Search

Compared with other organs, the nervous system is the most susceptible and a top target for lead-induced poisoning. At higher dosages, lead poisoning can be fatal or severely brain-damaging. This study aimed to explore the protective effect of zingerone on rats induced-brain oxidative stress by lead acetate on some pathological alteration. Using a random selection process, 40 male mature rats were allocated into four identical groups for the experiment and given the following care for 28 days: The control group (G1) was given distilled water, G2: gavage 16 mg/kg. B.W. of lead acetate, G3: 125 mg/kg. B.W. of zingerone and 16 mg/kg. B.W. of lead acetate, G4: 125 mg/kg. B.W. of zingerone. After collecting tissue from the brain samples, the cerebral cortex and hippocampus were separated for histological analysis. The result showed normal cerebral cortex and hippocampus histological architecture in the control group. The histology architecture of brain tissues in the lead acetate-treated group (G2) showed degeneration of neuronal cells, disruption of the cellular layers and atrophy, nuclear pyknosis, and neuronal injury. The G3 and G4 treated groups showed repair in the histological changes of the cerebral cortex and hippocampus due to zingerone's antioxidant and neuroprotective effects. Conclusion: Zingerone has antioxidant activity and neuroprotective properties by improving brain histological changes in rats

Background: The available in vitro evidences suggest the inherent instability and interconvertibility of [6]-gingerol and [6]-shogaol. However, limited data on their in vivo interconversion hinder understanding of their influence on the pharmacokinetic profiles. Purpose: This study presents the first comprehensive in vivo investigation aiming to determine the interconversion pharmacokinetics in rats, and elucidate the oral bioavailability, target distribution, biotransformation, and excretion profiles of the key ginger constituents, [6]-gingerol, [6]-shogaol, and zingerone. Methods: The pharmacokinetics was investigated through single intravenous (3 mg/kg) or oral (30 mg/kg) administration of [6]-gingerol, [6]-shogaol, or zingerone, followed by the determination of their tissue distribution after oral dosing (30 mg/kg). Intravenous pharmacokinetics was leveraged to evaluate the interconversion, circumventing potential confounders associated with the oral route. Results: All rats tolerated these compounds throughout the pharmacokinetic study. The parent compounds exhibited rapid but partial absorption, and extensive organ distribution with substantial biotransformation, thereby limiting the oral bioavailability of each compound to below 2% when administered as pure compounds. Conversion of [6]-gingerol to [6]-shogaol after intravenous administration, demonstrated a significantly larger clearance compared to the reverse conversion ([6]-shogaol to [6]-gingerol). The irreversible metabolic clearance for both compounds was significantly greater than their reversible bioconversions. Furthermore, [6]-gingerol underwent biotransformation to zingerone. Conjugated glucuronides were eliminated partly through renal excretion, with minimal fecal excretion. Conclusion: This in vivo investigation demonstrates the influence of interconversion on the disposition kinetics of [6]-gingerol, [6]-shogaol, and zingerone, as evidenced by the findings in the systemic circulation. The study further highlights the importance of considering this interconversion and tissue distribution when determining the administration dosage of ginger constituent combinations for therapeutic benefits and clinical applications. [ABSTRACT FROM AUTHOR]

Background and Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of nosocomial and community acquired infections. Nanoparticles are considered as proper tools to overcome the therapeutic problem of antimicrobial-resistant infections because of the drug concentration increment at the desired location and protection from enzymatic degradation. The goal of this study was to evaluate the effect of the antibacterial and antibiofilm activities of zingerone and niosome containing zingerone against pre-formed biofilm of MRSA isolates. Materials and Methods: 62 MRSA isolates cultured from patients with diabetic ulcers were investigated. Niosomes were synthesized and characterized by X-ray diffraction, zeta potential and scanning electron microscopy (SEM). The size of niosomal particles measured by SEM and zetasizer. Results: The surface charge of prepared niosomes was about -37 mV. The effect of the zingerone and noisome containing zingerone was evaluated against biofilms of MRSA isolates. Also, the antibiofilm activity of prepared niosomes on gene expression of MRSA biofilms was evaluated using Real Time PCR. Our results demonstrated that the niosome containing zingerone had a diameter of 196.1 nm and a -37.3-mV zeta potential. Zingerone removed one and three-day old biofilms of MRSA at the concentration of 1000 µg/ml, while the zingerone-laoded niosomes removed 1, 3-and 5-days old biofilms at the concentration of 250 µg/ml, 250 µg/ml, and 500 µg/ml. Conclusion: The results indicated that niosome containing zingerone eliminated MRSA and its biofilms faster compared with free zingerone and it suggested that zingerone-encapsulated niosomes could be considered as a promising treatment against MRSA and its biofilms. [ABSTRACT FROM AUTHOR]

Objective(s): In the present study, the potential protective effects of zingerone (ZNG) against sciatic nerve damage caused by sodium arsenite (SA), a common environmental pollutant, were evaluated by various biochemical, molecular, and histological methods.Materials and Methods: In the study, SA and ZNG were given to 35 male Sprague Dawley rats for 14 days. At the end of the period, the sciatic nerve tissues were taken and the markers involved in oxidative stress, endoplasmic reticulum stress, inflammation, and apoptosis were analyzed.Results: The data obtained showed that SA decreased glutathione (GSH) levels and increased malondialdehyde (MDA) levels in the sciatic nerve tissue. However, it was determined that these markers approached the control group levels due to the anti-oxidant properties of ZNG. While SA triggered endoplasmic reticulum stress and apoptosis pathways, ZNG suppressed them. Moreover, SA up-regulated inflammatory markers such as nuclear factor kappa-B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-1-beta (IL-1β), and neuronal nitric oxide synthases (nNOS) in the sciatic nerves and caused neuro-inflammation and inhibited cell survival by suppressing serine/threonine-protein kinase 2 (Akt2) and forkhead box protein O1 (FOXO1) genes. It has also been shown histopathologically that SA causes degeneration in the sciatic nerves. In contrast, ZNG suppressed neuro-inflammation, activated Akt2/FOXO1 signaling, and repaired histological irregularities.Conclusion: In general, SA caused oxidative stress, inflammation, ER stress, and apoptosis in the sciatic nerves of rats, causing damage to the tissues, however, ZNG suppressed these pathways and protected the sciatic nerves from the destructive effect of SA.

Objective(s): In the present study, the potential protective effects of zingerone (ZNG) against sciatic nerve damage caused by sodium arsenite (SA), a common environmental pollutant, were evaluated by various biochemical, molecular, and histological methods. Materials and Methods: In the study, SA and ZNG were given to 35 male Sprague Dawley rats for 14 days. At the end of the period, the sciatic nerve tissues were taken and the markers involved in oxidative stress, endoplasmic reticulum stress, inflammation, and apoptosis were analyzed. Results: The data obtained showed that SA decreased glutathione (GSH) levels and increased malondialdehyde (MDA) levels in the sciatic nerve tissue. However, it was determined that these markers approached the control group levels due to the anti-oxidant properties of ZNG. While SA triggered endoplasmic reticulum stress and apoptosis pathways, ZNG suppressed them. Moreover, SA up-regulated inflammatory markers such as nuclear factor kappa-B (NF-κB), tumor necrosis factoralpha (TNF-α), interleukin-1-beta (IL-1β), and neuronal nitric oxide synthases (nNOS) in the sciatic nerves and caused neuro-inflammation and inhibited cell survival by suppressing serine/threonineprotein kinase 2 (Akt2) and forkhead box protein O1 (FOXO1) genes. It has also been shown histopathologically that SA causes degeneration in the sciatic nerves. In contrast, ZNG suppressed neuro-inflammation, activated Akt2/FOXO1 signaling, and repaired histological irregularities. Conclusion: In general, SA caused oxidative stress, inflammation, ER stress, and apoptosis in the sciatic nerves of rats, causing damage to the tissues, however, ZNG suppressed these pathways and protected the sciatic nerves from the destructive effect of SA. [ABSTRACT FROM AUTHOR]

Melanoma, an invasive class of skin cancer, originates from mutations in melanocytes, the pigment‐producing cells. Globally, approximately 132,000 new cases are reported each year, and in South Africa, the incidence stands at 2.7 per 100,000 people, signifying a worrisome surge in melanoma rates. Therefore, there is a need to explore treatment modalities that will target melanoma's signalling pathways. Melanoma metastasis is aided by ligand activity of transforming growth factor‐beta 1 (TGF‐β1), vascular endothelial growth factor‐C (VEGF‐C) and C‐X‐C chemokine ligand 12 (CXCL12) which bind to their receptors and promote tumour cell survival, lymphangiogenesis and chemotaxis. (3‐(4‐dimethylaminonaphthelen‐1‐ylmethylene)‐1,3‐dihydroindol‐2‐one) MAZ‐51 is an indolinone‐based molecule that inhibits VEGF‐C induced phosphorylation of vascular endothelial growth factor receptor 3 (VEGFR‐3). Despite the successful use of conventional cancer therapies, patients endure adverse side effects and cancer drug resistance. Moreover, conventional therapies are toxic to the environment and caregivers. The use of medicinal plants and their phytochemical constituents in cancer treatment strategies has become more widespread because of the rise in drug resistance and the development of unfavourable side effects. Zingerone, a phytochemical derived from ginger exhibits various pharmacological properties positioning it as a promising candidate for cancer treatment. This review provides an overview of melanoma biology and the intracellular signalling pathways promoting cell survival, proliferation and adhesion. There is a need to align health and environmental objectives within sustainable development goals 3 (good health and well‐being), 13 (climate action) and 15 (life on land) to promote early detection of skin cancer, enhance sun‐safe practices, mitigation of environmental factors and advancing the preservation of biodiversity, including medicinal plants. Thus, this review discusses the impact of cytostatic cancer drugs on patients and the environment and examines the potential use of phytochemicals as adjuvant therapy. Significance statement: Cytostatic drugs, despite being effective treatment agents, induce nontarget effects harming noncancerous cells.This review highlights the use of phytochemicals as adjuvant therapy in cancer treatment to combat the nontarget effects of cytostatic drugs.Additionally, phytochemicals as adjuvants decrease the environmental burden incurred by cytostatic drugs, promoting environmental sustainability. [ABSTRACT FROM AUTHOR]

Background: How to improve flap necrosis in distal flaps is still a popular topic in clinical flap research. Zingerone (ZIN), as a plant extract, has therapeutic effects on many diseases. The purpose of our study was to explore whether ZIN can promote the survival of ischaemic skin flaps and its specific mechanism. Methods: An ischemic flap model was established in the dorsal region of mice. The changes of angiogenesis, oxidative stress, apoptosis and Keap1-Nrf2 related proteins in the skin flap were detected by immunofluorescence, western blot and qPCR. Overexpression of Keap1 by adeno-associated virus (AAV) was used to study the specific pathway and mechanism. Results: The results showed that ZIN can induce angiogenesis and reduce oxidative stress and apoptosis to promote flap survival. Increased expression of Keap1 reversed the therapeutic effect of ZIN. Conclusion: ZIN activates Nrf2 by inhibiting Keap1 activation, thus promoting angiogenesis and inhibiting oxidative stress and apoptosis.

Background and Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of nosocomial and community acquired infections. Nanoparticles are considered as proper tools to overcome the therapeutic problem of antimicrobial-resistant infections because of the drug concentration increment at the desired location and protection from enzymatic degradation. The goal of this study was to evaluate the effect of the antibacterial and antibiofilm activities of zingerone and niosome containing zingerone against pre-formed biofilm of MRSA isolates. Materials and Methods: 62 MRSA isolates cultured from patients with diabetic ulcers were investigated. Niosomes were synthesized and characterized by X- ray diffraction, zeta potential and scanning electron microscopy (SEM). The size of niosomal particles measured by SEM and zetasizer. Results: The surface charge of prepared niosomes was about -37 mV. The effect of the zingerone and noisome containing zingerone was evaluated against biofilms of MRSA isolates. Also, the antibiofilm activity of prepared niosomes on gene expression of MRSA biofilms was evaluated using Real Time PCR. Our results demonstrated that the niosome containing zingerone had a diameter of 196.1 nm and a -37.3-mV zeta potential. Zingerone removed one and three-day old biofilms of MRSA at the concentration of 1000 µg/ml, while the zingerone-laoded niosomes removed 1, 3- and 5-days old biofilms at the concentration of 250 µg/ml, 250 µg/ml, and 500 µg/ml. Conclusion: The results indicated that niosome containing zingerone eliminated MRSA and its biofilms faster compared with free zingerone and it suggested that zingerone-encapsulated niosomes could be considered as a promising treatment against MRSA and its biofilms.

BackgroundThe available in vitro evidences suggest the inherent instability and interconvertibility of [6]-gingerol and [6]-shogaol. However, limited data on their in vivo interconversion hinder understanding of their influence on the pharmacokinetic profiles.PurposeThis study presents the first comprehensive in vivo investigation aiming to determine the interconversion pharmacokinetics in rats, and elucidate the oral bioavailability, target distribution, biotransformation, and excretion profiles of the key ginger constituents, [6]-gingerol, [6]-shogaol, and zingerone.MethodsThe pharmacokinetics was investigated through single intravenous (3 mg/kg) or oral (30 mg/kg) administration of [6]-gingerol, [6]-shogaol, or zingerone, followed by the determination of their tissue distribution after oral dosing (30 mg/kg). Intravenous pharmacokinetics was leveraged to evaluate the interconversion, circumventing potential confounders associated with the oral route.ResultsAll rats tolerated these compounds throughout the pharmacokinetic study. The parent compounds exhibited rapid but partial absorption, and extensive organ distribution with substantial biotransformation, thereby limiting the oral bioavailability of each compound to below 2% when administered as pure compounds. Conversion of [6]-gingerol to [6]-shogaol after intravenous administration, demonstrated a significantly larger clearance compared to the reverse conversion ([6]-shogaol to [6]-gingerol). The irreversible metabolic clearance for both compounds was significantly greater than their reversible bioconversions. Furthermore, [6]-gingerol underwent biotransformation to zingerone. Conjugated glucuronides were eliminated partly through renal excretion, with minimal fecal excretion.ConclusionThis in vivo investigation demonstrates the influence of interconversion on the disposition kinetics of [6]-gingerol, [6]-shogaol, and zingerone, as evidenced by the findings in the systemic circulation. The study further highlights the importance of considering this interconversion and tissue distribution when determining the administration dosage of ginger constituent combinations for therapeutic benefits and clinical applications.

The purpose of the present work was to encapsulate zingerone (a bioactive compound from ginger) by self-assembling peptides derived from fish viscera. The encapsulation conditions were investigated and the structure of fish peptides-zingerone complex was characterized. The interaction between zingerone and fish peptides was investigated using fluorescence spectroscopy. Further research was performed on the in vitro release of zingerone and fish peptide-zingerone as well as their antiproliferative effects on colon epithelial Caco-2 cells. The results demonstrated that zingerone can be successfully encapsulated by self-assembling peptides derived from fish viscera with high encapsulation efficiency and loading capacity. Furthermore, transmission electron microscope and confocal laser scanning microscope observations revealed the successful encapsulation of zingerone by fish viscera peptides. In addition, in vitro release and antiproliferative activity against Caco-2 cells can be significantly increased by encapsulating zingerone via peptide self-assembly. The current study advances knowledge of encapsulation of bioactive compounds through peptide self-assembly.

ABSTRACTThe rapid increase in agricultural waste is rising across the globe and is a big environmental challenge. The utilization of ginger waste as a valuable product is very limited. The up-cycling of ginger waste is an effective approach for valorization. Ginger waste contains many bio-active compounds. These bioactive compounds possess various functional and bio-active properties. The literature has indicated that ginger and its waste is a rich source of shogaol zingerone and gingerols, these bioactive components contribute to pungency and aroma characteristics These compounds have a wide range of antimicrobial, antioxidant, and anti-inflammatory properties. Furthermore, these have a key role in skin health and the digestive system. The current review consolidates the compositional, functional, medicinal, bioactive, and health-endorsing attributes of ginger waste. The use of ginger wastes for the development of various functional and nutraceutical products is also in the limelight of this paper.

Morphine (MPH) is widely used for pain management; however, long-term MPH therapy results in antinociceptive tolerance and physical dependence, limiting its clinical use. Zingerone (ZIN) is a natural phenolic compound with neuroprotective effects. We investigated the effects of single and repeated doses of ZIN on MPH-induced tolerance, dependence, and underlying biochemical mechanisms. After a dose-response experiment, tolerance was developed to MPH (10 mg/kg, i.p.) for seven days. In the single-dose study, ZIN was administered on day seven. In the repeated-dose study, ZIN was administered for seven days. Naloxone (5 mg/kg, i.p., 120 min after MPH) was injected to assess withdrawal signs on day seven. The levels of thiobarbituric acid reactive substances (TBARS), nitric oxide (NO), total thiol (TT), and glutathione peroxidase (GPx) were measured in the prefrontal cortex. The protein levels of interleukin-1 beta (IL-1β) and NLRP3-ASC-Caspase-1 axis were assessed by ELISA and Western blotting, respectively. Results showed that ZIN (100 mg/kg) had no antinociceptive activity, and subsequent experiments were performed at this dose. Repeated ZIN reversed MPH antinociceptive tolerance, whereas single ZIN did not. Single and repeated ZIN attenuated naloxone-induced jumping. In addition, repeated ZIN significantly inhibited weight loss. Repeated ZIN suppressed the MPH-induced increase in TBARS, NO, IL-1β, NLRP3, ASC, and Caspase-1. It also inhibited MPH-induced TT and GPx reduction. In contrast, single ZIN had no effect. Findings suggest that ZIN reduces MPH-induced tolerance and dependence by suppressing oxidative stress and NLRP3 inflammasome activation. This study provides a novel therapeutic approach to reduce the side effects of MPH. [ABSTRACT FROM AUTHOR]

A high-performance thin-layer chromatography (HPTLC) method was developed for the estimation of zingerone from ginger tablets. A CAMAG Linomat 5 sample applicator was used for the application of the sample. Chromatographic separation of the marker was performed over thin-layer chromatography (TLC) plates precoated with silica gel 60 F254 using toluene‒ethyl acetate (6:4, V/V) as the mobile phase via a linear ascending technique in a twin-trough chamber. Detection and quantification were carried out at a wavelength of 280 nm using a CAMAG TLC Scanner 4. This method showed good peak symmetry for the marker with a retention factor (RF) of 0.43 ± 0.03 for zingerone. The calibration curve was linear in the range of 200‒2000 ng/spot for zingerone, and the correlation coefficient (r2) was 0.9836. The method was validated according to the International Council for Harmonisation (ICH) Q2(R1) guidelines for linearity, limit of detection, limit of quantification, precision, accuracy (recovery), and robustness. In conclusion, the developed method is simple, reliable, and specific for the identification and quantification of zingerone. [ABSTRACT FROM AUTHOR]

Four new species of Zeugodacus Hendel are described from India viz., Zeugodacus momordicae David & Ajaykumara, sp. nov. from Arunachal Pradesh infesting male flower buds of Momordica dioica, Zeugodacus nasivittatus David & Abhishek, sp. nov. from Meghalaya, Zeugodacus (Sinodacus) sinuvittatus David & Abhishek, sp. nov. from Himachal Pradesh and Zeugodacus (Zeugodacus) umiam David & Kennedy, sp. nov. from Meghalaya. An illustrated key to all species of Zeugodacus from India is also included. Bactrocera (Parazeugodacus) abbreviata (Hardy) and Dacus (Mellesis) vijaysegarani Drew & Hancock are recorded for the first time from India. [ABSTRACT FROM AUTHOR]

Background: Doxorubicin, a commonly utilized anthracycline antibiotic and chemotherapeutic agent, has been associated with hepatotoxicity as an adverse effect. This study aimed to evaluate protective effects of zingerone, a bioactive compound derived from ginger renowned for its antioxidative attributes, on oxidative stress in doxorubicin-induced rat hepatotoxicity. Methods: In this experimental study, a total of 48 male Wistar rats were allocated into six distinct groups. The first group received a control treatment of normal saline. The second group was administered an intraperitoneal dose of 20 mg/kg of doxorubicin on day 5. The third group received an oral dose of 40 mg/kg of zingerone for 8 days. The fourth, fifth, and sixth groups were administered zingerone at doses of 10, 20, and 40 mg/kg, respectively, for the same 8-day period. On day 5, all groups, except the control group, received an intraperitoneal injection of doxorubicin. Following a 72-hour interval, the animals were anesthetized, and blood samples were collected to assess serum factors. Moreover, portions of the liver tissue were subjected to histopathological analysis and assessment of oxidative stress parameters. Results: The activity levels of serum enzymes, including aspartate transaminase (AST), alanine transaminase (ALT), and liver malondialdehyde (MDA), increased in the doxorubicin group. Conversely, the levels of other parameters such as glutathione peroxidase (GPX), superoxide dismutase (SOD), and glutathione (GSH) decreased. However, the co-administration of zingerone effectively reversed these levels, restoring them back to normal. Conclusion: These findings suggest that zingerone, particularly at a high dose, exhibit a hepatoprotective effect in the doxorubicin-induced hepatotoxicity model. [ABSTRACT FROM AUTHOR]

Bacteria-mediated cancer immunotherapy (BCI) suppresses tumor progression in two ways: the bacteria themselves kill tumor cells, and they elicit robust host immune responses. However, this does not eradicate tumors completely or prevent metastasis. Therefore, the immune responses elicited by BCI must be backed up by other therapies such as chemotherapy. Zingerone has anticancer activity and modulates T cell-mediated immune responses. Here, we examined the antitumor effects of zingerone/BCI combination therapy. We show that that zingerone 1) enhances St.ΔppGpp-mediated antitumor effects, but reduces survival of tumor-colonizing bacteria by promoting recruitment of tumor-infiltrating neutrophils; 2) amplifies St.ΔppGpp-mediated immune responses by stimulating tumor infiltration by macrophages, natural killer cells, and CD4+ and CD8+ T cells; and 3) enhances St.ΔppGpp-mediated macrophage phagocytosis, leading to tumor eradication. These findings suggest that the zingerone/St.ΔppGpp combination has synergistic antitumor effects, making it a promising approach to cancer immunotherapy.

Objective(s): Sodium arsenite (SA) exposure is toxic to the body. Zingerone (ZNG) is a flavonoid with many biological properties found naturally in honey and plants. This study aimed to determine the effects of ZNG on SA-induced rat lung toxicity.Materials and Methods: Thirty-five male Sprague rats were divided into Control, SA, ZNG, SA+ZNG25, and SA+ZNG50 groups (n=7). SA 10 mg/kg and ZNG were administered at two doses (25 and 50 mg/kg) (orally, 14 days). Analysis of oxidative stress, inflammation damage, apoptosis damage, and autophagic damage markers in lung tissue were determined by biochemical and histological methods. Results: The administration of ZNG reduced oxidative stress by increasing SA-induced decreased antioxidant enzyme activities, increasing Nrf-2, HO-1, and NQO1, and decreasing MDA level. ZNG administration reduced inflammation marker levels. Anti-apoptotic Bcl-2 increased and apoptotic Bax and Caspase-3 decreased with ZNG. ZNG promoted the regression of autophagy by reducing Beclin-1, LC3A, and LC3B levels.Conclusion: Evaluating all data showed that SA caused toxic damage to lung tissue by increasing inflammation, apoptosis, autophagy, and oxidant levels, whereas ZNG had a protective effect by reducing this damage.

Neonatal alcohol exposure (NAE) can induce oxidative stress. We determined whether zingerone (ZO), a phytochemical with anti-oxidant activity, can mitigate the negative impact of neonatal alcohol-induced oxidative stress. Seventy ten-day-old Sprague-Dawley rat pups (35 male, 35 female) were randomly assigned and administered the following treatment regimens daily from postnatal day (PND) 12–21: group 1 – nutritive milk (NM), group 2 – NM +1 g/kg ethanol (Eth), group 3 – NM + 40 mg/kg ZO, group 4 – NM + Eth + ZO. Growth performance, blood glucose and plasma triglycerides (TGs), total cholesterol, HDL-cholesterol, leptin and insulin concentration were determined. Cytochrome p450E21(CYP2E1) and thiobarbituric acid (TBARS); markers of hepatic oxidative stress and catalase, superoxide dismutase (SOD) and total glutathione (GSH), anti-oxidant markers of the pups were determined. Oral administration of ethanol (NM + Eth), zingerone (NM + ZO) and combined ethanol and zingerone (NM + Eth + ZO) did not affect the growth performance and insulin and leptin concentration of the rats (p > 0.05). Ethanol significantly reduced plasma TGs concentration of female rats (p = 0.04 vs control). However, ethanol and/or its combination with zingerone decreased hepatic GSH (p = 0.02 vs control) and increased CYP2E1 (p = 0.0002 vs control) activity in male rat pups. Zingerone had no effect (p > 0.05 vs control) on the rats' CYP2E1, GSH, SOD and catalase activities. Neonatal alcohol administration elicited hepatic oxidative stress in male rat pups only, showing sexual dimorphism. Zingerone (NM + ZO) prevented an increase in CYP2E1 activity and a decrease in GSH concentration but did not prevent the alcohol-induced hepatic oxidative stress in the male rat pups. [ABSTRACT FROM AUTHOR]

Malignant glioma is the deadliest form of brain cancer. Zingerone (ZO), a polyphenolic compound found in ginger, offers pharmacological properties that make it a promising agent for containing the growth of glioma cells. The present study was conducted to understand the efficacy of ZO in containing the growth of C6 glioma cells. The study also assessed the prophylactic role of ZO on rat brain glioma induced by C6 cell lines by addressing its antioxidative action on biochemical, behavioral, and histoarchitectural indices. For dose optimization, the animals were pretreated with different doses of ZO for a period of 2 weeks before the inoculation of glioma cells (1 × 105/10 µL phosphate‐buffered saline) in the caudate region of rat brain and the treatment with ZO continued for 4 more weeks post implantation. In vitro studies were done to assess the radical scavenging activity of ZO and also to determine its effects on viability of C6 glioma cells at different concentrations. Glioma‐bearing rats showed significant alterations in memory; exploratory and muscular activities which were appreciably improved upon simultaneous supplementation of ZO administered at a dose of 50 mg/kg body weight and were also visible even at a higher dose. Glioma‐bearing rats revealed a significant increase in reactive oxygen species, protein carbonyl contents, and lipid peroxidation, but showed a significant decrease in reduced glutathione and antioxidative enzymes in the brain tissue. Interestingly, all the biochemical indices and altered brain histoarchitecture displaying cellular atypia and hyperplasia showed appreciable improvement when supplemented with ZO at a dose of 50 mg/kg body weight. [ABSTRACT FROM AUTHOR]

Salmonella enterica serovar Typhi is a significant cause of typhoid fever and a major public health problem. The ability of S. Typhi to form biofilms on living and non-living surfaces results in antibiotic resistance and poses a major challenge in health care. In this study, we assessed the ability of zingerone alone and in combination with antibiotics against the motility phenotypes and biofilm-forming ability of S. Typhi. Results showed that zingerone effectively reduced the swimming, swarming, and twitching phenotypes and exhibited biofilm inhibition potential. Moreover, zingerone enhanced the antibiofilm activity of ciprofloxacin and kanamycin. Microscopic analysis revealed a thinner biofilm in the presence of zingerone, which may have enhanced the antibiofilm efficacy of the antibiotics. The microscopic analysis showed that the presence of zingerone resulted in a reduction in the thickness of the biofilm, potentially increasing the antibiofilm efficacy of the antibiotics. In silico molecular docking and simulation studies further indicated that zingerone may bind to the fimbriae subunits (FimA, FimC, FimH, and FimY) of S. Typhi and form stable interactions. These findings provide important insights into the potential of zingerone to target biofilm-associated Salmonella infections. Further research is considered a promising option for designing innovative approaches to prevent infections associated with biofilms. Schematic representation of the role of zingerone in biofilm, motility inhibition and molecular interactions with biofilm associated proteins. [ABSTRACT FROM AUTHOR]

Objective(s): Sodium arsenite (SA) exposure is toxic to the body. Zingerone (ZNG) is a flavonoid with many biological properties found naturally in honey and plants. This study aimed to determine the effects of ZNG on SA-induced rat lung toxicity. Materials and Methods: Thirty-five male Sprague rats were divided into Control, SA, ZNG, SA+ZNG25, and SA+ZNG50 groups (n=7). SA 10 mg/kg and ZNG were administered at two doses (25 and 50 mg/kg) (orally, 14 days). Analysis of oxidative stress, inflammation damage, apoptosis damage, and autophagic damage markers in lung tissue were determined by biochemical and histological methods. Results: The administration of ZNG reduced oxidative stress by increasing SA-induced decreased antioxidant enzyme activities, increasing Nrf-2, HO-1, and NQO1, and decreasing MDA level. ZNG administration reduced inflammation marker levels. Anti-apoptotic Bcl-2 increased and apoptotic Bax and Caspase-3 decreased with ZNG. ZNG promoted the regression of autophagy by reducing Beclin-1, LC3A, and LC3B levels. Conclusion: Evaluating all data showed that SA caused toxic damage to lung tissue by increasing inflammation, apoptosis, autophagy, and oxidant levels, whereas ZNG had a protective effect by reducing this damage. [ABSTRACT FROM AUTHOR]

Targeting Fibroblast-like synoviocytes (FLSs) is an attractive complementary approach for RA therapy. This study aimed to investigate the inhibitory effects of zingerone on TNFα-induced arthritic FLSs. MTS, EdU, wound healing, DHE staining and real-time PCR were used to determine the effects of zingerone on the destructive behaviors of arthritic FLSs induced by TNFα. Western blot analysis was used to analyze cell signaling pathways. Zingerone treatment significantly inhibited TNFα-induced proliferation, migration, ROS formation and pro-inflammatory cytokines expression of FLSs. Molecular mechanism studies revealed that zingerone could suppress TNFα-induced activations of MAPKs (ERK, JNK and p38) in arthritic FLSs. Zingerone attenuated pathological features of FLSs via MAPKs pathways, indicating its potential as a complementary or alternative drug for RA therapy. [ABSTRACT FROM AUTHOR]

Objective To investigate the efficacy of zingerone (Zin) on dextran sodium sulfate (DSS)-induced colitis in mice and its potential immunomodulatory mechanism. Methods SPF C57BL/6 male mice aged 6 to 8 weeks were divided into control group (Water), model group (DSS), and Zin intervention group (DSS+Zin), with 5 mice in each group. Acute ulcerative colitis model was constructed using DSS solution, and the changes in body weight, disease activity index (DAI), colon length, and histopathological scores were compared among the groups. RT-qPCR and corresponding reagents and kits were employed to detect the mRNA and protein expression of inflammatory cytokines in the colonic tissue, respectively. The effects of Zin on T cell subsets and on the expression of transcription factor RORγt were determined by flow cytometry in vitro and in vivo. Moreover, the transcriptional activity of RORγt and activity of Rorc promoter were examined using dual-luciferase reporter system. Results As compared with the control group, the mice in the DSS group showed shorter colon length, higher scores of DAI and histopathological index (P < 0.05), with increased mRNA levels of IL-17A, IL-21, IL-22, IL-6, IL-1 β and IFN-γ (P < 0.05), while decreased mRNA level of TGF-β(P < 0.05). The protein levels of IL-17A, IL-17F, IL-22, and IFN-γ were also upregulated in the DSS group (P < 0.05). However, Zin treatment significantly relieved the above clinical symptoms and reversed the expression of above inflammatory factors (P < 0.05). Flow cytometry indicated that Zin inhibited the differentiation of Th17 cells and the expression of RORγt, and promoted the differentiation of Treg cells both in vitro and in vivo (P < 0.05), but the differentiation of Th1 subset was not affected. The dual-luciferase reporter assay demonstrated that the transcriptional activity of RORγt and Rorc promoter activity were remarkably suppressed after Zin treatment (P < 0.05). Conclusion Zin alleviates DSS-induced colitis in mice by regulating the balance of Th17/Treg cells and inhibiting RORγt expression.

Background and Objective: The Osteoblast differentiation is an essential process that causes bone stability and homeostasis. Zingerone (ZG) 4-(4-hydroxy-3-methoxyphenyl)-2-butanone isolated from the ginger plant is involved in many biological processes and can be used to treat diseases as an anti-inflammatory and antidiabetic agent. This study aims to identify ZG potential to bone tissue regeneration by investigating the effect of Zingerone on human umbilical cord stem cells (hUC-MSCs) and their differentiation into osteoblasts. Methods: In this cross-sectional study, the effect of Zingerone toxicity on 2×106 hUC-MSCs cells was investigated in 4 groups; one control group without any ZG and 3 groups threated with 50µM, 100µM and 200µM ZG. Cell viability was evaluated by the MTT method after 24, 48 and 72 hours. The gene expression of miR-590 and Smad7 and differentiation markers such as Osterix (OSX) and runt-related transcription factor 2 (RUNX2) were investigated by quantitative real-time polymerase chain reaction (qRT-PCR). The expression level of this enzyme was checked by an alkaline phosphatase (ALP) reaction. Findings: Zingerone has significant proliferative effects on hUC-MSCs cells in 200µM (p

Polymeric permselective films are frequently used for amperometric biosensors to prevent electroactive interference present in the target matrix. Phenylenediamines are the most commonly used for the deposition of shielding polymeric films against interfering species; however, even phenolic monomers have been utilized in the creation of these films for microsensors and biosensors. The purpose of this paper is to evaluate the performances of electrosynthesized polymers, layered by means of constant potential amperometry (CPA), of naturally occurring compound zingerone (ZING) and its dimer dehydrozingerone (ZING DIM), which was obtained by straight oxidative coupling reaction. The polymers showed interesting shielding characteristics against the main interfering species, such as ascorbic acid (AA): actually, polyZING exhibited an AA shielding aptitude comprised between 77.6 and 99.6%, comparable to that obtained with PPD. Moreover, a marked capability of increased monitoring of hydrogen peroxide (HP), when data were compared with bare metal results, was observed. In particular, polyZING showed increases ranging between 55.6 and 85.6%. In the present work, the molecular structures of the obtained polymers have been theorized and docking analyses were performed to understand their peculiar characteristics better. The structures were docked using the Lamarckian genetic algorithm (LGA). Glutamate biosensors based on those polymers were built, and their performances were compared with biosensors based on PPD, which is the most widespread polymer for the construction of amperometric biosensors. [ABSTRACT FROM AUTHOR]

Periodontitis is caused by the inflammation of tooth-supporting tissue by pathogens such as Aggregatibacter actinomycetemcomitans. Interleukin-1β (IL-1β), a pro-inflammatory cytokine, triggers a series of inflammatory reactions and promotes bone resorption. The aim of this study was to examine the molecular mechanism and anti-inflammatory function of zingerone, a dietary phenolic found in Zingiber officinale, on periodontal inflammation induced by A. actinomycetemcomitans. Zingerone attenuated A. actinomycetemcomitans-induced nitric oxide (NO) production by inhibiting the expression of inducible nitric oxide synthase (iNOS) in THP-1 macrophages. Zingerone also inhibited the expression of tumor necrosis factor (TNF)-α, IL-1β, and their signal pathway molecules including the toll-like receptor (TLR)/mitogen-activated protein kinase (MAPKase). In particular, zingerone suppressed the expression of absent in melanoma 2 (AIM2) inflammasome components on IL-1β production. Moreover, zingerone enhanced autophagosome formation and the expressions of autophagy-associated molecules. Interestingly, zingerone reduced the intracellular survival of A. actinomycetemcomitans. This was blocked by an autophagy inhibitor, which reversed the decrease in IL-1β production by zingerone. Finally, zingerone alleviated alveolar bone absorption in an A. actnomycetemcomitans-induced periodontitis mice model. Our data suggested that zingerone has potential use as a treatment for periodontal inflammation induced by A. actinomycetemcomitans. [ABSTRACT FROM AUTHOR]

Background: Our environment exposes us to various neurotoxins that can invariably affect cognitive ability. Aim and Objectives: To evaluate the modulatory role of zingerone on cadmium induced memory impairment, oxidative stress and apoptosis on the hippocampus of male Wistar rats. Material and Methods: Thirty (30) adult male Wistar rats used were grouped into six (6) groups, (n = 5) as follows; Control group (A), Group B was given 5 mg/kg of cadmium for twenty one days, Group C received 200 mg/kg b.w.t. of zingerone (C) for 21 days, the treatment study Groups D-F were given 5 mg/kg of cadmium for seven days and treated using varying dose of zingerone for 14 days (50 mg/kg, 100 mg/kg and 200 mg/kg b.w.t.). Zingerone and cadmium chloride were dissolved in normal saline, the route of administration was oral and the administration period was twenty-one days. Y–maze neurobehavioral test was used to evaluate spatial activity and spatial memory using number of arm entries, time spent in novel arm, number of correct spontaneous alternation and percentage alternation. On day 22, the animals were sacrificed, brain was removed and samples collected for biochemical analysis, histological and immunohistochemical investigations. Results: Administration of zingerone resulted in significant increased (p< 0.05) time in novel arm, number of arm entries, spontaneous alternations and percentage alternations when compared to rats that received cadmium only. This is indicating that zingerone improve the memory ability of Wistar rats exposed to cadmium. Cadmium intoxication increased the levels of Superoxide Dismutase (SOD), Catalase (CAT), Glutathione Peroxide (GPx) and decreased level of Malondialdehyde (MDA) as shown in Group B, however this was attenuated in Groups C-F that were treated with zingerone. Result also showed neuronal cell death, degenerative changes fragmented pyramidal and granular layer, loss of cytoplasmic content and pyknotic nuclei, evident in the histology and immunohistochemical study of the hippocampus of rats in Group B; however, these effects were reversed by zingerone in all Groups D-F. Conclusion: These findings suggest that zingerone may protect against cadmium mediated memory impairment, apoptosis and oxidative stress in the hippocampus.

Trastuzumab (TZB) is a new medicine, used to treat cancers of the breast and stomach. However, the cardiotoxic potential of this drug edges out its clinical advantages. The present study was designed to find out the effect of zingerone against trastuzumab-mediated cardiotoxicity in rats. In this study, five groups of rats with eight animals in each group were used. Group 1 was treated with normal saline, as a normal control (NC); Group 2 was treated with TZB (6 mg/kg/week-for five weeks) intraperitoneally as a toxic control. Groups 3 and 4 were pre-treated with zingerone (50 and 100 mg/kg, as per their body weight orally) along with five doses of TZB for five weeks, and Group 5 was treated with zingerone (100 mg/kg, body weight orally) as a control. TZB treatment showed cardiotoxicity as evidenced by increased levels of aspartate aminotransferase (AST), creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), and lipid peroxidation (LPO) and decreased level of glutathione (GSH), and antioxidant enzymes such as glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-s- transferase (GST), catalase (CAT), and superoxide dismutase (SOD) activities. Zingerone pre-treatment significantly decreased the levels of AST, CK-MB, LDH, and LPO and increased GSH and antioxidant enzymes content toward their normal level. In the TZB-alone administered group, inflammatory cytokines (IL-2 and TNF-α) levels were also elevated. Pre-treatment with zingerone restored the level of IL-2 and TNF-α toward normal level. The current findings undoubtedly demonstrated zingerone's cardioprotective nature against TZB-mediated cardiotoxicity in rats with the evidence of histopathological recall. [ABSTRACT FROM AUTHOR]

Background: This study aimed to uncover the potential effects of zingerone (ZIN), one of the bioactive compounds in ginger, on the development of obesity as well as the mechanisms responsible for these effects in C57BL/6J mice fed with a high‐fat diet (HFD). Results: Supplementation with 0.2% (wt/wt) zingerone for 16 weeks significantly reduced the final body weight, liver weight, and epididymal white adipose tissue (eWAT) weight without changing the food intake of the mice when compared with the HFD group. The hyperlipidemia of HFD‐fed mice was ameliorated after zingerone administration, including decreased plasma triacylglycerol (TG) and total cholesterol (TC) level. The lipid content in liver was lower and the adipocyte size in eWAT and inguinal white adipose tissue (iWAT) was smaller in HFD + ZIN‐fed mice compared with HFD group. Zingerone also binds with nuclear hormone receptor peroxisome proliferator‐activated receptor alpha (PPARα) with an optimal docking energy of −7.31 kJ/mol. Uncoupling protein 1 (UCP1), PPAR‐γ coactivator‐1α (PGC‐1α), and PR domain containing 16 (PRDM16), the downstream genes of PPAR which are related to thermogenic function of adipocytes, were significantly increased in both brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT) after zingerone administration, in comparison with HFD fed mice. Zingerone intake also restructured the community composition of gut microbiota. The ratio of Firmicutes to Bacteroidetes was decreased, and the relative abundance of Akkermansia_mucinphila was increased. Conclusion: Zingerone can attenuate obesity and related symptoms in HFD‐fed mice, probably through the modulation of PPARα‐thermogenesis‐gut microbiota interactions. © 2022 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

The rapid increase in agricultural waste is rising across the globe and is a big environmental challenge. The utilization of ginger waste as a valuable product is very limited. The up-cycling of ginger waste is an effective approach for valorization. Ginger waste contains many bio-active compounds. These bioactive compounds possess various functional and bio-active properties. The literature has indicated that ginger and its waste is a rich source of shogaol zingerone and gingerols, these bioactive components contribute to pungency and aroma characteristics These compounds have a wide range of antimicrobial, antioxidant, and anti-inflammatory properties. Furthermore, these have a key role in skin health and the digestive system. The current review consolidates the compositional, functional, medicinal, bioactive, and health-endorsing attributes of ginger waste. The use of ginger wastes for the development of various functional and nutraceutical products is also in the limelight of this paper. [ABSTRACT FROM AUTHOR]

Alcohol intake at different developmental stages can lead to the development of alcohol-induced fatty liver disease (AFLD). Zingerone (ZO) possess hepato-protective properties; thus, when administered neonatally, it could render protection against AFLD. This study aimed to evaluate the potential long-term protective effect of ZO against the development of AFLD. One hundred and twenty-three 10-day-old Sprague–Dawley rat pups (60 males; 63 females) were randomly assigned to four groups and orally administered the following treatment regimens daily during the pre-weaning period from postnatal day (PND) 12–21: group 1—nutritive milk (NM), group 2—NM +1 g/kg ethanol (Eth), group 3—NM + 40 mg/kg ZO, group 4—NM + Eth +ZO. From PND 46–100, each group from the neonatal stage was divided into two; subgroup I had tap water and subgroup II had ethanol solution as drinking fluid, respectively, for eight weeks. Mean daily ethanol intake, which ranged from 10 to 14.5 g/kg body mass/day, resulted in significant CYP2E1 elevation (p < 0.05). Both late single hit and double hit with alcohol increased liver fat content, caused hepatic macrosteatosis, dysregulated mRNA expression of SREBP1c and PPAR-α in male and female rats (p < 0.05). However, neonatal orally administered ZO protected against liver lipid accretion and SREBP1c upregulation in male rats only and attenuated the alcohol-induced hepatic PPAR-α downregulation and macrosteatosis in both sexes. This data suggests that neonatal orally administered zingerone can be a potential prophylactic agent against the development of AFLD. [ABSTRACT FROM AUTHOR]

Background: Our environment exposes us to various neurotoxins that can invariably affect cognitive ability. Aim and Objectives: To evaluate the modulatory role of zingerone on cadmium induced memory impairment, oxidative stress and apoptosis on the hippocampus of male Wistar rats. Material and Methods: Thirty (30) adult male Wistar rats used were grouped into six (6) groups, (n = 5) as follows; Control group (A), Group B was given 5 mg/kg of cadmium for twenty one days, Group C received 200 mg/kg b.w.t. of zingerone (C) for 21 days, the treatment study Groups D-F were given 5 mg/kg of cadmium for seven days and treated using varying dose of zingerone for 14 days (50 mg/kg, 100 mg/kg and 200 mg/kg b.w.t.). Zingerone and cadmium chloride were dissolved in normal saline, the route of administration was oral and the administration period was twenty-one days. Y -maze neurobehavioral test was used to evaluate spatial activity and spatial memory using number of arm entries, time spent in novel arm, number of correct spontaneous alternation and percentage alternation. On day 22, the animals were sacrificed, brain was removed and samples collected for biochemical analysis, histological and immunohistochemical investigations. Results: Administration of zingerone resulted in significant increased (p< 0.05) time in novel arm, number of arm entries, spontaneous alternations and percentage alternations when compared to rats that received cadmium only. This is indicating that zingerone improve the memory ability of Wistar rats exposed to cadmium. Cadmium intoxication increased the levels of Superoxide Dismutase (SOD), Catalase (CAT), Glutathione Peroxide (GPx) and decreased level of Malondialdehyde (MDA) as shown in Group B, however this was attenuated in Groups C-F that were treated with zingerone. Result also showed neuronal cell death, degenerative changes fragmented pyramidal and granular layer, loss of cytoplasmic content and pyknotic nuclei, evident in the histology and immunohistochemical study of the hippocampus of rats in Group B; however, these effects were reversed by zingerone in all Groups D-F. Conclusion: These findings suggest that zingerone may protect against cadmium mediated memory impairment, apoptosis and oxidative stress in the hippocampus. [ABSTRACT FROM AUTHOR]

Carfilzomib (CFZ) is an anticancer medication acting as a selective proteasome inhibitor. However, it can cause cardiovascular problems, increasing mortality and morbidity. This study aimed to investigate whether zingerone (ZRN) could help reduce carfilzomib-induced cardiotoxicity in Wistar albino rats. Rats were divided into five groups of six animals each. The first group received normal saline as a control (NC); the second group received multiple doses (six) of CFZ (4 mg/kg) intraperitoneally (IP); the third and fourth groups received zingerone (50 mg/kg and 100 mg/kg oral) along with six doses of CFZ for 16 days; and the fifth group received only 100 mg/kg zingerone orally. Hematological, biochemical, oxidative stress, and histopathological studies confirmed the findings of CFZ-induced cardiotoxicity. We found that ZRN significantly attenuated the effects of CFZ on oxidative stress by enhancing the antioxidant properties of glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD). Additionally, ZRN reduces inflammatory cytokines and apoptotic markers, such as IL-1β, IL-6, TNFα, and caspase-3. Overall, zingerone prevents carfilzomib-induced cardiotoxicity in rats, as evidenced by histopathological studies. [ABSTRACT FROM AUTHOR]

Currently, various anti‐inflammatory drugs are used in intestinal bowel disease (IBD) treatment as first‐line management therapies. Although beneficial effects were observed with these drugs, unwanted exposure to healthy tissue causes side‐effects. Therefore, targeted delivery of anti‐inflammatory drugs to the inflamed tissue is still an unmet need. Herein, we have developed solid lipid nanoparticles with negative surface charge that can specifically adhere to transferrin, a protein that overexpressed at the inflamed tissue. Zingerone, a natural product based anti‐inflammatory agent, has been encapsulated into solid lipid nanoparticles (Zin‐SLNPs) and protected from the degradation by stomach and intestinal fluids. The Zin‐SLNPs consists of 250–350 nm in size, have negative surface charge (‐44.08 mV). These Zin‐SLNPs have shown appreciable cyto‐compatibility, they did not show any cytotoxicity even as high as 1000 μM concentration. Native zingerone and zingerone that released from Zin‐SLNPs show efficient anti‐inflammatory property by reducing the production of pro‐inflammatory cytokines from lipopolysaccharide (LPS)‐induced RAW 264.7 macrophages, in vitro. Based on these results, in the future studies, Zin‐SLNPs could be tested for their potential therapeutic efficacy in ulcerative colitis in vivo model. [ABSTRACT FROM AUTHOR]

Long-term exposure to arsenic has been linked to several illnesses, including hypertension, diabetes, hepatic and renal diseases and cardiovascular malfunction. The aim of the current investigation was to determine whether zingerone (ZN) could shield rats against the hepatotoxicity that sodium arsenite (SA) causes. The following five groups of thirty-five male Sprague Dawley rats were created: I) Control; received normal saline, II) ZN; received ZN, III) SA; received SA, IV) SA + ZN 25; received 10 mg/kg body weight SA + 25 mg/kg body weight ZN, and V) SA + ZN 50; received 10 mg/kg body weight SA + 50 mg/kg body weight ZN. The experiment lasted 14 days, and the rats were sacrificed on the 15th day. While oxidative stress parameters were studied by spectrophotometric method, apoptosis, inflammation and endoplasmic reticulum stress parameters were measured by RT-PCR method. The SA disrupted the histological architecture and integrity of the liver and enhanced oxidative damage by lowering antioxidant enzyme activity, such as those of glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), glutathione (GSH) level and increasing malondialdehyde (MDA) level in the liver tissue. Additionally, SA increased the mRNA transcript levels of Bcl2 associated x (Bax), caspases (−3, −6, −9), apoptotic protease-activating factor 1 (Apaf-1), p53, tumor necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB), interleukin-1β (IL-1β), interleukin-6 (IL-6), c-Jun NH2-terminal kinase (JNK), mitogen-activated protein kinase 14 (MAPK14), MAPK15, receptor for advanced glycation endproducts (RAGE) and nod-like receptor family pyrin domain-containing 3 (NLRP3) in the liver tissue. Also produced endoplasmic reticulum stress by raising the mRNA transcript levels of activating transcription factor 6 (ATF-6), protein kinase RNA-like ER kinase (PERK), inositol-requiring enzyme 1 (IRE1), and glucose-regulated protein 78 (GRP-78). These factors together led to inflammation, apoptosis, and endoplasmic reticulum stress. On the other hand, liver tissue treated with ZN at doses of 25 and 50 mg/kg showed significant improvement in oxidative stress, inflammation, apoptosis and endoplasmic reticulum stress. Overall, the study's data suggest that administering ZN may be able to lessen the liver damage caused by SA toxicity. [Display omitted] • Zingerone alleviated sodium arsenite-induced hepatotoxicity. • Zingerone modulated bisphenol A-induced apoptosis and endoplasmic reticulum stress. • Zingerone reduced bisphenol A-induced oxidative stress and inflammation. [ABSTRACT FROM AUTHOR]

Abstract Background As individuals live longer, elderly populations can be expected to face issues. This pattern urges researchers to investigate the aging concept further to produce successful anti-aging agents. In the current study, the effects of Zingerone (a natural compound) on epidermal tissues were analyzed using a bioinformatics approach. Methods For this purpose, we chose the GEO dataset GSE133338 to carry out the systems biology and systems pharmacology approaches, ranging from identifying the differentially expressed genes to analyzing the gene ontology, determining similar structures of Zingerone and their features (i.e., anti-oxidant, anti-inflammatory, and skin disorders), constructing the gene–chemicals network, analyzing gene–disease relationships, and validating significant genes through the evidence presented in the literature. Results The post-processing of the microarray dataset identified thirteen essential genes among control and Zingerone-treated samples. The procedure revealed various structurally similar chemical and herbal compounds with possible skin-related effects. Additionally, we studied the relationships of differentially expressed genes with skin-related diseases and validated their direct connections with skin disorders the evidence available in the literature. Also, the analysis of the microarray profiling dataset revealed the critical role of interleukins as a part of the cytokines family on skin aging progress. Conclusions Zingerone, and potentially any constituents of Zingerone (e.g., their similar compound scan functionality), can be used as therapeutic agents in managing skin disorders such as skin aging. However, the beneficial effects of Zingerone should be assessed in other models (i.e., human or animal) in future studies.

Inflammation highly fluctuates, and the level of inflammation varies in patients. Therefore, as opposed to conventional sustained release systems, delivering drugs in response to the inflammation and inflammation‐associated enzymes may have a beneficial effect in managing inflammatory diseases such as arthritis. Hence, we have developed an inflammation‐associated enzymes‐responsive hydrogel system. Zingerone is an active component in ginger and is known to exhibit a beneficial effect. We have studied the zingerone anti‐inflammatory properties using macrophages, and zingerone‐encapsulated self‐assembled hydrogels have been prepared and characterized in detail. Additionally, we have demonstrated that inflammation‐associated enzymes such as lipase could trigger the release of zingerone in a responsive manner, in vitro. In vivo efficacy of zingerone‐encapsulated hydrogel will be evaluated in preclinical models in the future. [ABSTRACT FROM AUTHOR]

Zingerone is a non‐volatile compound found mainly in dried ginger. Zingerone increases the expression of osteogenic markers and has antioxidant effects. A previous study showed that zingerone accelerated osteoblast differentiation by suppressing the expression of Smad7, a member of the inhibitory Smad (I‐Smad) family. However, it is not known if zingerone can induce osteoblast differentiation by regulating Smad1/5/9, a member of the receptor‐regulated Smad (R‐Smad) family. In addition, osteoblast differentiation induced by Smad1/5/9 mediated increases in the expression of heme oxygenase 1 (HO‐1) has not been reported. This study investigated the effects of zingerone on osteoblast differentiation and confirmed the relationship between Smad1/5/9 and HO‐1. Zingerone increased the expression of osteogenic genes including runt‐related transcription factor 2 (Runx2), distal‐less homeobox (Dlx5) and osteocalcin (OC) and also promoted Smad1/5/9 phosphorylation. Interestingly, HO‐1 expression was also elevated by zingerone, and an inhibitor of HO‐1 (Sn[IV] protoporphyrin IX dichloride [SnPP]) suppressed the zingerone‐induced increase in HO‐1 expression and expression of osteogenic marker genes such as Dlx5, Runx2 and OC. Protein phosphatase 2A Cα (PP2A Cα, an inhibitor of Smad1/5/9) suppressed the zingerone‐induced increase in HO‐1 expression and expression of osteogenic marker genes. The zingerone‐induced increase in HO‐1 luciferase activity was suppressed by PP2A Cα. Taken together; our data demonstrate that zingerone promotes osteoblast differentiation by increasing Smad1/5/9 mediated HO‐1 expression. [ABSTRACT FROM AUTHOR]

The tropical fruit fly (Diptera: Tephritidae: Dacinae) fauna of Australia has been reasonably well studied using the male lures methyl eugenol and cue-lure. However, there has been little sampling of biodiverse Gondwanan rainforests of eastern Australia. Additionally, recently identified male lures have trapped new, or previously non-responsive species in northern Australia, south-east Asia and the Pacific. We wanted to determine if previously unknown species exist in these biodiverse and poorly sampled areas. Therefore, we conducted fruit fly trapping surveys using the male lures methyl eugenol, cue-lure, isoeugenol, methyl isoeugenol, dihydroeugenol, zingerone and protein baits. Trapping targeted previously known locations of rare species, and remnant Gondwanan forests of eastern Australia between 2017 and 2019. We recorded new distributions for Bactrocera aurea (May) and occurrences of rare species Bactrocera mutabilis (May) and Bactrocera brunnea (Perkins and May). This represented the first record of Bactrocera brunnea in over 25 years. Additionally, new lure responses were recorded for previously non-responsive Bactrocera mutabilis, and a single Bactrocera phaleriae (May); both trapped with isoeugenol. Bactrocera (Bactrocera) clarkei sp. n., is described from Couchy Creek Nature Reserve and the Border Ranges National Park, New South Wales. [ABSTRACT FROM AUTHOR]

Adriamycin (ADM), known as doxorubicin, is one of the abundantly consumed and extremely efficient chemotherapeutic agents with subsequent health side effects as nephrotoxicity. Zingerone (ZG) is a phenolic compound present in ginger and possesses many therapeutic effects. The purpose of this study is to test the potential modulatory roles of ZG against ADM mediated nephrotoxicity. Thirty-two male Swiss albino mice were randomly assigned into four groups as follow: Control group (CNT); ZG group, which received an oral dose of 25 mg/kg b.w/day of ZG; ADM group, which are injected with single dose of ADM (25 mg/kg b.w, IV); and ZG/ADM group, this group received dual treatments with the same respective administration routes and doses. After 21 days, serum and kidneys were collected for further examinations. Co-administration of ZG along with ADM significantly lowered serum levels of urea, creatinine, kidney injury molecule-1 and lactate dehydrogenase activity, unlike ADM group. ZG significantly reduced kidney levels of malondialdehyde, nitric oxide and 8-hydroxy-2-deoxyguanosine. Moreover, it retained nuclear factor erythroid 2-related factor 2 mRNA expressions, and glutathione level, as well as catalase and superoxide dismutase activities compared to ADM. Furthermore, ZG permitted the reduction of renal levels for pro-inflammatory cytokines (comprising tumor necrosis factor-α, interleukin-1β, interleukin-6 and nuclear factor kappa B) as well as myeloperoxidase activity, and hence ZG suppresses inflammation induced by ADM. Collectively, our findings indicated that ZG exhibits potential nephroprotective effect toward ADM-mediated nephrotoxicity. [ABSTRACT FROM AUTHOR]

Background: Arsenic (As), a poisonous metalloid, is widely distributed in air, water, and soil and has been associated with the occurrence of diabetes and liver toxicity. Zingerone (ZNG), one of the active compounds in ginger, has several pharmacological benefits such as antioxidant and anti-inflammatory characteristics. The objective of this research was to assess the protective role of ZNG against arsenic (As)-induced glucose intolerance (GI) and hepatotoxicity in mice., Methods: Male NMRI mice were treated with ZNG (25, 50, and 100 mg/kg, oral gavage for 29 days) before As administration (10 mg/kg, oral gavage for 29 days). On the 29th day, fasting blood glucose (FBG) and glucose tolerance test were measured. The animals were euthanized (day 30), and samples from blood and tissue (liver and pancreas) were gathered for further evaluations., Results: Administration of ZNG inhibited As-induced elevation of FBG and GI. Moreover, hepatic tissue damage and decreased Langerhans islets' diameter caused by As administration were improved by ZNG treatment. Pretreatment with ZNG attenuated the elevation of serum liver enzymes induced by As (alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase). Also, the reduction in total thiol content, as well as the decline in antioxidant enzyme activities (catalase, superoxide dismutase, and glutathione peroxidase) and the increase in lipid peroxidation marker (thiobarbituric acid reactive substances) in the liver tissue of As-exposed mice were reversed in ZNG-treated mice. Furthermore, ZNG prevented the increase of hepatic inflammatory markers (nitric oxide and tumor necrosis factor-alpha levels, and protein expression of nuclear factor-kappa B) and apoptosis-related marker (caspase-3 protein expression) in As-treated mice., Conclusions: This study has provided evidence indicating that ZNG can act as a beneficial agent in preventing As-induced hepatotoxicity and diabetes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Polymeric permselective films are frequently used for amperometric biosensors to prevent electroactive interference present in the target matrix. Phenylenediamines are the most commonly used for the deposition of shielding polymeric films against interfering species; however, even phenolic monomers have been utilized in the creation of these films for microsensors and biosensors. The purpose of this paper is to evaluate the performances of electrosynthesized polymers, layered by means of constant potential amperometry (CPA), of naturally occurring compound zingerone (ZING) and its dimer dehydrozingerone (ZING DIM), which was obtained by straight oxidative coupling reaction. The polymers showed interesting shielding characteristics against the main interfering species, such as ascorbic acid (AA): actually, polyZING exhibited an AA shielding aptitude comprised between 77.6 and 99.6%, comparable to that obtained with PPD. Moreover, a marked capability of increased monitoring of hydrogen peroxide (HP), when data were compared with bare metal results, was observed. In particular, polyZING showed increases ranging between 55.6 and 85.6%. In the present work, the molecular structures of the obtained polymers have been theorized and docking analyses were performed to understand their peculiar characteristics better. The structures were docked using the Lamarckian genetic algorithm (LGA). Glutamate biosensors based on those polymers were built, and their performances were compared with biosensors based on PPD, which is the most widespread polymer for the construction of amperometric biosensors.

Periodontitis is caused by the inflammation of tooth-supporting tissue by pathogens such as Aggregatibacter actinomycetemcomitans. Interleukin-1β (IL-1β), a pro-inflammatory cytokine, triggers a series of inflammatory reactions and promotes bone resorption. The aim of this study was to examine the molecular mechanism and anti-inflammatory function of zingerone, a dietary phenolic found in Zingiber officinale, on periodontal inflammation induced by A. actinomycetemcomitans. Zingerone attenuated A. actinomycetemcomitans-induced nitric oxide (NO) production by inhibiting the expression of inducible nitric oxide synthase (iNOS) in THP-1 macrophages. Zingerone also inhibited the expression of tumor necrosis factor (TNF)-α, IL-1β, and their signal pathway molecules including the toll-like receptor (TLR)/mitogen-activated protein kinase (MAPKase). In particular, zingerone suppressed the expression of absent in melanoma 2 (AIM2) inflammasome components on IL-1β production. Moreover, zingerone enhanced autophagosome formation and the expressions of autophagy-associated molecules. Interestingly, zingerone reduced the intracellular survival of A. actinomycetemcomitans. This was blocked by an autophagy inhibitor, which reversed the decrease in IL-1β production by zingerone. Finally, zingerone alleviated alveolar bone absorption in an A. actnomycetemcomitans-induced periodontitis mice model. Our data suggested that zingerone has potential use as a treatment for periodontal inflammation induced by A. actinomycetemcomitans.

BACKGROUND: Ulcerative colitis (UC) is a relapsing and chronic inflammatory disease of the gastrointestinal tract, which seriously threatens human health. Zingerone (ZO) has been proven to be effective for many diseases. The purpose of this study is to investigate the protective effects and potential mechanisms of ZO extracted from ginger on dextran sulfate sodium (DSS)‐induced mouse ulcerative colitis (UC). RESULTS: The results showed that ZO alleviated the weight loss of UC model mice, reduced the disease activity index scores, and inhibited the shortening of colon length. ZO also improved DSS‐induced pathological changes in colon tissue and inhibited the secretion of pro‐inflammatory cytokines in colon and mesenteric lymph nodes. Further mechanism analysis found that ZO inhibited DSS‐induced nuclear factor‐κB pathway activation, and regulated peroxisome proliferator‐activated receptor γ (PPARγ) expression. To further explore whether PPARγ was involved in the anti‐UC effect of ZO, PPARγ inhibitor GW9662 was used. Although ZO also showed a protective effect on GW9662‐treated colitis mice, the protective role was significantly weakened. Importantly, the administration of GW9662 significantly aggravated UC compared with the ZO + DSS group. In addition, we preliminarily found that ZO had the effects of inhibiting DSS‐induced oxidative stress, maintaining intestinal barrier, and inhibiting the content of LPS and the population of Escherichia coli. CONCLUSIONS: These results indicated that supplementation with ZO might be a new dietary strategy for the treatment of UC. © 2022 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Pseudomonasaeruginosa, a WHO-prioritized multidrug-resistant Gram-negative bacteria, is one of the frequently implicated pathogen in surgical site infection (SSI) due to its virulence phenotypes and biofilm-forming ability. In the present study, cell-free supernatant (CFS) and biogenics (organic acids and precipitated protein fraction) of indigenous potential probiotic, Lactobacillus fermentum PUM both alone and in combination with zingerone were found to inhibit pyocyanin, pyochelin, protease, elastase, the virulence factors, and motility of P. aeruginosa PAO1. Furthermore, scanning electron microscopy indicated that biofilm formation was attenuated maximally by CFS of L. fermentum combined with zingerone. In vivo study revealed reduced P. aeruginosa burden, suppuration at surgical site vis-a-vis reduced levels of oxidants, pro-inflammatory cytokines, ameliorated anti-oxidants, and healed infected surgical site compared with counter controls. In totality, combination of L. fermentum PUM-derived biogenics and zingerone could be employed to treat P. aeruginosa-induced SSI that needs to be correlated clinically. [ABSTRACT FROM AUTHOR]

Previous studies have proved that zingerone was a therapeutic agent for many tumors. Metadherin (MTDH) acts as an oncogene and is involved in tumorigenesis. The purpose of this study was to explore the underlying mechanism of zingerone that regulates MTDH to affect hepatocellular carcinoma (HCC) progression. CCK-8 assay was performed to detect HCC cell proliferation. The invasion and migration abilities of HCC cells were evaluated using Transwell assay. The mRNA and protein levels in cells and tissues were measured using qRT-PCR and Western blot assays. Moreover, we established the HCC xenografts nude mice to evaluate the effect of zingerone on tumor growth. We found that zingerone treatment significantly inhibited HCC cell malignant phenotype and tumor growth. Moreover, MTDH was highly expressed in HCC tissues and cell lines and was positively associated with poor overall survival of patients with HCC. Knockdown of MTDH notably suppressed the proliferation, invasion, and migration capacities of HCC cells. Mechanistically, inhibition of MTDH by zingerone impeded the malignant biological behavior of HCC cells by inactivating the PI3K/Akt pathway. These results suggested that zingerone served as an effective therapeutic agent in HCC via blocking the MTDH-mediated PI3K/Akt pathway. [ABSTRACT FROM AUTHOR]

This study was conducted to test the protective potential of Zingerone against a high‐fat diet (HFD)‐mediated non‐alcoholic fatty liver disease (NAFLD) development in rats and examined in this protection is mediated modulating AMP‐activated protein kinase (AMPK). Animals were segregated based on their diet and treatment into four groups (n = 6 each): (a) fed standard diet (STD), (b) treated with Zingerone (100 mg/kg), (c) fed HFD, (d) HFD + Zingerone (100 mg/kg), and (e) HFD + Zingerone (100 mg/kg) + compound c (CC) (an AMPK inhibitor) (0.2 mg/kg). The treatment with Zingerone attenuated the gain in final body weights, preserved liver structure, and downregulated the transcription of Bax and cleaved caspase‐3. In the HFD and STD‐fed rats, Zingerone reduced levels of fasting glucose and insulin and circulatory levels of cholesterol (CHOL) and triglycerides (TGs). Concomitantly, Zingerone enhanced glutathione (GSH) and superoxide dismutase (SOD) levels, depleted levels of malondialdehyde (MDA), and enhanced the nuclear levels of the nuclear factor erythroid 2‐related factor 2 (Nrf2). In addition, it lowered the levels of inflammatory cytokines and the nuclear levels of the nuclear factor kappa beta p65 (NF‐κB p65). All these biochemical changes were associated with an increment in the phosphorylation of AMPK (p‐AMPK) (activation) and reduced mRNA levels of SREBP1 and SREBP2. All observed effects afforded by Zingerone were abolished by CC. In conclusion, Zingerone prevents hepatic oxidative stress, inflammation, and apoptosis by activating AMPK. Practical applications: The findings of this study identified Zingerone, isolated from ginger, as a very effective drug that not only can attenuate fasting hyperglycemia and hyperlipidemia, but also prevent hepatic deposition, steatosis, and oxidative damage induced by high‐fat‐fed rats by activating the AMPK/Nrf2 antioxidant axis and concomitant suppression of SREBP1, SREBp2, and NF‐κB p65. These data list Zingerone as a potent stimulator of AMPK which suggests an effective strategy to treat and alleviate NAFLD and encourages further translational and clinical trials. [ABSTRACT FROM AUTHOR]