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Fulltext Aedestech mosquito home system prevents the hatch of Aedes mosquito eggs and reduces its population

Latifah Saiful Yazan, Paskaran, Kaveinesh, Gopalsamy, Banulata, Roslaini Abd Majid

Pertanika Journal of Science & Technology, 2020;28(1):263-278.
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Dengue fever (DF) is a global health problem and considered to be endemic in Malaysia. Conventional mosquito traps currently applied as vector control do not effectively reduce Aedes mosquito population. AedesTech Mosquito Home System (AMHS) is an autocidal ovitraps for Aedes mosquitoes that uses the ‘lure and kill’ concept and is expected to be able to reduce Aedes mosquito population. The effectiveness of AMHS in reducing Aedes mosquito population was investigated in Block A, B and D (control) of the 17th College, Universiti Putra Malaysia (UPM). For the first two weeks (pre-intervention), the conventional ovitraps were used to obtain the initial abundance of mosquito population in Block A, B and D. Subsequently, AMHS was used for the next three months and again followed by the conventional ovitrap for the final two weeks (post-intervention). Ovitrap Index, Hatching Index and percentage of emergence of adult mosquitoes were calculated once every two weeks. Data were analysed using Paired Sample T-test. Values were considered significant at p≤0.05. The Ovitrap Index that indicates the mosquito population at Block A and B was significantly higher (p≤0.05) than of Block D. Hatching Index of AMHS was significantly lower (p≤0.05) then conventional ovitraps. All mosquito eggs collected in AMHS did not develop into adult mosquitoes. There was a significant reduction (p≤0.05) in the mosquito population between the pre- and post-intervention. In conclusion, AMHS was effective in reducing the mosquito population in 17th College, UPM. Therefore, it is believed to be a very promising vector management option to control the incidence of DF.
Fulltext Anti-microbial, anti-cancer and immunomodulatory properties of proteinaceous postbiotic metabolite produced by Lactobacillus plantarum I-UL4

Noraina Muhamad Zakuan, Foo Hooi Ling, Latifah Saiful Yazan

Malaysian Journal of Medicine and Health Sciences, 2019;15(202):81-84.
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Bacteria and their metabolites are shown to be a potential therapeutic agent for cancer treatment. Much attention has been directed to Lactic acid bacteria (LAB) which exhibits several killing mechanisms via invasion and coloni- zation of solid tumors. Discovery of the characteristics of postbiotic metabolites that exert the same probiotic effects has attracted immense attention towards anti-cancer effect. It is known that LAB improves health and composition of microbiota in the gut. Supplementation of LAB is proven to enhance the host immunity and modulation of the immune system to fight diseases including cancers. Lactobacillus plantarum I-UL4 is the LAB species isolated from Malaysian fermented food, Tapai Ubi which capable of producing bioactive metabolic products. In this review, the properties of UL4-PPM will be discussed including anti-microbial, anti-cancer and immunomodulatory effects. Overall, it would be beneficial to discover the potential effects of UL4-PPM to possibly serve as an alternative treat- ment for cancer.
Fulltext Acute toxicity study of intravenous administration of thymoquinone-loaded nanostructured lipid carrier (TQ-NLC) in Sprague dawley rats

Latifah Saiful Yazan, Siti Nabilahuda Mohd Azlan, Fatin Hannani Zakarial Ansar, Banulata Gopalsamy

Malaysian Journal of Medicine and Health Sciences, 2019;15(202):51-57.
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Introduction: Thymoquinone (TQ), a bioactive compound from Nigella sativa is known for its various medicinal properties. Due to the low solubility of TQ, nanostructured lipid carrier (NLC) has been used as a delivery system to improve its efficacy. Nevertheless, the effect of TQ-NLC when administered intravenously is unclear. This study investigated the acute toxicity profile of intravenous administration of TQ-NLC in an in vivo model. Methods: Twelve female Sprague dawley rats were assigned randomly into two groups (n=6); a control and a treatment group that received normal saline and 25 mg/kg TQ-NLC, respectively, via intravenous injection. The rats were observed for 14 days for any alterations to their usual physical conditions such as behaviour and mortality, body weight, food intake, organ-to-body weight ratio, and haematological, biochemical and histopathological profile. Results: There were no significant changes (p>0.05) in the body weight, food intake, organ-to-body weight ratio, and haematological, bio- chemical and histopathological profile between TQ-NLC treatment and the control group. However, inflammation was observed at the site of injection on the rat’s tail. Conclusion: Intravenous administration of TQ-NLC (25 mg/kg) did not exert acute toxic effect in female Sprague dawley rats. The data can be used as a basis to further develop TQ- NLC as a potential therapeutic drug.
Fulltext Betulinic acid was more cytotoxic towards the human breast cancer cell line MDA-MB-231 than the human promyelocytic leukaemia cell line HL-60

Latifah Saiful Yazan, Faujan Ahmad, Ooi, Choong Li, Raha Abdul Rahim, Hisyam Abdul Hamid, Lee, Pei Sze

Malaysian Journal of Pharmaceutical Science, 2009;7(1):23-37.
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Betulinic acid (BA) is a pentacyclic triterpene found in several botanical sources that has been shown to cause apoptosis in a number of cell lines. This study was undertaken to determine the in vitro cytotoxic properties of BA towards the human mammary carcinoma cell line MDA-MB-231 and the human promyelocytic leukaemia cell line HL-60 and the mode of the induced cell death. The cytotoxicity and mode of cell death of BA were determined using the MTT assay and DNA fragmentation analysis, respectively. In our study, the compound was found to be cytotoxic to MDA-MB-231 and HL-60 cells with IC50 values of 58 μg/mL and 134 μg/mL, respectively. Cells treated with high concentrations of BA exhibited features characteristic of apoptosis such as blebbing, shrinking and a number of small cytoplasm body masses when viewed under an inverted light microscope after 24h. The incidence of apoptosis in MDA-MB-231 was further confirmed by the DNA fragmentation analysis, with the formation of DNA fragments of oligonucleosomal size (180-200 base pairs), giving a ladder-like pattern on agarose gel electrophoresis. BA was more cytotoxic towards MDA-MB-231 than HL-60 cells, and induced apoptosis in MDA-MB-231 cells.
Fulltext Potential implications of GRP58 expression and susceptibility of cervical cancer to cisplatin and thymoquinone-based therapy

Hafiza WA, Latifah SY

Onco Targets Ther, 2014;7:1375-87.
PMID: 25143744 DOI: 10.2147/OTT.S62928

A new therapeutic approach of looking at the expression of glucose-regulated protein (GRP) 58 as an indication of cisplatin sensitivity may eradicate fruitless treatment and side effects in patients with cervical cancer. Thymoquinone, the bioactive compound in Nigella sativa, has been reported to have an antiproliferative effect on cervical cancer cells. This study compared the cytotoxic effects of cisplatin, a drug commonly used in the treatment of cervical cancer, and thymoquinone in cervical cancer (HeLa and SiHa) cell lines by 3-(4,5-Dimethyl thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and measured GRP58 expression in the cells by quantitative real-time polymerase chain reaction and Western blotting. Cisplatin had higher antiproliferative activity towards the cervical cancer cell lines than thymoquinone in a dose-dependent and time-dependent manner. However, cisplatin was more toxic to normal 3T3 and Vero cell lines than thymoquinone. The half maximal inhibitory concentration (IC50) of cisplatin in HeLa and SiHa cells at 72 hours was 13.3±2.52 μM and 19.5±2.12 μM, respectively. Meanwhile, the IC50 of thymoquinone in HeLa and SiHa cells was 29.57±5.81 μM and 23.41±1.51 μM, respectively (P<0.05). A significant correlation was found between the cytotoxicity of cisplatin and expression of GRP58, but this relationship was not significant for thymoquinone. Therefore, the response of cervical cancer cells to cisplatin can be predicted on the basis of GRP58 expression.
Fulltext Dillenia suffruticosa dichloromethane root extract reduced metastasis of 4T1 cells to the liver and heart without causing toxicity in female BALB/C mice

Latifah Saiful Yazan, Siti Hanani Roslie, Razana Mohd Ali, Ahmad Amir Shabrin Mohd Khaidi, Ong Yong Sze, Fatin Hannani Zakarial Ansar, et al.

Malaysian Journal of Medicine and Health Sciences, 2019;15(202):25-32.
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Introduction: Breast cancer is ranked first among other cancers in women. Ineffectiveness of current treatments and adverse effects such as multiple organ failure and nephrotoxicity are the common problems faced in cancer therapy. Therefore, alternatives to treat breast cancer metastasis with fewer toxic effects are actively sought-after. Dillenia suffruticosa (DS) commonly known as ‘Simpoh air’ has been a traditional remedy for cancer growth. Therefore, this study investigated the metastasis inhibiting properties of DS root dichloromethane extract (DCMDS) in tumour bearing female BALB/c mice and sub-acute multiple dose oral toxicity upon treatment with this extract. Methods: Forty-eight tumour bearing mice were given either oral treatment of DCMDS (50, 100 and 200 mg/kg) or doxorubicin (2 mg/kg) for 28 days and the degree of metastasis was analysed in each group. Thirty other female BALB/c mice were treated with DCMDS (50, 100 and 200 mg/kg) and the general behaviours, biochemical, haematological and histo- pathological changes were observed. Data were analysed with One-way ANOVA and Dunnet’s test where p
Fulltext Copper complex Cu(SBCM)2 induced cell cycle arrest and apoptosis towards oestrogen-receptor positive MCF-7 breast cancer cells

Jhi Biau Foo, Li Shan Ng, Ji Hui Lim, Pau Xien Tan, Yan Zhi Lor, Jason Siau Ee Loo, et al.

Malaysian Journal of Medicine and Health Sciences, 2019;15(102):13-13.
MyJurnal

Introduction: Copper complexes can be developed as targeted agent for cancer due to increased uptake of copper by cancer cells for angiogenesis. Our previous published data showed that copper complex Cu(SBCM)2 induced apoptosis towards triple-negative MDA-MB-231 breast cancer cells. However, its effect towards other breast cancer subtype remains unknown. Current study was performed to explore the cytotoxicity of Cu(SBCM)2 towards oestrogen- receptor positive MCF-7 breast cancer cells. Methods: MTT assay was employed to study the growth inhibition of Cu(SBCM)2 towards MCF-7 breast cancer cells and human non-cancerous MCF10A breast cells. Morphological changes of Cu(SBCM)2-treated MCF-7 cells was observed under inverted light microscope. Induction of cell cycle arrest and apoptosis were accessed by flow cytometry. The expression of wild-type p53 protein was evaluated by western blotanalysis. Intracellular reactive oxygen species of MCF-7 treated with Cu(SBCM)2 was detected using DCFHDA assay. The cells were then co-treated with Cu(SBCM)2 and antioxidants to evaluate the involvement of ROS in the cytotoxicity of Cu(SBCM)2. Molecular docking study was performed to determine the interaction of Cu(SBCM)2 with DNA, DNA topoisomerase I, and human ribonucleotide reductase. Results: Cu(SBCM)2 induced G2/M phase cell cycle arrest and apoptosis in MCF-7 cells possibly via upregulation of p53 wild-type protein. Cu(SBCM)2 was less toxic towards MCF10A cells. Increased level of intracellular ROS was not detected in MCF-7 cells after treatment with Cu(SBCM)2. However, N-acetylcysteine antioxidant enhance the cytotoxicity of Cu(SBCM)2 in MCF-7 cells. Cu(SBCM)2 showed the greatest affinity for DNA topoisomerase I in comparison to DNA and human ribonucleotide reductase. Conclusions: Cu(SBCM)2 has a potential to be developed as a targeted agent for breast cancer.
Fulltext Development of nanoantibiotic delivery system using cockle shell-derived aragonite nanoparticles for treatment of osteomyelitis

Saidykhan L, Abu Bakar MZ, Rukayadi Y, Kura AU, Latifah SY

Int J Nanomedicine, 2016;11:661-73.
PMID: 26929622 DOI: 10.2147/IJN.S95885

A local antibiotic delivery system (LADS) with biodegradable drug vehicles is recognized as the most effective therapeutic approach for the treatment of osteomyelitis. However, the design of a biodegradable LADS with high therapeutic efficacy is too costly and demanding. In this research, a low-cost, facile method was used to design vancomycin-loaded aragonite nanoparticles (VANPs) with the aim of understanding its potency in developing a nanoantibiotic bone implant for the treatment of osteomyelitis. The aragonite nanoparticles (ANPs) were synthesized from cockle shells by a hydrothermal approach using a zwitterionic surfactant. VANPs were prepared using antibiotic ratios of several nanoparticles, and the formulation (1:4) with the highest drug-loading efficiency (54.05%) was used for physicochemical, in vitro drug release, and biological evaluation. Physiochemical characterization of VANP was performed by using transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray powder diffraction, and Zetasizer. No significant differences were observed between VANP and ANP in terms of size and morphology as both samples were cubic shaped with sizes of approximately 35 nm. The Fourier transform infrared spectroscopy of VANP indicated a weak noncovalent interaction between ANP and vancomycin, while the zeta potential values were slightly increased from -19.4±3.3 to -21.2±5.7 mV after vancomycin loading. VANP displayed 120 hours (5 days) release profile of vancomycin that exhibited high antibacterial effect against methicillin-resistant Staphylococcus aureus ATCC 29213. The cell proliferation assay showed 80% cell viability of human fetal osteoblast cell line 1.19 treated with the highest concentration of VANP (250 µg/mL), indicating good biocompatibility of VANP. In summary, VANP is a potential formulation for the development of an LADS against osteomyelitis with optimal antibacterial efficacy, good bone resorbability, and biocompatibility.
Fulltext Ampelopsin E Reduces the Invasiveness of the Triple Negative Breast Cancer Cell Line, MDA-MB-231

Tieng FYF, Latifah SY, Md Hashim NF, Khaza'ai H, Ahmat N, Gopalsamy B, et al.

Molecules, 2019 Jul 18;24(14).
PMID: 31323836 DOI: 10.3390/molecules24142619

Breast cancer is the most common and the second leading cause of cancer-related deaths in women. It has two distinctive hallmarks: rapid abnormal growth and the ability to invade and metastasize. During metastasis, cancer cells are thought to form actin-rich protrusions, called invadopodia, which degrade the extracellular matrix. Current breast cancer treatments, particularly chemotherapy, comes with adverse effects like immunosuppression, resistance development and secondary tumour formation. Hence, naturally-occurring molecules claimed to be less toxic are being studied as new drug candidates. Ampelopsin E, a natural oligostilbene extracted from Dryobalanops species, has exhibited various pharmacological properties, including anticancer and anti-inflammatory activities. However, there is yet no scientific evidence of the effects of ampelopsin E towards metastasis. Scratch assay, transwell migration and invasion assays, invadopodia and gelatin degradation assays, and ELISA were used to determine the effects of ampelopsin E towards the invasiveness of MDA-MB-231 cells. Strikingly in this study, ampelopsin E was able to halt migration, transmigration and invasion in MDA-MB-231 cells by reducing formation of invadopodia and its degradation capability through significant reduction (p < 0.05) in expression levels of PDGF, MMP2, MMP9 and MMP14. In conclusion, ampelopsin E reduced the invasiveness of MDA-MB-231 cells and was proven to be a potential alternative in treating TNBC.
Fulltext Anticancer Potential of Damnacanthal and Nordamnacanthal from Morinda elliptica Roots on T-lymphoblastic Leukemia Cells

Latifah SY, Gopalsamy B, Abdul Rahim R, Manaf Ali A, Haji Lajis N

Molecules, 2021 Mar 12;26(6).
PMID: 33808969 DOI: 10.3390/molecules26061554

BACKGROUND: This study reports on the cytotoxic properties of nordamnacanthal and damnacanthal, isolated from roots of Morinda elliptica on T-lymphoblastic leukaemia (CEM-SS) cell lines.
METHODS: MTT assay, DNA fragmentation, ELISA and cell cycle analysis were carried out.
RESULTS: Nordamnacanthal and damnacanthal at IC50 values of 1.7 μg/mL and10 μg/mL, respectively. At the molecular level, these compounds caused internucleosomal DNA cleavage producing multiple 180-200 bp fragments that are visible as a "ladder" on the agarose gel. This was due to the activation of the Mg2+/Ca2+-dependent endonuclease. The induction of apoptosis by nordamnacanthal was different from the one induced by damnacanthal, in a way that it occurs independently of ongoing transcription process. Nevertheless, in both cases, the process of dephosphorylation of protein phosphates 1 and 2A, the ongoing protein synthesis and the elevations of the cytosolic Ca2+ concentration were not needed for apoptosis to take place. Nordamnacanthal was found to have a cytotoxic effect by inducing apoptosis, while damnacanthal caused arrest at the G0/G1 phase of the cell cycle.
CONCLUSION: Damnacanthal and nordamnacanthal have anticancer properties, and could act as potential treatment for T-lymphoblastic leukemia.
Fulltext Antiulcer properties of Kelulut honey against Ethanol-induced gastric ulcer

Latifah Saiful Yazan, Nurul Amira Zainal, Muhamad Firdaus Shyfiq Muhamad Zali, Gopalsamy, Banulata, Ling, Voon Fui, Aminah Suhaila Haron, et al.

Pertanika Journal of Science & Technology, 2018;26(1):121-132.
MyJurnal

Ulcers in the gastrointestinal tract refer to any appreciable depth of break in the mucosa lining that may involve submucosa. Common types of ulcer include peptic, gastric and duodenal ulcer, which may lead to chronic inflammation. Ulcers may be caused by excessive alcohol intake or prolonged use of non-steroidal anti-inflammatory drugs (NSAID), in addition to several other factors. Conventional medication such as Omeprazole (proton pump inhibitor) and Ranitidine (H2 blockers) for management of ulcers may cause severe side effects such as myelosupression and abnormal heart rhythm. This has driven researchers to explore the potential of natural products for management of ulcers with reduced side effects. Kelulut honey (KH) is a type of honey that is produced by stingless bees from the Trigona species. It is believed to have a lot of medicinal properties such as being antimicrobial, antioxidant and antidiabetic. Yet, no scientific study has been carried out on its antiulcer properties. This study was carried out to determine the antiulcer properties of KH. Eighteen male Sprague dawley rats (5 to 6 weeks old, weighing between 200 and 300 g) were divided into three groups (n=6). The groups were 1) normal control group (without ulcer, without KH), 2) positive control group (with ulcer, without KH) and 3) treatment group (with ulcer, treated with KH). The treatment, KH (1183 mg/kg), was given twice daily for 30 consecutive days by oral administration. On Day 31, the rats were induced with absolute ethanol (5 mL/kg) via oral administration after being fasted for 24 h and were sacrificed 15 min after the induction. The stomach was collected for macroscopic and histopathological evaluation. Pretreatment with KH significantly reduced (p
Fulltext Germinated brown rice (GBR) reduces the incidence of aberrant crypt foci with the involvement of beta-catenin and COX-2 in azoxymethane-induced colon cancer in rats

Latifah SY, Armania N, Tze TH, Azhar Y, Nordiana AH, Norazalina S, et al.

Nutr J, 2010 Mar 26;9:16.
PMID: 20346115 DOI: 10.1186/1475-2891-9-16

Chemoprevention has become an important area in cancer research due to the failure of current therapeutic modalities. Epidemiological and preclinical studies have demonstrated that nutrition plays a vital role in the etiology of cancer. This study was conducted to determine the chemopreventive effects of germinated brown rice (GBR) in rats induced with colon cancer. GBR is brown rice that has been claimed to be richer in nutrients compared to the common white rice. The male Sprague Dawley rats (6 weeks of age) were randomly divided into 5 groups: (G1) positive control (with colon cancer, unfed with GBR), (G2) fed with 2.5 g/kg of GBR (GBR (g)/weight of rat (kg)), (G3) fed with 5 g/kg of GBR, (G4) fed with 10 g/kg of GBR and (G5) negative control (without colon cancer, unfed with GBR). GBR was administered orally once daily via gavage after injection of 15 mg/kg of body weight of azoxymethane (AOM) once a week for two weeks, intraperitonially. After 8 weeks of treatment, animals were sacrificed and colons were removed. Colonic aberrant crypt foci (ACF) were evaluated histopathologically. Total number of ACF and AC, and multicrypt of ACF, and the expression of beta-catenin and COX-2 reduced significantly (p < 0.05) in all the groups treated with GBR (G2, G3 and G4) compared to the control group (G1). Spearman rank correlation test showed significant positive linear relationship between total beta-catenin and COX-2 score (Spearman's rho = 0.616, p = 0.0001). It is demonstrated that GBR inhibits the development of total number of ACF and AC, and multicrypt of ACF, reduces the expression of beta-catenin and COX-2, and thus can be a promising dietary supplement in prevention of colon cancer.
Fulltext Pharmacokinetics and Biodistribution of Thymoquinone-loaded Nanostructured Lipid Carrier After Oral and Intravenous Administration into Rats

Zakarial Ansar FH, Latifah SY, Wan Kamal WHB, Khong KC, Ng Y, Foong JN, et al.

Int J Nanomedicine, 2020;15:7703-7717.
PMID: 33116496 DOI: 10.2147/IJN.S262395

Background: Thymoquinone (TQ), an active compound isolated from Nigella sativa, has been proven to exhibit various biological properties such as antioxidant. Although oral delivery of TQ is valuable, it is limited by poor oral bioavailability and low solubility. Recently, TQ-loaded nanostructured lipid carrier (TQ-NLC) was formulated with the aim of overcoming the limitations. TQ-NLC was successfully synthesized by the high-pressure homogenization method with remarkable physiochemical properties whereby the particle size is less than 100 nm, improved encapsulation efficiency and is stable up to 24 months of storage. Nevertheless, the pharmacokinetics and biodistribution of TQ-NLC have not been studied. This study determined the bioavailability of oral and intravenous administration of thymoquinone-loaded nanostructured lipid carrier (TQ-NLC) in rats and its distribution to organs.
Materials and Methods: TQ-NLC was radiolabeled with technetium-99m before the administration to the rats. The biodistribution and pharmacokinetics parameters were then evaluated at various time points. The rats were imaged at time intervals and the percentage of the injected dose/gram (%ID/g) in blood and each organ was analyzed.
Results: Oral administration of TQ-NLC exhibited greater relative bioavailability compared to intravenous administration. It is postulated that the movement of TQ-NLC through the intestinal lymphatic system bypasses the first metabolism and therefore enhances the relative bioavailability. However, oral administration has a slower absorption rate compared to intravenous administration where the AUC0-∞ was 4.539 times lower than the latter.
Conclusion: TQ-NLC had better absorption when administered intravenously compared to oral administration. However, oral administration showed greater bioavailability compared to the intravenous route. This study provides the pharmacokinetics and biodistribution profile of TQ-NLC in vivo which is useful to assist researchers in clinical use.

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