Two new diterpenoids from the rhizomes of Zingiber officinale

Abstract Two undescribed labdane diterpenoids (5S,8S,9R,10S,11E)-8,17-epoxy-13,14-dinorlabd-11-en-13-one (1) and (5S,9R,10S,12E)-17-hydroxy-labd-7,12-dien-15(16)-olide (2), together with seven known sesquiterpenoids (3–9) and two known monoterpenoids (10–11) were isolated from the dried rhizome of Zingiber officinale. Their structures were elucidated by detailed spectroscopic data (IR, UV, HR-ESI-MS, 1D and 2D NMR), X-ray crystallographic and ECD analysis. Moreover, all the 11 compounds were tested for α-glucosidase inhibitory effects and 9 was found to exhibit stronger inhibitory effects at IC50 = 4.8 μM against a positive control acarbose with IC50 = 414.6 μM. Graphical Abstract


a-glucosidase inhibitory activity
The hypoglycemic activities of 1-11 were evaluated using the a-glucosidase inhibitory assay with acarbose as the positive control. Compound 10 showed weak a-glucosidase inhibitory activity, whereas 3 and 9 exhibited excellent a-glucosidase inhibitory activity (IC 50 ¼ 288.5 and 4.8 lM, respectively) with a potency stronger than that of the positive control, acarbose (IC 50 ¼ 414.6 lM) (Supplementary material, Table S2 and Figure S23).

Plant material
Dried rhizomes of Z. officinale were collected from Jingxiang County, Shandong, China, in September 2016. The plant material was identified by Prof. Guang-Xiong Zhou of Jinan University. A voucher specimen (JNU-ZO-201609) was deposited at the Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou, China.

a-glucosidase inhibitory assay
The a-glucosidase inhibitory activity was assayed using the previously described method with slight modifications (Gao et al. 2017). In brief, 25 lL of various concentrations of tested compounds and 25 lL of 0.2 U/mL a-glucosidase (Sigma-Aldrich Chemical Co. Ltd, Saint Louis, USA) were added into 96-well plates. The mixture was preincubated at 37 C for 10 min, and 25 lL of 2.5 mM p-nitrophenyl glucopyranoside was added into each well. The mixture was incubated at 37 C for 5 min, and 80 lL of 0.2 M Na 2 CO 3 was put into each well to stop the reaction. The optical density was monitored at 405 nm using the Synergy HT microplate reader. Acarbose was used as the positive control, and all the reactions were performed in triplicate. The a-glucosidase inhibition percentage (Inhibition %) was calculated as follows: Inhibition% ¼ [(DAbs control À DAbs sample )/DAbs control ] Â 100.

Conclusions
In the present study, two new diterpenoids, together with nine known compounds were isolated from the rhizomes of Z. officinale. The structures of 1-2 were elucidated by extensive spectroscopic, X-ray crystallographic and ECD analysis. The a-glucosidase inhibitory activities of all the isolated compounds were assayed, and 9 exhibited significant inhibitory activity with IC 50 value 4.8 lM. The results indicated that the rhizomes of Z. officinale contained potential a-glucosidase inhibitors, which could provide a material basis for the discovery and development of hypoglycemic drugs.

Disclosure statement
No potential conflict of interest was reported by the authors.

Funding
This work was supported by grants from the Special Funds for transformation and upgrading of industrial informatization of industry and information technology department of jiangsu in 2020.