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  1. Sadikan MZ, Abdul Nasir NA
    Naunyn Schmiedebergs Arch Pharmacol, 2023 Dec;396(12):3395-3406.
    PMID: 37401966 DOI: 10.1007/s00210-023-02599-y
    Diabetic retinopathy (DR) is one of the leading causes of permanent central blindness worldwide. Despite the complexity and inadequate understanding of DR pathogenesis, many of the underlying pathways are currently partially understood and may offer potential targets for future treatments. Anti-VEGF medications are currently the main medication for this problem. This article provides an overview of the established pharmacological treatments and those that are being developed to cure DR. We firstly reviewed the widely utilized approaches including pan-retinal photocoagulation therapy, anti-VEGF therapy, corticosteroid therapy, and surgical management of DR. Next, we discussed the mechanisms of action and prospective benefits of novel candidate medications. Current management are far from being a perfect treatment for DR, despite mild-term favorable efficiency and safety profiles. Pharmacological research should work toward developing longer-lasting treatments or new drug delivery systems, as well as on identifying new molecular targets in the pathogenetical mechanism for DR. In order to find a treatment that is specifically designed for each patient, it is also necessary to properly characterize patients, taking into account elements like hereditary factors and intraretinal neovascularization stages for effective utilization of drugs. The current and potential approaches for diabetic retinopathy. Image was constructed using Biorender.com.
  2. Nasir NAA, Sadikan MZ, Agarwal R
    Asia Pac J Clin Nutr, 2021 Sep;30(3):537-555.
    PMID: 34587713 DOI: 10.6133/apjcn.202109_30(3).0020
    Tocotrienols have been reported to exert anticancer, anti-inflammatory, antioxidant, cardio-protective and boneprotective effects through modulation of NFκB signalling pathway. The objective of this systematic review is to evaluate available literature showing the effect of tocotrienols on NFκB signalling pathway and identify the potential mechanisms involved. A comprehensive search was conducted using PubMed and SCOPUS databases using the keywords "tocotrienol" and "NFκB" or "nuclear factor kappa b". Main inclusion criteria were English language original articles showing the effect of tocotrienol on NFκB signalling pathway. Fifty-nine articles were selected from the total of 117 articles initially retrieved from the literature search. Modulation of regulatory proteins and genes such as inhibition of farnesyl prenyl transferase were found to be the mechanisms underlying the tocotrienol-induced suppression of NFκB activation.
  3. Sadikan MZ, Nasir NAA, Agarwal R, Ismail NM
    Biomolecules, 2020 04 05;10(4).
    PMID: 32260544 DOI: 10.3390/biom10040556
    : Oxidative stress plays an important role in retinal neurodegeneration and angiogenesis associated with diabetes. In this study, we investigated the effect of the tocotrienol-rich fraction (TRF), a potent antioxidant, against diabetes-induced changes in retinal layer thickness (RLT), retinal cell count (RCC), retinal cell apoptosis, and retinal expression of vascular endothelial growth factor (VEGF) in rats. Additionally, the efficacy of TRF after administration by two different routes was compared. The diabetes was induced in Sprague-Dawley rats by intraperitoneal injection of streptozotocin. Subsequently, diabetic rats received either oral or topical treatment with vehicle or TRF. Additionally, a group of non-diabetic rats was included with either oral or topical treatment with a vehicle. After 12 weeks of the treatment period, rats were euthanized, and retinas were collected for measurement of RLT, RCC, retinal cell apoptosis, and VEGF expression. RLT and RCC in the ganglion cell layer were reduced in all diabetic groups compared to control groups (p < 0.01). However, at the end of the experimental period, oral TRF-treated rats showed a significantly greater RLT compared to topical TRF-treated rats. A similar observation was made for retinal cell apoptosis and VEGF expression. In conclusion, oral TRF supplementation protects against retinal degenerative changes and an increase in VEGF expression in rats with streptozotocin-induced diabetic retinopathy. Similar effects were not observed after topical administration of TRF.
  4. Sadikan MZ, Abdul Nasir NA, Bakar NS, Iezhitsa I, Agarwal R
    BMC Complement Med Ther, 2023 Jun 02;23(1):179.
    PMID: 37268913 DOI: 10.1186/s12906-023-04005-9
    BACKGROUND: Diabetic retinopathy (DR) is the second commonest microvascular complication of diabetes mellitus. It is characterized by chronic inflammation and angiogenesis. Palm oil-derived tocotrienol-rich fraction (TRF), a substance with anti-inflammatory and anti-angiogenic properties, may provide protection against DR development. Therefore, in this study, we investigated the effect of TRF on retinal vascular and morphological changes in diabetic rats. The effects of TRF on the retinal expression of inflammatory and angiogenic markers were also studied in the streptozotocin (STZ)-induced diabetic rats.

    METHODS: Male Sprague Dawley rats weighing 200-250 g were grouped into normal rats (N) and diabetic rats. Diabetes was induced by intraperitoneal injection of streptozotocin (55 mg/kg body weight) whereas N similarly received citrate buffer. STZ-injected rats with blood glucose of more than 20 mmol/L were considered diabetic and were divided into vehicle-treated (DV) and TRF-treated (DT) groups. N and DV received vehicle, whereas DT received TRF (100 mg/kg body weight) via oral gavage once daily for 12 weeks. Fundus images were captured at week 0 (baseline), week 6 and week 12 post-STZ induction to estimate vascular diameters. At the end of experimental period, rats were euthanized, and retinal tissues were collected for morphometric analysis and measurement of NFκB, phospho-NFκB (Ser536), HIF-1α using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA). Retinal inflammatory and angiogenic cytokines expression were measured by ELISA and real-time quantitative PCR.

    RESULTS: TRF preserved the retinal layer thickness (GCL, IPL, INL and OR; p 

  5. Abdul Ghani NA, Abdul Nasir NA, Lambuk L, Sadikan MZ, Agarwal R, Ramli N
    Graefes Arch Clin Exp Ophthalmol, 2023 Jun;261(6):1587-1596.
    PMID: 36622408 DOI: 10.1007/s00417-022-05965-3
    PURPOSE: Angiogenesis in diabetic retinopathy (DR) is associated with increased retinal expression of angiopoietin-2 (Ang-2) and protein kinase C (PKC). Tocotrienol-rich fraction (TRF) has been shown to reduce the expression vascular endothelial growth factor (VEGF) in several experimental models. However, its effect against other angiogenic markers such as Ang-2 and PKC in rat model of diabetes remains unknown. Therefore, we investigated the effect of TRF on the retinal vascular changes and Ang-2 and PKC expressions in rats with streptozotocin (STZ)-induced DR.

    METHODS: Sprague-Dawley rats were divided into normal control rats (N) which received vehicle, and diabetic rats which either received vehicle (DV) or 100 mg/kg of TRF (DT). Diabetes was induced with intraperitoneal injection of STZ (60 mg/kg body weight). Treatments were given orally, once daily, for 12 weeks after confirmation of hyperglycaemia. Fundus photographs were captured at baseline, 6- and 12-week post-STZ injection and average diameter of retinal veins and arteries were measured. At 12-week post-STZ injection, rats were euthanised, and retinae were collected for measurement of Ang-2 and PKC gene and protein expressions.

    RESULTS: Retinal venous and arterial diameters were significantly greater in DV compared to DT at week 12 post-STZ injection (p 

  6. Goh Y, Sadikan MZ, Jaiprakash H, Nasir NAA, Agarwal R, Iezhitsa I, et al.
    BMC Complement Med Ther, 2024 Aug 30;24(1):322.
    PMID: 39215295 DOI: 10.1186/s12906-024-04614-y
    BACKGROUND: Tocotrienol is a vitamin E analogue that is known to exert anti-inflammatory and antioxidant effects. Hence, in the current study, the effects of TRF on the expression of pro- and anti-apoptotic proteins in the streptozotocin-induced diabetic rat retinas were investigated. The effect of TRF on the visual behaviour of rats was also studied.

    METHODS: Diabetes was induced in rats by intraperitoneal injection of streptozotocin and was confirmed by a blood sugar level of at least 20 mmol/L, 48 h, post-injection. Diabetic rats were divided into a group treated with vehicle (DV) and the other treated with TRF (100 mg/kg; DT). A group of non-diabetic rats treated with vehicle (N) served as the control group. All treatments were administered orally for 12 weeks. Rats were then subjected to an assessment of general behaviour in an open field arena and a two-chamber mirror test to assess their visual behaviour. At the end of the experimental period, rats were sacrificed, and their retinas were isolated to measure the expression of pro- (Casp3, Bax) and anti-apoptotic (Bcl2) markers using RT-qPCR and ELISA. TUNEL staining was used to detect the apoptotic retinal cells.

    RESULTS: Treatment with TRF lowered the retinal expression of Casp3 protein by 2.26-folds (p 

  7. Hairi HA, Jusoh RR, Sadikan MZ, Hasan WNW, Shuid AN
    Int J Med Sci, 2025;22(4):819-833.
    PMID: 39991771 DOI: 10.7150/ijms.103241
    Moringa oleifera (MO) is renowned for its remarkable medicinal uses, supported by claims across various cultures and growing scientific evidence. Preclinical experimental evidence indicated that MO may effectively reduce bone loss and promote bone remodelling through its effects on osteoclasts and osteoblasts. In vivo studies demonstrated that MO enhances critical aspects of bone health, such as bone volume, trabecular thickness and overall bone density. Furthermore, MO positively influenced bone biomarkers including alkaline phosphatase and procollagen type 1 N-terminal propeptide, reflecting improved bone formation. Additionally, in vitro and ex vivo studies revealed that MO boosted bone regeneration, stimulated osteoblast activity and reduced inflammation. In terms of mechanisms, MO may modulate signalling pathways related to bone metabolism, such as BMP2, PI3K/Akt/FOXO1, p38α/MAPK14 and RANKL/RANK//OPG pathways. This evidence provides a strong foundation for future clinical research and potential therapeutic applications in managing and preventing bone loss conditions.
  8. Sofi MA, Sofi MA, Nanda A, Nayak BK, Othman Z, Sadikan MZ
    Scientifica (Cairo), 2025;2025:5100547.
    PMID: 40134767 DOI: 10.1155/sci5/5100547
    Medicinal plants have been used for centuries as therapeutic compounds to address various health issues. Their rich phytochemical composition offers diverse bioactive substances with potential health benefits. This study aimed to explore the therapeutic potential of Podophyllum hexandrum root extract by investigating its chemical composition and antimicrobial, antioxidant, and anticancer properties. The phytochemical profiling of P. hexandrum root was conducted using GC-MS analysis, which identified 26 compounds in the extract. The ethanolic root extract displayed strong inhibitory effects in the well diffusion assay against all tested microbes, with minimum inhibitory concentration (MIC) values ranging from 64 to 256 μg/mL. Candida albicans exhibited the lowest MIC value of 64 μg/mL. The antioxidant activity of the extracts was compared to standard antioxidant, revealing a dose-dependent response with a notable radical scavenging activity of 59.23% at 100 μg/mL. Furthermore, the extract demonstrated strong cytotoxic effects against the human cancer cell line HT-29, with IC50 values of 38.20 and 32.5 μg/mL for 24 and 48 h. Overall, this study emphasizes the remarkable antibacterial, antioxidant, and anticancer properties of P. hexandrum root extract.
  9. Sadikan MZ, Lambuk L, Reshidan N, Ahmad Hairi H, Abd Ghapor AA, Mohamud R, et al.
    J Ocul Pharmacol Ther, 2025 Apr;41(3):89-100.
    PMID: 39778903 DOI: 10.1089/jop.2024.0125
    Vitamin E is renowned for its potent antioxidant properties, crucial for shielding cells against oxidative stress and damage. Deficiency in this vitamin can lead to various health issues, including neurodegenerative diseases, due to its pivotal role in preserving cell membrane integrity and combating cellular oxidative damage. While its importance for overall health, including neurodegeneration, is acknowledged, the specific correlation between vitamin E deficiency and distinct ocular neurodegenerative disorders need to be further explored. This review delves into the molecular mechanisms of vitamin E in ocular neurodegenerative disorders; diabetic retinopathy, age-related macular degeneration, glaucoma, and cataracts, and emphasising the therapeutic implications drawn from existing evidence. Relationship between vitamin E and ocular neurodegenerative disorders is widely researched on, with its primary protective mechanisms attributed to its antioxidant and anti-inflammatory properties. However, studies on the supplementation of vitamin E among human subjects present mixed results, suggesting its complexities and variability depending on factors such as the specific disorder, disease stage, genetic differences, and form of vitamin E utilized. In conclusion, while vitamin E holds promise in mitigating ocular neurodegeneration through its antioxidant and anti-inflammatory properties, its supplementation's efficacy remains nuanced and context dependent. More research works are essential to elucidate its precise role and therapeutic potential in combating various ocular neurodegenerative disorders.
  10. Nordin NA, Sadikan MZ, Lambuk L, Hashim S, Airuddin S, Mohd Nasir NA, et al.
    J Pharm Pharmacol, 2025 Apr 03;77(4):475-491.
    PMID: 39579384 DOI: 10.1093/jpp/rgae129
    OBJECTIVES: Glaucoma is a leading cause of permanent blindness. Despite therapeutic advancements, glaucoma management remains challenging due to limitations of conventional drug delivery, primarily topical eye drops, resulting in suboptimal outcomes and a global surge in cases. To address these issues, liposomal drug delivery has emerged as a promising approach.

    KEY FINDINGS: This review explores the potential of liposomal-based medications, with a particular focus on topical administration as a superior alternative to enhance therapeutic efficacy and improve patient compliance compared to existing treatments. This writing delves into the therapeutic prospects of liposomal formulations across different administration routes, as evidenced by ongoing clinical trials. Additionally, critical aspects of liposomal production and market strategies are discussed herein.

    SUMMARY: By overcoming ocular barriers and optimizing drug delivery, liposomal topical administration holds the key to significantly improving glaucoma treatment outcomes.

  11. Sadikan MZ, Abdul Nasir NA, Lambuk L, Mohamud R, Reshidan NH, Low E, et al.
    BMC Ophthalmol, 2023 Oct 19;23(1):421.
    PMID: 37858128 DOI: 10.1186/s12886-023-03155-1
    Diabetic retinopathy (DR), one of the leading causes of visual impairment and blindness worldwide, is one of the major microvascular complications in diabetes mellitus (DM). Globally, DR prevalence among DM patients is 25%, and 6% have vision-threatening problems among them. With the higher incidence of DM globally, more DR cases are expected to be seen in the future. In order to comprehend the pathophysiological mechanism of DR in humans and discover potential novel substances for the treatment of DR, investigations are typically conducted using various experimental models. Among the experimental models, in vivo models have contributed significantly to understanding DR pathogenesis. There are several types of in vivo models for DR research, which include chemical-induced, surgical-induced, diet-induced, and genetic models. Similarly, for the in vitro models, there are several cell types that are utilised in DR research, such as retinal endothelial cells, Müller cells, and glial cells. With the advancement of DR research, it is essential to have a comprehensive update on the various experimental models utilised to mimic DR environment. This review provides the update on the in vitro, in vivo, and ex vivo models used in DR research, focusing on their features, advantages, and limitations.
  12. Sadikan MZ, Lambuk L, Reshidan NH, Abdul Ghani NA, Ahmad AI, Ahmad Kamal MS, et al.
    J Ocul Pharmacol Ther, 2025 Apr;41(3):150-161.
    PMID: 39895321 DOI: 10.1089/jop.2024.0123
    Age-related macular degeneration (AMD) poses a significant threat to visual health among the elderly, necessitating urgent preventive measures as the global population ages. Extensive research has implicated oxidative stress (OS)-induced retinal damage as a primary contributor to AMD pathogenesis, prompting investigations into potential therapeutic interventions. Among the various nutrients studied for their potential in AMD risk reduction, antioxidants have shown promise, with initial findings from the Age-Related Eye Disease Study suggesting a correlation between antioxidant supplementation and decreased AMD progression. This article explores the scientific foundation supporting the therapeutic efficacy of tocotrienol-rich fraction (TRF) as a viable candidate for slowing AMD progression, based on interventional studies. AMD is characterized by OS, inflammation, dysregulated lipid metabolism, and angiogenesis, all of which TRF purportedly addresses through its potent anti-inflammatory, lipid-lowering, antiangiogenic, and antioxidant properties. The review underscores TRF's promising attributes, aiming to deepen understanding of AMD pathogenesis and advocate for TRF-based pharmacological interventions to enhance therapeutic outcomes. Given the pressing need for effective AMD treatments, TRF represents a promising avenue for intervention, offering hope for improved vision outcomes and enhanced quality of life for individuals affected by this debilitating condition.
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