Potentilla tormentilla Extract Loaded Gel: Formulation, In Vivo and In Silico Evaluation of Anti-Inflammatory Properties.

The objective of the study was to develop a novel topical gel by mixing Potentilla tormentilla ethanolic extract, thermosensitive poloxamer 407, and carbomer 940 and evaluating its stability and rheological behavior. The irritation potential of the gel was evaluated in accordance with the Organization for Economic Cooperation and Development Guidelines 404. The potential anti-inflammatory effects of the developed gel were evaluated in vivo in rats using the carrageenan-induced paw edema test. Moreover, the in silico binding affinity for chlorogenic and ellagic acid, as dominant components in the extract, against cyclooxygenase (COX) 1 and 2 was also determined. Our findings suggest that the gel containing Potentilla tormentilla extract remained stable throughout the observation period, exhibited pseudoplastic behavior, and caused no irritation in rats, thus being considered safe for topical treatment. Additionally, the developed gel showed the capability to reduce rat paw edema, which highlights significant anti-inflammatory potential. In silico analysis revealed that chlorogenic and ellagic acid exhibited a reduced binding affinity against COX-1 but had a similar inhibitory effect on COX-2 as flurbiprofen, which was confirmed by molecular dynamics results. The study proposes the possible application of Potentilla tormentilla ethanolic extract gel for the alleviation of localized inflammatory diseases; however, future clinical evaluation is required.

Effects of direct pulp capping with recombinant human erythropoietin and/or mineral trioxide aggregate on inflamed rat dental pulp.

OBJECTIVE: This study aimed to evaluate the dental pulp responses to recombinant human erythropoietin (rhEPO) and/or mineral trioxide aggregate (MTA) in pulp capping of inflamed dental pulp in vivo. MATERIALS AND METHODS: In accordance with ARRIVE guidelines, pulp inflammation was induced by exposing the maxillary first molars (n = 64) of Wistar rats (n = 32) to the oral environment for two days. The exposed pulps were randomly assigned four groups based on the pulp capping material: rhEPO, MTA, MTA + rhEPO, or an inert membrane. An additional eight rats formed the healthy control group. After four weeks, the animals were euthanized, and histological, qRT-PCR, and spectrophotometric techniques were employed to analyze the left maxillary segments, right first maxillary molars, and blood samples, respectively. Statistical significance was set at p < 0.05 and < 0.001. RESULTS: Pulp capping with rhEPO, MTA, or MTA + rhEPO resulted in lower inflammation and higher mineralization scores compared to untreated control. MTA + rhEPO group exhibited significantly decreased expression of tumor necrosis factor-alpha, and interleukin 1-beta, while MTA group showed substantially reduced expression of interferon-gamma. Both rhEPO and MTA + rhEPO groups presented elevated dentin matrix protein 1 levels compared to untreated control. Furthermore, pulp capping with rhEPO and/or MTA led to increased transforming growth factor-beta 1 expression and reductions of pro-inflammatory/immunoregulatory cytokine ratios and prooxidative markers. Pulp capping with rhEPO also resulted in increase of systemic antioxidative stress markers. CONCLUSION: Capping with rhEPO or MTA + rhEPO resulted in a favorable effect that was similar or even superior to that of MTA.

Cardiac, biochemical and histopathological analysis reveals impaired heart function in hypertensive rats with apical periodontitis.

AIM: To investigate the association between experimentally induced apical periodontitis (AP) and heart function in hypertensive rats. METHODOLOGY: Forty-eight normotensive Wistar albino and spontaneously hypertensive (SHR) rats were divided into four equal groups: control (C), normotensive with AP (AP), SHR and SHR with AP (SHR + AP). AP was induced on the first right mandibular molars by exposing the pulp chambers to the oral environment for four weeks and confirmed radiographically. Thereafter, the animals were sacrificed by cervical dislocation, whilst hearts were isolated and perfused according to the Langendorff technique gradually increasing coronary perfusion pressures 40-120 cmH2 O. The hemimandibles were analysed radiographically (mm2 and pixels) to verify the presence of AP. Biomarkers of cardiac oxidative stress (OS) were determined in coronary venous effluent and cardiac tissue homogenate. Cardiac tissue was analysed histopathologically for signs of heart damage (oedema, fibrosis and necrosis). All data were analysed by Kruskal-Wallis and one-way anova tests (p < .05). RESULTS: The levels of the maximum left ventricular pressure development rate of the SHR + AP group were significantly increased compared to the AP and C groups, and of the SHR group compared with the C group (p < .05). The levels of the minimum left ventricular pressure development rate of the SHR + AP group were significantly decreased compared to the AP, SHR and C groups, and of the SHR group compared to the C group (p < .05). The radiographic AP area was significantly larger in the SHR + AP group than in the AP group (p < .01). The levels of superoxide anion were significantly higher in the SHR + AP group than in the AP, SHR and C groups (p < .05). The activities of superoxide dismutase in cardiac tissue homogenate were significantly lower in the SHR + AP and AP groups compared with the SHR and C groups (p < .05). CONCLUSIONS: In rats, AP was associated with impaired cardiodynamics, disturbed cardiac OS, antioxidant defence and cardiac pathologic changes in hypertensive conditions. Hypertension was associated with an increase in the AP radiographic area. Further studies should confirm whether root canal treatment can have a cardioprotective effect and reduce cardiac OS in hypertensive conditions.

Psoriasis between Autoimmunity and Oxidative Stress: Changes Induced by Different Therapeutic Approaches.

Psoriasis is defined as chronic, immune-mediated disease. Regardless of the development of new therapeutic approaches, the precise etiology of psoriasis remains unknown and speculative. The aim of this review was to systematize the results of previous research on the role of oxidative stress and aberrant immune response in the pathogenesis of psoriasis, as well as the impact of certain therapeutic modalities on the oxidative status in patients with psoriasis. Complex immune pathways of both the innate and adaptive immune systems appear to be major pathomechanisms in the development of psoriasis. Oxidative stress represents another important contributor to the pathophysiology of disease, and the redox imbalance in psoriasis has been reported in skin cells and, systemically, in plasma and blood cells, and more recently, also in saliva. Current immune model of psoriasis begins with activation of immune system in susceptible person by some environmental factor and loss of immune tolerance to psoriasis autoantigens. Increased production of IL-17 appears to be the most prominent role in psoriasis pathogenesis, while IL-23 is recognized as master regulator in psoriasis having a specific role in cross bridging the production of IL-17 by innate and acquired immunity. Other proinflammatory cytokines, including IFN-γ, TNF-α, IL-1ß, IL-6, IL-22, IL-26, IL-29, or IL-36, have also been reported to play important roles in the development of psoriasis. Oxidative stress can promote inflammation through several signaling pathways. The most noticeable and most powerful antioxidative effects exert various biologics compared to more convenient therapeutic modalities, such as methotrexate or phototherapy. The complex interaction of redox, immune, and inflammatory signaling pathways should be focused on further researches tackling the pathophysiology of psoriasis, while antioxidative supplementation could be the solution in some refractory cases of the disease.