Displaying publications 1 - 20 of 55 in total

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  1. Fazalul Rahiman SS, Basir R, Talib H, Tie TH, Chuah YK, Jabbarzare M, et al.
    Trop Biomed, 2013 Dec;30(4):663-80.
    PMID: 24522137 MyJurnal
    Interleukin-27 (IL-27) has a pleiotropic role either as a pro-inflammatory or anti-inflammatory cytokine in inflammatory related diseases. The role and involvement of IL-27 during malaria was investigated and the effects of modulating its release on the production of major inflammatory cytokines and the histopathological consequences in major affected organs during the infection were evaluated. Results showed that IL-27 concentration was significantly elevated throughout the infection but no positive correlation with the parasitaemia development observed. Augmentation of IL-27 significantly elevated the release of anti-inflammatory cytokine, IL-10 whereas antagonising and neutralising IL-27 produced the opposite. A significant elevation of pro-inflammatory cytokines (IFN-γ and IL-6) was also observed, both during augmentation and inhibition of IL-27. Thus, it is suggested that IL-27 exerts an anti-inflammatory activity in the Th1 type response by signalling the production of IL-10 during malaria. Histopathological examination showed sequestration of PRBC in the microvasculature of major organs in malarial mice. Other significant histopathological changes include hyperplasia and hypertrophy of the Kupffer cells in the liver, hyaline membrane formation in lung tissue, enlargement of the white and red pulp followed by the disappearance of germinal centre of the spleen, and tubular vacuolation of the kidney tissues. In conclusion, it is suggested that IL-27 may possibly acts as an anti-inflammatory cytokine during the infection. Modulation of its release produced a positive impact on inflammatory cytokine production during the infection, suggesting its potential in malaria immunotherapy, in which the host may benefit from its inhibition.
  2. Basir R, Hasballah K, Jabbarzare M, Gam LH, Abdul Majid AM, Yam MF, et al.
    Trop Biomed, 2012 Sep;29(3):405-21.
    PMID: 23018504 MyJurnal
    The involvement of interleukin-18 (IL-18) and the effects of modulating its release on the course of malaria infection were investigated using Plasmodium berghei ANKA infection in ICR mice as a model. Results demonstrated that plasma IL-18 concentrations in malarial mice were significantly elevated and positively correlated with the percentage parasitaemia development. Significant expressions of IL-18 were also observed in the brain, spleen and liver tissues. Slower development of parasitaemia was observed significantly upon inhibition and neutralization of IL-18, whereas faster development of parasitaemia was recorded when the circulating levels of IL-18 were further augmented during the infection. Inhibition and neutralization of IL-18 production also resulted in a significant decrease of plasma concentrations of pro-inflammatory cytokines (TNFα, IFNγ, IL-1α and IL-6), whereas the anti-inflammatory cytokine, IL-10, was significantly increased. Augmenting the release of IL- 18 during the infection on the other hand resulted in the opposite. Early mortality in malarial mice was also observed when the circulating levels of IL-18 were further augmented. Results proved the important role of IL-18 in immune response against malaria and suggest that IL-8 is pro-inflammatory in nature and may involve in mediating the severity of the infection through a pathway of elevating the pro-inflammatory cytokine and limiting the release of anti-inflammatory cytokine.
  3. Hassan WRM, Basir R, Ali AH, Embi N, Sidek HM
    Trop Biomed, 2019 Sep 01;36(3):776-791.
    PMID: 33597499
    Malarial pathogenesis involves among others, uncontrolled or excessive cytokine production arising from dysregulated immune responses mounted by the host to eliminate the plasmodial parasite. The ubiquitous serine/threonine kinase, glycogen synthase kinase3β (GSK3β) is a crucial regulator of the balance between pro- and anti-inflammatory cytokine productions in the inflammatory response to pathogenic infections. Andrographolide, a bioactive compound in Andrographis paniculata, displays GSK3- inhibitory effects. A previous study elsewhere has shown that this compound has antimalarial activity but the molecular basis of its action is yet to be elucidated. Here we aimed to study the anti-malarial activity of andrographolide in a murine model of malarial infection to investigate whether its mechanism of action involves cytokine modulation and inhibition of GSK3β. Andrographolide showed strong and selective anti-plasmodial activity (IC50 = 13.70±0.71 µM; SI = 30.43) when tested against cultures of P. falciparum 3D7. Intraperitoneal administration of andrographolide (5 mg/kg body weight (bw)) into P. berghei NK65-infected ICR mice resulted in chemo-suppression of 60.17±2.12%, and significantly (P<0.05) improved median survival time of infected mice compared to nontreated control. In addition, andrographolide treatment significantly (P<0.05) decreased the level of serum pro-inflammatory cytokine, IFN-γ (1.4-fold) whilst the anti-inflammatory cytokines, IL-10 and IL-4 were increased 2.3- and 2.6-fold respectively. Western blot analyses revealed that andrographolide treatment of P. berghei NK65-infected mice resulted in an increased level of phosphorylated GSK3β (Ser9) in liver of infected mice. Andrographolide administration also decreased the levels of phosphorylated NF-κB p65 (Ser536) and phosphorylated Akt (Ser473) in liver of malaria- infected animals. Taken together, our findings demonstrate that the cytokine-modulating effect of andrographolide in experimental malarial infection involves at least in part inhibition of NF-κB activation as a consequence of GSK3β inhibition. Based on its cytokine-modulating effects, andrographolide is thus a plausible candidate for adjunctive therapy in malaria subject to clinical evaluations.
  4. Soo KM, Tham CL, Khalid B, Basir R, Chee HY
    Trop Biomed, 2019 Dec 01;36(4):1027-1037.
    PMID: 33597472
    Dengue is a common infection, caused by dengue virus. There are four different dengue serotypes, with different capacity to cause severe dengue infections. Besides, secondary infections with heterologous serotypes, concurrent infections of multiple dengue serotypes may alter the severity of dengue infection. This study aims to compare the severity of single infection and concurrent infections of different combinations of dengue serotypes in-vitro. Human mast cells (HMC)-1.1 were infected with single and concurrent infections of multiple dengue serotypes. The infected HMC-1.1 supernatant was then added to human umbilical cord vascular endothelial cells (HUVEC) and severity of dengue infections was measured by the percentage of transendothelial electrical resistance (TEER). Levels of IL10, CXCL10 and sTRAIL in HMC-1.1 and IL-8, IL-10 and CXCL10 in HUVEC culture supernatants were measured by the ELISA assays. The result showed that the percentage of TEER values were significantly lower in single infections (p< 0.05), compared to concurrent infections on day 2 and 3, indicating that single infection increase endothelial permeability greater than concurrent infections. IL-8 showed moderate correlation with endothelial permeability (r > 0.4), indicating that IL-8 may be suitable as an in-vitro severity biomarker. In conclusion, this in-vitro model presented few similarities with regards to the conditions in dengue patients, suggesting that it could serve as a severity model to test for severity and levels of severity biomarkers upon different dengue virus infections.
  5. Zaid OI, Abd Majid R, Sidek HM, Noor SM, Abd Rachman-Isnadi MF, Bello RO, et al.
    Trop Biomed, 2020 Mar 01;37(1):29-49.
    PMID: 33612716
    Treatment Failure with chloroquine is one of the challenges that faced the dedicated efforts to eradicate malaria This study aims at investigating the impact of treatment failure with chloroquine on the progression of the disease-induced histo-pathogenic and immunogenic outcomes. To achieve this, Rane's protocol with modifications was applied on a model of Plasmodium berghei ANKA infected ICR mice to determine the dose response curve of chloroquine and to screen the treatment impact on the disease progression. Chloroquine was given at 1, 5, 10, 15 and 20 mg/kg once the parasitemia reached to 20-30% (the experimental initiation point). During the subsequent days, the mice were monitored for changes in the clinical signs, hematology parameters and the progress of the parasitemia until the parasitemia reached to 60-70% (the experimental termination point) or up to 10 days after chloroquine administration in case of achieving a complete eradication of the parasite. At the end, the mice were exsanguinated and their blood and organs were collected for the biochemistry and the histology study. A complete eradication of the parasite was achieved at 20 mg/kg while recrudescence was observed at the lower doses. At 1 mg/kg, the parasite growth was comparable to that of the positive control. The histo-pathogenic and immunogenic changes were stronger in the groups that experienced recrudescence (at 5 and 10 mg/kg). All in all, the study highlights the possibility of having a worsened clinical condition when chloroquine is given at its sub-therapeutic doses during malaria treatment.
  6. Aizuddin NNF, Ganesan N, Ng WC, Ali AH, Ibrahim I, Basir R, et al.
    Trop Biomed, 2020 Dec 01;37(4):1105-1116.
    PMID: 33612762 DOI: 10.47665/tb.37.4.1105
    Malaria is a life-threatening disease caused by the Plasmodium sp. parasite. Infection results in heightened pro-inflammatory response which contributes to the pathophysiology of the disease. To mitigate the overwhelming cytokine response, host-directed therapy is a plausible approach. Glycogen synthase kinase-3β (GSK3β), a serine/threonine kinase plays a pivotal role in the regulation of inflammatory response during pathogenic infections. The present study was conducted to investigate the chemo-suppressive and cytokine-modulating effects of insulin administration in malaria-infected mice and the involvement of GSK3β. Intraperitoneal administrations of 0.3 and 0.5 U/kg body weight insulin each for four consecutive days into Plasmodium berghei NK65 (PbN)-infected mice resulted in chemo-suppression exceeding 60% and improved median survival time of infected mice (20.5 days and 19 days respectively compared to 15.5 days for non-treated control). Western analysis revealed that pGSK3β (Ser9) intensity in brain samples from insulin-treated (0.3 and 0.5 U/kg body weight) infected mice each were 0.6 and 2.2 times respectively than that in control. In liver samples, pGSK3β (Ser9) intensity from insulin-treated infected mice were significantly higher (4.8 and 16.1 fold for 0.3 and 0.5 U/kg bw respectively) than that in control. Insulin administration decreased both brain and liver pNF-κB p65 (Ser536) intensities (to 0.8 and 0.6 times for 0.3 U/kg bw insulin; and to 0.2 and 0.1 times for 0.5 U/kg bw insulin respectively compared to control). Insulin treatment (0.5 U/kg bw) also significantly decreased the serum levels of pro-inflammatory cytokines (TNF-α (3.3 times) and IFN-γ (4.9 times)) whilst significantly increasing the levels of anti-inflammatory cytokines (IL-4 (4.9 fold) and IL-10 (2.1 fold)) in PbN-infected mice. Results from this study demonstrated that the cytokinemodulating effects of insulin at least in part involve inhibition of GSK3β and consequent inhibition of the activation of NF-κB p65 suggesting insulin as a potential adjunctive therapeutic for malaria.
  7. Ibraheem ZO, Farhan SS, Al Sumaidaee A, Al Sufi L, Bashir A, Balwa A, et al.
    Toxicol Res, 2021 Apr;37(2):221-235.
    PMID: 33868979 DOI: 10.1007/s43188-020-00059-w
    Metabolic syndrome is one of the major risk factors that lead to various serious complications like cardiovascular abnormalities, hyperlipidemia and diabetes. Its co-incidence with other organs dysfunction results in further deterioration of the condition or precipitation of other dysfunctions. This study aimed at studying the changes in the hepatic functions after the co-incidence of the high fat or fructose diets induced metabolic syndrome along with the gentamicin induced nephrotoxicity. Briefly, six groups of male Sprague Daley rats (n = 10-12) were fed with different feeding protocols; viz; standard rodent's chow, an experimental high fat or high fructose diets feedings. For each, two groups were allocated that one of them was injected with normal saline and the other with 80 mg/kg/day I.P gentamicin during the last 24 days of the feeding period. The rats were monitored for changes in the metabolic data, glycemic control, lipid profile, renal and hepatic functions, oxidative stress and the inflammatory response. The study revealed stronger hepatic changes in the renal failure groups fed with the high fat diet rather than that in the groups fed with the high fructose diet. Although, the latter experienced a stronger deterioration in the glycemic control. The study suggests that the incidence of the hepatic changes is more linked to the incidence of the deterioration in the lipids profile that was observed after the high fat diet feeding. Overall, the co-incidence of the high fat diet induced metabolic syndrome along with the renal failure constitutes a risk factor for the hepatic dysfunction.
  8. Yam MF, Basir R, Asmawi MZ, Ismail Z
    Am J Chin Med, 2007;35(1):115-26.
    PMID: 17265556
    Orthosiphon stamineus (OS), Benth. (Lamiaceae) is widely used in Malaysia for treatments of various kidney and liver ailments. In the experiment, DPPH* radicals scavenging, Fe(3+)-induced lipid peroxidation inhibiting activities and trolox equivalent antioxidant capacity (TEAC) of methanol/water extract of Orthosiphon stamineus (SEOS) were determined. The results indicated that SEOS exhibited antioxidant, lipid peroxidation inhibition and free radical scavenging activities. The hepatoprotective activity of the SEOS was studied using CCl(4)-induced liver toxicity in rats. The activity was assessed by monitoring liver function tests through the measurement of alanine transaminase (ALT) and aspartate transaminase (AST). Furthermore, hepatic tissues were also subjected to histopathological studies. Pretreatment of SEOS (125, 250, 500 and 1000 mg/kg p.o.) dose-dependently reduced the necrotic changes in rat liver and inhibited the increase of serum ALT and AST activities. The results of the present study indicated that the hepatoprotective effect of Orthosiphon stamineus might be ascribable to its antioxidant and free radical scavenging property.
  9. Yam MF, Ahmad M, Por LY, Ang LF, Basir R, Asmawi MZ
    Sensors (Basel), 2012;12(7):9603-12.
    PMID: 23012561
    The stepping forces of normal and Freund Complete Adjuvant (FCA)-induced arthritic rats were studied in vivo using a proposed novel analgesic meter. An infrared charge-coupled device (CCD) camera and a data acquisition system were incorporated into the analgesic meter to determine and measure the weight of loads on the right hind paw before and after induction of arthritis by FCA injection into the paw cavity. FCA injection resulted in a significant reduction in the stepping force of the affected hind paw. The stepping force decreased to the minimum level on day 4 after the injection and then gradually increased up to day 25. Oral administration of prednisolone significantly increased the stepping forces of FCA-induced arthritic rats on days 14 and 21. These results suggest that the novel device is an effective tool for measuring the arthritic pain in in vivo studies even though walking is a dynamic condition.
  10. Zaid OI, Majid RA, Hasidah MS, Sabariah MN, Al-Zihiry K, Rahi S, et al.
    Pharmacogn Mag, 2017 Jan;13(Suppl 1):S48-S55.
    PMID: 28479726 DOI: 10.4103/0973-1296.203982
    BACKGROUND: Emergence of chloroquine (CQ) resistance among different strains of Plasmodium falciparum is the worst catastrophe that has ever perplexed the dedicated efforts to eradicate malaria. This urged the scientists to search for new alternatives or sensitizers to augment its antiplasmodium effect.

    MATERIALS AND METHOD: In this experiment, the potential of embelin, isolated from Embelia ribes, to inhibit the growth and sensitize CQ action was screened using SYBRE-green-I based drug sensitivity and isobologram assays, respectively. Its effect on red blood cells stability was screened to assess its safety. To explore its molecular mechanism, its effect on plasmodial Hemozoin and the in vitro β-hematin formation was screened as well. Furthermore, its anti-oxidant activity was measured using the conventional in vitro tests and its molecular characters were obtained using Molispiration program.

    RESULTS: The results showed that its anti-plasmodial effect was weaker than CQ but synergism was obtained when they were combined at ratios lower than 5:5 CQ/embelin. Furthermore, β-hematin formation was inhibited by embelin without showing any synergism after mixing with CQ.

    CONCLUSION: Overall, embelin is not ideal to be suggested as a conventional antiplasmodium but it has a potential to ameliorate CQ resistance. Furthermore, its action is not related to its impact on hemozoin formation. Further, investigations are recommended to illustrate its detailed mechanism of action. Abbreviation used: CQ-DV-PBS-HEPES: Chloroquine-Digestive vacuole-Phosphate-buffer-saline-4-(2-hydroxyethyl-1-piperazin-ethan-sulphoni-acid), EDTA: Ethylen-diamin-tetra-acetic-acid, g.m.wt: Gram molecular weight, cMCM: Complete-malaria-culture-medium, Hct: Hematocrite, PRBCs: Parasitized-redblood-cells, nRBCs: Normal-red-blood-cells, RT: Room temperature, IC: Inhibitory concentration, FIC: Fractional inhibitory concentration, iCM: Incomplete-culturemedium, BSA: Bovin serum albumin, MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, DPPH: 2,2-diphenyl-1- picrylhydrazy, BHT: Butylatedhydroxyl-toleuen, PSA: Polar surface area, ClogP: Log partition coefficient (octanol/water), GPCR: G-protein-coupled-receptors, DMSO: Dimethylsulphoxide, NaOH: Sodium hydroxide.

  11. Zakaria ZA, Mahmood ND, Omar MH, Taher M, Basir R
    Pharm Biol, 2019 Dec;57(1):335-344.
    PMID: 31068038 DOI: 10.1080/13880209.2019.1606836
    CONTEXT: Muntingia calabura L. (Muntingiaceae) exerts antioxidant and anti-inflammatory activities, thus, it might be a good hepatoprotective agent.

    OBJECTIVE: This study investigates the effect of methanol extract of M. calabura leaves (MMCL) on hepatic antioxidant and anti-inflammatory activities in CCl4-induced hepatotoxic rat.

    MATERIALS AND METHODS: Sprague Dawley rats (n = 6) were treated (p.o.) with 10% DMSO (Groups 1 and 2), 50 mg/kg N-acetylcysteine (Group 3) or, 50, 250, or 500 mg/kg MMCL (Groups 4-6) for 7 consecutive days followed by pretreatment (i.p.) with vehicle (Group 1) or 50% CCl4 in olive oil (v/v) (Groups 2-6) on day 7th. Plasma liver enzymes and hepatic antioxidant enzymes and pro-inflammatory cytokines concentrations were measured while liver histopathology was examined.

    RESULTS: MMCL, at 500 mg/kg, significantly (p 

  12. Soo KM, Khalid B, Ching SM, Tham CL, Basir R, Chee HY
    PeerJ, 2017;5:e3589.
    PMID: 28929009 DOI: 10.7717/peerj.3589
    BACKGROUND: Dengue viral infection is an acute infection that has the potential to have severe complications as its major sequela. Currently, there is no routine laboratory biomarker with which to predict the severity of dengue infection or monitor the effectiveness of standard management. Hence, this meta-analysis compared biomarker levels between dengue fever (DF) and severe dengue infections (SDI) to identify potential biomarkers for SDI.

    METHODS: Data concerning levels of cytokines, chemokines, and other potential biomarkers of DF, dengue hemorrhagic fever, dengue shock syndrome, and severe dengue were obtained for patients of all ages and populations using the Scopus, PubMed, and Ovid search engines. The keywords "(IL1* or IL-1*) AND (dengue*)" were used and the same process was repeated for other potential biomarkers, according to Medical Subject Headings terms suggested by PubMed and Ovid. Meta-analysis of the mean difference in plasma or serum level of biomarkers between DF and SDI patients was performed, separated by different periods of time (days) since fever onset. Subgroup analyses comparing biomarker levels of healthy plasma and sera controls, biomarker levels of primary and secondary infection samples were also performed, as well as analyses of different levels of severity and biomarker levels upon infection by different dengue serotypes.

    RESULTS: Fifty-six studies of 53 biomarkers from 3,739 dengue cases (2,021 DF and 1,728 SDI) were included in this meta-analysis. Results showed that RANTES, IL-7, IL-8, IL-10, IL-18, TGF-b, and VEGFR2 levels were significantly different between DF and SDI. IL-8, IL-10, and IL-18 levels increased during SDI (95% CI, 18.1-253.2 pg/mL, 3-13 studies, n = 177-1,909, I(2) = 98.86%-99.75%). In contrast, RANTES, IL-7, TGF-b, and VEGFR2 showed a decrease in levels during SDI (95% CI, -3238.7 to -3.2 pg/mL, 1-3 studies, n = 95-418, I(2) = 97.59%-99.99%). Levels of these biomarkers were also found to correlate with the severity of the dengue infection, in comparison to healthy controls. Furthermore, the results showed that IL-7, IL-8, IL-10, TGF-b, and VEGFR2 display peak differences between DF and SDI during or before the critical phase (day 4-5) of SDI.

    DISCUSSION: This meta-analysis suggests that IL-7, IL-8, IL-10, TGF-b, and VEGFR2 may be used as potential early laboratory biomarkers in the diagnosis of SDI. This can be used to predict the severity of dengue infection and to monitor the effectiveness of treatment. Nevertheless, methodological and reporting limitations must be overcome in future research to minimize variables that affect the results and to confirm the findings.
  13. Nasiru Wana M, Mohd Moklas MA, Watanabe M, Zasmy Unyah N, Alhassan Abdullahi S, Ahmad Issa Alapid A, et al.
    Pathogens, 2020 Jul 16;9(7).
    PMID: 32708648 DOI: 10.3390/pathogens9070576
    The major route for Toxoplasma gondii (T. gondii) infection is through the ingestion of foods contaminated with oocyst from cat faeces. The microscopic detection of T. gondii oocysts in cat faeces is challenging, which contributes to the failure of detecting or differentiating it from other related coccidian parasites. This study aims to detect T. gondii oocysts in cat faeces using two multicopy-target PCR assays and to evaluate their genetic diversity. Cat faecal (200) samples were collected from pet cats (PCs; 100) and free-roaming cats (FRCs; 100) within Klang Valley, Malaysia, and screened for coccidian oocysts by microscopy using Sheather's sucrose floatation. PCR assays were performed on each faecal sample, targeting a B1 gene and a repetitive element (REP) gene to confirm T. gondii oocysts. Additionally, the PCR amplicons from the REP gene were sequenced to further confirm T. gondii-positive samples for phylogenetic analysis. Microscopy detected 7/200 (3.5%) T. gondii-like oocysts, while both the B1 gene and the REP gene detected 17/200 (8.5%) samples positive for T. gondii. All samples that were microscopically positive for T. gondii-like oocysts were also shown to be positive by both B1 and REP genes. The BLAST results sequenced for 16/200 (8.0%) PCR-positive T. gondii samples revealed homology and genetic heterogeneity with T. gondii strains in the GenBank, except for only one positive sample that did not show a result. There was almost perfect agreement (k = 0.145) between the two PCR assays targeting the B1 gene and the REP gene. This is the first report on microscopic, molecular detection and genetic diversity of T. gondii from cat faecal samples in Malaysia. In addition, the sensitivities of either the B1 gene or REP gene multicopy-target PCR assays are suitable for the accurate detection of T. gondii from cat faeces.
  14. Lee TY, Farah N, Chin VK, Lim CW, Chong PP, Basir R, et al.
    Nutr Res, 2023 Nov;119:1-20.
    PMID: 37708600 DOI: 10.1016/j.nutres.2023.08.010
    Riboflavin is a precursor of the essential coenzymes flavin mononucleotide and flavin adenine dinucleotide. Both possess antioxidant properties and are involved in oxidation-reduction reactions, which have a significant impact on energy metabolism. Also, the coenzymes participate in metabolism of pyridoxine, niacin, folate, and iron. Humans must obtain riboflavin through their daily diet because of the lack of programmed enzymatic machineries for de novo riboflavin synthesis. Because of its physiological nature and fast elimination from the human body when in excess, riboflavin consumed is unlikely to induce any negative effects or develop toxicity in humans. The use of riboflavin in pharmaceutical and clinical contexts has been previously explored, including for preventing and treating oxidative stress and reperfusion oxidative damage, creating synergistic compounds to mitigate colorectal cancer, modulating blood pressure, improving diabetes mellitus comorbidities, as well as neuroprotective agents and potent photosensitizer in killing bloodborne pathogens. Thus, the goal of this review is to provide a comprehensive understanding of riboflavin's biological applications in medicine, key considerations of riboflavin safety and toxicity, and a brief overview on the nanoencapsulation of riboflavin for various functions including the treatment of a range of diseases, photodynamic therapy, and cellular imaging.
  15. Suliman NA, Taib CNM, Moklas MAM, Basir R
    Neurotox Res, 2018 02;33(2):402-411.
    PMID: 28933048 DOI: 10.1007/s12640-017-9806-x
    Neurogenesis is influenced by various external factors such as enriched environments. Some researchers had postulated that neurogenesis has contributed to the hippocampal learning and memory. This project was designed to observe the effect of Delta-9-tetrahydrocannabinol (∆9-THC) in cognitive performance that influenced by the neurogenesis. Different doses of ∆9-THC were used for observing the neurogenesis mechanism occurs in the hippocampus of rats. The brains were stained with antibodies, namely BrdU, glial fibrillary acidic protein (GFAP), nestin, doublecortin (DCX) and class III β-tubulin (TuJ-1). The cognitive test was used novel-object discrimination test (NOD) while the proteins involved, DCX and brain-derived neurotrophic factor (BDNF), were measured. Throughout this study, ∆9-THC enhanced the markers involved in all stages of neurogenesis mechanism. Simultaneously, the cognitive behaviour of rat also showed improvement in learning and memory functions observed in behavioural test and molecular perspective. Administration of ∆9-THC was observed to enhance the neurogenesis in the brain, especially in hippocampus thus improved the cognitive function of rats.
  16. Hassan H, Bello RO, Adam SK, Alias E, Meor Mohd Affandi MMR, Shamsuddin AF, et al.
    Nanomaterials (Basel), 2020 Sep 09;10(9).
    PMID: 32916823 DOI: 10.3390/nano10091785
    Acyclovir is an antiviral drug used for the treatment of herpes simplex virus infection. Its oral bioavailability is low; therefore, frequent and high doses are prescribed for optimum therapeutic efficacy. Moreover, the current therapeutic regimen of acyclovir is associated with unwarranted adverse effects, hence prompting the need for a suitable drug carrier to overcome these limitations. This study aimed to develop solid lipid nanoparticles (SLNs) as acyclovir carriers and evaluate their in vivo pharmacokinetic parameters to prove the study hypothesis. During the SLN development process, response surface methodology was exploited to optimize the composition of solid lipid and surfactant. Optimum combination of Biogapress Vegetal 297 ATO and Tween 80 was found essential to produce SLNs of 134 nm. The oral bioavailability study showed that acyclovir-loaded SLNs possessed superior oral bioavailability when compared with the commercial acyclovir suspension. The plasma concentration of acyclovir-loaded SLNs was four-fold higher than the commercial suspension. Thus, this investigation presented promising results that the method developed for encapsulation of acyclovir offers potential as an alternative pathway to enhance the drug's bioavailability. In conclusion, this study exhibited the feasibility of SLNs as an oral delivery vehicle for acyclovir and therefore represents a new promising therapeutic concept of acyclovir treatment via a nanoparticulate drug delivery system.
  17. Yam MF, Lim V, Salman IM, Ameer OZ, Ang LF, Rosidah N, et al.
    Molecules, 2010 Jun 21;15(6):4452-66.
    PMID: 20657453 DOI: 10.3390/molecules15064452
    The aim of the present study was to verify the anti-inflammatory activity of Orthosiphon stamineus leaf extracts and to identify the active compound(s) contributing to its anti-inflammatory activity using a developed HPLC method. Active chloroform extract of O. stamineus was fractionated into three fractions using a dry flash column chromatography method. These three fractions were investigated for anti-peritoneal capillary permeability, in vitro nitric oxide scavenging activity, anti-inflammatory and nitric oxide (NO) inhibition using carrageenan-induced hind paw edema method. The flavonoid rich chloroform extract fraction (CF2) [containing sinensetin (2.86% w/w), eupatorin (5.05% w/w) and 3'-hydroxy-5,6,7,4'-tetramethoxyflavone (1.101% w/w)], significantly reduced rat hind paw edema, NO and decreased dye leakage to peritoneal cavity at p < 0.05. IC(50) of in vitro NO scavenging of CF2 was 0.3 mg/mL. These results suggest that the anti-inflammatory properties of these CF2 may possibly be due to the presence of flavonoid compounds capable of affecting the NO pathway.
  18. Hassan H, Adam SK, Alias E, Meor Mohd Affandi MMR, Shamsuddin AF, Basir R
    Molecules, 2021 Sep 07;26(18).
    PMID: 34576904 DOI: 10.3390/molecules26185432
    Treatment of herpes simplex infection requires high and frequent doses of oral acyclovir to attain its maximum therapeutic effect. The current therapeutic regimen of acyclovir is known to cause unwarranted dose-related adverse effects, including acute kidney injury. For this reason, a suitable delivery system for acyclovir was developed to improve the pharmacokinetic limitations and ultimately administer the drug at a lower dose and/or less frequently. In this study, solid lipid nanoparticles were designed to improve the oral bioavailability of acyclovir. The central composite design was applied to investigate the influence of the materials on the physicochemical properties of the solid lipid nanoparticles, and the optimized formulation was further characterized. Solid lipid nanoparticles formulated from Compritol 888 ATO resulted in a particle size of 108.67 ± 1.03 nm with an entrapment efficiency of 91.05 ± 0.75%. The analyses showed that the optimum combination of surfactant and solid lipid produced solid lipid nanoparticles of good quality with controlled release property and was stable at refrigerated and room temperature for at least 3 months. A five-fold increase in oral bioavailability of acyclovir-loaded solid lipid nanoparticles was observed in rats compared to commercial acyclovir suspension. This study has presented promising results that solid lipid nanoparticles could potentially be used as an oral drug delivery vehicle for acyclovir due to their excellent properties.
  19. Abdullahi SA, Unyah NZ, Nordin N, Basir R, Nasir WM, Alapid AA, et al.
    Mini Rev Med Chem, 2020;20(9):739-753.
    PMID: 31660810 DOI: 10.2174/1389557519666191029105736
    Identification of drug target in protozoan T. gondii is an important step in the development of chemotherapeutic agents. Likewise, exploring phytochemical compounds effective against the parasite can lead to the development of new drug agent that can be useful for prophylaxis and treatment of toxoplasmosis. In this review, we searched for the relevant literature on the herbs that were tested against T. gondii either in vitro or in vivo, as well as different phytochemicals and their potential activities on T. gondii. Potential activities of major phytochemicals, such as alkaloid, flavonoid, terpenoids and tannins on various target sites on T. gondii as well as other related parasites was discussed. It is believed that the phytochemicals from natural sources are potential drug candidates for the treatment of toxoplasmosis with little or no toxicity to humans.
  20. Alapid AAI, Abd Majid R, Ibraheem ZO, Mediani A, Ismail IS, Unyah NZ, et al.
    Metabolites, 2021 Jul 28;11(8).
    PMID: 34436427 DOI: 10.3390/metabo11080486
    Andrographolide (AG) has been shown to have several medicinal and pharmaceutical effects, such as antimicrobial, anti-inflammatory, antioxidant, anti-diabetic, and anti-malarial activities. Moreover, studies to assess the pharmacological effect of AG on the metabolic changes of uninfected red blood cells (uRBCs) have not yet been investigated. This study aims to evaluate the pharmacological effects of AG compared to chloroquine (CQ) on the metabolic variations of uRBCs in vitro using a proton nuclear magnetic resonance (1H-NMR)-based metabolomics approach coupled with multivariate data analysis (MVDA). Forty-one metabolites were successfully identified by 1H-NMR. The results of the unsupervised data analysis principal component analysis (PCA) showed ideal differentiation between AG and CQ. PC1 and PC2 accounted for 71.4% and 17.7% of the explained variation, respectively, with a total variance of 89.10%. Based on S-plot and VIP values, a total of 28 and 32 metabolites were identified as biomarkers in uRBCs-AG and uRBCs-CQ, respectively. In uRBCs treated with AG, ten metabolic pathways were determined to be disturbed, including riboflavin metabolism, d-glutamate and d-glutamine metabolism, phenylalanine metabolism, glutathione metabolism, proline and arginine metabolism, arginine biosynthesis, citrate cycle, glycolysis/gluconeogenesis, and pyruvate metabolism as well as alanine, aspartate, and glutamate metabolism. In contrast, in CQ-treated uRBCs, nine affected metabolic pathways were determined, which involved the same metabolic pathways for uRBCs-AG, except for glutathione metabolism. These findings suggest an evident relationship between AG and CQ associated with metabolic changes in intact RBCs after being exposed to the treatment. The metabolomics results could allow useful comprehensive insights into the underlying mechanism of the action of AG and CQ on red blood cells. Consequently, the 1H-NMR-based metabolomics approach was successfully utilized to identify the pharmacological effects of AG and CQ on the metabolic variations of uRBCs.
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