Baccharis dracunculifolia DC Consumption Improves Nociceptive and Depressive-like Behavior in Rats with Experimental Osteoarthritis.

Osteoarthritis (OA) persistently activates nociceptors, leading to chronic pain, which is often accompanied by the comorbid development of emotional impairments (anxiety and depression), an effect associated with microgliosis. Baccharis dracunculifolia DC (Asteraceae), a Brazilian edible plant, is an important source of active compounds with anti-inflammatory abilities. Thus, we evaluated its ability to reverse OA-induced nociceptive and emotional-like impairments in osteoarthritic ovariectomized female rats using the kaolin/carrageenan (K/C) model. Four weeks after OA induction, mechanical hyperalgesia was confirmed, and the treatment started. Control animals (SHAMs) were treated with phosphate-buffered saline (PBS), while arthritic animals (ARTHs) either received PBS or B. dracunculifolia 50 mg/kg (Bd50) and 100 mg/kg (Bd100), via gavage, daily for five weeks. At the end of the treatment, anxiety-like behavior was assessed using the Open Field Test (OFT), anhedonia was assessed using the Sucrose Preference Test (SPT), and learned helplessness was assessed using the Forced Swimming Test (FST). After occision, microglia were stained with IBA-1 and quantified in brain sections of target areas (prefrontal cortex, amygdala, and periaqueductal grey matter). Treatment with B. dracunculifolia extract reversed OA-induced mechanical hyperalgesia and partly improved depressive-like behavior in OA animals' concomitant to a decrease in the number of M1 microglia. Our findings suggest that B. dracunculifolia extracts can potentially be used in the food industry and for the development of nutraceuticals and functional foods.

Baccharin and p-coumaric acid from green propolis mitigate inflammation by modulating the production of cytokines and eicosanoids.

ETHNOPHARMACOLOGICAL RELEVANCE: Green propolis is produced by Apis mellifera honeybees using Baccharis dracunculifolia D.C. (Asteraceae) as substrate. This Southern Brazilian native plant and green propolis have been used in traditional medicine to treat gastric diseases, inflammation and liver disorders. AIM OF THE STUDY: Investigate the effects of baccharin (Bac) or p-coumaric acid (pCA) isolated from B. dracunculifolia D.C. (Asteraceae) over the inflammation induced by lipopolysaccharide (LPS) in vivo. MATERIALS AND METHODS: Inflammation was induced by LPS injection into air-pouches in mice, which were subsequently treated with Bac or pCA. Lavage fluid was collected from air pouches for the quantification of cellular influx via microscopy, and quantification of inflammatory mediators via colorimetric methods, ELISA and liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: LPS-induced inflammation increased cellular influx and increased the levels of parameters related to vascular permeability and edema formation, such as nitric oxide (NO) and protein extravasation. Moreover, LPS increased the levels of cytokines and eicosanoids in the air-pouches. Importantly, both Bac and pCA suppressed the infiltration of neutrophils, production of NO and protein extravasation. Notably, the compounds promote differential regulation of cytokine and eicosanoid production. CONCLUSIONS: Our results suggest that Bac from green propolis directly affects inflammation by inhibiting the production of cytokines and eicosanoids, while pCA may exert direct, but also indirect effects on inflammation by stimulating the production of regulatory effectors such as interkeukin-10 in vivo.

Artepillin C: A comprehensive review of its chemistry, bioavailability, and pharmacological properties.

Artepillin C (ARC), a prenylated derivative of p-coumaric acid, is one of the major phenolic compounds found in Brazilian green propolis (BGP) and its botanical source Baccharis dracunculifolia. Numerous studies on ARC show that its beneficial health effects correlate with the health effects of both BGP and B. dracunculifolia. Its wide range of pharmacological benefits include antioxidant, antimicrobial, anti-inflammatory, anti-diabetic, neuroprotective, gastroprotective, immunomodulatory, and anti-cancer effects. Most studies have focused on anti-oxidation, inflammation, diabetic, and cancers using both in vitro and in vivo approaches. Mechanisms underlying anti-cancer properties of ARC are apoptosis induction, cell cycle arrest, and the inhibition of p21-activated kinase 1 (PAK1), a protein characterized in many human diseases/disorders including COVID-19 infection. Therefore, further pre-clinical and clinical studies with ARC are necessary to explore its potential as intervention for a wide variety of diseases including the recent pandemic coronaviral infection. This review summarizes the comprehensive data on the pharmacological effects of ARC and could be a guideline for its future study and therapeutic usage.

Baccharis dracunculifolia (Asteraceae) essential oil displays anti-inflammatory activity in models of skin inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Baccharis dracunculifolia (Asteraceae) is a commonly used plant in traditional medicine known as "alecrim-do-campo". Popularly it has been used as an immunostimulant, antibiotic, anti-inflammatory among other applications. So far, only a few studies have investigated the B. dracunculifolia anti-inflammatory effect and none has investigated the effectiveness of essential oil on skin diseases. AIM OF THE STUDY: The study aimed at evaluating the topical anti-inflammatory activity of B. dracunculifolia essential oil (BdEO) in mice models of acute and chronic skin inflammation. MATERIALS AND METHODS: BdEO was obtained from leaves and it was analyzed with Gas Chromatograph. Topical anti-inflammatory activity of BdEO (0.1, 0.3 and 1.0 mg/ear) was evaluated in Arachidonic Acid or TPA-induced acute and chronic skin inflammation in mice. Parameters such edema, cell migration and keratinocytes proliferation were evaluated. In addition, safety and a possible mechanism of action for BdEO essential oil were also investigated. RESULTS: Our results indicate that mainly terpenoids compounds compose BdEO. In addition, topical treatment with BdEO inhibited inflammatory parameters in both acute and chronic models of skin inflammation. This protective effect was associated with reduced edema formation, smaller cellular influx into the inflamed tissue and reduction of keratinocytes hyperproliferation. Although BdEO appears to exert its anti-inflammatory effect through a corticosteroid pathway, no local or systemic side effects were observed. CONCLUSION: Taken together, the present results showed that the essential oil obtained by hydrodistillation from B. dracunculifolia leaf samples exhibit remarkable topical anti-inflammatory properties. Therefore, our study demonstrated evidence for BdEO topical anti-inflammatory efficacy and safety, suggesting that it could be considered for developing of a new phytotherapeutic formulation as treatment for skin diseases.

Efficacy of Baccharis dracunculifolia in the treatment of diversion colitis in rats / Eficácia da Baccharis dracunculifolia no tratamento da colite de desuso em ratos

Abstract Rationale: Disuse colitis is frequent in our country and the most effective treatment is high cost and there is a need for effective and low cost therapy. Objective: To evaluate the efficacy of Baccharis dracunculifolia (field rosemary) in the treatment of exclusion colitis in rats. Method: Eighteen Wistar rats were anesthetized and submitted to colostomy; they were then distributed into two groups: Control Group, receiving intrarectal saline infusion (n = 8) and Group BD receiving intrarectal infusion ofBaccharis dracunculifolia extract (n = 10); after 21 days of treatment they were euthanized, the intestinal segment excluded from intestinal transit was resected and submitted to histopathological study, classifying the degree of inflammation and degree of vascular congestion from 0 to 3. Results: Mean inflammation was 2.7 in Control Group versus 2.1 in BD Group (p = 0.049), while mean vascular congestion was 2.3 and 2, respectively, in Control and BD groups (p = 0.1642). Conclusion: Intra-rectal infusion ofBaccharis dracunculifolia extract significantly minimized the inflammatory process in the exclusion colitis of rats submitted to colostomy, without altering the degree of vascular congestion.

Resumo Racional A colite de desuso é frequente em nosso meio e o tratamento de maior eficácia é de alto custo, havendo necessidade de se encontrar uma terapêutica eficaz e de baixo custo. Objetivo Avaliar a eficácia da Baccharis dracunculifolia (alecrim-do-campo) no tratamento da colite de exclusão em ratos. Método Utilizou-se 18 ratos Wistar, os quais foram anestesiados e submetidos à colostomia; em seguida distribuídos em 2 grupos: Grupo Controle, recebendo infusão intrarretal de solução salina (n = 8) e Grupo BD, recebendo infusão intrarretal de extrato de Baccharis dracunculifolia (n = 10); após 21 dias de tratamento foram submetidos a eutanásia, o segmento intesinal excluso de trânsito intestinal foi ressecado e submetido a estudo histopatológico classificando-se o grau de inflamação e grau de congestão vascular de 0 a 3. Resultados Verificou-se média de inflamação 2,7 no Grupo Controle vs. 2,1 no Grupo BD (p = 0,049), enquanto as médias de congestão vascular foram 2,3 e 2, respectivamente, nos grupos controle e BD (p = 0,1642). Conclusão A infusão intrarretal do extrato de Baccharis dracunculifolia minimizou significantemente o processo inflamatório na colite de exclusão de ratos submetidos à colostomia, sem alterar o grau de congestão vascular.

Natural deep eutectic solvents and aqueous solutions as an alternative extraction media for propolis.

Ethanolic extracts of propolis are consumed for their health benefits even though direct consumption of alcoholic extracts is not always ideal. Natural Deep Eutectic Solvents (NADES) can potentially extract similar compounds as alcoholic extracts while being better for direct consumption. Therefore, in this work alternative solvents for the extraction of green propolis including its biomarker artepillin C were examined. Sixteen NADES made from low toxicity chemicals, including the essential amino acid l-lysine, were explored along with twelve individual NADES components and honey, which showed similar physical-chemical properties to NADES. At 50 °C NADES made from choline chloride-propylene glycol or lactic acid proved to be equal or better than the benchmark EtOH:Water 7:3 (v/v). Alternatively, aqueous l-lysine appeared as a potential solvent for the preparation of aqueous propolis extracts. From these findings NADES, honey and aqueous l-lysine solutions all demonstrated the potential to replace ethanol or water for extracting green propolis.

Hydroalcoholic extract from Baccharis dracunculifolia recovers the gastric ulcerated tissue, and p-coumaric acid is a pivotal bioactive compound to this action.

Baccharis dracunculifolia is a medicinal plant native to southeastern Brazil and is the main botanical source used by bees (Apis mellifera) in the manufacture of green propolis and display similar gastroprotective action and chemical profile. This article reports the healing gastric ulcer activity of the hydroethanolic extract of B. dracunculifolia (HEBD) in an acetic acid-induced ulcer model. In addition to the extract, the isolated compounds ferulic acid, p-coumaric acid, caffeic acid, baccharin, and aromadendrin-4'-O-methyl ether were also assayed. HEBD at a dose of 300 mg/kg reduced the ulcerated area by 49.4% after treatment for 7 days, twice a day. Histological analyses revealed that the margins and base of the ulcer obtained significant regeneration, and periodic acid Schiff base staining showed a 78.2% increase in the mucin levels. The action on the enzymatic antioxidant system demonstrated an increased activity of superoxide dismutase and glutathione-S-transferase, in addition to raising glutathione reduced levels and myeloperoxidase activity. HEBD did not show cytotoxicity in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylterazole bromine test. In vitro, HEBD inhibited the H+ /K+ -ATPase enzyme and showed antioxidant activity in the 2,2 diphenyl-1-picryllydrazyl test. Regarding the isolated compounds, oral administration of p-coumaric acid (15 mg/kg) reduced the ulcerated area by 66.2%. The results suggest that HEBD recovers the gastric ulcerated tissue, raising mucus and antioxidant enzyme levels, and reducing the H+ /K+ -ATPase activity. In addition, the findings confirm that p-coumaric acid is a pivotal bioactive compound on the gastric healing effects elicited by HEBD. © 2019 BioFactors, 45(3):479-489, 2019.

Baccharis dracunculifolia DC (Asteraceae) selectively modulates the effector functions of human neutrophils.

OBJECTIVES: To examine whether the hydroalcoholic extract from Baccharis dracunculifolia leaves (BdE) modulates the human neutrophil oxidative metabolism, degranulation, phagocytosis and microbial killing capacity. METHODS: In-vitro assays based on chemiluminescence, spectrophotometry, flow cytometry and polarimetry were used, as well as docking calculations. KEY FINDINGS: At concentrations that effectively suppressed the neutrophil oxidative metabolism elicited by soluble and particulate stimuli (<10 µg/ml), without clear signs of cytotoxicity, BdE (1) inhibited NADPH oxidase and myeloperoxidase activity; (2) scavenged H2 O2 and HOCl; (3) weakly inhibited phagocytosis; and (4) did not affect neutrophil degranulation and microbial killing capacity, the expression levels of TLR2, TLR4, FcγRIIa, FcγRIIIb and CR3 and the activity of elastase and lysozyme. Caffeic acid, one of the major B. dracunculifolia secondary metabolites, did not inhibit phagocytosis but interfered in the myeloperoxidase-H2 O2 -HOCl system by scavenging H2 O2 and HOCl, and interacting with the catalytic residues His-95, Arg-239 and Gln-91. CONCLUSIONS: BdE selectively modulates the effector functions of human neutrophils, inhibits the activity of key enzymes and scavenges physiological oxidant species. Caffeic acid contributes to lower the levels of oxidant species. Our findings help to unravel the mechanisms by which these natural products exert immunomodulatory action towards neutrophils.

Artepillin C and phenolic compounds responsible for antimicrobial and antioxidant activity of green propolis and Baccharis dracunculifolia DC.

AIMS: This study investigates the antimicrobial activity in Staphylococcus aureus isolates (methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA)) and antioxidant activity of green propolis, Baccharis dracunculifolia DC extracts and Artepillin C™. METHODS AND RESULTS: The amount of Artepillin C in different extracts was determined by high performance liquid chromatography analysis. Minimum inhibitory concentration 90 (MIC90) was determined using 40 isolates of S. aureus inoculated in Müeller-Hinton agar culture medium containing the green propolis and B. dracunculifolia DC extracts. PVEE (green propolis ethanolic extract) and BDEH (B. dracunculifolia hexanic extract) showed the greatest antimicrobial activity with MIC90 values of 246·3 and 295·5 µg ml-1 respectively. Green propolis ethanolic and hexanic extracts (PVEE and PVEH respectively) showed the greatest antioxidant activity assessed by DPPH (1,1-diphenyl-2-picryl hydrazyl radical) with IC50 values of 13·09 and 95·86 µg ml-1 respectively. CONCLUSIONS: Green propolis ethanolic displays better antimicrobial and antioxidant activities compared to other extracts. These activities may be related to the presence of Artepillin C in synergism with the other constituents of the extracts. SIGNIFICANCE AND IMPACT OF THE STUDY: In this study, the antimicrobial activity of the extracts of green propolis and B. dracunculifolia DC demonstrated in MRSA and MSSA clinical isolates indicated that they can be important tools to treat infections caused by these bacteria.

Baccharis dracunculifolia-based mouthrinse alters the exopolysaccharide structure in cariogenic biofilms.

Baccharis dracunculifolia is a native plant from Brazil with antimicrobial activity. The purpose of this study was to investigate whether a B. dracunculifolia-based mouthrinse (Bd) changes the structure of insoluble exopolysaccharides (IEPS) in Streptococcus mutans UA159 cariogenic biofilm. Biofilms were grown on glass slides and treated with Bd, its vehicle (VC), chlorhexidine digluconate (CHX), or saline solution (NaCl). Among the treatments, only CHX significantly reduced the biofilm biomass and bacterial viability (p<0.05). Gas chromatography-mass spectrometry and nuclear magnetic resonance analyses revealed that IEPS from the four biofilm samples were α- glucans containing different proportions of (1→6) and (1→3) glycosidic linkages. The structural differences among the four IEPS were compared by principal component analysis (PCA). PCA analysis indicated that IEPS from VC- and NaCl-treated biofilms were structurally similar to each other. Compared with the control, IEPS from Bd- and CHX-treated biofilms were structurally different and had distinct chemical profiles. In summary, the fact that Bd changed the IEPS chemical composition indicates that this mouthrinse may affect the cariogenic properties of the S. mutans biofilm formed.

Potencial de óleos essenciais de plantas medicinais no controle de fitopatógenos / Potential of essential oils from medicinal plants to control plant pathogens

Além do valor como recurso terapêutico, plantas medicinais também possuem potencial para serem utilizadas como fonte de princípios ativos contra fitopatógenos. O objetivo deste trabalho foi avaliar o efeito de óleos essenciais das espécies medicinais Baccharis dracunculifolia (alecrim-do-campo), Schinus terebinthifolius (aroeirinha) e Porophyllum ruderale (arnica-brasileira) sobre o crescimento dos fungos fitopatogênicos Fusarium oxysporum f. sp. phaseoli (Fop), F. solani f. sp. phaseoli (Fsp), Sclerotinia sclerotiorum (Ss), S. minor (Sm), Rhizoctonia solani (Rs), Sclerotium rolfsii (Sr) e Macrophomina phaseolina (Mp). Avaliou-se em placas de Petri o crescimento radial desses fungos em meio batata-dextrose-ágar (BDA) com cinco concentrações (0, 250, 500, 1000 e 3000 mg L-1) dos óleos essenciais. Discos de micélio (5 mm de diâmetro) de cada fungo em crescimento foram transferidos para placas de Petri que foram mantidas a 23°C no escuro por 48 horas. O óleo essencial de alecrim-do-campo foi o mais eficiente na redução do crescimento micelial de todos os fungos, com inibição completa quando se utilizou a concentração de 3000 mg L-1. A redução de crescimento variou de 29% (Fs) a 80% (Rs) a 250 mg L-1 do óleo essencial de alecrim-do-campo; a 500 mg L-1, variou de 29% (Fs) a 98% (Sr); e a 1000 mg L-1, de 41% (Fs) a 100% (Sr). A redução do crescimento dos fungos pelo óleo de aroeirinha na concentração de 3000 mg L-1 variou de 27% (Fsp) a 74% (Rs). Nessa concentração, o óleo de arnica-brasileira reduziu o crecimento micelial de Ss em 72%, o de Rs em 80% e o de Mp em 82%, sem efeitos significativos sobre o crescimento micelial de Fsp e Fop. Conclui-se que os óleos essenciais de alecrim-do-campo, aroeirinha e arnica-brasileira possuem potencial para o controle dos fungos fitopatogênicos estudados, com destaque para o óleo de alecrim-do-campo.

In addition to their value as therapeutic resources, medicinal plants also have the potential to be used as a source of alternative compounds against plant pathogens. The objective of this study was to evaluate the effect of essential oils extracted from the medicinal species Baccharis dracunculifolia, Schinus terebinthifolius and Porophyllum ruderale on the growth of the fungal plant pathogens Fusarium oxysporum f. sp. phaseoli (Fop), F. solani f. sp. phaseoli (Fsp), Sclerotinia sclerotiorum (Ss), S. minor (Sm), Rhizoctonia solani (Rs), Sclerotium rolfsii (Sr) and Macrophomina phaseolina (Mp). The radial mycelial growth of the fungi was evaluated on potato dextrose agar (PDA) in Petri dishes with five concentrations (0, 250, 500, 1000 and 3000 μL L-1) of the essential oils. Mycelial discs (5 mm diameter) of the growing colonies of each fungus were transferred to Petri dishes, which were maintained at 23 °C in the dark for 48 hours. The essential oil of B. dracunculifolia was the most effective oil in the reduction of the mycelial growth of all fungi. It completely inhibited their growth at 3000 mg L-1. At 250 mg L-1, the growth reduction caused by the oil of B. dracunculifolia varied from 29% (Fs) to 80% (Rs); at 500 mg L-1, it varied from 29% (Fs) to 98% (Sr); and at 1000 mg L-1, it varied from 41% (Fs) to 100% (Sr). The reduction of the mycelial growth caused by the oil of S. terebinthifolius at 3000 mg L-1 varied from 27% (Fsp) to 74% (Rs). At this concentration, the oil of P. ruderale reduced the mycelial growth of Ss by 72%, of Rs by 80% and of Mp by 82%, without significant effects on the mycelial growth of Fsp and Fop. We conclude that the essential oils of B. dracunculifolia, S. terebinthifolius and P. ruderale have the potential to be used to control the plant pathogens tested, especially the oil of B. dracunculifolia.

Inhibition of the human neutrophil oxidative metabolism by Baccharis dracunculifolia DC (Asteraceae) is influenced by seasonality and the ratio of caffeic acid to other phenolic compounds.

ETHNOPHARMACOLOGICAL RELEVANCE: The great potential of phytotherapic drugs for treating and preventing inflammatory diseases mediated by increased neutrophil reactive oxygen species (ROS) generation has guided the search for new natural products with antioxidant and immunomodulatory properties. Baccharis dracunculifolia D.C. (Asteraceae), the main botanical source of Brazilian green propolis, is a native plant from Brazil widely used in folk medicine as anti-inflammatory. This study aims: (a) to determine the influence of seasonality on the chemical profile and biological activity of Baccharis dracunculifolia (Asteraceae) leaf extracts (BdE); (b) to analyze the correlation between the major compounds and the ability of BdE to modulate the superoxide anion and total ROS generation by human neutrophils. MATERIALS AND METHODS: The extracts were obtained from leaf samples collected monthly during one year. The superoxide anion and total ROS generation were assessed by the lucigenin (CL-luc)- and luminol (CL-lum)-enhanced chemiluminescence assays. RESULTS: Seasonality influenced more the quantitative than the qualitative chemical profile of B. dracunculifolia, and affected its biological activity. The major compounds identified were caffeic acid, p-coumaric acid, aromadendrin-4'-methyl ether (AME), isosakuranetin and artepillin C. The IC50 values obtained for CL-lum and CL-luc inhibition by BdE ranged from 8.1-15.8 and 5.8-13.3µgmL(-1), respectively, and correlated positively with caffeic acid concentration. CL-luc inhibition correlated negatively with the concentration of artepillin C, AME, isosakuranetin and total flavonoids. The BdE sample from May/07 inhibited CL-lum and CL-luc the most strongly (IC50=8.1 ± 1.6 and 5.8 ± 1.0 µg mL(-1), respectively), and contained the highest ratio of caffeic acid to the other isolated compounds; so, this ratio could be employed as chemical marker for this biological activity of B. dracunculifolia. CONCLUSION: The ability of B. dracunculifolia to inhibit the neutrophil ROS generation depends more on the type and ratio of phenolic compounds and flavonoids than on their high absolute concentrations. Together, our results help select the most appropriate plant material for the production of phytotherapic drugs to be used in the treatment of inflammatory diseases mediated by increased neutrophil activation.

Parâmetros para análise de carqueja: comparação entre quatro espécies de Baccharis spp. (Asteraceae) / Parameters for carqueja analysis: comparison among four species of Baccharis spp. (Asteraceae)

Diferentes espécies de Baccharis são conhecidas popularmente como carqueja e empregadas indistintamente na medicina tradicional como estomáquicas e diuréticas. O presente trabalho teve como objetivo contribuir para a determinação de parâmetros para o controle de qualidade e aplicação na indústria de fitoterápicos, através da análise de quatro espécies de carqueja: Baccharis dracunculifolia DC., B. articulata (Lam.) Pers., B. cylindrica (Less.) DC. e B. gaudichaudiana DC. De um modo geral, B. dracunculifolia apresentou os maiores teores de umidade e de perda por dessecação, enquanto que B. articulata mostrou os maiores índices afrosimétrico e de amargor e teores de extratos secos a frio e a quente e de cinzas totais. B. dracunculifolia foi a espécie que apresentou maior rendimento do óleo volátil. Alguns componentes do óleo volátil ocorrem nas quatro espécies, porém cada uma delas apresentou um perfil cromatográfico característico.

Different species of Baccharis are commonly known as carqueja and are used indistinctly in the traditional medicine as stomachic and diuretic. This research aimed to carry out the drug analysis of Baccharis dracunculifolia DC., B. articulata (Lam.) Pers., B. cylindrica (Less.) DC. and B. gaudichaudiana DC. In general, B. dracunculifolia showed the highest results of water content, essential oil and loss on drying, while B. articulata showed the highest foam and bitter indices, ash and water soluble extractive results. Some components of the essential oil appeared in the four species, although each one showed a charateristic chromatographic profile by TLC analysis.