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  1. Tan WS, Arulselvan P, Ng SF, Mat Taib CN, Sarian MN, Fakurazi S
    BMC Complement Altern Med, 2019 Jan 17;19(1):20.
    PMID: 30654793 DOI: 10.1186/s12906-018-2427-y
    BACKGROUND: Impaired wound healing is a debilitating complication of diabetes that leads to significant morbidity, particularly foot ulcers. The risk of developing diabetic foot ulcers for diabetic patients is 15% over their lifetime and approximately 85% of limb amputations is caused by non-healing ulcers. Unhealed, gangrenous wounds destroy the structural integrity of the skin, which acts as a protective barrier that prevents the invasion of external noxious agents into the body. Vicenin-2 (VCN-2) has been reported to contain prospective anti-oxidant and anti-inflammatory properties that enhance cell proliferation and migration. Sodium Alginate (SA) is a natural polysaccharide that possesses gel forming properties and has biodegradable and biocompatible characteristics. Therefore, the objective of this study is to evaluate the effect of SA wound dressings containing VCN-2 on diabetic wounds.

    METHODS: Wounds were inflicted in type-1 diabetic-streptozotocin (STZ) induced male Sprague Dawley rats. Subsequently, relevant groups were topically treated with the indicated concentrations (12.5, 25 and 50 μM) of VCN-2 hydrocolloid film over the study duration (14 days). The control group was treated with vehicle dressing (blank or allantoin). Wounded tissues and blood serum were collected on 0, 7 and 14 days prior to sacrifice. Appropriate wound assessments such as histological tests, nitric oxide assays, enzyme-linked immunosorbent assays (ELISA) and immunoblotting assays were conducted to confirm wound healing efficacy in the in vivo model. One-way Analysis of Variance (ANOVA) was used for statistical analysis.

    RESULTS: Results showed that hydrocolloid film was recapitulated with VCN-2 enhanced diabetic wound healing in a dose-dependent manner. VCN-2 reduced pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α), mediators (iNOS and COX-2), and nitric oxide (NO) via the NF-κB pathway. Data suggests that the VCN-2 film facilitated healing in hyperglycemic conditions by releasing growth factors such as (VEGF and TGF-β) to enhance cell proliferation, migration, and wound contraction via the VEGF and TGF-β mechanism pathways.

    CONCLUSIONS: This study's findings suggest that VCN-2 may possess wound healing potential since topical treatment with VCN-2 hydrocolloid films effectively enhanced wound healing in hyperglycemic conditions.

  2. Ahmed QU, Alhassan AM, Khatib A, Shah SAA, Hasan MM, Sarian MN
    Antioxidants (Basel), 2018 Oct 08;7(10).
    PMID: 30297618 DOI: 10.3390/antiox7100137
    The objective of the present study was to investigate the antiradical and xanthine oxidase inhibitory effects of Averrhoa bilimbi leaves. Hence, crude methanolic leaves extract and its resultant fractions, namely hexane, chloroform, and n-butanol were evaluated for 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging effect and xanthine oxidase inhibitory activity. The active constituents were tentatively identified through LC-QTOF-MS/MS and molecular docking approaches. The n-butanol fraction of A. bilimbi crude methanolic leaves extract displayed significant DPPH radical scavenging effect with IC50 (4.14 ± 0.21 μg/mL) (p < 0.05), as well as xanthine oxidase inhibitory activity with IC50 (64.84 ± 3.93 μg/mL) (p < 0.05). Afzelechin 3-O-alpha-l-rhamnopyranoside and cucumerin A were tentatively identified as possible metabolites that contribute to the antioxidant activity of the n-butanol fraction.
  3. Tan WS, Arulselvan P, Ng SF, Taib CNM, Sarian MN, Fakurazi S
    Biomed Res Int, 2020;2020:4730858.
    PMID: 32382552 DOI: 10.1155/2020/4730858
    Chronic wounds represent serious globally health care and economic issues especially for patients with hyperglycemic condition. Wound dressings have a predominant function in wound treatment; however, the dressings for the long-lasting and non-healing wounds are still a significant challenge in the wound care management market. Astonishingly, advanced wound dressing which is embedded with a synthetic drug compound in a natural polymer compound that acts as drug release carrier has brought about promising treatment effect toward injured wound. In the current study, results have shown that Vicenin-2 (VCN-2) compound in low concentration significantly enhanced cell proliferation and migration of HDF. It also regulated the production of pro-inflammatory cytokines such as IL-6, IL-1β, and TNF-α from HDF in wound repair. Treatment of VCN-2 also has facilitated the expression of TGF-1β and VEGF wound healing maker in a dose-dependent manner. A hydrocolloid film based on sodium alginate (SA) incorporated with VCN-2 synthetic compound which targets to promote wound healing particularly in diabetic condition was successfully developed and optimized for its physico-chemical properties. It was discovered that all the fabricated film formulations prepared were smooth, translucent, and good with flexibility. The thickness and weight of the formulations were also found to be uniform. The hydrophilic polymer comprised of VCN-2 were shown to possess desirable wound dressing properties and superior mechanical characteristics. The drug release profiles have revealed hydrocolloid film, which is able to control and sustain the VCN-2 released to wound area. In short, hydrocolloid films consisting of VCN-2 formulations are suitably used as a potential wound dressing to promote restoration of wound injury.
  4. Sarian MN, Iqbal N, Sotoudehbagha P, Razavi M, Ahmed QU, Sukotjo C, et al.
    Bioact Mater, 2022 Jun;12:42-63.
    PMID: 35087962 DOI: 10.1016/j.bioactmat.2021.10.034
    Magnesium alloys are considered the most suitable absorbable metals for bone fracture fixation implants. The main challenge in absorbable magnesium alloys is their high corrosion/degradation rate that needs to be controlled. Various coatings have been applied to magnesium alloys to slow down their corrosion rates to match their corrosion rate to the regeneration rate of the bone fracture. In this review, a bioactive coating is proposed to slow down the corrosion rate of magnesium alloys and accelerate the bone fracture healing process. The main aim of the bioactive coatings is to enhance the direct attachment of living tissues and thereby facilitate osteoconduction. Hydroxyapatite, collagen type I, recombinant human bone morphogenetic proteins 2, simvastatin, zoledronate, and strontium are six bioactive agents that show high potential for developing a bioactive coating system for high-performance absorbable magnesium bone implants. In addition to coating, the substrate itself can be made bioactive by alloying magnesium with calcium, zinc, copper, and manganese that were found to promote bone regeneration.
  5. Sarian MN, Zulkefli N, Che Zain MS, Maniam S, Fakurazi S
    Turk J Biol, 2023;47(4):236-246.
    PMID: 38152620 DOI: 10.55730/1300-0152.2659
    A skin wound or perforation triggers a series of homeostatic reactions to safeguard internal organs from invasion by pathogens or other substances that could damage body tissues. An injury may occasionally heal quickly, leading to the closure of the skin's structure. Healing from chronic wounds takes a long time. Although many treatment options are available to manage wound healing, an unmet therapy need remains because of the complexity of the processes and the other factors involved. It is crucial to conduct consistent research on novel therapeutic approaches to find an effective healing agent. Therefore, this work aims to cover various in vitro and in vivo methodologies that could be utilised to examine wound recovery. Before deciding on the optimal course of action, several techniques' benefits, drawbacks, and factors need to be reviewed.
  6. Che Zain MS, Lee SY, Sarian MN, Fakurazi S, Shaari K
    Antioxidants (Basel), 2020 Apr 17;9(4).
    PMID: 32316665 DOI: 10.3390/antiox9040326
    Oil palm (Elaeis guineensis Jacq.) leaves (OPL) are widely available at zero cost in Southeast Asia countries, especially in Malaysia and Indonesia due to large scale oil palm plantations. OPLs contain a large amount of flavonoids in particular flavonoid C-glycosides, which are known to possess useful biological properties including antioxidant and wound healing properties. The present study aimed at evaluating the wound healing efficacy of OPL in various solvent extracts and flavonoid enriched fractions and to determine the contribution of flavonoid C-glycosides (orientin, isoorientin, vitexin and isovitexin) using in-vitro scratch assay on 3T3 fibroblast cells. Solvent crude extracts with different polarity were screened and the most active extract was subjected to acid hydrolysis. The crude and acid hydrolysed extracts were further enriched using macroporous resins, XAD7HP. UHPLC-UV/PDA and LC-MS/MS analysis were applied for identification and confirmation of flavonoid C-glycosides. The wound healing properties comprised of cell viability, cell proliferation and cell migration were studied. Allantoin was used as a positive control to compare the efficacy among the tested samples. The results revealed all OPL crude extracts, flavonoid enriched fractions and flavonoid C-glycosides were non-toxic at concentrations below 25 µg/mL and showed better cell proliferation and migration activities at low concentrations than higher concentrations.. This study also demonstrated orientin, isoorientin, vitexin and isovitexin presented in OPL extracts and flavonoid enriched fractions stimulated proliferation and migration of 3T3 fibroblast cells. Hence, these findings may pose potential therapeutic bioactive agents for wound healing by enhancing fibroblast proliferation and migration.
  7. Sarian MN, Ahmed QU, Mat So'ad SZ, Alhassan AM, Murugesu S, Perumal V, et al.
    Biomed Res Int, 2017;2017:8386065.
    PMID: 29318154 DOI: 10.1155/2017/8386065
    The best described pharmacological property of flavonoids is their capacity to act as potent antioxidant that has been reported to play an important role in the alleviation of diabetes mellitus. Flavonoids biochemical properties are structure dependent; however, they are yet to be thoroughly understood. Hence, the main aim of this work was to investigate the antioxidant and antidiabetic properties of some structurally related flavonoids to identify key positions responsible, their correlation, and the effect of methylation and acetylation on the same properties. Antioxidant potential was evaluated through dot blot, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, ABTS+ radical scavenging, ferric reducing antioxidant power (FRAP), and xanthine oxidase inhibitory (XOI) assays. Antidiabetic effect was investigated through α-glucosidase and dipeptidyl peptidase-4 (DPP-4) assays. Results showed that the total number and the configuration of hydroxyl groups played an important role in regulating antioxidant and antidiabetic properties in scavenging DPPH radical, ABTS+ radical, and FRAP assays and improved both α-glucosidase and DPP-4 activities. Presence of C-2-C-3 double bond and C-4 ketonic group are two essential structural features in the bioactivity of flavonoids especially for antidiabetic property. Methylation and acetylation of hydroxyl groups were found to diminish the in vitro antioxidant and antidiabetic properties of the flavonoids.
  8. Mia MAR, Ahmed QU, Ferdosh S, Helaluddin ABM, Awal MS, Sarian MN, et al.
    Metabolites, 2022 Dec 15;12(12).
    PMID: 36557305 DOI: 10.3390/metabo12121267
    The fruit of Phaleria macrocarpa have been traditionally used as an antidiabetic remedy in Malaysia and neighbouring countries. Despite its potential for diabetes treatment, no scientific study has ever been conducted to predict the inhibitor interaction of the protein α-glucosidase identified in an extract prepared with a non-conventional extraction technique. Hence, the major aim of this research was to evaluate the in vitro antioxidant, the α-glucosidase inhibitors, and the molecular dynamic simulations of the α-glucosidase inhibitors identified by Quadrupole Time-of-Flight Liquid Chromatography Mass Spectrometry (Q-ToF-LCMS) analysis. Initially, dry fruit were processed using non-conventional and conventional extraction methods to obtain subcritical carbon dioxide extracts (SCE-1 and SCE-2) and heating under reflux extract (HRE), respectively. Subsequently, all extracts were evaluated for their in vitro antioxidative and α-glucosidase inhibitory potentials. Subsequently, the most bioactive extract (SCE-2) was subjected to Q-ToF-LCMS analysis to confirm the presence of α-glucosidase inhibitors, which were then analysed through molecular dynamic simulations and network pharmacology approaches to confirm their possible mechanism of action. The highest inhibitory effects of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and α-glucosidase on SCE-2 was found as 75.36 ± 0.82% and 81.79 ± 0.82%, respectively, compared to the SCE-1 and HRE samples. The Q-ToF-LCMS analysis tentatively identified 14 potent α-glucosidase inhibitors. Finally, five identified compounds, viz., lupenone, swertianolin, m-coumaric acid, pantothenic acid, and 8-C-glucopyranosyleriodictylol displayed significant stability, compactness, stronger protein-ligand interaction up to 100 ns further confirming their potential as α-glucosidase inhibitors. Consequently, it was concluded that the SCE-2 possesses a strong α-glucosidase inhibitory effect due to the presence of these compounds. The findings of this study might prove useful to develop these compounds as alternative safe α-glucosidase inhibitors to manage diabetes more effectively.
  9. Hasan MM, Ahmed QU, Soad SZM, Latip J, Taher M, Syafiq TMF, et al.
    BMC Complement Altern Med, 2017 Aug 30;17(1):431.
    PMID: 28854906 DOI: 10.1186/s12906-017-1929-3
    BACKGROUND: Tetracera indica Merr. (Family: Dilleniaceae), known to the Malay as 'Mempelas paya', is one of the medicinal plants used in the treatment of diabetes in Malaysia. However, no proper scientific study has been carried out to verify the traditional claim of T. indica as an antidiabetic agent. Hence, the aims of the present study were to determine the in vitro antidiabetic potential of the T. indica stems ethanol extract, subfractions and isolated compounds.

    METHODS: The ethanol extract and its subfractions, and isolated compounds from T. indica stems were subjected to cytotoxicity test using MTT viability assay on 3T3-L1 pre-adipocytes. Then, the test groups were subjected to the in vitro antidiabetic investigation using 3T3-L1 pre-adipocytes and differentiated adipocytes to determine the insulin-like and insulin sensitizing activities. Rosiglitazone was used as a standard antidiabetic agent. All compounds were also subjected to fluorescence glucose (2-NBDG) uptake test on differentiated adipocytes. Test solutions were introduced to the cells in different safe concentrations as well as in different adipogenic cocktails, which were modified by the addition of compounds to be investigated and in the presence or absence of insulin. Isolation of bioactive compounds from the most effective subfraction (ethyl acetate) was performed through repeated silica gel and sephadex LH-20 column chromatographies and their structures were elucidated through (1)H-and (13)C-NMR spectroscopy.

    RESULTS: Four monoflavonoids, namely, wogonin, norwogonin, quercetin and techtochrysin were isolated from the T. indica stems ethanol extract. Wogonin, norwogonin and techtochrysin induced significant (P 

  10. Zulkefli N, Che Zahari CNM, Sayuti NH, Kamarudin AA, Saad N, Hamezah HS, et al.
    Int J Mol Sci, 2023 Feb 27;24(5).
    PMID: 36902038 DOI: 10.3390/ijms24054607
    Wounds are considered to be a serious problem that affects the healthcare sector in many countries, primarily due to diabetes and obesity. Wounds become worse because of unhealthy lifestyles and habits. Wound healing is a complicated physiological process that is essential for restoring the epithelial barrier after an injury. Numerous studies have reported that flavonoids possess wound-healing properties due to their well-acclaimed anti-inflammatory, angiogenesis, re-epithelialization, and antioxidant effects. They have been shown to be able to act on the wound-healing process via expression of biomarkers respective to the pathways that mainly include Wnt/β-catenin, Hippo, Transforming Growth Factor-beta (TGF-β), Hedgehog, c-Jun N-Terminal Kinase (JNK), NF-E2-related factor 2/antioxidant responsive element (Nrf2/ARE), Nuclear Factor Kappa B (NF-κB), MAPK/ERK, Ras/Raf/MEK/ERK, phosphatidylinositol 3-kinase (PI3K)/Akt, Nitric oxide (NO) pathways, etc. Hence, we have compiled existing evidence on the manipulation of flavonoids towards achieving skin wound healing, together with current limitations and future perspectives in support of these polyphenolic compounds as safe wound-healing agents, in this review.
  11. Sayuti NH, Zulkefli N, Tan JK, Saad N, Baharum SN, Hamezah HS, et al.
    Molecules, 2023 Sep 20;28(18).
    PMID: 37764502 DOI: 10.3390/molecules28186726
    Neuronal models are an important tool in neuroscientific research. Hydrogen peroxide (H2O2), a major risk factor of neuronal oxidative stress, initiates a cascade of neuronal cell death. Polygonum minus Huds, known as 'kesum', is widely used in traditional medicine. P. minus has been reported to exhibit a few medicinal and pharmacological properties. The current study aimed to investigate the neuroprotective effects of P. minus ethanolic extract (PMEE) on H2O2-induced neurotoxicity in SH-SY5Y cells. LC-MS/MS revealed the presence of 28 metabolites in PMEE. Our study showed that the PMEE provided neuroprotection against H2O2-induced oxidative stress by activating the Nrf2/ARE, NF-κB/IκB and MAPK signaling pathways in PMEE pre-treated differentiated SH-SY5Y cells. Meanwhile, the acetylcholine (ACH) level was increased in the oxidative stress-induced treatment group after 4 h of exposure with H2O2. Molecular docking results with acetylcholinesterase (AChE) depicted that quercitrin showed the highest docking score at -9.5 kcal/mol followed by aloe-emodin, afzelin, and citreorosein at -9.4, -9.3 and -9.0 kcal/mol, respectively, compared to the other PMEE's identified compounds, which show lower docking scores. The results indicate that PMEE has neuroprotective effects on SH-SY5Y neuroblastoma cells in vitro. In conclusion, PMEE may aid in reducing oxidative stress as a preventative therapy for neurodegenerative diseases.
  12. Maluin FN, Hussein MZ, Yusof NA, Idris AS, Daim LDJ, Sarian MN, et al.
    Pharmaceutics, 2020 May 29;12(6).
    PMID: 32486034 DOI: 10.3390/pharmaceutics12060497
    Health risks which result from exposure to pesticides have sparked awareness among researchers, triggering the idea of developing nanoencapsulation pesticides with the aim to enhance cytoprotection as well as genoprotection of the pesticides. In addition, nanocapsules of pesticides have slow release capability, high bioavailability, and site-specific delivery, which has attracted great interest from researchers. Hence, the objective of this work is to synthesize a nanoformulation of a fungicide of different sizes, namely, chitosan-hexaconazole nanoparticles (18 nm), chitosan-dazomet nanoparticles (7 nm), and chitosan-hexaconazole-dazomet nanoparticles (5 nm), which were then subjected to toxicological evaluations, including cytotoxicity, genotoxicity, cell death assay, and dermal irritation assays. Incubation of chitosan-based nanofungicides with V79-4 hamster lung cell did not reveal cytotoxicity or genotoxicity, potentially suggesting that encapsulation with chitosan reduces direct toxicity of the toxic fungicides. Meanwhile, pure fungicide revealed its high cytotoxic effect on V79-4 hamster lung cells. In addition, dermal exposure assessment on rabbits revealed that chitosan-hexaconazole nanoparticles are classified under corrosive subcategory 1C, while chitosan-dazomet nanoparticles are classified under corrosive subcategory 1B. Moreover, both chitosan-hexaconazole nanoparticles and chitosan-dazomet nanoparticles are classified as causing mild irritation.
  13. Annuar NAK, Azlan UK, Mediani A, Tong X, Han R, Al-Olayan E, et al.
    Biomed Pharmacother, 2024 Feb;171:116134.
    PMID: 38219389 DOI: 10.1016/j.biopha.2024.116134
    Mitragynine is one of the main psychoactive alkaloids in Mitragyna speciosa Korth. (kratom). It has opium-like effects by acting on μ-, δ-, and κ-opioid receptors in the brain. The compound also interacts with other receptors, such as adrenergic and serotonergic receptors and neuronal Ca2+ channels in the central nervous system to have its neuropharmacological effects. Mitragynine has the potential to treat diseases related to neurodegeneration such as Alzheimer's disease and Parkinson's disease, as its modulation on the opioid receptors has been reported extensively. This review aimed to provide an up-to-date and critical overview on the neuropharmacological effects, mechanisms of action, pharmacokinetics and safety of mitragynine as a prospective psychotropic agent. Its multiple neuropharmacological effects on the brain include antinociceptive, anti-inflammatory, antidepressant, sedative, stimulant, cognitive, and anxiolytic activities. The potential of mitragynine to manage opioid withdrawal symptoms related to opioid dependence, its pharmacokinetics and toxic effects were also discussed. The interaction of mitragynine with various receptors in the brain produce diverse neuropharmacological effects, which have beneficial properties in neurological disorders. However, further studies need to be carried out on mitragynine to uncover its complex mechanisms of action, pharmacokinetics, pharmacodynamic profiles, addictive potential, and safe dosage to prevent harmful side effects.
  14. Md Yusop AH, Wan Ali WFF, Jamaludin FH, Szali Januddi F, Sarian MN, Saad N, et al.
    Biotechnol J, 2024 Mar;19(3):e2300464.
    PMID: 38509814 DOI: 10.1002/biot.202300464
    The present study evaluates the corrosion behavior of poly[xylitol-(1,12-dodecanedioate)](PXDD)-HA coated porous iron (PXDD140/HA-Fe) and its cell-material interaction aimed for temporary bone scaffold applications. The physicochemical analyses show that the addition of 20 wt.% HA into the PXDD polymers leads to a higher crystallinity and lower surface roughness. The corrosion assessments of the PXDD140/HA-Fe evaluated by electrochemical methods and surface chemistry analysis indicate that HA decelerates Fe corrosion due to a lower hydrolysis rate following lower PXDD content and being more crystalline. The cell viability and cell death mode evaluations of the PXDD140/HA-Fe exhibit favorable biocompatibility as compared to bare Fe and PXDD-Fe scaffolds owing to HA's bioactive properties. Thus, the PXDD140/HA-Fe scaffolds possess the potential to be used as a biodegradable bone implant.
  15. Mediani A, Hamezah HS, Jam FA, Mahadi NF, Chan SXY, Rohani ER, et al.
    Front Nutr, 2022;9:1057366.
    PMID: 36518998 DOI: 10.3389/fnut.2022.1057366
    Preserving fresh food, such as meat, is significant in the effort of combating global food scarcity. Meat drying is a common way of preserving meat with a rich history in many cultures around the globe. In modern days, dried meat has become a well enjoyed food product in the market because of its long shelf-life, taste and health benefits. This review aims to compile information on how the types of meat, ingredients and the used drying technologies influence the characteristics of dried meat in physicochemical, microbial, biochemical and safety features along with technological future prospects in the dried meat industry. The quality of dried meat can be influenced by a variety of factors, including its production conditions and the major biochemical changes that occur throughout the drying process, which are also discussed in this review. Additionally, the sensory attributes of dried meat are also reviewed, whereby the texture of meat and the preference of the market are emphasized. There are other aspects and concerning issues that are suggested for future studies. It is well-known that reducing the water content in meat helps in preventing microbial growth, which in turn prevents the presence of harmful substances in meat. However, drying the meat can change the characteristics of the meat itself, making consumers concerned on whether dried meat is safe to be consumed on a regular basis. It is important to consider the role of microbial enzymes and microbes in the preservation of their flavor when discussing dried meats and dried meat products. The sensory, microbiological, and safety elements of dried meat are also affected by these distinctive changes, which revolve around customer preferences and health concerns, particularly how drying is efficient in eliminating/reducing hazardous bacteria from the fish. Interestingly, some studies have concentrated on increasing the efficiency of dried meat production to produce a safer range of dried meat products with less effort and time. This review compiled important information from all available online research databases. This review may help the food sector in improving the efficiency and safety of meat drying, reducing food waste, while maintaining the quality and nutritional content of dried meat.
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