Blood Biomarkers of Neonatal Sepsis with Special Emphasis on the Monocyte Distribution Width Value as an Early Sepsis Index.

Background and Objectives: Early detection of neonatal sepsis is critical because it is potentially fatal. Therefore, sepsis biomarkers of sufficient sensitivity and specificity are needed. This study aimed to evaluate the utility of peripheral blood parameters as neonatal sepsis biomarkers and the diagnostic performance of the monocyte distribution width (MDW) in sepsis in a neonatal intensive care unit. Materials and Methods: A cross-sectional study was conducted from September 2019 to August 2020 at the King Saud University Medical City in Riyadh, Saudi Arabia. Samples were collected and organised as follows: 77 study cases were subdivided into two subgroups (other health complication (49) and sepsis (28)), and there were 70 controls. The causative microorganisms of neonatal sepsis were isolated. Peripheral blood samples were collected from each neonate in an ethylenediaminetetraacetic acid tube for a complete blood count and a leukocyte differential count. Moreover, the receiver operating characteristic (ROC) curve analysis was used to measure the diagnostic performance of the MDW. Results: The haematological parameters and neonatal sepsis cases had a considerable correlation. The MDW was the most significant haematological parameter. The ROC analysis of the MDW demonstrated that the area under the curve was 0.89 (95% confidence interval: 0.867 to 0.998) with a sensitivity of 89.3%, a specificity of 88.2%, and a negative predictive value of 97.2% at the cut-off point of 23. Conclusions: The use of haematological parameters is feasible and can be performed rapidly. Neonatal sepsis showed a strong correlation with leukopenia, anaemia, thrombocytopenia, and an elevated MDW value. Moreover, the ROC curve analysis confirmed the high diagnostic ability of the MDW in neonatal sepsis prediction.

Biosynthesized Nanosilver from Ginger Extract Exhibits Antioxidant and Hepatic Responses during Eimeria papillata Infection.

Although several anticoccidial medications have long been used to prevent coccidiosis, their adverse effects necessitate the use of alternative control methods. In this study, Eimeria papillate was used to infect the mouse jejunum, and the response of the liver to induced coccidiosis on treatment with nanosilver synthesized from Zingiber officinale (NS) and the reference anticoccidial drug amprolium was compared. Mice were infected with 1000 sporulated oocysts to induce coccidiosis. NS was able to inhibit the sporulation of E. papillate by approximately 73%, and also, the NS treatment improved the liver function in mice, as proven by lower levels of the liver enzymes AST, ALT, and ALP. Furthermore, treatment with NS improved the parasite-induced liver histological injury. Also, glutathione and glutathione peroxidase levels increased following treatment. Moreover, the concentrations of metal ions, Fe, Mg, and Cu, were studied, where only the Fe concentration was affected after treatment of the E. papillate-infected mice with Bio-NS. The presence of phenolic and flavonoid compounds in NS is thought to be responsible for its positive effects. Overall, the current study found that NS outperformed amprolium in E. papillata-induced mice.

Assessment of Circulating lncRNA H19 in Ankylosing Spondylitis Patients and Its Correlation with Disease Activity.

Ankylosing spondylitis (AS) is a chronic inflammatory disease that results in severe pain and stiffness in the joints. The causes and pathophysiology of AS are still largely unknown. The lncRNA H19 plays key roles in the pathogenesis of AS by mediating inflammatory progression by acting in the axis of IL-17A/IL-23. The aims of this study were determining the role of lncRNA H19 in AS and assessing its clinical correlation. A case-control study was conducted and qRT-PCR was utilized to measure H19 expression. Comparing AS cases to healthy controls, it was found that H19 expression was significantly upregulated. For AS prediction, H19 demonstrated a 81.1% sensitivity, 100% specificity, and 90.6% diagnostic accuracy at a lncRNA H19 expression value of 1.41. lncRNA H19 had a significantly positive correlation with AS activity, MRI results, and inflammatory markers. lncRNA H19 seemed to be an independent predictor of AS (adjusted OR of 211 (95% CI: 4.7-939; p = 0.025)). After 3 months of clinical follow-up, seventeen patients (32.1%) showed minimal clinical improvement and fifteen patients (28.3%) showed major improvement. AS activity scores were significantly decreased in patients with high H19 expression. A significantly elevated lncRNA H19 expression was observed in AS cases compared with that in healthy controls. These results suggest that upregulation of lncRNA H19 expression may be involved in the pathogenesis of AS. The expression of the lncRNA H19 is related to the duration and activity of the disease. LncRNA H19 expression seems to be an independent predictor of AS.

Effect of biosynthesized nanoselenium using Azadirachta indica (Meliaceae) leaf extracts against Eimeria papillata infection.

Coccidiosis is a protozoan parasitic disease affecting different animal species. Resistance has been reported for all available anticoccidial drugs. Recently, green synthesis of nanoparticles is considered a new therapeutic tool against this parasitic disease. The present work aimed to study the effect of biosynthesized nanoselenium from Azadirachta indica leaf extracts (BNS) against Eimeria papillata-induced infection in mice. The phytochemical analysis of leaf extracts contained 33 phytochemical components. The BNS was spherical with ⁓68.12 nm in diameter and an absorption peak at 308 nm via UV-spectra. The data showed that mice infected with E. papillata revealed the highest oocyst output on the 5th-day post-infection (p.i.). Infection also induced injury and inflammation of the mice jejunum. Treatment with BNS resulted in a 97.21% suppression for the oocyst output. The treated groups with BNS showed enhancement in feed intake as compared to the infected group. Histological examinations showed a significant reduction in the intracellular developmental Eimeria stages in the jejunal tissues of infected-treated mice of about 24.86 ± 2.38 stages/10 villous crypt units. Moreover, there was a significant change in the morphometry for Eimeria stages after the treatment with BNS. Infection induced a disturbance in the level of carbohydrates and protein contents in the infected mice which enhanced after treatment with BNS. In addition, BNS counteracted the E. papillata-induced loss of the total antioxidant capacity. Collectively, BNS is considered a promising anticoccidial and antioxidant effector and could be used for the treatment of coccidiosis.

In vivo anticoccidial, antioxidant, and anti-inflammatory activities of avocado fruit, Persea americana (Lauraceae), against Eimeria papillata infection.

Apicomplexan parasites, especially Eimeria sp., are the main intestinal murine pathogens, that lead to severe injuries to farm and domestic animals. Many anticoccidial drugs are available for coccidiosis, which, leads to the development of drug-resistant parasites. Recently, natural products are considered as an alternative agent to control coccidiosis. This study was designed to evaluate the anticoccidial activity of the Persea americana fruit extract (PAFE) in male C57BL/6 mice. A total of 35 male mice were divided into seven equal groups (1, 2, 3, 4, 5, 6, and 7). At day 0, all groups except the first group which served as uninfected-untreated control were infected orally with 1 × 103E. papillata sporulated oocysts. Group 2 served as uninfected-treated control. Group 3 was considered an infected-untreated group. After 60 min of infection, groups 4, 5, and 6 were treated with oral doses of PAFE aqueous methanolic extract (100, 300, and 500 mg/kg of body weight, respectively). Group 7 was treated with amprolium (a reference drug for coccidiosis). PAFE with 500 mg/kg, was the most effective dose, inducing a significant reduction in the output of oocysts in mice feces (by about 85.41%), accompanied by a significant decrease in the number of the developmental parasite stages and a significant elevation of the goblet cells in the jejunal tissues. Upon treatment, a significant change in the oxidative status due to E. papillata infection was observed, where the levels of glutathione (GSH) increased, while, levels of malondialdehyde (MDA) and nitric oxide (NO) were decreased. In addition, the infection significantly upregulated the inflammatory cytokines of interleukin-1ß (IL-1ß), tumor necrosis factor-alpha (TNF-α), and interferon-γ (IFN-γ). This increase in mRNA expression of IL-1ß, TNF-α, and IFN-γ was about 8.3, 10.6, and 4.5-fold, respectively, which significantly downregulated upon treatment. Collectively, P. americana is a promising medicinal plant with anticoccidial, antioxidant, and anti-inflammatory activities and could be used for the treatment of coccidiosis.

LncRNA-GAS5 and ß-Catenin as Independent Predictors of Asymptomatic Organ Damage in Nondiabetic Hypertensive Patients.

Hypertension is a serious medical condition that can increase the risk of developing heart, brain, kidney, and other diseases. Many asymptomatic hypertension patients experience asymptomatic organ damage (AOD). The purpose of this study was to determine the roles of LncRNA-GAS5 and ß-catenin in predicting AOD in hypertensive nondiabetic patients. This study included 256 subjects, 128 hypertension patients (75 of whom had AOD, and 53 of whom did not) and 128 healthy controls. qRT-PCR was used to assess LncRNA-GAS5, and ELISA was used to assess ß-catenin. The LncRNA-GAS5 expression level was decreased in hypertensive patients compared to controls (p-value < 0.001). On the other hand, ß-catenin levels showed higher levels in the patients in comparison with controls (p-value < 0.001). A 0.38-fold change in LncRNA-GAS5 expression predicted AOD with 86.6% sensitivity and 88.7% specificity. ß-Catenin > 80.5 pg/mL predicted AOD with a sensitivity of 82.6% and specificity of 69.8%. LncRNA-GAS5 expression was a better diagnostic predictor of AOD than ß-catenin. According to multivariate logistic regression analysis, decreased LncRNA-GAS5 expression independently increased the risk of AOD (adjusted odds ratio = 0.03 (95% CI: 0.01-0.1) (p < 0.001). Furthermore, elevated ß-catenin levels may be an independent risk factor for AOD (adjusted odds ratio = 14.3 (95% confidence interval, 3.3-61.9) (p < 0.001). Collectively, in hypertensive patients, LncRNA GAS5 and ß-catenin can distinguish patients with AOD from those who do not have AOD. LncRNA GAS5 and ß-catenin can be used as independent predictors of AOD in hypertensive patients.

Biosynthesized silver nanoparticles have anticoccidial and jejunum-protective effects in mice infected with Eimeria papillata.

Eimeriosis, an infection with Eimeria spp. that affects poultry, causes huge economic losses. Silver nanoparticles (AgNPs) have antibacterial and antifungal properties, but their action against Eimeria infection has not yet been elucidated. This study demonstrates the action of AgNPs in the treatment of mice infected with Eimeria papillata. AgNPs were prepared from Zingiber officinale rhizomes. Phytochemical screening by gas chromatography-mass spectrometry analysis (GC-MS) was used to detect active compounds. Mice were divided into five groups: uninfected mice, uninfected mice that were administered AgNPs, untreated mice infected with 103 sporulated oocysts of E. papillata, infected mice treated with AgNPs, and infected mice treated with amprolium. Characterization of the samples showed the AgNPs to have nanoscale sizes and aspherical shape. Phytochemical screening by GC-MS demonstrated the presence of 38 phytochemical compounds in the extract of Z. officinale. Mice infected with E. papillata-sporulated oocysts were observed to have many histopathological damages in the jejuna, including a decrease in the goblet cell numbers affecting the jejunal mucosa. Additionally, an increased oocyst output was also observed. The treatment of infected mice with AgNPs resulted in the improvement of the jejunal mucosa, increase in the number of goblet cell, and decrease in the number of meronts, gamonts, and developing oocysts in the jejuna. Moreover, AgNPs also led to decreased oocyst shedding in feces. The results revealed AgNPs to have an anticoccidial effect in the jejunum of E. papillata-infected mice and, thus, could be a potential treatment for eimeriosis.

The effect of Moringa oleifera leaf extracts against urethane-induced lung cancer in rat model.

Lung cancer is one of the most common malignancies in the world, and chemotherapy can have unfavorable side effects. The aim of the present study is to evaluate the therapeutic anticancer role of Moringa oleifera leaf extracts (MLE) in urethane-induced lung cancer in adult male albino rats as compared to standard chemotherapy. Rats were categorized into four groups (10 rats/group), including negative control rats, urethane lung cancer model rats, MLE-treated lung cancer rats, and cisplatin-treated rats. Estimation of lung index, some biochemical markers of oxidative stress, quantitative real-time polymerase chain reaction (qRT-PCR), and histopathology and transmission electron microscopy were performed. The lung index was significantly increased about one-fold in urethane lung cancer model rats, but it decreased after MLE treatment. Also, MLE was able to improve the induced changes in glutathione, superoxide dismutase, and malondialdehyde concentration to be 3.8 ± 0.4 mg/g, 900.6 ± 58 U/g, and 172 ± 24 nmol/g, respectively. Additionally, after MLE treatment, the expression of EGFR-mRNA increased by about 50%. Our light and electron microscopic examination revealed that urethane group showed abnormally distributed excessive collagen fibers and the development of papillary adenocarcinoma from hyperplastic Clara cells in the lumen of terminal bronchiole with bronchiolar wall thickening, alveolar collapse, and inflammation. MLE group has moderate amount of collagen fiber and absence of tumor mass and provided more or less restoration of normal lung histology. Moreover, MLE was able to ameliorate the induced changes in mucin and PCNA positive cells in the lung by 10.8 ± 2.3%. Collectively, the current study showed that MLE could be used as anticancer agents alleviating changes associated with lung cancer in a urethane-induced lung cancer bearing rats thereby representing alternative options to toxic chemotherapy.

Hepatoprotective activity of Eucalyptus camaldulensis extract in murine malaria mediated by suppression of oxidative and inflammatory processes.

Herbal extracts are promising agents against various parasitic diseases, such as malaria. This study aimed to evaluate the ameliorative action of Eucalyptus camaldulensis extract (ECE) against hepatic damage caused by Plasmodium chabaudi infection. Mice were allocated into five groups as follows: two groups served as the control non-infected groups that received distilled water and ECE, respectively; subsequent three groups were infected with 106 P. chabaudi parasitized erythrocytes; the last two groups were infected with the parasite and then treated with ECE and chloroquine. On day 8 post-infection, the parasite count increased inside erythrocytes (59.4% parasitemia in the infected group). Parasitemia was successfully reduced to 9.4% upon ECE treatment. Phytochemical screening using GC mass spectrometry revealed that ECE contained 23 phytochemical components. Total phenolics and flavonoids in ECE were 104 ± 2 and 7.1± 3 µg/mL, respectively, with 57.2% antioxidant activity. ECE ameliorated changes in liver histopathology and enzymatic activity of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. In addition, ECE prevented oxidative damage induced by the parasite in the liver, as evidenced by the change in the liver concentrations of glutathione, nitric oxide, malondialdehyde, and catalase. Moreover, ECE was able to regulate the expression of liver cytokines, interleukins-1ß and 6, as well as IFN-γ mRNA. ECE possesses antiplasmodial, antioxidant, and anti-inflammatory activity against liver injury induced by the parasite P. chabaudi.

Zingiber officinale supplementation suppresses eimeriosis and regulates goblet cell response.

Coccidiosis affects both domestic and wild animals and negatively impacting industries worldwide. Medicinal plants are widely used against parasites. Using infected mice with Eimeria papillata, we assessed the anticoccidial impact of Zingiber officinale extract (ZE). The animals in the first group were just given distilled water, while the animals in the second group were given ZE. The parasite's oocysts were infected into the third and fourth groups. The fourth group was given ZE for five days. The oocysts in mice faeces were reduced after treatment with ZE. The total parasitic stages were reduced after treatments by about 50%. Also, gamonts, meronts and oocysts inside the jejunum were decreased after treatment with ZE. The infection caused hypoplasia of goblet cells of jejunum. ZE was able to ameliorate the goblet cells decrease. Behavioral response of animals to infection and treatment was investigated. All of these improvements could be attributed to the existence of active chemical classes of substances identified using infrared spectroscopy. Additional experiments are required to identify the phytochemical compounds in ZE and to understand their fighting mechanism against the parasite.

Treatment of Trypanosoma evansi-Infected Mice With Eucalyptus camaldulensis Led to a Change in Brain Response and Spleen Immunomodulation.

Surra is a parasitic disease caused by the eukaryotic, unicellular hemoprotozoan, Trypanosoma evansi, which affects the development of animal production and is widespread among both domestic and wild animals. As such, in this research, we studied the antiparasitic activity and the ameliorative impact of Eucalyptus camaldulensis leaf extracts (ELE) against T. evansi-induced brain injury and spleen immune response in mice. As a result, we found that ELE decreased the amount of trypanosomes in the blood and improved the weight loss caused by infection. In addition, ELE reduced the parasite-induced brain and spleen histopathological damage. The parasite affected the levels of dopamine and serotonin, but after treatment with ELE, their concentrations significantly decreased to 154 ± 7 and 258 ± 11 µg/g, respectively. We clearly observed the antioxidant activity of ELE because of its ability to increase the induced change in the brain's total antioxidant capacity and the nitric oxide level. The histopathological changes in the spleen also improved after ELE application. Based on our results, we concluded that ELE possesses antitrypanosomal antioxidant and protective effects in the brains of mice infected with T. evansi. Additional phytochemical screening and molecular studies are required to understand the mechanism underlying the effect of ELE.

Assessment of the oxidative status and goblet cell response during eimeriosis and after treatment of mice with magnesium oxide nanoparticles.

Magnesium nanoparticles have been the focus of study over the past few years because of its functionality in the body. Assessment of the impact of magnesium oxide nanoparticles (MgNPs) on eimeriosis has yet to be conducted. The goal of this study was to see how MgNPs affected the parasite Eimeria papillata infected jejunum. To induce eimeriosis, mice were infected with sporulated oocysts. For treatment, 5 mg / Kg MgNPs was used for 5 consecutive days. The infection reduced the number of intestinal goblet cells and their associated genes MUC2 and MUC4, as well as increasing oxidative damage in the jejunum. MgNPs significantly reduced the oocyst production in the feces by about 77 %. After treatment, the number of goblet cells per villus increased from 4.17% to 7.40.6%. Moreover, the MgNPs were able to upregulate the expression of MUC2 and MUC4-mRNA. MgNPs significantly increased the activity of catalase and superoxide dismutase, as well as the extent of glutathione, by day 5 after infection with the parasite. On contrary, MgNPs decreased the level of malondialdehyde and nitric oxide. The findings suggested that MgNPs could be an effective anti-eimeriosis agent due to their anti-eimerial and anti-oxidant roles, as well as the regulatory effect on the goblet cell mucin genes in the jejunum of mice.

Biosynthesized nanosilver as anti-oxidant, anti-apoptotic and anti-inflammatory agent against Plasmodium chabaudi infection in the mouse liver.

In recent years, the use of plant-mediated nanoparticle synthesis to combat infectious diseases has become increasingly significant. Malaria is one of the world's most infectious diseases caused by Plasmodium species. The antioxidant, anti-apoptotic, and anti-inflammatory properties of nanosilver biosynthesized from Indigofera oblongifolia leaf extracts (NS) against Plasmodium chabaudi infection of the mouse liver were investigated in this research. Male mice were infected with P. chabaudi infected erythrocytes then treated with NS for 7 days. The parasitemia was suppressed by approximately 24, 28, 47 and 75% on days 4, 5, 6 and 7 postinfection, respectively after treatment of mice with NS. Also, NS was able to regulate the leucocytes count and the IL1ß and TNF-α-mRNA expression in mice. Ns could increase the antioxidant activity in liver of mice and was able to regulate the apoptotic genes, Bcl2 and Casp3. We showed that NS has antioxidant, anti-apoptotic, and anti-inflammatory properties when it was used to treat the livers of mice infected with P. chabaudi.

Protective Role of Morus nigra Leaf Extracts against Murine Infection with Eimeria papillata.

BACKGROUND: Eimeriosis is a parasitic intestinal infection that affects the poultry industry; it is responsible for economic losses on a global scale. OBJECTIVE: This study investigated the protective role of Morus nigra leaf extracts (ME) against Eimeria papillata infection in mice. METHODS: C57Bl/6 mice were divided into six groups. The first group was gavaged daily with 100 µL 0.9% NaCl. The second group was treated daily by oral gavage with 100 µL M. nigra leaf extracts (ME) (200 mg/kg), while the third, fourth, fifth, and sixth groups were orally infected with 1000 E. papillata oocysts. The last three groups were daily treated for 5 days with 200, 400, and 800 mg/kg of ME, respectively. Samples of jejunum were obtained for examining the histopathological changes as well as changes in the nitric oxide and catalase levels. RESULTS: Infrared spectroscopy of ME showed the presence of several expected active classes of phytochemical compounds. ME was able to reduce the E. papillata oocysts in mice feces by about 80% and decrease the infection-induced jejunal histopathological injuries. This was quantified using the histological injury score. In addition, ME significantly recovered the changes in nitric oxide and catalase levels. CONCLUSION: Our findings showed that the M. nigra extract has an antioxidant activity which protects against murine eimeriosis. Further studies are required to determine the exact active compounds in ME and their mode of action.

Anthelmintic, anticoccidial and antioxidant activity of Salvadora persica root extracts.

Human infection with parasites is still one of the big problems worldwide. Medicinal plants succeeded to overcome a variety of protozoan and helminthic parasites. In this study, Salvadora persica root extracts (SE) were used to treat helminthosis and coccideosis. Three doses were used (200, 100 and 50 mg/ml) to study the anthelmintic activity of S. persica. Allolobophora caliginosa was used as a model worm. Also, Albendazole was used as a reference drug. In order to study the anticoccideal activity of SE, a group of mice were infected with Eimeria papillata sporulated oocysts. Experimental mice were treated with SE (300 mg/Kg) for 5 days. The extract was able to decrease the number of meronts and gamonts of the parasite in jejunum. Also, it regulates the level of glutathione and malondialdehyde and the activity of catalase as well. We conclude that S. persica possesses a powerful Anthelmintic, anticoccidial and antioxidant activity.

Indigofera oblongifolia protects against trypanosomiasis-induced spleen injury.

BACKGROUND: Trypanosomiasis is a neglected tropical disease, transmitted by blood-sucking insects and can affect humans and animals, depending on the species of Trypanosoma parasite. Trypanosoma has acquired resistance to the majority of drugs used; hence, alternative medicines are required. Indigofera oblongifolia leaf extract (IOE) has been shown to treat blood stage malaria. Here, IOE was used to demonstrate its effect on Trypanosoma evansi-infected mice. METHODS: Analysis of IOE by gas chromatography-mass spectrometry showed the presence of many active components like flavonoids and phenolics. The mice were divided into three groups as follows: vehicle control, T. evansi-infected mice and T. evansi-infected-treated mice. RESULTS: The findings demonstrate a significant effect of IOE treatment on T. evansi-infected mice. Parasitemia was decreased by 70%, weight loss was reduced, and splenomegaly was significantly decreased. Additionally, IOE improved the histological architecture of the spleen, as shown by the improved histological injury score post-treatment. Anemia was apparent during the course of infection in T. evansi-infected mice; this was reversed upon treatment with IOE to almost the normal level of hemoglobin and erythrocytes. Reduced glutathione and catalase were also ameliorated upon IOE treatment compared to T. evansi-infected mice. CONCLUSION: Overall, this study shows the ameliorative role of IOE against T. evansi-induced spleen injury in mice.

Myristica fragrans Kernels Prevent Paracetamol-Induced Hepatotoxicity by Inducing Anti-Apoptotic Genes and Nrf2/HO-1 Pathway.

Paracetamol is responsible for acute liver failure in humans and experimental animals when taken at high doses and transformed into a reactive metabolite by the liver cytochrome P450. On the other hand, nutmeg is rich with many phytochemical ingredients that are known for their ability to inhibit cytochrome P450. Hence, the present experiment was aimed at studying the hepatoprotective effect of Myristica fragrans (nutmeg), kernel extract (MFKE) in respect to paracetamol (acetaminophen; N-acetyl-p-amino-phenol (APAP))-induced hepatotoxicity in rats, focusing on its antioxidant, anti-inflammatory, and anti-apoptotic activities. Liver toxicity was induced in rats by a single oral administration of APAP (2 g/kg). To evaluate the hepatoprotective effect of MFKE against this APAP-induced hepatotoxicity, rats were pre-treated with either oral administration of MFKE at 300 mg/kg daily for seven days or silymarin at 50 mg/kg as a standard hepatoprotective agent. APAP intoxication caused a drastic elevation in liver function markers (transaminases, alkaline phosphatase, and total bilirubin), oxidative stress indicators (lipid peroxidation and nitric oxide), inflammatory biomarkers (tumour necrosis factor-α, interleukin-1ß, inducible nitric oxide synthase, and nuclear factor ĸB) and the pro-apoptotic BCL2 Associated X (Bax) and caspases-3 genes. Furthermore, analyses of rat liver tissue revealed that APAP significantly depleted glutathione and inhibited the activities of antioxidant enzymes in addition to downregulating two key anti-apoptotic genes: Cellular FLICE (FADD-like IL-1ß-converting enzyme)-inhibitory protein (c-FLIP) and B-cell lymphoma 2 (Bcl-2). Pre-treatment with MFKE, however, attenuated APAP-induced liver toxicity by reversing all of these toxicity biomarkers. This hepatoprotective effect of MFKE was further confirmed by improvement in histopathological findings. Interestingly, the hepatoprotective effect of MFKE was comparable to that offered by the reference hepatoprotector, silymarin. In conclusion, our results revealed that MFKE had antioxidant, anti-inflammatory, and anti-apoptotic properties, and it is suggested that this hepatoprotective effect could be linked to its ability to promote the nuclear factor erythroid 2⁻related factor 2 (Nrf2)/antioxidant responsive element (ARE) pathway.