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Screening for antihyperglycaemic activity in several local herbs of Malaysia

Husen R, Pihie AH, Nallappan M

J Ethnopharmacol, 2004 Dec;95(2-3):205-8.
PMID: 15507337 DOI: 10.1016/j.jep.2004.07.004

Screening of aqueous extract of Phyllantus niruri (PL), Zingiber zerumbet (ZG), Eurycoma longifolia (TA-a and TA-b) and Andrographis paniculata (AP) to determine their blood glucose lowering effect were conducted in normoglycaemic and Streptozotocin-induced hyperglycaemic rats. Significant reduction in blood glucose level at 52.90% was shown when hyperglycaemic rats were treated with 50 mg/kg body weight (BW) aqueous extract of AP. This effect is enhanced when freeze-dried material was used, where 6.25 mg/kg BW gave 61.81% reduction in blood glucose level. In the administration of TA-a and TA-b, positive results in hyperglyacaemic rats were only obtained when 150 mg/kg BW of the aqueous extract was used. No significant reduction in blood glucose level were shown in hyperglycaemic rats treated with PL and ZG at all concentrations used (50, 100 and 150 mg/kg BW). In normoglycaemic rats, no significant reduction was noted when all the same extracts were used.
Fulltext The first transcriptome dataset of roselle (Hibiscus sabdariffa L.) calyces during maturation

Hamzah NA, Yong CSY, Nallappan M

Data Brief, 2022 Dec;45:108613.
PMID: 36164310 DOI: 10.1016/j.dib.2022.108613

Roselle (Hibiscus sabdariffa L.) is recognized for its phytochemical compounds such as anthocyanins, which possess pharmacological potentials in the treatments of hypertension, diabetes, cancer, hyperlipidaemia and hyperglycaemia. The calyx is the most commercially valuable part of the roselle and usually harvested at maturation. However, genetic study to understand the transcriptome changes in the calyx during maturation has yet to be explored. In this study, we sequenced the transcriptomes of roselle calyces at maturation stages III and IV using Illumina NextSeq 500 platform. These are the two most critical maturation stages in roselle, as these stages are often associated with the quality of the calyx. Over 200 million good quality paired-end reads were generated and de novo assembled into a reference transcriptome consisting of 221,334 transcripts with N50 score of 491bp. Among these transcripts, 92,974 transcripts (42%) were successfully annotated. The total number of significantly differentially expressed genes (DEGs) and the top five most significantly regulated genes in each of the maturation stage were presented. Twenty-one genes implicated in the biosynthesis of anthocyanins and their relative expressions in the calyx tissues at the two maturation stages were reported. Two secondary metabolites biosynthesis pathways that attained a relatively higher number of DEG mappings compared to other pathways were also reported. The findings from this work provide novel insights to better understand the transcriptional changes in roselle during calyx maturation, and the data made available here is intended for continued genetic study on roselle. The work is registered under NCBI Bioproject PRJNA664826. The raw sequencing reads are available in Short Read Archive with the accession numbers SRX9171161, SRX9171162, SRX9171163, SRX9171164, SRX9171165 and SRX9171166.
Fulltext A novel hybrid classification model of genetic algorithms, modified k-Nearest Neighbor and developed backpropagation neural network

Salari N, Shohaimi S, Najafi F, Nallappan M, Karishnarajah I

PLoS One, 2014;9(11):e112987.
PMID: 25419659 DOI: 10.1371/journal.pone.0112987

Among numerous artificial intelligence approaches, k-Nearest Neighbor algorithms, genetic algorithms, and artificial neural networks are considered as the most common and effective methods in classification problems in numerous studies. In the present study, the results of the implementation of a novel hybrid feature selection-classification model using the above mentioned methods are presented. The purpose is benefitting from the synergies obtained from combining these technologies for the development of classification models. Such a combination creates an opportunity to invest in the strength of each algorithm, and is an approach to make up for their deficiencies. To develop proposed model, with the aim of obtaining the best array of features, first, feature ranking techniques such as the Fisher's discriminant ratio and class separability criteria were used to prioritize features. Second, the obtained results that included arrays of the top-ranked features were used as the initial population of a genetic algorithm to produce optimum arrays of features. Third, using a modified k-Nearest Neighbor method as well as an improved method of backpropagation neural networks, the classification process was advanced based on optimum arrays of the features selected by genetic algorithms. The performance of the proposed model was compared with thirteen well-known classification models based on seven datasets. Furthermore, the statistical analysis was performed using the Friedman test followed by post-hoc tests. The experimental findings indicated that the novel proposed hybrid model resulted in significantly better classification performance compared with all 13 classification methods. Finally, the performance results of the proposed model was benchmarked against the best ones reported as the state-of-the-art classifiers in terms of classification accuracy for the same data sets. The substantial findings of the comprehensive comparative study revealed that performance of the proposed model in terms of classification accuracy is desirable, promising, and competitive to the existing state-of-the-art classification models.
Regulation of p53-, Bcl-2- and caspase-dependent signaling pathway in xanthorrhizol-induced apoptosis of HepG2 hepatoma cells

Handayani T, Sakinah S, Nallappan M, Pihie AH

Anticancer Res, 2007 Mar-Apr;27(2):965-71.
PMID: 17465228

Xanthorrhizol is a sesquiterpenoid compound extracted from the rhizome of Curcuma xanthorrhiza. This study investigated the antiproliferative effect and the mechanism of action of xanthorrhizol on human hepatoma cells, HepG2, and the mode of cell death. An antiproliferative assay using methylene blue staining revealed that xanthorrhizol inhibited the proliferation of the HepG2 cells with a 50% inhibition of cell growth (IC50) value of 4.17 +/- 0.053 microg/ml. The antiproliferative activity of xanthorrhizol was due to apoptosis induced in the HepG2 cells and not necrosis, which was confirmed by the Tdt-mediated dUTP nick end labeling (TUNEL) assay. The xanthorrhizol-treated HepG2 cells showed typical apoptotic morphology such as DNA fragmentation, cell shrinkage and elongated lamellipodia. The apoptosis mediated by xanthorrhizol in the HepG2 cells was associated with the activation of tumor suppressor p53 and down-regulation of antiapoptotic Bcl-2 protein expression, but not Bax. The levels of Bcl-2 protein expression decreased 24-h after treatment with xanthorrhizol and remained lower than controls throughout the experiment, resulting in a shift in the Bax to Bcl-2 ratio thus favouring apoptosis. The processing of the initiator procaspase-9 was detected. Caspase-3 was also found to be activated, but not caspase-7. Xanthorrhizol exerts antiproliferative effects on HepG2 cells by inducing apoptosis via the mitochondrial pathway.
Fulltext Application of pattern recognition tools for classifying acute coronary syndrome: an integrated medical modeling

Salari N, Shohaimi S, Najafi F, Nallappan M, Karishnarajah I

Theor Biol Med Model, 2013 Sep 18;10:57.
PMID: 24044669 DOI: 10.1186/1742-4682-10-57

OBJECTIVE: The classification of Acute Coronary Syndrome (ACS), using artificial intelligence (AI), has recently drawn the attention of the medical researchers. Using this approach, patients with myocardial infarction can be differentiated from those with unstable angina. The present study aims to develop an integrated model, based on the feature selection and classification, for the automatic classification of ACS.
METHODS: A dataset containing medical records of 809 patients suspected to suffer from ACS was used. For each subject, 266 clinical factors were collected. At first, a feature selection was performed based on interviews with 20 cardiologists; thereby 40 seminal features for classifying ACS were selected. Next, a feature selection algorithm was also applied to detect a subset of the features with the best classification accuracy. As a result, the feature numbers considerably reduced to only seven. Lastly, based on the seven selected features, eight various common pattern recognition tools for classification of ACS were used.
RESULTS: The performance of the aforementioned classifiers was compared based on their accuracy computed from their confusion matrices. Among these methods, the multi-layer perceptron showed the best performance with the 83.2% accuracy.
CONCLUSION: The results reveal that an integrated AI-based feature selection and classification approach is an effective method for the early and accurate classification of ACS and ultimately a timely diagnosis and treatment of this disease.
Fulltext Hypolipidemic activities of xanthorrhizol purified from centrifugal TLC

Oon SF, Nallappan M, Kassim NK, Shohaimi S, Sa'ariwijaya MS, Tee TT, et al.

Biochem Biophys Res Commun, 2016 09 23;478(3):1403-8.
PMID: 27576204 DOI: 10.1016/j.bbrc.2016.08.136

Hyperlipidemia is defined as the presence of either hypertriglyceridemia or hypercholesterolemia, which could cause atherosclerosis. Although hyperlipidemia can be treated by hypolipidemic drugs, they are limited due to lack of effectiveness and safety. Previous studies demonstrated that xanthorrhizol (XNT) isolated from Curcuma xanthorrhizza Roxb. reduced the levels of free fatty acid and triglyceride in vivo. However, its ability to inhibit cholesterol uptake in HT29 colon cells and adipogenesis in 3T3-L1 cells are yet to be reported. In this study, XNT purified from centrifugal TLC demonstrated 98.3% purity, indicating it could be an alternative purification method. The IC50 values of XNT were 30.81 ± 0.78 μg/mL in HT29 cells and 35.07 ± 0.24 μg/mL in 3T3-L1 adipocytes, respectively. Cholesterol uptake inhibition study using HT29 colon cells showed that XNT (15 μg/mL) significantly inhibited the fluorescent cholesterol analogue NBD uptake by up to 27 ± 3.1% relative to control. On the other hand, higher concentration of XNT (50 μg/mL) significantly suppressed the growth of 3T3-L1 adipocytes (5.9 ± 0.58%) compared to 3T3-L1 preadipocytes (81.31 ± 0.55%). XNT was found to impede adipogenesis of 3T3-L1 adipocytes in a dose-dependent manner from 3.125 to 12.5 μg/mL, where 12.5 μg/mL significantly suppressed 36.13 ± 2.1% of lipid accumulation. We postulate that inhibition of cholesterol uptake, adipogenesis, preadipocyte and adipocyte number may be utilized as treatment modalities to reduce the prevalence of lipidemia. To conclude, XNT could be a potential hypolipidemic agent to improve cardiovascular health in the future.
Fulltext Synergistic antidiabetic activity of Taraxacum officinale (L.) Weber ex F.H.Wigg and Momordica charantia L. polyherbal combination

Perumal N, Nallappan M, Shohaimi S, Kassim NK, Tee TT, Cheah YH

Biomed Pharmacother, 2022 Jan;145:112401.
PMID: 34785415 DOI: 10.1016/j.biopha.2021.112401

Type 2 Diabetes Mellitus accounts for 90% of most diabetes cases. Many commercial drugs used to treat this disease come with adverse side effects and eventually fail to restore glucose homeostasis. Therefore, an effective, economical and safe antidiabetic remedy from dietary source is considered. Taraxacum officinale (L.) Weber ex F.H.Wigg and Momordica charantia L. were chosen since both are used for centuries as traditional medicine to treat various ailments and diseases. In this study, the antidiabetic properties of a polyherbal combination of T. officinale and M. charantia ethanol extracts are evaluated. The bioactive solvent extracts of the samples selected from in vitro antidiabetic assays; α-amylase, α-glucosidase, and dipeptidyl peptidase-4 (DPP-4) inhibition, and glucose-uptake in L6 muscle cells were combined (1:1) to form the polyherbal combination. The antidiabetic efficacy of polyherbal combination was evaluated employing the above stated in vitro antidiabetic assays and in vivo oral glucose tolerance test and streptozotocin-nicotinamide (STZ-NA) induced diabetic rat model. A quadrupole time-of-flight liquid chromatography-mass spectrometry (Q-TOF LCMS) analysis was done to identify active compounds. The polyherbal combination exerted improved antidiabetic properties; increased DPP-4, α-amylase, and α-glucosidase inhibition. The polyherbal combination tested in vivo on diabetic rats showed optimum blood glucose-lowering activity comparable to that of Glibenclamide and Metformin. This study confirms the polyherbal combination of T. officinale and M. charantia to be rich in various bioactive compounds, which exhibited antidiabetic properties. Therefore, this polyherbal combination has the potential to be further developed as complex phytotherapeutic remedy for the treatment of Type 2 Diabetes Mellitus.
Fulltext Xanthorrhizol: a review of its pharmacological activities and anticancer properties

Oon SF, Nallappan M, Tee TT, Shohaimi S, Kassim NK, Sa'ariwijaya MS, et al.

Cancer Cell Int, 2015;15:100.
PMID: 26500452 DOI: 10.1186/s12935-015-0255-4

Xanthorrhizol (XNT) is a bisabolane-type sesquiterpenoid compound extracted from Curcuma xanthorrhiza Roxb. It has been well established to possess a variety of biological activities such as anticancer, antimicrobial, anti-inflammatory, antioxidant, antihyperglycemic, antihypertensive, antiplatelet, nephroprotective, hepatoprotective, estrogenic and anti-estrogenic effects. Since many synthetic drugs possess toxic side effects and are unable to support the increasing prevalence of disease, there is significant interest in developing natural product as new therapeutics. XNT is a very potent natural bioactive compound that could fulfil the current need for new drug discovery. Despite its importance, a comprehensive review of XNT's pharmacological activities has not been published in the scientific literature to date. Here, the present review aims to summarize the available information in this area, focus on its anticancer properties and indicate the current status of the research. This helps to facilitate the understanding of XNT's pharmacological role in drug discovery, thus suggesting areas where further research is required.