BACKGROUND: Antimicrobial-resistant Helicobacter pylori (H. pylori) poses a significant public health concern, especially given the limited therapeutic options for azithromycin-resistant strains. Hence, there is a necessity for new studies to reconsider the use of azithromycin, which has diminished in effectiveness against numerous strains. Thus, we aimed to augment azithromycin\'s anti-Helicobacter properties by combining it with curcumin in different formulations, including curcumin in clove oil, curcumin nano-gold emulsion, and curcumin nanoemulsion.
METHODS: The antimicrobial activities of the investigated compounds, both individually and in combination with other anti-Helicobacter drugs, were evaluated. Their antibiofilm and anti-virulence properties were assessed using both phenotypic and genotypic methods, alongside molecular docking studies. Our findings were further validated through mouse protection assays and histopathological analysis.
RESULTS: We observed high anti-Helicobacter activities of curcumin, especially curcumin nanoemulsion. A synergistic effect was detected between curcumin nanoemulsion and azithromycin with fraction inhibitory concentration index (FICI) values <0.5. The curcumin nanoemulsion was the most active anti-biofilm and anti-virulence compound among the examined substances. The biofilm-correlated virulence genes (babA and hopQ) and ureA genes were downregulated (fold change <1) post-treatment with curcumin nanoemulsion. On the protein level, the anti-virulence activities of curcumin nanoemulsion were documented based on molecular docking studies. These findings aligned with histopathological scoring of challenge mice, affirming the superior efficacy of curcumin nanoemulsion/azithromycin combination.
CONCLUSIONS: The anti-Helicobacter activities of all curcumin physical forms pose significant challenges due to their higher  minimum inhibitory concentration (MIC) values exceeding the maximum permissible level. However, using curcumin nanoemulsion at sub-MIC levels could enhance the anti-Helicobacter activity of azithromycin and exhibit anti-virulence properties, thereby improving patient outcomes and addressing resistant pathogens. Therefore, more extensive studies are necessary to assess the safety of incorporating curcumin nanoemulsion into H. pylori treatment.

BACKGROUND: This study aimed to determine the therapeutic efficacy of curcumin nanoemulsion (CUR-NE) in mice infected with Echinococcus granulosus sensu stricto protoscoleces.
METHODS: Forty-two inbred BALB/c mice were divided into seven groups of six animals each. Six groups were inoculated intra-peritoneally with 1500 viable E. granulosus protoscoleces, followed for six months and used as infected groups. The infected groups were named as: CEI1 to CEI6 accordingly. The 7th group was not inoculated and was named cystic echinococcosis noninfected group (CENI7). CEI1 and CEI2 groups received 40 mg/kg/day and 20 mg/kg/day curcumin nanoemulsion (CUR-NE), respectively. CEI3 received nanoemulsion without curcumin (NE-no CUR), CEI4 received curcumin suspension (CUR-S) 40 mg/kg/day, CEI5 received albendazole 150 mg/kg/day and CEI6 received sterile phosphate-buffered saline (PBS). CENI7 group received CUR-NE 40 mg/kg/day. Drugs administration was started after six months post-inoculations of protoscoleces and continued for 60 days in all groups. The secondary CE cyst area was evaluated by computed tomography (CT) scan for each mouse before treatment and on the days 30 and 60 post-treatment. The CT scan measurement results were compared before and after treatment. After the euthanasia of the mice on the 60th day, the cyst area was also measured after autopsy and, the histopathological changes of the secondary cysts for each group were observed. The therapeutic efficacy of CUR-NE in infected groups was evaluated by two methods: CT scan and autopsied cyst measurements.
RESULTS: Septal calcification in three groups of infected mice (CEI1, CEI2, and CEI4) was revealed by CT scan. The therapeutic efficacy of CUR-NE 40 mg/kg/day (CEI1 group) was 24.6 ± 26.89% by CT scan measurement and 55.16 ± 32.37% by autopsied cysts measurements. The extensive destructive effects of CUR-NE 40 mg/kg/day (CEI1 group) on the wall layers of secondary CE cysts were confirmed by histopathology.
CONCLUSIONS: The current study demonstrated a significant therapeutic effect of CUR-NE (40 mg/kg/day) on secondary CE cysts in BALB/c mice. An apparent septal calcification of several cysts revealed by CT scan and the destructive effect on CE cysts observed in histopathology are two critical key factors that suggest curcumin nanoemulsion could be a potential treatment for cystic echinococcosis.

In this study, gelatin (GE) was composited with chitosan films (CH) and chitosan films incorporated with curcumin nanoemulsion (CH-CNE) through blending and layer-by-layer (LbL) assembly in order to overcome the physical limitations of the chitosan and its incorporated films. Furthermore, the distinctive effects of blending and LbL assembly on the physicochemical parameters of the composite films were assessed. The composite LbL films incorporated with GE exhibited improvement of water vapor barrier, tensile strength, solubility, which contributed to the enhanced antioxidant activity from the single components. By contrast, the composite films of the blending method exhibited greater elongation at break and increased swelling degree. Additionally, the films containing the nanoemulsion exhibited reduced light transmission and increased opacity. The thermal properties indicating the thermal stability and compatibility interactions of the composite films were examined by the glass transition temperature (Tg). Results revealed that the distinctive behavior of the Tg was affected by the compositing method. The LbL films exhibited substantially increased Tg, indicating enhanced thermal stability. The results indicated that the composited films formed via the LbL assembly attained better physicochemical properties and thermal stability, implying higher compatible film than the blending.

BACKGROUND: The aim of the present study was to assess in vitro protoscolicidal effects of curcumin nanoemulsion (CUR-NE) against protoscoleces of cystic echinococcosis (CE)/hydatid cysts.
METHODS: The CUR-NE was prepared via spontaneous emulsification of soybean as the oil phase, a mixture of Tween 80 and Tween 85 as the surfactant, ethanol as the co-surfactant and distilled water. Various concentrations of CUR-NE (156, 312, 625 and 1250 µg/ml) were exposed to collected protoscoleces of infected sheep liver hydatid cysts for 10, 20, 30, 60 and 120 min. Viability of the protoscoleces were assessed using eosin exclusion test. Morphological changes of the protoscoleces were observed using differential interference contrast (DIC) microscopy.
RESULTS: The mean particle size and zeta potential of CUR-NE included 60.4 ± 14.8 nm and - 16.1 ± 1.1 mV, respectively. Results showed that the viability of the protoscoleces decreased significantly with increases in CUR-NE concentrations (p < 0.001). The mortality rates of protoscoleces with exposure to concentrations of 1250 and 625 µg/ml of CUR-NE for 60 min were 94 and 73.33%, respectively. Mortality of the protoscoleces was 100% after 120 min of exposure to 1250 and 625 µg/ml concentrations of CUR-NE. Using NIC microscopy, extensively altered tegumental surface protoscoleces was observed after protoscoleces exposure to CUR-NE.
CONCLUSIONS: The findings of the present study revealed the in vitro protoscolicidal potential of CUR-NE. Therefore, CUR-NEs are addressed as novel protoscolicidal agents, which can be used as an alternative natural medicine to kill the protoscoleces, owing to their low toxicity and significant inhibition potency. However, further studies are necessary to investigate pharmacologic and pharmacokinetics of CUR-NEs.

The aim of this paper was to determine the effect of stabilized curcumin nanoemulsions (CUNE) as a food additive capable of directionally acting to inhibit molecules involved in dairy products\' quality and digestibility, especially cheese. The objects were cheeses made from the milk of higher grades with addition of a CUNE and a control sample. The cheeses were studied using a scanning electron microscope (SEM) in terms of organoleptic properties, such as appearance, taste, and aroma. The results show that the addition of CUNEs improved the organoleptic properties compared to the control cheese by 150% and improved its shelf life. The SEM study shows that formulation with CUNE promotes the uniform distribution of porosity. The CUNE-based cheese shows a better sensory evaluation compared to the emulsion without curcumin. CUNE-processed cheese provided better antioxidant and antimicrobial analysis than the control sample and offers added value to the dairy sector.

The review article concentrates on the potential uses of curcumin nanoemulsion in treatment and management of burn wound. Poor solubility and low bioavailability of curcumin limits the efficient and effective use of curcumin in management of bacterial infection related to burn wound. Nano particle based drug delivery system can be of great aid to solve this problem. Among this nanoemulsion is most favourable system due to its simplicity and low manufacturing cost. Nanoemulsion also enhances the skin permeation ability of curcumin and thus enhances its pharmacological efficacy specially as a potential antimicrobial agent, which can have applicability as a topical therapeutic agent in burn wound infection.

The relationship between the incidence of cardiovascular abnormalities and non-alcoholic fatty liver disease (NAFLD) has long been postulated. Curcumin (CUR) is a potential anti-atherosclerotic agent but its poor water solubility hinders its pharmacological use. Therefore, the present study aimed to investigate the effect of formulation of CUR nanoemulsion prepared using the spontaneous emulsification technique on high fat high fructose (HFHF)-induced hepatic and cardiac complications. Fifty Wistar rats were divided into five groups. CUR nanoemulsion at doses of 5 and 10 mg/kg and conventional powdered CUR at a dose of 50 mg/kg were orally administered daily to rats for two weeks, and compared with normal control and HFHF control. Results revealed that the high dose level of CUR nanoemulsion was superior to conventional CUR in ameliorating the HFHF-induced insulin resistance status and hyperlipidemia, with beneficial impact on rats\' recorded electrocardiogram (ECG), serum aspartate aminotransferase (ALT) and alanine aminotransferase (AST) levels, leptin, adiponectin, creatine phosphokinase, lactate dehydrogenase and cardiac troponin-I. In addition, hepatic and cardiac oxidative and nitrosative stresses, oxidative DNA damage and disrupted cellular energy statuses were counteracted. Results were also confirmed by histopathological examination. PRACTICAL APPLICATIONS: The use of curcumin nanoemulsion could be beneficial in combating hepatic and cardiac complications resulting from HFHF diets.

Milk powder is an important ingredient in various foods and pediatric formulations. The textural and digestion properties of the formulations depend on the preheat treatment of the milk powder during manufacture. Thus, it is interesting to know how these modifications can influence on the release of fortified bioactive compounds during digestion with a milk matrix. In this study, a curcumin nanoemulsion was incorporated into milks reconstituted from low-heat, medium-heat and high-heat skim milk powders (SMPs) and the milks were subjected to semi dynamic in vitro digestion. All the recombined milk systems formed a curd under gastric conditions, which reduced the gastric emptying of protein and curcumin-loaded oil droplets. Because of the formation of heat-induced casein/whey protein complexes, the open fragmented curd formed by the high-heat-treated reconstituted powder resulted in higher protein and oil droplets emptying to the intestine and higher curcumin bioaccessibility. This study provides useful information for how protein ingredients can govern the fate of added health-promoting compounds during digestion.

Diabetes mellitus has been implicated in the exacerbation of cerebral ischemic injuries. Among the most promising therapeutic approaches is the combination of nutraceuticals and nanotechnology. Curcumin has been termed \"the magic molecule\", and it was proven to exert several therapeutic actions. Therefore, the aim of the presented work was to investigate the therapeutic effects of curcumin nanoemulsion (NC) administered orally on the middle cerebral artery occlusion and reperfusion (MCAO/Re)-induced cerebral damage in rats with streptozotocin-induced diabetes. The cerebral injury was induced in rats by MCAO/Re 6 weeks after single intraperitoneal STZ injection (50 mg/kg; i.p.). MCAO/Re diabetic rats were then treated with NC (50 and 100 mg/kg; bw; p.o.) for two consecutive weeks. The results of the present study showed that oral treatment of MCAO/Re diabetic rats with NC was associated with a marked attenuation of the neurological deficit score as well as the brain imbalance of the redox homeostasis. NC treatment was also associated with decline in the brain expression of tumor necrosis factor, interleukin-1β, COX-2, cleaved caspase-3, and nuclear factor kappa B. In addition, the expression of glucose transporter 1 proteins upon treatment was restored. PRACTICAL APPLICATIONS: From all these results, it can be concluded that oral supplementation of curcumin nanoemulsion (NC) in diabetic rats reduced the brain injury via augmentation of the expression of glucose transporter 1, as well as its antioxidant and anti-inflammatory properties. Therefore, NC could be delineated as a promising treatment option for cerebral ischemia in diabetic patients.

BACKGROUND: The aim of this study was to prepare curcumin nanoemulsion (CR-NE) to solve the problems associated with poor water solubility and low bioavailability of CR and to test its efficiency in the treatment of acute and chronic toxoplasmosis in mouse models.
METHODS: CR-NE 1% was prepared using spontaneous emulsification by soybean as oil phase; a mixture of Tween 80 and Tween 85 as surfactant; ethanol as cosurfactant and distilled water. Particle size and zeta potential of NE were assessed using Nano-ZS90 dynamic light scattering. Stability testing of NE was assessed after storage for 2 months at room temperature. In vivo experiments were carried out using 50 BALB/c mice inoculated with virulent RH strain (type I) and 50 BALB/c mice inoculated with avirulent Tehran strain (type II) of Toxoplasma gondii and treated with CR-NE (1% w/v), CR suspension (CR-S, 1% w/v), and NE without CR (NE-no CR).
RESULTS: The mean particle size and zeta potential of CR-NE included 215.66±16.8 nm and -29.46±2.65 mV, respectively, and were stable in particle size after a three freeze-thaw cycle. In acute phase experiment, the survival time of mice infected with RH strain of T. gondii and treated with CR-NE extended from 8 to 10 days postinoculation. The differences were statistically significant between the survival time of mice in CR-NE-treated group compared with negative control group (P<0.001). Furthermore, CR-NE significantly decreased the mean counts of peritoneum tachyzoites from 5,962.5±666 in negative control group to 627.5±73 in CR-NE-treated mice (P<0.001). Growth inhibition rates of tachyzoites in peritoneum of mice receiving CR-NE, CR-S, and NE-no CR included 90%, 21%, and 11%, respectively, compared with negative control group. In chronic phase experiment, the average number and size of tissue cysts significantly decreased to 17.2±15.6 and 31.5±6.26 µm, respectively, in mice inoculated with bradyzoites of T. gondii Tehran strain and treated with CR-NE compared with that in negative control group (P<0.001). Decrease of cyst numbers was verified by downregulation of BAG1 in treatment groups compared with negative control group with a minimum relative expression in CR-NE (1.12±0.28), CR-S (11.76±0.87), and NE-no CR (14.67±0.77), respectively, (P<0.001).
CONCLUSIONS: Results from the current study showed the potential of CR-S and CR-NE in treatment of acute and chronic toxoplasmosis in mouse models for the first time. However, CR-NE was more efficient than CR-S, and it seems that CR-NE has a potential formula for the treatment of acute and chronic toxoplasmosis, especially in those with latent bradyzoites in brain.