Tinospinosides D, E, and Tinospin E, Further Clerodane Diterpenoids from <i>Tinospora sagittata</i>

Abstract

Chemical investigation on the roots of Tinospora sagittata resulted in the isolation of three novel cis-clerodane diterpenoids, tinospinosides D, E, and tinospin E, together with two known compounds, columbin and columbin glucoside, and their structures were determined by extensive spectroscopic analyses, chemical reactions and computer-assisted calculations. The inhibitory activity of the isolated compounds and their chemical derivatives on nitric oxide production in lipopolysaccharide and interferon-γ activited J774.1 macrophage-like cells was also evaluated.Key words Tinospora sagittata; Menispermaceae; clerodane diterpenoid; nitric oxideThe genus Tinospora (Menispermaceae) has about thirty species, mainly distributing in the tropic area of Asia and Africa, and many of the species have been used in traditional medicines, e.g., T. codifolia has been used in Ayurveda (Indian traditional medicines) as a hepatoprotectant 1) ; the stem of T. sinensis has been used in Traditional Chinese Medicine (TCM) in the treatment of rheumatism and muscle pain; the root of T. capillipes and T. sagittata has been used in TCM to relieve sore throat, expel superficial infection, and stop diarrhea.2) The main chemical constituents of Tinospora species have been reported to be diterpenoids, which has 12-furano cis-clerodane skeleton as their characteristic structure.3-5) As a part of our continuing phytochemical research on Tinospora species, we have previously reported the isolation of three novel clerodane diterpenoids, tinosposinensides A-C, from the stems of T. sinensis, 6) and three novel clerodane diterpenoids, tinospinosides A-C, from the roots of T. sagittata. 7) In a further investigation on the roots of T. sagittata, we herein report the isolation and structural determination of three new clerodane diterpenoids, tinospinoside D (1), tinospin E (2), and tinospinoside E (3) (Fig. 1). The inhibitory activity of these compounds and their chemical derivatives on nitric oxide production in lipopolysaccharide (LPS) and interferon (INF)-γ activited J774.1 macrophage-like cells was also evaluated. Results and DiscussionThe EtOAc fraction from the MeOH extract of roots of T. sagittata was fractionated by repeated column chromatography followed by HPLC purification to afford five compounds 1-5. The known compounds were identified to be columbin (4) and columbin glucoside (5) by comparing the physical and spectroscopic data in literature. 7) Namely, resonances of an epoxy moiety at δ C 54.8 (C-2) and 53.8 (C-3), and an oxyganated quaternary carbon resonance at δ C 83.9 (C-4) were observed in 1, instead of resonances of C-2 oxyganated methine and C-3, 4 olefin in tinospinoside C. The epoxy moiety was assigned at C-2 and C-3 by sequential 1 H-1 H correlation spectroscopy (COSY) correlations between resonances of H-10, H α,β -1, H-2, and H-3, and a heteronuclear multiple bond connectivity (HMBC) correlation from δ H 2.69 (H-10) to δ C 54.8 (C-2) (Fig. 2). The oxylated quaternary carbon resonance at δ C 83.9 was assigned to C-4, by HMBC ...

Clerodane diterpenes: sources, structures, and biological activities

“…353 Type IV glucoside 968 adopted a unique all boat conformation of its tricyclic ring system, as also indicated by energy calculations. 255 …”

Benefits of antioxidant supplements for knee osteoarthritis: rationale and reality

“…It contains withanaloids, most importantly withaferin A [ 90 ]. Tinospora cordifolia (Guduchi) is considered a divine herb and it contains diterpenoids termed tinosporides [ 91 ]. Emblica officinalis (or Phyllanthus emblica ) is termed amla or amlaki and is rich in vitamin C and emblicanins A and B [ 92 ].…”

New Clerodane Diterpenes from Tinospora sagittata var. yunnanensis

“…During the subsequent investigation of T. sagittata var. yunnanensis, four new clerodane diterpenes, named sagittatayunnanosides A-D (1-4), were isolated from the 95 % ethanol extract, together with two known ones, tinospinoside C (5) [9] and tinospinoside E (6) [10]. All six isolates were assayed for their cytotoxicity in HeLa, K562, HL60, and HepG2 cell lines and anti-settlement activity against B. amphitrite.…”

“…1 and named sagittatayunnanoside D (4). The known compounds 5 and 6 were identified by comparing their NMR data with those in the literatures [9,10]. The cytotoxic activities of compounds 1-6 were evaluated in vitro by using HeLa, K562, HL60, and HepG2 cell lines.…”