Chronic pain conditions, such as neuropathic pain, are a common problem that poses a major challenge to health‐care providers due to its complex natural history, unclear aetiology and poor response ...towards therapy. Despite the large number of drugs available, the adherence is limited by the large range of side effects and pharmacological ineffectiveness. Thus, the search for new chemical entities that can act as promising molecules to treat chronic pain conditions has emerged. The natural products remain as the most promising sources of new chemical entities with applicability for the medical approach. Hence, we performed a systematic review analysing pre‐clinical studies shown to be promising in a possible applicability in neuropathic pain. The search terms neuropathic pain, phytotherapy and medicinal plants were used to retrieve English language articles in LILACS, PUBMED and EMBASE published until 10 April 2013. From a total of 1529 articles surveyed, 28 met the inclusion and exclusion criteria established. The main chemical compounds studied were flavonoids (28%), terpenes (17%), alkaloids (14%), phenols (10%), carotenoids (10%) and others (21%). The mostly described animal models for the study of neuropathic pain included were chronic constriction injury (CCI – 32%), partial sciatic nerve ligation (PSNL – 28%), streptozotocin – induced diabetic (28%), alcoholic neuropathy (3.5%), sodium monoiodoacetate (MIA – 3.5%) and neuropathic pain induced by paclitaxel (3.5%). The opioids, serotonergic and cannabinoid systems are suggested as the most promising targets for the natural products described. Therefore, the data reviewed here suggest that these compounds are possible candidates for the treatment of chronic painful conditions, such as neuropathic pain.
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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.
Limonene (LIM) is a monoterpene, which is abundant in essential oils of Citrus fruits peels (Rutaceae). More recently, LIM, as a potential natural anticancer compound, has attracted major attention ...and exerted a chemopreventive activity, stimulating the detoxification of carcinogenic compounds and limiting tumor growth and angiogenesis in various cancer models. Twenty‐six (26) articles were selected based on previously established criteria. Anticancer activity of LIM was related to the inhibition of tumor initiation, growth, and angiogenesis and the induction of cancer cells apoptosis. LIM was able to increase Bax expression, release cytochrome c, and activate the caspase pathway. In addition, LIM increased the expression of p53 and decreased the activity of Ras/Raf/MEK/ERK and PI3K/Akt pathways. LIM also decreased the expression of VEGF and increased the activities of the Man‐6‐P / IGF2R and TGF‐βIIR receptors. These results highlight LIM as an abundant natural molecule with low toxicity and pleiotropic pharmacological activity in cancer cells, targeting various cell‐signaling pathways critically involved in the initiation, growth, and chemoresistance of cancer cells.
Flavonoids are a class of compounds with a wide variety of biological functions, being an important source of new products with pharmaceutical potential, including treatment of skin wounds.
This ...review aimed to summarize and evaluate the evidence in the literature in respect of the healing properties of flavonoids on skin wounds in animal models.
This is a systematic review following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.
This was carried out through a specialized search of four databases: PubMed, Scopus, Web of Science and Embase. The following keyword combinations were used: "flavonoidal" OR "flavonoid" OR "flavonoidic" OR "flavonoids" AND "wound healing" as well as MeSH terms, Emtree terms and free-text words.
Fifty-five (55) articles met the established inclusion and exclusion criteria. Flavonoids presented effects in respect of the inflammatory process, angiogenesis, re-epithelialization and oxidative stress. They were shown to be able to act on macrophages, fibroblasts and endothelial cells by mediating the release and expression of TGF-β1, VEGF, Ang, Tie, Smad 2 and 3, and IL-10. Moreover, they were able to reduce the release of inflammatory cytokines, NFκB, ROS and the M1 phenotype. Flavonoids acted by positively regulating MMPs 2, 8, 9 and 13, and the Ras/Raf/MEK/ERK, PI3K/Akt and NO pathways.
Flavonoids are useful tools in the development of therapies to treat skin lesions, and our review provides a scientific basis for future basic and translational research.
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Phytol is a diterpene constituent of chlorophyll and has been shown to have several pharmacological properties, particularly in relation to the management of painful inflammatory diseases. Arthritis ...is one of the most common of these inflammatory diseases, mainly affecting the synovial membrane, cartilage, and bone in joints. Proinflammatory cytokines, such as TNF-α and IL-6, and the NFκB signaling pathway play a pivotal role in arthritis. However, as the mechanisms of action of phytol and its ability to reduce the levels of these cytokines are poorly understood, we decided to investigate its pharmacological effects using a mouse model of complete Freund’s adjuvant (CFA)-induced arthritis. Our results showed that phytol was able to inhibit joint swelling and hyperalgesia throughout the whole treatment period. Moreover, phytol reduced myeloperoxidase (MPO) activity and proinflammatory cytokine release in synovial fluid and decreased IL-6 production as well as the COX-2 immunocontent in the spinal cord. It also downregulated the p38MAPK and NFκB signaling pathways. Therefore, our findings demonstrated that phytol can be an innovative antiarthritic agent due to its capacity to attenuate inflammatory reactions in joints and the spinal cord, mainly through the modulation of mediators that are key to the establishment of arthritic pain.
Monoterpenes modulating cytokines - A review Quintans, Jullyana S.S.; Shanmugam, Saravanan; Heimfarth, Luana ...
Food and chemical toxicology,
January 2019, 2019-Jan, 2019-01-00, 20190101, 2019-01, Letnik:
123
Journal Article
Recenzirano
Odprti dostop
Inflammatory response can be driven by cytokine production and is a pivotal target in the management of inflammatory diseases. Monoterpenes have shown that promising profile as agents which reduce ...the inflammatory process and also modulate the key chemical mediators of inflammation, such as pro and anti-inflammatory cytokines. The main interest focused on monoterpenes were to develop the analgesic and anti-inflammatory drugs. In this review, we summarized current knowledge on monoterpenes that produce anti-inflammatory effects by modulating the release of cytokines, as well as suggesting that which monoterpenoid molecules may be most effective in the treatment of inflammatory disease. Several different inflammatory markers were evaluated as a target of monoterpenes. The proinflammatory and anti-inflammatory cytokines were found TNF-α, IL-1β, IL-2, IL-5, IL-4, IL-6, IL-8, IL-10, IL-12 IL-13, IL-17A, IFNγ, TGF-β1 and IFN-γ. Our review found evidence that NF-κB and MAPK signaling are important pathways for the anti-inflammatory action of monoterpenes. We found 24 monoterpenes that modulate the production of cytokines, which appears to be the major pharmacological mechanism these compounds possess in relation to the attenuation of inflammatory response. Despite the compelling evidence supporting the anti-inflammatory effect of monoterpenes, further studies are necessary to fully explore their potential as anti-inflammatory compounds.
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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.
Many diseases, such as inflammatory and central nervous system disorders, currently have a limited number of effective side-effect free treatments. Citronellol (CT) is a monoterpene alcohol present ...in the essential oil of several plants used in cooking and traditional medicine, such as those of the genus Cymbopogon and Citrus, with pharmacological activities already described in the literature. The aim of this review was to summarize the pharmacological activities already attributed to CT that could be used in treatments for humans. The databases PubMed, MedLine, Scopus, Lilacs and Scielo were searched using the terms “Citronellol” and “Drug effect”. 32 articles were identified and used in the study. Twenty-one articles demonstrated CT activities, including antibiotic and antifungal effects in vitro, and 11 properties including analgesic and anticonvulsant effects in vivo, besides presenting low toxicity. In view of the need to discover new drugs and the activities reported for CT, it can be stated that CT is a promising molecule to target in future pharmacological studies.
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•Several diseases do not yet have effective treatment without side effects, demonstrating the need for new drug discovery.•Natural products, especially terpenes, have been presented as promising alternatives for the discovery of new drugs.•Citronellol is a monoterpene present in the essential oil of several medicinal plants used in food.•Citronellol has several pharmacological activities, such as anti-inflammatory and analgesic that can be better investigated.•Citronellol presents low toxicological activity, making it an alternative in the search for new drugs.
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