Displaying publications 1 - 20 of 192 in total

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  1. Elnager A, Hassan R, Idris Z, Mustafa Z, Wan-Arfah N, Sulaiman SA, et al.
    Biomed Res Int, 2015;2015:627471.
    PMID: 25664321 DOI: 10.1155/2015/627471
    Background. Caffeic acid phenethyl ester (CAPE) has been reported to possess time-dependent fibrinolytic activity by in vitro assay. This study is aimed at investigating fibrinolytic dose-dependent activity of CAPE using in vitro assays. Methods. Standardized human whole blood (WB) clots were incubated in either blank controls or different concentrations of CAPE (3.75, 7.50, 15.00, 22.50, and 30.00 mM). After 3 hours, D-dimer (DD) levels and WB clot weights were measured for each concentration. Thromboelastography (TEG) parameters were recorded following CAPE incubation, and fibrin morphology was examined under a confocal microscope. Results. Overall, mean DD (μg/mL) levels were significantly different across samples incubated with different CAPE concentrations, and the median pre- and postincubation WB clot weights (grams) were significantly decreased for each CAPE concentration. Fibrin removal was observed microscopically and indicated dose-dependent effects. Based on the TEG test, the Ly30 fibrinolytic parameter was significantly different between samples incubated with two different CAPE concentrations (15.0 and 22.50 mM). The 50% effective dose (ED50) of CAPE (based on DD) was 1.99 mg/mL. Conclusions. This study suggests that CAPE possesses fibrinolytic activity following in vitro incubation and that it has dose-dependent activities. Therefore, further investigation into CAPE as a potential alternative thrombolytic agent should be conducted.
  2. Rozak NI, Ahmad I, Gan SH, Abu Bakar R
    Sci Pharm, 2014 07 18;82(3):631-42.
    PMID: 25853073 DOI: 10.3797/scipharm.1406-01
    An insertion/deletion polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) and a polymorphism (rs6313) in the serotonin 2A receptor gene (5-HT2A) have previously been linked to smoking behavior. The objective of this study was to determine the possible association of the 5-HTTLPR and 5-HT2A gene polymorphisms with smoking behavior within a population of Malaysian male smokers (n=248) and non-smokers (n=248). The 5-HTTLPR genotypes were determined using the polymerase chain reaction (PCR) and were classified as short (S) alleles or long (L) alleles. The 5HT2A genotypes were determined using PCR-restriction fragment length polymorphisms (PCR-RFLP). No significant differences in the distribution frequencies of the alleles were found between the smokers and the non-smokers for the 5-HTTLPR polymorphism (x(2) = 0.72, P>0.05) or the 5HT2A polymorphism (x(2) = 0.73, P>0.05). This is the first study conducted on Malaysian Malay males regarding the association of 5-HTTLPR and 5HT2A polymorphisms and smoking behavior. However, the genes were not found to be associated with smoking behavior in our population.
  3. Ramatillah DL, Gan SH, Pratiwy I, Syed Sulaiman SA, Jaber AAS, Jusnita N, et al.
    PLoS One, 2022;17(1):e0262438.
    PMID: 35077495 DOI: 10.1371/journal.pone.0262438
    BACKGROUND AND AIM: Coronavirus Disease 2019 (COVID-19) has become a worldwide pandemic and is a threat to global health. Patients who experienced cytokine storms tend to have a high mortality rate. However, to date, no study has investigated the impact of cytokine storms.

    MATERIALS AND METHODS: This retrospective cohort study included only COVID-19 positive patients hospitalized in a Private Hospital in West Jakarta between March and September 2020. All patients were not vaccinated during this period and treatment was based on the guidelines by the Ministry of Health Indonesia. A convenience sampling method was used and all patients who met the inclusion criteria were enrolled.

    RESULTS: The clinical outcome of COVID-19 patients following medical therapy was either cured (85.7%) or died (14.3%), with 14.3% patients reported to have cytokine storm, from which 23.1% led to fatalities. A plasma immunoglobulin (Gammaraas®) and/or tocilizumab (interleukin-6 receptor antagonist; Actemra®) injection was utilised to treat the cytokine storm while remdesivir and oseltamivir were administered to ameliorate COVID-19. Most (61.5%) patients who experienced the cytokine storm were male; mean age 60 years. Interestingly, all patients who experienced the cytokine storm had hypertension or/ and diabetes complication (100%). Fever, cough and shortness of breath were also the common symptoms (100.0%). Almost all (92.3%) patients with cytokine storm had to be treated in the intensive care unit (ICU). Most (76.9%) patients who had cytokine storm received hydroxychloroquine and all had antibiotics [1) azithromycin + levofloxacin or 2) meropenam for critically ill patients] and vitamins such as vitamins C and B-complex as well as mineral. Unfortunately, from this group, 23.1% patients died while the remaining 70% of patients recovered. A significant (p<0.05) correlation was established between cytokine storms and age, the presence of comorbidity, diabetes, hypertension, fever, shortness of breath, having oxygen saturation (SPO2) less than 93%, cold, fatigue, ward of admission, the severity of COVID-19 disease, duration of treatment as well as the use of remdesivir, Actemra® and Gammaraas®. Most patients recovered after receiving a combination treatment (oseltamivir + remdesivir + Antibiotics + Vitamin/Mineral) for approximately 11 days with a 90% survival rate. On the contrary, patients who received oseltamivir + hydroxychloroquine + Gammaraas® + antibiotics +Vitamin/Mineral, had a 83% survival rate after being admitted to the hospital for about ten days.

    CONCLUSION: Factors influencing the development of a cytokine storm include age, duration of treatment, comorbidity, symptoms, type of admission ward and severity of infection. Most patients (76.92%) with cytokine storm who received Gammaraas®/Actemra®, survived although they were in the severe and critical levels (87.17%). Overall, based on the treatment duration and survival rate, the most effective therapy was a combination of oseltamivir + favipiravir + hydroxychloroquine + antibiotics + vitamins/minerals.

  4. Khalil MI, Ahmmed I, Ahmed R, Tanvir EM, Afroz R, Paul S, et al.
    Biomed Res Int, 2015;2015:624159.
    PMID: 26539517 DOI: 10.1155/2015/624159
    We investigated the protective role of Withania somnifera leaf extract (WSLEt) on isoproterenol- (ISO-) induced myocardial infarction (MI) in rats. Subcutaneous injection of ISO (85 mg/kg body weight (b.w.)) administered to rats for two consecutive days caused a significant increase in cardiac troponin I (cTnI) levels and serum lipid profiles, as well as the activities of some marker enzymes. In addition to these diagnostic markers, there were increased levels of lipid peroxidation (LPO) and decreased activities of enzymatic antioxidants (superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GRx), and glutathione-S-transferase (GST)) in the myocardium. However, oral pretreatment (100 mg/kg b.w.) with WSLEt for 4 weeks elicited a significant cardioprotective activity by lowering the levels of cTnI, lipid profiles, and marker enzymes. The levels of LPO products were also significantly decreased. Elevated activities of antioxidant enzymes were also observed in rats pretreated with WSLEt. As further confirmed histopathologically, our findings strongly suggest that the cardioprotective effect of WSLEt on myocardium experiencing ISO-induced oxidative damage may be due to an augmentation of the endogenous antioxidant system and an inhibition of LPO in the myocardial membrane. We conclude that WSLEt confers some protection against oxidative damage in ISO-induced MI in rats.
  5. Maddin N, Husin A, Gan SH, Aziz BA, Ankathil R
    Oncol Ther, 2016;4(2):303-314.
    PMID: 28261657 DOI: 10.1007/s40487-016-0035-x
    INTRODUCTION: Imatinib mesylate (IM), a selective inhibitor of the BCR-ABL tyrosine kinase, is a well-established first-line treatment for chronic myeloid leukemia (CML). IM is metabolized mainly by cytochrome P450 (CYP) in the liver, specifically the CYP3A4 and CYP3A5 enzymes. Polymorphisms in these genes can alter the enzyme activity of IM and may affect its response. In this study, the impact of two single-nucleotide polymorphisms (SNPs), CYP3A5*3 (6986A>G) and CYP3A4*18 (878T>C), on IM treatment response in CML patients (n = 270; 139 IM resistant and 131 IM good responders) was investigated.

    METHODS: Genotyping of CYP3A4*18 and CYP3A5*3 was performed using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) technique. The association between allelic variants and treatment response was assessed by means of odds ratio (OR) with 95% confidence intervals calculated by logistic regression.

    RESULTS: Our results indicated that CML patients carrying the heterozygous (AG) and homozygous variant (GG) genotype of CYP3A5*3 were associated with a significantly lower risk of acquiring resistance with OR 0.171; 95% CI: 0.090-0.324, p 

  6. Malik A, Ashraf MAB, Khan MW, Zahid A, Shafique H, Waquar S, et al.
    Arch Environ Contam Toxicol, 2020 Apr;78(3):329-336.
    PMID: 31620805 DOI: 10.1007/s00244-019-00673-2
    The use of leaded gasoline adversely affects cardiovascular, nervous, and immune systems. Study projects to rule out different variables of prognostic importance in lead-exposed subjects. A total of 317 traffic wardens with 5 years of outdoor experience and Hb levels
  7. Bender O, Shoman ME, Ali TFS, Dogan R, Celik I, Mollica A, et al.
    Arch Pharm (Weinheim), 2023 Feb;356(2):e2200407.
    PMID: 36403191 DOI: 10.1002/ardp.202200407
    FMS-like tyrosine kinase 3 (FLT3) mutations occur in approximately 30% of acute myeloid leukemia (AML) patients. In the current study, the oxindole chemotype is employed as a structural motif for the design of new FLT3 inhibitors as potential hits for AML irradiation. Cell-based screening was performed with 18 oxindole derivatives and 5a-c inhibited 68%-73% and 83%-91% of internal tandem duplication (ITD)-mutated MV4-11 cell growth for 48- and 72-h treatments while only 0%-2% and 27%-39% in wild-type THP-1 cells. The most potent compound 5a inhibited MV4-11 cells with IC50 of 4.3 µM at 72 h while it was 8.7 µM in THP-1 cells, thus showing two-fold selective inhibition against the oncogenic ITD mutation. The ability of 5a to modulate cell death was examined. High-throughput protein profiling revealed low levels of the growth factors IGFBP-2 and -4 with the blockage of various apoptotic inhibitors such as Survivin. p21 with cellular stress mechanisms was characterized by increased expression of HSP proteins along with TNF-β. Mechanistically, compounds 5a and 5b inhibited FLT3 kinase with IC50 values of 2.49 and 1.45 µM, respectively. Theoretical docking studies supported the compounds' ability to bind to the FLT3 ATP binding site with the formation of highly stable complexes as evidenced by molecular dynamics simulations. The designed compounds also provide suitable drug candidates with no violation of drug likeability rules.
  8. Lum PT, Sekar M, Gan SH, Pandy V, Bonam SR
    Saudi J Biol Sci, 2021 Jan;28(1):917-927.
    PMID: 33424383 DOI: 10.1016/j.sjbs.2020.11.037
    Memory impairment (MI) is one of the predominant criteria generally used to identify schizophrenia, dementia and amnesia that are associated with neurodegenerative disorders by evaluating patient's cognitive symptoms. To date, there is no available treatment that can completely mitigate MI. Currently, there is a trend in recent investigations towards symptomatic therapy approaches using a variety of natural compounds. Mangiferin is one of them that have been investigated extensively. Mangiferin is a naturally occurring potent glucoxilxanthone and is mainly isolated from the Mangifera indica (Mango) plant. This review is aimed at providing a comprehensive overview on the efficacy of mangiferin on MI, based on in-vivo animal studies. After screening through articles identified from Scopus and PubMed based on the inclusion and exclusion criteria, a total of 11 articles between 2009 and 2019 were included. The minimum and maximum dose of mangiferin were 10 and 200 mg/kg respectively and administered over the period of 12-154 days. The results of 11 articles showed that mangiferin effectively improved spatial recognition, episodic aversive events, short- and long-term memories primarily occurring via its antioxidant and anti-inflammatory effects. The outcomes of the review revealed that mangiferin improves memory and cognitive impairment in different animal models, indicating that it has potential preventive and therapeutic roles in MI.
  9. Haque ST, Islam RA, Gan SH, Chowdhury EH
    Int J Mol Sci, 2020 Sep 14;21(18).
    PMID: 32937817 DOI: 10.3390/ijms21186721
    Background: The limitations of conventional treatment modalities in cancer, especially in breast cancer, facilitated the necessity for developing a safer drug delivery system (DDS). Inorganic nano-carriers based on calcium phosphates such as hydroxyapatite (HA) and carbonate apatite (CA) have gained attention due to their biocompatibility, reduced toxicity, and improved therapeutic efficacy. Methods: In this study, the potential of goose bone ash (GBA), a natural derivative of HA or CA, was exploited as a pH-responsive carrier to successfully deliver doxorubicin (DOX), an anthracycline drug into breast cancer cells (e.g., MCF-7 and MDA-MB-231 cells). GBA in either pristine form or in suspension was characterized in terms of size, morphology, functional groups, cellular internalization, cytotoxicity, pH-responsive drug (DOX) release, and protein corona analysis. Results: The pH-responsive drug release study demonstrated the prompt release of DOX from GBA through its disintegration in acidic pH (5.5-6.5), which mimics the pH of the endosomal and lysosomal compartments as well as the stability of GBA in physiological pH (pH 7.5). The result of DOX binding with GBA indicated an increment in binding affinity with increasing concentrations of DOX. Cell viability and cytotoxicity analysis showed no innate toxicity of GBA particles. Both qualitative and quantitative cellular uptake analysis in both cell lines displayed an enhanced cellular internalization of DOX-loaded GBA compared to free DOX molecules. The protein corona spontaneously formed on the surface of GBA particles exhibited its affinity toward transport proteins, structural proteins, and a few other selective proteins. The adsorption of transport proteins could extend the circulation half-life in biological environment and increase the accumulation of the drug-loaded NPs through the enhanced permeability and retention (EPR) effect at the tumor site. Conclusion: These findings highlight the potential of GBA as a DDS to successfully deliver therapeutics into breast cancer cells.
  10. Azman S, Sekar M, Bonam SR, Gan SH, Wahidin S, Lum PT, et al.
    J Asthma Allergy, 2021;14:641-662.
    PMID: 34163178 DOI: 10.2147/JAA.S296391
    Asthma is a chronic inflammatory disease of the respiratory tract in which the numerous immune cells, including eosinophils, neutrophils, macrophages, T-lymphocytes, mast cells and epithelial lining play key roles. The numerous anti-asthmatic drugs are available in modern medicine to treat asthma, but they have several disadvantages, including side effects and the cost variations, which compromise treatment compliance. The literature review reveals that traditional herbal medicines have good potential as alternative treatment and management for asthma. However, communities hesitated to use the traditional herbal medicines due to lack of established mechanism of action about their anti-asthmatic potential. The present review aimed to summarise the information stated in the literature about the potential effect of traditional medicinal plants (TMPs) conferring protection against ovalbumin (OVA)-induced asthma model. The literature search was conducted in database like PubMed, Scopus, Google Scholar and ScienceDirect. After screening through the literature from 2011 to date, a total of 27 medicinal plants and two polyherbal extracts have been reported to be used as traditional herbal medicines and also utilised to be tested against OVA-induced asthma, were included. We found them to be an important alternative source of treatment for asthma, since some have comparable efficacies with drugs commonly used in the modern system against asthma. All the reported medicinal plants confirmed their traditional use against asthma or its related inflammation. The present review provides faith in traditional information and also offers new insight into the potential of natural products against asthma.
  11. Muhamad Fadzil NS, Sekar M, Gan SH, Bonam SR, Wu YS, Vaijanathappa J, et al.
    Drug Des Devel Ther, 2021;15:2721-2746.
    PMID: 34188450 DOI: 10.2147/DDDT.S299753
    Swertiamarin, a seco-iridoid glycoside, is mainly found in Enicostemma littorale Blume (E. littorale) and exhibits therapeutic activities for various diseases. The present study aimed to provide a review of swertiamarin in terms of its phytochemistry, physicochemical properties, biosynthesis, pharmacology and therapeutic potential. Relevant literature was collected from several scientific databases, including PubMed, ScienceDirect, Scopus and Google Scholar, between 1990 and the present. This review included the distribution of swertiamarin in medicinal plants and its isolation, characterization, physicochemical properties and possible biosynthetic pathways. A comprehensive summary of the pharmacological activities, therapeutic potential and metabolic pathways of swertiamarin was also included after careful screening and tabulation. Based on the reported evidence, swertiamarin meets all five of Lipinski's rules for drug-like properties. Thereafter, the physicochemical properties of swertiamarin were detailed and analyzed. A simple and rapid method for isolating swertiamarin from E. littorale has been described. The present review proposed that swertiamarin may be biosynthesized by the mevalonate or nonmevalonate pathways, followed by the seco-iridoid pathway. It has also been found that swertiamarin is a potent compound with diverse pharmacological activities, including hepatoprotective, analgesic, anti-inflammatory, antiarthritis, antidiabetic, antioxidant, neuroprotective and gastroprotective activities. The anticancer activity of swertiamarin against different cancer cell lines has been recently reported. The underlying mechanisms of all these pharmacological effects are diverse and seem to involve the regulation of different molecular targets, including growth factors, inflammatory cytokines, protein kinases, apoptosis-related proteins, receptors and enzymes. Swertiamarin also modulates the activity of several transcription factors, and their signaling pathways in various pathological conditions are also discussed. Moreover, we have highlighted the toxicity profile, pharmacokinetics and possible structural modifications of swertiamarin. The pharmacological activities and therapeutic potential of swertiamarin have been extensively investigated. However, more advanced studies are required including clinical trials and studies on the bioavailability, permeability and administration of safe doses to offer swertiamarin as a novel candidate for future drug development.
  12. Nabihah Nasir N, Sekar M, Ravi S, Wong LS, Sisinthy SP, Gan SH, et al.
    Drug Des Devel Ther, 2023;17:1065-1078.
    PMID: 37064433 DOI: 10.2147/DDDT.S388490
    Streptonigrin is an aminoquinone alkaloid isolated from Streptomyces flocculus and is gaining attention as a drug molecule owing to its potential antitumor and antibiotic effects. It was previously used as an anticancer drug but has been discontinued because of its toxic effects. However, according to the most recent studies, the toxicity of streptonigrin and its structurally modified derivatives has been reduced while maintaining their potential pharmacological action at lower concentrations. To date, many investigations have been conducted on this molecule and its derivatives to determine the most effective molecule with low toxicity to enable new drug discovery. Therefore, the main objective of this study is to provide a comprehensive review and to discuss the prospects for streptonigrin and its derived compounds, which may boost the molecule as a highly interesting target molecule for new drug design, development and therapy. To complete this review, relevant literature was collected from several scientific databases, including Google Scholar, PubMed, Scopus and ScienceDirect. Following a complete screening, the obtained information is summarized in the present review to provide a good reference and accelerate the development and utilization of streptonigrin and its derivatives as pharmaceuticals.
  13. Amir Yusri MA, Sekar M, Wong LS, Gan SH, Ravi S, Subramaniyan V, et al.
    Drug Des Devel Ther, 2023;17:1079-1096.
    PMID: 37064431 DOI: 10.2147/DDDT.S389977
    Celastrol is a naturally occurring chemical isolated from Tripterygium wilfordii Hook. f., root extracts widely known for their neuroprotective properties. In this review, we focus on the efficacy of celastrol in mitigating memory impairment (MI) in both in vivo and in vitro models. Scopus, PubMed and Web of Science databases were utilised to locate pertinent literatures that explore the effects of celastrol in the brain, including its pharmacokinetics, bioavailability, behavioral effects and some of the putative mechanisms of action on memory in many MI models. To date, preclinical studies strongly suggest that celastrol is highly effective in enhancing the cognitive performance of MI animal models, particularly in the memory domain, including spatial, recognition, retention and reference memories, via reduction in oxidative stress and attenuation of neuro-inflammation, among others. This review also emphasised the challenges and potential associated enhancement of medication delivery for MI treatment. Additionally, the potential structural alterations and derivatives of celastrol in enhancing its physicochemical and drug-likeness qualities are examined. The current review demonstrated that celastrol can improve cognitive performance and mitigate MI in several preclinical investigations, highlighting its potential as a natural lead molecule for the design and development of a novel neuroprotective medication.
  14. Chowdhury MA, Jahan I, Karim N, Alam MK, Abdur Rahman M, Moniruzzaman M, et al.
    Biomed Res Int, 2014;2014:145159.
    PMID: 24711991 DOI: 10.1155/2014/145159
    In the present study, the residual pesticide levels were determined in eggplants (Solanum melongena) (n = 16), purchased from four different markets in Dhaka, Bangladesh. The carbamate and organophosphorus pesticide residual levels were determined by high performance liquid chromatography (HPLC), and the efficiency of gamma radiation on pesticide removal in three different types of vegetables was also studied. Many (50%) of the samples contained pesticides, and three samples had residual levels above the maximum residue levels determined by the World Health Organisation. Three carbamates (carbaryl, carbofuran, and pirimicarb) and six organophosphates (phenthoate, diazinon, parathion, dimethoate, phosphamidon, and pirimiphos-methyl) were detected in eggplant samples; the highest carbofuran level detected was 1.86 mg/kg, while phenthoate was detected at 0.311 mg/kg. Gamma radiation decreased pesticide levels proportionately with increasing radiation doses. Diazinon, chlorpyrifos, and phosphamidon were reduced by 40-48%, 35-43%, and 30-45%, respectively, when a radiation strength of 0.5 kGy was utilized. However, when the radiation dose was increased to 1.0 kGy, the levels of the pesticides were reduced to 85-90%, 80-91%, and 90-95%, respectively. In summary, our study revealed that pesticide residues are present at high amounts in vegetable samples and that gamma radiation at 1.0 kGy can remove 80-95% of some pesticides.
  15. Fuloria S, Yusri MAA, Sekar M, Gan SH, Rani NNIM, Lum PT, et al.
    Molecules, 2022 Jan 01;27(1).
    PMID: 35011497 DOI: 10.3390/molecules27010265
    Genistein is a naturally occurring polyphenolic molecule in the isoflavones group which is well known for its neuroprotection. In this review, we summarize the efficacy of genistein in attenuating the effects of memory impairment (MI) in animals. Scopus, PubMed, and Web of Science databases were used to find the relevant articles and discuss the effects of genistein in the brain, including its pharmacokinetics, bioavailability, behavioral effects, and some of the potential mechanisms of action on memory in several animal models. The results of the preclinical studies highly suggested that genistein is highly effective in enhancing the cognitive performance of the MI animal models, specifically in the memory domain, including spatial, recognition, retention, and reference memories, through its ability to reduce oxidative stress and attenuate neuroinflammation. This review also highlighted challenges and opportunities to improve the drug delivery of genistein for treating MI. Along with that, the possible structural modifications and derivatives of genistein to improve its physicochemical and drug-likeness properties are also discussed. The outcomes of the review proved that genistein can enhance the cognitive performance and ameliorate MI in different preclinical studies, thus indicating its potential as a natural lead for the design and development of a novel neuroprotective drug.
  16. Khattulanuar FS, Sekar M, Fuloria S, Gan SH, Rani NNIM, Ravi S, et al.
    Molecules, 2022 Jan 20;27(3).
    PMID: 35163934 DOI: 10.3390/molecules27030673
    Cardiovascular disorders (CVDs) are the leading risk factor for death worldwide, and research into the processes and treatment regimens has received a lot of attention. Tilianin is a flavonoid glycoside that can be found in a wide range of medicinal plants and is most commonly obtained from Dracocephalum moldavica. Due to its extensive range of biological actions, it has become a well-known molecule in recent years. In particular, numerous studies have shown that tilianin has cardioprotective properties against CVDs. Hence, this review summarises tilianin's preclinical research in CVDs, as well as its mechanism of action and opportunities in future drug development. The physicochemical and drug-likeness properties, as well as the toxicity profile, were also highlighted. Tilianin can be a natural lead molecule in the therapy of CVDs such as coronary heart disease, angina pectoris, hypertension, and myocardial ischemia, according to scientific evidence. Free radical scavenging, inflammation control, mitochondrial function regulation, and related signalling pathways are all thought to play a role in tilianin's cardioprotective actions. Finally, we discuss tilianin-derived compounds, as well as the limitations and opportunities of using tilianin as a lead molecule in drug development for CVDs. Overall, the scientific evidence presented in this review supports that tilianin and its derivatives could be used as a lead molecule in CVD drug development initiatives.
  17. Selvaraj LK, Jeyabalan S, Wong LS, Sekar M, Logeshwari B, Umamaheswari S, et al.
    Front Pharmacol, 2022;13:990799.
    PMID: 36386131 DOI: 10.3389/fphar.2022.990799
    Baicalein is a flavonoid mainly obtained from plants with wide range of biological activities, including neuroprotection. An acute and unexpected chronic stress (UCS) protocol has recently been adapted to zebrafish, a popular vertebrate model in brain research. The present study was aimed to evaluate baicalein's anti-anxiety potential in a zebrafish model by induction, which included neuropharmacological evaluation to determine behavioural parameters in the novel tank diving test (NTDT) and light-dark preference test (LDPT). The toxicity was also assessed using the brine shrimp lethality assay, and the 50% lethal concentration (LC50) was determined. The animals were then stressed for 7 days before being treated with different doses of baicalein (1 and 2 mg/L) for another 7 days in UCS condition. Due to acute stress and UCS, the frequency of entries and time spent in the 1) top region and 2) light area of the novel tank reduced significantly, indicating the existence of elevated anxiety levels. The biological activity of baicalein was demonstrated by its high LC50 values (1,000 μg/ml). Additionally, baicalein administration increased the frequency of entries and duration spent in the light region, indicating a significant decrease in anxiety levels. Overall, the present results showed that baicalein has a therapeutic advantage in reversing the detrimental consequences of UCS and acute stress, making it is a promising lead molecule for new drug design, development, and therapy for stress.
  18. Subramanian A, Tamilanban T, Sekar M, Begum MY, Atiya A, Ramachawolran G, et al.
    Front Pharmacol, 2023;14:1212376.
    PMID: 37781695 DOI: 10.3389/fphar.2023.1212376
    Background: Excitotoxicity is a condition in which neurons are damaged/injured by the over-activation of glutamate receptors. Excitotoxins play a crucial part in the progression of several neurological diseases. Marsilea quadrifolia Linn (M. quadrifolia) is a very popular aquatic medicinal plant that has been utilised for a variety of therapeutic benefits since ancient times. Its chemical composition is diverse and includes phenolic compounds, tannins, saponins, flavonoids, steroids, terpenoids, alkaloids, carbohydrates and several others that possess antioxidant properties. Objective: The objective of the present study was to investigate the neuroprotective potential of M. quadrifolia against monosodium glutamate (MSG)-induced excitotoxicity in rats. Methods: A high-performance thin-layer chromatography (HPTLC) analysis of chloroform extract of M. quadrifolia (CEMQ) was conducted to identify the major constituents. Further, the in silico docking analysis was carried out on selected ligands. To confirm CEMQ's neuroprotective effects, the locomotor activity, non-spatial memory, and learning were assessed. Results and discussion: The present study confirmed that CMEQ contains quercetin and its derivatives in large. The in-silico findings indicated that quercetin has a better binding affinity (-7.9 kcal/mol) towards the protein target 5EWJ. Animals treated with MSG had 1) a greater reduction in the locomotor score and impairment in memory and learning 2) a greater increase in the blood levels of calcium and sodium and 3) neuronal disorganization, along with cerebral edema and neuronal degeneration in the brain tissues as compared to normal control animals. The changes were however, significantly improved in animals which received standard drug memantine (20 mg/kg) and CEMQ (200 and 400 mg/kg) as compared to the negative control. It is plausible that the changes seen with CEMQ may be attributed to the N-methyl-D-aspartate (NMDA) antagonistic properties. Conclusion: Overall, this study indicated that M. quadrifolia ameliorated MSG-induced neurotoxicity. Future investigations are required to explore the neuroprotective mechanism of M. quadrifolia and its active constituents, which will provide exciting insights in the therapeutic management of neurological disorders.
  19. Fuloria S, Mehta J, Talukdar MP, Sekar M, Gan SH, Subramaniyan V, et al.
    Front Microbiol, 2022;13:950913.
    PMID: 35910609 DOI: 10.3389/fmicb.2022.950913
    Fermented foods have been an important component of the human diet from the time immemorial. It contains a high amount of probiotics that have been associated to a wide range of health benefits, including improved digestion and immunity. This review focuses on the indigenously prepared prebiotic- and probiotic-containing functional fermented rice (named Xaj-pani) by the Ahom Community from Assam, in Northeast India, including all the beneficial and potential effects on human health. Literature was searched from scientific databases such as PubMed, ScienceDirect and Google Scholar. Glutinous rice (commonly known as bora rice of sali variety) is primarily employed to prepare beverages that are recovered through the filtration process. The beer is normally consumed during religious rites, festivals and ritual practices, as well as being used as a refreshing healthy drink. Traditionally, it is prepared by incorporating a variety of medicinal herbs into their starter culture (Xaj-pitha) inoculum which is rich in yeasts, molds and lactic acid bacteria (LAB) and then incorporated in alcoholic beverage fermentation. The Ahom communities routinely consume this traditionally prepared alcoholic drink with no understanding of its quality and shelf life. Additionally, a finally produced dried cake, known as vekur pitha act as a source of Saccharomyces cerevisiae and can be stored for future use. Despite the rampant use in this community, the relationship between Xaj-pani's consumption, immunological response, infectious and inflammatory processes remains unknown in the presence of factors unrelated or indirectly connected to immune function. Overall, this review provides the guidelines to promote the development of prebiotic- and probiotic-containing functional fermented rice that could significantly have an impact on the health of the consumers.
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