Displaying publications 1 - 20 of 148 in total

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  1. Fulltext Bioactive substances of cyanobacteria and microalgae: Sources, metabolism, and anticancer mechanism insights
    Bouyahya A, Bakrim S, Chamkhi I, Taha D, El Omari N, El Mneyiy N, et al.
    Biomed Pharmacother, 2024 Jan;170:115989.
    PMID: 38103309 DOI: 10.1016/j.biopha.2023.115989
    Cyanobacteria and microalgae contain various phytochemicals, including bioactive components in the form of secondary metabolites, namely flavonoids, phenolic acids, terpenoids, and tannins, with remarkable anticancer effects. This review highlights the recent advances in bioactive compounds, with potential anticancer activity, produced by cyanobacteria and microalgae. Previous in vitro investigations showed that many of these bioactive compounds exhibit potent effects against different human cancer types, such as leukemia and breast cancers. Multiple mechanisms implicated in the antitumor effect of these compounds were elucidated, including their ability to target cellular, subcellular, and molecular checkpoints linked to cancer development and promotion. Recent findings have highlighted various mechanisms of action of bioactive compounds produced by cyanobacteria and microalgae, including induction of autophagy and apoptosis, inhibition of telomerase and protein kinases, as well as modulation of epigenetic modifications. In vivo investigations have demonstrated a potent anti-angiogenesis effect on solid tumors, as well as a reduction in tumor volume. Some of these compounds were examined in clinical investigations for certain types of cancers, making them potent candidates/scaffolds for antitumor drug development.
  2. Fulltext Ardisia crispa root hexane fraction suppressed angiogenesis in human umbilical vein endothelial cells (HUVECs) and in vivo zebrafish embryo model
    Wen Jun L, Pit Foong C, Abd Hamid R
    Biomed Pharmacother, 2019 Oct;118:109221.
    PMID: 31545225 DOI: 10.1016/j.biopha.2019.109221
    Ardisia crispa Thunb. A. DC. (Primulaceae) has been used extensively as folk-lore medicine in South East Asia including China and Japan to treat various inflammatory related diseases. Ardisia crispa root hexane fraction (ACRH) has been thoroughly studied by our group and it has been shown to exhibit anti-inflammatory, anti-hyperalgesic, anti-arthritic, anti-ulcer, chemoprevention and suppression against inflammation-induced angiogenesis in various animal model. Nevertheless, its effect against human endothelial cells in vitro has not been reported yet. Hence, the aim of the study is to investigate the potential antiangiogenic property of ACRH in human umbilical vein endothelial cells (HUVECs) and zebrafish embryo model. ACRH was separated from the crude ethanolic extract of the plant's root in prior to experimental studies. MTT assay revealed that ACRH exerted a concentration-dependent antiproliferative effect on HUVEC with the IC50 of 2.49 ± 0.04 μg/mL. At higher concentration (10 μg/mL), apoptosis was induced without affecting the cell cycle distribution. Angiogenic properties including migration, invasion and differentiation of HUVECs, evaluated via wound healing, trans-well invasion and tube formation assay respectively, were significantly suppressed by ACRH in a concentration-dependent manner. Noteworthily, significant antiangiogenic effects were observed even at the lowest concentration used (0.1 μg/mL). Expression of proMMP-2, vascular endothelial growth factor (VEGF)-C, VEGF-D, Angiopoietin-2, fibroblast growth factor (FGF)-1, FGF-2, Follistatin, and hepatocyte growth factor (HGF) were significantly reduced in various degrees by ACRH. The ISV formation in zebrafish embryo was significantly suppressed by ACRH at the concentration of 5 μg/mL. These findings revealed the potential of ACRH as antiangiogenic agent by suppressing multiple proangiogenic proteins. Thus, it can be further verified via the transcription of these proteins from their respective DNA, in elucidating their exact pathways.
  3. Fulltext Involvement of the uridine cytidine kinase 2 enzyme in cancer cell death: A molecular crosstalk between the enzyme and cellular apoptosis induction
    Malami I, Abdul AB
    Biomed Pharmacother, 2019 Jan;109:1506-1510.
    PMID: 30551402 DOI: 10.1016/j.biopha.2018.10.200
    Apoptosis is a series of molecular signalling regulating normal cellular growth and development. Cells resistance to apoptosis, however, leads to uncontrolled proliferation. Research involving cancer cell death is one of the most important targeted areas in the discovery of novel anticancer therapy. There are several biochemical pathways that are liked towards cancer cell death of which, uridine-cytidine kinase 2 (UCK2) was recently linked to cell apoptosis induction. UCK2 is responsible for the phosphorylation of uridine and cytidine to their corresponding monophosphate in a salvage pathway of pyrimidine nucleotides biosynthesis. Cytotoxic ribonucleoside analogues that target UCK2 enzyme activity are currently being investigated in clinical trials useful for cancer treatment. Whilst findings have clearly shown that these antimetabolites inhibit cancer development in clinical settings, they have yet to establish linking cytotoxic nucleoside analogues to cancer cell death. In this present review, we propose the probable molecular crosstalk involving UCK2 protein and cancer cell death through cell cycle arrest and triggering of apoptosis involving proteins, MDM2 and the subsequent activation of p53.
  4. Fulltext The role of natural antioxidants in cisplatin-induced hepatotoxicity
    Abd Rashid N, Abd Halim SAS, Teoh SL, Budin SB, Hussan F, Adib Ridzuan NR, et al.
    Biomed Pharmacother, 2021 Dec;144:112328.
    PMID: 34653753 DOI: 10.1016/j.biopha.2021.112328
    Cisplatin is a potent platinum-based anticancer drug approved by the Food Drug Administration (FDA) in 1978. Despite its advantages against solid tumors, cisplatin confers toxicity to various tissues that limit its clinical uses. In cisplatin-induced hepatotoxicity, few mechanisms have been identified, which started as excess generation of reactive oxygen species that leads to oxidative stress, inflammation, DNA damage and apoptosis in the liver. Various natural products, plant extracts and oil rich in flavonoids, terpenoids, polyphenols, and phenolic acids were able to minimize oxidative stress by restoring the level of antioxidant enzymes and acting as an anti-inflammatory agent. Likewise, treatment with honey and royal jelly was demonstrated to decrease serum transaminases and scavenge free radicals in the liver after cisplatin administration. Medicinal properties of these natural products have a promising potential as a complementary therapy to counteract cisplatin-induced hepatotoxicity. This review concentrated on the protective role of several natural products, which has been proven in the laboratory findings to combat cisplatin-induced hepatotoxicity.
  5. Dioscorea bulbifera induced apoptosis through inhibition of ERK 1/2 and activation of JNK signaling pathways in HCT116 human colorectal carcinoma cells
    Ahmad Hidayat AF, Chan CK, Mohamad J, Abdul Kadir H
    Biomed Pharmacother, 2018 Aug;104:806-816.
    PMID: 29860114 DOI: 10.1016/j.biopha.2018.05.073
    Dioscorea bulbifera, also known as air potato, has been cultivated as food crop mainly in tropical countries in Asia and Australia. The tubers are edible and have often been used in Traditional Chinese Medicine (TCM) and Ayurvedic medicine to treat cancer, diabetes, thyroid disease, and inflammation. This study aimed to investigate the effects of D. bulbifera on HCT116 human colorectal carcinoma cells and to unravel the plausible mechanisms underlying its apoptotic effects. The ethanol crude and fractions (hexane, ethyl acetate and water) of D. bulbifera were subjected to cell viability MTT assay against various cancer cell lines. The lowest IC50 of the extract and fractions on selected cancer cells were selected for further apoptosis assay and western blot analysis. HCT116 cancer cells were treated with D. bulbifera and stained with Annexin/PI or Hoechst 33342/PI for preliminary confirmation of apoptosis. The dissipation of mitochondria membrane potential (MMP) was determined by flow cytometry. The protein expressions of apoptosis-related proteins such as Bcl-2 family, caspases, Fas, PARP, ERK1/2 and JNK were detected by western blot analysis. Moreover, the HCT116 cells were treated with UO126 and SP600125 inhibitors to verify the involvement of ERK1/2 and JNK protein expressions in inducing apoptotic cell death. Based on the result, D. bulbifera ethyl acetate fraction (DBEAF) exhibited the most compelling cytotoxicity on HCT116 cells with an IC50 of 37.91 ± 1.30 µg/mL. The induction of apoptosis was confirmed by phosphatidylserine externalization and chromatin condensation. Depolarization of MMP further conferred the induction of apoptosis was through the regulation of Bcl-2 family proteins. Activation of caspase cascades (caspase-3, -9, -8 and -10) was elicited followed by the observation of cleaved PARP accumulation in DBEAF-treated cells. Furthermore, death receptor, Fas was activated upon exposure to DBEAF. Collective apoptotic evidences suggested the involvement of intrinsic and extrinsic pathways by DBEAF in HCT116 cells. Interestingly, the attenuation of ERK1/2 phosphorylation accompanied by the activation of JNK was detected in DBEAF-treated cells. In conclusion, the findings revealed that DBEAF induced apoptosis through intrinsic and extrinsic pathways involving ERK1/2 and JNK.
  6. Fulltext Establishment of in vitro and in vivo anti-colon cancer efficacy of essential oils containing oleo-gum resin extract of Mesua ferrea
    Asif M, Yehya AHS, Dahham SS, Mohamed SK, Shafaei A, Ezzat MO, et al.
    Biomed Pharmacother, 2019 Jan;109:1620-1629.
    PMID: 30551416 DOI: 10.1016/j.biopha.2018.10.127
    Proven the great potential of essential oils as anticancer agents, the current study intended to explore molecular mechanisms responsible for in vitro and in vivo anti-colon cancer efficacy of essential oil containing oleo-gum resin extract (RH) of Mesua ferrea. MTT cell viability studies showed that RH had broad spectrum cytotoxic activities. However, it induced more profound growth inhibitory effects towards two human colon cancer cell lines i.e., HCT 116 and LIM1215 with an IC50 values of 17.38 ± 0.92 and 18.86 ± 0.80 μg/mL respectively. RH induced relatively less toxicity in normal human colon fibroblasts i.e., CCD-18co. Cell death studies conducted, revealed that RH induced characteristic morphological and biochemical changes in HCT 116. At protein level it down-regulated expression of multiple pro-survival proteins i.e., survivin, xIAP, HSP27, HSP60 and HSP70 and up-regulated expression of ROS, caspase-3/7 and TRAIL-R2 in HCT 116. Furthermore, significant reduction in invasion, migration and colony formation potential was observed in HCT 116 treated with RH. Chemical characterization by GC-MS and HPLC methods revealed isoledene and elemene as one the major compounds. RH showed potent antitumor activity in xenograft model. Overall, these findings suggest that RH holds a promise to be further studied for cheap anti-colon cancer naturaceutical development.
  7. Fulltext Prospective role of mitochondrial apoptotic pathway in mediating GMG-ITC to reduce cytotoxicity in H2O2-induced oxidative stress in differentiated SH-SY5Y cells
    Jaafaru MS, Nordin N, Rosli R, Shaari K, Bako HY, Noor NM, et al.
    Biomed Pharmacother, 2019 Nov;119:109445.
    PMID: 31541852 DOI: 10.1016/j.biopha.2019.109445
    The antioxidant and neuroprotective activity of Glucomoringin isothiocyanate (GMG-ITC) have been reported in in vivo and in vitro models of neurodegenerative diseases. However, its neuroprotective role via mitochondrial-dependent pathway in a noxious environment remains unknown. The main objective of the present study was to unveil the mitochondrial apoptotic genes' profile and prospectively link with neuroprotective activity of GMG-ITC through its ROS scavenging. The results showed that pre-treatment of differentiated SH-SY5Y cells with 1.25 μg/mL purified isolated GMG-ITC, significantly reduced reactive oxygen species (ROS) production level, compared to H2O2 control group, as evidenced by flow cytometry-based evaluation of ROS generation. Presence of GMG-ITC prior to development of oxidative stress condition, downregulated the expression of cyt-c, p53, Apaf-1, Bax, CASP3, CASP8 and CASP9 genes with concurrent upregulation of Bcl-2 gene in mitochondrial apoptotic signalling pathway. Protein Multiplex revealed significant decreased in cyt-c, p53, Apaf-1, Bax, CASP8 and CASP9 due to GMG-ITC pre-treatment in oxidative stress condition. The present findings speculated that pre-treatment with GMG-ITC may alleviate oxidative stress condition in neuronal cells by reducing ROS production level and protect the cells against apoptosis via neurodegenerative disease potential pathways.
  8. Fulltext Differential expression of entorhinal cortex and hippocampal subfields α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors enhanced learning and memory of rats following administration of Centella asiatica
    Wong JH, Muthuraju S, Reza F, Senik MH, Zhang J, Mohd Yusuf Yeo NAB, et al.
    Biomed Pharmacother, 2019 Feb;110:168-180.
    PMID: 30469081 DOI: 10.1016/j.biopha.2018.11.044
    Centella asiatica (CA) is a widely used traditional herb, notably for its cognitive enhancing effect and potential to increase synaptogenesis. The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) and N-methyl-D-aspartate receptors (NMDARs) mediate fast excitatory neurotransmission with key roles in long-term potentiation which is believed to be the cellular mechanism of learning and memory. Improved learning and memory can be an indication to the surface expression level of these receptors. Our previous study demonstrated that administration of CA extract improved learning and memory and enhanced expression of AMPAR GluA1 subunit while exerting no significant effects on GABAA receptors of the hippocampus in rats. Hence, to further elucidate the effects of CA, this study investigated the effects of CA extract in recognition memory and spatial memory, and its effects on AMPAR GluA1 and GluA2 subunit and NMDAR GluN2 A and GluN2B subunit expression in the entorhinal cortex (EC) and hippocampal subfields CA1 and CA3. The animals were administered with saline, 100 mg/kg, 300 mg/kg, and 600 mg/kg of CA extract through oral gavage for 14 days, followed by behavioural analysis through Open Field Test (OFT), Novel Object Recognition Task (NORT), and Morris Water Maze (MWM) and lastly morphological and immunohistochemical analysis of the surface expression of AMPAR and NMDAR subunits were performed. The results showed that 14 days of administration of 600 mg/kg of CA extract significantly improved memory assessed through NORT while 300 mg/kg of CA extract significantly improved memory of the animals assessed through MWM. Immunohistochemical analysis revealed differential modulation effects on the expressions of receptor subunits across CA1, CA3 and EC. The CA extract at the highest dose (600 mg/kg) significantly enhanced the expression of AMPAR subunit GluA1 and GluA2 in CA1, CA3 and EC, and NMDAR subunit GluN2B in CA1 and CA3 compared to control. At 300 mg/kg, CA significantly increased expression of AMPAR GluA1 in CA1 and EC, and GluA2 in CA1, CA3 and EC while 100 mg/kg of CA significantly increased expression of only AMPAR subunit GluA2 in CA3 and EC. Expression of NMDAR subunit GluN2 A was significantly reduced in the CA3 (at 100, 300, and 600 mg/kg) while no significant changes of subunit expression was observed in CA1 and EC compared to control. The results suggest that the enhanced learning and memory observed in animals administered with CA was mainly mediated through increased expression of AMPAR GluA1 and GluA2 subunits and differential expression of NMDAR GluN2 A and GluN2B subunits in the hippocampal subfields and EC. With these findings, the study revealed a new aspect of cognitive enhancing effect of CA and its therapeutic potentials through modulating receptor subunit expression.
  9. Fulltext Gene regulation by antisense transcription: A focus on neurological and cancer diseases
    Najafi S, Tan SC, Raee P, Rahmati Y, Asemani Y, Lee EHC, et al.
    Biomed Pharmacother, 2022 Jan;145:112265.
    PMID: 34749054 DOI: 10.1016/j.biopha.2021.112265
    Advances in high-throughput sequencing over the past decades have led to the identification of thousands of non-coding RNAs (ncRNAs), which play a major role in regulating gene expression. One emerging class of ncRNAs is the natural antisense transcripts (NATs), the RNA molecules transcribed from the opposite strand of a protein-coding gene locus. NATs are known to concordantly and discordantly regulate gene expression in both cis and trans manners at the transcriptional, post-transcriptional, translational, and epigenetic levels. Aberrant expression of NATs can therefore cause dysregulation in many biological pathways and has been observed in many genetic diseases. This review outlines the involvements and mechanisms of NATs in the pathogenesis of various diseases, with a special emphasis on neurodegenerative diseases and cancer. We also summarize recent findings on NAT knockdown and/or overexpression experiments and discuss the potential of NATs as promising targets for future gene therapies.
  10. An insight on the future therapeutic application potential of Stevia rebaudiana Bertoni for atherosclerosis and cardiovascular diseases
    Ilias N, Hamzah H, Ismail IS, Mohidin TBM, Idris MF, Ajat M
    Biomed Pharmacother, 2021 Sep 23;143:112207.
    PMID: 34563950 DOI: 10.1016/j.biopha.2021.112207
    Stevia rebaudiana Bertoni is a native plant to Paraguay. The extracts have been used as a famous sweetening agent, and the bioactive components derived from stevia possess a broad spectrum of therapeutical potential for various illnesses. Among its medicinal benefits are anti-hypertensive, anti-tumorigenic, anti-diabetic, and anti-hyperlipidemia. Statins (3-hydro-3-methylglutaryl-coenzyme A reductase inhibitor) are a class of drugs used to treat atherosclerosis. Statins are explicitly targeting the HMG-CoA reductase, an enzyme in the rate-limiting step of cholesterol biosynthesis. Despite being widely used in regulating plasma cholesterol levels, the adverse effects of the drug are a significant concern among clinicians and patients. Hence, steviol glycosides derived from stevia have been proposed as an alternative in replacing statins. Diterpene glycosides from stevia, such as stevioside and rebaudioside A have been evaluated for their efficacy in alleviating cholesterol levels. These glycosides are a potential candidate in treating and preventing atherosclerosis provoked by circulating lipid retention in the sub-endothelial lining of the artery. The present review is an effort to integrate the pathogenesis of atherosclerosis, involvement of lipid droplets biogenesis and its associated proteins in atherogenesis, current approaches to treat atherosclerosis, and pharmacological potential of stevia in treating the disease.
  11. Phytosterols as a natural anticancer agent: Current status and future perspective
    Shahzad N, Khan W, Md S, Ali A, Saluja SS, Sharma S, et al.
    Biomed Pharmacother, 2017 Apr;88:786-794.
    PMID: 28157655 DOI: 10.1016/j.biopha.2017.01.068
    Phytosterols are naturally occurring compounds in plants, structurally similar to cholesterol. The human diet is quite abundant in sitosterol and campesterol. Phytosterols are known to have various bioactive properties including reducing intestinal cholesterol absorption which alleviates blood LDL-cholesterol and cardiovascular problems. It is indicated that phytosterol rich diets may reduce cancer risk by 20%. Phytosterols may also affect host systems, enabling antitumor responses by improving immune response recognition of cancer, affecting the hormone dependent endocrine tumor growth, and by sterol biosynthesis modulation. Moreover, phytosterols have also exhibited properties that directly inhibit tumor growth, including reduced cell cycle progression, apoptosis induction, and tumor metastasis inhibition. The objective of this review is to summarize the current knowledge on occurrences, chemistry, pharmacokinetics and potential anticancer properties of phytosterols in vitro and in vivo. In conclusion, anticancer effects of phytosterols have strongly been suggested and support their dietary inclusion to prevent and treat cancers.
  12. Fulltext Oxidative stress cytotoxicity induced by platinum-doped magnesia nanoparticles in cancer cells
    Al-Fahdawi MQ, Al-Doghachi FAJ, Abdullah QK, Hammad RT, Rasedee A, Ibrahim WN, et al.
    Biomed Pharmacother, 2021 Jun;138:111483.
    PMID: 33744756 DOI: 10.1016/j.biopha.2021.111483
    The aim of this study was to prepare, characterize, and determine the in vitro anticancer effects of platinum-doped magnesia (Pt/MgO) nanoparticles. The chemical compositions, functional groups, and size of nanoparticles were determined using X-ray diffraction, Fourier transform infrared spectroscopy, energy dispersive X-ray spectroscopy, transmission electron microscopy, and scanning electron microscopy. Pt/MgO nanoparticles were cuboid and in the nanosize range of 30-50 nm. The cytotoxicity of Pt/MgO nanoparticles was determined via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay on the human lung and colonic cancer cells (A549 and HT29 respectively) and normal human lung and colonic fibroblasts cells (MRC-5 and CCD-18Co repectively). The Pt/MgO nanoparticles were relatively innocuous to normal cells. Pt/MgO nanoparticles downregulated Bcl-2 and upregulated Bax and p53 tumor suppressor proteins in the cancer cells. Pt/MgO nanoparticles also induced production of reactive oxygen species, decreased cellular glutathione level, and increased lipid peroxidation. Thus, the anticancer effects of Pt/MgO nanoparticles were attributed to the induction of oxidative stress and apoptosis. The study showed the potential of Pt/MgO nanoparticles as an anti-cancer compound.
  13. Fulltext Epidemiology, clinical ramifications, and cellular pathogenesis of COVID-19 mRNA-vaccination-induced adverse cardiovascular outcomes: A state-of-the-heart review
    Almas T, Rehman S, Mansour E, Khedro T, Alansari A, Malik J, et al.
    Biomed Pharmacother, 2022 May;149:112843.
    PMID: 35325848 DOI: 10.1016/j.biopha.2022.112843
    The coronavirus disease 2019 (COVID-19) has overwhelming healthcare systems globally. To date, a myriad of therapeutic regimens has been employed in an attempt to curb the ramifications of a severe COVID-19 infection. Amidst the ongoing pandemic, the advent and efficacious uptake of COVID-19 vaccination has significantly reduced disease-related hospitalizations and mortality. Nevertheless, many side-effects are being reported after COVID-19 vaccinations and myocarditis is the most commonly reported sequelae post vaccination. Majority of these diseases are associated with COVID-19 mRNA vaccines. Various studies have established a temporal relationship between these complications, yet the causality and the underlying pathogenesis remain hypothetical. In this review, we aim to critically appraise the available literature regarding the cardiovascular side effects of the various mRNA vaccines and the associated pathophysiology.
  14. d-galactose and aluminium chloride induced rat model with cognitive impairments
    Chiroma SM, Mohd Moklas MA, Mat Taib CN, Baharuldin MTH, Amon Z
    Biomed Pharmacother, 2018 Jul;103:1602-1608.
    PMID: 29864948 DOI: 10.1016/j.biopha.2018.04.152
    Cognitive impairments and cholinergic dysfunctions have been well reported in old age disorders including Alzheimer's disease (AD). d-galactose (D-gal) has been reported as a senescence agent while aluminium act as a neurotoxic metal, but little is known about their combined effects at different doses. The aim of this study was to establish an animal model with cognitive impairments by comparing the effects of different doses of co-administrated D-gal and aluminium chloride (AlCl3). In this study male albino wistar rats were administered with D-gal 60 mg/kg.bwt intra peritoneally (I.P) injected and AlCl3 (100, 200, or 300 mg/kg.bwt.) was orally administered once daily for 10 consecutive weeks. Performance of the rats were evaluated through behavioural assessments; Morris water maze (MWM) and open field tests (OFT); histopathological examination was performed on the hippocampus; moreover biochemical measurements of acetylcholinesterase (AChE) and hyperphosphorylated tau protein (p-tau) were examined. The results of this experiment on rats treated with D-gal 60 + AlCl3 200 mg/kg.bwt showed near ideal cognitive impairments. The rats exhibited an obvious memory and learning deficits, marked neuronal loss in hippocampus, showed increase in AChE activities and high expression of p-tau within the tissues of the brain. This study concludes that D-gal 60 + AlCl3 200 mg/kg.bwt as the ideal dose for mimicking AD like cognitive impairments in albino wistar rats. It is also crucial to understand the pathogenesis of this neurodegenerative disease and for drug discovery.
  15. Association of genotypes and haplotypes of multi-drug transporter genes ABCB1 and ABCG2 with clinical response to imatinib mesylate in chronic myeloid leukemia patients
    Au A, Aziz Baba A, Goh AS, Wahid Fadilah SA, Teh A, Rosline H, et al.
    Biomed Pharmacother, 2014 Apr;68(3):343-9.
    PMID: 24581936 DOI: 10.1016/j.biopha.2014.01.009
    The introduction and success of imatinib mesylate (IM) has become a paradigm shift in chronic myeloid leukemia (CML) treatment. However, the high efficacy of IM has been hampered by the issue of clinical resistance that might due to pharmacogenetic variability. In the current study, the contribution of three common single nucleotide polymorphisms (SNPs) of ABCB1 (T1236C, G2677T/A and C3435T) and two SNPs of ABCG2 (G34A and C421A) genes in mediating resistance and/or good response among 215 CML patients on IM therapy were investigated. Among these patients, the frequency distribution of ABCG2 421 CC, CA and AA genotypes were significantly different between IM good response and resistant groups (P=0.01). Resistance was significantly associated with patients who had homozygous ABCB1 1236 CC genotype with OR 2.79 (95%CI: 1.217-6.374, P=0.01). For ABCB1 G2677T/A polymorphism, a better complete cytogenetic remission was observed for patients with variant TT/AT/AA genotype, compared to other genotype groups (OR=0.48, 95%CI: 0.239-0.957, P=0.03). Haplotype analysis revealed that ABCB1 haplotypes (C1236G2677C3435) was statistically linked to higher risk to IM resistance (25.8% vs. 17.4%, P=0.04), while ABCG2 diplotype A34A421 was significantly correlated with IM good response (9.1% vs. 3.9%, P=0.03). In addition, genotypic variant in ABCG2 421C>A was associated with a major molecular response (MMR) (OR=2.20, 95%CI: 1.273-3.811, P=0.004), whereas ABCB1 2677G>T/A variant was associated with a significantly lower molecular response (OR=0.49, 95%CI: 0.248-0.974, P=0.04). However, there was no significant correlation of these SNPs with IM intolerance and IM induced hepatotoxicity. Our results suggest the usefulness of genotyping of these single nucleotide polymorphisms in predicting IM response among CML patients.
  16. Pharmacological insights into antioxidants against colorectal cancer: A detailed review of the possible mechanisms
    Gothai S, Muniandy K, Gnanaraj C, Ibrahim IAA, Shahzad N, Al-Ghamdi SS, et al.
    Biomed Pharmacother, 2018 Nov;107:1514-1522.
    PMID: 30257369 DOI: 10.1016/j.biopha.2018.08.112
    Colorectal cancer (CRC) is ranked as the fourth most lethal and commonly diagnosed cancer in the world according to the National Cancer Institute's latest report. Treatment methods for CRC are constantly being studied for advancement, which leads for more clinically effective cancer curing strategy. Patients with prolonged chronic inflammation caused by ulcerative colitis or similar inflammatory bowel disease are known to have high risks of developing CRC. But at a molecular level, oxidative stress due to reactive oxygen species (ROS) is an important trigger for cancer. Hence, in recent years, exogenous antioxidants have been immensely experimented in pre-clinical and clinical trials, considering it as a potential cure for CRC. Significantly, potential antioxidant compounds especially derivatives of medicinal plants have received great attention in the current research trend for CRC treatment. Though antioxidant compounds seem to have beneficial properties for the treatment of CRC, there are also limitations for pure compounds to be tested clinically. Therefore, this review aims to delineate the pharmacological awareness among researchers on using antioxidant compounds to treat CRC and the measures taken to prove the effectiveness of such compounds as impending drug candidates for CRC treatment in modern medication.
  17. Fulltext From nature to nanotechnology: The interplay of traditional medicine, green chemistry, and biogenic metallic phytonanoparticles in modern healthcare innovation and sustainability
    Puri A, Mohite P, Maitra S, Subramaniyan V, Kumarasamy V, Uti DE, et al.
    Biomed Pharmacother, 2024 Jan;170:116083.
    PMID: 38163395 DOI: 10.1016/j.biopha.2023.116083
    As we navigate the modern era, the intersection of time-honoured natural remedies and contemporary scientific approaches forms a burgeoning frontier in global healthcare. For generations, natural products have been foundational to health solutions, serving as the primary healthcare choice for 80% to 85% of the world's population. These herbal-based, nature-derived substances, significant across diverse geographies, necessitate a renewed emphasis on enhancing their quality, efficacy, and safety. In the current century, the advent of biogenic phytonanoparticles has emerged as an innovative therapeutic conduit, perfectly aligning with principles of environmental safety and scientific ingenuity. Utilizing green chemistry techniques, a spectrum of metallic nanoparticles including elements such as copper, silver, iron, zinc, and titanium oxide can be produced with attributes of non-toxicity, sustainability, and economic efficiency. Sophisticated herb-mediated processes yield an array of plant-originated nanomaterials, each demonstrating unique physical, chemical, and biological characteristics. These attributes herald new therapeutic potentials, encompassing antioxidants, anti-aging applications, and more. Modern technology further accelerates the synthesis of natural products within laboratory settings, providing an efficient alternative to conventional isolation methods. The collaboration between traditional wisdom and advanced methodologies now signals a new epoch in healthcare. Here, the augmentation of traditional medicine is realized through rigorous scientific examination. By intertwining ethical considerations, cutting-edge technology, and natural philosophy, the realms of biogenic phytonanoparticles and traditional medicine forge promising pathways for research, development, and healing. The narrative of this seamless integration marks an exciting evolution in healthcare, where the fusion of sustainability and innovation crafts a future filled with endless possibilities for human well-being. The research in the development of metallic nanoparticles is crucial for unlocking their potential in revolutionizing fields such as medicine, catalysis, and electronics, promising groundbreaking applications with enhanced efficiency and tailored functionalities in future technologies. This exploration is essential for harnessing the unique properties of metallic nanoparticles to address pressing challenges and advance innovations across diverse scientific and industrial domains.
  18. Fulltext Review of anticancer potentials and structure-activity relationships (SAR) of rhodanine derivatives
    Yin LJ, Bin Ahmad Kamar AKD, Fung GT, Liang CT, Avupati VR
    Biomed Pharmacother, 2022 Jan;145:112406.
    PMID: 34785416 DOI: 10.1016/j.biopha.2021.112406
    Rhodanine has been recognized as a privileged scaffold in medicinal chemistry due to its well-known ability to demonstrate a broad range of biological activities. The possibility of structural diversification has contributed to the significance of rhodanine structure in effective drug discovery and design. Many studies have confirmed the potential of rhodanine-derived compounds in the treatment of different types of cancer through the apoptosis induction mechanism. Furthermore, most of the rhodanine derivatives exhibited remarkable anticancer activity in the micromolar range while causing negligible cytotoxicity to normal cells. This review critically describes the anticancer activity profile of reported rhodanine compounds and the structure-activity relationships (SAR) to highlight the value of rhodanine as the core structure for future cancer drug development as well as to assist the researchers in rational drug design.
  19. Fulltext 2D nanostructures: Potential in diagnosis and treatment of Alzheimer's disease
    Tufail S, Sherwani MA, Shamim Z, Abdullah, Goh KW, Alomary MN, et al.
    Biomed Pharmacother, 2024 Jan;170:116070.
    PMID: 38163396 DOI: 10.1016/j.biopha.2023.116070
    Two-dimensional (2D) nanomaterials have garnered enormous attention seemingly due to their unusual architecture and properties. Graphene and graphene oxide based 2D nanomaterials remained the most sought after for several years but the quest to design superior 2D nanomaterials which can find wider application gave rise to development of non-graphene 2D materials as well. Consequently, in addition to graphene based 2D nanomaterials, 2D nanostructures designed using macromolecules (such as DNAs, proteins, peptides and peptoids), transition metal dichalcogenides, transition-metal carbides and/or nitrides (MXene), black phosphorous, chitosan, hexagonal boron nitrides, and graphitic carbon nitride, and covalent organic frameworks have been developed. Interestingly, these 2D nanomaterials have found applications in diagnosis and treatment of various diseases including Alzheimer's disease (AD). Although AD is one of the most debilitating neurodegenerative conditions across the globe; unfortunately, there remains a paucity of effective diagnostic and/or therapeutic intervention for it till date. In this scenario, nanomaterial-based biosensors, or therapeutics especially 2D nanostructures are emerging to be promising in this regard. This review summarizes the diagnostic and therapeutic platforms developed for AD using 2D nanostructures. Collectively, it is worth mentioning that these 2D nanomaterials would seemingly provide an alternative and intriguing platform for biomedical interventions.
  20. Fulltext Pharmacokinetics and antiangiogenic studies of potassium koetjapate in rats
    Jafari SF, Al-Suede FSR, Yehya AHS, Ahamed MBK, Shafaei A, Asif M, et al.
    Biomed Pharmacother, 2020 Oct;130:110602.
    PMID: 32771894 DOI: 10.1016/j.biopha.2020.110602
    PURPOSE: Koetjapic acid is an active compound of a traditional medicinal plant, Sandoricum koetjape. Although koetjapic acid has a promising anticancer potential, yet it is highly insoluble in aqueous solutions. To increase aqueous solubility of koetjapic acid, we have previously reported a chemical modification of koetjapic acid to potassium koetjapate (KKA). However, pharmacokinetics of KKA has not been studied. In this study, pharmacokinetics and antiangiogenic efficacy of KKA are investigated.

    METHODS: Pharmacokinetics of KKA was studied after intravenous and oral administration in SD rats using HPLC. Anti-angiogenic efficacy of KKA was investigated in rat aorta, human endothelial cells (EA.hy926) and nude mice implanted with matrigel.

    RESULTS: Pharmacokinetic study revealed that KKA was readily absorbed into blood and stayed for a long time in the body with Tmax 2.89 ± 0.12 h, Cmax 7.24 ± 0.36 μg/mL and T1/2 1.46 ± 0.03 h. The pharmacological results showed that KKA significantly suppressed sprouting of microvessels in rat aorta with IC50 18.4 ± 4.2 μM and demonstrated remarkable inhibition of major endothelial functions such as migration, differentiation and VEGF expression in endothelial cells. Further, KKA significantly inhibited vascularization in matrigel plugs implanted in nude mice.

    CONCLUSIONS: The results indicate that bioabsorption of KKA from oral route was considerably efficient with longer retention in body than compared to that of the intravenous route. Further, improved antiangiogenic activity of KKA was recorded which could probably be due to its increased solubility and bioavailability. The results revealed that KKA inhibits angiogenesis by suppressing endothelial functions and expression of VEGF.

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