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A new nor-ent-kaurene diterpene and ten other compounds were isolated from Annona vepretorum stems, including four kaurene diterpenes, three alkamides, one sesquiterpene and two steroids. Their chemical structures were elucidated using spectroscopic methods, including 1D-, 2D-NMR, and HRESIMS. The absolute configuration of compounds 1, 5, 8, 9 and 10 was confirmed by CD experiments. Compounds 1–5 and 8–10 were evaluated for cytotoxic activity using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT method, against three human carcinoma cell lines: human colon (HCT-116), glioblastoma (SF295) and prostate (PC3). However, all isolated compounds exhibited low cytotoxic activity. [ABSTRACT FROM AUTHOR]

Plants of Hyptidinae subtribe (Lamiaceae – family), as Mesosphaerum sidifolium, are a source of bioactive molecules. In the search for new drug candidates, we perform chemical characterization of diterpenes isolated from the aerial parts of M. sidifolium was carried out with uni- and bidimensional NMR spectral data, and evaluate in silico through the construction of a predictive model followed by in vitro testing Mycobacterium tuberculosis and Mycobacterium smegmatis. Resulted in the isolation of four components: Pomiferin D (1), Salviol (2), Pomiferin E (3) and 2α-hydroxysugiol (4), as well as two phenolic compounds, rosmarinic and caffeic acids. In silico model identified 48 diterpenes likely to have biological activity against M. tuberculosis. The diterpenes isolated were tested in vitro against M. tuberculosis demonstrating MIC = 125 µM for 4 and 1, while 2 and 3 -MIC = 250 µM. These compounds did not show biological activity at these concentrations for M. smegmatis. [ABSTRACT FROM AUTHOR]

Campomanesia xanthocarpa popularly known as gabiroba is used as a medicinal plant for the treatment of inflammatory diseases, ulcers, among other uses, requiring studies to assist in proving these activities. In this study, the extract of leaves from C. xanthocarpa (CxHE) was submitted to assays of formalin-induced paw-licking, peritonitis induced by lipopolysaccharide and carrageenan-induced mechanical hyperalgesia tests. In chemical analysis, a preliminary phytochemical screening and the determination of phenol and flavonoid content were carried out, in addition to analysis by ESI-MS/MS system and HPLC-DAD system. The CxHE presented compounds such as tannins, triterpenoids, steroids and saponins and content of phenols (35.9 ± 1.3 GAE/g extract) and flavonoids (23.3 ± 2.1 mg EQ/g extract). Protocatechuic acid, gallic acid, ethyl gallate, quercetin, and 3-methyl epigallocatechin gallate, alpha and beta-amyrins were identified. CxHE at doses of 10-1000 mg/kg p.o. demonstrated anti-inflammatory and antinociceptive effects in all in vivo assays employed in this study. [ABSTRACT FROM AUTHOR]

Pharmacological studies show spasmolytic activity for various species of Varronia. Thus, based on the taxonomy criteria, the aim of this study was to contribute to chemical and biological knowledge, especially regarding the evaluation of spasmolytic activity of the ethanolic extract from Varronia dardani leaves (VD-EtOHL) on rat aorta and trachea, guinea-pig ileum and rat uterus. Were used High and Medium Performance Liquid Chromatography. Wistar rats and guinea-pigs were used for pharmacological assays. All experimental protocols were approved by Animal Ethics Committee of UFPB (126/2017). Two chalcones (pinostrobin chalcone and gymnogrammene), five flavanones (pinocembrin, isosakuranetin, pinostrobin, sakuranetin 4'-methyl ether, naringenin) and a flavonoid glycosilated (astragalin) were identified based on data of 1H and 13C Nuclear Magnetic Resonance. This study also showed that VD-EtOHL has a non-selective spasmolytic activity, presenting greater relaxing potency in rat uterus, suggesting that flavonoids isolated from VD-EtOHL may be responsible for spasmolytic activity of this extract. [ABSTRACT FROM AUTHOR]

Leonotis nepetifolia (L.) Br. (Lamiaceae) is an African shrub popularly known as 'cordão-de-frade' in Brazil, traditionally used to treat infectious diseases, among other uses. This study aimed to investigate the phytochemical composition of hydroethanolic extracts from L. nepetifolia prepared from stems, leaves, roots and glomerulus, as well as their cytotoxicity, antileishmanial and antimicrobial activities. The chemical composition of the extracts was assessed by UPLC-ESI-MS/MS, whereas the antileishmanial activity was evaluated against promastigote and amastigote forms of Leishmania amazonensis. Cytotoxicity was tested on murine macrophages and the antimicrobial activity was investigated by a microdilution assay against several strains of fungi, Gram-positive and Gram-negative bacteria. The flavonoids apigenin, cirsiliol apigenin-7-O-glucoside, luteolin, luteolin-4′-O-glucoside, luteolin-4′-O- glucuronide and luteolin-7-O-glucoside were identified in all tested extracts. Extracts from leaves and roots showed more potent antileishmanial activity (IC50 32.90 µg mL−1 and 57.70 µg mL−1, respectively) against amastigotes forms in comparison to the other extracts. The leaf extract inhibited Bacillus cereus and Staphylococcus aureus growth (125 µg mL−1 and 100 µg mL−1, respectively), and also showed anti-Candida activity (10–125 µg mL−1). The biological effect can be related to the identified flavonoids. Our findings disclose the potential of L. nepetifolia as a source of bioactive compounds for the development of new therapeutic options for treating infectious diseases, especially flavonoids. [ABSTRACT FROM AUTHOR]

One new diterpene (4R,7R,14S)-4α,7α-diacetoxy-10-one-14α-hydroxydolasta-1(15),8-diene (1), and five known compounds (4R,7R,14S)-4α,7α-diacetoxy-14α-hydroxydolasta-1(15),8-diene (2), (4R,14S)-4α,14α-dihydroxydolasta-1(15),8-diene (3), (4S,9R,14S)-4α-acetoxy-9β,14α-dihydroxydolasta-1(15),7-diene (4), 4-acetoxy-14-hydroxydolasta-1(15),7,9-triene (5) and isolinearol (6), were isolated from Canistrocarpus cervicornis. In this study, dolastane diterpenes were isolated from the alga C. cervicornis and evaluated as modifiers of antibiotic activity in Staphylococcus aureus: SA-1199B, which overexpresses the norA gene RN-4220, which encodes for the protein efflux of macrolides (MRSA), and IS-58 which has the gene encoding the protein TetK. The minimum inhibitory concentrations (MICs) for norfloxacin, tetracycline and erythromycin were determined by the microdilution broth nutrient in the absence and presence of diterpenes at a sub-inhibitory concentration (MIC/4). The extracts of C. cervicornis and isolated diterpenes showed no antibacterial activity, but showed modulatory activity, decreasing the MIC of antibiotics by 4–256 fold. The results indicate that seaweed extracts and diterpenes are potential sources of antibiotic adjuvant, acting as potential inhibitors of efflux pump. [ABSTRACT FROM AUTHOR]

Xylopia langsdorfiana A. St.-Hil. &Tul. (Annonaceae) is popularly known in the northeast of Brazil as 'pimenteira da terra', and an essential oil (XL-OE) was extracted from its leaves. Since Xylopia species are cited in folk medicine and diterpenes from X. langsdorfiana have spasmolytic activity, this study aimed to investigate a possible spasmolytic action of XL-OE on smooth muscle models. XL-OE (243 and 729 µg/mL) showed low pharmacologic efficacy on guinea pig trachea and rat aorta and uterus. However, in guinea pig ileum, XL-OE (27-729 µg/mL) inhibited carbachol or histamine-induced phasic contractions (1 µM) in a significant and concentrationdependent manner. In addition, XL-OE (81 µg/mL) reduced fluorescence intensity in ileal myocytes stimulated by histamine, indicating a decrease in cytosolic calcium concentration, which could explain the spasmolytic activity. Thus, XL-OE proved to be a promising natural product to be used in gastrointestinal diseases acting by modulating the cytosolic calcium concentration. [ABSTRACT FROM AUTHOR]

Two new caffeoyl triterpenes, cis -lupacosmeol (1) alone and in mixture with trans -lupacosmeol (2), and two known compounds, 16β-hydroxy-3β- trans -caffeoyl-olean-12-ene (3) and 16β-hydroxy-3β-p-coumaroyl-lup-20(29)-ene (4), were isolated from the roots of Acosmium diffusissimum . The structures were chemically characterised using 1D and 2D NMR, IR spectroscopy, and HRESIMS techniques. Cytotoxicity was evaluated against three different cancer cell lines (MCF-7, HCT-116, SK-MEL-28). Only mixture 2 showed activity against all strains tested, with more pronounced ability to inhibit SK-MEL-28 growth (IC 50 : 25.45 µg/mL). Molecular docking studies suggested that the cytotoxic activity of 2 was strongly attributed to interactions between cis -lupacosmeol and trans -lupacosmeol, which are present in mixtures used to treat melanoma and exhibit activities towards different molecular targets of importance.

Monnieriside A (MoA) is a chromone isolated from Evolvulus linarioides . This study investigated the antinociceptive potential of MoA in mice. MoA (0.01-100 mg/kg, i.p.) inhibited nociception in the inflammatory phase of the formalin test without causing motor impairment. MoA (0.1-100 mg/kg, i.p.) also reduced hindpaw mechanical allodynia caused by either intraplantar injection of Complete Freund's Adjuvant (CFA) or surgical paw incision to simulate postoperative pain. Postoperative antinociception was accompanied by reduced IL-1β levels in the incised paw, assessed by ELISA. The antinociceptive action of MoA (100 mg/kg, i.p.) was preserved in IL-10 knockout mice submitted to paw incision, indicating that IL-10 is not essential to the antinociceptive effect. Interestingly, MoA (100 mg/kg, i.p.) increased the expression of TGF-β in IL-10 knockout mice, which could be a compensation mechanism leading to an antinociceptive effect in the absence of IL-10.

Skin lesions are considered a public health problem, compromising patients' quality of life. This work aimed to evaluate the effects of fraxetin and monnieriside A on Cultured L929 Fibroblasts through the scratch assay. Supernatants and cells from the fibroblast culture treated with the compounds were used to evaluate essential markers of the tissue repair process (IGF-1, VEGF, IL-8, IL-10, FGF-2, COL1A2, COL4A, PDGF) using ELISA and qRT-PCR. The results showed that fraxetin and MOA were non-cytotoxic and could stimulate cellular migration. Fraxetin induced IGF-1, VEGF, IL-8, and IL-10 expression, while MOA induced FGF2, COL1A2, and IL-10 expression. Altogether, these results set provides evidence that fraxetin and MOA have healing potential for tissue repair, paving the way for in vivo studies and clinical trials to validate the in vitro results.

Mosquitoes of the Aedes genus are responsible for transmitting many vector-borne viral diseases worldwide. Hundreds of thousands of people die annually from vector-borne diseases, including West Nile fever, dengue, tick-borne diseases, yellow fever, chikungunya, Rift Valley fever, and Zika. Billions of people are at the risk of infection on all continents, which is a cause of international concern. Therefore, new vector-control methods are essential for mitigating these illnesses. The bioactive hydrocarbons isolated from Xylopia langsdorfiana St. Hilaire & Tulasne are trachylobanes, a rare class of diterpenes found in the n -hexane fraction of the stem and leaf ethanolic extracts. These were tested against Ae. aegypti fourth-instar larvae over 48 h of exposure, with LC 50 values ranging from 19.84 to 72.9 µg/mL, comparable to that of the positive control. The findings highlight the potential of Xylopia langsdorfiana St. Hilaire & Tulasne metabolites for controlling the main vectors of arthropod-borne viruses.

Xylopia langsdorfiana A. St.-Hil. &Tul. (Annonaceae) is popularly known in the northeast of Brazil as 'pimenteira da terra', and an essential oil (XL-OE) was extracted from its leaves. Since Xylopia species are cited in folk medicine and diterpenes from X. langsdorfiana have spasmolytic activity, this study aimed to investigate a possible spasmolytic action of XL-OE on smooth muscle models. XL-OE (243 and 729 μg/mL) showed low pharmacologic efficacy on guinea pig trachea and rat aorta and uterus. However, in guinea pig ileum, XL-OE (27-729 μg/mL) inhibited carbachol or histamine-induced phasic contractions (1 μM) in a significant and concentration-dependent manner. In addition, XL-OE (81 μg/mL) reduced fluorescence intensity in ileal myocytes stimulated by histamine, indicating a decrease in cytosolic calcium concentration, which could explain the spasmolytic activity. Thus, XL-OE proved to be a promising natural product to be used in gastrointestinal diseases acting by modulating the cytosolic calcium concentration.

In this study, we investigated the antinociceptive effect of 7-methoxyflavone (7MF) in mice using the following tests: acetic acid-induced writhing, glutamate- and formalin-induced nociception and hotplate. 7MF (30, 50, 100 and 300 μmol/kg, i.p.) reduced the number of writhes, with ID₅₀ = 82.5 ± 11.7 μmol/kg and E max = 58.4%. 7MF treatment (100 μmol/kg, i.p.) inhibited paw-licking time in the neurogenic phase of the formalin pain response (65.6%) and did not decrease the nociceptive response in the inflammatory phase. In addition, in glutamate-induced nociception, 7MF inhibited 26% of the nociceptive answer. On the other hand, 7MF did not increase the latency time of the animals in the hotplate test. These results suggest that 7MF has peripheral antinociceptive activity.

We aimed to investigate the possible spasmolytic activity of ent-7α-acetoxytrachyloban-18-oic acid (1) and ent-7α-hydroxytrachyloban-18-oic acid (2) on smooth muscle models. In male rat aorta and rat uterus, both diterpenes were unable to trigger spasmolytic action. However, 2 relaxed guinea-pig trachea: Compounds 1 and 2 antagonised, significantly and concentration-dependently, carbachol- and histamine-induced phasic contractions in guinea-pig ileum. Moreover, they induced a significant and concentration-dependent relaxation in pre-contracted (KCl, carbachol or histamine) guinea-pig ileum, with 2 being 15 times more potent than 1 in histamine-contracted ileum. These dissimilar results may be due to chemical differences between them. Thus, we demonstrated that 1 and 2 seem to be promising spasmolytic agents, although further studies are required to elucidate the spasmolytic action mechanism.

Three new pyranonaphthoquinones: 5-hydroxy-6-methoxy-alpha-lapachone, 5,6-dihydroxy-a-lapachone and 4',5-dihydroxy-6-methoxy-alpha-lapachone, and two known compounds: lapachol and 5,5'-dihydroxy-3',4',7-trimethoxyflavanone, were isolated from the stem bark of Melloa quadrivalvis. Their structures were established by spectrometric data, mainly 1D- and 2D-NMR and mass spectra. The methylazoetetrazolium (MTT) method using viable cells of the strain Hep2 and the strain NCIH-292 demonstrated cytotoxic activity. The CI50 was also calculated. The chloroform extract and 5-hydroxy-6-methoxy-alpha-lapachone inhibited cell growth.