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  1. Azlina MFN, Qodriyah MS, Kamisah Y
    Curr Drug Targets, 2018;19(12):1456-1462.
    PMID: 29173163 DOI: 10.2174/1389450118666171122130338
    BACKGROUND: Scientific reports had shown that stress is related to numerous pathological changes in the body. These pathological changes can bring about numerous diseases and can significantly cause negative effects in an individual. These include gastric ulcer, liver pathology and neurobehavioral changes. A common pathogenesis in many diseases related to stress involves oxidative damage. Therefore, the administration of antioxidants such as vitamin E is a reasonable therapeutic approach. However, there is conflicting evidence about antioxidant supplementation.

    OBJECTIVE: The aim of this work was to summarize documented reports on the effects of tocopherol and tocotrienol on various pathological changes induced by stress.

    RESULTS AND CONCLUSION: This review will reveal the scientific evidence of enteral supplementation of vitamin E in the forms of tocotrienol and tocopherol in animal models of stress. These models mimic the stress endured by critically ill patients in a clinical setting and psychological stress in individuals. Positive outcomes from enteral feeding of vitamin E in reducing the occurrence of stress-induced pathological changes are discussed in this review. These positive findings include their ability to reduced stress-induced gastric ulcers, elevated liver enzymes and improved locomotors activity. Evidences showing tocotrienol and tocopherol effects are not just related to its ability to reduce oxidative stress but also acting on other mechanism, are discussed.

  2. Azlina MFN, Qodriyah HMS, Akmal MN, Ibrahim IAA, Kamisah Y
    Arch Med Sci, 2019 Jan;15(1):223-231.
    PMID: 30697274 DOI: 10.5114/aoms.2016.63156
    Introduction: Piper sarmentosum (Piperaceae) is traditionally used by Asians to treat numerous common ailments including asthma, fever and gastritis. The aim of the research was to determine and compare the effects of Piper sarmentosum (PS) with omeprazole (OMZ) on gastric parameters in rats exposed to restraint stress.

    Material and methods: The methanolic extract of PS was prepared in the dose of 500 mg/kg. Twenty-eight male Wistar rats were assigned to 4 equal sized groups: two control groups and two treated groups which were supplemented with either PS or OMZ orally at a dose of 500 mg/kg and 20 mg/kg body weight respectively. After 28 days of treatment, one control group, the PS and OMZ group were subjected to a single exposure of water-immersion restraint stress for 3.5 h. After the last exposure to stress, the stomach was excised for evaluation of the parameters.

    Results: Oral supplementation of PS was as effective in preventing the formation of gastric lesion when compared with OMZ (p < 0.05). The increased gastric acidity and MDA due to stress was also reduced with supplementation of PS and OMZ. Only PS had the ability to reduce prostaglandin E2 loss (p = 0.0067) and have the ability to down regulate cyclooxygenase-2 (COX-2) mRNA expression (p = 0.01) with stress exposure.

    Conclusions: Piper sarmentosum possesses a similar protective effect against stress-induced gastric lesions as omeprazole. The protective effect was associated with decreased lipid peroxidation, increased prostaglandin E2, reduction in gastric acidity and reduction in COX-2 mRNA expression which was altered by stress.

  3. Alzahrani AR, Ibrahim IAA, Shahzad N, Shahid I, Alanazi IM, Falemban AH, et al.
    Int J Biol Macromol, 2023 Sep 13;253(Pt 4):126889.
    PMID: 37714232 DOI: 10.1016/j.ijbiomac.2023.126889
    Gold nanoparticles have been broadly investigated as cancer diagnostic and therapeutic agents. Gold nanoparticles are a favorable drug delivery vehicle with their unique subcellular size and good biocompatibility. Chitosan, agarose, fucoidan, porphyran, carrageenan, ulvan and alginate are all examples of biologically active macromolecules. Since they are biocompatible, biodegradable, and irritant-free, they find extensive application in biomedical and macromolecules. The versatility of these compounds is enhanced because they are amenable to modification by functional groups like sulfation, acetylation, and carboxylation. In an eco-friendly preparation process, the biocompatibility and targeting of GNPs can be improved by functionalizing them with polysaccharides. This article provides an update on using carbohydrate-based GNPs in liver cancer treatment, imaging, and drug administration. Selective surface modification of several carbohydrate types and further biological uses of GNPs are focused on.
  4. Ahmmed F, Hossain MJ, Sutopa TS, Al-Mamun M, Alam M, Islam MR, et al.
    Front Public Health, 2022;10:988016.
    PMID: 36504941 DOI: 10.3389/fpubh.2022.988016
    Exclusive breastfeeding (EBF) is essential for infant and child health. This study aimed to explore the trend in the EBF over the last decade in Bangladesh and investigated if there was a significant association with maternal employment by analyzing the data extracted from three consecutive nationally representative surveys: Bangladesh Demographic and Health Surveys (BDHS) of 2011, 2014, and 2017-2018. Prevalence of EBF (95% confidence interval) with the Cochran-Armitage test was reported to see the trend in EBF. A chi-square (χ2) test was applied to find the potential factors associated with EBF. Finally, a three-level logistic regression was utilized to find the significant association between maternal employment and EBF while adjusting other covariates. We observed no increase in the practice of EBF over the last decade (P = 0.632). The prevalence of EBF was 64.9% (95% CI: 61.41, 68.18) in 2011, followed by 60.1% (95% CI: 56.25, 64) in 2014, and 64.9% (95% CI: 61.82, 67.91) in 2017. Regression results showed that employed mothers had 24% (p < 0.05) lower odds of EBF than unemployed mothers. Early initiation of breastfeeding was also found to be significantly associated [Adjusted odds ratio (AOR): 1.22, P < 0.05] with EBF. Government and policymakers must come forward with new interventions to increase the practice of EBF, providing basic education and campaigns on the topic of EBF. Maternity leave should be extended up to 6 months of the child's age to achieve an optimal level of EBF.
  5. Ibrahim IAA, Alzahrani AR, Alanazi IM, Shahzad N, Shahid I, Falemban AH, et al.
    Int J Biol Macromol, 2023 Dec 31;253(Pt 2):126581.
    PMID: 37652322 DOI: 10.1016/j.ijbiomac.2023.126581
    Carbohydrate polymers-based surface-modified nano-delivery systems have gained significant attention in recent years for enhancing targeted delivery to colon cancer. These systems leverage carbohydrate polymers' unique properties, such as biocompatibility, biodegradability, and controlled release. These properties make them suitable candidates for drug delivery applications. Nano-delivery systems loaded with bioactive compounds are well-studied for targeted colorectal cancer delivery. However, those drugs' target reach is still limited in various nano-delivery systems. To overcome this limitation, surface modification of nanoparticles with carbohydrate polymers like chitosan, pectin, alginate, and guar gum showed enhanced target-reaching capacity along with enhanced anticancer efficacy. Recently, a chitosan-decorated PLGA nanoparticle was constructed with tannic acid and vitamin E and showed long-term release of specific targets along with higher anticancer efficacy. Similarly, Chitosan-conjugated glucuronic acid-coated silica nanoparticles loaded with capecitabine were studied against colon cancer and found to be the pH-responsive controlled release of capecitabine with higher anticancer efficacy. Surface-modified carbohydrate polymers have promising potential for improving colon cancer target delivery. By leveraging the unique properties of these polymers, such as surface modification, pH responsiveness, mucoadhesion, controlled drug release, and combination therapy, researchers are working toward developing more effective and targeted treatment strategies for colon cancer.
  6. Ibrahim IAA, Alzahrani AR, Alanazi IM, Shahzad N, Shahid I, Falemban AH, et al.
    Int J Biol Macromol, 2023 Dec 31;253(Pt 7):127334.
    PMID: 37820908 DOI: 10.1016/j.ijbiomac.2023.127334
    Our study produced GO-TiO2-chitosan-escin nanocomposites (GTCEnc), characterized them using physical and biological methods, and evaluated their potential as cancer treatment candidates. Standard protocols were used to produce GTCEnc. Nanocomposites are created using XRD, FTIR, UV-Vis, and PL spectroscopy analysis. The morphology and ultrastructure of nanocomposites were investigated using SEM and TEM. Nanocomposites containing TiO2, GO, chitosan, and escin nanostructures were characterized using diffraction, microscopy, and spectroscopy; the antimicrobial activity of GTCEnc was investigated. Various methods were used to test the anticancer activity of GTCEnc against COLO 205 cell lines, including MTT, EtBr/AO, DAPI, JC-1, Annexin-V/FITC, cell cycle analysis, and activation of pro-apoptotic markers, such as caspase-3, -8, and -9. The nanocomposites were cytotoxic to COLO 205 cells, with an IC50 of 22.68 μg/mL, but not to 293T cells. In cells treated with nanomaterials, cytotoxicity, nuclear damage, apoptosis induction, and free radical production were significantly increased. Our finding suggests that GTCEnc has potent anticancer and antibacterial activity in vitro because of its unique nanocomposite properties and antibacterial and anticancer activity in vitro. Additional research is required to understand the clinical efficacy of these nanocomposites.
  7. Jadhav PB, Jadhav SB, Zehravi M, Mubarak MS, Islam F, Jeandet P, et al.
    Molecules, 2022 Dec 24;28(1).
    PMID: 36615348 DOI: 10.3390/molecules28010149
    Dipeptidyl peptidase-4 (DPP-IV) inhibitors are known as safe and well-tolerated antidiabetic medicine. Therefore, the aim of the present work was to synthesize some carbohydrazide derivatives (1a-5d) as DPP-IV inhibitors. In addition, this work involves simulations using molecular docking, ADMET analysis, and Lipinski and Veber's guidelines. Wet-lab synthesis was used to make derivatives that met all requirements, and then FTIR, NMR, and mass spectrometry were used to confirm the structures and perform biological assays. In this context, in vitro enzymatic and in vivo antidiabetic activity evaluations were carried out. None of the molecules had broken the majority of the drug-likeness rules. Furthermore, these molecules were put through additional screening using molecular docking. In molecular docking experiments (PDB ID: 2P8S), many molecules displayed more potent interactions than native ligands, exhibiting more hydrogen bonds, especially those with chloro- or fluoro substitutions. Our findings indicated that compounds 5b and 4c have IC50 values of 28.13 and 34.94 µM, respectively, under in vitro enzymatic assays. On the 21st day of administration to animals, compound 5b exhibited a significant reduction in serum blood glucose level (157.33 ± 5.75 mg/dL) compared with the diabetic control (Sitagliptin), which showed 280.00 ± 13.29 mg/dL. The antihyperglycemic activity showed that the synthesized compounds have good hypoglycemic potential in fasting blood glucose in the type 2 diabetes animal model (T2DM). Taken all together, our findings indicate that the synthesized compounds exhibit excellent hypoglycemic potential and could be used as leads in developing novel antidiabetic agents.
  8. Shahzad N, Alzahrani AR, Aziz Ibrahim IA, Shahid I, Alanazi IM, Falemban AH, et al.
    Heliyon, 2024 Jan 30;10(2):e24207.
    PMID: 38298622 DOI: 10.1016/j.heliyon.2024.e24207
    High blood glucose levels are a hallmark of the metabolic syndrome known as diabetes mellitus. More than 600 million people will have diabetes by 2045 as the global prevalence of the disease continues to rise. Contemporary antidiabetic drugs reduce hyperglycemia and its consequences. However, these drugs come with undesirable side effects, so it's encouraging that research into plant extracts and bioactive substances with antidiabetic characteristics is on the rise. Natural remedies are preferable to conventional anti-diabetic drugs since they are safer for the body, more affordable and have fewer potential adverse effects. Biological macromolecules such as liposomes, niosomes, polymeric nanoparticles, solid lipid nanoparticles, nanoemulsions and metallic nanoparticles are explored in this review. Current drug restrictions have been addressed, and the effectiveness of plant-based antidiabetic therapies has enhanced the merits of these methods. Plant extracts' loading capacity and the carriers' stability are the primary obstacles in developing plant-based nanocarriers. Hydrophilic, hydrophobic, and amphiphilic drugs are covered, and a brief overview of the amphipathic features of liposomes, phospholipids, and lipid nanocarriers is provided. Metallic nanoparticles' benefits and attendant risks are highlighted to emphasize their efficiency in treating hyperglycemia. Researchers interested in the potential of nanoparticles loaded with plant extracts as antidiabetic therapeutics may find the current helpful review.
  9. Almaimani G, Jabbar AAJ, Ibrahim IAA, Alzahrani AR, Bamagous GA, Almaimani RA, et al.
    Environ Sci Pollut Res Int, 2024 Jan;31(3):4439-4452.
    PMID: 38103135 DOI: 10.1007/s11356-023-31349-z
    Herbal medicine is one of the most common fields explored for combating colon cancers, and Pimpinella anisum L. seeds (PAS) have been utilized widely as medicinal agents because of their increased essential oil (trans-anethole) contents. In this essence, our study investigates the toxic effect and chemoprotective potentials of PAS against azoxymethane (AOM)-induced colon cancer in rats. The toxicity trial for PAS conducted by clustering fifteen rats into three groups (five rats each): A, normal control had 10% Tween 20; B, ingested with 2 g/kg PAS; and C, supplemented with 4 g/kg PAS. The in vivo cancer trial was performed by using 30 rats (Sprague-Dawley) that were randomly adapted in five steel cages (six rats each): group A, normal controls received two subcutaneous injections of normal saline 0.09% and ingested orally 10% Tween 20; groups B-E, rats received two injections of 15 mg/kg of azoxymethane (AOM) subcutaneously in 2 weeks and treated orally with 10% Tween 20 (group B) or intraperitoneal injection of 5-fluorouracil (35 mg/kg) (group C), or orally given 200 mg/kg PAS (group D) and 400 mg/kg PAS (group E) for 8 weeks. After the scarification of rats, the colon tissues were dissected for gross and histopathological evaluations. The acute toxicity trial showed the absence of any toxic signs in rats even after 14 days of ingesting 4 g/kg of PAS. The chemoprotective experiment revealed significant inhibitory potentials (65.93%) of PAS (400 mg/kg) against aberrant crypto foci incidence that could be correlated with its positive modulation of the immunohistochemically proteins represented by a significant up-regulation of the Bax protein and a decrease of the Bcl-2 protein expressions in colon tissues. Furthermore, PAS-treated rats had notably lower oxidative stress in colon tissues evidenced by decreased MDA levels and increased antiradical defense enzymes (SOD, CAT, and GPx). The outcomes suggest 400 mg/kg PAS as a viable additive for the development of potential pharmaceuticals against colorectal cancer.
  10. Vawhal PK, Jadhav SB, Kaushik S, Panigrahi KC, Nayak C, Urmee H, et al.
    Molecules, 2023 Jan 19;28(3).
    PMID: 36770672 DOI: 10.3390/molecules28031004
    Recent research on dipeptidyl peptidase-IV (DPP-IV) inhibitors has made it feasible to treat type 2 diabetes mellitus (T2DM) with minimal side effects. Therefore, in the present investigation, we aimed to discover and develop some coumarin-based sulphonamides as potential DPP-IV inhibitors in light of the fact that molecular hybridization of many bioactive pharmacophores frequently results in synergistic activity. Each of the proposed derivatives was subjected to an in silico virtual screening, and those that met all of the criteria and had a higher binding affinity with the DPP-IV enzyme were then subjected to wet lab synthesis, followed by an in vitro biological evaluation. The results of the pre-ADME and pre-tox predictions indicated that compounds 6e, 6f, 6h, and 6m to 6q were inferior and violated the most drug-like criteria. It was observed that 6a, 6b, 6c, 6d, 6i, 6j, 6r, 6s, and 6t displayed less binding free energy (PDB ID: 5Y7H) than the reference inhibitor and demonstrated drug-likeness properties, hence being selected for wet lab synthesis and the structures being confirmed by spectral analysis. In the in vitro enzyme assay, the standard drug Sitagliptin had an IC50 of 0.018 µM in the experiment which is the most potent. All the tested compounds also displayed significant inhibition of the DPP-IV enzyme, but 6i and 6j demonstrated 10.98 and 10.14 µM IC50 values, respectively, i.e., the most potent among the synthesized compounds. Based on our findings, we concluded that coumarin-based sulphonamide derivatives have significant DPP-IV binding ability and exhibit optimal enzyme inhibition in an in vitro enzyme assay.
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