Displaying publications 1 - 20 of 39 in total

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  1. Schmitz RF, Abu Bakar MH, Omar ZH, Kamalanathan S, Schulpen TW, van der Werken C
    Trop Doct, 2001 Jul;31(3):152-4.
    PMID: 11444337
    This study evaluates the safety and results of surgery usingTaraKlamp Circumcision Device during a group circumcision. Atotal of 64 circumcisions of Muslim boys were performed by Medical Assistants supervised by Medical Doctors in a hall in Kuala Lumpur, Malaysia. A new type disposable clamp was used, which was removed 4 days after the operation. No major complications occurred and the boys experienced in general mild pain postoperatively. Mostly good cosmetic results were obtained and 90% of the parents would recommend this new clamp to others. Group circumcisions withTaraKlamp Circumcision Device (Kuala Lumpur, Malaysia) are safe, although proper patient selection and adequate training in using the device are mandatory.
  2. Naing NN, Ahmad Z, Musa R, Hamid FR, Ghazali H, Bakar MH
    Tob Induc Dis, 2004 Sep 15;2(3):133-40.
    PMID: 19570279 DOI: 10.1186/1617-9625-2-3-133
    A cross-sectional study was conducted to identify the factors related to smoking habits of adolescents among secondary school boys in Kelantan state, Malaysia. A total of 451 upper secondary male students from day, boarding and vocational schools were investigated using a structured questionnaire. Cluster sampling was applied to achieve the required sample size. The significant findings included: 1) the highest prevalence of smoking was found among schoolboys from the vocational school; 2) mean duration of smoking was 2.5 years; 3) there were significant associations between smoking status and parents' smoking history, academic performance, perception of the health hazards of smoking, and type of school attended. Peer influence was the major reason students gave for taking up the habit. Religion was most often indicated by non-smokers as their reason for not smoking. Approximately 3/5 of the smokers had considered quitting and 45% of them had tried at least once to stop smoking. Mass media was indicated as the best information source for the students to acquire knowledge about negative aspects of the smoking habit. The authors believe an epidemic of tobacco use is imminent if drastic action is not taken, and recommend that anti-smoking campaigns with an emphasis on the religious aspect should start as early as in primary school. Intervention programs to encourage behavior modification of adolescents are also recommended.
  3. Salehmin MNI, Hil Me MF, Daud WRW, Mohd Yasin NH, Abu Bakar MH, Sulong AB, et al.
    Sci Total Environ, 2023 Jan 10;855:158527.
    PMID: 36096221 DOI: 10.1016/j.scitotenv.2022.158527
    Microbial electrodialysis cells (MEDCs) offer simultaneous wastewater treatment, water desalination, and hydrogen production. In a conventional design of MEDCs, the overall performance is retarded by the accumulation of protons on the anode due to the integration of an anion exchange membrane (AEM). The accumulation of protons reduces the anolyte pH to become acidic, affecting the microbial viability and thus limiting the charge carrier needed for the cathodic reaction. This study has modified the conventional MEDC with an internal proton migration pathway, known as the internal proton migration pathway-MEDC (IP-MEDC). Simulation tests under abiotic conditions demonstrated that the pH changes in the anolyte and catholyte of IP-MEDC were smaller than the pH changes in the anolyte and catholyte without the proton pathways. Under biotic conditions, the performance of the IP-MEDC agreed well with the simulation test, showing a significantly higher chemical oxygen demand (COD) removal rate, desalination rate, and hydrogen production than without the migration pathway. This result is supported by the lowest charge transfer resistance shown by EIS analysis and the abundance of microbes on the bioanode through field emission scanning electron microscopy (FESEM) observation. However, hydrogen production was diminished in the second-fed batch cycle, presumably due to the active diffusion of high Cl¯ concentrations from desalination to the anode chamber, which was detrimental to microbial growth. Enlarging the anode volume by threefold improved the COD removal rate and hydrogen production rate by 1.7- and 3.4-fold, respectively, owing to the dilution effect of Cl¯ in the anode. This implied that the dilution effect satisfies both the microbial viability and conductivity. This study also suggests that the anolyte and catholyte replacement frequencies can be reduced, typically at a prolonged hydraulic retention time, thus minimizing the operating cost (e.g., solution pumping). The use of a high concentration of NaCl (35 g L-1) in the desalination chamber and catholyte provides a condition that is close to practicality.
  4. Sulaiman R, Azeman NH, Mokhtar MHH, Mobarak NN, Abu Bakar MH, Bakar AAA
    PMID: 37708761 DOI: 10.1016/j.saa.2023.123327
    Accurate, label-free, and rapid methods for measuring phosphorus concentrations are essential in a hydroponic system, as excessive or insufficient phosphorus levels can adversely affect plant growth, human health, and environmental sustainability. In this study, we demonstrate the advantages of hybrid machine learning models compared to single machine learning models in predicting phosphorus concentration based on the absorbance dataset. Three machine learning classifiers- Random Forest (RF), Support Vector Machine (SVM), and K-Nearest Neighbors (KNN)- were employed as bases for single and hybrid machine learning models. Three ensemble techniques (voting, bagging, and stacking) were used to hybridize the classifiers. Among the single models, KNN demonstrated the fastest computational time of 18.07 s, while SVM achieved the highest accuracy of 99.6%. The hybrid SVM/KNN model using a voting classifier showed a significant increase in accuracy for KNN with only a slight increase in computational time. Bagging techniques increased the accuracy but at a longer computational time. The stacking technique, which combined SVM, KNN, and RF, achieved the highest accuracy of 99.73% with a short computational time of 36.18 s compared to the bagging and voting technique. This study demonstrates that the machine learning method can effectively distinguish phosphorus concentrations. In contrast, hybrid machine learning techniques can improve accuracy for predicting phosphorus without using labels, despite requiring longer computational time.
  5. Abu Bakar MH, Azeman NH, Mobarak NN, Nazri NAA, Daniyal WMEMM, Othman MQ, et al.
    PMID: 38733916 DOI: 10.1016/j.saa.2024.124419
    The utilization of UV-Vis spectroscopy with amino-functionalized carbon quantum dots (NCQD) as a positive fluorophore reagent for chloride sensing in oil marks a notable advancement in analytical spectroscopy chemistry. This approach streamlines the detection process by eliminating the need for lengthy procedures and pretreatment steps typically associated with chloride detection in edible oil. By incorporating NCQD in chloride detection within the oil matrix, the wavelength analysis transitions from the UV to the visible region. This shift eliminates interference from oil matrix interactions, ensuring more accurate results. Molecular analysis of NCQD reveals significant shifts in its Fourier Transformation Infrared and photoluminescence spectroscopy peaks due to interaction with chloride in edible oil. It has two impressive sensitivity ranges spanning from 0.1-1.0 to 1.0-8.0 ppm, with a value of -0.4656 au. ppm-1 (R2 = 0.998) and -0.0361 au. ppm-1 (R2 = 0.931), respectively, the technique meets regulatory standards while achieving a low limit of detection (LOD) of 0.1 ppm. This places it on par with conventional methods and commercial sensors. The NCQD-UV-Vis spectroscopy method not only enhances the efficiency and accuracy of chloride detection but also holds promise for various industrial applications requiring simple and precise monitoring of chloride levels in oil samples.
  6. Abu Hassan MR, Abu Bakar MH, Dambul K, Adikan FR
    Sensors (Basel), 2012;12(11):15820-6.
    PMID: 23202233 DOI: 10.3390/s121115820
    In this paper, we present the development and testing of an optical-based sensor for monitoring the corrosion of reinforcement rebar. The testing was carried out using an 80% etched-cladding Fibre Bragg grating sensor to monitor the production of corrosion waste in a localized region of the rebar. Progression of corrosion can be sensed by observing the reflected wavelength shift of the FBG sensor. With the presence of corrosion, the etched-FBG reflected spectrum was shifted by 1.0 nm. In addition, with an increase in fringe pattern and continuously, step-like drop in power of the Bragg reflected spectrum was also displayed.
  7. Mustapha Kamil Y, Al-Rekabi SH, Yaacob MH, Syahir A, Chee HY, Mahdi MA, et al.
    Sci Rep, 2019 09 17;9(1):13483.
    PMID: 31530893 DOI: 10.1038/s41598-019-49891-7
    The exponential escalation of dengue cases has indeed become a global health crisis. This work elaborates on the development of a biofunctionalized tapered optical fiber (TOF) based sensor with the integration of polyamidoamine (PAMAM) dendrimer for the detection of dengue E protein. The dimension of the TOF generated an evanescent field that was sensitive to any changes in the external medium while the integration of PAMAM promoted more adhesion of bio-recognition molecules; anti-DENV II E protein antibodies; that were complementary to the targeted protein. This in return created more active sites for the absorption of DENV II E proteins onto the tapered region. The resolution and detection limit of the sensor are 19.53 nm/nM and 1 pM, respectively with Kd = 1.02 × 10-10 M.
  8. Mohd Radzuan SN, Phongphane L, Abu Bakar MH, Che Omar MT, Nor Shahril NS, Supratman U, et al.
    RSC Adv, 2024 Feb 29;14(11):7684-7698.
    PMID: 38444963 DOI: 10.1039/d3ra08642a
    New phenylisoxazole quinoxalin-2-amine hybrids 5a-i were successfully synthesised with yields of 53-85% and characterised with various spectroscopy methods. The synthesised hybrids underwent in vitro α-amylase and α-glucosidase inhibitory assays, with acarbose as the positive control. Through the biological study, compound 5h exhibits the highest α-amylase inhibitory activity with IC50 = 16.4 ± 0.1 μM while compounds 5a-c, 5e and 5h exhibit great potential as α-glucosidase inhibitors, with 5c being the most potent (IC50 = 15.2 ± 0.3 μM). Among the compounds, 5h exhibits potential as a dual inhibitor for both α-amylase (IC50 = 16.4 ± 0.1 μM) and α-glucosidase (IC50 = 31.6 ± 0.4 μM) enzymes. Through the molecular docking studies, the inhibition potential of the selected compounds is supported. Compound 5h showed important interactions with α-amylase enzyme active sites and exhibited the highest binding energy of -8.9 ± 0.10 kcal mol-1, while compound 5c exhibited the highest binding energy of -9.0 ± 0.20 kcal mol-1 by forming important interactions with the α-glucosidase enzyme active sites. The molecular dynamics study showed that the selected compounds exhibited relative stability when binding with α-amylase and α-glucosidase enzymes. Additionally, compound 5h demonstrated a similar pattern of motion and mechanism of action as the commercially available miglitol.
  9. Abu Bakar MH, Azeman NH, Mobarak NN, Mokhtar MHH, A Bakar AA
    Polymers (Basel), 2020 Sep 08;12(9).
    PMID: 32911662 DOI: 10.3390/polym12092040
    This research demonstrates a one-step modification process of biopolymer carrageenan active sites through functional group substitution in κ-carrageenan structures. The modification process improves the electronegative properties of κ-carrageenan derivatives, leading to enhancement of the material's performance. Synthesized succinyl κ-carrageenan with a high degree of substitution provides more active sites for interaction with analytes. The FTIR analysis of succinyl κ-carrageenan showed the presence of new peaks at 1068 cm-1, 1218 cm-1, and 1626 cm-1 that corresponded to the vibrations of C-O and C=O from the carbonyl group. A new peak at 2.86 ppm in 1H NMR represented the methyl proton neighboring with C=O. The appearance of new peaks at 177.05 and 177.15 ppm in 13C NMR proves the substitution of the succinyl group in the κ-carrageenan structure. The elemental analysis was carried out to calculate the degree of substitution with the highest value of 1.78 at 24 h of reaction. The XRD diffractogram of derivatives exhibited a higher degree of crystallinity compared to pristine κ-carrageenan at 23.8% and 9.2%, respectively. Modification of κ-carrageenan with a succinyl group improved its interaction with ions and the conductivity of the salt solution compared to its pristine form. This work has a high potential to be applied in various applications such as sensors, drug delivery, and polymer electrolytes.
  10. Abu Bakar MH, Azeman NH, Mobarak NN, Ahmad Nazri NA, Tengku Abdul Aziz TH, Md Zain AR, et al.
    Polymers (Basel), 2022 Jan 14;14(2).
    PMID: 35054734 DOI: 10.3390/polym14020329
    This research investigates the physicochemical properties of biopolymer succinyl-κ-carrageenan as a potential sensing material for NH4+ Localized Surface Plasmon Resonance (LSPR) sensor. Succinyl-κ-carrageenan was synthesised by reacting κ-carrageenan with succinic anhydride. FESEM analysis shows succinyl-κ-carrageenan has an even and featureless topology compared to its pristine form. Succinyl-κ-carrageenan was composited with silver nanoparticles (AgNP) as LSPR sensing material. AFM analysis shows that AgNP-Succinyl-κ-carrageenan was rougher than AgNP-Succinyl-κ-carrageenan, indicating an increase in density of electronegative atom from oxygen compared to pristine κ-carrageenan. The sensitivity of AgNP-Succinyl-κ-carrageenan LSPR is higher than AgNP-κ-carrageenan LSPR. The reported LOD and LOQ of AgNP-Succinyl-κ-carrageenan LSPR are 0.5964 and 2.7192 ppm, respectively. Thus, AgNP-Succinyl-κ-carrageenan LSPR has a higher performance than AgNP-κ-carrageenan LSPR, broader detection range than the conventional method and high selectivity toward NH4+. Interaction mechanism studies show the adsorption of NH4+ on κ-carrageenan and succinyl-κ-carrageenan were through multilayer and chemisorption process that follows Freundlich and pseudo-second-order kinetic model.
  11. Al-Asadi HA, Abu Bakar MH, Al-Mansoori MH, Adikan FR, Mahdi MA
    Opt Express, 2011 Dec 5;19(25):25741-8.
    PMID: 22273966 DOI: 10.1364/OE.19.025741
    This paper details a theoretical modeling of Brillouin ring fiber laser which incorporates the interaction between multiple Brillouin Stokes signals. The ring cavity was pumped at several Brillouin pump (BP) powers and the output was measured through an optical coupler with various coupling ratios. The first-order Brillouin Stokes signal was saturated with the presence of the second-order Stokes signal in the cavity as a result of energy transfer between them. The outcome of the study found that the optimum point for the first-order Stokes wave performance is at laser power reduction of 10%. Resultantly, at the optimum output coupling ratio of 90%, the BFL was able to produce 19.2 mW output power at BP power and Brillouin threshold power of 60 and 21.3 mW respectively. The findings also exhibited the feasibility of the theoretical models application to ring-type Brillouin fiber laser of various design parameters.
  12. Sarmani AR, Abu Bakar MH, Bakar AA, Adikan FR, Mahdi MA
    Opt Express, 2011 Jul 18;19(15):14152-9.
    PMID: 21934778 DOI: 10.1364/OE.19.014152
    We report an ultra-long Raman laser that implemented a variable pumping scheme in backward and forward configurations. Rayleigh backscattering effects were realized in the 51 km fiber length that functioned as a virtual mirror at one fiber end. With the employment of a fiber Bragg grating that has a peak reflection wavelength at 1553.3 nm, spectral broadening effects were observed. These occurred as the pump power level was diverted more to the forward direction. Owing to this fact, a maximum width of 0.9 nm was measured at 100% forward pumping. The obtained results show that the efficient exploitation of four-wave mixing interactions as well as strong Rayleigh backscattering are beneficial to influence the lasing performances. Both of these nonlinear responses can be adjusted by varying pumping distributions along the fiber longitudinal dimension.
  13. Zailan AAD, Karunakaran T, Abu Bakar MH, Mian VJY
    Nat Prod Res, 2021 Oct 12.
    PMID: 34636709 DOI: 10.1080/14786419.2021.1982936
    Genus Calophyllum from the family of Calophyllaceae is an evergreen broad-leaved tree that is endemic to Southeast Asia, especially Malaysia. They have been reported for various ethnomedicinal uses in traditional medicine. Previous studies of Malaysian Calophyllum species revealed them to be a rich source of bioactive phytoconstituents such as xanthones, coumarins, terpenoids, and chromanone acids. To date, the extracts and compounds from Malaysian Calophyllum species have shown a broad spectrum of pharmacological activities. For example, calanolide A, a coumarin isolated from Malaysian C. lanigerum, has now reached clinical development to become an anti-HIV drug. This article presents an overview of the significant phytochemical and pharmacological activities of Malaysian Calophyllum species to aid researchers in further discovery of potential benefits of various species of this genus.
  14. Tanazi NNH, Aziz AN, Azmi MN, Abu Bakar MH, Hassim MFN, Wahab NHA, et al.
    Nat Prod Res, 2023 Nov 27.
    PMID: 38009213 DOI: 10.1080/14786419.2023.2283759
    Phytochemical investigation on the bark of E. kingiana plant afforded ten compounds, including six polyketides namely kingianin A 1, kingianin B 2, kingianin E 3, kingianin F 4, kingianin K 5 and kingianin L 6, three endiandric acids; kingianic acid A 7, tsangibeilin B 8 and endiandric acid M 9, and one sesquiterpene; daibuoxide 10. All compounds were separated as racemic mixture by recycling high-performance liquid chromatography (RHPLC), except for daibuoxide. Their structures were elucidated by detailed spectroscopic and comparative literature data analysis. This is the first report on the presence of the sesquiterpene; daibuoxide in Endiandra genus. In vitro enzymatic bio-evaluation of the isolated compounds against α-amylase and α-glucosidase showed that 4 demonstrated the best α-amylase and α-glucosidase inhibitory activity with IC50 values of 181.54 ± 6.27 µg/mL and 237.87 ± 0.07 µg/mL, respectively. In addition, molecular docking analysis confirmed the α-amylase and α-glucosidase inhibitory activities demonstrated by 4.
  15. Firouz NS, Karunakaran T, Mokhtar N, Santhanam R, Jong VYM, Abu Bakar MH
    Nat Prod Res, 2024 Jan 22.
    PMID: 38247357 DOI: 10.1080/14786419.2024.2305222
    Bioactive phenolics can be found in abundance in Calophyllum species. Phytochemical studies are carried out on the stem bark of Calophyllum recurvatum and Calophyllum andersonii, which has led to the isolation and elucidation of phytochemicals, thwaitesixanthone (1), teysmanone A (2), soulattrolide (3), calanone (4), isocalanone (5) and friedelin (6), respectively. The cytotoxic activities of compounds (2), (3), (4) and (5) as well as plant extracts were tested against HeLa Chang liver, HepG2 and HL-7702 cell lines. Phenylpyranocoumarins, teysmanone A (2) and soulattrolide (3) portrayed appreciable cytotoxicity activities at 42.57 ± 1.20 and 34.53 ± 3.41 µg/mL, respectively against HepG2 cell line comparable to the positive control, curcumin. Meanwhile, n-hexane extract from C. recurvatum exhibited cytotoxicity with the IC50 value of 36.43 ± 0.64 and 26.25 ± 4.83 µg/mL against HeLa Chang liver and HepG2 cell lines. All the tested compounds and plant extracts displayed non-cytotoxic properties on HL-7702 cell line.
  16. Mokhtar N, Karunakaran T, Santhanam R, Abu Bakar MH, Jong VYM
    Nat Prod Res, 2024;38(5):873-878.
    PMID: 37005001 DOI: 10.1080/14786419.2023.2196075
    Genus Calophyllum is well-known for its phenolic constituents, especially coumarins, which have shown to have a wide range of significant biological activities. In this study, four known phenolic constituents and two triterpenoids have been isolated from the stem bark of Calophyllum lanigerum. The compounds were two pyranochromanone acids are known as caloteysmannic acid (1), isocalolongic acid (2), a simple dihydroxyxanthone, namely euxanthone (3), one coumarin named calanone (4), and two common triterpenoids, friedelin (5), and stigmasterol (6). Chromanone acids were reported for the first time in this Calophyllum species. Cytotoxic evaluations were carried out on n-hexane extract (87.14 ± 2.04 µg/mL; 81.46 ± 2.42 µg/mL) followed by the chromanone acids (1 [79.96 ± 2.39 µM; 83.41 ± 3.39 µM] & 2 [57.88 ± 2.34; 53.04 ± 3.18 µM]) against two cancerous cell lines, MDA-MB-231 and MG-63 cell lines, respectively. The results showed that all tested samples exhibited moderate cytotoxicity.
  17. Abu Bakar MH, Cheng KK, Sarmidi MR, Yaakob H, Huri HZ
    Molecules, 2015 May 07;20(5):8242-69.
    PMID: 25961164 DOI: 10.3390/molecules20058242
    Mitochondrial dysfunction and inflammation are widely accepted as key hallmarks of obesity-induced skeletal muscle insulin resistance. The aim of the present study was to evaluate the functional roles of an anti-inflammatory compound, celastrol, in mitochondrial dysfunction and insulin resistance induced by antimycin A (AMA) in human skeletal muscle cells. We found that celastrol treatment improved insulin-stimulated glucose uptake activity of AMA-treated cells, apparently via PI3K/Akt pathways, with significant enhancement of mitochondrial activities. Furthermore, celastrol prevented increased levels of cellular oxidative damage where the production of several pro-inflammatory cytokines in cultures cells was greatly reduced. Celastrol significantly increased protein phosphorylation of insulin signaling cascades with amplified expression of AMPK protein and attenuated NF-κB and PKC θ activation in human skeletal muscle treated with AMA. The improvement of insulin signaling pathways by celastrol was also accompanied by augmented GLUT4 protein expression. Taken together, these results suggest that celastrol may be advocated for use as a potential therapeutic molecule to protect against mitochondrial dysfunction-induced insulin resistance in human skeletal muscle cells.
  18. Goh YS, Karunakaran T, Murugaiyah V, Santhanam R, Abu Bakar MH, Ramanathan S
    Molecules, 2021 Jun 17;26(12).
    PMID: 34204457 DOI: 10.3390/molecules26123704
    Mitragyna speciosa Korth (kratom) is known for its psychoactive and analgesic properties. Mitragynine is the primary constituent present in kratom leaves. This study highlights the utilisation of the green accelerated solvent extraction technique to produce a better, non-toxic and antinociceptive active botanical extract of kratom. ASE M. speciosa extract had a dry yield (0.53-2.91 g) and showed a constant mitragynine content (6.53-7.19%) when extracted with organic solvents of different polarities. It only requires a shorter extraction time (5 min) and a reduced amount of solvents (less than 100 mL). A substantial amount of total phenolic (407.83 ± 2.50 GAE mg/g and flavonoids (194.00 ± 5.00 QE mg/g) were found in ASE kratom ethanol extract. The MTT test indicated that the ASE kratom ethanolic leaf extract is non-cytotoxic towards HEK-293 and HeLa Chang liver cells. In mice, ASE kratom ethanolic extract (200 mg/kg) demonstrated a better antinociceptive effect compared to methanol and ethyl acetate leaf extracts. The presence of bioactive indole alkaloids and flavonols such as mitragynine, paynantheine, quercetin, and rutin in ASE kratom ethanolic leaf extract was detected using UHPLC-ESI-QTOF-MS/MS analysis supports its antinociceptive properties. ASE ethanolic leaf extract offers a better, safe, and cost-effective choice of test botanical extract for further preclinical studies.
  19. Rusli SFN, Daud SM, Abu Bakar MH, Loh KS, Masdar MS
    Molecules, 2022 Feb 03;27(3).
    PMID: 35164309 DOI: 10.3390/molecules27031045
    The biocathode in a microbial fuel cell (MFC) system is a promising and a cheap alternative method to improve cathode reaction performance. This study aims to identify the effect of the electrode combination between non-chemical modified stainless steel (SS) and graphite fibre brush (GFB) for constructing bio-electrodes in an MFC. In this study, the MFC had two chambers, separated by a cation exchange membrane, and underwent a total of four different treatments with different electrode arrangements (anodeǁcathode)-SSǁSS (control), GFBǁSS, GFBǁGFB and SSǁGFB. Both electrodes were heat-treated to improve surface oxidation. On the 20th day of the operation, the GFBǁGFB arrangement generated the highest power density, up to 3.03 W/m3 (177 A/m3), followed by the SSǁGFB (0.0106 W/m3, 0.412 A/m3), the GFBǁSS (0.0283 W/m3, 17.1 A/m3), and the SSǁSS arrangements (0.0069 W/m-3, 1.64 A/m3). The GFBǁGFB had the lowest internal resistance (0.2 kΩ), corresponding to the highest power output. The other electrode arrangements, SSǁGFB, GFBǁSS, and SSǁSS, showed very high internal resistance (82 kΩ, 2.1 kΩ and 18 kΩ, respectively) due to the low proton and electron movement activity in the MFC systems. The results show that GFB materials can be used as anode and cathode in a fully biotic MFC system.
  20. Soib HH, Ismail HF, Husin F, Abu Bakar MH, Yaakob H, Sarmidi MR
    Molecules, 2020 Jan 24;25(3).
    PMID: 31991676 DOI: 10.3390/molecules25030517
    Herbal plants are traditionally utilized to treat various illnesses. They contain phytochemicals that can be extracted using conventional methods such as maceration, soxhlet, and boiling, as well as non-conventional methods including ultrasonic, microwave, and others. Carica papaya leaves have been used for the treatment of dengue, fungal, and bacterial infections as well as an ingredient in anti-aging products. Phytochemicals analysis detected the presence of kaempferol, myricetin, carpaine, pseudocarpaine, dehydrocarpaine I and II, ferulic acid, caffeic acid, chlorogenic acid, β-carotene, lycopene, and anthraquinones glycoside. Conventional preparation by boiling and simple maceration is practical, simple, and safe; however, only polar phytochemicals are extracted. The present study aims to investigate the effects of three different non-conventional extraction techniques (ultrasonic-assisted extraction, reflux, and agitation) on C. papaya phytochemical constituents, the antioxidant capacity, and wound-healing activities. Among the three techniques, the reflux technique produced the highest extraction yield (17.86%) with the presence of saponins, flavonoids, coumarins, alkaloids, and phenolic metabolites. The reflux technique also produced the highest 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging with an IC50 value of 0.236 mg/mL followed by ultrasonic-assisted extraction (UAE) (IC50: 0.377 mg/mL) and agitation (IC50: 0.404 mg/mL). At tested concentrations (3.125 µg/mL to 500 µg/mL), all extracts do not exhibit a cytotoxicity effect on the human skin fibroblast, HSF1184. Interestingly, reflux and UAE were active fibroblast proliferators that support 85% (12.5 µg/mL) and 41% (6.25 µg/mL) better cell growth, respectively. Additionally, during the early 24 h of the scratch assay, the migration rate at 12.5 µg/mL was faster for all extracts with 51.8% (reflux), 49.3% (agitation), and 42.5% (UAE) as compared to control (21.87%). At 48 h, proliferated cells covered 78.7% of the scratch area for reflux extract, 63.1% for UAE, 61% for agitation, and 42.6% for control. Additionally, the collagen synthesis was enhanced for 31.6% and 65% after 24 and 48 h of treatment for reflux. An HPLC-MS/MS-QTOF (quadruple time-of-flight) analysis of reflux identified nine phytochemicals, including carpaine, kaempferol 3-(2G-glucosylrutinoside), kaempferol 3-(2″-rhamnosylgalactoside), 7-rhamnoside, kaempferol 3-rhamnosyl-(1->2)-galactoside-7-rhamnoside, luteolin 7-galactosyl-(1->6)-galactoside, orientin 7-O-rhamnoside, 11-hydroperoxy-12,13-epoxy-9-octadecenoic acid, palmitic amide, and 2-hexaprenyl-6-methoxyphenol. The results suggested that reflux was the best technique as compared to ultrasonic and agitation.
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