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Fulltext A Review on the Prevalence of Toxoplasma gondii in Humans and Animals Reported in Malaysia from 2008-2018

Nasiru Wana M, Mohd Moklas MA, Watanabe M, Nordin N, Zasmy Unyah N, Alhassan Abdullahi S, et al.

Int J Environ Res Public Health, 2020 07 03;17(13).
PMID: 32635389 DOI: 10.3390/ijerph17134809

Toxoplasmosis is a disease caused by the protozoan parasite Toxoplasma gondii (T. gondii). Human toxoplasmosis seroprevalence in Malaysia has increased since it was first reported in 1973 as shown in previous reviews of 1991 and 2007. However, over a decade since the last review, comprehensive data on toxoplasmosis in Malaysia is lacking. This work aimed at reviewing articles on toxoplasmosis research in Malaysia in order to identify the research gaps, create public awareness, and efforts made so far and proffer management options on the disease. The present review examines the available published research articles from 2008 to 2018 related to toxoplasmosis research conducted in Malaysia. The articles reviewed were retrieved from nine credible databases such as Web of Science, Google Scholar, ScienceDirect, PubMed, Scopus, Springer, Wiley online library, Ovid, and Cochrane using the keywords; Malaysia, toxoplasmosis, Toxoplasma gondii, toxoplasma encephalitis, seroprevalence, human immunodeficiency virus (HIV) patients, pregnant women, genotype strain, anti-toxoplasma antibodies, felines, and vaccine. The data highlighted seropositive cases from healthy community members in Pangkor Island (59.7%) and among migrant workers (57.4%) at alarming rates, as well as 42.5% in pregnant women. Data on animal seroprevalence were limited and there was no information on cats as the definitive host. Genetic characterization of Toxoplasma gondii from HIV patients; pregnant women, and domestic cats is lacking. This present review on toxoplasmosis is beneficial to researchers, health workers, animal health professionals, and policymakers. Therefore, attention is required to educate and enlighten health workers and the general public about the risk factors associated with T. gondii infection in Malaysia.
Anatomical variations of median nerve formation, distribution and possible communication with other nerves in preserved human cadavers

Mat Taib CN, Hassan SN, Esa N, Mohd Moklas MA, San AA

Folia Morphol (Warsz), 2016 09 26;76(1):38-43.
PMID: 27665953 DOI: 10.5603/FM.a2016.0045

Formation, distribution and possible communication of the median nerve are essential to know in treatment and surgeries of various conditions of injuries e.g. repair or reconstruction of the median nerve post traumatic accident. In the present study, 44 upper limbs were dissected. Root forming the median nerve, the median nerve in relation with the axillary artery and communication of the median nerve with other nerves were noted.
Fulltext Anticancer Molecular Mechanism of Protocatechuic Acid Loaded on Folate Coated Functionalized Graphene Oxide Nanocomposite Delivery System in Human Hepatocellular Carcinoma

Buskaran K, Bullo S, Hussein MZ, Masarudin MJ, Mohd Moklas MA, Fakurazi S

Materials (Basel), 2021 Feb 09;14(4).
PMID: 33572054 DOI: 10.3390/ma14040817

Liver cancer is listed as the fifth-ranked cancer, responsible for 9.1% of all cancer deaths globally due to its assertive nature and poor survival rate. To overcome this obstacle, efforts have been made to ensure effective cancer therapy via nanotechnology utilization. Recent studies have shown that functionalized graphene oxide (GO)-loaded protocatechuic acid has shown some anticancer activities in both passive and active targeting. The nanocomposites' physicochemical characterizations were conducted. A lactate dehydrogenase experiment was conducted to estimate the severity of cell damage. Subsequently, a clonogenic assay was carried out to examine the colony-forming ability during long-term exposure of the nanocomposites. The Annexin V/ propidium iodide analysis showed that nanocomposites induced late apoptosis in HepG2 cells. Following the intervention of nanocomposites, cell cycle arrest was ascertained at G2/M phase. There was depolarization of mitochondrial membrane potential and an upregulation of reactive oxygen species when HepG2 cells were induced by nanocomposites. Finally, the proteomic profiling array and quantitative reverse transcription polymerase chain reaction revealed the expression of pro-apoptotic and anti-apoptotic proteins induced by graphene oxide conjugated PEG loaded with protocatechuic acid drug folic acid coated nanocomposite (GOP-PCA-FA) in HepG2 cells. In conclusion, GOP-PCA-FA nanocomposites treated HepG2 cells exhibited significant anticancer activities with less toxicity compared to pristine protocatechuic acid and GOP-PCA nanocomposites, due to the utilization of a folic acid-targeting nanodrug delivery system.
Fulltext Antidepressant-Like Properties of Fish Oil on Postpartum Depression-Like Rats Model: Involvement of Serotonergic System

Abdul Aziz NU, Chiroma SM, Mohd Moklas MA, Adenan MI, Ismail A, Hidayat Baharuldin MT

Brain Sci, 2020 Oct 13;10(10).
PMID: 33066310 DOI: 10.3390/brainsci10100733

Pathophysiology of postpartum depression (PPD) has been associated with many factors, such as neuroendocrine, neuroinflammation and neurotransmitter changes. Fish oil (FO) improves PPD both in humans and animals. However, little is known with regards to its pharmacology on a PPD-like rat model. Hence, the current study aimed at investigating the effects of FO on a PPD-like rat model. Female rats were induced with PPD-like symptoms and then randomly divided into six groups (n = 6) for two experimental protocols. Protocol 1 consisted of PPD-like rats (2 mL distilled water), PPD-like + FO (9 g/kg/d) and PPD-like + Fluoxetine (FLX) (15 mg/kg/d) groups of rats, whereas Protocol 2 consisted of PPD-like rats (2 mL distilled water) + PCPA (p-chlorophenylalanine) 150 mg/kg, PPD-like + FO (9 g/kg/d) + PCPA 150 mg/kg and PPD-like + FLX (15 mg/d) + PCPA 150 mg/kg groups of rats, respectively. All treatments were administered orally for 10 days postpartum, except PCPA, which was given intraperitoneally. Prior to euthanasia, the antidepressant-like effect of the FO was evaluated using the forced swimming test (FST) and open field test (OFT) on day 10 postpartum. Biochemical analysis of serotonin, serotonin metabolite and serotonin turnover from their prefrontal cortex and hippocampus were also measured. The results showed that FO decreased immobility time and increased swimming time significantly, but not climbing time in FST. Further, it also decreased serotonin metabolite and turnover significantly in the hippocampus of the PPD-like rats. In contrast, administration with PCPA reversed all the outcomes. The antidepressant-like effects of FO were found to be similar with that of FLX. Thus, it can be concluded that FO exerts its antidepressant-like effects in PPD-like rats through modulation of serotonergic system.
Fulltext Antioxidant Properties of Crude Extract, Partition Extract, and Fermented Medium of Dendrobium sabin Flower

Abu F, Mat Taib CN, Mohd Moklas MA, Mohd Akhir S

Evid Based Complement Alternat Med, 2017;2017:2907219.
PMID: 28761496 DOI: 10.1155/2017/2907219

Antioxidant properties of crude extract, partition extract, and fermented medium from Dendrobium sabin (DS) flower were investigated. The oven-dried DS flower was extracted using 100% methanol (w/v), 100% ethanol (w/v), and 100% water (w/v). The 100% methanolic crude extract showed the highest total phenolic content (40.33 ± mg GAE/g extract) and the best antioxidant properties as shown by DPPH, ABTS, and FRAP assays. A correlation relationship between antioxidant activity and total phenolic content showed that phenolic compounds were the dominant antioxidant components in this flower extract. The microbial fermentation on DS flower medium showed a potential in increasing the phenolic content and DPPH scavenging activity. The TPC of final fermented medium showed approximately 18% increment, while the DPPH of fermented medium increased significantly to approximately 80% at the end of the fermentation. Dendrobium sabin (DS) flower showed very good potential properties of antioxidant in crude extract and partition extract as well as better antioxidant activity in the flower fermented medium.
Fulltext Antioxidant and anti-inflammatory properties of Erythroxylum cuneatum alkaloid leaf extract

Li LS, Chiroma SM, Hashim T, Adam SK, Mohd Moklas MA, Yusuf Z, et al.

Heliyon, 2020 Jun;6(6):e04141.
PMID: 32637674 DOI: 10.1016/j.heliyon.2020.e04141

Erythroxylum cuneatum (E. cuneatum) which belongs to Erythroxylaceae family is a tropical flowering plant from the genus of Erythroxylum. It is used in Malaysia and Thailand's traditional medicines, yet there is limited scientific reports on its medicinal value. This study aimed at exploring the antioxidative and anti-inflammatory properties of E. cuneatum alkaloid leaf extract. The alkaloid extract was obtained through Soxhlet heat extraction method, while the antioxidantive properties were assessed via 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging, ferric reducing antioxidant power (FRAP) and xanthine oxidase inhibition (XOI) assays. Further, anti-inflammatory property of the extract was evaluated on rat's model of carrageenan induced paw model of edema via physical measurements and histology. The extract exhibited antioxidant activity with an EC50 value of 1482 μg/ml in the DPPH radical scavenging assay, an EC1 value of 2191 μg/ml in the FRAP assay and 10.15 ± 6.20% in the XOI assay. Rats pretreated with the extract have shown dose dependent decrease in paw edema when compared to non-treated group of rats. The highest dose (50 mg/kg) of extract exhibited similar effects to aspirin in terms of reducing paw thickness, leucocytes infiltration and disruption of collagen. In conclusion, the E. cuneatum alkaloid leaf extract possesses both antioxidative and anti-inflammatory properties suggesting its potentials for future development of antioxidant and anti-inflammatory drugs.
Barrier protective effect of asiatic acid in TNF-α-induced activation of human aortic endothelial cells

Fong LY, Ng CT, Cheok ZL, Mohd Moklas MA, Hakim MN, Ahmad Z

Phytomedicine, 2016 Feb 15;23(2):191-9.
PMID: 26926181 DOI: 10.1016/j.phymed.2015.11.019

Endothelial cell activation is characterized by increased endothelial permeability and increased expression of cell adhesion molecules (CAMs). This allows monocyte adherence and migration across the endothelium to occur and thereby initiates atherogenesis process. Asiatic acid is a major triterpene isolated from Centella asiatica (L.) Urban and has been shown to possess anti-oxidant, anti-hyperlipidemia and anti-inflammatory activities.
Fulltext Curcumin-loaded cockle shell-derived calcium carbonate nanoparticles: A novel strategy for the treatment of lead-induced hepato-renal toxicity in rats

Mailafiya MM, Abubakar K, Chiroma SM, Danmaigoro A, Rahim EBA, Mohd Moklas MA, et al.

Saudi J Biol Sci, 2020 Jun;27(6):1538-1552.
PMID: 32489292 DOI: 10.1016/j.sjbs.2020.03.009

Lead (Pb) toxicity affects the hepatic and renal systems resulting to homeostasis imbalance. Curcumin is a strong antioxidant but has restrained clinical applications due to its poor bioavailability. Nanomedicine showed promising potentials in drug delivery and has brought forth the use of cockle shell-derived aragonite calcium carbonate nanoparticles (CSCaCO3NP) to enhance the effectiveness and targeted delivery of curcumin (Cur). Thus, this study aimed at evaluating the therapeutic effect of curcumin-loaded CSCaCO3NP (Cur- CSCaCO3NP) on lead-induced hepato-renal toxicity in rats. Thirty-six male adults Sprague-Dawley rats were randomly assigned into five groups. All groups contained six rats each except for group A, which contained 12 rats. All rats apart from the rats in group A (control) were orally administered a flat dose of 50 mg/kg of lead for four weeks. Six rats from group A and B were euthanized after four weeks of lead induction. Oral administration of curcumin (100 mg/kg) for group C and Cur-CSCaCO3NP (50 and 100 mg/kg) for groups D and E respectively, commenced immediately after 4 weeks of lead induction which lasted for 4 weeks. All rats were euthanized at the 8th week of the experiment. Further, biochemical, histological and hematological analysis were performed. The findings revealed a biochemical, hematological and histological changes in lead-induced rats. However, treatments with the Cur-CSCaCO3NP and free curcumin reversed the aforementioned changes. Although, Cur-CSCaCO3NP presented better therapeutic effects on lead-induced toxicity in rats when compared to free curcumin as there was significant improvements in hematological, biochemical and histological changes which is parallel with attenuation of oxidative stress. The findings of the current study hold great prospects for Cur-CSCaCO3NP as a novel approach for effective oral treatment of lead-induced hepato-renal impairments.
Fulltext Establishing Natural Nootropics: Recent Molecular Enhancement Influenced by Natural Nootropic

Suliman NA, Mat Taib CN, Mohd Moklas MA, Adenan MI, Hidayat Baharuldin MT, Basir R

Evid Based Complement Alternat Med, 2016;2016:4391375.
PMID: 27656235 DOI: 10.1155/2016/4391375

Nootropics or smart drugs are well-known compounds or supplements that enhance the cognitive performance. They work by increasing the mental function such as memory, creativity, motivation, and attention. Recent researches were focused on establishing a new potential nootropic derived from synthetic and natural products. The influence of nootropic in the brain has been studied widely. The nootropic affects the brain performances through number of mechanisms or pathways, for example, dopaminergic pathway. Previous researches have reported the influence of nootropics on treating memory disorders, such as Alzheimer's, Parkinson's, and Huntington's diseases. Those disorders are observed to impair the same pathways of the nootropics. Thus, recent established nootropics are designed sensitively and effectively towards the pathways. Natural nootropics such as Ginkgo biloba have been widely studied to support the beneficial effects of the compounds. Present review is concentrated on the main pathways, namely, dopaminergic and cholinergic system, and the involvement of amyloid precursor protein and secondary messenger in improving the cognitive performance.
Fulltext Graphene Oxide⁻PEG⁻Protocatechuic Acid Nanocomposite Formulation with Improved Anticancer Properties

Saifullah B, Buskaran K, Shaikh RB, Barahuie F, Fakurazi S, Mohd Moklas MA, et al.

Nanomaterials (Basel), 2018 Oct 11;8(10).
PMID: 30314340 DOI: 10.3390/nano8100820

The treatment of cancer through chemotherapy is limited by its toxicity to healthy tissues and organs, and its inability to target the cancer site. In this study, we have designed an anticancer nanocomposite delivery system for protocatechuic acid (PCA) using graphene oxide⁻polyethylene glycol as the nanocarrier, and coated with folic acid (GO⁻PEG⁻PCA⁻FA) for targeting the cancer cells. The designed anticancer delivery system was found to show much better anticancer activity than the free drug PCA against liver cancer HEP-G2 cells and human colon cancer HT-29 cells; at same time, it was found to be less toxic to normal fibroblast 3T3 cells. The folate-coated anticancer delivery system was found to show better activity then the free drug and the uncoated anticancer delivery system. The in vitro release of the PCA was found to be sustained in human physiological pHs, i.e., blood pH 7.4 and intracellular lysosomal pH 4.8. These in vitro findings are highly encouraging for further in vivo evaluation studies.
Fulltext Inhibitory Activity of Ficus deltoidea var. trengganuensis Aqueous Extract on Lipopolysaccharide-Induced TNF-α Production from Microglia

Wang H, Vidyadaran S, Mohd Moklas MA, Baharuldin MTH

Evid Based Complement Alternat Med, 2017;2017:2623163.
PMID: 29358962 DOI: 10.1155/2017/2623163

Objective: To explore the effect of Ficus deltoidea (FD) aqueous extracts on the release of tumor necrosis factor-α (TNF-α), the expression of CD40, and the morphology of microglial cells in lipopolysaccharide- (LPS-) activated BV2 cells.
Methods: The cytotoxicity of FD extract was assessed by MTS solution. BV2 cells were divided into 5 experimental groups, intervened, respectively, by FD (4 mg/mL) and LPS + FD (0, 1, 2, and 4 mg/mL). Besides, a blank control group was set up without any intervention. TNF-α release was assessed by enzyme linked immunosorbent assay (ELISA). The expression of CD40 was examined by flow cytometry. Immunocytochemical staining was used to show the morphology of BV2 cells.
Results: FD extract of different concentrations (1, 2, and 4 mg/mL) had no significant toxic effects on the BV2 cells. FD suppressed the activation of microglia in morphology and reduced TNF-α production and expression of CD40 induced by LPS.
Conclusion: FD extract has a therapeutic potential against neuroinflammatory diseases.
Interleukin-18 Antagonism Improved Histopathological Conditions of Malaria Infection in Mice

Jabbarzare M, Chin VK, Talib H, Yam MF, Adam SK, Hassan H, et al.

Iran J Parasitol, 2015 Jul-Sep;10(3):389-401.
PMID: 26622294

Interleukin 18 (IL-18) exerts pleiotropic roles in many inflammatory-related diseases including parasitic infection. Previous studies have demonstrated the promising therapeutic potential of modulating IL-18 bioactivity in various pathological conditions. However, its involvement during malaria infection has yet to be established. In this study, we demonstrated the effect of modulating IL-18 on the histopathological conditions of malaria infected mice.
Menhaden fish oil attenuates postpartum depression in rat model via inhibition of NLRP3-inflammasome driven inflammatory pathway

Abdul Aziz NU, Chiroma SM, Mohd Moklas MA, Adenan MI, Ismail A, Basir R, et al.

J Tradit Complement Med, 2021 Sep;11(5):419-426.
PMID: 34522636 DOI: 10.1016/j.jtcme.2021.02.007

Background and aim: Postpartum depression (PPD) is a familiar problem which is associated with about 10-20% of women after child delivery. Fish oil (FO) has a therapeutic potentials to many diseases including mood disorders. However, there is paucity of data on the effects of FO supplementation on PPD rat model. Hence, this study aimed at investigating the potentials of FO in ameliorating depressive-like behaviors in PPD rat by evaluating the involvement of NLRP3-inflammasome.
Experimental procedure: Thirty six virgin adult female rats (n = 6) were randomly divided into six groups; Group 1-3 were normal control (NC), Sham (SHAM) and ovariectomized group (OVX) respectively whereas group 4-6 were PPD rats forced-fed once daily with distilled water (PPD), fish oil (PPD + FO; 9 g/kg) and Fluoxetine (PPD + FLX; 15 mg/kg) respectively from postpartum day 1 and continued for 10 consecutive days. Rats behaviors were evaluated on postpartum day 10 through open field test (OFT) and forced swimming test (FST), followed by biochemical analysis of NLRP3 inflammasome proteins pathway in their brain and determination of neutrophil to lymphocyte ratio (NLR).
Results: PPD-induced rats exhibited high immobility and low swimming time in FST with increased inflammatory status; NLR, IL-1β and NFкB/NLRP3/caspase-1 activity in their hippocampus. However, administration of FO or fluoxetine reversed the aforementioned abnormalities.
Conclusion: In conclusion, 10 days supplementation with FO ameliorated the depressive-like behaviors in PPD rats by targeting the NFкB/NLRP3/caspase-1/IL-1β activity. This has shed light on the potential of NLRP3 as a therapeutic target in treatment of PPD in rats.
Fulltext Molecular Detection and Genetic Diversity of Toxoplasma gondii Oocysts in Cat Faeces from Klang Valley, Malaysia, Using B1 and REP Genes in 2018

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.
Fulltext Morphological Changes and Cellular Uptake of Functionalized Graphene Oxide Loaded with Protocatechuic Acid and Folic Acid in Hepatocellular Carcinoma Cancer Cell

Buskaran K, Hussein MZ, Mohd Moklas MA, Fakurazi S

Int J Mol Sci, 2020 Aug 16;21(16).
PMID: 32824281 DOI: 10.3390/ijms21165874

The development of nanocomposites has swiftly changed the horizon of drug delivery systems in defining a new platform. Major understanding of the interaction of nanocomposites with cells and how the interaction influences intracellular uptake is an important aspect to study in order to ensure successful utilisation of the nanocomposites. Studies have suggested that the nanocomposites' ability to permeate into biological cells is attributable to their well-defined physicochemical properties with nanoscale size, which is relevant to the nanoscale components of biology and cellular organelles. The functionalized graphene oxide coated with polyethylene glycol, loaded with protocatechuic acid and folic acid (GOP-PCA-FA) nanocomposite intracellular uptake was analysed using transmission electron microscope. The accumulation of fluorescent-labelled nanocomposites in the HepG2 cell was also analysed using a fluorescent microscope. In vitro cellular uptake showed that there was uptake of the drug from 24 h into the cells and the release study using fluorescently tagged nanocomposite demonstrated that release and accumulation were observed at 24 h and 48 h. Moreover, the migration ability of tumor cells is a key step in tumor progression which was observed 48 h after treatment. The GOP serves as a potential nanocarrier system which is capable of improving the therapeutic efficacy of drugs and biomolecules in medical as well as pharmaceutical applications through the enhanced intracellular release and accumulation of the encapsulated drugs. Nonetheless, it is essential to analyse the translocation of our newly developed GOP-PCA-FA, and its efficiency for drug delivery, effective cellular uptake, and abundant intracellular accumulation would be compromised by possible untoward side effects.
Fulltext Protective effect of Centella asiatica against D-galactose and aluminium chloride induced rats: Behavioral and ultrastructural approaches

Chiroma SM, Hidayat Baharuldin MT, Mat Taib CN, Amom Z, Jagadeesan S, Adenan MI, et al.

Biomed Pharmacother, 2019 Jan;109:853-864.
PMID: 30551539 DOI: 10.1016/j.biopha.2018.10.111

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder and the commonest cause of dementia among the aged people. D-galactose (D-gal) is a senescence agent, while aluminium is a known neurotoxin linked to pathogenesis of AD. The combined administration of rats with d-gal and aluminium chloride (AlCl3) is considered to be an easy and a cheap method to obtain an animal model of AD. The plant Centella asiatica (CA) is reported to exert neuroprotective effects both in vitro and in vivo. Therefore, this study explored the protective effects of CA on cognition and brain ultrastructure in d-gal and AlCl3 induced rats.
MATERIALS AND METHODS: Rats were exposed to d-gal 60 mg/kg/b.wt/day + AlCl3 200 mg/kg/b.wt/day and CA (200, 400 and 800 mg/kg/b.wt/day) and 1 mg/kg/b.wt/day of donepezil for 70 days. Different cognitive paradigms viz. T maze spontaneous alternation, modified elevated plus maze and novel object recognition test, were used to evaluate full lesions of the hippocampus, spatial learning and memory and non-spatial learning and memory respectively. Nissl's staining was used to determine the survival of hippocampus CA1 pyramidal cells, while transmission electron microscopy was used to check the ultrastructural changes.
RESULTS: The results revealed that d-gal and AlCl3 could significantly impair behavior and cognitive functions, besides causing damage to the hippocampal CA1 pyramidal neurons in rats. In addition, it also caused ultrastructural morphological alterations in rat hippocampus. Conversely, co-administration o;f CA, irrespective of the dosage used, alleviated the cognitive impairments and pathological changes in the rats comparable to donepezil.
CONCLUSION: In conclusion the results suggest that CA could protect cognitive impairments and morphological alterations caused by d-gal and AlCl3 toxicity in rats. Biochemical and molecular studies are ongoing to elucidate the probable pharmacodynamics of CA.
Regulatory role of the endocannabinoid system on glial cells toward cognitive function in Alzheimer's disease: A systematic review and meta-analysis of animal studies

Kamaruzzaman MA, Romli MH, Abas R, Vidyadaran S, Hidayat Baharuldin MT, Nasaruddin ML, et al.

Front Pharmacol, 2023;14:1053680.
PMID: 36959856 DOI: 10.3389/fphar.2023.1053680

Objective: Over the last decade, researchers have sought to develop novel medications against dementia. One potential agent under investigation is cannabinoids. This review systematically appraised and meta-analyzed published pre-clinical research on the mechanism of endocannabinoid system modulation in glial cells and their effects on cognitive function in animal models of Alzheimer's disease (AD). Methods: A systematic review complying with PRISMA guidelines was conducted. Six databases were searched: EBSCOHost, Scopus, PubMed, CINAHL, Cochrane, and Web of Science, using the keywords AD, cannabinoid, glial cells, and cognition. The methodological quality of each selected pre-clinical study was evaluated using the SYRCLE risk of bias tool. A random-effects model was applied to analyze the data and calculate the effect size, while I2 and p-values were used to assess heterogeneity. Results: The analysis included 26 original articles describing (1050 rodents) with AD-like symptoms. Rodents treated with cannabinoid agonists showed significant reductions in escape latency (standard mean difference [SMD] = -1.26; 95% confidence interval [CI]: -1.77 to -0.76, p < 0.00001) and ability to discriminate novel objects (SMD = 1.40; 95% CI: 1.04 to 1.76, p < 0.00001) compared to the control group. Furthermore, a significant decrease in Aβ plaques (SMD = -0.91; 95% CI: -1.55 to -0.27, p = 0.006) was observed in the endocannabinoid-treated group compared to the control group. Trends were observed toward neuroprotection, as represented by decreased levels of glial cell markers including glial fibrillary acid protein (SMD = -1.47; 95% CI: -2.56 to -0.38, p = 0.008) and Iba1 (SMD = -1.67; 95% CI: -2.56 to -0.79, p = 0.0002). Studies on the wild-type mice demonstrated significantly decreased levels of pro-inflammatory markers TNF-α, IL-1, and IL-6 (SMD = -2.28; 95% CI: -3.15 to -1.41, p = 0.00001). Despite the non-significant decrease in pro-inflammatory marker levels in transgenic mice (SMD = -0.47; 95% CI: -1.03 to 0.08, p = 0.09), the result favored the endocannabinoid-treated group over the control group. Conclusion: The revised data suggested that endocannabinoid stimulation promotes cognitive function via modulation of glial cells by decreasing pro-inflammatory markers in AD-like rodent models. Thus, cannabinoid agents may be required to modulate the downstream chain of effect to enhance cognitive stability against concurrent neuroinflammation in AD. Population-based studies and well-designed clinical trials are required to characterize the acceptability and real-world effectiveness of cannabinoid agents. Systematic Review Registration: [https://inplasy.com/inplasy-2022-8-0094/], identifier [Inplasy Protocol 3770].
Fulltext The Role of Piper sarmentosum Aqueous Extract as a Bone Protective Agent, a Histomorphometric Study

Mohamad Asri SF, Soelaiman IN, Mohd Moklas MA, Mohd Nor NH, Mohamad Zainal NH, Mohd Ramli ES

Int J Mol Sci, 2020 Oct 19;21(20).
PMID: 33086468 DOI: 10.3390/ijms21207715

Glucocorticoids are one of the causes of secondary osteoporosis. The aqueous extract of Piper sarmentosum contains flavonoids that possess antioxidant effects. In this study, we determined the effects of aqueous Piper sarmentosum leaf extract on structural, dynamic and static histomorphometric changes from osteoporotic bones of rats induced with glucocorticoids. Thirty-two Sprague-Dawley rats were divided equally into four groups-Sham control group given vehicles (intramuscular (IM) olive oil and oral normal saline); AC: Adrenalectomised (Adrx) control group given IM dexamethasone (DEX) (120 μg/kg/day) and vehicle (oral normal saline); AP: Adrx group administered IM DEX (120 μg/kg/day) and aqueous Piper sarmentosum leaf extract (125 mg/kg/day) orally; and AG: Adrx group administered IM DEX (120 μg/kg/day) and oral glycyrrhizic acid (GCA) (120 mg/kg/day). Histomorphometric measurements showed that the bone volume, trabecular thickness, trabecular number, osteoid and osteoblast surfaces, double-labelled trabecular surface, mineralizing surface and bone formation rate of rats given aqueous Piper sarmentosum leaf extract were significantly increased (p < 0.05), whereas the trabecular separation and osteoclast surface were significantly reduced (p < 0.05). This study suggests that aqueous Piper sarmentosum leaf extract was able to prevent bone loss in prolonged glucocorticoid therapy. Thus, Piper sarmentosum has the potential to be used as an alternative medicine against osteoporosis and osteoporotic fractures in patients undergoing long-term glucocorticoid therapy.
Fulltext Toxoplasma gondii induced cognitive impairment in rats via dysregulation of dopamine receptors and indoleamine 2,3 dioxygenase

Wana MN, Watanabe M, Chiroma SM, Unyah NZ, Abdullahi SA, Nordin S, et al.

Heliyon, 2023 Mar;9(3):e14370.
PMID: 36950587 DOI: 10.1016/j.heliyon.2023.e14370

Toxoplasma gondii (T. gondii) is a parasite capable of residing in the brain of their host which influences behaviour changes due to alterations in the neurotransmitters. Consequently, dopamine receptors (DRD) and indoleamine 2, 3 dioxygenase (IDO) dysregulation facilitate the progression of behaviour changes in a host as a response to infection. This study tested the effect of neurotransmitter changes as a result of T. gondii infection on rats cognitive impairment. The T. gondii strain of type I, II and III from Malaysia were previously identified by standard procedures. Sporulated oocysts each of type I, II and III were inoculated separately into three groups of Wistar rats (n = 9) respectively. Two separate control groups received either phosphate buffered saline (PBS) or MK-801 (dizocilpine). Behaviour changes were evaluated at nine weeks post infection in a square box, elevated plus maze and gene expression level of DRD and IDO compounds. The study revealed increased fatal feline attraction, reduced anxiety, decreased DRD and increased IDO gene expression in the T. gondii infected groups and MK-801 compared to the PBS control group. In conclusion, T. gondii infection alter the level of neurotransmitters in rat which cause cognitive impairment. This implies that all the T. gondii strain can cause behaviour changes if human were infected.
Fulltext Transient prenatal ruxolitinib treatment suppresses astrogenesis during development and improves learning and memory in adult mice

Lee HC, Hamzah H, Leong MP, Md Yusof H, Habib O, Zainal Abidin S, et al.

Sci Rep, 2021 Feb 15;11(1):3847.
PMID: 33589712 DOI: 10.1038/s41598-021-83222-z

Ruxolitinib is the first janus kinase 1 (JAK1) and JAK2 inhibitor that was approved by the United States Food and Drug Administration (FDA) agency for the treatment of myeloproliferative neoplasms. The drug targets the JAK/STAT signalling pathway, which is critical in regulating the gliogenesis process during nervous system development. In the study, we assessed the effect of non-maternal toxic dosages of ruxolitinib (0-30 mg/kg/day between E7.5-E20.5) on the brain of the developing mouse embryos. While the pregnant mice did not show any apparent adverse effects, the Gfap protein marker for glial cells and S100β mRNA marker for astrocytes were reduced in the postnatal day (P) 1.5 pups' brains. Gfap expression and Gfap+ cells were also suppressed in the differentiating neurospheres culture treated with ruxolitinib. Compared to the control group, adult mice treated with ruxolitinib prenatally showed no changes in motor coordination, locomotor function, and recognition memory. However, increased explorative behaviour within an open field and improved spatial learning and long-term memory retention were observed in the treated group. We demonstrated transplacental effects of ruxolitinib on astrogenesis, suggesting the potential use of ruxolitinib to revert pathological conditions caused by gliogenic-shift in early brain development such as Down and Noonan syndromes.

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