ABSTRACT
OBJECTIVE: Gather scientific evidence on the application of inhalation aromatherapy for pain relief and estimate the effect measure of this practice on pain reduction. METHODS: Searches were performed in 2021 in the Pubmed, Scopus, Web of Science, Cochrane, Science direct, Lilacs, Scielo databases. We selected 44 articles demonstrating the effect of aromatherapy on different painful conditions, of which 17 were inserted in the meta-analysis. The risk of bias was assessed according to Cochrane methodology. RESULTS: In 35 (79.55%) studies was observed a significant reduction in pain, especially pain labor and postoperative pain. Through the meta-analysis, it was found that inhalation aromatherapy reduces by up to -1.73 points of the visual analog scale (VAS), indicating that this practice contributes to the reduction of pain perception in different painful conditions. In addition, the meta-analysis indicated that the time after inhalation, the type of oil used and the type of pain treated are important variables that interfere with the magnitude of the effect. These effects are attributed to the ability of essential oils to modulate nerve control centers and neurotransmission systems involved in pain control. CONCLUSION: From the gathering of articles on aromatherapy, it can be noted that aromatherapy appears to be helpful in alleviating acute pain, however there is an imminent need to improve aromatherapy studies to reduce the risk of bias and increase the power of its clinical evidence. PROSPERO: CRD42019121665.
Subject(s)
Aromatherapy , Oils, Volatile , Humans , Aromatherapy/methods , Pain Management , Oils, Volatile/therapeutic use , Pain Measurement , Pain, PostoperativeABSTRACT
BACKGROUND: Epilepsy affects more than 65 million people worldwide. Treatment for epileptic seizures is ineffective and has many adverse effects. For this reason, the search for new therapeutic options capable of filling these limitations is necessary. HYPOTHESIS/PURPOSE: In this sense, natural products, such as monoterpenes, have been indicated as a new option to control neurological disorders such as epilepsy. STUDY DESIGN: Therefore, the objective of this study was to review the monoterpenes that have anticonvulsive activity in animal models. METHODS: The searches were performed in the PubMed, Web of Science and Scopus databases in September, 2020 and compiled studies using monoterpenes as an alternative to seizure. Two independent reviewers performed the study selection, data extraction and methodological quality assessment using the Syrcle tool. RESULTS: 51 articles that described the anticonvulsant activity of 35 monoterpenes were selected with action on the main pharmacological target, including GABAA receptors, glutamate, calcium channels, sodium and potassium. In addition, these compounds are capable of reducing neuronal inflammation and oxidative stress caused by seizure. CONCLUSION: These compounds stand out as a promising alternative for acting through different pharmacological mechanisms, which may not only reduce seizure, but also promote neuroprotective effect by reducing toxicity in brain regions. However, further studies are needed to determine the mechanism of action and safety assessment of these compounds.
Subject(s)
Anticonvulsants/pharmacology , Monoterpenes/chemistry , Monoterpenes/pharmacology , Seizures/drug therapy , Animals , Brain/drug effects , Brain/metabolism , Humans , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Seizures/metabolismABSTRACT
BACKGROUND: Oncological pain is one of the most prevalent and difficult-to-treat symptoms in patients with cancer. p-Cymene (PC) is a monoterpene found in more than 100 different plant species, endowed with various pharmacological properties-particularly antinociceptive. HYPOTHESIS/PURPOSE: PC has antinociceptive effect in a model of oncologic pain due to the activation of the descending inhibitory pathway of pain. STUDY DESIGN: A pre-clinical, longitudinal, blind and randomized study. METHODS: Male Swiss mice were induced with S180 cells in the right hind paw, then treated daily with PC (12.5, 25 and 50â¯mg/kg, s.c.) and screened for mechanical hyperalgesia, spontaneous nociception, nociception induced by non-noxious palpation, tumor growth, changes in the neuromuscular function and existence of bone degradation in the tumor area. The effect of PC on Ca2+ currents (electrophysiological records), histological and neurochemical changes (immunofluorescence for Fos) were also evaluated. RESULTS: PC reduced (p < 0.05) the mechanical hyperalgesia, the spontaneous (p < 0.001) and non-noxious palpation (p < 0.001) nociceptions, not changing the tumor development, neuromuscular function or histopathological aspects of the paw affected. PC reduced Fos expression in the spinal cord (p < 0.001) and increased this expression in the PAG (p < 0.05) and in the NRM (p < 0.01). PC decreased the density of calcium channel currents (p < 0.05). CONCLUSION: These results suggest the antinociceptive effect of PC on oncologic pain, probably acting in both ascending and descending pain pathways, and modulating the calcium channel currents in order to exert its effects.
Subject(s)
Calcium/metabolism , Cancer Pain/drug therapy , Cymenes/pharmacology , Analgesics, Non-Narcotic/pharmacology , Animals , Cancer Pain/metabolism , Hyperalgesia/drug therapy , Male , Mice , Neurons/drug effects , Neurons/metabolism , Nociceptive Pain/drug therapy , Proto-Oncogene Proteins c-fos/metabolism , Random Allocation , Sarcoma 180/complications , Spinal Cord/drug effects , Spinal Cord/metabolismABSTRACT
BACKGROUND: Arthritis is a syndrome associated with exacerbated inflammation, joint destruction and chronic pain and disability. Chronic treatment of arthritis is associated with several side effects and high abandonment. Therefore, there has been an ongoing search for alternative treatments to overcome these problems. PURPOSE: Natural products, which are already widely used for their biological, cosmetic and pharmacotechnic properties, are a possible source for new drugs. Terpenes, a large class of organic compounds produced mainly by plants and trees, are a promising natural product and have already been shown to be effective in treating chronic pain, particularly of an inflammatory origin. STUDY DESIGN AND METHODS: This review identifies the main terpenes with anti-arthritic activity reported in the last 10 years. A survey was conducted between December 2017 and June 2018 in the PUBMED, SCOPUS and Science Direct databases using combinations of the descriptors terpenes, arthritis and inflammation. RESULTS: The results showed that terpenes have promising biological effects in relation to the treatment of arthritis, with the 24 terpenes identified in our survey being effective in the modulation of inflammatory mediators important to the physiopathology of arthritis, such as IL-6, IL-17, TNF-α, NFκB, and COX-2, among others. It is important to note that most of the studies used animal models, which limits, at least in part, the direct translation to humans of the experimental evidence produced by the studies. CONCLUSION: Together, our finds suggest that terpenes can modulate the immuno-regulatory and destructive tissue events that underlie the clinical presentation and the progression of arthritis and are worthy of further clinical investigation.
Subject(s)
Arthritis/drug therapy , Inflammation/drug therapy , Terpenes/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Arthritis/metabolism , Arthritis/physiopathology , Biological Products/pharmacology , Biological Products/therapeutic use , Cyclooxygenase 2/metabolism , Disease Models, Animal , Humans , Inflammation/metabolism , Inflammation Mediators/metabolism , Molecular Targeted Therapy/methods , NF-kappa B/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
INTRODUCTION: Terpenes are a class of secondary metabolites that can be found in a variety of animal and plants species. They are considered the most structurally diversified and abundant of all natural compounds. Several studies have shown the application of terpenes, such as carvacrol, linalool, and limonene in many pharmaceutical and medicinal fields, including cardiovascular disorders, the leading cause of death worldwide. AREAS COVERED: In this review, the authors outlined patents from the last 10 years relating to the therapeutic application of terpenes for the treatment and/or prevention of cardiovascular diseases found in different databases, emphasizing the possibility of these compounds becoming new drugs that may help to decrease the burden of these disorders. EXPERT OPINION: There has been a growing awareness over recent years of the therapeutic use of terpenes and their derivatives as new pharmaceutical products. Patents involving the use of terpenes have been especially important in the technological development of new strategies for the treatment of cardiovascular diseases by bringing new scientific knowledge into the pharmaceutical industry. Therefore, the development of biotechnologies using natural products should be encouraged in order to increase the variety of drugs available for the treatment of cardiovascular diseases.
Subject(s)
Cardiovascular Agents/therapeutic use , Cardiovascular Diseases/drug therapy , Terpenes/therapeutic use , Animals , Biological Products/chemistry , Biological Products/isolation & purification , Biological Products/therapeutic use , Biotechnology/methods , Cardiovascular Agents/chemistry , Cardiovascular Agents/isolation & purification , Cardiovascular Diseases/physiopathology , Drug Development , Humans , Patents as Topic , Terpenes/chemistry , Terpenes/isolation & purificationABSTRACT
INTRODUCTION: Fibromyalgia (FM) is a musculoskeletal condition characterized by chronic widespread pain, tenderness and often accompanied by other comorbid conditions such as depression, anxiety, chronic fatigue, among others. Now, we aimed to survey the recent patents describing new drugs or alternative therapy for FM. Areas covered: This review covers the therapeutic patents published between 2010 and 2017 from specialized search databases (WIPO, DERWENT, INPI, ESPANET and USPTO) that report the discovery of new drugs or pharmacologic alternative for the treatment of FM. Expert opinion: New therapeutic substances have been proposed in the last seven years. At least as it has been found in our survey, most are still in the pre-clinical phase of the study, and its clinical applicability is unclear. However, other therapeutic approaches were found in patents such as well-established drugs in the market in combination or drug repositioning that combines the 'new analgesic' effects with the old side effects. Hence, it is a safe approach for pharmaceutical market, but poorer to patients who need a radical innovation. So, there is the emerging need for further studies on the safety and efficacy of such therapeutic measures and the search for improvement of side effects, as well as the development of new drugs that are unorthodox for different FM symptoms.
Subject(s)
Drug Design , Drug Discovery/methods , Fibromyalgia/drug therapy , Analgesics/adverse effects , Analgesics/pharmacology , Analgesics/therapeutic use , Animals , Drug Repositioning , Fibromyalgia/physiopathology , Humans , Patents as TopicABSTRACT
BACKGROUND: Citronellal (CT) is a monoterpene with antinociceptive acute effect. ß-Cyclodextrin (ßCD) has enhanced the analgesic effect of various substances. HYPOTHESIS/PURPOSE: To evaluate the effect of CT both complexed in ß-cyclodextrin (CT-ßCD) and non-complexed, in a chronic muscle pain model (CMP) in mice. STUDY DESIGN: The complex containing CT in ßCD was obtained and characterized in the laboratory. The anti-hyperalgesic effect of CT and CT-ßCD was evaluated in a pre-clinical in vivo study in a murine CMP. METHODS: The complex was characterized through differential scanning calorimetry, derivative thermogravimetry, moisture determination, infrared spectroscopy and scanning electron microscopy. Male Swiss mice were pre-treated with CT (50mg/kg, po), CT-ßCD (50mg/kg, po), vehicle (isotonic saline, po) or standard drug (tramadol4 mg/kg, ip). 60 min after the treatment and then each 1h, the mechanic hyperalgesia was evaluated to obtain the time effect. In addition, the muscle strength using grip strength meter and hyperalgesia were also performed daily, for 7 days. We assessed by immunofluorescence for Fos protein on brains and spinal cords of mice. The involvement of the CT with the glutamatergic system was studied with molecular docking. RESULTS: All characterization methods showed the CT-ßCD complexation. CT-induced anti-hyperalgesic effect lasted until 6h (p <0.001) while CT-ßCD lasted until 8h (p <0.001vs vehicle and p <0.001vs CT from the 6th h). CT-ßCD reduced mechanical hyperalgesia on all days of treatment (p <0.05), without changing muscle strength. Periaqueductal gray (p <0.01) and rostroventromedular area (p <0.05) showed significant increase in the Fos protein expression while in the spinal cord, there was a reduction (p <0.001). CT showed favorable energy binding (-5.6 and -6.1) to GluR2-S1S2J protein based in the docking score function. CONCLUSION: We can suggest that ßCD improved the anti-hyperalgesic effect of CT, and that effect seems to involve the descending pain-inhibitory mechanisms, with a possible interaction of the glutamate receptors, which are considered as promising molecules for the management of chronic pain such as CMP.
Subject(s)
Aldehydes/chemistry , Aldehydes/pharmacology , Analgesics/pharmacology , Chronic Pain/prevention & control , Cymbopogon/chemistry , Hyperalgesia/prevention & control , Monoterpenes/chemistry , Monoterpenes/pharmacology , Myalgia/prevention & control , Oils, Volatile/chemistry , Oils, Volatile/pharmacology , beta-Cyclodextrins/chemistry , Acyclic Monoterpenes , Animals , Brain Chemistry/drug effects , Hand Strength , Male , Mice , Molecular Docking Simulation , Muscle Strength/drug effects , Spinal Cord/drug effects , Spinal Cord/metabolismABSTRACT
BACKGROUND: Annona vepretorum Mart. (Annonaceae) is a native tree from Caatinga (Brazilian Northeastern savanna biome), popularly known as "araticum" and "pinha da Caatinga". In this study, we investigated the effects of the crude ethanolic extract (Av-EtOH) in models of pain and inflammation in rodents. METHODS: The evaluation of antinociceptive activity was carried out by the acetic acid-induced writhing, formalin, hot plate and tail flick tests, while paw edema induced by carrageenan or histamine, and leukocyte migration to the peritoneal cavity were used for anti-inflammatory profile. Histological analyses also were carried out. RESULTS: Av-EtOH (25, 50 and 100 mg/kg, p.o) significantly reduced the number of writhing (P < 0.01) and decreased (P < 0.01) the paw licking time in both phases of the formalin test. In the hot plate and tail flick tests, this extract increased the reaction time, consequently reduced painful behavior. The effects in the formalin and hot plate tests were antagonized by naloxone. Av-EtOH inhibited significantly (P < 0.01) the increase in the edema volume after administration of carrageenan and histamine. In the peritonitis test, acute pre-treatment with Av-EtOH inhibited leukocyte migration. Histological analysis showed less inflammation in the groups treated with the extract when the inflammation was induced by carrageenan or histamine. CONCLUSION: Thus, Av-EtOH has significant antinociceptive and anti-inflammatory properties, which are related probably with the activation of opioid receptors and inhibition of release of mediators of the inflammatory process. This specie is a potential target for drug discovery.
Subject(s)
Analgesics , Annona/chemistry , Anti-Inflammatory Agents , Edema/drug therapy , Inflammation/drug therapy , Plant Extracts , Analgesics/pharmacology , Analgesics/therapeutic use , Animals , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Behavior, Animal/drug effects , Pain , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , RatsABSTRACT
INTRODUCTION: Ultraviolet irradiation has deleterious effects on human skin, including tanning, sunburn, cancer and connective tissue degradation (photoaging). Botanical antioxidants have been shown to be associated with reduced incidence of photocarcinogenesis and photoaging through their photoprotective profile. AREAS COVERED: Here, the authors summarized therapeutic patent applications concerning the employment of medicinal plants on the technological development of a formulation with photoprotective or photoaging application. So, the patent search was conducted in the databases WIPO, Espacenet, USPTO and Derwent, using the keywords - photoaging, photoprotection and the IPC A61K 8/97 (cosmetics or similar cleaning supplies obtained from vegetable origin, for example, plant extracts) and A61K 36/00 (medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, for example, traditional herbal medicines). We found 180 patents, out of which 25 were evaluated using inclusion criteria as application of natural products with photoprotective or photoaging application. EXPERT OPINION: We found that some patents related to the cosmetic compositions for improving skin wrinkle and either preventing or reducing the signs of photoaging and sunburn. The cosmetic compositions are manufactured in the form of a lotion, gel, soluble liquid, cream, essence, oil-in-water-type or water-in-oil-type formulation, containing the vegetal extracts as an active ingredient.
Subject(s)
Cosmetics/pharmacology , Plant Extracts/pharmacology , Sunscreening Agents/pharmacology , Animals , Antioxidants/isolation & purification , Antioxidants/pharmacology , Cosmetics/isolation & purification , Humans , Patents as Topic , Plants, Medicinal/chemistry , Skin/drug effects , Skin/radiation effects , Skin Aging/drug effects , Skin Aging/radiation effects , Skin Neoplasms/etiology , Skin Neoplasms/prevention & control , Sunscreening Agents/isolation & purification , Ultraviolet Rays/adverse effectsABSTRACT
INTRODUCTION: Terpenes are natural compounds found in several organisms belonging to the animal and plant kingdoms. They constitute the largest class of natural products with > 55,000 known compounds structurally diversified. Several studies have attributed to this big family of compounds a range of pharmacological properties, such as anticancer, antimicrobial, antifungal, antiviral, antihyperglycemic, analgesic, anti-inflammatory and antiparasitic. AREAS COVERED: In this review, the authors summarize therapeutic patent applications concerning the employment of terpenes for pain relief, focusing on the perspective for these compounds to become candidates for new drugs intended to control painful syndromes. EXPERT OPINION: Over years of tremendous academic and industrial investment in the characterization of the analgesic action of terpenes, there was the development of a successful product that has been well-accepted clinically. Furthermore, there is still hope that new therapeutic options for the control of painful syndromes will be developed from terpenes, which have been shown to be great candidates for this purpose because of the range of pharmacological mechanisms in important target sites.
Subject(s)
Analgesics/therapeutic use , Pain Management/methods , Pain/drug therapy , Terpenes/therapeutic use , Analgesics/chemistry , Animals , Cannabinoids/therapeutic use , Diterpenes/therapeutic use , Humans , Legislation, Drug , Molecular Structure , Monoterpenes/therapeutic use , Pain/diagnosis , Pain/physiopathology , Patents as Topic , Sesquiterpenes/therapeutic use , Structure-Activity Relationship , Terpenes/chemistry , Triterpenes/therapeutic useABSTRACT
There is still the need for efficacious therapies for pain. In the search for new therapeutic options, plants are a major source of novel biomolecules. Monoterpenes constitute 90% of essential oils, and there is a growing interest in understanding the mechanisms underlying their pharmacological activity. This systematic review reports what is so far known about the analgesic activity of monoterpenes and also provides an overview of their mechanisms of action. The search terms analgesia, anti-inflammatory, anaesthetic and antioxidant were used to retrieve English language articles in SCOPUS, PUBMED and EMBASE published between 1990 and 2012. Forty-five papers were found concerning the potential analgesic activity of 27 monoterpenes. The data reviewed here suggest these compounds are possible candidates for the treatment of painful conditions.
Subject(s)
Analgesia , Analgesics/therapeutic use , Monoterpenes/therapeutic use , Pain/drug therapy , Animals , Mice , Oils, Volatile/chemistry , Oils, Volatile/therapeutic use , RatsABSTRACT
This study reports a pharmacological evaluation of anti-inflammatory and anti-ulcer activities of carvacrol, a phenolic monoterpene constituent of essential oils produced by oregano and other several aromatic plants and spices, in experimental models of edema induced by different phlogistic agents and gastric lesions induced by acetic acid. In models of paw edema induced by dextran or histamine, carvacrol was effective at 50 mg/kg (46% and 35%, respectively); in these models, cyproheptadine reduced edema formation (61% and 43%, respectively). In edema induced by substance P, carvacrol (100 mg/kg) and ruthenium red (3 mg/kg) also decreased the edema formation (46% and 40%, respectively). Carvacrol significantly reduced the ear edema induced by 12-O-tetradecanoylphorbol acetate and arachidonic acid at 0.1 mg per ear (43% and 33%, respectively), similar to indomethacin at 0.5 mg per ear or 2.0 mg per ear (55% and 57%, respectively). Carvacrol (at doses of 25, 50, and 100 mg/kg) showed a healing capacity on gastric lesions induced by acid acetic (60%, 91%, and 81%, respectively) after 14 days of treatment. These results suggest that carvacrol acts on different pharmacological targets, probably interfering in release and/or synthesis of inflammatory mediators, such as the prostanoids, and thus favoring the healing process for gastric ulcers.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Anti-Ulcer Agents/pharmacology , Inflammation/drug therapy , Monoterpenes/pharmacology , Oils, Volatile/pharmacology , Origanum/chemistry , Stomach Ulcer/drug therapy , Animals , Arachidonic Acid/adverse effects , Cymenes , Edema/chemically induced , Edema/drug therapy , Female , Indomethacin/adverse effects , Male , Mice , Rats , Rats, Wistar , Ruthenium Red/pharmacology , Stomach Ulcer/chemically induced , Substance P/adverse effects , Tetradecanoylphorbol Acetate/adverse effects , Tetradecanoylphorbol Acetate/analogs & derivativesABSTRACT
We describe the antinociceptive and anti-inflammatory properties of citronellol (CT) in rodents. CT, a monoterpene alcohol, is a naturally occurring monoterpene compound prevalent in essential oils of various aromatic plant species, such as Cymbopogon citratus. In mice, when evaluated against acetic-acid-induced abdominal writhing, CT (25, 50 and 100 mg/kg, i.p.) reduced (P < 0.001) the amount of writhing compared to the control group. In the formalin test, CT also significantly inhibited both the early (neurogenic pain) and the late (inflammatory pain) phases of formalin-induced licking (P < 0.001). When assessed in a thermal model of pain, CT (100 mg/kg, i.p.) caused a significant increase (P < 0.05) in the latency response on the hot-plate test. Such results were unlikely to be caused by motor abnormality. The anti-inflammatory activity of CT was investigated through carrageenan-induced pleurisy in mice. Pretreatment with CT was able to inhibit both neutrophil infiltration and the increase in TNF-α level in the exudates from carrageenan-induced pleurisy. In in vitro experiments, CT (1 and 100 µg/ml) also decreased nitric oxide production by LPS-stimulated macrophage. Together, these results indicate that CT is effective as an analgesic compound in various pain models, with its action probably mediated by the inhibition of peripheral mediators as well as central inhibitory mechanisms that could be related to its strong antioxidant effect observed in vitro.
Subject(s)
Analgesics/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Monoterpenes/therapeutic use , Nociception/drug effects , Acetic Acid/toxicity , Acyclic Monoterpenes , Animals , Carrageenan/toxicity , Lipopolysaccharides/toxicity , Macrophages/drug effects , Macrophages/metabolism , Male , Mice , Nitric Oxide/metabolism , Pleurisy/chemically induced , Pleurisy/drug therapy , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Lippia gracilis Schauer is an aromatic plant widely found in Northeastern Brazil. The leaf infusions or decoctions and alcoholic macerate are used for some inflammatory diseases and headache. This paper reports the isolation of naringenin by semi-preparative liquid chromatography from the methanolic extract of L. gracilis (ELg) and the evaluation of the analgesic and anti-inflammatory activities of this extract by measuring nociception through acetic acid, formalin, and hot-plate tests in carrageenan-induced inflammation in mice. Following oral administration, ELg (100, 200, and 400 mg/kg) significantly reduced the number of writhes in the writhing test and the time of paw licks in both phases of the formalin test when compared to the control group animals. Mice treated with ELg did not exhibit any behavioral alteration during the hot plate and rota-rod tests, suggesting non-participation of the supraspinal components in the modulation of pain by ELg and no motor abnormality. The oral administration of 400 mg/kg of ELg produced an anti-inflammatory effect on peritonitis induced by carrageenan. These effects can be associated with a decrease of inflammatory mediator synthesis by compounds of ELg, such as naringenin, which has anti-inflammatory action as already described.
Subject(s)
Analgesics/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Lippia/chemistry , Pain/drug therapy , Plant Extracts/therapeutic use , Analgesics/chemistry , Animals , Anti-Inflammatory Agents/chemistry , Brazil , Male , Mice , Plant Extracts/chemistryABSTRACT
Carvacrol is a phenolic monoterpene present in the essential oil of the family Lamiaceae, as in the genera Origanum and Thymus. We previously reported that carvacrol is effective as an analgesic compound in various nociceptive models, probably by inhibition of peripheral mediators that could be related with its strong antioxidant effect observed in vitro. In this study, the anti-hypernociceptive activity of carvacrol was tested in mice through models of mechanical hypernociception induced by carrageenan, and the involvement of important mediators of its signaling cascade, as tumor necrosis factor-alpha (TNF-α), prostaglandin E(2) (PGE(2)), and dopamine, were assessed. We also investigated the anti-inflammatory effect of carvacrol on the model of carrageenan-induced pleurisy and mouse paw edema, and the lipopolysaccharide (LPS)-induced nitrite production in murine macrophages was observed. Systemic pretreatment with carvacrol (50 or 100 mg/kg; i.p.) inhibited the development of mechanical hypernociception and edema induced by carrageenan and TNF-α; however, no effect was observed on hypernociception induced by PGE(2) and dopamine. Besides this, carvacrol significantly decreased TNF-α levels in pleural lavage and suppressed the recruitment of leukocytes without altering the morphological profile of these cells. Carvacrol (1, 10, and 100 µg/mL) also significantly reduced (p < 0.001) the LPS-induced nitrite production in vitro and did not produce citotoxicity in the murine peritoneal macrophages in vitro. The spontaneous locomotor activity of mice was not affected by carvacrol. This study adds information about the beneficial effects of carvacrol on mechanical hypernociception and inflammation. It also indicates that this monoterpene might be potentially interesting in the development of novel tools for management and/or treatment of painful conditions, including those related to inflammatory and prooxidant states.
Subject(s)
Analgesics/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Inflammation/drug therapy , Monoterpenes/therapeutic use , Pain/drug therapy , Pleurisy/drug therapy , Analgesics/pharmacology , Animals , Anti-Inflammatory Agents/pharmacology , Behavior, Animal/drug effects , Carrageenan/adverse effects , Cell Survival/drug effects , Cymenes , Dinoprostone/adverse effects , Dopamine/adverse effects , Inflammation/physiopathology , Lipopolysaccharides/pharmacology , Macrophages, Peritoneal/drug effects , Macrophages, Peritoneal/metabolism , Male , Mice , Monoterpenes/pharmacology , Motor Activity/drug effects , Nitric Oxide/metabolism , Pain/chemically induced , Pain/physiopathology , Pleurisy/chemically induced , Pleurisy/metabolism , Tumor Necrosis Factor-alpha/adverse effects , Tumor Necrosis Factor-alpha/metabolismABSTRACT
The composition of three samples of essential oil (EO) extracted from the leaves and flowers of Hyptis fruticosa (Lamiaceae) were investigated by GC/MS and GC-FID. The variability of the constituents and biological activity were evaluated in the oil samples. Acetic acid-induced abdominal constrictions and formalin-induced pain tests in mice were used for screening the antinociceptive activity. The possible antagonism of the essential oils or morphine (MOR) antinociceptive effects by pretreatment with naloxone, showed no influence on the antinociceptive action of the oils in the acetic acid-induced writhing test. All examined oil samples presented antinociceptive activity. The oil sample obtained from the leaves collected during the vegetative growth stage, near São Cristóvão at Sítio Tujubeba exhibited the highest effect. The same oil sample had a main percentage of 1,8-cineole (18.70%). Nevertheless, the oil obtained from flowers collected at the same location, showed a significant difference (p < 0.05) in the response intensity in the first phase of paw licking (100 mg/kg) possibly due to the higher contents of α-pinene (20.51%) and ß-pinene (13.64%). The results provide evidence for the use of H. fruticosa by traditional medicine practitioners in the management of pain.
Subject(s)
Analgesics/pharmacology , Hyptis/chemistry , Nociception/drug effects , Oils, Volatile/pharmacology , Acetic Acid , Animals , Bicyclic Monoterpenes , Bridged Bicyclo Compounds/chemistry , Flowers/chemistry , Formaldehyde , Male , Mice , Monoterpenes/chemistry , Oils, Volatile/analysis , Plant Extracts/pharmacology , Plant Leaves/chemistryABSTRACT
CONTEXT: α-Terpineol (TPN) is a monoterpenoid alcohol present in the essential oils of several species of the Eucalyptus genus (Myrtaceae). OBJECTIVE: TPN was assessed for its antinociceptive activity in rodents. MATERIALS AND METHODS: The antinociceptive effect of TPN was examined using the acetic acid writhing reflex, formalin, glutamate, and capsaicin-induced nociception tests. RESULTS: TPN produced a significant (P < 0.01 or P < 0.001) analgesic effect by reduction at the early and late phases of paw licking and reduced the writhing reflex in mice (formalin and writhing tests, respectively). In the glutamate test, all doses of TPN produced significant (P < 0.01) nociceptive protection. When the capsaicin-induced nociception test was conducted, TPN produced dose-related inhibition of the nociceptive behavior. In addition, the results of a hot plate test showed central analgesic properties for TPN (P < 0.01 or P < 0.001). Such results were unlikely to be provoked by motor abnormality. CONCLUSION: Our results suggest that TPN might represent an important tool for management and/or treatment of painful conditions.
Subject(s)
Analgesics/pharmacology , Cyclohexenes/pharmacology , Monoterpenes/pharmacology , Pain Measurement/methods , Animals , Cyclohexane Monoterpenes , Drug Evaluation, Preclinical , Male , Mice , Motor Activity/drug effects , Rotarod Performance Test/methodsABSTRACT
We examined the antioxidant properties in vitro and the antinociceptive effect of carvacrol (CARV) in several models of pain in mice. CARV presented a strong antioxidant potential according to the TRAP/TAR evaluation; it also presented scavenger activity against nitric oxide and prevented lipid peroxidation in vitro. In mice, when evaluated against acetic acid-induced abdominal writhing, CARV (25, 50 and 100 mg/kg, i.p.) reduced (p < 0.001) the number of writhing compared to the control group, without opioid participation. In the formalin test, CARV also significantly inhibited both the early (neurogenic pain) and the late (inflammatory pain) phases of formalin-induced licking, with inhibition percentage values of 56.8% (100 mg/kg) for the neurogenic phase and 41.2% (25 mg/kg), 73.8% (50 mg/kg) and 99.7% (100 mg/kg) for the inflammatory phase. CARV also produced a significant inhibition of the pain caused by capsaicin (63.1, 67.1 and 95.8%, p < 0.001) and glutamate (46.4, 61.4 and 97.9%, p < 0.01). When assessed in a thermal model of pain, CARV (100 mg/kg, i.p.) caused a significant increase (p < 0.05) in the latency response on the hot-plate test. Such results were unlikely to be provoked by motor abnormality. Together, these results indicate that the properties of CARV should be more thoroughly examined in order to achieve newer tools for management and/or treatment of painful conditions, including those related to pro-oxidant states.
Subject(s)
Analgesics/pharmacology , Antioxidants/pharmacology , Monoterpenes/pharmacology , Pain Measurement , Pain/prevention & control , Animals , Capsaicin/pharmacology , Cymenes , Drug Evaluation , Formaldehyde/adverse effects , Male , Mice , Pain/chemically induced , Plant Extracts/pharmacology , Reaction TimeABSTRACT
Eugenia candolleana DC. (Myrtaceae), commonly known as "murta" or "murtinha", is a plant species without any chemical or pharmacological study described in the literature. It has been popularly used for the treatment of pain and fever. This report aimed to investigate the possible antinociceptive and anti-inflammatory effects of the essential oil extracted from fresh leaves of Eugenia candolleana DC. (EOEc) in rodents. Following intraperitoneal injection, EOEc (25, 50 and 100 mg/kg) reduced the number of writhes significantly in a writhing test and the number of paw licks during phase two of formalin test (p < 0.001). However, administration of EOEc did not alter the time of reaction in hot plate test. Furthermore, EOEc inhibited (p < 0.01) the carrageenan-induced leukocyte migration to the peritoneal cavity. These results indicate antinociceptive and anti-inflammatory properties of EOEc probably mediated via inhibition of prostaglandin synthesis or other peripherally pathway.
Eugenia candolleana DC. (Myrtaceae), conhecida popularmente como "murta" ou "murtinha", é uma espécie vegetal sem estudos químicos e farmacológicos descritos na literatura, distribuída no Nordeste brasileiro, principalmente, na Zona da Mata. Na medicina popular do Estado de Sergipe é utilizada no tratamento de distúrbios febris e da dor. O presente estudo buscou avaliar as possíveis atividades antinociceptiva e antiinflamatória do óleo essencial extraído das folhas de E. candolleana DC (OEEc) em roedores. A administração intraperitoneal (i.p.) do OEEc (25, 50 e 100 mg/kg) reduziu significativamente o número de contorções no teste das contorções abdominais e a duração da lambida da pata na segunda fase do teste da formalina (p < 0,001). Entretanto, a administração do OEEc não alterou o tempo de reação no teste da placa quente. No experimento de peritonite induzido por carragenina, o OEEc reduziu de forma significativa (p < 0,01) a migração de leucócitos para a cavidade peritoneal. Os resultados obtidos sugerem que o OEEc possui ação antinociceptiva, provavelmente mediado por mecanismos periféricos, e ação antiinflamatória.