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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.

Raspberry ketone is an important ingredient in the flavor and fragrance industries. Due to its low content in fruits and vegetables, the production of natural raspberry ketone using heterologous synthesis in microbial strains is recently attracting increased attention. In this work, a heterologous pathway to produce raspberry ketone from p -coumaric acid, including 4-coumarate: CoA ligase (4CL), benzalacetone synthase (BAS), and raspberry ketone/zingerone synthase (RZS1) from plants, was successfully assembled in Escherichia coli . When the RZS1 gene was introduced into E. coli and co-expressed with two other genes, the intermediate 4-hydroxybenzylidene acetone in the pathway was almost completely transformed into a raspberry ketone. Substituting TB medium for M9 medium increased raspberry ketone titers by 3–4 times. Furthermore, the heterologous pathway was partitioned into two modules; module one produced p -coumaroyl-CoA from p -coumaric acid by 4CL, and module two produced raspberry ketone from coumaroyl-CoA by the action of BAS and RZS1. Optimizing the balanced expression of the two modules, it was shown that moderate expression of module one and high expression of module two was the best combination to enhance raspberry ketone production. The engineered strain CZ-8 reached 90.97 mg/l of raspberry ketone, which was 12 times higher than previously reported. In addition, the preferred approach of the heterologous pathway was related to the heterologous genes from different sources; for example, 4CL from Arabidopsis thaliana seemed to be more suitable for raspberry ketone production than that from Petroselinum crispum . This work paves an alternative way for future economic production of natural raspberry ketone.

Ginger ( Zingiber officinale ) is one of the most widely used natural products consumed as a spice and medicine for treating diabetes, flatulent intestinal colic, indigestion, infertility, inflammation, insomnia, a memory booster, nausea, rheumatism, stomach ache, and urinary tract infections. To date, over 400 bioactive components, such as diarylheptanoids, gingerol analogues, phenylalkanoids, sulfonates, monoterpenoid glycosides, steroids, and terpene compounds have been derived from ginger. Increasing evidence has revealed that ginger possesses a broad range of biological activities, especially protective effects against male infertility, nausea and vomiting, analgesic, anti-diabetic, anti-inflammatory, anti-obesity, and other effects. The pharmacological activities of ginger were mainly attributed to its active phytoconstituents such as 6-gingerol, gingerdiol, gingerol, gingerdione, paradols, shogaols, sesquiterpenes, zingerone, besides other phenolics and flavonoids. In recent years, in silico molecular docking studies revealed that gingerol (6-gingerol, 8-gingerol, and 10-gingerol) and Shogaol (6-shogaol, 8-shogaol, 10-shogaol) had the best binding affinities to the receptor protein in disease conditions such as diabetes, inflammation, obesity, and SARS-CoV-2. Furthermore, some clinical trials have indicated that ginger can be consumed for alleviation of nausea and vomiting induced by surgery, pain, diabetes, obesity, inflammation, male infertility. This review provides an updated understanding of the scientific evidence on the development of ginger and its active compounds as health beneficial agents in future clinical trials.

AbstractInflammation is the body’s response against various pathogens and has a critical role in numerous diseases. Zingerone (Zing), a bioactive substance derived from ginger root, has a variety of pharmacological properties, such as reducing inflammation, and antioxidant effects. We aimed to evaluate the beneficial effects of Zing in a carrageenan-induced inflammation model. Paw edema induced by carrageenan (100 μl of 1%) was used to induce acute inflammation in rats. Different doses of Zing (10, 20, and 40 mg/kg) were administered intraperitoneally. Paw tissue levels of MDA, NO, CAT, SOD, GPx, GSH, COX-2, PGE2, TNF-α, and IL-1β were estimated. Our results showed that Zing, especially at the highest dose of 40 mg/kg, significantly reduced paw swelling in carrageenan-injected animals. Zing significantly increased paw enzymatic and nonenzymatic antioxidants except CAT. It also decreased paw levels of MDA, NO, COX-2, PGE2, TNF-α, and IL-1β. The results of this study show that Zing may provide an alternative for the clinical control of inflammation through antioxidant and anti-inflammatory activities.

Epilepsy is an intricate neurological disease where the neurons are severely affected, leading to the mortality of millions worldwide. Status epilepticus (SE), induced by lithium chloride (LiCl) and pilocarpine, is the most accepted model for epilepsy. The current work aims to unravel the mechanisms underlying the anti-epileptic efficacy of zingerone (an active ingredient of ginger), which has beneficial pharmacological activities on seizure-induced behavioral, histological, neurochemical, and molecular patterns in mice. Zingerone restored cognitive function by diminishing seizure activity, escape latency, and subsequent hippocampal damage manifested in histology. Seizures are associated with local inflammation, redox imbalance, and neural loss, confirmed by the present study of SE, and was attenuated by zingerone treatment. Nuclear factor-kappa B and its downstream signaling molecules (TNF-α, IL-1β, IL-6, NO, MPO) were activated in the LiCl-and-pilocarpine-induced group leading to inflammatory signaling, which was substantially ameliorated by zingerone treatment. The intrinsic apoptotic process was triggered subsequent to SE, as demonstrated by augmentation of cleaved caspase-3, downregulation of Bcl-2. However, zingerone treatment downregulated caspase-3 and upregulated Bcl-2, increasing cell survival and decreasing hippocampal neural death, deciphering involvement of apoptosis in SE. Therefore, zingerone plays an essential role in neuroprotection, probably by precluding oxidative stress, inflammation, and obstructing the mitochondrial pathway of apoptosis.

The available evidences suggest the inherent instability and interconvertibility of [6]-gingerol and [6]-shogaol. However, limited data on their interconversion hinder understanding of their influence on the pharmacokinetic profiles. This study presents the first comprehensive 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. 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. 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. This 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.

Ginger ( Zingiber officinale ) is one of the most well-known spices and medicinal plants worldwide that has been used since ancient times to treat a plethora of diseases including cold, gastrointestinal complaints, nausea, and migraine. Beyond that, a growing body of literature demonstrates that ginger exhibits anti-inflammatory, antioxidant, anti-cancer and neuroprotective actions as well. The beneficial effects of ginger can be attributed to the biologically active compounds of its rhizome such as gingerols, shogaols, zingerone and paradols. Among these compounds, gingerols are the most abundant in fresh roots, and shogaols are the major phenolic compounds of dried ginger. Over the last two decades numerous in vitro and in vivo studies demonstrated that the major ginger phenolics are able to influence the function of various immune cells including macrophages, neutrophils, dendritic cells and T cells. Although the mechanism of action of these compounds is not fully elucidated yet, some studies provide a mechanistic insight into their anti-inflammatory effects by showing that ginger constituents are able to target multiple signaling pathways. In the first part of this review, we summarized the current literature about the immunomodulatory actions of the major ginger compounds, and in the second part, we focused on the possible molecular mechanisms that may underlie their anti-inflammatory effects.

The cumulative damage skin sustains from exposure to environmental stressors throughout life exerts significant effects on skin aging and cancer development. One of the main ways by which environmental stressors mediate their effects within skin is through induction of reactive oxygen species (ROS). In this review, we chronicle the multiple properties by which acetyl zingerone (AZ) as a skincare ingredient can benefit skin (1) by helping manage overproduction of ROS through multiple routes as an antioxidant, physical quencher and selective chelator, (2) by fortifying protection after UV exposure ends to prevent the type of epidermal DNA damage that correlates with development of skin cancer, (3) by modulating matrisome activity and nurturing the integrity of the extracellular matrix (ECM) within the dermis and (4) through its proficient ability to neutralize singlet oxygen, by stabilizing the ascorbic acid precursor tetrahexyldecyl ascorbate (THDC) in the dermal microenvironment. This activity improves THDC bioavailability and may blunt pro-inflammatory effects of THDC, such as activation of type I interferon signaling. Moreover, AZ is photostable and can sustain its properties during UV exposure, in contrast to α-tocopherol. All these properties of AZ translate into measurable clinical benefits to improve the visual appearance of photoaged facial skin and to strengthen the skin’s own defenses against sun damage.

Despite their clinical benefits in cancer treatment, the deleterious effects on heart following chemo/radiotherapy are of increasing importance. Zingerone, a natural polyphenol, possesses multiple biological activities, such as antioxidant and anti-inflammatory. Thus, the current study was designed to assess the potential cardioprotective effects of zingerone against cisplatin or γ-radiation. Zingerone was given by intragastric intubation (25 mg/kg) daily for three successive weeks prior to the induction of cardiotoxicity using a single dose of cisplatin (20 mg/kg, i.p.) or a whole body γ-irradiation at a single dose of 6 Gy. Zingerone pre-treatment significantly reduced the abnormalities in heart histology and the increase in the cardiotoxicity indices, serum lactate dehydrogenase, and creatine kinase-MB activities, as well as plasma cardiac troponin T and B-natriuretic peptide, induced by cisplatin or γ-radiation. Further, zingerone, except for superoxide dismutase, notably ameliorated the state of oxidative stress as evidenced by a significant decrease in malondialdehyde level accompanied with a significant increase in the reduced glutathione content and catalase activity. Additionally, zingerone mitigated the increase in the inflammatory markers including serum level of tumor necrosis factor-alpha, cardiac myeloperoxidase activity, and cyclooxygenase-2 protein expression. Moreover, zingerone alleviated the elevation of caspase-3 gene expression and the prominent nuclear DNA fragmentation and attenuated the decrease in mitochondrial complexes’ activities. This study sheds the light on a probable protective role of zingerone as an antioxidant, anti-inflammatory, and antiapoptotic agent against cisplatin- or γ-radiation-induced cardiotoxicity and holds a potential in regard to therapeutic intervention for chemo/radiotherapy mediated cardiac damage.

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with limited treatment options. Zingerone found in ginger ( Zingiber officinale L .) has many pharmacological effects, especially antiinflammatory and antioxidant activity. However, the effect of zingerone on pulmonary fibrosis (PF) is not fully known. The aim of this study was to investigate the effect of zingerone on bleomycin (BLM)-induced PF and its underlying mechanisms. Wistar-albino rats were given single dose of BLM (5 mg/kg, intratracheal) or vehicle (saline). In treatment groups, zingerone (50 and 100 mg/kg, p.o.) was administered orally for 14 days after BLM administration. Rats and lung tissue were weighed to determine lung index. Antioxidant, antiinflammatory effects, and hydroxyproline content of zingerone were determined by ELISA method. Pulmonary inflammation, collagen deposition, and fibrosis score were determined with Hematoxylin-Eosin (HxE) and Masson’s trichrome staining. Transforming growth factor-beta 1 (TGF-β1) and inducible nitric oxide synthase (iNOS) expressions were detected immunohistochemically. BLM administration increased lipid peroxidation (MDA) and decreased superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity. In addition, BLM caused increased levels of tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) in bronchoalveolar lavage fluid (BALF) and accumulation of collagen bundles. Zingerone administration decreased collagen accumulation, TNF-α and IL-1β levels, MDA level, TGF-β1, and iNOS expression and increased SOD and GPx activity. Histopathological findings supported the results. These results show that zingerone (50 and 100 mg/kg) at both doses significantly contributes to healing of PF by improving inflammation, oxidative stress, and histopathological alterations and by affecting TGF-β1 and iNOS signaling pathways.