Role of honey and its chemical constituents on Neuroprotection

Abstract: Honey is a viscous, sweet food substance made by honeybees. It has been consumed since ancient time due to its nutritional and medicinal values. Honey is composed of a variety of chemical constituents such as sugars, amino acids, proteins mainly of enzymes, vitamins, minerals and polyphenols such as flavonoids and phenolic acids. The composition and quality of different types of honey vary depending on the geographical location, floral sources, honeybees, climate changes etc. In recent times there is an increasing trend towards understanding the effects of honey in wound healing, diabetes, cancer, neuroprotection etc. The neuroprotective potential of honey has been shown in many studies and is suggested to be due to the synergistic action of polyphenols and other bioactive compounds present in it. Oxidative stress and neuroinflammation play the key role in the mechanism of neurodegeneration. In oxidative stress, there is an excessive generation of reactive oxygen species (ROS) and reduction of antioxidant capacity leading to oxidation of cellular structures such as lipids, protein and nucleic acids. Honey ameliorates the oxidative stress by attenuating the levels of lipid peroxidation, protein carbonyl content and DNA damage, while it also enhances the antioxidant defence system and reduces the neuroinflammation by minimizing the elevation of pro-inflammatory markers. In our study also we have shown the neuroprotective action of Malaysian Tualang honey in the kainic acid induced excitotoxic rats where the pre-treatment with Tualang honey significantly reduced the elevation of thiobarbituric acid reactive substances (TBARS) and increased the total antioxidant status, reflecting the reduction of oxidative stress. Further, reduction in the neuroinflammation was evidenced by low elevation of TNF-α, IL-1β, glial fibrillary acidic protein etc. and suppression of elevation of apoptotic marker caspase-3 in rat brain. Although pre-clinical studies with honey showed encouraging results, further clinical studies are warranted to elucidate its potential role in neuroprotection

Evaluation of wound healing biomarkers of Interleukin 6 (IL-6), Vascular Endothelial Growth Factor (VEGF) and Matrix Metalloproteinases 9 (MMP-9) in post Lower Segment Caesarean Section (LSCS) patients consuming Channa Striatus extract

Background: Wound healing is a dynamic process which is divided into four phases; haemostasis, inflammatory, proliferation and tissue remodelling phases, that encompasses inflammatory cells, cytokines and growth factors. Interleukin-6 (IL-6), Vascular Endothelial Growth Factor (VEGF) and Matrix Metalloproteinase 9 (MMP-9) involve at the different phases of wound healing. Channa striatus (C.striatus) is a fresh water fish that is believed to have natural properties to promote wound healing. Currently, the effects of C.striatus on the cytokines and growth factors are not available. Objective: This study was conducted to evaluate the wound healing biomarkers; IL-6, VEGF and MMP-9 on post Lower Segment Caesarean Section (LSCS) women consuming oral C.striatus extract. Methods: This was a randomised, double-blinded study amongst LSCS women consuming C.striatus extract versus a placebo at Universiti Sains Malaysia Hospital and Raja Perempuan Zainab II Hospital from May 2011 to January 2013. After randomization, the treatment group received freeze dried C.striatus extract 500 mg daily while the placebo group received maltodextrin 500 mg daily for 6 weeks. Blood samples for IL-6, VEGF and MMP-9 were taken from both groups post-operatively at day 3, week 2, week 4 and week 6. The data were analysed using SPSS version 22. Results: A total of 39 patients from C.striatus and 34 patients from placebo group were included in this study. Within C.striatus group, the results of IL-6, MMP-9 and VEGF showed significant differences (P<0.05) for all the study period. Between group comparison showed significant difference (P<0.05) on week 4 and week 6 for IL-6 and MMP-9 whereas VEGF showed significant difference (P<0.05) on day 1, day 3, week 4 and week 6. The trend of IL-6 and MMP-9 exhibit decreasing trend in both groups however, VEGF in C.striatus group exhibit increasing trend till week 6 compared to placebo group. Conclusion: This study showed C.striatus extract had effects on IL-6, VEGF and MMP-9 in post LSCS women

The ameliorative effects of Tualang honey mediated silver nanoparticles on hippocampal damages following kainic acid administration in male rats

Kainic acid (KA) was shown to be associated in the mechanism of excitotoxicity-induced neurodegeneration in the brain. Tualang honey (TH) was reported to have protection against neurodegeneration but no study has explored on its silver nanoparticles (THSN). Therefore, present study aimed to investigate the effects of THSN on glutathione status and hippocampal histology in KA-induced rats. Sprague-Dawley rats (n=42) were divided into seven groups such as control, THSN 10 mg, THSN 50 mg, KA alone, THSN 10 mg + KA, THSN 50 mg + KA and Topiramate + KA, and each group were pretreated orally with either distilled water, THSN (10 mg/kg or 50 mg/kg) or Topiramate (40 mg/kg), respectively, five times at 12 h intervals. Saline or KA (15 mg/kg body weight) were injected subcutaneously 30 min after last oral treatment. All animals were sacrificed 24 h post KA injection and the hippocampus was harvested for histological examination using cresyl violet staining. The reduced glutathione (GSH) and oxidized glutathione (GSSG) was determined using commercially available ELISA kits. The significant (p<0.05) decrease in the level of cresyl violet-positive cells in hippocampal CA3 in KA alone group was ameliorated by THSN (10 mg/kg) pretreatment group. Meanwhile, the KA induced reduction in GSH:GSSG ratio in KA alone group was significantly (p<0.05) increased by both doses of THSN pretreatments. In conclusion, THSN showed potential protective effects by improving the glutathione status and reduce hippocampal cells injury in the rats after KA induced

Tualang honey attenuates glutathione depletion in the rat hippocampus following kainic acid administration

Excitotoxicity mediated neurodegeneration by kainic acid (KA) was shown to cause oxidative stress in rats’ brains. Tualang honey (TH), a potential natural medicinal agent, was reported to have many therapeutic properties; however, its protection against neurodegenerative disorders was limited. This study aimed to investigate the protective effects of TH on glutathione levels following KA administration in the rats’ hippocampus. Sprague Dawley male rats (n=24) were randomly divided into four groups which are: (i) control, (ii) KA alone, (iii) TH + KA, and (iv) Topiramate (TPM) + KA, and each group was pre-treated orally with either distilled water, TH (1.0 g/kg) or Topiramate (40 mg/kg), respectively, five times at 12 h intervals. Saline or KA (15 mg/kg body weight) were injected subcutaneously 30 min after the last oral treatment. All animals were sacrificed 24 h after KA injection and their hippocampus was harvested to assay the level of reduced glutathione (GSH), oxidized glutathione (GSSG), and GSH:GSSG ratio by using commercially available ELISA kits. The result showed a significant (p<0.05) decrease in the level of GSH in the KA alone group and was improved by TH pretreatment. Meanwhile, the elevation of GSSG level in the KA-induced group was significantly (p<0.05) reduced by pre-treatments of TH and Topiramate. Remarkably, the pre-treatment of TH was significantly (p<0.05) increases the GSH:GSSG ratio after KA administration. In conclusion, TH showed potential protective effects to prevent oxidative stress-related consequences by attenuating the glutathione system in the rats’ hippocampus after KA administration

Green synthesis of silver nanoparticles by tualang honey modulating Hippocampal glutathione in kainic acid-induced seizure in male rats

In recent years, green synthesis of nanoparticles using plant-mediated process has been an emerging research and development in the field of medicinal biotechnology. Tualang honey, a potential natural antioxidant medicinal agent, has been shown to protect against neurodegenerative disorders. Present study explored the ameliorative effects of silver nanoparticles (AgNPs) synthesized using Tualang honey on glutathione level following kainic acid (KA)-induced seizure in the rats' hippocampus. Sprague Dawley male rats (n=42) were randomly divided into seven groups such as control, AgNPs 10 mg,AgNPs50mg, KA alone, AgNPs 10 mg+KA, AgNPs 50 mg+KA and Topiramate+KA, and each group were pre-treated orally with either distilled water, AgNPs (10 mg/kg or 50 mg/kg) or Topiramate (40 mg/kg), respectively, five times at 12 h intervals. Saline or KA (15 mg/kg body weight) were injected subcutaneously 30 min after last oral treatment. All animals were sacrificed 24 h after KA injection and their hippocampus were harvested for determination the level of reduced glutathione (GSH), oxidized glutathione (GSSG) and GSH:GSSG ratio by using commercially available ELISA kits. The significant(p<0.05) decrease in the level of GSH in KA alone group was ameliorated by both doses of AgNPs pre-treatments. Meanwhile, the elevation of GSSG level in KA alone group was significantly(p<0.05)reduced by the pre-treatments of AgNPs 10 mg and Topiramate of KA-induced groups. Remarkably, only AgNPs 1 0+KA group was significantly (p<0.05) increases the GSH:GSSG ratio after KA induced. In conclusion, AgNPs showed potential protective effects by modulating the glutathione system in the rats hippocampus after KA induced

DHA-rich fish oil and Tualang honey reduce chronic stress-induced oxidative damage in the brain of rat model

Background: Exposure to chronic stress induces oxidative damage which alters the dynamic balance between antioxidant and pro-oxidant activities in the brain. Tualang honey (TH) is a Malaysian wild multifloral honey which has been shown to contain high amount antioxidants. DHA-rich fish oil is a form of omega-3 fatty acids found in fish which also possesses some antioxidant activity. This study aimed to evaluate anti-stress activity of DHA-rich fish oil, TH and their combination on several parameters of oxidative stress in chronic stress rat model. Methods: Fifty male Sprague Dawley rats were divided into (i) control, (ii) stress-exposed, (iii) stressexposed and treated with TH (1 g/kg body weight twice daily), (iv) stress-exposed and treated with DHA-rich fish oil (450 mg/kg body weight twice daily), and (v) stress-exposed and treated with a combination of TH and DHA-rich fish oil. The chronic stress regimen consisted of a combination of restraint stress and a swim stress test for 28 days. Results: DHA-rich fish oil and TH significantly (p < 0.05) supressed stress-induced elevation of serum corticosterone and lipid peroxidation, and caused a significant increase in total antioxidant capacity. For glutathione status, only TH significantly reduced stress-induced elevation of oxidised glutathione (GSSG) and normalised GSH/GSSG ratio. Conclusion: Both DHA-rich fish oil and TH have protective effects against brain oxidative stress but consuming these substances together does not seem to provide an additional benefit compared to consuming them separately

Preliminary study on the effect of Tualang Honey and its silver nanoparticles on Kainic Acid-Induced memory deficits and oxidative damage in rat hippocampus

Kainic acid (KA) mediated excitotoxicity has been shown to cause memory impairment and oxidative stress in rats brain. The aim of this study was to investigate the effect of Tualang honey (TH) and its silver nanoparticles (THSN) on the KA-induced memory deficits and oxidative damage in rats’ hippocampus.Twenty-four adult male Sprague-Dawley rats were randomized into eight groups: (i) control, (ii) THSN (10mg/kg), (iii) THSN (50mg/kg), (iv) KA only, (v) KA+TH, (vi) KA+THSN (10mg/kg), (vii) KA+THSN (50mg/kg), and (viii) KA+Topiramate. Based on their respective groups, rats were pretreated orally with either distilled water, THSN (10 or 50 mg/kg body weight), Tualang honey (1.0 g/kg body weight), or Topiramate (40 mg/kg body weight), five times at 12 hours intervals. Saline or KA (15 mg/kg body weight) were injected subcutaneously 30 min after last oral treatment.Novel object recognition test (NORT) was performedfor memory assessment. The rats were sacrificed 24 hours post KA induction and hippocampus was harvested. Malondialdehyde (MDA) and superoxide dismutase (SOD) were measured using commercially available ELISA kits. The results showed that there was a trend of decreased in MDA level in both TH and THSN groups, however there were no significance difference. There wassignificantly increased level in SOD following pretreatment with TH and THSN groups compared to KA only group. Interestingly, these pretreatmentgroups also demonstrated enhanced memory as evidenced by significant increase in recognition index in NORT when compared to KA only group. In conclusion, this preliminary finding suggests that the pretreatment with TH and THSN might have potential role toimprove the memory and ameliorate oxidative stress in the KA-induced exitotoxicity rats. However, further study needs to be carried out to understand the precise mechanism

Profiling the research landscape on cognitive aging: a bibliometric analysis and network visualization

Objectives: This study aimed to profile the cognitive aging research landscape from 1956 to 2021. Methods: A total of 3,779 documents were retrieved from the Scopus database for the bibliometric analysis and network visualization. By comparing each keyword’s overall connection strength (centrality), frequency (density), and average year of publication (novelty) to the calculated median values acquired from the overlay view of the VOSviewer map, the enhanced strategic diagrams (ESDs) were constructed. Results: The findings showed an increasing trend in the number of publications. The United States leads the contributing countries in cognitive aging research. The scientific productivity pattern obeyed Lotka’s law. The most productive researcher was Deary, I. J., with the highest number of publications. The collaborative index showed an increasing trend from 1980 onwards. Frontiers in Aging Neuroscience is the most prestigious journal in the field of cognitive aging research. In Bradford core journals zone 1, the top 10 core journals of cognitive aging research provided more than half of the total articles (697, or 55.36 percent). Conclusions: For the next decades, the trending topics in cognitive aging research include neuropsychological assessment, functional connectivity, human immunodeficiency virus (HIV), decision-making, gender, compensation, default mode network, learning and memory, brain-derived neurotrophic factor (BDNF), obesity, Dgalactose, epigenetics, frailty, mortality, mini-mental state examination (MMSE), anxiety, and gait speed

The value of c-reactive protein/albumin ratio in the severity and mortality in COVID-19 patients

The continuing coronavirus disease 2019 (COVID-19) pandemic provides several concerns for physicians. Thus, saving maximum lives as possible and finding people at risk of serious problems is essential. This study aimed to determine the association of CRP/albumin ratio with severity, duration of hospital stay and mortality in COVID-19 patients. The patient aged 18 to 80 with positive COVID-19 at Hospital Raja Perempuan Zainab II (HRPZ II), Kota Bharu, Kelantan, with available CRP/albumin ratio data on admission, were retrospectively evaluated from March 2021 to March 2022. Disease severity was categorized based on Annex 2e guidelines by Malaysia's Ministry of Health, which further classified them into mild to moderate disease (Stage 1-3) and severe to critical illness (Stage 4- 5). The CRP/albumin ratio levels on Day 1 admission were archived from the electronic medical record system and compared between the two groups. The study included 141 COVID-19 patients with a mean age of 51.11(SD± 16.66) for mild to moderate and 58.06 (SD± 13.87) for severe to critical. The severe to critical group had significantly higher values of patients’ age (p=0.015). The frequency of patients according to severity, 36(26%) were mild to moderate, and 105(74%) were severe to critical. CRP/Alb ratio was significantly elevated in the severe to critical illness group (p<0.001). 28 (20%) patients died, 113 (80%) survived, and median CRP/albumin ratio values were higher in non-survivors compared to survivors (p<0.001). High CRP/albumin ratio levels were associated with longer hospital stay (correlation coefficients 0.295, p<0.001). Receiver operator characteristic analysis showed that the area under the curve (AUC) for CRP/albumin ratio was 0.755 (95% CI: 0.670- 0.840). The optimal cut-off point of CRP/albumin ratio was 1.494 (sensitivity 60%, specificity 89%, PPV 0.94, NPV 0.43, LR+ 5.41, LR- 0.45, DOR 12). CRP/Alb ratio on Day 1 admission is associated with COVID-19 severity and mortality

AST, ALT, Bilirubin and AST/ALT Ratio role; Covid- 19 Patients

Background Impaired liver function upon admission has been linked to the severity of COVID-19 infection, yet the data is debated [1]. Therefore, this retrospective study aimed to evaluate the liver function among COVID-19 patients during hospitalization and its association with the disease severity. Methodology The patient aged 18 to 80 with positive COVID-19 at Hospital Raja Perempuan Zainab II (HRPZ II), Kota Bharu, Kelantan, with available AST, ALT, Bilirubin, and AST/ALT ratio data on admission, were retrospectively evaluated from March 2021 to March 2022. Disease severity was categorized based on Annex 2e guidelines by Malaysia's Ministry of Health, which further classified them into mild to moderate disease (Stage 1-3) and severe to critical illness (Stage 4-5). The AST, ALT, Bilirubin, and AST/ALT ratio levels on Day 1 admission were archived from the electronic medical record system and compared between the two groups. The statistical analysis was using SPSS version 27. This study was approved by (JEPeM-USM) protocol code USM/JEPeM/21100691 and Ministry of Health Malaysia NMRR-21-762-58458 (IIR). Results and Discussion The study included a total of 168 COVID-19 patients with a mean (SD) age of 46.67(16.10) for mild to moderate and 56.66(12.41) for severe to critical. There is a significant age group for both groups (p-value=0.002). During hospitalization, 16(14.41%) patients progressed to death from severe to critically ill patients. Upon admission, the median (IQR) of AST and ALT were significantly higher in the severe to critical group compared to in the mild to moderate group, [AST; 39.0(49.0) and 24.0(14.0), ALT 38.0(43.0) and 21.0(18.0)], p<0.05. However, no significant difference between both groups for bilirubin level and AST/ALT ratio. Non-survivors had a higher AST and ALT level compared to survivors, with a median (IQR) of [AST 98.0(88.0) and 32.0 (26.0), ALT of 67.5(90.0) and 28.0(31.0), (p<0.05). Similarly, no significant difference between non-survivors and survivors for bilirubin and AST/ALT ratio. Our study support that, abnormal liver function at admission has been shown to be associated with the disease severity and mortality of COVID-19 infection. However, there is also a need to observe the COVID-19 survivors' hepatobiliary sequelae and dynamic liver function changes following hospital discharge. Conclusion Abnormal AST and ALT level at admission has been shown to be associated with the disease severity and mortality of COVID-19 infection. Further study needed to evaluate liver damage in COVID-19 post-discharge