zataria multiflora

We aimed to determine the effect of Zataria multiflora Nanoemulsion gel on surgical wound healing.

This experimental study was conducted in the years 2021-2022 at the Animal Research Center of Mazandaran University of Medical Sciences, northern Iran. Forty two male Westar rats were randomly divided into six groups (n=7). After a surgical incision of full thickness with a 3 cm diameter, they were treated for 21 days with diltiazem 2% (positive control), placebo, and Z. multiflora emulsions and nanoemulsions at 2% and 4%, respectively. Macroscopic parameters of wound area and contraction, as well as pathological factors such as granulation, angiogenesis, epithelialization, collagen organization, bacterial colony, inflammation, creatine and epidermal thickness, hair follicles, and lymphatic ducts, were examined.

The mean wound size and contraction of the placebo group differed significantly from the other groups on all days, and on some days, the results indicated more favorable effects of nanoemulsions than Diltiazem. Based on the microscopic findings, the average scores on the seventh day were nearly different (P= 0.051); however, all groups scored higher than the placebo group. On the 21st day, the best results were related to the 4% Nanoemulsion (242.5), 2% Nanoemulsion (159.4), and 4% emulsion (159.3), followed by diltiazem (154.60), 2% emulsion (146.5), and placebo (70.7).

Z. multiflora emulsions and nanoemulsions at 2% and 4% could be effective in healing surgical wounds, and the use of 4% Nanoemulsion yields the best results. This is recommended for use in clinical trial studies.

Pseudomonas aeruginosa (P. aeruginosa) is one of the most important microorganisms causing burn wound infection. Due to the rapid increase in resistance to the currently used antimicrobial agents, finding new antibiotics is one of the research priorities. This study was designed to investigate antibacterial and wound healing effects of Zataria multiflora essential oil (ZMEO) on burn wounds infected with P. aeruginosa in Sprague-Dawley rats. Experimental burn wounds were created on the back of the animals and infected with P. aeruginosa. The animals were randomly divided into 4 groups of 7 to 10 as follow: negative control (no treatment), carrier gel group treated with carboxymethyl cellulose (CMC) gel, ZMEO group that received CMC gel loaded with ZMEO, and positive control group that received silver sulfadiazine (SSD). All medications were applied topically once daily for 28 days. On the days 7th, 14th, 21st, and 28th after the start of treatments, the surfaces of the wounds were measured and some samples were collected for histopathological evaluations. The tensile strengths of ratsʼ skins were also measured on the 28th day. The results showed that on the 7th day, while a significant healing of the wounds was observed in the ZMEO group, the other groups did not show remarkable wound healing (P<0.05). Therefore, ZMEO showed an accelerating effect on the healing process of burn wounds and could be considered for further evaluations in order to develop new medications for the treatment of burn wounds infected with P. aeruginosa.

The present study aimed to assess the impact of the aqueous-ethanolic extract of Zataria multiflora (ZM), carvacrol (Car), and their co-administration with a PPAR activator, pioglitazone (Pio), on oxidative stress and inflammation induced by paraquat (PQ) inhalation at a systemic level.

The rats in the control group were exposed to saline and those of other groups to PQ (54 mg/m3) aerosols for 8 times on alternate days. Nine PQ groups were treated with saline, Car (20 and 80 mg/kg/day), ZM (200 and 800 mg/kg/day), Pio (5 mg/kg/day), dexamethasone (Dexa, 0.03 mg/kg/day), and low-dose ZM or Car + Pio for 16 days during the period of PQ exposure (n=6).

Differential and total WBC counts, and malondialdehyde (MDA), interleukin (IL)-10, and tumor necrosis factor (TNF)-α levels were enhanced but catalase (CAT), thiol, and superoxide dismutase (SOD) levels were reduced in the blood in the PQ group (p<0.01 to p<0.001). All measured variables improved in groups treated with both doses of ZM, Car, Pio, ZM + Pio, Car+Pio, and Dexa vs the PQ group (p<0.05 to p<0.001). Most variables were more improved in combined treatment groups in comparison with three agents alone. The combination of ZM or Car, and Pio showed an impact on PQ inhalation-induced systemic changes.

The synergistic effect between Pio with ZM or Car indicates that these substances work together to enhance their individual effects.

Cancer therapy necessitates innovative approaches with enhanced efficacy and reduced side effects. Essential oils have gained attention because of their diverse biological properties and relatively low toxicity. Zataria multiflora essential oil (ZEO) and Oliveria decumbens essential oil (OEO) exhibit promising anti-cancer effects, particularly in modifying oxidative stress and inflammation. Both oils boast complex compositions rich in bioactive compounds, including oxygenated monoterpenes and phenolic compounds like carvacrol and thymol. Hence, this study investigates essential oils’ anti-cancer, anti-oxidant and immunomodulatory effects, focusing on ZEO and OEO.

This review briefly considers the intricate mechanisms of several essential oils, encompassing anti-oxidant, anti-inflammatory and anti-cancer properties. Then the review delves into the multifaceted mechanisms underlying the anti-cancer properties of ZEO and OEO. 

Studies showcase the ability of ZEO and OEO to induce apoptosis in cancer cells through various pathways, such as mitochondrial dysfunction, reactive oxygen species (ROS) generation and DNA damage while sparing normal cells. Our studies further validated the immunomodulatory effects of OEO and ZEO in tumor-bearing mice, resulting in reduced tumor volume. Additionally, this review confirmed the synergistic effect of ZEO when combined with doxorubicin to inhibit cancer cells. 

Some essential oils, such as ZEO and OEO, present promising natural compounds in cancer therapy, offering diverse mechanisms of action targeting various aspects of tumor biology.

Liver is an important player in regulation of body homeostasis. Study investigated the effects of hydro-alcohol extract of Zataria multiflora (ZM) on oxidative damage, level of IL-6 and enzymes of liver in lipopolysaccharide (LPS)-treated rats. The rats were distributed into 5 groups: 1) Control; 2) LPS; and 3-5) ZM-Extract (Ext) 50, ZM-Ext 100, and ZM-Ext 200. ZM-Ext groups received 50, 100 and 200 mg/kg of extract 30 min before LPS. Drugs were injected intraperitoneally. The entire period of this project was 17 days. In first three days, only extract was injected and then, ZM was injected along with LPS. LPS increased the level of ALT (Alanine aminotransferase), AST (Aspartate aminotransferase ), ALK-P (Alkaline Phosphatase), IL-6, malondialdehyde (MDA), and nitric oxide (NO) metabolites and lowered thiol, superoxide dismutase (SOD) and catalase (CAT) concentration. ZM extract not only reduced ALT, AST, ALK-P, IL-6, MDA, and NO metabolites concentrations but also increased thiol content, and SOD and CAT levels. Extract of ZM prevented LPS-induced hepatotoxicity. This protective effect was associated with reduction in inflammation and oxidative stress.

The anti-inflammatory effects of exercise training and zataria multiflora have been proven. In the present study, researcher investigated the effect of eight weeks combined exercise training and Zataria multiflora (Z. multiflora) supplement on the levels of IL-1β and insulin resistance in overweight and obese men.

The 40 overweight and obese men with average age of 27.73 ± 2.15 years old and average body mass index (BMI) 28.41 ± 1.75 kg/m2 were randomly divided into four groups including the placebo, Z. multiflora, combined training, and training + Z. multiflora. Combined exercise training program conducted for eight weeks and three sessions per week. Z. multiflora supplement was also consumed at 500 mg daily. Blood sampling was performed before and 48 hours after the eight weeks intervention. The levels of IL-1β and insulin were measured by ELISA method. Data were analyzed by analysis of covariance and Bonferroni post hoc test.

The levels of IL-1β in training and training + Z. multiflora groups significantly decreased compared to placebo and Z. multiflora groups (P < 0.001). In addition, significant decrease of insulin resistance in training group compared to placebo (P < 0.001) and Z. multiflora (P = 0.003) groups, and also in training + Z. multiflora group compared to placebo and Z. multiflora groups were observed (P < 0.001).

Combined training alone or in combination with Z. multiflora supplementation can exert anti-inflammatory effects. Moreover, Z. multiflora supplementation cause the relative increase in exercise training effect for decrease in IL-1β and insulin resistance.

The use of various nanoparticles and plant-based antibacterial substances can be a suitable alternative to conventional mouthwashes. The aim of this study was to investigate the antimicrobial effect of synthesized ZnO nanoparticles in combination with Zataria multiflora essential oil against Streptococcus mutans. ZnO-NPs were synthesized by zinc acetate and potassium hydroxide and their characteristics are evaluated by FE-SEM and XRD. Z. multiflora essential oil is extracted and its chemical compounds are analyzed by GC–MS. Antibacterial activity of essential oil and nanoparticles was studied by broth microdilution method against standard and clinical strains of S. mutans and was determined minimum inhibitory concentration (MIC). The antibacterial interactions of these materials are tested by checkerboard titration. The results showed that ZnO-NPs were spherical and were synthesized with an average diameter of 23.77nm. MIC of ZnO-NPs against S. mutans strains was reported in the range of 12.5-50 μg/ml, and the MIC of Z. multiflora essential oil was in the range of 0.031-0.25 μl/ml. It was observed that ZnO nanoparticles with essential oil of Z. multiflora have synergistic effects against S. mutans and can be a suitable alternative to mouthwashes such as chlorhexidine.

This study aimed to examine the effect of Zataria multiflora Boiss. mouthwash on the microbial load of the oral cavity in patients under mechanical ventilation. This randomized controlled trial was conducted in 2019 on patients under mechanical ventilation. Sampling was performed using the consecutive method. Using a block randomization method, 90 patients were allocated to three equal groups of 30 to receive mouth care using chlorhexidine, Z. multiflora, or normal saline. Mouthwash was used three times a day for a week. Eight hours before and after the intervention, sterile samples of saliva were collected and cultured in the laboratory. Chi-square, Fisher's exact test, paired t and McNemar’s tests, and analysis of variance were used to analyze the data. After the interventions, a significant difference in the microbial load was found between the three groups (P < 0.021). The Tukey post hoc test showed a significant difference between the group treated with Z. multiflora and those who received chlorhexidine (P value = 0.016). The frequency of patients with positive cultures was lower in the group treated with Z. multiflora and the differences were statistically significant in terms of Acinetobacter (P = 0.01) and Klebsiella pneumonia (P = 0.02). Z. multiflora mouthwash was effective in decreasing the microbial load of the oral cavity. This mouthwash can be used to reduce the microbial load of the oral cavity in patients under mechanical ventilation and reduce the risk of ventilator-associated pneumonia.

Cystic echinococcosis (CE) is a life‑threatening disease in many countries. Albendazole, as the drug of choice for medical treatment of CE, is accompanied by adverse effects and may be ineffective in 20%–40% of cases; hence, new and more effective compounds are urgently needed to optimize the management of the disease. This study was performed to evaluate the efficacy of Zataria multiflora essential oil (ZMEO) versus albendazole against human liver CE.

In this nonrandomized and single‑blinded clinical trial, thirty patients who were infected with liver CE were divided into two groups (15 in each) and treated with albendazole (800 mg daily) and ZMEO (60 mg daily), respectively. Albendazole and ZMEO were administered orally for 180 consecutive days. The volume of hydatid cysts was measured by ultrasonography before and 2, 4 and 6 months after the start of treatment. Simultaneously, biochemical analysis was performed on the blood samples of patients to assess the possible side effects of the two treatment regimens.

Two, 4 and 6 months after the start of treatment, ZMEO indicated a significantly higher ability in reduction of the volume of the hydatid cysts, compared to albendazole (P < 0.05). The mean values of aspartate aminotransferase, alanine transaminase and alkaline phosphatase were also significantly lower in the patients treated with ZMEO in comparison to those treated with albendazole (P < 0.05). No clinical adverse effects were observed in the patients treated by ZMEO.

From the point of view of efficacy and safety, ZMEO indicated a significant superiority to albendazole. Hence, ZMEO may be considered as an alternative for albendazole in the medical treatment of liver CE.

The post-harvest damage to fruits is estimated to be about 10-30% of the total products, which reaches up to 30-50% in some perishable fruits. About 25 species of fungi and bacteria including Botrytis spp. and in particular Botrytis cinerea are known to contaminate fruits, vegetables and ornamental greenhouse plants. The aim of this study was to investigate the antifungal activity of different concentrations of Zataria multiflora essential oil (ZEO) against B. cinerea.

The ZEO was extracted through steam distillation and analyzed by gas chromatography-mass spectrometry. The strawberries packages were exposed to ZEO with different concentrations (0, 200, 400, 600, and 800 ppm) and satarch nanoparticles. The exposed fruits were kept for 24 days at two temperatures of 20°C and 4°C.

The ZEO decreased mycelium growth even when only 200 ppm of it was added to each container. The response was dose-dependent, so that the 800 ppm dose of ZEO showed complete inhibitory effect. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values for ZEO against B. cinerea were 200 µg/mL and 500 µg/mL, respectively. Additionally, ZEO preserved the sensory characteristics.

The ZEO may be effectively used in packaging of strawberry to increase its shelf life by inhibition of B. cinerea.

Mosquito is a vector of several life threatening diseases affecting humans. The use of synthetic insecticides in the vector control is not advisable due to concern about environmental sustainability, harmful effect on human health and increasing insecticide resistance. So, the objective of this study was to assess larvicidal activity of essential oils (EOs) of Zataria multiflora, Eucalyptus caesia Benth, and Mentha piperita against the Culex mosquito.

The larvicidal activity of the essential oils were tested according to the WHO procedure. The larvae exposed to three-fold serial dilution of oils (2.5-400 ppm) using a dipping method for 24 h and then simultaneously each replicate was incubated in separate petri dishes at 27°C and 80-90% relative humidity. Mortality rate was recorded after an exposure of 24 h. LC50 and LC90 were calculated using Probit analysis and all data were analyzed using ANOVA and post hoc Tukey test.

In the comparative analysis of the essential oils, LC50 & LC90 of Z. multiflora, E. caesia Benth and M. piperita were5.09429 and26.9919, 3.66376 and 35.3173, and 8.3115 and 218.888 ppm, respectively. Also, as the concentration of essential oil increased, mortality rate of larvae increased too.

This study concluded that the essential oils of Z. multiflora, E. caesia Benth and M. piperita have appropriate larvicidal activity against Culex, therefore, they can be used as good alternative to the Culex biological control.

Statement of the Problem:

 Zataria multiflora (ZM) is a thyme-like plant that belongs to the Lamiaceae family. It is native to the center and south of Iran, Pakistan, and Afghanistan. Evidence shows that ZM contains thymol and carvacrol and is therefore, effective for the treatment of many conditions especially fungal infections. Oral candidiasis is the most common opportunistic infection of the oral mucosa that plays a role in the development of denture stomatitis.

This study aimed to compare the antifungal efficacy of ZM and nystatin suspension for the treatment of denture stomatitis.

This single-blind clinical trial evaluated 28 patients (> 18 years old) suffering from type II or III denture stomatitis. Patients were divided into two groups. The control group used nystatin suspension while the case group used ZM drop. The number of Candida albicans (C. albicans) colony-forming units (CFUs) and erythema of the palate were evaluated at baseline and at 14 days after treatment. Data were analyzed using SPSS version 11 via Student’s t test and repeated measure ANOVA.

The results showed similar efficacy of nystatin and ZM in the reduction of C. albicans CFUs compared to the baseline value (p = 0.593). Both medications significantly decreased the colony count (p < 0.001). Nystatin and ZM had similar efficacy for the reduction of erythema as well (p = 0.256) and both caused a significant reduction in erythema of the palate (p < 0.001).

ZM drop was as effective as the nystatin drop in the resolution of erythema of the palate and reduction of C. albicans colony count.

Hydatidosis is a common disease of both humans and animals, resulting from infection with the larvae of Echinococcus granulosus tapeworm. The aim of this study was to investigate the antiparasitic (protoscolicidal) activities of three essential oils in vitro.

This study was designed to evaluate the biochemical composition and in vitro antiparasitic effects of Zataria multiflora, Origanum vulgare and Mentha pulegium essential oils. Gas chromatography was performed to identify the main components of the herbal oils. To determine the antiparasitic properties of the essential oils, live protoscoleces from hydatid cysts were exposed to three concentrations of the herbal oils and were incubated at 37°C for 5, 10, 15, 20 or 25 minutes. 

The biochemical analysis of these oils indicated that carvacrol and thymol were the major compounds of the Zataria oil. Further, carvacrol and thymol in Origanum essential oil and pulegone and piperitone in Mentha oil were the major compounds. The quickest and slowest antiparasitic effect was achieved from Zataria and Origanum (10%) or from Zataria (0.6%), respectively. The statistical analysis showed a significant difference between the mortality rate of protoscoleces exposed to 0.6% and 1% concentrations, respectively, of Zataria and Origanum at the predetermined exposure times (P<0.05). The three concentrations of Mentha had the same significant statistical differences (P<0.05).

Essential oils, Zataria multiflora, Origanum vulgare and Mentha pulegium had significant protoscolicidal activities that were dependent on the concentration of the oils and the exposure times.

Breast cancer is the most common cause of cancer death among women; thus, developing new drugs is crucial. Essential oils (EO)s with a wide range of bioactivities, such as anticancer effects, have provided a valuable source for this purpose. In this study, components of two medicinally important EOs were identified using GC-MS analysis. Moreover, antioxidant effects, as well as anti-cancer properties, were evaluated.The EOs formulated into nanoemulsion using the spontaneous emulsification approach, separately. Comprehensive stability tests were performed to select the optimum nanoemulsions of each EO. Anticancer effect of the most stable nanoemulsion of Zataria multiflora with a particle size of 43 ± 4 nm (PDI 0.4 ± 0.2 and SPAN 0.6 ± 0.1) was significantly better non-formulated form against four human breast cancer cell lines, MCF-7, MDA-MB-175, MDA-MB-231, and MDA-MB-468. Interestingly, the anticancer effect of Artemisia dracunculus nanoemulsion (16 ± 4 nm, 0.2 ± 0.1, and 0.4 ± 0.1) was also significantly improved in compassion to the essential oil. Considering the results, prepared nanoemulsions could be used as supplementary drugs or food additives.

Paraquat (PQ) is a herbicide which induces oxidative stress and inflammation. Anti-inflammatory and anti-oxidant effects were shown for Zataria multiflora (Z. multiflora) and carvacrol previously. The effects of Z. multiflora hydroalcoholic extract and carvacrol on systemic inflammation and oxidative stressinduced by inhaled PQ were examined in this study.

Six groups of male rats used in this study were as follows: control group exposed to normal saline aerosol, one group exposed to PQ 54 mg/m3 aerosol, animals exposed to PQ 54 mg/m3 and treated with Z. multiflora (200 and 800 mg/kg/day) or carvacrol (20 and 80 mg/kg/day) for 16 days after the end of exposure to PQ. Exposure to PQ was performed 8 times, every other day, each time for 30 min. After the end of the treatment period, different variables were measured.

Significant increases in nitrite (NO2), malondialdehyde (MDA) and interleukin (IL)-6 serum levels but significant reduction of interferon-gamma (IFN-γ) serum levels as well as IFN-γ/IL-6 ratio were observed in PQ-exposed compared to control group (p2, and IL-6 but increased IFN-γ and IFN-γ/IL-6 ratio compared to un-treated PQ exposed group (p

Treatment with Z. multiflora and carvacrol improved systemic inflammation oxidative biomarkers induced by inhaled PQ which may indicate therapeutic potential of the plant and its constituent, carvacrol in systemic inflammation and oxidative biomarkers induced by inhaled PQ.

The effects of PPAR-γ agonist alone and in combination with carvacrol and Zataria multiflora on inhaled paraquat (PQ) induced-systemic inflammation and oxidative stress were examined. Control group exposed to normal saline aerosol, one group exposed to 54 mg/m3 PQ aerosol and four groups exposed to PQ aerosol and treated with 5 mg/kg/day pioglitazone, pioglitazone + 200 mg/kg/day Z. multiflora extract, pioglitazone + 20 mg/kg/day carvacrol, and 0.03 mg /kg/day dexamethasone for 16 days after the end of exposure to PQ were studied. Exposure to normal saline or PQ was performed every other days for 30 min (8 times). Different variables were measured after the end of treatment period. PQ exposure significantly increased serum levels of NO2, MDA and IL-6 but dexreased CAT and IFN-γ levels and IFN-γ/IL-6 ratio compared to control group (P The effects of combination therapy of pioglitazone with Z. multiflora or carvacrol on inhaled paraquat (PQ) induced-oxidative stress and systemic inflammation were higher than the effects of pioglitazone alone. These results suggested that the effects of the extract and carvacrol may mediated through PPAR-γ receptors.

 The aim of this study was to evaluate and compare antibacterial and antifungal effects of different concentrations of Zataria multiflora extract mouthrinse.

 In this lab trial study, 128 elastomeric ligatures were divided into 2 groups of 64. Before disinfection eight ligatures of each group were randomly selected to evaluate the microbial load. The remaining ligatures in each group (n = 58) were divided into 7 subgroups of 8. All samples in group 1 (G1) contaminated with Streptococcus mutans (S. mutans) and in group 2 (G2) contaminated with Candida albicans (C. albicans). Then, Zataria multiflora extract in 1%, 0.1%, 0.01%, 0.001%, 0.0001% concentrations as decontamination agent were used in 5 subgroups of each group. Positive control consisted of penicillin in G1 and nystatin in G2. For the negative control in both groups phosphate buffered saline was used. The average number of adhered viable bacterial cell after performing the disinfection protocols were calculated and compared. The collected data was statistically analyzed by Kruskal-wallis, Wilcoxon and Mann-Whitney test using SPSS software version 18 at a significant level of 0.05.

 Results showed that penicillin, nystatin, Zataria multiflora extract in 1% and 0.1% concentrations completely eliminated C. albicans and S. mutans on elastomeric ligatures. Statistically significant differences were found between the number of adhered S. mutans and C. albicans before and after performing the all five concentrations of disinfection solutions (P = 0.01). Also higher concentrations of Zataria multiflora showed more antibacterial effectse in both groups.

 Zataria multiflora extract mouthrinse showed antibacterial and antifungal characteristics and could be useful for patients under orthodontic treatment.