Displaying publications 1 - 20 of 106 in total

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  1. Ahmad A, Ramasamy K, Majeed AB, Mani V
    Pharm Biol, 2015 May;53(5):758-66.
    PMID: 25756802 DOI: 10.3109/13880209.2014.942791
    Soybean and its fermented products are the most common source of isoflavones in human food.
  2. Ahmad A, Ramasamy K, Jaafar SM, Majeed AB, Mani V
    Food Chem Toxicol, 2014 Mar;65:120-8.
    PMID: 24373829 DOI: 10.1016/j.fct.2013.12.025
    The present study was undertaken to compare the neuroprotective effects between total isoflavones from soybean and tempeh against scopolamine-induced cognitive dysfunction. Total isoflavones (10, 20 and 40mg/kg) from soybean (SI) and tempeh (TI) were administered orally to different groups of rats (n=6) for 15days. Piracetam (400mg/kg, p.o.) was used as a standard drug while scopolamine (1mg/kg, i.p.) was used to induce amnesia in the animals. Radial arm and elevated plus mazes served as exteroceptive behavioural models to measure memory. Brain cholinergic activities (acetylcholine and acetylcholinesterase) and neuroinflammatory activities (COX-1, COX-2, IL-1β and IL10) were also assessed. Treatment with SI and TI significantly reversed the scopolamine effect and improved memory with TI group at 40mg/kg, p.o. exhibiting the best improvement (p<0.001) in rats. The TI (10, 20 and 40mg/kg, p.o.) significantly increased (p<0.001) acetylcholine and reduced acetylcholinesterase levels. Meanwhile, only a high dose (40mg/kg, p.o.) of SI showed significant improvement (p<0.05) in the cholinergic activities. Neuroinflammation study also showed that TI (40mg/kg, p.o.) was able to reduce inflammation better than SI. The TI ameliorates scopolamine-induced memory in rats through the cholinergic neuronal pathway and by prevention of neuroinflammation.
  3. Ahmad Alwi NA, Lim SM, Mani V, Ramasamy K
    J Diet Suppl, 2023;20(5):717-734.
    PMID: 35876040 DOI: 10.1080/19390211.2022.2103608
    This study explored mechanisms underpinning enhanced memory in amyloid precursor protein (APP) transgenic mice (male; 10-12 months; n = 6/group) supplemented with Lactobacillus plantarum LAB12 (LAB12)/Lactobacillus casei Shirota (LcS). Morris Water Maze test was performed before brains were harvested for gene expression and biochemical studies. LAB-supplemented mice exhibited reduced escape latency and distance but significant increased time spent in platform zone. This was associated with downregulated beta-site APP cleaving enzyme-1 (BACE1) mRNA and significant reduced nitric oxide in brains. LAB12 also significantly increased glutathione. The LAB-enhanced memory is strain-dependent and could be mediated, in part, through amyloidogenic pathway and anti-oxidant/oxidative stress interplay.
  4. Ahmad N, Anouar EH, Tajuddin AM, Ramasamy K, Yamin BM, Bahron H
    PLoS One, 2020;15(4):e0231147.
    PMID: 32287324 DOI: 10.1371/journal.pone.0231147
    This paper reports the synthesis, characterization, anticancer screening and quantum chemical calculation of a tetradentate Schiff base 2,2'-((1E,1'E)-((2,2-dimethylpropane-1,3-diyl)bis- (azanylylidene))bis(methanylylidene))bis(4-fluorophenol) (L2F) and its Pd (II) complex (PdL2F). The compounds were characterized via UV-Visible, NMR, IR spectroscopy and single crystal x-ray diffraction. Density Functional Theory (DFT) and time-dependent DFT calculations in gas and solvent phases were carried out using B3LYP, B3P86, CAM-B3LYP and PBE0 hybrid functionals combined with LanL2DZ basis set. Complexation of L2F to form PdL2F was observed to cause a bathochromic shift of the maximum absorption bands of n-π* from 327 to 410 nm; an upfield shift for δ (HC = N) from 8.30 to 7.96 ppm and a decreased wavenumber for ν(C = N) from 1637 to 1616 cm-1. Overall, the UV-Vis, NMR and IR spectral data are relatively well reproduced through DFT and TD-DFT methods. L2F and PdL2F showed IC50 of 90.00 and 4.10 μg/mL, respectively, against human colorectal carcinoma (HCT116) cell lines, signifying increased anticancer activity upon complexation with Pd (II).
  5. Appukutty M, Ramasamy K, Rajan S, Vellasamy S, Ramasamy R, Radhakrishnan AK
    Benef Microbes, 2015;6(4):491-6.
    PMID: 25691103 DOI: 10.3920/BM2014.0129
    Probiotics are live microorganisms that confer health benefits through the gastrointestinal microbiota. This nutritional supplement may benefit athletes who undergo rigorous training by maintaining their gastrointestinal functions and overall health. In this study the influence of moderate physical exercise using a graded treadmill exercise, alone or in combination with the consumption of a soy product fermented with Lactobacillus plantarum LAB12 (LAB12), on tumour necrosis factor alpha (TNF-α) responses was investigated in a murine model. Male BALB/c mice were randomly divided into four groups of six mice each (control, exercise alone, LAB12 and LAB12 + exercise). Mice treated with the potential probiotic LAB12 were orally gavaged for 42 days. At autopsy, blood and spleen from the animals were collected. The splenocytes were cultured in the presence of a mitogen, concanavalin A (Con A). The amount of TNF-α produced by the Con A-stimulated splenocytes was quantified using ELISA, while their proliferation was determined using the [(3)H]-thymidine incorporation method. This study shows that LAB12-supplemented and exercise-induced mice showed marked increase (P<0.05) in cell proliferation compared to the control animals. TNF-α production was suppressed (P<0.05) in the LAB12 group compared to the untreated mice. These results demonstrate that supplementation with LAB12 has immunomodulatory effects, under conditions of moderate physical exercise, which may have implications for human athletes. Further investigation in human trials is warranted to confirm and extrapolate these findings.
  6. Appukutty M, Radhakrishnan AK, Ramasamy K, Ramasamy R, Abdul Majeed AB, Noor MI, et al.
    BMC Res Notes, 2012;5:649.
    PMID: 23173926 DOI: 10.1186/1756-0500-5-649
    This study examined the effects of bovine colostrum on exercise -induced modulation of antioxidant parameters in skeletal muscle in mice. Adult male BALB/c mice were randomly divided into four groups (control, colostrum alone, exercise and exercise with colostrum) and each group had three subgroups (day 0, 21 and 42). Colostrum groups of mice were given a daily oral supplement of 50 mg/kg body weight of bovine colostrum and the exercise group of mice were made to exercise on the treadmill for 30 minutes per day. Total antioxidants, lipid hydroperoxides, xanthine oxidase and super oxide dismutase level was assayed from the homogenate of hind limb skeletal muscle.
  7. Aravindhan K, Mat S, Hamid TA, Shahar S, Abdul Majeed AB, Teh PL, et al.
    Gerontology, 2021 Aug 17.
    PMID: 34515120 DOI: 10.1159/000517946
    BACKGROUND: Rapid population aging occurring in developing nations necessitates innovation to ensure we continue to gain ground on aging research despite pandemic threats. While developed nations have resorted to virtual communications, this is challenging in developing nations due to poor internet connectivity and digital literacy.

    OBJECTIVES: The aim of this study was to determine the feasibility of virtual data collection for a longitudinal study of aging assessing cognitive frailty in a middle-income Southeast Asian country.

    METHODS: The Transforming Cognitive Frailty into Later-Life Self-Sufficiency (AGELESS) longitudinal study of aging involved community-dwelling participants aged 60 years and above. A semi-structured focus group discussion was conducted via videoconferencing with selected representatives from existing participants. The survey instrument was compiled during a hybrid meeting and refined using a virtual Delphi process involving 51 AGELESS investigators. The final draft survey and recruitment strategy were then piloted among selected participants.

    RESULTS: Twelve individuals participated in the virtual focus group interview. Smartphone, tablet computer, laptops, and desktop personal computers were used for information gathering, communication, banking, shopping, leisure, religion, and education, within this group. The survey instrument was redacted from 362 items in 18 sections to 141 items in 12 sections through 3 virtual Delphi rounds facilitated by email, social media messaging, and videoconferencing which attracted 213 comments. Of 45 participants selected for the pilot survey, 30 were successfully contacted after one attempt and 18 completed the survey. Cognitive frailty was present in 13%, cognitive impairment in 20%, frailty in 20%, and 47% were robust.

    CONCLUSION: A virtual survey instrument was developed for the AGELESS longitudinal survey of aging which was vital for determining the effects of the COVID-19 pandemic on our older population as well as sustaining research into aging despite barriers posed by the pandemic.

  8. Ashraf K, Halim H, Lim SM, Ramasamy K, Sultan S
    Saudi J Biol Sci, 2020 Jan;27(1):417-432.
    PMID: 31889866 DOI: 10.1016/j.sjbs.2019.11.003
    Background: Medicinal plants are important source of drugs with pharmacological activities. Therefore, there is always rising demands to discover more therapeutic agents from various species. Orthosiphon stamineus, Gynura procumbens and Ficus deltoidea are high valued medicinal plants of Malaysia contain rich source of phenolic and flavonoid compounds. The aims of the present study were to evaluate anti-oxidant, antimicrobial and anti-proliferative effects on A549, HeGP2 and MCF7 cell lines of four different extracts of Orthosiphon stamineus, Gynura procumbens and Ficus deltoidea.

    Methodology: The leaves of all selected plants were extracted with methanol, chloroform, ethyl acetate and butanol separately with simple cold maceration. Antioxidant activity of all crude extracts were quantitatively measured against DPPH and Ferric Reducing Assay. Antimicrobial evaluation was done by Microdilution and MTT assay and antipoliferative activity of all extracts of selected plant were evaluated against A549, HePG2 and MCF7 cell lines.

    Results: Results showed that methanol extract exhibited highest percentage free radical scavenging activity of almost all extracts of selected plants. Antimicrobials results showed chloroform and methanol extracts of O. stamineus extract were the two most active extracts against resistant MRSA but not S. aureus. Only methanol extract of G. procumbens showed antimicrobial activity against the tested pathogens. Chloroform and methanol extracts of F. deltoidea elicited antimicrobial activity against S. aureus but not MRSA. Antiproliferative activity against three tested cell lines results showed that ethyl acetate extract of O. stamineus showed good effect whereas methanol extract of F. deltoidea and G. procumbens exhibited good antiproliferative activity.

    Conclusions: The results of the present investigation demonstrated significant variations in the antioxidant, antimicrobial and antiproliferative effects of different solvent extracts. These data could be helpful in isolation of pure potent compounds with good biological activities from the extracts of plants.

  9. Darawi MN, Ai-Vyrn C, Ramasamy K, Hua PP, Pin TM, Kamaruzzaman SB, et al.
    BMC Med Genet, 2013;14:27.
    PMID: 23419238 DOI: 10.1186/1471-2350-14-27
    The incidence of Alzheimer's disease, particularly in developing countries, is expected to increase exponentially as the population ages. Continuing research in this area is essential in order to better understand this disease and develop strategies for treatment and prevention. Genome-wide association studies have identified several loci as genetic risk factors of AD aside from apolipoprotein E such as bridging integrator (BIN1), clusterin (CLU), ATP-binding cassette sub-family A member 7 (ABCA7), complement receptor 1 (CR1) and phosphatidylinositol binding clathrin assembly protein (PICALM). However genetic research in developing countries is often limited by lack of funding and expertise. This study therefore developed and validated a simple, cost effective polymerase chain reaction based technique to determine these single nucleotide polymorphisms.
  10. Enche Ady CNA, Lim SM, Teh LK, Salleh MZ, Chin AV, Tan MP, et al.
    J Neurosci Res, 2017 Oct;95(10):2005-2024.
    PMID: 28301062 DOI: 10.1002/jnr.24048
    The rapid increase in the older population has made age-related diseases like Alzheimer's disease (AD) a global concern. Given that there is still no cure for this neurodegenerative disease, the drastic growth in the number of susceptible individuals represents a major emerging threat to public health. The poor understanding of the mechanisms underlying AD is deemed the greatest stumbling block against progress in definitive diagnosis and management of this disease. There is a dire need for biomarkers that can facilitate early diagnosis, classification, prognosis, and treatment response. Efforts have been directed toward discovery of reliable and distinctive AD biomarkers but with very little success. With the recent emergence of high-throughput technology that is able to collect and catalogue vast datasets of small metabolites, metabolomics offers hope for a better understanding of AD and subsequent identification of biomarkers. This review article highlights the potential of using multiple metabolomics platforms as useful means in uncovering AD biomarkers from body fluids. © 2017 Wiley Periodicals, Inc.
  11. Fareez IM, Lim SM, Mishra RK, Ramasamy K
    Int J Biol Macromol, 2015 Jan;72:1419-28.
    PMID: 25450046 DOI: 10.1016/j.ijbiomac.2014.10.054
    The vulnerability of probiotics at low pH and high temperature has limited their optimal use as nutraceuticals. This study addressed these issues by adopting a physicochemical driven approach of incorporating Lactobacillus plantarum LAB12 into chitosan (Ch) coated alginate-xanthan gum (Alg-XG) beads. Characterisation of Alg-XG-Ch, which elicited little effect on bead size and polydispersity, demonstrated good miscibility with improved bead surface smoothness and L. plantarum LAB12 entrapment when compared to Alg, Alg-Ch and Alg-XG. Sequential incubation of Alg-XG-Ch in simulated gastric juice and intestinal fluid yielded high survival rate of L. plantarum LAB12 (95%) at pH 1.8 which in turn facilitated sufficient release of probiotics (>7 log CFU/g) at pH 6.8 in both time- and pH-dependent manner. Whilst minimising viability loss at 75 and 90 °C, Alg-XG-Ch improved storage durability of L. plantarum LAB12 at 4 °C. The present results implied the possible use of L. plantarum LAB12 incorporated in Alg-XG-Ch as new functional food ingredient with health claims.
  12. Fareez IM, Lim SM, Zulkefli NAA, Mishra RK, Ramasamy K
    Probiotics Antimicrob Proteins, 2018 09;10(3):543-557.
    PMID: 28493103 DOI: 10.1007/s12602-017-9284-8
    The susceptibility of probiotics to low pH and high temperature has limited their use as nutraceuticals. In this study, enhanced protection of probiotics via microencapsulation was achieved. Lactobacillus plantarum LAB12 were immobilised within polymeric matrix comprised of alginate (Alg) with supplementation of cellulose derivatives (methylcellulose (MC), sodium carboxymethyl cellulose (NaCMC) or hydroxypropyl methylcellulose (HPMC)). L. plantarum LAB12 encapsulated in Alg-HPMC(1.0) and Alg-MC(1.0) elicited improved survivability (91%) in simulated gastric conditions and facilitated maximal release (∼100%) in simulated intestinal condition. Alg-HPMC(1.0) and Alg-MC(1.0) significantly reduced (P 7 log CFU g-1. Alg-MC and Alg-HPMC improved the survival of LAB12 against simulated gastric condition (9.24 and 9.55 log CFU g-1, respectively), temperature up to 90 °C (9.54 and 9.86 log CFU g-1, respectively) and 4-week of storage at 4 °C (8.61 and 9.23 log CFU g-1, respectively) with sustained release of probiotic in intestinal condition (>9 log CFU g-1). These findings strongly suggest the potential of cellulose derivatives supplemented Alg bead as protective micro-transport for probiotic strains. They can be safely incorporated into new functional food or nutraceutical products.
  13. Fareez IM, Lim SM, Ramasamy K
    Probiotics Antimicrob Proteins, 2019 06;11(2):447-459.
    PMID: 30003409 DOI: 10.1007/s12602-018-9442-7
    Lactic acid bacteria (LAB) with probiotic properties are useful options for prophylactic and therapeutic applications against gastrointestinal diseases. The safety of probiotics should, however, be verified before incorporation into food or drinks. The present study had encapsulated Lactobacillus plantarum LAB12 within microcapsules that could withstand extremely high temperature (up to 100 °C) during pelletisation. The microencapsulated LAB12 were then tested for their acute (single dosing) and sub-chronic (a 90-day feeding) toxicity. For acute toxicity study, six male Sprague-Dawley rats were being administered with a single dose of freeze-dried microencapsulated LAB12 at 11 log CFU/kg BW through oral gavage. No clear treatment-related effects were observed after 14 days. For sub-chronic toxicity study, rodents were randomly divided into four groups (6 rats/sex/group) and treated with 0, 8, 9 and 10 log CFU/kg BW of microencapsulated LAB12 in pellet form. No mortality or treatment-related findings were observed in terms of clinical body weight, water intake, or food consumption. No treatment-related adverse effects were observed in blood and tissue samples. The no-observed-adverse-effect-level (NOAEL) for microencapsulated LAB12 was 2.5 × 1010 CFU/kg BW for both genders. These results imply that LAB12 are likely non-pathogenic and non-toxic.
  14. Fareez IM, Lim SM, Ramasamy K
    Probiotics Antimicrob Proteins, 2024 Feb;16(1):99-112.
    PMID: 36508139 DOI: 10.1007/s12602-022-10020-y
    The pathogenesis of colorectal cancer (CRC) is associated with gut dysbiosis that is attributed to unhealthy lifestyles and dietary habits. Consumption of microencapsulated probiotics may potentially restore the gut microbiota in favour of prevention against CRC. This study determined the fate of microencapsulated Lactiplantibacillus plantarum (formerly known as Lactobacillus plantarum) LAB12 in the gastrointestinal tract (GIT) and assessed the chemopreventive effect of microencapsulated L. plantarum LAB12 in vivo. The targeted release of L. plantarum LAB12 from Alg-based microcapsules at the stomach, ileum, caecum and colon of Sprague-Dawley rats was examined by confocal microscopy and qPCR. Microcapsules loaded with L. plantarum LAB12 remained intact in the stomach. Free L. plantarum LAB12 were present in abundance (> 7 log CFU) only in the intestines. Subsequently, the chemopreventive properties of microencapsulated L. plantarum LAB12 were validated against NU/NU nude mice bearing orthotopic transplanted CT-26 CRC (12 female mice; 4-6 weeks old; 20-22 g; n = 6/group). Orthotopic mice pre-supplemented with microencapsulated L. plantarum LAB12 (10 log CFU kg-1 BW for 11 weeks) were presented with significantly (p 
  15. Gopinathan S, Kaur AH, Ramasamy K, Raman M
    F1000Res, 2021;10:927.
    PMID: 35035891 DOI: 10.12688/f1000research.72860.3
    The pandemic has created challenges in all sectors of the economy and education. Traditional teaching approaches seem futile in the new context, thus the need to constantly reinvent the delivery to meet the fast-paced changes in the education domain. Hence, Design Thinking (DT) is an alternative approach that might be useful in the given context. DT is known to be a human-centric approach to innovative problem-solving processes. DT could be employed in the delivery process to develop twenty-first-century skills and enhance creativity and innovation, in an attempt to identify alternative solutions. The study explores the role of design thinking (DT) in the form of empathy, thinking process, gamified lessons and curriculum enhancement, which leads to innovative delivery among teachers. It enhances and facilitates innovative content delivery by leveraging creativity. The study targeted 131 teachers, whereby 61 are primary school teachers and 70 are secondary school teachers. A questionnaire constituting of 23 close-ended questions using the 5-point Likert scale was used to collect data. Data was analyzed using SmartPLS to establish relationships between DT and Innovative Delivery in schools. The data was further analyzed to seek co-relations between the DT steps and the successful transformation of content delivery by teachers. The study established a framework for the application of design thinking for teachers as the primary support in developing activities for their students. It shows that thinking process, gamifying lessons and curriculum enhancement have positive significance in innovative delivery, whereas empathy did not show a significant positive relationship. The outcome of this study will help fill the gap towards creating an interesting method of delivery in schools and constantly innovating the method to suit the evolving generation. This insight is crucial for the Ministry of Education and policymakers to enhance teachers' ability to innovatively deliver content to students.
  16. Hamdan NKA, Lean QY, Neoh CF, Abdullah AH, Lim SM, Ramasamy K, et al.
    PMID: 32831870 DOI: 10.1155/2020/5713134
    Introduction: Facial candling is a traditional method used for relieving symptoms of allergic rhinitis (AR). This study aims to investigate the knowledge and perception of facial candling in a sample of staff and students in a public university in Malaysia.

    Methods: An online questionnaire survey method was used. Based on sample size calculation, a total of 1,508 UiTM staff and students from ten selected campuses of Universiti Teknologi MARA (UiTM) were invited to participate in this survey. An up-to-date e-mail list of staff in the selected campuses was used as the sampling frame for the study, whereas the students were recruited from the official university student Facebook portal.

    Results: A total of 788 respondents participated in this survey, 72.2% of them knew about facial candling, though only 35.4% had tried the treatment. Approximately one-fifth of respondents agreed that facial candling might treat AR. It was found that a higher number of users than nonusers agreed that facial candling was a traditional medicine (78.9% vs 55.0%); could be used on the face and ears (83.5% vs 45.4%); and could be self-administered at home (83.5 vs 45.4%). Interestingly, more than half of them were uncertain about its long-term effects and adverse reactions.

    Conclusion: This study confirms the facial candling use among patients with AR although the percentage is low. The patients and general public need to be better informed about the use of facial candling in AR and its associated risks.

  17. Harun A, Vidyadaran S, Lim SM, Cole AL, Ramasamy K
    PMID: 26047814 DOI: 10.1186/s12906-015-0685-5
    Excessive production of inflammatory mediators such as nitric oxide (NO) and proinflammatory cytokines like tumour necrosis factor-alpha (TNF-α) from activated microglia contributes to uncontrolled inflammation in neurodegenerative diseases. This study investigated the protective role of five endophytic extracts (HAB16R12, HAB16R13, HAB16R14, HAB16R18 and HAB8R24) against LPS-induced inflammatory events in vitro. These endophytic extracts were previously found to exhibit potent neuroprotective effect against LPS-challenged microglial cells.
  18. Harun A, James RM, Lim SM, Abdul Majeed AB, Cole AL, Ramasamy K
    BMC Complement Altern Med, 2011 Sep 24;11:79.
    PMID: 21943123 DOI: 10.1186/1472-6882-11-79
    BACKGROUND: BACE1 was found to be the major β-secretase in neurons and its appearance and activity were found to be elevated in the brains of AD patients. Fungal endophytic extracts for BACE1 inhibitory activity and cytotoxicity against PC-12 (a rat pheochromocytoma with neuronal properties) and WRL68 (a non-tumorigenic human hepatic) were investigated.

    METHODS: Endophytes were isolated from plants collected from Kuala Pilah, Negeri Sembilan and the National Park, Pahang and the extracts were tested for BACE1 inhibition. For investigation of biological activity, the pure endophytic cultures were cultivated for 14 days on PDA plates at 28°C and underwent semipolar extraction with ethyl acetate.

    RESULTS: Of 212 endophytic extracts (1000 μg/ml), 29 exhibited more than 90% inhibition of BACE1 in the preliminary screening. Four extracts from isolates HAB16R13, HAB16R14, HAB16R18 and HAB8R24 identified as Cytospora rhizophorae were the most active with IC(50(BACE1)) values of less than 3.0 μg/ml. The most active extract HAB16R13 was shown to non-competitively inhibit BACE1 with K(i) value of 10.0 μg/ml. HAB16R13 was considered non-potent against PC-12 and WRL68 (IC(50(CT))) of 60.0 and 40.0 μg/ml, respectively).

    CONCLUSIONS: This first report on endophytic fungal extract with good BACE1 inhibitory activity demonstrates that more extensive study is required to uncover the potential of endophytes.

  19. Hazalin NA, Lim SM, Cole AL, Majeed AB, Ramasamy K
    Anticancer Drugs, 2013 Sep;24(8):852-61.
    PMID: 23764760 DOI: 10.1097/CAD.0b013e3283635a47
    There is growing interest in the discovery of bioactive metabolites from endophytes as an alternative source of therapeutics. Identification of their therapeutic targets is essential in understanding the underlying mechanisms and enhancing the resultant therapeutic effects. As such, bioactive compounds produced by endophytic fungi from plants at the National Park, Pahang, Malaysia, were investigated. Five known compounds were identified using LC-UV-MS-NMR and they include trichodermol, 7-epi-brefeldin A, (3R,4S)-4-hydroxymellein, desmethyl-lasiodiplodin and cytochalasin D. The present study went on to investigate the potential anticancer effects of these compounds and the corresponding molecular mechanisms of the lead compound against human breast adenocarcinoma, MCF-7. For the preliminary screening, the cytotoxicity and apoptotic effects of these compounds against MCF-7 were examined. The compounds were also tested against noncarcinogenic hepatocytes (WRL68). The differential cytotoxicity was then determined using the MTT assay. Desmethyl-lasiodiplodin was found to suppress the growth of MCF-7, yielding an inhibitory concentration (IC50) that was seven-fold lower than that of the normal cells. The cytotoxic effect of desmethyl-lasiodiplodin was accompanied by apoptosis. Subsequent analysis demonstrated increased expression levels of caspase 3, c-myc and p53. Further, desmethyl-lasiodiplodin resulted in inhibition of monocyte chemotactic protein (MCP)-3, a cytokine involved in cell survival and metastasis. Hence, this study proposed that desmethyl-lasiodiplodin inhibited growth and survival of MCF-7 through the induction of apoptosis. This anticancer effect is mediated, in part, by upregulation of apoptotic genes and downregulation of MCP-3. As desmethyl-lasiodiplodin elicited minimal impact against normal hepatocytes, our findings also imply its potential use as a specific apoptotic agent in breast cancer treatment.
  20. Hazalin NA, Ramasamy K, Lim SM, Cole AL, Majeed AB
    Phytomedicine, 2012 May 15;19(7):609-17.
    PMID: 22397996 DOI: 10.1016/j.phymed.2012.01.007
    Endophytic fungi have been shown to be a promising source of biologically active natural products. In the present study, extracts of four endophytic fungi isolated from plants of the National Park, Pahang were evaluated for their cytotoxic activity and the nature of their active compounds determined. Those extracts exhibiting activity with IC(50) values less than 17 μg/ml against HCT116, MCF-7 and K562 cell lines were shown to induce apoptosis in these cell lines. Molecular analysis, based on sequences of the rDNA internal transcribed spacers ITS1 and ITS4, revealed all four endophytic fungi to be ascomycetes: three sordariomycetes and a dothideomycete. Six known compounds, cytochalasin J, dechlorogriseofulvin, demethylharzianic-acid, griseofulvin, harzianic acid and 2-hexylidene-3-methyl-succinic acid were identified from a rapid dereplication technique for fungal metabolites using an in-house UV library. The results from the present study suggest the potential of endophytic fungi as cytotoxic agents, and there is an indication that the isolates contain bioactive compounds that mainly kill cancer cells by apoptosis.
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