Effect of Melissa officinalis on Chemotherapy-Induced Peripheral Neuropathy in Cancer Patients: A Randomized Trial.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a significant cancer treatment side effect that can influence both quality of life and treatment course. Melissa Officinalis (MO), due to its high content of flavonoids, has antioxidant, anti-inflammatory, and neuroprotective properties.  Materials and Methods: The cancer patients diagnosed with CIPN attended a referral center in Sari (Iran). The hydroalcoholic extract of MO leaves was extracted by the maceration method. The control group received a placebo along with gabapentin as the standard treatment, and the intervention group received 500 mg Melissa officinalis 2 times daily for 3 months plus gabapentin. Patients were evaluated at the baseline and 3 months later, according to Common Terminology Criteria for Adverse Effects (CTCAE) and EORTC QLQ-C30 (Integrated System for Quality of Life Assessment).  Results: A total of 40 patients were considered as group D (intervention group), and 35 patients completed the study. Out of 40 subjects in the placebo group (P), 3 patients could not tolerate the drug due to gastrointestinal disturbances. The final values of CTCAE showed a statistically significant difference (p=0.010). Indicators related to the quality of life in both groups showed a significant improvement. In the intervention group, the pain perception and diarrhea experience were significantly reduced. Conclusion: Quality of life indicators were improved by prescribing gabapentin with and without Melissa officinalis. The addition of Melissa officinalis to the chemotherapy regimen may improve diarrhea and pain perception.

Corrigendum: The neuroprotective effects of fisetin, a natural flavonoid in neurodegenerative diseases: focus on the role of oxidative stress.

[This corrects the article DOI: 10.3389/fphar.2022.1015835.].

Flaxseed powder and magnesium hydroxide syrup on the intestinal function of patients with acute myocardial infarction in intensive care units.

Background: Flaxseed powder seems to improve bowel movements in these patients. Therefore, this study compares the effects of flaxseed powder and magnesium hydroxide on bowel movements of acute myocardial infarction patients hospitalized in ICU. Methods: The population of the present parallel randomized controlled clinical trial included 70 acute myocardial infarction patients hospitalized in ICU who had no history of chronic constipation. The patients in the intervention group were given three sachets of flaxseed powder (each sachet was 3 g) twice a day for four days. The patients in the control group were given 20 cc of magnesium hydroxide syrup each morning. The Bristol scale was used to describe stool consistency. Results: The mean and standard deviation of the number of bowel movements within five days after intervention are 1.86 ± 1.08 and 1.6 ± 0.65 in the intervention and the control groups, respectively. The frequency of normal stool consistency of the first bowel movement is 94.3% for the intervention group and 85.7% for the control group, which shows no significant differences between the two groups in terms of stool consistency and bowel movement frequency (P=0.510). The bowel movements started on average after 35.2±97.97 hours in the flaxseed group and 24.771±2.677 hours in the magnesium hydroxide group (P=0.023). Conclusion: The results showed that flaxseed powder increases bowel movement frequency and improves the patients' stool consistency, but the differences between the two groups are insignificant. Finally, the time to the first defecation was shorter in the magnesium hydroxide group.

Evaluation of antioxidant properties and cytotoxicity of brown algae (nizamuddinia zanardinii) in uterine (hela) and pancreatic cancer cell lines (paca-2).

INTRODUCTION: Pancreatic cancer and cervical cancer are among the most common cancers. Brown algae have anti-inflammatory, anti-cancer, anti-fungal, antioxidant, and immune-boosting properties. This study investigated the antioxidant properties and the effect of brown algae extract on pancreatic and uterine cancer cells. MATERIALS AND METHODS: In this study, Cervical (Hela) and pancreas (Paca-2) cancer cell lines were examined. The algae materials were extracted by sequential maceration method and amount of fucoxanthin content in the sample was determined by using High Performance Liquid Chromatography (HPLC) system. The cytotoxic effect of different concentrations of brown algae was measured by the MTT assay. All statistical calculations for comparing IC50 were analyzed using Graph Pad Prism software. RESULTS: the algal sample contained an average of 102.52 ± 0.12 µg of fucoxanthin per 100 g. IC50 for 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and hydrogen peroxide free radical scavenging activity for methanolic extract was 2.02 and 11.98 ± 0.13 respectively. Brown algae in all fractions inhibited cell growth and survival. In Hela cell lines, the methanolic extract was the most effective inhibitor, while in Paca cell lines, hexane and methanolic extracts were particularly potent. The methanolic extract was more toxic than other fractions on Hela and Paca cell lines. CONCLUSION: This study highlights brown algae extracts strong anticancer effects on uterine and pancreatic cancer cells, suggesting its potential as a natural anticancer drug. Different fractions of the extract showed superior apoptotic and cytotoxic effects, with higher concentrations leading to increased apoptotic effects and reduced survival rates of cancer cells.

Oxidative stress in liver of streptozotocin-induced diabetic mice fed a high-fat diet: A treatment role of Artemisia annua L.

Objective. The aim of this study was the investigation of a treatment role of Artemisia annua L. (AA) on liver dysfunction and oxidative stress in high-fat diet/streptozotocin-induced diabetic (HFD/STZ) mice. Methods. Sixty mice were divided into 12 groups including control, untreated diabetic, and treated diabetic ones with metformin (250 mg/kg), and doses of 100, 200, and 400 mg/kg of water (hot and cold) and alcoholic (methanol) extracts of AA. Type 2 diabetes mellitus (T2DM) was induced in mice by high-fat diet for 8 weeks and STZ injection in experimental animals. After treatment with doses of 100, 200 or 400 mg/kg of AA extracts in HFD/STZ diabetic mice for 4 weeks, oxidative stress markers such as malondialdehyde (MDA), glutathione (GSH), and free radicals (ROS) were determined in the liver tissue in all groups. Results. Diabetic mice treated with metformin and AA extracts showed a significant decrease in ROS and MDA concentrations and a notable increase in GSH level in the liver. Effectiveness of higher doses of AA extracts (200 and 400 mg/kg), especially in hot-water and alcoholic ones, were similar to and/or even more effective than metformin. Conclusion. Therapeutic effects of AA on liver dysfunction showed that antioxidant activity of hot-water and alcoholic AA extracts were similar or higher than of metformin.

Immunomodulatory Activity of Polysaccharide from Trametes gibbosa (Pers.) Fr (Basidiomycota, Fungi) Mediated by TLR4 Signaling Pathway.

Background: Trametes species possess remarkable immunomodulatory and anticancer effects which are mainly related to the activation of innate immune receptors by their polysaccharide constituents. In this study, we investigate the effect of Trametes gibbosa (Pers.) Fr. polysaccharide fraction (TGP) on activation of TLR-4 receptor and subsequent release of IL-8 in HEK-Blue™ hTLR4 cells. Materials and Methods: The polysaccharide fraction was purified using ethanol precipitation and dialysis methods. The total sugar content and monosaccharide composition were analyzed by phenol-sulfuric acid and chromatographic methods. FT-IR spectroscopy was also performed for structure characterization of the polysaccharide. The activation of TLR4 was determined by measuring the secreted embryonic alkaline phosphatase in the culture media. Results: The results indicated that the total sugar content of TGP was about 90%, which glucose was the major constituents. FT-IR analysis showed the characteristic bands of polysaccharides. TGP was able to activate the TLR-4 signaling pathway in a dose-dependent manner. Moreover, the significant increase of IL-8 was observed in cells treating with TGP. The HEK-Blue Null2™ reporter cells lacking TLR4, did not respond to LPS and TGP. Conclusion: The results suggest that TLR4 signaling cascade serve as targets for immunomodulatory activity of T. gibbosa which could address the anticancer properties of Trametes species.

Corrigendum: The neuroprotective effects of fisetin, a natural flavonoid in neurodegenerative diseases: Focus on the role of oxidative stress.

[This corrects the article DOI: 10.3389/fphar.2022.1015835.].

The neuroprotective effects of fisetin, a natural flavonoid in neurodegenerative diseases: Focus on the role of oxidative stress.

Oxidative stress (OS) disrupts the chemical integrity of macromolecules and increases the risk of neurodegenerative diseases. Fisetin is a flavonoid that exhibits potent antioxidant properties and protects the cells against OS. We have viewed the NCBI database, PubMed, Science Direct (Elsevier), Springer-Nature, ResearchGate, and Google Scholar databases to search and collect relevant articles during the preparation of this review. The search keywords are OS, neurodegenerative diseases, fisetin, etc. High level of ROS in the brain tissue decreases ATP levels, and mitochondrial membrane potential and induces lipid peroxidation, chronic inflammation, DNA damage, and apoptosis. The subsequent results are various neuronal diseases. Fisetin is a polyphenolic compound, commonly present in dietary ingredients. The antioxidant properties of this flavonoid diminish oxidative stress, ROS production, neurotoxicity, neuro-inflammation, and neurological disorders. Moreover, it maintains the redox profiles, and mitochondrial functions and inhibits NO production. At the molecular level, fisetin regulates the activity of PI3K/Akt, Nrf2, NF-κB, protein kinase C, and MAPK pathways to prevent OS, inflammatory response, and cytotoxicity. The antioxidant properties of fisetin protect the neural cells from inflammation and apoptotic degeneration. Thus, it can be used in the prevention of neurodegenerative disorders.

Artemisia annua L. Extracts Improved Insulin Resistance via Changing Adiponectin, Leptin and Resistin Production in HFD/STZ Diabetic Mice.

Objectives: Insulin resistance (IR) is major cause of type 2 diabetes (T2D), and adipokines (e.g., adiponectin, leptin, and resistin) play an important role in insulin sensitivity. Medicinal plants are frequently used for T2D treatment. This study investigates the effect of Artemisia annua L. (AA) extracts on adipokines in mice with high-fat-diet (HFD)/streptozotocin (STZ)-induced T2D. Methods: We divided 60 mice into 12 groups (n = 5 per group) control, untreated T2D, treated T2D, and 9 other groups. T2D was induced in all groups, except controls, by 8 weeks of HFD and STZ injection. The treated T2D group was administered 250 mg/kg of metformin (MTF), while the nine other groups were treated with 100, 200, and 400 mg/kg of hot-water extract (HWE), cold-water extract (CWE), and alcoholic extract (ALE) of AA (daily oral gavage) along with 250 mg/kg of MTF for 4 weeks. The intraperitoneal glucose tolerance test (IPGTT) was performed, and the homeostasis model assessment of adiponectin (HOMA-AD) index and blood glucose and serum insulin, leptin, adiponectin, and resistin levels were measured. Results: Similar to MTF, all three types of AA extracts (HWEs, CWEs, and ALEs) significantly (p < 0.0001) decreased the area under the curve (AUC) of glucose during the IPGTT, the HOMA-AD index, blood glucose levels, and serum insulin, leptin, and resistin levels and increased serum adiponectin levels in the MTF group compared to the T2D group (p < 0.0001). The HWEs affected adipokine release, while the CWEs and ALEs decreased leptin and resistin production. Conclusion: Water and alcoholic AA extracts have an antihyperglycemic and antihyperinsulinemic effect on HFD/STZ diabetic mice. In addition, they decrease IR by reducing leptin and resistin production and increasing adiponectin secretion from adipocytes.

Phytochemical identification, acute and subchronic oral toxicity assessments of hydroalcoholic extract of Acroptilon repens in BALB/c mice: A toxicological and mechanistic study.

Acroptilon repens (L.) DC, commonly known as Rhaponticum repens, is a popular traditional phytomedicine. The current study was conducted to evaluate the acute and subchronic toxicity of the hydroalcoholic extract of this herb with regard to its terpenoid contents in a BALB/c mice model and to investigate the toxicity of this medicinal herb. Identification of extract components of the plant was done using gas chromatography (GC)-mass spectrometry. In order to establish the acute toxicity model, a single dose of 2000 mg/kg of the extract was given orally to male mice and in the subchronic toxicity study, the extract was consecutively administered at doses 250, 500, and 1000 mg/kg for 28 days. After 28 and 42 days, signs of toxicity and mortality were observed. Organ weight changes and the toxicity-associated parameters such as biochemical indicators, oxidative stress indices, mitochondrial parameters, apoptosis-associated gene expression levels, and pro-inflammatory cytokines were evaluated along with the histopathological examination. GC analysis showed that the terpenoids are the major components of the extract. The LD50 value (2 g/kg) was obtained in the acute toxicity assay; the subchronic administration caused a significant elevation in the serum biomarkers as well as in the levels of lipid peroxidation, protein carbonyl, and ROS. Besides, significant reductions in the superoxide dismutase and catalase activities were observed. This toxic effect was further confirmed by histological studies, cytokine assay, and gene expression assays. Following the treatment discontinuation, the abnormalities in the values of biochemical parameters and histopathological changes returned to normal. These findings demonstrate that the subchronic administration of the hydroalcoholic extract of A. repens can reversibly cause toxicity by inducing oxidative stress and mitochondrial dysfunction.

Anti-Microbial Potential of Nano-Emulsion form of Essential Oil Obtained from Aerial Parts of Origanum Vulgare L. as Food Additive.

Purpose: Foodborne diseases are still a serious problem in public health and natural compounds are being widely considered for their potential industrial protective additive in food products. Origanum vulgare L. has been known as an antimicrobial effective herb. This present study was carried out to examine the antimicrobial effect of O. vulgare essential oil nanoemulsion in comparison with conventional emulsion. Methods: The essential oil was obtained by hydrodistillation, analyzed by GC-Mass and formulated as a nanoemulsion to improve water dispersion by high-energy emulsification method. The antimicrobial activity of the prepared formulation was assessed by measuring the minimum inhibitory concentration (MIC), minimum bactericidal/fungicidal concentration (MBC/MFC) and zone of inhibition against some main foodborne pathogen microorganisms. Results: The main component of the oregano essential oil was carvacrol (78%) and the selected nanoemulsion formulation demonstrated low polydispersity (0.11) and mean droplet (72.26 nm) and it was stable even after 30 days of storage. The nanoemulsion form displayed significant activity against the Staphylococcus aureus, Candida albicans and Aspergillus niger with inhibition zones ranging from 8.7-22.3 mm. The MIC of nanoemulsion against the tested bacteria was within the range of 0.156 to 0.312 (mg/mL) and against the tested fungi were in the range of 0.078 to 0.156 (mg/mL). The MBC/MFC of nanoemulsion against the tested microorganisms were in the range of 0.312 to 5 (mg/mL). Conclusion: The study's results demonstrated the possibility of using the nanoemulsion form of oregano essential oil as a food additive to inhibit the growth of some foodborne microorganisms and extending the shelf life of food products.

Pulmonoprotective Action of Zataria multiflora Ethanolic Extract on Cyclophosphamide-Induced Oxidative Lung Toxicity in Mice.

OBJECTIVE: To evaluate the protective effect of Zataria multiflora extract, an antioxidative medicinal plant, against cyclophosphamide (CP)-induced oxidative lung damage in mice. METHODS: Mice were intraperitoneally pre-treated with various doses of Zataria multiflora extract (50, 100, 200, and 400 mg/kg) once daily for 7 consecutive days. Animals were then injected with a single 200 mg/kg intraperitoneal dose of CP 1 h after the last administration of O. vulgare. Twenty-four hours later, mice were euthanized, the lungs were immediately removed, and biochemical and histological studies were conducted. RESULTS: A single dose of CP markedly altered the levels of several biomarkers associated with oxidative stress in lung homogenates. Pretreatment with Zataria multiflora significantly inhibited the elevation of lipid peroxidation level and the depletion in glutathione content, and superoxide dismutase and catalase activities induced by CP in lung. In addition, Zataria multiflora effectively alleviated CP-induced histopathological abnormality and pulmonary damages in mice lung tissues. CONCLUSIONS: The results reveal that Zataria multiflora protects lung tissues from CP-induced toxicity and suggest a role for oxidative stress in the pathogenesis of lung toxicity produced by CP in mice. Because Zataria multiflora has been extensively used as an additive agent and is regarded as safe, it may be used concomitantly as a good supplement for reducing organ toxicity in patients undergoing chemotherapy, besides their consolidated ethnopharmacological uses.

Nigella sativa L. for prevention of acute radiation dermatitis in breast cancer: A randomized, double-blind, placebo-controlled, clinical trial.

OBJECTIVE: The present study aimed to evaluate the effectiveness of Nigella sativa L. (N. sativa) extract on preventing the incidence of acute radiation dermatitis (ARD) in breast cancer patients. METHODS: Sixty-two breast cancer patients undergoing radiotherapy (RT) were randomly assigned to receiveN. sativa 5% gel or placebo. Patients were instructed to apply the medications twice daily during RT period. The severity of ARD, the incidence of moist desquamation, worst experienced pain, and skin-related quality of life (SRQOL) scores were assessed weekly during RT. RESULTS: Patients who were treated with the N. sativa gel developed ARD significantly less frequently compared to those who used the placebo (p < 0.05 for all weeks except week 2, p = 0.36). The incidence time of grade 2 and 3 of Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer (RTOG/EORTC) toxicity was prolonged significantly with N. sativa gel as compared to placebo (35 vs. 29 days, p = 0.00 and 42 vs. 40 days, p = 0.01, respectively). Furthermore, the occurrence of moist desquamation was delayed in the N. sativa gel group compared with the placebo group (37 vs. 33 days, p = 0.01). The mean score of the worst pain that patients experienced in the placebo group was significantly higher than that of the N. sativa gel group at week 3 (2.5 ±â€¯0.5 vs. 1.2 ±â€¯0.3, p < 0.05). Nonetheless, the application of N. sativa gel had no significant effect on the SRQOL of patients at any week. CONCLUSION: N. sativa extract significantly decreases the severity of ARD and delays the onset of moist desquamation in breast cancer patients.

Effects of some natural products from fungal and herbal sources on Giardia lamblia in vivo.

Giardia lamblia (G. lamblia) is the most widely known protozoan parasite that causes human gastrointestinal infection worldwide. Some natural compounds exhibited pivotal effects against different infectious diseases. In this research, the antigiardial activity and cytotoxicity of fungal chitosan, nano-chitosan, Rhamnus cathartica (R. cathartica) and emodin were evaluated in Balb/c mice. Genotyping of G. lamblia was assessed by PCR-RFLP technique. Different concentrations of mentioned compounds were used to check their antigiardial and cytotoxicity effects on human intestinal epithelial cells (HT-29) after 24, 48 and 72 h. The G. lamblia strain used in the current work was genotyped and revealed as an AII assemblage. All the concentration showed acceptable activity against G. lamblia cysts and trophozoites in comparison to the negative and positive controls (furazolidone and metronidazole) in vitro (P 0.05). The maximum mortality rate (100%) was achieved at 100 and 50 µg kg-1 concentrations after 48 and 72 h of exposure time, respectively. Our results provide significant information about the new antigiardial agent and proposed the nano-chitosan and emodin for the development of new drugs against G. lamblia in the future.

Modulatory effects of Viola odorata flower and leaf extracts upon oxidative stress-related damage in an experimental model of ethanol-induced hepatotoxicity.

Ethanol is the most widely abused drug in the world and its long-term use induces oxidative stress in the liver tissue. The aim of this study was to evaluate protective effect of Viola odorata against ethanol-induced hepatotoxicity in Wistar rat. Animals were divided into 9 groups as follows: control (normal saline), ethanol (10 mg/kg, intraperitoneally), ethanol with 3 doses (125, 250, and 500 mg/kg) of ethyl acetate flower and leaf extracts, and positive control (vitamin E 80 mg/kg). Animals were gavaged 30 min before ethanol injection for 28 days. Then, animals were killed and the livers were separated. Oxidative stress parameters, including reactive oxygen species, lipid peroxidation, and protein carbonyl as well as glutathione content, were evaluated. Also, histopathological examination was performed and assessment of blood alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total antioxidant capacity were evaluated. Ethanol significantly increased oxidative stress markers in liver. Interestingly, administration of both extracts significantly decreased oxidative stress markers in liver tissue and biochemical parameters in the plasma. In addition, abnormal pathological features were improved after treatment with flower and leaf extracts. These results suggested that V. odorata can be considered a candidate for improving conditions due to ethanol-induced tissue oxidative damage because of its antioxidant activity.

Efficacy of Camellia sinensis extract against Candida species in patients with denture stomatitis.

BACKGROUND AND PURPOSE: Denture stomatitis is a chronic inflammation disease of the oral mucosa, which is specified by erythematous lesions mainly in the upper palate. Nystatin as a polyene, a class of antifungal agents, is one of the effective drugs to treat denture stomatitis. Considering the expansion of utilizing herbal drugs to cure many kinds of diseases, the present study was conducted to investigate the effects of Camellia sinensis (green tea), which has the most chemical and influence similarity with nystatin, against denture stomatitis. MATERIALS AND METHODS: This study was conducted on 22 patients with a positive mycological evidence for denture stomatitis caused by Candida species. The study population was divided into two groups, namely green tea and nystatin, receiving green tea mouthwash 0.5% and nystatin suspension 100,000 U/ml, respectively. The lesion size and number of yeast colonies were measured before and after the treatment. RESULTS: According to the results, both groups showed reduced lesion size, clinical improvement, and significant reduction of Candida colony count in both group of patients were showedafter the therapeutic. Based on the results of polymerase chain reaction, Candida albicans was the most common species isolated from denture stomatitis. There was no significant difference between the two study groups in terms of Candida species distribution (P =0.700). CONCLUSION: Green tea demonstrated a comparable anti-Candida activity with regard to nystatin; therefore, it could be recommended as an alternative treatment.

Cytotoxic and genotoxic studies of essential oil from Rosa damascene Mill., Kashan, Iran.

Aim Rosa damascene Mill. belongs to the family of Roseaceae and its essential oil is produced in large amounts in Iran. The wide application of rose oil has raised questions about potential adverse health effects. We have investigated cytotoxic activity and genotoxic effects of Rosa oil from Kashan, Iran. Methods The cytotoxic effect and IC50 of the essential oil on the cell lines was studied followed by MTT assay. In this assay mitochondrial oxidoreductase enzymes with reducing the tetrazolium dye MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) reflect the number of viable cells. Genotoxic effect of the oil was evaluated by micronucleus assay by evaluating produced micronuclei due to cytogenetic damage in binucleated lymphocytes. Results The results showed that essential oil significantly had cytotoxic and genotoxic effects at doses over 10µg/mL (p<0.05). Also, essential oil of Rose showed lower IC50 in cancer cell line (A549) in comparison with the normal cell line (NIH3T3). Conclusion Cytotoxic and genotoxic properties of essential oil of Rose in Kashan, Iran, are safe at a dose of 10µg/mL. Also, a good cytotoxic effect was shown and could be introduced as an anticancer compound. Further studies are needed with regard to anti-cancer effects of Rose essential oil.

Mycochemical Investigation of the Turkey Tail Medicinal Mushroom Trametes versicolor (Higher Basidiomycetes): A Potential Application of the Isolated Compounds in Documented Pharmacological Studies.

The purpose of this study was to elucidate the chemical properties of the n-hexane, chloroform, and ethyl acetate extracts of the fruiting body of the medicinal mushroom Trametes versicolor. The study led to the isolation of 5 sterols, 2 triterpene derivatives, 1 hydroquinone-derived aromatic compound, and, finally, 1 cerebroside and 1 triglyceride derivative. These compounds were identified for first time in T. versicolor and were named as follows: 4-isobutoxyphenyl palmitate (5), N-D-2'-hydroxyheptanoic-1-O-ß-D-glucopyranosyl-9-methyl-4,8-sphinga-dienine(cerebroside) (6), 3ß-linoleyloxyergosta-7,22-diene (7), 3ß-linoleyloxyergosta-7-ene (8), and betulinic acid (9). Other compounds elucidated in our study were ergosterol (1), ergosterol peroxide (2), trilinolein (3), ergosta-7, 22-dien-3ß-ol (4), and betuline (10). These compounds were obtained via column or thin-layer chromatography before being identified by nuclear magnetic resonance spectroscopic analyses and infrared data. In addition, the beneficial pharmacological effects of the compounds are described here.

Genoprotective effects of Origanum vulgare ethanolic extract against cyclophosphamide-induced genotoxicity in mouse bone marrow cells.

CONTEXT: Cyclophosphamide (CP), an alkylating chemotherapeutic agent, can bind DNA, causing chromosome breaks, micronucleus (Mn) formation, and cell death. Because Origanum vulgare L. (Lamiaceae) has antioxidative properties, it might protect against DNA damage. OBJECTIVE: The genoprotective effect of O. vulgare ethanolic extract against CP-induced genotoxicity in mouse bone marrow cells was evaluated using a Mn assay. MATERIALS AND METHODS: Mice were pre-treated with aerial parts of O. vulgare ethanolic extract at different doses (50, 100, 200, or 400 mg/kg) for 7 d. One hour after the last administration of O. vulgare, animals were injected with CP at 200 mg/kg. After 24 h, the bone marrow cells of both femurs were flushed and the frequency of MnPCEs was evaluated to measure the chromosomal damages. In addition, the number of PCEs per 1000 NCEs in each animal was recorded to evaluate the bone-marrow suppression; mitotic activity was calculated as [PCE/(PCE + NCE)] × 100 to assess the cell division. RESULTS: At 400 mg/kg, O. vulgare displayed its maximum protective effect, reduced the number of MnPCEs from 10.52 ± 1.07 for CP group to 2.17 ± 0.26 and completely normalized the mitotic activity (p < 0.001). Origanum vulgare also led to significant proliferation and hypercellularity of immature myeloid elements after the mice were treated with CP, mitigating the bone marrow suppression. DISCUSSION AND CONCLUSION: Origanum vulgare ethanolic extract exerts a potent genoprotective effect against CP-induced genotoxicity in mice bone marrow, which might be possibly due to the scavenging of free radicals during oxidative stress conditions.

Protective effects of Origanum vulgare ethanol extract against cyclophosphamide-induced liver toxicity in mice.

UNLABELLED: Abstract Context: Despite its wide clinical use, cyclophosphamide (CP), an alkylating chemotherapeutic agent, possesses many adverse effects, including hepatotoxicity. Because Origanum vulgare L. (Lamiaceae) has antioxidative properties, it might protect against above-mentioned damage. OBJECTIVE: This study evaluated the protective effects of O. vulgare extract on CP-induced liver toxicity. MATERIALS AND METHODS: Mice were pretreated with aerial parts of O. vulgare ethanolic extract (intraperitoneally) at doses of 50, 100, 200, and 400 mg/kg for 7 consecutive days before the administration of a single 200 mg/kg intraperitoneal dose of CP 1 h after the last injection of O. vulgare. After 24 h, animals were anesthetized, blood samples and hepatic tissues were collected and used for biochemical and histological examination. RESULTS: Serum levels of hepatic markers were increased after CP treatment but restored in the O. vulgare-pretreated groups. The serum ALT, AST, and ALP of the CP group were 196.49 ± 3.82, 143.78 ± 4.79, and 203.18 ± 3.81 IU/l, respectively. However, pretreatment with 400 mg/kg O. vulgare significantly decreased the serum ALT, AST, and ALP to 52.49 ± 2.18, 44.78 ± 2.06, and 65.62 ± 1.73 IU/l, respectively (p < 0.001). Histological examinations also confirmed the protective effects of O. vulgare against CP-induced liver toxicity. DISCUSSION AND CONCLUSION: Our results reveal that O. vulgare with high amount of flavonoids and phenolic compounds induces potent hepatoprotective mechanisms against CP. Therefore, O. vulgare might help defend the body against the side effects, particularly hepatic damages induced by chemotherapeutic agents.