Displaying publications 1 - 20 of 195 in total

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  1. Ramli AH, Swain P, Mohd Fahmi MSA, Abas F, Leong SW, Tejo BA, et al.
    Heliyon, 2024 Mar 15;10(5):e27462.
    PMID: 38495201 DOI: 10.1016/j.heliyon.2024.e27462
    Malaria remains a major public health problem worldwide, including in Southeast Asia. Chemotherapeutic agents such as chloroquine (CQ) are effective, but problems with drug resistance and toxicity have necessitated a continuous search for new effective antimalarial agents. Here we report on a virtual screening of ∼300 diarylpentanoids and derivatives, in search of potential Plasmodium falciparum lactate dehydrogenase (PfLDH) inhibitors with acceptable drug-like properties. Several molecules with binding affinities comparable to CQ were chosen for in vitro validation of antimalarial efficacy. Among them, MS33A, MS33C and MS34C are the most promising against CQ-sensitive (3D7) with EC50 values of 1.6, 2.5 and 3.1 μM, respectively. Meanwhile, MS87 (EC50 of 1.85 μM) shown the most active against the CQ-resistant Gombak A strain, and MS33A and MS33C the most effective P. knowlesi inhibitors (EC50 of 3.6 and 5.1 μM, respectively). The in vitro cytotoxicity of selected diarylpentanoids (MS33A, MS33C, MS34C and MS87) was tested on Vero mammalian cells to evaluate parasite selectivity (SI), showing moderate to low cytotoxicity (CC50 > 82 μM). In addition, MS87 exhibited a high SI and the lowest resistance index (RI), suggesting that MS87 may exert effective parasite inhibition with low resistance potential in the CQ-resistant P. falciparum strain. Furthermore, the in vivo toxicity of the molecules on early embryonic development, the cardiovascular system, heart rate, motor activity and apoptosis were assessed in a zebrafish animal model. The overall results indicate the preliminary potential of diarylpentanoids, which need further investigation for their development as new antimalarial agents.
  2. Wong PL, Zolkeflee NKZ, Ramli NS, Tan CP, Azlan A, Tham CL, et al.
    J Ethnopharmacol, 2024 Jan 10;318(Pt B):117015.
    PMID: 37572932 DOI: 10.1016/j.jep.2023.117015
    ETHNOPHARMACOLOGICAL RELEVANCE: Ardisia elliptica Thunb. (AE) (Primulaceae) is a medicinal plant found in the Malay Peninsula and has been traditionally used to treat diabetes. However, limited studies to date in providing scientific evidence to support the antidiabetic efficacy of this plant by in-vitro and in-vivo models.

    AIM OF THE STUDY: To investigate the anti-hyperglycemic potential of AE through in-vitro enzymatic activities and streptozotocin-nicotinamide (STZ-NA) induced diabetic rat models using proton-nuclear magnetic resonance (1H-NMR)-based metabolomics approach.

    MATERIALS AND METHODS: Anti-α-amylase and anti-α-glucosidase activities of the hydroethanolic extracts of AE were evaluated. The absolute quantification of bioactive constituents, using ultra-high performance liquid chromatography (UHPLC) was performed for the most active extract. Three different dosage levels of the AE extract were orally administered for 4 weeks consecutively in STZ-NA induced diabetic rats. Physical assessments, biochemical analysis, and an untargeted 1H-NMR-based metabolomics analysis of the urine and serum were carried out on the animal model.

    RESULTS: Type 2 diabetes mellitus (T2DM) rat model was successfully developed based on the clear separation observed between the STZ-NA induced diabetic and normal non-diabetic groups. Discriminating biomarkers included glucose, citrate, succinate, allantoin, hippurate, 2-oxoglutarate, and 3-hydroxybutyrate, as determined through an orthogonal partial least squares-discriminant analysis (OPLS-DA) model. A treatment dosage of 250 mg/kg body weight (BW) of standardized 70% ethanolic AE extract mitigated increase in serum glucose, creatinine, and urea levels, providing treatment levels comparable to that obtained using metformin, with flavonoids primarily contribute to the anti-hyperglycemic activities. Urinary metabolomics disclosed that the following disturbed metabolism pathways: the citrate cycle (TCA cycle), butanoate metabolism, glycolysis and gluconeogenesis, pyruvate metabolism, and synthesis and degradation of ketone bodies, were ameliorated after treatment with the standardized AE extract.

    CONCLUSIONS: This study demonstrated the first attempt at revealing the therapeutic effect of oral treatment with 250 mg/kg BW of standardized AE extract on chemically induced T2DM rats. The present study provides scientific evidence supporting the ethnomedicinal use of Ardisia elliptica and further advances the understanding of the fundamental molecular mechanisms affected by this herbal antidote.

  3. Zolkeflee NKZ, Wong PL, Maulidiani M, Ramli NS, Azlan A, Abas F
    Planta Med, 2023 Aug;89(9):916-934.
    PMID: 36914160 DOI: 10.1055/a-2053-0950
    Diabetes mellitus (DM) is a metabolic endocrine disorder caused by decreased insulin concentration or poor insulin response. Muntingia calabura (MC) has been used traditionally to reduce blood glucose levels. This study aims to support the traditional claim of MC as a functional food and blood-glucose-lowering regimen. The antidiabetic potential of MC is tested on a streptozotocin-nicotinamide (STZ-NA)-induced diabetic rat model by using the 1H-NMR-based metabolomic approach. Serum biochemical analyses reveal that treatment with 250 mg/kg body weight (bw) standardized freeze-dried (FD) 50% ethanolic MC extract (MCE 250) shows favorable serum creatinine (37.77 ± 3.53 µM), urea (5.98 ± 0.84 mM) and glucose (7.36 ± 0.57 mM) lowering capacity, which was comparable to the standard drug, metformin. The clear separation between diabetic control (DC) and normal group in principal component analysis indicates the successful induction of diabetes in the STZ-NA-induced type 2 diabetic rat model. A total of nine biomarkers, including allantoin, glucose, methylnicotinamide, lactate, hippurate, creatine, dimethylamine, citrate and pyruvate are identified in rats' urinary profile, discriminating DC and normal groups through orthogonal partial least squares-discriminant analysis. Induction of diabetes by STZ-NA is due to alteration in the tricarboxylic acid (TCA) cycle, gluconeogenesis pathway, pyruvate metabolism and nicotinate and nicotinamide metabolism. Oral treatment with MCE 250 in STZ-NA-induced diabetic rats shows improvement in the altered carbohydrate metabolism, cofactor and vitamin metabolic pathway, as well as purine and homocysteine metabolism.
  4. Leong SW, Wang J, Okuda KS, Su Q, Zhang Y, Abas F, et al.
    Eur J Med Chem, 2023 Apr 20;254:115335.
    PMID: 37098306 DOI: 10.1016/j.ejmech.2023.115335
    Unpleasant side effects and resistance development remained the Achilles heel of chemotherapy. Since low tumor-selectivity and monotonous effect of chemotherapy are closely related to such bottleneck, targeting tumor-selective multi-functional anticancer agents may be an ideal strategy in the search of new safer drugs. Herein, we report the discovery of compound 21, a nitro-substituted 1,5-diphenyl-3-styryl-1H-pyrazole that possesses dual functional characteristics. The 2D- and 3D-culture-based studies revealed that 21 not only could induce ROS-independent apoptotic and EGFR/AKT/mTOR-mediated autophagic cell deaths in EJ28 cells simultaneously but also has the ability in inducing cell death at both proliferating and quiescent zones of EJ28 spheroids. The molecular modelling analysis showed that 21 possesses EGFR targeting capability as it forms stable interactions in the EGFR active site. Together with its good safety profile in the zebrafish-based model, the present study showed that 21 is promising and may lead to the discovery of tumor-selective multi-functional anti-cancer agents.
  5. Kow ASF, Khoo LW, Tan JW, Abas F, Lee MT, Israf DA, et al.
    J Ethnopharmacol, 2023 Mar 01;303:116003.
    PMID: 36464074 DOI: 10.1016/j.jep.2022.116003
    ETHNOPHARMACOLOGICAL RELEVANCE: Allergy is mediated by the crosslinking of immunoglobulins (Ig) -E or -G to their respective receptors, which degranulates mast cells, macrophages, basophils, or neutrophils, releasing allergy-causing mediators. The removal of these mediators such as histamine, platelet-activating factor (PAF) and interleukins (ILs) released by effector cells will alleviate allergy. Clinacanthus nutans (C. nutans), an herbal plant in Southeast Asia, is used traditionally to treat skin rash, an allergic symptom. Previously, we have reported that C. nutans aqueous leaves extract (CNAE) was able to suppress the release of β-hexosaminidase and histamine but not interleukin-4 (IL-4) and tumor necrosis factor-alpha (TNF-α) in the IgE-induced mast cell degranulation model at 5 mg/mL and above. We also found that CNAE could protect rats against ovalbumin-challenged active systemic anaphylaxis (OVA-ASA) through the downregulation and upregulation of certain metabolites using proton nuclear magnetic resonance (1H-NMR) metabolomics approach.

    AIM OF THE STUDY: As allergy could be mediated by both IgE and IgG, we further evaluated the anti-allergy potential of CNAE in both in vitro model of IgG-induced macrophage activation and in vivo anaphylaxis models to further dissect the mechanism of action underlying the anti-allergic properties of CNAE.

    MATERIAL & METHODS: The anti-allergy potential of CNAE was evaluated in in vivo anaphylaxis models of ovalbumin-challenged active systemic anaphylaxis (OVA-ASA) and IgE-challenged passive systemic anaphylaxis (PSA) using Sprague Dawley rats as well as IgG-challenged passive systemic anaphylaxis (IgG-PSA) using C57BL/6 mice. Meanwhile, in vitro model of IgG-induced macrophage activation model was performed using IC-21 macrophages. The release of soluble mediators from both IgE and IgG-mediated pathways were measured using enzyme-linked immunosorbent assay (ELISA). The signaling molecules targeted by CNAE were identified by performing Western blot.

    RESULTS: IgG, platelet-activating factor (PAF) and IL-6 was suppressed by CNAE in OVA-ASA, but not IgE. In addition, CNAE significantly suppressed PAF and IL-6 in IgG-PSA but did not suppress histamine, IL-4 and leukotrienes C4 (LTC4) in IgE-PSA. CNAE also inhibited IL-6 and TNF-α by inhibiting the phosphorylation of ERK1/2 in the IgG-induced macrophage activation model.

    CONCLUSION: Overall, our findings supported that CNAE exerts its anti-allergic properties by suppressing the IgG pathway and its mediators by inhibiting ERK1/2 phosphorylation, thus providing scientific evidence supporting its traditional use in managing allergy.

  6. Hasbullah FY, Mohd Yusof BN, Abdul Ghani R, Mat Daud Z', Appannah G, Abas F, et al.
    Int J Environ Res Public Health, 2022 Dec 14;19(24).
    PMID: 36554678 DOI: 10.3390/ijerph192416797
    While it is known that women with a previous history of gestational diabetes mellitus (post-GDM) have a higher risk of metabolic syndrome (MetS), evidence of lifestyle practices from low- and middle-income countries (LMICs) is still scarce. This study aimed to determine the factors associated with MetS in women post-GDM. This cross-sectional study involved 157 women post-GDM (mean age 34.8 ± 5.6 years) sampled from Selangor, Malaysia. We collected data on sociodemographic characteristics and obstetric history. Food intake was assessed using a food frequency questionnaire, and dietary patterns were derived from principal component analysis. MetS was diagnosed according to the 2009 Harmonized criteria. The prevalence of MetS in this study was 22.3%. Western dietary pattern consumption was correlated with MetS, body mass index (BMI), waist circumference, and triglyceride levels. Independent factors associated with MetS were lower education level (odds ratio, OR 4.017, p = 0.007), pre-pregnancy BMI (OR 1.192, p = 0.002), and Caesarean delivery (OR 3.798, p = 0.009). The study identified the maternal and dietary factors associated with MetS in women post-GDM in Malaysia. Community-based interventions that include dietary modification are warranted to prevent MetS and its complications, thus helping to reduce the overall disease burden.
  7. Mostofa F, Yasid NA, Shamsi S, Ahmad SA, Mohd-Yusoff NF, Abas F, et al.
    Molecules, 2022 Nov 28;27(23).
    PMID: 36500396 DOI: 10.3390/molecules27238304
    The bone morphogenic protein (BMP) family is a member of the TGF-beta superfamily and plays a crucial role during the onset of gut inflammation and arthritis diseases. Recent studies have reported a connection with the gut-joint axis; however, the genetic players are still less explored. Meanwhile, BDMC33 is a newly synthesized anti-inflammatory drug candidate. Therefore, in our present study, we analysed the genome-wide features of the BMP family as well as the role of BMP members in gut-associated arthritis in an inflammatory state and the ability of BDMC33 to attenuate this inflammation. Firstly, genome-wide analyses were performed on the BMP family in the zebrafish genome, employing several in silico techniques. Afterwards, the effects of curcumin analogues on BMP gene expression in zebrafish larvae induced with TNBS (0.78 mg/mL) were determined using real time-qPCR. A total of 38 identified BMP proteins were revealed to be clustered in five major clades and contain TGF beta and TGF beta pro peptide domains. Furthermore, BDMC33 suppressed the expression of four selected BMP genes in the TNBS-induced larvae, where the highest gene suppression was in the BMP2a gene (an eight-fold decrement), followed by BMP7b (four-fold decrement), BMP4 (four-fold decrement), and BMP6 (three-fold decrement). Therefore, this study reveals the role of BMPs in gut-associated arthritis and proves the ability of BDMC33 to act as a potential anti-inflammatory drug for suppressing TNBS-induced BMP genes in zebrafish larvae.
  8. Lau ZC, Mohd Yusof BN, Abas F, Abd Wahab N, Wan Zukiman WZH, Ismail A
    Malays J Med Sci, 2022 Oct;29(5):5-16.
    PMID: 36474545 DOI: 10.21315/mjms2022.29.5.2
    The Identifying the dynamic metabolome of the individual in response to a particular stimulus using a metabolomic approach is an emerging research area. Measuring the postprandial metabolite response utilising a meal-challenge test (MCT) provides information beyond the fasting state, which is especially important since human beings spend most of their time in the postprandial state. This is pertinent as an excessive rise in postprandial glycaemia is common in individuals with type 2 diabetes mellitus (T2DM), which puts them at a high risk of developing cardiovascular disease (CVD). While a low glycaemic index (GI) meal improves postprandial glycaemia and insulin levels in MCT studies among individuals with T2DM, its effect on metabolite changes in the postprandial state is unclear. This review summarises the perturbation in postprandial metabolites following a low GI meal in comparison to that following a usual or high GI meal and maps the metabolites in their metabolic pathways. We undertook a literature review using electronic databases, with the Medical Subject Headings (MeSH) terms, to retrieve relevant studies based on specific criteria. A total of seven related studies were documented. For the majority of metabolites studied, it was identified that metabolic regulation following an MCT extends beyond the glucose pathway. Altered metabolic pathways after the consumption of a low GI meal include: i) essential amino acid metabolism by altering the levels of plasma phenylalanine, tyrosine, lysine, leucine, isoleucine and valine; ii) glycolysis and tricarboxylic acid (TCA) metabolism by altering citrate and alanine, and iii) gut microbiota metabolism by altering betaine and acetate. The altered metabolites regulated the pancreatic insulin secretion and related to other dietary factors beyond GI modifications. These metabolomics data need to be interpreted cautiously because the metabolic changes analysed might not be due to the beneficial effects of a low GI meal. Validation of the putative metabolomic biomarkers following a dietary intervention MCT is suggested because researchers need to fully understand the kinetics and metabolism of individuals metabolite before reaching a solid conclusion. Further research characterising the metabotype based on habitual dietary patterns is warranted.
  9. Jibril MM, Haji-Hamid A, Abas F, Karrupan J, Mohammed AS, Jaafar AH, et al.
    J Food Biochem, 2022 Feb;46(2):e14058.
    PMID: 34981526 DOI: 10.1111/jfbc.14058
    The present research aimed to investigate the attenuative effects of watermelon (Citrullus lanatus) leaf extract on biochemical and histological parameters in a high-fat diet combined with a low-dose streptozotocin (HFD/STZ)-induced type 2 diabetes mellitus. Forty male Sprague Dawley rats were divided into five groups, including three supplemented groups: 10 mg metformin/kg BW (HFD/STZ +M), 200 mg watermelon leaf extract /kg BW (HFD/STZ + LD), and 400 mg watermelon leaf extract /kg BW (HFD/STZ + HD). The efficacy of the 6-week intervention was evaluated by measuring body weight, fasting blood sugar, serum insulin, lipid profile, superoxide dismutase, catalase, malondialdehyde, and serum liver markers. Kidneys and liver structure were defined by histopathological examination. Results revealed that intervention with watermelon leaf extract attenuated the biochemical parameters and the structural changes in kidneys and liver. In brief, the watermelon leaf extract treatment could effectively decrease complications associated with diabetes better than metformin, and that the treatment with 400 mg/kg BW is the most potent. PRACTICAL APPLICATIONS: This was the first study to investigate the antidiabetic potential of watermelon leaf extract in obese diabetic rats. Data revealed that the watermelon leaf extract significantly attenuated the HFD/STZ-induced diabetes changes, as evidenced by the biochemical and histological data. Hence, watermelon leaf could be an excellent candidate to be developed as a functional food ingredients or nutraceuticals for holistic management of diabetes mellitus and its complications.
  10. Mediani A, Hamezah HS, Jam FA, Mahadi NF, Chan SXY, Rohani ER, et al.
    Front Nutr, 2022;9:1057366.
    PMID: 36518998 DOI: 10.3389/fnut.2022.1057366
    Preserving fresh food, such as meat, is significant in the effort of combating global food scarcity. Meat drying is a common way of preserving meat with a rich history in many cultures around the globe. In modern days, dried meat has become a well enjoyed food product in the market because of its long shelf-life, taste and health benefits. This review aims to compile information on how the types of meat, ingredients and the used drying technologies influence the characteristics of dried meat in physicochemical, microbial, biochemical and safety features along with technological future prospects in the dried meat industry. The quality of dried meat can be influenced by a variety of factors, including its production conditions and the major biochemical changes that occur throughout the drying process, which are also discussed in this review. Additionally, the sensory attributes of dried meat are also reviewed, whereby the texture of meat and the preference of the market are emphasized. There are other aspects and concerning issues that are suggested for future studies. It is well-known that reducing the water content in meat helps in preventing microbial growth, which in turn prevents the presence of harmful substances in meat. However, drying the meat can change the characteristics of the meat itself, making consumers concerned on whether dried meat is safe to be consumed on a regular basis. It is important to consider the role of microbial enzymes and microbes in the preservation of their flavor when discussing dried meats and dried meat products. The sensory, microbiological, and safety elements of dried meat are also affected by these distinctive changes, which revolve around customer preferences and health concerns, particularly how drying is efficient in eliminating/reducing hazardous bacteria from the fish. Interestingly, some studies have concentrated on increasing the efficiency of dried meat production to produce a safer range of dried meat products with less effort and time. This review compiled important information from all available online research databases. This review may help the food sector in improving the efficiency and safety of meat drying, reducing food waste, while maintaining the quality and nutritional content of dried meat.
  11. Ong HM, Azmi AFA, Leong SW, Abas F, Perimal EK, Farouk AAO, et al.
    Sci Rep, 2021 12 16;11(1):24121.
    PMID: 34916536 DOI: 10.1038/s41598-021-02961-1
    A novel synthetic compound from the 2-benzoyl-6-benzylidenecyclohexanone analogue, namely 2-benzoyl-6-(3-bromo-4-hydroxybenzylidene)cyclohexen-1-ol (BBHC), showed pronounced nitric oxide inhibition in IFN-γ/LPS-induced RAW 264.7 cells. Based on this previous finding, our present study aimed to investigate the antinociceptive effects of BBHC via chemical and thermal stimuli in vivo. The investigation of the antinociceptive activity of BBHC (0.1, 0.3, 1.0 and 3.0 mg/kg, i.p.) was initiated with 3 preliminary screening tests, then BBHC was subjected to investigate its possible involvement with excitatory neurotransmitters and opioid receptors. The potential acute toxicity of BBHC administration was also studied. Administration of BBHC significantly inhibited acetic acid-induced abdominal constrictions, formalin-induced paw licking activity and developed notable increment in the latency time. BBHC's ability to suppress capsaicin- and glutamate-induced paw licking activities, as well as to antagonise the effect of naloxone, had indicated the possible involvement of its antinociception with TRPV1, glutamate and opioid receptors, respectively. The antinociceptive activities of BBHC was not related to any sedative action and no evidence of acute toxic effect was detected. The present study showed that BBHC possessed significant peripheral and central antinociceptive activities via chemical- and thermal-induced nociceptive murine models without any locomotor alteration and acute toxicity.
  12. Abu Bakar Sajak A, Azlan A, Abas F, Hamzah H
    Nutrients, 2021 Oct 12;13(10).
    PMID: 34684574 DOI: 10.3390/nu13103573
    An herbal mixture composed of lemon, apple cider, garlic, ginger and honey as a polyphenol-rich mixture (PRM) has been reported to contain hypolipidemic activity on human subjects and hyperlipidemic rats. However, the therapeutic effects of PRM on metabolites are not clearly understood. Therefore, this study aimed to provide new information on the causal impact of PRM on the endogenous metabolites, pathways and serum biochemistry. Serum samples of hyperlipidemic rats treated with PRM were subjected to biochemistry (lipid and liver profile) and hydroxymethylglutaryl-CoA enzyme reductase (HMG-CoA reductase) analyses. In contrast, the urine samples were subjected to urine metabolomics using 1H NMR. The serum biochemistry revealed that PRM at 500 mg/kg (PRM-H) managed to lower the total cholesterol level and low-density lipoprotein (LDL-C) (p < 0.05) and reduce the HMG-CoA reductase activity. The pathway analysis from urine metabolomics reveals that PRM-H altered 17 pathways, with the TCA cycle having the highest impact (0.26). Results also showed the relationship between the serum biochemistry of LDL-C and HMG-CoA reductase and urine metabolites (trimethylamine-N-oxide, dimethylglycine, allantoin and succinate). The study's findings demonstrated the potential of PRM at 500 mg/kg as an anti-hyperlipidemic by altering the TCA cycle, inhibiting HMG-CoA reductase and lowering the LDL-C in high cholesterol rats.
  13. Choo BKM, Kundap UP, Faudzi SMM, Abas F, Shaikh MF, Samarut É
    Biomed Pharmacother, 2021 Oct;142:112035.
    PMID: 34411917 DOI: 10.1016/j.biopha.2021.112035
    Seizures are the outward manifestation of abnormally excessive or synchronous brain activity. While seizures can be somewhat symptomatically managed with anti-epileptic drugs (AEDs), many patients are still refractory to the currently available AEDs. As a result, there is a need to identify new molecules with anti-seizure properties. Curcumin is the principle curcuminoid of Curcuma longa, or colloquially turmeric, and has been experimentally proven to have anti-convulsive properties, but its poor bioavailability has dampened further therapeutic interest. Hence, this study aimed to ask if structural analogues of curcumin with an adequate bioavailability could have an anti-seizure effect in vivo. To do so, we tested these analogues following a multipronged approach combining the use of several zebrafish seizure models (chemically-induced and genetic) and complementary assays (behavioural and brain activity). Overall, from the 68 analogues tested, we found 15 different derivatives that were able to significantly decrease the behavioural hyperactivity induced by pentylenetetrazol. Of those, only a few showed an effect on the hyperactivity phenotype of two genetic models of brain seizures that are the gabra1 and gabrg2 knockouts. Two analogues, CA 80(1) and CA 74(1), were able to significantly alleviate brain seizures of gabrg2-mutant larvae. As a result, these analogues are good candidates as novel anti-seizure agents.
  14. Kadir NAAA, Azlan A, Abas F, Ismail IS
    Molecules, 2021 Sep 13;26(18).
    PMID: 34577016 DOI: 10.3390/molecules26185545
    There has been growing interest among food scientists in producing a toxin-free fat as an end product with varying physical or nutritional properties of interest to the food industry. Oleoresin is a rich source of bioactive compounds which consumers can easily add to a large variety of food. Dabai (Canarium odontophyllum) pulp oleoresin (DPL) was extracted using supercritical carbon dioxide (SC-CO2) extraction, a green extraction technology. This study investigates the quality of SC-CO2 extracted DPL in discovering its potential as a new alternative fat. The extraction experiment was carried out at a pressure of 40 MPa and a temperature of 40 °C. DPL is a saturated fatty acid (SFA)-rich fat due to its high SFA composition (47.72 ± 0.01%). In addition, the low content of peroxide value (PV) (5.60 ± 0.09 mEq/kg) and free fatty acids (FFA) (3.40 ± 0.03%) indicate the quality and stability of DPL for various applications besides food consumption. DPL also has a low slip melting point (SMP) (20.20 ± 0.03 °C), and HPLC-FID revealed that DPL contained 0.13 ± 0.02 mg/100 g of vitamin E (α-tocopherol), indicating its potential application as a solid fat with a bioactive compound. This present work demonstrates the possible prospect of DPL in the formulation of end products for food industries.
  15. Wong PL, Ramli NS, Tan CP, Azlan A, Abas F
    Phytochem Anal, 2021 Sep;32(5):685-697.
    PMID: 33295100 DOI: 10.1002/pca.3015
    INTRODUCTION: Ardisia elliptica Thunb. (Primulaceae) is a medicinal herb that is traditionally used for the treatment of fever, diarrhoea, measles and herpes. However, there is limited information regarding the correlation of its phytoconstituents with the bioactivity. Optimisation of solvent extraction is vital for maximising retention of bioactive molecules.

    OBJECTIVE: This study investigated the metabolite variations in A. elliptica leaves and the correlation with antioxidant activities.

    METHODOLOGY: Total phenolic content (TPC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) radicals scavenging assays were performed on A. elliptica leaves extracted with four different ethanol ratios (0%, 50%, 70% and absolute ethanol). The correlation of metabolites with antioxidant activities was evaluated using a nuclear magnetic resonance (NMR)-based metabolomics approach.

    RESULTS: The results showed that the 50% and 70% ethanolic extracts retained the highest TPC, and the 70% ethanolic extract was the most active, exhibiting half maximal inhibitory concentration (IC50 ) values of 10.18 ± 0.83 and 43.05 ± 1.69 μg/mL, respectively, in both radical scavenging assays. A total of 46 metabolites were tentatively identified, including flavonoids, benzoquinones, triterpenes and phenolic derivatives. The 50% and 70% ethanolic extracts showed similarities in metabolites content and were well discriminated from water and absolute ethanol extracts in a principal component analysis (PCA) model. Moreover, 31 metabolites were found to contribute significantly to the differentiation and antioxidant activity.

    CONCLUSION: This study provides information on bioactive compounds in A. elliptica leaves, which is promising as a functional ingredient for food production or for the development of phytomedicinal products.

  16. Ado MA, Maulidiani M, Ismail IS, Ghazali HM, Shaari K, Abas F
    Nat Prod Res, 2021 Sep;35(17):2992-2996.
    PMID: 31631709 DOI: 10.1080/14786419.2019.1679138
    Phytochemical investigation on the soluble fractions of n-hexane and dichloromethane of methanolic leaves extract of the Callicarpa maingayi K. & G. led to the isolation of three triterpenoids [euscaphic acid (1), arjunic acid (2), and ursolic acid (3)] together with two flavones [apigenin (4) and acacetin (5)], two phytosterols [stigmasterol 3-O-β-glycopyranoside (6) and sitosterol 3-O-β-glycopyranoside (7)], and a fatty acid [n-hexacosanoic acid (8)]. Six (6) compounds (1, 2, 3, 4, 5, and 8) are reported for the first time from this species. Their structures were elucidated and identified by extensive NMR techniques, GC-MS and comparison with the previously reported literature. Compound 3 was found to displayed good inhibition against acetylcholinesterase with an IC50 value of 21.5 ± 0.022 μM, while 1 and 2 exhibited pronounced α-glucosidase inhibitory activity with IC50 values of 22.4 ± 0.016 μM and 24.9 ± 0.012 μM, respectively.
  17. Basheer AS, Abas F, Othman I, Naidu R
    Cancers (Basel), 2021 Aug 23;13(16).
    PMID: 34439380 DOI: 10.3390/cancers13164226
    Gliomas are the most common, highly malignant, and deadliest forms of brain tumors. These intra-cranial solid tumors are comprised of both cancerous and non-cancerous cells, which contribute to tumor development, progression, and resistance to the therapeutic regimen. A variety of soluble inflammatory mediators (e.g., cytokines, chemokines, and chemotactic factors) are secreted by these cells, which help in creating an inflammatory microenvironment and contribute to the various stages of cancer development, maintenance, and progression. The major tumor infiltrating immune cells of the tumor microenvironment include TAMs and TANs, which are either recruited peripherally or present as brain-resident macrophages (microglia) and support stroma for cancer cell expansion and invasion. These cells are highly plastic in nature and can be polarized into different phenotypes depending upon different types of stimuli. During neuroinflammation, glioma cells interact with TAMs and TANs, facilitating tumor cell proliferation, survival, and migration. Targeting inflammatory mediators along with the reprogramming of TAMs and TANs could be of great importance in glioma treatment and may delay disease progression. In addition, an inhibition of the key signaling pathways such as NF-κB, JAK/STAT, MAPK, PI3K/Akt/mTOR, and TLRs, which are activated during neuroinflammation and have an oncogenic role in glioblastoma (GBM), can exert more pronounced anti-glioma effects.
  18. Buzgaia N, Lee SY, Rukayadi Y, Abas F, Shaari K
    Plants (Basel), 2021 Aug 11;10(8).
    PMID: 34451703 DOI: 10.3390/plants10081659
    The genus Arbutus (Ericaceae) has been traditionally used in folk medicine due to its phytomedicinal properties, especially Arbutus pavarii Pamp. However, this plant has not been evaluated for its efficacy, quality, and consistency to support the traditional uses, potentially in treating diabetes. Despite previous studies that revealed the biological activities of A. pavarii as antioxidant and α-glucosidase inhibitory agents, scientific reports on the bioactive compounds that contribute to its health benefits are still scarce. Therefore, this research focused on the evaluation of antioxidant and α-glucosidase inhibitory activities of the methanol crude extracts and various fractions of the leaf and stem bark, as well as on metabolite profiling of the methanol crude extracts. The extracts and fractions were evaluated for total phenolic (TPC) and total flavonoid (TFC) contents, as well as the DPPH free radical scavenging, ferric reducing antioxidant power (FRAP), and α-glucosidase inhibitory activities. Methanol crude extracts of the leaf and stem bark were then subjected to UHPLC-ESI-MS/MS. To the best of our knowledge, the comparative evaluation of the antioxidant and α-glucosidase inhibitory activities of the leaf and stem bark of A. pavarii, as well as of the respective solvent fractions, is reported herein for the first time. Out of these extracts, the methanolic crude extracts and polar fractions (ethyl acetate and butanol fractions) showed significant bioactivities. The DPPH free radical and α-glucosidase inhibitions was highest in the leaf ethyl acetate fraction, with IC50 of 6.39 and 4.93 µg/mL, respectively, while the leaf methanol crude extract and butanol fraction exhibited the highest FRAP with 82.95 and 82.17 mmol Fe (II)/g extract. The UHPLC-ESI-MS/MS analysis resulted in the putative identification of a total of 76 compounds from the leaf and stem bark, comprising a large proportion of plant phenolics (flavonoids and phenolic acids), terpenoids, and fatty acid derivatives. Results from the present study showed that the different parts of A. pavarii had potent antioxidant and α-glucosidase inhibitory activities, which could potentially prevent oxidative damage or diabetes-related problems. These findings may strengthen the traditional claim on the medicinal value of A. pavarii.
  19. Kim YM, Abas F, Park YS, Park YK, Ham KS, Kang SG, et al.
    Molecules, 2021 Jul 21;26(15).
    PMID: 34361562 DOI: 10.3390/molecules26154405
    Fruit used in the common human diet in general, and kiwifruit and persimmon particularly, displays health properties in the prevention of heart disease. This study describes a combination of bioactivity, multivariate data analyses and fluorescence measurements for the differentiating of kiwifruit and persimmon, their quenching and antioxidant properties. The metabolic differences are shown, as well in the results of bioactivities and antioxidant capacities determined by ABTS, FRAP, CUPRAC and DPPH assays. To complement the bioactivity of these fruits, the quenching properties between extracted polyphenols and human serum proteins were determined by 3D-fluorescence spectroscopy studies. These properties of the extracted polyphenols in interaction with the main serum proteins in the human metabolism (human serum albumin (HSA), α-β-globulin (α-β G) and fibrinogen (Fgn)), showed that kiwifruit was more reactive than persimmon. There was a direct correlation between the quenching properties of the polyphenols of the investigated fruits with serum human proteins, their relative quantification and bioactivity. The results of metabolites and fluorescence quenching show that these fruits possess multiple properties that have a great potential to be used in industry with emphasis on the formulation of functional foods and in the pharmaceutical industry. Based on the quenching properties of human serum proteins with polyphenols and recent reports in vivo on human studies, we hypothesize that HSA, α-β G and Fgn will be predictors of coronary artery disease (CAD).
  20. Wan Mohd Tajuddin WNB, Abas F, Othman I, Naidu R
    Int J Mol Sci, 2021 Jul 10;22(14).
    PMID: 34299042 DOI: 10.3390/ijms22147424
    Diarylpentanoid (DAP), an analog that was structurally modified from a naturally occurring curcumin, has shown to enhance anticancer efficacy compared to its parent compound in various cancers. This study aims to determine the cytotoxicity, antiproliferative, and apoptotic activity of diarylpentanoid MS13 on two subtypes of non-small cell lung cancer (NSCLC) cells: squamous cell carcinoma (NCI-H520) and adenocarcinoma (NCI-H23). Gene expression analysis was performed using Nanostring PanCancer Pathways Panel to determine significant signaling pathways and targeted genes in these treated cells. Cytotoxicity screening revealed that MS13 exhibited greater inhibitory effect in NCI-H520 and NCI-H23 cells compared to curcumin. MS13 induced anti-proliferative activity in both cells in a dose- and time-dependent manner. Morphological analysis revealed that a significant number of MS13-treated cells exhibited apoptosis. A significant increase in caspase-3 activity and decrease in Bcl-2 protein concentration was noted in both MS13-treated cells in a time- and dose-dependent manner. A total of 77 and 47 differential expressed genes (DEGs) were regulated in MS13 treated-NCI-H520 and NCI-H23 cells, respectively. Among the DEGs, 22 were mutually expressed in both NCI-H520 and NCI-H23 cells in response to MS13 treatment. The top DEGs modulated by MS13 in NCI-H520-DUSP4, CDKN1A, GADD45G, NGFR, and EPHA2-and NCI-H23 cells-HGF, MET, COL5A2, MCM7, and GNG4-were highly associated with PI3K, cell cycle-apoptosis, and MAPK signaling pathways. In conclusion, MS13 may induce antiproliferation and apoptosis activity in squamous cell carcinoma and adenocarcinoma of NSCLC cells by modulating DEGs associated with PI3K-AKT, cell cycle-apoptosis, and MAPK pathways. Therefore, our present findings could provide an insight into the anticancer activity of MS13 and merits further investigation as a potential anticancer agent for NSCLC cancer therapy.
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