Network Pharmacology and Molecular Docking Analysis of Active Compounds in Tualang Honey against Atherosclerosis.

Atherosclerosis, a pathological condition marked by the accumulation of lipids and fibrous substances in the arterial walls, is a leading cause of heart failure and death. The present study aimed to utilize network pharmacology to assess the potential pharmacological effects of bioactive compounds in Tualang honey on atherosclerosis. This is significant as previous studies have indicated the cardioprotective effects of Tualang honey, yet a comprehensive evaluation using network pharmacology has yet to be conducted. The bioactive compounds in Tualang honey were screened and the potential gene targets for these compounds were predicted through Swiss Target Prediction and SuperPred databases. Atherosclerosis genes were retrieved from the OMIM, DisGeNet, and GeneCards databases. The interaction between these compounds and atherosclerosis genes was established through protein-protein interaction, gene ontology, and KEGG pathway analysis. The results of these analyses were then further confirmed through molecular docking studies using the AutoDock Tools software. The results revealed that 6 out of 103 compounds in Tualang honey met the screening criteria, with a total of 336 potential gene targets, 238 of which were shared with atherosclerosis. Further analysis showed that these active compounds had a good affinity with key targets and were associated with biological processes related to protein phosphorylation and inflammation as well as pathways related to lipid and atherosclerosis and other signaling pathways. In conclusion, the study provides insight into the potential pharmacological effects of Tualang honey bioactive compounds on atherosclerosis, supporting its use as a promising treatment for the disease.

Large animal models for cardiac remuscularization studies: A methodological review.

Myocardial infarction is the most common cause of heart failure, one of the most fatal non-communicable diseases worldwide. The disease could potentially be treated if the dead, ischemic heart tissues are regenerated and replaced with viable and functional cardiomyocytes. Pluripotent stem cells have proven the ability to derive specific and functional cardiomyocytes in large quantities for therapy. To test the remuscularization hypothesis, the strategy to model the disease in animals must resemble the pathophysiological conditions of myocardial infarction as in humans, to enable thorough testing of the safety and efficacy of the cardiomyocyte therapy before embarking on human trials. Rigorous experiments and in vivo findings using large mammals are increasingly important to simulate clinical reality and increase translatability into clinical practice. Hence, this review focus on large animal models which have been used in cardiac remuscularization studies using cardiomyocytes derived from human pluripotent stem cells. The commonly used methodologies in developing the myocardial infarction model, the choice of animal species, the pre-operative antiarrhythmics prophylaxis, the choice of perioperative sedative, anaesthesia and analgesia, the immunosuppressive strategies in allowing xenotransplantation, the source of cells, number and delivery method are discussed.

The Potential Chemopreventive Effect of Andrographis paniculata on 1,2-Dimethylhydrazine and High-Fat-Diet-Induced Colorectal Cancer in Sprague Dawley Rats.

Colorectal cancer (CRC) is responsible for a notable rise in the overall mortality rate. Obesity is found to be one of the main factors behind CRC development. Andrographis paniculata is a herbaceous plant famous for its medicinal properties, particularly in Southeast Asia for its anti-cancer properties. This study examines the chemopreventive impact of A. paniculata ethanolic extract (APEE) against a high-fat diet and 1,2-dimethylhydrazine-induced colon cancer in Sprague Dawley rats. Sprague Dawley rats were administered 1,2-dimethylhydrazine (40 mg/kg, i.p. once a week for 10 weeks) and a high-fat diet (HFD) for 20 weeks to induce colorectal cancer. APEE was administered at 125 mg/kg, 250 mg/kg, and 500 mg/kg for 20 weeks. At the end of the experiment, blood serum and organs were collected. DMH/HFD-induced rats had abnormal crypts and more aberrant crypt foci (ACF). APEE at a dose of 500 mg/kg improved the dysplastic state of the colon tissue and caused a 32% reduction in the total ACF. HFD increased adipocyte cell size, while 500 mg/kg APEE reduced it. HFD and DMH/HFD rats had elevated serum insulin and leptin levels. Moreover, UHPLC-QTOF-MS analysis revealed that APEE was rich in anti-cancer phytochemicals. This finding suggests that APEE has anti-cancer potential against HFD/DMH-induced CRC and anti-adipogenic and anti-obesity properties.

Mesenchymal Stromal Cells-Derived Exosome and the Roles in the Treatment of Traumatic Brain Injury.

Traumatic brain injury (TBI) could result in life-long disabilities and death. Though the mechanical insult causes primary injury, the secondary injury due to dysregulated responses following neuronal apoptosis and inflammation is often the cause for more detrimental consequences. Mesenchymal stromal cell (MSC) has been extensively investigated as the emerging therapeutic for TBI, and the functional properties are chiefly attributed to their secretome, especially the exosomes. Delivering these nanosize exosomes have shown to ameliorate post-traumatic injury and restore brain functions. Recent technology advances also allow engineering MSC-derived exosomes to carry specific biomolecules of interest to augment their therapeutic outcome. In this review, we discuss the pathophysiology of TBI and summarize the recent progress in the applications of MSCs-derived exosomes, the roles and the signalling mechanisms underlying the protective effects in the treatment of the TBI.

Tualang and Kelulut Honey Reduced Lipopolysaccharidesstimulated Inflammatory Responses of Mic

@#Microglial activity is crucial in maintaining the central nervous system (CNS) homeostasis. However, prolonged microglial activation have been implicated in the pathology of neurodegenerative diseases. Activated microglia will increase the production of inflammatory cytokines, reactive oxygen species (ROS) and alter their surface marker expression levels. This study used Malaysian honey, Tualang honey (TH), and Kelulut honey (KH) to determine lipopolysaccharide (LPS)-stimulated inflammatory responses of microglia. TH and KH at 0.1% were used in the current study as our findings showed no significant difference in the cell viability between BV2 cells treated with 0.1 % of TH and KH and control group. TH and KH reduced the ROS level significantly by 41.62±1.06% and 49.16±0.63%, respectively, and slightly reduced the expression of co-stimulatory molecules, CD40 and CD11b in LPS-activated BV2 cells. Our preliminary findings proposed an in-depth future study on the anti-inflammatory effect of TH and KH on microglial activation.

Antimicrobial and Cytotoxic Effects of Cannabinoids: An Updated Review with Future Perspectives and Current Challenges.

The development of new antibiotics is urgently needed to combat the threat of bacterial resistance. New classes of compounds that have novel properties are urgently needed for the development of effective antimicrobial agents. The extract of Cannabis sativa L. has been used to treat multiple ailments since ancient times. Its bioactivity is largely attributed to the cannabinoids found in its plant. Researchers are currently searching for new anti-infective agents that can treat various infections. Although its phytocannabinoid ingredients have a wide range of medical benefits beyond the treatment of infections, they are primarily associated to psychotropic effects. Different cannabinoids have been demonstrated to be helpful against harmful bacteria, including Gram-positive bacteria. Moreover, combination therapy involving the use of different antibiotics has shown synergism and broad-spectrum activity. The purpose of this review is to gather current data on the actions of Cannabis sativa (C. sativa) extracts and its primary constituents such as terpenes and cannabinoids towards pathogens in order to determine their antimicrobial properties and cytotoxic effects together with current challenges and future perspectives in biomedical application.

Synthesis of Zinc Oxide Nanoparticles with Bioflavonoid Rutin: Characterisation, Antioxidant and Antimicrobial Activities and In Vivo Cytotoxic Effects on Artemia Nauplii.

This study aims to synthesise zinc oxide nanoparticles with rutin (ZnO-R NPs) using a green synthesis approach and characterise the nanostructures for diverse biomedical applications. In this study, the optical and chemical properties of synthesised ZnO-R NPs were verified through Fourier transform infrared (FTIR) spectroscopy and ultraviolet-visible (UV-Vis) spectroscopy. The FTIR spectroscopy revealed a symmetric bending vibration peak of 460 cm-1 for ZnO-R NPs, whereas UV-Vis spectroscopy showed a distinct absorption band at 395 nm. Moreover, the oval-shaped morphology of ZnO-R NPs was verified through scanning electron microscopy and transmission electron microscopy. The synthesised nanoformulation revealed a wurtzite structure with a crystallite size of 13.22 nm; however, the zeta potential value was recorded as -8.50 ± 0.46 mV for ZnO-R NPs. According to an antioxidant study, ZnO-R NPs demonstrated lower free-radical scavenging activity than pure rutin. The cytotoxicity study was conducted using a human breast cancer cell line (MCF-7). In vitro analysis verified that ZnO-R NPs exhibited significantly higher anticancer and microbial growth inhibition activities than standard ZnO NPs (ZnO Std NPs) and pure rutin. In addition, ZnO-R NPs revealed a significantly lower IC50 value than the commercial ZnO Std NPs and pure rutin in MCF-7 cells (16.39 ± 6.03 µg/mL, 27 ± 0.91 µg/mL and 350 ± 30.1 µg/mL, respectively) after 48 h. However, synthesised ZnO-R NPs demonstrated no significant toxicity towards Artemia nauplii. These results highlight the synthesis of rutin-mediated ZnO NPs and their possible chemotherapeutic potential.

Adverse Effects of Bisphenol A on the Liver and Its Underlying Mechanisms: Evidence from In Vivo and In Vitro Studies.

BPA is a known endocrine-disrupting agent that is capable of binding to the estrogen receptor and has exhibited adverse effects in many laboratory animal and in vitro studies. Moreover, it also been shown to have estrogenic, antiandrogenic, inflammatory, and oxidative properties. The widespread presence of BPA in the environment presents a considerable threat to humans. BPA has been shown to be leached into the human ecosystem, where it is commonly found in food products consumed by humans. Although the concentration is relatively low, its prolonged consumption may cause a variety of deleterious health effects. The liver is an important organ for metabolizing and detoxifying toxic metabolites to protect organisms from potentially toxic chemical insults. BPA that is ingested will be eliminated by the liver. However, it has also induced hepatoxicity and injury via various mechanisms. To find research demonstrating the effects of BPA on kidney, a number of databases, including Google Scholar, MEDLINE, PubMed, and the Directory of Open Access Journals, were searched. Thus, this review summarizes the research on the relationship between BPA and its effects on the liver-derived from animals and cellular studies. The underlying mechanism of liver injury caused by BPA is also elucidated.

Vascular Protective Effect and Its Possible Mechanism of Action on Selected Active Phytocompounds: A Review.

Vascular endothelial dysfunction is characterized by an imbalance of vasodilation and vasoconstriction, deficiency of nitric oxide (NO) bioavailability and elevated reactive oxygen species (ROS), and proinflammatory factors. This dysfunction is a key to the early pathological development of major cardiovascular diseases including hypertension, atherosclerosis, and diabetes. Therefore, modulation of the vascular endothelium is considered an important therapeutic strategy to maintain the health of the cardiovascular system. Epidemiological studies have shown that regular consumption of medicinal plants, fruits, and vegetables promotes vascular health, lowering the risk of cardiovascular diseases. This is mainly attributed to the phytochemical compounds contained in these resources. Various databases, including Google Scholar, MEDLINE, PubMed, and the Directory of Open Access Journals, were searched to identify studies demonstrating the vascular protective effects of phytochemical compounds. The literature had revealed abundant data on phytochemical compounds protecting and improving the vascular system. Of the numerous compounds reported, curcumin, resveratrol, cyanidin-3-glucoside, berberine, epigallocatechin-3-gallate, and quercetin are discussed in this review to provide recent information on their vascular protective mechanisms in vivo and in vitro. Phytochemical compounds are promising therapeutic agents for vascular dysfunction due to their antioxidative mechanisms. However, future human studies will be necessary to confirm the clinical effects of these vascular protective mechanisms.

Vibrational Spectroscopy-Based Chemometrics Analysis of Clinacanthus nutans Extracts after Postharvest Processing and Extract Effects on Cardiac C-Kit Cells.

Chemical constituents in plants can be greatly affected by postharvest processing, and it is important to identify the factors that lead to significant changes in chemistry and bioactivity. In this study, attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy was used to analyze extracts of Clinacanthus nutan (C. nutans) leaves generated using different parameters (solvent polarities, solid-liquid ratios, ultrasonic durations, and cycles of extraction). In addition, the effects of these extracts on the viability of cardiac c-kit cells (CCs) were tested. The IR spectra were processed using SIMCA-P software. PCA results of all tested parameter sets were within acceptable values. Solvent polarity was identified as the most influential factor to observe the differences in chemical profile and activities of C. nutans extracts. Ideal extraction conditions were identified, for two sample groups (G1 and G2), as they showed optimal total phenolic content (TPC) yield of 44.66 ± 0.83 mg GAE/g dw and 45.99 ± 0.29 mg GAE/g dw and CC viability of 171.81 ± 4.06% and 147.53 ± 6.80%, respectively. Validation tools such as CV-ANOVA (p < 0.05) and permutation (R 2 and Q 2 plots were well intercepted to each other) have further affirmed the significance and reliability of the partial least square (PLS) model of solvent polarity employed in extraction. Hence, these approaches help optimize postharvest processes that encourage positive TPC and CCs results in C. nutans extracts.

Protective Effects of Alternanthera sessilis Ethanolic Extract against TNF-α or H2O2-Induced Endothelial Activation in Human Aortic Endothelial Cells.

Activation of the endothelium has been shown to contribute to the early stage of vascular diseases such as atherosclerosis and hypertension. In endothelial activation, excess reactive oxygen species (ROS) production and increased expression of cell adhesion molecules cause an increase in vascular permeability. Alternanthera sessilis (L.) R. Br. is an edible traditional herbal plant, which has previously been shown to possess antioxidant and anti-inflammatory effects. However, the effect of A. sessilis on the activation of human aortic endothelial cells (HAECs) remains unknown. This study aimed to investigate the effects of A. sessilis on endothelial permeability, vascular cell adhesion-1 (VCAM-1) expression, production of ROS and hydrogen peroxide (H2O2), and superoxide dismutase (SOD) and catalase (CAT) activities. The viability of HAECs was first determined using the MTT viability assay. The effect of A. sessilis on endothelial permeability was examined using the FITC-dextran permeability assay. Besides, enzyme-linked immunosorbent assay (ELISA) was done to assess soluble VCAM-1 (sVCAM-1) expression. The production of ROS and H2O2 was studied using 2',7'-dichlorodihydrofluorescein diacetate (H2-DCFDA) and Amplex Red fluorescent dyes, respectively. SOD and CAT activities were also measured using commercial kits. Our results showed that 25-200 µg/mL of A. sessilis ethanolic extract did not cause significant death in HAECs. A. sessilis at 200 µg/mL significantly inhibited TNF-α-induced hyperpermeability of HAECs. However, A. sessilis did not reduce increased VCAM-1 expression induced by TNF-α. A. sessilis also significantly reduced TNF-α-induced increased ROS production, but not H2O2 production. Furthermore, 100 µM of H2O2 decreased both SOD and CAT activities in HAECs at 2 h. A. sessilis ethanolic extract dramatically increased both reduced SOD and CAT activities caused by H2O2. The liquid chromatography-mass spectrometry (LC-MS) analysis of A. sessilis ethanolic extract demonstrated the presence of arachidonic acid, azadirachtin, astaxanthin, flavanole base + 3O, 2Prenyl, and vicenin 2, while the gas chromatography-mass spectrometry (GC-MS) analysis showed that the extract contains 1,3,5-dihydroxy-6-methyl-2,3-dihydro-4H-pyran-4-one, 3-deoxy-d-mannoic lactone, 4-pyrrolidinobenzaldehyde, and n-hexadecanoic acid. In conclusion, our findings suggest that A. sessilis ethanolic extract protects against endothelial hyperpermeability and oxidative stress elicited by pro-inflammatory or prooxidant stimulus. This study reveals a therapeutic potential of A. sessilis in preventing endothelial activation, which is a key event in early atherosclerosis.

Gastroprotective Effect of Polypeptide-K Isolated from Momordica charantia's Seeds on Multiple Experimental Gastric Ulcer Models in Rats.

Peptic ulcer disease is a multifactorial disorder and is the most significant public health concern nowadays. Previous study showed that essential oil extracted from Momordica charantia's seed exhibited gastroprotective effect. However, the evidence for the gastroprotective effect of its active compound, polypeptide K (PPK), remains unclear. This study aimed to examine the preventive effect of PPK against different experimental gastric lesions models in rats. The possible gastroprotective effect of PPK was assessed in hydrochloride ethanol- and indomethacin-induced gastric ulcer models in Sprague Dawley rats and was further evaluated macroscopically and microscopically. Pyloric ligation experiments were used to investigate gastric secretion. Oral administration of PPK at all concentrations (10, 25, and 50 mg/kg) showed significant (p < 0.05) reduction in total area of lesion in both hydrochloride ethanol- and indomethacin-induced gastric ulcer models. The highest inhibition rate was seen in PPK dose of 50 mg/kg with 64.9% and 72.2% on hydrochloride ethanol and indomethacin models, respectively. Microscopically, PPK preserved the normal architectures of the gastric tissues from being damaged by hydrochloride ethanol and indomethacin. Further, in the pyloric ligation studies, PPK significantly (p < 0.05) decreased the ulcer area where the highest protection was exhibited by 50 mg/kg with 70% inhibition rate. Moreover, all concentrations of PPK also significantly (p < 0.05) enhanced the gastric wall mucus secretion. Collectively, this study demonstrated the gastroprotective effect of PPK on hydrochloride ethanol- and indomethacin-induced gastric ulcer models. The possible mechanism might be associated with enhanced mucus secretion and thus lowering the total acidity.

Evaluation of Anti-Hyperlipidaemic Activity of a Mixture of Zinger officinale, Allium sativum, Citrus Lemon, Honey, and Malus domestica Vinegar (ZACAH) Extracts in Rats Fed with High Cholesterol Diet

@#Introduction: The incidence and complications of hyperlipidemia associated co-morbidities and mortalities are grossly increasing globally. Intervention with natural products preparation has been identified as an alternative for the management of hyperlipidaemia and its related cardiovascular complications. This study investigated the anti-hyperlipidaemic activities of a mixture of Zinger officinale, Allium sativum, Citrus lemon, honey, and Malus domestica vinegar (ZACAH) extracts in in Sprague Dawley (SD) rats fed with high cholesterol diet. Methods: Thirty-six male SD rats were randomly distributed into 6 groups, including normal chow diet-fed (NC), high cholesterol diet (HCD), HCD+ Simvastatin (standard drug) while the remaining three groups were fed with HCD + ZACAH extracts at different doses (1, 3 and 5mg/kg body weight) for 18 weeks. Simvastatin at 10 mg/kg of bodyweight was used as control. High-performance liquid chromatography (HPLC) was used to determine phenolic compounds present in ZACAH extracts, elastase inhibitory assay was determined using spectrometric with a substrate (N-Succ-(Ala)3-pnitroanilide (SANA) while 2,2-diphenyl-1-picrylhydrazyl (DPPH) was performed based by the method described by Blois, 1958. Results: In vitro; ZACAH extracts had oxygen radical absorbance capacity (ORAC) value of 2000 µmol TE/100 mL, total phenolic content (TPC) of 7537 ± 54.5%, DPPH free radical scavenging activity of 27.34 ± 2.71%, elastase inhibitory assay of 29.29 ± 1.65% and lipoxygenase inhibitory assay of 98.58 ± 1.42%. In vivo, ZACAH extracts showed decreased bodyweight, adipose tissue, improved lipid profiles and hepatic biochemical enzymes. Conclusion: These results suggested that ZACAH extracts supplementation improved hyperlipidaemia in SD rats and might be a promising adjuvant for the treatment of hyperlipidaemia.

Immunomodulatory potential of Clinacanthus nutans extracts in the co-culture of triple-negative breast cancer cells, MDA-MB-231, and THP-1 macrophages.

Triple-negative breast cancer is the main type of breast carcinoma that causes mortality among women because of the limited treatment options and high recurrence. Chronic inflammation has been linked with the tumor microenvironment (TME) in breast cancer progression. Clinacanthus nutans (CN) has gained much attention because of its anticancer properties, but its mechanism remains unclear. We aimed to study the qualitative phytochemical content and elucidate the cytotoxicity effects of CN on human triple-negative breast cancer (TNBC), MDA-MB-231 and human macrophage-like cells such as THP-1 by using sulforhodamine B (SRB) assay. As highly metastatic cells, MDA-MB-231 cells can migrate to the distal position, the effect of CN on migration were also elucidated using the scratch assay. The CN effects on ameliorating chronic inflammation in TME were studied following the co-culture of MDA-MB-231/THP-1 macrophages. The cytokine expression levels of IL-6, IL-1ß and tumor necrosis factor-alpha (TNF-α) were determined using ELISA assays. The results showed that both ethanolic and aqueous CN extracts contained alkaloid, phenol and tannin, flavonoid, terpenoid, glycoside and steroid. However, saponin was only found in the aqueous extract of CN. CN was not cytotoxic to both MDA-MB-231 and THP-1 cells. The ability of MDA-MB-231 to migrate was also not halted by CN treatment. However, CN ethanol extract decreased IL-6 at 25 µg/mL (p = 0.02) and 100 µg/mL (p = 0.03) but CN aqueous extract increased IL-6 expression at 50 µg/mL (p = 0.08) and 100 µg/mL (p = 0.02). IL-1ß showed decreased expression after treated with CN ethanol and CN aqueous both at 25 µg/mL (p = 0.03). TNF-α were significantly decreased after CN ethanol treatment at concentration 25- (p = 0.001), 50- (p = 0.000) and 100 µg/mL (p = 0.000). CN aqueous extract slightly inhibited TNF-α at all 25-50- and 100 µg/mL (p = 0.001, p = 0.000, p = 0.000, respectively). Overall, CN acts by ameliorating the pro-inflammatory condition in the TME and may be a potential strategy for its anticancer mechanism on highly metastatic breast cancer condition. The major pathways that link both cancer and inflammation were NF-κB and STATs thus further study on the upstream and downstream pathways is needed to fully understand the mechanism of CN extracts in cooling the inflamed TME in breast cancer.

Biogenic Silver Nanoparticles of Clinacanthus nutans as Antioxidant with Antimicrobial and Cytotoxic Effects.

Silver nanoparticles (AgNPs) previously synthesised using leaf (AgNP-L) and stem (AgNP-S) extracts of Clinacanthus nutans (C. nutans) were tested to evaluate antimicrobial, antioxidant, and cytotoxicity activities. The AgNPs showed good inhibition against bacteria, but not fungi. The inhibition results showed the highest activity against Staphylococcus aureus (S. aureus) with 11.35 mm (AgNP-L) and 11.52 mm (AgNP-S), while the lowest inhibition was against Escherichia coli (E. coli) with 9.22 mm (AgNP-L) and 9.25 mm (AgNP-S) in the disc diffusion method. The same trend of results was noted in the well diffusion method. The IC50 of AgNP-L and AgNP-S in 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays was 417.05 µg/mL and 434.60 µg/mL, as well as 304.31 µg/mL and 326.83 µg/mL, respectively. Ferric reducing power (FRAP) assay showed that AgNP-L [872.389 µmol/L Fe(II)] and AgNP-S [612.770 µmol/L Fe(II)] exhibited significantly (p < 0.05) greater antioxidant activities than leaf extract (CNL) [152.260 µmol/L Fe(II)] and stem extract (CNS) [110.445 µmol/L Fe(II)] of C. nutans. The AgNPs were also proven to possess cytotoxic effects on the breast (MCF-7), cervical (HeLa), and colon (HT-29) cancer cells in a dose-dependent manner. AgNP-S and AgNP-L showed significantly (p < 0.05) higher cytotoxicity against MCF-7 (117.43 µg/mL) and HT-29 (78.47 µg/mL), respectively. In conclusion, the biosynthesised AgNPs from aqueous extract leaves and stem of C. nutans have demonstrated promising potential towards antioxidant, antimicrobial, and cytotoxicity activities.

Essential Oils Derived from Momordica charantia Seeds Exhibited Antiulcer Activity against Hydrogen Chloride/Ethanol and Indomethacin.

Momordica charantia (MC) is popular for its medicinal uses especially for treating diabetic-related complications. However, the antiulcer activity of essential oil derived from the seeds has not been systematically studied. This study aims to evaluate the gastroprotective activities of essential oil derived from the seed of MC induced by hydrochloride acid/ethanol (HCl/EtOH) and indomethacin and pylorus-ligation model. Gastric ulceration was induced by oral administration of HCl/EtOH solution or indomethacin on day 7 after animals have been pretreated with testing compounds. The first group received just distilled water and the second group received ranitidine (100 mg/kg). Groups 3, 4, and 5 received 10, 50, and 100 mg/kg of essential oil based on their body weight (10 mL/kg), respectively. Macroscopically, pretreatment of essential oil extracted from MC significantly decreased ulceration induced by HCl/EtOH and indomethacin in vivo. Microscopically, essential oil also significantly suppressed the formation of edema, epithelial disruption, and mucosa erosions. Moreover, essential oil significantly elevated the pH without decreasing the total acidity of the gastric juice and was able to increase the amount of adherent mucus compared to control. Current results provide scientific basis to the ethno-pharmacological usage of the MC in preventing ulcer formation induced by HCl/EtOH and indomethacin.

Cytoprotective Role of Omentin Against Oxidative Stress-Induced Vascular Endothelial Cells Injury.

Endothelial cell injury caused by reactive oxygen species (ROS) plays a critical role in the pathogenesis of cardiovascular diseases. Omentin, an adipocytokine that is abundantly expressed in visceral fat tissue, has been reported to possess anti-inflammatory and antidiabetic properties. However, endothelial protective effects of omentin against oxidative stress remain unclear. This study aimed to evaluate the protective effect of omentin against hydrogen peroxide (H2O2)-induced cell injury in human umbilical vein endothelial cells (HUVECs). Cytotoxicity and cytoprotective effects of omentin were evaluated using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The apoptotic activity of HUVECs was detected using Annexin-V/PI and Hoechst 33258 staining methods. Antioxidant activity of omentin was evaluated by measuring both reactive oxygen species (ROS) levels and glutathione peroxidase (GPx) activity. No cytotoxicity effect was observed in HUVECs treated with omentin alone at concentrations of 150 to 450 ng/ml. MTT assay showed that omentin significantly prevented the cell death induced by H2O2 (p < 0.001). Hoechst staining and flow cytometry also revealed that omentin markedly prevented H2O2-induced apoptosis. Moreover, omentin not only significantly inhibited ROS production (p < 0.01) but also significantly (p < 0.01) increased GPx activity in HUVECs. In conclusion, our data suggest that omentin may protect HUVECs from injury induced by H2O2.

Biocompatible Nutmeg Oil-Loaded Nanoemulsion as Phyto-Repellent.

Plant essential oils are widely used in perfumes and insect repellent products. However, due to the high volatility of the constituents in essential oils, their efficacy as a repellent product is less effective than that of synthetic compounds. Using a nanoemulsion as a carrier is one way to overcome this disadvantage of essential oils. Nutmeg oil-loaded nanoemulsion (NT) was prepared using a high speed homogenizer and sonicator with varying amounts of surfactant, glycerol, and distilled water. Using a phase diagram, different formulations were tested for their droplet size and insect repellent activity. The nanoemulsion containing 6.25% surfactant and 91.25% glycerol (NT 6) had the highest percentage of protection (87.81%) in terms of repellent activity among the formulations tested for the 8 h duration of the experiment. The droplet size of NT 6 was 217.4 nm, and its polydispersity index (PDI) was 0.248. The zeta potential value was -44.2 mV, and the viscosity was 2.49 Pa.s at pH 5.6. The in vitro release profile was 71.5%. When the cytotoxicity of NT 6 at 400 µg/mL was tested using the MTS assay, cell viability was 97.38%. Physical appearance and stability of the nanoemulsion improved with the addition of glycerol as a co-solvent. In summary, a nutmeg oil-loaded nanoemulsion was successfully formulated and its controlled release of the essential oil showed mosquito repellent activity, thus eliminating the disadvantages of essential oils.

Endothelial Dysfunction in Obesity-Induced Inflammation: Molecular Mechanisms and Clinical Implications.

Obesity is characterized by the excessive deposition of fat that may interfere with the normal metabolic process of the body. It is a chronic condition associated with various metabolic syndromes, whose prevalence is grossly increasing, and affects both children and adults. Accumulation of excessive macronutrients on the adipose tissues promotes the secretion and release of inflammatory mediators, including interleukin-6 (IL-6), interleukin 1ß, tumor necrotic factor-α (TNF-α), leptin, and stimulation of monocyte chemoattractant protein-1 (MCP-1), which subsequently reduce the production of adiponectin thereby initiating a proinflammatory state. During obesity, adipose tissue synthesizes and releases a large number of hormones and cytokines that alter the metabolic processes, with a profound influence on endothelial dysfunction, a situation associated with the formation of atherosclerotic plaque. Endothelial cells respond to inflammation and stimulation of MCP-1, which is described as the activation of adhesion molecules leading to proliferation and transmigration of leukocytes, which facilitates their increase in atherogenic and thromboembolic potentials. Endothelial dysfunction forms the cornerstone of this discussion, as it has been considered as the initiator in the progression of cardiovascular diseases in obesity. Overexpression of proinflammatory cytokines with subsequent reduction of anti-inflammatory markers in obesity, is considered to be the link between obesity-induced inflammation and endothelial dysfunction. Inhibition of inflammatory mechanisms and management and control of obesity can assist in reducing the risks associated with cardiovascular complications.

Human Wharton's Jelly-Derived Mesenchymal Stem Cells Minimally Improve the Growth Kinetics and Cardiomyocyte Differentiation of Aged Murine Cardiac c-kit Cells in In Vitro without Rejuvenating Effect.

Cardiac c-kit cells show promise in regenerating an injured heart. While heart disease commonly affects elderly patients, it is unclear if autologous cardiac c-kit cells are functionally competent and applicable to these patients. This study characterised cardiac c-kit cells (CCs) from aged mice and studied the effects of human Wharton's Jelly-derived mesenchymal stem cells (MSCs) on the growth kinetics and cardiac differentiation of aged CCs in vitro. CCs were isolated from 4-week- and 18-month-old C57/BL6N mice and were directly co-cultured with MSCs or separated by transwell insert. Clonogenically expanded aged CCs showed comparable telomere length to young CCs. However, these cells showed lower Gata4, Nkx2.5, and Sox2 gene expressions, with changes of 2.4, 3767.0, and 4.9 folds, respectively. Direct co-culture of both cells increased aged CC migration, which repopulated 54.6 ± 4.4% of the gap area as compared to aged CCs with MSCs in transwell (42.9 ± 2.6%) and CCs without MSCs (44.7 ± 2.5%). Both direct and transwell co-culture improved proliferation in aged CCs by 15.0% and 16.4%, respectively, as traced using carboxyfluorescein succinimidyl ester (CFSE) for three days. These data suggest that MSCs can improve the growth kinetics of aged CCs. CCs retaining intact telomere are present in old hearts and could be obtained based on their self-renewing capability. Although these aged CCs with reduced growth kinetics are improved by MSCs via cell-cell contact, the effect is minimal.