Displaying publications 1 - 20 of 192 in total

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  1. Zuraini NZA, Sekar M, Wu YS, Gan SH, Bonam SR, Mat Rani NNI, et al.
    Vasc Health Risk Manag, 2021;17:739-769.
    PMID: 34858028 DOI: 10.2147/VHRM.S328096
    Cardiovascular diseases (CVDs) are one of the leading causes of morbidity and mortality in both developed and developing countries, affecting millions of individuals each year. Despite the fact that successful therapeutic drugs for the management and treatment of CVDs are available on the market, nutritional fruits appear to offer the greatest benefits to the heart and have been proved to alleviate CVDs. Experimental studies have also demonstrated that nutritional fruits have potential protective effects against CVDs. The aim of the review was to provide a comprehensive summary of scientific evidence on the effect of 10 of the most commonly available nutritional fruits reported against CVDs and describe the associated mechanisms of action. Relevant literatures were searched and collected from several scientific databases including PubMed, ScienceDirect, Google Scholar and Scopus. In the context of CVDs, 10 commonly consumed nutritious fruits including apple, avocado, grapes, mango, orange, kiwi, pomegranate, papaya, pineapple, and watermelon were analysed and addressed. The cardioprotective mechanisms of the 10 nutritional fruits were also compiled and highlighted. Overall, the present review found that the nutritious fruits and their constituents have significant benefits for the management and treatment of CVDs such as myocardial infarction, hypertension, peripheral artery disease, coronary artery disease, cardiomyopathies, dyslipidemias, ischemic stroke, aortic aneurysm, atherosclerosis, cardiac hypertrophy and heart failure, diabetic cardiovascular complications, drug-induced cardiotoxicity and cardiomyopathy. Among the 10 nutritional fruits, pomegranate and grapes have been well explored, and the mechanisms of action are well documented against CVDs. All of the nutritional fruits mentioned are edible and readily accessible on the market. Consuming these fruits, which may contain varying amounts of active constituents depending on the food source and season, the development of nutritious fruits-based health supplements would be more realistic for consistent CVD protection.
  2. Zunura'in Z, Almardhiyah AR, Gan SH, Arifin WN, Sirajudeen K, Bhavaraju V, et al.
    Asian Pac J Cancer Prev, 2016;17(9):4439-4444.
    PMID: 27797258
    The objective of this case-control study was to determine anthropometric and reproductive factors associated with the development of breast cancer among women. Fifty-six newly diagnosed breast cancer patients were recruited from the Oncology Clinic, Universiti Sains Malaysia (USM), and 56 healthy female hospital employees were recruited as controls. Socio-demographic and reproductive data were obtained using a standard questionnaire. Anthropometric factors (body weight, height, body fat percentage, visceral fat and waist and hip circumference) were assessed. A high waist circumference (adjusted OR= 1.04, [95% CI: 1.00, 1.09]) and being more than 30 years of age at rst full-term pregnancy (adjusted OR=3.77, [95% CI: 1.10, 12.90]) were predictors of breast cancer development. The results of this study indicate that weight and reproductive health management should be emphasized for breast cancer prevention in Malaysia.

    Study site: Oncology clinic, Hospital Universiti Sains Malaysia (HUSM)
  3. Zakaria Z, Zainal Abidin ZF, Gan SH, Wan Abdul Hamid WZ, Mohamed M
    J Taibah Univ Med Sci, 2018 Dec;13(6):535-540.
    PMID: 31435374 DOI: 10.1016/j.jtumed.2018.04.013
    Objectives: In this study, we aimed to determine the effect of honey supplementation on the safety profiles of postmenopausal breast cancer patients.

    Methods: Seventy-two postmenopausal women with stage I, II, or III breast cancer from the Oncology Clinic, Universiti Sains Malaysia Hospital were treated with anastrozole (1 mg/day). Patients were randomly assigned to one of the two groups (n = 36/group): a control group (no honey) and a honey group (20 g/day of honey for 12 weeks). Fasting blood samples were obtained pre- and post-intervention to investigate differences in the haematological, renal, and liver profiles of patients in both the groups.

    Results: Post-intervention, alanine aminotransferase levels were significantly higher in the control group than in the honey group. In the honey group, white blood cell counts, platelet counts, and creatinine levels were significantly higher following honey supplementation for 12 weeks. Nevertheless, the values were still within normal ranges.

    Conclusions: The present study suggests that honey supplementation of 20 g/day for 12 weeks is safe and beneficial for postmenopausal breast cancer patients.

  4. Yusof W, Gan SH
    Clin Chim Acta, 2009 May;403(1-2):105-9.
    PMID: 19361454 DOI: 10.1016/j.cca.2009.01.032
    CYP2A6 gene encodes the principal enzyme involved in the metabolism of many drugs including artesunate. We developed a simplified duplex nested PCR method for the detection of the CYP2A61B, CYP2A62, CYP2A64, CYP2A67, CYP2A68 and CYP2A69 variant alleles highly prevalent among Malaysian population.
  5. Yap KM, Sekar M, Seow LJ, Gan SH, Bonam SR, Mat Rani NNI, et al.
    PMID: 34548817 DOI: 10.2147/BCTT.S316667
    Globally, breast cancer is the most common cancer type and is one of the most significant causes of deaths in women. To date, multiple clinical interventions have been applied, including surgical resection, radiotherapy, endocrine therapy, targeted therapy and chemotherapy. However, 1) the lack of therapeutic options for metastatic breast cancer, 2) resistance to drug therapy and 3) the lack of more selective therapy for triple-negative breast cancer are some of the major challenges in tackling breast cancer. Given the safe nature of natural products, numerous studies have focused on their anti-cancer potentials. Mangifera indica, commonly known as mango, represents one of the most extensively investigated natural sources. In this review, we provide a comprehensive overview of M. indica extracts (bark, kernel, leaves, peel and pulp) and phytochemicals (mangiferin, norathyriol, gallotannins, gallic acid, pyrogallol, methyl gallate and quercetin) reported for in vitro and in vivo anti-breast cancer activities and their underlying mechanisms based on relevant literature from several scientific databases, including PubMed, Scopus and Google Scholar till date. Overall, the in vitro findings suggest that M. indica extracts and/or phytochemicals inhibit breast cancer cell growth, proliferation, migration and invasion as well as trigger apoptosis and cell cycle arrest. In vivo results demonstrated that there was a reduction in breast tumor xenograft growth. Several potential mechanisms underlying the anti-breast cancer activities have been reported, which include modulation of oxidative status, receptors, signalling pathways, miRNA expression, enzymes and cell cycle regulators. To further explore this medicinal plant against breast cancer, future research directions are addressed. The outcomes of the review revealed that M. indica extracts and their phytochemicals may have potential benefits in the management of breast cancer in women. However, to validate its utility in the creation of innovative and potent therapeutic agents to treat breast cancer, more dedicated research, especially clinical studies are needed to explore the anti-breast cancer potentials of M. indica extracts and their phytochemicals.
  6. Yap KM, Sekar M, Wu YS, Gan SH, Rani NNIM, Seow LJ, et al.
    Saudi J Biol Sci, 2021 Dec;28(12):6730-6747.
    PMID: 34866972 DOI: 10.1016/j.sjbs.2021.07.046
    Breast cancer (BC) has high incidence and mortality rates, making it a major global health issue. BC treatment has been challenging due to the presence of drug resistance and the limited availability of therapeutic options for triple-negative and metastatic BC, thereby urging the exploration of more effective anti-cancer agents. Hesperidin and its aglycone hesperetin, two flavonoids from citrus species, have been extensively evaluated for their anti-cancer potentials. In this review, available literatures on the chemotherapeutic and chemosensitising activities of hesperidin and hesperetin in preclinical BC models are reported. The safety and bioavailability of hesperidin and hesperetin as well as the strategies to enhance their bioavailability are also discussed. Overall, hesperidin and hesperetin can inhibit cell proliferation, migration and BC stem cells as well as induce apoptosis and cell cycle arrest in vitro. They can also inhibit tumour growth, metastasis and neoplastic changes in tissue architecture in vivo. Moreover, the co-administration of hesperidin or hesperetin with doxorubicin, letrozole or tamoxifen can enhance the efficacies of these clinically available agents. These chemotherapeutic and chemosensitising activities of hesperidin and hesperetin have been linked to several mechanisms, including the modulation of signalling pathways, glucose uptake, enzymes, miRNA expression, oxidative status, cell cycle regulatory proteins, tumour suppressor p53, plasma and liver lipid profiles as well as DNA repair mechanisms. However, poor water solubility, extensive phase II metabolism and apical efflux have posed limitations to the bioavailability of hesperidin and hesperetin. Various strategies for bioavailability enhancement have been studied, including the utilisation of nano-based drug delivery systems and the co-administration of hesperetin with other flavonoids. In particular, nanoformulated hesperidin and hesperetin possess greater chemotherapeutic and chemosensitising activities than free compounds. Despite promising preclinical results, further safety and efficacy evaluation of hesperidin and hesperetin as well as their nanoformulations in clinical trials is required to ascertain their potentials to be developed as clinically useful agents for BC treatment.
  7. Yap KM, Sekar M, Fuloria S, Wu YS, Gan SH, Mat Rani NNI, et al.
    Int J Nanomedicine, 2021;16:7891-7941.
    PMID: 34880614 DOI: 10.2147/IJN.S328135
    Despite recent advances in the diagnosis and treatment of breast cancer (BC), it remains a global health issue affecting millions of women annually. Poor prognosis in BC patients is often linked to drug resistance as well as the lack of effective therapeutic options for metastatic and triple-negative BC. In response to these unmet needs, extensive research efforts have been devoted to exploring the anti-BC potentials of natural products owing to their multi-target mechanisms of action and good safety profiles. Various medicinal plant extracts/essential oils and natural bioactive compounds have demonstrated anti-cancer activities in preclinical BC models. Despite the promising preclinical results, however, the clinical translation of natural products has often been hindered by their poor stability, aqueous solubility and bioavailability. There have been attempts to overcome these limitations, particularly via the use of nano-based drug delivery systems (NDDSs). This review highlights the tumour targeting mechanisms of NDDSs, the advantages and disadvantages of the major classes of NDDSs and their current clinical status in BC treatment. Besides, it also discusses the proposed anti-BC mechanisms and nanoformulations of nine medicinal plants' extracts/essential oils and nine natural bioactive compounds; selected via the screening of various scientific databases, including PubMed, Scopus and Google Scholar, based on the following keywords: "Natural Product AND Nanoparticle AND Breast Cancer". Overall, these nanoformulations exhibit improved anti-cancer efficacy against preclinical BC models, with some demonstrating biocompatibility with normal cell lines and mouse models. Further clinical studies are, however, warranted to ascertain their efficacy and biocompatibility in humans.
  8. Yahya DN, Guad RM, Wu YS, Gan SH, Gopinath SCB, Zakariah HA, et al.
    J Pers Med, 2023 Jan 31;13(2).
    PMID: 36836504 DOI: 10.3390/jpm13020270
    SLC1A2 is a gene encoded for the excitatory amino acid transporter 2 which is responsible for glutamate reuptake from the synaptic cleft in the central nervous system. Recent studies have suggested that polymorphisms on glutamate transporters can affect drug dependence, leading to the development of neurological diseases and psychiatric disorders. Our study investigated the association of rs4755404 single nucleotide polymorphism (SNP) of the SLC1A2 gene with methamphetamine (METH) dependence and METH-induced psychosis and mania in a Malaysian population. The rs4755404 gene polymorphism was genotyped in METH-dependent male subjects (n = 285) and male control subjects (n = 251). The subjects consisted of the four ethnic groups in Malaysia (Malay, Chinese, Kadazan-Dusun, and Bajau). Interestingly, there was a significant association between rs4755404 polymorphism and METH-induced psychosis in the pooled METH-dependent subjects in terms of genotype frequency (p = 0.041). However, there was no significant association between rs4755404 polymorphism and METH dependence. Also, the rs455404 polymorphism was not significantly associated with METH-induced mania for both genotype frequencies and allele frequencies in the METH-dependent subjects, regardless of stratification into the different ethnicities. Our study suggests that the SLC1A2 rs4755404 gene polymorphism confers some susceptibility to METH-induced psychosis, especially for those who carry the GG homozygous genotype.
  9. Wei LK, Sutherland H, Au A, Camilleri E, Haupt LM, Gan SH, et al.
    Biomed Res Int, 2015;2015:167976.
    PMID: 25705649 DOI: 10.1155/2015/167976
    Stroke is a multifactorial disease that may be associated with aberrant DNA methylation profiles. We investigated epigenetic dysregulation for the methylenetetrahydrofolate reductase (MTHFR) gene among ischemic stroke patients. Cases and controls were recruited after obtaining signed written informed consents following a screening process against the inclusion/exclusion criteria. Serum vitamin profiles (folate, vitamin B12, and homocysteine) were determined using immunoassays. Methylation profiles for CpGs A and B in the MTHFR gene were determined using a bisulfite-pyrosequencing method. Methylation of MTHFR significantly increased the susceptibility risk for ischemic stroke. In particular, CpG A outperformed CpG B in mediating serum folate and vitamin B12 levels to increase ischemic stroke susceptibility risks by 4.73-fold. However, both CpGs A and B were not associated with serum homocysteine levels or ischemic stroke severity. CpG A is a potential epigenetic marker in mediating serum folate and vitamin B12 to contribute to ischemic stroke.
  10. Wei LK, Menon S, Griffiths LR, Gan SH
    J Hum Hypertens, 2015 Feb;29(2):99-104.
    PMID: 25055800 DOI: 10.1038/jhh.2014.53
    Irregular atrial pressure, defective folate and cholesterol metabolism contribute to the pathogenesis of hypertension. However, little is known about the combined roles of the methylenetetrahydrofolate reductase (MTHFR), apolipoprotein-E (ApoE) and angiotensin-converting enzyme (ACE) genes, which are involved in metabolism and homeostasis. The objective of this study is to investigate the association of the MTHFR 677 C>T and 1298A>C, ACE insertion-deletion (I/D) and ApoE genetic polymorphisms with hypertension and to further explore the epistasis interactions that are involved in these mechanisms. A total of 594 subjects, including 348 normotensive and 246 hypertensive ischemic stroke subjects were recruited. The MTHFR 677 C>T and 1298A>C, ACE I/D and ApoEpolymorphisms were genotyped and the epistasis interaction were analyzed. The MTHFR 677 C>T and ApoE polymorphisms demonstrated significant associations with susceptibility to hypertension in multiple logistic regression models, multifactor dimensionality reduction and a classification and regression tree. In addition, the logistic regression model demonstrated that significant interactions between the ApoE E3E3, E2E4, E2E2 and MTHFR 677 C>T polymorphisms existed. In conclusion, the results of this epistasis study indicated significant association between the ApoE and MTHFR polymorphisms and hypertension.
  11. Wei LK, Au A, Menon S, Gan SH, Griffiths LR
    J Stroke Cerebrovasc Dis, 2015 Sep;24(9):2017-25.
    PMID: 26187788 DOI: 10.1016/j.jstrokecerebrovasdis.2015.04.011
    The purpose of this study was threefold. First, it was to determine the relationship between serum vitamin profiles and ischemic stroke. The second purpose was to investigate the association of methylenetetrahydrofolate reductase (MTHFR), endothelial nitric oxide synthase (eNOS), angiotensin converting enzyme (ACE), and apolipoprotein-E (ApoE) gene polymorphisms with ischemic stroke and further correlate with serum vitamin profiles among ischemic stroke patients. The third purpose of the study was to highlight the interaction of MTHFR and eNOS haplotypes with serum vitamin profiles and ischemic stroke risks.
  12. Wei LK, Sutherland H, Au A, Camilleri E, Haupt LM, Gan SH, et al.
    J Clin Lab Anal, 2016 Jul;30(4):335-44.
    PMID: 26109141 DOI: 10.1002/jcla.21860
    BACKGROUND: Determination of the differential DNA methylation patterns of methylenetetrahydrofolate reductase (MTHFR) that are associated with differential MTHFR activity is important to understand the pathogenesis of ischemic stroke. However, to date, no data are available on the differential DNA methylation profiles of Kelantanese Malays. Therefore, we developed a rapid and efficient serial pyrosequencing assay to determine differential DNA methylation profiles of MTHFR, which help to further our understanding of the pathogenesis of ischemic stroke. The developed assay also served as the validation platform for our previous computational epigenetic research on MTHFR.

    METHODS: Polymerase chain reaction primers were designed and validated to specifically amplify the cytosine that is followed by guanine residues (CpGs) A and B regions. Prior epigenotyping on 110 Kelantanese Malays, the serial pyrosequencing assays for the CpGs A and B regions were validated using five validation controls. The mean values of the DNA methylation profiles of CpGs A and B were calculated.

    RESULTS: The mean DNA methylation levels for CpGs A and B were 0.984 ± 0.582 and 2.456 ± 1.406, respectively. The CpGs 8 and 20 showed the highest (5.581 ± 4.497) and the lowest (0.414 ± 2.814) levels of DNA methylation at a single-base resolution.

    CONCLUSION: We have successfully developed and validated a pyrosequencing assay that is fast and can yield high-quality pyrograms for DNA methylation analysis and is therefore applicable to high throughput study. Using this newly developed pyrosequencing assay, the MTHFR DNA methylation profiles of 110 Kelantanese Malays were successfully determined. It also validated our computational epigenetic research on MTHFR.

  13. Wei K, Sutherland H, Camilleri E, Haupt LM, Griffiths LR, Gan SH
    Mol Biol Rep, 2014 Dec;41(12):8285-92.
    PMID: 25213548 DOI: 10.1007/s11033-014-3729-x
    Computational epigenetics is a new area of research focused on exploring how DNA methylation patterns affect transcription factor binding that affect gene expression patterns. The aim of this study was to produce a new protocol for the detection of DNA methylation patterns using computational analysis which can be further confirmed by bisulfite PCR with serial pyrosequencing. The upstream regulatory element and pre-initiation complex relative to CpG islets within the methylenetetrahydrofolate reductase gene were determined via computational analysis and online databases. The 1,104 bp long CpG island located near to or at the alternative promoter site of methylenetetrahydrofolate reductase gene was identified. The CpG plot indicated that CpG islets A and B, within the island, contained 62 and 75 % GC content CpG ratios of 0.70 and 0.80-0.95, respectively. Further exploration of the CpG islets A and B indicates that the transcription start sites were GGC which were absent from the TATA boxes. In addition, although six PROSITE motifs were identified in CpG B, no motifs were detected in CpG A. A number of cis-regulatory elements were found in different regions within the CpGs A and B. Transcription factors were predicted to bind to CpGs A and B with varying affinities depending on the DNA methylation status. In addition, transcription factor binding may influence the expression patterns of the methylenetetrahydrofolate reductase gene by recruiting chromatin condensation inducing factors. These results have significant implications for the understanding of the architecture of transcription factor binding at CpG islets as well as DNA methylation patterns that affect chromatin structure.
  14. Wan Yusuf WN, Wan Mohammad WMZ, Gan SH, Mustafa M, Abd Aziz CB, Sulaiman SA
    J Tradit Complement Med, 2019 Oct;9(4):249-256.
    PMID: 31453119 DOI: 10.1016/j.jtcme.2018.05.003
    This is the first study to report on the effects of honey in asymptomatic HIV positive subjects in ameliorating CD4 count, viral load (VL) and quality of life (QOL). It is a randomized, controlled, open labelled study, comparing the effects of Tualang honey (TH) administration for six months at three different doses: 20 g (THL), 40 g (THI) or 60 g (THH) daily compared with control (no administered treatment, THC). Only asymptomatic HIV positive subjects (n=95) having CD4 count 250-600 cell/ml, not on antiretrovirals were enrolled. Blood, (together with QOL questionnaires administration) were investigated at baseline, three and six months (CD4 cell count) while VL was determined only at baseline and six months. Significant reductions in CD4 counts in THL and THC groups (p= 0.003 for both) were seen with no significant reductions in the CD4 counts in THI and THH groups (p=0.447 and 0.053 respectively). There was improvement in VL in THC and THI (130% and 32% respectively) and reductions in THL and THH (26% and 8% respectively). Within and between group analyses for VL indicated significant differences between THL and THH compared to THC. In addition, significant improvement in QOL of groups which received TH was noted. TH has the potential to improve the QOL (physical and psychological) and CD4 counts. There was a trend of lower VL in asymptomatic HIV subjects following TH administration thus supporting the possible role of TH in boosting the immune system by improving CD4 counts, causing VL reductions in HIV positive subjects.
  15. Wan Raihana WA, Gan SH, Tan SC
    PMID: 21147046 DOI: 10.1016/j.jchromb.2010.10.037
    Amphetamine-type stimulants (ATS) are a group of chiral amine drugs which are commonly abused for their sympathomimetic and stimulant properties. ATS are extensively metabolised by hepatic cytochrome P450 enzymes. As metabolism of ATS has been shown to be highly stereospecific, stereoselective analytical methods are essential for the quantitative determination of ATS concentrations for both in vivo and in vitro studies of ATS metabolism. This paper describes a new stereoselective method for the simultaneous determination of amphetamine (AM), methamphetamine (MA), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxymethamphetamine (HMMA), 4-hydroxy-3-methoxyamphetamine (HMA), 3,4-hydroxymethamphetamine (HHMA) and 3,4-hydroxyamphetamine (HHA) in human urine samples validated according to the United States Food and Drug Administration guidelines. In this method, analytes are simultaneously extracted and derivatized with R-(-)-α-methoxy-α-(trifluoromethyl)phenylacetyl chloride (R-MTPCl) as the chiral derivatization reagent. Following this, the analytes were subjected to a second derivatization with N-methyl-N-trimethylsilyltrifluoroacetamide (MSTFA) which targets the hydroxyl groups present in HMMA, HMA, HHMA and HHA. The derivatized analytes were separated and quantified using gas chromatography-mass spectrometry (GC-MS). The method was evaluated according to the established guidelines for specificity, linearity, precision, accuracy, recovery and stability using a five-day protocol. Intra-day precision ranged from 0.89 to 11.23% RSD whereas inter-day precision was between 1.03 and 12.95% RSD. Accuracy values for the analytes ranged from -5.29% to 13.75%. Limits of quantitation were 10 μg/L for AM, MA, MDMA, HMA and HMMA and 2μg/L for MDA, HMA and HHA. Recoveries and stability values were also within accepted values. The method was applied to authentic ATS-positive samples.
  16. Visweswara Rao P, Madhavi K, Dhananjaya Naidu M, Gan SH
    PMID: 24204387 DOI: 10.1155/2013/102901
    The present study was designed to investigate the total carbohydrate, total protein, and glycogen levels in the liver and to measure functional liver markers such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in streptozotocin-(STZ-) induced diabetic rats after treatment with methanolic extract of Rhinacanthus nasutus (R. nasutus). The methanolic extract of R. nasutus was orally administered at 200 mg/kg/day while glibenclamide was administered at 50 mg/kg/day. All animals were treated for 30 days before being sacrificed. The amounts of carbohydrate, glycogen, proteins, and liver markers (AST and ALT) were measured in the liver tissue of the experimental animals. The levels of carbohydrate, glycogen, and proteins were significantly reduced in the diabetic rats but were augmented considerably after 30 days of R. nasutus treatment. The elevated AST and ALT levels in diabetic rats showed a significant decline after treatment with R. nasutus for 30 days. These results show that the administration of R. nasutus ameliorates the altered levels of carbohydrate, glycogen, proteins, and AST and ALT observed in diabetic rats and indicate that R. nasutus restores overall metabolism and liver function in experimental diabetic rats. In conclusion, the outcomes of the present study support the traditional belief that R. nasutus could ameliorate the diabetic state.
  17. Visweswara Rao P, Madhavi K, Dhananjaya Naidu M, Gan SH
    PMID: 23662138 DOI: 10.1155/2013/486047
    The present study was conducted to evaluate the therapeutic efficacy of Rhinacanthus nasutus (R. nasutus) on mitochondrial and cytosolic enzymes in streptozotocin-induced diabetic rats. The rats were divided into five groups with 6 rats in each group. The methanolic extract of R. nasutus was orally administered at a dose of 200 mg/kg/day, and glibenclamide was administered at a dose of 50 mg/kg/day. All animals were treated for 30 days and were sacrificed. The activities of both intra- and extramitochondrial enzymes including glucose-6-phosphate dehydrogenase (G6PDH), succinate dehydrogenase (SDH), glutamate dehydrogenase (GDH), and lactate dehydrogenase (LDH) were measured in the livers of the animals. The levels of G6PDH, SDH, and GDH were significantly reduced in the diabetic rats but were significantly increased after 30 days of R. nasutus treatment. The increased LDH level in diabetic rats exhibited a significant reduction after treatment with R. nasutus. These results indicate that the administration of R. nasutus altered the activities of oxidative enzymes in a positive manner, indicating that R. nasutus improves mitochondrial energy production. Our data suggest that R. nasutus should be further explored for its role in the treatment of diabetes mellitus.
  18. Velayutham NK, Thamaraikani T, Wahab S, Khalid M, Ramachawolran G, Abullais SS, et al.
    Front Pharmacol, 2024;15:1343756.
    PMID: 38299157 DOI: 10.3389/fphar.2024.1343756
    [This corrects the article DOI: 10.3389/fphar.2023.1150270.].
  19. Velayutham NK, Thamaraikani T, Wahab S, Khalid M, Ramachawolran G, Abullais SS, et al.
    Front Pharmacol, 2023;14:1150270.
    PMID: 37056983 DOI: 10.3389/fphar.2023.1150270
    Vascular endothelial growth factor (VEGF) signals cell survival, cell migration, osteogenesis, cell proliferation, angiogenesis, and vascular permeability by binding to VEGF receptor 2 (VEGFR-2). Osteosarcoma is the most common primary bone cancer, majorly affects young adults. Activation of VEGFR-2 signaling is a therapeutic target for osteosarcoma. The present study aimed to evaluate the potency of stylopine in regulation of the VEGFR-2 signaling pathway and its anti-tumour effect human MG-63 osteosarcoma cells. The in silico study on benzylisoquinoline alkaloids was carried out for analyzing and shortlisting of compounds using a virtual screening, Lipinski's rule, bioavailability graphical RADAR plot, pharmacokinetics, toxicity, and molecular docking studies. Among the benzylisoquinoline alkaloids, stylopine was selected and subjected to in-vitro studies against human MG-63 osteosarcoma cells. Various experiments such as MTT assay, EtBr/AO staining, mitochondrial membrane potential assessment, transwell migration assay, gene expression analysis by a quantitative real time polymerase chain reaction (qRT-PCR) method, SDS-PAGE followed by immunoblotting were performed to evaluate its anti-tumour effect as compared to standard axitinib. The MTT assay indicates that stylopine inhibits cell proliferation in MG-63 cells. Similarly, as confirmed by the EtBr/Ao staining method, the MMP assay indicates that stylopine induces mitochondrial membrane damage and apoptosis as compared to axitinib. Moreover, stylopine inhibits the VEGF-165 induced MG-63 cell migration by a trans-well migration assay. The immunoblotting and qRT-PCR analysis showed that stylopine inhibits the VEGF-165 induced VEGFR2 expression in MG-63 cells. It is concluded that stylopine has potential to regulate VEGFR2 and can inhibit osteosarcoma cells to offer a new drug candidate for the treatment of bone cancer in future.
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