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•Cyclodextrin-terpene complexes are promising host-guest systems.•Insolubility in water and a short life-time limit the therapeutic use of terpenes.•CD inclusion complexes enhance ...bioavailability, pharmacological efficacy and safety of terpenes.
Terpenes constitute the largest class of natural products and are important resources for the pharmaceutical, food and cosmetics industries. However, due to their low water solubility and poor bioavailability there has been a search for compounds that could improve their physicochemical properties. Cyclodextrins (natural and derived) have been proposed for this role and have been complexed with different types of terpenes. This complexation has been demonstrated by using analytical techniques for characterizing complexes such as DSC, NMR, XRD, FTIR, and TGA. The formation of inclusion complexes has been able to improve drug characteristics such as bioavailability, solubility and stability; and to enhance biological activity and efficacy. This review shows strong experimental evidence that cyclodextrins improve the pharmacological properties of terpenes, and therefore need to be recognized as being possible targets for clinical use.
Chronic diseases such as cancer, diabetes, neurodegenerative and cardiovascular diseases are characterized by an enhanced state of oxidative stress, which may result from the overproduction of ...reactive species and/or a decrease in antioxidant defenses. The search for new chemical entities with antioxidant profile is still thus an emerging field on ongoing interest. Due to the lack of reviews concerning the antioxidant activity of lichen-derived natural compounds, we performed a review of the antioxidant potential and mechanisms of action of natural compounds isolated from lichens. The search terms "lichens", "antioxidants" and "antioxidant response elements" were used to retrieve articles in LILACS, PubMed and Web of Science published until February 2014. From a total of 319 articles surveyed, 32 met the established inclusion and exclusion criteria. It was observed that the most common isolated compound studied was usnic acid, cited in 14 out of the 32 articles. The most often described antioxidant assays for the study of in vitro antioxidant activity were mainly DPPH, LPO and SOD. The most suggested mechanisms of action were scavenging of reactive species, enzymatic activation and inhibition of iNOS. Thus, compounds isolated from lichens are possible candidates for the management of oxidative stress, and may be useful in the treatment of chronic diseases.
Abstract Cyclodextrins (CDs) have been used as important pharmaceutical excipients for improve the physicochemical properties of the drugs of low solubility as the essential oil of Hyptis martiusii. ...This oil is important therapeutically, but the low solubility and bioavailability compromises your use. Therein, the aim of this study was to obtain and to characterize physico-chemically the samples obtained by physical mixture (PM), paste complexation (PC) and slurry complexation (SC) of the essential oil Hyptis martiusii (EOHM) in β-CD, and to compare the antibacterial and modulatory-antibiotic activity of products obtained and oil free. The physicochemical characterization was performed by differential scanning calorimetry (DSC), thermogravimetry/derivative thermogravimetry (TG/DTG), scanning electron microscopy (SEM), X-ray diffraction (XRD) and Karl Fischer titration. Additionally, the antibacterial tests were performed by microdilution technique. Thus, it was observed that the PM method showed low complexing capacity, unlike PC and SC in which it was observed the formation of inclusion complexes. In addition, the second stage of the TG/DTG curves showed that SC was the best method inclusion with mass loss of 6.9% over the PC that was 6.0%. The XRD results corroborate with the results above suggesting the formation of new solid phase and the SEM photomicrographs showed the porous surface of the samples PC and SC. The essential oil alone demonstrated an antibacterial and modulatory effect against the S. aureus and the Gram negative strain, respectively. However, the β-CD and the inclusion complex did not demonstrate any biological activity in the performed antibacterial assays.
The aim of this present study was to evaluate the effect of solid lipid nanoparticles (SLN) containing carvacrol over the lung damage of airway smoke inhalation. The study was conducted with 30 rats ...subjected to smoke inhalation and divided into 5 groups such as, normal control, negative control, oxygen group, SLN alone, and SLN+CARV group. The animals were sacrificed 24 h after the induction of inhalation injury further, the tissues of larynx, trachea, and lungs were collected for the histological, hematological, myeloperoxidase, and malondialdehyde analysis. The obtained results showed that treatment with CARV+SLN minimized the inhalation injury, since it reduced malondialdehyde significantly, when compared to the negative control group and minimized the histological changes which proves the absence of pulmonary emphysema and exudate in laryngeal and tracheal lumen in the CARV+SLN-treated group. Meanwhile, the presence of lesion with chronic characteristics was observed in the negative control and oxygen groups. It is suggested that the SLN containing carvacrol minimized oxidative stress and histological damages generated from smoke inhalation in rodents.
Under heterotrophic conditions, carbohydrate oxidation inside the mitochondrion is the primary energy source for cellular metabolism. However, during energy-limited conditions, alternative substrates ...are required to support respiration. Amino acid oxidation in plant cells plays a key role in this by generating electrons that can be transferred to the mitochondrial electron transport chain via the electron transfer flavoprotein/ubiquinone oxidoreductase system. Autophagy, a catabolic mechanism for macromolecule and protein recycling, allows the maintenance of amino acid pools and nutrient remobilization. Although the association between autophagy and alternative respiratory substrates has been suggested, the extent to which autophagy and primary metabolism interact to support plant respiration remains unclear. To investigate the metabolic importance of autophagy during development and under extended darkness, Arabidopsis (Arabidopsis thaliana) mutants with disruption of autophagy (atg mutants) were used. Under normal growth conditions, atg mutants showed lower growth and seed production with no impact on photosynthesis. Following extended darkness, atg mutants were characterized by signatures of early senescence, including decreased chlorophyll content and maximum photochemical efficiency of photosystem II coupled with increases in dark respiration. Transcript levels of genes involved in alternative pathways of respiration and amino acid catabolism were up-regulated in atg mutants. The metabolite profiles of dark-treated leaves revealed an extensive metabolic reprogramming in which increases in amino acid levels were partially compromised in atg mutants. Although an enhanced respiration in atg mutants was observed during extended darkness, autophagy deficiency compromises protein degradation and the generation of amino acids used as alternative substrates to the respiration.
The search for more effective and lower cost therapeutic approaches for wound healing remains a challenge for modern medicine. In the search for new therapeutic options, plants and their metabolites ...are a great source of novel biomolecules. Among their constituents, the monoterpenes represent 90% of essential oils, and have a variety of structures with several activities such as antimicrobial, anti-inflammatory, antioxidant and wound healing. Based on that, and also due to the lack of reviews concerning the wound-healing activity of monoterpenes, we performed this systematic review-which provides an overview of their characteristics and mechanisms of action. In this search, the terms "terpenes", "monoterpenes", "wound healing" and "wound closure techniques" were used to retrieve articles published in LILACS, PUBMED and EMBASE until May 2013. Seven papers were found concerning the potential wound healing effect of five compouds (three monoterpenes and two iridoid derivatives) in preclinical studies. Among the products used for wound care, the films were the most studied pharmaceutical form. Monoterpenes are a class of compounds of great diversity of biological activities and therapeutic potential. The data reviewed here suggest that monoterpenes, although poorly studied in this context, are promising compounds for the treatment of chronic wound conditions.
The treatment of orofacial pain remains a major challenge for modern medicine. Thus, we prepared and physicochemically characterized a new β‐cyclodextrin complex containing Lippia grata leaf ...essential oil (β‐CD/EO) to investigate their possible antinociceptive activity in animal models of orofacial pain. The results of Differential scanning calorimeter (DSC) and Thermogravimetry/derivative thermogravimetry (TG/DTG) showed that the products prepared by Slurry complexation (SC) method were able to incorporate greater amounts of EO. In the X‐ray diffractogram, it was shown that complex between EO and β‐CD was formed. Male Swiss mice were pre‐treated with β‐CD/EO (6, 12 or 24 mg/kg, per os, gavage, p.o.), morphine (5 mg/kg, i.p.) or vehicle (distilled water, p.o.) 1 hr before treatment with formalin (20 μL, 2%), capsaicin (20 μL, 2.5 μg) or glutamate (40 μL, 25 μM) into the right upper lip. Our results demonstrated that p.o. treatment with β‐CD/EO was significantly (p < 0.05 or p < 0.001) capable of reducing the nociceptive face‐rubbing behaviour in both phases of the formalin test. β‐CD/EO‐treated mice were also significantly (p < 0.05 or p < 0.001) protected against nociception induced by capsaicin and glutamate. For the action in the central nervous system (CNS), ninety minutes after the treatment, the mice were perfused, the brains collected, crioprotected, cut in a criostate and submitted to an immunofluorescence protocol for Fos protein. The immunofluorescence protocol demonstrated that the β‐CD/EO significantly activated (p < 0.05; p < 0.01 or p < 0.001) the motor cortex, the Locus ceruleus, the nucleus raphe magnus and the periaqueductal gray of the CNS. These effects apparently did not alter, in tested doses, the motor coordination of mice in the rota‐rod test. Our results proposed that β‐CD/EO might present an important draft of drug to the study of new compounds for the treatment of orofacial pain.
Spinal Cord Injury (SCI) promotes a cascade of inflammatory events that are responsible for neuronal death and glial scar formation at the site of the injury, hindering tissue neuroregeneration. ...Among the main approaches for the treatment of SCI, the use of biomaterials, especially gelatin methacryloyl (GelMA), has been proposed because it is biocompatible, has excellent mechanical properties, favoring cell adhesion and proliferation. In addition, it can act as a carrier of anti-inflammatory drugs, preventing the formation of glial scars. The present work presents the development and in situ application of a light-curing formulation based on GelMA containing a natural extract rich in anti-inflammatory, antioxidant and neuroprotective substances (hydroalcoholic extract of red propolis-HERP) in an experimental model of SCI in rats. The formulations were prepared and characterized by time of UV exposition, FTIR, swelling and degradation. The hydrogels containing 1 mg/mL of HERP were obtained by the exposure to UV radiation of 2 μL of the formulation for 60 s. The locomotor evaluation of the animals was performed by the scale (BBB) and demonstrated that after 3 and 7 days of the injury, the GelMA-HERP group (BBB = 5 and 7) presented greater recovery compared to the GelMA group (BBB = 4 and 5). Regarding the inflammatory process, using histomorphological techniques, there was an inflammation reduction in the groups treated with GelMA and GelMA-HERP, with decreases of cavitation in the injury site. Therefore, it is possible to conclude that the use of GelMA and GelMA-HERP hydrogel formulations is a promising strategy for the treatment of SCI when applied in situ, as soon as possible after the injury, improving the clinical and inflammatory conditions of the treated animals.
Citral (CIT) is a monoterpene formed by the geranial and neral stereoisomers. CIT is the major compound of Cymbopogon citratus essential oil, commonly known as “lemongrass”, and has demonstrated ...potential antihyperalgesic, anti-nociceptive and anti-inflammatory effects. However, CIT shows high volatility, low solubility in water and consequent low bioavailability, which limits its use. Therefore, the aim of this study was to evaluate cell viability, anti-hyperalgesic and anti-inflammatory effects of inclusion complexes of CIT on β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD). Initially, physical mixture (PM) and freeze-dried inclusion (FD) complexes of CIT/β-CD and CIT/HP-β-CD were obtained in the molar ratio (1:1). The samples were characterized by DSC, TG/DTG, FT-IR, XRD, SEM and the complexation efficiency were performed by HPLC. Cell viability assay was performed by rezasurin reduction technique in J774 macrophages cell line. The motor activity through rota rod apparatus, mechanical hyperalgesia and pleurisy induced by carrageenan were evaluated in mice. The complexation of CIT was evidenced with β-CD and HP-β-CD by the characterization techniques analyzed. The complexation efficiency of CIT/β-CD and CIT/HP-β-CD were 78.6% and 71.7%, respectively. The CIT, CIT/β-CD and CIT/HP-β-CD showed cell viability in macrophages and did not interfere in the motor activity of mice. Besides that, the samples demonstrated antihyperalgesic and anti-inflammatory activity due to the reduction in total leukocytes and TNF-α levels. However, CIT/β-CD has better pharmacological effects among the three samples evaluated. Therefore, CIT/β-CD has potential for the development of products to treat inflammatory and pain reactions.
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•Cyclodextrins are widely used for the inclusion complex preparation.•Different biological activities are enhanced by using the cyclodextrins complex preparation.•β-CD, HB-β-CD with citral significantly improve the anti-hyperalgesic and anti-inflammatory activities.
Abstract Background Due to its unclear pathophysiology, the pharmacological treatment of fibromyalgia is a challenge for researchers. Studies using medicinal plants, such as those from the genus ...Lippia, complexed with cyclodextrins (CDs) have shown innovative results. Objective The present research intended to evaluate the effect of an inclusion complex containing β-cyclodextrin (βCD) inclusion complex with Lippia grata (LG) essential oil in a chronic musculoskeletal pain model, its central activity and its possible interaction with neurotransmitters involved in pain. Methods After acid saline-induced chronic muscle pain, male mice were evaluated for primary and secondary hyperalgesia and muscle strength. Moreover, an antagonist assay was performed to assess the possible involvement of the opioidergic, serotonergic and noradrenergic pathways. In addition, Fos protein in the spinal cord was assessed, and a docking study and antioxidant assays were performed. Results The treatment with LG-βCD, especially in the dose of 24 mg/kg, was able to significantly decrease (p < 0.05) the paw withdrawal and muscle threshold. Furthermore, LG-βCD was shown to affect the opioidergic and serotonergic pathways. There were no significant changes in muscle strength. Fos protein immunofluorescence showed a significant decrease in expression in the dorsal horn of the spinal cord. The main compounds of LG showed through the docking study interaction energies with the alpha-adrenergic and μOpioid receptors. In all antioxidant assays, LG exhibited stronger antioxidant activities than LG-βCD. Conclusion This study suggested that LG-βCD could be considered as a valuable source for designing new drugs in the treatment of chronic pain, especially musculoskeletal pain.
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