Incorporating two different nanoparticles in nanocomposite films is promising as their synergistic effects could significantly enhance polymer performance. Our previous work conferred the remarkable antimicrobial (AM) properties of the polylactic acid (PLA)-based film using optimal formulations of synergistic graphene oxide (GO)/zinc oxide (ZnO) nanocomposites. This study further explores the release profile of GO/ZnO nanocomposite and their impact on the antimicrobial properties. A fixed 1.11 wt% GO and different ZnO concentrations were well dispersed in the PLA matrix. Increasing ZnO concentrations tended to increase agglomeration, as evident in rougher surfaces. Agglomeration inhibited water penetration, leading to a significant reduction in water permeability (46.3 %), moisture content (31.6 %) but an improvement in Young's Modulus (52.6 %). The overall and specific migration of GO/ZnO nanocomposites was found to be within acceptable limits. It is inferred that the release of Zn2+ ions followed pseudo-Fickian behavior with an initial burst effect. AM film with the highest concentration of ZnO (1.25 wt%) exhibited the highest inhibition rate against Escherichia coli (68.0 %), Bacillus cereus (66.5 %), Saccharomyces cerevisiae (70.9 %). Results suggest that GO/ZnO nanocomposites with optimal ZnO concentrations have the potential to serve as promising antimicrobial food packaging materials, offering enhanced barrier, antimicrobial properties and a controlled release system.
Moringa oleifera is one of the popular functional foods that has been tremendously exploited for synthesis of a vast majority of metal nanoparticles (NPs). The diverse secondary metabolites present in this plant turn it into a green tool for synthesis of different NPs with various biological activities. In this review, we discussed different types of NPs including silver, gold, titanium oxide, iron oxide, and zinc oxide NPs produced from the extract of different parts of M. oleifera. Different parts of M. oleifera take a role as the reducing, stabilizing, capping agent, and depending on the source of extract, the color of solution changes within NP synthesis. We highlighted the role of polyphenols in the synthesis of NPs among major constituents of M. oleifera extract. The different synthesis methods that could lead to the formation of various sizes and shapes of NPs and play crucial role in biomedical application were critically discussed. We further debated the mechanism of interaction of NPs with various sizes and shapes with the cells, and further their clearance from the body. The application of NPs made from M. oleifera extract as anticancer, antimicrobial, wound healing, and water treatment agent were also discussed. Small NPs show better antimicrobial activity, while they can be easily cleared from the body through the kidney. In contrast, large NPs are taken by the mono nuclear phagocyte system (MPS) cells. In case of shape, the NPs with spherical shape penetrate into the bacteria, and show stronger antibacterial activity compared to the NPs with other shapes. Finally, this review aims to correlate the key characteristics of NPs made from M. oleifera extract, such as size and shape, to their interactions with the cells for designing and engineering them for bio-applications and especially for therapeutic purposes.
Coumarins have received a considerable attention in the last three decades as a lead structures for the discovery of orally bioavailable non-peptidic antiviral agents. A lot of structurally diverse coumarins analogues were found to display remarkable array of affinity with the different molecular targets for antiviral agents and slight modifications around the central motif result in pronounced changes in its antiviral spectrum. This manuscript thoroughly reviews the design, discovery and structure-activity relationship studies of the coumarin analogues as antiviral agents focusing mainly on lead optimization and its development into clinical candidates.
A comprehensive literature search was conducted in PubMed, Cochrane Library, Web of Science, Scopus, the National Library of Medicine (NLM) catalog, and Google Scholar from January 1980 up until October 2023 on plants in the Gundelia genus. Gundelia L. (Asteraceae) has been treated as a monospecific genus with Gundelia tournefortii L. (1753: 814) in most recent floras with wide variation in corolla color, but nowadays, the genus consists of 17 species. The unripe inflorescences of these species, especially G. tournefortii L., are consumed in many ways. 'Akkoub' or 'akko' in Arabic, "Kangar" in Persian, and "Silifa" in Greek are the common names of G. tournefortii L., also known as tumble thistle in English. They have been used in traditional medicine to treat bronchitis, kidney stones, diarrhea, stomach pain, inflammation, liver and blood diseases, bacterial and fungal infections, and mumps. Based on recent studies, their extracts have exhibited hepatoprotective, hypolipidemic, antioxidant, anti-inflammatory, and antimicrobial effects. Moreover, a variety of phytochemicals, including terpenoids, sterols, and fatty acids, as well as vitamins and minerals, have been identified in this genus. This study reviewed the ethnobotany, phytochemicals, and biological activities of the plants in the Gundelia genus as functional foods and herbal remedies.
To understand the global changes in non-susceptibility rates of Streptococcus pneumoniae to ceftriaxone, we conducted a study using the Antimicrobial Testing Leadership and Surveillance database. A total of 15,717 S. pneumoniae isolates were collected from 2016 to 2021. The minimum inhibitory concentrations (MICs) were determined using broth microdilution. The overall susceptibility rates of S. pneumoniae isolates to penicillin, ceftriaxone and ceftaroline were 63.4%, 94.0% and 99.6%, respectively. The geometric mean of MICs and MIC50/MIC90 values of ceftriaxone were higher in Asia than in other continents. China (33.9%), South Korea (33.8%) and Taiwan (27.6%) had the highest ceftriaxone non-susceptibility rates, followed by Turkey, India, Brazil, Malaysia, South Africa and Colombia, with rates between 10% and 20%. During the study period from 2020 to 2021, Asia had the highest MIC90 value (4 mg/L) for ceftriaxone in S. pneumoniae isolates, and the geometric mean of MICs increased from 0.25 mg/L in 2016-2017 to 0.39 mg/L in 2020-2021. Both Asia (from 83.4% to 75.1%) and Latin America (from 94.2% to 86.3%) showed a decreasing trend in ceftriaxone susceptibility rates from 2016 to 2021. In North America, Europe and Oceania, the susceptibility rate was higher than 95%, and there was no obvious change in the rate during the 6 y. Further analysis of the data from Asia revealed that individuals younger than 6 y of age had a lower susceptibility rate to ceftriaxone (71.6% vs. 81.7%, P < 0.05) than patients ≥6 y. The higher non-susceptibility rates of ceftriaxone in S. pneumoniae in Asia may lead to therapeutic challenges in community-acquired pneumonia.
Plastics are still the most popular food packaging material and many of them end up in the environment for a long period. Due to packaging material's inability to inhibit microbial growth, beef often contains microorganisms that affect its aroma, colour and texture. Cinnamic acid is categorized as generally recognised as safe and is permitted for use in food. The development of biodegradable food packaging film with cinnamic acid has never been conducted before. This present study was aimed to develop a biodegradable active packaging material for fresh beef using sodium alginate and pectin. The film was successfully developed with solution casting method. The films' thickness, colour, moisture level, dissolution, water vapour permeability, bending strength and elongation at break were comparable to those of polyethylene plastic film in terms of these attributes. The developed film also showed the degradability in soil of 43.26% in a duration of 15 days. Fourier Transform Infrared (FTIR) spectra showed that cinnamic acid was successfully incorporated with the film. The developed film showed significant inhibitory activity on all test foodborne bacteria. On Hohenstein challenge test, a 51.28-70.45% reduction on bacterial growth was also observed. The antibacterial efficacy of the established film by using fresh beef as food model. The meats wrapped with the film showed significant reduction in bacterial load throughout the experimental period by 84.09%. The colour of the beef also showed significant different between control film and edible film during 5 days test. Beef with control film turned into dark brownish and beef with cinnamic acid turn into light brownish. Sodium alginate and pectin film with cinnamic acid showed good biodegradability and antibacterial activity. Further studies can be conducted to investigate the scalability and commercial viability of this environmental-friendly food packaging materials.
Hypoxia-inducible factor prolyl hydroxylase domain 2 (PHD2) is an important oxygen sensor in animals. By using the CO-releasing molecule-2 (CORM-2) as an in situ CO donor, we demonstrate that CO is an inhibitor of PHD2. This report provides further evidence about the emerging role of CO in oxygen sensing and homeostasis.
This study documents for the first time the phytochemical composition and biological activities of Tambourissa peltata Baker, an endemic plant from Mauritius. Phytochemical extraction was performed using ethyl acetate, methanol and distilled water as solvents. The phytochemical composition was determined through HPLC-MS and other standard assays. The DPPH, ABTS, FRAP, CUPRAC and phosphomolybdenum assays were employed for the determination of the antioxidant potential, whereas cell viability assays were used to determine the cytotoxicity. The highest phenolic and phenolic acid contents were obtained in the aqueous extract (179.91 ± 0.67 gallic acid equivalents/g and 55.74 ± 1.43 caffeic acid equivalents/g). The highest quantity of flavonoids was obtained in the ethyl acetate extract (28.97 ± 0.46 rutin equivalents/g). The methanolic extract was the highest source of flavonols (33.71 ± 0.13 mg catechin equivalents/g). A total of 34 phytochemicals were identified, mainly proanthocyanidins and flavonoid glycosides. The highest antioxidant activity in DPPH (973.40 ± 5.65 mg TE (Trolox equivalents)/g), ABTS (2030.37 ± 40.83 mg TE/g), FRAP (1461.39 ± 5.95 mg TE/g), CUPRAC (1940.99 ± 20.95 mg TE/g) and phosphomolybdenum (8.37 ± 0.23 mmol TE/g) assays was recorded for the aqueous extract. The ethyl acetate extract was the most active metal chelator. The highest acetylcholinesterase inhibitor was the methanolic extract, whereas the ethyl acetate extract was the most active against BChE. The tyrosinase enzyme was most inhibited by the methanolic extract. Alpha-amylase and glucosidase were most inhibited by the aqueous extract. The methanolic extract was capable of inducing cell cytotoxicity to the human colorectal carcinoma without damaging normal cells. T. peltata warrants further attention from the scientific community given its multifaceted biological properties.
α-Mangostin, initially identified in 1855, is a xanthone derivative compound predominantly located in the pericarp of the mangosteen fruit (Garcinia mangostana L). This compound is known for its beneficial properties as an antioxidant and anti-inflammatory agent, still holding promise for potential benefits in other related pathologies. In the investigative process, computational studies have proven highly valuable in providing evidence and initial screening before progressing to preclinical and clinical studies. This review aims to present the pharmacological findings and mechanisms of action of α-mangostin based on computational studies. The compilation of this review is founded on the analysis of relevant articles obtained from PubMed, Scopus, and ScienceDirect databases. The study commences with an elucidation of the physicochemical characteristics, drug-likeness, pharmacokinetics, and toxicity profile of α-mangostin, which demonstrates that α-mangostin complies with the Lipinski's Rule of Five, exhibits favorable profiles of absorption, distribution, metabolism, and excretion, and presents low toxicity. Subsequent investigations have revealed that computational studies employing various software tools including ArgusLab, AutoDock, AutoDock Vina, Glide, HEX, and MOE, have been pivotal to comprehend the pharmacology of α-mangostin. Beyond its well established roles as an antioxidant and anti-inflammatory agent, α-mangostin is now recognized for its pharmacological effects in Alzheimer's disease, diabetes, cancer, chronic kidney disease, chronic periodontitis, infectious diseases, and rheumatoid arthritis. Moreover, α-mangostin is projected to have applications in pain management and as a potent mosquito larvicide. All of these findings are based on the attainment of adequate binding affinity to specific target receptors associated with each respective pathological condition. Consequently, it is anticipated that these findings will serve as a foundation for future scientific endeavours, encompassing both in vitro and in vivo studies, as well as clinical investigations, to better understand the pharmacological effects of α-mangostin.
The global pandemic of COVID-19 is a serious public health concern. Over 625 million confirmed cases and more than 6 million deaths have been recorded worldwide. Although several vaccines and antiviral medications have been developed, their efficacy is limited by the emerging new SARS-CoV-2 strains. Peptide-based therapeutics is a fast-growing class of new drugs and have unique advantages over large proteins and small molecules. Antiviral peptides (AVPs) are short polycationic antivirals with broad-spectrum effects, which have been shown to exert both prophylactic and therapeutic actions against reported coronaviruses. The potential therapeutic targets of AVPs are located either on the virus (e.g., E-protein and S-protein) to prohibit viral binding or host cells, particularly, those present on the cell surface (e.g., ACE2 and TMPRSS2). Despite AVPs having promising antiviral effects, their efficacy is limited by low bioavailability. Thus, nanoformulation is a prerequisite for prolonged bioavailability and efficient delivery. This review aimed to present an insight into the therapeutic AVP targets on both virus and host cells by discussing their antiviral activities and associated molecular mechanisms. Besides, it described the technique for discovering and developing possible AVPs based on their targets, as well as the significance of using nanotechnology for their efficient delivery against SARS-CoV-2.
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which emerged in December 2019 and caused the coronavirus disease 2019 (COVID-19) pandemic, took the world by surprise with an unprecedented public health emergency. Since this pandemic began, extraordinary efforts have been made by scientists to understand the pathogenesis of COVID-19, and to fight the infection by providing various preventive, diagnostic and treatment opportunities based on either novel hypotheses or past experiences. Despite all the achievements, COVID-19 continues to be an accelerating health threat with no specifically approved vaccine or therapy. This review highlights the recent advances in COVID-19 infection, with a particular emphasis on nanomedicine applications that can help in the development of effective vaccines or therapeutics against COVID-19. A novel future perspective has been proposed in this review based on utilizing polymersome nano-objects for effectively suppressing the cytokine storm, which may reduce the severity of COVID-19 infection.
Primarily sourced from Asteraceae family herbs such as the Dandelion, Taraxasterol is a pentacyclic triterpenoid lauded for its extensive biological functionalities. Its therapeutic potency is demonstrated in various disease models, encompassing enteritis, arthritis, acute hepatic injury, and pneumonia. Scientific literature underscores its anti-inflammatory, antioxidant, and antineoplastic attributes. The primary aim of this study is to thoroughly explore the diseasemodulating mechanisms and effects of taraxasterol. We endeavor to provide an exhaustive review of the experimental subjects, intervention components, distinct action modalities, contributing factors, and protein pathway expressions associated with taraxasterol, systematically represented via diagrams and tables. Such a schematic representation encourages a continued academic dialogue concerning taraxasterol's pharmacological characteristics. This review is envisioned as a practical guide for the selection of experimental subjects and methodologies in prospective research. It is intended to further illuminate taraxasterol's pharmacodynamics, thereby offering theoretical and empirical justification for its clinical application.
Polysaccharide-based edible films have been widely developed as food packaging materials in response to the rising environmental concerns caused by the extensive use of plastic packaging. In recent years, the integration of carboxymethyl cellulose (CMC) and chitosan (CS) for a binary edible film has received considerable interest because this binary edible film can retain the advantages of both constituents (e.g., the great oxygen barrier ability of CMC and moderate antimicrobial activity of CS) while mitigating their respective disadvantages (e.g., the low water resistance of CMC and poor mechanical strength of CS). This review aims to present the latest advancements in CMC-CS edible films. The preparation methods and properties of CMC-CS edible films are comprehensively introduced. Potential additives and technologies utilized to enhance the properties are discussed. The applications of CMC-CS edible films on food products are summarized. Literature shows that the current preparation methods for CMC-CS edible film are solvent-casting (main) and thermo-mechanical methods. The CMC-CS binary films have superior properties compared to films made from a single constituent. Moreover, some properties, such as physical strength, antibacterial ability, and antioxidant activity, can be greatly enhanced via the incorporation of some bioactive substances (e.g. essential oils and nanomaterials). To date, several applications of CMC-CS edible films in vegetables, fruits, dry foods, dairy products, and meats have been studied. Overall, CMC-CS edible films are highly promising as food packaging materials.
Human liver fluke, Opisthorchis viverrini poses a significant risk for development of cholangiocarcinoma (CCA) in Thailand, primarily attributed to consumption of undercooked cyprinoid fishes. The current use of anthelmintic drug treatment such as praziquantel (PZQ), as the main therapeutic agent against O. viverrini. There is a need to explore the efficacy of alternative anthelmintic drugs for O. viverrini treatment. This study aimed to assess the efficacy of anthelmintic drugs, which are commonly use in endemic areas of Southeast Asian countries; PZQ, albendazole (AL), niclosamide (NI), and mebendazole (ME) at concentrations of 600, 400, 500, and 500 mg/ml. The study included a negative and positive control group treated with roswell park memorial institute (RPMI) and PZQ. Reactive oxygen species (ROS) levels, indicative of oxidative stress, were quantified using 2',7'-dichlorofluorescein diacetate staining. Morphological changes were observed using scanning electron microscopy. Furthermore, motility assessments were conducted at various time points (0, 5, 30 minutes, 1, 3, 6, 12, and 24 hours), calculating relative motility (RM) and survival index (SI). The results revealed a significant increase of ROS levels with the intensity and corrected total worm fluorescence (CTWF) mostly observed in order of PZQ, followed by NI, ME, and AL, respectively. Morphological damage was presented the tegumental swelling, papillae changes, and disruption of microvilli (Mv), particularly in the group treated with the most effective anthelmintics PZQ, NI, ME, and AL, while negative control group did not exhibit such alterations. Also, the most efficacy for suppressing the motility of adult worms were displayed in PZQ treatment group, followed by NI, ME, and AL, respectively. Overall, first novel findings suggest that apart from NI, ME, and AL demonstrate potential as alternative therapeutic options for O. viverrini infection. Furthermore, animal model is needed to investigate the efficacy of NI, ME, and AL compare with standard treatment.
Ebola virus is notorious for causing severe and even deadly haemorrhagic fever in infected humans and non-human primates. The high fatality rate of Ebola virus disease (EVD) has highlighted the need for effective diagnosis and treatment. Two monoclonal antibodies (mAbs) have been approved by USFDA for treatment of EVD. Virus surface glycoprotein is the common target for diagnostic and therapy including vaccines. Even so, VP35, a viral RNA polymerase cofactor and interferon inhibitor could be a potential target to curb EVD. The present work describes the isolation of three mAb clones from a phage-displayed human naïve scFv library against recombinant VP35. The clones showed binding against rVP35 in vitro and inhibition of VP35 in luciferase reporter gene assay. Structural modelling analysis was also carried out to identify the binding interactions involved in the antibody-antigen interaction model. This allows some insight into the "fitness" of the binding pocket between the paratope and target epitope which would be useful for the design of new mAbs through in silico means in the future. In conclusion, the information obtained from the 3 isolated mAbs could be potentially useful in the quest to improve VP35 targeting for therapeutic development in the future.
Colorectal cancer is one of the most prevalent noncommunicable diseases worldwide. 5-Fluorouracil is the mainstay of chemotherapy for colorectal cancer. Previously, we have demonstrated that high glucose diminishes the cytotoxicity of 5-fluorouracil by promoting cell cycle progression. The synergistic impact of rosiglitazone on 5-fluorouracil-induced apoptosis was further investigated in this study. Besides control cell lines (CCD-18Co), two human colonic carcinoma cell lines (HCT 116 and HT 29) were exposed to different treatments containing 5-fluorouracil, rosiglitazone or 5-fluorouracil/rosiglitazone combination under normal glucose (5.5 mM) and high-glucose (25 mM) conditions. The cellular oxidative stress level was evaluated with biomarkers of nitric oxide, advanced oxidation protein products, and reduced glutathione. The cell apoptosis was assessed using flow cytometry technique. High glucose caused the production of reduced glutathione in HCT 116 and HT 29 cells. Correspondingly, high glucose suppressed the apoptotic effect of 5-fluorouracil and rosiglitazone. As compared to 5-fluorouracil alone (2 µg/mL), addition of rosiglitazone significantly enhanced the apoptosis (increment rate of 5-20%) in a dose-dependent manner at normal glucose and high glucose levels. This study indicates that high-glucose-induced reduced glutathione confers resistance to apoptosis, but it can be overcome upon treatment of 5-fluorouracil and 5-fluorouracil/rosiglitazone combination. Rosiglitazone may be a promising antidiabetic drug to reduce the chemotherapeutic dose of 5-fluorouracil for colorectal cancer complicated with hyperglycemia.
Vibriosis and parasitic leech infestations cause the death of various farmed fish, such as groupers, hybrid groupers, sea bass, etc., in Malaysia and other Southeast Asian countries. In the absence of natural control agents, aquaculture operators rely on toxic chemicals to control Vibrio infections and parasitic leeches, which can have a negative impact on the environment and health. In the present study, we investigated the antivibrio and antiparasitic activities of the aqueous extract of giant sword fern (GSF) (Nephrolepis biserrata, Nephrolepidaceae, locally known as "Paku Pedang") against four Vibrio spp. and the parasitic leech Zeylanicobdella arugamensis, as well as its metabolic composition using the ultra-high-performance liquid chromatography-high-resolution mass spectrometry system (UHPLC-HRMS). The data show that the aqueous extract of GSF at a concentration of 100 mg/mL exhibits potent bactericidal activity against V. parahaemolyticus with a zone of inhibition of 19.5 mm. In addition, the extract showed dose-dependent activity against leeches, resulting in the complete killing of the parasitic leeches within a short period of 11-43 min when tested at concentrations ranging from 100 to 25 mg/mL. The UHPLC-HRMS analysis detected 118 metabolites in the aqueous extract of GSF. Flavonoids were the primary metabolites, followed by phenolic, aromatic, fatty acyl, terpenoid, vitamin and steroidal compounds. Notably, several of these metabolites possess antibacterial and antiparasitic properties, including cinnamaldehyde, cinnamic acid, apigenin, quercetin, cynaroside, luteolin, naringenin, wogonin, 6-gingerol, nicotinamide, abscisic acid, daidzein, salvianolic acid B, etc. Overall, our study shows the significant antibacterial and antiparasitic potential of the GSF aqueous extract, which demonstrates the presence of valuable secondary metabolites. Consequently, the aqueous extract is a promising natural alternative for the effective control of Vibrio infections and the treatment of parasitic leeches in aquaculture systems.
Antibiotic resistance is a growing concern that is affecting public health globally. The search for alternative antimicrobial agents has become increasingly important. Antimicrobial peptides (AMPs) produced by Bacillus spp. have emerged as a promising alternative to antibiotics, due to their broad-spectrum antimicrobial activity against resistant pathogens. In this review, we provide an overview of Bacillus-derived AMPs, including their classification into ribosomal (bacteriocins) and non-ribosomal peptides (lipopeptides and polyketides). Additionally, we delve into the molecular mechanisms of AMP production and describe the key biosynthetic gene clusters involved. Despite their potential, the low yield of AMPs produced under normal laboratory conditions remains a challenge to large-scale production. This review thus concludes with a comprehensive summary of recent studies aimed at enhancing the productivity of Bacillus-derived AMPs. In addition to medium optimization and genetic manipulation, various molecular strategies have been explored to increase the production of recombinant antimicrobial peptides (AMPs). These include the selection of appropriate expression systems, the engineering of expression promoters, and metabolic engineering. Bacillus-derived AMPs offer great potential as alternative antimicrobial agents, and this review provides valuable insights on the strategies to enhance their production yield, which may have significant implications for combating antibiotic resistance. KEY POINTS: • Bacillus-derived AMP is a potential alternative therapy for resistant pathogens • Bacillus produces two main classes of AMPs: ribosomal and non-ribosomal peptides • AMP yield can be enhanced using culture optimization and molecular approaches.
Mitragynine (MG) is the primary active constituent of Mitragyna speciosa Korth (kratom), a psychoactive Southeast Asian plant with potential therapeutic use. Numerous studies support roles of dopaminergic system in drug reward. However, the involvement of the dopaminergic system in mediating MG reward and drug-seeking is poorly understood. Using conditioned place preference (CPP) paradigm, the present study aims to evaluate the roles of the dopamine (DA) D1 receptor in the acquisition and expression of MG-induced CPP in rats. The effects of SCH-23390, a selective DA D1 receptor antagonist, on the acquisition of MG-induced CPP were first investigated. Rats were pre-treated systemically with SCH-23390 (0, 0.1 and 0.3 mg/kg, i.p.) prior to MG (10 mg/kg) conditioning sessions. Next, we tested the effects of the DA D1 receptor antagonist on the expression of MG-induced CPP. Furthermore, the effects of a MG-priming dose (5 mg/kg) on the reinstatement of extinguished CPP were tested. The results showed that SCH-23390 dose-dependently suppressed the acquisition of a MG-induced CPP. In contrast, SCH-23390 had no effect on the expression of a MG-induced CPP. The findings of this study suggested a crucial role of the DA D1 receptor in the acquisition, but not the expression of the rewarding effects of MG in a CPP test. Furthermore, blockade of the D1-like receptor during conditioning did not prevent MG priming effects on CPP reinstatement test, suggesting no role for the DA D1 receptor in reinstatement sensitivity.
Mitragynine (MG) is a pharmacologically active alkaloid derived from the leaves of Mitragyna speciosa Korth (Kratom). This plant has sparked significant interest as a potential alternative treatment for managing opioid dependence and withdrawal due to its opioid-like pharmacological effects. However, whether MG exposure would trigger opioid-seeking behaviour following abstinence has not been investigated. The present study examined the effects of MG priming on morphine-seeking behaviour in rats. Male Sprague-Dawley rats were initially trained to intravenously self-administer morphine (0.5 mg/kg/infusion) under a fixed ratio-3 schedule of reinforcement. Removal of both morphine infusions and drug-associated cues led to the subsequent extinction of the drug-seeking behaviour. Tests of reinstatement were made following exposure to a randomised order of intraperitoneal injections of MG (3, 10 and 30 mg/kg), morphine (5 mg/kg) and vehicle. Significant levels of drug-seeking behaviour were observed following extended access to morphine self-administration, which was extinguished following removal of morphine and cues indicative of morphine-seeking behaviour, supporting the relapse model. The present finding demonstrated that MG priming in a dose of 10 mg/kg resulted in the reinstatement of morphine-seeking behaviour, whereas the higher MG dose (30 mg/kg) tested suppressed the seeking response. This study indicated that exposure to a low MG dose may increase the likelihood of relapsing to opioids, suggesting that the potential of MG as a treatment for opioid management merits further scientific assessment of its ability to trigger relapse to opioid abuse.