HYSSOP and POLIUM could help to prevent COVID-19 in high-risk population: The results of a parallel randomized placebo-controlled field trial

243-253This study was conducted to evaluate the effect of HYSSOP (composed of Hyssopus officinalis L., Echium amoenum Fisch & C. A. Mey and Glycyrrhiza glabra L.) and POLIUM (contained Teucrium polium L., Cuscuta epithymum Murr and Cichorium intybus L.) combined distilled herbal medicines compared to placebo in the prevention of COVID-19. This is a double-blind parallel placebo-controlled field trial conducted on 751 asymptomatic individuals whose one of the family members recently had a positive RT-PCR test for COVID-19. They were divided into three groups including POLIUM, HYSSOP and placebo using random blocks with a 1:1:1 allocation ratio. Participants received daily 5 cc (under 12 years) or 10 cc (over 12 years) of allocated oral medications for 20 days. The primary outcome was the frequency of positive RT-PCR test among participants who became symptomatic. The mean age of participants was 36.6. Nineteen participants get infected by COVID-19 during the intervention; fifteen of them belonged to the placebo and four to the POLIUM group. Fisher's exact test indicated significant differences between HYSSOP and placebo (p<0.001) as well as POLIUM and placebo (p=0.009) groups in terms of COVID-19 confirmed by PCR tests. Cox regression model adjusted for confounders illustrated that the hazard of getting infection by COVID-19 in POLIUM and HYSSOP groups decreased by 66% (OR (95% CI): 0.34 (0.12 to 0.94); p=0.038) and 93% (OR (95% CI): 0.07 (0.01to 0.56); p=0.012) respectively, compared to placebo .Oral administration of HYSSOP and POLIUM with the other supportive health care could decrease the risk of getting COVID-19

Synergistic Antifungal Effects of Lactobacillus Strains and Nano Selenium on Growth Inhibition of Candida albicans

Background and Aims: Candidiasis is a fungal infection caused by Candida albicans. Uncontrolled use of antibiotics has resulted in drug resistance. This study has been conducted to find a suitable alternative for these drugs. Materials and Methods: Primarily, standard and clinical isolates of C.albicans were collected. In order to indentify clinical isolates from lambs, the conventional mycological methods CHROM candida agar and germ tube production were used. The Antifungal effects of experimental treatments were evaluated against C.albicans by disk diffusion and measuring the growth inhibition zone in well diffusion method. Moreover, the MIC and MFC of experimental treatments were determined by microdilution method. Results: The results of the well and disk diffusion methods showed that in both tests, the highest growth inhibition zone of the "Nano selenium-loaded lactobacillus" treatment was 29/41 and 27.64 mm, respectively on the standard strain of C.albicans. The results of MIC and MFC determination showed that in all experimental periods, "Nano selenium-loaded lactobacillus" and "Nano selenium+Lactobacillus" treatments with 473.80 and 511.91 μg/ml for MIC and 807.66 and 845.28 μg/ml for MFC had the lowest amounts compared to other treatments (P<0.05). Conclusions: The results of microbial tests on C.albicans confirm the antifungal ability of "Nano selenium-loaded lactobacillus" treatment. Therefore, provided that this test is repeated in future studies and the accuracy of these results is ensured, manufacturing of this product or industrial supplements with this formulation may be advised for prevention or treatment of fungal infections

The Effects of Cetirizine on P-glycoprotein Expression and Function In vitro and In situ

Purpose: P-glycoprotein (P-gp) plays a major role in oral absorption of drugs. Induction or inhibition of P-gp by drugs contributes to variability of its transport activity and often results in clinically relevant drug-drug interactions. The purpose of this study was to investigate the effect of cetirizine, a second generation H1 antihistamine, on P-gp function and expression in vitro and in situ. Methods: The in-vitro rhodamin-123 (Rho123) efflux assay in Caco-2 cells was used to study the effect of cetirizine on P-gp function. Western blot analysis was used for surveying the effect of cetirizine on expression of P-gp in Caco-2 cells. Rat in situ single-pass intestinal permeability technique was used to calculate the intestinal permeability of a known P-gp substrate (digoxin) in the presence of cetirizine. The amounts of digoxin and cetirizine in intestinal perfusion samples were analyzed using a HPLC method. Results: The results showed significant increase in Rho123 uptake (P < 0.05) and also P-gp band intensity decrease in cetirizine-treated cells in vitro. Furthermore the intestinal permeability of digoxin was also increased significantly in the presence of cetirizine (P < 0.01). Conclusion: Therefore it is concluded that cetirizine is a P-gp inhibitor and this should be considered in co administration of cetrizine with other P-gp substrate drugs. Further investigations are required to confirm our results and to determine the mechanism underlying P-gp inhibition by cetirizine

Inhibitory effect of clemastine on P-glycoprotein expression and function: an in vitro and in situ study

Objective(s):Transporters have an important role in pharmacokinetics of drugs. Inhibition or induction of drug transporters activity can affect drug absorption, safety, and efficacy. P-glycoprotein (P-gp) is the most important membrane transporter that is responsible for active efflux of drugs. It is important to understand which drugs are substrates, inhibitors, or inducers of P-gp to minimize or avoid unwanted interactions. The aim of this study was to investigate the effects of clemastine on the expression and function of P-gp. Materials and Methods: The effect of clemastine on P-gp function and expression was evaluated in vitro byrhodamine-123 (Rho123) efflux assay in Caco-2 cells and Western blot analysis. Rat in situ single pass intestinal permeability model was used to investigate the clemastine effect on digoxin Peff, as a known P-gp substrate. Digoxin levels in intestinal perfusates were assayed by high performance liquid chromatography (HPLC) method. Results:The Caco-2 intracellular accumulation of Rho123 in clemastine and verapamil treated cells was 90.8 ± 9.8 and 420.6±25.4 pg/mg protein, respectively which was significantly higher than that in control cells (50.2±6.0;

Gamma Oryzanol Bearing Nanoliposome Produced by Modified Thermal Method: Thermal Property, Encapsulation Efficiency, Oscillatory Rheometry

Nanoliposomes are one of the most important polar lipid-based nanocarriers which can be used for encapsulation of both hydrophilic and hydrophobic active compounds. In this research, nanoliposomes based on lecithin-polyethylene glycol-gamma oryzanol were prepared by using a modified thermal method. Only one melting peak in DSC curve of gamma oryzanol bearing liposomes was observed which could be attributed to co-crystallization of both compounds. The addition of gamma oryzanol, caused to reduce the melting point of 5% (w/v) lecithin-based liposome from 207°C to 163.2°C. At high level of lecithin, increasing of liposome particle size (storage at 4°C for two months) was more obvious and particle size increased from 61 and 113 to 283 and 384 nanometers, respectively. The encapsulation efficiency of gamma oryzanol increased from 60% to 84.3% with increasing lecithin content. The encapsulation stability of oryzanol in liposome was determined at different concentrations of lecithin 3, 5, 10, 20% (w/v) and different storage times (1, 7, 30 and 60 days). In all concentrations, the encapsulation stability slightly decreased during 30 days storage. The scanning electron microscopy (SEM) images showed relatively spherical to elliptic particles which indicated to low extent of particles coalescence. The oscillatory rheometry showed that the loss modulus of liposomes were higher than storage modulus and more liquid-like behavior than solid-like behavior. The samples storage at 25°C for one month, showed higher viscoelastic parameters than those having been stored at 4°C which were attributed to higher membrane fluidity at 25°C and their final coalescence.Nanoliposomes are one of the most important polar lipid based nanocarriers which can be used for encapsulation of both hydrophilic and hydrophobic active compounds. In this research, nanoliposomes based on lecithin-polyethylene glycol-gamma oryzanol were prepared by using modified thermal method. Only one melting peak in DSC curve of gamma oryzanol bearing liposomes was observed which could be attributed to co-crystallization of both compounds. The adding of gamma oryzanol, caused to reduce the melting point of 5% (W/V) lecithin based liposome from 207 ˚C to 163.2 ˚C. In high level of lecithin, increasing of liposome particle size (storage at 4 ˚C for two months) was more observable and particle size increased from 61 and 113 to 283 and 384 nanometers, respectively. The encapsulation efficiency of gamma oryzanol increased from 60% to 84.3 % with increasing lecithin content. The encapsulation stability of oryzanol in liposome was determined at different concentration of lecithin 3, 5, 10, 20% (W/V) and different storage time (1,7, 30 and 60 days). In all concentration, encapsulation stability slightly decreased during 30 days storage. The scanning electron microscopy (SEM) images showed relatively spherical to elliptic particle which indicating low extent of particles coalescence. The oscillatory rheometry showed that the loss modulus of liposome samples were higher than storage modulus and more liquid like behavior than solid like behavior. The samples storage at 25 ˚C for one month, showed higher viscoelastic parameters than those storage at 4 ˚C which attributed to higher membrane fluidity at 25 ˚C and resulting coalescence

Engineered bioadhesive Self-Healing nanocomposite hydrogel to fight infection and accelerate cutaneous wound healing

The emergence of multifunctional wound dressings for cutaneous tissue injuries represents a paradigm shift in wound care, offering advanced solutions that transcend traditional wound protection. Inspired by the recent advances in nano-reinforcement and mussel-inspired chemistry, an innovative bioadhesive self-healing hydrogel was developed using dopamine-grafted oxidized sodium alginate/gelatin containing Myrtus communis L. extract@ZIF-8 NPs (MC@ZIF-8/DA-OSA/Gel) through dual cross-linking. The resulting optimized hydrogel demonstrated good physicochemical, and hemostatic properties, rapid self-repair, and firm adhesion to tissues. In vitro analysis confirmed excellent cytocompatibility and adhesion in cultured fibroblasts. Notably, the incorporation of MC@ZIF-8 NPs into hydrogel enhanced antioxidant and antibacterial activities. Applying the engineered hydrogel at the injury site significantly accelerated the healing process in a mouse model of cutaneous wound injury, as evident in increased cutaneous tissue thickness and improved collagen disposition. Moreover, the local increase of CD31+ cells and COL1A+ strands indicated enhanced vascularization, and fibroblast proliferation compared to the other groups. Overall, our results demonstrate the potential efficacy of the engineered system as an advanced wound-covering material, suggesting it could be effective for treating various forms of acute and chronic wounds as well

Therapeutic Efficacy of Orally Delivered Doxorubicin Nanoparticles in Rat Tongue Cancer Induced by 4-Nitroquinoline 1-Oxide

Purpose: Oral cancer is one of the most significant cancers in the world, and squamous cell carcinoma makes up about 94% of oral malignancies. The aim of the present study was to compare the efficacy of doxorubicin plus methotrexate - loaded nanoparticles on tongue squamous cell carcinoma induced by 4NQO and compare it with the commercial doxorubicin and methotrexate delivered orally on seventy SD male rats. Methods: 70 rats were divided into five groups. During the study, the animals were weighed by a digital scale once a week. Number of mortalities was recorded in the data collection forms. At the end of the treatment, biopsy samples were taken from rat tongues in order to evaluate the severity of dysplasia and the extent of cell proliferation. The results were analyzed using ANOVA, descriptive statistics and chi-square test. Results: No statistically significant difference was found in the mean weight of five groups (p>0.05). No significant relationship was found between groups and mortality rate (P = 0. 39). In addition, there was a significant relationship between groups and the degree of dysplasia (P <0.001). The statistical analysis showed a significant relationship between groups and the rate of cell proliferation (p <0.001). Conclusion: The results of the present study showed that the use of doxorubicin plus methotrexate - loaded nanoparticles orally had more therapeutic effects than commercial doxorubicin plus methotrexate

The effect of penetration enhancers on drug delivery through skin: a QSAR study

Skin penetration enhancers are used to allow formulation of transdermal delivery systems for drugs that are otherwise insufficiently skin-permeable. A full understanding of the mode of action could be beneficial for the design of potent enhancers and for the choice of the enhancer to be used in the topical formulation of a special drug. In this study, the structural requirements of penetration enhancers have been investigated using the Quantitative Structure–Activity Relationship (QSAR) technique. Activities of naturally occurring terpenes, pyrrolidinone and N-acetylprolinate derivatives on the skin penetration of 5-fluorouracil, diclofenac sodium (DFS), hydrocortisone (HC), estradiol and benazepril have been considered. The resulting QSARs indicated that for 5-fluorouracil and diclofenac sodium, less hydrophobic enhancers were the most active. More precisely, molecular descriptors in the corresponding QSARs indicated the possible involvement of intermolecular electron donor–acceptor interactions. This was in contrast to the skin permeation promotion of hydrocortisone, estradiol and benazepril by enhancers, where a linear relationship between enhancement activity and n-octanol/water partition coefficients of enhancers was evident. The possible mechanisms of penetration enhancement as suggested by the QSARs will be discussed

HYSSOP and POLIUM could help to prevent COVID-19 in high-risk population: The results of a parallel randomized placebo-controlled field trial

This study was conducted to evaluate the effect of HYSSOP (composed of Hyssopus officinalis, Echium amoenum, and Glycyrrhiza glabra L) and POLIUM (contained Teucrium polium L, Cuscuta epithymum Murr, and Cichorium intybus L) combined distilled herbal medicines compared to placebo in prevention of COVID-19. This is a double-blind parallel placebo-controlled field trial conducted on 751 asymptomatic individuals who one of the family members recently had a positive RT-PCR test for COVID-19. They were divided into three groups including POLIUM, HYSSOP, and placebousing random blocks with a 1:1:1 allocation ratio. Participants received daily 5 cc (under 12 years) or 10 cc (over 12 years) of allocated oral medications for 20 days. The primary outcome was the frequency of positive RT-PCR test among participants who became symptomatic. The mean age of participants was 36.6. Nineteen participants get infected by COVID-19 during the intervention; fifteen of them belonged to the placebo and four to the POLIUM group. Fisher's exact test indicated significant differences between HYSSOP and placebo (p&lt;0.001) as well as POLIUM and placebo (p=0.009) groups in terms of COVID-19 confirmed by PCR test. Cox regression model adjusted for confounders illustrated that the hazard of getting infection by COVID-19 in POLIUM and HYSSOP groups decreased by 66% (OR (95% CI): 0.34 (0.12 to 0.94); p=0.038) and 93% (OR (95% CI): 0.07 (0.01to 0.56); p=0.012) respectively, compared to placebo. Oral administration of HYSSOP and POLIUM with the other supportive health care could decrease the risk of getting COVID-19