatment of glutamate-treated cultures normalised stress-induced downregulation of neuronal markers (MAP-2, GAP-43, NF200) and anti-apoptotic marker (B-TCE) expression (Bcl-xL). B-TCE was found to stimulate cerebellar neuron proliferation, migration, and plasticity, which was previously inhibited by glutamat. B-TCE pretreatment of glutamate-treated cultures normalised stress-induced downregulation of neuronal markers (MAP-2, GAP-43, NF200) and anti-apoptotic marker (B-TCE) expression (Bcl-xL). These findings indicate that B-TCE could have neuroprotective and neuroregenerative properties in the face of glutamate-mediated toxicity, and that it may be a promising therapeutic target for neurodegenerative diseases.⁶

A research quotes that Ayurvedic drug formulations Tinospora cordifolia (Tc) and Phyllanthus emblica (Pe) affected learning and memory in mice with and without Bhavana samskara. Mice administered with all the medications demonstrated a tendency towards reducing transmission latencies, but with comparable vehicle control values. A substantial decrease in latency of transfer was found in all drug-treated categories after 24 hours. Both formulations were compared to individual plant drugs Tc and Pe to improve learning and memory. The plant medications demonstrated learning and memory changes. In comparison to individual agents the fixed-dose formulations of Bhavana samskara had promising effects, but the difference was not statistically important. However, these medicinal products displayed better results than current medicinal products, so their therapeutic potential as nootropics must be further investigated.⁷

An intensive research Explores Bhavana samskara using Tinospora cordifolia and Phyllanthus emblica combination forlearning and memory in mice. Five groups of animals were used: sham controlled, negative control, positive control (levodopa 6 mg/kg), and two study groups (n = 6 each). For 30 days, the experimental groups were given 200 and 400 mg/ kg of TCEE by oral gavage. The researchers looked at biochemical parameters like dopamine levels, oxidative stress, complex I function, and the brain iron asymmetry ratio, as well as locomotor activity like skeletal muscle coordination and catatonia. As compared to the negative control sample, TCEE at 200 mg/kg (1.57 0.18) and 400 mg/kg (1.11 0.15) greatly reduced iron asymmetry ratio. Reduced oxidative stress and restored locomotor function in therapy units backed up TCEE's neuroprotection. The findings suggest that TCEE protects dopaminergic neurons and reduces iron accumulation in 6OHDA-induced PD.⁸

Kapikachhu (Mucuna pruriens)

MPEP (Mucuna pruriens endocarp powder) contains a number of compounds, including natural LD (levodopa), and has been shown to be free of drug-induced dyskinesias. In hemiparkinsonian (HP) monkeys, firstly comparison was MPEP with and without carbidopa (CD), as well as LD+CD. Parkinsonism was enhanced by each therapy. To assess basal ganglia circuitry alterations, the neuronal firing properties of the substantia nigra reticulata (SNR) and subthalamic nucleus (STN) in HP monkeys with MPEP+CD and LD+CD were compared. In comparison to the HP state, both treatments reduced SNR firing rate. However, LD+CD treatments increased SNR bursting fire behaviors in a manner that MPEP+CD treatments did not.

STN shooting properties did not change significantly. The results of an MPEP water extract were then analysed. Oral MPWE improved parkinsonism without inducing dyskinesias caused by the treatment. In the basal ganglia the distinctive neurophysiological results and the capacity to improve parkinsonism without cause dyskinesies indicate strongly that Mucuna pruriens works using new and unique mechanisms from LD.⁹

In a study, The MPTP-induced neurotoxicity is substantially alleviated by a Mucuna pruriens extract treatment containing L-DOPA and a mixture of rich novel phytochemicals through the NF-kB and pAkt pathways. The results show that MP extract may have reduced MPTP-induced neuroinflammation, restored biochemical and behavioural abnormalities in PD mice, and thus established a theoretical foundation for its traditional use.¹¹

One of the study was planned to see if Mucuna pruriens (MP), a levodopa-containing leguminous plant that grows in all tropical areas around the world, could be used as an alternative source of levodopa for people with Parkinson's disease (PD) who can't afford long-term treatment with commercially available levodopa preparations. Single dose of MP powder made from roasted seeds without any pharmacologic processing was prepared. Eighteen patients with advanced Parkinson's disease were given the following therapies in a randomised order: (1) levodopa dispersible LD1DDCI; the reference treatment; (2) high-dose MP (MP-Hd; 17.5 mg/kg); (3) low-dose MP (MP-Ld; 12.5 mg/kg); (4) prescription preparation of LD without DDCI (LD2DDCI; 17.5 mg/kg); (5) MP plus benserazide (MP1DDCI; 3.5 mg/kg); (6) placebo. The length of on state and the improvement in motor response at 90 and 180 minutes were the efficacy outcomes. Any adverse event (AE), increases in blood pressure and heart rate, and the seriousness of dyskinesias were all taken into account as safety steps. MP-Ld showed a similar motor reaction to LD1DDCI, less dyskinesia and EI, although 90-180 minutes improved motor strength, longer ON time, and less dyskinesia were caused by the MP-Hd. Less AEs than LD1DDCI and LD2DCI were induced by MP-Hd. No cardiovascular reaction variations have been noted. In contrast to dispersible levodopa/benserazide, single-dose MP intake met both noninferiority efficacy and safety outcome tests. High-dose MP clinical results with more favourable tolerability profile were comparable to levodopa alone at the same dose.¹¹

Mucuna pruriens contains water-soluble ingredients that have DDCI-like activity or reduce the need for a second DDCI to treat parkinsonism. The long-term antiparkinsonian effects of a parenterally administered water extract of Mucuna pruriens seed powder could pave the way for new drug discoveries and treatment strategies for Parkinson's disease.¹² M. pruriens seeds extract (MPE) 40 g/mL reduced the precipitation of innate negative geotaxis activity in D. melanogaster by 35.3 and 32.8 percent respectively, when dopaminergic neurotoxins (6-OHDA and rotenone) were used. MPE, in addition to L-dopa, produces bioactive compounds that may have neuroprotective properties against PD.[13] Fruit fly Drosophila melanogaster (Dm) mutant for PTEN-induced putative kinase 1 (PINK1B9) gene is a powerful tool to investigate physiopathology of Parkinson’s disease (PD). Mpe has several sites of action, implying that its effects are not solely dependent on its L-Dopa material. These findings support clinical observations of Mpe as an effective drug capable of delaying the onset of chronic L-Dopa-induced long-term motor complications. Overall, this finding support the use of PINK1B9 Dm as a translational model to investigate the properties of Mucuna pruriens for the treatment of Parkinson's disease.¹⁴

A randomised, controlled, double-blind crossover trial involving eight Parkinson's disease patients with a short-term L-dopa response and time dyskinesias was completed.T he clinical effects and pharmacokinetics of levodopa (L-dopa) after two separate doses of mucuna preparation were compared to normal L-dopa/carbidopa (LD/CD).The rapid ontake and longer term without any concomitant increase of dyskinesias for the formulation of mucuna seed powder indicate this natural source of L-dopa may have advantages in the long term management of PD over traditional L-dopa preparations¹⁵ Boiled and fermented seed n-propanol extract could have a stronger neuroprotective activity against dopaminergic neurons compared to the fresh seeds in a PD rat model.¹⁶

Shankhapushpi (Convolvulus pluricaulis)

In comparison to the scopolamine treated population, oral administration of CP extract (150 mg/kg) to scopolamine treated rats reduced increased tau protein and mRNA levels, accompanied by a reduction in AβPP levels levels. The ability of the extract to inhibit scopolamine neurotoxicity was also demonstrated at the microscopic level, indicating that it has neuroprotective properties. The fact that CP therapy reduced scopolamine's neurotoxic effects indicates that it has the ability to be a powerful neuroprotective agent.¹⁷

In one of the studies, Pretreatment with C. pluricaulis restored as well as controlled the antioxidant and apoptosis markers including SOD, CAT, p53, and caspase-3, prevented reactive oxygen species production and mitochondrial membrane depolarization. The flavonoids and polyphenols in C. pluricaulis are abundant, according to GC-MS analysis.¹⁸

Mandukparni (Centella asiatica)

The open field test and the water T-maze test were used to measure locomotor function, learning, and memory. Cresyl violet and apoptosis staining is used to look at improvements in neuronal cell morphology. In the same animals' hippocampus, we used immunohistochemistry to look at the expression of the glutamate AMPA receptor (-amino-3-hydroxy-5-methyl-4-isoxazole propionicacid) GluA1 subunit and the GABA receptor (-Aminobutyric Acid) subtype GABAA 1 subunit. The water T-maze results revealed that a 30 mg/kg dosage increased comprehension, memory, and the memory consolidation process substantially (p 0.05), but had little effect on reversal learning.¹⁹

Centella asiatica water extract (CAW) and some of the compounds present in it have been shown to increase dendritic arborization and synaptic differentiation in the presence of exposure, which may explain the cognitive benefits. Furthermore, since CAW and its constituent compounds strengthened these endpoints in neurons, these findings may indicate that the extract has therapeutic potential beyond Alzheimer's disease.²⁰ E. alsinoides and C. asiatica have been used as a neuroprotective agent in traditional Indian medicine, and they are promising in the treatment of inflammatory disorders, wound healing, and immunomodulatory action. Both herb extracts have a neuroprotective function due to the inhibition of AChE development and improved visual memory development.²¹

Haridra (Curcumin)

In a research it was shown that Faint stain neurofibrillary tangle of curcumin, its isoforms, conjugates and bio-available forms bind to fibrillar A ß plaques and CAA in post-mortem of alzheimers brain tissue. Since conjugates and bio-available curcumin derivatives have similar binding properties, curcumin may be a good choice for in-vivo diagnostics in Alzheimer's disease, such as retinal fluorescent imaging.²² Curcumin contains important anti-inflammatory and antioxidant effects which make it possible for many emerging diseases to be treated.²³

Curcumin pharmacology gives new insights into its medicinal ability and limitations in the treatment of neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease, as well as brain malignancies.²⁴ Curcumin also has anti-amyloidogenic properties and has an effect on the tau protein in the brain. Some findings reflect the potential of curcumin in neurodegenerative brain diseases as prevention and treatment agent²⁵ In various central nervous system (CNS) disorders like Parkinson's disease, Huntington disease, Alzheimer's syndrome, the curcumin nanoparticles and their potential mechanism(s) of action have been clarified²⁶

Curcumin, known as a TNFα blocker in various cell types and tissues, is chemically optimised to provide an injectable depot for the continuous local release of curcumin to treat neuroinflammation and combined with a heat sensitive polypeptide like elastin. ELPs are biopolymers successfully used in various applications as drug carriers and biomaterials.

Strong drug loads, rapid releases of curcumin in vitro via degradable carbamate bonds, and sustains in vitro bioactivity against TNFα-induced cytotoxicity and monocyte activation were demonstrated in ELP curcumin conjugates.²⁷ Curcumin is a pleiotropic molecule which not only binds and restricts the addition of the β-sheet conformations of the amyloid characteristic of many neurodegenerative disorders, but also restores inflammatory systems to homeostasis, increases thermal impact systems for improved clearing of toxic aggregates, scavenges and free radicals.²⁸

Amla (Emblica officinalis)

A study reports that the pharmacological activity of enhanced portions of Emblica officinalis (EOT) tannins, a fruit traditionally used over several decades for the treatment of numbers of disorders was assessed by inducing cognitive dysfunction in rodents, by the High Salt and Cholesterol Diet (HSCD), During Silicone trials, the E. tannins exhibited a strong affinity to Nrf2 receptors. The above-mentioned oxidative stress biomarkers, altered in the model community, and enhanced the success of rats in Morris water maze test. There was substantial growth in Nrf2 expression in hippocampal and cortical CA1 areas with the EOT supplementation. A new action mechanism for EOT (which clearly indicates the Nrf2–ARE pathway) shows the ability to be used for cognitive insufficiency therapy.^29-30

Yasti madhu (Glycrhiza glabra)

Glyccrhiza developed neuroprotective effects in rats and strengthened motor impairments and cognitive disorders with the suppression of microglia activation and proinflammatory induction of the cytokine in the postishemic brain with middle cerebral artery occlusion (MCAO). In this research, we studied whether Glycrhiza has a positive impact on neuronal death model caused by kainic acid (KA). Typical neuronal death in both the hippocampus CA1 and CA3 regions is causes by the injection of 0.94 nmole (0.2 μg) intracerebroventricular (i.c.v) KA.In combination with these findings, it gives neuroprotection in the anti-inflammatory and anti-excittoxic properties of the KA-treated brain.³¹

One research stated that the protective effects of HypoE22 cells and isolated rat striatum specimens with 6-hydroxydopamine have been investigated for V. faba, U. rhyncophylla and G. glabra water extracts. Extract actions were tested with either a single extract treatment (LDH), nitrites or 8-IsO-Prostaglandin (PG)F2_ or a pharmacology association treatment. The pharmacology of these extracts are mostly effective in examining the increased levels of LDH and nitrite and in the reduction of striatal DA turnover.³²

Neem (Azdirachtica indica)

In an intensive study it was found out that the Azadirachta indica (AI) has analgesic, antiviral and antioxidant characteristics. Evaluation of the neuroprotective effect of standardised AI extract in animal neuropathy models caused by partial sciatic nervous binding; (PSNL). PSNL was induced with close ligation of nerve in male Wistar rats (180-200 g). Rats have been treated for 28 days with either the vehicle, that is to say, Pyridoxine (100 mg/kg, p.o.) or AI (100, 200 and 400 mg/kg, p.o.). Cytometrically, AI (200 and 400 mg/kg) therapy showed that neural and reactive oxygen levels were greatly reduced. In addition, AI therapy has reduced PSNL mediated histological aberration. Azadirachta indica exercises neuroprotection against neuropathic pains caused by the PSNL.³³Chronic hyperglycemia allows nerves to feel more compressive, often due to oxidative stress caused by hyperglycemia. Oxidative tension affects nerve activity and retards regeneration of nerves. Anti oxidant and anti-diabetic properties of A. indica floral extract has been proven for functional healing from a diabetes mellitus diabetic nerve crush wound in rats (DM).³⁴

CONCLUSION:

Alzheimer's disease and other dementias are being epidemics. Symptomatic therapies could not control them successfully. Two core-acting medicinal products, tacrine and donepezil, are now used to improve the amount of acetylcholine in the brain. Many herbs of ethno-medicinal and ayurvedic origin have been investigated in the treatment of AD for their experimental ability. In the management of AD one can be use a sensible mix of Ayurvedic methodology and established herbs of varied origins. About the fact that the number of studies published is limited, all of the bioactive compounds mentioned have shown to have a major neuroprotective effect in Parkinson's disease models. As a result, bioactive compounds derived from natural products can be used as a valuable source of anti-Parkinsonian medicines. More systematic study focusing on identifying active ingredients in plants and studying their mechanisms of action is needed by the scientific community. Clinical trials assessing the potential of the featured herbal products in dementia care would be aided by this study and may contribute to the discovery of novel dementia therapeutics.

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Received on 07.05.2021 Modified on 10.05.2021

Res. J. Pharmacology and Pharmacodynamics.2021; 13(2):69-74.

DOI: 10.52711/2321-5836.2021.00015