{"id":43174,"date":"2022-03-31T11:42:46","date_gmt":"2022-03-31T11:42:46","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=43174"},"modified":"2022-04-07T07:26:01","modified_gmt":"2022-04-07T07:26:01","slug":"silibinin-improves-the-clinical-scores-of-memory-function-in-patients-with-mild-cognitive-impairment-a-double-blind-placebo-controlled-pilot-study","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol15no1\/silibinin-improves-the-clinical-scores-of-memory-function-in-patients-with-mild-cognitive-impairment-a-double-blind-placebo-controlled-pilot-study\/","title":{"rendered":"Silibinin Improves the Clinical Scores of Memory Function in Patients with Mild Cognitive Impairment: A Double-Blind, Placebo-Controlled Pilot Study"},"content":{"rendered":"

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

Minor “cognitive impairment” (MCI) is a broad clinical disorder marked by mild loss of\u00a0memory that is an etiology for Alzheimer’s dementia.1<\/sup> MCI affects 10\u201320% of people older\u00a0than 65 years. Furthermore, around 10% of MCI cases progress to AD after one year, and\u00a030\u201350% of them progress to AD after five years.2<\/sup> It is thought to have a substantially higher\u00a0progression rate to AD than people who do not have MCI.3<\/sup> AD is accompanied by\u00a0pathological changes associated with neuropsychological symptoms, with no therapeutic\u00a0option available. As a result, an early diagnosis at the “MCI stage” is critical for preventing\u00a0and managing AD.4<\/sup> The goals of MCI treatment are to alleviate current clinical\u00a0manifestations, slow the deterioration of cognitive impairment, and prevent the onset of\u00a0AD. Unfortunately, no effective drug therapy exists for MCI. Changing dietary habits, on\u00a0the other hand, may help in the treatment of MCI. According to epidemiological studies,\u00a0the Mediterranean diet can reduce the risk of Alzheimer’s disease (AD) and the progression\u00a0of MCI to AD.5,6<\/sup> This dietary strategy has been found to protect the brain by reducing\u00a0inflammation and oxidative stress. As a result, certain dietary changes could help to reduce\u00a0the risk of cognitive impairment.7,8<\/sup> Silibinin is the main active component in the extracts\u00a0of the\u00a0Silybum marianum <\/em>seeds. It is characterized as the first of a natural compound class\u00a0called flavonolignans and is traditionally used as folk medicine in many countries to treat\u00a0hepatic diseases of different etiologies.9<\/sup> In an in vitro study, silibinin shows a\u00a0concentration-dependent inhibition of the A\u03b2(1-42) peptide aggregation.10<\/sup> Moreover,\u00a0silibinin acts as a dual blocker of A\u03b2 peptide aggregation and acetylcholinesterase enzyme,\u00a0thus being suggested as a treatment choice for Alzheimer’s disease (AD) and evaluated in\u00a0a mouse model of AD.11<\/sup> Previous studies have shown that silibinin protects against high-fat-diet-induced liver damage via the inhibition of lipogenesis and enhances fatty acid\u00a0oxidation in animal models.12<\/sup> Additionally, various studies have revealed the capacity of\u00a0silibinin to improve memory and learning in LPS-treated mice.13,14<\/sup> In a most recent study,\u00a0a nutraceutical containing silibinin improves cognitive ability in aged LDLR (+\/-) golden\u00a0Syrian hamsters through maintaining the integrity of the blood-brain barrier, among other\u00a0mechanisms.15<\/sup>\u00a0The present pilot study aims to provide clinical data on the protective role\u00a0of silibinin against cognitive impairment in older adults.<\/p>\n

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

Participants<\/strong><\/p>\n

After the study was approved by the local Research Ethics Committee, Faculty of Pharmacy, Al-Rafidain University College (Certificate ID: REC-23-2021), it was carried\u00a0out in accordance with the Good Clinical Practice Criteria of the International Conference on Harmonization (ICH GCP). The investigation was carried out in compliance with the\u00a0Helsinki Declaration’s laws and clinical trial management standards (IGCP). All participants signed an informed consent form and received a general clinical assessment\u00a0before being included in the study. Eighty-five elderly adults with memory impairment were found to be qualified for the study and were randomized into 2 groups: the SIL-treated\u00a0(42 patients) and the placebo-treated (43 patients) groups. The required sample size was calculated based on previous data that explained how to calculate the required sample\u00a0size.16<\/sup> To achieve 90% power for a 5% significance level with a two-sided test, each group needs 40 participants. Under the assumption of a 20% dropout rate, a total of 85 AD\u00a0patients were required. As a consequence, 85 subjects with Alzheimer’s disease were recruited and randomized to either the SIL group (42 patients) or 43 patients included in\u00a0the placebo group.<\/p>\n

Inclusion and exclusion criteria<\/strong><\/p>\n

The current study’s inclusion criteria are as follows: subjects must be over the age of 60 at the time of screening; subjects must be able to understand both English and Arabic\u00a0translation; and subjects must have memory index scores in the neuropsychological component of the “Consortium to Establish a Registry for Alzheimer’s Disease Assessment\u00a0Packet (CERAD-NB)” that differed by more than one standard deviation (SD) compared with the normal level of each item in the test (worse). In the meantime, the individual was\u00a0ruled out if any of the following were present: A three-year history of therapy for Axis I diseases (SCID) according to the Structured Clinical Interview for DSM-IV; has been\u00a0abusing or relying on alcohol over the last three months; the presence of any of certain chronic co-morbidities (epilepsy, mental retardation, CNS illness, endocrine dysfunction,\u00a0hematological malignancies, cardiovascular ailments, and\/or Crohn’s disease); those with abnormal laboratory values such as AST, ALT, or any abnormal laboratory values that\u00a0exceeded the top limit of the normal range by more than three times; those who received prescriptions or herbal medicines within two weeks after the initial day of ingestion were\u00a0excluded from the study, those who had taken any OTC medication or vitamin supplements within one week of the first day of ingestion were also excluded. Moreover, those who had\u00a0participated in another clinical study in the three months prior to the first day of intake, those who donated whole blood or a blood component within two weeks of the first day of\u00a0consumption or a month prior to the first day of intake, and those who the research supervisor determined were unsuitable for inclusion in this clinical trial for any other\u00a0reason were also excluded.<\/p>\n

Study Design and Randomization<\/strong><\/p>\n

For 16 weeks, researchers conducted a multi-center, randomized, double-blind, placebo-controlled clinical investigation. Prior to the start of the investigation, an authorized subject\u00a0manually generated a sequence of random A and B numbers for the random assignment table. Subjects were enrolled four weeks before the screening test to review the eligibility\u00a0criteria for inclusion and exclusion after the first visit. Subjects were randomly assigned to the SIL group (42 patients) or the placebo group (43 patients) in a 1:1 random ratio to\u00a0complete the baseline by the first visit date. Patients in the SIL group were given the test product (Silibinin 250 mg capsules, specially produced for the trial) and told to take it twice\u00a0a day for 16 weeks. Patients in the placebo group were given a microcrystalline cellulose-based placebo mixture. Volunteers were requested to come to the hospital in the eighth\u00a0week for an assessment of drug tolerance, vital signs, and the occurrence of side effects. Other safety-related testing was also carried out. The effects of the medication on cognitive\u00a0function were measured using three different tests. During the pre-inclusion screening, the first test was performed. The second test (week 0) was conducted before the subjects started\u00a0using the test product, and the third test (week 16) was conducted after the 16-week period had ended.<\/p>\n

Clinical Outcomes Measurement<\/strong><\/p>\n

Changes in memory function tests were the study’s key outcome indicator. The \u201cvisual\u00a0learning test (Visual LT)\u201d and the \u201cverbal learning test (Verbal LT)\u201d were shown to be adequate measures for assessing cognitive performance among the CNT’s 18 sub-categories.16<\/sup> Memory loss is one of the most common symptoms of MCI, and memory encoding necessitates attention. Therefore, worsening in these cognitive skills is\u00a0common.17<\/sup> As a result, we chose the best subtests to investigate these cognitive domains in subjects with dementia. As the study participant glanced at the touch screen display, the\u00a0CNT replied by pressing the monitor by hand or pressing a button device, and the CNT tester did so using standardized phrases. The “Visual LT” test involves memorizing the\u00a0first of 30 figures that are displayed on a computer monitor.\u00a0By repeating the technique five times, the visual LT was computed (A1 to A5). After 20 minutes of Visual LT, the\u00a0participant was shown a total of 30 values on a monitor before being reminded of the previous statistics. In the \u201cVerbal LT,\u201d participants listened to a list of 15 words (A list)\u00a0five times through the computer speaker’s recorded voice (Trial A1A5) and recalled as many words as possible after each trial (immediate recall). A new interference list (list B)\u00a0was supplied and recalled after the sixth trial (A5). The patients remembered the terms\u00a0from list A after seeing list B, “Verbal LT B.” The patients were asked to recall as many\u00a0original words from list A as possible after a 20-minute wait (Verbal LT A20 delayed\u00a0recall). They were then instructed to choose 15 keywords from List A from a list of 50\u00a0words displayed on the computer screen (Verbal LT REC delay recognition).\u00a0In the current\u00a0study we utilized the following scores as outcome indicators: 1) The total number of words\u00a0recalled immediately after trials A1 to A5 (A1+A2+A3+A4+A5; Verbal LT A1A5 total\u00a0learning index), 2) the difference between A5 and A1 (A5-A1; Verbal LT learning Slope\u00a0A5-A1), 3) the total number of words recalled after a 20-min delay (Verbal LT A20 delayed\u00a0recall), and 4) the total number of words recalled after a 20-min (A5-A20; Verbal LT A5-A20 memory retention). A visual working memory test was decided upon \u201cVisual WMT\u201d.\u00a0The \u201cVisual WMT\u201d was determined by having the patients say a total of 15 words with the\u00a0same frequency of usage over a computer speaker, regardless of their memory order.<\/p>\n

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

The SPSS version 24 software was used for all statistical analyses (IBM Co., Armonk, NY,\u00a0USA). The means \u00b1 SD of continuous variables were shown, whereas the frequencies of\u00a0categorical variables were shown. Chi-square tests (Fisher’s exact test) were used to\u00a0determine the significance of differences in categorical variables, and the independent t-test was used to compare the means of the two groups. To see if the observed difference in\u00a0verbal learning between the two groups was independent of visual working memory tasks,\u00a0the researchers employed an analysis of covariance (ANCOVA) corrected for visual\u00a0working memory items. The Z-scores were evaluated and compared using subgroup\u00a0(Visual LT, Verbal LT, and Visual WMT). The positive Z-score of the individual indicates\u00a0that they outperformed the placebo group’s average score. To achieve a composite memory\u00a0score, the standardized Z-scores of the three tests were calculated and averaged. An\u00a0independent t-test was used to compare the composite score and the combined composite\u00a0score of visual memory, verbal learning memory, and working memory between the two\u00a0groups. Less than 0.05 was chosen as the statistical significance limit.<\/p>\n

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

A total of 100 people who agreed to participate in this clinical investigation were chosen and given the required exam, with 85 of them meeting our inclusion and exclusion criteria.\u00a0Table 1 shows the overall demographic characteristics of the participants. Male and female individuals were 71.5% and 28.5% in the SIL group, respectively, and 67.4% and 32.6%\u00a0in the placebo group, respectively. The two groups did not differ significantly in terms of gender distribution, age, drinking, smoking, blood pressure, physical measurement indices,\u00a0or cognitive function ratings. A total of 85 patients completed the human research protocol’s procedures in its entirety. The findings were based on data from 85% of the\u00a0participants (Figure 1). After 16 weeks of treatment, the changes in the SIL group’s cognitive function scores were considerably greater than those treated with placebo\u00a0formula (Table 2). The SIL group showed a statistically significant increase in the “Verbal LT delayed recognition” item score when compared to the placebo group. The “Verbal LT”\u00a0score in the SIL group was significantly higher after 16 weeks of treatment than before treatment (p<\/em><0.05). There was also a statistically significant difference in “Verbal LT”\u00a0ratings between the SIL and placebo groups after 16 weeks (p<\/em><0.05). The “Visual WMT” accuracy in the placebo group was significantly improved after 16 weeks of therapy,\u00a0although there was no significant difference in “Visual WMT” scores between the two groups after baseline correction (p<\/em>>0.05). Table 3 illustrates the results of a sub-analysis\u00a0of the change in the Z-score for each memory function item in this study, removing people who were taking medications for metabolic illness (blood pressure, thyroid function).\u00a0When compared to the placebo group, the Z-score of recognition and the composite z-score of the verbal memory domain of the verbal memory function significantly increased after\u00a016 weeks of SIL treatment (p<\/em><0.05). Furthermore, the average value of the overall domain composite scores of “Visual LT”, “Visual WMT,” and “Verbal LT” was utilized to assess\u00a0global cognitive function change, with the SIL group exhibiting a significant improvement in memory (z = 3.4, p<\/em> = 0.016) compared to the placebo group.<\/p>\n

Table 1:<\/strong>\u00a0Demographic features of the study participants.<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
Parameter<\/td>\nSIL group<\/p>\n

(n<\/em>=42)<\/td>\n

Placebo group (n<\/em>=43)<\/td>\np<\/em>-value<\/td>\n<\/tr>\n
Age (year)<\/td>\n69.5\u00b16.2<\/td>\n71.2\u00b15.8<\/td>\n0.06(1)<\/sup><\/td>\n<\/tr>\n
Gender (male\/female)%<\/td>\n30(71.5)\/12(28.5)<\/td>\n29(67.4)\/14(32.6)<\/td>\n0.07(2)<\/sup><\/td>\n<\/tr>\n
Alcohol consumption n<\/em>(%)<\/td>\n2(4.8)<\/td>\n3(6.9)<\/td>\n0.81(2)<\/sup><\/td>\n<\/tr>\n
Smokers n<\/em>(%)<\/td>\n5(11.9)<\/td>\n4(9.3)<\/td>\n0.9(2)<\/sup><\/td>\n<\/tr>\n
Blood pressure (mmHg)<\/td>\n<\/td>\n<\/td>\n<\/td>\n<\/tr>\n
SBP<\/td>\n132.7\u00b112.2<\/td>\n134.1\u00b111.7<\/td>\n0.67(1)<\/sup><\/td>\n<\/tr>\n
DBP<\/td>\n79.2\u00b18.3<\/td>\n78.8\u00b19.1<\/td>\n0.53(1)<\/sup><\/td>\n<\/tr>\n
Pulse (beats\/min)<\/td>\n72.0\u00b18.3<\/td>\n71.2\u00b17.1<\/td>\n0.64(1)<\/sup><\/td>\n<\/tr>\n
Academic ability (years)<\/td>\n8.12\u00b12.2<\/td>\n9.2\u00b12.1<\/td>\n0.24(1)<\/sup><\/td>\n<\/tr>\n
BMI (kg\/m2<\/sup>)<\/td>\n24.8\u00b11.7<\/td>\n25.2\u00b11.9<\/td>\n0.71(1)<\/sup><\/td>\n<\/tr>\n
CERAD-NB word list memory<\/td>\n12.9\u00b12.5<\/td>\n13.1\u00b12.6<\/td>\n0.5(1)<\/sup><\/td>\n<\/tr>\n
CERAD-NB word list recall<\/td>\n4.1\u00b10.9<\/td>\n3.9\u00b11.1<\/td>\n0.31(1)<\/sup><\/td>\n<\/tr>\n
CERAD-NB word list recognition<\/td>\n7.4\u00b11.4<\/td>\n7.3\u00b11.6<\/td>\n0.28(1)<\/sup><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Values are expressed as means\u00b1SD or number (percentage); (1)<\/sup> unpaired t<\/em>-test; (2)<\/sup> Chi-square test; BMI: body mass index; CERAD-NB: The Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery.<\/p>\n\n\n\n
\"Vol15No1_Sil_Saa_fig1\"<\/a><\/td>\nFigure 1: <\/strong>Work-flow chart shows selection and allocation of participants in the study.\u00a0\u00a0SIL: silibinin; n: number of patients.<\/strong><\/p>\n

Click here to view figure<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Table 2:\u00a0Changes in Neurocognitive function test (NCT) pre-and 16-week post-SIL consumption by AD patients compared with placebo.<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n
Variable<\/strong><\/td>\nSIL group (n<\/em>=42)<\/strong><\/td>\nPlacebo group (n<\/em>=43)<\/strong><\/td>\np <\/em>(1)<\/sup><\/strong><\/td>\n<\/tr>\n
Baseline<\/strong><\/td>\n16 week<\/strong><\/td>\nBaseline<\/strong><\/td>\n16 week<\/strong><\/td>\n<\/tr>\n
Visual LT (recognition)<\/td>\n9.8\u00b11.2<\/td>\n12.1\u00b11.4*a<\/sup><\/td>\n10.6\u00b11.5<\/td>\n10.0\u00b12.0b<\/sup><\/td>\n0.26<\/td>\n<\/tr>\n
Visual WMT (accuracy)<\/td>\n35.7\u00b118.2<\/td>\n33.1\u00b116.3a<\/sup><\/td>\n28.3\u00b113.2<\/td>\n32.4\u00b114.1*a<\/sup><\/td>\n0.09<\/td>\n<\/tr>\n
Visual WMT (reaction time)<\/td>\n614.1\u00b182.3<\/td>\n598\u00b178.82a<\/sup><\/td>\n624.2\u00b180.6<\/td>\n610.5\u00b176.8a<\/sup><\/td>\n0.51<\/td>\n<\/tr>\n
Verbal LT A20 (delayed recall) (2)<\/sup><\/td>\n5.27\u00b11.8<\/td>\n9.2\u00b12.1*a<\/sup><\/td>\n6.21\u00b12.3<\/td>\n7.1\u00b13.1*b<\/sup><\/td>\n0.41<\/td>\n<\/tr>\n
Verbal LT REC (delayed recognition) (3)<\/sup><\/td>\n11.5\u00b11.2<\/td>\n14.3\u00b11.4*a<\/sup><\/td>\n10.5\u00b12.0<\/td>\n11.3\u00b11.7b<\/sup><\/td>\n0.03<\/td>\n<\/tr>\n
Verbal LT A1A5 (Total) (4)<\/sup><\/td>\n36.4\u00b15.1<\/td>\n44.3\u00b16.2*a<\/sup><\/td>\n39.7\u00b17.5<\/td>\n40.8\u00b18.2a<\/sup><\/td>\n0.4<\/td>\n<\/tr>\n
Verbal LT A1A5 (average)<\/td>\n7.4\u00b11.3<\/td>\n9.4\u00b11.4*a<\/sup><\/td>\n7.6\u00b11.6<\/td>\n7.9\u00b11.8b<\/sup><\/td>\n0.31<\/td>\n<\/tr>\n
Verbal LT (Learning slope A5-A1) (5)<\/sup><\/td>\n3.6\u00b11.1<\/td>\n5.2\u00b10.9*a<\/sup><\/td>\n3.9\u00b11.2<\/td>\n3.6\u00b10.8b<\/sup><\/td>\n0.05<\/td>\n<\/tr>\n
Verbal LT A5-A20 Memory retention (6)<\/sup><\/td>\n3.6\u00b11.1<\/td>\n2.1\u00b10.8a<\/sup><\/td>\n2.5\u00b11.4<\/td>\n2.1\u00b11.3a<\/sup><\/td>\n0.6<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Values are expressed as mean\u00b1SD;* significant compared with baseline within the same group (p<\/em><0.05); values with non-identical superscripts (a,b) among post-treatment of different groups are significantly different (p<\/em><0.05); SIL: silibinin; Visual LT: visual learning test; Visual WMT: visual working memory test; Verbal LT: verbal learning test; \u00a0(1)<\/sup> ANCOVA (baseline values included as covariates; visual working memory test p<\/em>=0.03); (2)<\/sup> The total words recalled after 20 min; (3)<\/sup> Total words correctly selected from the 50-word list; (4)<\/sup> The total words recalled immediately after trials A1-A5; (5)<\/sup> The difference between A5 and A1; (6)<\/sup> The difference between A5 and A20 delayed recall.<\/p>\n

Table 3:\u00a0Differences in composite Z-score of each cognitive domain and combine cognitive function between the SIL and placebo groups.<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
Variable<\/td>\nSIL group<\/td>\nPlacebo group<\/td>\nZ**<\/td>\np<\/em>-value*<\/td>\n<\/tr>\n
16 Week<\/td>\n16 Week<\/td>\n<\/tr>\n
Visual memory function<\/td>\n<\/tr>\n
Immediate recall<\/td>\n0.35\u00b10.9<\/td>\n0.39\u00b10.42<\/td>\n– 0.12<\/td>\n0.8<\/td>\n<\/tr>\n
Recognition<\/td>\n0.14\u00b10.8<\/td>\n– 0.22\u00b10.68<\/td>\n1.4<\/td>\n0.31<\/td>\n<\/tr>\n
Domain composite score<\/td>\n0.28\u00b10.62<\/td>\n0.19\u00b10.44<\/td>\n0.8<\/td>\n0.51<\/td>\n<\/tr>\n
Verbal memory function<\/td>\n<\/tr>\n
Immediate recall<\/td>\n0.69\u00b10.32<\/td>\n0.17\u00b10.82<\/td>\n2.1<\/td>\n0.05<\/td>\n<\/tr>\n
Delayed recall<\/td>\n0.96\u00b10.41<\/td>\n0.51\u00b10.76<\/td>\n1.5<\/td>\n0.06<\/td>\n<\/tr>\n
Recognition<\/td>\n0.72\u00b10.22<\/td>\n0.06\u00b10.32<\/td>\n4.1<\/td>\n0.001<\/td>\n<\/tr>\n
Domain composite score<\/td>\n0.84\u00b10.28<\/td>\n0.11\u00b10.43<\/td>\n2.7<\/td>\n0.011<\/td>\n<\/tr>\n
Working memory function<\/td>\n<\/tr>\n
Visual WMT (adjusted accuracy)<\/td>\n0.45\u00b10.32<\/td>\n0.12\u00b10.71<\/td>\n1.12<\/td>\n0.2<\/td>\n<\/tr>\n
Visual WMT Reaction time<\/td>\n– 0.62\u00b10.51<\/td>\n– 0.44\u00b10.9<\/td>\n– 0.51<\/td>\n0.31<\/td>\n<\/tr>\n
Domain composite score<\/td>\n– 0.14\u00b10.23<\/td>\n– 0.21\u00b10.66<\/td>\n0.48<\/td>\n0.32<\/td>\n<\/tr>\n
Combined cognitive function<\/td>\n<\/tr>\n
Domain composite score<\/td>\n0.52\u00b10.21<\/td>\n0.032\u00b10.4<\/td>\n3.4<\/td>\n0.016<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Values are expressed as mean z score \u00b1 SD; * unpaired t<\/em>-test; ** Z-test between the two groups; WMT: working memory test.<\/p>\n

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

This is the first randomized clinical study conducted in Iraq to evaluate the efficacy of SIL supplementation in avoiding mild cognitive impairment in Alzheimer’s disease patients.\u00a0Other polyphenols, such as resveratrol,18<\/sup> curcumin,19<\/sup> and berry polyphenols20<\/sup> have previously been studied and shown promising results. In the current study, a dose of 250\u00a0mg of SIL twice a day improved verbal memory in the SIL group compared to the placebo group. Many in vitro<\/em> and animal investigations have shown that silymarin, a plant extract\u00a0that includes SIL, enhances memory function in animal models of cognitive impairment.21,22<\/sup> The A\u03b2 peptide has been suggested to disrupt anti-oxidative defenses in\u00a0the brain, which may contribute to the etiology of Alzheimer’s disease.23<\/sup> Reduced glutathione (GSH) is one of the most common non-protein thiols in the central nervous\u00a0system, where it serves an important anti-oxidant role in both neurons and non-neuronal cells. A\u03b225\u201335<\/sub> lowered GSH levels in the hippocampus in our investigation, which is\u00a0consistent with studies of GSH depletion in the brains of Alzheimer’s patients.24<\/sup> Furthermore, silibinin administration reduced the A\u03b225\u201335<\/sub>-induced drop in GSH levels,\u00a0showing that silibinin’s protective impact on A\u03b225\u201335<\/sub>-induced cognitive impairment includes the activation of anti-oxidative defenses.25 In terms of the mechanisms of action,\u00a0silibinin has free radical scavenging properties, increases intracellular GSH and superoxide dismutase (SOD) levels, and protects neuroblastoma cells from A\u03b2-induced toxicity,10\u00a0while in vivo it prevents neurodegeneration in mice fed a high fat diet26 and reduces memory impairment in mice given intracerebral injection of A\u03b2.27<\/sup> Silibinin has antioxidant\u00a0and anti-inflammatory effects, as well as inhibiting amyloid aggregation and neuronal\u00a0apoptosis.28 Pretreatment with silibinin protects PC12 cells against A\u03b2-induced toxicity via modulating the AKT\/MDM2\/p53 pathway and may provide a new therapeutic strategy\u00a0for treating Alzheimer’s disease.29<\/sup> Similarly, Lu et al<\/em>. discovered that silibinin protects against memory loss and oxidative damage caused by A\u03b225\u201335<\/sub>, suggesting that it could be\u00a0used to treat Alzheimer’s disease.26<\/sup> The poor oral bioavailability of SIL due to poor absorption and fast hepatic biotransformation may limit its therapeutic usage,30<\/sup> despite its\u00a0acceptable safety profile. This previously published research demonstrates that the SIL protects neurons from A\u03b2-induced apoptosis. SIL supplementation thereby protects nerve\u00a0cells by scavenging oxidative radicals and altering MAPK signaling.31<\/sup> In this study, computerized neurocognitive function tests (CNTs) were used to detect minor degrees of\u00a0cognitive impairment, and they can also be used to assess treatment efficacy for cognitive impairment. The Verbal Learning and Memory Test (Verbal LT) is a clinical evaluation of\u00a0verbal learning and memory that can be used to investigate the effects of a range of neurological illnesses, including MCI. The “Verbal LT” score of the SIL group was\u00a0significantly higher than that of the placebo group. The SIL group confirmed a boost in their “Verbal LT” index after 16 weeks of SIL supplementation. A higher “Verbal LT”\u00a0score indicates that following related information has less of an impact on the recall of previously learned content (List B). During “Verbal LT” scoring in the SIL group, the\u00a0short-term store competes with new information (List B) that is unrelated to previous knowledge (List A). Memory retrieval and cognitive control are both aided by this method.\u00a0In this study, SIL supplementation may have aided memory recollection. Furthermore, patients in the SIL group performed better on the “Verbal LT REC delay recognition”\u00a0index.<\/p>\n

Study limitations<\/strong><\/p>\n

There are certain limitations to the research. The results cannot be extended due to the limited number of participants, and the test does not test attention, which is the primary\u00a0ability for encoding information. The likelihood of interfering with numerous polyphenols\u00a0and other natural dietary products that may be ingested during daily food consumption, as\u00a0most of these constituents have potential antioxidant and cyto-protective capabilities, is\u00a0one of the main constraints. To address the constraints, it will be required to conduct comprehensive research with a large number of volunteers. However, major findings from\u00a0this study imply that SIL supplementation in older people with memory loss is safe and may aid in the prevention and management of Alzheimer’s disease.<\/p>\n

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

In older people with memory impairment, sixteen weeks of silibinin treatment improves overall cognitive function, particularly verbal learning and memory function, when\u00a0compared to placebo.<\/p>\n

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

The authors thank Al-Rafidain University College for supporting the project.<\/p>\n

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

There is no conflict of interest.<\/p>\n

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

There is no funding source.<\/p>\n

Ethical Committee Approval<\/strong><\/p>\n

Study protocol has been evaluated and approved by Institutional Research Ethics Committee, Faculty of Pharmacy, Al-Rafidain University College after taking informed consent from study participants.<\/p>\n

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