Antinociceptive effect of garlic, garlic preparations and derivative compounds.

BACKGROUND AND OBJECTIVE: The antinociceptive effects of garlic have shown promise in treating different chronic diseases in humans, such as knee osteoarthritis, rheumatoid arthritis and peripheral arterial occlusive disease stage II. The most common garlic products are garlic powder (dried garlic), steam distilled garlic oils, garlic oil macerate and aged garlic extract. These commercial products contain organosulphur compounds (OSCs) that have been extensively evaluated in preclinical models and some clinical assays to treat different diseases against pain. In this review, we describe the importance of some bioactive compounds found in garlic and their role in treating pain. MATERIALS & METHODS: A systematic search of the literature in Dimensions, PubMed, Scopus, and Web of Science was performed. Terms and preselected keywords relating to garlic, its derivatives and organusulphure compounds in acute, chronic and neuropathic pain, were used to perform a systematic literature search. Two independent reviewers screened the papers for inclusion and assessed the methodological quality. RESULTS & DISCUSSION: The antinociceptive activity of garlic and its OSC is related to its antioxidant and anti-inflammatory properties, which may be explained by the ability to block the synthesis of PGs, pro-inflammatory cytokines and interferon-γ, by the reduction COX-2 activity and increasing the levels of anti-inflammatory cytokines. Besides, garlic extract is an activator of TRPA1 and TRPV1, where the principal responsible for this activation are OSC. CONCLUSION: The relationship between these pathways allows a better understanding how garlic and its derivates could be carrying out its pharmacological action over the management of acute and chronic pain and provide a base by further investigations. SIGNIFICANCE: Antinociceptive effect of garlic and its OSCs has been extensively evaluated in preclinical models and clinical assays to treat different diseases, contributing to the modulation of inflammation as an essential factor in reducing pain. The current review emphasizes the potential therapeutic effect of garlic and its derivatives in treatment of pain and related mechanisms of action. Moreover, it provides information about the potential clinical use in patients with painful conditions.

Antinociceptive effects of Salvia divinorum and bioactive salvinorins in experimental pain models in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia divinorum Epling & Játiva is a Mexican plant used not only in rituals but also in traditional medicine for pain relief. One of the most known bioactive compounds is salvinorin A, which acts centrally in kappa-type opioid receptors. AIM OF THE STUDY: Despite its traditional use as a medicinal plant, there is not enough scientific investigation to reinforce its potential as analgesic. In this study, Salvia divinorum antinociceptive activity was evaluated in experimental models of nociceptive pain; the writhing test and formalin-induced licking behavior in mice. MATERIAL AND METHODS: Different Salvia divinorum extracts were prepared by maceration at room temperature in increased polarity (hexane, ethyl acetate and methanol). The ethyl acetate extract (EAEx) was chosen in order to be fractioned and to obtain a mixture of salvinorins. The antinociceptive effect of EAEx (3, 10, 30, and 100 mg/kg, i.p.) was compared with that of tramadol (a partial opioid agonist analgesic drug, 30 mg/kg, i.p.) and the mixture of salvinorins (30 mg/kg, i.p.). In addition, a participation of opioids (naloxone, NX 1 and/or 3 mg/kg, i.p.) and serotonin 5-HT1A receptors (WAY100635, 0.32 mg/kg, i.p.) was investigated as possible inhibitory neurotransmission involved. RESULTS: As a result, the EAEx produced significant and dose-dependent antinociceptive effect concerning salvinorins constituents. This effect was blocked in the presence of NX and WAY100635 in the abdominal test, but only by NX in the formalin-induced licking behavior. Whereas, the effect of salvinorins mixture involved opioids and serotonin 5-HT1A receptors. CONCLUSION: Data provide evidence of the potential of this species, where salvinorin A is in part responsible bioactive constituent involving participation of the opioids and/or 5-HT1A serotonin receptors depending on the kind of pain model explored.

Central and peripheral anti-hyperalgesic effects of diosmin in a neuropathic pain model in rats.

Flavonoids are natural compounds showing anti-hyperalgesic activity in models of pain. Diosmin is a compound poorly studied in the treatment of neuropathic pain. This study evaluates the anti-hyperalgesic actions of diosmin and possible mechanisms of action involved by using a neuropathic pain model in rats. Experimental neuropathic pain was induced by chronic constriction injury (CCI) in male Wistar rats, then aesthesiometric index and plantar tests were assessed to evaluate mechanical and thermal hyperalgesia, respectively, in order to explore the analgesic effects of acute and sub-chronic treatment with diosmin. The GABAA, 5-HT1A, D2-like and opioid receptors participation, as well as levels of TNF-α, IL-1ß and IL-6, were evaluated in the spinal cord and sciatic nerve tissues after acute and subchronic diosmin administration. In addition, the presence of diosmin on cerebral samples was determined by UHPLC-MS analysis. Acute and sub-chronic treatment with diosmin significantly diminished the mechanical and thermal hyperalgesia induced by CCI in rats. This anti-hyperalgesic effects of diosmin were modified in the presence of naloxone (1mg/kg, i.p.) and haloperidol (0.1mg/kg, i.p.), but not by GABAA and 5-HT1A receptor antagonists. The anti-hyperalgesic effects of diosmin were also linked with reduced levels of TNF-α, IL-1ß and IL-6. The presence of diosmin in the cerebral samples was confirmed by chromatographic analysis. In conclusion, our results provide evidence that diosmin produces significant anti-hyperalgesic effects acting at central level by an opioid and D2 dopaminergic receptors participation, and at peripheral level by reducing proinflammatory cytokines.

Anxiolytic-like effects and toxicological studies of Brickellia cavanillesii (Cass.) A. Gray in experimental mice models.

ETHNOPHARMACOLOGICAL RELEVANCE: Brickellia cavanillesii (Asteraceae) (Cass.) A. Gray is one of the popular plants consumed in Central America and Mexico for the treatment of several diseases such as hypertension, diabetes and anxiety, among others. AIM OF THE STUDY: To determine the anxiolytic-like effect of B. Cavanillesii and the safety of its use through toxicological studies. MATERIAL AND METHODS: Anxiolytic-like effects of soluble-methanol extract of B. cavanillesii (MEBc) were evaluated in ambulatory activity (open-field test), hole-board test, cylinder of exploration, the elevated plus-maze and the potentiation of the sodium pentobarbital-induced hypnosis mice models. On the other hand, in vivo toxicological studies were conducted on acute and sub-acute mice models recommended by OECD. Active MEBc was subjected to phytochemical studies through conventional chromatographic techniques to isolate bioactive compounds. RESULTS: MEBc (100mg/Kg) showed significant anxiolytic-like effect on animal model used (p<0.05). The phytochemical analysis of MEBc allowed the isolation of two major compounds nicotiflorin and acacetin, among others. Both compounds were found to be partially responsible for the anxiolytic-like effects. Moreover, a median lethal dose (LD50) higher than 2000mg/Kg was determined in mice and sub-acute oral administration of MEBc (100mg/Kg) did not alter body weight, clinical chemistry parameters (ALT and AST) and it did not induce any toxic nor alteration in the liver, kidney and heart functions. CONCLUSIONS: In current investigation, we have shown that MEBc has a wide range of pharmacology-toxicology patterns. The results support further investigation of MEBc as a potential anxiolytic phytomedicinal agent.