Evaluation of the vitamin D response index in a Saudi cohort.

The concept of the vitamin D response index was developed based on vitamin D intervention studies conducted with Finnish cohorts. In this study, we challenged the concept by performing a single vitamin D3 bolus (80,000 IU) intervention with a cohort of 100 native Saudis. The change of serum levels of the proinflammatory cytokines interleukin 6, interleukin 8 and tumor necrosis factor measured directly before intervention in comparison to samples taken one and thirty days after vitamin D3 supplementation were used as biomarkers for distinguishing low, mid and high responders. Interestingly, we identified 39 % of the study participants as low responders. In contrast, when we used in a subset of 37 study participants whole blood expression changes of seven well-known vitamin D target genes one and thirty days after supplementation as alternative biomarkers, only 9 persons (24 %) were identified as low responders. In conclusion, in Saudi Arabia the rate of low vitamin D responders is equal or even higher than that in Finland. Therefore, similar to Nordic countries also in Saudi Arabia appropriate vitamin D3 supplementation is essential, in order to fulfill the needs of low responders.

Unleashing the potential of catalytic RNAs to combat mis-spliced transcripts.

Human transcriptome can undergo RNA mis-splicing due to spliceopathies contributing to the increasing number of genetic diseases including muscular dystrophy (MD), Alzheimer disease (AD), Huntington disease (HD), myelodysplastic syndromes (MDS). Intron retention (IR) is a major inducer of spliceopathies where two or more introns remain in the final mature mRNA and account for many intronic expansion diseases. Potential removal of such introns for therapeutic purposes can be feasible when utilizing bioinformatics, catalytic RNAs, and nano-drug delivery systems. Overcoming delivery challenges of catalytic RNAs was discussed in this review as a future perspective highlighting the significance of utilizing synthetic biology in addition to high throughput deep sequencing and computational approaches for the treatment of mis-spliced transcripts.

Review of the potential pharmacological role of erucic acid: a monounsaturated omega-9 fatty acid.

This comprehensive review aims to provide an overview of the pharmacological properties of erucic acid (EA) and highlight areas that require further research. EA is an omega-9 fatty acid found in certain vegetable oil, such as rapeseed oil has demonstrated favourable effects in rodents, including ameliorating myocardial lipidosis (fat accumulation in the heart muscle), congestive heart disease, hepatic steatosis (fat accumulation in the liver), and memory impairments. These findings have prompted regulatory bodies to establish limits on EA content in food oils. The studies were performed on rodents and led to caution on ingesting the EA at high levels. Moreover, EA is frequently utilized as a nutritional supplement for the treatment of adrenoleukodystrophy, myocardial disease, and memory improvement. The review of the article indicated that EA improves cognitive function, has a part in Huntington's disease, interacts with peroxisome proliferator-activated receptors, inhibits elastase and thrombin, has anti-inflammatory, antioxidant, and anti-tumour properties, and inhibits influenza A virus. This article elucidates the pharmacological effects of EA, an omega-9 fatty acid.

Influence of rosiridin on streptozotocin-induced diabetes in rodents through endogenous antioxidants-inflammatory cytokines pathway and molecular docking study.

The research was undertaken to assess the antidiabetic activity of rosiridin in the streptozotocin (STZ)-induced diabetic model. Type 2 diabetes mellitus was elicited chemically in experimental animals using STZ (60 mg/kg, i.p.). Experimental rats were arbitrarily allocated to normal control, rosiridin perse, diabetic control, and STZ + rosiridin groups. After the confirmation of diabetes, rosiridin (10 mg/kg) was given orally to the experimental animals for 30 days. Various anti-diabetic (blood glucose, insulin), hypolipidemic, anti-inflammatory (Nuclear factor kappa B, tumour necrosis factor-α, interleukin beta (IL-1ß), and IL-6), antioxidant (and malondialdehyde level, hepatic function and others markers (ALT, AST, adiponectin, and FNDC5) and histopathological indices of injury were evaluated. In addition, the rosinidin was docked into the active site of NF-Kß (1SVC), FNDC5 (4LSD) and adiponectin (5LXG) proteins with AutoDock tools. MD simulations were carried out for the complexes of rosiridin with NF-Kß, myokine and human adiponectin receptor 1. Rosiridin treatment restored the biochemical parameters and preserved the histopathological building of the pancreas as compared to the diabetic rats. Histopathological analysis of the pancreas confirmed that rosiridin antidiabetic efficacy in the STZ-induced diabetes mellitus model. The 5LXG_rosinidin showed favourable affinity with the best binding energies at -7.534 kcal/mol. MD simulations were carried out for the complexes of rosiridin with NF-Kß, myokine and human adiponectin receptor 1, the complex of myokine and rosiridin exhibited the most stable complex. Rosiridin may exhibit considerable anti-diabetic activity in the STZ-induced diabetes mellitus model.Communicated by Ramaswamy H. Sarma.

Protective effect of fustin against adjuvant-induced arthritis through the restoration of proinflammatory response and oxidative stress.

Rheumatoid arthritis causes irreparable damage to joints. The present research sought to check fustin's anti-arthritic efficacy against the complete Freund's adjuvant-induced arthritis paradigm in animals by altering the inflammatory response. In the rats, complete Freund's adjuvant was used to trigger arthritis and they received fustin at 50 and 100 mg/kg for 21 days. At regular intervals, the hind paw volume and arthritic score were assessed. After the trial period, hematological, antioxidant, pro-inflammatory cytokines, and other biochemical parameters were estimated. Fustin-treated rats showed the down-regulation of hind paw volume, arthritic score, and altered hematological parameters (TLC, DLC (neutrophil, lymphocyte, monocyte, eosinophil, basophil)). Furthermore, fustin significantly mitigates proinflammatory cytokine (reduced interleukin, tumor necrosis factor-a (TNF-α), IL-6, IL-1ß), oxidative stress (attenuated malondialdehyde (MDA), catalase (CAT), glutathione (GSH), superoxide dismutase (SOD)), attenuated production of prostaglandin E2 and myeloperoxidase (MPO) and improved nuclear factor erythroid 2-related factor (Nrf2) action. Fustin led to the benefit in arthritis-prone animals elicited by complete Freund's adjuvant via pro-inflammatory cytokine.

Rosinidin inhibits NF-κB/ Nrf2/caspase-3 expression and restores neurotransmitter levels in rotenone-activated Parkinson's disease.

Objectives: The examination was sighted to study the preventive effects of rosinidin against rotenone-activated Parkinson's disease in rats. Methods: Animals were randamoized into five groups: I-saline, II-rotenone (0.5 mg/kg/b.wt.), III- IV-10 and 20 mg/kg rosinidin after rotenone and V-20 mg/kg rosinidin per se for 28 days and were assigned for behavioral analysis., Biochemical parameters i.e. lipid peroxidation, endogenous antioxidants, nitrite level, neurotransmitter levels, proinflammatory biomarkers such as interleukin- 6 (IL-6), tumor necrosis factor-α, IL-1ß, nuclear factor kappa B, nuclear factor erythroid 2-related factor 2, and caspase-3 were assessed on the 29th day of the research. Results: Rosinidin augmented the effectiveness of rotenone on akinesia, catalepsy, forced-swim test, rotarod, and open-field test. Biochemical findings indicated that treatment of rosinidin showed restoring neuroinflammatory cytokines, antioxidants, and neurotransmitter levels in rotenone-injected rats. Conclusion: As a result of rosinidin treatment, the brain was protected from oxidative stress-induced neuronal damage and inhibited neuroinflammatory cytokines.

Barbigerone prevents scopolamine-induced memory impairment in rats by inhibiting oxidative stress and acetylcholinesterase levels.

The current study was designed for the evaluation of barbigerone on memory loss. In this experimental study, 24 Wistar rats (n = 6) were used. Control rats and scopolamine (SCOP)-treated control group rats were orally administered with 3 ml of 0.5% sodium carboxymethyl cellulose (vehicle), whereas barbigerone was (10 and 20 mg kg-1) administered orally to the rats from the test group. During the 14-day treatment, control group rats were given 3 ml kg-1 day-1 saline, and all other groups were administered SCOP (1 mg kg-1 day-1, i.p.) 1 h after barbigerone p.o. treatment. The spontaneous alternation activities, learning capacities of a rat's memory were tested with Morris water maze and Y-maze. Reduced glutathione, malondialdehyde, acetylcholine esterase (AChE) and catalase (CAT) levels were measured in rat brain tissue as oxidative stress/antioxidant markers. Moreover, the levels of tumour necrosis factor, interleukin-6 (IL-6) and IL-1ß were also estimated. Treatment with barbigerone in SCOP-administered rats dramatically reduced SCOP-induced neurobehavioural deficits, oxidative stress and neuroinflammatory markers, improved endogenous antioxidants, and restored AChE activity. By improving cholinergic function and reducing oxidative damage, barbigerone could mitigate the effects of SCOP-induced changes in the brain.

Neuroprotective Effect of Barbaloin on Streptozotocin-Induced Cognitive Dysfunction in Rats via Inhibiting Cholinergic and Neuroinflammatory Cytokines Pathway-TNF-α/IL-1ß/IL-6/NF-κB.

Streptozotocin (STZ) impairs memory in rats through altering the central nervous systems (CNS) as a result of impaired cholinergic dysfunction, oxidative stress, persistent hyperglycemia, and alterations in the glucagon-like peptide (GLP). In this model cholinergic agonist, antioxidant and antihyperglycemic treatment has been shown to have positive effects. Barbaloin has a variety of pharmacological effects. However, there is no evidence on how barbaloin improves memory dysfunction caused by STZ. Thus, we examined its effectiveness against cognitive damage caused by STZ at a dose of 60 mg/kg i.p. in Wistar rats. Blood glucose levels (BGL) and body weight (BW) were assessed. To assess learning and memory skills, the Y-maze test and Morris water maze (MWM) test were utilized. Superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), and glutathione (GSH) as oxidative stress markers were regulated to reverse the cognitive deterioration, and choline-acetyltransferase (ChAT) and acetyl-cholinesterase (AChE) as indicators of cholinergic dysfunction, nuclear factor kappa-B (NF-κB), IL-1ß (interleukin-1ß), IL-6, and tumor necrosis factor-α (TNF-α) contents were used. Barbaloin treatment thereby significantly decreased the BW and learning and memory capacities, resulting in substantial behavioral improvement in the Y-maze and MWM test. BGL, SOD, CAT, MDA, GSH, AChE, ChAT, NF-κB, IL-6, TNF-α, and IL-1ß levels were also altered. In conclusion, the findings revealed that barbaloin had a protective impact against cognitive dysfunction caused by STZ.

Investigating a Library of Flavonoids as Potential Inhibitors of a Cancer Therapeutic Target MEK2 Using in Silico Methods.

The second leading cause of death in the world is cancer. Mitogen-activated protein kinase (MAPK) and extracellular signal-regulated protein kinase (ERK) 1 and 2 (MEK1/2) stand out among the different anticancer therapeutic targets. Many MEK1/2 inhibitors are approved and widely used as anticancer drugs. The class of natural compounds known as flavonoids is well-known for their therapeutic potential. In this study, we focus on discovering novel inhibitors of MEK2 from flavonoids using virtual screening, molecular docking analyses, pharmacokinetic prediction, and molecular dynamics (MD) simulations. A library of drug-like flavonoids containing 1289 chemical compounds prepared in-house was screened against the MEK2 allosteric site using molecular docking. The ten highest-scoring compounds based on docking binding affinity (highest score: -11.3 kcal/mol) were selected for further analysis. Lipinski's rule of five was used to test their drug-likeness, followed by ADMET predictions to study their pharmacokinetic properties. The stability of the best-docked flavonoid complex with MEK2 was examined for a 150 ns MD simulation. The proposed flavonoids are suggested as potential inhibitors of MEK2 and drug candidates for cancer therapy.

Neuroprotectant Effects of Hibiscetin in 3-Nitropropionic Acid-Induced Huntington's Disease via Subsiding Oxidative Stress and Modulating Monoamine Neurotransmitters in Rats Brain.

BACKGROUND: Previously reported data suggest that hibiscetin, isolated from roselle, contains delphinidin-3-sambubioside and cyanidin-3-sambubioside including anthocyanidins and has a broad range of physiological effects. In this study, we aim to analyze the effect of hibiscetin neuroprotective ability in rats against 3-nitropropionic acid (3-NPA)-induced Huntington's disease (HD). METHODS: To investigate possible toxicities in animals, oral acute toxicity studies of hibiscetin were undertaken, and results revealed the safety of hibiscetin in animals with a maximum tolerated dose. Wistar rats were divided into four groups (n = 6); (group-1) treated with normal saline, (group-2) hibiscetin (10 mg/kg) only, (group-3) 3-NPA only, and (group-4) 3-NPA +10 mg/kg hibiscetin. The efficacy of hibiscetin 10 mg/kg was studied with the administration of 3-NPA doses for the induction of experimentally induced HD symptoms in rats. The mean body weight (MBW) was recorded at end of the study on day 22 to evaluate any change in mean body weight. Several biochemical parameters were assessed to support oxidative stress (GSH, SOD, CAT, LPO, GR, and GPx), alteration in neurotransmitters (DOPAC, HVA, 5-HIAA, norepinephrine, serotonin, GABA, and dopamine), alterations in BDNF and cleaved caspase (caspase 3) activity. Additionally, inflammatory markers, i.e., tumor necrosis factor alpha (TNF-α), interleukins beta (IL-1ß), and myeloperoxidase (MPO) were evaluated. RESULTS: The hibiscetin-treated group exhibits a substantial restoration of MBW than the 3-NPA control group. Furthermore, 3-NPA caused a substantial alteration in biochemical, neurotransmitter monoamines, and neuroinflammatory parameters which were restored successfully by hibiscetin. CONCLUSION: The current study linked the possible role of hibiscetin by offering neuroprotection in experimental animal models.

Protective Effect of Fustin against Huntington's Disease in 3-Nitropropionic Treated Rats via Downregulation of Oxidative Stress and Alteration in Neurotransmitters and Brain-Derived Neurotrophic Factor Activity.

Researchers have revealed that Rhus verniciflua heartwood, which contains fustin as an important component, possesses antioxidant-mediated, anti-mutagenic, and anti-rheumatoid arthritis characteristics. Additionally, out of the numerous plant-derived secondary metabolites, there are various research papers concentrating on flavonoids for potential advantages in neurological illnesses. The current study aims to assess the neuroprotective potential of fustin in rodents over 3-nitropropionic acid (3-NPA)-induced Huntington's disease (HD)-like consequences. The efficacy of fustin 50 and 100 mg/kg was studied with multiple-dose administrations of 3-NPA, which experimentally induced HD-like symptoms in rats for 22 days. At the end of the study, several behavioral tests were performed including a beam walk, rotarod, and grip strength tests. Similarly, some biochemical parameters were assessed to support oxidative stress (reduced glutathione-GSH, superoxide dismutase-SOD, catalase-CAT, and malondialdehyde-MDA), alteration in neurotransmitters (gamma-aminobutyric acid-GABA-and glutamate), alteration in brain-derived neurotrophic factor activity, and nitrite levels. Additionally, pro-inflammatory parameters were carried out to evaluate the neuroinflammatory responses associated with streptozotocin such as TNF-α, IL-1ß, and COX in the perfused brain. The fustin-treated group exhibited a significant restoration of memory function via modulation in behavioral activities. Moreover, 3-NPA altered biochemical, neurotransmitters, brain protein levels, and neuroinflammatory measures, which fustin efficiently restored. This is the first report demonstrating the efficacy of novel phytoconstituent fustin as a potential future candidate for the treatment of HD via offering neuroprotection by subsiding the oxidative and enzymatic activity in the 3-NPA experimental animal paradigm.

A Single Vitamin D3 Bolus Supplementation Improves Vitamin D Status and Reduces Proinflammatory Cytokines in Healthy Females.

Vitamin D deficiency is a global health problem that not only leads to metabolic bone disease but also to many other illnesses, most of which are associated with chronic inflammation. Thus, our aim was to investigate the safety and effectiveness of a single high dose of vitamin D3 (80,000 IU) on vitamin D status and proinflammatory cytokines such as interleukin (IL)6, IL8 and tumor necrosis factor (TNF) in healthy Saudi females. Fifty healthy females were recruited and orally supplemented with a single vitamin D3 bolus (80,000 IU). All participants donated fasting blood samples at baseline, one day and thirty days after supplementation. Serum 25-hydroxyvitamin D3 (25(OH)D3), IL6, IL8, TNF, calcium, phosphate, parathyroid hormone (PTH) and blood lipid levels were determined. Serum 25(OH)D3 significantly increased one and thirty days after supplementation when compared with baseline without causing elevation in calcium or phosphate or a decrease in PTH to abnormal levels. In contrast, the concentrations of the three representative proinflammatory cytokines decreased gradually until the end of the study period. In conclusion, a single high dose (80,000 IU) is effective in improving serum vitamin D status and reducing the concentration of the proinflammatory cytokines in a rapid and safe way in healthy females.

A Single Oral Vitamin D3 Bolus Reduces Inflammatory Markers in Healthy Saudi Males.

Vitamin D deficiency has increased in the general population and is a public health issue. Vitamin D plays an important role in regulating the immune system, e.g., by modulating the production of inflammatory cytokines. In most countries, the recommended maximal daily dose of vitamin D3 is 4000 IU (100 µg) per day. In this study, we investigated whether a single vitamin D3 bolus can reduce the levels of the inflammatory markers interleukin (IL) 6, IL8 and tumor necrosis factor (TNF) within one month. Fifty healthy Saudi males were recruited from the local community in Jeddah city and were orally supplemented with a single dose of 80,000 IU vitamin D3. Serum samples were collected at time points 0, 1 and 30 days, and serum levels of IL6, IL8 and TNF, parathyroid hormone (PTH), 25-hydroxyvitamin D3 (25(OH)D3), triglycerides, cholesterol, calcium (Ca2+) and phosphate (PO4-) were determined. On average, the vitamin D3 bolus resulted in a significant increase in vitamin D status as well as in a significant decrease in the levels of inflammatory cytokines even one month after supplementation without changing serum Ca2+, PO4- or lipid levels. In conclusion, single high-dose vitamin D3 supplementation is safe for reducing inflammation markers and may lead to an update of current recommendations for vitamin D intake, in order to prevent critical health problems.

Colon Targeted Eudragit Coated Beads Loaded with Optimized Fluvastatin-Scorpion Venom Conjugate as a Potential Approach for Colon Cancer Therapy: In Vitro Anticancer Activity and In Vivo Colon Imaging.

Preclinical studies suggest that most of statins or 3­hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors possess pleiotropic anticancer activity. The aim of the present work was to investigate the conjugation of the statin fluvastatin (FLV) with scorpion venom (SV), a natural peptide with proven anticancer properties, to enhance FLV cytotoxic activity and prepare colon targeted FLV-SV nanoconjugate beads for management of colon cancer. Response surface design was applied for the optimization of FLV-SV nanoconjugates. FLV-SV particle size and zeta potential were selected as responses. Cytotoxicity of optimized FLV-SV nanoconjugates was carried out on Caco2 cell line. Colon targeted alginate coated Eudragit S100 (ES100) beads for the optimized formula were prepared with the utilization of barium sulfate (BaSO4) as radiopaque contrast substance. Results revealed that optimized FLV-SV nanoconjugates showed a size of 71.21 nm, while the zeta potential was equal to 29.13 mV. Caco2 cells were considerably more sensitive to the FLV-SV formula (half-maximal inhibitory concentration (IC50) = 11.91 µg/mL) compared to SV and FLV used individually, as shown by values of IC50 equal to 30.23 µg/mL and 47.68 µg/mL, respectively. In vivo imaging of colon targeted beads, carried out by employing real-time X-ray radiography, confirmed the efficiency of colon targeted beads. Overall our results indicate that the optimized FLV-SV nanoconjugate loaded alginate coated ES100 beads could represent a promising approach for colon cancer with efficient colon targeting ability.

Optimized 2-methoxyestradiol invasomes fortified with apamin: a promising approach for suppression of A549 lung cancer cells.

Certain anticancer agents selectively target the nucleus of cancer cells. One such drug is 2-methoxyestradiol (2ME), which is used for treating lung cancer. To improve the therapeutic effectiveness of these agents, many new methods have been devised. 2ME was entrapped into the core of hydrophobic invasomes (INVA) covered with Phospholipon 90G and apamin (APA). The Box-Behnken statistical design was implemented to enhance the composition. Using Design-Expert software (Stat-Ease Inc., Minneapolis, MN), the INVA component quantities were optimized to obtain spherical particles with the smallest size, that is, a diameter of 167.8 nm. 2ME-INVA-APA significantly inhibited A549 cells and exhibited IC50 of 1.15 ± 0.04 µg/mL, which is lower than raw 2ME (IC50 5.6 ± 0.2 µg/mL). Post 2ME-INVA-APA administration, a significant rise in cell death and necrosis was seen among the A549 cells compared to those treated with plain formula or 2ME alone. This effect was indicated by increased Bax expression and reduced Bcl-2 expression, as well as mitochondrial membrane potential loss. Moreover, the cell cycle analysis showed that 2ME-INVA-APA arrests the G2-M phase of the A549 cells. Additionally, it was observed that the micellar formulation of the drug increased the cell count in pre-G1, thereby exhibiting phenomenal apoptotic potential. Furthermore, it up-regulates caspase-9 and p53 and downregulates TNF-α and NF-κß. Collectively, these findings showed that our optimized 2ME-INVA-APA could easily seep through the cell membrane and induce apoptosis in relatively low doses.

Exploring the Natural Compounds in Flavonoids for Their Potential Inhibition of Cancer Therapeutic Target MEK1 Using Computational Methods.

The Mitogen-Activated Protein Kinase (MAPK) signaling pathway plays an important role in cancer cell proliferation and survival. MAPKs' protein kinases MEK1/2 serve as important targets in drug designing against cancer. The natural compounds' flavonoids are known for their anticancer activity. This study aims to explore flavonoids for their inhibition ability, targeting MEK1 using virtual screening, molecular docking, ADMET prediction, and molecular dynamics (MD) simulations. Flavonoids (n = 1289) were virtually screened using molecular docking and have revealed possible inhibitors of MEK1. The top five scoring flavonoids based on binding affinity (highest score for MEK1 is -10.8 kcal/mol) have been selected for further protein-ligand interaction analysis. Lipinski's rule (drug-likeness) and absorption, distribution, metabolism, excretion, and toxicity predictions were followed to find a good balance of potency. The selected flavonoids of MEK1 have been refined with 30 (ns) molecular dynamics (MD) simulation. The five selected flavonoids are strongly suggested to be promising potent inhibitors for drug development as anticancer therapeutics of the therapeutic target MEK1.

Ceftriaxone and Melittin Synergistically Promote Wound Healing in Diabetic Rats.

High glucose levels in diabetic patients are implicated in delay wound healing that could lead to more serious clinical complications. The aim of the present work was to examine the formulation of ceftriaxone (CTX) and melittin (MEL) as nanoconjugate (nanocomplex)-loaded hydroxypropyl methylcellulose (HPMC) (1.5% w/v)-based hydrogel for healing of acute wounds in diabetic rats. The CTX-MEL nanoconjugate, formulated by ion-pairing at different molar ratio, was characterized for size and zeta potential and investigated by transmission electron microscopy. CTX-MEL nanoconjugate was prepared, and its preclinical efficacy evaluated in an in vivo model of acute wound. In particular, the potential ability of the innovative CTX-MEL formulation to modulate wound closure, oxidative status, inflammatory markers, and hydroxyproline was evaluated by ELISA, while the histopathological examination was obtained by using hematoxylin and eosin or Masson's trichrome staining techniques. Quantitative real-time PCR (qRT-PCR) of the excised tissue to measure collagen, type I, alpha 1 (Col1A1) expression and immunohistochemical assessment of vascular endothelial growth factor A (VEGF-A) and transforming growth factor beta 1 (TGF-ß1) were also carried out to shed some light on the mechanism of wound healing. Our results show that the CTX-MEL nanocomplex has enhanced ability to regenerate epithelium, also giving better keratinization, epidermal proliferation, and granulation tissue formation, compared to MEL, CTX, or positive control. The nanocomplex also significantly ameliorated the antioxidant status by decreasing malondialdehyde (MDA) and increasing superoxide dismutase (SOD) levels. The treatment of wounded skin with the CTX-MEL nanocomplex also showed a significant reduction in interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) pro-inflammatory cytokines combined with a substantial increase in hydroxyproline, VEFG-A, and TGF-ß1 protein expression compared to individual components or negative control group. Additionally, the CTX-MEL nanocomplex showed a significant increase in mRNA expression levels of Col1A1 as compared to individual compounds. In conclusion, the ion-pairing nanocomplex of CTX-MEL represents a promising carrier that can be topically applied to improve wound healing.

Synthesis and in vitro antitumor activity of novel acylspermidine derivative N-(4-aminobutyl)-N-(3-aminopropyl)-8-hydroxy-dodecanamide (AAHD) against HepG2 cells.

Naturally occurring polyamines like Putrescine, Spermidine, and Spermine are polycations which bind to the DNA, hence stabilizing it and promoting the essential cellular processes. Many synthetic polyamine analogues have been synthesized in the past few years, which have shown cytotoxic effects on different tumours. In the present study, we evaluated the antiproliferative effect of a novel, acylspermidine derivative, (N-(4-aminobutyl)-N-(3-aminopropyl)-8-hydroxy-dodecanamide) (AAHD) on HepG2 cells. Fluorescence staining was performed with nuclear stain (Hoechst 33342) and acridine orange/ethidium bromide double staining. Dose and the time-dependent antiproliferative effect were observed by WST-1 assays, and radical scavenging activity was measured by ROS. Morphological changes such as cell shrinkage & blebbing were analyzed by fluorescent microscopy. It was found that AAHD markedly suppressed the growth of HepG2 cells in a dose- and time-dependent manner. It was also noted that the modulation of ROS levels confirmed the radical scavenging activity. In the near future, AAHD can be a promising drug candidate in chalking out a neoplastic strategy to control the proliferation of tumour cells. This study indicated that AAHD induced anti-proliferative and pro-apoptotic activities on HCC. Since AAHD was active at micromolar concentrations without any adverse effects on the healthy cells (Fibroblasts), it is worthy of further clinical investigations.