Displaying publications 61 - 80 of 95 in total

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  1. Mahdi HJ, Khan NAK, Asmawi MZB, Mahmud R, A/L Murugaiyah V
    Integr Med Res, 2018 Mar;7(1):85-94.
    PMID: 29629295 DOI: 10.1016/j.imr.2017.11.002
    Background: The medicinal uses of plants are in many cases based exclusively on traditional knowledge without enough scientific evidences. Different parts of Moringa oleifera were traditionally used for the treatment of wide variety of ailments including arthritis and joints pain. The present study had been designed to evaluate the anti-arthritic and anti-nociceptive activities of ethanol extract of Moringa leaves, this being the most abundant plant part suitable for commercial mass production of botanical medicinal products.

    Methods: Complete Freund's adjuvant (CFA)-induced arthritis in rats was used as disease model. CFA-induced inflammatory paw edema, body weight, arthritic index, X-ray radiography, hematological parameters, and walk track and locomotion analysis were all evaluated for the assessment of disease progression. In addition to that, anti-nociceptive activity was examined at different dose levels in both normal and arthritic-induced rats using Eddy's hot plate and tail flick thermal analgesia.

    Results: The analysis of various arthritic assessment parameters used in this study revealed that Moringa extract has a considerable effect in preventing development or ameliorate arthritis disease severity. Moreover, the ethanol extract of Moringa leaves revealed significant anti-nociceptive activity at in both normal and CFA-induced arthritis rats in a dose-dependent manner.

    Conclusion: Ethanol extract of Moringa leaves appears to be a really promising as analgesic and arthritis medication, but a larger and more detailed preclinical and clinical studies especially in human is highly recommended.

  2. Khan AA, Abdulbaqi IM, Abou Assi R, Murugaiyah V, Darwis Y
    Nanoscale Res Lett, 2018 Oct 15;13(1):323.
    PMID: 30324291 DOI: 10.1186/s11671-018-2744-6
    Verapamil is a calcium channel blocker and highly effective in the treatment of hypertension, angina pectoris, and other diseases. However, the drug has a low bioavailability of 20 to 35% due to the first pass effect. The main objective of this study was to develop hybrid verapamil-dextran nanostructured lipid carriers (HVD-NLCs) in an attempt to increase verapamil cellular uptake. The formulations were successfully prepared by a high-shear homogenization method and statistically optimized using 24 full factorial design. The HVD-NLCs formulations were freeze-dried using trehalose as a cryoprotectant. The results showed that the optimized formula (VER-9) possessed a particle size (PS), polydispersity index (PDI), and the percentage of entrapment efficiency (%EE) of 192.29 ± 2.98, 0.553 ± 0.075, and 93.26 ± 2.66%, respectively. The incorporation of dextran sulfate in the formulation had prolonged the release of verapamil (~ 85% in 48 h) in the simulated gastric fluid (pH 1.2) and simulated intestinal fluid (pH 6.8). The differential scanning calorimetry analysis showed no chemical interaction between verapamil and the excipients in the formulation. While wide-angle X-ray scattering studies demonstrated the drug in the amorphous form after the incorporation in the NLCs. The transmission electron microscopy and scanning electron microscopy images revealed that the nanoparticles had spherical shape. The cellular uptake study using Caco-2 cell line showed a higher verapamil uptake from HVD-NLCs as compared to verapamil solution and verapamil-dextran complex. The optimized formulation (VER-9) stored in the refrigerated condition (5 °C ± 3 °C) was stable for 6 months. In conclusion, the HVD-NLCs were potential carriers for verapamil as they significantly enhanced the cellular uptake of the drug.
  3. Parambi DGT, Aljoufi F, Murugaiyah V, Mathew GE, Dev S, Lakshminarayanan B, et al.
    PMID: 30451121 DOI: 10.2174/1871524918666181119114016
    BACKGROUND: Dual-acting human monoamine oxidase B (hMAO-B) and cholinesterase (ChE) inhibitors are more effective than the classic one-drug one-target therapy for Alzheimer's disease (AD).

    METHODS: The ChE inhibitory ability of some halogenated thiophene chalcone-based molecules known to be selective hMAO-B inhibitors was evaluated.

    RESULTS: Based on the IC50 values, the selected compounds were found to moderately inhibit ChE, with IC50 values in the range of 14-70 µM. Among the synthesised molecules, T8 and T6 showed the most potent inhibitory activity against AChE and BChE, respectively.

    CONCLUSION: Taken together, the data revealed that T8 could be further optimized to enhance its AChE inhibitory activity.

  4. Sundarasekar J, Sahgal G, Murugaiyah V, Lay LK, Thong OM, Subramaniam S
    Pak J Pharm Sci, 2018 Nov;31(6):2537-2543.
    PMID: 30473529
    Spider lily (Hymenocallis littoralis) belongs to Amaryllidaceae family is a well-known plant species for its medicinal properties. The inhibitory effects of H. littoralis methanol sonication extracts were evaluated for wound healing activity. This is the first report on the wound healing activity of Malaysian origin H. littoralis. The bulb, flower, root, anther, stem and leaves of H. littoralis methanol sonication extracts were used for scratch-wound assay. The cell line was treated with two different concentrations; 1 and 10μg/ml of extracts. The extracts were prepared freshly by dissolving in sterile phosphate saline buffer (PBS) and the healing activity was observed from 2, 4, 8, 12, 24, 36 and 48 h. The bulb, root, stem and anther methanol extracts demonstrated active wound healing activities at 1 μg mL-1at 36 h of treatment. At the low concentration the bulb, root, stem and anther methanol extracts heals the wound compared to leaf and flower extracts. It's demonstrated that these extracts contain effective phytochemical substances which are responsible for wound healing process. This finding suggests the potential application of H. littoralis methanol extract in wound healing activity.
  5. Yeong KY, Khaw KY, Takahashi Y, Itoh Y, Murugaiyah V, Suzuki T
    Bioorg Chem, 2020 01;94:103403.
    PMID: 31711765 DOI: 10.1016/j.bioorg.2019.103403
    Studies have suggested that sirtuin inhibition may have beneficial effects on several age-related diseases such as neurodegenerative disorders and cancer. Garcinia mangostana is a well-known tropical plant found mostly in South East Asia with several positive health effects. Some of its phytochemicals such as α-mangostin was found to be able to modulate sirtuin activity in mice and was implicated with inflammation, diabetes and obesity. However, comprehensive studies on sirtuin activity by the prenylated xanthones extracted from Garcinia mangostana have yet to be reported. The present study led to the discovery and identification of γ-mangostin as a potent and selective SIRT2 inhibitor. It was demonstrated that γ-mangostin was able to increase the α-tubulin acetylation in MDA-MD-231 and MCF-7 breast cancer cells. It was also found to possess potent antiproliferative activity against both cell lines. In addition, it was able to induce neurite outgrowth in the N2a cells.
  6. Saghir SA, Sadikun A, Al-Suede FS, Majid AM, Murugaiyah V
    Curr Pharm Biotechnol, 2016 6 6;17(10):915-25.
    PMID: 27262321 DOI: 10.2174/1389201017666160603013434
    BACKGROUND: Star fruit (Averrhoa carambola) is a well-known plant in Malaysia which bears a great significance in traditional medicine.

    OBJECTIVES: This study aimed to evaluate the antihyperlipidemic effect, antioxidant potential and cytotoxicity of aqueous and methanolic extracts of ripe and unripe fruits, leaves and stem of A. carambola.

    METHODS: Antihyperlipidemic activity was assessed in poloxamer-407 (P-407) induced acute hyperlipidemic rat's model. The antioxidant activity was assessed in vitro using 2, 2'-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical scavenging, 1-diphenyl-2-dipicrylhydrazyl radical scavenging (DPPH) and ferric reducing antioxidant power (FRAP) assays. In addition, cytotoxicity of A. carambola extracts was assessed using MTS assay on four leukemic cell lines (human colon cancer, human promyeloid leukemia, erythroid leukemia, acute myeloid leukemia) and one normal cell (human umbilical vein endothelial cells).

    RESULTS: Methanolic extract of leaves had the most potent antihyperlipidemic activity in P-407 model, whereby it significantly reduced serum levels of total cholesterol (P<0.01), triglycerides (P<0.01), low-density lipoprotein (P<0.05), verylow- density lipoprotein (P<0.01) and atherogenic index (P<0.01). On the other hand, methanolic extracts of A. carambola stem and leaves showed the strongest antioxidant activity. Total phenolic and flavonoid contents of the extracts exhibited significant correlations with antioxidant but not with antihyperlipidemic activities. All plant parts showed no cytotoxic effect on the selected cancer or normal cell lines.

    CONCLUSION: Antihyperlipidemic activity of different parts of A. carambola is greatly affected by extraction solvents used. Methanolic extract of A. carambola leaves exhibited higher antihyperlipidemic and antioxidant potentials compared to other parts of the plant.
  7. Wan Othman WNN, Liew SY, Khaw KY, Murugaiyah V, Litaudon M, Awang K
    Bioorg Med Chem, 2016 09 15;24(18):4464-4469.
    PMID: 27492195 DOI: 10.1016/j.bmc.2016.07.043
    Alzheimer's disease is the most common form of dementia among older adults. Acetylcholinesterase and butyrylcholinesterase are two enzymes involved in the breaking down of the neurotransmitter acetylcholine. Inhibitors for these enzymes have potential to prolong the availability of acetylcholine. Hence, the search for such inhibitors especially from natural products is needed in developing potential drugs for Alzheimer's disease. The present study investigates the cholinesterase inhibitory activity of compounds isolated from three Cryptocarya species towards acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Nine alkaloids were isolated; (+)-nornantenine 1, (-)-desmethylsecoantofine 2, (+)-oridine 3, (+)-laurotetanine 4 from the leaves of Cryptocarya densiflora BI., atherosperminine 5, (+)-N-methylisococlaurine 6, (+)-N-methyllaurotetanine 7 from the bark of Cryptocarya infectoria Miq., 2-methoxyatherosperminine 8 and (+)-reticuline 9 from the bark of Cryptocarya griffithiana Wight. In general, most of the alkaloids showed higher inhibition towards BChE as compared to AChE. The phenanthrene type alkaloid; 2-methoxyatherosperminine 8, exhibited the most potent inhibition against BChE with IC50 value of 3.95μM. Analysis of the Lineweaver-Burk (LB) plot of BChE activity over a range of substrate concentration suggested that 2-methoxyatherosperminine 8 exhibited mixed-mode inhibition with an inhibition constant (Ki) of 6.72μM. Molecular docking studies revealed that 2-methoxyatherosperminine 8 docked well at the choline binding site and catalytic triad of hBChE (butyrylcholinesterase from Homo sapiens); hydrogen bonding with Tyr 128 and His 438 residues respectively.
  8. Murugesu K, Murugaiyah V, Saghir SAM, Asmawi MZ, Sadikun A
    Curr Pharm Biotechnol, 2017;18(14):1132-1140.
    PMID: 29564975 DOI: 10.2174/1389201019666180322111800
    BACKGROUND: Ethanolic extract of G. procumbens leaves has been previously shown to possess antihyperlipidemic effects.

    OBJECTIVE: This study was designed to prepare caffeoylquinic acids rich and poor fractions of the ethanolic extract using resin column technology and compare their antihyperlipidemic and antioxidant potentials.

    RESULTS: Among the treatment groups, caffeoylquinic acids rich fraction (F2) and chlorogenic acid (CA, one of the major caffeoylquinic acids) showed potent antihyperlipidemic effects, with significant reductions in total cholesterol (TC), triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C), very low-density lipoprotein-cholesterol (VLDL-C), atherogenic index (AI) and coronary risk index (CRI) (p<0.01 or better) compared to the hyperlipidemic control at the 58 h. The effect was better than that of ethanolic extract. In addition, only F2 significantly increased the high-density lipoproteincholesterol (HDL-C) level (p<0.05). F2 showed better effect than CA alone (60 mg) despite the fact that it only contained 9.81 mg CA/1000 mg dose. The findings suggest that the di-caffeoylquinic acids (86.61 mg/g dose) may also in part be responsible for the potent antihyperlipidemic effect shown by the F2. Likewise, F2 showed the highest antioxidant activity. Thus, simple fractionation of ethanolic extract using the Amberlite XAD-2 resin technique had successfully enriched the caffeoylquinic acids into F2 with improved antihyperlipidemic and antioxidant capacities than that of the ethanolic extract.

    CONCLUSION: The resin separation technology may find application in caffeoylquinic acids enrichment of plant extracts for pre-clinical studies. The F2 has potential for development into phytopharmaceuticals as adjunct therapy for management of hyperlipidemia.

  9. Wong LC, Poh JH, Tan WT, Khor BK, Murugaiyah V, Leh CP, et al.
    Int J Biol Macromol, 2023 Jan 01;224:483-495.
    PMID: 36273545 DOI: 10.1016/j.ijbiomac.2022.10.138
    Hydrogels are an attractive platform for drug delivery to the skin. Current cellulose hydrogel developments commonly focus on readily available bleached woody cellulose. Considering the detrimental environmental impacts of bleaching reagents, unbleached non-woody biomass was proposed as an alternative. Herein, this study aims to develop hydrogel from native cellulose extracted from oil palm empty fruit bunches for dermal drug delivery with an emphasis on evaluating the effect of alkali solvent compositions on hydrogel formation. Unbleached dissolving pulps were solubilized in alkali solvents containing sodium hydroxide (NaOH) (6-8%w/v) and urea (4-6%w/v) before crosslinking. Hydrogels were loaded with ibuprofen for skin permeation studies. Light brownish hydrogels formed are aesthetically acceptable and biodegradable with low cytotoxicity. NaOH content has a dominant role over urea where thinner and deformable crosslinked network walls in a porous hydrogel structure are associated with high NaOH content. Synergistic effects (cellulose solubility: 94 %; swelling ratio: ~2800 %) were observed at 7%w/v NaOH and 4%w/v urea with low toxicity. Most hydrogels showed >80 % of ibuprofen permeated into the skin and this increased with the swelling ratio of hydrogels. Unbleached cellulose pulps have excellent potential for hydrogel fabrication with outstanding physicomechanical properties for dermal drug delivery.
  10. Mat NH, Bakar SNS, Murugaiyah V, Chawarski MC, Hassan Z
    Behav Brain Res, 2023 Feb 15;439:114251.
    PMID: 36503042 DOI: 10.1016/j.bbr.2022.114251
    Mitragynine exerts its analgesic effect mainly via opioid receptors activation. Additionally, the effect may be mediated via mitragynine's anti-inflammatory property and non-opioid receptor pain pathways, namely through the TRPV1 receptor. No studies identify hitherto, hence, the current study aimed to investigate the mitragynine's analgesic effect via the anti-inflammatory property, non-opioid receptor (TRPV1) and the effective dose (ED) to alleviate pain. Male and female Sprague Dawley rats were pre-treated intraperitoneally with either mitragynine (1, 5, 10, 13, 15 or 30 mg/kg), vehicle, or indomethacin (1 mg/kg) 30 min before inducing inflammatory pain using acetic acid. The writhes and pain-related withdrawal behaviour occurrence were counted within a 1-h duration. Percentage of writhes inhibition, pain-related withdrawal behaviour aggregate, ED50 and ED95 were determined. The body temperature was recorded and TRPV1 expression in the rats' brains was measured. Mitragynine (except 1 mg/kg) significantly reduced the number of writhes compared with the vehicle administered group. Mitragynine (30 mg/kg) demonstrated 99.5% inhibition of writhing behaviour and low withdrawal behaviour score compared with vehicle and indomethacin and successfully blocked the hypothermia induced by acetic acid. The overall ED50 and ED95 values of mitragynine were 3.62 and 20.84 mg/kg, respectively. The percentage of writhing inhibition and withdrawal behaviour were similar in both genders. Mitragynine (15 and 30 mg/kg) significantly reduced the TRPV1 expression in the brain of the rats. Mitragynine alleviated pain-like behaviour and showed analgesic effects via anti-inflammatory and non-opioid receptor pathways. The findings also suggest that mitragynine might regulate some physiological functions of the rat.
  11. Ganeson K, Alias AH, Murugaiyah V, Amirul AA, Ramakrishna S, Vigneswari S
    Pharmaceutics, 2023 Feb 23;15(3).
    PMID: 36986606 DOI: 10.3390/pharmaceutics15030744
    Cancer is the leading cause of death, acting as a global burden, severely impacting the patients' quality of life and affecting the world economy despite the expansion of cumulative advances in oncology. The current conventional therapies for cancer which involve long treatment duration and systemic exposure of drugs leads to premature degradation of drugs, a massive amount of pain, side effects, as well as the recurrence of the condition. There is also an urgent demand for personalized and precision-based medicine, especially after the recent pandemic, to avoid future delays in diagnosis or treatments for cancer patients as they are very essential in reducing the global mortality rate. Recently, microneedles which consist of a patch with tiny, micron-sized needles attached to it have been quite a sensation as an emerging technology for transdermal application to diagnose or treat various illnesses. The application of microneedles in cancer therapies is also being extensively studied as they offer a myriad of benefits, especially since microneedle patches offer a better treatment approach through self administration, painless treatment, and being an economically and environmentally friendly approach in comparison with other conventional methods. The painless gains from microneedles significantly improves the survival rate of cancer patients. The emergence of versatile and innovative transdermal drug delivery systems presents a prime breakthrough opportunity for safer and more effective therapies, which could meet the demands of cancer diagnosis and treatment through different application scenarios. This review highlights the types of microneedles, fabrication methods and materials, along with the recent advances and opportunities. In addition, this review also addresses the challenges and limitations of microneedles in cancer therapy with solutions through current studies and future works to facilitate the clinical translation of microneedles in cancer therapies.
  12. Ahad MA, Chear NJ, Keat LG, Has ATC, Murugaiyah V, Hassan Z
    Ageing Res Rev, 2023 Aug;89:101990.
    PMID: 37343678 DOI: 10.1016/j.arr.2023.101990
    Research employing a bio-enhanced fraction of Clitoria ternatea (CT) to treat cognitive decline in the animal model has not yet been found. This study aimed to determine the neuroprotective effect of CT root bioactive fraction (CTRF) in chronic cerebral hypoperfusion (CCH) rat model. CTRF and its major compound, clitorienolactones A (CLA), were obtained using column chromatography. A validated HPLC-UV method was employed for the standardization of CTRF. CCH rats were given orally either vehicle or fraction (10, 20 and 40 mg/kg). Behavioural and hippocampal neuroplasticity studies were conducted following 4 weeks post-surgery. The brain hippocampus was extracted for proteins and neurotransmitters analyses. HPLC analysis showed that CTRF contained 25% (w/w) of CLA. All tested doses of CTRF and CLA (10 mg/kg) significantly restored cognitive deficits and reversed the inhibition of neuroplasticity by CCH. However, only CTRF (40 mg/kg) and CLA (10 mg/kg) significantly reversed the elevation of amyloid-beta plaque. Subsequently, treatment with CTRF (40 mg/kg) and CLA (10 mg/kg) alleviated the downregulation of molecular synaptic signalling proteins levels caused by CCH. The neurotransmitters level was restored following treatment of CTRF and CLA. Our finding suggested that CTRF improves memory and neuroplasticity in CCH rats which was mainly contributed by CLA.
  13. Aruldass CA, Marimuthu MM, Ramanathan S, Mansor SM, Murugaiyah V
    Microsc Microanal, 2013 Feb;19(1):254-60.
    PMID: 23332129 DOI: 10.1017/S1431927612013785
    Mesua ferrea is traditionally used for treating bleeding piles, fever, and renal diseases. It has been reported to have antimircobial activity. In the present study, antibacterial efficacy of leaf and fruit extracts on the growth and morphology of Staphylococcus aureus is evaluated. Both extracts display good antibacterial activity against S. aureus with a minimum inhibition concentration of 0.048 mg/mL. Both extracts are bacteriostatic at a minimum bacteriostatic concentration of 0.39 mg/mL. The bacteriostatic activity lasts for 24 h, and then cells start to grow as normal as shown in time-kill analysis. Scanning electron microscopy study indicated potential detrimental effect of the extracts of leaf and fruits of M. ferrea on the morphology of S. aureus. The treatment with the extracts caused extensive lysis of the cells, leakage of intracellular constituents, and aggregation of cytoplasmic contents forming an open meshwork of the matrix.
  14. Almansour AI, Kumar RS, Arumugam N, Basiri A, Kia Y, Ali MA, et al.
    Molecules, 2015 Jan 29;20(2):2296-309.
    PMID: 25642838 DOI: 10.3390/molecules20022296
    A series of novel dimethoxyindanone embedded spiropyrrolidines were synthesized in ionic liquid, [bmim]Br and were evaluated for their inhibitory activities towards cholinesterases. Among the spiropyrrolidines, compound 4f exhibited the most potent activity with an IC50 value of 1.57 µM against acethylcholinesterase (AChE). Molecular docking simulation for the most active compound was employed with the aim of disclosing its binding mechanism to the active site of AChE receptor.
  15. Tan SM, Abou Assi R, Dianita R, Murugaiyah V, Chan SY
    Drug Dev Ind Pharm, 2024 May 09.
    PMID: 38530403 DOI: 10.1080/03639045.2024.2335527
    Objective: This research aimed to investigate the application of the coaxial electrospun method for the production of natural extracts (papaya leaf extract) fibre films. This was achieved through utilising different polymers and with a focus on the conductivity and the viscosity of polymer solutions as critical parameters to generate successful fibres.Significance: Electrospinning is a promising trending manufacturing method for incorporating thermolabile herbal extracts using coaxial electrospun features. However, the complexity of the electrospinning process and the feasibility of the product required precise scrutiny.Methods: The electrospinning solution parameters (conductivity and viscosity) were evaluated by employing various ratios of Eudragit L100 (EL100) and Eudragit L100-55 (EL100-55) pre-spinning polymeric blend solutions. The electrospinning process and ambient parameters were optimised. Following that, the in-silico physicochemical properties of phytochemical marker, rutin, were illustrated using SwissADME web tool. Both freeze-dried Carica papaya leaf extract and its produced films were characterised using Scanning Electron Microscopy (SEM), Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR), polarised light microscopy, and X-ray Powder Diffraction (XRPD).Results: The optimal values of conductivity (≈40-44 × 10-4 S/m) and viscosity (≈32-42 × 10-3 Pa·s) were determined for producing evenly distributed and small fibre diameters in SEM images. These parameters significance was highlighted in acquiring and maintaining adequate tangential stress for fibre elongation, which would consequently affect the morphology and diameter of the fibres formed.Conclusion: In conclusion, the solution, process, and ambient parameters are significant in developing natural extracts into films via electrospinning technology, and this includes the promising Carica papaya leaf extract films produced by coaxial electrospinning.
  16. Boudriga S, Haddad S, Murugaiyah V, Askri M, Knorr M, Strohmann C, et al.
    Molecules, 2020 Apr 23;25(8).
    PMID: 32340203 DOI: 10.3390/molecules25081963
    A novel one-pot [3+2]-cycloaddition reaction of (E)-3-arylidene-1-phenyl-succinimides, cyclic 1,2-diketones (isatin, 5-chloro-isatin and acenaphtenequinone), and diverse α-aminoacids such as 2-phenylglycine or sarcosine is reported. The reaction provides succinimide-substituted dispiropyrrolidine derivatives with high regio- and diastereoselectivities under mild reaction conditions. The stereochemistry of these N-heterocycles has been confirmed by four X-ray diffraction studies. Several synthetized compounds show higher inhibition on acetylcholinesterase (AChE) than butyrylcholinesterase (BChE). Of the 17 synthesized compounds tested, five exhibit good AChE inhibition with IC50 of 11.42 to 22.21 µM. A molecular docking study has also been undertaken for compound 4n possessing the most potent AChE inhibitory activity, disclosing its binding to the peripheral anionic site of AChE enzymes.
  17. Alshehade SA, Al Zarzour RH, Murugaiyah V, Lim SYM, El-Refae HG, Alshawsh MA
    Saudi Pharm J, 2022 Nov;30(11):1572-1588.
    PMID: 36465851 DOI: 10.1016/j.jsps.2022.09.001
    Non-alcoholic fatty liver disease (NAFLD) is one of the most common complications of a metabolic syndrome caused by excessive accumulation of fat in the liver. Orthosiphon stamineus also known as Orthosiphon aristatus is a medicinal plant with possible potential beneficial effects on various metabolic disorders. This study aims to investigate the in vitro inhibitory effects of O. stamineus on hepatic fat accumulation and to further use the computational systems pharmacology approach to identify the pharmacokinetic properties of the bioactive compounds of O. stamineus and to predict their molecular mechanisms against NAFLD.

    METHODS: The effects of an ethanolic extract of O. stamineus leaves on cytotoxicity, fat accumulation and antioxidant activity were assessed using HepG2 cells. The bioactive compounds of O. stamineus were identified using LC/MS and two bioinformatics databases, namely the Traditional Chinese Medicine Integrated Database (TCMID) and the Bioinformatics Analysis Tool for the Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). Pathway enrichment analysis was performed on the predicted targets of the bioactive compounds to provide a systematic overview of the molecular mechanism of action, while molecular docking was used to validate the predicted targets.

    RESULTS: A total of 27 bioactive compounds corresponding to 50 potential NAFLD-related targets were identified. O. stamineus exerts its anti-NAFLD effects by modulating a variety of cellular processes, including oxidative stress, mitochondrial β-oxidation, inflammatory signalling pathways, insulin signalling, and fatty acid homeostasis pathways. O. stamineus is significantly targeting many oxidative stress regulators, including JNK, mammalian target of rapamycin (mTOR), NFKB1, PPAR, and AKT1. Molecular docking analysis confirmed the expected high affinity for the potential targets, while the in vitro assay indicates the ability of O. stamineus to inhibit hepatic fat accumulation.

    CONCLUSION: Using the computational systems pharmacology approach, the potentially beneficial effect of O. stamineus in NAFLD was indicated through the combination of multiple compounds, multiple targets, and multicellular components.

  18. Liew SY, Khaw KY, Murugaiyah V, Looi CY, Wong YL, Mustafa MR, et al.
    Phytomedicine, 2015 Jan 15;22(1):45-8.
    PMID: 25636869 DOI: 10.1016/j.phymed.2014.11.003
    Nine monoterpenoid indole alkaloids; naucletine (1), angustidine (2), nauclefine (3), angustine (4), naucline (5), angustoline (6), harmane (7), 3,14-dihydroangustoline (8), strictosamide (9) and one quinoline alkaloid glycoside; pumiloside (10) from Nauclea officinalis were tested for cholinesterase inhibitory activity. All the alkaloids except for pumiloside (10) showed strong to weak BChE inhibitory effect with IC50 values ranging between 1.02-168.55 μM. Angustidine (2), nauclefine (3), angustine (4), angustoline (6) and harmane (7) showed higher BChE inhibiting potency compared to galanthamine. Angustidine (2) was the most potent inhibitor towards both AChE and BChE. Molecular docking (MD) studies showed that angustidine (2) docked deep into the bottom gorge of hBChE and formed hydrogen bonding with Ser 198 and His 438. Kinetic study of angustidine (2) on BChE suggested a mixed inhibition mode with an inhibition constant (Ki) of 6.12 μM.
  19. Yoon YK, Ali MA, Wei AC, Choon TS, Khaw KY, Murugaiyah V, et al.
    Bioorg Chem, 2013 Aug;49:33-9.
    PMID: 23886696 DOI: 10.1016/j.bioorg.2013.06.008
    Two series of novel acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors containing benzimidazole core structure were synthesized by a four-step reaction pathway starting from 4-fluoro-3-nitrobenzoic acid as the basic compound. The structure of the novel benzimidazoles was characterized and confirmed by the elemental and mass spectral analyses as well as (1)H NMR spectroscopic data. Of the 34 novel synthesized compounds, three benzimidazoles revealed AChE inhibition with IC50<10 μM. The highest inhibitory activity (IC50=5.12 μM for AChE and IC50=8.63 μM for BChE) corresponds to the compound 5IIc (ethyl 1-(3-(1H-imidazol-1-yl)propyl)-2-(4-nitrophenyl)-1H-benzo[d]imidazole-5-carboxylate). The relationship between lipophilicity and the chemical structures as well as their limited structure-activity relationship was discussed.
  20. Alagasamy SV, Ramanathan S, Chear NJ, Tan WN, Ramachandram DS, Ching-Ga AT, et al.
    J Complement Integr Med, 2021 Jan 01;18(2):339-345.
    PMID: 34187118 DOI: 10.1515/jcim-2019-0316
    OBJECTIVES: Mesua ferrae, from the family of Calophyllaceae, is traditionally used for the treatment of piles, fever and renal disorders. The present study was aimed to examine the antibacterial compounds from the leaves of M. ferrae and their β-lactam antibiotic potentiate activities against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA).

    METHODS: Stigmasterol (1) and β-caryophyllene oxide (2) were isolated from the n-hexane fraction of the leaves of M. ferrae using a bioassay-guided fractionation approach.

    RESULTS: The isolated compounds displayed anti-Staphylococcus and anti-MRSA activities. It is worth to note that both compounds demonstrated synergism with β-lactam antibiotics against S. aureus and MRSA. Gas chromatography-mass spectrometry (GC-MS) analysis indicated the n-hexane fraction was dominated by triterpenes and sesquiterpenes, suggesting the total antibacterial activity exhibited by the fraction.

    CONCLUSION: Based on the findings, it could conclude that M. ferrae is a promising natural source for the discovery of new anti-MRSA lead compounds.

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