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(À)-Linalool produces antinociception in two experimental models of pain
Abstract
Linalool is a monoterpene compound commonly found as a major component of the essential oils of several aromatic plant species, many of which are used in traditional medical systems as analgesic and anti-inflammatory remedies. We previously reported that (-)-linalool, the natural occurring enantiomer, plays a major role in the anti-inflammatory activity displayed by different essential oils, suggesting that linalool-producing species are potentially anti-inflammatory agents. In this study, the antinociceptive activity of (-)-linalool was examined in two different pain models in mice: the acetic acid-induced writhing response, a model of inflammatory pain, and the hot plate test, a model of supraspinal analgesia. Moreover, the effect of (-)-linalool on spontaneous locomotor activity (25, 50, 75 and 100 mg/kg) was evaluated. The results show that this compound induced a significant reduction of the acid-induced writhing at doses ranging from 25 to 75 mg/kg. Such effect was completely reversed both by the opioid receptor antagonist naloxone and by the unselective muscarinic receptor antagonist atropine. In the hot plate test, only the dose of 100 mg/kg of (-)-linalool resulted in a significant effect. (-)-Linalool induced a dose dependent increase of motility effects, thus ruling out the confounding influence of a possible sedative effect. The more pronounced effect of (-)-linalool on the writhing test with respect to the hot plate test is consistent with the observation that (-)-linalool possesses anti-inflammatory activity. Finally, the activation of opioidergic and cholinergic systems appears to play a crucial role in (-)-linalool-induced antinociception.
... There is significant literature suggesting linalool has uses as an antinociceptive agent. These studies have observed significant effects in multiple modes/models of nociception, including evoked thermal nociception in naıve animals (Peana et al., 2003(Peana et al., , 2004a(Peana et al., , 2006Tashiro et al., 2016), nocifensive behaviors induced by chemical irritants (Peana et al., 2003(Peana et al., , 2004aBatista et al., 2008;Sakurada et al., 2011;Katsuyama et al., 2015;Tashiro et al., 2016), and hyperalgesic and allodynic responses in inflammatory and neuropathic models (Peana et al., 2004b;Batista et al., 2010;Katsuyama et al., 2012;Kuwahata et al., 2013;Li et al., 2016). Within these studies, a range of routes of administration have been assessed, including systemic (intraperitoneal or subcutaneous) (Batista et al., 2008(Batista et al., , 2010Peana et al., 2003Peana et al., , 2004aPeana et al., ,b, 2006, oral (Batista et al., 2008), transdermal , intrathecal (Batista et al., 2008), local (intraplantar) (Batista et al., 2008;Sakurada et al., 2011;Katsuyama et al., 2012Katsuyama et al., , 2015Kuwahata et al., 2013), and even through inhalation (intranasal) (Tashiro et al., 2016). ...
... There is significant literature suggesting linalool has uses as an antinociceptive agent. These studies have observed significant effects in multiple modes/models of nociception, including evoked thermal nociception in naıve animals (Peana et al., 2003(Peana et al., , 2004a(Peana et al., , 2006Tashiro et al., 2016), nocifensive behaviors induced by chemical irritants (Peana et al., 2003(Peana et al., , 2004aBatista et al., 2008;Sakurada et al., 2011;Katsuyama et al., 2015;Tashiro et al., 2016), and hyperalgesic and allodynic responses in inflammatory and neuropathic models (Peana et al., 2004b;Batista et al., 2010;Katsuyama et al., 2012;Kuwahata et al., 2013;Li et al., 2016). Within these studies, a range of routes of administration have been assessed, including systemic (intraperitoneal or subcutaneous) (Batista et al., 2008(Batista et al., , 2010Peana et al., 2003Peana et al., , 2004aPeana et al., ,b, 2006, oral (Batista et al., 2008), transdermal , intrathecal (Batista et al., 2008), local (intraplantar) (Batista et al., 2008;Sakurada et al., 2011;Katsuyama et al., 2012Katsuyama et al., , 2015Kuwahata et al., 2013), and even through inhalation (intranasal) (Tashiro et al., 2016). ...
... These studies have observed significant effects in multiple modes/models of nociception, including evoked thermal nociception in naıve animals (Peana et al., 2003(Peana et al., , 2004a(Peana et al., , 2006Tashiro et al., 2016), nocifensive behaviors induced by chemical irritants (Peana et al., 2003(Peana et al., , 2004aBatista et al., 2008;Sakurada et al., 2011;Katsuyama et al., 2015;Tashiro et al., 2016), and hyperalgesic and allodynic responses in inflammatory and neuropathic models (Peana et al., 2004b;Batista et al., 2010;Katsuyama et al., 2012;Kuwahata et al., 2013;Li et al., 2016). Within these studies, a range of routes of administration have been assessed, including systemic (intraperitoneal or subcutaneous) (Batista et al., 2008(Batista et al., , 2010Peana et al., 2003Peana et al., , 2004aPeana et al., ,b, 2006, oral (Batista et al., 2008), transdermal , intrathecal (Batista et al., 2008), local (intraplantar) (Batista et al., 2008;Sakurada et al., 2011;Katsuyama et al., 2012Katsuyama et al., , 2015Kuwahata et al., 2013), and even through inhalation (intranasal) (Tashiro et al., 2016). The compiled literature provides compelling evidence for linalool acting as an antinociceptive compound, albeit with individual variability between studies. ...
Pain prevalence among adults in the United States has increased 25% over the past two decades, resulting in high health-care costs and impacts to patient quality of life. In the last 30 years, our understanding of pain circuits and (intra)cellular mechanisms has grown exponentially, but this understanding has not yet resulted in improved therapies. Options for pain management are limited. Many analgesics have poor efficacy and are accompanied by severe side effects such as addiction, resulting in a devastating opioid abuse and overdose epidemic. These problems have encouraged scientists to identify novel molecular targets and develop alternative pain therapeutics. Increasing preclinical and clinical evidence suggests that cannabis has several beneficial pharmacological activities, including pain relief. Cannabis sativa contains more than 500 chemical compounds, with two principle phytocannabinoids, Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). Beyond phytocannabinoids, more than 150 terpenes have been identified in different cannabis chemovars. Although the predominant cannabinoids, Δ9-THC and CBD, are thought to be the primary medicinal compounds, terpenes including the monoterpenes β-myrcene, α-pinene, limonene, and linalool, as well as the sesquiterpenes β-caryophyllene and α-humulene may contribute to many pharmacological properties of cannabis, including anti-inflammatory and antinociceptive effects. The aim of this review is to summarize our current knowledge about terpene compounds in cannabis and to analyze the available scientific evidence for a role of cannabis-derived terpenes in modern pain management. SIGNIFICANCE STATEMENT: Decades of research have improved our knowledge of cannabis polypharmacy and contributing phytochemicals, including terpenes. Reform of the legal status for cannabis possession and increased availability (medicinal and recreational) have resulted in cannabis use to combat the increasing prevalence of pain and may help to address the opioid crisis. Better understanding of the pharmacological effects of cannabis and its active components, including terpenes, may assist in identifying new therapeutic approaches and optimizing the use of cannabis and/or terpenes as analgesic agents.
... Regardless of the route of administration (subcutaneous, topical, intraplantar, oral, intraperitoneal, intrathecal), linalool produced antinociception against acute inflammatory pain induced by capsaicin (Sakurada et al., 2011), formalin (Katsuyama et al., 2015;Li et al., 2016;Peana et al., 2004a), carrageenan (Peana et al., 2004b), glutamate (Batista et al., 2008;Peana et al., 2004b) and prostaglandin E 2 (PGE 2 ) (Peana et al., 2004b). Similar results were demonstrated with acute orofacial inflammation (Venâncio et al., 2011), visceral pain (Peana et al., 2003), acute thermal pain (Peana et al., 2003;Peana et al., 2004a) and with linalool oxide (Souto-Maior et al., 2017). Linalool was also effective against persistent pain, including neuropathy induced by paclitaxel or nerve damage (Berliocchi et al., 2009;Batista et al., 2010;Kuwahata et al., 2013), muscle pain (Nascimento et al., 2014;de Araujo Andrade et al., 2020) and chronic inflammatory pain (Batista et al., 2010). ...
... Regardless of the route of administration (subcutaneous, topical, intraplantar, oral, intraperitoneal, intrathecal), linalool produced antinociception against acute inflammatory pain induced by capsaicin (Sakurada et al., 2011), formalin (Katsuyama et al., 2015;Li et al., 2016;Peana et al., 2004a), carrageenan (Peana et al., 2004b), glutamate (Batista et al., 2008;Peana et al., 2004b) and prostaglandin E 2 (PGE 2 ) (Peana et al., 2004b). Similar results were demonstrated with acute orofacial inflammation (Venâncio et al., 2011), visceral pain (Peana et al., 2003), acute thermal pain (Peana et al., 2003;Peana et al., 2004a) and with linalool oxide (Souto-Maior et al., 2017). Linalool was also effective against persistent pain, including neuropathy induced by paclitaxel or nerve damage (Berliocchi et al., 2009;Batista et al., 2010;Kuwahata et al., 2013), muscle pain (Nascimento et al., 2014;de Araujo Andrade et al., 2020) and chronic inflammatory pain (Batista et al., 2010). ...
... The mechanisms of action underlying linalool antinociception are diverse. Linalool reduced mechanical allodynia by decreasing spinal ERK activation and attenuated nociception through both central and peripheral opioid-related mechanisms (Peana et al., 2003;Sakurada et al., 2011;Kuwahata et al., 2013;Katsuyama et al., 2015). The antinociceptive properties of linalool have also been attributed to cholinergic, dopaminergic and local anesthetic mechanisms (Peana et al., 2004a). ...
Cannabis has been used for centuries for its medicinal properties. Given the dangerous and unpleasant side effects of existing analgesics, the chemical constituents of Cannabis have garnered significant interest for their antinociceptive, anti-inflammatory and neuroprotective effects. To date, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) remain the two most widely studied constituents of Cannabis in animals. These studies have led to formulations of THC and CBD for human use; however, chronic pain patients also use different strains of Cannabis (sativa, indica and ruderalis) to alleviate their pain. These strains contain major cannabinoids, such as THC and CBD, but they also contain a wide variety of cannabinoid and noncannabinoid constituents. Although the analgesic effects of Cannabis are attributed to major cannabinoids, evidence indicates other constituents such as minor cannabinoids, terpenes and flavonoids also produce antinociception against animal models of acute, inflammatory, neuropathic, muscle and orofacial pain. In some cases, these constituents produce antinociception that is equivalent or greater compared to that produced by traditional analgesics. Thus, a better understanding of the extent to which these constituents produce antinociception alone in animals is necessary. The purposes of this review are to (1) introduce the different minor cannabinoids, terpenes, and flavonoids found in Cannabis and (2) discuss evidence of their antinociceptive properties in animals.
... It has a sweet, floral aroma and is commonly used in perfumes and aromatherapy. LIN may also possess anti-inflammatory and sedative properties [62]. β-CAR is a natural sesquiterpene compound found in various plants, particularly in essential oils derived from spices such as black pepper, cloves, and oregano. ...
... Conversely, four out of the fourteen VOCs, namely β-PIN, β-MYR, IND, and MAT, were not detected to be emitted by the 'Brda', 'Lidka' and 'Zofia' cultivars ( Table 2). This is interesting since β-PIN and β-MYR are connected to antimicrobial properties [65,66], and IND is a molecule involved in a plant's defense responses [61,62,67]. Moreover, the β-PIN and β-MYR were found to be the least representative, being absent in four cultivars, 'Beata', 'Lidka', 'Polka', and 'Zofia'. ...
This study investigated the effects of Rhizoctonia solani J.G. Kühn infestation on the volatile organic compound (VOC) emissions and biochemical composition of ten cultivars of chrysanthemum (Chrysanthemum × morifolium /Ramat./ Hemsl.) to bring new insights for future disease management strategies and the development of resistant chrysanthemum cultivars. The chrysanthemum plants were propagated vegetatively and cultivated in a greenhouse under semi-controlled conditions. VOCs emitted by the plants were collected using a specialized system and analyzed by gas chromatography/mass spectrometry. Biochemical analyses of the leaves were performed, including the extraction and quantification of chlorophylls, carotenoids, and phenolic compounds. The emission of VOCs varied among the cultivars, with some cultivars producing a wider range of VOCs compared to others. The analysis of the VOC emissions from control plants revealed differences in both their quality and quantity among the tested cultivars. R. solani infection influenced the VOC emissions, with different cultivars exhibiting varying responses to the infection. Statistical analyses confirmed the significant effects of cultivar, collection time, and their interaction on the VOCs. Correlation analyses revealed positive relationships between certain pairs of VOCs. The results show significant differences in the biochemical composition among the cultivars, with variations in chlorophyll, carotenoids, and phenolic compounds content. Interestingly, R. solani soil and leaf infestation decreased the content of carotenoids in chrysanthemums. Plants subjected to soil infestation were characterized with the highest content of phenolics. This study unveils alterations in the volatile and biochemical responses of chrysanthemum plants to R. solani infestation, which can contribute to the development of strategies for disease management and the improvement of chrysanthemum cultivars with enhanced resistance to R. solani.
... Este monoterpeno apresenta várias atividades farmacológicas promissoras, tais como ação antinociceptiva e anti-inflamatória e causa redução da alodinia em modelos de dor neuropática [31][32][33] . Apresenta ainda atividade sedativa, com modulação glutamatérgica por mecanismos centrais 34 . ...
... O LIN é uma substância muito utilizada na indústria farmacêutica e de alimentos como fixador de fragrâncias e componente de produtos de perfumaria, sendo consumido há muito tempo em infusões/decocções de produtos naturais pela medicina popular para fins anti-inflamatórios, antinociceptivos e anti-hipertensivos 29,31,36 . ...
Introdução: O monoterpeno linalol (LIN) apresenta várias atividades farmacológicas, inclusive como anti-hipertensivo, porém, apresenta problemas de solubilidade devido ao seu caráter lipofílico. Dessa forma, estratégias de estabilização e melhoria de parâmetros farmacocinéticos e farmacodinâmicos vem sendo estudadas, como a formação de complexos de inclusão com ciclodextrinas (CDs). Objetivo: O objetivo desta revisão é reunir informações sobre os efeitos cardiovasculares do LIN e avaliar a possibilidade do uso de CDs para melhorar as propriedades biológicas do LIN. Metodologia: Esta revisão de literatura abrangeu artigos no período entre 1998 e 2022, coletadas nas bases de dados PUBMED, SciELO, LILACS e MEDLINE. Resultados: Em ratos normotensos, o LIN induziu hipotensão associada à taquicardia, enquanto em ratos hipertensos, reduziu a pressão arterial sem alterar a frequência cardíaca. O LIN tem ação direta sobre a vasculatura promovendo relaxamento vascular e melhora da função cardíaca. Interessantemente, a complexação de LIN com β-CDs melhorou a atividade anti-hipertensiva do monoterpeno. Conclusão: Foi evidenciado nesta revisão o potencial farmacológico do LIN como agente hipotensor, relaxante vascular e anti-hipertensivo. Além disso, há evidências que é possível melhorar o efeito anti-hipertensivo do LIN com a utilização de sistemas de inclusão com CDs, porém, estudos adicionais sobre este tema deverão ser realizados.
... [12][13][14] For example, in vivo studies have proven the analgesic and antinociceptive properties of linalool. 15,16 Nociception refers to the response of the sensory nervous system to a potentially noxious stimulus. Kuwahata et al. 17 conducted behavioral tests and observed that local intraplantar injection of linalool in mouse models with neuropathic hypersensitivity induced by partial sciatic nerve ligation (PSNL) resulted in a reduction in pain symptoms. ...
Developing effective and targeted drug delivery systems is crucial in searching for improved pain management strategies. Here, it is shown the preparation of a nanocarrier using chitosan hydrogel, and polymeric nanocapsules loaded with linalool for enhancing transdermal permeation and targeted delivery of this antinociceptive monoterpene for the pain treatment. Extensive characterization was conducted to evaluate the properties of the nanocarrier, and several in vitro studies were performed to investigate the release kinetics of linalool from the nanocarrier and its permeation through the layers of the skin. As results, the prepared polymeric nanocarrier exhibited an average size of 160 ± 9 nm, with a polydispersion index of 0.12 ± 0.01. The kinetic study revealed that the nanocarrier effectively controlled and prolonged the release of linalool, following a pseudo‐second order model (R² = 0.98). To evaluate the permeation of the nanocarrier through the transdermal barrier, swine ear skin was employed. The nanocarrier efficiently penetrated the transdermal barrier and successfully delivered linalool to the skin layers. Additionally, an in vivo toxicity study indicated no toxicity for the nanocarrier at the tested concentrations (<0.950 μg mL⁻¹). The release kinetics showed a controlled and sustained release of the linalool, suggesting its potential for prolonged therapeutic effects.
... Our analysis revealed significant insights into the binding interactions of the compounds with COX-1 (PDB ID: 5wbe) and COX-2 (PDB ID: 5ikq). Among the compounds investigated, some of them, like {1,6-octadien-3-ol, 3,7-dimethyl-}, isopulegol, and geranyl acetate, revealed analgesic behaviors (Nazimova et al., 2016;Peana et al., 2003Quintans-Júnior et al., 2013, while alpha-linolenic acid, {bicyclo[3.1.1]heptan-3one, 2,6,6-trimethyl-, (1.alpha.,2.beta.,5.alpha.)-}, ...
The medicinal potential of Coelogyne suaveolens , a traditional medicinal plant, was investigated through in vivo and molecular docking studies. The ethyl acetate fraction of the plant's acetonic extract was subjected to various bioactivity tests to assess its analgesic, anxiolytic, and sedative effects on Swiss albino mice. Furthermore, we used GCMS to identify the bioactive chemicals in the extract's ethyl acetate fraction. The root and bulb extracts demonstrated significant analgesic activity in acetic acid‐induced writhing, hot plate, and tail immersion tests in a dose‐dependent manner when compared to the control. Again, the extract exhibited moderate anxiolytic activity in the elevated plus maze test at a dosage of 400 mg/kg body weight, while the root extract showed significant anxiolytic activity in the hole board test at the same dosage. Significant sedative activity was observed in the hole cross, open field, and rotarod tests at a dosage of 400 mg/kg. According to molecular docking studies, the extract has the potential to serve as an analgesic medication by reducing the enzymatic activity of cyclooxygenases 1 and 2. Overall, the findings suggest that C. suaveolens has substantial therapeutic potential for the development of novel treatments for pain, anxiety, and sleep disorders.
... Indeed, a previous study demonstrated the anti-nociceptive effect of linalool both on the inflammatory pain induced by acetic acid during the writhing test, and on neurogenic pain during the hotplate test. 23 They also demonstrated the antinociceptive effect of linalool on formalin-induced pain during formaldehyde testing phases. 24 The anti-nociceptive properties of linalool have been mainly attributed to a positive effect on the opioid, dopaminergic and muscarinic signal pathways as well as to the negative modulation of glutamatergic pathway. ...
Abstract
Introduction: Solenostemma argel is a Saharan plant used in traditional medicine to cure pain. The present work investigated the quantitative
analysis of the composition of the essential oil of S. argel leaves (EOSA) as well as its acute toxicity and anti-nociceptive activity.
Materials and Methods: The chemical characterization of EOSA was carried out by GC-MS and NMR. EOSA acute oral toxicity study was
performed according to the OECD-420 method. EOSA anti-nociceptive activities were evaluated by acetic acid-induced abdominal writhing
test, hot plate test, and formalin test.
Results: Twenty components were identified by GC-MS including Linanool (57.10%), terpineol (12.95%), trans-geraniol (12.65%), and nerol
(4.67%). The main compound linalool was isolated by NMR. The EOSA at 250 and 400 mg/kg significantly attenuated acetic acid-induced
writhing by 72.71 and 92.41%, respectively. Moreover, Ingestion of EOSA at doses of 250 and 400 mg/kg caused a significant and dose�dependent anti-nociceptive effect in both neurogenic and inflammatory phases of formalin-induced licking. EOSA impacts the pain latency in
the hot plate test.
Conclusions: The results of this study showed that EOSA has an anti-nociceptive effect on central and peripheral pain.
Keywords: GC-MS, NMR, Acute Toxicity, Analgesic, Solenostemma argel
... A strong anti-inflammatory property was found in essential oil constituents, largely terpenoids and flavonoids. Peana et al. (2003), also studied anti-inflammatory, analgesic and edema-reducing properties of linalool from lavender oil and 1,8-cineole from eucalyptus oil, which are also present in O. basilicum in high percentage. According to Amrani et al. (2009) The protection and control of inflammatory airway disease with 1,8-cineole was also reported by Juergens et al. (2020) and according to Peana et al. (2002), linalool as well as its acetate derivatives play a vital role in anti-inflammatory activity, suggesting the essential oil rich in these constituents have potential to be used as anti-inflammatory agents. ...
Rich biodiversity of natural products offers a vast area for phytochemical and pharmacological investigations. Therefore, at present over 80% of known(approximately 30,000) natural products have originated from plants worldwide. Amongst some of the astonishing herbs, family Labiate (syn. Lamiaceae) includes more than 252 genera and 7000 species. The genus Ocimum
is one of the extensively used member of Lamiaceae family and comprising 150 species. This study elaborated the vast global applicability of Ocimum
bascilicum and Ocimum sanctum extracts as well as their essential oils in recent markets as important components in organic cosmetics, perfumery, food packaging, storages, neutraceuticals, ethnomedicinal, therapeutic and pharmacology. Moreover, O. bascilicum and O. sanctum could be an important valuable source of substances, which possesses remarkable antioxidant, antibacterial, antifungal, anti-hepatotoxicity, anticancer, antiviral, antidiabetic, antimicrobial, anti-inflammatory, analgesic and various other activities. Thus, a systematic review was performed toinvestigate the phytochemical and pharmacological potential of O. sanctum
and O. basilicum to search the possibilities of these metabolites in the health sector for discovery and development of new drugs. Additionally, essential oils of O. sanctum and O. basilicum were developed for the determination of various micro and nano herbal drug substances via nanotechnology. They also have important roles in emerging development of herbal cosmacuticals which reduces the risk of side effects of some synthetic chemicals.
In this context, the proposed chapter is the outcome of various collaborative works from all over the world, which includes a brief introduction along with historical content. Thereafter, phytochemistry and biological potential of extracts as well as essential oils of both species will be discussed. Ending section of this chapter highlights the advantages, conclusions and future prospectives.
... In addition, linalool lowered "nuclear factor-erythroid 2 ′′ levels, a modulator of anti-oxidant strain [56]. Also, linalool causes anti nociception when appraised in formalin and acetic-acid-mediated nociception in mice [36,37]. In addition, linalool had an analgesic impact in a study of acute pain mediated by paclitaxel, a commonly used chemotherapy substance [21]. ...
Interleukin-17 has a positive role in the initial induction and late chronic phases of many inflammatory disorders like arthritis. This cytokine has a strong option for therapeutic targeting due to the fact that it was found in the inflamed joints of individual with rheumatoid arthritis (RA) and persuasive evidence from experimental arthritis models indicating its pro-inflammatory actions. IL-17 suppression lessened the asperity of arthritis. The present study aimed to assess the anti-arthritic potential of linalool in a model of chronic joint inflammation (CFA-mediated rheumatoid arthritis) in rats. Linalool markedly lowered spleen and thymus indices as opposed to arthritic control. The over-formation of IL-17, COX-2, TNF-α IL-1β, iNOS and IL-6 were markedly impaired in all linalool treated rats, but IL-10 was raised as compared to arthritic animals in Real time-PCR. There was reduction in associated parameters like paw volume, arthritic index, mobility score, and flexion pain score and a marked increase in stance score in CFA model as compared to the arthritic control group. Furthermore, there was improvement in body weight, hematological, tissue, and radiological parameters in the CFA-model. Molecular docking study exhibited strong binding interaction of linalool with IL-17, PGE-2, iNOS and COX-2, thus providing a good correlation among experimental and theoretical results. The current findings show that linalool reduces adjuvant arthritis by suppressing pro-inflammatory mediators, arthritic development, and spleen and thymus indices. Thus, linalool may be employed therapeutically to alleviate arthritis in humans.
... Linalool was found to be more effective against Gram-positive bacteria than Gram-negative bacteria at a concentration of 0.1% (v/v), wherein its antibacterial property has been related to functional membrane destabilization and increased susceptibility of bacterial strains to conventional antimicrobial drugs [31] . Malassezia furfur, a fungus and a known cause of dandruff, has been found to be inhibited by O. sanctum by its antifungal properties [32] . However, there is no sufficient data to understand and provide a profound explanation of its activity against dandruff hence. ...
Dandruff is a common scalp disorder affecting almost 50% of the human population caused by M. globosa and M. furfur which are two naturally occurring skin fungus. This review discusses in detail the anatomy, pathophysiology, causes and symptoms, and treatment methods available for Dandruff. It also highlights the herbal ingredients with anti-dandruff activity that are used in novel shampoo formulations as a treatment strategy. This review discusses various bioactivities through which these compounds treat dandruff such as anti-inflammatory, antifungal, as well as their mechanism of action. Due to its amphibious status, dandruff is the most commercially exploited skin and scalp disorder/disease by personal care enterprises because there is less medical intervention for treatment.
... The blocking activity of naloxone, a particular antagonist of morphinomimetic receptors, supported this central analgesic action (Mundey et al., 2000). These results imply like other monoterpenes like citronellal , a-terpineol and linalool (Peana et al., 2003), C.T.'s analgesic efficacy may involve the opioid system. ...
... Lavender has antimicrobial activity against oral pathogens and antibiotic-resistant bacteria and has potent antioxidant effects [18]. The anti-analgesic effects of this herbal extract have been repeatedly evaluated and confirmed [19]. ...
Objectives:
In this study, natural substances were introduced as primary dental pulp caps for use in pulp therapy, and the antimicrobial and cytotoxic properties of these substances were investigated.
Materials and methods:
In this in vitro study, the antimicrobial properties of calcium-enriched mixture (CEM) cement, propolis, and propolis individually combined with the extracts of several medicinal plants were investigated against Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. Then, the cytotoxicity of each substance or mixture against pulp stem cells extracted from 30 primary healthy teeth was evaluated at 4 concentrations. Data were gathered via observation, and optical density values were obtained using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) test and recorded. SPSS software version 23 was used to analyze the data. Data were evaluated using 2-way analysis of variance and the Tukey test.
Results:
Regarding antimicrobial properties, thyme alone and thyme + propolis had the lowest minimum inhibitory concentrations (MICs) against the growth of S. aureus, E. coli, and P. aeruginosa bacteria. For E. faecalis, thyme + propolis had the lowest MIC, followed by thyme alone. At 24 and 72 hours, thyme + propolis, CEM cement, and propolis had the greatest bioviability in the primary dental pulp stem cells, and lavender + propolis had the lowest bioviability.
Conclusions:
Of the studied materials, thyme + propolis showed the best results in the measures of practical performance as a dental pulp cap.
... Activity: analgesic activity [100]; antibacterial, antifungal, antioxidant, anti-inflammatory, and anticancer activities [101]. ...
Orchids are widely used in traditional medicine for the treatment of a whole range of different health conditions, and representatives of the Neotropical subtribe Maxillariinae are not an exception. They are utilized, for instance, for their spasmolytic and anti-inflammatory activities. In this work, we analyze the literature concerning the chemical composition of the plant extracts and secretions of this subtribe's representatives published between 1991 and 2022. Maxillariinae is one of the biggest taxa within the orchid family; however, to date, only 19 species have been investigated in this regard and, as we report, they produce 62 semiochemicals of medical potential. The presented review is the first summary of biologically active compounds found in Maxillariinae.
... Borneol (a chemical variant of C. camphora) showed significant anti-nociceptive activity in various pain models [50]. Another constituent of Kafūr is linalool which has shown to ease pain and might be due to the suppression of proinflammatory cytokines and regulation of NMDA receptor [68] and eugenol, that block calcium from into the cell and thus loss the pain sensation [69]. C. camphora essential oils reduced serum and brain tissue nitric oxide and PGE2 levels. ...
The objective of present review was to provide comprehensive information on Cinnamomum camphora L. on its ethnomedicinal uses,
phytochemical, and pharmacological activities and provide insights into potential opportunities for future research. A thorough literature search
was done to gather all the available updates on Kafūr for its mizāj (temperament), medicinal properties, and traditional uses. Classical Unani books
and books on ethnomedicine and ethnobotany in English were referred for literature review. The information on phytochemical and
pharmacological activities of C. camphora was collected from PubMed, Science Direct, Google Scholar, and Research Gate using keywords C.
camphora, Kafū r, kapur, and camphor. The species name was checked with www. theplantlist. org. The material published in Urdu, Persian, Arabic,
and English was included in the review. C. camphora is used as an analgesic and antiseptic in Unani and other traditional systems of medicine for a
long. It possesses various bioactive compounds viz. terpenoids, flavonoids, glycosides, coumarins, fatty acids, lignans, alkaloids, etc. Out of all these,
camphor is one of the volatile compounds which has many pharmacological activities including anti-nociceptive, anti-oxidant, anti-bacterial, anti�microbial, wound healing, and hepatoprotective.
... The stem bark of U. chamae has antimicrobial activity (Ebi et al., 1999;Lim, 2012). The leaf extract of U. chamae (linalool) has antimicrobial activities (Peana et al., 2003). Several subfractions, containing glycosides (8, 11-15) and tannins (18), have shown activity against a number of microorganisms, being in some cases more active than penicillin G and chloramphenicol, several extracts of the species have shown antibacterial activity in vitro (Ogbulie et al., 2007;Lim, 2012). ...
Uvaria chamae P. Beauv is known as a key shrub species providing several goods and services for sustaining livelihoods in Sub-Saharan Africa. Despite its great medicinal importance for local communities, little is known about its conservation status and sustainable management strategies regarding the current overexploitation of the species’ fruits through traditional agroforestry systems. Here, we addressed a global systematic review of the current state of knowledge on several aspects of research of U. chamae for setting further breeding programmes and conservation initiatives. A total of 744 publications were identified based on the extensive bibliometric review of its sustainable management and conservation status over the last three decades (1991-2021) through existing online databases. Only 257 publications were finally included in the current review after deep scrutinization which were in line with several aspects of the conservation ecology and management of U. chamae in Africa. All retained papers came globally from the five sub-regions, and particularly 13 countries in Africa. Most of them were recorded in West Africa (n = 245) compared to the other sub-regions where few studies exist on this intensively harvested shrub species. Approximately 89% of the retained publications came from five of West African countries including Nigeria (n = 151), Benin (n = 30), Côte d'Ivoire (n = 18), Guinea (n = 16), and Togo (n = 14). In-depth bibliometric analysis revealed critical knowledge gaps on U. chamae in terms of its geographic distribution; conservation status; tree growth, productivity and propagation; morphological diversity; molecular genetic diversity; reproductive biology; ecophysiological performances; socio-economic importance; biochemical analysis; and structural characterization. The current review paves the way for developing further long-term management programs of U. chamae in Africa.
... Borneol (a chemical variant of C. camphora) showed significant anti-nociceptive activity in various pain models [50]. Another constituent of Kafūr is linalool which has shown to ease pain and might be due to the suppression of proinflammatory cytokines and regulation of NMDA receptor [68] and eugenol, that block calcium from into the cell and thus loss the pain sensation [69]. C. camphora essential oils reduced serum and brain tissue nitric oxide and PGE2 levels. ...
The objective of present review was to provide comprehensive information on Cinnamomum camphora L. on its ethnomedicinal uses, phytochemical, and pharmacological activities and provide insights into potential opportunities for future research. A thorough literature search was done to gather all the available updates on Kafūr for its mizāj (temperament), medicinal properties, and traditional uses. Classical Unani books and books on ethnomedicine and ethnobotany in English were referred for literature review. The information on phytochemical and pharmacological activities of C. camphora was collected from PubMed, Science Direct, Google Scholar, and Research Gate using keywords C. camphora, Kafūr, kapur, and camphor. The species name was checked with www. theplantlist. org. The material published in Urdu, Persian, Arabic, and English was included in the review. C. camphora is used as an analgesic and antiseptic in Unani and other traditional systems of medicine for a long. It possesses various bioactive compounds viz. terpenoids, flavonoids, glycosides, coumarins, fatty acids, lignans, alkaloids, etc. Out of all these, camphor is one of the volatile compounds which has many pharmacological activities including anti-nociceptive, anti-oxidant, anti-bacterial, anti-microbial, wound healing, and hepatoprotective.
... Gas chromatographymass spectrometry (GC-MS) analysis of the volatile oil of H. aromatica has shown the presence of different terpenoids with the chief constituent being linalool, the concentration of which ranges from 62.5% to 80% (5,7). Linalool is a noncyclic, alcoholic monoterpenoid of immense importance because of its wide range of therapeutic applications, which include antianxiety (11), anticonvulsant (12), anti-Alzheimer's (13), anti-inflammatory (14), analgesic (15), sedative (16), anti-leishmanial (17) and, molluscicidal (18). ...
Homalomena aromatica is a herb of tremendous ethnomedicinal importance to various communities residing in northeast India. In this study, a high-performance thin-layer chromatography–based densitometric method was developed for identification, quantification and stability study of linalool. Mass spectrometry was hyphenated to HPTLC for streamlining the method. The stability of linalool was studied by analyzing the effect of acid, base, UV, sunlight, thermal stress and H2O2 on linalool. The chromatographic plates were developed to a height of 70 mm in toluene:ethyl acetate solvent system at a ratio of 9.5:0.5 and visualized with p-anisaldehyde reagent. The developed method was found to be precise, accurate and reproducible according to International Conference on Harmonization guidelines, and compact bands of linalool were observed at Rf of 0.351 ± 0.001. The content of linalool in the volatile oil of H. aromatica was found to be 58% v/v. By application of the hyphenated MS technique, linalool was identified at m/z 137, (M + H)+. It was observed that acidic pH has the highest effect on linalool with a percentage degradation of 65. The developed method can be used in the analysis and quality control of herbal materials and volatile oils containing linalool and quality control of rhizomes of H. aromatica.
... Another leading mechanism proposed for migraine is the release of pro-inflammatory mediators (Aurora et al., 2011). Linalool has anti-inflammatory and analgesic effects, leading to migraine relief (Delavar Kasmaei et al., 2016;Peana et al., 2003). Linalool can be an antagonist of the glutamatergic receptor; thus, it can inhibit glutamate transmission and ameliorate migraine (Batista et al., 2008). ...
Coriandrum sativum (coriander) is an edible herb in the family Q1 Q2 Apiaceae. The leaves, fruits, and stems of C. sativum have long been used as culinary spice due to their favorable odor. Traditional practitioners used this plant for treating different diseases like blepharitis, scabies, aphthous stom-atitis, laryngitis, headache, and palpitation. In modern researches, coriander has demonstrated anxiolytic, anticonvulsant, antimigraine, neuroprotective, analgesic, diuretic, hypoglycemic, hypolipidemic, hypotensive, anticancer, and antioxidant activities. Coriander contains a wide range of bioactive phytochem-icals among which phenylpropenes, terpenoids, isocoumarins, phytosterols, and fatty acids are the most important. This review provides information about the botanical and ethnobotanical aspects, chemical profile, therapeutic uses in Islamic traditional medicine (ITM), and recent pharmacological studies of coriander effects. The results have shown that coriander and its monoterpenoid compound, linalool, can be considered as potential drug candidates for treating metabolic syndrome and different inflammatory conditions especially neural and CNS diseases.
... Terpenoids and flavonoids which are components of essential oils are known to have anti-inflammatory features and these properties reduce the absorption of prostaglandins (Krishan and Narang 2014). It is observed that other compounds which are found in EOs have pain reducing, edema relieving and anti-inflammatory characteristics e.g., 1,8-cineole (found in eucalyptus oil) and linalool from lavender oil (Peana et al. 2003). Other examples of plants which possess anti-inflammatory potential are anise, chamomile, liquorice and marigold (Srinivasan 2005). ...
Now-a-days poultry production has high demand all over the world and for this purpose performance parameters are maximized for example fast growing of chicken with low usage of feed and with better health status of the flock. This increasing demand has led to use of many antibiotic free products. There is an increased pressure to decrease the amount of antibiotics which is used as bacteriostatic or bactericidal agents for poultry so there is an utmost need for unconventional resolutions to sustain the productivity and efficacy of poultry. Amongst the substitutions, essential oils (EOs) have a prodigious potential and are usually thought to be natural, also free from hazardous deposits and chemicals and less toxic. EOs are plant-based extracts and there are about 3,000 known Eos out of which 300 are identified as useful and commercially important. It is proven that EOs have abundant in vitro and in vivo research to yield special effects on numerous pathogens including bacteria, viruses, fungi, and parasites. The current review provides information on the fundamentals of EOs, the anti-oxidation and immunomodulatory characteristics, the growth-promoting effects, and the activities of EOs against variety of pathogens in animals/poultry.
... However, the presence of the receptors. The beneficial effect of linalool in pentyletelrazole seizure models as well as its analgesic effects has been 22,23 suggested. , It can be suggested that the beneficial effects of the extracts which were observed in the present study are at least in part 24 due to linalool which is a main compound in coriander. ...
INTRODUCTION: Pain has been described by the International Association for the Study of Pain as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. Although NSAIDS and OPIOIDS are available for the treatment, still pain (chronic) is major problem. The present study was designed to study the analgesic effect of ethanolic extract of Coriandrum sativum using hot plate method and acetic acid induced writhing method in experimental animals (Swiss albino mice). MATERIAL AND METHODS:The analgesic effect of leaves and seeds of Coriandrum sativum was assessed using hot plate method and acetic acid induced writhing method in Swiss albino mice. The animals were treated with the ethanolic extract of leaves and seeds of Coriandrum sativum orally at two doses of 100, 500 mg/kg body weight after electric heat and acetic acid induced pain in mice. RESULTS: The study showed that ethanolic extract of leaves and seeds of Coriandrum sativum presented significant (p<0.05) and (p<0.05) analgesic activity in mice simultaneously. The data were analyzed by one-way ANOVA followed by Dunette's multiple comparison test. The results demonstrate that ethanolic extract of leaves and seeds of Coriandrum sativum has got analgesic potential. CONCLUSION: The results demonstrate that ethanolic extract of leaves and seeds of Coriandrum sativum has got significant analgesic effect.
... These antiinflammatory properties may explain the delayed onset and rapid disappearance of mild clinical signs and lesions post-NDV challenge in ACEO treated chickens. Also Peana et al. (2003) showed that essential oils have anti-inflammatory, pain-relieving, or edema-reducing properties, also Dorrigiv et al. (2021) showed that Allum cepa is a chelating agent with antioxidant effect, antiinflammatory, apoptosis suppression effect and signaling pathways modulation activity, which may explain the significant decrease (p 0.05) in pathological lesions scoring in ACEO treated groups G3 and G5 compared with the control group (G2), especially in lymphoid organs thymus, spleen, cecal tonsils and proventriculus beside brain tissue (cerebrum), indicating lowered NDV multiplication, antiviral and immune stimulant influence of ACEO onion extract against NDV experimental infection, these results 0.00 ± 0.00 c 0.00 ± 0.00 b 0.00 ± 0.00 b 0.00 ± 0.00 b 0.00 ± 0.00 c 0.00 ± 0.00 b G2 ...
Fifty broiler chicks were divided into five groups to study the antiviral and immune-stimulant effect of Allium cepa essential oils (ACEO). The effect of Allium cepa essential oils administration single or combined with NVD vaccine in broilers, more than one parameter was studied in this study i.e., the clinical symptoms that appeared on the chicks after the experimental infection with velogenic Newcastle disease virus, postmortem lesions, pathological lesions scoring, mortality rate (MR), and viral shedding, birds immunity was assessed by HI test and protection percent post-challenge with vNDV. Our result showed that mild clinical signs, lesion scoring, decreased viral shedding in ACEO treated groups 3 (G 3) more than control groups post-challenge with vNDV. Delayed onset of mild clinical signs in G3 followed by complete recovery 7th-day post-challenge (DPC). Low MR (40 and 0%) and high protection percent (100 and 60%) in ACEO treated G3 and G5, respectively. spleen, thymus, cecal tonsil, proventriculus, and cerebrum lesions scoring in G3 and G5 were significantly ((p ≤ 0.05).) lower than the control group, proving a decrease in NDV replication and effective antiviral activity of ACEO. HI titer significantly increased (p ≤ 0.05) In G3, G4 and G5 compared with control groups. There is no significant difference in HI titer in ACEO treated groups and vaccinated groups. In conclusion, oral administration of ACEO combined with NDV vaccines significantly reduces or eliminates lethal clinical signs, lesions, viral shedding, and enhances immune response and protection percent after vNDV challenge proving the natural antiviral and immune stimulant effect of ACEO onion extract. Implementing such a regime might aid NDV control in broiler flocks in endemic areas and reduce the epidemiological load of NDV in the environment.
... Among monocyclic monoterpenes, D-limonene and p-cymene have been shown to reduce allergic lung inflammation in mice (Amorim et al., 2016;Games et al., 2016;Hansen et al., 2016). Regarding the acyclic monoterpenes, linalool inhibits acute lung inflammation by producing IL-6, IL-1β, IL-8, TNF-α and monocyte chemoattractant protein-1 (MCP-1), which are involved in neuroinflammatory processes and several diseases (Peana et al., 2002;Peana et al., 2003;Sabogal-Guáqueta et al., 2016;Kim et al., 2019). Additionally, after in vitro studies, 1,8 cineole (Kahn et al., 2014), D-limonene (Shin et al., 2020) and β-caryophyllene (Hu et al., 2017) show inhibitory actions against neuro-inflammation. ...
The Mediterranean basin represents one of the key hotspots in terms of biodiversity and endemic floristic richness in the world (i.e., a reservoir of plant biodiversity). With ongoing climate change, the Mediterranean vegetation is increasingly exposed to different sources of environmental stresses, such as drought, heat, and solar irradiance. To cope with these severe abiotic stresses, beside morpho-anatomical traits, Mediterranean endemic species enhance the production of secondary metabolites, especially terpenes and polyphenols. These compounds have different roles in plants. Terpene and polyphenol compounds play a key antioxidant function (quenching Reactive Oxygen Species) thus improving ozone and drought tolerance, while also acting as pollinator attractors and repellents for dangerous herbivorous insects (contributing to the taste and odour of different plant tissues). In addition to their roles in plants, these bioactive compounds provide multiple health-promoting benefits for humans. Indeed, they can be used in different types of industries, such as pharmaceutical, nutraceutical, green (as supplements to fossil fuel and insecticides) and cosmetic industries. In conclusion, these compounds may be considered as key innovative components in different technological domains
... Linalool is a monoterpene compound present in essential oils from aromatic plants. Due to the presence in its structure of an asymmetry center, linalool exists in nature as racemate of the two enantiomers, sesses anti-hyperalgesic and anti-nociceptive effects in different animal models of pain ( Peana et al., 2003( Peana et al., , 2004a( Peana et al., , 2004b. The anti-nociceptive and anti-hyperalgesic properties of LIN have been ascribed to many factors including its capacity of stimulating the opioidergic, cholinergic and dopaminergic systems as well as its interaction with K + channels ( Peana et al., 2004a , b) or its negative modulation of glutamate transmission ( Peana et al., 2004a ;Batista et al., 2008 ). ...
Background
Oxidative stress plays an important role in neurodegeneration, pain and inflammation. (R)-(-)-linalool (LIN) is endowed with neuroprotective, anti-nociceptive and anti-inflammatory properties.
Purpose
The present study aims at investigating the hypothesis that LIN's neuroprotective, antinociceptive and anti-inflammatory properties descend from its ability to act as antioxidant. The study challenges this hypothesis by verifying whether LIN may counteract hydrogen peroxide (H2O2)-induced oxidative stress in PC12 cells.
Methods
In H2O2-exposed PC12 cells, LIN was tested on a) cell viability, measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), b) damage of plasma membrane, measured by lactate dehydrogenase (LDH) release, c) intracellular levels of reactive-oxygen-species (ROS), d) apoptosis and e) cell cycle distribution.
Results
Under H2O2-induced cell viability reduction, LIN protects PC12 cells. Likewise, LIN protects cells from oxidative damage by preventing the H2O2-dependent increase of LDH release, counteracts intracellular ROS overproduction and reduces H2O2-induced apoptosis. Finally, the results of the cell cycle analysis from cells exposed to H2O2 indicate that LIN incubation reduces the number of cells induced into quiescence by H2O2 in the G2/M phase.
Conclusions
These findings indicate that LIN protects PC12 cells from H2O2-induced oxidative stress. This mechanism could justify the neuroprotective, anti-nociceptive and anti-inflammatory effects of this compound and suggest LIN as a potential therapeutic agent for the management oxidative stress-mediated pain.
... Linalool is found in birch trees, coriander, citrus, lavender, laurels, rosewood, and many other plants. It presents properties like anti-nociception through activation of cholinergic and opioidergic systems (Peana et al., 2003), anti-anxiety/stress (Cline et al., 2008;Cheng et al., 2014), sedation (Buchbauer et al., 1991), anti-depressant, modulation of motor movements and locomotion (Cline et al., 2008), and anticonvulsant properties through anti-glutamatergic and GABA neurotransmitter systems (Elisabetsky et al., 1995;de Sousa et al., 2010). ...
Psychiatric disorders are frequently encountered in many neurological disorders, such as Alzheimer’s and Parkinson diseases along with epilepsy, migraine, essential tremors, and stroke. The most common comorbid diagnoses in neurological diseases are depression and anxiety disorders along with cognitive impairment. Whether the underlying reason is due to common neurochemical mechanisms or loss of previous functioning level, comorbidities are often overlooked. Various treatment options are available, such as pharmacological treatments, cognitive-behavioral therapy, somatic interventions, or electroconvulsive therapy. However oral antidepressant therapy may have some disadvantages, such as interaction with other medications, low tolerability due to side effects, and low efficiency. Natural compounds of plant origin are extensively researched to find a better and safer alternative treatment. Experimental studies have shown that phytochemicals such as alkaloids, terpenes, flavonoids, phenolic acids as well as lipids have significant potential in in vitro and in vivo models of psychiatric disorders. In this review, various efficacy of natural products in in vitro and in vivo studies on neuroprotective and their roles in psychiatric disorders are examined and their neuro-therapeutic potentials are shed light.
... In this study, we examined the contribution of orexinergic descending inhibition to the analgesic effect of linalool odor. In addition to the olfactory sensory route, systemic [43][44][45][46] or intrathecal 47 administration of linalool also mediate the analgesic effects. Though the involvement of adenosine A1 and A2a receptors for systemic administration-induced analgesic effect 45 , the involvement of orexinergic system for the analgesic effects of linalool via systemic rout has not yet examined and further analysis is required to address the point. ...
Linalool odor exposure induces an analgesic effect in mice. This effect disappeared in the anosmic model mice, indicating that olfactory input evoked by linalool odor triggered this effect. Furthermore, hypothalamic orexinergic neurons play a pivotal role in this effect. However, the neuronal circuit mechanisms underlying this effect have not been fully addressed. In this study, we focused on the descending orexinergic projection to the spinal cord and examined whether this pathway contributes to the effect. We assessed the effect of intrathecal administration of orexin receptor antagonists on linalool odor-induced analgesia in the tail capsaicin test. We found that the selective orexin type 1 receptor antagonist, but not the selective orexin type 2 receptor antagonist, prevented the odor-induced analgesic effect. Furthermore, immunohistochemical analyses of c-Fos expression induced by the capsaicin test revealed that neuronal activity of spinal cord neurons was suppressed by linalool odor exposure, which was prevented by intrathecal administration of the orexin 1 receptor antagonist. These results indicate that linalool odor exposure drives the orexinergic descending pathway and suppresses nociceptive information flow at the spinal level.
... [31] The essential oil of Erythrophleum suaveolens contained β-linalool (4.06%), a naturally occurring monoterpene alcohol found in flowers and plants. β-linalool is known to exhibit biological activities such as anti-inflammatory, [32] analgesic, [33] anticonvulsant, [34] sedative [35] and anti-anxiety, [36] βmyrcene (1.85%) is an acyclic monoterpene commonly found in nature alongside other terpenes essential oils. [37] β-myrcene has been proven to possess antiinflammatory, [38] anticonvulsant and anti-nociceptive activities. ...
The leaf of Erythrophleum suaveolens (E. suaveolens) is applied to wounds and also
used to repel pest and insects. However, there is no report on the chemical composition
of the leaf essential oil of the plant. This study aims to determine the chemical
composition and antimicrobial activity of the essential oil of the leaf of E. suaveolens.
The essential oil was obtained by hydrodistillation method with the aid of a Clavenger
type apparatus. The GC-MS analysis of the essential oil was done using Shimadzu QP2010plus GC-MS. Individual constituents were identified by comparing their mass
spectra with known compounds and NIST Mass Spectral Library. The antibacterial
activities of the essential oil against Staphylococcus aureus, Pseudomonas aeruginosa,
Klebsiella pneumonia, Escherichia coli, Candida albicans and Mycobacterium bovis
were evaluated using microdilution broth method using 96-well microplates.
Ciprofloxacin and Fluconazole were used as the standard drugs. The minimum
inhibitory concentration (MIC) value of the essential oil was also determined. The GCMS
analysis showed that the oil contained 10 compounds with α-citral, β-citral and
squalene as the major compounds at 36.96%, 25.41% and 20.07% respectively. Other
constituents were β-linalool (4.06 %), α-thujenal (3.73 %), hydroxylneoisolongifolane
(2.91%), β-myrcene (1.85%), 2-hydroperoxyhexane (1.82%), α-farnesene (1.61%) and
1,2-epoxy-3-propoxy propane (1.59%). The antimicrobial assay showed that the
essential oil possessed antimicrobial activity against E. coli with an MIC of 25μg/ml.
The isomeric composition of citral in E. Suaveolens is 59.3% α-citral and 40.7% βcitral.
The antimicrobial activity of the oil against E. coli may be due to high content of citral.
Ethnopharmacological relevance
Plants possess the ability to synthesize a diverse array of primary and secondary metabolites. Secondary metabolites are of great importance as a result of their status as natural substances that have the potential to provide therapeutic benefits for human health. Due to its many uses in traditional medicine, Syzygium guineense (Willd.) DC extracts have been the subject of numerous pharmacological studies. African traditional medicine uses it to treat a variety of ailments, including epilepsy, diarrhea, stomach pain, malaria, coughs, fractures, wounds, asthma, sore throats, intercostal pain, and as a tonic. No comprehensive reviews of S. guineense have been found, according to our literature search. Consider the great potential of S. guineense to serve as valuable sources of discovery of medicinal substances. Aim of the study: The study compiles ethnobotany, bioactive compounds, and pharmacology of Syzygium guineense.
Terpenes form part of a huge and diverse class of naturally occurring and volatile secondary metabolites produced by many plants, fruits, animals, insects, and other organisms. They are the largest group of naturally occurring metabolites, with over 55,000 types of terpenes produced by plants alone, primarily as essential oils. In humans, they contain significant biological properties such as antifungal, antiviral, antimicrobial, anti-inflammatory, antiparasitic, antihyperglycemic, anti-cancer, and analgesic agents. In plants, terpenes also play significant roles in defensive mechanisms against herbivores and invasive plants, disease resistance, chemical signaling and communication between plants, protection against photo-oxidation, plant-environment mediation, thermo-protection, and the attraction of pollinators. In addition, terpenes are responsible for a plant’s scent, taste, flavor, and pigmentation, leading to their commercial use as fragrances and food dyes. Terpenes are also used in the production of synthetic polymers, natural rubbers (polyisoprene), organic solvents, varnishes, inks, adhesives, cleaning products, biofuels, pesticides, and food and drink products. For these reasons, terpenes have significant value in modern medicine, pharmacy, nutraceuticals, cosmetics, and other industries.
Natural raw materials such as essential oils have received more and more attention in recent decades, whether in the food industry, as flavorings and preservatives, or as insecticides and insect repellents. They are, furthermore, very popular as fragrances in perfumes, cosmetics, and household products. In addition, aromatherapy is widely used to complement conventional medicine. This review summarizes investigations on the chemical composition and the most important biological impacts of essential oils and volatile compounds extracted from selected aromatic blossoms, including Lavandula angustifolia, Matricaria recutita, Rosa x damascena, Jasminum grandiflorum, Citrus x aurantium, Cananga odorata, and Michelia alba. The literature was collected from PubMed, Google Scholar, and Science Direct. Blossom essential oils discussed in this work are used in a wide variety of clinical issues. The application is consistently described as safe in studies and meta-analyses, although there are notes that using essential oils can also have side effects, especially dermatologically. However, it can be considered as confirmed that essential oils have positive influences on humans and can improve quality of life in patients with psychiatric disorders, critically ill patients, and patients in other exceptional situations. Although the positive effect of essential oils from blossoms has repeatedly been reported, evidence-based clinical investigations are still underrepresented, and the need for research is demanded.
Various plant species from the Litsea genus have been claimed to be beneficial for pain relief. The PRISMA approach was adopted to identify studies that reported analgesic properties of plants from the Litsea genus. Out of 450 records returned, 19 primary studies revealed the analgesic potential of nine Litsea species including (1) Litsea cubeba, (2) Litsea elliptibacea, (3) Litsea japonica, (4) Litsea glutinosa, (5) Litsea glaucescens, (6) Litsea guatemalensis, (7) Litsea lancifolia, (8) Litsea liyuyingi and (9) Litsea monopetala. Six of the species, 1, 3, 4, 7, 8 and 9, demonstrated peripheral antinociceptive properties as they inhibited acetic-acid-induced writhing in animal models. Species 1, 3, 4, 8 and 9 further showed effects via the central analgesic route at the spinal level by increasing the latencies of heat stimulated-nocifensive responses in the tail flick assay. The hot plate assay also revealed the efficacies of 4 and 9 at the supraspinal level. Species 6 was reported to ameliorate hyperalgesia induced via partial sciatic nerve ligation (PSNL). The antinociceptive effects of 1 and 3 were attributed to the regulatory effects of their bioactive compounds on inflammatory mediators. As for 2 and 5, their analgesic effect may be a result of their activity with the 5-hydroxytryptamine 1A receptor (5-HT1AR) which disrupted the pain-stimulating actions of 5-HT. Antinociceptive activities were documented for various major compounds of the Litsea plants. Overall, the findings suggested Litsea species as good sources of antinociceptive compounds that can be further developed to complement or substitute prescription drugs for pain management.
Pain is characterized by the unpleasant sensory and emotional sensation associated with actual or potential tissue damage, whereas nociception refers to the mechanism by which noxious stimuli are transmitted from the periphery to the CNS. The main drugs used to treat pain are nonsteroidal anti-inflammatory drugs (NSAIDs) and opioid analgesics, which have side effects that limit their use. Therefore, in the search for new drugs with potential antinociceptive effects, essential oils have been studied, whose constituents (monoterpenes) are emerging as a new therapeutic possibility. Among them, linalool and its metabolites stand out. The present study aims to investigate the antinociceptive potential of linalool and its metabolites through a screening using an in silico approach. Molecular docking was used to evaluate possible interactions with important targets involved in antinociceptive activity, such as α2-adrenergic, GABAergic, muscarinic, opioid, adenosinergic, transient potential, and glutamatergic receptors. The compounds in the investigated series obtained negative energies for all enzymes, representing satisfactory interactions with the targets and highlighting the multi-target potential of the L4 metabolite. Linalool and its metabolites have a high likelihood of modulatory activity against the targets involved in nociception and are potential candidates for future drugs.
Pain continues to be an enormous global health challenge, with millions of new untreated or inadequately treated patients reported annually. With respect to current clinical applications, opioids remain the mainstay for the treatment of pain, although they are often associated with serious side effects. To optimize their tolerability profiles, medicinal chemistry continues to study novel ligands and innovative approaches. Among them, natural products are known to be a rich source of lead compounds for drug discovery, and they hold potential for pain management. Traditional medicine has had a long history in clinical practice due to the fact that nature provides a rich source of active principles. For instance, opium had been used for pain management until the 19th century when its individual components, such as morphine, were purified and identified. In this review article, we conducted a literature survey aimed at identifying natural products interacting either directly with opioid receptors or indirectly through other mechanisms controlling opioid receptor signaling, whose structures could be interesting from a drug design perspective.
Natural products have dominated our lives since ancient times. Today, they are an inexhaustible source of new medications for disease treatment. The practice of evaluating bioactive compounds extracted from natural sources has also advanced significantly, prompting a need to understand current methods to identify and evaluate them.
This book covers basic scientific aspects of preclinical research on natural products for specific conditions and diseases. These include aging, gynecological disorders, inflammatory disorders, renal disorders and cardiovascular disorders. Each of the 10 book chapters give a structured overview on preclinical methods on the etiology of diseases, natural products as the materials for the bioassays, extract types, concentration of the extracts/compounds for in vitro and in vivo assays, preparation of the test materials, application of the test materials, step-by-step methods and related calculations.
The book is intended as a quick reference for natural product researchers, pharmacists and postgraduate students in pharmacognosy. Medical doctors working in preclinical research on natural products will also benefit from the information provided.
Lavender essential oil is economically important and widely used in aromatherapy perfumery, food industry and pharmacy. Bulgaria is a global leader in lavender cultivation overtaking countries such as France, UK, China, India, and Spain during the last few years. The aim of this research is: 1) to characterize a lavender essential oil sample obtained from agricultural plantation near Pomorie, Bulgaria; 2) to perform descriptive statistical test based on a data set of 13 samples available in 4 publications, 3) to compare the varieties regarding the quantity of the most important components such as linalool and linalyl acetate 4) to summarize the pharmacological effects of the main components. As a result of GS/MS analysis of the essential oil sample obtained from agricultural plantation near Pomorie, we identified 44 compounds. The major constituents were linalyl acetate (27.5%) linalool (24.1%), E -β-ocimene (7.0%), terpinen-4-ol (5.1%) caryophyllene (4.5%), carvacrol (4.4%), lavandulyl acetate (3.5%), Z -β-farnesene (3.3%), and - Z -β-ocimene (3.2%). Linalool and linalyl acetate are the main ingredients based on which the quality of the essential oil is evaluated. In the studied samples they fluctuated between varieties depending on the year of extraction and the locations of origin in Bulgaria. Some varieties were characterized by a more stable ratio of linalool – linalyl acetate, compared to others. The main other components of our sample as well as the other examined Bulgarian samples fit the standards according to the requirements of ISO (2002) and the of European Pharmacopoeia (10 th edn., Council of Europe 2020) with few exceptions. Lavender oil has numerous pharmacological applications based on its anxiolytic, sedative, antioxidant, anti-inflammatory, antitumor and antimicrobial activities. Although linalool and linalyl acetate largely contribute to these effects, the overall efficacy of lavender oil is proven to be due synergistic relationships between the components.
Ethnopharmacological relevance:
Lippia lacunosa Mart. & Schauer is an endemic plant from the Serra do Espinhaço mountain range located on the Atlantic plateau, Brazil. It is known as "chá de pedestre" and "rosmaninho" in folk medicine. This species has a characteristic mango aroma and is widely used by the population for flu, colds, sinus infections, coughing, relaxing baths, and foot baths after long walks. It is often confused with and, therefore, used interchangeably with L. rotundifolia and L. pseudothea.
Aim of the study:
This study aimed to increase scientific knowledge on the ethnopharmacological use of Lippia lacunosa through the evaluation of the micromolecular composition and anti-inflammatory and antinociceptive activities of the hexane and ethanolic extracts, essential oil, and fractions in mice.
Materials and methods:
The chemical profile of L. lacunosa extracts and fractions were obtained by chromatographic methods such as Ultra-Performance Liquid Chromatography (UPLC), Gas Chromatography (GC), Column Chromatography (CC), and Thin Layer Chromatography (TLC). Carrageenan-induced paw edema was used to investigate the anti-inflammatory activity in mice. Mechanical allodynia induced by carrageenan and hot plate tests were employed to evaluate the antinociceptive activity.
Results:
The main constituents found in the essential oil were the monoterpenes myrcene (13.81%), linalool (6.84%), ipsenone (21.2%), and myrcenone (25.44%); and sesquiterpenes elemol (7.30%) and spathulenol (3.15%). The chromatograph fractionation of essential oil yielded a fraction rich in the main compounds (F33), ipsenone and mircenone. In experimental models of paw edema and mechanical allodynia induced by carrageenan (600 μg, 30 μL, i.pl.), the administration of hexane extract, essential oil (50 or 100 mg/kg, p.o.) or majority fraction (10 mg/kg, p.o.) reduced paw edema. The ethanolic extract (100 mg/kg) reduced mechanical allodynia only in the 2 nd h of evaluation. On the other hand, the hexane extract (50 or 100 mg/kg) and essential oil (100 mg/kg), as well as the majority fraction (10 mg/kg), reduced mechanical allodynia throughout the evaluation period. The hexane extract, essential oil, and majority fraction F33 also reduced the heat-induced nociceptive response. Also, majority fraction F33 did not affect the time mice spent in the rota-rod apparatus.
Conclusions:
The elucidation of the composition of the essential oil and the demonstration of the activity of L. lacunosa in experimental models of acute inflammation and also in models of nociceptive and inflammatory pain can help to increase knowledge on the ancient ethnopharmacological use by the Bandeirantes, aiming at the evaluation of the species as a candidate for herbal medicine or phytopharmaceutical in the treatment of patients with inflammatory and painful conditions.
Lavender (Lavandula angustifolia L.) is one of the world's top 15 most traded essential oil plants. Lavender oil is obtained from lavender which is widely used as an independent alternative medication as well as a component in medicine and cosmetic products. Lavender oils include over 100 chemicals, with linalool and linalyl acetate being the two most prominent. Furthermore, it also contains phytosterols, coumaric acid, anthocyanins, monosaccharides, valeric acid, glycolic acid and its esters, ursolic acid, coumarin, and herniarin. These components are beneficial for human health due to their functional and nutraceutical properties. Moreover, lavender oil has many nutritional and therapeutic effects, i.e., antiinflammatory, antioxidant, hypnotic, antidepressant, anticonvulsive, antihair fall, antimicrobial, and antifibrotic. Due to its antimicrobial activity, it is also used as preservative agent in many food products. Furthermore, it is also used in many food, cosmetics, and pharmaceutical industries as a functional ingredient. In this chapter, we discussed the historical background, production, nutritional composition, and therapeutic potential of lavender oil.
In the present investigation the chemical composition and biological activities of essential oils (EOs) of the five Strobilanthes species viz., S. angustifrons C. B. Clarke, S. pentastemonoid M, (Nees) T. Anderson, S. tomentosa (Nees) J.R.I.Wood, S. attenuata (Wall. ex Nees) Jacq. ex Nees and S. glutinosa (Nees) collected from different locations of Kumaon region, Uttarakhand, India were examined and reported for the first time. The essential oils were analysed for their chemical composition by GC-MS. The yield of the hydro distilled essential oils was ranging from 0.2 to 0.3% (v/w). GC-MS results revealed a wide variability in the chemical composition among the studied Strobilanthes species. Among the biological activities, highest anti-inflammatory activity was recorded for S. angustifrons EO (IC 50 = 9.6 ± 0.57 μL/mL). Highest antioxidant activity in terms of DPPH and metal chelating activity was shown by S. pentastemonoid EO (IC 50 = 15.32 ± 0.48 μL/mL and 23.29 ± 0.13 μL/mL, respectively). Highest antioxidant activity in terms of H 2 O 2 scavenging activity and highest antidiabetic activity was shown by S. attenuate EO (IC 50 = 21.82 ± 0.53 μL/mL) and S. tomentosa EO (IC 50 = 21.82 ± 0.53 μL/mL), respectively. The biological activity data revealed the significant antioxidant, anti-inflammatory and antidiabetic activities of the studied Strobilanthes species. Therefore, the essential oils of these species can be a good natural product to be used as ecofriendly antioxidant, anti-inflammatory and antidiabetic agents.
The Mediterranean basin represents a rich source of medicinal and aromatic plants. These species contain different metabolites such as phenolics, flavonoids, tannins, coumarins and sterols known for their beneficial properties. The essential oils (EOs) of Lavandula austroapennina and Lavandula angustifolia from the Pollino massif (southern Italy) were characterized using gas chromatography-mass spectrometry and their anti-denaturation effect was assessed using in vitro models with heat-treated bovine serum albumin (BSA) chosen as a protein model. L. austroapennina EO showed a better in vitro anti-denaturation activity compared to L. angustifolia, with IC50 values equal to 260.4 ± 4.2 and 480.0 ± 2.6 µg/mL, respectively. In order to relate the observed results to the most interesting identified phytochemicals, some major components were also tested. Linalool and terpinen-4-ol proved to be effective in protecting BSA from heat denaturation. Moreover, the inhibitory properties on nitric oxide production were verified in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Both lavender EOs showed concentration-dependent inhibitory properties, as well as the monoterpene linalool. Taken together, these results suggest that L. austroapennina EO and its main constituent linalool could be good candidates for further investigations, aimed at finding new drugs with anti-arthritic potential.
Visceral pain (VP) is the organ-derived nociception in which increased inflammatory reaction and exaggerated activation of the central nucleus of the amygdala (CeA) may contribute to this deficiency. Considering the amygdala also serves as the integration center for olfaction, the present study aimed to determine whether olfactory stimulation (OS) would effectively depress over-activation and inflammatory reaction in CeA, and successfully relieve VP-induced abnormalities. Adult rats subjected to intraperitoneal injection of acetic acid inhaled lavender essential oil for 2 or 4 h. The potential benefits of OS were determined by measuring the pro-inflammatory cytokine level, intracellular potassium and the upstream small-conductance calcium-activated potassium (SK) channel expression, together with detecting the stress transmitters that participated in the modulation of CeA activity. Results indicated that in VP rats, strong potassium intensity, reduced SK channel protein level, and increased corticotropin-releasing factor, c-fos, and substance P immuno-reactivities were detected in CeA. Enhanced CeA activation corresponded well with increased inflammatory reaction and decreased locomotion, respectively. However, in rats subjected to VP and received OS, all above parameters were significantly returned to normal levels with higher change detected in treating OS of 4h. As OS successfully depresses inflammation and CeA over-activation, application of OS may serve as an alternative and effective strategy to efficiently relieve VP-induced deficiency.
Nature offers us spices, which are a significant part of healthy and nutritious foods. The presence of abundant bioactive compounds in these spices makes them interesting from a scientific and health perspective. Extracts obtained from spice materials possess many health benefits and are rich sources of antioxidants, which suppress reactive oxygen species.
Spice Bioactive Compounds: Properties, Applications, and Health Benefits collects such information together in one book, presenting all necessary features related to spices and their properties. Exploring the most recent research related to the extraction, isolation, encapsulation, identification, and characterization of bioactive compounds present in spices, this book also covers the health element of spices and its utilization as a treatment for various disorders.
Key Features:
Discusses about 14 different spices and their salient features
Presents the novel technologies used in the extraction, isolation, and identification of bioactive compounds from spices
Explores the utilization of spices for culinary use in food
Industries such as the food and pharmaceutical industries have great interest in the use of bioactive compounds for the production of drugs and functional foods. Written by experts in their field, this book will be useful to anyone in either industry, as well as those who have an interest in the use of such bioactive compounds for the production of drugs and functional foods.
Aim- To evaluate the analgesic activity of the aqueous and ethanolic extracts Coriandrum sativum (C. sativum) seeds by thermal pain stimulus. Materials & methods- After an acute toxicity study performed as per OECD-425 Guidelines, doses of 100 mg/kg, 250 mg/kg and 500 mg/kg of each extract were selected. Wistar albino rats of either sex (100-200 g) were tested for the mean response time by Eddy’s hot plate method. Statistical significance (p<0.05) was analyzed using ANOVA with post-hoc Dunnett’s test. Results- Both the aqueous and ethanolic extracts showed significant and dose-dependent analgesic activity. The activity of aqueous extracts peaked at 30 min with the mean response time increasing to 5.90s, 5.92s and 6.10s with the 100 mg/kg, 250 mg/kg and 500 mg/kg doses respectively while the activity of ethanolic extracts peaked at 60 min with the mean response time increasing to 5.02s, 6.52s and 6.75s with the 100 mg/kg, 250 mg/kg and 500 mg/kg doses respectively. Conclusion- Coriandrum sativum is a plant with analgesic potential. However, further evaluation is required for analysis of the phytochemical constituents responsible for this activity.
Essential oils (EOs) have been traditionally used as ancient remedies to treat many health disorders due to their enormous biological activities. As mainstream allopathic medication currently used for CNS disorders is associated with adverse effects, the search to obtain safer alternatives as compared to the currently marketed therapies is of tremendous significance. Research conducted suggests that concurrent utilization of allopathic medicines and EOs is synergistically beneficial. Due to their inability to show untoward effects, various scientists have tried to elucidate the pharmacological mechanisms by which these oils exert beneficial effects on the CNS. In this regard, our review aims to improve the understanding of EOs’ biological activity on the CNS and to highlight the significance of the utilization of EOs in neuronal disorders, thereby improving patient acceptability of EOs as therapeutic agents. Through data compilation from library searches and electronic databases such as PubMed, Google Scholar, etc., recent preclinical and clinical data, routes of administration, and the required or maximal dosage for the observation of beneficial effects are addressed. We have also highlighted the challenges that require attention for further improving patient compliance, research gaps, and the development of EO-based nanomedicine for targeted therapy and pharmacotherapy.
The search for molecules that contribute to the relief of pain is a field of research in constant development. Lamiaceae is one of the most recognized families world-wide for its use in traditional medicine to treat diseases that include pain and inflammation. Mexico can be considered one of the most important centers of diversification, and due to the high endemism of this family, it is crucial for the in situ conservation of this family. Information about the most common genera and species found in this country and their uses in folk medicine are scarcely reported in the literature. After an extensive inspection in bibliographic databases, mainly Sciencedirect, Pubmed and Springer, almost 1200 articles describing aspects of Lamiaceae were found; however, 217 articles were selected because they recognize the Mexican genera and species with antinociceptive and/or anti-inflammatory potential to relieve pain, such as Salvia and Agastache. The bioactive constituents of these genera were mainly terpenes (volatile and non-volatile) and phenolic compounds such as flavonoids (glycosides and aglycone). The aim of this review is to analyze important aspects of Mexican genera of Lamiaceae, scarcely explored as a potential source of secondary metabolites responsible for the analgesic and anti-inflammatory properties of these species. In addition, we point out the possible mechanisms of action involved and the modulatory pathways investigated in different experimental models. As a result of this review, it is important to mention that scarce information has been reported regarding species of this family from Mexican genera. In fact, despite Calosphace being one of the largest subgenera of Salvia in the world, found mainly in Mexico, it has been barely investigated regarding its potential biological activities and recognized bioactive constituents. The scientific evidence regarding the different bioactive constituents found in species of Lamiaceae demonstrates that several species require further investigation in preclinical studies, and of course also in controlled clinical trials evaluating the efficacy and safety of these natural products to support their therapeutic potential in pain relief and/or inflammation, among other health conditions. Since Mexico is one of the most important centers of diversification, and due to the high endemism of species of this family, it is crucial their rescue, in situ conservation, and investigation of their health benefits.
The extensive use of antibiotics has caused the global spread of multidrug-resistant bacteria and genes, seriously reducing antibiotic efficacy and threatening animal and human health. As an alternative, traditional Chinese veterinary medicine (TCVM) was used in this study for its lack of drug resistance and low toxicity. Huangqin-honghua-pugongying-jinyinhua extract (HHPJE), a novel TCVM, consists of the extracts of Huangqin (Scutellaria baicalensis), Honghua (Carthami Flos), Pugongying (Taraxacum) and Jinyinhua (Lonicerae Japonicae Flos), and was developed to treat bovine mastitis. In this study, we evaluated the toxicity, bacteriostatic, analgesic, anti-inflammatory, and antipyretic activities of HHPJE. Our results show that HHPJE did not show any acute oral toxicity and can be considered safe for oral administration. Additionally, HHPJE possessed a dose-dependent antibacterial effect on Staphylococcus aureus, Escherichia coli, Streptococcus agalactiae and Streptococcus dysgalactiae. HHPJE (60, 30 and 15 g/kg) can reduce the abdominal pain by 44.83 ± 7.69%, 43.15 ± 9.50% and 26.14 ± 4.17%, respectively. The percentages of anti-inflammation inhibition (60, 30 and 15 g/kg) were 35.34 ± 2.17%, 22.29 ± 2.74% and 12.06 ± 3.61%, respectively. The inhibition rates (60, 30 and 15 g/kg) of antipyretic activity were 82.05%, 65.71% and 52.80%, respectively. The evaluation of pharmacodynamics and toxicity indicate that HHPJE possesses significant bacteriostatic, analgesic, anti-inflammatory and antipyretic potential, and also that it is safe for acute oral toxicity, which means it has potential value for treating bovine mastitis in future and alleviating clinical symptoms with no drug resistance or side effects.
Trichophyton rubrum (T. rubrum) is the main cause of chronic dermatophytosis which is highly prevalent worldwide. This study was aimed to fabricate and characterize polymeric emulgel of eugenol and linalool for the treatment of T. rubrum infections. Using the slow emulsification method, the emulgel was prepared and characterized for thermodynamic stability, pH analysis, viscosity, spreadability, swelling behavior, %drug content, surface morphology, globules size, polydispersity index, surface charge (mV), thermal behavior, in vitro drug release and XRD studies. Biological activities of emulgel were conducted against T. rubrum in vitro and in vivo. Results indicated that emulgel formulations were thermodynamically stable. The pH of the formulations was within an acceptable range for skin. The viscosity and spreadability were optimum for the better patient compliance. The swelling behavior was 111.10 ± 1.25% after 90 min. The drug content was within the official pharmacopeia limit i.e., 100 ± 10%. The surface morphology revealed by scanning electron microscopy showed a spherical-shaped structure with characteristic larger cracks and wrinkles. The droplet size, PDI, and surface charge of the optimized emulgel were 888.45 ± 8.78 nm, 0.44 and −20.30 mV, respectively. The emulgel released 84.32% of eugenol and 76.93% of linalool after 12 h. There was complete disappearance of the diffraction peaks corresponding to the drugs after XRD analysis. In rabbits, the infection was safely and completely recovered after 12 days and the emulgel produced significant effects (p < 0.05) similar to the standard product Clotrim®. It is concluded that the eugenol–linalool emulgel best described all its physical properties and can be applied topically for the treatment of T. rubrum infections
Trichophyton rubrum (T. Rubrum) is responsible for chronic cases of dermatophytosis which have high rates of resistance to antifungal drugs worldwide. The aim of this study was to formulate an emulgel of Eugenol-Linalool for the treatment of T. Rubrum infections. The emulgel was prepared by slow emulsification method and characterized for physical examination, pH analysis, swelling index, stability studies, spreading coefficient, SEM analysis, thermal analysis and PXRD studies. In-vitro antifungal activities were performed by growing T. rubrum on specialized media in petri dishes. In-vivo antifungal activity was performed in rabbits by inducing the skin infection by application of fungal strain. Results indicated that the emulgel formulation is highly stable and the physical properties of the emulgel remained quite feasible. No deterioration was observed in the formulation and the pH remained the same as the pH of skin. The viscosity and spreadability of the emulgel remained highly compatible. The results of in vitro and in vivo studies indicated that the Eugenol and Linalool both inhibited the growth of T. rubrum. Eugenol was more effective in inhibition of zone (38±0.01 mm) of T. rubrum as compared to Linalool (32.9±0.03 mm). Similarly it was observed that when the combination of both Linalool and Eugenol was used, the growth of T. rubrum (42±0.01 mm) was significantly (P < 0.05) inhibited. It is hence concluded that the emulgel containing Eugenol and Linalool possess strong in vitro and in vivo antifungal activities against the commercial strains of anthrophilic dermophytic T. Rubrum.
Background:
Myocardial infarction (MI), a life-threatening disorder, arises from the imbalance between oxygen supply and myocardial demand. Linalool is a naturally occurring monoterpenes with proved numerous pharmacological actions. This study investigated the cardioprotective effect of Linalool on isoproterenol (ISO)-induced MI in rat models and explored part of the underlying molecular mechanisms.
Methods:
Rats were divided into five groups; groups I and II served as normal and linalool control groups, Group III administered ISO alone; groups V and VI received two different doses of Linalool and were challenged by ISO. Different biochemical parameters were determined, including hemodynamic, infarction size, cardiac enzymes, apoptotic markers, and inflammatory mediators.
Results:
Linalool limited the infarcted area size and diminished the elevated cardiac enzymes. Linalool escalated HO-1 and Nrf2, both nuclear and cytosol fractions, and reduced Keap 1. Linalool enhanced cardiac antioxidant activities, reduced inflammatory cytokines (tumor necrosis factor-alpha (TNF-α), nuclear factor-κ-B (NF-κB), interleukin 1 beta (IL-1β), interleukin 6 (IL-6)), apoptotic markers (Caspase-3, Caspase-9, and Bax), and elevated Bcl2.
Conclusion:
Linalool could act as an effective cardioprotective agent in the MI model through improving the oxidative condition, probably via the Nrf2/HO-1 pathway and by abolishing both apoptotic and inflammatory responses.
Activity against the acute inflammatory process induced by carrageenin and histamine in rats and the anti-nociceptive effect in mice were investigated after administration of Salvia sclarea oil and some of its constituents. The oil showed a significant anti-inflammatory effect and moderate analgesic action after subcutaneous injection at a dose of 250 mg/kg. The anti-inflammatory action was more conspicuous in the carrageenin-induced edema, where it produced the equivalent effect of a 5 mg/kg dose of indomethacin, than in the histamine-induced edema. The effect was correlated to the presence of methyl chavicol, linalool, α-terpineol and linalyl acetate. The results show that these constituents produce less anti-inflammatory action when administered separately than the oil in toto, and are also less effective than the oxygenated fractions obtained by Flash chromatography of the oil. This indicates that the action of the oil is determined by synergistic action of its constituents. The moderate peripheral analgesia (evaluated by writhing test) produced by S. sclarea oil appears to be mainly attributable to its alcoholic component.
Pharmacological properties of S. sclarea and S. desoleana oils are discussed in relation to their chemical composition. After systemic administration, these oils had a depressant action on the CNS in mice and a hydrocholeretic effect in rats. Otherstudies demonstrated also a good anti-inflammatory activity in rats as well as a peripheral analgesic action in mice. These essential oils possess invitro antimicrobial properties against some humanpathogen strains and their activity is comparable to S. officinalis oil, well known for its antiseptic properties. In vitro studies carried out on mucoadhesive preparations showed the ability of the oil components to permeate the oral mucous. This could be of interest in the treatment of humaninflammatory diseases of mucous tissues, frequently associated with microbial infections. These oils are also able to inhibit the growth of some phytopathogenic fungi and could therefore be useful in the agronomic field as an alternative to synthetic compounds, with a view to reducing environmental pollution. Some biological effects were correlated with the chemical composition and the kind of the formulations utilized in order to examine some possible applications of these oils in human medicine. All pharmacological activities seem to be attributable to the content of some oxygenated compounds, like alcohols (mainly linalool and alpha-terpineol) and esters (linalyl and alpha-terpinyl acetate). Experimental observations point the hypothesis of a synergic action between the different components, even if the oils in toto were more active than their fractions or single components.
The sedative properties of the essential oil of Lavender (Lavandula angustifolia Miller) and of its main constituents--linalool and linalyl acetate--were investigated in mice followed up in a series of experimental procedures. The significant decrease in the motility of female and male laboratory animals under standardized experimental conditions is found to be closely dependent on the exposure time to the drugs. Nevertheless after an injection of caffeine into mice a hyperactivity was observed which was reduced to nearly a normal motility only by inhalation of these fragrance drugs. In particular the correlation of the motility of the animals to linalool in serum is experimentally proven, thus furnishing evidence of the aromatherapeutical use of herbal pillows employed in folk medicine since ancient times in order to facilitate falling asleep or to minimize stressful situations of man.
Linalool is a monoterpene compound reported to be a major component of essential oils in various aromatic species. Several linalool-producing species are used in traditional medical systems. Among these is Aeolanthus suaveolens G. Dom (Labiatae) which is used as an anticonvulsant in the Brazilian Amazon. Psychopharmacological in vivo evaluation of linalool showed that this compound has dose-dependent marked sedative effects at the central nervous system (CNS), including hypnotic, anticonvulsant and hypothermic properties. It has been suggested that these neurochemical effects might be ascribed to the local anaesthetic activity of linalool. The present study reports an inhibitory effect of linalool on the acetylcholine (ACh) release and on the channel open time in the mouse neuromuscular junction. These findings could provide a rational basis to confirm the traditional medical use of linalool-producing plant species. Indeed, our data demonstrate some interactions in the modulation of the ACh release at the mouse neuromuscular junction, which are well correlated with the suggested molecular mechanisms. Linalool induced a reduction of the ACh-evoked release. The possibility that this effect could be ascribed to some interaction with pre-synaptic function is noteworthy. Moreover, the inhibitory effect induced on the kinetics of the miniature end-plate current decay demonstrates a local anaesthetic action, either on the voltage or on the receptor-activated channels.
Linalool, a monoterpene compound prevalent in essential oil of plant species traditionally used as sedatives, has been characterized as anticonvulsant in several experimental models. Linalool inhibits the binding of [3H]glutamate and [3H]dizocilpine to brain cortical membranes, indicating a participation of the glutamatergic transmission its mechanism of action. In this study, we investigated the effects of linalool on [3H]glutamate release (basal and potassium-stimulated) and [3H]glutamate uptake in mice cortical synaptosomes. Linalool significantly reduced potassium-stimulated glutamate release as well as glutamate uptake, not interfering with basal glutamate release. The data indicates that linalool may interfere with several relevant elements of the glutamatergic transmission, including detriment of the K+-stimulated glutamate release.
In the central nervous systems, intracellular and extracellular movement of potassium ions plays an important role in regulating neuronal excitability and the release of neurotransmitters. The purpose of our study was to determine whether nicorandil (adenosine triphosphate-sensitive K+ channel opener) exerts antinociceptive effects by itself or in combination with fentanyl, clonidine and bethanechol and whether glibenclamide (adenosine triphosphate-sensitive K+ channel blocker) and charybdotoxin (Ca2+-activated K+ channel blocker) may antagonize the antinociceptive action of fentanyl, clonidine and bethanechol. Antinociceptive effects were assessed using the tail-flick test in rats. Nicorandil (100 microg) and antinociceptively ineffective doses of fentanyl (1 microg), clonidine (2.5 microg) or bethanechol (10,ug) were coadministered intrathecally (i.t.). Glibenclamide (100 microg) or charybdotoxin (2.5 ng) were administered i.t. at 5 min before each effective dose of fentanyl (2.5 microg), clonidine (10 microg) or bethanechol (40 microg). The present findings demonstrated that i.t. administration of nicorandil alone exerted no influence on the tail-flick latency. However, concomitant administrations of antinociceptively inactive doses of fentanyl, clonidine or bethanechol with nicorandil elicited significant suppression of the thermonociceptive response. Also, each antinociception induced by fentanyl, clonidine or bethanechol was partially antagonized by both glibenclamide and charybdotoxin. These findings showed that activation of the K+ channel might enhance the antinociceptive effects of fentanyl, clonidine and bethanechol.
Linalool and linalyl acetate are the principal components of many essential oils known to possess several biological activities, attributable to these monoterpene compounds. In this work, we evaluated individually the anti-inflammatory properties of (-) linalool, that is, the natural occurring enantiomer, and its racemate form, present in various amounts in distilled or extracted essential oils. Because in the linalool-containing essential oils, linalyl acetate, is frequently present, we also examined the anti-inflammatory action of this monoterpene ester. Carrageenin-induced edema in rats was used as a model of inflammation. The experimental data indicate that both the pure enantiomer and its racemate induced, after systemic administration, a reduction of edema. Moreover, the pure enantiomer, at a dose of 25 mg/kg, elicited a delayed and more prolonged effect, while the racemate form induced a significant reduction of the edema only one hour after carrageenin administration. At higher doses, no differences were observed between the (-) enantiomer and the racemate; a further increase in the dose of both forms did not result in an increased effect at any time of observation. The effects of equi-molar doses of linalyl acetate on local edema were less relevant and more delayed than that of the corresponding alcohol. These finding suggest a typical pro-drug behavior of linalyl acetate. The results obtained indicate that linalool and the corresponding acetate play a major role in the anti-inflammatory activity displayed by the essential oils containing them, and provide further evidence suggesting that linalool and linalyl acetate-producing species are potentially anti-inflammatory agents.
Spinal cholinergic receptors are involved in mediating antinociceptive effects.To characterize the receptor subtypes modulating nociceptive transmission, we first determined the antinociceptive effects of intrathecally administered muscarinic agonists (McN-A-343 and carbachol) and a cholinesterase inhibitor (neostigmine) in rats. The antagonist potencies of muscarinic antagonists with different preferences for muscarinic receptors [atropine, pirenzepine (M1), methoctramine (M2), and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP; M3)] were then examined for McN-A-343, carbachol, and neostigmine. After determining the time of peak effect for each antagonist, the just maximally effective (JME) dose of each agonist was given in conjunction with one of the several doses of the antagonists. The three agents produced a dose-dependent increase in paw withdrawal latency, with the following 50% effective dose and the following JME doses: neostigmine 6 and 14 nmol, carbachol 29 and 110 nmol, and McN-A-343 354 and 630 nmol. The rank of order of potency (and median infective dose in nanomoles) for the antagonists was: neostigmine = (atropine 14 > 4-DAMP 44 >> methoctramine >137, and pirenzepine >236); carbachol = (pirenzepine 0.5 = atropine 0.6 > 4-DAMP 5 >> methoctramine >137); McN-A-343 = (pirenzepine 0.5 > atropine 3 > 4-DAMP 6 >> methoctramine >137). Our results suggest that the M1 and possibly the M3 muscarinic receptors mediate spinal antinociception in the rat. Implications: Spinal muscarinic agonists, such as carbachol and the cholinesterase inhibitor neostigmine, induce a potent analgesia in the rat. Using selective receptor antagonists, we have shown that these effects are likely mediated by spinal M1 and/or M3 receptor subtypes.
(Anesth Analg 1997;85:847-53)
In order to investigate the pharmacodynamic basis of the previously-established anticonvulsant properties of linalool, we examined the effects of this compound on behavioral and neurochemical aspects of glutamate expression in experimental seizure models. Specifically, linalool effects were investigated to determine its inhibition of (i) L-[H-3]glutamate binding at CNS (central nervous system membranes), (ii) N-methyl-D-aspartate (NMDA)-induced convulsions, (iii) quinolinic acid (QUIN)-induced convulsions, and the behavioral and neurochemical correlates of PTZ-kindling. The data indicate that linalool modulates glutamate activation expression in vitro (competitive antagonism of L-[H-3]glutamate binding) and in vivo (delayed NMDA convulsions and blockage of QUIN convulsions). Linalool partially inhibited and significantly delayed the behavioral expression of PTZ-kindling, but did not modify the PTZ-kindling-induced increase in L-[H-3]glutamate binding.
Linalool is a monoterpene compound reported to be a major component of essential oils of several aromatic species. Several linalool-producing species are used in traditional medical systems, including A. suaveolens, used as anticonvulsant in the Brazilian Amazon. We evaluated the effects of linalool given systematically to mice on experimental models useful for detecting psychopharmacological activity. The results show that this compound has dose dependent marked effects at the Central Nervous System, including hypnotic, anticonvulsant and hypothermic. The effects of linalool revealed by this evaluation are useful to understand the traditional medical use of several plant species in different continents and point to the validity of exploring terpenes as sources of new anticonvulsant agents.
The anti-hyperalgesic action, antinociception, and also the possible mechanisms involved in the action of gallic acid ethyl ester (GAEE) isolated from the aerial part of Phyllanthus urinaria, have been investigated in different models of chemical, mechanical and thermal nociception in mice and rats. GAEE given by intraperitoneal (i.p.), oral (p.o.), intrathecal (i.t.) or by intracerebroventricular (i.c.v.) routes produced dose-related antinociception when assessed against chemical nociception in mice. GAEE significantly inhibited the hyperalgesia induced by bradykinin or substance P in rat paw, but did not affect the hyperalgesia caused by carrageenan or prostaglandin E2. Furthermore, GAEE, in contrast to morphine, was completely ineffective in the hot-plate test in mice. The antinociception produced by GAEE (i.p.) in the formalin test was significantly reversed by i.c.v. treatment of animals with pertussis toxin and by i.t. administration of K+ channel blockers such as apamin, charybdotoxin or glibenclamide, but not by tetraethylammonium. In contrast, GAEE (i.p.) antinociception was unaffected by i.p. treatment of animals with naloxone or by nitric oxide precursor, l-arginine, and this action was not secondary to its anti-inflammatory effect, nor was it associated with non-specific effects such as muscle relaxation or sedation. Thus, GAEE produces dose-dependent and pronounced systemic, spinal and supraspinal antinociception in mice, probably via activation of K+ channels and by a Gi/o pertussis toxin-sensitive mechanism.
Lavender (Lavandula angustifolia, P. Miller) is used in aromatherapy as a holistic relaxant and is said to have carminative, antiflatulence and anticolic properties. Its sedative nature, on inhalation, has been shown both in animals and man. Lavender has a spasmolytic activity on guineapig ileum and rat uterus in vitro and it also decreases the tone in the skeletal muscle preparation of the phrenic nerve–diaphragm of rats. As the mechanism of action has not been studied previously, the spasmolytic activity was studied in vitro using a guinea-pig ileum smooth muscle preparation. The mechanism of action was postsynaptic and not atropine-like. The spasmolytic effect of lavender oil was most likely to be mediated through cAMP, and not through cGMP. The mode of action of linalool, one of lavender's major components, reflected that of the whole oil. The mode of action of lavender oil resembled that of geranium and peppermint oils. Copyright © 1999 John Wiley & Sons, Ltd.
Linalool is a monoterpene compound reported to be a major component of essential oils of several aromatic species. Several linalool-producing species are used in traditional medical systems for sedative purposes, including the interruption and prevention of seizures. Previous studies in mice revealed that linalool modulates glutamatergic (competitive antagonism of L-[3H]glutamate binding, delayed intraperitoneal NMDA-induced convulsions and blockade of intracerebroventricular Quin-induced convulsions) and GABAergic transmission (protection against pentylenetetrazol and picrotoxin-induced convulsions). To further clarify the anticonvulsive mechanisms of linalool, we studied the effects of linalool on binding of [3H]MK801 (NMDA antagonist) and [3H]muscimol (GABAA agonist) to mouse cortical membranes. Linalool showed a dose dependent non-competitive inhibition of [3H]MK801 binding (IC50 = 2.97 mM) but no effect on [3H]muscimol binding. The data suggest that the anticonvulsant mode of action of linalool includes a direct interaction with the NMDA receptor complex. The data do not, however, support a direct interaction of linalool with GABAA receptors, although changes in GABA-mediated neuronal inhibition or effects on GABA release and uptake cannot be ruled out.
A single unilateral injection of carrageenan (4.5-6.0 mg in 0.15-0.20 ml saline) into the rat hindpaw induced behavioral hyperalgesia as evidenced by a significant reduction in hindpaw withdrawal latency to a noxious thermal stimulus. The involvement of N-methyl-D-aspartate (NMDA) receptors in this model of hyperalgesia was examined by intrathecal administration of the selective excitatory amino acid (EAA) receptor antagonists: (+/-)-2-amino-5-phosphonopentanoic acid (AP-5), (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), ketamine hydrochloride (ketamine), 7-chlorokynurenic acid (7-Cl kynurenic acid), and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). The effects of dizocilpine maleate (MK-801) were studied under the same conditions and published previously (Ren et al., 1992) and the data are presented for comparison. While the withdrawal latencies of the non-injected paws and of the paws of naive rats were not significantly affected by application of the EAA receptor antagonists at doses tested, the paw withdrawal latencies of the carrageenan-injected paws were elevated dose dependently. The rank order of potency of these agents to reduce hyperalgesia was: MK-801 greater than or equal to AP-5 greater than or equal to CPP = 7-Cl kynurenic acid = ketamine much greater than CNQX greater than 0. In contrast, intrathecal injection of the opioid receptor agonists, [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAMGO, mu-selective) and [D-Pen2,D-Pen5] enkephalin (DPDPE, delta-selective), produced antinociception in both injected and non-injected paws. DAMGO was much more potent, while DPDPE was less potent, than MK-801.(ABSTRACT TRUNCATED AT 250 WORDS)
Dorsal horn nociceptive neurones exhibit wind up, a frequency dependent potentiation of their responses to repeated C-fibre stimulation. Intrathecal morphine (5 micrograms) significantly reduces the initial responses of the neurones but not wind up whereas the reverse is true for N-methyl-D-aspartate (NMDA) antagonists. The combination of intrathecal morphine (5 micrograms) and 7-chlorokynurenate (2.5 micrograms), an antagonist at the glycine site of the NMDA receptor, abolishes both the input and wind up of these neurones.
The fragrance compounds linalool (1) and linalyl acetate (2) could be detected, identified and quantified (1: 7-9 ng ml-1; and 2: 1-2 ng ml-1 and 4-5 ng ml-1 as free linalool) in blood samples after inhalation in animal experiments (mice) by gas chromatography/mass spectrometry (GC/MS) with chemical ionization (CI) (ammonia); selected ion monitoring (SIM) mode (1: m/z 81, 137 and 154; 2: 47, 57 and 137) and GC/flame ionization detection (FID). The inhalation of these monoterpenes in concentrations of 5 mg l-1 air leads to a significant reduction of the motility of the test animals down to 30-40% with respect to the control group.
Although pharmacological data provide strong evidence for different types of opioid receptors (e.g., mu, delta, and kappa), they share many common properties in their ability to couple to second messenger systems. All opioid receptor types are coupled to G-proteins, since agonist binding is diminished by guanine nucleotides and agonist-stimulated GTPase activity has been identified in several preparations. Moreover, all three types inhibit adenylyl cyclase. This second messenger system has been identified for opioid receptors in both isolated brain membranes and in transformed cell culture. Studies with chronic treatment with opioid agonists suggest that the coupling of receptors with G-proteins and second messenger effectors may play important roles in development of opioid tolerance.
Subcutaneous injection of formalin into the hindpaw peripheral receptive field of deep dorsal horn multireceptive (convergent) nociceptive neurones was used to produce a prolonged (1 h) activation of the cells. This chemical noxious stimulus produced a first peak of firing which lasted 10 min followed by a second peak of prolonged activity which was monitored for 50 min. gamma-D-glutamylglycine (DGG), a non-selective N-methyl-D-aspartate (NMDA) and quisqualate/kainate (non-NMDA) receptor antagonist was applied intrathecally both as a pretreatment and after the formalin. A complete abolition of both peaks of the formalin response was produced by DGG pretreatment (1000 micrograms) (n = 4). This dose produced profound inhibition of the acute C-fibre evoked responses of the same cells. However, no inhibitions were produced when the antagonist was applied once the formalin response had developed (n = 4). The selective NMDA receptor antagonist 5-amino-phosphonovaleric acid (AP5) was administered intrathecally (250 and 500 micrograms) as a 40 min pretreatment and caused a small inhibition of the first peak but a marked dose-related reduction in the second prolonged phase (n =7). AP5 did not influence the C-fibre inputs onto the cells. The non-competitive NMDA receptor channel blockers, ketamine and MK801, were administered i.v. during the second phase of firing. Ketamine (1-8 mg/kg) caused a short-lasting but marked and dose-related inhibition of the neuronal responses to formalin (n = 11). MK801 (0.5-1 mg/kg) resulted in a prolonged inhibition of cell firing during the second phase of the response (n = 11).(ABSTRACT TRUNCATED AT 250 WORDS)
There is now substantial evidence that acetylcholinesterase inhibitors and muscarinic receptor agonists increase the pain threshold after both systemic and spinal administration. In rats, physostigmine gave a significant dose-dependent increase in latency times in the tail immersion test following intrathecal administration. The effect was antagonized with atropine. Neostigmine gave more prolonged latencies as did the muscarinic receptor agonist carbachol. Spinal cholinergic pathways for antinociception interacted with the spinal opioid and adrenergic nerve tracts. No cross-tolerance to the selective alpha 2-adrenoreceptor agonist guanfacine or to morphine was seen in rats tolerant of spinal carbachol antinociception. The mechanism of spinal cholinergic antinociception is not known but a muscarinic interneuron may explain the interactions with other neurotransmitters. Clinically, the centrally active cholinesterase inhibitor physostigmine has been shown to give postoperative pain relief although of short duration. Severe neurogenic pain has been successfully treated with physostigmine or distigmine.
The analgesic effect of morphine sulfate (3-5 mg/kg, i.p.) was assessed by both tail-flick and hot-plate tests in unanesthetized restrained rats. Intrathecal administration of atropine sulfate (10 micrograms) in the lumbar region of the spinal cord powerfully reduced the analgesia induced by systemic administration of morphine. This action did not result from the diffusion of atropine from its administration site to more rostral sites in the central nervous system. In spinal rats, atropine failed to reverse morphine analgesia, thus strongly suggesting that either a cholinergic descending pathway or a spinal local cholinergic circuit activated by an unknown descending pathway may be involved in the systemic morphine analgesia. In addition, the involvement of the alpha-adrenergic descending pathway in morphine analgesia is confirmed, whereas that of the serotonergic descending pathway is less prominent.
The antinociceptive effects of systemically‐administered procaine, lignocaine and bupivacaine were examined in mice and rats by using the hot‐plate, writhing and tail flick tests.
In both species all three local anaesthetics produced significant antinociception which was prevented by atropine (5 mg kg ⁻¹ , i.p.) and by hemicholinium‐3 (1 μg per mouse, i.c.v.), but not by naloxone (3 mg kg ⁻¹ , i.p.), α‐methyl‐ p ‐tyrosine (100 mg kg ⁻¹ , s.c.), reserpine (2 mg kg ⁻¹ , i.p.) or atropine methylbromide (5.5 mg kg ⁻¹ , i.p.).
Atropine (5 mg kg ⁻¹ , i.p.) which totally antagonized oxotremorine (40 μg kg ⁻¹ , s.c.) antinociception did not modify morphine (5 mg kg ⁻¹ , s.c.) or baclofen (4 mg kg ⁻¹ , s.c.) antinociception. On the other hand, hemicholinium, which antagonized local anaesthetic antinociception, did not prevent oxotremorine, morphine or baclofen antinociception.
Intracerebroventricular injection in mice of procaine (200 μg), lignocaine (150 μg) and bupivacaine (25 μg), doses which were largely ineffective by parenteral routes, induced an antinociception whose intensity equalled that obtainable subcutaneously. Moreover, the i.c.v. injection of antinociceptive doses did not impair performance on the rota‐rod test.
Concentrations below 10 ⁻¹⁰ m of procaine, lignocaine and bupivacaine did not evoke any response on the isolated longitudinal muscle strip of guinea‐pig ileum, or modify acetylcholine (ACh)‐induced contractions. On the other hand, they always increased electrically‐evoked twitches.
The same concentrations of local anaesthetics which induced antinociception did not inhibit acetylcholinesterase (AChE) in vitro.
On the basis of the above findings and the existing literature, a facilitation of cholinergic transmission by the local anaesthetics is postulated; this could be due to blockade of presynaptic muscarinic receptors.
The effects of galanthamine, an alkaloidal anticholinesterase agent whose chemical structure bears similarity to codeine, was studied in various animal and isolated organ tests. Antinociceptive activity of galanthamine given subcutaneously was detected and compared to physostigmine and morphine in the rat hot plate test. Naloxone partially blocked the effect of galanthamine but not that of physostigmine. Both cholinesterase inhibitors provided analgesia in the mouse acetic acid writhing test. They potentiated the effect of morphine in the rat hot plate test but inhibited the barbiturate anaesthesia potentiation of morphine in the rat. While galanthamine provided analgesia in the intact animal, it failed to produce opiate-like activity in such isolated organs as longitudinal muscle strip of the guinea-pig ileum, mouse vas deferens, and cat nictitating membrane.
The present study was performed to assess the utility of excitatory amino acid (EAA) antagonists as analgesia agents. The antinociceptive activity of various classes of EAA antagonists was assessed in mechanical and thermal flexion reflexes tests, as well as in the formalin test. Additional testing assessed the motor dysfunction associated with antinociceptive dose levels of the agents used, by examining placing, grasping and righting reflexes, as well as occurrences of balance loss during locomotion. No antinociceptive activity was observed on any of the nociceptive measures for the non-NMDA receptor antagonists CNQX or L-AP-3. High doses of the non-competitive (PCP-site) NMDA receptor antagonist MK-801 and the allosteric-glycine receptor antagonist 7-CKA produced antinociception on both the mechanical and thermal flexion reflex measures, while a high dose of the competitive NMDA receptor antagonist CPP produced antinociception only on the thermal flexion reflex measure. Hyperalgesic effects on thermal flexion reflexes were obtained with all doses of the polyamine receptor antagonist ARCA, and with the highest dose of the allosteric-glycine receptor antagonist FICA. Formalin nociceptive behaviours were significantly reduced only by high doses of competitive (APV) and non-competitive (MK-801) NMDA receptor antagonists. The doses of EAA receptor antagonists which produced antinociceptive effects on any of the 3 nociceptive tests also produced evidence of motor dysfunction. Both competitive NMDA receptor antagonists (APV and CPP) produced disruptions of placing, grasping and righting reflexes, while 2 of the allosteric-glycine receptor antagonists (7-CKA and DCQX) significantly disrupted placing and righting reflexes.(ABSTRACT TRUNCATED AT 250 WORDS)
Behavioral effects of PCP-type noncompetitive antagonists of N-methyl-D-aspartate (NMDA) receptors overlap with those of a host of other centrally acting compounds. In the present experiment, locomotor activity and performance on an inverted screen test in untrained mice were used to differentiate PCP-type non-competitive NMDA antagonists from other drug classes. These uncompetitive NMDA antagonists [PCP, dizocilpine, (-)-MK-801, TCP, (+)-SKF 10,047, dextrorphan, ketamine] produced dose-related increases in locomotor activity and the percentage of mice falling off an inverted, elevated wire mesh screen. Both effects demonstrated stereoselectivity, occurred at comparable dose levels, and were within the range of doses producing other biological effects (e.g., anticonvulsant). The potencies of these drugs for producing behavioral effects were positively correlated with affinities for PCP ([3H]MK-801) but not sigma([3H]SKF 10,047) receptors. Although muscarinic antagonists (benactyzine, atropine) produced effects in the same direction, locomotor stimulation was small and occurred at lower doses than those inducing screen failures. Competitive NMDA antagonists (LY 274614, LY 233536, CPP, NPC 12626), sigma receptor ligands (DTG, dextromethorphan), postsynaptic dopamine agonists (quinpirole, SKF 38393) and antagonists (haloperidol, SCH 39166), and some depressant compounds (morphine, diazepam) increased failures on the screen test but decreased locomotor activity. Ligands of the polyamine regulatory site of the NMDA receptor (ifenprodil, SL 82.0715-10) and the AMPA receptor antagonist NBQX decreased locomotor activity without increasing screen failures. An antagonist of the strychnine-insensitive glycine receptor (7-chlorokynurenic acid) did not affect performance on either test. Psychomotor stimulants (cocaine and methamphetamine) stimulated locomotor activity without affecting screen performance. The only false positives occurred with barbiturates (pentobarbital, phenobarbital). Nonetheless, the present procedure demonstrates excellent sensitivity and power for rapid discrimination of uncompetitive NMDA antagonists.
Blocking glutamatergic transmission at the N-methyl-D-aspartate (NMDA) receptor complex with MK-801 (0.15-0.5 mg/kg, IP) was found to induce a robust, dose-dependent increase in locomotor activity. This behavioural activation was similar in intensity to that observed after d-amphetamine (1 mg/kg, SC). The locomotor stimulation induced by MK-801 at 0.3 mg/kg was significantly inhibited by the D2 dopamine receptor antagonist raclopride (0.1-0.3 mg/kg, SC) and by the D1 receptor antagonist SCH 23390 (0.04 mg/kg, SC). The locomotor activity induced by a higher dose of MK-801 (0.5 mg/kg) was reduced by higher doses of raclopride or SCH 23390 administered alone (0.3 and 0.08 mg/kg, respectively), and was inhibited by simultaneous administration of ineffective doses. Raclopride significantly reduced d-amphetamine-induced locomotor activity at a dose (0.2 mg/kg) that also blocked the effects of a low dose of MK-801. In contrast, SCH 23390 blocked the effects of d-amphetamine at a dose (i.e. 0.01 mg/kg) lower than that needed to block MK-801. These results suggest that the dopaminergic system may in part mediate the locomotor effects induced by the NMDA antagonist, MK-801, in rats. However, the locomotor activity induced by MK-801 appears to be less sensitive to dopaminergic receptor blockade than that induced by d-amphetamine, suggesting that the underlying mechanisms, although similar, are not identical.
The present study was designed to characterize the antinociception produced by the administration of a potent muscarinic agonist into the intrathecal space of the lumbar spinal cord of male Sprague-Dawley rats. Seven days after surgical implantation of intrathecal catheters, animals were injected with graded doses of (+)-cis-methyldioxolane. (+)-cis-Methyldioxolane produced hot-plate and tail-flick antinociception for up to 90 min, peaking 5 to 30 min after injection. The dose of (+)-cis-methyldioxolane that inhibited nociception by 50% was 12 nmol in both the hot-plate and tail-flick tests. This antinociception was not accompanied by a general depression of other spontaneous motor responses. The tissue concentration of (+)-cis-methyl-dioxolane in the lumbar spinal cord present at the time of maximal hot-plate and tail-flick antinociception was approximately 12 microM. In similarity to (+)-cis-methyldioxolane, intrathecally administered (+)-muscarine also produced strong hot-plate and tail-flick antinociceptive responses. In contrast, intrathecally administered N-methylcarbachol, a nicotinic agonist, had no effect on nociception. Five-minute pretreatment with graded doses of pirenzepine, methoctramine, idazoxan, LY53857, or S-(-)-zacopride each significantly antagonized hot-plate and tail-flick antinociception produced by 37.5 nmol of (+)-cis-methyldioxolane in a dose-related manner with median effective antagonist doses in the range of 0.4 to 2.2 nmol. Intrathecal pretreatment with graded doses of prazosin or naloxone enhanced the antinociception produced by (+)-cis-methyldioxolane in the tail-flick but not the hot-plate tests. Intrathecal vehicle, S(-)-propranolol or mecamylamine did not alter (+)-cis-methyldioxolane-induced antinociception. The data suggest that the antinociceptive responses produced by intrathecally administered (+)-cis-methyldioxolane involve the stimulation of muscarinic M1 and/or M2 cholinergic receptors, and may also involve activation of alpha-2 adrenergic, 5-hydroxytryptamine1c/2 and 5-hydroxytryptamine3 serotonergic receptor systems at the level of the lumbar cord.
The possible effect of ifenprodil--a potent antagonist at the polyamine site of the NMDA receptor complex--on nociceptive threshold and morphine analgesia was investigated in mice. In the hot plate test, the intraperitoneal (i.p.) injection of ifenprodil significantly prolonged the reaction time of mice at the dose of 30 mg/kg, and increased the analgesic effect of morphine. In the phenylquinone writhing test, ifenprodil reduced the number of abdominal constrictions of mice starting from the dose of 2.5 mg/kg i.p., and increased the effect of morphine. The effect of ifenprodil on pain threshold was prevented by naloxone. Moreover, ifenprodil antagonized the pain threshold-reducing effect of alpha-melanocyte-stimulating hormone (0.05 microgram/mouse, intracerebroventricularly). These data show that blockade of the polyamine site of the NMDA receptor complex produces analgesia and increases the analgesic effect of morphine.
The present study was aimed at investigating the effects of the competitive N-methyl-D-aspartate (NMDA) receptor antagonists D-CPPene (3-(2-carboxypiperazine-4-yl)-propenyl-1-phosphonic acid) and CGS 19755 (cis-4-(phosphonomethyl)piperidine-2-carboxylic acid) on dopamine (DA) transmission and motor activity in mice and rats. As measures of DA release we used mouse brain 3-methoxytyramine (3-MT) levels, and indirect estimate of DA release, and striatal dialysate measures of DA in conscious and freely moving rats by means of microdialysis. To obtain additional information about monoaminergic neurotransmission, brain tissue levels of DA, DOPAC, HVA, 5-HT and 5-HIAA were measured in both mice and rats. The animals were sacrificed at the time when NMDA antagonist-induced locomotor stimulation was maximal. In mice, D-CPPene and CGS 19755 decreased striatal 3-MT levels, whereas, in general, 3-MT levels in the limbic forebrain were not significantly altered. Treatment with CGS 19755 decreased rat st