Rapid and simultaneous determination of curcuminoids and gingerols in food products containing turmeric and ginger using paper spray mass spectrometry.

Turmeric and ginger are extensively employed as functional ingredients due to their high content of curcuminoids and gingerols, considered the key bioactive compounds found in these roots. In this study, we present an innovative and fast method for the assay of curcuminoids and gingerols in different foods containing the two spices, with the aim of monitoring the quality of products from a nutraceutical perspective. The proposed approach is based on paper spray tandem mass spectrometry coupled with the use of a labeled internal standard, which has permitted to achieve the best results in terms of specificity and accuracy. All the calculated analytical parameters were satisfactory; accuracy values are around 100% for all spiked samples and the precision data result lower than 15%. The protocol was applied to several real samples, and to demonstrate its robustness and reliability, the results were compared to those arising from the common liquid chromatographic method.

Exploring Zingiber officinale bioactive compounds for inhibitory effects on Streptococcus pneumoniae capsular polysaccharide biosynthesis proteins: In silico study.

The capsule is a major virulence factor for Streptococcus pneumoniae which causes global morbidity and mortality. It is already known that there are few conserved genes in the capsular biosynthesis pathway, which are common among all known serotypes, called CpsA, CpsB, CpsC and CpsD. Inhibiting capsular synthesis can render S. pneumoniae defenseless and vulnerable to phagocytosis. The Inhibitory potential of active Zingiber officinale compounds was investigated against the 3D (3-dimensional) structural products of Cps genes using in silico techniques. A 3D compound repository was created and screened for drug-likeness and the qualified compounds were used for molecular docking and dynamic simulation-based experiments using gallic acid for outcome comparison. Cavity-based docking revealed five different cavities in the CpsA, CpsB and CpsD proteins, with gallic acid and selected compounds of Zingiber in a binding affinity range of -6.8 to -8.8 kcal/mol. Gingerenone A, gingerenone B, isogingerenone B and gingerenone C showed the highest binding affinities for CpsA, CpsB and CpsD, respectively. Through the Molegro Virtual Docker re-docking strategy, the highest binding energies (-126.5 kcal/mol) were computed for CpsB with gingerenone A and CpsD with gingerenone B. These findings suggest that gingerenone A, B and C are potential inhibitors of S. pneumoniae-conserved capsule-synthesizing proteins.

In-silico prediction of anti-breast cancer activity of ginger (Zingiber officinale) using machine learning techniques.

INTRODUCTION: Indonesian civilization extensively uses traditional medicine to cure illnesses and preserve health. The lack of knowledge on the security and efficacy of medicinal plants is still a significant concern. Although the precise chemicals responsible for this impact are unknown, ginger is a common medicinal plant in Southeast Asia that may have anticancer qualities. METHOD: Using data from Dudedocking, a machine-learning model was created to predict possible breast anticancer chemicals from ginger. The model was used to forecast substances that block KIT and MAPK2 proteins, essential elements in breast cancer. RESULT: Beta-carotene, 5-Hydroxy-74'-dimethoxyflavone, [12]-Shogaol, Isogingerenone B, curcumin, Trans-[10]-Shogaol, Gingerenone A, Dihydrocurcumin, and demethoxycurcumin were all superior to the reference ligand for MAPK2, according to molecular docking studies. Lycopene, [8]-Shogaol, [6]-Shogaol, and [1]-Paradol exhibited low toxicity and no Lipinski violations, but beta carotene had toxic predictions and Lipinski violations. It was anticipated that all three substances would have anticarcinogenic qualities. CONCLUSION: Overall, this study shows the value of machine learning in drug development and offers insightful information on possible anticancer chemicals from ginger.

The MYB family and their response to abiotic stress in ginger (Zingiber officinale Roscoe).

BACKGROUND: Zingiber officinale Roscoe, colloquially known as ginger, is a crop of significant medicinal and culinary value that frequently encounters adversity stemming from inhospitable environmental conditions. The MYB transcription factors have garnered recognition for their pivotal role in orchestrating a multitude of plant biological pathways. Nevertheless, the enumeration and characterization of the MYBs within Z. officinale Roscoe remains unknown. This study embarks on a genome-wide scrutiny of the MYB gene lineage in ginger, with the aim of cataloging all ZoMYB genes implicated in the biosynthesis of gingerols and curcuminoids, and elucidating their potential regulatory mechanisms in counteracting abiotic stress, thereby influencing ginger growth and development. RESULTS: In this study, we identified an MYB gene family comprising 231 members in ginger genome. This ensemble comprises 74 singular-repeat MYBs (1R-MYB), 156 double-repeat MYBs (R2R3-MYB), and a solitary triple-repeat MYB (R1R2R3-MYB). Moreover, a comprehensive analysis encompassing the sequence features, conserved protein motifs, phylogenetic relationships, chromosome location, and gene duplication events of the ZoMYBs was conducted. We classified ZoMYBs into 37 groups, congruent with the number of conserved domains and gene structure analysis. Additionally, the expression profiles of ZoMYBs during development and under various stresses, including ABA, cold, drought, heat, and salt, were investigated in ginger utilizing both RNA-seq data and qRT-PCR analysis. CONCLUSION: This work provides a comprehensive understanding of the MYB family in ginger and lays the foundation for the future investigation of the potential functions of ZoMYB genes in ginger growth, development and abiotic stress tolerance of ginger.

Ginger inhibits the invasion of ovarian cancer cells SKOV3 through CLDN7, CLDN11 and CD274 m6A methylation modifications.

BACKGROUND: Ginger is a common aromatic vegetable with a wide range of functional ingredients and considerable medicinal and nutritional properties. Numerous studies have shown that ginger and its active ingredients have suppressive effects on manifold tumours, including ovarian cancer (OC). However, the molecular mechanism by which ginger inhibits OC is not clear. The aim of this study was to investigate the function and mechanism of ginger in OC. METHODS: The estimation of n6-methyladenosine (m6A) levels was performed using the m6A RNA Methylation Quantification Kit, and RT-qPCR was used to determine the expression of m6A-related genes and proteins. The m6A methylationome was detected by MeRIP-seq, following analysis of the data. Differential methylation of genes was assessed utilizing RT-qPCR and Western Blotting. The effect of ginger on SKOV3 invasion in ovarian cancer cells was investigated using the wound healing assay and transwell assays. RESULTS: Ginger significantly reduced the m6A level of OC cells SKOV3. The 3'UTR region is the major site of modification for m6A methylation, and its key molecular activities include Cell Adhesion Molecules, according to meRIP-seq results. Moreover, it was observed that Ginger aids significantly in downregulating the CLDN7, CLDN11 mRNA, and protein expression. The results of wound healing assay and transwell assay showed that ginger significantly inhibited the invasion of OC cells SKOV3. CONCLUSIONS: Ginger inhibits ovarian cancer cells' SKOV3 invasion by regulating m6A methylation through CLDN7, CLDN11, and CD274.

The effect of ginger (Zingiber officinale L.) liquid extract on growth, immune response, antioxidant defence mechanism, and general health of Holstein calves.

This study was carried out to examine the effects of ginger liquid extract (GLE) on the growth, immune response, antioxidative defence mechanism, and general health of Holstein calves. Sixteen calves (4-d old) were included in the experiment and randomly assigned to groups, and they were fed whole milk containing GLE at a rate of 0, 0.50, 0.72, and 1% of the milk amount consumed. Calves consuming 1% GLE were weaned at an earlier age and gained better body weight (BW) compared to the other groups. The group fed with 0.50% GLE consumed less daily starter than the other groups. The administration of GLE resulted in a non-significant decrease in fecal score (FS), the number of days with diarrhea (DDN), and illness (IDN) among the calves. Notably, the 1% GLE exhibited a significant inhibitory effect on the growth of E. coli, while its effect on the growth of other pathogenic bacteria was not statistically significant. Despite the non-significant reduction in malondialdehyde (MDA), total oxidative status (TOS), and oxidative stress index (OSI) values, the 1% GLE demonstrated support for antioxidative defence mechanism and immune response. The results indicated that 1% GLE can be effective in promoting the health of calves by enhancing their immune response and antioxidant capacity. This suggests that incorporating 1% GLE into their overall well-being, potentially leading to improved health outcomes and performance in calf rearing operations.

Residue levels, processing factors and risk assessment of pesticides in ginger from market to table.

Ginger is consumed as a spice and medicine globally. However, pesticide residues in ginger and their residue changes during processing remain poorly understood. Our results demonstrate that clothianidin, carbendazim and imidacloprid were the top detected pesticides in 152 ginger samples with detection rates of 17.11-27.63%, and these pesticides had higher average residues of 44.07-97.63 µg/kg. Although most samples contained low levels of pesticides, 66.45% of the samples were detected with pesticides, and 38.82% were contaminated with 2-5 pesticides. Peeling, washing, boiling and pickling removed different amounts of pesticides from ginger (processing factor range: 0.06-1.56, most <1). By contrast, pesticide residues were concentrated by stir-frying and drying (0.50-6.45, most >1). Pesticide residues were influenced by pesticide physico-chemical parameters involving molecular weight, melting point, degradation point and octanol-water partition coefficient by different ginger processing methods. Chronic and acute dietary risk assessments suggest that dietary exposure to pesticides from ginger consumption was within acceptable levels for the general population. This study sheds light on pesticide residues in ginger from market to processing and is of theoretical and practical value for ensuring ginger quality and safety.

Microencapsulation of ginger essential oil using mung bean protein isolate-chitosan complex coacervates: Application in the preservation of crab meatballs and the prediction of shelf life.

Crab meatballs with more unsaturated fat tend to spoil. Ginger essential oil (GEO) with oxidation resistance was encapsulated into microcapsules (GM) by complex cohesion of mung bean protein isolate (MBPI) and chitosan (CS) in a ratio of 8:1 at pH = 6.4, encapsulation efficiency (EE) and payload (PL) of GM (D50 = 26.16 ± 0.45 µm) with high thermal stability were 78.35 ± 1.02% and 55.43 ± 0.64%. GM (0.6%, w/w) did not interfere with the original flavor of crab meatballs, and lowered values of pH, thiobarbituric acid reactive substances (TBARS) and total bacteria counts (TBC) of the products than those spiked with GEO and the control. The prediction accuracy of the logistic first-order growth kinetic equation in line with TBC (2.84%) was better than that of zero-order and Arrhenius coupled equation based on pH (7.48%) and TBARS (5.94%), but all of them could predict the shelf life of crab meatballs containing GM stored at 4-25 °C.

Integrative Bioinformatics Analysis Reveals Potential Target Genes and PTEN Signaling in Breast Cancer and Effect of Zingiber officinale (Ginger) and Allium sativum (Garlic) extract on It.

INTRODUCTION: Breast cancer is the most common type of cancer in women. The construction of a competing gene network is an important step in the identification of the role of hub genes in breast cancers. In the current research, we used a number of bioinformatics tools to construct this network in breast cancer and investigated the combined effect of garlic and ginger on mice model of breast cancer. MATERIALS AND METHODS: We chose female mice weighing 18-20 g that were divided into 7 groups including; the cancer group receiving normal saline, different doses of ginger extract (100 and 500 mg/kg), different doses of garlic (50 and 100 mg/kg), tamoxifen (10 mg/ kg) and simultaneous garlic (100 mg/kg) and ginger (500 mg/kg) for 3 weeks intraperitoneal. Then we anesthetized the mice, isolated the tumor, and determined its size. Glutathione reductase and peroxidase levels and HER2, PTEN, and Cullin3 genes expression were measured. RESULTS: We identified 20 hub genes for breast cancer. In animal phase we found that tumor size in all mice receiving garlic and ginger showed a significant decrease compared to the control. Glutathione reductase showed a significant increase in all groups, especially in ginger 500 and combined groups. Glutathione peroxidase increased almost in all groups, especially in ginger 500. Expression of HER2 decreased in all treated groups. Expression of PTEN increased just in the combined group. CONCLUSION: Taken together, we introduce a number of novel promising diagnostic biomarkers for breast cancer. The use of garlic and ginger in the treatment of cancer can be useful. This action is probably through the antioxidant mechanism, and regulation of the expression of cancer related genes such as PTEN.

Studies on photocatalytic mineralization of organic pesticides by bimetallic Cu-Zn nanoparticles derived from Zingiber officinale Roscoe (ginger) using green chemistry approach.

Compared to monometallic nanoparticles, bimetallic nanoparticle synthesis and characterization have attracted more attention due to their superior environmental protection properties. In this study, we discuss the preparation and characterization of Cu-Zn bimetallic nanoparticles using Zinger extract, as well as their potential role in photocatalytic degradation of carbendazim, chlorpyrifos, monocrotophos, and cypermethrin. Surface properties were assessed with SEM and TEM, while UV-VIS, XRD, FTIR, and fluorescence spectroscopy were used to characterize the materials. It was observed that higher pH conditions were more conducive to the development of stable Cu-Zn BMNPs with diameters ranging from 60 to 100 nm. UV-VIS spectroscopy showed that the Cu-Zn bimetallic nanoparticles photodegraded 53-95% of the pesticides, monocrotophos, chlorpyrifos, and carbendazim during the 24-72-h incubation period. A number of pesticides may be photocatalytically degraded by primary reactive radicals produced by nanoparticles. We propose that the use of bimetallic nanoparticles could be one alternative strategy for pesticide mineralization.

Zingiber Officinale Roscoe: The Antiarthritic Potential of a Popular Spice-Preclinical and Clinical Evidence.

The health benefits of ginger rhizomes (Zingiber officinale Roscoe) have been known for centuries. Recently, ginger root has gained more attention due to its anti-inflammatory and analgesic activities. Many of the bioactive components of ginger may have therapeutic benefits in treating inflammatory arthritis. Their properties seem especially helpful in treating diseases linked to persistent inflammation and pain, symptoms present in the course of the most prevalent rheumatic diseases, such as osteoarthritis (OA) and rheumatoid arthritis (RA). This review analyzes the current knowledge regarding ginger's beneficial anti-inflammatory effect in both in vitro and in vivo studies as well as clinical trials. The drug delivery systems to improve ginger's bioavailability and medicinal properties are discussed. Understanding ginger's beneficial aspects may initiate further studies on improving its bioavailability and therapeutic efficacy and achieving more a comprehensive application in medicine.

8-shogaol derived from dietary ginger alleviated acute and inflammatory pain by targeting TRPV1.

Ginger, a well-known spice plant, has been used widely in medicinal preparations for pain relief. However, little is known about its analgesic components and the underlying mechanism. Here, we ascertained, the efficacy of ginger ingredient 8-Shogaol (8S), on inflammatory pain and tolerance induced by morphine, and probed the role of TRPV1 in its analgesic action using genetic and electrophysiology approaches. Results showed that 8S effectively reduced nociceptive behaviors of mice elicited by chemical stimuli, noxious heat as well as inflammation, and antagonized morphine analgesic tolerance independent on opioid receptor function. Genetic deletion of TRPV1 significantly abolished 8S' analgesia action. Further calcium imaging and patch-clamp recording showed that 8S could specifically activate TRPV1 in TRPV1-expressing HEK293T cells and dorsal root ganglion (DRG) neurons. The increase of [Ca2+]i in DRG was primarily mediated through TRPV1. Mutational and computation studies revealed the key binding sites for the interactions between 8S and TRPV1 included Leu515, Leu670, Ile573, Phe587, Tyr511, and Phe591. Further studies showed that TRPV1 activation evoked by 8S resulted in channel desensitization both in vitro and in vivo, as may be attributed to TRPV1 degradation or TRPV1 withdrawal from the cell surface. Collectively, this work provides the first evidence for the attractive analgesia of 8S in inflammatory pain and morphine analgesic tolerance mediated by targeting pain-sensing TRPV1 channel. 8S from dietary ginger has potential as a candidate drug for the treatment of inflammatory pain.

Effect of Aromatic Herbs and Spices Present in the Mediterranean Diet on the Glycemic Profile in Type 2 Diabetes Subjects: A Systematic Review and Meta-Analysis.

BACKGROUND: The Mediterranean Diet (MedDiet) is the dietary pattern par excellence for managing and preventing metabolic diseases, such as Type 2 Diabetes (T2DM). The MedDiet incorporates spices and aromatic herbs, which are abundant sources of bioactive compounds. The aim of this study was to analyze the effect of all aromatic herbs and spices included in the MedDiet, such as black cumin, clove, parsley, saffron, thyme, ginger, black pepper, rosemary, turmeric, basil, oregano, and cinnamon, on the glycemic profile in T2DM subjects. METHODS: PubMed, Web of Science, and Scopus databases were searched for interventional studies investigating the effect of these aromatic herbs and spices on the glycemic profile in T2DM subjects. RESULTS: This systematic review retrieved 6958 studies, of which 77 were included in the qualitative synthesis and 45 were included in the meta-analysis. Our results showed that cinnamon, turmeric, ginger, black cumin, and saffron significantly improved the fasting glucose levels in T2DM subjects. The most significant decreases in fasting glucose were achieved after supplementation with black cumin, followed by cinnamon and ginger, which achieved a decrease of between 27 and 17 mg/dL. CONCLUSIONS: Only ginger and black cumin reported a significant improvement in glycated hemoglobin, and only cinnamon and ginger showed a significant decrease in insulin.

Effect of ginger and P6 acupressure on chemotherapy-induced nausea and vomiting: a randomized controlled study.

OBJECTIVE: To evaluate the effect of ginger with P6 acupressure in preventing and treating chemotherapy-induced nausea and vomiting (CINV) in cancer patients. METHOD: A total of 172 participants were randomly divided into the control, ginger, acupressure, and joint groups, who were hospitalized in the Affiliated Hospital of Xuzhou Medical University from February and September 2022. The baseline characteristics, nausea, vomiting, and retching, benefit finding, functional living index-emesis, treatment satisfaction, and adverse reaction, were used in data collection. RESULTS: No significant difference was found in benefit finding and adverse reactions among the four groups (P > 0.05). Ginger significantly improved delayed CINV and function living index-nausea (P < 0.05) but had no significant effect on acute CINV, retching, and delayed vomiting, functional living index-emesis, and treatment satisfaction (P>0.05). Acute nausea and retching, delayed nausea, vomiting, and retching, functional living index-emesis, and treatment satisfaction were effectively improved in the acupressure and joint groups (P < 0.05). CONCLUSION: Ginger with P6 acupressure may contribute to improving CINV in patients undergoing chemotherapy.

The Effects of Body Fat Reduction through the Metabolic Control of Steam-Processed Ginger Extract in High-Fat-Diet-Fed Mice.

The prevalence of metabolic syndrome is increasing globally due to behavioral and environmental changes. There are many therapeutic agents available for the treatment of chronic metabolic diseases, such as obesity and diabetes, but the data on their efficacy and safety are lacking. Through a pilot study by our group, Zingiber officinale rhizomes used as a spice and functional food were selected as an anti-obesity candidate. In this study, steam-processed ginger extract (GGE) was used and we compared its efficacy at alleviating metabolic syndrome-related symptoms with that of conventional ginger extract (GE). Compared with GE, GGE (25-100 µg/mL) had an increased antioxidant capacity and α-glucosidase inhibitory activity in vitro. GGE was better at suppressing the differentiation of 3T3-L1 adipocytes and lipid accumulation in HepG2 cells and promoting glucose utilization in C2C12 cells than GE. In 16-week high-fat-diet (HFD)-fed mice, GGE (100 and 200 mg/kg) improved biochemical profiles, including lipid status and liver function, to a greater extent than GE (200 mg/kg). The supplementation of HFD-fed mice with GGE (200 mg/kg) resulted in the downregulation of SREBP-1c and FAS gene expression in the liver. Collectively, our results indicate that GGE is a promising therapeutic for the treatment of obesity and metabolic syndrome.

Effect of subcritical water temperature on the chain conformation and immune activity of ginger polysaccharides.

In this study, the ginger polysaccharides extracted from hot water (HW-G) were modified with subcritical water (SW-G) to effectively regulate their immune activity, and the relationship between polysaccharide chain conformation and immune activity at different subcritical water temperatures was investigated. The results indicated that, compared with HW-G, the xylose and mannose were degraded at high temperatures. The molecular weight of ginger polysaccharide decreased from 1.083 × 106 g/mol to 3.113 × 105 g/mol after subcritical water modification (100-160 °C). The chain conformation transitioned from rigid rod chain to semi-rigid chain and eventually to random coil. The degree of relaxation of the polysaccharide chains showed a continuous increase trend. Additionally, ginger polysaccharide modified by subcritical water at 130 °C was found to promote the proliferation and phagocytosis of 264.7 cells more obviously and signally increase the secretion levels of NO, IL-6, TNF-α and IL-1ß. When the subcritical water temperature exceeds 130 °C, the activity of ginger polysaccharide begins to decline rapidly. These findings demonstrate a close correlation between polysaccharide chain conformation and immunomodulatory activity, confirming the feasibility of the subcritical water temperature effect as a means of immune activity regulation, which opens up a new approach to obtaining highly active polysaccharides.

Preparation, characterization and drug release properties of pH sensitive Zingiber officinale polysaccharide hydrogel beads.

The aim of this study was to prepare a drug carrier that could deliver oral insulin to the intestine. A hydrogel beads composed of sodium carboxymethyl cellulose (CMC), Zingiber offtcinale polysaccharide (ZOP) and chitosan (CS) were prepared by ionic gel method as insulin carrier. Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), Scanning electron microscopy (SEM) and thermogravimetric (TGA) showed that the hydrogel was formed by metal ion coordination between ZOP and CMC and Fe3+, and CS was coated on the surface of the hydrogel ball in the form of non covalent bond. The results showed that the swelling process of hydrogel spheres has significant pH sensitivity. In addition, the hydrogel beads successfully coated insulin, and the drug loading rate (DL) of (ZOP/CMC-Fe3+)@CS could reach 69.43 ± 7.32 mg/g, and the entrapment efficiency (EE) could reach 66.94 ± 7.43 %. In vitro release experiments, the release rate of (CMC/ZOP-Fe3+)@CS in simulated gastric fluid (SGF) for 2 h was <20 %, and the cumulative release rate of insulin after 9 h in simulated intestinal fluid (SIF) reached over 90 %. The results showed that the hydrogel beads prepared in this work could be used as a potential carrier for delivering oral insulin.

Ginger-derived bioactive compounds attenuate the Toll-like receptor mediated responses of human dendritic cells.

Ginger has been used for thousands of years for the treatment of many illnesses, from nausea to migraines. Recently, an interest has grown in ginger compounds in the context of autoimmune and inflammatory diseases due to their significant anti-inflammatory effects. Nevertheless, the effects and mechanism of action of these phytochemicals in human immune cells, particularly in dendritic cells (DCs) are unclear. In the present study, we investigated the effects of 6-gingerol and 6-shogaol, the major compounds found in ginger rhizome, on the functionality of primary human monocyte-derived DCs (moDCs). Here we report for the first time that 6-gingerol and 6-shogaol dampen the immunogenicity of human DCs by inhibiting their activation, cytokine production and T cell stimulatory ability. In particular, the bioactive compounds of ginger dose-dependently inhibited the upregulation of activation markers, and the production of different cytokines in response to synthetic Toll-like receptor (TLR) ligands. Moreover, both compounds could significantly reduce the Escherichia coli-triggered cytokine production and T cell stimulatory capacity of moDCs. We also provide evidence that the ginger-derived compounds attenuate DC functionality via inhibiting the nuclear factor-κB (NF-kB), mitogen activated protein kinase (MAPK), and mammalian target of rapamycin (mTOR) signaling cascades. Further, 6-shogaol but not 6-gingerol activates the AMP-activated protein kinase (AMPK) and nuclear factor erythroid 2-related factor 2 (NRF2) pathways that might contribute to its anti-inflammatory action. Altogether, our results indicate that ginger-derived phytochemicals exert their anti-inflammatory activities via multiple mechanisms and suggest that 6-shogaol is more potent in its ability to suppress DC functionality than 6-gingerol.

Zingiber officinale Root Capsule Extract Synergistically Enhance the Anti-Inflammatory Effects of Diclofenac Sodium in Experimental Acute Inflammation.

The present study aimed to evaluate the anti-inflammatory effects of ginger (Zingiber officinale) root capsule extract (GRCE) in doses of 100 mg/kg b.w. (body weight) and 200 mg/kg b.w. alone and in combination with a low dose (5 mg/kg b.w.) of diclofenac sodium (D) on carrageenan-induced acute inflammation (AI). The association of GRCE in a dose of 200 mg/kg b.w. with D offered the highest inhibition percentage for edema, reaching the maximum level of inhibition (95%) after 24 h. The association of GRCE in a dose of 200 mg/kg b.w. with D showed the ability to reduce tissue inflammatory changes when compared to D alone, while GRCE alone did not exhibit such properties. The association of both doses of GRCE with D showed significantly lower plasma and tissue levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) by up to 55% (p ≤ 0.0317), with the best results obtained by the group who received GRCE in the higher dose. These associations reduced the serum and tissue levels of prostaglandin-endoperoxide synthase 2 (COX-2) by up to 71% (p ≤ 0.0371). In conclusion, the association of GRCE with a low dose of D could be an appropriate combination to decrease the dose used to reduce serum and tissue levels of inflammatory molecules, edema, and histological changes in acute inflammation. Further research will be necessary to achieve clinical evaluation.