Phytochemical analysis, in vitro anoxidant and in vivo an-inﬂammatory ac- vies of a hydroethanolic extract of Zingiber oﬃcinale Roscoe rhizome Análisis ﬁtoquímico, acvidad anoxidante in vitro y aninﬂamatoria in vivo de un extracto hidroetanólico de rizoma de Zingiber oﬃcinale Roscoe Ismahane Derafa 1 , Ahlem Karbab 2* , Noureddine Charef 2 , Amina Belmahdi 3 , Salim Chenni 1 , Amira Seﬀari 1 , Chahrazed Kaoudoun 1 ¹ Sef-1 University Ferhat Abbas, Faculty of Natural and Life Sciences, Laboratory of Medicinal Plants Applied to Chronic Diseases. 19000, Algeria. ² Sef-1 University Ferhat Abbas, Faculty of Nature and Life Science, Department of Biochemistry, Laboratory of Applied Biochemistry. 19000, Algeria. ³ Abdelhaﬁd Bousouf University, Instute of Nature and Life Sciences, Laboratory of Natural Sciences and Materials. Mila, BP N°26 RP Mila 43000 Algeria. *Corresponding author: ahlem.karbab@univ-sef.dz 1 of 9 Received: 29/12/2025 Accepted: 20/03/2026 Published: 15/04/2026 UNIVERSIDAD DEL ZULIA Serbiluz Sistema de Servicios Bibliotecarios y de Información Biblioteca Digital Repositorio Académico Revista Cienﬁca, FCV-LUZ / Vol. XXXVI hps://doi.org/10.52973/rcfcv-e362889 ABSTRACT This present study aims to evaluate the in vitro anoxidant and the in vivo an-inﬂammatory acvies of the ethanolic extract of Zingiber oﬃcinale Roscoe rhizome. The extract is obtained by maceraon (80 %). The analysis of total phenolic and ﬂavonoid contents showed that the ethanolic extract is rich in polyphenols (206.95 ± 11.78 µg equivalent gallic acid) and ﬂavonoids (11.62 ± 0.00 µg equivalent quercen/mg dry extract). According to the 1-diphenyl-2-picrylhydrazyl assay, the ethanolic extract exhibits an important anoxidant acvity with an IC 50 of 0.11 ± 0.00 mg/ mL. Furthermore, the ethanolic extract demonstrates a higher reducing power compared to the butylated hydroxytoluene, with IC 50 values of 0.01 ± 0.00 mg/mL. The ethanolic extract shows the highest inhibion in the β-carotene assay, with an inhibion of 82 %. The two induced inﬂammaon tests, Xylene-Induced Ear Edema and Carrageenan-Induced Paw Edema, showed that the ethanolic extract of Zingiber oﬃcinale produced a remarkable an-edematous eﬀect, with a dose of 400 mg/kg for Xylene-Induced Ear Edema and a dose of 200 mg/kg for Carrageenan-Induced Paw Edema. In conclusion, the rhizome extract of Zingiber oﬃcinale has demonstrated both anoxidant and an-inﬂammatory properes, as can be jusﬁed by its tradional uses. Key words: Zingiber oﬃcinale Roscoe; an-inﬂammatory; anoxidant; phenolic compounds. RESUMEN Este estudio ene como objevo evaluar las acvidades anoxidantes in vitro y aninﬂamatorias in vivo del extracto etanólico del rizoma de Zingiber oﬃcinale Roscoe. El extracto se obene por maceración (80 %). El análisis de los contenidos totales de fenólicos y ﬂavonoides mostró que el extracto etanólico es rico en polifenoles (206.95 ± 11.78 µg de ácido gálico equivalente) y ﬂavonoides (11.62 ± 0.00 µg de quercena equivalente/mg de extracto seco). Según el ensayo 1-difenil- 2-picrilhidrazilo, el extracto etanólico exhibe una importante acvidad anoxidante con una CI 50 de 0.11 ± 0,00 mg/mL. Además, el extracto etanólico demuestra un mayor poder reductor en comparación con el hidroxitolueno bulado, con valores de CI 50 de 0.01 ± 0.00 mg/mL. El extracto etanólico muestra la mayor inhibición en el ensayo de β-caroteno, con una inhibición del 82 %. Las dos pruebas de inﬂamación inducida, Edema de Oído Inducido por Xileno y Edema de Pata Inducido por Carragenina, mostraron que el extracto etanólico de Zingiber oﬃcinale produjo un notable efecto anedematoso, con una dosis de 400 mg/kg para Edema de Oído Inducido por Xileno y una dosis de 200 mg/kg para Edema de Pata Inducido por Carragenina. En conclusión, el extracto de rizoma de Zingiber oﬃcinale ha demostrado propiedades anoxidantes y aninﬂamatorias, como lo jusﬁcan sus usos tradicionales. Palabras clave: Zingiber oﬃcinale Roscoe; aninﬂamatorio; anoxi- dante; compuestos fenólicos.

Revista Cienﬁca, FCV-LUZ / Vol. XXXV UNIVERSIDAD DEL ZULIA Serbiluz Sistema de Servicios Bibliotecarios y de Información Biblioteca Digital Repositorio Académico INTRODUCTION Oxidave stress is a proven biological phenomenon that takes place as a consequence of an overproducon of reacve oxygen species (ROS) in either cells or ssues. This leads to macromolecular damage from oxidaon and the disrupon of gene regulaon, ulmately resulng in cell death [1 , 2 , 3]. At controlled levels, ROS act as signaling molecules that mediate plant responses to bioc and environmental stresses by modulang physiological funcons and parcipang in diverse metabolic pathways [4 ,5]. However, their accumulaon may lead to the formaon of pro-inﬂammatory molecules, contribung to inﬂammaon and ssue injury, which can ulmately result in chronic inﬂammatory diseases [6 , 7]. In order to counteract these harmful consequences, anoxidants of natural origin, in parcular those derived from medicinal plants with bioacve compounds capable of modulang oxidave stress and inﬂammaon, have received considerable interest from scholars in recent years [8 , 9]. In fact, for a long me in the history of medical pracces, plants have been used as remedies for many diseases, with secondary metabolites playing a vital role as precursors for numerous drugs and pharmaceucals in modern medicine [10 , 11]. Under this group, Zingiber oﬃcinale (Z. oﬃcinale), generally known as ginger in English or “gingembre” in French [12 , 13]. In Asian countries such as India, was used as a spice for over two thousand years and as a ﬂavoring agent throughout anquity. It is a seasonal, herbaceous, erect plant with a pseudo-stem growing to a height of 0.3 to 1 meter. Its leaves have hairy peoles with lengths of 2 to 4 mm, with leaves themselves measuring 15 to 23 cm in length and 8 to 15 mm in width. Its morphological characteriscs include roots, stems, rhizomes, leaves, and ﬂowers. Its rhizomes can last for long in the soil and display the capability to produce new shoot growth to compensate for shed leaves and stems [14]. Its rhizome is ﬂat with a pale-yellow interior and is strongly ﬁbrous. Its roots grow from the juncon at the lower side of the rhizome, with shoots developing at the top. Variees of ginger are diﬀerent in shape and have diﬀerences in taste as well [14]. Ginger (Zingiber oﬃcinale, Roscoe) has bioacve compounds such as shogaol, gingerol, and ﬂavonoids, making it a natural source of various secondary compounds and an anoxidant-rich plant (FIG. 1), [15 , 16]. It has tradionally been used in the prevenon and treatment of stomach-upseng dilemmas such as dyspepsia, intesnal- derived ailments, and various types of food poisoning [17]. Ginger has also been proven useful in combang arthric diseases, aiding in transport-related complaints, and reducing pregnancy-related voming. Raw ginger is richest in enzymes that aid digeson and has tradionally been used as an andote for burned skin [16 , 18 , 19]. FIGURE 1. Zingiber oﬃcinale rhizome The increase in body warmth has further been linked to strengthened circulaon and a possible reducon in blood pressure [20]. Zingiberene is primarily idenﬁed as the main component found in Z. oﬃcinale essenal oil (19.71 %), accompanied by (+)-β-cedrene, farnesene, α-curcumene, and β-elemene in larger amounts [21]. The major acve and stable phenolic compounds found in the acve component of ginger, such as shogaols, paradols, zingerone and gingerols, have been known to exhibit anoxidant, an-angiogenic, an-atheroscleroc, and ancancer acvies as suggested by previous studies [22 , 23]. Taking into consideraon the aforemenoned factors, the aim of this present study is to evaluate the in vitro anoxidant, in vivo an-inﬂammatory acvity, as well as the total phenolic compound content of Z. oﬃcinale. MATERIALS AND METHODS Plant material Dried rhizomes of Z. oﬃcinale were purchased from a local market and ground to a ﬁne light-yellow powder. The powder was prepared immediately before extracon. Extracon procedure With a few minor adjustments, the plant’s ethanolic extract was prepared [24]. In short, 85 % ethanol was used to extract the dried powder of Z. oﬃcinale for 72 hours (h) at room temperature. Aﬅer ﬁltering the resultant mixture, the ﬁltrate was evaporated (Buchi rotavap R-205, Switzerland), at 45 °C. The pharmacological characteristics of the dried extract were examined. Total phenolic contents The total phenolic content was measured using a modiﬁed Folin-Ciocalteu (FC) assay, as described previously [25]. In summary, a 0.1 mL aliquot of plant extract or standard was mixed with a 0.5 mL aliquot of FC reagent, which was previously diluted 1:10. Aﬅer a 4-min reacon me, a 0.4 mL aliquot of a 7.5 % sodium carbonate soluon was added. Absorbance was then measured (Shimadzu UV1800 spectrophotometer, Germany), at 765 nm, and total phenolics were calculated as gallic acid (GA) equivalents (FIG. 2). 2 of 9

In vitro and in vivo invesgaons of Zingiber oﬃcinale rhizome / Derafa et. al. UNIVERSIDAD DEL ZULIA Serbiluz Sistema de Servicios Bibliotecarios y de Información Biblioteca Digital Repositorio Académico FIGURE 2. Standard curve for gallic acid. Total ﬂavonoid contents Total ﬂavonoid content in each of the plant extracts was determined using the aluminum chloride (AlCl 3 ) colorimetric assay [26]. A detailed descripon of this method involves mixing 1 mL of extract with 1 mL of 2 % AlCl₃ in methanol, which is then allowed for 10 minutes (min) of incubaon, with measurements conducted at 430 nm to calculate in terms of quercen equivalent, (FIG. 3). FIGURE 3. Standards curve for quercen. Anoxidant potenals 1-diphenyl-2-picrylhydrazyl radical scavenging assay The scavenging capacity of extract was determined using the 1-diphenyl-2-picrylhydrazyl (DPPH) assay, according to the method of Burits and Bucar [27]. Brieﬂy, a mixture of each extract (0.05 mL) and a soluon of DPPH (1.25 mL, containing 0.004 % DPPH in methanol) was used, with butylated hydroxytoluene (BHT) serving as the posive control. Aﬅer 30 min of incubaon, the absorbance was measured at 517 nm. The scavenging acvity was esmated from the relevant formula. It expresses further the anoxidant acvity as IC₅₀ (mg/mL), where : is the absorbance of the control and : is the absorbance of the sample β-carotene bleaching assay Anoxidant acvies were evaluated using the ability to suppress the accumulaon of conjugated dienes and volale oxidaon products of linoleic acid, based on the method of Dapkevicius et al. [28]. Brieﬂy, a mixture of 0.5 mg of β-carotene in 1 mL of Chloroform was prepared, to which were added 200 mg of Tween-40 and 0.025 mL of Linoleic acid. Oxygen-saturated dislled water (100 mL) was added aﬅer complete evaporaon of the Chloroform at 40 °C to achieve the emulsion. To each test tube pre-loaded with 0.350 mL of sample soluon (2 mg/mL), 2.5 mL of the aforemenoned emulsion was added. All were kept at room temperature in the darkness. Posive controls used were GA and BHT. Absorbances were recorded at 490 nm at intervals of 0, 1, 2, 3, 4, 6, 12, and 24 h. Relave anoxidant acvies (A %) was esmated using the following formula: where and represent the absorbances of the control and sample at , respecvely. Reducing power assay The previously published approach was used to determine the extract’s reducing power [29]. Brieﬂy, 0.1 mL volumes of the methanol-facilitated extracts, K 3 Fe(CN) 6 , and 0.2 M phosphate buﬀer soluon, pH 6.6, were allowed to react. Aﬅer a 20- min incubaon period at 50 °C, the reacons were stopped through the addion of 0.25 mL volumes of 1 % trichloroacec acid. About 0.25 mL volumes were mixed with 0.25 mL volumes of dislled water and 0.5 mL volumes of 0.1 % FeCl 3 soluon. The absorbance was measured (Shimadzu UV1800 spectrophotometer, Germany) at 700 nm. An-inﬂammatory capacies Xylene induced ear edema As outlined by the process designed by Aa and Alkohaﬁ [30], the Xylene-induced edema of the ears was performed using Xylene. The study involved four groups with six mice (Mus musculus) each. Edema was induced by the topical applicaon of 40 μL Xylene to the outer part of the ears. The ﬁrst group was the standard treatment and was given 100 mg/kg of indomethacin. The second group was the negave control and given NaCl soluon (0.9 %) as treatment, while the third and the fourth groups received the plant extract with a dose of 200 and 400 mg/kg, respecvely. The ears were measured using the digital caliper (caliper to DIN 862, Germany) before and two hours aﬅer the inducon of the inﬂammaon. The percentage inhibion of the inﬂammaon or the edema was measured using the formula: Where D Control is the diﬀerence in edema thickness in the control group, and D Treated is the diﬀerence in edema thickness for the treated group. 3 of 9

Revista Cienﬁca, FCV-LUZ / Vol. XXXV UNIVERSIDAD DEL ZULIA Serbiluz Sistema de Servicios Bibliotecarios y de Información Biblioteca Digital Repositorio Académico Carrageenan-induced rat paw edema In this experiment, four groups of adult mice (each consisng of n = 6) were administered diclofenac at doses of 50 mg/kg, ginger extract at doses of 200 and 400 mg/kg, and the negave control, which included the administraon of 0.9 % NaCl soluon. Before the treatment, the mice had free access to drinking water. The animals were made to fast for 12 h, aﬅer which the test subjects received compounds orally via gavage. Acute inﬂammaon was elicited by the subplantar injecon of 0.02 mL of 1 % w/v carrageenan in normal saline into the right hind paw of the test subjects, thirty min following treatment, as done in the research study conducted by Belay and Makonnen [31] on the model menoned above. The measurement of the paw thickness for each test subject involved using the digital caliper. The percentage of paw swelling was esmated as follow: D0 is the paw thickness, and Dt is the paw thickness aﬅer carrageenan injecon at a given me point. Stascal analysis GraphPad Prism, ver. 6.01 for Windows, was applied for stascal analysis. Values are esmated as mean ± SD. For the anoxidant test, we used t-test cause wa have only two samples, the rest we used anova because we have more then two samples. RESULTS AND DISCUSSION Yield, total phenolic and ﬂavonoid contents The focus of this study is the determinaon of the phytochemical constuon of a hydroethanolic extract (HEE) of the rhizome of Z. oﬃcinale, speciﬁcally in terms of the total phenolic and ﬂavonoid contents using the spectrophotometric method. The esmate of yield in relaon to the total powder weight (100 g) of plant, shows that the HEE present a 7.4 % of yield (TABLE I). The total phenolic and ﬂavonoid contents of the sample were 203.12 ± 06.95 µg GAE/mg extract and 11.62 ± 0.00 µg QE/mg extract, respecvely. In Comparison, Lukia et al. [32] reported a phenolic content of 155.78 µg GAE/mg extract, indicang a higher phenolic content in the current study. The results are presented in TABLE I. As for ﬂavonoid content, the results obtained are similar to the ﬁndings of Bekkouch et al. [33]. Previous invesgaons have revealed that Z. oﬃcinale is rich with various phenolic compounds, including 6-paradol, 6-shogaol, 6-gingerol, methyl 6-gingerol, 8-gingerol, 5-gingerol, 1-dehydro-6-gingerol and 10-gingerol, [34]. In general, Variaons in total phenolic content (TPC) and total ﬂavonoid content (TFC) values in plant extracts may be aributed to the presence of non-ﬂavonoid polyphenols like phenolic acids and tannins. Rhizomes of Z. oﬃcinale contain major bioacve compounds gingerols and shogaols; they are polyphenols but not ﬂavonoids. This may be a plausible reason for the higher values of TPC over TFC in the HEE. Variaons in the type of solvents used for the extracon process may aﬀect the polyphenol and ﬂavonoid contents. Hydroethanolic solvents tend to increase the recovery of various polyphenolic compounds. TABLE I Yield, total polyphenols and ﬂavonoids contents of Z. oﬃcinale extract. Extract Yield (%) Total phenolic content (a) Total ﬂavonoids content (b) GEE 7.4 203.12 ± 06.95 11.62 ± 0.00 (a): µg gallic acid equivalent (GA)/mg dried extract (DE), (b): µg quercen equivalent (QE)/ mg dried extract (DE), GEE: ginger ethanol extract Generally, 6-gingerol is known to be more prevalent in fresh forms, whereas 6-shogaol is more prevalent in dried forms of ginger, aributed to the dehydrang properes of gingerols. The disparity in concentraons of 8-gingerol and 10-gingerol may also be aributed to variaons in extracon and stability. These compounds are known to be the main bioacve markers for ginger and are believed to be responsible for its anoxidant and an-inﬂammatory properes. Thus, the quantave analysis of these compounds is essenal for standardizaon, quality, and eﬃcacy of ginger-based pharmaceucals for uniform therapeuc eﬀects. Anoxidant acvity 2,2-Diphenyl-1-picrylhydrazyl free radical scavenging assay In vitro anoxidant tests are used extensively as a ﬁrst step to screen plant extracts for the ability to scavenge free radicals. Among these tests, the DPPH radical-scavenging assay is the most frequently used technique for its simplicity, speed, and reproducibility. The DPPH free radical has been shown to be a stable nitrogen-centered radicals, which changes color to yellow upon reducon by an anoxidant, hence perming quantave measure of the radical-scavenging ability. The amount of extract needed to scavenge 50 % of the DPPH radicals has been shown to serve as an indicator for the potency of the anoxidave eﬀect. The extract showed a clear dose-dependent ability to scavenge DPPH radicals, with an IC 50 of 0.12 ± 0.00 mg/mL. The results are presented in TABLE II. While this level was signiﬁcantly lower than the standard anoxidant: BHT, (P < 0.0001), which had an IC 50 of 0.01 ± 0.00 mg/mL, the extract sll proved its capacity to neutralize free radicals. The IC 50 value observed is considerably lower than that reported by [35] (IC₅₀ = 4.25 mg/mL). TABLE II Anoxidant acvity of hydroethanolic Z. oﬃcinale extract Anoxidant acvity/Inhibion concentraon (IC 50 ) Extract/ standards DPPH radical scavenging Reducing power GEE 26.06 ± 0.00 *** 39.43 ± 0.00 *** BHT 87.26 ± 0.00 ND Vitamin C ND 21. 91 ± 0.48 GEE: ginger ethanol extract. BHT: butylated hydroxytoluene The HEE of Z. oﬃcinale rhizomes had a strong concentraon- dependent ability to scavenge the DPPH radicals. The higher the concentraon of the extract, the higher the ability to scavenge the radicals, thereby indicang a strong ability to donate hydrogen or electron density to scavenge the radicals. The low IC₅₀ value obtained depicts that only a low concentraon of the 4 of 9

In vitro and in vivo invesgaons of Zingiber oﬃcinale rhizome / Derafa et. al. UNIVERSIDAD DEL ZULIA Serbiluz Sistema de Servicios Bibliotecarios y de Información Biblioteca Digital Repositorio Académico extracts is required to scavenge 50 % of the DPPH radicals, thus signifying a high ability to scavenge free radicals. This remarkable acvity is likely linked to the extract’s high phenolic content, consistent with previous studies highlighng the pivotal role of phenolic compounds in free radical neutralizaon [35]. This strong anoxidave property can be aributed to the high phenolic content presented in the extract. Phenolics, such as the gingerols present in Z. oﬃcinale, are known to tame the free radicals by the phenomenon of resonance. This is because the phenolics prevent the oxidaon reacon by the free radicals. This concentraon-dependent property also conﬁrms the presence of the bioacve compounds, as the concentraon increases the amount of the anoxidave molecules that can interact with the DPPH molecules [36]. Taken together, the high DPPH scavenging capacity shown by the HEE of the Z. oﬃcinale rhizome reported in the present study supports the tradional use and provides further raonale to the reported ﬁndings demonstrang the anoxidant role of ginger phenolic compounds. Such anoxidant acvity may be shown to be responsible for the an-inﬂammatory acvity exhibited by the HEE. Reducing power assay The extract exhibited a strong reducing power, with an IC 50 of 0.013 ± 0.00 mg/ml, a result comparable to that of the standard BHT, measured at 0.0012 ± 0.00 mg/ml. This suggests that the extract has a strong ability to donate electrons and can eﬀecvely reduce Fe 3+ to Fe 2+ . Comparave study on diﬀerent ginger plant parts noted that ethanolic extracts excel in electron transfer-based anoxidant assays, such as ferric reducing power, which highlights the contribuon of phenolic compounds to reducing capacity [37 , 38]. Overall, the DPPH, β-carotene-linoleic, and reducing power results show that Zingiber oﬃcinale’s ethanolic extract has potent anoxidant acvity. This eﬀect largely stems from its high levels of phenolic and ﬂavonoid compounds such as shogaol, gingerol, zingerone, and paradol. These compounds work synergiscally to reduce the producon of ROS. Ginger helps boost glutathione levels, stops lipid peroxidaon, inhibits the generaon of nitric oxide, scavenges hydroxyl radicals, promotes the acvity of anoxidant enzymes like superoxide dismutase and catalase, and lowers the expression of inducible nitric oxide synthase, further supporng its role as a powerful anoxidant [39]. β-carotene/linoleic acid bleaching assay In the β-carotene–linoleic acid assay, anoxidants inhibit the formaon of volale compounds and conjugated diene hydroperoxides that result from linoleic acid oxidaon [40]. The ethanolic extract of ginger showed a strong result in prevenng lipid peroxidaon, with 82 % inhibion. This result is comparable with BHT, which reached an inhibion of 99, and is signiﬁcantly higher than GA with 46 % inhibion (FIG. 4). FIGURE 4. The inhibion percentage of Z. oﬃcinale ethanolic extract was evaluated by β-carotene-linoleic acid assay. Samples were analyzed aﬅer 24 hours, Posive controls used were GA and BHT. Data are presented as mean ± SD (n = 3). *P < 0.05 stascally signiﬁcant, ***P < 0.0001. GEE: Z. oﬃcinale ethanol extract. The β-carotene-linoleic acid assay is one common method that has been widely accepted for the determinaon of the anoxidant acvity of plant extracts using their ability to block the oxidaon of lipids. In the β-carotene-linoleic acid assay, the linoleic acid undergoes an oxidave breakdown when heated in the presence of oxygen, forming free radicals and conjugated diene hydroperoxides. The highly unsaturated molecules of β-carotene are aacked by the reacve oxidaon product. The results obtained align with previous studies reporng that ethanolic plant extracts protect ssues against lipid peroxidaon in vivo and eﬀecvely scavenge reacve oxygen species in lipid rich environments [41 , 42]. Xylene induced ear edema Inﬂammaon serves as the body’s defense system to get rid of infecons, burns, and toxins, as well as to iniate the healing process. According to Ayustaningwarno et al. [43], it results in discomfort, swelling, heat, redness, and disrupons of physiological processes. Unchecked acute inﬂammaon develops into chronic inﬂammaon, which leads to chronic inﬂammatory disorders [44]. This leads to the considerable producon of inﬂammatory mediators, including NO, PGE2, TNF- , IL-1, IL-6, and COX-2, which are linked to the pathophysiology of ssue damage [45]. Many inﬂammatory diseases are characterized by excessive acvity of macrophages and the formaon of free radicals that cause ssue destrucon [46]. Topical administraon of xylene induces acute edema in mice’s ears, which serves as a widely accepted model for evaluang an-inﬂammatory acvity [6 , 47]. Xylene is known to trigger the release of inﬂammatory mediators, leading to vasodilaon and increased vascular permeability, resulng in edema formaon [47]. In the present study, ear edema induced using xylene and treated with ethanolic extract of Z. oﬃcinale at doses of 200 and 400 mg/kg resulted in signiﬁcant edema reducon measured at 57 and 54 %, respecvely (FIG. 5). These results are comparable 5 of 9

Revista Cienﬁca, FCV-LUZ / Vol. XXXV UNIVERSIDAD DEL ZULIA Serbiluz Sistema de Servicios Bibliotecarios y de Información Biblioteca Digital Repositorio Académico with those obtained using the well-known an-inﬂammatory drug, indomethacin, with 76% reducon of edema. Zhang et al. [20] also demonstrated the an-inﬂammatory eﬃciency of Z. Oﬃcinale’s oils compared to ibuprofen. According to previous invesgaons, the beneﬁcial eﬀects are largely aributed to bioacve compounds like 6-shogaol, which play a role in modulang inﬂammatory mediators such as COX-2, INOS, NF- κB, and MAPK signaling pathways [48]. FIGURE 5. Eﬀect of Z. oﬃcinale ethanolic extract on xylene-induced ear edema in mice compared to indomethacin at 100 mg/kg. GEE: Ethanol extract, values represent means ± SEM (n=6), ns: not signiﬁcant. Carrageenan-induced acute inﬂammaon in mice Carrageenan, a linear sulfated polysaccharide, induces local edema and serves as a standard model for evaluang an-inﬂammatory acvity [49]. Early-phase mediators of carrageenan-induced edema include bradykinin, histamine, and endothelial-derived nitric oxide, which increase vascular permeability through speciﬁc signaling pathways [50 , 51]. In this study, Z. oﬃcinale extracts eﬀecvely inhibited carrageenan- induced paw edema during both the ﬁrst and second phases of inﬂammaon. The result of the an-edematous acvity of the oral administraon of Z. oﬃcinale extract in carrageenan-induced paw edema in mice is given in FIG.6. The subplantar injecon of carrageenan in the negave control group increased paw edema progressively in the ﬁrst hour post-injecon (31.61 %), aaining the maximum at the fourth hour (54.26 %). Treatment of the animals with diclofenac resulted in a signiﬁcant reducon in paw edema two h aﬅer sub plantar injecon of carrageenan (27.16 %), with the eﬀect persisng for up to 4 h (20.23 %), compared to the control group. Oral administraon of the ethanolic extract appears to be more eﬀecve at 400 mg/kg, compared to the 200 mg/kg dose. FIGURE 6. Inhibion Kinecs of GE extract vs. Control Standards Over 4 hours. GE: ginger hydroethanolic extract The an-edematous eﬀect may be mediated by inhibion of prostaglandin producon and antagonism of serotonin, consistent with previous reports [52]. Addionally, the presence of polyphenols and gingerols in the extract might help reduce inﬂammaon by inhibing cyclooxygenase and lipoxygenase pathways, reducing neutrophil and macrophage acvaon, and ulmately leading to limitaons in monocyte and leukocyte migraon [34 , 53]. It is important to point out the clear dose- dependent eﬀect where higher concentraons lead to a greater reducon in pro-inﬂammatory cytokines and an increase in anoxidant capacies, which further supports the role of secondary metabolites in the observed an-inﬂammatory eﬀects [54]. The an-inﬂammatory acvity and the capacity to stop the release of cytokines that cause inﬂammaon are also part of the Z. oﬃcinale extract [55]. The plant has been known to have pharmacological acvity, especially an-inﬂammatory acvity and anoxidant acvity. The major bioacve compounds found in ginger are gingerols, shogaols, and paradols, which play a vital role in the pharmacological acvity of ginger. The an- inﬂammatory acvity of ginger can be explained by its capacity to inhibit key enzymes such as cyclooxygenase-2 (COX-2) and lipoxygenase (LOX) that are involved in the inﬂammatory process. This helps to alleviate the inﬂammaon process in diseases such as rheumatoid arthris and osteoarthris [56 , 57]. Hence, the role of plant-based phytochemicals, which have ethnopharmacological potenal, is to act as the main source of medicine for early drug discovery and to establish the structure for structure-acvity relaonship studies. Phytochemicals are potent sources of anoxidants, and this property helps in the reducon of various health risks associated with oxidave damage. This is due to the presence of various secondary metabolites such as alkaloids, glycosides, ﬂavonoids, and saponins in the plant, and this property of scavenging free radicals helps in amelioraon [58 , 59]. CONCLUSION The study invesgates the phytochemical contents, the anoxidant capacies and the in vivo an-inﬂammatory acvity of Z. oﬃcinale HEE. The collecve outcome revealed ta notable 6 of 9

In vitro and in vivo invesgaons of Zingiber oﬃcinale rhizome / Derafa et. al. UNIVERSIDAD DEL ZULIA Serbiluz Sistema de Servicios Bibliotecarios y de Información Biblioteca Digital Repositorio Académico anoxidant and an-inﬂammatory capacies when compared to the reference compounds used in the study. While the synthec compounds demonstrated a stronger potency, the consistency of the acvity displayed by the extract cannot be overlooked. This highlights the unique advantage of the plant, acng on mulple pathways simultaneously, in contrast to the one- component pharmacology of the synthec compounds. This mul-target approach posions ginger as a valuable addion to complementary and prevenve medicine for dealing with issues related to oxidave stress and inﬂammaon. However, the ﬁndings call for more rigorous studies, emphasizing the requirement of the extract being biochemically standardized, the characterizaon of the acve compounds, and the mechanisc evaluaon at the molecular level. Future research should be directed towards conducng in vivo bioavailability studies to assess the absorpon of these compounds, as well as their clinical eﬃcacy for long-term use. This strategy should aid in the scienﬁc validaon of Zingiber oﬃcinale based preparaons, parcularly for the treatment of oxidave stress-related diseases. ACKNOWLEDGEMENTS The authors would like to acknowledge the Algerian Ministry (MESRS) and the Directorate Scienﬁc Research (DGRSDT) for their ﬁnancial support. Ethical approvals The experimental assays were approved only aﬅer clearance from the Algerian Associaon of Sciences in Animal Experimentaon (AASEA) Commiee (hp://aasea.asso.dz/ arcles/), in compliance with Law Number 88-08 of 1988, regulang veterinary medicine, and published in Oﬃcial Journal Number 004/1988. In addion, these experiments were carried out in accordance with the Internaonal Standards on the care and use of experimental animals (Direcve, 2010/63/EU of the European Parliament and of the Council). Declaraon of compeng interest The authors have no known conﬂict of interest. BIBLIOGRAPHIC REFERENCES [1] Holze C, Michaudel C, Mackowiak C, Haas DA, Benda C, Hubel P, Pennemann FL, Schnepf D, Wemarshausen J, Braun M, Leung DW, Amarasinghe GK, Perocchi F, Staeheli P, Ryﬀel B, Pichlmair A. Oxeiptosis, a ROS- induced caspase-independent apoptosis-like cell-death pathway. Nat. Immunol. [Internet]. 2018; 19(2):130–140. doi: hps://doi.org/gcxq3d [2] Sevindik M, Akgul H, Pehlivan M, Selamoglu Z. Determinaon of therapeuc potenal of Mentha longifolia ssp. longifolia. Fresenius Environ. Bull. [Internet]. 2017; [cited 22 Oct 2025]; 26(7):4757–4763. Available in: hps://goo.su/jzBpjlE [3] Korkmaz N, Dayangaç A, Sevindik M. Anoxidant, anmicrobial, and anproliferave acvies of Galium aparine. Ankara Ecz. Fak. Derg. [Internet]. 2021; 45(3): 554–564. doi: hps://doi.org/qxgd [4] Kına E, Uysal İ, Mohammed FS, Doğan M, Sevindik M. In-vitro anoxidant and oxidant properes of Centaurea rigida. Turkish J. Agric. Food Sci. Technol. [Internet]. 2021; 9(10):1905–1907. doi: hps://doi.org/qxgf [5] Akgül H, Mohammed FS, Kına E, Uysal İ, Sevindik M, Doğan M. Total Anoxidant and Oxidant Status and DPPH Free radical acvity of Euphorbia eriophora. Turkish J. Agric. Food Sci. Technol. [Internet]. 2022; 10(2):272– 275. doi: hps://doi.org/g9xkr6 [6] Hussain T, Tan B, Yin Y, Blachier F, Tossou MC, Rahu N. Oxidave Stress and Inﬂammaon: What Polyphenols Can Do for Us? Oxid. Med. Cell. Longev. [Internet]. 2016; 2016:7432797. doi: hps://doi.org/f8w9 [7] Malik J, Tauchen J, Landa P, Kul Z, Marsik P, Kloucek P, Havlik J, Kokoska L. In vitro an-inﬂammatory and anoxidant potenal of root extracts from Ranunculaceae species. S. Afr. J. Bot. [Internet]. 2017; 109:128–137. doi: hps://doi.org/f97bmw [8] Xu DP, Li Y, Meng X, Zhou T, Zhou Y, Zheng J, Zhang JJ, Li HB. Natural Anoxidants in Foods and Medicinal Plants: Extracon, Assessment and Resources. Int. J. Mol. Sci. [Internet]. 2017; 18(1):96. doi: hps://doi.org/f9zdpd [9] Agbor GA, Kuiaté J-R, Sangiovanni E, Ojo OO. Editorial: The role of medicinal plants and natural products in modulang oxidave stress and inﬂammatory related disorders, Volume II. Front. Pharmacol. [Internet]. 2023; 14:1310291. doi: hps://doi.org/qxgg [10] Pehlivan M, Mohammed FS, Şabik AE, Kına E, Dogan M, Yumrutaş Ö, Sevindik M. Some Biological acvies of the ethanol extract of Marrubium globosum. Turkish J. Agric. Food Sci. Technol. [Internet]. 2021; 9(6):1129–1132. doi: hps://doi.org/qxgh [11] Uysal İ, Mohammed FS, Şabik AE, Kına E, Sevindik M. Anoxidant and Oxidant status of medicinal plant Echium italicum collected from diﬀerent regions. Turkish J. Agric. Food Sci. Technol. [Internet]. 2021; 9(10):1902–4. Available in: hps://doi.org/g65436 [12] Zhang M, Zhao R, Wang D, Wang L, Zhang Q, Wei S, Lu F, Peng W, Wu C. Ginger (Zingiber oﬃcinale Rosc.) and its bioacve components are potenal resources for health beneﬁcial agents. Phytother Res. [Internet]. 2021; 35(2):711–742. doi: hps://doi.org/gppxkk [13] Ghédira K. Zingiber oﬃcinale (Zingiberaceae). Phytothérapie. [Internet]. 2025 [cited 22 Oct 2025]; 23(3):149–158. Available in: hps://goo.su/R65N [14] Ayustaningwarno F, Anjani G, Ayu AM, Fogliano V. A crical review of Ginger’s (Zingiber oﬃcinale) anoxidant, an- inﬂammatory, and immunomodulatory acvies. Front. Nutr. [Internet]. 2024; 11:1364836. doi: hps://doi.org/ qxgk [15] Gigon F. Le gingembre, une épice contre la nausée. Phytothérapie [Internet]. 2012; 10(2):87–91. doi: hps:// doi.org/gt7zkt [16] Karbab A, Charef N, Wardana AP, Abdjan MI, Shakya AK, Aminah NS. Andiabec, anoxidant, and an- inﬂammatory acvies of Paronychia capitata L. and 7 of 9

Revista Cienﬁca, FCV-LUZ / Vol. XXXV UNIVERSIDAD DEL ZULIA Serbiluz Sistema de Servicios Bibliotecarios y de Información Biblioteca Digital Repositorio Académico Paronychia argentea L. from Algerian medicinal plants and idenﬁcaon of its bioacve compounds by LC-MS/ MS phytochemical analysis. Kuwait J. Sci. [Internet]. 2026; 53(1):100509. doi: hps://doi.org/qxgm [17] Haniadka R, Saldanha E, Sunita V, Palay PL, Fayad R, Baliga MS. A review of the gastroprotecve eﬀects of ginger (Zingiber oﬃcinale Roscoe). Food. Funct [Internet]. 2013; 4(6):845-855. doi: hps://doi.org/gf975q [18] Funk JL, Frye JB, Oyarzo JN, Chen J, Zhang H, Timmermann BN. An-inﬂammatory eﬀects of the essenal oils of ginger (Zingiber oﬃcinale Roscoe) in experimental rheumatoid arthris. PharmaNutrion. [Internet]. 2016; 4(3):123–131. doi: hps://doi.org/gbnrkb [19] Lete I, Alluέ J. The Eﬀecveness of Ginger in the Prevenon of Nausea and Voming during Pregnancy and Chemotherapy. Integr. Med. Insight. [Internet]. 2016; 11:11–17. doi: hps://doi.org/grjszv [20] Zhang S, Zhang L, Yu M, Luo D, Chen S, Liu W, Zhang Y, Zhang L, Zhao T. Essenal oils of Zingiber oﬃcinale: Chemical composion, in vivo alleviaon eﬀects on TPA induced ear swelling in mice and in vitro bioacvies. Front. Nutr. [Internet]. 2022; 9:1043175. doi: hps://doi. org/qxgn [21] Ahmad B, Rehman MU, Amin I, Arif A, Rasool S, Bhat SA, Afzal I, Hussain I, Bilal S, Mir Mu. A Review on Pharmacological Properes of Zingerone (4-(4-Hydroxy- 3-methoxyphenyl)-2-butanone). Sci. World J. [Internet]. 2015; 2015:816364. doi: hps://doi.org/gb5qvc [22] Choi JS, Ryu J, Bae WY, Park A, Nam S, Kim JE, Jeong JW. Zingerone Suppresses Tumor Development through Decreasing Cyclin D1 Expression and Inducing Mitoc Arrest. Int. J. Mol. Sci. [Internet]. 2018; 19(9):2832. doi: hps://doi.org/gfp7r6 [23] Wollenweber E. Techniques of ﬂavonoid idenﬁcaon: By K. R. Markham. Academic Press, London, 1982. 113 pp. $419.50. Phytochemistry [Internet]. 1983; 22(5):1310. doi: hps://doi.org/dwsq2v [24] Amari S, Ahlem K, Arrar L, Noureddine C. Fraconaon, phytochemical screening and anoxidant acvity of diﬀerent sub-fracons from leaves and ﬂowers of Erica arborea L. Turk, J, Agric. Food Sci. Technol. [Internet]. 2023; 11(4):830-837. doi: hps://doi.org/pqpz [25] Sánchez-Rangel JC, Benavides J, Heredia JB, Cisneros- Zevallos L, Jacobo-Velázquez DA. The Folin–Ciocalteu assay revisited: improvement of its speciﬁcity for total phenolic content determinaon. Anal. Methods [Internet]. 2013; 5(21):5990-5999. doi: hps://doi.org/ gf7vmb [26] Bahorun T, Gressier B, Tron F, Brunet C, Dine T, Luyckx M, Vasseur J, Cazin M, Cazin JC, Pinkas M. Oxygen species scavenging acvity of phenolic extracts from hawthorn fresh plant organs and pharmaceucal preparaons. Arzneimielforschung [Internet]. 1996 [cited 22 Oct 2025]; 46(11):1086–1089. PMID: 8955870 Available in: hps://goo.su/EoVX [27] Burits M, Bucar F. Anoxidant acvity of Nigella sava essenal oil. Phytother. Res. [Internet]. 2000; 14(5):323– 328. doi: hps://doi.org/b639sn [28] Dapkevicius A, Venskutonis R, van Beek TA, Linssen JPH. Anoxidant acvity of extracts obtained by diﬀerent isolaon procedures from some aromac herbs grown in Lithuania. J. Sci. Food Agric. [Internet]. 1998; 77(1):140- 146. doi: hps://doi.org/dc6447 [29] Chung YC, Chen SJ, Hsu CK, Chang CT, Chou ST. Studies on the anoxidave acvity of Graptopetalum paraguayense E. Walther. Food Chem. [Internet]. 2005; 91(3):419–424. doi: hps://doi.org/b757kz [30] Aa AH, Alkofahi A. An-nocicepve and an- inﬂammatory eﬀects of some Jordanian medicinal plant extracts. J. Ethnopharmacol. [Internet]. 1998; 60(2):117– 124. doi: hps://doi.org/dwt4jn [31] Belay R, Makonnen E. An-inﬂammatory acvies of ethanol leaves extract and solvent fracons of Zehneria scabra (Cucurbitaceae) in rodents. Asian J. Nat. Prod. Biochem. [Internet]. 2020; 18(1):42-56. doi: hps://doi. org/qxhd [32] Lukia B, Sulisejono, Nugrahaningsih, Masita R. Determinaon of total phenol and ﬂavonoid levels and anoxidant acvity of methanolic and ethanolic extract Zingiber oﬃcinale Rosc var. Rubrum rhizome. AIP Conference Proceedings [Internet]. 2020; 2232(1):040003. doi: hps://doi.org/qxhf [33] Bekkouch O, Harnaﬁ M, Touiss I, Khab S, Harnaﬁ H, Alem C, Amrani S. In Vitro Anoxidant and In Vivo Lipid- Lowering Properes of Zingiber oﬃcinale Crude Aqueous Extract and Methanolic Fracon: A Follow-Up Study. Evid. Based Complement. Alternat. Med. [Internet]. 2019; 2019:9734390. doi: hps://doi.org/qxhh [34] Ezzat SM, Ezzat MI, Okba MM, Menze ET, Abdel-Naim AB. The hidden mechanism beyond ginger (Zingiber oﬃcinale Rosc.) potent in vivo and in vitro an-inﬂammatory acvity. J. Ethnopharmacol. [Internet]. 2018; 214:113– 123. doi: hps://doi.org/gjnqsh [35] Mošovská S, Nováková D, Kaliňák M. Anoxidant acvity of ginger extract and idenﬁcaon of its acve components. Acta Chim. Slov. [Internet]. 2015; 8(2):115– 119. doi: hps://doi.org/gjzzbc [36] Karbab A, Mokhnache K, Ouhida S, Charef N, Djabi F, Arrar L, Mubarak MS. An-inﬂammatory, analgesic acvity, and toxicity of Pituranthos scoparius stem extract: An ethnopharmacological study in rat and mouse models. J. Ethnopharmacol. [Internet]. 2020; 258:112936. doi: hps://doi.org/grsd8s [37] Formoso P, Tundis R, Pellegrino MC, Leporini M, Sicari V, Romeo R, Gervasi L, Corrente GA, Beneduci A, Loizzo MR. Preparaon, characterizaon, and bioacvity of Zingiber oﬃcinale Roscoe powder-based Pickering emulsions. J. Sci. Food Agric. [Internet]. 2022; 102(14):6566–6577. doi: hps://doi.org/qxhj [38] Chew YL, Chan EWL, Tan PL, Lim YY, Stanslas J, Goh JK. Assessment of phytochemical content, polyphenolic composion, anoxidant and anbacterial acvies of Leguminosae medicinal plants in Peninsular Malaysia. BMC Complement. Altern. Med. [Internet]. 2011; 11(1):12. doi: hps://doi.org/cqq3sm [39] Tanweer S, Mehmood T, Zainab S, Ahmad Z, Shehzad A. Comparison and HPLC quanﬁcaon of anoxidant proﬁling of ginger rhizome, leaves and ﬂower extracts. Clin. Phytosci. [Internet]. 2020; 6(1):12. doi: hps://doi. org/gp63ph [40] Amari S, Karbab A, Charef N, Arrar L, Mubarak MS. An-urolithiac, anbacterial, an-inﬂammatory and 8 of 9

In vitro and in vivo invesgaons of Zingiber oﬃcinale rhizome / Derafa et. al. UNIVERSIDAD DEL ZULIA Serbiluz Sistema de Servicios Bibliotecarios y de Información Biblioteca Digital Repositorio Académico analgesic eﬀects of Erica arborea ﬂowers and leaves hydromethanolic extracts: An ethnopharmacological study. Saudi J. Biol. Sci [Internet]. 2023; 30(10):103785. doi: hps://doi.org/pqqc [41] Waché Y, Bosser-DeRatuld A, Lhuguenot JC, Belin JM. Eﬀect of cis/trans Isomerism of β-Carotene on the Raos of Volale Compounds Produced during Oxidave Degradaon. J. Agric. Food Chem. [Internet]. 2003; 51(7):1984–1987. doi: hps://doi.org/bdms6n [42] Bhandari U, Kanojia R, Pillai KK. Eﬀect of ethanolic extract of Zingiber oﬃcinale on dyslipidaemia in diabec rats. J. Ethnopharmacol. [Internet]. 2005; 97(2):227–230. doi: hps://doi.org/dmk8qz [43] Ayustaningwarno F, Anjani G, Ayu AM, Fogliano V. A crical review of Ginger’s (Zingiber oﬃcinale) anoxidant, an- inﬂammatory, and immunomodulatory acvies. Front. Nutr. [Internet]. 2024; 11:1364836. doi: hps://doi.org/ qxgk [44] Ma H, Wang F, Jiang J, Cheng L, Zhang H, Zhang G. In vivo an-inﬂammatory acvity of Liquidambar formosana Hance infructescence extract. Trop. J. Pharm. Res. [Internet]. 2017; 16(10):2403–2410. doi: hps://doi.org/ qxhk [45] Singsai K, Charoongchit P, Chaikaew W, Boonma N, Fhanjaksai P, Chaisatan K. Anlipoxygenase and an- Inﬂammatory acvies of Streblus asper leaf extract on Xylene-induced ear edema in Mice. Adv. Pharmacol. Pharm. Sci. [Internet]. 2020; 2020:3176391. doi: hps:// doi.org/qxhm [46] Karbab A, Charef N, Abu-zarga M, Qadri M, Mubarek MS. Ethnomedicinal documentaon and an-inﬂammatory eﬀects of n-butanol extract and of four compounds isolated from the stems of Pituranthos scoparius: An in vitro and in vivo invesgaon. J. Ethnopharmacol. [Internet]. 2021; 267:113488. doi: hps://doi.org/pqp2 [47] Mondal M, Quispe C, Sarkar C, Bepari TC, Alam MdJ, Saha S, Ray P, Rahim MA, Islam MT, Setzer WN, Salehi B, Ahmadi M, Abdalla M, Shariﬁ-Rad J, Kundu SK. Analgesic and an-inﬂammatory potenal of essenal oil of Eucalyptus camaldulensis Leaf: In vivo and in silico Studies. Nat. Prod. Commun [Internet]. 2021; 16(4):1-16. doi: hps://doi.org/qxhn [48] Bischoﬀ-Kont I, Fürst R. Beneﬁts of ginger and its constuent 6-Shogaol in inhibing inﬂammatory processes. Pharmaceucals. [Internet]. 2021; 14(6):571. doi: hps://doi.org/qxhp [49] Charlie-Silva I, Feitosa NM, Pontes LG, Fernandes BH, Nóbrega RH, Gomes JMM, Prata MNL, Ferraris FK, Melo DC, Conde G, Rodrigues LF, Araca MF, Corrêa-Junior JD, Manrique WG, Superio J, Garcez AS, Conceição K, Yoshimura TM, Núñez SC, Eto SF, Fernandes DC, Freitas AZ, Ribeiro MS, Nedoluzhko A, Lopes-Ferreira M, Borra RC, Barcellos LJG, Perez AC, Malafaia G, Cunha TM, Belo MAA, Galindo-Villegas J. Plasma proteome responses in zebraﬁsh following λ-carrageenan-Induced inﬂammaon are mediated by PMN leukocytes and correlate highly with their human counterparts. Front. Immunol. [Internet]. 2022; 13:1019201. doi: hps://doi.org/qxhq [50] Di Lorenzo A, Fernández-Hernando C, Cirino G, Sessa WC. Akt1 is crical for acute inﬂammaon and histamine- mediated vascular leakage. Proc. Natl. Acad. Sci. [Internet]. 2009; 106(34):14552–14557. doi: hps://doi. org/cng9zh [51] Kim KH, Im HW, Karmacharya MB, Kim S, Min BH, Park SR, Choi BH. Low-intensity ultrasound aenuates paw edema formaon and decreases vascular permeability induced by carrageenan injecon in rats. J. Inﬂamm. [Internet]. 2020; 17(1):7. doi: hps://doi.org/gjgjsk [52] Zammel N, Saeed M, Bouali N, Elkahoui S, Alam JM, Rebai T, Kausar MA, Adnan M, Siddiqui AJ, Badraoui R. Anoxidant and An-Inﬂammatory Eﬀects of Zingiber oﬃcinale roscoe and Allium subhirsutum: In Silico, biochemical and histological study. Foods. [Internet]. 2021; 10(6):1383. doi: hps://doi.org/qxm9 [53] Tjendraputra E, Tran VH, Liu-Brennan D, Roufogalis BD, Duke CC. Eﬀect of ginger constuents and synthec analogues on cyclooxygenase-2 enzyme in intact cells. Bioorg. Chem. [Internet]. 2001; 29(3):156–163. doi: hps://doi.org/bxg8rh [54] Mengie T, Mequanente S, Nigussie D, Legesse B, Makonnen E. Invesgaon of wound healing and an-Inﬂammatory acvies of solvent fracons of 80% methanol leaf extract of Achyranthes aspera L. (Amaranthaceae) in Rats. J. Inﬂamm. Res. [Internet]. 2021; 14:1775–1787. doi: hps://doi.org/gkzwgv [55] Song MY, Lee DY, Park SY, Seo SA, Hwang JS, Heo SH, Kim EH. Steamed Ginger Extract Exerts An-inﬂammatory Eﬀects in Helicobacter pylori-infected Gastric Epithelial Cells through Inhibion of NF-κB. J. Cancer Prev. [Internet]. 2021; 26(4):289-297. doi: hps://doi.org/ qxnc [56] Shashikala BVS. An-inﬂammatory eﬀects of Zingiber oﬃcinale: A comprehensive review of its bioacve compounds and therapeuc potenal. Medgo J. Pharmacol. [Internet]. 2024; 1(1):2–3. doi: hps://doi. org/qxnd [57] Ayustaningwarno F, Anjani G, Ayu AM, Fogliano V. A crical review of ginger (Zingiber oﬃcinale) anoxidant, an-inﬂammatory, and immunomodulatory acvies. Front. Nutr. [Internet]. 2024; 11:1364836. doi: hps:// doi.org/qxgk [58] Buhian WP, Rubio RO, Valle DL Jr, Marn-Puzon JJ. Bioacve metabolite proﬁles and anmicrobial acvity of ethanolic extracts from Munngia calabura L. leaves and stems. Asian Pac. J. Trop. Biomed. [Internet]. 2016; 6(8):682–685. doi: hps://doi.org/qxnf [59] Sharma P, Raina R, Verma PK, Nashiruddullah N, Pankaj N, Kour H. Hepatoprotecve potenal of Cynara scolymus in cisplan-induced hepatotoxicity in rats. J. Vet. Pharmacol. Toxicol. [Internet]. 2018 [cited 22 Oct 2025]; 17(2):57–62. Available in: hps://goo.su/LQ4J6J 9 of 9