Biotransformation of cannabinoids using plant tissue culture and their activity

本实验室利用植物组织培养技术对药用植物的选育和天然生物活性化合物的生产进行了研究。在这个项目中，我们开始研究大麻素的生物转化，利用植物细胞和/或组织作为植物催化剂，以创造一些新的大麻素作为新药的资源。四氢大麻酚（THC）、大麻二酚（CBD）、大麻二酸（CBDA）和大麻酚（CBN）分别与半夏原球茎段在添加2,4- d （0.25 mg/l）的培养基中孵育1-3周，孵育条件为25ºC。从原球茎体和培养基中提取生物转化产物，然后进行纯化。这些结构分别通过13bbbc、1HNMR和FAB-MS鉴定为thc -单糖苷、cbd -单糖苷和二糖苷、cbda -单糖苷和羟基- cbda -单糖苷、cbn -单糖苷和羟基- cbn -单糖苷。结果表明，thc -单糖苷、cbn -单糖苷（Kd bbb8 ^<mu>M）和cbd -单糖苷（Kd>20 ^<mu>M）与大麻素受体具有亲和力。根据这些结果，将对三种新型大麻素的药理活性进行预期。

The breeding of medicinal plants and the production of naturally occurring biologically active compounds have been investigated by plant tissue culture technique in this laboratory. In this project we started to study the biotransformation of cannabinoids using the plant cell and/or tissue as a plant catalyst in ordsr to create some new cannabinoids for resources of new drugs.Tetrahydrocannabinol (THC), cannabidiol (CBD), cannabidiolic acid (CBDA) and cannabinol (CBN) were incubated individually with the protocorm segment of Pinellia ternata in the medium supplemented with 2,4-D (0.25 mg/l) at 25ﾟC in the dark condition for 1-3 weeks. The biotransformed products were extracted from the protocorm body and the medium, then purified. These structures were elucidated as THC-monoglycoside, CBD-mono and diglycosides, CBDA-monoglycoside and hydroxy-CBDA-monoglycoside, CBN-mono glycoside and hydroxy-CBN-monoglycoside by ^<13>C and ^1HNMR and FAB-MS,respectively. It became evident that THC-monoglycoside and CBN-monoglycoside (Kd>8 ^<mu>M) and CBD-monoglycoside (Kd>20 ^<mu>M) have the affinity with cannabinoid receptor. From these results, the pharmacological activities of three new cannabinoids will be expected.