Displaying publications 1 - 20 of 69 in total

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  1. Phipps ME, Chan KK, Naidu R, Mohamad NW, Hoh BP, Quek KF, et al.
    BMC Public Health, 2015 Jan 31;15:47.
    PMID: 25636170 DOI: 10.1186/s12889-015-1384-3
    BACKGROUND: South East Asia (SEA) is home to over 30 tribes of indigenous population groups who are currently facing rapid socio-economic change. Epidemiological transition and increased prevalence of non-communicable diseases (NCD) has occured. In Peninsular Malaysia, the Orang Asli (OA) indigenous people comprise 0 · 6% (150,000) of the population and live in various settlements. OA comprise three distinct large tribes with smaller sub-tribes. The three large tribes include Proto-Malay (sub-tribes: Orang Seletar and Jakun), Senoi (sub-tribes: Mahmeri and Semai), and Negrito (sub-tribes: Jehai, Mendriq and Batek).

    METHODS: We studied the health of 636 OA from seven sub-tribes in the Peninsular. Parameters that were assessed included height, weight, BMI and waist circumference whilst blood pressure, cholesterols, fasting blood glucose and HbA1c levels were recorded. We then analysed cardio-metabolic risk factor prevalences and performed multiple pair-wise comparisons among different sub-tribes and socio-economic clusters.

    RESULTS: Cardio-metabolic risk factors were recorded in the seven sub-tribes.. Prevalence for general and abdominal obesity were highest in the urbanized Orang Seletar (31 · 6 ± 5 · 7%; 66 · 1 ± 5 · 9%). Notably, hunter gatherer Jehai and Batek tribes displayed the highest prevalence for hypertension (43 · 8 ± 9 · 29% and 51 · 2 ± 15 · 3%) despite being the leanest and most remote, while the Mendriq sub-tribe, living in the same jungle area with access to similar resources as the Batek were less hypertensive (16.3 ± 11.0%), but displayed higher prevalence of abdominal obesity (27.30 ± 13.16%).

    CONCLUSIONS: We describe the cardio-metabolic risk factors of seven indigenous communities in Malaysia. We report variable prevalence of obesity, cholesterol, hypertension and diabetes in the OA in contrast to the larger ethnic majorities such as Malays, Chinese and Indians in Malaysia These differences are likely to be due to socio-economic effects and lifestyle changes. In some sub-tribes, other factors including genetic predisposition may also play a role. It is expected that the cardio-metabolic risk factors may worsen with further urbanization, increase the health burden of these communities and strain the government's resources.

  2. Kok YY, Chu WL, Phang SM, Mohamed SM, Naidu R, Lai PJ, et al.
    J Zhejiang Univ Sci B, 2011 May;12(5):335-45.
    PMID: 21528487 DOI: 10.1631/jzus.B1000336
    This study aimed to assess the inhibitory activities of methanol extracts from the microalgae Ankistrodesmus convolutus, Synechococcus elongatus, and Spirulina platensis against Epstein-Barr virus (EBV) in three Burkitt's lymphoma (BL) cell lines, namely Akata, B95-8, and P3HR-1. The antiviral activity was assessed by quantifying the cell-free EBV DNA using real-time polymerase chain reaction (PCR) technique. The methanol extracts from Ankistrodesmus convolutus and Synechococcus elongatus displayed low cytotoxicity and potent effect in reducing cell-free EBV DNA (EC(50)<0.01 µg/ml) with a high therapeutic index (>28000). After fractionation by column chromatography, the fraction from Synechococcus elongatus (SEF1) reduced the cell-free EBV DNA most effectively (EC(50)=2.9 µg/ml, therapeutic index>69). Upon further fractionation by high performance liquid chromatography (HPLC), the sub-fraction SEF1'a was most active in reducing the cell-free EBV DNA (EC(50)=1.38 µg/ml, therapeutic index>14.5). This study suggests that microalgae could be a potential source of antiviral compounds that can be used against EBV.
  3. Hee CS, Gun SC, Naidu R, Das Gupta E, Somnath SD, Radhakrishnan AK
    Mod Rheumatol, 2007;17(5):429-35.
    PMID: 17929139 DOI: 10.1007/s10165-007-0612-9
    In this study, three single nucleotide polymorphisms (SNPs) located within the promoter of the human interleukin (IL)-10 gene [rs1800896 (position: -1087G>A), rs1800871 (position: -824C>T) and rs1800872 (position: -597C>A)] were investigated in 84 rheumatoid arthritis (RA) patients and 95 age- and sex-matched healthy subjects using polymerase chain reaction-restriction fragment length polymorphism method. Production of IL-10 by peripheral blood lymphocytes from the RA patients and healthy subjects cultured in the presence of Concanavalin A (Con A) was determined by using enzyme-linked immunosorbent assay. The results show that the distribution of the IL-10 genotypes did not differ significantly between RA patients and healthy subjects (P>0.05). However, a significant difference was observed in allele frequencies of -824CT, -824TT, -597CA, and -597AA between the RA patients and healthy volunteers (P=0.04). The -1087A/-824T/-597A (ATA) haplotype, which comprises all mutant alleles, was associated with lower IL-10 production when compared with the other haplotypes. In contrast, the RA patients who did not display the ATA haplotype produced significantly higher levels of IL-10 when compared with those carrying either one (P=0.012) or two (P=0.005) ATA haplotypes. Our findings suggest that there is an association between SNPs in the promoter of the human IL-10 gene and susceptibility to RA.
    Study site: Hospital Tuanku Ja’afar, (Hospital Seremban), Seremban, Negeri Sembilan, Malaysia
  4. Jabir RS, Naidu R, Annuar MA, Ho GF, Munisamy M, Stanslas J
    Pharmacogenomics, 2012 Dec;13(16):1979-88.
    PMID: 23215890 DOI: 10.2217/pgs.12.165
    Interindividual variability in drug response and the emergence of adverse drug effects are the main causes of treatment failure in cancer therapy. Functional membrane drug transporters play important roles in altering pharmacokinetic profile, resistance to treatment, toxicity and patient survival. Pharmacogenetic studies of these transporters are expected to provide new approaches for optimizing therapy. Taxanes are approved for the treatment of various cancers. Circulating taxanes are taken up by SLCO1B3 into hepatocytes. The CYP450 enzymes CYP3A4, CYP3A5 and CYP2C8 are responsible for the conversion of taxanes into their metabolites. Ultimately, ABCB1 and ABCC2 will dispose the metabolites into bile canaliculi. Polymorphisms of genes encoding for proteins involved in the transport and clearance of taxanes reduce excretion of the drugs, leading to development of toxicity in patients. This review addresses current knowledge on genetic variations of transporters affecting taxanes pharmacokinetics and toxicity, and provides insights into future direction for personalized medicine.
  5. Paulraj F, Abas F, Lajis NH, Othman I, Hassan SS, Naidu R
    Molecules, 2015;20(7):11830-60.
    PMID: 26132907 DOI: 10.3390/molecules200711830
    In an effort to study curcumin analogues as an alternative to improve the therapeutic efficacy of curcumin, we screened the cytotoxic potential of four diarylpentanoids using the HeLa and CaSki cervical cancer cell lines. Determination of their EC50 values indicated relatively higher potency of 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one (MS17, 1.03 ± 0.5 μM; 2.6 ± 0.9 μM) and 1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadiene-3-one (MS13, 2.8 ± 0.4; 6.7 ± 2.4 μM) in CaSki and HeLa, respectively, with significantly greater growth inhibition at 48 and 72 h of treatment compared to the other analogues or curcumin. Based on cytotoxic and anti-proliferative activity, MS17 was selected for comprehensive apoptotic studies. At 24 h of treatment, fluorescence microscopy detected that MS17-exposed cells exhibited significant morphological changes consistent with apoptosis, corroborated by an increase in nucleosomal enrichment due to DNA fragmentation in HeLa and CaSki cells and activation of caspase-3 activity in CaSki cells. Quantitative real-time PCR also detected significant down-regulation of HPV18- and HPV16-associated E6 and E7 oncogene expression following treatment. The overall data suggests that MS17 treatment has cytotoxic, anti-proliferative and apoptosis-inducing potential in HPV-positive cervical cancer cells. Furthermore, its role in down-regulation of HPV-associated oncogenes responsible for cancer progression merits further investigation into its chemotherapeutic role for cervical cancer.
  6. Aghakhanian F, Yunus Y, Naidu R, Jinam T, Manica A, Hoh BP, et al.
    Genome Biol Evol, 2015 May;7(5):1206-15.
    PMID: 25877615 DOI: 10.1093/gbe/evv065
    Indigenous populations of Malaysia known as Orang Asli (OA) show huge morphological, anthropological, and linguistic diversity. However, the genetic history of these populations remained obscure. We performed a high-density array genotyping using over 2 million single nucleotide polymorphisms in three major groups of Negrito, Senoi, and Proto-Malay. Structural analyses indicated that although all OA groups are genetically closest to East Asian (EA) populations, they are substantially distinct. We identified a genetic affinity between Andamanese and Malaysian Negritos which may suggest an ancient link between these two groups. We also showed that Senoi and Proto-Malay may be admixtures between Negrito and EA populations. Formal admixture tests provided evidence of gene flow between Austro-Asiatic-speaking OAs and populations from Southeast Asia (SEA) and South China which suggest a widespread presence of these people in SEA before Austronesian expansion. Elevated linkage disequilibrium (LD) and enriched homozygosity found in OAs reflect isolation and bottlenecks experienced. Estimates based on Ne and LD indicated that these populations diverged from East Asians during the late Pleistocene (14.5 to 8 KYA). The continuum in divergence time from Negritos to Senoi and Proto-Malay in combination with ancestral markers provides evidences of multiple waves of migration into SEA starting with the first Out-of-Africa dispersals followed by Early Train and subsequent Austronesian expansions.
  7. Saleem H, Htar TT, Naidu R, Zengin G, Ahmad I, Ahemad N
    Nat Prod Res, 2020 Sep;34(18):2602-2606.
    PMID: 30600720 DOI: 10.1080/14786419.2018.1543684
    In this study, phytochemical composition, antioxidant, enzyme inhibition and cytotoxic activities of methanol and dichloromethane (DCM) extracts of Bougainvillea glabra (B. glabra) flowers were investigated. Methanol extract was found to have higher total bioactive contents and UHPLC-MS analysis of methanol extract revealed the presence of well-known phenolic and flavonoid compounds. Antioxidant activities were performed by radical scavenging (DPPH and ABTS), reducing power (FRAP and CUPRAC), phosphomolybdenum (TAC) and metal chelating assays. From our result, we observed that methanol extract had many antioxidant compounds. The DCM extract exhibited higher cholinesterases and α-glucosidase enzyme inhibition, while methanol extract showed significant urease inhibition. Both extracts exhibited strong to moderate cytotoxicity against MCF-7, MDA-MB-231, CaSki, DU-145 and SW-480 cancer cells with IC50 values ranging from 88.49 to 304.7 µg/mL. The findings showed the B. glabra to possess considerable antioxidant, enzyme inhibition and cytotoxic potentials and therefore has potential to discover novel bioactive molecules.
  8. Saleem H, Htar TT, Naidu R, Ahmad I, Zengin G, Ahmad M, et al.
    J Pharm Biomed Anal, 2019 Mar 20;166:128-138.
    PMID: 30640043 DOI: 10.1016/j.jpba.2019.01.007
    In this study, different solvent extracts (methanol, dichloromethane and n-hexane) from aerial and stem parts of Buxus papillosa C.K. Schneid (Buxaceae) were investigated for a panoply of bioassays. Biological profiles were established by determining antioxidant and enzyme inhibition profiles. Toxicity was tested using MTT cell viability assay on five different human cancer cell lines i.e, MCF-7, MDA-MB-231, CaSki, DU-145 and SW-480. For chemical fingerprinting, total bioactive contents and UHPLC-MS secondary metabolites profile were determined. Generally, both aerial and stem methanol extracts had highest total bioactive contents, radical scavenging and reducing power potential. DCM and n-hexane extracts were found to be most active for total antioxidant and metal chelating activity. The UHPLC-MS analysis of methanol extracts revealed the presence of several phenolic, flavonoid, alkaloid, saponin and depsipeptide derivatives. All the extracts were significantly active against butyrylcholinesterase, whereas moderate inhibition was observed for acetylcholinesterase, α-glucosidase and urease. Similarly, a considerable level of cytotoxicity was observed against all the tested cell lines with IC50 values ranging from 26 to 225.9 μg/mL. Aerial methanol and stem n-hexane extracts were found to be most cytotoxic. Principal component analysis was also performed to find any possible correlation between biological activities and total bioactive contents. On the basis of our findings, B. papillosa may be considered as promising source of bioactive molecules.
  9. Saleem H, Htar TT, Naidu R, Nawawi NS, Ahmad I, Ashraf M, et al.
    Food Chem Toxicol, 2019 Jan;123:363-373.
    PMID: 30419323 DOI: 10.1016/j.fct.2018.11.016
    We investigated into the effects of methanol and dichloromethane extracts from aerial and roots of Filago germanica (L.) Huds (Astearaceae) on key enzymes (cholinesterases, α-glucosidase and urease), antioxidant capabilities, cytotoxic potential and secondary metabolomics profile. Total phenolic and flavonoids were determined by spectrophotometric technique and secondary metabolites composition by UHPLC-MS. Antioxidant activities were assessed employing free radical scavenging, ferric reducing power and phosphomolybdenum assays. The cell-toxicity was evaluated by MTT assay against breast (MCF-7, MDA-MB-231), cervix (CaSki) and prostate (DU-145) cancers. Overall, methanol extracts were found to have higher total bioactive contents and antioxidant potential. UHPLC-MS analysis revealed significant variation in the secondary metabolites in the methanol extracts. The most common derivatives belong to seven groups i.e. alkaloids, benzoic acids, flavones, flavonols, flavan-3-ols, terpenoids and saponins. The major polyphenolic compounds were found to be kampferol, robinin, luteolin, ferulic acid, benzoic acid and salicylic acid. All the extracts showed moderate cholinesterases inhibition, whereas methanol extracts exhibited highest urease inhibition and all extracts presented a relatively high inhibition against α-glucosidase. Similarly, all extracts showed strong to moderate cytotoxicity with IC50 values ranging from 53.02 to 382.7 μg/mL. Overall, results have suggested F. germanica to be a lead source for novel natural products.
  10. Ching HC, Naidu R, Seong MK, Har YC, Taib NA
    Int J Oncol, 2011 Sep;39(3):621-33.
    PMID: 21687935 DOI: 10.3892/ijo.2011.1081
    Breast cancer is a heterogeneous disease, marked by extensive chromosomal aberrations. In this study, we aimed to explicate the underlying chromosomal copy number (CN) alterations and loss of heterozygosity (LOH) implicated in a cohort of Malaysian hospital-based primary breast carcinoma samples using a single nucleotide polymorphism (SNP) array platform. The analysis was conducted by hybridizing the extracted DNA of 70 primary breast carcinomas and 37 normal peripheral blood samples to the Affymetrix 250K Sty SNP arrays. Locus-specific CN aberrations and LOH were statistically summarized using the binary segmentation algorithm and hidden Markov model. Selected genes from the SNP array analysis were also validated using quantitative real-time PCR. The merging of CN and LOH data fabricated distinctive integrated alteration profiles, which were comprised of finely demarcated minimal sites of aberrations. The most prevalent gains (≥ 30%) were detected at the 8q arm: 8q23.1, 8q23.3, 8q24.11, 8q24.13, 8q24.21, 8q24.22, 8q24.23 and 8q24.3, whilst the most ubiquitous losses (≥ 20%) were noted at the 8p12, 8p21.1, 8p21.2, 8p21.1-p21.2, 8p21.3, 8p22, 8p23.1, 8p23.1‑p23.2, 8p23.3, 17p11.2, 17p12, 17p11.2-p12, 17p13.1 and 17p13.2 regions. Copy-neutral LOH was characterized as the most prevailing LOH event, in which the most frequent distributions (≥ 30%) were revealed at 3p21.31, 5q33.2, 12q24.12, 12q24.12‑q24.13 and 14q23.1. These findings offer compre-hensive genome-wide views on breast cancer genomic changes, where the most recurrent gain, loss and copy-neutral LOH events were harboured within the 8q24.21, 8p21.1 and 14q23.1 loci, respectively. This will facilitate the uncovering of true driver genes pertinent to breast cancer biology and the develop-ment of prospective therapeutics.
  11. Khan SU, Ahemad N, Chuah LH, Naidu R, Htar TT
    J Biomol Struct Dyn, 2020 Nov 08.
    PMID: 33164654 DOI: 10.1080/07391102.2020.1844059
    G protein-coupled receptors (GPCRs) belong to the largest family of protein targets comprising over 800 members in which at least 500 members are the therapeutic targets. Among the GPCRs, G protein-coupled estrogen receptor-1 (GPER-1) has shown to have the ability in estrogen signaling. As GPER-1 plays a critical role in several physiological responses, GPER-1 has been considered as a potential therapeutic target to treat estrogen-based cancers and other non-communicable diseases. However, the progress in the understanding of GPER-1 structure and function is relatively slow due to the availability of a only a few selective GPER-1 modulators. As with many GPCRs, the X-ray crystal structure of GPER-1 is yet to be resolved and thus has led the researchers to search for new GPER-1 modulators using homology models of GPER-1. In this review, we aim to summarize various approaches used in the generation of GPER-1 homology model and their applications that have resulted in new GPER-1 ligands.
  12. Khan SU, Ahemad N, Chuah LH, Naidu R, Htar TT
    J Biomol Struct Dyn, 2020 Oct 15.
    PMID: 33054574 DOI: 10.1080/07391102.2020.1830853
    Cancer ranks in second place among the cause of death worldwide. Cancer progress in multiple stages of carcinogenesis and metastasis programs through complex pathways. Sex hormones and their receptors are the major factors in promoting cancer progression. Among them, G protein-coupled estrogen receptor-1 (GPER) has shown to mediate cellular signaling pathways and cancer cell proliferation. However, the lack of GPER protein structure limited the search for new modulators. In this study, we curated an extensive database of natural products to discover new potential GPER modulators. We used a combination of virtual screening techniques to generate a homology model of GPER and subsequently used that for the screening of 30,926 natural products from a public database to identify potential active modulators of GPER. The best hits were further screened through the ADMET filter and confirmed by docking analysis. Moreover, molecular dynamics simulations of best hits were also carried out to assess the stability of the ligand-GPER complex. This study predicted several potential GPER modulators with novel scaffolds that could be further investigated and used as the core for the development of novel GPER modulators.Communicated by Ramaswamy H. Sarma.
  13. Saleem H, Zengin G, Ahmad I, Htar TT, Naidu R, Mahomoodally MF, et al.
    Food Res Int, 2020 11;137:109651.
    PMID: 33233230 DOI: 10.1016/j.foodres.2020.109651
    Anagallis arvensis (L.) is a wild edible food plant that has been used in folklore as a natural remedy for treating common ailments. This study aimed to explore the biochemical properties and toxicity of methanol (MeOH) and dichloromethane (DCM) extracts of A. arvensis (aerial and root parts). Bioactive contents were assessed spectrophotometrically, and the secondary metabolites were identified by UHPLC-MS analysis. DPPH, ABTS, FRAP, CUPRAC, phosphomolybdenum, and metal chelating assays were employed to assess antioxidant activity. Inhibitory potential against key enzymes (α-glucosidase, urease, lipoxygenase (LOX), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE)) were also assessed. MTT assay was employed to test toxicity against SW-480, MDA-MB-231, CaSki, MCF-7, and DU-145 cancer cell lines. Methanolic extracts showed highest phenolic (aerial-MeOH: 27.5 mg GAE/g extract; root-MeOH: 21.17 mg GAE/g extract) and flavonoid (aerial-MeOH: 26.15 mg QE/g extract; root-MeOH: 19.07 mg QE/g extract) contents, and potent antioxidant activities. The aerial-MeOH extract was most potent for DPPH (IC50: 231 ug/mL), ABTS (131.12 mg TE/g extract), FRAP (82.97 mg TE/g extract), and CUPRAC (137.15 mg TE/g extract) antioxidant assays. All extracts were cytotoxic towards tested cancer cells with IC50 values ranging from 12.57 to 294.5 µg/mL and conferred a comparatively strong inhibition against α-glucosidase (aerial-DCM extract showed the highest inhibition against α-glucosidase with IC50 value of 20.97 µg /mL), while aerial extracts were also considerably active against BChE (aerial-MeOH IC50: 224.63 µg /mL), LOX (aerial-DCM IC50: 385.7 µg /mL). Likewise, aerial-MeOH extract was most active against urease enzyme (IC50: 129.72 µg /mL). UHPLC-MS investigation of methanolic extracts showed the existence of important phenolics, flavonoids, and saponins, including methyl gallte, quercetin, lanceoletin, and balanitesin, amongst others. Moreover, principal component analysis (PCA) highlighted the correlation amongst bioactive contents and observed biological activities. A. arvensis extracts could be regarded as a natural source of bioactive antioxidants, enzyme inhibitors and anticancer agents and can be further investigated as a lead source for food and pharmaceutical products. However, further studies to isolate, purify, and to characterize its bioactive phytochemicals are needed.
  14. 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.
  15. 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.
  16. Abd Wahab NA, Lajis NH, Abas F, Othman I, Naidu R
    Nutrients, 2020 Mar 02;12(3).
    PMID: 32131560 DOI: 10.3390/nu12030679
    Prostate cancer (PCa) is a heterogeneous disease and ranked as the second leading cause of cancer-related deaths in males worldwide. The global burden of PCa keeps rising regardless of the emerging cutting-edge technologies for treatment and drug designation. There are a number of treatment options which are effectively treating localised and androgen-dependent PCa (ADPC) through hormonal and surgery treatments. However, over time, these cancerous cells progress to androgen-independent PCa (AIPC) which continuously grow despite hormone depletion. At this particular stage, androgen depletion therapy (ADT) is no longer effective as these cancerous cells are rendered hormone-insensitive and capable of growing in the absence of androgen. AIPC is a lethal type of disease which leads to poor prognosis and is a major contributor to PCa death rates. A natural product-derived compound, curcumin has been identified as a pleiotropic compound which capable of influencing and modulating a diverse range of molecular targets and signalling pathways in order to exhibit its medicinal properties. Due to such multi-targeted behaviour, its benefits are paramount in combating a wide range of diseases including inflammation and cancer disease. Curcumin exhibits anti-cancer properties by suppressing cancer cells growth and survival, inflammation, invasion, cell proliferation as well as possesses the ability to induce apoptosis in malignant cells. In this review, we investigate the mechanism of curcumin by modulating multiple signalling pathways such as androgen receptor (AR) signalling, activating protein-1 (AP-1), phosphatidylinositol 3-kinases/the serine/threonine kinase (PI3K/Akt/mTOR), wingless (Wnt)/ß-catenin signalling, and molecular targets including nuclear factor kappa-B (NF-κB), B-cell lymphoma 2 (Bcl-2) and cyclin D1 which are implicated in the development and progression of both types of PCa, ADPC and AIPC. In addition, the role of microRNAs and clinical trials on the anti-cancer effects of curcumin in PCa patients were also reviewed.
  17. Saleem H, Zengin G, Ahmad I, Lee JTB, Htar TT, Mahomoodally FM, et al.
    J Pharm Biomed Anal, 2019 Jun 05;170:132-138.
    PMID: 30921647 DOI: 10.1016/j.jpba.2019.03.027
    The current research work was conducted in order to probe into the biochemical and toxicological characterisation of methanol and dichloromethane (DCM) extracts of Bougainvillea glabra (Choisy.) aerial parts. Biological fingerprints were assessed for in vitro antioxidant, key enzyme inhibitory and cytotoxicity potential. Total bioactive contents were determined spectrophotometrically and the secondary metabolite components of methanol extract was assessed by UHPLC mass spectrometric analysis. The antioxidant capabilities were evaluated via six different in vitro antioxidant assays namely DPPH, ABTS (free radical scavenging), FRAP, CUPRAC (reducing antioxidant power), phosphomolybdenum (total antioxidant capacity) and ferrous chelating activity. Inhibition potential against key enzymes urease, α-glucosidase and cholinesterases were also determined. Methanol extract exhibited higher phenolic (24.01 mg GAE/g extract) as well as flavonoid (41.51 mg QE/g extract) contents. Phytochemical profiling of methanol extract identified a total of twenty secondary metabolites and the major compounds belonged to flavonoids, phenolics and alkaloid derivatives. The findings of antioxidant assays revealed the methanol extract to exhibit stronger antioxidant (except phosphomolybdenum) activities. Similarly, the methanol extract showed highest butyrylcholinesterase and urease inhibition. The DCM extract was most active for phosphomolybdenum and α-glucosidase inhibition assays. Moreover, both extracts exhibited significant cytotoxic potential against five (MCF-7, MDA-MB-231, CaSki, DU-145, and SW-480) human carcinoma cell lines with half maximal inhibitory concentration values of 22.09 to 257.2 μg/mL. Results from the present study highlighted the potential of B. glabra aerial extracts to be further explored in an endeavour to discover novel phytotherapeutics as well as functional ingredients.
  18. Saleem H, Htar TT, Naidu R, Anwar S, Zengin G, Locatelli M, et al.
    Plants (Basel), 2020 Mar 20;9(3).
    PMID: 32245104 DOI: 10.3390/plants9030388
    The plants of the Bougainvillea genus are widely explored regarding nutritive and medicinal purposes. In this study, dichloromethane (DCM) and methanol (MeOH) extracts of Bougainvillea glabra (Choisy.) aerial and flower parts were analyzed for high-performance liquid chromatography with photodiode array detection (HPLC-PDA), ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) phytochemical composition, and enzyme inhibition potential against key enzymes involved in diabetes (α-amylase), skin problems (tyrosinase), and inflammatory disorders (lipoxygenase (LOX)). HPLC-PDA quantification revealed the identification of nine different polyphenolics, amongst which both flower extracts were richest. The flower MeOH extract contained the highest amount of catechin (6.31 μg/g), gallic acid (2.39 μg/g), and rutin (1.26 μg/g). However, none of the quantified compounds were detected in the aerial DCM extract. UHPLC-MS analysis of DCM extracts revealed the tentative identification of 27 secondary metabolites, where the most common belonged to terpenoid, alkaloid, and phenolic derivatives. Similarly, for enzyme inhibition, all the extracts presented moderate activity against tyrosinase and α-amylases, whereas, for LOX, both methanolic extracts showed higher percentage inhibition compared with DCM extracts. Based on our findings, B. glabra could be regarded as a perspective starting material for designing novel pharmaceuticals.
  19. 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.
  20. 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.
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