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Fulltext Insights into the Role of microRNAs in Colorectal Cancer (CRC) Metabolism

Wai Hon K, Zainal Abidin SA, Othman I, Naidu R

Cancers (Basel), 2020 Aug 31;12(9).
PMID: 32878019 DOI: 10.3390/cancers12092462

Colorectal cancer (CRC) is one of the most frequently diagnosed cancers, with a high mortality rate globally. The pathophysiology of CRC is mainly initiated by alteration in gene expression, leading to dysregulation in multiple signalling pathways and cellular processes. Metabolic reprogramming is one of the important cancer hallmarks in CRC, which involves the adaptive changes in tumour cell metabolism to sustain the high energy requirements for rapid cell proliferation. There are several mechanisms in the metabolic reprogramming of cancer cells, such as aerobic glycolysis, oxidative phosphorylation, lactate and fatty acids metabolism. MicroRNAs (miRNAs) are a class of non-coding RNAs that are responsible for post-transcriptional regulation of gene expression. Differential expression of miRNAs has been shown to play an important role in different aspects of tumorigenesis, such as proliferation, apoptosis, and drug resistance, as well as metabolic reprogramming. Increasing evidence also reports that miRNAs could function as potential regulators of metabolic reprogramming in CRC cells. This review provides an insight into the role of different miRNAs in regulating the metabolism of CRC cells as well as to discuss the potential role of miRNAs as biomarkers or therapeutic targets in CRC tumour metabolism.
Fulltext The Crosstalk Between Signaling Pathways and Cancer Metabolism in Colorectal Cancer

Hon KW, Zainal Abidin SA, Othman I, Naidu R

Front Pharmacol, 2021;12:768861.
PMID: 34887764 DOI: 10.3389/fphar.2021.768861

Colorectal cancer (CRC) is one of the most frequently diagnosed cancers worldwide. Metabolic reprogramming represents an important cancer hallmark in CRC. Reprogramming core metabolic pathways in cancer cells, such as glycolysis, glutaminolysis, oxidative phosphorylation, and lipid metabolism, is essential to increase energy production and biosynthesis of precursors required to support tumor initiation and progression. Accumulating evidence demonstrates that activation of oncogenes and loss of tumor suppressor genes regulate metabolic reprogramming through the downstream signaling pathways. Protein kinases, such as AKT and c-MYC, are the integral components that facilitate the crosstalk between signaling pathways and metabolic pathways in CRC. This review provides an insight into the crosstalk between signaling pathways and metabolic reprogramming in CRC. Targeting CRC metabolism could open a new avenue for developing CRC therapy by discovering metabolic inhibitors and repurposing protein kinase inhibitors/monoclonal antibodies.
Fulltext Cytotoxic, Anti-Proliferative and Apoptosis Activity of l-Amino Acid Oxidase from Malaysian Cryptelytrops purpureomaculatus (CP-LAAO) Venom on Human Colon Cancer Cells

Zainal Abidin SA, Rajadurai P, Hoque Chowdhury ME, Othman I, Naidu R

Molecules, 2018 06 08;23(6).
PMID: 29890640 DOI: 10.3390/molecules23061388

The aim of this study is to investigate the potential anti-cancer activity of l-amino acid oxidase (CP-LAAO) purified from the venom of Cryptelytrops purpureomaculatus on SW480 and SW620 human colon cancer cells. Mass spectrometry guided purification was able to identify and purify CP-LAAO. Amino acid variations identified from the partial protein sequence of CP-LAAO may suggest novel variants of these proteins. The activity of the purified CP-LAAO was confirmed with o-phenyldiamine (OPD)-based spectrophotometric assay. CP-LAAO demonstrated time- and dose-dependent cytotoxic activity and the EC50 value was determined at 13 µg/mL for both SW480 and SW620 cells. Significant increase of caspase-3 activity, reduction of Bcl-2 levels, as well as morphological changes consistent with apoptosis were demonstrated by CP-LAAO. Overall, these data provide evidence on the potential anti-cancer activity of CP-LAAO from the venom of Malaysian C. purpureomaculatus for therapeutic intervention of human colon cancer.
Cytotoxic, Antiproliferative and Apoptosis-inducing Activity of L-Amino Acid Oxidase from Malaysian Calloselasma rhodostoma on Human Colon Cancer Cells

Zainal Abidin SA, Rajadurai P, Chowdhury MEH, Ahmad Rusmili MR, Othman I, Naidu R

Basic Clin Pharmacol Toxicol, 2018 Nov;123(5):577-588.
PMID: 29908095 DOI: 10.1111/bcpt.13060

The aim of this study was to investigate the cytotoxic, antiproliferative activity and the induction of apoptosis by L-amino acid oxidase isolated from Calloselasma rhodostoma crude venom (CR-LAAO) on human colon cancer cells. CR-LAAO was purified using three chromatographic steps: molecular exclusion using G-50 gel filtration resin, ion-exchange by MonoQ column and desalted on a G25 column. The purity and identity of the isolated CR-LAAO was confirmed by SDS-PAGE and LC-MS/MS. CR-LAAO demonstrated time- and dose-dependent cytotoxic activity on SW480 (primary human colon cancer cells) and SW620 (metastatic human colon cancer cells) with an EC50 values of 6 μg/ml and 7 μg/ml at 48 hr, respectively. Quantification of apoptotic cells based on morphological features demonstrated significant increase in apoptotic cell population in both SW480 and SW620 cells which peaked at 48 hr. Significant increase in caspase-3 activity and reduction in Bcl-2 levels were demonstrated following CR-LAAO treatment. These data provide evidence on the potential anticancer activity of CR-LAAO from the venom of C. rhodostoma for therapeutic intervention of human colon cancer.
Fulltext Receptor Tyrosine Kinases and Their Signaling Pathways as Therapeutic Targets of Curcumin in Cancer

Sudhesh Dev S, Zainal Abidin SA, Farghadani R, Othman I, Naidu R

Front Pharmacol, 2021;12:772510.
PMID: 34867402 DOI: 10.3389/fphar.2021.772510

Receptor tyrosine kinases (RTKs) are transmembrane cell-surface proteins that act as signal transducers. They regulate essential cellular processes like proliferation, apoptosis, differentiation and metabolism. RTK alteration occurs in a broad spectrum of cancers, emphasising its crucial role in cancer progression and as a suitable therapeutic target. The use of small molecule RTK inhibitors however, has been crippled by the emergence of resistance, highlighting the need for a pleiotropic anti-cancer agent that can replace or be used in combination with existing pharmacological agents to enhance treatment efficacy. Curcumin is an attractive therapeutic agent mainly due to its potent anti-cancer effects, extensive range of targets and minimal toxicity. Out of the numerous documented targets of curcumin, RTKs appear to be one of the main nodes of curcumin-mediated inhibition. Many studies have found that curcumin influences RTK activation and their downstream signaling pathways resulting in increased apoptosis, decreased proliferation and decreased migration in cancer both in vitro and in vivo. This review focused on how curcumin exhibits anti-cancer effects through inhibition of RTKs and downstream signaling pathways like the MAPK, PI3K/Akt, JAK/STAT, and NF-κB pathways. Combination studies of curcumin and RTK inhibitors were also analysed with emphasis on their common molecular targets.
Fulltext Isolation and Characterization of A2-EPTX-Nsm1a, a Secretory Phospholipase A2 from Malaysian Spitting Cobra (Naja sumatrana) Venom

Abdullah NAH, Rusmili MRA, Zainal Abidin SA, Shaikh MF, Hodgson WC, Othman I

Toxins (Basel), 2021 12 02;13(12).
PMID: 34941697 DOI: 10.3390/toxins13120859

Phospholipase A2 (PLA2) toxins are one of the main toxin families found in snake venom. PLA2 toxins are associated with various detrimental effects, including neurotoxicity, myotoxicity, hemostatic disturbances, nephrotoxicity, edema, and inflammation. Although Naja sumatrana venom contains substantial quantities of PLA2 components, there is limited information on the function and activities of PLA2 toxins from the venom. In this study, a secretory PLA2 from the venom of Malaysian N. sumatrana, subsequently named A2-EPTX-Nsm1a, was isolated, purified, and characterized. A2-EPTX-Nsm1a was purified using a mass spectrometry-guided approach and multiple chromatography steps. Based on LC-MSMS, A2-EPTX-Nsm1a was found to show high sequence similarity with PLA2 from venoms of other Naja species. The PLA2 activity of A2-EPTX-Nsm1 was inhibited by 4-BPB and EDTA. A2-EPTX-Nsm1a was significantly less cytotoxic in a neuroblastoma cell line (SH-SY5Y) compared to crude venom and did not show a concentration-dependent cytotoxic activity. To our knowledge, this is the first study that characterizes and investigates the cytotoxicity of an Asp49 PLA2 isolated from Malaysian N. sumatrana venom in a human neuroblastoma cell line.
Proteomic Characterization and Comparison of Malaysian Tropidolaemus wagleri and Cryptelytrops purpureomaculatus Venom Using Shotgun-Proteomics

Zainal Abidin SA, Rajadurai P, Chowdhury ME, Ahmad Rusmili MR, Othman I, Naidu R

Toxins (Basel), 2016 10 18;8(10).
PMID: 27763534

Tropidolaemus wagleri and Cryptelytrops purpureomaculatus are venomous pit viper species commonly found in Malaysia. Tandem mass spectrometry analysis of the crude venoms has detected different proteins in T. wagleri and C. purpureomaculatus. They were classified into 13 venom protein families consisting of enzymatic and nonenzymatic proteins. Enzymatic families detected in T. wagleri and C. purpureomaculatus venom were snake venom metalloproteinase, phospholipase A₂, ʟ-amino acid oxidase, serine proteases, 5'-nucleotidase, phosphodiesterase, and phospholipase B. In addition, glutaminyl cyclotransferase was detected in C. purpureomaculatus. C-type lectin-like proteins were common nonenzymatic components in both species. Waglerin was present and unique to T. wagleri-it was not in C. purpureomaculatus venom. In contrast, cysteine-rich secretory protein, bradykinin-potentiating peptide, and C-type natriuretic peptide were present in C. purpureomaculatus venom. Composition of the venom proteome of T. wagleri and C. purpureomaculatus provides useful information to guide production of effective antivenom and identification of proteins with potential therapeutic applications.
Fulltext A scaffolded approach to unearth potential antibacterial components from epicarp of Malaysian Nephelium lappaceum L

Asghar A, Tan YC, Zahoor M, Zainal Abidin SA, Yow YY, Khan E, et al.

Sci Rep, 2021 Jul 05;11(1):13859.
PMID: 34226594 DOI: 10.1038/s41598-021-92622-0

The emergence and spread of antimicrobial resistance have been of serious concern to human health and the management of bacterial infectious diseases. Effective treatment of these diseases requires the development of novel therapeutics, preferably free of side effects. In this regard, natural products are frequently conceived to be potential alternative sources for novel antibacterial compounds. Herein, we have evaluated the antibacterial activity of the epicarp extracts of the Malaysian cultivar of yellow rambutan fruit (Nephelium lappaceum L.) against six pathogens namely, Bacillus subtilis, methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pyogenes, Pseudomonas aeruginosa, Klebsiella pneumoniae and Salmonella enterica. Among a series of solvent extracts, fractions of ethyl acetate and acetone have revealed significant activity towards all tested strains. Chemical profiling of these fractions, via HPLC, LC-MS and GC-MS, has generated a library of potentially bioactive compounds. Downstream virtual screening, pharmacological prediction, and receptor-ligand molecular dynamics simulation have eventually unveiled novel potential antibacterial compounds, which can be extracted for medicinal use. We report compounds like catechin, eplerenone and oritin-4-beta-ol to be computationally inhibiting the ATP-binding domain of the chaperone, DnaK of P. aeruginosa and MRSA. Thus, our work follows the objective to propose new antimicrobials capable of perforating the barrier of resistance posed by both the gram positives and the negatives.
Fulltext The utilization of small non-mammals in traumatic brain injury research: A systematic review

Zulazmi NA, Arulsamy A, Ali I, Zainal Abidin SA, Othman I, Shaikh MF

CNS Neurosci Ther, 2021 Apr;27(4):381-402.
PMID: 33539662 DOI: 10.1111/cns.13590

Traumatic brain injury (TBI) is the leading cause of death and disability worldwide and has complicated underlying pathophysiology. Numerous TBI animal models have been developed over the past decade to effectively mimic the human TBI pathophysiology. These models are of mostly mammalian origin including rodents and non-human primates. However, the mammalian models demanded higher costs and have lower throughput often limiting the progress in TBI research. Thus, this systematic review aims to discuss the potential benefits of non-mammalian TBI models in terms of their face validity in resembling human TBI. Three databases were searched as follows: PubMed, Scopus, and Embase, for original articles relating to non-mammalian TBI models, published between January 2010 and December 2019. A total of 29 articles were selected based on PRISMA model for critical appraisal. Zebrafish, both larvae and adult, was found to be the most utilized non-mammalian TBI model in the current literature, followed by the fruit fly and roundworm. In conclusion, non-mammalian TBI models have advantages over mammalian models especially for rapid, cost-effective, and reproducible screening of effective treatment strategies and provide an opportunity to expedite the advancement of TBI research.
Fulltext Chronic unpredictable stress (CUS) reduced phoenixin expression, induced abnormal sperm and testis morphology in male rats

Mohamed ZI, Sivalingam M, Radhakrishnan AK, Jaafar F, Zainal Abidin SA

Neuropeptides, 2024 Oct;107:102447.
PMID: 38870753 DOI: 10.1016/j.npep.2024.102447

Chronic stress caused by prolonged emotional pressure can lead to various physiological issues, including reproductive dysfunction. Although reproductive problems can also induce chronic stress, the impact of chronic stress-induced reproductive dysfunction remains contentious. This study investigates the effects of chronic unpredictable stress (CUS) on reproductive neuropeptides, sperm quality, and testicular morphology. Sixteen twelve-week-old Sprague Dawley rats were divided into two groups: a non-stress control group and a CUS-induced group. The CUS regimen involved various stressors over 28 days, with both groups undergoing behavioural assessments through sucrose-preference and forced-swim tests. Hypothalamic gene expression levels of CRH, PNX, GPR173, kisspeptin, GnRH, GnIH, and spexin neuropeptides were measured via qPCR, while plasma cortisol, luteinizing hormone (LH), and testosterone concentrations were quantified using ELISA. Seminal fluid and testis samples were collected for sperm analysis and histopathological evaluation, respectively. Results showed altered behaviours in CUS-induced rats, reflecting stress impacts. Hypothalamic corticotropin-releasing hormone (CRH) expression and plasma cortisol levels were significantly higher in CUS-induced rats compared to controls (p
Fulltext Potential economic and clinical implications of improving access to snake antivenom in five ASEAN countries: A cost-effectiveness analysis

Patikorn C, Ismail AK, Zainal Abidin SA, Othman I, Chaiyakunapruk N, Taychakhoonavudh S

PLoS Negl Trop Dis, 2022 Nov;16(11):e0010915.
PMID: 36383562 DOI: 10.1371/journal.pntd.0010915

BACKGROUND: Despite domestic production of antivenoms in the Association of Southeast Asian Nations (ASEAN) countries, not all victims with snakebite envenomings indicated for antivenom received the appropriate or adequate effective dose of antivenom due to insufficient supply and inadequate access to antivenoms. We aimed to conduct a cost-effectiveness analysis to project the potential economic and clinical impact of improving access to antivenoms when all snakebite envenomings in ASEAN countries were hypothetically treated with geographically appropriate antivenoms.
METHODOLOGY: Using a decision analytic model with input parameters from published literature, local data, and expert opinion, we projected the impact of "full access" (100%) to antivenom, compared to "current access" in five most impacted ASEAN countries, including Indonesia (10%), Philippines (26%), Vietnam (37%), Lao PDR (4%), and Myanmar (64%), from a societal perspective with a lifetime time horizon. Sensitivity analyses were performed.
PRINCIPAL FINDINGS: In base-case analyses, full access compared to current access to snake antivenom in the five countries resulted in a total of 9,362 deaths averted (-59%), 230,075 disability-adjusted life years (DALYs) averted (-59%), and cost savings of 1.3 billion USD (-53%). Incremental cost-effectiveness ratios (ICERs) of improving access to antivenom found higher outcomes but lower costs in all countries. Probabilistic sensitivity analyses of 1,000 iterations found that 98.1-100% of ICERs were cost-saving.
CONCLUSION/SIGNIFICANCE: Improving access to snake antivenom will result in cost-saving for ASEAN countries. Our findings emphasized the importance of further strengthening regional cooperation, investment, and funding to improve the situation of snakebite victims in ASEAN countries.
Fulltext Anticancer activity of a sub-fraction of dichloromethane extract of Strobilanthes crispus on human breast and prostate cancer cells in vitro

Yaacob NS, Hamzah N, Nik Mohamed Kamal NN, Zainal Abidin SA, Lai CS, Navaratnam V, et al.

BMC Complement Altern Med, 2010;10:42.
PMID: 20684795 DOI: 10.1186/1472-6882-10-42

The leaves of Strobilanthes crispus (S. crispus) which is native to the regions of Madagascar to the Malay Archipelago, are used in folk medicine for their antidiabetic, diuretic, anticancer and blood pressure lowering properties. Crude extracts of this plant have been found to be cytotoxic to human cancer cell lines and protective against chemically-induced hepatocarcinogenesis in rats. In this study, the cytotoxicity of various sub-fractions of dichloromethane extract isolated from the leaves of S. crispus was determined and the anticancer activity of one of the bioactive sub-fractions, SC/D-F9, was further analysed in breast and prostate cancer cell lines.
Fulltext Evaluation of the Phytochemical, Antioxidant, Enzyme Inhibition, and Wound Healing Potential of Calotropis gigantea (L.) Dryand: A Source of a Bioactive Medicinal Product

Alafnan A, Sridharagatta S, Saleem H, Khurshid U, Alamri A, Ansari SY, et al.

Front Pharmacol, 2021;12:701369.
PMID: 34483902 DOI: 10.3389/fphar.2021.701369

Traditionally, plants of the genus Calotropis have been used to cure various common diseases. The present research work explores the chemical and biological characterization of one of the most common species of this genus, i.e., Calotropis gigantea (L.) Dryand (syn. Calotropis gigantea (L.) Dryand.), having multiple folklore applications. The ethanolic extract of leaves of Calotropis gigantea (L.) Dryand was analyzed for the phytochemical composition by determining the total bioactive (total phenolic and total flavonoid) contents and UHPLC-MS secondary metabolites analysis. For phytopharmacological evaluation, in vitro antioxidant (including DPPH, ABTS, FRAP, CUPRAC, phosphomolybdenum, and metal chelation antioxidant assays) activities, enzyme inhibition potential (against AChE, BChE, α-amylase, and tyrosinase enzymes), and in vivo wound healing potential were determined. The tested extract has been shown to contain considerable flavonoid (46.75 mg RE/g extract) and phenolic (33.71 mg GAE/g extract) contents. The plant extract presented considerable antioxidant potential, being the most active for CUPRAC assays. Secondary metabolite UHPLC-MS characterization, in both the positive and negative ionization modes, indicated the tentative presence of 17 different phytocompounds, mostly derivatives of sesquiterpene, alkaloids, and flavonoids. Similarly, the tested extract exhibited considerable inhibitory effects on tyrosinase (81.72 mg KAE/g extract), whereas it showed weak inhibition ability against other tested enzymes. Moreover, in the case of in vivo wound healing assays, significant improvement in wound healing was observed in both the tested models at the doses of 0.5 percent w/w (p < 0.001) and 2.0 percent w/w (p < 0.01) on the 16th day. The outcomes of the present research work suggested that C. gigantea (L.) Dryand plant extract could be appraised as a potential origin of bioactive molecules having multifunctional medicinal uses.
Pharmacological, phytochemical and in-vivo toxicological perspectives of a xero-halophyte medicinal plant: Zaleya pentandra (L.) Jeffrey

Saleem H, Zengin G, Locatelli M, Ahmad I, Khaliq S, Mahomoodally MF, et al.

Food Chem Toxicol, 2019 Sep;131:110535.
PMID: 31154083 DOI: 10.1016/j.fct.2019.05.043

This study endeavours to investigate the phytochemical composition, biological properties and in vivo toxicity of methanol and dichloromethane extracts of Zaleya pentandra (L.) Jeffrey. Total bioactive contents, antioxidant (phosphomolybdenum and metal chelating, DPPH, ABTS, FRAP and CUPRAC) and enzyme inhibition (cholinesterases, tyrosinase α-amylase, and α-glucosidase) potential were assessed utilizing in vitro bioassays. UHPLC-MS phytochemical profiling was carried out to identify the essential compounds. The methanol extract was found to contain highest phenolic (22.60 mg GAE/g) and flavonoid (31.49 mg QE/g) contents which correlate with its most significant radical scavenging, reducing potential and tyrosinase inhibition. The dichloromethane extract was most potent for phosphomolybdenum, ferrous chelation, α-amylase, α-glucosidase, and cholinesterase inhibition assays. UHPLC-MS analysis of methanol extract unveiled to identify 11 secondary metabolites belonging to five sub-groups, i.e., phenolic, alkaloid, carbohydrate, terpenoid, and fatty acid derivatives. Additionally, in vivo toxicity was conducted for 21 days and the methanol extract at different doses (150, 200, 250 and 300 mg/kg) was administered in experimental chicks divided into five groups each containing five individuals. Different physical, haematological and biochemical parameters along with the absolute and relative weight of visceral body organs were studied. Overall, no toxic effect was noted for the extract at tested doses.
Investigation into the biological properties, secondary metabolites composition, and toxicity of aerial and root parts of Capparis spinosa L.: An important medicinal food plant

Saleem H, Khurshid U, Sarfraz M, Ahmad I, Alamri A, Anwar S, et al.

Food Chem Toxicol, 2021 Sep;155:112404.
PMID: 34246708 DOI: 10.1016/j.fct.2021.112404

Capparis spinose L. also known as Caper is of great significance as a traditional medicinal food plant. The present work was targeted on the determination of chemical composition, pharmacological properties, and in-vitro toxicity of methanol and dichloromethane (DCM) extracts of different parts of C. spinosa. Chemical composition was established by determining total bioactive contents and via UHPLC-MS secondary metabolites profiling. For determination of biological activities, antioxidant capacity was determined through DPPH, ABTS, CUPRAC, FRAP, phosphomolybdenum, and metal chelating assays while enzyme inhibition against cholinesterase, tyrosinase, α-amylase and α-glucosidase were also tested. All the extracts were also tested for toxicity against two breast cell lines. The methanolic extracts were found to contain highest total phenolic and flavonoids which is correlated with their significant radical scavenging, cholinesterase, tyrosinase and glucosidase inhibition potential. Whereas DCM extracts showed significant activity for reducing power, phosphomolybdenum, metal chelation, tyrosinase, and α-amylase inhibition activities. The secondary metabolites profiling of both methanolic extracts exposed the presence of 21 different secondary metabolites belonging to glucosinolate, alkaloid, flavonoid, phenol, triterpene, and alkaloid derivatives. The present results tend to validate folklore uses of C. spinose and indicate this plant to be used as a potent source of designing novel bioactive compounds.
Fulltext Phytopharmacological Evaluation of Different Solvent Extract/Fractions From Sphaeranthus indicus L. Flowers: From Traditional Therapies to Bioactive Compounds

Ahmad HI, Nadeem MF, Shoaib Khan HM, Sarfraz M, Saleem H, Khurshid U, et al.

Front Pharmacol, 2021;12:708618.
PMID: 34776946 DOI: 10.3389/fphar.2021.708618

Sphaeranthus indicus L. is a medicinal herb having widespread traditional uses for treating common ailments. The present research work aims to explore the in-depth phytochemical composition and in vitro reactivity of six different polarity solvents (methanol, n-hexane, benzene, chloroform, ethyl acetate, and n-butanol) extracts/fractions of S. indicus flowers. The phytochemical composition was accomplished by determining total bioactive contents, HPLC-PDA polyphenolic quantification, and UHPLC-MS secondary metabolomics. The reactivity of the phenolic compounds was tested through the following biochemical assays: antioxidant (DPPH, ABTS, FRAP, CUPRAC, phosphomolybdenum, and metal chelation) and enzyme inhibition (AChE, BChE, α-glucosidase, α-amylase, urease, and tyrosinase) assays were performed. The methanol extract showed the highest values for phenolic (94.07 mg GAE/g extract) and flavonoid (78.7 mg QE/g extract) contents and was also the most active for α-glucosidase inhibition as well as radical scavenging and reducing power potential. HPLC-PDA analysis quantified rutin, naringenin, chlorogenic acid, 3-hydroxybenzoic acid, gallic acid, and epicatechin in a significant amount. UHPLC-MS analysis of methanol and ethyl acetate extracts revealed the presence of well-known phytocompounds; most of these were phenolic, flavonoid, and glycoside derivatives. The ethyl acetate fraction exhibited the highest inhibition against tyrosinase and urease, while the n-hexane fraction was most active for α-amylase. Moreover, principal component analysis highlighted the positive correlation between bioactive compounds and the tested extracts. Overall, S. indicus flower extracts were found to contain important phytochemicals, hence could be further explored to discover novel bioactive compounds that could be a valid starting point for future pharmaceutical and nutraceuticals applications.
Deciphering the toxicological and computational assessment of Verbascum yemenese.: Integrating phytochemistry and bioinformatics tools

Alghamdi A, A Awadh Ali N, Alafnan A, Zainal Abidin SA, Alamri A, Hussein W, et al.

Food Chem Toxicol, 2024 Nov;193:115028.
PMID: 39368542 DOI: 10.1016/j.fct.2024.115028

This study explores the phytochemical composition and biological activities of Verbascum yemenense, a plant known for its medicinal properties. The plant extract revealed a rich presence of bioactive compounds that exhibited significant antioxidant properties against free radicals. The enzyme inhibition potential was particularly notable against cholinesterases (AChE: 2.56 mg GALAE/g; BChE: 1.98 mg GALAE/g), and tyrosinase (87.94 mg KAE/g), α-glucosidase suggesting potential therapeutic applications in neurodegenerative diseases, skin disorders and diabetes. Molecular docking studies and Molecular Dynamics simulations, providing insights into the interaction mechanisms of the identified compounds with the target proteins. Molecular docking studies revealed high binding affinities of the phytoconstituents, with compounds like VY4 and phyllanthusol-A (VY15) showing substantial docking scores against AChE (-9.840 kcal/mol) and BChE (-9.853 kcal/mol), respectively. For instance, the RMSD values during the MD simulations for compound VY17 in the AML complex showed a stable conformation, fluctuating within a range of 0.75 Å to 1.75 Å, indicating a strong and consistent interaction with the enzyme. MESP studies highlighted VY17's distinctive electrostatic features, notably a pronounced electronegative region, which might contribute to its binding efficiency. These findings suggest that V. yemenense is a promising candidate for developing novel therapeutic agents.
Fulltext Estimating economic and disease burden of snakebite in ASEAN countries using a decision analytic model

Patikorn C, Blessmann J, Nwe MT, Tiglao PJG, Vasaruchapong T, Maharani T, et al.

PLoS Negl Trop Dis, 2022 Sep;16(9):e0010775.
PMID: 36170270 DOI: 10.1371/journal.pntd.0010775

BACKGROUND: Understanding the burden of snakebite is crucial for developing evidence-informed strategies to pursue the goal set by the World Health Organization to halve morbidity and mortality of snakebite by 2030. However, there was no such information in the Association of Southeast Asian Nations (ASEAN) countries.
METHODOLOGY: A decision analytic model was developed to estimate annual burden of snakebite in seven countries, including Malaysia, Thailand, Indonesia, Philippines, Vietnam, Lao PDR, and Myanmar. Country-specific input parameters were sought from published literature, country's Ministry of Health, local data, and expert opinion. Economic burden was estimated from the societal perspective. Costs were expressed in 2019 US Dollars (USD). Disease burden was estimated as disability-adjusted life years (DALYs). Probabilistic sensitivity analysis was performed to estimate a 95% credible interval (CrI).
PRINCIPAL FINDINGS: We estimated that annually there were 242,648 snakebite victims (95%CrI 209,810-291,023) of which 15,909 (95%CrI 7,592-33,949) were dead and 954 (95%CrI 383-1,797) were amputated. We estimated that 161,835 snakebite victims (69% of victims who were indicated for antivenom treatment) were not treated with antivenom. Annual disease burden of snakebite was estimated at 391,979 DALYs (95%CrI 187,261-836,559 DALYs) with total costs of 2.5 billion USD (95%CrI 1.2-5.4 billion USD) that were equivalent to 0.09% (95%CrI 0.04-0.20%) of the region's gross domestic product. >95% of the estimated burdens were attributed to premature deaths.
CONCLUSION/SIGNIFICANCE: The estimated high burden of snakebite in ASEAN was demonstrated despite the availability of domestically produced antivenoms. Most burdens were attributed to premature deaths from snakebite envenoming which suggested that the remarkably high burden of snakebite could be averted. We emphasized the importance of funding research to perform a comprehensive data collection on epidemiological and economic burden of snakebite to eventually reveal the true burden of snakebite in ASEAN and inform development of strategies to tackle the problem of snakebite.
Quadrupole-Time-of-Flight Mass Spectrometric Identification of Hemoglobin Subunits α, β, γ and δ in Unknown Peaks of High Performance Liquid Chromatography of Hemoglobin in β-Thalassemias

Abdullah UYH, Ibrahim HM, Mahmud NB, Salleh MZ, Kek TL, Noorizhab MNFB, et al.

Hemoglobin, 2019 May;43(3):182-187.
PMID: 31298599 DOI: 10.1080/03630269.2019.1632893

This is the first report of quadrupole time-of-flight (Q-TOF) mass spectrometric identification of the hemoglobin (Hb) subunits, α, β, δ and γ peptides, derived from enzymatic-digestion of proteins in the early unknown peaks of the cation exchange chromatography of Hb. The objectives were to identify the unknown high performance liquid chromatography (HPLC) peaks in healthy subjects and in patients with β-thalassemia (β-thal). The results demonstrate the existence of pools of free globin chains in red blood cells (RBCs). The α-, β-, δ- and γ-globin peptides were identified in the unknown HPLC peaks. The quantification and role of the free globin pool in patients with β-thal requires further investigation. Identification of all types of Hb subunits in the retention time (RT) before 1 min. suggests that altered Hbs is the nature of these fast-eluting peaks. Relevancy of thalassemias to the protein-aggregation disorders will require review of the role of free globin in the pathology of the disease.

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