Propolis as a Potential Therapeutic Agent to Counteract Age-Related Changes in Cartilage: An In Vivo Study.

Aging is intricately linked to chronic low-grade systemic inflammation, which plays a significant role in various age-related conditions, including osteoarthritis (OA). The aging process significantly influences the development of OA due to alterations in cartilage composition, reduced proteoglycan content, dysregulation of growth factor signaling, and heightened oxidative stress. Propolis, a natural product renowned for its potent antioxidant and anti-inflammatory properties, has the potential to mitigate age-induced changes in cartilage. The primary objective of this study was to rigorously assess the impact of in vivo propolis treatment on the histopathological characteristics of knee articular cartilage in senescent rats. This study involved a cohort of twenty male Sprague-Dawley rats, randomly allocated into four distinct groups for comparative analysis: YR (control group consisting of young rats), SR (senescent rats), SR-EEP (senescent rats treated with an ethanolic extract of propolis, EEP), and SR-V (senescent rats administered with a control vehicle). This study employed comprehensive histological and stereological analyses of knee articular cartilage. Propolis treatment exhibited a significant capacity to alleviate the severity of osteoarthritis, enhance the structural integrity of cartilage, and augment chondrocyte density. These promising findings underscore the potential of propolis as a compelling therapeutic agent to counteract age-related alterations in cartilage and, importantly, to potentially forestall the onset of osteoarthritis.

Ethnobotany, Phytochemistry, Biological Activities, and Health-Promoting Effects of the Genus Bulbophyllum.

The genus Bulbophyllum is of scientific interest due to the phytochemical components and diverse biological activities found across species of the genus. Most Bulbophyllum species are epiphytic and located in habitats that range from subtropical dry forests to wet montane cloud forests. In many cultures, the genus Bulbophyllum has a religious, protective, ornamenting, cosmetic, and medicinal role. Detailed investigations into the molecular pharmacological mechanisms and numerous biological effects of Bulbophyllum spp. remain ambiguous. The review focuses on an in-depth discussion of studies containing data on phytochemistry and preclinical pharmacology. Thus, the purpose of this review was to summarize the therapeutic potential of Bulbophyllum spp. biocompounds. Data were collected from several scientific databases such as PubMed and ScienceDirect, other professional websites, and traditional medicine books to obtain the necessary information. Evidence from pharmacological studies has shown that various phytoconstituents in some Bulbophyllum species have different biological health-promoting activities such as antimicrobial, antifungal, antioxidant, anti-inflammatory, anticancer, and neuroprotective. No toxicological effects have been reported to date. Future clinical trials are needed for the clinical confirmation of biological activities proven in preclinical studies. Although orchid species are cultivated for ornamental purposes and have a wide traditional use, the novelty of this review is a summary of biological actions from preclinical studies, thus supporting ethnopharmacological data.

Cyperus spp.: A Review on Phytochemical Composition, Biological Activity, and Health-Promoting Effects.

Cyperaceae are a plant family of grass-like monocots, comprising 5600 species with a cosmopolitan distribution in temperate and tropical regions. Phytochemically, Cyperus is one of the most promising health supplementing genera of the Cyperaceae family, housing ≈950 species, with Cyperus rotundus L. being the most reported species in pharmacological studies. The traditional uses of Cyperus spp. have been reported against various diseases, viz., gastrointestinal and respiratory affections, blood disorders, menstrual irregularities, and inflammatory diseases. Cyperus spp. are known to contain a plethora of bioactive compounds such as α-cyperone, α-corymbolol, α-pinene, caryophyllene oxide, cyperotundone, germacrene D, mustakone, and zierone, which impart pharmacological properties to its extract. Therefore, Cyperus sp. extracts were preclinically studied and reported to possess antioxidant, anti-inflammatory, antimicrobial, anticancer, neuroprotective, antidepressive, antiarthritic, antiobesity, vasodilator, spasmolytic, bronchodilator, and estrogenic biofunctionalities. Nonetheless, conclusive evidence is still sparse regarding its clinical applications on human diseases. Further studies focused on toxicity data and risk assessment are needed to elucidate its safe and effective application. Moreover, detailed structure-activity studies also need time to explore the candidature of Cyperus-derived phytochemicals as upcoming drugs in pharmaceuticals.

The Therapeutic Potential of Wogonin Observed in Preclinical Studies.

Wogonin is a flavonoid found in different plants such as roots of Scutellaria baicalensis Georgi distributed mainly in Asia and Europe. Dried root extracts of S. baicalensis with high content of wogonin, popularly known as "Huang-Qin" or Chinese or baical skullcap, have been used for long time in traditional Chinese medicine. Several health benefits are attributed to wogonin and derivatives showing anti-inflammatory, antiviral, anticancer, and antioxidant effects and more recently antineurodegenerative properties. Preclinical pharmacological activities of wogonin against diverse types of cancer such as breast, colorectal, and human gastric cancer will be presented in this review. In addition, studies on oxidative stress and bioavailability of wogonin will be discussed together with antineurodegenerative potential with special focus on Alzheimer's disease. Outcomes extracted from the last preclinical studies related to therapeutic applications of wogonin will be commented and updated in this review. The scientific evidence collected in this review aims to encourage transfer of the preclinical evidence of wogonin to new clinical studies.

Ethnopharmacology, Phytochemistry and Biological Activities of Native Chilean Plants.

The native flora of Chile has unique characteristics due to the geographical situation of the country, with the vast desert in the North, Patagonia in the South, the Andean Mountains on the east and the Pacific Ocean on the west. This exclusivity is reflected in high concentrations of phytochemicals in the fruits and leaves of its native plants. Some examples are Aristotelia chilensis (Molina), Stuntz (maqui), Berberis microphylla G. Forst. (calafate), Peumus boldus Molina (boldo), Ribes magellanicum Poir. (Magellan currant), Ugni molinae Turcz. (murtilla), Rubus geoides Sm. (miñe miñe), Drimys winteri J.R.Forst. & G.Forst. (canelo), Luma apiculata (DC.) Burret (arrayán) distributed throughout the entire Chilean territory. Some of these Chilean plants have been used for centuries in the country's traditional medicine. The most recent studies of phytochemical characterization of parts of Chilean plants show a wide spectrum of antioxidant compounds, phenolic components, terpenoids and alkaloids, which have shown biological activity in both in vitro and in vivo studies. This manuscript covers the entire Chilean territory characterizing the phytochemical profile and reporting some of its biological properties, focusing mainly on antioxidant, anti-inflammatory, antimicrobial, chemopreventive and cytotoxic activity, and potential against diabetes, metabolic syndrome and gastrointestinal disorders.

Protective effect of Pinot noir pomace extract against the cytotoxicity induced by polycyclic aromatic hydrocarbons on endothelial cells.

Polycyclic Aromatic Hydrocarbons (PAHs) are pollutants found in the air generated mainly by the combustion of coal or biomass burning. Exposure to Polycyclic Aromatic Hydrocarbons is positively correlated with cardiovascular diseases. Phenolic compounds are widely found in the plant kingdom, and their availability from agri-food processing waste has led to an increased interest in their recovery. The production of large amounts of organic waste created by the wine industry has emphasized the valuation of these wastes to generate high-added-value by-products. The objective of this work was to investigate the protective effect of Pinot noir pomace extract on human endothelial cells against PAHs found in the polluted air of Temuco, Chile. The pomace extract was characterized by spectrophotometric analysis and high-performance liquid chromatography (HPLC). Results revealed the presence of 5 glycosylated anthocyanins and 9 low molecular weight polyphenols. Molecular docking indicated that cyanidin-3-glucoside (-9.2 kcal/mol) and quercetin (-9.6 kcal/mol) had the highest affinities for the Nrf2 binding site in the Keap1 protein, suggesting a possible competition with this transcription factor. Endothelial cells from the human umbilical vein were exposed to increasing concentrations of Phenanthrene, Fluoranthene, and Pyrene diluted in DMSO in a ratio of 3:1:1 (10 µM-200 µM). Viability through the MTS assay showed that 150 µM of PAHs was sufficient to reduce viability by 75% (p ˂ 0.0001). When the cells were pre-treated with 400 µg/ml of the extract, 150 µM of PAHs did not exert cell death (80% viability). Our preliminary results show that polyphenolic components found in Pinot noir pomace might have a beneficial effect as a protective agent.

Evaluation of Alternative Methods to Assess the Biological Properties of Propolis on Metabolic Activity and Biofilm Formation in Streptococcus mutans.

Several biological activities have been reported for the Chilean propolis, among their antimicrobial and antibiofilm properties, due to its high polyphenol content. In this study, we evaluate alternative methods to assess the effect of Chilean propolis on biofilm formation and metabolic activity of Streptococcus mutans (S. mutans), a major cariogenic agent in oral cavity. Biofilm formation was studied by using crystal violet and by confocal microscopy. The metabolic activity of biofilm was evaluated by MTT and by flow cytometry analysis. The results show that propolis reduces biofilm formation and biofilm metabolic activity in S. mutans. When the variability of the methods to measure biofilm formation was compared, the coefficient of variation (CV) fluctuated between 12.8 and 23.1% when using crystal violet methodology. On the other hand, the CV ranged between 2.2 and 3.3% with confocal microscopy analysis. The CV for biofilm's metabolic activity measured by MTT methodology ranged between 5.0 and 11.6%, in comparison with 1.9 to 3.2% when flow cytometry analysis was used. Besides, it is possible to conclude that the methods based on colored compounds presented lower precision to study the effect of propolis on biofilm properties. Therefore, we recommend the use of flow cytometry and confocal microscopy in S. mutans biofilm analysis.

ERK1/2 and HIF1α Are Involved in Antiangiogenic Effect of Polyphenols-Enriched Fraction from Chilean Propolis.

Propolis has been shown to modulate the angiogenesis in both in vitro and in vivo models. Thus, we aimed to evaluate the antiangiogenic properties of an ethanolic extract of Chilean propolis (EEP) and Pinocembrin (Pn). Migration, formation of capillary-like structures of endothelial cells, and sprouting from rat aortic rings were used to assess the antiangiogenic properties of EEP or Pn. In addition, microRNAs and VEGFA mRNA expression were studied by qPCR. ERK1/2 phosphorylation and HIF1α stabilization were assessed by western blot. EEP or Pn attenuated the migration, the capillary-like tube formation, and the sprouting in the in vitro assays. In addition, the activation of HIF1α and ERK1/2 and the VEGFA mRNA expression was significantly inhibited in a dose-dependent manner. In summary, these results suggest that HIF1α and ERK1/2 phosphorylation could be involved in the antiangiogenic effect of Chilean propolis, but more studies are needed to corroborate these findings.

Medicinal value of the Berberis genus as hypoglycemic agent / Valor medicinal del género Berberis como agente hipoglicemiante

Type 2 diabetes mellitus (T2DM) is a common chronic disease whose prevalence is currently increasing worldwide. Nowadays, the main antidiabetic agent used is metformin. However, between 10 and 30 percent of patients undergoing metformin therapy have nonspecific gastric alterations as an undesired secondary effect. Therefore, the search for new therapeutic alternatives is especially useful, where plant- derived products emerge as an excellent phytochemical resource. The objective of this review is to present and discuss the state of the art of current research conducted on the Berberis gender with hypoglycemic activity, which is normally used in alternative medicine therapy for the treatment of T2DM, and its possible mechanisms of action described in literature.

La diabetes mellitus tipo 2 (DM2) es una enfermedad crónica común, cuya prevalencia está actualmente aumentando en todo el mundo. Al presente, el principal fármaco antidiabético utilizado es la metformina. Sin embargo, entre un 10 y 30 por ciento de los pacientes tratados presentan como efecto no deseado de alteraciones gástricas inespecíficas. Por lo tanto, la búsqueda de nuevas alternativas terapéuticas es de gran utilidad, en donde los productos derivados de plantas emergen como un excelente recurso fitoquímico. El objetivo de esta revisión es presentar y discutir sobre el estado del arte de investigaciones realizadas en las especies del género Berberis con actividad hipoglicemiante, las cuales son normalmente utilizadas en medicina alternativa como terapia para el tratamiento de DM, y sus posibles mecanismos de acción descritos en la literatura.

Chemical and botanical characterization of Chilean propolis and biological activity on cariogenic bacteria Streptococcus mutans and Streptococcus sobrinus.

Propolis is a non-toxic natural substance with multiple pharmacological properties including anti-cancer, antioxidant, fungicidal, antibacterial, antiviral, and anti-inflammatory among others. The aim of this study was to determine the chemical and botanical characterization of Chilean propolis samples and to evaluate their biological activity against the cariogenic bacteria Streptococcus mutans and Streptococcus sobrinus. Twenty propolis samples were obtained from beekeeping producers from the central and southern regions of Chile. The botanical profile was determined by palynological analysis. Total phenolic contents were determined using colorimetric assays. Reverse phase HPLC and HPLC-MS were used to determine the chemical composition. The minimum inhibitory concentration (MIC) was determined on S. mutans and S. sobrinus. All propolis samples were dominated by structures from native plant species. The characterization by HPLC/MS, evidenced the presence of quercetin, myricetin, kaempferol, rutine, pinocembrin, coumaric acid, caffeic acid and caffeic acid phenethyl ester, that have already been described in these propolis with conventional HPLC. Although all propolis samples inhibited the mutans streptococci growth, it was observed a wide spectrum of action (MIC 0.90 to 8.22 µg mL(-1)). Given that results it becomes increasingly evident the need of standardization procedures, where we combine both the determination of botanical and the chemical characterization of the extracts. Research conducted to date, describes a promising effectiveness of propolis in the prevention of caries and other diseases of the oral cavity, making it necessary to develop studies to identify and understand the therapeutic targets or mechanisms of molecular action of the various compounds present on them.

Chemical and botanical characterization of Chilean propolis and biological activity on cariogenic bacteria Streptococcus mutans and Streptococcus sobrinus

Propolis is a non-toxic natural substance with multiple pharmacological properties including anticancer, antioxidant, fungicidal, antibacterial, antiviral, and anti-inflammatory among others. The aim of this study was to determine the chemical and botanical characterization of Chilean propolis samples and to evaluate their biological activity against the cariogenic bacteria Streptococcus mutans and Streptococcus sobrinus. Twenty propolis samples were obtained from beekeeping producers from the central and southern regions of Chile. The botanical profile was determined by palynological analysis. Total phenolic contents were determined using colorimetric assays. Reverse phase HPLC and HPLC-MS were used to determine the chemical composition. The minimum inhibitory concentration (MIC) was determined on S. mutans and S. sobrinus. All propolis samples were dominated by structures from native plant species. The characterization by HPLC/MS, evidenced the presence of quercetin, myricetin, kaempferol, rutine, pinocembrin, coumaric acid, caffeic acid and caffeic acid phenethyl ester, that have already been described in these propolis with conventional HPLC. Although all propolis samples inhibited the mutans streptococci growth, it was observed a wide spectrum of action (MIC 0.90 to 8.22 µgmL-1). Given that results it becomes increasingly evident the need of standardization procedures, where we combine both the determination of botanical and the chemical characterization of the extracts. Research conducted to date, describes a promising effectiveness of propolis in the prevention of caries and other diseases of the oral cavity, making it necessary to develop studies to identify and understand the therapeutic targets or mechanisms of molecular action of the various compounds present on them.

Análisis morfométrico del número de odontoblastos en recubrimientos directos con hidróxido de calcio y propóleos en canes / Morphometric analysis of odontoblasts number in direct capping with calcium hydroxide and propolis in dogs

El propóleos se ha utilizado en medicina desde épocas antiguas, una de sus indicaciones en medicina oral y odontológica es como material de recubrimiento directo. Así, el objetivo de este estudio fue cuantificar la neoformación odontoblástica en piezas dentarias de canes en recubrimientos directos. Se realizaron perforaciones en un total de 12 piezas dentarias, la mitad de las cuales fueron recubiertas con propóleos y la otra mitad con hidróxido de calcio. En todos los casos se obturaron las piezas dentarias con cemento de vidrio-ionómero. Al cabo de dos semanas, se realizaron las extracciones de las piezas dentarias, fijándolas en formalina tamponada; se efectuaron cortes histológicos de las piezas, los cuales se tiñeron con hematoxilina-eosina, con el fin de poder realizar la cuantificación de los núcleos odontoblásticos presentes tanto en las zonas alejadas de la perforación, como en las zonas cercanas a las lesiones. Se observó una similar actividad odontoblástica en las zonas cercanas a las lesiones al utilizar cualquiera de los dos materiales (p=0,9325), diferenciándose solamente en la disposición de las células neoformadas, que en el caso de utilizar propóleos fueron en empalizada, semejante a las zonas sanas, en cambio, al utilizar hidróxido de calcio no se observó dicho ordenamiento.

Since ancient times, propolis has been used in medicine, while in oral medicine and dentistry it has been indicated as a direct capping material.The aim of this study was to quantify the odontoblast activity in drilling holes on dog's teeth (canine and incisor) during direct capping.Perforations were carried out in a total sample of 12 dental pieces. In half of the sample teeth were capped with propolis, and in the other half with calcium hydroxide. In all cases teeth were obturated with glass ionomer cement. Extraction of the teeth was realized after two weeks, and teeth were fixed in buffered formalin. Histological cuts of the pieces were made and stained with hematoxylin-eosin in order to carry out quantification of nuclei presence in healthy areas (away from the perforation, as well as in areas adjacent to injuries. Results showed similar odontoblast activity while using either of the materials, (p=0.9325), only differing in the arrangement of newly formed cells which in the cases where propolis was used, were palisading, similar to healthy areas. On the other hand, the same order was not observed when calcium hydroxide was used.