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Fulltext Bioactivity of mesona palustris (Black Cincau) as a nutraceutical agent

Sasmita, Andrew Octavian, Ling, Anna Pick Kiong

Journal of Engineering and Science Research, 2017;1(2):47-53.
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Mesona palustris, colloquially known as ‘Black Cincau’, can commonly be found in East and South East Asian regions. Traditionally, M. palustris extracts have been used as herbal drinks to promote vitality and health. With advancements in technology, M. palustris may now be processed into more nutraceutical options, including edible jellies. Studies have also come up with efficient extraction processes to better characterize its chemical constituents. Containing phenolic compounds like flavonoid and tannins, M. palustris has recently been reported to yield many exciting pre-clinical observations that are comparable to bioactive metabolites found in plants from the same genus, including Mesona procumbens and Mesona chinensis, alongside unrelated herbaceous plant species which have been utilized as natural remedy options. Thus, this review discusses the recently observed pre-clinical applications of M. palustris by highlighting its ability in promoting antidiabetic, anticancer, and antihypertensive properties, which are closely tied to its antioxidative nature. Given the developing nature of M. palustris utilization in pre-clinical and possibly clinical research, more thorough characterization, pharmacological, and molecular studies should be conducted not only to avoid adverse risks or derogatory interactions with existing drugs, but also to properly direct its use as a nutraceutical agent for specific indications.
Current viral-mediated gene transfer research for treatment of Alzheimer's disease

Sasmita AO

Biotechnol Genet Eng Rev, 2019 Apr;35(1):26-45.
PMID: 30317930 DOI: 10.1080/02648725.2018.1523521

Alzheimer's disease (AD) is the most common form of dementia and has affected millions of individuals worldwide. The hallmarks of AD include the amyloid beta plaque deposits, tau neurofibrillary tangles, altered neuronal signaling, alongside decline in memory and cognitive functions. Conventional drug therapies do exist, such as donepezil or aducanumab, but these drugs mostly focus on halting AD progression instead of causing a reversal within the disease. In an effort to ameliorate and ultimately cure AD, researchers have delved into viral-mediated gene therapy to fix this disease from its root molecular causes. To date, adeno-associated virus and lentiviral vectors have remained the most vastly studied among other viral vectors to combat AD. These vectors could be employed alongside various genetic materials based on the types of processes we want to alter to yield a positive effect, such as disruption of amyloidogenic pathway, neuroprotection and lipid metabolism pathways. Recent studies and trials were reviewed in this article, highlighting their clinical significance, differences and limitations between each method. By learning from the different combinations and possibilities of viral-mediated gene transfer, researchers would then get a step closer in ameliorating symptoms and possibly in curing AD.
Fulltext Microarray-Based Genomic Analysis Identifies Germline and Somatic Copy Number Variants and Loss of Heterozygosity in Acute Myeloid Leukaemia

Ambayya, Angeli, Sasmita, Andrew Octavian, Zainina Seman, Chang, Kian Meng, Sathar, Jameela, Yegappan, Subramanian, et al.

Malaysian Journal of Medicine and Health Sciences, 2018;14(103):1-14.
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Insights into molecular karyotyping using comparative genomic hybridization (CGH) and single nucleotide polymorphism (SNP) arrays enable the identification of copy number variations (CNVs) at a higher resolution and facilitate the detection of copy neutral loss of heterozygosity (CN-LOH) otherwise undetectable by conventional cytogenetics. The applicability of a customised CGH+SNP 180K DNA microarray in the diagnostic evaluation of Acute Myeloid Leukaemia (AML) in comparison with conventional karyotyping was assessed in this study. Methods: Paired tumour and germline post induction (remission sample obtained from the same patient after induction) DNA were used to delineate germline variants in 41 AML samples and compared with the karyotype findings. Results: After comparing the tumour versus germline DNA, a total of 55 imbalances (n 5-10 MB = 21, n 10-20 MB = 8 and n >20 MB = 26) were identified. Gains were most common in chromosome 4 (26.7%) whereas losses were most frequent in chromosome 7 (28.6%) and X (25.0%). CN-LOH was mostly seen in chromosome 4 (75.0%). Comparison between array CGH+SNP and karyotyping revealed 20 cases were in excellent agreement and 13 cases did not concord whereas in 15 cases finding could not be confirmed as no karyotypes available. Conclusion: The use of a combined array CGH+SNP in this study enabled the detection of somatic and germline CNVs and CN-LOHs in AML. Array CGH+SNP accurately determined chromosomal breakpoints compared to conventional cytogenetics in relation to presence of CNVs and CN-LOHs.
Harnessing neuroplasticity: modern approaches and clinical future

Sasmita AO, Kuruvilla J, Ling APK

Int J Neurosci, 2018 Nov;128(11):1061-1077.
PMID: 29667473 DOI: 10.1080/00207454.2018.1466781

Background and purpose: Neurological diseases and injuries to the nervous system may cause inadvertent damage to neuronal and synaptic structures. Such phenomenon would lead to the development of neurological and neurodegenerative disorders which might affect memory, cognition and motoric functions. The body has various negative feedback systems which can induce beneficial neuroplastic changes in mediating some neuronal damage; however, such efforts are often not enough to ameliorate the derogatory changes. Materials and methods: Articles discussing studies to induce beneficial neuroplastic changes were retrieved from the databases, National Center for Biotechnology Information (NCBI) and MEDLINE, and reviewed. Results: This review highlights the significance of neuroplasticity in restoring neuronal functions and current advances in research to employ this positive cellular event by inducing synaptogenesis, neurogenesis, clearance of toxic amyloid beta (Aβ) and tau protein aggregates, or by providing neuroprotection. Compounds ranging from natural products (e.g. bilobalides, curcumin) to novel vaccines (e.g. AADvac1, RG7345) have been reported to induce long-lasting neuroplasticity in vitro and in vitro. Activity-dependent neuroplasticity is also inducible by regimens of exercises and therapies with instances in human studies proving major successes. Lastly, mechanical stimulation of brain regions through therapeutic hypothermia or deep brain stimulation has given insight on the larger scale of neuroplasticity within the nervous system. Conclusion: Harnessing neuroplasticity may not only offer an arm in the vast arsenal of approaches being taken to tackle neurological disorders, such as neurodegenerative diseases, but from ample evidence, it also has major implications in neuropsychological disorders.
Fulltext Neuroprotective mechanisms of orientin against hydrogen peroxide-induced oxidative damage in SH-SY5Y cells

Lam, Kit Ying, Ling, Anna Pick Kiong, Sasmita, Andrew Octavian, Koh, Rhun Yian, Wong, Ying Pei, Voon, Kenny Gah Leong, et al.

Journal of Biochemistry, Microbiology and Biotechnology, 2018;6(1):10-18.
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Natural products or plant derivatives could be used to prevent or treat neurodegenerative diseases (ND). Oxidative stress has been highly implicated in the progression of ND;thus, this leads to the study on the effects of orientin in regulating Nrf2/Keap-1 redox signalling, PI3K/Akt survival and MAPK/ERK apoptosis pathways in the hydrogen peroxide (H2O2)-induced oxidative damage in SH-SY5Y cells. The cells were treated with half maximum non-toxic dose (½ MNTD) or maximum non-toxic dose (MNTD) of orientin and subsequently with H2O2. Cells were then subjected to the measurement of nitric oxide (NO), intracellular calcium (Ca2+), mitochondrial membrane potential (MMP) and annexin V/propidium iodide apoptosis assays. Regulation of the signalling pathways was analysed by Western blotting. Results showed that ½ MNTD of orientin reduced the NO levels. The intracellular Ca2+ level was also reduced by ½ MNTD and MNTD of orientin. The orientin treatment at ½ MNTD and MNTD restored the loss of MMP. Pre-treatment of orientin reduced the early and late apoptotic cells as well as necrotic cells. Orientin was found to up-regulate the Nrf2/Keap-1 and PI3K/Akt pathways whilst down-regulate the MAPK/ERK pathway. The findings from this study will be useful for the prevention of ND in the near future.
Therapeutic potential of combined viral transduction and CRISPR/Cas9 gene editing in treating neurodegenerative diseases

Kuruvilla J, Sasmita AO, Ling APK

Neurol Sci, 2018 Nov;39(11):1827-1835.
PMID: 30076486 DOI: 10.1007/s10072-018-3521-0

BACKGROUND AND PURPOSE: The central nervous system (CNS) faces unique difficulties in attaining permanent therapy for neurodegenerative disorder (ND). Genomic level forms of therapy have garnered interest in the recent decade, with the novel CRISPR/Cas9 gene editing tool continuing to be explored due to its efficiency, safety, and adaptability to varying conditions. With the aid of viral vectors as transport vectors, the gene editing tool has produced promising in vitro and in vivo findings in study models. Thus, this review focuses on the recent advancements and update of CRISPR/Cas9 to combat neurodegenerative diseases.
METHODS: Articles detailing potential applications of CRISPR/Cas9 in neurodegenerative settings were retrieved from PubMed and Google Scholar with the keywords "CRISPR," "gene editing," and "neurodegenerative diseases." Relevant information was collected and critically reviewed.
RESULTS: The utility of CRISPR/Cas9 coupled with viral transduction ranges from the disruption of amyloid precursor protein (APP) production at a genomic level in Alzheimer's disease (AD) to the deletion of varying exon portions of the Dmd gene in Duchenne muscular dystrophy (DMD) which would increase dystrophin expression. This usage of CRISPR/Cas9 also extends to experimentally ameliorate the neurodegenerative effects caused by viral infections.
CONCLUSION: The CRISPR/Cas9 gene editing tool is a powerful arsenal in the field of gene therapy and molecular medicine; hence, more research should be called to focus on the ample potential this tool has to offer in the field of neurodegenerative diseases.
Biomarkers and therapeutic advances in glioblastoma multiforme

Sasmita AO, Wong YP, Ling APK

Asia Pac J Clin Oncol, 2018 Feb;14(1):40-51.
PMID: 28840962 DOI: 10.1111/ajco.12756

Glioblastoma multiforme (GBM) is a malignant tumor within the brain. Generally classified as primary and secondary with several different subtypes, ample molecular biomarkers have risen throughout the years which have garnered the attention of researchers. The advancements in genomics and proteomics have allowed researchers to gather prominent molecular biomarkers. All these biomarkers are gathered by means of biopsy or bodily fluid sample collection and are quantitatively analyzed by polymerase chain reaction coupled with other computational technologies. This review highlights the significance, regulation and prevalence of molecular biomarkers such as O6 -methylguanine-DNA methyltransferase, epidermal growth factor receptor vIII, isocitrate dehydrogenase mutation and several others which expressed differently in different types and molecular subtypes of GBM. The discoveries and roles of GBM-specific microRNAs including miR-21 and miR-10b as biomarkers with promising prognostic values were also delineated. The role and mechanism of biomarkers in GBM tumorigenesis are essential in the development of therapy for patients suffering from the disease itself. Thus, this review also discusses the mechanisms, effects and limitations of therapy such as temozolomide, viral gene transfer, biomarker-based vaccines or even engineered T cells for more specific responses. Biomarkers have displayed a high value and could eventually be utilized as drug targets. It is hoped that by combining different aspects of the disease which present with different biomarkers could lead to the development of a robust, effective and innovative take on GBM therapy.
Madecassoside activates anti‑neuroinflammatory mechanisms by inhibiting lipopolysaccharide‑induced microglial inflammation

Sasmita AO, Ling APK, Voon KGL, Koh RY, Wong YP

Int J Mol Med, 2018 May;41(5):3033-3040.
PMID: 29436598 DOI: 10.3892/ijmm.2018.3479

Neurodegeneration is typically preceded by neuroinflammation generated by the nervous system to protect itself from tissue damage, however, excess neuroinflammation may inadvertently cause more harm to the surrounding tissues. Attenuating neuroinflammation with non‑steroidal anti‑inflammatory drugs can inhibit neurodegeneration. However, such treatments induce chronic side effects, including stomach ulcers. Madecassoside, a triterpene derived from Centella asiatica, is considered to be an alternative treatment of inflammation. In the present study, the anti‑neuroinflammatory properties of madecassoside were assessed in BV2 microglia cells, which were pre‑treated with madecassoside at a maximum non‑toxic dose (MNTD) of 9.50 µg/ml and a ½ MNTD of 4.75 µg/ml for 3 h and stimulated with 0.1 µg/ml lipopolysaccharide (LPS). The effect of madecassoside was assessed by determining reactive oxygen species (ROS) levels in all groups. Furthermore, the expression of pro‑ and anti‑neuroinflammatory genes and proteins were analyzed using reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. The results demonstrated that ROS levels in cells treated with the MNTD of madecassoside were significantly reduced compared with cells treated with LPS alone (P<0.05). The expression of pro‑neuroinflammatory genes, including inducible nitric oxide synthase, cyclooxygenase‑2, signal transducer and activator of transcription 1 and nuclear factor‑κB, were significantly downregulated in a dose‑independent manner following treatment with madecassoside. Conversely, the anti‑neuroinflammatory component heme oxygenase 1 was significantly upregulated by 175.22% in the MNTD‑treated group, compared with cells treated with LPS alone (P<0.05). The gene expression profiles of pro‑ and anti‑inflammatory genes were also consistent with the results of western blotting. The results of the present study suggest that madecassoside may be a potent anti‑neuroinflammatory agent. The antioxidative properties of madecassoside, which serve a major role in anti‑neuroinflammation, indicate that this compound may be a functional natural anti‑neuroinflammatory agent, therefore, further in vivo or molecular studies are required.