Phytochemical Compounds Involved in the Bone Regeneration Process and Their Innovative Administration: A Systematic Review.

Bone metabolism is a complex process which is influenced by the activity of bone cells (e.g., osteocytes, osteoblasts, osteoclasts); the effect of some specific biomarkers (e.g., parathyroid hormone, vitamin D, alkaline phosphatase, osteocalcin, osteopontin, osteoprotegerin, osterix, RANKL, Runx2); and the characteristic signaling pathways (e.g., RANKL/RANK, Wnt/ß, Notch, BMP, SMAD). Some phytochemical compounds-such as flavonoids, tannins, polyphenols, anthocyanins, terpenoids, polysaccharides, alkaloids and others-presented a beneficial and stimulating effect in the bone regeneration process due to the pro-estrogenic activity, the antioxidant and the anti-inflammatory effect and modulation of bone signaling pathways. Lately, nanomedicine has emerged as an innovative concept for new treatments in bone-related pathologies envisaged through the incorporation of medicinal substances in nanometric systems for oral or local administration, as well as in nanostructured scaffolds with huge potential in bone tissue engineering.

Determination of the Bioactive Compounds from Echinacea purpurea (L.) Moench Leaves Extracts in Correlation with the Antimicrobial Activity and the In Vitro Wound Healing Potential.

This study aimed at the relationship between antioxidant capacity, antimicrobial activity, and in vitro evaluation of the wound healing effect of the extract obtained from Echinaceae purpureae folium (EPF). This study's objective was to assess the bioactive components (total phenol and flavonoid content) and antioxidant activity of EPF extracts using the DPPH test method. The antioxidant capacity and the quantities of the compounds with antioxidant capacity were evaluated by spectrophotometric methods. Antimicrobial activity has been investigated against various pathogenic microorganisms. The minimum inhibitory concentration was determined by the microdilution method. Additionally, our work used a scratch test to examine the in vitro wound healing effects of EPF extract on NHDF cells. Statistical analysis was used to quantify the rate of migration and proliferation of fibroblast cells within the wound. Microscope pictures of fibroblast cells exposed to various EPF extract dosages were processed to estimate the width of the wound, area of the wound, and cell density inside the wound. The study proved that there was a relationship between the antioxidant, antimicrobial, and wound healing ability of EPF extracts.

Formulation and Characterization of Mucoadhesive Polymeric Films Containing Extracts of Taraxaci Folium and Matricariae Flos.

Taraxaci folium and Matricariae flos plant extracts contain a wide range of bioactive compounds with antioxidant and anti-inflammatory effects. The aim of the study was to evaluate the phytochemical and antioxidant profile of the two plant extracts to obtain a mucoadhesive polymeric film with beneficial properties in acute gingivitis. The chemical composition of the two plant extracts was determined by high-performance liquid chromatography coupled with mass spectrometry. To establish a favourable ratio in the combination of the two extracts, the antioxidant capacity was determined by the method of reduction of copper ions Cu2+ from neocuprein and by reduction of the compound 1.1-diphenyl-2-2picril-hydrazyl. Following preliminary analysis, we selected the plant mixture Taraxaci folium/matricariae flos in the ratio of 1:2 (m/m), having an antioxidant capacity of 83.92% ± 0.02 reduction of free nitrogen radical of 1.1-diphenyl-2-2picril-hydrazyl reagent. Subsequently, bioadhesive films of 0.2 mm thickness were obtained using various concentrations of polymer and plant extract. The mucoadhesive films obtained were homogeneous and flexible, with pH ranging from 6.634 to 7.016 and active ingredient release capacity ranging from 85.94-89.52%. Based on in vitro analysis, the film containing 5% polymer and 10% plant extract was selected for in vivo study. The study involved 50 patients undergoing professional oral hygiene followed by a 7-day treatment with the chosen mucoadhesive polymeric film. The study showed that the film used helped accelerate the healing of acute gingivitis after treatment, with anti-inflammatory and protective action.

In Vitro and Human Pilot Studies of Different Topical Formulations Containing Rosa Species for the Treatment of Psoriasis.

The aim of this study was to evaluate the phytochemical profile and antioxidant properties of the extracts from three Rosa species (R. canina, R. damascena, R. cairo), to develop and investigate topical formulations with lyophilized forms of extracts for the treatment of psoriasis. Phytochemical screening and in vitro total antioxidant capacity (DPPH, FRAP, CUPRAC, SOD) of studied samples were examined and compared. Lyophilized extracts of roses were dissolved in Transcutol HP and different formulations of creams were prepared. Franz diffusion method was used to evaluate the drug release and biocompatibility was tested on HaCaT cells. Rosa damascene had the best results regarding all the analyses that were conducted. After the evaluation of topical products, the formulation with Rosa damascena extract in a self-emulsifying drug delivery system was tested on a human clinical study that involved 20 patients. At the end of the clinical study an improvement in the quality of life of the patients was observed and erythema, induration and scaling were reduced. The present study indicates that our examined extracts exhibited great phenolic content, antioxidant capacity and safety profile of topical formulation and therefore can be used as a reliable source of natural antioxidants and may be used as a complementary treatment to improve the quality life of patients with psoriasis or may be tested on another diseases.

Topical Dosage Formulation of Lyophilized Philadelphus coronarius L. Leaf and Flower: Antimicrobial, Antioxidant and Anti-Inflammatory Assessment of the Plant.

Philadelphus coronarius is a versatile plant and its use in folk medicine has a long tradition; however, scientifically, the medical utilization of the herb is a less explored research field. The aim of our study was to identify and determine the quantity of the bioactive compounds of both the leaf and the flower and prepare a lyophilized product of them, from which medical ointments were formulated, since the topical application of P. coronarius has also not been studied. In vitro drug release, texture analysis and biocompatibility experiments were carried out, as well as the investigation of microbiological, antioxidant and anti-inflammatory properties. According to our results the composition and the selected excipients of the ointments have a great impact on the drug release, texture and bioavailability of the preparation. During the microbiological testing, the P. coronarius leaf was effective against Escherichia coli and Staphylococcus aureus, but it did not significantly decrease IL-4 production when it was tested on HaCaT cells. P. coronarius is a promising herb, and its topical application in antimicrobial therapy can be a useful addition to modern medical therapy.

Echinacea purpurea (L.) Moench: Biological and Pharmacological Properties. A Review.

Echinacea purpurea (L.) Moench (EP)is a perennial herbaceous flowering plant, commonly known as purple coneflower and it belongs to the Asteraceae family. The Echinacea genus is originally from North America, in the United States, and its species are widely distributed throughout. There are nine different species of Echinacea, but only three of them are used as medicinal plants with wide therapeutic uses: Echinacea purpurea (L.) Moench, Echinacea pallida (Nutt.) Nutt. and Echinacea angustifolia DC. Several significant groups of bioactive compounds with pharmacological activities have been isolated from Echinacea species. Numerous beneficial effects have been demonstrated about these compounds. The immunomodulatory effect was initially demonstrated, but over time other effects have also been highlighted. The present review gives a comprehensive summary of the chemical constituents, bioactive compounds, biological effects and therapeutical uses of purple coneflower. Research shows that such a well-known and recognized species needs to be further studied to obtain efficient products with a guarantee of the safety.

Formulation of Topical Dosage Forms Containing Synthetic and Natural Anti-Inflammatory Agents for the Treatment of Rheumatoid Arthritis.

Topical anti-inflammatory and analgesic effect for the treatment of rheumatoid arthritis is of major interest because of their fewer side effects compared to oral therapy. The purpose of this study was to prepare different types of topical formulations (ointments and gels) containing synthetic and natural anti-inflammatory agents with different excipients (e.g.,: surfactants, gel-forming) for the treatment of rheumatoid arthritis. The combination of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), diclofenac sodium, a topical analgesic agent methyl salicylate, and a lyophilized extract of Calendula officinalis with antioxidant effect were used in our formulations. The aim was to select the appropriate excipients and dosage form for the formulation in order to enhance the diffusion of active substances and to certify the antioxidant, analgesic, and anti-inflammatory effects of these formulations. To characterize the physicochemical properties of the formulations, rheological studies, and texture profile analysis were carried out. Membrane diffusion and permeability studies were performed with Franz-diffusion method. The therapeutic properties of the formulations have been proven by an antioxidant assay and a randomized prospective study that was carried out on 115 patients with rheumatoid arthritis. The results showed that the treatment with the gel containing diclofenac sodium, methyl salicylate, and lyophilized Calendula officinalis as active ingredients, 2-propenoic acid homopolymer (Synthalen K) as gel-forming excipient, distilled water, triethanolamine, and glycerol had a beneficial analgesic and local anti-inflammatory effect.

Physalis alkekengi L. Extract Reduces the Oxidative Stress, Inflammation and Apoptosis in Endothelial Vascular Cells Exposed to Hyperglycemia.

To find new natural remedies in diabetes, this study investigated the biological activity of two extracts obtained from the fruits (PhyF) and herba (PhyH) of Physalis alkekengi var. franchetii L. on human umbilical vein endothelial cells (HUVECs) exposed to normo- and hyperglycemic conditions. The biological effect was quantified by malondialdehyde, IL-31 and IL-33 levels in correlation with physico-chemical characterization and antioxidant activity. Additionally, from PhyP extract, the caspase-3, IL-6, IL-10, tumor necrosis factor (TNF)-α and nuclear transcription factor NFkB expressions were evaluated. HPLC analysis revealed a significant number of phenolic compounds, especially in PhyF extract, with a good antioxidant activity as highlighted by TEAC, CUPRAC or DPPH methods. On HUVECS cells, the extracts were not toxic even at high concentrations. Particularly PhyF extract, diminished lipid peroxidation and inhibited the IL-31 and IL-33 secretions induced by hyperglycemia. The inhibitory effect on proinflammatory cytokines was noticed after both doses of PhyF extract in parallel with the upregulation of anti-inflammatory cytokine IL-10. Moreover, PhyF, especially in a low dose, reduced caspase-3 active form. These experimental findings suggest that Physalis fruits extract exerted beneficial effects in hyperglycemia by inhibition of oxidative stress, inflammation and apoptosis being a good adjuvant option in diabetes.

A Phytocomplex Consisting of Tropaeolum majus L. and Salvia officinalis L. Extracts Alleviates the Inflammatory Response of Dermal Fibroblasts to Bacterial Lipopolysaccharides.

BACKGROUND: The antimicrobial activity and effects of a phytocomplex consisting of Tropaeolum flos (T) and Salviae folium (S) extracts on the cytokine levels and transcription factors on dermal fibroblast BJ exposed to bacterial lipopolysaccharides were examined. METHODS: In order to select the most optimal combination ratio of the two extracts for using in vitro, the physicochemical characterization of vegetal extract mixtures was performed and the antioxidant and antibacterial activities were evaluated on five different formulations of T : S, namely, 1 : 1, 1 : 2, 2 : 1, 3 : 1, and 1 : 3. The best combination of bioactive compounds with regard to antioxidant and antibacterial activities (T : S 1 : 2) was selected for in vitro evaluation of the anti-inflammatory effect. Human dermal fibroblast BJ cells were treated with two doses of the extract mixture and then exposed to bacterial lipopolysaccharides (LPS). The levels of the cytokines involved in inflammatory response, namely, interleukin- (IL-) 6, tumor necrosis factor- (TNF-) α, IL-31, and IL-33, were quantified by ELISA, and the expression of transcription factors, namely, signal transducer and activator of transcription (STAT) 3, nuclear factor kappa B (NFκB), and phosphorylated NFκB (pNFκB), were evaluated by western blot analysis. RESULTS: The results have shown that the mixture of T : S 1 : 2 exhibited significant antibacterial effects on Staphylococcus aureus ATCC 25923. LPS exposure increased the cytokine levels in BJ cells and enhanced the NFκB expression. The pretreatment of BF cells exposed to LPS with the two doses of the extract mixture markedly inhibited the increase of IL-33 and TNF-α levels and amplified the NFκB expression and its activation, especially with the high dose. The low doses of the extract reduced NFκB expression but increased its activation. CONCLUSIONS: These experimental findings suggest that the mixture of T : S 1 : 2 can exert some protection against bacterial infections and inflammation induced by LPS in BJ cells being a good therapeutic option in related conditions associated with inflammation.

Equisetum arvense L. Extract Induces Antibacterial Activity and Modulates Oxidative Stress, Inflammation, and Apoptosis in Endothelial Vascular Cells Exposed to Hyperosmotic Stress.

BACKGROUND: The antimicrobial activity of the Equisetum arvense L. extract and the mechanisms involved in the in vitro effects on endothelial vascular cells exposed to hyperosmotic stress were evaluated. METHODS: Antimicrobial activity was evaluated by disk diffusion method and minimum inhibitory concentration (MIC) determination, and oxidative stress, inflammation, and apoptosis, in pretreatment with Equisetum arvense L., caffeic acid, and cathechin, were quantified. RESULTS: The results have shown that Equisetum arvense L. exhibited antibacterial effects only on pathogenic gram-positive cocci. The modulatory activity of Equisetum arvense L. on endothelial cells exposed to hypertonic medium was different and depended on the concentration used. Low concentrations of tested compounds exerted antioxidant effect and diminished the activity of caspase-8 and also increased IκB expression while in high doses, Equisetum arvense L. was prooxidant, induced apoptosis, and decreased IL-6 secretion. CONCLUSIONS: These experimental findings suggest that Equisetum arvense L. has antibacterial effects on gram-positive cocci and, administered in low dose, may be a new therapeutic approach for diseases associated with hypertonic conditions or oxidative stress and apoptosis.