Active Potential of Bacterial Cellulose-Based Wound Dressing: Analysis of Its Potential for Dermal Lesion Treatment.

The use of innate products for the fast and efficient promotion of healing process has been one of the biomedical sector's main bets for lesion treatment modernization process. The aim of this study was to develop and characterize bacterial cellulose-based (BC) wound dressings incorporated with green and red propolis extract (2 to 4%) and the active compounds p-coumaric acid and biochanin A (8 to 16 mg). The characterization of the nine developed samples (one control and eight active wound dressings) evidenced that the mechanics, physics, morphological, and barrier properties depended not only on the type of active principle incorporated onto the cellulosic matrix, but also on its concentration. Of note were the results found for transparency (28.59-110.62T600 mm-1), thickness (0.023-0.046 mm), swelling index (48.93-405.55%), water vapor permeability rate (7.86-38.11 g m2 day-1), elongation (99.13-262.39%), and antioxidant capacity (21.23-86.76 µg mL-1). The wound dressing based on BC and red propolis was the only one that presented antimicrobial activity. The permeation and retention test revealed that the wound dressing containing propolis extract presented the most corneal stratum when compared with viable skin. Overall, the developed wound dressing showed potential to be used for treatment against different types of dermal lesions, according to its determined proprieties.

Biochanin A as a modulator of the inflammatory response: An updated overview and therapeutic potential.

Uncontrolled inflammation and failure to resolve the inflammatory response are crucial factors involved in the progress of inflammatory diseases. Current therapeutic strategies aimed at controlling excessive inflammation are effective in some cases, though they may be accompanied by severe side effects, such as immunosuppression. Phytochemicals as a therapeutic alternative can have a fundamental impact on the different stages of inflammation and its resolution. Biochanin A (BCA) is an isoflavone known for its wide range of pharmacological properties, especially its marked anti-inflammatory effects. Recent studies have provided evidence of BCA's abilities to activate events essential for resolving inflammation. In this review, we summarize the most recent findings from pre-clinical studies of the pharmacological effects of BCA on the complex signaling network associated with the onset and resolution of inflammation and BCA's potential protective functionality in several models of inflammatory diseases, such as arthritis, pulmonary disease, neuroinflammation, and metabolic disease.

Chickpeas from a Chilean Region Affected by a Climate-Related Catastrophe: Effects of Water Stress on Grain Yield and Flavonoid Composition.

The Valparaiso region in Chile was decreed a zone affected by catastrophe in 2019 as a consequence of one of the driest seasons of the last 50 years. In this study, three varieties ('Alfa-INIA', 'California-INIA', and one landrace, 'Local Navidad') of kabuli-type chickpea seeds produced in 2018 (control) and 2019 (climate-related catastrophe, hereafter named water stress) were evaluated for their grain yield. Furthermore, the flavonoid profile of both free and esterified phenolic extracts was determined using liquid chromatography-mass spectrometry, and the concentration of the main flavonoid, biochanin A, was determined using liquid chromatography with diode array detection. The grain yield was decreased by up to 25 times in 2019. The concentration of biochanin A was up to 3.2 times higher in samples from the second season (water stress). This study demonstrates that water stress induces biosynthesis of biochanin A. However, positive changes in the biochanin A concentration are overshadowed by negative changes in the grain yield. Therefore, water stress, which may be worsened by climate change in the upcoming years, may jeopardize both the production of chickpeas and the supply of biochanin A, a bioactive compound that can be used to produce dietary supplements and/or nutraceuticals.

Biochanin A Regulates Key Steps of Inflammation Resolution in a Model of Antigen-Induced Arthritis via GPR30/PKA-Dependent Mechanism.

Biochanin A (BCA) is a natural organic compound of the class of phytochemicals known as flavonoids and isoflavone subclass predominantly found in red clover (Trifolium pratense). It has anti-inflammatory activity and some pro-resolving actions, such as neutrophil apoptosis. However, the effect of BCA in the resolution of inflammation is still poorly understood. In this study, we investigated the effects of BCA on the neutrophilic inflammatory response and its resolution in a model of antigen-induced arthritis. Male wild-type BALB/c mice were treated with BCA at the peak of the inflammatory process (12 h). BCA decreased the accumulation of migrated neutrophils, and this effect was associated with reduction of myeloperoxidase activity, IL-1ß and CXCL1 levels, and the histological score in periarticular tissues. Joint dysfunction, as seen by mechanical hypernociception, was improved by treatment with BCA. The resolution interval (Ri) was also quantified, defining profiles of acute inflammatory parameters that include the amplitude and duration of the inflammatory response monitored by the neutrophil infiltration. BCA treatment shortened Ri from ∼23 h observed in vehicle-treated mice to ∼5.5 h, associated with an increase in apoptotic events and efferocytosis, both key steps for the resolution of inflammation. These effects of BCA were prevented by H89, an inhibitor of protein kinase A (PKA) and G15, a selective G protein-coupled receptor 30 (GPR30) antagonist. In line with the in vivo data, BCA also increased the efferocytic ability of murine bone marrow-derived macrophages. Collectively, these data indicate for the first time that BCA resolves neutrophilic inflammation acting in key steps of the resolution of inflammation, requiring activation of GPR30 and via stimulation of cAMP-dependent signaling.

Biochanin A attenuates zymosan-induced arthritis in mice similarly to 17-ß estradiol: an alternative to hormone replacement therapy?

OBJECTIVE AND DESIGN: Biochanin A (BCA), a phytoestrogen, has various pharmacological properties. This study was conducted to compare BCA's therapeutic property against 17-ß estradiol replacement therapy in zymosan-induced arthritis (ZIA) in mice. Additionally, we further investigated in vitro the anti-inflammatory action on neutrophils. TREATMENT: Ovariectomized (OVX) and non-OVX mice were pretreated with BCA (1, 3 and 9 mg/kg) or estrogen (50 µg/kg) for 14 days prior to ZIA. Neutrophils were pretreated with BCA (1, 10 and 100 µM) for 1 h prior to phorbol 12-myristate 13-acetate. METHODS: Anti-inflammatory effects of BCA were evaluated by cellular infiltrate, paw edema and cytokine measurement. In vitro, apoptosis was assessed by morphology and flow cytometry. Neutrophil extracellular traps (NET) were determined by fluorescent microscopy and DNA release. Statistical differences were determined by one- or two-way ANOVA. RESULTS: BCA inhibited neutrophil accumulation, paw edema and proinflammatory cytokine (TNF-α and IFN-γ) and increased anti-inflammatory cytokines (IL-4 and IL-10) in OVX and non-OVX mice, similar to 17-ß estradiol replacement therapy. In vitro, BCA increased apoptosis and consequently reduced NETs. CONCLUSION: BCA has a notable anti-inflammatory effect, similar to 17-ß estradiol, and is especially effective for treatment of ZIA. These results suggest that BCA may be promising for the treatment of postmenopausal arthritis.

Biochanin A attenuates myocardial ischemia/reperfusion injury through the TLR4/NF-κB/NLRP3 signaling pathway

Abstract Purpose: Myocardial ischemia/reperfusion (Ml/R) injury is a leading cause of damage in cardiac tissues, with high rates of mortality and disability. Biochanin A (BCA) is a main constituent of Trifolium pratense L. This study was intended to explore the effect of BCA on Ml/R injury and explore the potential mechanism. Methods: In vivo MI/R injury was established by transient coronary ligation in Sprague-Dawley rats. Triphenyltetrazolium chloride staining (TTC) was used to measure myocardial infarct size. ELISA assay was employed to evaluate the levels of myocardial enzyme and inflammatory cytokines. Western blot assay was conducted to detect related protein levels in myocardial tissues. Results: BCA significantly ameliorated myocardial infarction area, reduced the release of myocardial enzyme levels including aspartate transaminase (AST), creatine kinase (CK-MB) and lactic dehydrogenase (LDH). It also decreased the production of inflammatory cytokines (IL-1β, IL-18, IL-6 and TNF-α) in serum of Ml/R rats. Further mechanism studies demonstrated that BCA inhibited inflammatory reaction through blocking TLR4/NF-kB/NLRP3 signaling pathway. Conclusion: The present study is the first evidence demonstrating that BCA attenuated Ml/R injury through suppressing TLR4/NF-kB/NLRP3 signaling pathway-mediated anti-inflammation pathway.

Biochanin A attenuates myocardial ischemia/reperfusion injury through the TLR4/NF-B/NLRP3 signaling pathway

Purpose: Myocardial ischemia/reperfusion (Ml/R) injury is a leading cause of damage in cardiac tissues, with high rates of mortality and disability. Biochanin A (BCA) is a main constituent of Trifolium pratense L. This study was intended to explore the effect of BCA on Ml/R injury and explore the potential mechanism. Methods: In vivo MI/R injury was established by transient coronary ligation in Sprague-Dawley rats. Triphenyltetrazolium chloride staining (TTC) was used to measure myocardial infarct size. ELISA assay was employed to evaluate the levels of myocardial enzyme and inflammatory cytokines. Western blot assay was conducted to detect related protein levels in myocardial tissues. Results: BCA significantly ameliorated myocardial infarction area, reduced the release of myocardial enzyme levels including aspartate transaminase (AST), creatine kinase (CK-MB) and lactic dehydrogenase (LDH). It also decreased the production of inflammatory cytokines (IL-1, IL-18, IL-6 and TNF-) in serum of Ml/R rats. Further mechanism studies demonstrated that BCA inhibited inflammatory reaction through blocking TLR4/NF-kB/NLRP3 signaling pathway. Conclusion: The present study is the first evidence demonstrating that BCA attenuated Ml/R injury through suppressing TLR4/NF-kB/NLRP3 signaling pathway-mediated anti-inflammation pathway.(AU)

Peptides and isoflavones in gastrointestinal digests contribute to the anti-inflammatory potential of cooked or germinated desi and kabuli chickpea (Cicer arietinum L.).

It is largely unknown how processing affects bioactive potential of chickpea proteins to prevent bowel inflammatory diseases. The aim was to investigate the anti-inflammatory activity of protein concentrates from germinated and cooked chickpeas (GC and CC, respectively) and its relationship with protein and isoflavone composition before and after in vitro gastrointestinal digestion and absorption. Anti-inflammatory activity of GC digests was almost 2-fold higher than CC digests (p < 0.05), which was associated to greater content of peptides, formononetin and biochanin A (p < 0.05). Anti-inflammatory activity of phenolic fraction in digests was 7-fold higher than the protein fraction (p < 0.05). The most active peptide fraction from GC digest (IC50 = 93 µg/mL) contained a total of 24 peptides derived from legumin and vicilin. In conclusion, this study stands out the potential of germinated chickpea proteins concentrates to exert anti-inflammatory effects in the lower gut which may contribute to the prevention of bowel inflammatory diseases.

Hydroxypropyl-ß-cyclodextrin-containing hydrogel enhances skin formononetin permeation/retention.

OBJECTIVES: This study was aimed to investigate the in vitro permeation potential of hydrogel formulations containing the isoflavones formononetin and biochanin A and cyclodextrins in different combinations. METHODS: The permeation assay was performed using porcine skin discs on Franz diffusion cells model. The isoflavone contents of the formulations were quantified in the different layers of the skin using a validated HPLC-PDA method. KEY FINDINGS: The isoflavones individually incorporated into the formulations showed high permeation potential, especially formononetin, after the incorporation of hydroxypropyl-ß-cyclodextrin that enhanced its permeation in the epidermis and dermis. Biochanin A showed 2.7 times of permeation capacity in the epidermis and dermis mainly after incorporation of cyclodextrins in the formulations. Formononetin showed reduction in its permeation when incorporated in the formulations together to biochanin A, showing the absence of synergism. CONCLUSIONS: Our results indicated a noticeable skin permeation promoting effect of HPßCD in formononetin formulation. Furthermore, formononetin and biochanin A can permeate the skin being mostly retained in the epidermis and dermis, revealing its potential use in cosmetic preparations intended to prevent skin aging.

Antioxidant Effects of Biochanin A in Streptozotocin Induced Diabetic Rats

ABSTRACT Bioflavonoid-containing diets have been reported to be beneficial in diabetes. In the current study, the effect of Biochanin A (BCA) on blood glucose, antioxidant enzyme activities and oxidative stress markers in diabetic rats were investigated. 30 male Wistar rats were divided into five groups. Two of them were selected as control; group1: control (receiving 0.5%DMSO), and group2: Control+BCA (receiving 10 mg/kg.bw BCA). Diabetes was induced in other rats with injection of (55 mg/kg.bw) streptozotocin; group3: diabetic control (receiving 0.5%DMSO), groups 4 and 5 were treated with 10 and 15 mg/kg.bw BCA respectively. After 6 weeks the following results were obtained. Fasting blood glucose (FBG), Triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C) and malondialdehyde (MDA) levels significantly increased and body weight, high density lipoprotein cholesterol (HDL-C), superoxide dismutase (SOD) and catalase (CAT) activity and total antioxidant status (TAS) significantly decreased in diabetic rats as compared to control rats. Oral administration of BCA in 10 and 15 mg/kg.bw, FBG, TG, TC, LDL-C, VLDL-C were decreased significantly in all treated rats. MDA was decreased in all treated rats but it was significant just in 15 mg/kg.bw BCA. HDL, CAT, SOD, and TAS were significantly increased in treated group with 15 mg/kg.bw. The obtained results indicated hypoglycemic and hypolipidemic effect of BCA. Also BCA reduced oxidative stress in diabetic rats.

Efeito regulatório de flavonóides e de carmim nos níveis de lipídeos em ratos Wistar / Regulatory effect of flavonoids and carmim colorant dye on the lipid levels in Wistar rats

Estudou-se a ação de biochanina A isolada e em associação com os corantes naturais antocianina e carmin sobre o metabolismo lipídico de ratos. Foram dosados colesterol, colesterol-HDL e triacilgliceróis após administração de duas doses dos compostos isoladamente e em misturas, sendo a primeira imediatamente após a administração do triton e a segunda 20 horas depois. O sangue foi analisado 43 horas após a administração do triton. Os resultados mostraram que a associação biochanina A + antocianina e biochanina A + carmin apresentaram os melhores resultados para colesterol total e triacilglicerol.(AU)

The effects of biochanin A, isolated or in association with the natural dyes anthocyanin and carmin, on the metabolism of lipids in rats were investigated. The compounds, dissolved in propylene glycol, were given intraperitoneally using two doses of 5mg/kg of body weigth. The first dose of these substances was given after using triton to induce high levels of blood lipids, and the second dose was given 20 hours later. Cholesterol, cholesterol-HDL, and triacylglyceriols were measured in the blood 43 hours after inoculation. Results showed that the association biochanin A + anthocyanin, and biochanin A + carmin resulted in the largest reduction of blood cholesterol and triacylglycerols.(AU)