Cornusides A–O, Bioactive Iridoid Glucoside Dimers from the Fruit of Cornus officinalis

Abstract

Fifteen new and rare iridoid glucoside dimers, cornusides A-O (1-15), and 10 known iridoid glucosides (16-25) were isolated from the fruit of Cornus officinalis. These new chemical structures were established through spectroscopic analysis (UV, IR, HRESIMS, 1D and 2D NMR). Compounds 1-25 were tested for their inhibitory activities by measuring IL-6-induced STAT3 promoter activity in HepG2 cells, and 3, 12, 17, 22, and 23 showed inhibitory effects, with IC values of 11.9, 12.2, 14.0, 7.0, and 6.9 μM, respectively.

Cornus mas and Cornus Officinalis—Analogies and Differences of Two Medicinal Plants Traditionally Used

“…Additionally, apart from typical iridoids described previously, less-known compounds such as logmalicids A and B ( 19–20 ) as well as cornusfurosides A-D ( 22–24 ) were found in fruits of C. officinalis (Ma et al, 2014; He et al, 2017). Fifteen rare iridoid glucoside dimers, named cornusides A-O ( 31–45 ) (Figure 2), have been isolated from an aqueous extract of C. officinalis fruits (Ye et al, 2017). …”

Cornusglucosides A and B, Two New Iridoid Glucosides from the Fruit of Cornus officinalis

“…Compound 2 , colorless powder, was determined as C 20 H 32 O 13 according to the HR‐ESI‐MS signal at m / z 503.1732 [M+Na] + . The NMR data of 2 ( Table ) were similar to those of 7 α ‐ O ‐morroniside, except for the extra carbons signals ( δ (C) 64.2 (CH 2 ), 71.5 (CH 2 ) and 71.7 (CH)), and the chemical shifts of C‐7 ( 2 : δ (C) 103.7; 7 α ‐ O ‐morroniside: δ (C) 96.0) . The HMBC spectrum ( Figure ) showed the correlations of H‐2′ ( δ (H) 3.76–3.80) with the C‐1′ ( δ (C) 71.5) and C‐3′ ( δ (C) 64.2), which indicated the presence of glycerin groups .…”

“…The 13 C‐NMR spectrum ( Table ) exhibited 25 carbon signals, including one methyl, two methoxy, three methylene, two methine, and four O‐bearing methine groups, one O‐bearing quaternary carbon, two acetal carbons ( δ (C) 95.9 and 104.3), two olefinic carbons ( δ (C) 111.0 and 154.5), two carbonyl carbons ( δ (C) 168.6 and 175.8), together with signals for one glucopyranosyl moiety ( δ (C) 100.0, 75.1, 78.5, 71.8, 78.0, and 63.0). The NMR data of 1 ( Table ) were similar to those of 7 α ‐ O ‐morroniside, except for the chemical shifts of C‐7 ( 1 : δ (C) 104.3; 7 α ‐ O ‐morroniside: δ (C) 96.0), and the extra carbons signals ( δ (C) 38.1 (CH 2 ), 41.1 (CH 2 ), 52.9 (MeO), 71.6 (CH), 75.2 (CH), 76.6 (CH), 76.7 (C) and 175.8 (C=O)), which was closely similar to those of methyl quinate . The 1 H, 1 H‐COSY correlations ( Figure ) (H‐2′ ( δ (H) 2.00–2.02, 2.04–2.06) with H‐3′ ( δ (H) 4.07–4.11), H‐6′ ( δ (H) 1.91–1.96, 2.28–2.33) with H‐5′ ( δ (H) 3.52–3.55), and H‐4′ ( δ (H) 4.12–4.16) with H‐3′ ( δ (H) 4.07–4.11) and H‐5′ ( δ (H) 3.52–3.55)) and the HMBC correlations ( Figure ) (H‐2′ ( δ (H) 2.00–2.02, 2.04–2.06), H‐3′ ( δ (H) 4.07–4.11), H‐5′ ( δ (H) 3.52–3.55), H‐6′ ( δ (H) 1.91–1.96, 2.28–2.33) with the C‐1′ ( δ (C) 76.7), and H‐3′ ( δ (H) 4.07–4.11), H‐5′ ( δ (H) 3.52–3.55) with the C‐4′ ( δ (C) 76.6)) further confirmed the presence of methyl quinate groups.…”

“…The inhibitory abilities of 1 and 2 were evaluated on IL‐6‐induced STAT3 activation in HepG2 cells, whereas genistein was used as the positive drug. The detailed processes were based on the reported method …”

“…is a well‐known traditional Chinese medicine used for nourishing the liver and kidney in China, which has been used for thousands of years. The chemical and pharmacological studies on the fruit of C. officinalis have been lasting for many years in our group . Recently, further chemical investigation on the title plant led two new iridoid glucosides, cornusglucoside A ( 1 ) and cornusglucoside B ( 2 ) ( Figure ).…”