{"id":63192,"date":"2024-12-30T11:10:59","date_gmt":"2024-12-30T11:10:59","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=63192"},"modified":"2025-01-06T18:39:49","modified_gmt":"2025-01-06T18:39:49","slug":"the-cognitive-enhancing-properties-of-the-aqueous-extract-from-the-fruits-of-terminalia-belliricagaertn-roxb","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol17no4\/the-cognitive-enhancing-properties-of-the-aqueous-extract-from-the-fruits-of-terminalia-belliricagaertn-roxb\/","title":{"rendered":"The Cognitive-Enhancing\u00a0Properties of\u00a0the\u00a0Aqueous Extract from\u00a0the Fruits of\u00a0 Terminalia bellirica(Gaertn.) Roxb."},"content":{"rendered":"

Introduction<\/strong><\/p>\n

Dementia is derived from the Latin phrase \u2018demens\u2019, which means ‘being out of one’s mind‘.1 <\/sup>The medical term “dementia” represents a clinical condition typified by a progressive decline\u00a0in cognitive abilities, which inhibits an individual’s ability to operate independently.2<\/sup> Dementia strikes a\u00a0person in the globe every three seconds.3<\/sup> There are around ten million\u00a0fresh cases every single year. Currently, around fifty-five million people worldwide suffer from cognitive impairment, especially over sixty percent of those inhabiting nations with low to middle incomes.4 <\/sup>There exist multiple types of dementia, such as ‘mixed dementia’, ‘frontotemporal lobar degeneration’, ‘Lewy body dementia’, ‘vascular dementia’, ‘Creutzfeldt-Jakob disease’, and ‘normal pressure hydrocephalus’.5<\/sup> Alzheimer’s is its most prevalent type.6<\/sup><\/p>\n

The main objective of the present dementia\u00a0treatment is to activate the NMDA (N-methyl-D-aspartate)\u00a0receptors and enhance the transmission of cholinergic neurons by using acetylcholinesterase inhibitors (galantamine, rivastigmine, donepezil) and memantine, an antagonist of\u00a0NMDA\u00a0receptor.7 <\/sup>Donepezil may trigger syncopal episodes\u00a0and heart block because of its vagotonic characteristics.8<\/sup>Galantamine increases the risk of QT interval prolongation, while rivastigmine may raise the risk of\u00a0stroke, torsade de pointes and myocardial infarction.\u00a0 A Higher rate of memantine discontinuation occurs as a result of adverse events.9<\/sup><\/p>\n

There\u00a0exists\u00a0a\u00a0recent unprecedented drive in modern medical practices for the utilization of herb-based remedies due to their\u00a0multi-target potential and various pharmacological effects.10<\/sup>This impetus arise from a multitude of factors, primary amongst those is the\u00a0interpretation that herbal\u00a0medications are safer and cost-effective\u00a0as compared with current standard therapies.11<\/sup>Therefore, the formulation of novel compounds with a superior pharmacological profile aided by herbal medications is critical.12<\/sup><\/p>\n

The Terminalia bellirica<\/em> tree, which is a member of the Terminalia<\/em> Linn<\/em>. genus and Combretaceae family, yields Terminalia bellirica<\/em> fruit. Its distribution is primarily in Southeast Asia.13<\/sup> Bangladesh, India, Cambodia,\u00a0Bhutan,\u00a0China,\u00a0Laos,\u00a0Indonesia,\u00a0Malaysia, Pakistan,\u00a0Nepal,\u00a0Sri\u00a0Lanka, Vietnam \u00a0and\u00a0Thailand\u00a0are\u00a0the\u00a0native\u00a0habitats\u00a0of\u00a0Terminalia\u00a0bellerica.<\/em>14<\/sup><\/em>Throughout the Indian subcontinent, Terminalia<\/em> is frequently found in native woods in Karnataka, West Bengal, Uttar Pradesh, Madhya Pradesh, Maharashtra, Tamil Nadu, Assam, Rajasthan, Punjab and\u00a0 Kerala.15<\/sup><\/p>\n

Roxburgh W, Banks J, Bulmer W, Mackenzie D and Nicol G wrote the\u00a0 first\u00a0scientific\u00a0description\u00a0of\u00a0Terminalia\u00a0bellerica<\/em>.16<\/sup><\/p>\n

Terminalia bellerica<\/em> is a gigantic deciduous tree up to 50 meters\u00a0tall and approximately 3 meters\u00a0in diameter, featuring a round crown. Fruit is broadly ellipsoid to sub-globular (20-40 x 18-22 millimeters), thickly velutinous or sericeous, mild-yellow, seemingly 5-angled, and precisely brown tomentosa. The name ‘Terminalia<\/em>‘ is derived from the Latin word ‘terminus’ and alludes to the clustering of leaves on the terminals of branches.17<\/sup><\/p>\n

Many traditional medical systems, including\u00a0Unani,\u00a0Ayurveda, Siddha,\u00a0and Chinese traditional\u00a0medicine, have used Terminalia\u00a0bellirica<\/em>.18<\/sup> Terminalia bellerica <\/em>possesses components that protect the liver from damage, stimulate the immune system, combat cancer, control diabetes, and have antimicrobial, antihypertensive,\u00a0antioxidant, and anti-diarrheal properties.19<\/sup> Terminalia bellerica<\/em> is used as an astringent, laxative, antipyretic and anthelmintic. Terminalia bellerica<\/em> fruits are often used as a hair tonic and to treat a variety of conditions, including bronchitis,\u00a0hepatitis, asthma, piles,\u00a0dyspepsia,\u00a0diarrhea, hoarseness of the voice,\u00a0coughs, eye disorders, and scorpion stings.20<\/sup>The well-known Ayurvedic medicine triphala is a compound made up of the dried fruits of three different plant species: Terminalia bellirica<\/em> (family- Combretaceae), Terminalia chebula<\/em> (family- Combretaceae)\u00a0and Emblica officinalis<\/em> (family- Euphorbiaceae).21<\/sup>Extract from Terminalia chebula<\/em> prevents amnesia induced by scopolamine.22<\/sup>Tannoid components found in Emblica officinalis<\/em> have been observed for restoring High-sodium, high-cholesterol diet and aluminum chloride-induced cognitive deficiencies. 23,24<\/sup><\/p>\n

Consequently, the researchers sought to determine whether the third component of Triphala, Terminalia bellirica<\/em> fruit pulp\u00a0possessed characteristics that would enhance cognition. Furthermore, the current study can serve as a reference for future investigations on the molecular process behind the given results.<\/p>\n

Materials and Methods<\/strong><\/p>\n

Ethical Consideration<\/strong><\/p>\n

The protocol\u00a0received Institutional Animal Ethics Committee (IAEC) approval for a three-month research period\u00a0involving forty-two\u00a0\u2018Wistar albino rats\u2019 (IAEC approval number: KMC.MNG\/IAEC\/08\/2023). The CCSEA\u00a0registration number assigned to the IAEC\u00a0is 213\/PO\/Re\/S\/2000\/CPCSEA07\/09\/2022 (Valid up to 06\/09\/2027). The rodents were reared in the Pharmacology department\u2019s animal house, KMC\u00a0Mangalore, Karnataka, India. The research\u00a0study was conducted in the Experimental laboratory, Pharmacology department, Kasturba Medical College, Mangalore, India.<\/p>\n

Experimental animals<\/strong><\/p>\n

Forty-two Wistar albino male\u00a0rats weighing 180 to 220 grams and aged between three and five months were\u00a0housed in hygienic cages made of polypropylene at standardized environmental conditions (Temperature: 22\u00b130\u00b0C, Humidity: 50-60%; dark\/light\u00a0cycle: 12 hours.). Rodents were provided with water and a standard diet ad libitum. A one-week acclimatization period was\u00a0provided to ensure that rodents\u00a0adapt to the study settings. To reduce disparities, readings were taken in a calm environment between nine in the morning and noon consistently. The study adhered to the guidelines\u00a0established by the CCSEA (Committee for Control and Supervision of Experiments on Animals).<\/p>\n

Study plant material and Drugs<\/strong><\/p>\n

Positive control \u2013 Normal saline, Negative control Scopolamine hydrobromide (Sigma-Aldrich) and Standard control- Piracetam (Intas Pharmaceuticals Ltd) were procured from KMC Mangalore Hospital Pharmacy, Karnataka, India. All Terminalia bellerica<\/em> fruit pulps\u00a0were obtained from Lakshmi Ayurveda Pharmacy, Mangalore, Karnataka, India.<\/p>\n

Authentication<\/strong><\/p>\n

Dr. Jyothi Miranda currently an Associate Professor in the Botany department, St. Aloysius College, Mangalore, Karnataka, India, authenticated\u00a0the\u00a0Terminalia bellirica<\/em> fruit pulps.<\/p>\n

Preparation of\u00a0\u2018aqueous extract of Terminalia bellirica<\/em> fruit pulp\u2019 (AETBFP)<\/strong><\/p>\n

Fruit pulps were rinsed with flowing water and thoroughly dried out in shady conditions. Dried fruit pulps\u00a0were then\u00a0finely ground up utilizing a grinder. Soxhlet extraction was used to extract 1,000 grams of raw AETBFP granules which was then air-dried over 36 hours. Rotator evaporation was utilized to dehydrate the powder under regulated pressure at 40-50\u00b0C temperature. AETBFP\u00a0yielded a brownish lump\u00a0weighing 145 grams. The dehydrated crude\u00a0powder of extract\u00a0produced approximately 14.5 percent by weight\/weight.<\/p>\n

Treatment grouping and dosage<\/strong><\/p>\n

The rats were\u00a0randomly separated into seven groups, comprising six rats per group (n = 3 males and 3 females) as seen in Table 1, they are housed in different cages. Group one acted as the positive control (0.9% normal saline, 10 ml\/kg body weight, oral). Group two served as\u00a0a negative control (scopolamine, 1 mg\/kg body weight, intraperitoneal.). Group three served as a standard\u00a0control (Piracetam at 600 mg\/kg body weight\u00a0per oral +\u00a0scopolamine).25<\/sup> Groups four to six received the test drug (AETBFP 143, 200, and 334 mg \/kg body weight per oral + scopolamine) respectively.26<\/sup> Group seven received\u00a0AETBFP (334mg\/kg body weight per oral) +\u00a0piracetam and scopolamine. Apart from\u00a0scopolamine, all other drugs were\u00a0administered once every day for 14 days. On day fourteen, all the rats\u00a0received\u00a0scopolamine (1 mg \/\u00a0kg body weight, intraperitoneal), one\u00a0hour\u00a0after administering either the standard\u00a0drug or the AETBFP\u00a0to the appropriate groups, except the normal control group.<\/p>\n

Table 1: Treatment Groups<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n
Group <\/strong><\/p>\n

(n=6)<\/strong><\/td>\n

Treatment received <\/strong><\/td>\n<\/tr>\n
1<\/td>\nPositive control \u2013 Normal saline (10ml\/kg b.w), p.o. for 14 days<\/td>\n<\/tr>\n
2<\/td>\nNegative control- Scopolamine (1mg\/kg b.w), i.p. on 14th<\/sup> day<\/td>\n<\/tr>\n
3<\/td>\nStandard control- Piracetam (600mg\/kg b.w), p.o. for 14 days + Scopolamine (1mg\/kg b.w), i.p. on 14th<\/sup> day<\/td>\n<\/tr>\n
4<\/td>\nTest 1- AETBFP (143mg\/kg b.w), p.o. for 14 days + Scopolamine (1mg\/kg b.w), i.p. on 14th<\/sup> day<\/td>\n<\/tr>\n
5<\/td>\nTest 2- AETBFP (200mg\/kg b.w), p.o. for 14 days + Scopolamine (1mg\/kg b.w), i.p. on 14th<\/sup> day<\/td>\n<\/tr>\n
6<\/td>\nTest 3-AETBFP (334mg\/kg b.w), p.o. for 14 days + Scopolamine (1mg\/kg b.w), i.p. on 14th<\/sup> day<\/td>\n<\/tr>\n
7<\/td>\nAETBFP (334mg\/kg b.w), i.p. for 14 days + Piracetam (600 mg\/kg b.w), p.o. for 14 days + Scopolamine (1mg\/kg b.w ), i.p. on 14th<\/sup> day<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

p.o. \u2013 Per oral, i.p.- Intraperitoneal, b.w- body weight, AETBFP- \u2018aqueous extract of Terminalia bellirica<\/em> fruit pulp<\/p>\n

Experimental procedure <\/strong><\/p>\n

On day 14, cognitive paradigms were assessed 45 minutes after the scopolamine injection\u00a0using the Hebb-William Maze and the\u00a0elevated plus maze. This is referred to as the ‘acquisition trial (AT)’ and is related to learning. Furthermore, on day 15 shortly after 24 hours of the scopolamine injection, a ‘retention trial (RT)’ was performed to evaluate the index for memory.27,28<\/sup><\/p>\n

Screening Methods<\/strong><\/p>\n

Hebb William\/ <\/strong>Rectangular maze<\/strong><\/p>\n

This\u00a0maze is a reward-restricted behavioral model intended to assess rodents’ working memory. It\u00a0is designed as\u00a0an entirely sealed rectangular box having an\u00a0entering chamber A and a\u00a0rewarding\u00a0chamber B attached\u00a0at opposite ends. The rectangular\u00a0box is segmented with wooden boards into blind passageways, leaving merely a\u00a0twisting corridor C that leads from entering chamber\u00a0A to rewarding chamber\u00a0B.27<\/sup> The learning assessment for all\u00a0the control and treated rats was\u00a0performed after the treatments. On the day one, all rats were\u00a0acquainted with the\u00a0rectangle maze\u00a0for 10 minutes. From days two to five, the rats had\u00a0four consecutive training trials every day\u00a0in the maze, each lasting 8 to 10 minutes. In every trial, it\u00a0was\u00a0positioned in the entering\u00a0chamber, and\u00a0the timing device was activated when the rat\u00a0exited the chamber. The time it took the rat to arrive in the rewarding\u00a0chamber (TRC) was calculated\u00a0as the day’s learning score. Lower assessment scores suggested sufficient learning, but rather higher scores suggested poor learning in rats. To warrant\u00a0motivation to explore the rewarding area\u00a0throughout the learning assessments, the rats\u00a0were provided with water and\u00a0food ad libitum for only\u00a0one hour soon\u00a0after the rectangle\u00a0maze exposure\u00a0of the day had been completed.<\/p>\n

Elevated Plus Maze (EPM)<\/strong><\/p>\n

The EPM is utilized as an exteroceptive behavioral paradigm to assess memory and learning in rats. It\u00a0comprises\u00a0 a 10×10 cm\u00a0central platform connected with two 50×10 cm\u00a0open- arms\u00a0and two 50x40x10 cm\u00a0closed arms. It is mounted\u00a050 cm\u00a0above the floor. The experiment was conducted in two stages. On the 14th day,\u00a0acquisition testing was done. Each\u00a0rat was positioned at the extremity of anyone\u00a0open arm. They were positioned in such a way that they were\u00a0facing opposite the central platform. The time required to enter either of the two closed arms has been documented as (TL)\u00a0transfer latency. All four feet in a closed arm were considered as one entry. The cut-off time for every individual rat was 180 seconds. Rats that failed to enter any one of the\u00a0closed arms before the specified period were eliminated from the research study. Retention tests were\u00a0performed 24 hours following the initial trial, and the TL was recorded in the same manner as previously described. Shortened TL was perceived as an indicator of improvement in memory.29<\/sup><\/p>\n

Statistical Analysis<\/strong><\/p>\n

The results are expressed as mean \u00b1 standard error of the mean. To compare the variations in the parameters evaluated between the groups, a One-way ANOVA plus\u00a0Dunnett’s Multiple Comparison Test was performed. A (p-value) probability value\u00a0that was below 0.05 was inferred as\u00a0statistically significant. SPSS version 25(\u2018IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp\u2019) was utilized for statistical analysis<\/p>\n

Results and Discussion<\/strong><\/p>\n

Hebb-William Maze<\/strong><\/p>\n

In the analysis of TRC in \u2018Hebb-William Maze\u2019 as shown in Table 2, \u2018the time taken by the animal to reach the reward chamber\u2019 was significantly increased in group 2 (negative control- scopolamine) on day 14 (160.00\u00b17.60) and 15(149.67\u00b19.21) when compared to the group 1(normal control) illustrating the amnesic effect of scopolamine.\u00a0 The TRC decreased significantly in group 3 (standard control-Piracetam) on days 14(82.50\u00b13.43) and 15 (58.33\u00b14.38) when compared to group 2 (negative control- scopolamine) demonstrating increase in memory and learning scores. The data revealed that the TRC on day 14 in group 4 treated with AETBFP 143 mg\/kg was 118.50 \u00b14.39, group 5 treated with AETBFP 200 mg\/kg was 112.83 \u00b12.37, and in group 6 treated with AETBFP 334 mg\/kg was 109.33\u00b14.77(p<0.05). On day 15 the TRC in the group 4 treated with AETBFP 143 mg\/kg was 105.33\u00b11.97, group 5 treated with AETBFP 200 mg\/kg was 107.50\u00b12.17, and group 6 treated with AETBFP 334 mg\/kg was 99.50\u00b13.31 (p<0.05). The above results depict a significant dose-dependent decline in the TRC when compared to the group 2 (negative control- scopolamine). Group 7 receiving AETBFP 334mg\/kg and Piracetam decreased TRC considerably lower than other test groups on day 14 (103.67\u00b13.39) and 15 (92.67\u00b11.22) which was significant (p<0.05) when compared to the group 2 (negative control- scopolamine). There was a decrease in TRC in piracetam and AETBFP treated groups demonstrating their learning and memory enhancing effect in animal models. The TRC did not significantly differ within groups between days 14 and 15.<\/p>\n

Table 2: Time to reach Reward Chamber in Hebb-William Maze on day 14 and 15<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n
Group <\/strong><\/td>\nDrugs (dose)<\/strong><\/td>\nDay 14 (TRC)<\/strong><\/p>\n

Acquisition\u00a0 <\/strong><\/p>\n

Time in seconds <\/strong><\/td>\n

Day 15\u00a0 <\/strong><\/p>\n

\u00a0(TRC)<\/strong><\/p>\n

Retention\u00a0 <\/strong><\/p>\n

Time in seconds<\/strong><\/td>\n<\/tr>\n

1<\/td>\nNormal saline (1ml\/kg b.w.)<\/td>\n102.33\u00b11.58<\/td>\n96\u00b15.83<\/td>\n<\/tr>\n
2<\/td>\nScopolamine (1mg\/kg b.w.)<\/td>\n160.00\u00b17.60<\/td>\n149.67\u00b19.21<\/td>\n<\/tr>\n
3<\/td>\nPiracetam (600mg\/kg b.w.)<\/td>\n82.50\u00b13.43$<\/sup><\/td>\n58.33\u00b14.38$<\/sup><\/td>\n<\/tr>\n
4<\/td>\nAETBFP (143mg\/kg b.w.) plus Scopolamine (1mg\/kg b.w.)<\/td>\n118.50 \u00b14.39*<\/sup><\/td>\n105.33\u00b11.97*<\/td>\n<\/tr>\n
5<\/td>\nAETBFP (200mg\/kg b.w.) plus Scopolamine (1mg\/kg b.w.)<\/td>\n112.83 \u00b12.37*<\/td>\n107.50\u00b12.17*<\/td>\n<\/tr>\n
6<\/td>\nAETBFP (334mg\/kg b.w.) plus Scopolamine (1mg\/kg b.w.)<\/td>\n109.33\u00b14.77*<\/sup><\/td>\n99.50\u00b13.31*<\/sup><\/td>\n<\/tr>\n
7<\/td>\nAETBFP (334mg\/kg b.w.)) plus Piracetam (600 mg\/kg b.w.) + Scopolamine (1mg\/kg b.w.)<\/td>\n103.67\u00b13.39*<\/sup><\/td>\n92.67\u00b11.22*<\/sup><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

AETBFP- \u2018aqueous extract of Terminalia bellirica<\/em> fruit pulp\u2019, b.w- body weight<\/p>\n

Values are expressed as mean\u00b1 SEM, TRC-\u2018Time to reach reward chamber\u2019.<\/p>\n

$ <\/sup>p <\/em>< 0.05 group 3 compared to group 1, *<\/sup> p <\/em>< 0.05 test groups compared to group 2.<\/p>\n

Elevated Plus Maze (EPM)<\/strong><\/p>\n

In the analysis of TL using an elevated plus maze as tabulated in table 3, \u2018the time taken by the animal to enter any one of the closed arms\u2019 significantly increased on day 14 (80.83\u00b13.99) and 15 (72.17\u00b13.92) in group 2 (negative control- scopolamine) when compared to normal control depicting the learning and memory impairment induced by scopolamine. The group 3 treated with piracetam showed a significant decrease in TL on day 14 (35.17\u00b12.28) and 15(29.50\u00b12.70) in comparison to group 2 (negative control- scopolamine) indicating an improvement in learning score and memory. The data revealed that the TL on day 14 in the group 4 treated with AETBFP 143 mg\/kg was 62.00\u00b12.62, group 5 treated with AETBFP 200 mg\/kg was50.00\u00b12.30(p<0.05), and in group 6 treated with AETBFP 334 mg\/kg was 42.17\u00b11.70(p<0.05). On day15 the TL in the group 4 treated with AETBFP 143 mg\/kg was 54.50\u00b12.69, group 5 administered with AETBFP 200 mg\/kg was 41.67\u00b1.66(p<0.05), and group 6 treated with AETBFP 334 mg\/kg was 35.50\u00b11.38(p<0.05). The above results depict a dose dependent decrease in TL compared to group 2(negative control- scopolamine). The groups treated with AETBFP 200, 334 mg\/kg showed a significant decrease in TL on both day 14 and 15. The group 7 receiving AETBFP 334 mg\/kg and piracetam decreased TL on day 14(34.50\u00b11.25) and day 15 ((2733\u00b11.49) which was significant when compared to group 2(negative control- scopolamine). Though there was a decrease in TL in group treated with AETBFP and piracetam compared to piracetam alone, it was not significant. It was observed that there was no significant difference in the decrease in TL within groups on days 14 and 15.<\/p>\n

Table 3: Effect on transfer latency using elevated plus maze on day 14 and 15<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n
Group <\/strong><\/td>\nDrugs (dose)<\/strong><\/td>\nDay 14<\/strong><\/p>\n

(TL)<\/strong><\/p>\n

Acquisition\u00a0 <\/strong><\/p>\n

Time in seconds <\/strong><\/td>\n

Day 15<\/strong><\/p>\n

(TL)<\/strong><\/p>\n

Retention <\/strong><\/p>\n

Time in seconds<\/strong><\/td>\n<\/tr>\n

1<\/td>\nNormal saline (1ml\/kg b.w.)<\/td>\n39.33\u00b12.12<\/td>\n34.17\u00b11.01<\/td>\n<\/tr>\n
2<\/td>\nScopolamine (1mg\/kg b.w.)<\/td>\n80.83\u00b13.99<\/td>\n72.17\u00b13.92<\/td>\n<\/tr>\n
3<\/td>\nPiracetam (600mg\/kg b.w.)<\/td>\n35.17\u00b12.28$<\/sup><\/td>\n29.50\u00b12.70$<\/sup><\/td>\n<\/tr>\n
4<\/td>\nAETBFP (143mg\/kg b.w.) plus Scopolamine (1mg\/kg b.w.)<\/td>\n62.00\u00b12.62<\/td>\n54.50\u00b12.69<\/td>\n<\/tr>\n
5<\/td>\nAETBFP (200mg\/kg b.w.) plus Scopolamine (1mg\/kg b.w.)<\/td>\n50.00\u00b12.30*<\/sup><\/td>\n41.67\u00b1.66*<\/sup><\/td>\n<\/tr>\n
6<\/td>\nAETBFP (334mg\/kg b.w.) plus Scopolamine (1mg\/kg b.w.)<\/td>\n42.17\u00b11.70*<\/sup><\/td>\n35.50\u00b11.38*<\/sup><\/td>\n<\/tr>\n
7<\/td>\nAETBFP (334mg\/kg b.w.)) plus Piracetam (600 mg\/kg b.w.) + Scopolamine (1mg\/kg b.w.)<\/td>\n34.50\u00b11.25*<\/sup><\/td>\n27.33\u00b11.49*<\/sup><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

AETBFP- \u2018aqueous extract of Terminalia bellirica<\/em> fruit pulp\u2019, b.w- body weight<\/p>\n

Values are expressed as mean\u00b1 SEM, TL- \u2018Transfer latency\u2019.<\/p>\n

$ <\/sup>p <\/em>< 0.05 group 3 compared to group 1, *<\/sup> p <\/em>< 0.05 test groups compared to group 2<\/p>\n

Dementia is described as any medical condition in which a considerable decline in one’s prior level of cognitive ability impairs\u00a0social,\u00a0occupational\u00a0and domestic\u00a0functioning.30<\/sup> In recent decades, dementia triggered by a variety of aetiologies\u00a0has become more widespread among the elderly.31 <\/sup>Alzheimer’s disease constitutes the primary reason for dementia and has quickly grown into the most pricey, life-threatening and debilitating disease\u00a0in this\u00a0century.32<\/sup> The brain gets exposed to oxidative damage. as its \u2018reactive oxygen species\u2019\u00a0(ROS) levels rise, and\u00a0antioxidant defenses decline. Increased ROS levels may adversely affect cellular components or molecules, causing RNA, DNA, lipid, or protein oxidation. Oxidative damages are implicated in the molecular pathways that connect the build-up of two major aberrant proteins: extracellular “amyloid-beta “plaques and improperly phosphorylated “microtubule-associated protein tau”\u00a0neurofibrillary tangles.33,34<\/sup>Terminalia bellirica<\/em> fruit pulp\u00a0contain phytoconstituents such as bellericanin,\u00a0gallotannic acid,\u00a0ellagic acid, termilignan,\u00a0gallic acid,\u00a0thannilignan, anolignanB,\u00a0flavone, tannins, ethyl gallate,\u00a0ellargic acid,\u00a0galloyl, chebulaginic acid,\u00a0glucose, phenyllemblin, sitisrerol, fructose,\u00a0\u00a0mannitol,\u00a0and rhamnose.35<\/sup> Secondary plant\u00a0metabolites, phenol compounds\u00a0and flavonoids exhibit antioxidant activities. The investigations proved that Terminalia bellerica<\/em> fruit pulp possesses antioxidant activity by demonstrating significant reducing power, overall antioxidant capacity, hydroxyl radical scavenging and free radical scavenging.36<\/sup> In light of the aforementioned, the following research was carried out.<\/p>\n

As far as the researchers are aware, no prior pharmacological investigation into Terminalia belleric<\/em>a fruit pulp’s efficacy against dementia in rodents has been documented. Scopolamine was utilized to induce Alzheimer’s-type dementia, while piracetam was employed as the standard control in both the Hebb\u2019s William and the Elevated Plus Maze models. Scopolamine induces dementia of Alzheimer’s-type by enhancing inflammation, AChE levels and oxidative stress. These are found to be intimately connected to cognition and memory issues.37<\/sup> Piracetam, a GABA\u00a0derivative\u00a0nootropic agent, has significant effectiveness in improving age-dependent cognitive impairment.\u00a0 It acts in the brain by\u00a0modulating\u00a0activating and inhibitory\u00a0pathways, enhancing oxygen consumption, antioxidant actions,\u00a0and increasing cholinergic\u00a0receptors.38<\/sup> Similarly, the test drug, Terminalia bellirica<\/em> fruit pulp, may provide comparable antioxidant effects.<\/p>\n

Research on aging, brain damage, and neurological illnesses have all made use of the \u2018Hebb-Williams maze\u2019 test, which is a popular and reliable technique for evaluating both rodents’ spatial learning and rodents’ memory. The maze is named after the designers, Richard Williams and Donald Hebb, who developed it as early as the 1940s.39,40<\/sup><\/p>\n

In \u2018Hebbs William maze model\u2019, \u00a0(table 2) it was revealed that the TRC of group 4 (AETBFP 143 mg\/kg) on day 14 (118.50 \u00b14.39) and day15 (105.33\u00b11.97) and the TRC of group 5 (AETBFP 200 mg\/kg) on day 14 (112.83 \u00b12.37) and day15 (107.50\u00b12.17) were significantly reduced when compared to the group 2 (negative control- scopolamine) on the day 14 (160.00\u00b17.60) and the day 15 (149.67\u00b19.21), demonstrating adequate drug dosage resulting in an adequate drug concentration at the site of action. The TRC of group 6 (AETBFP 334mg\/kg) on day 14 (109.33\u00b14.77) and day 15 (99.50\u00b13.31) and the TRC of group 7 (AETBFP 334mg\/kg + Piracetam) on day 14 (103.67\u00b13.39) and day 15 (92.67\u00b11.22) significantly reduced when compared to the group 2 (negative control- scopolamine) on the day 14 (160.00\u00b17.60) and the day 15 (149.67\u00b19.21). A higher dosage has resulted in a higher concentration of the drug at the site of action bringing about elevated pharmacological response. A higher reduction in TRC is noted in group 7 (AETBFP 334mg\/kg + Piracetam) compared to group 6 (AETBFP 334mg\/kg) which is due to the addition of standard drug Piracetam to the test drug. When TRC of day 14 (acquisition parameter) and day 15 (memory retention parameter) were compared in figure 1, it is shown that there was a minor drop of TRC on day 15 in all the groups, this can be attributed to retrieval of the stored memory.<\/p>\n\n\n\n
\"\"<\/td>\nFigure 1: Time to reach Reward Chamber (TRC) in Hebb-William Maze on day 14 and 15.<\/strong><\/p>\n

Click here to View Figure<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

The experimental model, elevated plus maze model is a widely accepted methodology for training, memory, and learning processes in rodents. It is made up of open and closed arms arranged perpendicularly, which are crossed in the centre by a platform. Rodents are free to navigate the maze amid open and closed arms.\u00a0 The amount of time that takes for an animal to locomote from one open arm to one closed arm is the TL. The reduction in TL serves as an indicator of memory. 41<\/sup><\/p>\n

In the elevated plus maze model, (table 3) it was revealed that group 4 did not show any significant decrease in TL on day 14 and 15 which may be because of the inadequate drug concentration at the site of action.\u00a0 TL of group 5 (AETBFP 200 mg\/kg) on day 14 (50.00\u00b12.30) and day15 (41.67\u00b1.66) and TL of group 6 (AETBFP 334mg\/kg) on day 14 (42.17\u00b11.70) and day 15 (35.50\u00b11.38) were significantly reduced when compared to the group 2 (negative control- scopolamine) on the day 14 (80.83\u00b13.99) and the day 15 (72.17\u00b13.92), demonstrating adequate drug dosage resulting in an adequate drug concentration at the site of action. The TL of group 7 (AETBFP 334mg\/kg + Piracetam) on the day 14 (34.50\u00b11.25) and the day 15 (27.33\u00b11.49) significantly reduced when compared to the group 2 (negative control- scopolamine) on the day 14 (80.83\u00b13.99) and the day 15 (72.17\u00b13.92). A higher reduction in TL is noted in group 7 (AETBFP 334mg\/kg + Piracetam) which can be ascribed to a higher concentration of the drug at the site of action and the addition of standard drug Piracetam to the test drug bringing about the elevated pharmacological response. When TL of the day 14 (acquisition parameter) and day 15 (memory retention parameter) were compared in figure 2, it is shown that there was a minor drop of TL on day 15 in all the groups, this can be linked to retrieval of the consolidated memory.<\/p>\n\n\n\n
\"\"<\/td>\nFigure 2: Effect on transfer latency using elevated plus maze on day 14 and 15<\/strong><\/p>\n

Click here to View Figure<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Conclusion<\/strong><\/p>\n

In essence, \u2018the aqueous extract of Terminalia bellirica<\/em> fruit pulp\u2019 revealed potential anti-dementia efficacy in rat brain tissue. A significant cognitive enhancing effect was reported at extraction dosages of 200, and 334mg\/kg. By the occurrence of organic materials such as flavonoids, phenol groups\u00a0and tannins, the plant material\u2019s antioxidant potential could be attributed to the neuroprotective action. In this viewpoint, natural compounds are valuable leads in \u00a0the discovery of innovative drugs, having a potential significance in medical treatments. Further studies\u00a0focusing on the determination of the chemical structure of molecules, pharmacokinetics, and pharmacodynamics that are liable for the cognition-enhancing activity can be explored.<\/p>\n

Acknowledgement<\/strong><\/p>\n

We are grateful to Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, for providing us with amenities for this research project.<\/p>\n

Funding source<\/strong><\/p>\n

The author(s) received no financial support for the research, authorship, and\/or publication of this article.<\/p>\n

Conflict of interest<\/strong><\/p>\n

The author(s) do not have any conflict of interest.<\/p>\n

Data Availability Statement<\/strong><\/p>\n

This statement does not apply to this article.<\/p>\n

Ethics Statement<\/strong><\/p>\n

The protocol\u00a0received Institutional Animal Ethics Committee (IAEC) approval for a three-month research period\u00a0involving forty-two\u00a0\u2018Wistar albino rats\u2019 (IAEC approval number: KMC.MNG\/IAEC\/08\/2023). The CCSEA\u00a0registration number assigned to the IAEC\u00a0is 213\/PO\/Re\/S\/2000\/CPCSEA07\/09\/2022 (Valid up to 06\/09\/2027). The rodents were reared in the Pharmacology department\u2019s animal house, KMC\u00a0Mangalore, Karnataka, India. The research\u00a0study was conducted in the Experimental laboratory, Pharmacology department, Kasturba Medical College, Mangalore, India.<\/p>\n

Informed Consent Statement<\/strong><\/p>\n

This study did not involve human participants, and therefore, informed consent was not required<\/p>\n

Clinical Trial Registration<\/strong><\/p>\n

This research does not involve any clinical trials<\/p>\n

Authors\u2019 Contribution<\/strong><\/p>\n

Poovizhi Bharathi R- Conceptualization, Formal analysis, Funding acquisition Project administration; Software; Supervision; Validation; Visualization; Roles\/Writing – original draft; and Writing – review & editing,\u00a0 Shamitha Rai- Data curation; Funding acquisition; Investigation; Methodology, Rashmi R Rao- Conceptualization, Formal analysis, Supervision, Validation; Visualization, Roles\/Writing – original draft; and Writing – review & editing, Trishna Sudarshan- Data curation; Funding acquisition; Investigation; Methodology , Ashitha Leslie Mariam- Investigation; Methodology. Each author mentioned has significantly and directly contributed intellectually to the project and has given their approval for its publication.\u00a0<\/strong><\/p>\n

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