Edible Bird's Nest Regulates Hepatic Cholesterol Metabolism through Transcriptional Regulation of Cholesterol Related Genes.

Objective: Hypercholesterolemia is a strong risk factor for cardiovascular diseases. Side effects associated with the use of pharmaceutical agents can cancel out their benefits. Dietary management of hypercholesterolemia is, therefore, receiving much attention due to fewer side effects. In this study, we explored the effectiveness of edible bird's nest (EBN) in the prevention of hypercholesterolemia in rats. Methods: High-cholesterol diet (HCD) (4.5% cholesterol and 0.5% cholic acid) with or without EBN (low (2.5%) or high dose (20%)) was given to rats for 12 weeks, and their weights were observed. Simvastatin (10 mg/kg/day) was administered for the same period as a control drug. Serum and tissue samples were collected at the end of the study, from which biochemical parameters (lipid profiles, oxLDL, liver enzymes, urea, creatinine, uric acid, and lipase activity) and hepatic mRNA levels were measured. Results: The HCD group had higher levels of serum lipids, liver enzymes, uric acid, urea, and lipase activity compared with those of the other groups. The hepatic mRNA levels of cholesterol metabolism genes (APOB, PCSK9, HMGCR, LDLR, and CYP7A1) in the HCD group also tended toward increased cholesterol production and reduced cholesterol clearance. EBN, especially the highest dose, attenuated the HCD-induced changes, partly through improving the transcriptional regulation of hepatic cholesterol metabolism genes with fold changes of 0.7, 0.6, 0.5, 1.7, and 2.7, respectively, in comparison to the HCD group. In fact, EBN produced better results than simvastatin. Conclusion: Thus, the results suggest that EBN can regulate cholesterol metabolism and, therefore, be a source of functional ingredients for the management of hypercholesterolemia.

Efficacy of Edible Bird's Nest on Cognitive Functions in Experimental Animal Models: A Systematic Review.

Edible bird's nest (EBN) is constructed from saliva of swiftlets birds and consumed largely by Southeast and East Asians for its nutritional value and anti-aging properties. Although the neuroprotection of EBN in animals has been reported, there has not been yet systemically summarized. Thus, this review systemically outlined the evidence of the neuroprotective activity of EBN in modulating the cognitive functions of either healthy or with induced-cognitive dysfunction animals as compared to placebos. The related records from 2010 to 2020 were retrieved from PubMed, Scopus, Web of Science and ScienceDirect using pre-specified keywords. The relevant records to the effect of EBN on cognition were selected according to the eligibility criteria and these studies underwent appraisal for the risk of bias. EBN improved the cognitive functions of induced-cognitive dysfunction and enhanced the cognitive performance of healthy animals as well as attenuated the neuroinflammations and neuro-oxidative stress in the hippocampus of these animals. Malaysian EBN could improve the cognitive functions of experimental animals as a treatment in induced cognitive dysfunction, a nutritional cognitive-enhancing agent in offspring and a prophylactic conservative effect on cognition against exposure to subsequent noxious cerebral accidents in a dose-depended manner through attenuating neuroinflammation and neuro-oxidative stress. This systemic review did not proceed meta-analysis.

Edible Bird's Nest Attenuates Menopause-Related Bone Degeneration in Rats via Increaing Bone Estrogen-Receptor Expression / 中国结合医学杂志

OBJECTIVE@#To investigate the mechanistic basis for the attenuation of bone degeneration by edible bird's nest (EBN) in ovariectomized rats.@*METHODS@#Forty-two female Sprage-Dawley rats were randomized into 7 groups (6 in each group). The ovariectomized (OVX) and OVX + 6%, 3%, and 1.5% EBN and OVX +estrogen groups were given standard rat chow alone, standard rat chow +6%, 3%, and 1.5% EBN, or standard rat chow +estrogen therapy (0.2mg/kg per day), respectively. The sham-operation group was surgically opened without removing the ovaries. The control group did not have any surgical intervention. After 12 weeks of intervention, blood samples were taken for serum estrogen, osteocalcin, and osteoprotegerin, as well as the measurement of magnesium, calcium abd zinc concentrations. While femurs were removed from the surrounding muscles to measure bone mass density using the X-ray edge detection technique, then collected for histology and estrogen receptor (ER) immunohistochemistry.@*RESULTS@#Ovariectomy altered serum estrogen levels resulting in increased food intake and weight gain, while estrogen and EBN supplementation attenuated these changes. Ovariectomy also reduced bone ER expression and density, and the production of osteopcalcin and osteorotegerin, which are important pro-osteoplastic hormones that promote bone mineraliztion and density. Conversely, estrogen and EBN increased serum estrogen levels leading to increased bone ER expression, pro-osteoplastic hormone production and bone density (all P<0.05).@*CONCLUSION@#EBN could be used as a safe alternative to hormone replacement therapys for managing menopausal complications like bone degeneration.

Nanoemulsification of Rice Bran Wax Policosanol Enhances Its Cardio-protective Effects via Modulation of Hepatic Peroxisome Proliferator-activated Receptor gamma in Hyperlipidemic Rats.

Policosanol, a mixture of long-chain alcohols found in animal and plant waxes, has several biological effects including lipid-lowering that have been extensively studied. However, its bioavailability is low. To investigate the effect of nanoemulsified rice bran wax policosanol (NPOL) on plasma homocysteine, heart and liver histology in hyperlipidemic rats, high-fat diet containing 2.5% cholesterol was used to induce hyperlipidemia in Sprague Dawley rats. The hyperlipidemic rats were treated with NPOL and rice bran wax policosanol (POL) in comparison with normal diet (ND), high-cholesterol diet (HCD) and simvastatin-treated rats. Plasma homocysteine, heart and liver histology, and hepatic mRNA expression of peroxisome proliferator-activated receptor gamma (PPARG) were evaluated. The NPOL group, similar to the simvastatin group, showed reduced plasma homocysteine, preserved heart and liver histology, and down-regulated hepatic PPARG mRNA in comparison to the control group, and was better than the POL group. The results suggest that the modest effect of NPOL on homocysteine and preservation of heart and liver histology could be through the regulation of PPARG expression on a background of increased assimilation of rice bran wax policosanol.

Correlation of Mortality Burdens of Cerebrovascular Disease and Diabetes Mellitus with Domestic Consumption of Soya and Palm Oils.

BACKGROUND: Cerebrovascular diseases (CBVDs) and diabetes mellitus (DM) are interrelated and cumbersome global health burdens. However, the relationship between edible oils consumption and mortality burdens of CBVDs and DM has not yet been evaluated. This review aims to explore correlations between per capita mortality burdens of CBVDs and DM, as well as food consumption of palm or soya oils in 11 randomly selected countries in 2005, 2010, and 2016. METHODS: After obtaining data on food consumption of palm and soya oils and mortality burdens of CBVDs and DM, correlations between the consumption of oils and mortality burdens of diseases were explored. RESULTS: There was a positive correlation between the consumption of soya oil with the mortality burden of CBVDs in Australia, Switzerland, and Indonesia, as well as the mortality burden of DM in the USA. The consumption of palm oil had a positive correlation with the mortality burden of DM in Jordan only. CONCLUSIONS: Food consumption of soya oil in several countries possibly contributes to the mortality burden of CBVDs or DM more than food consumption of palm oil, which could be a possible risk factor in the mortality burdens of CBVDs and DM.

Safety and Neuroprotective Efficacy of Palm Oil and Tocotrienol-Rich Fraction from Palm Oil: A Systematic Review.

BACKGROUND: Several natural products have been reported to elicit beneficial effects against neurodegenerative disorders due to their vitamin E contents. However, the neuroprotective efficacy of palm oil or its tocotrienol-rich fraction (TRF) from the pre-clinical cell and animal studies have not been systematically reviewed. METHODS: The protocol for this systematic review was registered in "PROSPERO" (CRD42019150408). This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The Medical Subject Heading (MeSH) descriptors of PubMed with Boolean operators were used to construct keywords, including ("Palm Oil"[Mesh]) AND "Nervous System"[Mesh], ("Palm Oil"[Mesh]) AND "Neurodegenerative Diseases"[Mesh], ("Palm Oil"[Mesh]) AND "Brain"[Mesh], and ("Palm Oil"[Mesh]) AND "Cognition"[Mesh], to retrieve the pertinent records from PubMed, Scopus, Web of Science and ScienceDirect from 1990 to 2019, while bibliographies, ProQuest and Google Scholar were searched to ensure a comprehensive identification of relevant articles. Two independent investigators were involved at every stage of the systematic review, while discrepancies were resolved through discussion with a third investigator. RESULTS: All of the 18 included studies in this review (10 animal and eight cell studies) showed that palm oil and TRF enhanced the cognitive performance of healthy animals. In diabetes-induced rats, TRF and α-tocotrienol enhanced cognitive function and exerted antioxidant, anti-apoptotic and anti-inflammatory activities, while in a transgenic Alzheimer's disease (AD) animal model, TRF enhanced the cognitive function and reduced the deposition of ß-amyloid by altering the expression of several genes related to AD and neuroprotection. In cell studies, simultaneous treatment with α-tocotrienols and neurotoxins improved the redox status in neuronal cells better than ϒ- and δ-tocotrienols. Both pre-treatment and post-treatment with α-tocotrienol relative to oxidative insults were able to enhance the survival of neuronal cells via increased antioxidant responses. CONCLUSIONS: Palm oil and its TRF enhanced the cognitive functions of healthy animals, while TRF and α-tocotrienol enhanced the cognitive performance with attenuation of oxidative stress, neuroinflammation and apoptosis in diabetes-induced or transgenic AD animal models. In cell studies, TRF and α-tocotrienol exerted prophylactic neuroprotective effects, while α-tocotrienol exerted therapeutic neuroprotective effects that were superior to those of ϒ- and δ-tocotrienol isomers.

Aqueous leaf extract of Clinacanthus nutans improved metabolic indices and sorbitol-related complications in type II diabetic rats (T2D).

Clinacanthus nutans (Burm. f.) Lindau (C. nutans) has been reported to lower blood glucose level; however, evidence on its efficacy in lowering diabetic complications is limited. The antidiabetic properties of C. nutans aqueous leaf extract on serum metabolic indices, sorbitol production, and aldose reductase enzyme activities in the kidneys, lens, and sciatic nerve of type II diabetic (T2D) rats were evaluated. All rats except normal control rats were fed with a high-fat diet for 8 weeks to induce obesity and subsequently injected with 35 mg/kg streptozotocin to induce type II diabetes. Aqueous leaf extract of C. nutans (100 and 200 mg kg-1 day-1) and quercetin (10 mg kg-1 day-1) were fed orally for 4 weeks. Diabetic rats administered with C. nutans at 100, 200 mg kg-1 day-1 and quercetin had significantly (p < 0.05) lower fasting blood glucose levels post-intervention: 14.2, 14.0, and 19.9 mm, respectively, compared with the untreated group (22.1 mm). Total cholesterol was significantly (p < 0.05) lower in the C. nutans groups in comparison with the diabetic control group. Levels of F2-isoprostane, a marker of oxidative stress, were attenuated in the presence of the extract. Aldose reductase enzyme activity increased by 64, 99, and 0% and total antioxidant activities by 22, 29, and 126%, respectively. Sorbitol levels in the kidney, lens, and nerve were reduced in diabetic rats administered with C. nutans and quercetin group (by 8, 16, and 3%, respectively). The protective effect of the extract to the liver and kidney was confirmed through liver and kidney enzyme markers and histological analyses. The C. nutans has the potential to attenuate T2D-induced metabolic perturbations and complications related to sorbitol accumulation.

Increased fucoxanthin in Chaetoceros calcitrans extract exacerbates apoptosis in liver cancer cells via multiple targeted cellular pathways.

In this study, anti-proliferative effects of C. calcitrans extract and its fucoxanthin rich fraction (FxRF) were assessed on human liver HepG2 cancer cell line. Efficacy from each extract was determined by cytotoxicity assay, morphological observation, and cell cycle analysis. Mechanisms of action observed were evaluated using multiplex gene expression analysis. Results showed that CME and FxRF induced cytotoxicity to HepG2 cells in a dose and time-dependent manner. FxRF (IC50: 18.89 µg.mL-1) was found to be significantly more potent than CME (IC50: 87.5 µg.mL-1) (p < 0.05). Gene expression studies revealed that anti-proliferative effects in treated cells by C. calcitrans extracts were mediated partly through the modulation of numerous genes involved in cell signaling (AKT1, ERK1/2, JNK), apoptosis (BAX, BID, Bcl-2, APAF, CYCS) and oxidative stress (SOD1, SOD2, CAT). Overall, C. calcitrans extracts demonstrated effective intervention against HepG2 cancer cells where enhanced apoptotic activities were observed with increased fucoxanthin content.

Probiotic Properties of Bacillus Strains Isolated from Stingless Bee (Heterotrigona itama) Honey Collected across Malaysia.

This study aimed to isolate, identify, and evaluate the probiotic properties of Bacillus species from honey of the stingless bee Heterotrigona itama. Bacillus spp. were isolated from five different H. itama meliponicultures, and the isolates were characterized through Gram-staining and a catalase test. Tolerance to acidic conditions and bile salt (0.3%), hydrophobicity, and autoaggregation tests were performed to assess the probiotic properties of the selected isolates, B. amyloliquefaciens HTI-19 and B. subtilis HTI-23. Both Bacillus isolates exhibited excellent antimicrobial activity against both Gram-positive and Gram-negative bacteria and possessed significantly high survival rates in 0.3% bile solution for 3 h. Their survival rates in acidic conditions were also comparable to a commercial probiotic strain, Lactobacillus rhamnosus GG. Interestingly, the hydrophobicity and autoaggregation percentage showed no significant difference from L. rhamnosus GG, a commercial probiotic strain. The results from this study suggest that B. amyloliquefaciens HTI-19 and B. subtilis HTI-23 isolated from stingless bee honey have considerably good probiotic properties. Therefore, more studies should be done to investigate the effects of these bacteria cultures on gastrointestinal health.

Curculigoside and polyphenol-rich ethyl acetate fraction of Molineria latifolia rhizome improved glucose uptake via potential mTOR/AKT activated GLUT4 translocation.

Adipose tissue is one of the major organs responsible for rapid restoration of postprandial glucose fluxes. Being the major isoform of glucose transporter in adipose tissue, regulations of insulin-dependent GLUT4 trafficking have always been of research interest. The present study aimed to examine the molecular mechanisms underlying the efficacy of curculigoside and polyphenol-rich ethyl acetate fraction (EAF) of Molineria latifolia rhizome in triggering glucose uptake. We assessed the adipogenic potential and glucose uptake stimulatory activity of curculigoside and EAF by employing a murine 3T3-L1 adipocyte model. The transcriptional and translational expressions of selected intermediates in the insulin signalling pathway were evaluated. While curculigoside neither promoted adipogenesis nor activated peroxisome proliferator activated receptor gamma, treatment with polyphenol-rich EAF resulted otherwise. However, both treatments enhanced insulin-stimulated uptake of glucose. This was coupled with increased availability of GLUT4 at the plasma membrane of the differentiated adipocytes although the total GLUT4 protein level was unaffected. In addition, the treatment increased the phosphorylation of both AKT and mTOR, which have been reported to be associated with GLUT4 translocation. The present findings proposed that curculigoside and EAF increased glucose transport activity of 3T3-L1 adipocytes via GLUT4 translocation as a result of potential mTOR/AKT activation. The more potent efficacy observed with EAF suggested potential synergistic and multi-targeted action.

Defatted Kenaf (Hibiscus cannabinus L.) Seed Meal and Its Phenolic-Saponin-Rich Extract Protect Hypercholesterolemic Rats against Oxidative Stress and Systemic Inflammation via Transcriptional Modulation of Hepatic Antioxidant Genes.

The present study aimed to investigate the antioxidant and anti-inflammatory properties of defatted kenaf seed meal (DKSM) and its phenolic-saponin-rich extract (PSRE) in hypercholesterolemic rats. Hypercholesterolemia was induced using atherogenic diet feeding, and dietary interventions were conducted by incorporating DKSM (15% and 30%) or PSRE (at 2.3% and 4.6%, resp., equivalent to the total content of DKSM-phenolics and saponins in the DKSM groups) into the atherogenic diets. After ten weeks of intervention, serum total antioxidant capacities of hypercholesterolemic rats were significantly enhanced by DKSM and PSRE supplementation (p < 0.05). Similarly, DKSM and PSRE supplementation upregulated the hepatic mRNA expression of antioxidant genes (Nrf2, Sod1, Sod2, Gsr, and Gpx1) of hypercholesterolemic rats (p < 0.05), except for Gpx1 in the DKSM groups. The levels of circulating oxidized LDL and proinflammatory biomarkers were also markedly suppressed by DKSM and PSRE supplementation (p < 0.05). In aggregate, DKSM and PSRE attenuated the hypercholesterolemia-associated oxidative stress and systemic inflammation in rats, potentially by enhancement of hepatic endogenous antioxidant defense via activation of the Nrf2-ARE pathway, which may be contributed by the rich content of phenolics and saponins in DKSM and PSRE. Hence, DKSM and PSRE are prospective functional food ingredients for the potential mitigation of atherogenic risks in hypercholesterolemic individuals.

Compositional analyses of white, brown and germinated forms of popular Malaysian rice to offer insight into the growing diet-related diseases.

Diet-related metabolic diseases, and especially obesity, are metabolic disorders with multifactorial aetiologies. Diet has been a cornerstone in both the aetiology and management of this metabolic disorders. Rice, a staple food for over half of the world's population, could be exploited as part of the solution to check this menace which has been skyrocketing in the last decade. The present study investigated nine forms of rice from three widely grown Malaysian rice cultivars for in vitro and in vivo (glycaemic index and load) properties that could translate clinically into a lower predisposition to diet-related diseases. The germinated brown forms of MRQ 74 and MR 84 rice cultivars had high amylose content percentages (25.7% and 25.0%), high relative percentage antioxidant scavenging abilities of 85.0% and 91.7%, relatively low glycaemic indices (67.6 and 64.3) and glycaemic load (32.3 and 30.1) values, and modest glucose uptake capabilities of 33.69% and 31.25%, respectively. The results show that all things being equal, rice cultivars that are germinated and high in amylose content when compared to their white and low amylose counterparts could translate into a lower predisposition to diet-related diseases from the dietary point of view in individuals who consume this cereal as a staple food.

Dietary supplementation of defatted kenaf (Hibiscus cannabinus L.) seed meal and its phenolics-saponins rich extract effectively attenuates diet-induced hypercholesterolemia in rats.

Kenaf is one of the important commercial fiber crops worldwide and defatted kenaf seed meal (DKSM) is a secondary by-product from the kenaf industry. Thus, efforts to turn this low-cost agricultural waste into value-added functional food ingredients will definitely bring advantageous impacts to the community health, environment and economy. The present study was aimed to investigate the cardioprotective properties of DKSM and its phenolics-saponins rich extract (PSRE) in diet-induced hypercholesterolemic rat model. Hypercholesterolemia was induced in Sprague-Dawley rats via atherogenic diet feeding and dietary interventions were conducted by incorporating DKSM (15% and 30%) and equivalent levels of PSRE (2.3% and 4.6%, respectively, equivalent to the total content of phenolics and saponins in DKSM groups) into the atherogenic diets. After 10 weeks of DKSM and PSRE supplementation, the hepatosomatic index, hepatosteatosis, serum lipid profile, Castelli risk indexes as well as hepatic and renal functions of hypercholesterolemic rats were significantly improved (p < 0.05). Besides, the levels of hepatic Hmgcr and serum Pcsk9 were lowered, along with transcriptional upregulations of hepatic Cyp7a1, Abca1, Lcat, ApoA2 and ApoE (p < 0.05). The gene expression of hepatic Ldlr was marginally enhanced by DKSM supplementation (p > 0.05), but superiorly upregulated by PSRE (p < 0.05). The combined results showed that hypercholesterolemia and the atherogenic risk in rats were effectively attenuated by DKSM and PSRE supplementation, possibly via modulations of multiple vital processes in hepatic cholesterol metabolism. Furthermore, phenolics and saponins may be the bioactives conferring DKSM and PSRE with their anti-hypercholesterolemic properties. In conclusion, DKSM and PSRE are prospective cardioprotective functional food ingredients for hypercholesterolemic individuals.

Polyphenol-rich ethyl acetate fraction isolated from Molineria latifolia ameliorates insulin resistance in experimental diabetic rats via IRS1/AKT activation.

This study aimed to evaluate the effect of ethyl acetate fraction (EAF) isolated from Molineria latifolia rhizome as dietary interventions for type 2 diabetes mellitus (T2DM) and its underlying molecular mechanisms in vivo. Experimental rats were induced by high fat diet feeding coupled with combined exposure to streptozotocin and nicotinamide. Treatment with EAF improved glucose tolerance and lipid profiles, but the insulin secretion was unaltered. Gene expression analyses on insulin/adipocytokine signalling-related genes demonstrated tissue-specific transcriptional responses. In skeletal muscle and liver tissues, Socs1, Tnf and Mapk8 showed consistent transcript regulation. Furthermore, hepatic translational analyses revealed sensitization on proximal insulin signalling, with reduced expression of IRS1 serine phosphorylation, increased IRS1 tyrosine phosphorylation and increased phospho-AKT (Ser473). The present findings suggested that EAF exerted its effect by modulating insulin signalling, potentially via IRS1/AKT activation. The pharmacological attributes of EAF may implicate its potential therapeutic applications for diabetes management.

Therapeutic Properties of Stingless Bee Honey in Comparison with European Bee Honey.

Both honeybees (Apis spp.) and stingless bees (Trigona spp.) produce honeys with high nutritional and therapeutics value. Until recently, the information regarding potential health benefits of stingless bee honey (SBH) in medical databases is still scarce as compared to the common European bee honey (EBH) which is well known for their properties as therapeutic agents. Although there have been very few reports on SBH, empirically these products would have similar therapeutic quality as the EBH. In addition, due to the structure of the nest, few studies reported that the antimicrobial activity of SBH is a little bit stronger than EBH. Therefore, the composition of both the types of honey as well as the traditional uses and clinical applications were compared. The results of various studies on EBH and SBH from tissue culture research to randomised control clinical trials were collated in this review. Interestingly, there are many therapeutic properties that are unique to SBH. Therefore, SBH has a great potential to be developed for modern medicinal uses.

Strobilanthes crispus Extract Reduces Respiratory Exchange Ratio in Obese Mice Fed High Fat and Low Fat Diets.

BACKGROUND: Strobilanthes crispus (S. crispus) leaves were traditionally consumed for its body weight lowering effect. In this study, we investigated the anti-obesity effect of S. crispus leaves extract (SCE). METHODS: Mice (n = 48) were fed high-fat diet (HFD) for 25 weeks to induce obesity, after which half were maintained on HFD and half switched to low-fat diet (LFD)while they were given normal water (H2O) or 0.1% (w/v) SCE in water at week 0-4 which was increased to 1% (w/v) at week 5-9. Effects of treatment with SCE were compared between HFDH2O, HFDSCE, LFDH2O and LFDSCE groups. Respiratory exchange ratios (RER) were measured at weeks 0, 5 and 10. Food, water intake and body weight were measured weekly. Plasma lipid profile and organ weights were determined at week 10. RESULTS: SCE had significantly reduced RER at week 9 (P = 0.011). Food intake, body weight, and abdominal adipose tissue weight were not altered by SCE at weeks 5 and 10. However, significant increase in plasma and liver cholesterol (P < 0.050) was observed. CONCLUSION: Our findings suggest that SCE induced lipolysis and body fat oxidation and increased energy expenditure. Further studies in other animal models should be done to confirm the consistency of these results.

Effects of temperature, time, and solvent ratio on the extraction of phenolic compounds and the anti-radical activity of Clinacanthus nutans Lindau leaves by response surface methodology.

BACKGROUND: Clinacanthus nutans Lindau is a well-known plant, native to tropical Asian countries. Reports on this plant that is rich in phenolic compounds have focused on its therapeutic anti-inflammatory, anti-herpes simplex, antioxidant, and anti-cancer characteristics. In this paper, the influence of the extraction parameters-temperatures (60-80 °C), times (80-120 min), and solvent ratios (70:30-90:10) of water:ethanol were investigated using response surface methodology in order to determine the optimum extraction conditions that could produce maximum extraction yields of the phenolic compounds and the highest anti-radical activity of the C. nutans extract. RESULTS: The optimum conditions suggested by the predicted model were: an extraction temperature of 60 °C, an extraction time of 120 min and a water:ethanol solvent ratio of 90:10 v/v%. The residual standard error of 0.2% indicated that there was no significant difference between the actual and predicted values and it proved that the models were adequate to predict the relevant responses. All the independent variables had a significant effect (p < 0.05) on all the responses which indicated that all extraction parameters employed in this study were important in the optimization process. The R2 values for three responses, extraction yields, DPPH radical scavenging activity and TPC were 0.9999, 0.9999 and 0.9983 respectively, suggesting that the quadratic polynomial models developed were satisfactorily accurate to be used in analyzing the interactions of the parameters (response and independent variables). CONCLUSION: This study could be useful in the development of cosmeceutical products containing extracts of C. nutans.

Edible Bird's Nest Prevents Menopause-Related Memory and Cognitive Decline in Rats via Increased Hippocampal Sirtuin-1 Expression.

Menopause causes cognitive and memory dysfunction due to impaired neuronal plasticity in the hippocampus. Sirtuin-1 (SIRT1) downregulation in the hippocampus is implicated in the underlying molecular mechanism. Edible bird's nest (EBN) is traditionally used to improve general wellbeing, and in this study, we evaluated its effects on SIRT1 expression in the hippocampus and implications on ovariectomy-induced memory and cognitive decline in rats. Ovariectomized female Sprague-Dawley rats were fed with normal pellet alone or normal pellet + EBN (6, 3, or 1.5%), compared with estrogen therapy (0.2 mg/kg/day). After 12 weeks of intervention, Morris water maze (four-day trial and one probe trial) was conducted, and serum estrogen levels, toxicity markers (alanine transaminase, alkaline phosphatase, urea, and creatinine), and hippocampal SIRT1 immunohistochemistry were estimated after sacrifice. The results indicated that EBN and estrogen enhanced spatial learning and memory and increased serum estrogen and hippocampal SIRT1 expression. In addition, the EBN groups did not show as much toxicity to the liver as the estrogen group. The data suggested that EBN treatment for 12 weeks could improve cognition and memory in ovariectomized female rats and may be an effective alternative to estrogen therapy for menopause-induced aging-related memory loss.

Thymoquinone-rich fraction nanoemulsion (TQRFNE) decreases Aß40 and Aß42 levels by modulating APP processing, up-regulating IDE and LRP1, and down-regulating BACE1 and RAGE in response to high fat/cholesterol diet-induced rats.

Though the causes of Alzheimer's disease (AD) are yet to be understood, much evidence has suggested that excessive amyloid-ß (Aß) accumulation due to abnormal amyloid-ß precursor protein (APP) processing and Aß metabolism are crucial processes towards AD pathogenesis. Hence, approaches aiming at APP processing and Aß metabolism are currently being actively pursued for the management of AD. Studies suggest that high cholesterol and a high fat diet have harmful effects on cognitive function and may instigate the commencement of AD pathogenesis. Despite the neuropharmacological attributes of black cumin seed (Nigella sativa) extracts and its main active compound, thymoquinone (TQ), limited records are available in relation to AD research. Nanoemulsion (NE) is exploited as drug delivery systems due to their capacity of solubilising non-polar active compounds and is widely examined for brain targeting. Herewith, the effects of thymoquinone-rich fraction nanoemulsion (TQRFNE), thymoquinone nanoemulsion (TQNE) and their counterparts' conventional emulsion in response to high fat/cholesterol diet (HFCD)-induced rats were investigated. Particularly, the Aß generation; APP processing, ß-secretase 1 (BACE1), γ-secretases of presenilin 1 (PSEN1) and presenilin 2 (PSEN2), Aß degradation; insulin degrading enzyme (IDE), Aß transportation; low density lipoprotein receptor-related protein 1 (LRP1) and receptor for advanced glycation end products (RAGE) were measured in brain tissues. TQRFNE reduced the brain Aß fragment length 1-40 and 1-42 (Aß40 and Aß42) levels, which would attenuate the AD pathogenesis. This reduction could be due to the modulation of ß- and γ-secretase enzyme activity, and the Aß degradation and transportation in/out of the brain. The findings show the mechanistic actions of TQRFNE in response to high fat and high cholesterol diet associated to Aß generation, degradation and transportation in the rat's brain tissue.

Beneficial effects of TQRF and TQ nano- and conventional emulsions on memory deficit, lipid peroxidation, total antioxidant status, antioxidants genes expression and soluble Aß levels in high fat-cholesterol diet-induced rats.

The study determined the effect of thymoquinone rich fraction (TQRF) and thymoquinone (TQ) in the forms of nano- and conventional emulsions on learning and memory, lipid peroxidation, total antioxidant status, antioxidants genes expression and soluble ß-amyloid (Aß) levels in rats fed with a high fat-cholesterol diet (HFCD). The TQRF was extracted from Nigella sativa seeds using a supercritical fluid extraction system and prepared into nanoemulsion, which later named as TQRF nanoemulsion (TQRFNE). Meanwhile, TQ was acquired commercially and prepared into thymoquinone nanoemulsion (TQNE). The TQRF and TQ conventional emulsions (CE), named as TQRFCE and TQCE, respectively were studied for comparison. Statin (simvastatin) and non-statin (probucol) cholesterol-lowering agents, and a mild-to-severe Alzheimer's disease drug (donepezil) were served as control drugs. The Sprague Dawley rats were fed with HFCD for 6 months, and treated with the intervention groups via oral gavage daily for the last 3 months. As a result, HFCD-fed rats exhibited hypercholesterolaemia, accompanied by memory deficit, increment of lipid peroxidation and soluble Aß levels, decrement of total antioxidant status and down-regulation of antioxidants genes expression levels. TQRFNE demonstrated comparable effects to the other intervention groups and control drugs in serum biomarkers as well as in the learning and memory test. Somehow, TQRFNE was more prominent than those intervention groups and control drugs in brain biomarkers concomitant to gene and protein expression levels. Supplementation of TQRFNE into an HFCD thus could ameliorate memory deficit, lipid peroxidation and soluble Aß levels as well as improving the total antioxidant status and antioxidants genes expression levels.