RESUMO
Neuropathy is a disturbance of function or a pathological change in nerves causing poor health and quality of life. A proportion of chronic pain patients in the community suffer persistent neuropathic pain symptoms because current drug therapies may be suboptimal so there is a need for new therapeutic modalities. This study investigated the neuroprotective flavonoid, 6-methoxyflavone (6MF), as a potential therapeutic agent and gabapentin as the standard comparator, against neuropathic models. Thus, neuropathic-like states were induced in Sprague-Dawley rats using sciatic nerve chronic constriction injury (CCI) mononeuropathy and systemic administration of streptozotocin (STZ) to induce polyneuropathy. Subsequent behaviors reflecting allodynia, hyperalgesia, and vulvodynia were assessed and any possible motoric side-effects were evaluated including locomotor activity, as well as rotarod discoordination and gait disruption. 6MF (25-75 mg/kg) antagonized neuropathic-like nociceptive behaviors including static- (pressure) and dynamic- (light brushing) hindpaw allodynia plus heat/cold and pressure hyperalgesia in the CCI and STZ models. 6MF also reduced static and dynamic components of vulvodynia in the STZ induced polyneuropathy model. Additionally, 6MF reversed CCI and STZ suppression of locomotor activity and rotarod discoordination, suggesting a beneficial activity on motor side effects, in contrast to gabapentin. Hence, 6MF possesses anti-neuropathic-like activity not only against different nociceptive modalities but also impairment of motoric side effects.
Assuntos
Flavonas , Hiperalgesia , Neuralgia , Ratos Sprague-Dawley , Animais , Ratos , Neuralgia/tratamento farmacológico , Neuralgia/etiologia , Flavonas/farmacologia , Flavonas/uso terapêutico , Hiperalgesia/tratamento farmacológico , Masculino , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Gabapentina/farmacologia , Gabapentina/uso terapêutico , Nociceptividade/efeitos dos fármacos , Neuropatias Diabéticas/tratamento farmacológico , Neuropatias Diabéticas/metabolismo , Feminino , Ácido gama-Aminobutírico/metabolismo , Aminas/farmacologia , Aminas/uso terapêutico , Nervo Isquiático/lesões , Nervo Isquiático/efeitos dos fármacos , Vulvodinia/tratamento farmacológico , Constrição , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Analgésicos/farmacologia , Analgésicos/uso terapêuticoRESUMO
N-Aryl-3,4-dihydroisoquinoline carbothioamide analogues 1-22 were synthesized by a simple one-step reaction protocol and subjected to in vitro urease inhibition studies for the first time. All compounds 1-22 were found active and showed significant to moderate urease inhibitory potential. Specifically, analogues 1, 2, 4, and 7 were identified to be more potent (IC50 = 11.2 ± 0.81-20.4 ± 0.22 µM) than the standard thiourea (IC50 = 21.7 ± 0.34 µM). The structure-activity relationship showed that compounds bearing electron-donating groups showed superior activity. Molecular docking study on the most active derivatives revealed a good protein-ligand interaction profile against the corresponding target with key interactions, including hydrogen bonding, hydrophobic, and π-anion interactions.
RESUMO
The methanolic extract of aerial parts of Tithonia tubaeformis showed significant antioxidant activity in DPPH assay. It was subjected to bioassay guided fractionation affording more active ethyl acetate fraction which on further purification led to the isolation and identification of a series of bioactive phenolic compounds having important biosynthetic relationship. Of these, 4-hydroxyphenethyl henicosanoate (tithonoid) is a new compound. Moreover, in the carrageenan induced paw edema test, significant attenuation of inflammation was also produced by the extract at 50-200 mg/kg. The structures of all the constituents were determined through spectroscopic methods. It is the first systematic biological and chemical investigation on T. tubaeformis, which showed that phenolics may play an important role in the antioxidant and anti-inflammatory activity of the plant, probably through synergism.
Assuntos
Antioxidantes , Tithonia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Carragenina , Edema/tratamento farmacológico , Fenóis/farmacologia , Fenóis/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Tirosina/uso terapêuticoRESUMO
BACKGROUND: Chemotherapy induced peripheral neuropathy (CIPN) is a painful side-effect of commonly used chemotherapeutic agents that profoundly impair the quality of life of patients as the current pharmacotherapeutic strategies are inefficient in providing adequate pain relief. Complementary and alternative medicine (CAM) therapies are preferred by patients with neuropathic pain as they experience insufficient control of pain with conventional medications. This study describes the antinociceptive effect of Tithonia tubaeformis (Jacq.) Cass. in a vincristine mouse model of established CIPN. METHODS: Tithonia tubaeformis hydromethanolic extract was tested for preliminary qualitative phytochemical analysis and acute oral toxicity test in mice. The antinociceptive effect was investigated using the abdominal constriction (writhing) and tail immersion tests (25-200â¯mg/kg). The anti-neuropathic effect was determined in the vincristine mouse model, established by daily administration of vincristine (0.1â¯mg/kg/day, i.p) for consecutive 14 days. Acute treatment with Tithonia tubaeformis (100 and 200â¯mg/kg) and the positive control, gabapentin (75â¯mg/kg) was carried out on the 15th day of the last vincrsitine dose and the animals were tested for allodynia and thermal hyperalgesia at 30-120â¯min post extract/drug administration. RESULTS: Vincristine produced significant temporal tactile allodynia and thermal hyperalgesia (Pâ¯<â¯0.01 and Pâ¯<â¯0.001 on day 7 and 14) and was maintained for the subsequent day (Pâ¯<â¯0.001 during 30-120â¯min). Tithonia tubaeformis was effective in attenuating the vincristine-induced allodynia and thermal hyperalgesia at 100â¯mg/kg (Pâ¯<â¯0.05, Pâ¯<â¯0.01) and 200â¯mg/kg (Pâ¯<â¯0.01, Pâ¯<â¯0.001). Similarly, gabapentin also showed a robust antinociceptive effect in counteracting the vincristine associated behavioral alterations. CONCLUSIONS: Tithonia tubaeformis can be an effective CAM therapeutic remedy for established CIPN due to its potential antinociceptive effect in attenuating vincristine-induced neuropathy.