EFFECT OF CENTELLA ASIATICA ON MILD COGNITIVE IMPAIRMENT (MCI) AND OTHER COMMON AGE-RELATED CLINICAL PROBLEMS
ABSTRACT Centella asiatica is a herb used since ancient times in Ayurveda to improve cognitive functioning. The current study aimed at managing the cognitive decline in elderly with mild cognitive impairment (MCI) and other age related problems. MCI is a serious problem which may be converted into Alzheimer disease. Although the concept of MCI is based on the presence of specific cognitive deficits, several studies show that these subjects can develop depression, disruptive behavior (e.g agitation, aggression). The present study was conducted in sixty elderly subjects with written consent obtained, registered at the geriatric out patient clinic at S.S. Hospital, BHU aged 65 and above. The Diagnostic tools used in this study were Mini Mental State Examination, Activities of Daily Living, Instrumental Activities of Daily living and Yesavage Geriatric Depression scale. The Centella asiatica extract was prescribed in dosage of 500mg twice a day (1000 mg daily) for 6 months. A favorable improvement is observed in cognitive functioning, depression and other age related conditions like Hypertension, insomnia, loss of appetite, constipation etc.
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ABSTRACT: Centella asiatica (CA), commonly named gotu kola, is an Ayurvedic herb used to enhance memory and nerve function. To investigate the potential use of CA in Alzheimer's disease (AD), we examined the effects of a water extract of CA (GKW) in the Tg2576 mouse, a murine model of AD with high β-amyloid burden. Orally administered GKW attenuated β-amyloid-associated behavioral abnormalities in these mice. In vitro, GKW protected SH-SY5Y cells and MC65 human neuroblastoma cells from toxicity induced by exogenously added and endogenously generated β-amyloid, respectively. GKW prevented intracellular β-amyloid aggregate formation in MC65 cells. GKW did not show anticholinesterase activity or protect neurons from oxidative damage and glutamate toxicity, mechanisms of current AD therapies. GKW is rich in phenolic compounds and does not contain asiatic acid, a known CA neuroprotective triterpene. CA thus offers a unique therapeutic mechanism and novel active compounds of potential relevance to the treatment of AD.International journal of Alzheimer's disease. 01/2012; 2012:381974.
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ABSTRACT: This paper covers the studies relevant to neuroprotective activity of Centella asiatica (L.) Urban, also known as "Gotu Kola." The plant is native to the Southeast Asia and has been used traditionally as brain tonic in ayurvedic medicine. The neuroprotective effect of C. asiatica has been searched using the key words "Centella, Centella asiatica, gotu kola, Asiatic pennywort, neuroprotection, and memory" through the electronic databases including Sciencedirect, Web of Science, Scopus, Pubmed, and Google Scholar. According to the literature survey, C. asiatica (gotu kola) has been reported to have a comprehensive neuroprotection by different modes of action such as enzyme inhibition, prevention of amyloid plaque formation in Alzheimer's disease, dopamine neurotoxicity in Parkinson's disease, and decreasing oxidative stress. Therefore, C. asiatica could be suggested to be a desired phytopharmaceutical with neuroprotective effect emerged from traditional medicine.Evidence-based Complementary and Alternative Medicine 01/2012; 2012:946259. · 1.72 Impact Factor
- Journal of medicinal plant research 01/2011; 5(11):2201-2109. · 0.59 Impact Factor
Digest Journal of Nanomaterials and Biostructures Vol. 3, No.4, December 2008, p. 215 – 220
EFFECT OF CENTELLA ASIATICA ON MILD COGNITIVE IMPAIRMENT
(MCI) AND OTHER COMMON AGE-RELATED CLINICAL PROBLEMS
Sushma Tiwari, Shinjini Singha, Kishor Patwardhan, Sangeeta Gehlot, I.S.Gambhira*
Department of Kriya Sharir, Faculty of Ayurveda, Institute of Medical sciences, Banaras
Hindu University, Varanasi, India
aDepartment of Medicine, Institute of Medical Sciences, Banaras Hindu University,
Centella asiatica is a herb used since ancient times in Ayurveda to improve cognitive functioning.
The current study is aimed at managing mild cognitive impairment (MCI) and other age-related
problems in elderly. MCI is a problem which may convert into Alzheimer’s disease in later stages.
Although the concept of MCI is based on the presence of specific cognitive deficits, several studies
show that subjects with MCI can develop depression and disruptive behaviour (e.g agitation,
aggression). The present study was conducted in sixty elderly subjects of age group 65 and above
with written consent, registered at the geriatric out patient clinic at S.S. Hospital, BHU. The
Diagnostic tool used in this study was Mini Mental State Examination. Also, parameters like
Activities of Daily Living, Instrumental Activities of Daily living and Yesavage Geriatric Depression
scale were used to monitor the subjects. Centella asiatica aqueous extract was prescribed in a dose of
500mg twice a day (1000 mg daily) for 6 months. A favourable improvement was observed in MCI
along with other problems like Hypertension, insomnia, loss of appetite, constipation.
(Received September 18, 2008; accepted September 22, 2008)
Keywords: Mild cognitive impairment, Age-related clinical problems, Centella Asiatica
In recent years, the term ‘Mild Cognitive Impairment’ (MCI) is commonly being used to
refer a stage of cognitive impairment prior to attaining clinical dementia in Alzheimer disease (AD)
and related disorders. The recent formulation of MCI follows previous attempts to characterize
cognitive decline associated with aging, including benign senescent forgetfulness, age-associated
memory impairment and age-associated cognitive decline [2, 3]. Therefore, this new concept is
perhaps best considered as a stage in the difficult process of understanding and characterizing mild
defects in cognition that do not fit clearly within the scope of established neurological and
psychiatric disorders. This does not mean that someone with MCI will inevitably get Alzheimer's in
their lifetime, but their likelihood of doing so is substantially increased . MCI has now been
categorized into two sub-types: those with the amnesic subtype (MCI-A) have memory impairments
only, while those with the multiple cognitive domain subtype (MCI-MCD) have other types of mild
impairments, such as in judgment or language, and mild or no memory loss. Both subtypes progress
to Alzheimer's disease at the same rate, but they do have different pathologies in the brain . MCI
has been suggested as a term for a boundary area between normal aging and dementia, especially
Alzheimer's disease. The search for an ideal drug or other treatment modality to manage this
* Corresponding author: firstname.lastname@example.org
condition is essential because it may be helpful to prevent the MCI patients for advancing into
Centella asiatica is a small creeping herb with shovel shaped leaves emerging alternately in
clusters at stem nodes found in the Himalayan range. Extract of plant contains asiaticoside, in which
a trisaccharide moiety is linked to the aglycone asiatic acid. In ‘Ayurveda’, this herb is used to
promote healthy long life, improve memory and other cognitive domains. The other probable
clinical uses of this plant are in venous insufficiency, wound healing, anxiety, anti-tumor,
hypertension and peptic ulcer [6-13].
This study was an attempt to validate the effect of Centella asiatica extract in the
management of mild cognitive impairment and other age-related problems among elderly patients.
2. Materials and methods
This study was conducted in the geriatric clinic of Department of Medicine at Sir Sunderlal
Hospital, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India, during the
period of December 2006 to February 2008 (15 months), in accordance with the declaration of
Helsinki guidelines on good clinical practice. This study was approved by Authors institutional
ethical review board. A total of sixty subjects matched with our inclusion criteria, enrolled in the
study with written consent from each patient.
All the subjects were aged 65 yrs and above, were screened for MCI using Mini Mental
State Examination (MMSE) adjusted to educational status and age of the patient as the diagnostic
tool . The number of patients diagnosed to have MCI was sixty. These patients were prescribed
powdered Centella asiatica extract in the form of capsules in a dose of 500 mg twice a day for 6
months. A control group could not be had in the present study because of low prevalence of MCI.
For the preparation of drug dried leaves were obtained from the pharmacy of the faculty of
Ayurveda, Banaras Hindu University, Varanasi. Cleaned leaves of Centella asiatica were dried in
the shade (no direct exposure to the sunlight) and the aqueous extract was prepared in the powdered
form. The appearance of the powder was brownish black. The powder was filled in capsules to
distribute among the patients.
2.1 Inclusion criteria
Patients aged 65 years and above with MCI, diagnosed on the basis of MMSE scores
adjusted to educational status and age of the patient were included in this group.
2.2 Exclusion criteria
Dementia according to DSM IV criteria, history of significant hearing or visual impairment,
unable to participate in an interview in a meaningful manner, history of neurological disorders
(stroke, Parkinson’s disease, active epilepsy) or psychiatric illnesses (schizophrenia, mental
retardation, depression and mania), other secondary causes of dementia including endocrine
abnormalities and vitamin deficiencies. Individuals who were living alone were also excluded
because the history and complaints could not be corroborated with another person.
2.3 Assessment criteria
History and clinical examination: A detailed history was taken and physical
MMSE: The mini-mental state examination (MMSE) was used as a screening test
for cognitive impairment which is developed by the Indo-US Cross-National Dementia
Interview from care-giver: Information about elderly social or occupational
functioning, daily activity, and any risk factor- were obtained from caregiver according to proforma
Activities of daily living: Information regarding normal routine work of elderly
people was assessed by this scale. This is highly informative and closely related to mild cognitive
impairment. This is adapted from Katz scale .
5. Instrumental activities of daily living: For this Lawton Instrumental Activities
of Daily living (IADL) has been useful in rehabilitation settings to monitor improvements over
time. IADLs are those activities whose accomplishment is necessary for continued independent
residence in the community. The instrumental activities of daily living are more sensitive for
subtle functional deficiency than the ADLs.
6. Yesavage Geriatric Depression scale: Yesavage Geriatric Depression Scale
(short – version) was used to screen the subjects for depression. It contains 15 questions and each
“depressed’’ answer is awarded one score. According to its norms, the scoring above 5 indicates
depression. While 7± 2 scores indicate mild depression and scoring 11± 2 indicates severe
Hematological investigations: Apart from the physical, physiological and
psychological assessments, certain hematological investigation likes hemoglobin, Erythrocyte
sedimentation rate, total serum protein, Total Leukocyte Count , DLC, CBC, PT were also
8. Liver function tests: SGPT and SGOT were conducted in the hospital laboratory.
9. ECG: ECG was done in a few patients depending on the need.
2.4 Statistical analysis
The data analysis was done by using Statistical Package for Social Sciences (SPSS)
Software Version 11.5. χ2 and paired t test was done. All the results were considered statistically
significant at p value ≤ 0.05.
MMSE scoring was done in sixty patients. A control group could not be had in the present
study because of low prevalence of MCI. Family ignorance, economical problems and
unawareness towards the disease are other common problems making a low patient input in the
clinic. Also, retirement from the employment at this age leading to clinical depression is probably
the other cause of reluctance of patients in seeking medical help.
A statistically highly significant (t= 9.68 p< 0.01) improvement in mean MMSE scores
was observed after treatment with the drug (Table 1).
Table 1: Effect of Centella asiatica on Mini- Mental State Examination
Mean ± ± S.D.
25.05 ± 1.19
Intra group comparison
t = 9.68
28.35 ± 1.39
A statistically highly significant decrease in mean Diastolic BP (before treatment= 85.70
±18.56, after treatment= 78.50 ± 10.82) was observed after treatment with the drug (t = 2.22
p<0.05). The drug had a statistically significant effect of improving the appetite among the
patients (χ2 = 17.50, p<0.001). A significant improvement in the sense of well-being was observed
in most of the patients after treatment (χ2 = 32.48 p<0.001) (Table 2).
Table 2: Effect of Centella asiatica on sense of well being.
Sense of well-being
No. of cases
No. of cases
Before treatment, the total number of individuals complaining of loss of sleep was 54
(90%), after treatment the number reduced to 3 (5%). (χ2 = 25.66 p<0.001) (Table 3).
Table 3: Effect of Centella asiatica on Insomnia
No. of cases %
Absent 6 10
Present 54 90
Table 4 Distribution of cases as per type of MCI.
Table 4. Distribution of cases as per type of MCI
Type of MCI No. of cases
No. of cases
Amnestic 54 90
Multiple cognitive domain 6 10
Total 60 100
Table 5 Normative Data on the MMSE, as per Crum et al. (13)
Table 5. Normative Data on the MMSE, as per Crum et al. 1993.
24 29 34 39
4th grade 22 25 25 23
8th grade 27 27 26 26
29 29 29 28
25- 30-35- 40-
29 29 29 29 29 29 29 29 29 29 28 28 27 27
In the present study, the MMSE scoring showed significant improvement after
administration of Centella asiatica for 6 months in elderly with Mild Cognitive Impairment. This
finding indicates that Centella asiatica is useful clinically in the patients suffering from MCI. The
mode of action of Centella asiatica in this condition is probably due to its cholinergic activity, anti
oxidant activity or anti inflammatory activity. A few studies have already shown that Centella
asiatica has cholinomimetic, anti inflammatory and antioxidant properties. In the study of Somchit
et al, the water extract of the herb revealed significant antinociceptive activity which was
statistically similar to aspirin. The extract also revealed significant anti-inflammatory activity
which was statistically similar to the non-steroidal anti-inflammatory drug, mefenamic acid .
In the study of Sakina et al, the Centella asiatica extract has been shown to have potentially
cholinomimetic activities in vivo . Another significant effect of Centella asiatica is that it acts
as an anti oxidant . Centella asiatica also accelerates nerve regeneration upon oral
administration and contains multiple active fractions increasing neurite elongation in vitro .
The present study shows that maximum patients with MCI were in the age group of 65-69
years. In the present study, maximum number of patient with MCI had education of collegiate
level. This finding is also not consistent with other studies [17, 18]. But, with a small sample size,
no conclusive remarks can be drawn on this aspect.
There was no statistically significant change observed in mean SGOT and SGPT levels
after treatment with Centella asiatica. Jorge et al had reported the hepatotoxicity due to Centella
asiatica in few patients . The present study is not suggestive of any hepatotoxicity and
therefore, the drug may be generally considered safe enough to be administered among elderly.
In the present study, before treatment, the total number of individuals complaining of
numbness and burning was 45 (75) % and after treatment, the number reduced to 15 (25%) (χ2 =
8.10, p<0.01). This observation is suggestive of a possible role of Centella asiatica in the
management of peripheral neuritis. The mode of action requires to be investigated. Sun et al had
already reported that Centella asiatica is effective in numbness and burning .
A significant improvement in the sense of well-being was observed in most of the patients
after treatment with Centella asiatica (χ2 = 32.48 p<0.001). This may be probably due to
anxiolytic and tranquilizing effects of the drug, which have been proposed by some other workers
as well . Present study shows that the total number of individuals complaining loss of sleep
(either problem in initiation of sleep or in maintenance of sleep) before treatment was 54 (90%)
and after treatment the number reduced to 3 (5%) (χ2 = 25.66 p<0.001). This shows that the drug
has a potential tranquilizing effect which has been proposed by some earlier studies also .
Total number of individuals complaining loss of appetite was 45 (75 %) before treatment;
and after treatment the number reduced to 15 (25%) (χ2 = 25.66 p<0.001). This effect needs to be
A statistically highly significant decrease in mean Diastolic Blood Pressure was observed
after treatment with the drug. The effects of Centella asiatica on cardiovascular system have not
been investigated so far and this finding may be of value in treating the hypertensive individuals
with MCI. The probability is that the drug may be causing a fall in peripheral resistance by
producing vaso-dilatation through some un-known mechanism.
The aim of present study was to assess the role of Centella asiatica in the management of
Mild Cognitive Impairment (MCI) among elderly, aged 65 years and above and also to assess its
utility in other age-related clinical problems. The mean MMSE scoring showed significant
improvement after administration of Centella asiatica for 6 months in elderly with MCI. This
finding indicates that Centella asiatica is useful clinically in the patients suffering from MCI. This
drug is also having favorable effects in diastolic blood pressure, peripheral neuritis, insomnia, loss
of appetite etc. In a nutshell, the present study is indicative of multiple useful clinical effects of
Centella asiatica especially in the age-related cognitive decline. However, the mechanism of
action and possible toxicity needs to be further investigated in a large sample. Also, a double blind
randomized clinical trial is essential.
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