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  1. Pandy V, Narasingam M, Kunasegaran T, Murugan DD, Mohamed Z
    ScientificWorldJournal, 2014;2014:909586.
    PMID: 25045753 DOI: 10.1155/2014/909586
    This study examined the effect of methanolic extract of Morinda citrifolia Linn. (MMC) and its bioactive principles, scopoletin and rutin, on dopamine- and noradrenaline-evoked contractility in isolated rat vas deferens preparations. MMC (1-40 mg/mL), scopoletin (1-200 μg/mL), and rutin hydrate (0.6-312.6 μg/mL) dose-dependently inhibited the contractility evoked by submaximal concentrations of both dopamine and noradrenaline, respectively. Haloperidol and prazosin, reference dopamine D2, and α 1-adrenoceptors antagonists significantly reversed the dopamine- and noradrenaline-induced contractions, respectively, in a dose-dependent manner. Interestingly, MMC per se at higher doses (60-100 mg/mL) showed dose-dependent contractile response in rat vas deferens which was partially inhibited by high doses of haloperidol but not by prazosin. These results demonstrated the biphasic effects of MMC on dopaminergic system; that is, antidopaminergic effect at lower concentrations (<40 mg/mL) and dopaminergic agonistic effect at higher concentrations (>60 mg/mL). However, similar contractile response at high doses of scopoletin (0.5-5 mg/mL) and rutin hydrate (0.5-5 mg/mL) per se was not observed. Therefore, it can be concluded that the bioactive principles of MMC, scopoletin, and rutin might be responsible for the antidopaminergic and antiadrenergic activities of MMC.
  2. Kunasegaran T, Mustafa MR, Murugan DD, Achike FI
    Biochimie, 2016 Jun;125:131-9.
    PMID: 27012965 DOI: 10.1016/j.biochi.2016.03.008
    This study investigated the effects of combined minimal concentrations of quercetin and pioglitazone on angiotensin II-induced contraction of the aorta from fructose-streptozotocin (F-STZ)-induced type 2 diabetic rats and the possible role of superoxide anions (O2(-)) and nitric oxide (NO) in their potential therapeutic interaction. Contractile responses to Ang II of aortic rings from Sprague-Dawley (SD) and F-STZ rats were tested following pre-incubation of the tissues in the vehicle (DMSO; 0.05%), quercetin (Q, 0.1 μM), pioglitazone (P, 0.1 μM) or their combination (P + Q; 0.1 μM each). The amount of superoxide anion was evaluated by lucigenin-enhanced chemiluminescence and dihydroethidium fluorescence, and NO by assay of total nitrate/nitrite, and 4-Amino-5-Methylamino-2',7'-Difluorofluorescein (DAF-FM) diacetate. The synergistic reduction of Ang II-induced contraction of diabetic but not normal aorta with minimally effective concentrations of P + Q occurs through inhibiting O2(-) and increasing NO bioavailability. This finding opens the possibility of maximal vascular protective/antidiabetic effects with low dose pioglitazone combined with quercetin, thus minimizing the risk of adverse effects.
  3. Kunasegaran T, Mustafa MR, Achike FI, Murugan DD
    Eur J Pharmacol, 2017 Mar 15;799:160-170.
    PMID: 28213289 DOI: 10.1016/j.ejphar.2017.02.022
    Pioglitazone is an anti-diabetic drug with potential to cause adverse effects following prolonged use. This study, therefore, investigated the effects of combination treatment of a subliminal concentration of pioglitazone and quercetin, a potent antioxidant, on vascular reactivity of aorta isolated from fructose-streptozotocin (F-STZ)-induced diabetic rats. Relaxation to acetylcholine and sodium nitroprusside, and contraction to phenylephrine were tested in organ bath chambers following pre-incubation with vehicle (DMSO; 0.05%), quercetin (10-7 M), pioglitazone (10-7 M), or their combination (P+Q; 10-7 M each drug). Subliminal concentration of quercetin or pioglitazone did not alter the acetylcholine- induced relaxation nor the phenylephrine-induced contraction in both normal rat and diabetic F-STZ induced tissues. However, P+Q combination synergistically improved the impaired acetylcholine-induced relaxation and decreased the elevated phenylephrine-induced contraction in aortic rings from diabetic, but not in the normal rats. Neither mono nor combination treatment altered sodium nitroprusside-induced relaxation. The combination also synergistically decreased superoxide anion and increased nitric oxide production compared to the individual treatments in aorta from diabetic rats. Overall, these data demonstrated a synergistic effect, in which, a combination (P+Q; 10-7 M each drug) caused a significantly greater effect than 10-6 M of either agent in improving endothelial function of isolated diabetic aorta. In conclusion, a combination of subliminal concentrations of pioglitazone and quercetin is able to decrease oxidative stress and provide synergistic vascular protection in type 2 diabetes mellitus and thus the possibility of using quercetin as a supplement to pioglitazone in the treatment of diabetes with the goal of reducing pioglitazone toxicity.
  4. Sidhu SRK, Kok CW, Kunasegaran T, Ramadas A
    Nutrients, 2023 Mar 21;15(6).
    PMID: 36986240 DOI: 10.3390/nu15061510
    Plant-based diets have grown increasingly popular across the globe, mainly for their health and environmental benefits. Several studies have identified a link between plant-based diets and the decreased risk of developing cardiovascular diseases, obesity, and other health issues. We systematically reviewed human interventions to identify the relationship between various plant-based food items and the gut microbiome, alongside the biochemical and anthropometric measurements as secondary findings. The study selection process was completed using the COVIDENCE platform. Overall, 203 studies were identified, of which 101 were chosen for title and abstract screening by two independent authors. Following this process, 78 studies were excluded, and the full texts and the reference lists of the remaining 23 records were reviewed using the review eligibility criteria. A manual search yielded five additional articles. In the end, 12 studies were included in the systematic review. We found evidence for short- to moderate-term beneficial effects of plant-based diets versus conventional diets (duration ≤ 13 months) on gut microbiome composition and biochemical and anthropometric measurements in healthy participants as well as obese, cardiovascular, and rheumatoid arthritis patients. However, contradictory results were observed for Enterobacteriaceae, at the family level, and for Faecalibacterium and Coprococcus, at the genus level, of gut microbiome composition. The relationship between plant-based diets and the gut microbiome, alongside their underlying metabolic and inflammatory effects, remains largely unexplored. Hence more interventional studies are needed to address these questions.
  5. Kunasegaran T, Balasubramaniam VRMT, Arasoo VJT, Palanisamy UD, Ramadas A
    PMID: 33572656 DOI: 10.3390/ijerph18031272
    A rapid increase in the prevalence of gestational diabetes mellitus (GDM) has been associated with various factors such as urbanization, lifestyle changes, adverse hyperglycemic intrauterine environment, and the resulting epigenetic changes. Despite this, the burden of GDM has not been well-assessed in Southeast Asia. We comprehensively reviewed published Southeast Asian studies to identify the current research trend in GDM in this region. Joanna Briggs Institute's methodology was used to guide the scoping review. The synthesis of literature findings demonstrates almost comparable clinical evidence in terms of risk factors and complications, challenges presented in diagnosing GDM, and its disease management, given the similarities of the underlying population characteristics in Southeast Asia. Evidence suggests that a large proportion of GDM risk in women may be preventable by lifestyle modifications. However, the GDM burden across countries is expected to rise, given the heterogeneity in screening approaches and diagnostic criteria, mainly influenced by economic status. There is an urgent need for concerted efforts by government and nongovernmental sectors to implement national programs to prevent, manage, and monitor the disease.
  6. Kunasegaran T, Balasubramaniam VRMT, Arasoo VJT, Palanisamy UD, Ramadas A
    Biology (Basel), 2021 Oct 11;10(10).
    PMID: 34681126 DOI: 10.3390/biology10101027
    General gut microbial dysbiosis in diabetes mellitus, including gestational diabetes mellitus (GDM), has been reported in a large body of literature. However, evidence investigating the association between specific taxonomic classes and GDM is lacking. Thus, we performed a systematic review of peer-reviewed observational studies and trials conducted among women with GDM within the last ten years using standard methodology. The National Institutes of Health (NIH) quality assessment tools were used to assess the quality of the included studies. Fourteen studies investigating microbial interactions with GDM were found to be relevant and included in this review. The synthesis of literature findings demonstrates that Bacteroidetes, Proteobacteria, Firmicutes, and Actinobacteria phyla, such as Desulfovibrio, Ruminococcaceae, P. distasonis, Enterobacteriaceae, Collinsella, and Prevotella, were positively associated with GDM. In contrast, Bifidobacterium and Faecalibacterium, which produce butyrate, are negatively associated with GDM. These bacteria were associated with inflammation, adiposity, and glucose intolerance in women with GDM. Lack of good diet management demonstrated the alteration of gut microbiota and its impact on GDM glucose homeostasis. The majority of the studies were of good quality. Therefore, there is great potential to incorporate personalized medicine targeting microbiome modulation through dietary intervention in the management of GDM.
  7. Kunasegaran T, Balasubramaniam VRMT, Arasoo VJT, Palanisamy UD, Ramadas A
    Curr Nutr Rep, 2023 Mar;12(1):203-214.
    PMID: 36810808 DOI: 10.1007/s13668-023-00453-4
    PURPOSE OF REVIEW: Although gut microbiota have been associated with the etiology of some diseases, the influence of foods on gut microbiota, especially among pregnant women, remains unclear. Hence, a systematic review was performed to investigate the association between diet and gut microbiota and their influence on metabolic health in pregnant women.

    RECENT FINDINGS: We performed the systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 protocol to investigate the association between diet and gut microbiota and their influence on metabolic role in pregnant women. Five databases were searched for relevant peer-reviewed articles published in English since 2011. Two-staged screening of 659 retrieved records resulted in the inclusion of 10 studies. The collated findings suggested associations between nutrient intakes and four key microbes: Collinsella, Lachnospira, Sutterella, Faecalibacterium, and the Firmicutes/Bacteroidetes ratio in pregnant women. Dietary intakes in pregnancy were found to modify the gut microbiota and positively influence the cell metabolism in pregnant women. This review, however, emphasizes the importance of conducting well-designed prospective cohorts to investigate the role of changes in dietary intakes within the pregnancy and the influence of such changes on gut microbiota.

  8. Kunasegaran T, Balasubramaniam VRMT, Thirunavuk Arasoo VJ, Palanisamy UD, Tan YK, Ramadas A
    Sci Rep, 2024 Mar 22;14(1):6891.
    PMID: 38519592 DOI: 10.1038/s41598-024-57627-5
    The study addressed a significant gap in the profiling and understanding of the gut microbiota's influence on Malaysian Malay women with gestational diabetes mellitus (GDM). This prospective cohort study aimed to explore the intricate relationship between gut microbiota, dietary choices, and lifestyle factors among Malay women, both with and without GDM. The research specifically focused on participants during the second (T0) and third (T1) trimesters of pregnancy in Johor Bahru, Malaysia. In Part 1 of the study, a diverse pool of pregnant women at T0 was categorized into two groups: those diagnosed with GDM and those without GDM, with a total sample size of 105 individuals. The assessments encompassed demographic, clinical, lifestyle, and dietary factors at the T0 and T1 trimesters. Part 2 of the study delved into microbiome analysis, targeting a better understanding of the gut microbiota among the participants. Stool samples were randomly collected from 50% of the individuals in each group (GDM and non-GDM) at T0 and T1. The collected samples underwent processing, and 16s rRNA metagenomic analysis was employed to study the microbial composition. The results suggested an association between elevated body weight and glucose levels, poor sleep quality, lack of physical activity, greater intake of iron and meat, and reduced fruit consumption among women with GDM compared to non-GDM groups. The microbiome analysis revealed changes in microbial composition over time, with reduced diversity observed in the GDM group during the third trimester. The genera Lactiplantibacillus, Parvibacter, Prevotellaceae UCG001, and Vagococcus positively correlated with physical activity levels in GDM women in the second trimester. Similarly, the genus Victivallis exhibited a strong positive correlation with gravida and parity. On the contrary, the genus Bacteroides and Roseburia showed a negative correlation with omega-3 polyunsaturated fatty acids (PUFAs) in women without GDM in the third trimester. The study highlighted the multifaceted nature of GDM, involving a combination of lifestyle factors, dietary choices, and changes in gut microbiota composition. The findings emphasized the importance of considering these interconnected elements in understanding and managing gestational diabetes among Malaysian Malay women. Further exploration is essential to comprehend the mechanisms underlying this relationship and develop targeted interventions for effective GDM management.
  9. Rouhollahi E, Moghadamtousi SZ, Al-Henhena N, Kunasegaran T, Hasanpourghadi M, Looi CY, et al.
    Drug Des Devel Ther, 2015;9:3911-22.
    PMID: 26251570 DOI: 10.2147/DDDT.S84560
    Curcuma purpurascens BI. rhizome, a member of the Zingiberaceae family, is a popular spice in Indonesia that is traditionally used in assorted remedies. Dichloromethane extract of C. purpurascens BI. rhizome (DECPR) has previously been shown to have an apoptosis-inducing effect on colon cancer cells. In the present study, we examined the potential of DECPR to prevent colon cancer development in rats treated with azoxymethane (AOM) (15 mg/kg) by determining the percentage inhibition in incidence of aberrant crypt foci (ACF). Starting from the day immediately after AOM treatment, three groups of rats were orally administered once a day for 2 months either 10% Tween 20 (5 mL/kg, cancer control), DECPR (250 mg/kg, low dose), or DECPR (500 mg/kg, high dose). Meanwhile, the control group was intraperitoneally injected with 5-fluorouracil (35 mg/kg) for 5 consecutive days. After euthanizing the rats, the number of ACF was enumerated in colon tissues. Bax, Bcl-2, and proliferating cell nuclear antigen (PCNA) protein expressions were examined using immunohistochemical and Western blot analyses. Antioxidant enzymatic activity was measured in colon tissue homogenates and associated with malondialdehyde level. The percentage inhibition of ACF was 56.04% and 68.68% in the low- and high-dose DECPR-treated groups, respectively. The ACF inhibition in the treatment control group was 74.17%. Results revealed that DECPR exposure at both doses significantly decreased AOM-induced ACF formation, which was accompanied by reduced expression of PCNA. Upregulation of Bax and downregulation of Bcl-2 suggested the involvement of apoptosis in the chemopreventive effect of DECPR. In addition, the oxidative stress resulting from AOM treatment was significantly attenuated after administration of DECPR, which was shown by the elevated antioxidant enzymatic activity and reduced malondialdehyde level. Taken together, the present data clearly indicate that DECPR significantly inhibits ACF formation in AOM-treated rats and may offer protection against colon cancer development.
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