RESUMO
Cannabis sativa L. (hemp) is a herbaceous plant rich in cannabinoids with a long history of use in pain treatment. The most well-characterized cannabinoids, cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC), garnered much attention in chemotherapy-induced peripheral neuropathy (CIPN) treatment. However, few studies have investigated the biological benefits and mechanism of hemp extract on CIPN. In the present study, hemp extract (JG) rich in cannabinoids was extracted by supercritical fluid carbon dioxide extraction (SFCE). The antinociceptive efficacy was evaluated using a paclitaxel-induced peripheral neuropathy (PIPN) rat model based on behavioral tests. Further omics-based approaches were applied to explore the potential mechanisms. The results showed that JG decreased mechanical allodynia, thermal hyperalgesia, and inflammatory cytokines in PIPN rats significantly. Transcriptome analysis identified seven key genes significantly regulated by JG in PIPN model rats, mainly related to the neuroactive ligand-receptor interaction pathway, PPAR signaling pathway, and cAMP signaling pathway. In metabolomic analysis, a total of 39 significantly altered metabolites were identified, mainly correlated with pentose and glucuronate interconversions and the glycerophospholipid metabolism pathway. Gut microbiota analysis suggested that increased community Lachnoclostridium and Lachnospiraceae_UCG-006 in PIPN rats can be reversed significantly by JG. In conclusion, hemp extract exhibited antinociceptive effects on PIPN. The analgesic mechanism was probably related to the regulation of inflammation, neuroactive ligand-receptor interaction pathway, sphingolipid metabolism, etc. This study provides novel insights into the functional interactions of Cannabis sativa L. extract on PIPN.
Assuntos
Analgésicos , Cannabis , Neuralgia , Paclitaxel , Extratos Vegetais , Animais , Cannabis/química , Neuralgia/induzido quimicamente , Neuralgia/tratamento farmacológico , Neuralgia/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Ratos , Analgésicos/farmacologia , Analgésicos/química , Paclitaxel/efeitos adversos , Masculino , Metabolômica , Modelos Animais de Doenças , Hiperalgesia/tratamento farmacológico , Hiperalgesia/induzido quimicamente , Hiperalgesia/metabolismo , Canabinoides/farmacologia , MultiômicaRESUMO
A new enzyme-linked immunosorbent assay (ELISA) method for quantitative determination of monoester-type aconitic alkaloids was developed. The antibodies derived from the immunogen of benzoylmesaconine (BM) could be electively affined to benzoylaconitine-type alkaloids with an ester bond (14-benzoyl-), especially to benzoylhypaconine (BH, 140.02% of cross-reactivity). The effective working range of BH was 1 ng/ml to 5 µg/ml; the lower limit of detection and the quantification were 0.35 and 0.97 ng/ml, respectively. The values of CV for intra-day and inter-day assays and recovery ratios were in acceptable ranges. The results of stability experiments were also satisfactory. This validated method was employed for pharmacokinetic study of BH in rats and the bioavailability orally administered was estimated to be 16.3%.
Assuntos
Alcaloides/análise , Ensaio de Imunoadsorção Enzimática/métodos , Aconitina/análogos & derivados , Aconitum/química , Alcaloides/farmacocinética , Animais , Cromatografia Líquida de Alta Pressão/métodos , Estrutura Molecular , RatosRESUMO
A series of flavone glycosides were isolated from Fructus Kochiae for the first time, including two new flavone glycosides. The structures were established by interpretation of their spectroscopic data. Two new flavone glycosides are quercetin 3-O-ß-d-apiofuranosyl-(1 â 2)-ß-d-galactopyranosyl-7-O-ß-d-glucopyranoside (1) and quercetin 3-O-α-l-rhamnopyranosyl-(1 â 6)-ß-d-galactopyranosyl-7-O-ß-d-sophoroside (2). The others are quercetin 7-O-ß-d-glucopyranoside (3), quercetin 3-O-ß-d-apiofuranosyl-(1 â 2)-ß-d-galactopyranoside (4), quercetin 3-O-ß-d-galactopyranosyl-7-O-ß-d-glucopyranoside (5), and quercetin 7-O-ß-d-sophoroside (6).
Assuntos
Bassia scoparia/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Flavonas/isolamento & purificação , Glicosídeos/isolamento & purificação , Quercetina/análogos & derivados , Medicamentos de Ervas Chinesas/química , Flavonas/química , Frutas/química , Glicosídeos/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Folhas de Planta/química , Quercetina/química , Quercetina/isolamento & purificaçãoRESUMO
Hemp (Cannabis sativa L.), an annual dioecious plant, has shown extensive application in the fields of fibers, food, oil, medicine, etc. Currently, most attention has been paid to the therapeutic properties of phytocannabinoids. However, the pharmaceutical research on essential oil from hemp is still lacking. In this study, hemp essential oil (HEO) was extracted from hemp flowers and leaves, and the components were analyzed by GC-MS. Quatitative analysis of three main compounds ß-caryophyllene, ß-caryophyllene oxide, α -humulene were determined by GC-FID. The anti-tumor and anti-neuropathic pain effects of HEO were evaluated. In the paclitaxel induced neuropathic mice model, HEO reduced the serum level of inflammatory cytokines TNF-α to achieve the analgesic effect, which was tested by evaluating mechanical and thermal hyperalgesia. Further investigation with cannabinoid receptor 2 (CB2 R) antagonist AM630 revealed the mechanism of reversing mechanical hyperalgesia may be related to CB2 R. In Lewis lung cancer grafted mice model, the tumor growth was significantly inhibited, the levels of tumor inflammatory cytokines TNF-α and IL-6 were downregulated, immune organ index was modified and immune-related CD4+, CD8+ T lymphocytes level, CD4+/CD8+ ratio were increased when administered with HEO. These results reveal that HEO plays a role not only in tumor chemotherapy induced peripheral neuropathy treatment, but also in anti-tumor treatment which offers key information for new strategies in cancer treatment and provides reference for the medicinal development of hemp.
Assuntos
Antineoplásicos Fitogênicos , Cannabis , Carcinoma Pulmonar de Lewis , Neuralgia , Óleos Voláteis , Animais , Óleos Voláteis/farmacologia , Cannabis/química , Camundongos , Neuralgia/tratamento farmacológico , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Masculino , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Analgésicos/farmacologia , Camundongos Endogâmicos C57BL , Folhas de Planta/química , Flores/química , Hiperalgesia/tratamento farmacológico , Paclitaxel , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/metabolismo , Sesquiterpenos Policíclicos/farmacologia , Receptor CB2 de Canabinoide , Óleos de Plantas/farmacologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Jiawei-Yupingfeng-Tang (JYT) is a Chinese herbal formula that is widely used to treat respiratory tract illness. However, the effect of JYT on respiratory viruses remains unknown. The influenza virus (IFV) and the human respiratory syncytial virus (HRSV) cause millions of cases of severe illness per year, and many of these illnesses develop into lethal pneumonia. The aim of this study is to evaluate whether JYT can be used to treat these infections. MATERIALS AND METHODS: The effect of JYT against IFV and HRSV was tested using a plaque reduction assay in the lower respiratory tract cell line A549. The expression of ICAM-1 was determined by real-time RT-PCR and western blotting. A mouse model infected with lethal influenza developing into interstitial pneumonia was used to evaluate the effect of JYT in vivo. RESULTS: JYT extract inhibited both IFV and HRSV in a dose-dependent manner when given before, during and after a viral infection. JYT was effective in blocking the entry of the virus. Furthermore, pre-treatment with JYT reduced the susceptibility of cells to the invasion of HRSV by inhibiting the expression of ICAM-1. Importantly, JYT extract increased the survival rate of lethal influenza-infected mice, prolonged the survival time and alleviated the virus-induced lung lesions, which is comparable with the effects of ribavirin treatment. CONCLUSIONS: These data support JYT as an alternative modality to be used in the treatment of respiratory viral infection induced by HRSV and IFV.