Artemisinin-type drugs for the treatment of hematological malignancies.

Qinghaosu, known as artemisinin (ARS), has been for over two millennia, one of the most common herbs prescribed in traditional Chinese medicine (TCM). ARS was developed as an antimalarial drug and currently belongs to the established standard treatments of malaria as a combination therapy worldwide. In addition to the antimalarial bioactivity of ARS, anticancer activities have been shown both in vitro and in vivo. Like other natural products, ARS acts in a multi-specific manner also against hematological malignancies. The chemical structure of ARS is a sesquiterpene lactone, which contains an endoperoxide bridge essential for activity. The main mechanism of action of ARS and its derivatives (artesunate, dihydroartemisinin, artemether) toward leukemia, multiple myeloma, and lymphoma cells comprises oxidative stress response, inhibition of proliferation, induction of various types of cell death as apoptosis, autophagy, ferroptosis, inhibition of angiogenesis, and signal transducers, as NF-κB, MYC, amongst others. Therefore, new pharmaceutically active compounds, dimers, trimers, and hybrid molecules, could enhance the existing therapeutic alternatives in combating hematologic malignancies. Owing to the high potency and good tolerance without side effects of ARS-type drugs, combination therapies with standard chemotherapies could be applied in the future after further clinical trials in hematological malignancies.

Antinociception induced by artemisinin nanocapsule in a model of postoperative pain via spinal TLR4 inhibition.

Artemisinin (ART) was initially described for the control of inflammation and pain. However, the mechanisms involved with its antinociceptive effect are still poorly understood. Thus, this present study aimed to investigate the effect of ART in both free and nanocapsulated form on postoperative pain, as well as the participation of the spinal Toll-like receptor 4 (TLR4) in this process. Postoperative pain was induced using the skin/muscle incision retraction (SMIR) model in male Swiss mice. After 3 and 28 days of SMIR, the animals received an intrathecal injection of free or nanocapsulated ART, and the nociceptive threshold was evaluated by von Frey filament test. To evaluate the involvement of the microglia, astrocytes, and TLR4, minocycline (a microglia inhibitor), fluorocitrate (an astrocyte inhibitor), and Lipopolysaccharide Rhodobacter sphaeroides (LPS-RS), a TLR4 antagonist, were intrathecally injected on the third day of SMIR. The levels of spinal TLR4 protein and proinflammatory cytokines tumor necrosis factor-alpha (TNF-α), and interleukin-1-beta (IL-1ß) were quantified by western blot and enzyme-linked immunosorbent assay, respectively. The results showed that free ART reduced postoperative pain (P < 0.001, F5,30 = 7.49, 16.66% for 1000 ng dose; and P < 0.01, F5,30 = 7.49, 14.58% for 500 ng dose) on the 3rd day of SMIR; while the ART nanocapsule had this effect on both the third (P < 0.001; F5,30 = 4.94; 43.75, 39.58 and 72.91% for the 250, 500 and 1000 ng doses, respectively) and 28th (P < 0.05; F5,30 = 7.71; 29.16 and 33.33% for the 500 and 1000 ng doses, respectively) day. The ART nanocapsule had a more potent and longer antinociceptive effect than free ART or morphine. Postoperative pain was also reduced by minocycline and LPS-RS. The ART nanocapsule also reduced the increased levels of TLR4, TNF-α, and IL-1ß induced by SMIR. These data suggest that the ART nanocapsule has a potent analgesic effect on postoperative pain at the spinal level, and this response involves the inhibition of TLR4 and the proinflammatory cytokines TNF-α and IL-1ß.

Flexible, dense and porous chitosan and alginate membranes containing the standardized extract of Arrabidaea chica Verlot for the treatment of skin lesions.

The combination of chitosan (C) with alginate (A) has been explored for the production of dressings due to the positive results on wound healing. CA films can show a dense or porous flexible structure, with characteristics tunable for different applications. Porosity and flexibility can be achieved, respectively, by the addition of surfactants such as Kolliphor® P188 (P) and silicone-based compounds as Silpuran® 2130 A/B (S). Furthermore, composite matrices of these polysaccharides have potential applications as devices for releasing bioactive compounds to skin lesions. The purpose of this study was to evaluate the physicochemical and biological characteristics of flexible dense and porous CA membranes incorporating the standardized extract of Arrabidaea chica Verlot (A. chica), and also to analyze the release mechanism of the extract from different membrane formulations. The results show that the inclusion of P in the formulation allows obtaining porous matrices, promotes greater homogeneity of the mixture of the silicone gel with the suspension of polysaccharides, and increases the swelling of the polymer matrix. All formulations presented high stability, reaching a maximum mass loss of 18% after seven days. The formulations with S showed the best performance in terms of flexibility and strain at break. The presence of A. chica standardized extract did not affect negatively the characteristics of the membranes. Incorporation efficiencies of the bioactive compound above 87% were achieved, and the addition of P and S to the membrane formulation changed the release of the A. chica extract kinetics. In addition, the developed formulations did not significantly affect Vero cells proliferation.

The role of short-range magnetic correlations in the gap opening of topological Kondo insulators.

In this article we investigate the effects of short-range anti-ferromagnetic correlations on the gap opening of topological Kondo insulators. We add a Heisenberg term to the periodic Anderson model at the limit of strong correlations in order to allow a small degree of hopping of the localized electrons between neighboring sites of the lattice. This new model is adequate for studying topological Kondo insulators, whose paradigmatic material is the compound [Formula: see text]. The main finding of the article is that the short-range antiferromagnetic correlations, present in some Kondo insulators, contribute decisively to the opening of the Kondo gap in their density of states. These correlations are produced by the interaction between moments on the neighboring sites of the lattice. For simplicity, we solve the problem on a two dimensional square lattice. The starting point of the model is the [Formula: see text] ions orbitals, with [Formula: see text] multiplet in the presence of spin-orbit coupling. We present results for the Kondo and for the antiferromagnetic correlation functions. We calculate the phase diagram of the model, and as we vary the [Formula: see text] level position from the empty regime to the Kondo regime, the system develops metallic and topological Kondo insulator phases. The band structure calculated shows that the model describes a strong topological insulator.

Derivatives of furanditerpenes from Pterodon genus: Pharmacological studies disclose their potential as chronic pain relief in mice.

Pterodon genus fruits are commercially available at the Brazilian medicinal market used in folk medicine due to their anti-inflammatory, analgesic, and anti-rheumatic effects. Previous studies demonstrated that furanditerpenes possessing vouacapan skeleton, isolated from Pterodon genus, possess expressive antinociceptive activities, with promising moiety for the development of new analgesic products. The antinociceptive properties of compounds 6α,7ß-6α-hidroxivouacapan-7ß-17ß-lactone (HVL) and 6α-oxovouacapan-7ß-17ß-lactone (OVL), semi-synthetic analogues of furanditerpenes previously reported as analgesic agents were evaluated on animal experimental models (Spindola et al., 2010, 2011). The chemical-induced pain methods used in the present work, demonstrated for the first time that both compounds HVL and OVL have potential as important templates for the development of chronic pain control drugs. The main findings of this work were that both compounds were: effective in the writhing test; reduced paw edema in the carrageenan test; effective in the inflammatory phase of the formalin test corroborating their activity against inflammatory pain conditions; effective on reducing pain through the stimulation of vanilloid receptors sensible to capsaicin (an important pathway for chronic pain maintenance); reduced the pain stimulus caused by PGE2 injection (a pathway involved in chronic pain hypersensitivity); effective on decreasing mechanical allodynia in the CFA-model, demonstrating their potential use against chronic pain disorders.

Effects of Arctium lappa on Cadmium-Induced Damage to the Testis and Epididymis of Adult Wistar Rats.

The protective role of Arctium lappa (AL) on the testes of rats acutely exposed to cadmium (Cd) was tested. The rats were randomly divided into a control group (C-group) and three major experimental groups, which were further subdivided into minor groups (n = 6) according to the experimental period (7 or 56 days). The C-group was subdivided into C-7 and C-56 [receiving a single saline solution, intraperitoneal (i.p.), on the first day]; the AL-group, AL-7, and AL-56, received AL extract (300 mg/kg/daily); the Cd group, Cd-7 and Cd-56, received a single i.p. dose of CdCl2 (1.2 mg/kg body weight (BW)) on the first day; the CdAL group, CdAL-7 and CdAL-56, received the same Cd dose, followed by AL extract. Water or AL extract was administered daily by gavage. After either 7 or 56 days, the testis and accessory glands were removed after whole-body perfusion. Exposure to Cd and CdAL decreased the weight of the testis and epididymis, the gonadosomatic index, seminiferous tubular (ST) diameter, and ST volumetric proportion, and increased the volumetric proportion of interstitium after 56 days. In the epididymis caput, the tubular volumetric proportion decreased along with an increase of interstitial volumetric proportion and epithelium height after 56 days. The alterations observed were less severe only after 7 days. A progressive testicular damage resulted mainly in tubules lined only by Sertoli cells. The sperm number and cell debris decreased in the epididymis. We demonstrated that the testicular damage induced by single acute i.p. exposure to Cd occurred despite the daily oral intake of AL extract.

Plant-based active photoprotectants for sunscreens.

Excessive exposure to the sun's radiation is the major exogenous mediator of skin damage, which accelerates skin ageing and increases the risk of developing skin cancer. Compounds with photoprotectant activity are extremely useful for decreasing the effect of ultraviolet (UV) radiation on the skin; however, numerous sun filters, especially organic sunscreens, are allergenic. Therefore, the development of formulations containing plant extracts, which may be potentially safer, is extensively being explored. Plant-based cosmetics are commonly used to avoid skin ageing because they contain antioxidant agents that minimize free radical activity, and numerous studies have investigated the skin-protectant effects of related plant species. In addition to their antioxidant properties, plant-based cosmetics protect the skin against solar radiation because they contain polyphenols such as flavonoids and carotenoids. Therefore, this study aims to present a review of plant species commonly used in sunscreens to protect the skin against damage due to sunlight exposure.

Phenolic compounds of Hibiscus sabdariffa and influence of organic residues on its antioxidant and antitumoral properties.

The aim of this study was to evaluate the phenolic and flavonoids contents and the antioxidant and antitumoral activity of leaf and calyx methanolic extracts from Hibiscus sabdariffa (roselle) cultivated with poultry litter and organosuper® under three modes of application. The total phenolic content in the each extract was determined using the Folin-Ciocalteu reagent and for aluminium chloride flavonoids. The antioxidant parameters were analyzed using a 2, 2-diphenyl-1-picrylhydrazyl (DPPH.) free radical scavenging assay. An antitumor colorimetric assay using sulforhodamine B. The highest contents of phenolic and flavonoids were observed in leaf extracts (389.98 and 104.52 mg g-1, respectively) and calyx extracts (474.09 and 148.35 mg g-1, respectively) from plants cultivated with organosuper®, although these values did not differ significantly from those observed for the other treatments. The average IC50 of leaves (43.48 µg mL-1) and calyces (37.15 µg mL-1) demonstrated that both have substances that may contribute to free radical scavenging action. The methanol extract from calyces showed significant selective activity against a leukemia line (K-562), with IC50 values of 0.12 mg mL-1 (organosuper®) and 1.16 mg mL-1 (poultry litter), with concentration-dependent, cytotoxic and cytocidal effects.

In vitro biological screening of the anticholinesterase and antiproliferative activities of medicinal plants belonging to Annonaceae

The aim of this research was to investigate the antiproliferative and anticholinesterase activities of 11 extracts from 5 Annonaceae species in vitro. Antiproliferative activity was assessed using 10 human cancer cell lines. Thin-layer chromatography and a microplate assay were used to screen the extracts for acetylcholinesterase (AchE) inhibitors using Ellman's reagent. The chemical compositions of the active extracts were investigated using high performance liquid chromatography. Eleven extracts obtained from five Annonaceae plant species were active and were particularly effective against the UA251, NCI-470 lung, HT-29, NCI/ADR, and K-562 cell lines with growth inhibition (GI50) values of 0.04-0.06, 0.02-0.50, 0.01-0.12, 0.10-0.27, and 0.02-0.04 µg/mL, respectively. In addition, the Annona crassiflora and A. coriacea seed extracts were the most active among the tested extracts and the most effective against the tumor cell lines, with GI50 values below 8.90 µg/mL. The A. cacans extract displayed the lowest activity. Based on the microplate assay, the percent AchE inhibition of the extracts ranged from 12 to 52%, and the A. coriacea seed extract resulted in the greatest inhibition (52%). Caffeic acid, sinapic acid, and rutin were present at higher concentrations in the A. crassiflora seed samples. The A. coriacea seeds contained ferulic and sinapic acid. Overall, the results indicated that A. crassiflora and A. coriacea extracts have antiproliferative and anticholinesterase properties, which opens up new possibilities for alternative pharmacotherapy drugs.

In vitro biological screening of the anticholinesterase and antiproliferative activities of medicinal plants belonging to Annonaceae.

The aim of this research was to investigate the antiproliferative and anticholinesterase activities of 11 extracts from 5 Annonaceae species in vitro. Antiproliferative activity was assessed using 10 human cancer cell lines. Thin-layer chromatography and a microplate assay were used to screen the extracts for acetylcholinesterase (AchE) inhibitors using Ellman's reagent. The chemical compositions of the active extracts were investigated using high performance liquid chromatography. Eleven extracts obtained from five Annonaceae plant species were active and were particularly effective against the UA251, NCI-470 lung, HT-29, NCI/ADR, and K-562 cell lines with growth inhibition (GI50) values of 0.04-0.06, 0.02-0.50, 0.01-0.12, 0.10-0.27, and 0.02-0.04 µg/mL, respectively. In addition, the Annona crassiflora and A. coriacea seed extracts were the most active among the tested extracts and the most effective against the tumor cell lines, with GI50 values below 8.90 µg/mL. The A. cacans extract displayed the lowest activity. Based on the microplate assay, the percent AchE inhibition of the extracts ranged from 12 to 52%, and the A. coriacea seed extract resulted in the greatest inhibition (52%). Caffeic acid, sinapic acid, and rutin were present at higher concentrations in the A. crassiflora seed samples. The A. coriacea seeds contained ferulic and sinapic acid. Overall, the results indicated that A. crassiflora and A. coriacea extracts have antiproliferative and anticholinesterase properties, which opens up new possibilities for alternative pharmacotherapy drugs.

Chemical composition and free radical-scavenging, anticancer and anti-inflammatory activities of the essential oil from Ocimum kilimandscharicum.

OBJECTIVE: The essential oil from the leaves of Ocimum kilimandscharicum (EOOK), collected in Dourados-MS, was investigated for anticancer, anti-inflammatory and antioxidant activity and chemical composition. MATERIALS AND METHODS: The essential oil was extracted by hydrodistillation, and the chemical composition was performed by gas chromatography-mass spectrometry. The essential oil was evaluated for free radical-scavenging activity using the DPPH assay and was tested in an anticancer assay against ten human cancer cell lines. The response parameter (GI50) was calculated for the cell lines tested. The anti-inflammatory activity was evaluated using carrageenan-induced pleurisy in mice. RESULTS: The chemical composition showed 45 components with a predominance of monoterpenes, such as camphor (51.81%), 1,8 cineole (20.13%) and limonene (11.23%). The EOOK exhibited potent free radical-scavenging activity by the DPPH assay with a GI50 of 8.31 µg/ml. The major constituents, pure camphor (IC50=12.56 µg/ml) and mixture of the limonene: 1, 8 cineole (IC50=23.25 µg/ml) displayed a potent activity. The oral administration of EOOK (at 30 and 100 mg kg(-1)), as well as the pure camphor or a mixture of 1,8 cineole with limonene, significantly inhibited the carrageenan (Cg) induced pleurisy, reducing the migration of total leukocytes in mice by 82 ± 4% (30 mg kg(-1) of EOOK), 95 ± 4% (100 mg kg(-1) of EOOK), 83 ± 9% (camphor) and 80 ± 5% (mixture of 1,8 cineole:limonene 1:1). In vitro cytotoxicity screening against a human ovarian cancer cell line displayed high selectivity and potent anticancer activity with GI50=31.90 mg ml(-1). This work describes the anti-inflammatory, anticancer and antioxidant effects of EOOK for the first time. CONCLUSIONS: The essential oil exhibited marked anti-inflammatory, antioxidant and anticancer effects, an effect that can be attributed the presence of majorital compounds, and the response profiles from chemical composition differed from other oils collected in different locales.

In vitro, in vivo and in silico analysis of the anticancer and estrogen-like activity of guava leaf extracts.

Anticancer drug research based on natural compounds enabled the discovery of many drugs currently used in cancer therapy. Here, we report the in vitro, in vivo and in silico anticancer and estrogen-like activity of Psidium guajava L. (guava) extracts and enriched mixture containing the meroterpenes guajadial, psidial A and psiguadial A and B. All samples were evaluated in vitro for anticancer activity against nine human cancer lines: K562 (leukemia), MCF7 (breast), NCI/ADR-RES (resistant ovarian cancer), NCI-H460 (lung), UACC-62 (melanoma), PC-3 (prostate), HT-29 (colon), OVCAR-3 (ovarian) and 786-0 (kidney). Psidium guajava's active compounds displayed similar physicochemical properties to estradiol and tamoxifen, as in silico molecular docking studies demonstrated that they fit into the estrogen receptors (ERs). The meroterpene-enriched fraction was also evaluated in vivo in a Solid Ehrlich murine breast adenocarcinoma model, and showed to be highly effective in inhibiting tumor growth, also demonstrating uterus increase in comparison to negative controls. The ability of guajadial, psidial A and psiguadials A and B to reduce tumor growth and stimulate uterus proliferation, as well as their in silico docking similarity to tamoxifen, suggest that these compounds may act as Selective Estrogen Receptors Modulators (SERMs), therefore holding significant potential for anticancer therapy.

Dissimilaridade genética em variedades de Artemisia annua L. embasada em caracteres agronômicos, fisiológicos e fitoquímicos / Genetic dissimilarity in varieties of Artemisia annua L. based on agronomic, physiological and phytochemical characters

O presente estudo objetivou estimar a variabilidade genética existente entre caracteres agronômicos, fisiológicos e fitoquímicos em variedades de A. annua. O delineamento experimental foi inteiramente casualizado e os tratamentos foram as variedades Artemis, 2/39x5x3M, e 2/39x1V de A. annua, submetidas a avaliações agronômicas, fisiológicas e fitoquímicas. Para a realização das estimativas de distância genética foram geradas matrizes de dissimilaridade utilizando a distância Euclidiana e os métodos de agrupamento de Tocher e UPGMA. Além disso, avaliou-se a importância relativa dos caracteres para divergência genética pelo método de Singh. As análises foram realizadas pelo software Genes e os dendrogramas obtidos pelo NTSYS. A presença de variabilidade genética dentro das variedades permitiu a identificação de acessos dissimilares e com média elevada para as características estudadas. O número de ramificações, concentração intracelular de CO2, e o rendimento de óleo essencial foram os caracteres que mais contribuíram para a dissimilaridade genética de A. annua. Os acessos B24, C5 e C32 foram os mais promissores dentro das variedades e devem ser conservados para futuras hibridações, sendo que as hibridações mais promissoras na obtenção de populações segregantes desejadas são B24 x C5, B24 x C32 e C5 x C32.

This study aimed to estimate the genetic variability among agronomic, physiological, and phytochemical characters in varieties of A. annua. The experimental design was completely randomized and the treatments were the varieties Artemis, 2/39x5x3M and 2/39x1V of A. annua, subject to agronomic, physiological and phytochemical evaluations. To estimate the genetic distances, dissimilarity matrices were generated using the Euclidean distance and the Tocher and UPGMA grouping methods. Moreover, we evaluated the relative importance of the characters for genetic divergence through the method of Singh. The analyses were performed in the Genes software and the dendrograms were obtained from the NTSYS program. The presence of genetic variability within the varieties allowed the identification of dissimilar accessions with high average for all traits. The number of branches, intracellular concentration of CO2 and oil yield were the traits that contributed most to the genetic dissimilarity of A. annua. The accessions B24, C5 and C32 were the most promising within the populations and must be conserved for future crossings, and the most promising crosses to obtain the desired segregant populations were B24 x C5, B24 x C32 and C5 x C32.

Effect of the Arrabidaea chica extract on collagen fiber organization during healing of partially transected tendon.

AIMS: After undergoing lesions, tendons have disorganized collagen fibers compared to undamaged tendons. Arrabidaea chica leaves have the aglycones carajurin and carajurone, components of the antocyanins, with a strong pharmacological potential due to their healing properties. Thus, the aim of this study was to investigate the effect of topical application of A. chica extract during tendon healing. MAIN METHODS: The calcaneal tendon of Wistar rats was partially transected with subsequent treatment with A. chica extract (2.13 g/mL) followed by excision on the 7th, 14th and 21st days. Control rats received only saline treatment. KEY FINDINGS: Transmission electron microscopy analysis showed the presence of a large amount of small segments of collagen fibrils in the transected region of the tendons on the 7th day in both the control and plant-treated groups. Considering the organization of the collagen fibers, higher values of birefringence were observed under polarization microscopy in the tendons of the plant-treated group on the 14th day compared to the control group. A larger quantity of dermatan sulfate was also detected after plant treatment in the same period. However, lesser dermatan and chondroitin sulfate were detected in the plant-treated group than in the control group on the 21st day. No differences were found in the values of birefringence between these groups. Intense metachromasy was observed in both transected groups on the 21st day. SIGNIFICANCE: In conclusion, the use of A. chica extract improves collagen organization and increases the quantity of dermatan sulfate on the 14th day of the tendon healing.

In vitro and in vivo antitumor activity of crude extracts obtained from Brazilian Chromobacterium sp isolates

Natural products produced by microorganisms have been an important source of new substances and lead compounds for the pharmaceutical industry. Chromobacterium violaceum is a Gram-negative β-proteobacterium, abundant in water and soil in tropical and subtropical regions and it produces violacein, a pigment that has shown great pharmaceutical potential. Crude extracts of five Brazilian isolates of Chromobacterium sp (0.25, 2.5, 25, and 250 µg/mL) were evaluated in an in vitro antitumor activity assay with nine human tumor cells. Secondary metabolic profiles were analyzed by liquid chromatography and electrospray ionization mass spectrometry resulting in the identification of violacein in all extracts, whereas FK228 was detected only in EtCE 308 and EtCE 592 extracts. AcCE and EtCE 310 extracts showed selectivity for NCI/ADR-RES cells in the in vitro assay and were evaluated in vivo in the solid Ehrlich tumor model, resulting in 50.3 and 54.6% growth inhibition, respectively. The crude extracts of Chromobacterium sp isolates showed potential and selective antitumor activities for certain human tumor cells, making them a potential source of lead compounds. Furthermore, the results suggest that other compounds, in addition to violacein, deoxyviolacein and FK228, may be involved in the antitumor effect observed.

Arrabidaea chica extract improves gait recovery and changes collagen content during healing of the Achilles tendon.

INTRODUCTION: Tendon lesions are still a serious clinical problem. The leaves of the Bignoniaceae Arrabidaea chica (Humb. & Bonpl.) B. Verlot. (syn. Bignonia chica (Bonpl.)) have been used in traditional medicine and described in the literature for its healing properties. However, no study has shown the effects of A. chica during tendon healing. The aim of this study was to investigate the healing properties of the A. chica leaves extract on tendons after partial transection. METHODS: A partial transection in the tension region of the Achilles tendon of rats was performed with subsequent posterior topical application of A. chica extract (2.13g/mL in 0.85% saline solution) at the site of the injury. The animals (n=154) were separated into 7 groups: N - rats with tendons without transection; S7, S14 and S21 - rats with tendons treated with topical applications of saline for 7 days and sacrificed on the 7th, 14th and 21st days after surgery, respectively; A7, A14 and A21 - rats with tendons treated with topical applications of the plant extract. The transected regions of the tendons were analyzed through biochemical, morphological and functional analyses. To evaluate the type and concentration of collagen, Western blotting for collagen types I and III was performed, and the hydroxyproline concentration was determined. The participation of metalloproteinases (MMP)-2 and -9 during tendon remodelling was investigated through zymography. Gait recovery was analyzed using the catwalk system. The organization of the extracellular matrix and morphometry were detected in sections stained with haematoxylin-eosin. RESULTS: The application of A. chica extract in the region of tendon injury led to an increase in the amount of hydroxyproline (mg/g tissue) on the 7th (91.5±18.9) and 21st (95.8±11.9) days after the tendon lesion relative to the control groups treated with saline (S7: 75.2±7.2; and S21: 71.9±7.9). There were decreases in collagen types I and III (as determined by densitometry) in the groups treated with the plant extract 7 days after injury (type I: 103.9±15.9; type III: 206.3±8.1) compared to the saline-treated groups (type I: 165.2±31.1; type III: 338.6±48.8). The plant extract stimulated the synthesis of MMP-2 on the 21st day after the lesion and decreased the amount of latent and active isoforms of MMP-9 on the 14th day. Analysis by the catwalk system (max contact intensity) showed that the A. chica extract improved the gait of rats on the 7th day of the healing process when compared to the saline group. CONCLUSIONS: The use of A. chica extract during the healing process of the tendon leads to an increase in collagen content and improved gait recovery. Further studies will be performed to analyze the effect of this plant extract on the organization of the collagen bundles of tendons after lesions and to study its probable anti-inflammatory effect.

Pterodon pubescens oil: characterisation, certification of origin and quality control via mass spectrometry fingerprinting analysis.

INTRODUCTION: The oil obtained from Pterodon pubescens (Leguminosae) seeds are known to display anti-cancer, anti-dermatogenic and anti-nociceptive activitiy. Phytochemical studies have demonstrated that its main constituents are diterpenoids with voucapan skeletons. Considering the potential biological activities of the oil, rapid and efficient methods for assessing its quality would facilitate certification and quality control. OBJECTIVE: To develop a direct mass spectrometric fingerprinting method for the P. pubescens seed oil that would focus on the major diterpenoids constituents, enabling quality control, origin certification and recognition of marker species in commercially available products. METHOD: Two techniques were used: (i) direct infusion electrospray ionisation (ESI) mass spectrometry after solvent extraction and dilution and (ii) ambient desorption/ionisation via easy ambient sonic-spray ionisation, EASI(+)-MS, performed directly on the seed surface or at a paper surface imprinted with the oil. RESULTS: From a combination of ESI-MS, HRESI-MS and ESI-MS/MS data, 12 diterpenes were characterised, and typical profiles were obtained for the oil extract or the crude oil via both ESI-MS and EASI-MS. These techniques require no or very simple sample preparation protocols and the whole analytical processes with spectra acquisition take just a few minutes. CONCLUSION: Both techniques, but particularly EASI-MS, provide simple, fast and efficient MS fingerprinting methodologies to characterise the P. pubescens oil with typical (di)terpene profiles being applicable to quality control and certification of authenticity and origin.

In vitro and in vivo antitumor activity of crude extracts obtained from Brazilian Chromobacterium sp isolates.

Natural products produced by microorganisms have been an important source of new substances and lead compounds for the pharmaceutical industry. Chromobacterium violaceum is a Gram-negative ß-proteobacterium, abundant in water and soil in tropical and subtropical regions and it produces violacein, a pigment that has shown great pharmaceutical potential. Crude extracts of five Brazilian isolates of Chromobacterium sp (0.25, 2.5, 25, and 250 µg/mL) were evaluated in an in vitro antitumor activity assay with nine human tumor cells. Secondary metabolic profiles were analyzed by liquid chromatography and electrospray ionization mass spectrometry resulting in the identification of violacein in all extracts, whereas FK228 was detected only in EtCE 308 and EtCE 592 extracts. AcCE and EtCE 310 extracts showed selectivity for NCI/ADR-RES cells in the in vitro assay and were evaluated in vivo in the solid Ehrlich tumor model, resulting in 50.3 and 54.6% growth inhibition, respectively. The crude extracts of Chromobacterium sp isolates showed potential and selective antitumor activities for certain human tumor cells, making them a potential source of lead compounds. Furthermore, the results suggest that other compounds, in addition to violacein, deoxyviolacein and FK228, may be involved in the antitumor effect observed.

Correlation among agronomic, physiological and phytochemical traits in Artemisia annua L. varieties / Correlação entre caracteres agronômicos, fisiológicos e fitoquímicos em variedades de Artemisia annua L

The aim of this study was to estimate the correlations among agronomic, physiological and phytochemical traits of two varieties of Artemisia annua and to identify correlations that can be used in selection and breeding processes for this species. The design was completely randomized and the treatments were for Artemisia annua varieties 2/39x5x3M and 2/39x1V, which were subjected to agronomic, physiological and phytochemical evaluations. The relationship among the studied traits was estimated with Pearson's correlation coefficient, and the significance level of correlations was established by the t-test using Genes software. A significant positive correlation was found between the traits canopy volume and essential oil yield for 2/39x5x3M variety, showing that the selection of plants with a larger canopy volume would facilitate indirect selection of the trait essential oil yield. This correlation was not found for the 2/39x1V variety. In both varieties, there was a significant negative correlation between canopy volume and artemisinin content, which suggested that the selection of plants with a large canopy volume and a large number of branches should be avoided if the goal is to increase artemisinin content.

O objetivo deste trabalho foi estimar as correlações existentes entre caracteres agronômicos, fisiológicos e fitoquímicos em duas variedades de Artemisia annua e identificar correlações que possam ser utilizadas em processos de seleção e melhoramento da espécie. O delineamento foi inteiramente casualizado e os tratamentos foram às variedades 2/39x5x3M e 2/39x1V de Artemisia annua, submetidas a avaliações agronômicas, fisiológicas e fitoquímicas. A relação existente entre os caracteres estudados foi estimada através do coeficiente de correlação de Pearson e o nível de significância das correlações pelo teste t, realizadas no programa Genes. Encontrou-se correlação positiva e significativa entre os caracteres volume de dossel e rendimento de óleo essencial na variedade 2/39x5x3M, evidenciando que a seleção de plantas com maior volume de dossel possibilitaria a seleção indireta para o cárater rendimento de óleo essencial. Esta correlação não foi encontrada na variedade 2/39x1V. Em ambas as variedades, observou-se correlação negativa e significativa entre volume de dossel e teor de artemisinina indicando que deve-se evitar a seleção de plantas com grande volume de dossel e número de ramificações, se o interesse do melhoramento for maior teor de artemisinina.