Holy Basil (Ocimum Sanctum Linn.) Leaf Extract Enhances Specific Cognitive Parameters in Healthy Adult Volunteers: A Placebo Controlled Study

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Introduction

            Ocmum sanctum (Holy Basil), known as “Tulsi” in India and locally in the Philippines as “Sulasi”, belongs to the family of Lamiaceae. It is a well known plant grown all over India.  The plant is native in Indian subcontinent and cultivated throughout Southeast Asia. It is also abundantly grown in Australia, West Africa, and some Arab countries.

 

            Its medicinal properties have been described in the Indian medicinal text Ayurveda (The Science of Life) which is believed to be about 5000 years old. Several medicinal properties have been attributed in the traditional system of medicine. The leaves, seeds, and roots contain several medicinal properties. The leaves contain essential oils, which included eugenol, eugenal, carvacrol, methylchavicol, limatrol and caryophylline. The seeds and roots contain sitosterol.

 

            Experimental and clinical studies are widely available regarding the therapeutic effects of Ocimum sanctum. Giridharan, V., et al in 2011 established that the ethanolic extract of Ocimum sanctum improved the cognitive dysfunction in rat model and enhanced learning and memory in alzheimer’s rat model. In addition, the study of Chatterjee, M., et al in 2011 also showed that Ocimum sanctum has anti-anxiety and anti-depressant effect.

 

            A clinical trial was performed by Bhattacharyya, D., et al in 2018 to assess the effect of Ocimum sanctum leaf extract on generalized anxiety disorders. Thirty-five subjects were given 500 milligrams capsules of the plant extract twice a day after meals. They were thoroughly investigated and assessed using Hamilton’s brief psychiatric rating scale (BPRS) at baseline (day 0), mid-term (day 30), and final (day 60). Ocimum sanctum significantly decreased the generalized anxiety disorder among the subjects and its associated stress and depression. Cognitive attention was also improved.

 

            Singh, N., et al in 2012 reviewed the therapeutic potential of Ocimum sanctum in the prevention and treatment of cancer and exposure to radiation. It has been shown to be effective in human cancer in vivo like human cell fibrosarcoma and in vitro in human cervical cancer cell line (HeLa) and human laryngeal epithelial carcinoma cell line (HEp-2).

 

            A randomized controlled cross-over trial by Mondal, S., et al in 2011 was conducted to evaluate the immunomodulatory effect of Tulsi (Ocimum sanctum Linn.) leaf extract. Twenty-four healthy subjects were given 300 milligrams capsules of ethanolic extracts of leaves of Tulsi or placebo on an empty stomach. Th1 and Th2 cytokines (interferon  and interleukin-4) during pre and post intervention period were measured in blood culture supernatants. Other immunological parameters such as T-helper and T-cytotoxic cells, B-cells and NK-cells were also analyzed using flow cytometry.

 

Results showed a significant increase in the levels of IFN-γ, IL-4, T-helper cells and NK-cells after 4 weeks in the intervention group in contrast to the placebo group, hence proving the immunomodulatory effect of Ocimum sanctum leaf extract.

 

            An in vitro study was done by Kandhan, T., et al in 2018 to evaluate the anticholinesterase activity of ethanolic extract of Ocimum sanctum. Acetylcholinesterase is an enzyme known to play an important role in cognitive functioning. It degrades acetylcholine leading to inhibition or termination of synaptic transmission and is mainly found in the neuromuscular junctions and junctions of chemical synapses of the cholinergic type. In this study, the acetylcholinesterase inhibition activity of the ethanolic extract of Ocimum sanctum leaf was analyzed in various concentrations.

 

The study showed that the ethanolic extract of Ocimum sanctum was a potent inhibitor of acetycholinesterase and consequently acts as an anticholinergic agent. In Alzheimer disease and dementia, there is an increase in acetylcholinesterase activity leading to impairment of cognitive functioning. This study enabled further research and pharmacologic breakthroughs to pave way in the future.

 

Relevance

            Cognitive functioning is an important aspect in well-being. Memory decline may be irreversible especially in Alzheimer disease and dementia but several studies have shown the promising effects of ethanolic extract of Ocimum sanctum. This study was done to provide more discoveries in cognitive therapy and enable future groundbreaking developments and advacments in the field of medicine.

 

Objectives

            The double-blinded randomized control trial aims to determine the effect of ethanolic extract of Ocimum sanctum on cognitive parameters like short-term memory, cognitive flexibility, and attention.

 

Highlights

            Sampath, S., et al in 2015 conducted a double-blinded, randomized control study on the cognitive enhacing properties of Ocimum sanctum. Forty-four apparently healthy male subjects, aged 18-30 years old were recruited in the study. Those suffering from long term disabilities, chronic smokers, and on any long term medication were excluded from the study.

 

Subjects were randomly allocated into either group A or B. Twenty-three subjects were included in group A and 21 were included in group B. Recordings were done on day 0, day 15 and day 30. Two subjects in group A and one subject in group B were lost to follow-up due to work- time restriction and one subject in group A discontinued the medication due to nausea. A total of 20 subjects in each group completed the study.

 

            The 70% ethanolic extract of Ocimum sanctum (EtOS) was prepared from dried leaves. The leaves of Ocimum sanctum were procured at Dindigal area of Tamil Nadu, South India in October 2006. Authenticity and identity was established carefully through the literature Flora of Presidency of Madras.

 

            Thirty 300 milligram capsules of EtOS or placebo were packaged in identical air-sealed bottles labelled A or B, by the GLP certified laboratory of Dabur research foundation, India. Both the subject and the experimenter were blinded to the identity of the capsules. Each subject took one capsule a day from bottle A or B, each morning, on an empty stomach.

 

            Sternberg and Stroop task were administered to assess cognitive function. The Sternberg memory task measures the accuracy and speed of short-term memory load. A set of to-be-remembered digits was presented. The subjects responded as quickly as possible by pushing the forward slash key if the probe was a member of the set, or the Z key if the probe was not a member of the set. The reaction time (RT) and error rate (ER) were subsequently measured. In the study, there was a significant improvement in the RT of the Sternberg in both groups over time.  ER was reduced in both groups. The inter-group comparison in ER at  day 30 was significant.

 

            The Stroop test measures cognitive flexibility. The subjects responded to the color in which the word is printed by pressing the appropriate key as quickly as possible. Facilitation, neutral and interference tasks were determined in separate blocks. In facilitation task, the letter string is the name of the color that the letters are printed in. In neutral task, the letter string is composed of Xs. In interference task, the letter string is one of the words red, green, blue, or yellow printed in a color different from the named color.

 

In facilitation task, inter-group comparisons of RT and ER at day 15 or day 30 were not significant. In neutral task, there was an improvement in the RT in both the placebo and EtOS groups over time. The inter-group comparison in RT at day 30 was significant. In interference task, there was an improvement in the RT and a significant reduction in the ER in both the placebo and EtOS group.

 

            The event related potential was recorded using the EEG activity. The latency of P300 was measured. P300 plays an important role in selective attention and stimulus response. P300 latency remained fairly constant in the placebo group and showed significant improvement beyond Day 15 in the EtOS group.

 

            Saliva was collected on the recording day and at the beginning of tests. ELISA kits were used to estimate cortisol levels. There was a significant reduction in the salivary cortisol values in the EtOS group alone. To assess mental and emotional acute stress, the Spielberger state and trait anxiety inventory (STAI) was administered before the testing for cognitive parameters. There was a significant reduction in the scores in the EtOS group alone.

 

            Inter-group comparison showed a significant improvement of the RT and ER of Sternberg test, RT of neutral task of Stroop, and RT and ER of interference task of Stroop in the EtOS group as compared to the placebo. The intra-group comparison of P300 latency, salivary cortisol, and STAI showed improvement over time in the EtOS group alone.

 

            Further studies therefore may be recommended in a larger population, in an older population or in the vulnerable age group. Increasing the dose and duration of intake of Ocimum Sanctum will also further investigate its improvement on cognitive function.

                                                         

Conclusion

            The study showed that that Ocimum sanctum does seem to have a promising effect on the cognitive function in humans.

 

This article was originally posted in Pharexmedics.com

References:

1. Shasany, A. The Holy Basil (Ocimum Sanctum L.) and its Genome. Indian Journal of History of Science. 2016.

2. Krishna, G., et al. “Tulsi”- the Wonder Herb (Pharmacological Activities of OcimumSanctum). American Journal of Ethnomedicine. 2014.

3. Giridharan, V., et al. Ocimum sanctum Linn. leaf extracts inhibit acetylcholinesterase and improve cognition in rats with experimentally induced dementia. Journal of Medicinal Food. 2011.

4. Chatterjee, M., et al. Evaluation of ethanol leaf extract of Ocimum sanctum in experimental models of anxiety and depression. Pharmaceutical Biology. 2011.

5. Bhattacharyya, D., et al. Controlled programmed trial of Ocimum sanctum leaf on generalized anxiety disorders. Nepal Medical College Journal. 2008.

6. Singh, N., et al. Therapeutic potential of Ocimum sanctum in prevention and treatment of cancer and exposure to radiation: An Overview. International Journal of Pharmaceutical Sciences & Drug Research. 2012.

7. Mondal, S., et al. Double-blinded randomized controlled trial for immunomodulatory effects of Tulsi (Ocimum sanctum Linn.) leaf extract on healthy volunteers. Journal of Ethnopharmacology. 2011. 8. Kandhan, T., et al. Acetylcholinesterase activity of Ocimum sanctum leaf extract. Journal of Advanced Pharmacy Education and Research. 2018.