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Management of Cognitive Determinants in Senile Dementia of Alzheimer’s Type: Therapeutic Potential of a Novel Polyherbal Drug Product

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Abstract

Background and Objective

The enigmatic etiology of neurodegenerative diseases poses a challenge for the development of novel and efficient drugs. The objective of the present study was to evaluate the efficacy of a polyherbal (test) formulation on cognitive functions, inflammatory markers and oxidative stress in healthy elderly as well as senile dementia of Alzheimer’s type (SDAT) patients.

Method

A randomized double-blind placebo- and active-controlled clinical trial was performed in healthy elderly subjects and SDAT patients with an age range of 60–75 years. The polyherbal test formulation along with a placebo was given to healthy elderly subjects while the SDAT patients received either the test formulation containing extracts of Bacopa monnieri (whole plant), Hippophae rhamnoides (leaves and fruits) and Dioscorea bulbifera (bulbils) at a dose of 500 mg or donepezil drug (Aricept) at a dose of 10 mg, twice daily, for a period of 12 months. After every three months, cognitive functions were assessed by determining the mini mental state examination (MMSE) score, digital symbol substitution (DSS; subtest of the Wechsler Adult Intelligence Scale—Revised), immediate and delayed word recall (digital memory apparatus—Medicaid systems, Chandigarh, India), attention span (Attention Span Apparatus—Medicaid systems, Chandigarh, India), functional activity questionnaire (FAQ) and depression (geriatric depression scale) scores. Further inflammatory markers and level of oxidative stress were analyzed using standard biochemical tests.

Results

The trial was performed in 109 healthy subjects and 123 SDAT patients of whom 97 healthy subjects and 104 SDAT patients completed the study. Administration of the test formulation for a period of 12 months was effective in improving cognitive functions in the SDAT patients, when compared to the donepezil-treated group, as determined by the DSS (38.984 ± 3.016 vs 35.852 ± 4.906, P = 0.0001), word recall immediate (3.594 ± 1.003 vs 2.794 ± 0.593, P < 0.0001) and attention span (4.918 ± 1.239 vs 4.396 ± 0.913, P = 0.0208) scores. A significant improvement in the FAQ (11.873 ± 2.751 vs 9.801 ± 1.458, P < 0.0001) and depression (16.387 ± 2.116 vs 21.006 ± 2.778, P < 0.0001) scores was also observed, whereas no significant differences were observed in the MMSE and word recall delayed scores. The level of inflammation and oxidative stress was markedly reduced in the SDAT patients treated with the test formulation when compared to the donepezil-treated group indicating a likely mechanism of action of the test formulation (homocysteine 30.22 ± 3.87 vs 44.73 ± 7.11 nmol/L, P < 0.0001; C-reactive protein [CRP] 4.751 ± 1.149 vs 5.887 ± 1.049 mg/L, P < 0.0001; tumour necrosis factor alpha [TNF–α] 1139.45 ± 198.87 vs 1598.77 ± 298.52 pg/ml, P < 0.0001; superoxide dismutase [SOD] 1145.92 ± 228.75 vs 1296 ± 225.72 U/g Hb, P = 0.0013; glutathione peroxidase [GPx] 20.78 ± 3.14 vs 25.99 ± 4.11 U/g Hb, P < 0.0001; glutathione [GSH] 9.358 ± 2.139 vs 6.831 ± 1.139 U/g Hb, P < 0.0001; thiobarbituric acid reactive substances [TBARS] 131.62 ± 29.68 vs 176.40 ± 68.11 nmol/g Hb, P < 0.0001). Similarly, when healthy elderly subjects treated with the test formulation for 12 months were compared to the placebo group, a significant (P < 0.001) improvement in cognitive measures (MMSE, DSS, word recall delayed but not immediate, attention span, FAQ and depression scores) and a reduction in inflammation (reduction in homocysteine, CRP, IL-6 and TNF-α levels) and oxidative stress levels (reduction in SOD, GPx and TBARS and increase in GSH) was observed. This indicated a protective effect of the test formulation in managing cognitive decline associated with the ageing process.

Conclusion

The results of this study demonstrate the therapeutic potential of this novel polyherbal formulation for the management and treatment of SDAT.

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Acknowledgments

This study was supported in part by UGC Grant No. Dev./D/CPBM/2015, AYUSH and DST India. Additional support was provided by SRM University, Chennai and Adesh University Punjab. The tablets were manufactured by Varanasi Bioresearch at no cost. The clinical study was performed at Banaras Hindu University, Varanasi, SRM University, Chennai and Adesh University, Punjab, India. Thanks to the clinical investigators Prof. V N Mishra and Prof. Malvin George for their help and support in conducting the clinical trial. No competing financial interests exist for any authors. All authors declare no conflicts of interest. The clinical trial titled “Prevention and management of age related neurodegenerative disorders- an Ayurvedic intervention”, was registered (No. K.11022/10/2009-DCC) with Dept. of AYUSH (Ministry of health and family welfare, Govt. of India).

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Authors and Affiliations

  1. Collabrative programme, Institute of Medical Science, Banaras Hindu University, Varanasi, India

    Ananya Sadhu, Prabhat Upadhyay & Govind Prasad Dubey

  2. Department of Kriya Sharir, Faculty of Ayurveda, IMS, BHU, Varanasi, India

    Aruna Agrawal

  3. Interdisciplinary School of Indian System of Medicine (ISISM), SRM University, Kattankulathur, 603203, Tamil Nadu, India

    Kaliappan Ilango

  4. Arvind Remedies Ltd., 190, Poonamallee high road, Aminjikarai, Chennai, 600084, Tamil Nadu, India

    Dipankar Karmakar

  5. Adesh University, Barnala Road, Bathinda, Punjab, India

    Gur Prit Inder Singh

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  1. Ananya Sadhu
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Sadhu, A., Upadhyay, P., Agrawal, A. et al. Management of Cognitive Determinants in Senile Dementia of Alzheimer’s Type: Therapeutic Potential of a Novel Polyherbal Drug Product. Clin Drug Investig 34, 857–869 (2014). https://doi.org/10.1007/s40261-014-0235-9

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