Hashim Embong

After a careful and comprehensive review of our data and the figures in our manuscript, we have identified an area where we believe a correction is warranted in order to enhance the clarity and precision of our findings

Maternal obesity, characterized by an elevated body mass index (BMI) during pregnancy, is known to have adverse effects on the offspring. However, a recent study suggests that Elateriospermum tapos (E. tapos) yogurt may hold potential in mitigating excessive weight retention post-pregnancy. Thus, this study aims to employ network pharmacology to explore the pharmacological effects of the bioactive compounds present in E. tapos yogurt against maternal obesity. Initially, a screening process is conducted to identify the bioactive compounds in E. tapos yogurt, followed by the prediction of potential gene targets for these compounds using Swiss Target Prediction and the SuperPred databases. Maternal obesity-associated genes are sourced from the OMIM, DisGeNet, and GeneCards databases. The interaction between the identified compounds and maternal obesity genes is established via protein–protein interaction analysis, gene ontology examination, and KEGG pathway analysis. To validate the results, molecular docking studies are conducted using AutoDock Tools software. The findings reveal that out of the 64 compounds analyzed, three meet the screening criteria, resulting in a total of 380 potential gene targets. Among these targets, 240 are shared with maternal obesity-related genes. Further analysis demonstrates the favorable affinity of these active compounds with key targets, linking them to biological processes involving protein phosphorylation, inflammation, as well as the pathways related to lipid metabolism, atherosclerosis, and the other signaling pathways. In conclusion, this study provides valuable insights into the potential pharmacological effects of the bioactive compounds found in E. tapos yogurt against maternal obesity. These findings open avenues for further exploration and potential therapeutic interventions targeting maternal obesity.

Obesity is known as a transgenerational vicious cycle and has become a global burden due to its unavoidable complications. Modern approaches to obesity management often involve the use of pharmaceutical drugs and surgeries that have been associated with negative side effects. In contrast, natural antioxidants, such as flavonoids, have emerged as a promising alternative due to their potential health benefits and minimal side effects. Thus, this narrative review explores the potential protective role of flavonoids as a natural antioxidant in managing obesity. To identify recent in vivo studies on the efficiency of flavonoids in managing obesity, a comprehensive search was conducted on Wiley Online Library, Scopus, Nature, and ScienceDirect. The search was limited to the past 10 years; from the search, we identified 31 articles to be further reviewed. Based on the reviewed articles, we concluded that flavonoids offer novel therapeutic strategies for preventing obesity and its associated co-morbidities. This is because the appropriate dosage of flavonoid compounds is able to reduce adipose tissue mass, the formation of intracellular free radicals, enhance endogenous antioxidant defences, modulate the redox balance, and reduce inflammatory signalling pathways. Thus, this review provides an insight into the domain of a natural product therapeutic approach for managing obesity and recapitulates the transgenerational inheritance of obesity, the current available treatments to manage obesity and its side effects, flavonoids and their sources, the molecular mechanism involved, the modulation of gut microbiota in obesity, redox balance, and the bioavailability of flavonoids. In toto, although flavonoids show promising positive outcome in managing obesity, a more comprehensive understanding of the molecular mechanisms responsible for the advantageous impacts of flavonoids—achieved through translation to clinical trials—would provide a novel approach to inculcating flavonoids in managing obesity in the future as this review is limited to animal studies.

Indoleamine 2,3-dioxygenase (IDO) and the tryptophan–kynurenine pathway (TRP-KP) are upregulated in ageing and could be implicated in the pathogenesis of delirium. This study evaluated the role of IDO/KP in lipopolysaccharide (LPS)-induced delirium in an animal model of chronic cerebral hypoperfusion (CCH), a proposed model for delirium. CCH was induced by a permanent bilateral common carotid artery ligation (BCCAL) in Sprague Dawley rats to trigger chronic neuroinflammation-induced neurodegeneration. Eight weeks after permanent BCCAL, the rats were treated with a single systemic LPS. The rats were divided into three groups: (1) post-BCCAL rats treated with intraperitoneal (i.p.) saline, (2) post-BCCAL rats treated with i.p. LPS 100 μg/kg, and (3) sham-operated rats treated with i.p. LPS 100 μg/kg. Each group consisted of 10 male rats. To elucidate the LPS-induced delirium-like behaviour, natural and learned behaviour changes were assessed by a buried food test (BFT), open field test (OFT), and Y-maze test at 0, 24-, 48-, and 72 h after LPS treatment. Serum was collected after each session of behavioural assessment. The rats were euthanised after the last serum collection, and the hippocampi and cerebral cortex were collected. The TRP-KP neuroactive metabolites were measured in both serum and brain tissues using ELISA. Our data show that LPS treatment in CCH rats was associated with acute, transient, and fluctuated deficits in natural and learned behaviour, consistent with features of delirium. These behaviour deficits were mild compared to the sham-operated rats, which exhibited robust behaviour impairments. Additionally, heightened hippocampal IDO expression in the LPS-treated CCH rats was associated with reduced serum KP activity together with a decrease in the hippocampal quinolinic acid (QA) expression compared to the sham-operated rats, suggested for the presence of endotoxin tolerance through the immunomodulatory activity of IDO in the brain. These data provide new insight into the underlying mechanisms of delirium, and future studies should further explore the role of IDO modulation and its therapeutic potential in delirium.

Maternal obesity can be considered an intergenerational cycle and is also an important indicator of cognitive impairments. It is thought that using natural products is the best and safest way to combat maternal obesity and associated complications. Recent studies have shown that Elateriospermum tapos (E. tapos) contains bioactive compounds with anti-obesity effects, and yoghurt is a convenient medium for supplementing obese maternal rats with E. tapos extract. Thus, the aim of this study is to investigate the impact of E. tapos in yoghurt on maternally obese rats’ cognitive function supplemented with a high-fat diet (HFD). In this study, 48 female Sprague-Dawley rats were used. The rats were fed HFD for a period of 16 weeks to induce obesity, after which they were allowed to mate. Upon confirmation of pregnancy, obese rats were given varying doses of E. tapos (5, 50, and 500 mg/kg) in yoghurt until postnatal (PND) day 21. On PND 21, the dams’ body mass index (BMI), Lee index, abdominal circumference, oxidative status, and metabolic profile were measured. The behavioral tests (open field, place, and object recognition) were conducted on PND 21 to access memory. The results show that the 50 and 500 mg/kg E. tapos in yoghurt supplemented groups had similar BMI, Lee index, abdominal circumference, lipid profile, FBG, insulin, FRAP, and GSH levels, as well as a similar recognition index, in comparison with the control group supplemented with saline. In conclusion, the results of this study indicate that the newly formulated E. tapos in yogurt can act as an anti-obesity agent in maternal obesity, alleviate anxiety, and enhance hippocampal-dependent memory.

Obesity is a chronic low-grade inflammatory condition that induces the generation of oxidative stress and inflammation. This oxidative stress and inflammation stimulate brain atrophy and some morphological changes in the brain that eventually result in cognitive impairments. However, there is no exact study that has summarized the role of oxidative stress and inflammation in obesity and its impact on cognitive impairments. Thus, the objective of this review is to recapitulate the current role of oxidative stress and inflammation in cognitive decline based on in vivo evidence. A comprehensive search was performed in Nature, Medline and Ovid, ScienceDirect, and PubMed, and the search was limited to the past 10 years of publication. From the search, we identified 27 articles to be further reviewed. The outcome of this study indicates that a greater amount of fat stored in individual adipocytes in obesity induces the formation of reactive oxygen species and inflammation. This will lead to the generation of oxidative stress, which may cause morphological changes in the brain, suppress the endogenous antioxidant system, and promote neuroinflammation and, eventually, neuronal apoptosis. This will impair the normal function of the brain and specific regions that are involved in learning, as well as memory. This shows that obesity has a strong positive correlation with cognitive impairments. Hence, this review summarizes the mechanism of oxidative stress and inflammation that induce memory loss based on animal model evidence. In conclusion, this review may serve as an insight into therapeutic development focusing on oxidative stress and inflammatory pathways to manage an obesity-induced cognitive decline in the future.

Emerging evidence suggests that cognitive impairments may result from various factors, such as neuroinflammation, oxidative stress, mitochondrial damage, impaired neurogenesis, synaptic plasticity, blood–brain barrier (BBB) disruption, amyloid β protein (Aβ) deposition, and gut dysbiosis. Meanwhile, dietary polyphenol intake in a recommended dosage has been suggested to reverse cognitive dysfunction via various pathways. However, excessive intake of polyphenols could trigger unwanted adverse effects. Thus, this review aims to outline possible causes of cognitive impairments and how polyphenols alleviate memory loss via various pathways based on in vivo experimental studies. Thus, to identify potentially relevant articles, the keywords (1) nutritional polyphenol intervention NOT medicine AND neuron growth OR (2) dietary polyphenol AND neurogenesis AND memory impairment OR (3) polyphenol AND neuron regeneration AND memory deterioration (Boolean operators) were used in the Nature, PubMed, Scopus, and Wiley online libraries. Based on the inclusion and exclusion criteria, 36 research papers were selected to be further reviewed. The outcome of all the studies included supports the statement of appropriate dosage by taking into consideration gender differences, underlying conditions, lifestyle, and causative factors for cognitive decline, which will significantly boost memory power. Therefore, this review recapitulates the possible causes of cognitive decline, the mechanism of polyphenols involving various signaling pathways in modulating the memory, gut dysbiosis, endogenous antioxidants, bioavailability, dosage, and safety efficacy of polyphenols. Hence, this review is expected to provide a basic understanding of therapeutic development for cognitive impairments in the future.

Maternal obesity is an intergenerational vicious cycle and one of the primary causes of cognitive deficits and high anxiety levels in offspring, which often manifest independently of sex. It is proven that curbing the intergenerational inheritance of obesity through early intervention during the gestation period has a positive outcome on the body composition, cognitive function, and anxiety level of the offspring. A recent discovery shows that the consumption of Elateriospermum tapos (E. tapos) seed extract modulates body mass and ameliorates stress hormones in obese dams, while a probiotic bacterial strain can cross the placenta and boost a child’s memory. Thus, we speculate that probiotics are the best medium to integrate plant extract (E. tapos extract) to access the effect on the child’s cognition. Thus, this study aimed to investigate the early intervention of E. tapos yoghurt in obese dams in the cognition and anxiety levels of male offspring. In this study, 40 female rats were fed with a high-fat diet (HFD) to induce obesity before pregnancy, while another 8 rats were fed with standard rat pellets for 16 weeks. Upon successful copulation, treatment was initiated for the obese dams up to the postnatal day (PND) 21. The groups included normal chow and saline (NS), HFD and saline (HS), HFD and yoghurt (HY), HFD and 5 mg/kg E. tapos yoghurt (HYT5), HFD and 50 mg/kg E. tapos yoghurt (HYT50), and HFD and 500 mg/kg E. tapos yoghurt (HYT500). All rats were euthanised on PND 21, and the body mass index (BMI), Lee index, and waist circumference were measured for the male offspring. Hippocampal-dependent memory tests and open field tests were conducted to access for cognition and anxiety status. Fasting blood glucose (FBG), total fat (%), insulin, leptin, lipid profile, and antioxidant parameter on serum and hypothalamus (FRAP and GSH) were accessed on PND 21. The result shows male offspring of 50 mg/kg-supplemented obese dams have comparable total fat (%), lipid profile, insulin level, FBG level, plasma insulin level, recognition index, low anxiety level, and improved hypothalamic FRAP and GSH levels to the normal group. In conclusion, this study highlights that the effect of early intervention of our novel formulation of E. tapos yoghurt in obese dams alleviates cognitive deficits and anxiety in male offspring by modulating metabolic profiles at the dose of 50 mg/kg.

Delirium, a common form of acute brain dysfunction, is associated with increased morbidity and mortality, especially in older patients. The underlying pathophysiology of delirium is not clearly understood, but acute systemic inflammation is known to drive delirium in cases of acute illnesses, such as sepsis, trauma, and surgery. Based on psychomotor presentations, delirium has three main subtypes, such as hypoactive, hyperactive, and mixed subtype. There are similarities in the initial presentation of delirium with depression and dementia, especially in the hypoactive subtype. Hence, patients with hypoactive delirium are frequently misdiagnosed. The altered kynurenine pathway (KP) is a promising molecular pathway implicated in the pathogenesis of delirium. The KP is highly regulated in the immune system and influences neurological functions. The activation of indoleamine 2,3-dioxygenase, and specific KP neuroactive metabolites, such as quinolinic acid and kynurenic acid, could play a role in the event of delirium. Here, we collectively describe the roles of the KP and speculate on its relevance in delirium.

Maternal obesity is a key predictor of childhood obesity and a determining factor for a child’s body composition. Thus, any form of maternal nutrition during the gestational period plays a vital role in influencing the growth of the fetus. Elateriospermum tapos (E. tapos) yogurt has been found to comprise many bioactive compounds such as tannins, saponins, α-linolenic acid, and 5′-methoxy-bilobate with apocynoside I that could cross the placenta and exhibit an anti-obesity effect. As such, this study aimed to investigate the role of maternal E. tapos yogurt supplementation on offspring body composition. In this study, 48 female Sprague Dawley (SD) rats were induced with obesity using a high-fat diet (HFD) and were allowed to breed. Upon confirmation of pregnancy, treatment was initiated with E. tapos yogurt on the obese dams up to postnatal day 21. The weaning offspring were then designated into six groups according to their dam’s group (n = 8) as follows; normal food and saline (NS), HFD and saline (HS), HFD and yogurt (HY), HFD and 5 mg/kg of E. tapos yogurt (HYT5), HFD and 50 mg/kg of E. tapos yogurt (HYT50), and HFD and 500 mg/kg of E. tapos yogurt (HYT500). The body weight of the offspring was accessed every 3 days up to PND 21. All the offspring were euthanized on PND 21 for tissue harvesting and blood sample collection. The results showed that both male and female offspring of obese dams treated with E. tapos yogurt showed growth patterns similar to NS and reduced levels of triglycerides (TG), cholesterol, LDL, non-HDL, and leptin. Liver enzymes such as ALT, ALP, AST, GGT, and globulin, and renal markers such as sodium, potassium, chloride, urea, and creatinine levels significantly reduced (p < 0.05) in the offspring of E. tapos yogurt-treated obese dams with the normal histological architecture of the liver, kidney, colon, RpWAT, and visceral tissue that is comparable to NS. In toto, E. tapos yogurt supplementation of obese dams exerted an anti-obesity effect by preventing intergenerational obesity by reversing HFD-induced damage in the fat tissue of the offspring.