The aim of this study was to investigate the cytotoxic and apoptotic effects of Nephelium ramboutan-ake (pulasan) rind in selected human cancer cell lines. The crude ethanol extract and fractions (ethyl acetate and aqueous) of N. ramboutan-ake inhibited the growth of HT-29, HCT-116, MDA-MB-231, Ca Ski cells according to MTT assays. The N. ramboutan-ake aqueous fraction (NRAF) was found to exert the greatest cytotoxic effect against HT-29 in a dose-dependent manner. Evidence of apoptotic cell death was revealed by features such as chromatin condensation, nuclear fragmentation and apoptotic body formation. The result from a TUNEL assay strongly suggested that NRAF brings about DNA fragmentation in HT-29 cells. Phosphatidylserine (PS) externalization on the outer leaflet of plasma membranes was detected with annexin V-FITC/PI binding, confirming the early stage of apoptosis. The mitochondrial permeability transition is an important step in the induction of cellular apoptosis, and the results clearly suggested that NRAF led to collapse of mitochondrial transmembrane potential in HT-29 cells. This attenuation of mitochondrial membrane potential (Δψm) was accompanied by increased production of ROS and depletion of GSH, an increase of Bax protein expression, and induced-activation of caspase-3/7 and caspase-9. These combined results suggest that NRAF induces mitochondrial-mediated apoptosis.
Nerolidol (3,7,11-trimethyl-1,6,10-dodecatrien-3-ol) is a naturally occurring sesquiterpene alcohol that is present in various plants with a floral odor. It is synthesized as an intermediate in the production of (3E)-4,8-dimethy-1,3,7-nonatriene (DMNT), a herbivore-induced volatile that protects plants from herbivore damage. Chemically, nerolidol exists in two geometric isomers, a trans and a cis form. The usage of nerolidol is widespread across different industries. It has been widely used in cosmetics (e.g., shampoos and perfumes) and in non-cosmetic products (e.g., detergents and cleansers). In fact, U.S. Food and Drug Administration (FDA) has also permitted the use of nerolidol as a food flavoring agent. The fact that nerolidol is a common ingredient in many products has attracted researchers to explore more medicinal properties of nerolidol that may exert beneficial effect on human health. Therefore, the aim of this review is to compile and consolidate the data on the various pharmacological and biological activities displayed by nerolidol. Furthermore, this review also includes pharmacokinetic and toxicological studies of nerolidol. In summary, the various pharmacological and biological activities demonstrated in this review highlight the prospects of nerolidol as a promising chemical or drug candidate in the field of agriculture and medicine.
Epinecidin-1 is an antimicrobial peptide derived from the orange-spotted grouper (Epinephelus coioides). The mature epinecidin-1 peptide is predicted to have an amphipathic α-helical structure and a non-helical hydrophilic domain at the C-terminal RRRH. The majority of work studying the potential pharmacological activities of epinecidin-1, utilize synthesized epinecidin-1 (Epi-1), which is made up of 21 amino acids, from the amino acid sequence of 22-42 residues of Epi-1-GFIFHIIKGLFHAGKMIHGLV. The synthetized Epi-1 peptide has been demonstrated to possess diverse pharmacological activities, including antimicrobial, immunomodulatory, anticancer, and wound healing properties. It has also been utilized in different clinical and agricultural fields, including topical applications in wound healing therapy as well as the enhancement of fish immunity in aquaculture. Hence, the present work aims to consolidate the current knowledge and findings on the characteristics and pharmacological properties of epinecidin-1 and its potential applications.
OBJECTIVES: Metabolic syndrome (MetS), a multiplex risk factor for cardiovascular disease and type 2 diabetes, is increasingly prevalent worldwide. Ellagitannin geraniin, a polyphenol found in the rind of rambutan (Nephelium lappaceum), has demonstrated therapeutic effects against metabolism dysfunction. The aim of this study was to characterize the metabolic effects and possible mechanism of geraniin in rats with MetS induced by a high-fat diet (HFD).
METHODS: MetS was induced in Sprague Dawley rats on an HFD, followed by a daily oral gavage of geraniin (25 mg/kg) for 4 wk. The outcomes of geraniin-treated rats were compared with those of untreated rats on either a control diet or an HFD and with rats with MetS treated with metformin on a daily basis (200 mg/kg).
RESULTS: The supplementation of geraniin ameliorated multiple metabolic abnormalities caused by HFD, including hypertension, impaired glucose and lipid metabolism, ectopic fat deposition in the visceral fat and liver, and disturbed antioxidant mechanism and inflammatory response. The benefits conferred by geraniin were comparable to metformin. Transcriptomic analysis revealed a profound influence of geraniin on the hepatic expression profiles. The lipid and steroid metabolic processes that were aberrantly activated by HFD were suppressed by geraniin. Based on the differential transcriptomes, geraniin also exerted a significant modulatory effect on the expression of mitochondrial genes, potentially influencing the mitochondrial activity and leading to the observed beneficial effects.
CONCLUSION: Geraniin supplementation mitigated metabolic anomalies of MetS in rats, making it an attractive drug candidate for further investigation.
Colorectal cancer (CRC) is a global public health issue which poses a substantial humanistic and economic burden on patients, healthcare systems and society. In recent years, intestinal dysbiosis has been suggested to be involved in the pathogenesis of CRC, with specific pathogens exhibiting oncogenic potentials such as Fusobacterium nucleatum, Escherichia coli and enterotoxigenic Bacteroides fragilis having been found to contribute to CRC development. More recently, it has been shown that initiation of CRC development by these microorganisms requires the formation of biofilms. Gut microbial biofilm forms in the inner colonic mucus layer and is composed of polymicrobial communities. Biofilm results in the redistribution of colonic epithelial cell E-cadherin, increases permeability of the gut and causes a loss of function of the intestinal barrier, all of which enhance intestinal dysbiosis. This literature review aims to compile the various strategies that target these pathogenic biofilms and could potentially play a role in the prevention of CRC. We explore the potential use of natural products, silver nanoparticles, upconverting nanoparticles, thiosalicylate complexes, anti-rheumatic agent (Auranofin), probiotics and quorum-sensing inhibitors as strategies to hinder colon carcinogenesis via targeting colon-associated biofilms.
The skin is the first line of defense against pathogen and other environmental pollutant. The body is constantly exposed to reactive oxygen species (ROS) that stimulates inflammatory process in the skin. Many studies have linked ROS to various inflammatory skin diseases. Patients with skin diseases face various challenges with inefficient and inappropriate treatment in managing skin diseases. Overproduction of ROS in the body will result in oxidative stress which will lead to various cellular damage and alter normal cell function. Multiple signaling pathways are seen to have significant effects during ROS-mediated oxidative stress. In this review, microalgae have been selected as a source of natural-derived antioxidant to combat inflammatory skin diseases that are prominent in today's society. Several studies have demonstrated that bioactive compounds isolated from microalgae have anti-inflammation and anti-oxidative properties that can help remedy various skin diseases. These compounds are able to inhibit production of pro-inflammatory cytokines and reduce the expression of inflammatory genes. Bioactive compounds from microalgae work in action by altering enzyme activities, regulating cellular activities, targeting major signaling pathways related to inflammation.
Ultrasound-assisted extraction (UAE) is an effective tool for the extraction of natural antioxidants. Thus, differentially roasted Arabica-coffee beans known as light (LC), medium (MC), and dark coffee (DC) were prepared and extracted under the influence of UAE. Following that, they were examined specifically on theirs physicochemical and biological characteristics: nutritional values, pH, °Brix, antioxidant activities, polyphenol content, caffeine, and chlorogenic-acid levels. Various parameters, such as extraction temperatures (20, 40, and 80°C) and extraction time periods (5, 10, and 20 min), were examined. DC extract was less acidic than those on MC and LC extracts. LC showed higher moisture content than the MC and DC (1.56, 1.3, and 0.92%, respectively). MC displayed the highest polyphenol content and potent antioxidant activity. Caffeine and chlorogenic acid contents trend to decrease during roasting. The maximum caffeine level was found in MC at 80°C for 5 min (27.65 mg/g extract). The highest chlorogenic acid content was in LC at 80°C for 10 min (16.67 mg/g extract). The caffeine and chlorogenic acid contents were related to the polyphenol content and depended on the roasting and extraction conditions. These results suggest that the UAE at various temperature and extraction time period may alter the physicochemical and biological characteristics of different coffee roasts.
Azadirachta indica A. Juss var. siamensis Valeton or commonly known as Siamese neem is one of the most well-known plant in traditional Ayurvedic medicine. The aim of the present study was to investigate the relaxant effects of A. indica on isolated rat ileum contractions and its potential underlying mechanisms involved. The isometric contractions of ileum segments were investigated in organ baths for spontaneous activity and response to aqueous extract of Siamese neem flower (SNF). The spasmolytic action of the extract was also assessed on contraction induced by acetylcholine and high potassium. Our findings indicate that cumulative concentrations of SNF aqueous extract induced relaxant effect on spontaneous rat ileum contractions. The extract has also suppressed the cumulative concentration response curve for acetylcholine and pottasium ions-induced contraction. The presence and absence of propranol (antagonist of β-adrenergic receptor) and l-Name (antagonist of nitric oxide synthase) in SNF aqeous extract co-treatment demonstrated no significant different in term of contraction activity when compared to SNF extract treatment alone. The treatment of SNF extract caused a significant inhibition in tissue contraction stimulated by accumulation of calcium ions. Our results showed the relaxant effect of SNF aqueous extract on the isolated rat ileum. In short, the SNF aqueous extract exhibited an inhibitory effect on the spontaneous ileum contactions particularly on the contraction stimulated by acetylcholine and high potassium. The observed effect might acted through the modulation of calcium channels. This findings provide a pharmacological basis for the traditional use of SNF for the treatment of gastrointestinal spasms.
Azadirachta indica has long been used in traditional medicine. This study focused on isolation and characterisation of active ingredients in the extract, its fractions (NF-EA, NF-AQ, NF-G) and its effect on the cholesterol absorption activity. The NF-EA fraction was identified by marker compounds by LC-ESI-QTOF/MS. Cholesterol absorption activity was performed by measuring the solubility and size of cholesterol micelles. The intestinal motility was also examined by isolated rat's ileum to test the contraction. The extract and its fractions consist of flavonoids and phenolic compounds, like quercetin, kaempferol and myricetin. We found that A. indica extract and NF-EA increase cholesterol micelles size, while the extract, NF-AQ, myricetin and quercetin, reduced the solubility of cholesterol in micelles. The extract and quercetin inhibited the contraction induced by KCl up to 29 and 18%, respectively, and also decreased CaCl2-induced contraction. This finding is in support to traditional uses of A. indica as cholesterol-lowering agents and regulator of gastrointestinal motility.
Lavandula stoechas, a Mediterranean plant, renowned in traditional medicine for its health benefits, is also arousing strong interest associated with its essential oils (EOs) with promising therapeutic properties. The aim of this study was to analyze the chemical composition of the plant, as well as to study its major activities, including antioxidant, anti-diabetic, dermatoprotective, anti-inflammatory, and antibacterial effects, focusing on its major molecules. Using the GC-MS method, the main compounds identified in L. stoechas EO (LSEO) were fenchone (31.81 %) and camphor (29.60 %), followed by terpineol (13.14 %) and menthone (8.96 %). To assess their antioxidant activity, three in vitro methods were used (DPPH, FRAP, and ABTS). The results revealed that LSEO exhibited the best antiradical property (54 ± 62 μg/mL) according to the DPPH test, while fenchone demonstrated the highest antioxidant capacity (87 ± 92 μg/mL) in the FRAP test, and camphor displayed the highest antioxidant capacity (96 ± 32 μg/mL) in the ABTS test. However, these results were lower than those obtained by Trolox used as a reference. In addition, study also explored the anti-diabetic potential of LSEO and its major compounds by evaluating their inhibitory activity towards two digestive enzymes, α-glucosidase and α-amylase. Camphor (76.92 ± 2.43 μg/mL) and fenchone (69.03 ± 2.31 μg/mL) exhibited the best inhibitory activities for α-amylase and α-glucosidase assays, respectively. Interestingly, all elements of the study exerted activities superior to those of acarbose, regardless of the test performed. In contrast, the evaluation of the dermatoprotective potential was carried out in vitro by targeting two enzymes involved in cutaneous processes, tyrosinase and elastase. In this light, fenchone (53.14 ± 3.06 μg/mL) and camphor (48.39 ± 1.92 μg/mL) were the most active against tyrosinase and elastase, respectively. It should be noted that the effect of both molecules, as well as that of LSEO, ranged between 53.14 ± 3.06 and 97.45 ± 5.22 μg/mL, which was significantly lower than the standard, quercetin (IC50 of 246.90 ± 2 0.54 μg/mL) against tyrosinase. Furthermore, the anti-inflammatory potential of these elements has been studied by evaluating their ability to inhibit lipooxygenase (LOX), a class of enzymes involved in the inflammatory process in the human body. As a result, the LSEO demonstrated a remarkable effect with an IC50 of 6.34 ± 1.29 μg/mL, which was almost comparable to the standard, quercetin (IC50 = 3.93 ± 0.45 μg/mL). Concerning the antibacterial potential, we carried out a quantitative analysis of the various products tested, revealing a bactericidal activity of the LSEO against the strain L. monocytogenes ATCC 13932 at a minimum effective concentration (MIC = CMB = 0.25). Overall, LSEOs offer significant potential as a source of natural antioxidants, and antidiabetic and anti-inflammatory agents, as well as dermatoprotective and antibacterial compounds. Its major molecules, fenchone and camphor, showed promising activity in these areas of study, making it a valuable candidate for future research and development in the field of natural medicine.
Swietenia macrophylla King is a traditional herb used to treat various diseases including hypertension, diabetes and cancer. Previous study demonstrated its anti-tumor effect but the potential mechanisms have not been clearly defined. The current study was to further investigate the underlying mechanism of ethyl acetate fraction of Swietenia macrophylla (SMEAF)-induced anti-proliferative effect and apoptosis in HCT116 colorectal carcinoma cell.
Mixed-use developments (MXDs) are a single development project that integrates and interacts with different land uses. Traffic is estimated to be reduced with such development. However, there is no standard procedure is available to estimate the MXD trip generation rates in Malaysia. The Malaysian Trip Generation Manual (MTGM) is the guidelines currently been used to forecast future trips for single land use. If the trip generation rates for multiple land uses are summed as MXD trips, the total trips will be overestimated without considering the internal trip capture. This study aimed to establish an improved method for estimating the MXD trip generation rates. Four MXD observation sites were selected in Klang Valley. Traffic survey counts were conducted considering person-trip, including passengers in vehicles and pedestrians. The results revealed that the MXD trip generation rates with MTGM were higher than actual traffic counts during peak hours. The MXD adjustment factor was established as 0.63, which can be applied by multiplying the MTGM trip generation rates to reduce the generated MXD trips in PCU per hour. This research has formulated a new data collection method by integrating person counts, alongside with new guidelines for pedestrian counts. The findings provide an option to adjust the MXD trips and prevent from overestimating future trips, which may result in overdevelopment and spending on mitigation measures in urban planning and road infrastructure.
The search for effective methods of cancer treatment and prevention has been a continuous effort since the disease was discovered. Recently, there has been increasing interest in exploring plants and fruits for molecules that may have potential as either adjuvants or as chemopreventive agents against cancer. One of the promising compounds under extensive research is nobiletin (NOB), a polymethoxyflavone (PMF) extracted exclusively from citrus peel. Not only does nobiletin itself exhibit anti-cancer properties, but its derivatives are also promising chemopreventive agents; examples of derivatives with anti-cancer activity include 3'-demethylnobiletin (3'-DMN), 4'-demethylnobiletin (4'-DMN), 3',4'-didemethylnobiletin (3',4'-DMN) and 5-demethylnobiletin (5-DMN). In vitro studies have demonstrated differential efficacies and mechanisms of NOB and its derivatives in inhibiting and killing of colon cancer cells. The chemopreventive potential of NOB has also been well demonstrated in several in vivo colon carcinogenesis animal models. NOB and its derivatives target multiple pathways in cancer progression and inhibit several of the hallmark features of colorectal cancer (CRC) pathophysiology, including arresting the cell cycle, inhibiting cell proliferation, inducing apoptosis, preventing tumour formation, reducing inflammatory effects and limiting angiogenesis. However, these substances have low oral bioavailability that limits their clinical utility, hence there have been numerous efforts exploring better drug delivery strategies for NOB and these are part of this review. We also reviewed data related to patents involving NOB to illustrate the extensiveness of each research area and its direction of commercialisation. Furthermore, this review also provides suggested directions for future research to advance NOB as the next promising candidate in CRC chemoprevention.
Nephrotic syndrome affects both children and adults. Idiopathic nephrotic syndrome is reported to be one of the most frequent renal pathologies in childhood. Nephrotic children are at high risk for severe pneumococcal infections as one of the life-threatening complications of nephrotic syndrome due to involvement of the immunosuppressive regimen and the acquired immune deficiency induced by nephrotic syndrome including decreased plasma IgG and low complement system components. Aiming to prevent pneumococcal infection is of paramount importance especially in this era of ever-increasing pneumococcal resistance to penicillins and cephalosporins. The pneumococcal vaccines currently available are inactivated vaccines-the two main forms in use are polysaccharide vaccines and conjugated vaccines. However, the data supporting the use of these vaccines and to guide the timing and dosage recommendations is still limited for nephrotic children. Thus, this review discusses the evidences of immunogenicity and safety profile of both vaccinations on nephrotic patients as well as the effect of nephrotic syndrome treatment on vaccine seroresponses.
With the ever-growing number of cancer deaths worldwide, researchers have been working hard to identify the key reasons behind the failure of cancer therapies so the efficacy of those therapies may be improved. Based on extensive research activities and observations done by researchers, chemoresistance has been identified as a major contributor to the drastic number of deaths among cancer patients. Several factors have been linked to formation of chemoresistance, such as chemotherapy drug efflux, immunosuppression, and epithelial-mesenchymal transition (EMT). Lately, increasing evidence has shed light on the role of extracellular vesicles (EVs) in the regulation of chemoresistance. However, there is limited research into the possibility that inhibiting EV release or uptake in cancer cells may curb chemoresistance, allowing chemotherapy drugs to target cancer cells without restriction. Prominent inhibitors of EV uptake and release in cancer cells have been compiled and contrasted in this review. This is in the hope of sparking greater interest in the field of EV-mediated chemoresistance, as well as to provide an overview of the field for fundamental and clinical research communities, particularly in the field of cancer resistance research. In-depth studies of EV-mediated chemoresistance and EV inhibitors in cancer cells would spur significant improvement in cancer treatments which are currently available.
Vibrio vulnificus is a Gram negative, rod shaped bacterium that belongs to the family Vibrionaceae. It is a deadly, opportunistic human pathogen which is responsible for the majority of seafood-associated deaths worldwide. V. vulnificus infection can be fatal as it may cause severe wound infections potentially requiring amputation or lead to sepsis in susceptible individuals. Treatment is increasingly challenging as V. vulnificus has begun to develop resistance against certain antibiotics due to their indiscriminate use. This article aims to provide insight into the antibiotic resistance of V. vulnificus in different parts of the world as well as an overall review of its clinical manifestations, treatment, and prevention. Understanding the organism's antibiotic resistance profile is vital in order to select appropriate treatment and initiate appropriate prevention measures to treat and control V. vulnificus infections, which should eventually help lower the mortality rate associated with this pathogen worldwide.
The utilization of zebrafish in biomedical research is very common in the research world nowadays. Today, it has emerged as a favored vertebrate organism for the research in science of reproduction. There is a significant growth in amount numbers of scientific literature pertaining to research discoveries in reproductive sciences in zebrafish. It has implied the importance of zebrafish in this particular field of research. In essence, the current available literature has covered from the very specific brain region or neurons of zebrafish, which are responsible for reproductive regulation, until the gonadal level of the animal. The discoveries and findings have proven that this small animal is sharing a very close/similar reproductive system with mammals. More interestingly, the behavioral characteristics and along with the establishment of animal courtship behavior categorization in zebrafish have laid an even stronger foundation and firmer reason on the suitability of zebrafish utilization in research of reproductive sciences. In view of the immense importance of this small animal for the development of reproductive sciences, this review aimed at compiling and describing the proximate close similarity of reproductive regulation on zebrafish and human along with factors contributing to the infertility, showing its versatility and its potential usage for fertility research.
Nigella sativa L. is one of the most extensively used traditional medicinal plants. This widely studied plant is known to display diverse pharmacological actions, including antimicrobial activities. Current literature has documented its multi-target mode of antimicrobial actions. N. sativa or its bioactive compounds, such as thymoquinone, can induce oxidative stress, cell apoptosis (by producing reactive oxygen species), increase membrane permeability, inhibit efflux pumps, and impose strong biocidal actions. Despite its well-documented antimicrobial efficacy in the experimental model, to the best of our knowledge its antimicrobial mechanisms highlighting the multi-targeting properties have yet to be well discussed. Is N. sativa or thymoquinone a valuable lead compound for therapeutic development for infectious diseases? Are N. sativa's bioactive compounds potential antimicrobial agents or able to overcome antimicrobial resistance? This review aims to discuss the antimicrobial pharmacology of N. sativa-based treatments. Additionally, it provides a holistic overview of the ethnobotany, ethnopharmacology, and phytochemistry of N. sativa.
Hyaluronic acid (HA), a major component of extracellular matrix has been widely applied in pharmaceutical and cosmetic industries due to its reported pharmacological properties. Various types of HA drug delivery system including nanoparticles, cryogel-based formulations, microneedle patches, and nano-emulsions were developed. There are studies reporting that several HA-based transdermal delivery systems exhibit excellent biocompatibility, enhanced permeability and efficient localized release of anti-psoriasis drugs and have shown to inhibit psoriasis-associated skin inflammation. Similarly HA is found in abundant at epidermis of atopic dermatitis (AD) suggesting its role in atopic AD pathology. Anti-allergenic effect of atopic eczema can be achieved through the inhibition of CD44 and protein kinase C alpha (PKCα) interaction by HA. Herein, we aim to evaluate the current innovation on HA drug delivery system and the other potential applications of HA in inflammatory skin diseases, focusing on atopic dermatitis and psoriasis. HA is typically integrated into different delivery systems including nanoparticles, liposomes, ethosomes and microneedle patches in supporting drug penetration through the stratum corneum layer of the skin. For instance, ethosomes and microneedle delivery system such as curcumin-loaded HA-modified ethosomes were developed to enhance skin retention and delivery of curcumin to CD44-expressing psoriatic cells whereas methotrexate-loaded HA-based microneedle was shown to enhance skin penetration of methotrexate to alleviate psoriasis-like skin inflammation. HA-based nanoparticles and pluronic F-127 based dual responsive (pH/temperature) hydrogels had been described to enhance drug permeation through and into the intact skin for AD treatment.