Displaying publications 1 - 20 of 25 in total

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  1. Bakhsh A, Mustapha NM, Mohamed S
    Nutrition, 2013 Apr;29(4):667-72.
    PMID: 23290096 DOI: 10.1016/j.nut.2012.09.005
    Postmenopausal estrogen deficiency often causes bone density loss and osteoporosis. This study evaluated the effects of an oral administration of oil palm leaf extract (OPL) on bone calcium content and structure, bone density, ash weights, and serum total alkaline phosphatase (T-ALP) of estrogen-deficient ovariectomized (OVX) rats.
  2. Kassem AA, Abu Bakar MZ, Yong Meng G, Mustapha NM
    ScientificWorldJournal, 2012;2012:851437.
    PMID: 22489205 DOI: 10.1100/2012/851437
    The objective of this paper is to study the effects of varying dietary levels of n-6 : n-3 fatty acid ratio on plasma and tissue fatty acid composition in rat. The treatment groups included control rats fed chow diet only, rats fed 50% soybean oil (SBO): 50% cod liver oil (CLO) (1 : 1), 84% SBO: 16% CLO (6 : 1), 96% SBO: 4% CLO (30 : 1). Blood samples were taken at day 15 of pregnancy, and the plasma and tissue were analyzed for fatty acid profile. The n-3 PUFA in plasma of Diet 1 : 1 group was significantly higher than the other diet groups, while the total n-6 PUFA in plasma was significantly higher in Diet 30 : 1 group as compared to the control and Diet 1 : 1 groups. The Diet 1 : 1 group showed significantly greater percentages of total n-3 PUFA and docosahexaenoic acid in adipose and liver tissue, and this clearly reflected the contribution of n-3 fatty acids from CLO. The total n-6 PUFA, linoleic acid, and arachidonic acid were significantly difference in Diet 30 : 1 as compared to Diet 1 : 1 and control group. These results demonstrated that the dietary ratio of n-6 : n-3 fatty acid ratio significantly affected plasma and tissue fatty acids profile in pregnant rat.
  3. Shukri R, Mohamed S, Mustapha NM, Hamid AA
    J Sci Food Agric, 2011 Nov;91(14):2697-706.
    PMID: 21744354 DOI: 10.1002/jsfa.4516
    Jering (Archidendron jiringa) is eaten in the tropics and traditionally extolled for treating diabetes, high blood pressure and eliminating bladder stones. Jering contains an unusual amino acid-djenkolic acid (S,S'-methylenebiscysteine)-which may form sharp crystals in the urinary tract, causing pain and haematuria. This study evaluates the beneficial and toxic effects of dietary jering on tissues and organs in normal and diabetic rats.
  4. Mohamad Shalan NAA, Mustapha NM, Mohamed S
    Regul Toxicol Pharmacol, 2017 Feb;83:46-53.
    PMID: 27871867 DOI: 10.1016/j.yrtph.2016.11.022
    Noni (Morinda citrifolia) leaf and fruit are used as food and medicine. This report compares the chronic toxicity of Noni fruit and edible leaf water extracts (two doses each) in female mice. The 6 months study showed the fruit extract produced chronic toxicity effects at the high dose of 2 mg/ml drinking water, evidenced through deteriorated liver histology (hepatocyte necrosis), reduced liver length, increased liver injury marker AST (aspartate aminotransferase) and albumin reduction, injury symptoms (hypoactivity, excessive grooming, sunken eyes and hunched posture) and 40% mortality within 3 months. This hepatotoxicity results support the six liver injury reports in humans which were linked to chronic noni fruit juice consumption. Both doses of the leaf extracts demonstrated no observable toxicity. The hepatotoxicity effects of the M. citrifolia fruit extract in this study is unknown and may probably be due to the anthraquinones in the seeds and skin, which had potent quinone reductase inducer activity that reportedly was 40 times more effective than l-sulforaphane. This report will add to current data on the chronic toxicity cases of Morinda citrifolia fruit. No report on the chronic toxicity of Morinda citrifolia fruit in animal model is available for comparison.
  5. Mohamad Shalan NA, Mustapha NM, Mohamed S
    Food Chem, 2016 Dec 01;212:443-52.
    PMID: 27374554 DOI: 10.1016/j.foodchem.2016.05.179
    Morinda citrifolia fruit, (noni), enhanced performances in athletes and post-menopausal women in clinical studies. This report shows the edible noni leaves water extract enhances performance in a weight-loaded swimming animal model better than the fruit or standardized green tea extract. The 4weeks study showed the extract (containing scopoletin and epicatechin) progressively prolonged the time to exhaustion by threefold longer than the control, fruit or tea extract. The extract improved (i) the mammalian antioxidant responses (MDA, GSH and SOD2 levels), (ii) tissue nutrient (glucose) and metabolite (lactate) management, (iii) stress hormone (cortisol) regulation; (iv) neurotransmitter (dopamine, noradrenaline, serotonin) expressions, transporter or receptor levels, (v) anti-inflammatory (IL4 & IL10) responses; (v) skeletal muscle angiogenesis (VEGFA) and (v) energy and mitochondrial biogenesis (via PGC, UCP3, NRF2, AMPK, MAPK1, and CAMK4). The ergogenic extract helped delay fatigue by enhancing energy production, regulation and efficiency, which suggests benefits for physical activities and disease recovery.
  6. Shalan NA, Mustapha NM, Mohamed S
    Nutrition, 2017 Jan;33:42-51.
    PMID: 27908549 DOI: 10.1016/j.nut.2016.08.006
    OBJECTIVE: Black tea and Nonileaf are among the dietary compounds that can benefit patients with bone resorption disorders. Their bone regeneration effects and their mechanisms were studied in estrogen-deficient rats.

    METHODS: Noni leaves (three doses) and black tea water extracts were fed to ovariectomized rats for 4 mo, and their effects (analyzed via mechanical measurements, micro-computed tomography scan, and reverse transcriptase polymerase chain reaction mRNA) were compared with Remifemin (a commercial phytoestrogen product from black cohosh).

    RESULTS: The water extracts (dose-dependently for noni leaves) increased bone regeneration biomarker (runt-related transcription factor 2, bone morphogenetic protein 2, osteoprotegerin, estrogen receptor 1 [ESR1], collagen type I alpha 1A) expressions and reduced the inflammatory biomarkers (interleukin-6, tumor necrosis factor-α, nuclear factor [NF]-κB, and receptor activator of NF-κB ligand) mRNA expressions/levels in the rats. The extracts also improved bone physical and mechanical properties. The extracts demonstrated bone regeneration through improving bone size and structure, bone mechanical properties (strength and flexibility), and bone mineralization and density.

    CONCLUSIONS: The catechin-rich extract favored bone regeneration and suppressed bone resorption. The mechanisms involved enhancing osteoblast generation and survival, inhibiting osteoclast growth and activities, suppressing inflammation, improving bone collagen synthesis and upregulating ESR1 expression to augment phytoestrogenic effects. Estrogen deficiency bone loss and all extracts studied (best effect from Morinda leaf at 300 mg/kg body weight) mitigated the loss, indicating benefits for the aged and menopausal women.

  7. Nahar N, Mohamed S, Mustapha NM, Fong LS
    J Diabetes Metab Disord, 2022 Jun;21(1):1-11.
    PMID: 35673507 DOI: 10.1007/s40200-021-00905-0
    PURPOSE: Diabetes accelerates peripheral, distal symmetric polyneuropathy, small fiber predominant neuropathy, radiculoplexopathy, and autonomic neuropathy. This study investigated the neuroprotective effects of gallic acid and myricetin-rich Labisia pumila extract in a diabetic neuropathy rat model and evaluated the neuropathy correlationship with serum inflammatory biomarkers.

    METHODS: Thirty male rats were divided into 5 groups (n = 6), namely: healthy control; non-treated diabetic control; and diabetic-rats treated with 200 mg/kg metformin; Labisia pumila ethanol extract (LP) at 150 mg/kg or 300 mg/kg doses. Diabetes was induced by 60 mg streptozotocin /kg intraperitoneal injection. Rats were orally treated daily for ten weeks. Their fasting blood glucose (FBG), neurological functions (hot plate and tail immersion; thermal hyperalgesia; cold allodynia; motor walking function), biomarkers for inflammation and oxidative stress, the neuro-histopathological changes, and brain somatic index were measured.

    RESULTS: The extract significantly prevented abnormal increases in FBG and decreases in body weight gain. It attenuated behavioral dysfunctions (hot plate and tail immersion; thermal hyperalgesia; cold allodynia; motor walking function), systemic inflammation (serum TNF-α, prostaglandin-E2) oxidative tension (malondialdehyde), histological brain and sciatic nerve injuries in the diabetic-rats, better than Metformin.

    CONCLUSION: LP mitigated neural dysfunction better than metformin partly by amending diabetic systemic inflammation, oxidative tension, and diabetic abnormalities. The nerve injuries were strongly correlated to serum prostaglandin-E2, TNF-α levels, and walking functions. The motor function was correlated to sensory neuronal functions, inflammation, and oxidation. The sensory neuronal functions were more affected by TNF-α than prostaglandin-E2 or oxidation. Diabetic brain and sciatic nerve deteriorations were influenced by serum TNF-α, PGE2, and MDA levels.

    SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-021-00905-0.

  8. Matanjun P, Mohamed S, Muhammad K, Mustapha NM
    J Med Food, 2010 Aug;13(4):792-800.
    PMID: 20482284 DOI: 10.1089/jmf.2008.1212
    This study was designed to investigate the comparative in vivo cardiovascular protective effects of red, green, and brown tropical seaweeds, namely, Kappaphycus alvarezii (or Eucheuma cottonii), Caulerpa lentillifera, and Sargassum polycystum, in rats fed on high-cholesterol/high-fat (HCF) diets. Male Sprague-Dawley rats (weighing 260-300 g) on the HCF diet had significantly increased body weight, plasma total cholesterol (TC), plasma low-density lipoprotein cholesterol (LDL-C), plasma triglycerides (TG), lipid peroxidation, and erythrocyte glutathione peroxidase (GSH-Px) and superoxide dismutase levels after 16 weeks. Supplementing 5% seaweeds to HCF diet significantly reduced plasma TC (-11.4% to -18.5%), LDL-C (-22% to -49.3%), and TG (-33.7% to -36.1%) levels and significantly increased HDL-C levels (16.3-55%). Among the seaweeds, S. polycystum showed the best anti-obesity and blood GSH-Px properties, K. alvarezii showed the best antihyperlipemic and in vivo antioxidation effects, and C. lentillifera was most effective at reducing plasma TC. All seaweeds significantly reduced body weight gain, erythrocyte GSH-Px, and plasma lipid peroxidation of HCF diet rats towards the values of normal rats.
  9. Mustapha NM, Tarr JM, Kohner EM, Chibber R
    J Ophthalmol, 2010;2010:746978.
    PMID: 20652059 DOI: 10.1155/2010/746978
    Objectives. Using apocynin (inhibitor of NADPH oxidase), and Mitoquinol 10 nitrate (MitoQ; mitochondrial-targeted antioxidant), we addressed the importance of mitochondria versus NADPH oxidase-derived ROS in glucose-induced apoptosis of pericytes. Methods. NADPH oxidase was localised using Western blot analysis and cytochrome C reduction assay. Apoptosis was detected by measuring caspase-3 activity. Intracellular glucose concentration, ROS formation and Nepsilon-(carboxymethyl) lysine (CML) content were measured using Amplex Red assay kit, dihydroethidium (DHE), and competitive immunoabsorbant enzyme-linked assay (ELISA), respectively. Results. NADPH oxidase was localised in the cytoplasm of pericytes suggesting ROS production within intracellular compartments. High glucose (25 mM) significantly increased apoptosis, intracellular glucose concentration, and CML content. Apoptosis was associated with increased gp91phox expression, activity of NADPH oxidase, and intracellular ROS production. Apocynin and not MitoQ significantly blunted the generation of ROS, formation of intracellular CML and apoptosis. Conclusions. NADPH oxidase and not mitochondria-derived ROS is responsible for the accelerated apoptosis of pericytes in diabetic retinopathy.
  10. Buhari S, Hashim K, Yong Meng G, Mustapha NM, Gan SH
    ScientificWorldJournal, 2012;2012:564939.
    PMID: 22778699 DOI: 10.1100/2012/564939
    Subcutaneous (SC) administration of tramadol was compared with intravenous (IV) administration to evaluate analgesia following canine ovariohysterectomy (OHE). Healthy female dogs (n = 12) between 1 and 3 years of age (1.95 ± 0.65 years), weighing between 10.5 and 17.1 kg (13.12 ± 1.95 kg), were used. Pain was assessed at baseline before surgery and then hourly for 8 hr after surgery. Tramadol was administered both SC and IV at a dose of 3 mg/kg and provided significant postoperative analgesia, as indicated by analgesiometry, β-endorphin levels, and interleukin 6 (IL-6) levels. The respiratory rates and rectal temperatures remained normal and were not significantly different between or within the groups. A significant increase in heart rate was observed at 4 hr for dogs in both groups relative to the baseline, but there was no significant difference in heart rates between the groups at any time point. A significant decrease in mechanical pain threshold was observed within each group after surgery, but both groups responded similarly, suggesting that SC administration of tramadol is as effective as IV administration. Increased serum levels of both IL-6 and β-endorphin 3 hr postoperatively further indicate that both routes of administration achieve similar pain control. Thus, the relative analgesic efficacy of SC tramadol is comparable to that of IV administration and can be used to achieve similar effects for postsurgical pain management in dogs undergoing OHE.
  11. Jaffri JM, Mohamed S, Ahmad IN, Mustapha NM, Manap YA, Rohimi N
    Food Chem, 2011 Sep 15;128(2):433-41.
    PMID: 25212153 DOI: 10.1016/j.foodchem.2011.03.050
    Catechin-rich oil palm (Elaeis guineensis) leaf extract (OPLE) possesses good ex vivo vasodilation, antioxidant and cardiovascular properties. This study evaluated the beneficial or toxic effects of OPLE on the liver and kidneys of normal and hypertensive rats. The OPLE (500mg/kg body weight) were administered orally to normal Wistar Kyoto rats, spontaneously hypertensive rats (SHR) and N-ω-nitro-l-arginine methyl ester (l-NAME)-induced NO-deficient hypertensive rats. The OPLE reduced hypertension in NO-deficient rats, but not in SHR. Hepatocytes or glomeruli injury and oxidative markers were high in hypertensive rats compared to normal rats, and they were reduced (p<0.05) by OPLE supplementation, even when there was no blood pressure reduction. Unlike the hypertensive drug captopril, the OPLE showed no toxicity to normal rats. The dose reported is equivalent 0.5g of catechins/day for humans or 2.5cups of tea. The catechins are from an abundant alternative source for potential use as functional food.
  12. Fadilah NIM, Rahman MBA, Yusof LM, Mustapha NM, Ahmad H
    Pharmaceutics, 2021 Feb 01;13(2).
    PMID: 33535623 DOI: 10.3390/pharmaceutics13020193
    The standard treatment of open wounds via the direct usage of therapeutic agents is not without limitations with respect to healing. Small peptides can create a favorable milieu for accelerating the healing of wounds. This study presents the potential of a novel fatty acid conjugated tetrapeptide (palmitic acid-glycine-aspartic acid-proline-histidine; Palmitoyl-GDPH) in alleviating wound healing. Tetracycline was employed as a standard control drug following its significance in wound healing including biologically active and antimicrobial effects. The peptide in liquid form was applied on to a 4 cm2 full thickness wound surgically induced at the dorsum of Sprague Dawley (SD) rats. The in vivo wound treatment with Palmitoyl-GDPH for eighteen days, histologically demonstrated an almost perfect healing exhibited by increased re-epithelialization, enhanced collagen deposition, and diminished scar formation compared to the controls. In addition, the well-developed epidermal-dermal junction and ultimate stimulation of hair follicle-growth in the Palmitoyl-GDPH treated group indicated the wound to have healed as functionally viable tissues. In general, the much lower hemogram values in the Palmitoyl-GDPH group indicated that the ongoing healing is en route to an earlier recovery. Additionally, the liver, kidney, and pancreas function biomarkers being within normal limits indicated the relatively non-toxic nature of Palmitoyl-GDPH at the used dosage. These results indisputably supported the great potential of this newly synthesized Palmitoyl-GDPH to be used as an effective therapeutic agent for wound healing (this actually means creating a new wound).
  13. Zohdi RM, Zakaria ZA, Yusof N, Mustapha NM, Abdullah MN
    PMID: 21504052 DOI: 10.1002/jbm.b.31828
    Malaysian sea cucumber was incorporated into hydrogel formulation by using electron beam irradiation technique and was introduced as novel cross-linked Gamat Hydrogel dressing. This study investigated whether Gamat Hydrogel enhanced repair of deep partial skin thickness burn wound in rats and its possible mechanism. Wounds were treated with either Gamat Hydrogel, control hydrogel, OpSite® film dressing or left untreated. Skin samples were taken at 7, 14, 21, and 28 days post burn for histological and molecular evaluations. Gamat Hydrogel markedly enhanced wound contraction and improved histological reorganization of the regenerating tissue. Furthermore, the dressing modulated the inflammatory responses, stimulated the activation and proliferation of fibroblasts, and enhanced rapid production of collagen fiber network with a consequently shorter healing time. The level of proinflammatory cytokines; IL-1α, IL-1β, and IL-6, were significantly reduced in Gamat Hydrogel treated wounds compared with other groups as assessed by reverse transcription-polymerase chain reaction (RT-PCR). In summary, our results showed that Gamat Hydrogel promoted burn wound repair via a complex mechanism involving stimulation of tissue regeneration and regulation of pro-inflammatory cytokines. The resultant wound healing effects were attributed to the synergistic effect of the hydrogel matrix and incorporated sea cucumber.
  14. Humam AM, Loh TC, Foo HL, Izuddin WI, Zulkifli I, Samsudin AA, et al.
    Poult Sci, 2021 Mar;100(3):100908.
    PMID: 33518339 DOI: 10.1016/j.psj.2020.12.011
    The aim of this work was to evaluate the impacts of feeding different levels of postbiotic RI11 on antioxidant enzyme activity, physiological stress indicators, and cytokine and gut barrier gene expression in broilers under heat stress. A total of 252 male broilers Cobb 500 were allocated in cages in environmentally controlled chambers. All the broilers received the same basal diet from 1 to 21 d. On day 22, the broilers were weighed and grouped into 7 treatment groups and exhibited to cyclic high temperature at 36 ± 1°C for 3 h per day until the end of the experiment. From day 22 to 42, broilers were fed with one of the 7 following diets: negative control, basal diet (0.0% RI11) (NC group); positive control, NC diet + 0.02% (w/w) oxytetracycline (OTC group); antioxidant control, NC diet + 0.02% (w/w) ascorbic acid. The other 4 other groups were as follows: NC diet + 0.2% cell-free supernatant (postbiotic RI11) (v/w), NC diet + 0.4% cell-free supernatant (postbiotic RI11) (v/w), NC diet + 0.6% cell-free supernatant (postbiotic RI11) (v/w), and NC diet + 0.8% cell-free supernatant (postbiotic RI11) (v/w). Supplementation of different levels (0.4, 0.6, and 0.8%) of postbiotic RI11 increased plasma glutathione peroxidase, catalase, and glutathione enzyme activity. Postbiotic RI11 groups particularly at levels of 0.4 and 0.6% upregulated the mRNA expression of IL-10 and downregulated the IL-8, tumor necrosis factor alpha, heat shock protein 70, and alpha-1-acid glycoprotein levels compared with the NC and OTC groups. Feeding postbiotic RI11, particularly at the level of 0.6%, upregulated ileum zonula occludens-1 and mucin 2 mRNA expressions. However, no difference was observed in ileum claudin 1, ceruloplasmin, IL-6, IL-2, and interferon expression, but downregulation of occludin expression was observed as compared with the NC group. Supplementation of postbiotic RI11 at different levels quadratically increased plasma glutathione peroxidase, catalase and glutathione, IL-10, mucin 2, and zonula occludens-1 mRNA expression and reduced plasma IL-8, tumor necrosis factor alpha, alpha-1-acid glycoprotein, and heat shock protein 70 mRNA expression. The results suggested that postbiotics produced from Lactiplantibacillus plantarum RI11 especially at the level of 0.6% (v/w) could be used as an alternative to antibiotics and natural sources of antioxidants in poultry feeding.
  15. Reduan FH, Shaari RM, Sayuti NSA, Mustapha NM, Abu Bakar MZ, Sithambaram S, et al.
    Toxicol Res, 2020 Jul;36(3):203-210.
    PMID: 32685424 DOI: 10.1007/s43188-019-00013-5
    Melastoma malabathricum is a well-known herb in Malaysia where it being used in various ways for treatment of different diseases and ailments including skin problems. The study aims to investigate acute and subacute dermal toxicity of ethanolic extract of M. malabathricum leaves following to a single or repeated doses exposure. A total of 30 female Sprague-Dawley rats were grouped into 5 groups (n = 6 per group) for both acute and subacute toxicity study. The duration for each study was determined at 14 days for acute toxicity and 28 days for subacute toxicity. The rats were topically applied with the plant extract at three different doses; 2.5%, 5.0% and 10.0% on the shaved area of dorsal skin. For acute toxicity study, rats in all three groups received single application of the extract on the first day of the experimental period, while rats in subacute toxicity study were topically applied with the extract once daily for 28 days. Throughout the respective 14-day and 28-day study periods, all rats were monitored for any changes in their physical appearance and behavioural patterns that might develop due to toxic effects of the plant. There were no mortality or abnormal physical appearance, and physiological and behavioural changes observed in all rats in both studies. Body weights, kidney and liver weights, and both haematology and serum biochemistry results showed no significant (p > 0.05) differences between all groups in both studies. All of the findings were supported by normal macroscopic and microscopic architectures of liver, kidneys and skin of all rats applied topically with the extract. This study suggests that topical application of M. malabathricum leaf ethanolic extract at 2.5%, 5% and 10% does not induce acute and subacute adverse effects on the skin or systemic toxic reactions in rats.
  16. Lim SL, Mustapha NM, Goh YM, Bakar NA, Mohamed S
    Mol Cell Biochem, 2016 May;416(1-2):85-97.
    PMID: 27106908 DOI: 10.1007/s11010-016-2698-x
    Metastasized lung and liver cancers cause over 2 million deaths annually, and are amongst the top killer cancers worldwide. Morinda citrifolia (Noni) leaves are traditionally consumed as vegetables in the tropics. The macro and micro effects of M. citrifolia (Noni) leaves on metastasized lung cancer development in vitro and in vivo were compared with the FDA-approved anti-cancer drug Erlotinib. The extract inhibited the proliferation and induced apoptosis in A549 cells (IC50 = 23.47 μg/mL) and mouse Lewis (LL2) lung carcinoma cells (IC50 = 5.50 μg/mL) in vitro, arrested cancer cell cycle at G0/G1 phases and significantly increased caspase-3/-8 without changing caspase-9 levels. The extract showed no toxicity on normal MRC5 lung cells. Non-small-cell lung cancer (NSCLC) A549-induced BALB/c mice were fed with 150 and 300 mg/kg M. citrifolia leaf extract and compared with Erlotinib (50 mg/kg body weight) for 21 days. It significantly increased the pro-apoptotic TRP53 genes, downregulated the pro-tumourigenesis genes (BIRC5, JAK2/STAT3/STAT5A) in the mice tumours, significantly increased the anti-inflammatory IL4, IL10 and NR3C1 expression in the metastasized lung and hepatic cancer tissues and enhanced the NFE2L2-dependent antioxidant responses against oxidative injuries. The extract elevated serum neutrophils and reduced the red blood cells, haemoglobin, corpuscular volume and cell haemoglobin concentration in the lung cancer-induced mammal. It suppressed inflammation and oedema, and upregulated the endogenous antioxidant responses and apoptotic genes to suppress the cancer. The 300 mg/kg extract was more effective than the 50 mg/kg Erlotinib for most of the parameters measured.
  17. Nahar N, Mohamed S, Mustapha NM, Fong LS, Mohd Ishak NI
    J Food Biochem, 2021 11;45(11):e13948.
    PMID: 34622461 DOI: 10.1111/jfbc.13948
    Diabetes affected about a quarter of a billion people globally, and one out of four diabetics has eye or vision problems. This study investigated whether gallic acid and myricetin-rich Labisia pumila extract (LP) consumption would help prevent diabetic eye disorders and some probable biochemistry involved relating to inflammation, vascular leakage, and oxidative tension. Male rats were divided into four groups (n = 6), namely healthy control, diabetic non-treated control, and hyperglycemic rats treated with 150 or 300 mg/kg LP. Intraperitoneal injection of 60 mg/kg streptozotocin was used to induce diabetes. Rats were fed in the morning and evening. Diabetic retinopathy was graded in rats using a dilated retinal digital ophthalmoscopy. Rats were sacrificed at 12 weeks and the retina, optic nerve, cornea, lens, sclera, ciliary bodies, iris, and conjunctiva were examined histologically. The diabetic rats consuming LP for 10 weeks showed dose-dependent, histopathologically-reduced eye abnormalities (keratopathy, cataract, sclera, conjunctiva, ciliary bodies, iris, limbus, corneal edema, epithelial barrier inefficiency, shallow punctate keratitis, lower basal layer cell density, retinopathy, glaucoma, and corneal changes). The LP significantly suppressed inflammation [increased serum tumor necrosis factor-α (TNF-α), prostaglandin-E2 (PGE2)], vascular leakage [claudin-1], abnormal vascularization [vascular endothelial growth factor (VEGF)], oxidative tension [malondialdehyde/reduced glutathione ratio], and hyperglycemia [fasting blood glucose] of the diabetic rats. The LP consumption was significantly protective against diabetic eye disorders and optic nerve dysfunction which were related to inflammation, vascular leakage, abnormal vascularization, and oxidative tension, which most likely influenced eye hemorrhage and collagen cross-linkage. PRACTICAL APPLICATIONS: The study shows that gallic acid and myricetin-rich Labisia pumila (LP) leaf consumption may be used as a complementary therapy for managing diabetes (fasting blood glucose) and preventing diabetic eye disorders (keratopathy, cataract, sclera, conjunctiva, ciliary bodies, iris, limbus, corneal edema, epithelial barrier inefficiency, shallow punctate keratitis, lower basal layer cell density, retinopathy, glaucoma, and corneal abnormalities). The LP consumptions reduced the serum biomarkers for inflammation (serum tumor necrosis factor-α TNF-α; prostaglandin-E2), vascular leakage/abnormalities (claudin-1 and vascular endothelial growth factor VEGF), and oxidative tension (malondialdehyde/reduced glutathione MDA/GSH ratio). The LP was eye-protective probably by normalizing fasting blood glucose, reducing inflammation, oxidative tension, vascular leakage, and irregular vascularization.
  18. Mustafa H, Cheng CH, Radzi R, Fong LS, Mustapha NM, Dyary HO
    Pol J Vet Sci, 2021 Sep;24(3):365-373.
    PMID: 34730299 DOI: 10.24425/pjvs.2021.138727
    Periodontitis is a highly prevalent, chronic immune-inflammatory disease of the periodontium that results in the periodontium and alveolar bone loss's progressive destruction. In this study, the induction of periodontal disease via retentive ligature, lipopolysaccharide, and their combination at three different times were compared in a rat model. Seventy-two Sprague Dawley rats were distributed into four treatment groups: 1) control group with no treatment; 2) application of 4/0 nylon ligature around second maxillary molars; 3) combination of ligature and LPS injection (ligature-LPS); 4) intragingival injection of Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) to the palatal mucosa of the second maxillary molars. Six rats were sacrificed from each group after 7, 14, and 30 days of periodontal disease induction. Alveolar bone loss, attachment loss, number of inflammatory cells, and blood vessels were evaluated histologically. A micro-CT scan was used as a parameter to know the rate of alveolar bone loss. Parametric data were analyzed using two-way ANOVA followed by Bonferroni correction with a significance set at 5%. Non-parametric data were analyzed using Kruskal-Wallis, followed by multiple comparisons with Bonferroni correction. The histological results revealed significant destructive changes in the periodontal tissues and alveolar bone following the ligature and ligature-LPS induction techniques. These changes were evident as early as seven days, maintained until 14 days post-treatment, and declined with time. The ligature technique was effective in inducing acute periodontal disease. The LPS injection technique did not induce alveolar bone loss, and its combination to ligature added insignificant effects.
  19. Ishak NIM, Mohamed S, Madzuki IN, Mustapha NM, Esa NM
    Naunyn Schmiedebergs Arch Pharmacol, 2021 09;394(9):1907-1915.
    PMID: 34009457 DOI: 10.1007/s00210-021-02101-6
    Inflammation and compromised immune responses often increase colorectal cancer (CRC) risk. The immune-modulating effects of limonin on carcinogen/inflammation-induced colorectal cancer (CRC) were studied in mice. Male Balb/c mice were randomly assorted into three groups (n = 6): healthy control, non-treated CRC-induced (azoxymethane/dextran-sulfate-sodium AOM/DSS) control, and CRC-induced + 50 mg limonin/kg body weight. The CRC developments were monitored via macroscopic, histopathological, ELISA, and mRNA expression analyses. Limonin downregulated inflammation (TNF-α, tumor necrosis factor-α), enhanced the adaptive immune responses (CD8, CD4, and CD19), and upregulated antioxidant defense (Nrf2, SOD2) mRNA expressions. Limonin reduced serum malondialdehyde (MDA, lipid peroxidation biomarker), prostaglandin E2, and histopathology inflammation scores, while increasing reduced glutathione (GSH) in CRC-induced mice. Limonin significantly (p 
  20. Ruslee SS, Zaid SSM, Bakrin IH, Goh YM, Mustapha NM
    BMC Complement Med Ther, 2020 May 29;20(1):160.
    PMID: 32471398 DOI: 10.1186/s12906-020-02960-1
    BACKGROUND: To investigate the protective effects of Tualang honey against the toxicity effects induced by cadmium (Cd) on the ovary.

    METHODS: A total of 32 female Sprague Dawley rats were taken and randomly divided into four groups (n = 8). Throughout the experimental period of 6 weeks, negative control-NC (vehicle deionized water), positive control-CD (Cd at 5 mg/kg), Tualang honey followed by Cd exposure-TH (Tualang honey at 200 mg/kg and Cd at 5 mg/kg) and Tualang honey control-THC (Tualang honey at 200 mg/kg) groups, were administered orally on a daily basis.

    RESULTS: Rats exposed to Cd were significantly higher in ovarian weight, number of antral and atretic follicles as compared to the NC group. The disruptive effects of Cd on ovarian follicles were associated with a disruption in gonadotropin hormones and decreases in follicular stimulating hormone (FSH) and luteinizing hormone (LH). Moreover, a significant formation of oxidative stress in ovarian Cd-exposed rats has been proven by increasing the level of lipid peroxidation products (malondialdehyde) and decreasing the levels of enzymatic antioxidant (catalase). Interestingly, a daily supplementation of high antioxidant agents such as Tualang honey in these animals, caused significant improvements in the histological changes. Additionally, less atretic follicles were observed, restoring the normal level of LH and FSH (P 

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