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Staphylococcus aureus, particularly multi-drug resistant strains, presents significant challenges in dairy farming due to its role in causing bovine mastitis, which leads to substantial economic losses and limited treatment options. Seeking alternative therapies, we investigated the potential of a topical formulation derived from the medicinal herb Salvia officinalis to combat S. aureus growth and biofilms associated with bovine mastitis. Through systematic extraction in different solvents and fractionation by column chromatography, we isolated and identified three key multicyclic terpenoids-ferruginol, sugiol, and sclareol-exhibiting significant antimicrobial activity. The formulation effectively inhibited biofilm formation, with minimum inhibitory concentration (MIC) values ranging from 0.09 to 0.74 mg ml-1 against clinical S. aureus strains, comparable to or lower than those of the pure compounds. Moreover, it displayed robust anti-adhesive properties, reducing biofilm formation by 20%-79% at subinhibitory concentrations. Furthermore, the formulation successfully disrupted pre-existing biofilms, achieving reductions ranging from 30% to 82%. Cytotoxicity assays confirmed the safety of the formulation on mammary epithelial cells, with cell viability maintained at 100% at MIC. Our findings underscore the therapeutic potential of Sa. officinalis-derived compounds in managing bovine mastitis caused by S. aureus, emphasizing their antimicrobial efficacy and safety profile., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)

Purpose: To evaluate the modulatory properties of Calendula officinalis L. (Asteraceae) (C. officinalis) extract on cafeteria diet-fed rats., Methods: A cafeteria diet was administered ad libitum for 45 days to induce dyslipidemia. Then, the rats were treated with the formulations containing C. officinalis in the doses of 50, 100, and 150 mg/kg or only with the vehicle formulation; the control group received a commercial ration., Results: The cafeteria diet decreased glutathione S-transferase activity and high-density lipoprotein plasmatic levels and damaged the hepatic architecture. The C. officinalis extract was able to reduce lipid infiltration in liver tissue and to modulate oxidative stress and lipid profile markers., Conclusions: The correlations between the variables suggest a pathological connection between oxidative stress markers and serum lipid profile.

The prophylactic and therapeutic overuse of antimicrobials on the farm has contributed to the emergence of hard-to-fight bacterial strains causing bovine mastitis. Aiming at alternative therapies, this study evaluated the antimicrobial activity of 20 essential oils against clinical Staphylococcus aureus strains. Of them, five with strong activities were selected and evaluated for their minimum inhibitory concentrations (MIC) in culture medium and milk, cytotoxicity against bovine mammary cells (MAC-T), antiadhesive properties, and interactions among themselves and with cefoperazone. The oils remained active on milk, were not cytotoxic, and some concentrations stimulated MAC-T cells growth, suggesting healing potential. Subinhibitory concentrations of Coriandrum sativum, Origanum vulgare, Syzygium aromaticum, and Thymus vulgaris reduced biofilm formation by at least 80%. Several oil and cefoperazone combinations displayed additive interaction, with O. vulgare and C. sativum showing the most promising results. We developed formulations for being used as prophylactic postdipping solutions in the field, containing different concentrations (1% or 3%) of the active oils, alone or in combination, with 3% glycerin, 1% Tween 80, and water. The formulations showed strong antimicrobial activity in milk and enhanced antiadhesive properties, specially when two oils were combined in the formula, indicating promising biotechnological and therapeutical applications., (© The Author(s) 2023. Published by Oxford University Press on behalf of Applied Microbiology International.)

Inflammatory bowel diseases are a group of inflammatory disorders of the gastrointestinal tract. Their prevalence is still low in Brazil, but the incidence is increasing annually. A variety of compounds present in Curcuma longa L., particularly curcumin, have been shown to reduce oxidative stress and aid in the prevention of associated diseases. This study aimed to assess the effect of curcumin transdermal gel on oxidative stress and intestinal inflammation in IL-10 knockout mice. Female mice were divided into four groups: a control group (C0) treated with vehicle and three experimental groups treated with transdermal gel containing 50 (C50), 75 (C75), and 100 (C100) mg curcumin kg-1 body weight. Colon malondialdehyde concentrations were lower in C50 and C75 groups. C100 treatment led to reduced catalase activity in the small intestine, whereas C50, C75, and C100 treatments resulted in decreased catalase activity in the colon. In contrast, superoxide dismutase activity increased in the small intestine of C50 and C75 mice and decreased in the colon of C50, C75, and C100 mice. Glutathione S-transferase activity increased in the small intestine and decreased in the colon of C75 animals. These findings suggest that curcumin transdermal gel exerts a protective effect against oxidative stress.

Ethnopharmacological Relevance: Remijia ferruginea DC. (Rubiaceae) (syn. Cinchona ferruginea A.St.-Hil.) is used in traditional medicine for the treatment of wounds, fever and malaria., Aim: This study investigated in vitro the proliferative and antioxidant effects of hydroalcoholic extract of leaves of R. ferruginea (HERF) and in vivo the healing effect of ointment based on HERF., Materials and Methods: The plant extract was characterized by liquid chromatography/mass spectrometry. Cell proliferation assays and in vitro antioxidant activity were performed. In in vivo assays, wound contraction ax was evaluated, as well as histological analyzes such as cellularity, proportion of blood vessels and collagen type I and III index. In addition, analyzes of the antioxidant enzymes SOD, CAT and GST were performed., Results: Our results showed in the chromatographic analysis that catechin, rutin and quercetin were the main phenolic compounds in the plant extract and may be responsible for the antioxidant and proliferative effects (p < 0.05). In addition, these compounds were found in higher concentration in leaves collected in spring. The ointment containing HERF was able to modulate tissue morphology, increasing cell proliferation, blood vessels, being able to stimulate the production of collagen fibers type I and III, (p < 0.05) contributing to scar tissue maturation and resistance., Conclusion: Our findings indicated that the three doses of HERF tested (1%, 3% and 5%) can modulate the skin repair process, but the best effects were observed after exposure to the highest dose., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Malignant melanoma has a low incidence, but is the most lethal type of skin cancer. Studies have shown that dibenzoylmethanes (DBMs) have interesting biological activities, including antineoplastic properties. These findings led us to investigate whether news DBM derivatives exert antitumor effects against skin cancers. In a previous study, we found that 1,3-diphenyl-2-benzyl-1,3-propanedione (DPBP) has high in vitro antineoplastic activity against murine B16F10 melanoma cells, with an IC 50 of 6.25 μg/mL. In the current study, we used transdermal and topical formulations of DPBP to evaluate its activity and molecular mechanism of action in a murine model of melanoma. The compound induces tumor cell death with high selectivity (selectivity index of 41.94) by triggering apoptosis through intrinsic and extrinsic pathways. DPBP treatment reduced tumor volume as well as serum VEGF-A and uric acid levels. Hepatomegaly and nephrotoxicity were not observed at the tested doses. Histopathological analysis of sentinel lymph nodes revealed no evidence of metastases. According to the observed data, the DPBP compound was effective for the topical treatment of melanoma cancer, suggesting that it acts as a chemotherapeutic or chemopreventive agent., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The aquatic plant Salvinia auriculata has been shown to possess promising properties for the treatment of Staphylococcus aureus bovine mastitis. The disease affects cattle health and compromises dairy cattle productivity, resulting in reduced milk production and higher mortality rates. The aim of this study was to evaluate the antimicrobial activity, antibiofilm activity, and toxicity of S. auriculata root extracts using bovine mammary epithelial cells (MAC-T); determine the chemical composition of the most active extract; and develop an S. auriculata antiseptic solution for pre- and post-milking teat disinfection. Plants were collected during the four seasons of the year. The most active hexane extract was subjected to bioguided fractionation, which resulted in the isolation of six known compounds, stigmast-22-ene-3,6-dione, stigmasterol, friedelinol, β-sitosterol, octadecyl alcohol, and octadecanoic acid. The antimicrobial and antibiofilm activities of the most active extract and isolated compounds were determined against nine S. aureus strains isolated from cows with mastitis. The efficacy of the S. auriculata teat dip formulation was tested using an excised teat model (ex vivo), and promising results were obtained. The S. auriculata extract formulation proved to be as effective as commercial antimicrobials in reducing log counts in excised teats., (© 2021. Sociedade Brasileira de Microbiologia.)

Objective: This study aimed to assess the antibacterial and antibiofilm effects of essential oils and herbal toothpastes against bacteria associated with oral diseases., Methods: The minimum inhibitory concentration (MIC) and antibiofilm activity of 13 essential oils against Staphylococcus aureus, Streptococcus mutans, Lactobacillus lactis, and Enterococcus faecalis. were determined. Toothpastes were formulated with different concentrations of the most active essential oils, alone and in combination, and evaluated for antibacterial and antibiofilm activities., Results: Clove, oregano, thyme, and cinnamon essential oils were effective in inhibiting all bacterial strains. The antibacterial activity of cinnamon essential oil was similar to that of the control (0.12 % chlorhexidine gluconate mouthwash). Cinnamon essential oil was a strong inhibitor of S. mutans growth. The antibiofilm activity of clove, oregano, thyme, and cinnamon essential oils at 1, 2, and 4 × MIC against S. mutans did not differ from that of the control. In the hole-plate diffusion assay, 17 out of the 18 tested toothpastes produced an inhibition halo at least half as large as that of the control. Toothpastes containing clove, clove and oregano, or clove, oregano, thyme, and cinnamon essential oils were able to completely disrupt S. mutans biofilms, not differing from the control. Thyme essential oil was found to act synergistically with chlorhexidine against S. mutans., Conclusions: The results indicate that clove, oregano, thyme, and cinnamon essential oils may be added to fluoride-free toothpastes to enhance inhibitory effects against bacteria associated with cavities and periodontal disease. Thyme essential oil may increase the efficiency of chlorhexidine-containing dentifrices., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interests regarding the publication of this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

This study investigated the ability of formulation containing Zingiber officinale (ginger) to reverse health changes promoted by unhealthy diet in Wistar rats. Five compounds from the gingerol family and three from the shogaol family were identified in the chromatographic analyzes of the extract. The animals were fed a combination of unhealthy foods, the cafeteria diet, which promoted increases in body weight, hepatocyte nucleus area, total hepatocyte area and liver fat accumulation, as well as reduced hepatic glutathione S-transferase concentration, compared to the control group, which received commercial chow. The treatment with ginger improved all these results, highlighting the reduction of 10% of body weight and 66% of the total area of lipid droplets deposited, compared to the group that received the cafeteria diet. Ginger treatments also attenuated lipid peroxidation, with a mean reduction of 41% in malondialdehyde levels and a mean increase of 222% in glutathione S-transferase activity in the liver. The cafeteria diet and ginger extract did not promote significant changes in glycemic and lipid profile, liver weight and liver enzymes compared to the control group. We suggest that ginger can have beneficial effects on health complications associated with unhealthy diet, such as excessive adiposity, oxidative stress and hepatic injury.

Objective: To assess the effects of atorvastatin calcium in the treatment of dexamethasone-induced osteoporosis., Methods: Osteoporosis induction consisted of the administration of an intramuscular dose of 7.5 mg/kg of body weight of dexamethasone, once a week for four weeks, except for the control animals (G1). The animals were divided into the following groups: G1 (control group without osteoporosis), G2 (control group with untreated osteoporosis), G3 (control group with osteoporosis treated with sodium alendronate 0.2 mg/kg) and G4 (group with osteoporosis treated with atorvastatin calcium 1.2 mg/kg). Serum alkaline phosphatase, bone alkaline phosphatase, and biometric and bone histomorphometric assessments were performed after 30 and 60 days of treatment onset., Results: In relation to the biometric and histomorphometric analyses, at 60 days of treatment, G4 presented bone density (Seedor index), bone trabecular density, and cortical thickness of 0.222 ± 0.004 g/cm, 59.167 ± 2.401%, and 387,501 ± 8573 μm, respectively, with a positive and statistically significant difference ( p  < 0.05), in relation to G2. At 30 and 60 days of treatment, G4 presented statistically significant serum levels of alkaline phosphatase alkaline phosphatase ( p  < 0.05) that were higher than all groups (7.451 ± 0.173 μg/L and 7.473 ± 0.529 μg/L, respectively)., Conclusion: Treatment with atorvastatin calcium demonstrated the ability of this drug to increase osteoblastic activity and bone tissue repair activity, acting differently from alendronate sodium, which demonstrated predominantly antirebsorptive activity.

Osteoporosis is a public health concern associated with an increased risk of bone fractures and vascular calcification. Vitamin K presents unique benefits on these issues, although understudied. The two main forms of vitamin K are phylloquinone (vitamin K 1 ) and menaquinone (vitamin K 2 ). In this study, it was especially investigated the action of vitamin K 2 in bones and vessels. Vitamin K 2 has shown to stimulate bone formation by promoting osteoblast differentiation and carboxylation of osteocalcin, and increasing alkaline phosphatase, insulin-like growth factor-1, growth differentiation factor-15, and stanniocalcin 2 levels. Furthermore, vitamin K 2 reduces the pro-apoptotic proteins Fas and Bax in osteoblasts, and decreases osteoclast differentiation by increasing osteoprotegerin and reducing the receptor activator of nuclear factor kappa-B ligand. In blood vessels, vitamin K 2 reduces the formation of hydroxyapatite, through the carboxylation of matrix Gla protein and Gla rich protein, inhibits the apoptosis of vascular smooth muscle cells, by increasing growth arrest-specific gene 6, and reduces the transdifferentiation of vascular smooth muscle cells to osteoblasts. The commonly used dosage of vitamin K 2 in human studies is 45 mg/day and its application can be an interesting strategy in benefitting bone and vascular health, especially to osteoporotic post-menopausal women.

The dichloromethane extract of Plectranthus ornatus Codd., a tradicional medicinal plant, showed antibiotic activity with minimum inhibitory concentration (MIC) values of 0.4 mg.mL-1 and 100 percent of biofilm inhibition against Staphylococcus aureus strains isolated from animals with mastitis infections. Based on these antibacterial activities, in addition to ethnopharmacological reports from healing men and farmers in Brazil, an herbal soap was produced from this active extract and was tested both in vitro and in vivo. In vivo assays conducted on these herbal soaps led to results similar to those previously conducted with the active extract. These results indicated the great potential of this plant for use as an excipient by preparing herbal antibacterial soaps as an alternative veterinary medicine aimed at controlling bovine mastitis infections on small Brazilian farms.

The aim of this study was to investigate the effect of Naringin on pre-neoplastic colorectal lesions induced by chemical carcinogen in rats. Female Wistar rats weighing 130.8±27.1 g received weekly one subcutaneous injection of 1,2-dimethylhydrazine (DMH, 20 mg/kg) for 10 weeks. The animals were divided into 5 groups with 6 animals in each group. Group 1: 0.9% saline; Group 2: DMH+0.9% saline; Group 3: DMH+Naringin (10 mg/kg); Group 4: DMH+Naringin (100 mg/kg); Group 5: DMH+Naringin (200 mg/kg). G2 and G3 showed a significant increase in ACF number, AgNOR/nucleus and mitosis compared to G1. G4 and G5 presented a significant reduction in these parameters compared to G2. The number of cells producing acidic and neutral mucins, red blood cells and the level of antioxidant minerals, such as copper, magnesium, selenium and zinc, were significantly reduced in G2 and G3, but similar in G4 and G5 compared to G1. Naringin, especially at 200 mg/kg, was effective in reducing the number of pre-neoplastic lesions in rats exposed to DMH. Some of these effects may be due to reduction in cellular proliferation and tissue levels of iron together with the recovery of antioxidant mineral levels induced by this flavonoid., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Phenolic compounds are naturally occurring, bioactive substances with marked antioxidant and anti-inflammatory potential. The flavonoid chrysin, found in high levels in honey bee propolis, inhibits the activity of enzymes involved in carcinogenesis. We have investigated the effect of chrysin on pre-neoplastic colorectal lesions (ACF, aberrant crypt foci) in a rat model of chemical carcinogenesis induced by 1,2-dimethylhydrazine (DMH). Female Wistar rats weighing 137.2 ± 24.3 g received weekly one subcutaneous injection of DMH (20 mg/kg) for 10 weeks. The animals were divided into five groups each with seven animals: Group 1, 0.9% saline; Group 2, DMH+0.9% saline; Group 3, DMH+chrysin (10 mg/kg); Group 4, DMH+chrysin (100 mg/kg); Group 5, DMH+chrysin (200 mg/kg). Groups 2 and 3 showed a significant increase in ACF number, nucleolus organizer regions per enterocyte nucleus and nitrite/nitrate serum levels compared with Group 1. Groups 4 and 5 presented a significant reduction in all these parameters compared with Group 2. The levels of antioxidant minerals (copper, magnesium, selenium, zinc) and the number of enteroendocrine and mucin-producing cells were significantly reduced in Groups 2 and 3 but were similar in Groups 4 and 5 compared with Group 1. Chrysin, at 100 mg/kg and 200 mg/kg, was effective in attenuating pathological colorectal remodeling, reducing the number of pre-neoplastic lesions in rats exposed to DMH. Some of these effects might be attributable to the recovery of antioxidant mineral levels, a reduction in systemic nitrosative stress and an inhibition of the cellular proliferation induced by this flavonoid.

The aim of this study was to develop a new approach to testing the impact of nickel antigen on in vitro cell-proliferation assay, to identify adverse reactions to casting alloys among orthodontic patients. Cell-proliferation assay in vitro was used as the basic methodology to assess the influence of such variables as source of nickel antigen, type of serum used to supplement the culture medium, and number of cells in the culture. We selected 35 orthodontic patients who were classified as nickel sensitive and non-nickel sensitive, based on their clinical records. Our results showed that hexahydrated nickel sulfate at 10 microg/mL, 10% of autologous sera, and 2 x 10(5) cells was the best condition for inducing the most marked nickel proliferation response in vitro. This optimized method was able to distinguish nickel-sensitive from non-nickel-sensitive dental patients and also to discriminate those with positive skin tests. Our data suggest that continuous exposure to nickel casting alloys might lead to oral tolerance mechanisms that modulate nickel sensitivity, as evidenced by the lower cell proliferation index in patients undergoing orthodontic treatment over 24 months. Finally, our findings demonstrated a known nickel-induced type 2 immune response and a marked lack of type 1 immunity (interferon gamma) as the hallmarks of nickel-sensitive patients. Further studies are needed to clarify the major cell phenotype associated with this type 2 immune response and the lack of type 1 immunity observed in nickel-sensitive people.