非精神活性药用大麻的应用及开发

非精神活性药用大麻即四氢大麻酚(THC)质量分数0. 3%且大麻二酚(CBD)含量高(原则上应 2. 0%),主要用于药用的大麻植物。大麻的药用性历史悠久,笔者基于大麻的本草考证以及国际药用历史,阐述了大麻素类化合物特别是CBD在开发抗癫痫药品、精神疾病药品、镇痛抗炎药品及抗肿瘤药品上的应用,并对其在食品、保健品、化妆品等领域的应用情况进行总结。基于目前高CBD含量药用大麻的新品种匮乏、基础研究薄弱等问题,建议应加强CBD等有效成分的基础研究,推动药用大麻五类新药及保健品等的开发,通过挖掘药用大麻遗传信息,建立其综合鉴定体系并加快高CBD含量新品种选育,保障药用大麻的安全性及有效性,促进药用大麻产业的可持续发展。     

Antihyperalgesic effect of a Cannabis sativa extract in a rat model of neuropathic pain: mechanisms involved

This study aimed to give a rationale for the employment of phytocannabinoid formulations to treat neuropathic pain. It was found that a controlled cannabis extract, containing multiple cannabinoids, in a defined ratio, and other non-cannabinoid fractions (terpenes and flavonoids) provided better antinociceptive efficacy than the single cannabinoid given alone, when tested in a rat model of neuropathic pain. The results also demonstrated that such an antihyperalgesic effect did not involve the cannabinoid CB1 and CB2 receptors, whereas it was mediated by vanilloid receptors TRPV1. The non-psychoactive compound, cannabidiol, is the only component present at a high level in the extract able to bind to this receptor: thus cannabidiol was the drug responsible for the antinociceptive behaviour observed. In addition, the results showed that after chronic oral treatment with cannabis extract the hepatic total content of cytochrome P450 was strongly inhibited as well as the intestinal P-glycoprotein activity. It is suggested that the inhibition of hepatic metabolism determined an increased bioavailability of cannabidiol resulting in a greater effect. However, in the light of the well known antioxidant and antiinflammatory properties of terpenes and flavonoids which could significantly contribute to the therapeutic effects, it cannot be excluded that the synergism observed might be achieved also in the absence of the cytochrome P450 inhibition.     

大麻二酚抗肿瘤作用机制的研究进展

大麻二酚是非生理依赖性成分,不具有大麻的成瘾性,可被有选择地应用于晚期癌症。大麻二酚对癌细胞有抑制作用,是一种具有良好前景的新型抗肿瘤药物。综述了大麻二酚调控癌细胞凋亡、抑制癌细胞增殖、减轻癌细胞侵袭性的抗肿瘤作用机制,为大麻二酚的抗肿瘤研究提供参考。     

Evaluation of pharmacokinetics and acute anti‐inflammatory potential of two oral cannabidiol preparations in healthy adults

Cannabidiol (CBD) is a dietary supplement with numerous purported health benefits and an expanding commercial market. Commercially available CBD preparations range from tinctures, oils, and powders, to foods and beverages. Despite widespread use, information regarding bioavailability of these formulations is limited. The purpose of this study was to test the bioavailability of two oral formulations of CBD in humans and explore their potential acute anti‐inflammatory activity. We conducted a pilot randomized, parallel arm, double‐blind study in 10 healthy adults to determine differences in pharmacokinetics of commercially available water and lipid‐soluble CBD powders. Participants consumed a single 30 mg dose, which is within the range of typical commercial supplement doses, and blood samples were collected over 6 hr and analyzed for CBD concentrations. Peripheral blood mononuclear cells (PBMCs) were collected at baseline and T = 90 min, cultured and stimulated with bacterial lipopolysaccharide (LPS) to induce an inflammatory response. Cell supernatants were assayed for IL‐10 and TNF, markers of inflammation, using enzyme‐linked immunosorbent assays. The water‐soluble powder had C_max = 2.82 ng/ml, T_max = 90 min, and was approximately ×4.5 more bioavailable than the lipid‐soluble form. TNF was decreased in LPS‐stimulated PBMCs collected 90 min after CBD exposure relative to cells collected at baseline. This study provides pilot data for designing and powering future studies to establish the anti‐inflammatory potential and bioavailability of a larger variety of commercial CBD products consumed by humans.     

不同产地火麻仁脂溶性成分GC-MS分析

目的 分析10个不同产地火麻仁中脂溶性成分组成及含量的差异.方法 采用索氏提取法提取火麻仁中脂溶性成分,进行甲酯化处理,利用气相色谱质谱联用技术分离和鉴定其组成及含量.结果 火麻仁含有多种脂肪酸,不饱和脂肪酸含量较高,且各种不饱和脂肪酸比例适中.不同产地火麻仁样品脂溶性组分在组成成分及含量上,除安徽和河南两个产地差异较...     

以成纤维细胞生长因子受体1为靶点的姜黄素类似物的抗肿瘤活性研究

目的寻找以成纤维细胞生长因子受体1(FGFR1)为靶点,并具有良好抗肿瘤活性的小分子抑制剂。方法通过改造单羰基姜黄素类似物3,5-双(2-氟苯亚甲基)哌啶-4-酮(EF24),合成了其类似物[3,5-双(2-溴苯亚甲基)哌啶-4-酮,B6];采用FGFR1酪氨酸激酶实验验证其靶向性;MTT法检测EF24和B6对正常人肝细胞HL7702、4种肿瘤细胞(人大细胞肺癌NCl-H460、人胃癌细胞SGC-7901、人小细胞肺癌A549、人星形胶质瘤细胞株U251)增殖的影响;Western blotting法检测B6(2.5、5、10μmol/L)对NCl-H460细胞bFGF/FGFR下游信号蛋白表达的影响;Caspase-3试剂盒检测Caspase-3因子的表达。结果 EF24类似物B6可以以FGFR1为靶点,抑制NCI-H460细胞FGFR1以及下游信号蛋白丝氨酸/苏氨酸蛋白激酶(AKT)和细胞外调节蛋白(ERK1/2)的磷酸化,抑制肿瘤细胞的增殖,促进细胞凋亡。结论成功改造并获得靶向FGFR1的EF24类似物B6,其具有良好的体外抗肿瘤活性,为寻找FGFR1抑制剂候选抗肿瘤药物提供新思路。     

火麻仁中脂肪油和蛋白质成分含量比较研究

目的 测定来自21个不同产地的火麻仁品种,比较火麻仁中脂肪油和蛋白质的含量.方法 以有机溶剂抽提法无水乙醚为溶剂提取8 h,测定火麻仁中脂肪油和蛋白质的含量.结果 各样品中脂肪油的含量在22.40%～34.22%之间;蛋白含量在17.90%～27.48%之间,有显著差异.结论 对不同产地火麻仁中的脂肪油和蛋白质成分含量...     

土震素B类似物的合成及其抑制乙酰胆碱酯酶作用的研究

 目的　探索土震素B结构类似物对乙酰胆碱酯酶抑制作用的构效关系。方法　以强效乙酰胆碱酯酶抑制剂土震素B为先导化合物 ,对天然产物酸枣仁皂苷元进行结构简化和改造 ,使其形成A/B环与土震素B一致的立体结构 ,并再引入土震素系列化合物中的芳基结构。用Elisa法测试了所合成的化合物对乙酰胆碱酯酶的抑制活性。结果　合成了两个系列的土震素B的类似物,其中化合物7c和15在10^-4mol·L^-1条件下分别显示出乙酰胆碱酯酶26%和32%的抑制活性。结论　初步探明了此类具有与土震素B的A/B环的立体化学一致的2-烯-1-酮A环结构以及含芳基酯基药效团的化合物对乙酰胆碱酯酶有一定的抑制活性。     

Beneficial effects of a Cannabis sativa extract treatment on diabetes‐induced neuropathy and oxidative stress

Neuropathy is the most common complication of diabetes and it is still considered to be relatively refractory to most of the analgesics. The aim of the present study was to explore the antinociceptive effect of a controlled cannabis extract (eCBD) in attenuating diabetic neuropathic pain. Repeated treatment with cannabis extract significantly relieved mechanical allodynia and restored the physiological thermal pain perception in streptozotocin (STZ)‐induced diabetic rats without affecting hyperglycemia. In addition, the results showed that eCBD increased the reduced glutathione (GSH) content in the liver leading to a restoration of the defence mechanism and significantly decreased the liver lipid peroxidation suggesting that eCBD provides protection against oxidative damage in STZ‐induced diabetes that also strongly contributes to the development of neuropathy. Finally, the nerve growth factor content in the sciatic nerve of diabetic rats was restored to normal following the repeated treatment with eCBD, suggesting that the extract was able to prevent the nerve damage caused by the reduced support of this neurotrophin. These findings highlighted the beneficial effects of cannabis extract treatment in attenuating diabetic neuropathic pain, possibly through a strong antioxidant activity and a specific action upon nerve growth factor. Copyright © 2009 John Wiley & Sons, Ltd.