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Fulltext Celastrol: A Potential Natural Lead Molecule for New Drug Design, Development and Therapy for Memory Impairment

Amir Yusri MA, Sekar M, Wong LS, Gan SH, Ravi S, Subramaniyan V, et al.

Drug Des Devel Ther, 2023;17:1079-1096.
PMID: 37064431 DOI: 10.2147/DDDT.S389977

Celastrol is a naturally occurring chemical isolated from Tripterygium wilfordii Hook. f., root extracts widely known for their neuroprotective properties. In this review, we focus on the efficacy of celastrol in mitigating memory impairment (MI) in both in vivo and in vitro models. Scopus, PubMed and Web of Science databases were utilised to locate pertinent literatures that explore the effects of celastrol in the brain, including its pharmacokinetics, bioavailability, behavioral effects and some of the putative mechanisms of action on memory in many MI models. To date, preclinical studies strongly suggest that celastrol is highly effective in enhancing the cognitive performance of MI animal models, particularly in the memory domain, including spatial, recognition, retention and reference memories, via reduction in oxidative stress and attenuation of neuro-inflammation, among others. This review also emphasised the challenges and potential associated enhancement of medication delivery for MI treatment. Additionally, the potential structural alterations and derivatives of celastrol in enhancing its physicochemical and drug-likeness qualities are examined. The current review demonstrated that celastrol can improve cognitive performance and mitigate MI in several preclinical investigations, highlighting its potential as a natural lead molecule for the design and development of a novel neuroprotective medication.
Fulltext Bitter Gourd Honey Ameliorates Hepatic and Renal Diabetic Complications on Type 2 Diabetes Rat Models by Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Mechanisms

Arigela CS, Nelli G, Gan SH, Sirajudeen KNS, Krishnan K, Abdul Rahman N, et al.

Foods, 2021 Nov 20;10(11).
PMID: 34829154 DOI: 10.3390/foods10112872

Honey has several pharmacological effects, including anti-diabetic activity. However, the effectiveness of bitter gourd honey (BGH) in the treatment of diabetes mellitus (DM) is unknown. The aim of this study was to determine the antioxidant, anti-inflammatory, and anti-apoptotic properties of BGH on the kidney and liver of a streptozotocin-induced diabetes rat model.
METHODS: A single dose (nicotinamide 110 mg/kg, streptozotocin (STZ) 55 mg/kg, intraperitoneal (i.p.)) was used to induce DM in male rats. For 28 days, normal or diabetic rats were administered 1 g/kg/day and 2 g/kg/day of BGH orally. After the treatment, blood, liver, and kidney samples were collected and analysed for biochemical, histological, and molecular parameters. In addition, liquid chromatography-mass spectrometry (LC-MS) was used to identify the major bioactive components in BGH.
RESULTS: The administration of BGH to diabetic rats resulted in significant reductions in alanine transaminase (ALT),aspartate aminotransferase (AST), creatinine, and urea levels. Diabetic rats treated with BGH showed lesser pathophysiological alterations in the liver and kidney as compared to non-treated control rats. BGH-treated diabetic rats exhibited reduced levels of oxidative stress (MDA levels), inflammatory (MYD88, NFKB, p-NFKB, IKKβ), and apoptotic (caspase-3) markers, as well as higher levels of antioxidant enzymes (SOD, CAT, and GPx) in the liver and kidney. BGH contains many bioactive compounds that may have antioxidative stress, anti-inflammatory, and anti-apoptotic effects.
CONCLUSION: BGH protected the liver and kidney in diabetic rats by reducing oxidative stress, inflammation, and apoptosis-induced damage. As a result, BGH can be used as a potential therapy to ameliorate diabetic complications.
Therapeutic Suppression of Nonsense Mutation: An Emerging Target in Multiple Diseases and Thrombotic Disorders

Asiful Islam M, Alam F, Kamal MA, Gan SH, Wong KK, Sasongko TH

Curr Pharm Des, 2017;23(11):1598-1609.
PMID: 27875971 DOI: 10.2174/1381612823666161122142950

Nonsense mutations contribute to approximately 10-30% of the total human inherited diseases via disruption of protein translation. If any of the three termination codons (UGA, UAG and UAA) emerges prematurely [known as premature termination codon (PTC)] before the natural canonical stop codon, truncated nonfunctional proteins or proteins with deleterious loss or gain-of-function activities are synthesized, followed by the development of nonsense mutation-mediated diseases. In the past decade, PTC-associated diseases captured much attention in biomedical research, especially as molecular therapeutic targets via nonsense suppression (i.e. translational readthrough) regimens. In this review, we highlighted different treatment strategies of PTC targeting readthrough therapeutics including the use of aminoglycosides, ataluren (formerly known as PTC124), suppressor tRNAs, nonsense-mediated mRNA decay, pseudouridylation and CRISPR/Cas9 system to treat PTC-mediated diseases. In addition, as thrombotic disorders are a group of disease with major burdens worldwide, 19 potential genes containing a total of 705 PTCs that cause 21 thrombotic disorders have been listed based on the data reanalysis from the 'GeneCards® - Human Gene Database' and 'Human Gene Mutation Database' (HGMD®). These PTC-containing genes can be potential targets amenable for different readthrough therapeutic strategies in the future.
Traditional Medicinal Plants Conferring Protection Against Ovalbumin-Induced Asthma in Experimental Animals: A Review

Azman S, Sekar M, Bonam SR, Gan SH, Wahidin S, Lum PT, et al.

J Asthma Allergy, 2021;14:641-662.
PMID: 34163178 DOI: 10.2147/JAA.S296391

Asthma is a chronic inflammatory disease of the respiratory tract in which the numerous immune cells, including eosinophils, neutrophils, macrophages, T-lymphocytes, mast cells and epithelial lining play key roles. The numerous anti-asthmatic drugs are available in modern medicine to treat asthma, but they have several disadvantages, including side effects and the cost variations, which compromise treatment compliance. The literature review reveals that traditional herbal medicines have good potential as alternative treatment and management for asthma. However, communities hesitated to use the traditional herbal medicines due to lack of established mechanism of action about their anti-asthmatic potential. The present review aimed to summarise the information stated in the literature about the potential effect of traditional medicinal plants (TMPs) conferring protection against ovalbumin (OVA)-induced asthma model. The literature search was conducted in database like PubMed, Scopus, Google Scholar and ScienceDirect. After screening through the literature from 2011 to date, a total of 27 medicinal plants and two polyherbal extracts have been reported to be used as traditional herbal medicines and also utilised to be tested against OVA-induced asthma, were included. We found them to be an important alternative source of treatment for asthma, since some have comparable efficacies with drugs commonly used in the modern system against asthma. All the reported medicinal plants confirmed their traditional use against asthma or its related inflammation. The present review provides faith in traditional information and also offers new insight into the potential of natural products against asthma.
Fulltext Embelin Alleviates Severe Airway Inflammation in OVA-LPS-Induced Rat Model of Allergic Asthma

Azman S, Sekar M, Wahidin S, Gan SH, Vaijanathappa J, Bonam SR, et al.

J Asthma Allergy, 2021;14:1511-1525.
PMID: 34938083 DOI: 10.2147/JAA.S298613

BACKGROUND: Asthma is a chronic lung disease, which causes wheezing, tightness in the chest, shortness of breath and coughing. In the wake of coronavirus disease 2019 (COVID-19), which affect the lungs, asthma patients are at high risk. Embelin, a natural benzoquinone obtained mainly from Embelia ribes Burm, has excellent biological properties, including protection against acute asthma. However, since asthma is a chronic and multi-factorial inflammatory disease, asthma conferred by a single allergen in an animal may not be clinically significant. Therefore, the purpose of the current study was to evaluate the effectiveness of embelin against ovalbumin (OVA)-lipopolysaccharide (LPS)-induced severe airway inflammation in experimental animals and to investigate the plausible mechanism of action.
METHODS: Rats (n=36) were divided into six groups. Group I served as a normal control. Groups II-VI were sensitised with severe allergens (OVA and LPS) on day 7, 14 and 21, followed by OVA and LPS challenge for 30 min three times/week for 3 weeks. Group II acted as an asthmatic disease control and received only vehicle. On the other hand, groups III-V received embelin (12.5, 25 and 50 mg/kg, P.O. respectively) while group VI received a standard dexamethasone (2.5 mg/kg, P.O.) for 15 days from day 27. Lung function parameters, including the respiratory rate, tidal volume and airflow rate were measured at the end of the experiment (day 42). The total and differential counts of leukocytes in the blood and bronchoalveolar fluid (BALF) were calculated. Th2-mediated serum pro-inflammatory cytokines such as interleukin (IL)-4, IL-5 and IL-13 levels were analyzed. At the end of the study protocol, the lung tissues were removed for a histopathology study. Additionally, a molecular docking simulation on embelin and standard dexamethasone was applied to support the in vivo findings.
RESULTS: Significant inhibition of eosinophils, neutrophils, lymphocytes and monocytes in the blood and the BALF was seen in the groups, which received embelin (25 and 50 mg/kg) and dexamethasone (2.5 mg/kg). Moreover, the lung function parameters were normalised by embelin (25 and 50 mg/kg) treatment significantly. The lung histopathological changes confirmed the protective effect of embelin against severe airway inflammation. The docking findings indicated good binding efficacy of embelin to IL-13.
CONCLUSION: Overall, our findings indicate that embelin can alleviate severe airway inflammation in OVA-LPS-induced model of allergic asthma occurring by suppression of Th2-mediated immune response. Due to its promising anti-asthmatic effect, it is recommended that embelin should be investigated in clinical trials against asthma. It should also be further explored against COVID-19 or COVID-like diseases due to its ameliorative effects on cytokines and immune cell infiltration.
Fulltext An Indo-Pacific coral spawning database

Baird AH, Guest JR, Edwards AJ, Bauman AG, Bouwmeester J, Mera H, et al.

Sci Data, 2021 01 29;8(1):35.
PMID: 33514754 DOI: 10.1038/s41597-020-00793-8

The discovery of multi-species synchronous spawning of scleractinian corals on the Great Barrier Reef in the 1980s stimulated an extraordinary effort to document spawning times in other parts of the globe. Unfortunately, most of these data remain unpublished which limits our understanding of regional and global reproductive patterns. The Coral Spawning Database (CSD) collates much of these disparate data into a single place. The CSD includes 6178 observations (3085 of which were unpublished) of the time or day of spawning for over 300 scleractinian species in 61 genera from 101 sites in the Indo-Pacific. The goal of the CSD is to provide open access to coral spawning data to accelerate our understanding of coral reproductive biology and to provide a baseline against which to evaluate any future changes in reproductive phenology.
Discovery of oxindole-based FLT3 inhibitors as a promising therapeutic lead for acute myeloid leukemia carrying the oncogenic ITD mutation

Bender O, Shoman ME, Ali TFS, Dogan R, Celik I, Mollica A, et al.

Arch Pharm (Weinheim), 2023 Feb;356(2):e2200407.
PMID: 36403191 DOI: 10.1002/ardp.202200407

FMS-like tyrosine kinase 3 (FLT3) mutations occur in approximately 30% of acute myeloid leukemia (AML) patients. In the current study, the oxindole chemotype is employed as a structural motif for the design of new FLT3 inhibitors as potential hits for AML irradiation. Cell-based screening was performed with 18 oxindole derivatives and 5a-c inhibited 68%-73% and 83%-91% of internal tandem duplication (ITD)-mutated MV4-11 cell growth for 48- and 72-h treatments while only 0%-2% and 27%-39% in wild-type THP-1 cells. The most potent compound 5a inhibited MV4-11 cells with IC50 of 4.3 µM at 72 h while it was 8.7 µM in THP-1 cells, thus showing two-fold selective inhibition against the oncogenic ITD mutation. The ability of 5a to modulate cell death was examined. High-throughput protein profiling revealed low levels of the growth factors IGFBP-2 and -4 with the blockage of various apoptotic inhibitors such as Survivin. p21 with cellular stress mechanisms was characterized by increased expression of HSP proteins along with TNF-β. Mechanistically, compounds 5a and 5b inhibited FLT3 kinase with IC50 values of 2.49 and 1.45 µM, respectively. Theoretical docking studies supported the compounds' ability to bind to the FLT3 ATP binding site with the formation of highly stable complexes as evidenced by molecular dynamics simulations. The designed compounds also provide suitable drug candidates with no violation of drug likeability rules.
Fulltext Subcutaneous administration of tramadol after elective surgery is as effective as intravenous administration in relieving acute pain and inflammation in dogs

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.
Fulltext Prevalence of Drug-Related Problems and Complementary and Alternative Medicine Use in Malaysia: A Systematic Review and Meta-Analysis of 37,249 Older Adults

Chang CT, Ang JY, Islam MA, Chan HK, Cheah WK, Gan SH

Pharmaceuticals (Basel), 2021 Feb 25;14(3).
PMID: 33669084 DOI: 10.3390/ph14030187

Drug-related problems (DRPs) in the elderly include polypharmacy, potentially inappropriate medications, nonadherence, and drug-related falls. In this systematic review and meta-analysis, the prevalence of DRPs and complementary and alternative medicine (CAM) use among the Malaysian elderly was estimated. PubMed, Scopus, Web of Science, and Google Scholar databases were searched to identify studies published since their inception up to 24 August 2020. A random-effects model was used to generate the pooled prevalence of DRPs along with its corresponding 95% confidence interval (CI). The heterogeneity of the results was estimated using the I2 statistics, and Cochran's Q test and sensitivity analyses were performed to confirm the robustness of the results. We identified 526 studies, 23 of which were included in the meta-analysis. (n = 29,342). The pooled prevalence of DRPs among Malaysian elderly was as follows: (1) polypharmacy: 49.5% [95% CI: 20.5-78.6], (2) potentially inappropriate medications: 28.9% [95% CI: 25.4-32.3], (3) nonadherence to medications: 60.6% [95% CI: 50.2-70.9], and (4) medication-related falls 39.3% [95% CI: 0.0-80.8]. Approximately one in two Malaysian elderly used CAM. The prevalence of polypharmacy and potentially inappropriate medications among the Malaysian elderly population was high, calling for measures and evidence-based guidelines to ensure the safe medication use.
Fulltext Pharmacist-led counselling intervention to improve antiretroviral drug adherence in Pakistan: a randomized controlled trial

Chatha ZF, Rashid U, Olsen S, Din FU, Khan A, Nawaz K, et al.

BMC Infect Dis, 2020 Nov 23;20(1):874.
PMID: 33228562 DOI: 10.1186/s12879-020-05571-w

BACKGROUND: Pakistan is facing a growing population of people living with human immunodeficiency (HIV). In this randomized controlled trial, we investigate if a pharmacist-led intervention can increase adherence to antiretroviral therapy (ART) for people living with HIV (PLWH).
METHODS: Adults with HIV, who have been taking ART for more than 3 months were randomly assigned to receive either a pharmacist-led intervention or their usual care. Measures of adherence were collected at 1) baseline 2) just prior to delivery of intervention and 3) 8 weeks later. The primary outcomes were CD4 cell count and self-reported adherence measured with the AIDS Clinical Trial Group (ACTG) questionnaire.
RESULTS: Post-intervention, the intervention group showed a statistically significant increase in CD4 cell counts as compared to the usual care group (p = 0.0054). In addition, adherence improved in the intervention group, with participants being 5.96 times more likely to report having not missed their medication for longer periods of time (p = 0.0086) while participants in the intervention group were 7.74 times more likely to report missing their ART less frequently (p
Fulltext Determination of carbamate and organophosphorus pesticides in vegetable samples and the efficiency of gamma-radiation in their removal

Chowdhury MA, Jahan I, Karim N, Alam MK, Abdur Rahman M, Moniruzzaman M, et al.

Biomed Res Int, 2014;2014:145159.
PMID: 24711991 DOI: 10.1155/2014/145159

In the present study, the residual pesticide levels were determined in eggplants (Solanum melongena) (n = 16), purchased from four different markets in Dhaka, Bangladesh. The carbamate and organophosphorus pesticide residual levels were determined by high performance liquid chromatography (HPLC), and the efficiency of gamma radiation on pesticide removal in three different types of vegetables was also studied. Many (50%) of the samples contained pesticides, and three samples had residual levels above the maximum residue levels determined by the World Health Organisation. Three carbamates (carbaryl, carbofuran, and pirimicarb) and six organophosphates (phenthoate, diazinon, parathion, dimethoate, phosphamidon, and pirimiphos-methyl) were detected in eggplant samples; the highest carbofuran level detected was 1.86 mg/kg, while phenthoate was detected at 0.311 mg/kg. Gamma radiation decreased pesticide levels proportionately with increasing radiation doses. Diazinon, chlorpyrifos, and phosphamidon were reduced by 40-48%, 35-43%, and 30-45%, respectively, when a radiation strength of 0.5 kGy was utilized. However, when the radiation dose was increased to 1.0 kGy, the levels of the pesticides were reduced to 85-90%, 80-91%, and 90-95%, respectively. In summary, our study revealed that pesticide residues are present at high amounts in vegetable samples and that gamma radiation at 1.0 kGy can remove 80-95% of some pesticides.
Fulltext A new nested allele-specific multiplex polymerase chain reaction method for haplotyping of VKORC1 gene to predict warfarin sensitivity

Chua YA, Abdullah WZ, Yusof Z, Gan SH

Biomed Res Int, 2014;2014:316310.
PMID: 24790995 DOI: 10.1155/2014/316310

The vitamin K epoxide reductase complex 1 gene (VKORC1) is commonly assessed to predict warfarin sensitivity. In this study, a new nested allele-specific multiplex polymerase chain reaction (PCR) method that can simultaneously identify single nucleotide polymorphisms (SNPs) at VKORC1 381, 861, 5808, and 9041 for haplotype analysis was developed and validated. Extracted DNA was amplified in the first PCR DNA, which was optimized by investigating the effects of varying the primer concentrations, annealing temperature, magnesium chloride concentration, enzyme concentration, and the amount of DNA template. The amplification products produced from the first round of PCR were used as templates for a second PCR amplification in which both mutant and wild-type primers were added in separate PCR tubes, followed by optimization in a similar manner. The final PCR products were resolved by agarose gel electrophoresis and further analysed by using a VKORC1 genealogic tree to infer patient haplotypes. Fifty patients were identified to have H1H1, one had H1H2, one had H1H7, 31 had either H1H7 or H1H9, one had H1H9, eight had H7H7, and one had H8H9 haplotypes. This is the first method that is able to infer VKORC1 haplotypes using only conventional PCR methods.
Hyperthermic effects of Durio zibethinus and its interaction with paracetamol

Chua YA, Nurhaslina H, Gan SH

Methods Find Exp Clin Pharmacol, 2008 Dec;30(10):739-43.
PMID: 19271022 DOI: 10.1358/mf.2008.30.10.1316830

Because durian (Durio zibethinus), which is known in Southeast Asia as "the king of fruits", is thought to have special body-warming properties, it should not be consumed with paracetamol due to a risk of toxic effects. The claim of warming properties, however, has not been scientifically proven. This study was conducted to investigate durian's hyperthermic effect and its toxicity when consumed together with paracetamol in rats. Five groups of rats (n=6) were fed with: 1) distilled water (4 ml/250 g), 2) homogenized durian (4 g/250 g), 3) paracetamol solution (2400 mg/kg), 4) durian (4 g/250 g) followed by paracetamol solution (2400 mg/kg), or 5) prazosin solution (15 mg/kg, pregavaged) followed 1 h later by durian (4 g/250 g) and paracetamol solution (2400 mg/kg). Rectal temperature, systolic blood pressure and serum alanine aminotransferase (ALT) levels were taken from each rat at baseline and after the various administrations at 1, 2 and 5 h. Our results showed that the body temperature of rats in the durian-treated group was not significantly elevated when compared to the control. However, there was a significant decrease in body temperature over time in animals from groups 4 and 5. We did not, however, observe a consistent pattern of blood pressure change. Serum chemical analysis for ALT also did not show any significant change in any of the groups. In conclusion, contrary to what some believe, even though durian was found to increase body temperature in some rats, this increment was not significant. Rats receiving the durian-paracetamol combination showed a significant drop in body temperature, which may explain the belief that the two mixtures are toxic. However, the exact mechanism of toxicity is still unknown.
VKORC1 and CYP2C9 genotypic data-based dose prediction alone does not accurately predict warfarin dose requirements in some Malaysian patients

Chua YA, Abdullah WZ, Yusof Z, Gan SH

Turk J Med Sci, 2015;45(4):913-8.
PMID: 26422867

BACKGROUND/AIM: VKORC1 and CYP2C9 genetic polymorphisms may not accurately predict warfarin dose requirements. We evaluated an existing warfarin dosing algorithm developed for Malaysian patients that was based only on VKORC1 and CYP2C9 genes.
MATERIALS AND METHODS: Five Malay patients receiving warfarin maintenance therapy were investigated for their CYP2C9*2, CYP2C9*3, and VKORC1-1639G>A genotypes and their vitamin K-dependent (VKD) clotting factor activities. The records of their daily warfarin doses and international normalized ratio (INR) 2 years prior to and after the measurement of VKD clotting factors activities were acquired. The mean warfarin doses were compared with predicted warfarin doses calculated from a genotypic-based dosing model developed for Asians.
RESULTS: A patient with the VKORC1-1639 GA genotype, who was supposed to have higher dose requirements, had a lower mean warfarin dose similar to those having the VKORC1-1639 AA genotype. This discrepancy may be due to the coadministration of celecoxib, which has the potential to decrease warfarins metabolism. Not all patients' predicted mean warfarin doses based on a previously developed dosing algorithm for Asians were similar to the actual mean warfarin dose, with the worst predicted dose being 54.34% higher than the required warfarin dose.
CONCLUSION: Multiple clinical factors can significantly change the actual required dose from the predicted dose from time to time. The additions of other dynamic variables, especially INR, VKD clotting factors, and concomitant drug use, into the dosing model are important in order to improve its accuracy.
Fulltext Fibrinolytic activity and dose-dependent effect of incubating human blood clots in caffeic acid phenethyl ester: in vitro assays

Elnager A, Hassan R, Idris Z, Mustafa Z, Wan-Arfah N, Sulaiman SA, et al.

Biomed Res Int, 2015;2015:627471.
PMID: 25664321 DOI: 10.1155/2015/627471

Background. Caffeic acid phenethyl ester (CAPE) has been reported to possess time-dependent fibrinolytic activity by in vitro assay. This study is aimed at investigating fibrinolytic dose-dependent activity of CAPE using in vitro assays. Methods. Standardized human whole blood (WB) clots were incubated in either blank controls or different concentrations of CAPE (3.75, 7.50, 15.00, 22.50, and 30.00 mM). After 3 hours, D-dimer (DD) levels and WB clot weights were measured for each concentration. Thromboelastography (TEG) parameters were recorded following CAPE incubation, and fibrin morphology was examined under a confocal microscope. Results. Overall, mean DD (μg/mL) levels were significantly different across samples incubated with different CAPE concentrations, and the median pre- and postincubation WB clot weights (grams) were significantly decreased for each CAPE concentration. Fibrin removal was observed microscopically and indicated dose-dependent effects. Based on the TEG test, the Ly30 fibrinolytic parameter was significantly different between samples incubated with two different CAPE concentrations (15.0 and 22.50 mM). The 50% effective dose (ED50) of CAPE (based on DD) was 1.99 mg/mL. Conclusions. This study suggests that CAPE possesses fibrinolytic activity following in vitro incubation and that it has dose-dependent activities. Therefore, further investigation into CAPE as a potential alternative thrombolytic agent should be conducted.
Nonpharmacologic Interventions in Prevention and Treatment of Hypertension

Erejuwa OO, Gan SH, Romani AMP, Kamal MA, Nammi S

Int J Hypertens, 2019;2019:6709817.
PMID: 31001431 DOI: 10.1155/2019/6709817
Fulltext Erratum to "Nonpharmacologic Interventions in Prevention and Treatment of Hypertension"

Erejuwa OO, Gan SH, Romani AMP, Kamal MA, Nammi S

Int J Hypertens, 2019 10 13;2019:2907675.
PMID: 31737360 DOI: 10.1155/2019/2907675

[This corrects the article DOI: 10.1155/2019/6709817.].
Fulltext Methanolic Extract of Ficus carica Linn. Leaves Exerts Antiangiogenesis Effects Based on the Rat Air Pouch Model of Inflammation

Eteraf-Oskouei T, Allahyari S, Akbarzadeh-Atashkhosrow A, Delazar A, Pashaii M, Gan SH, et al.

Evid Based Complement Alternat Med, 2015;2015:760405.
PMID: 25977699 DOI: 10.1155/2015/760405

The antiangiogenesis effect of Ficus carica leaves extract in an air pouch model of inflammation was investigated in rat. Inflammation was induced by injection of carrageenan into pouches. After antioxidant capacity and total phenolic content (TPC) investigations, the extract was administered at 5, 25, and 50 mg/pouch, and then the volume of exudates, the cell number, TNFα, PGE2, and VEGF levels were measured. Angiogenesis of granulation tissues was determined by measuring hemoglobin content. Based on the DPPH assay, the extract had significant antioxidant activity with TPC of 11.70 mg GAE/100 g dry sample. In addition, leukocyte accumulation and volume of exudate were significantly inhibited by the extract. Moreover, it significantly decreased the production of TNFα, PGE2, and VEGF, while angiogenesis was significantly inhibited by all administered doses. Interestingly, attenuation of angiogenesis and inflammatory parameters (except leukocyte accumulation) by the extract was similar to that shown by diclofenac. The extract has anti-inflammatory effects and ameliorated cell influx and exudation to the site of the inflammatory response which may be related to the local inhibition of TNFα, PGE2, and VEGF levels as similarly shown by diclofenac. The antiangiogenesis and anti-VEGF effects of Ficus carica may be correlated with its significant antioxidant potentials.
Fulltext Synbiotic Effects of Fermented Rice on Human Health and Wellness: A Natural Beverage That Boosts Immunity

Fuloria S, Mehta J, Talukdar MP, Sekar M, Gan SH, Subramaniyan V, et al.

Front Microbiol, 2022;13:950913.
PMID: 35910609 DOI: 10.3389/fmicb.2022.950913

Fermented foods have been an important component of the human diet from the time immemorial. It contains a high amount of probiotics that have been associated to a wide range of health benefits, including improved digestion and immunity. This review focuses on the indigenously prepared prebiotic- and probiotic-containing functional fermented rice (named Xaj-pani) by the Ahom Community from Assam, in Northeast India, including all the beneficial and potential effects on human health. Literature was searched from scientific databases such as PubMed, ScienceDirect and Google Scholar. Glutinous rice (commonly known as bora rice of sali variety) is primarily employed to prepare beverages that are recovered through the filtration process. The beer is normally consumed during religious rites, festivals and ritual practices, as well as being used as a refreshing healthy drink. Traditionally, it is prepared by incorporating a variety of medicinal herbs into their starter culture (Xaj-pitha) inoculum which is rich in yeasts, molds and lactic acid bacteria (LAB) and then incorporated in alcoholic beverage fermentation. The Ahom communities routinely consume this traditionally prepared alcoholic drink with no understanding of its quality and shelf life. Additionally, a finally produced dried cake, known as vekur pitha act as a source of Saccharomyces cerevisiae and can be stored for future use. Despite the rampant use in this community, the relationship between Xaj-pani's consumption, immunological response, infectious and inflammatory processes remains unknown in the presence of factors unrelated or indirectly connected to immune function. Overall, this review provides the guidelines to promote the development of prebiotic- and probiotic-containing functional fermented rice that could significantly have an impact on the health of the consumers.
Fulltext Genistein: A Potential Natural Lead Molecule for New Drug Design and Development for Treating Memory Impairment

Fuloria S, Yusri MAA, Sekar M, Gan SH, Rani NNIM, Lum PT, et al.

Molecules, 2022 Jan 01;27(1).
PMID: 35011497 DOI: 10.3390/molecules27010265

Genistein is a naturally occurring polyphenolic molecule in the isoflavones group which is well known for its neuroprotection. In this review, we summarize the efficacy of genistein in attenuating the effects of memory impairment (MI) in animals. Scopus, PubMed, and Web of Science databases were used to find the relevant articles and discuss the effects of genistein in the brain, including its pharmacokinetics, bioavailability, behavioral effects, and some of the potential mechanisms of action on memory in several animal models. The results of the preclinical studies highly suggested that genistein is highly effective in enhancing the cognitive performance of the MI animal models, specifically in the memory domain, including spatial, recognition, retention, and reference memories, through its ability to reduce oxidative stress and attenuate neuroinflammation. This review also highlighted challenges and opportunities to improve the drug delivery of genistein for treating MI. Along with that, the possible structural modifications and derivatives of genistein to improve its physicochemical and drug-likeness properties are also discussed. The outcomes of the review proved that genistein can enhance the cognitive performance and ameliorate MI in different preclinical studies, thus indicating its potential as a natural lead for the design and development of a novel neuroprotective drug.

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