Rohan R.Vakhariya*, Swati S.Talokar, Dr. V. R. Salunkhe, Dr. C.S. Magdum
Rajarambapu College of Pharmacy, Kasegaon. Tal- Walwa, Dist- Sangli, Maharashtra.
People with mild cognitive impairment have problems with memory, language, thinking or judgment that are greater than the cognitive changes associated with normal aging. Cognitive disorders can be objectively measured in cognitive tests, but the changes in cognitive abilities are usually not serious enough to interfere with daily life and independence. A person with cognitive impairment has an increased risk of developing Delirium, Dementia Alzheimer’s disease and Amnesia, but some people with cognitive impairment remain stable and others show improved cognitive abilities over time. There is no proper cure for the cognitive disorders and much of the treatments available have been able to only delay the progression of the disorders or provide symptomatic relief for a short time period. Therefore there is need for a different approach to the treatment of these cognitive disorders. Different medicinal plants have been used since ancient times in the treatment of various cognitive disorders. Therefore pharmacological screening of medicinal plants may provide useful leads in the discovery of new drugs for the treatment of cognitive disorders. Variety of medicinal plants which can be used in cognitive enhancement is reviewed in this article. Phytochemical substances such as alkaloids, curcuminoids, triterpenoids and withenolides with pharmacological activities related to cognitive disorders treatment are discussed in this review.
Cognitive disorders are a category of mental health disorders that primarily act learning, memory, perception, and problem solving, and include amnesia, dementia, and delirium. Anxiety mood and psychotic disorders are also believed to have an effect on cognitive and memory functions. Most of these disorders cause damage to the memory portions of the brain.
Treatments depend on how the disorder is caused. Medications are most common mode of treatment. However, for some types of disorders such as amnesia, treatments can suppress the symptoms but there is currently no cure.
1. Cognitive mental disorder perspective:
Cognitive disorders1 are generally considered mental disorder that develops on the basis of cognitive mental disorder perspective. These perspectives a theory which describes that psychological disorder originate from an interruption in basic cognitive functions. The major cognitive function includes memory processing, perception, problem solving and language.
Diagnostic and Statistical Manual of Mental Disorders have described 250 disorders and their symptoms. Cognitive disorders are classiﬁed under a psychological disorder in axis I. Cognitive disorders are described as “a signiﬁcant impairment of cognition or memory that represents deterioration in previous level of functions”. The three main areas of cognitive disorders are delirium, dementia, and amnesia. There are many sub categories in each of these areas as well.
2. Cognitive disorders:
A brief introduction of some of the cognitive disorders are given below-
Delirium is a state of mental confusion when a person is medically unwell. It is also known as acute confusional state. Medical problems, surgery and medications can all cause delirium. Delirium often starts suddenly, but enhances when the condition causing it increases. It can be frightening not only for the person who is unwell, but also for those around the patient.
Signs and symptoms:
· Less awareness of surrounding
· Unsure about activities happening around patient
· Unable to follow a conversation
· Dreams which may often be frightening and may continue when you wake up
· Hear random noises or voices when there no one to cause them
· Worry that other people are trying to harm you
· Restlessness and insomnia
· Sleep during the day but wake up at night
· Frequent changes in the mood
· Urine or chest infection
· High body temperature
· Side-effects of pain killers ,steroids etc
· Imbalance of vital constituents
· Liver or kidney disorders
· drugs or alcohol rehabilitation
· Major surgery and epilepsy
· Brain injury or infection
· Terminal illness and constipation
There is often more than one cause and sometimes the cause is not found.
Dementia is loss of the ability to think, remember, or reason. Dementia hampers behavioral abilities to such an extent that it interferes with a person’s daily life and activities.
Signs and symptoms of dementia result when healthy neurons lose connections with other brain cells and die. Everyone loses some neurons as they age but the people with dementia experience far greater loss.
Signs and symptoms2:
· Core functions of brain must be impaired. These functions include memory, language skills, visual perception, and the ability to focus and pay attention. The loss of brain function is severe enough that a person cannot perform its everyday tasks.
· Some people with dementia cannot control their emotions. Their personalities may change. They can have delusions. Delusions are strong beliefs which does not have any proof .They also may hallucinate.
· Vitamin B12 deﬁciency
· Lyme disease
· Alzheimer’s disease
Amnesia refers to the loss of memory. Memory loss may result from bilateral damage of the brain which is vital for memory storage, processing, or recall. Amnesia can be a symptom of several neurodegenerative diseases. People whose primary symptom is memory loss may be aware that they are suffering from a memory disorder.3
Signs and symptoms:
· People with amnesia have a distorted perception regarding their identity, body, and life that makes them uncomfortable. Symptoms may be temporary or persist or recur for many years. People with the disorder face difficulty while describing their symptoms and may believe that they are going crazy.
· Depersonalization disorder can be a minor, passing disturbance on behavior. Some people can adjust to it or even block its impact. Others are continuously surrounded with anxiety over their state of mind.
· Brain injury related to physical trauma
· Disease, Drug and alcohol abuse
· Reduced blood flow to the brain
· damage to the memory centers of the brain results from the use of alcohol
· Infections that damage brain tissue
2.4 Alzheimer’s disease:
Alzheimer’s disease is an irreversible, progressive brain disease that slowly destroys memory and thinking skills and eventually even the ability to carry out the simplest tasks.
Alzheimer’s disease (AD) is the most common form of the dementia which occurs among people above the 60 years of age. The Alzheimer’s disease was once considered as a rare disorder and is now seen as a major health problem that is seriously affecting millions of older people all over the world.
Stages of Alzheimer’s disease4:
Early stage of Alzheimer’s
· Forgetfulness, forgets names of family or friends
· Some confusion in situations outside the familiar environment
Middle stage Alzheimer’s
· Greater diﬃculty remembering recently performed activity
· Deepening of confusions
· Troubles in identification of surroundings
Late stage Alzheimer’s
· Poor ability to think
· Problems during speaking
· Repetition of conversations
· More abusive, anxious behavior
The cause for most Alzheimer’s cases is still unknown except for 1% to 5% of cases where genetic differences have been identiﬁed.
Several causes of the Alzheimer’s disease are:
2. Cholinergic hypothesis
3. Amyloid hypothesis
4. Tau hypothesis
3. Herbal Remedies to deal with cognitive disorders:
Herbal remedies for Cognitive disease have become more and more popular in the recent years. Many natural herbal treatments have been researched and the benefits derived from using herbal treatments for these diseases have been very promising. Medicinal herbs hold the key to the cure to this devastating disease. In addition, these herbs are inexpensive and can be easily obtained. research has been conducted world over to test the efficacy of this herbal medicine. Herbal products have been found effective as prescription drugs but also have a fewer side effects. Herbal supplements may be used as a substitute for pharmaceutical drugs or can be used in conjunction with the latter. In the present review, attempts have been made to present state of art of studies made on the role of few herbal medicines in the treatment and management of Cognitive disease.
3.1 Ginkgo biloba:
Synonym: Ginkgo tree, Maidenhair tree
Ginkgo biloba is an herbal medicine used in traditional Chinese medicine for treatment of a various ailments. It has been shown to reduce memory loss, enhance the brain activity and to slow down the degenerative effects of cognitive disorder.5 An extract of Gingko biloba has been found to slow the progression of Alzheimer’s disease (AD). The clinical studies have demonstrated that extracts of Ginkgo biloba provide therapeutic benefits to Alzheimer’s similar to prescribed drugs such as Donepezil or Tactrin. The gingkolides present in Ginkgo biloba posses’ activities such as antioxidant, neuroprotective and cholinergic activities. 120- 240 mg of G. biloba has produced significant effect in Alzheimer’s patients and this herbal drug has shown no significant adverse effect.6 Gingko biloba extract has been shown to prevent Beta Amyloid toxicity to brain cells which is a key part of the development of the disease.
3.2 Galanthus caucasicus:
Synonym: Galanthus nivalis
Galantamine is an alkaloid derived from the bulbs and flowers of Galanthus caucasicus (Caucasian snowdrop), Galanthus woronowii (Amaryllidaceae) and related genera like Narcissus7 Galantamine have shown to be efficacious in treatment of mild to moderate Alzheimer’s disease, Dementia and other memory impairments. This drug has been found to be a acetyl cholinesterase (AChE) inhibitor. Galantamine are supposed to relieve some of the symptoms of Alzheimer's. This drug has also been shown to modulate nicotinic Ach to increase acetylcholine release. From the data obtained from clinical trials of Galantamine it is observed that patients who received Galantamine 24 mg/d for six months had improved cognition. This study suggests that patients with mild AD may get benefit from Galantamine treatment.8
3.3 Withania somnifera:
Synonym: Ashwagandha, Indian ginseng, winter cherry
Withania somnifera (Ashwagandha) has been described as a nervine tonic in Ayurveda and that is why it is a common ingredient of Ayurvedic tonic. Tonics, rejuvenators and vitalizers of Ayurveda appear to induce immunity and longevity in the users. Withania somnifera has been shown to reverse neuritic atrophy and synaptic loss, which may lead to major neurodegenerative disorders. It improves growth of new dendrites of neurons. Glycowithanolides withaferin- A and sitoindosides VII-X isolated from the roots of Withania somnifera have been shown to reverse the cognitive defects in Alzheimer’s disease model.9
3.4 Bacopa monniera:
Synonym: Water hyssop, Herb of grace, Bramhi
Studies have shown that patients suffering from cognitive decline gain significant benefit from Bacopa monniera in terms of memory as well as in maintaining quality of life. Bramhi consist of specific component which has capability to prevent the process of early aging. It is proved to be useful in improvement of memory and intelligence, life prolongvity and maintaining good health. Bacopa has been described as one of most popular medhya drug (Noo-tropic agent) in ancient Indian Culture. This medicinal herb is used as a potent nervine and mental tonic which may be used for the treatment of neurological and mental disorders.10 Bacopa has also been shown to decrease AChE activity which explains that Bacopa might prove to be a useful memory restorative agent.11Studies on human subjects have demonstrated the potential of Bacopa monniera in the treatment of Neuritis.
3.5 Curcuma longa:
Synonym: Curcuma domestica, Turmeric
Chronic inflammation of nerve cells is found to be playing a major role in pathogenesis of cognitive disease. Curcumin has remarkable anti- inflammatory effects therefore it may cure Alzheimer’s disease. Curcumin has been found to improve neurological deficit. It causes decrease in mortality and reduces the water content in the brain. The studies conducted on Alzheimer’s disease mice model have shown that the levels of beta Amyloid in AD mice that were given low doses of Curcumin are significantly decreased as compared to those not treated with Curcumin .These experimental studies have also revealed that the low doses of Curcumin for longer period is more effective rather than high doses in combating the neurodegenerative process. It has been shown that the antioxidant and anti-inflammatory property of Curcumin may be useful to ease symptoms of disorder. Curcumin has been found to reduce the level of lipid per oxidation and lipofuscin accumulation that is normally increased with aging. The studies have revealed that Curcumin is found to increase the activity of super oxide dismutase (SOD) and sodium-potassium ATPase that normally decreased with aging.12
3.6 Panax ginseng:
Synonym: Korean ginseng or Chinese ginseng
Ginsenosides are the Saponin of ginseng which is extracted from the rhizome and root of P. ginseng. The neuroprotective effects of Ginsenosides have been widely studied in different models of neurological deficits such as Parkinson’s disease, cerebral ischemia and memory impairments. Ginsenosides Rg1 is able to increase the amplitude of synaptic transmission.13 It has been revealed that Ginsenosides Rg1 and Rb1 are able to enhance cholinergic metabolism. They enable its properties by enhancing the level of acetylcholine in the CNS. Ginsenosides Rg1 with two sugars is more nootropic than Rb1, panaxadiol with four sugars. Increased protein concentration contributes to the memory consolidative effect.
3.7 Catharanthus roseus:
Synonym: Madagascar periwinkle, Rosy periwinkle
Vinpocetine is a chemical derived from vincamine. This a constituent found in the leaves of Catharanthus roseus, common name periwinkle.14It is used as a treatment for memory loss and mental impairments. Vinpocetine posses’ potential to enhance cerebral blood flow and neuroprotective effects. It is used as a drug for the treatment of cerebrovascular disorders and age-related memory impairment. Studies have proved Vinpocetine for the treatment of AD and related conditions..
3.8 Melissa officinalis:
Synonym: Lemon balm, balm
Melissa officinalis (Lemon Balm) has been shown to improve cognitive function and to reduce agitation in patients with cognitive disease. M. officinalis posses Ach receptor activity. It has both nicotinic and muscarinic binding properties.15 This plant modulates mood and cognitive performance when administered to young, healthy volunteer. The patients receiving M. officinalis extract experienced significant improvements in cognition after 16 weeks of treatment and no side effect between the placebo group and those receiving the herbs extract could be noticed.
3.9 Salvia officinalis:
Synonym: Garden sage, Sage
The extract of Salvia officinalis has been found to produce significant benefits in cognition. There are some reports on anticholinesterase activities of this species. Alpha-pinene and 1, 8-cineole which are monoterpene constituents, are found to inhibit acetyl cholinesterase and are therefore, responsible for inhibitory effect.
3.10 Celastrus paniculatus:
Synonym: Black oil plant, Climbing staff tree, Malkangni
Jothismati oil from seeds of Celastrus paniculatus is used for the treatment of brain related disease. It has been described to promote memory and to posses various pharmacological activities. CP oil causes an overall decrease in the turnover of all three central monoamines norepinephrine (NE), dopamine (DA) and serotonin (5-HT) and implicates the involvement of these aminergic systems in the learning and memory process. Celastrus paniculatus preferentially affects learning and recall of memory.16
Herbal medicine has been used traditionally for anxiety, aggression, depression, and sleep disturbances which are the indications of cognitive disorders. Constituents of herbal source have unlimited availability of Phytoconstituents which can be used for improving health. Single part of plant contains numerous secondary and bioactive metabolites which are used for cognitive functioning. Herbal drugs demonstrate a huge potential in detect and reducing the cognitive disorders. The above review article concludes that herbs and their constituents have promising effects in normal as well as elderly persons. In contrast to conventional medication medicinal plants appears more promising in general. Also the Herbal plants have very low or negligible side effects which make them more appealing.
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Received on 19.01.2017 Modified on 20.02.2017
Accepted on 10.03.2017 ©A&V Publications All right reserved
Res. J. Pharmacognosy and Phytochem. 2017; 9(1): 42-46.