Epinodosinol

Network Pharmacological Screening of the Active Ingredients and Hypoglycemic Effect of Isodon rubescens in the Treatment of Diabetes.[Pubmed:32294788]

Planta Med. 2020 May;86(8):556-564.

This study was firstly to study the relationship of "ingredient-target-pathway" and the pharmacological effects of Isodon rubescens for the treatment of diabetes. Based on a network pharmacology method, 138 active ingredients of Isodon rubescens were screened from the relative literatures, and their targets were confirmed by comparing these with the hypoglycemic targets in the DrugBank database. Results showed that Isodon rubescens contained 25 hypoglycemic ingredients, such as rabdoternin A, rabdoternin B, and Epinodosinol. These ingredients could activate 6 hypoglycemic targets, including 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), integrin alpha-L (ITGAL), integrin beta-2 (ITGB2), progesterone receptor (PGR), glucocorticoid receptor (NR3C1), and nuclear receptor subfamily 1 group I member 2 (NR1I2). These targets were involved in 94 signaling pathways, such as the Rap1, PI3K-Akt, and HIF-1 signaling pathways. The cell viability showed that the human umbilical vein endothelial cells (HUVECs) treated with alcohol extract (1.00 g/L) and the water extract (0.13 - 0.50 g/L) exhibited high viability compared to the model group (p < 0.05), respectively. 0In animal experiments, the rats treated with water extract of Isodon rubescens showed significant hypoglycemic effects compared to rats in the model group (p < 0.05). Overall, this approach provides an efficient strategy to explore hypoglycemic ingredients of Isodon rubescens and other traditional Chinese medicine.

[Studies on chemical constituents of Isodon henryi].[Pubmed:30989952]

Zhongguo Zhong Yao Za Zhi. 2019 Jan;44(2):319-323.

The chemical constituents of the water extraction of the aerial parts of Isodon henryi were investigated by various chromatographic methods including D-101 macroporous adsorptive resins,silica gel,sephadex LH-20,and semi-preparative HPLC. As a result,ten compounds were separated and purified. By analyses of the UV,IR,MS,NMR spectra,their structures were determined as rabdosinate( 1),lasiokaurin( 2),Epinodosinol( 3),rabdosichuanin C( 4),epinodosin( 5),hebeirubescensin k( 6),rubescensin C( 7),enmenol( 8),oridonin( 9),and enmenol-1-beta-glucoside( 10). Compounds 1-8 and 10 were isolated from I. henryi for the first time. Compounds 2 and 9 showed inhibitory effects against four tumor cells,with IC50 values of 2. 25-9. 32 mumol.L-1.

Molecular structure and vibrational bands and 13C chemical shift assignments of both enmein-type diterpenoids by DFT study.[Pubmed:24013676]

Spectrochim Acta A Mol Biomol Spectrosc. 2014 Jan 3;117:449-58.

We report here theoretical and experimental studies on the molecular structure and vibrational and NMR spectra of both natural enmein type diterpenoids molecule (6, 7-seco-ent-kaurenes enmein type), isolated from the leaves of Isodon japonica (Burm.f.) Hara var. galaucocalyx (maxin) Hara. The optimized geometry, total energy, NMR chemical shifts and vibrational wavenumbers of Epinodosinol and epinodosin have been determined using B3LYP method with 6-311G (d,p) basis set. A complete vibrational assignment is provided for the observed IR spectra of studied compounds. The calculated wavenumbers and 13C c.s. are in an excellent agreement with the experimental values. Quantum chemical calculations at the B3LYP/6-311G (d,p) level of theory have been carried out on studied compounds to obtain a set of molecular electronic properties (MEP,HOMO, LUMO and gap energies DeltaEg). Electrostatic potential surfaces have been mapped over the electron density isosurfaces to obtain information about the size, shape, charge density distribution and chemical reactivity of the molecules.

Chemical constituents of flowers and fruits of Rabdosia excisa.[Pubmed:23302530]

Chin J Nat Med. 2012 Jan;10(1):43-7.

AIM: To study the chemical constituents in the flowers and fruits of Rabdosia excisa. METHODS: The compounds were isolated and purified by silica gel column chromatography and their structures were identified by spectroscopic methods. RESULTS: Sixteen compounds isolated from the flowers and fruits of this plant were identified as: stigm asterol (I), alpha-amyrin palmitate (II), ursolic acid (III), 2alpha, 3alpha, 19-trihydroxy-urs-12-en-28-oic acid (IV), 2alpha-hydroxyursolic acid (V), maslinic acid (VI), isodonal (VII), maoyecrystal E (VIII), kamebakaurin (XI), macrocalyxin G (X), Epinodosinol (XI), rabdosichuanin C (XII), kamebacetal A (XIII), oridonin (XIV), enmenol-glucoside (XV), and lasiononin (XVI). CONCLUSION: All the constituents were found in Rabdosia excisa for the first time, except constituents III, IX, XII and XIV.

A sensitive analysis method for 7 diterpenoids in rat plasma by liquid chromatography-electrospray ionization mass spectrometry and its application to pharmacokinetic study of Isodon serra extract.[Pubmed:21930275]

J Chromatogr A. 2011 Oct 28;1218(43):7771-80.

A simple and sensitive LC-MS/MS method has been developed and validated for the identification and quantification of epinodosin, Epinodosinol, nodosin, oridonin, lasiokariurinol, lasiokaurin and rabdoternin A in rat plasma using sulfamethoxazole as the internal standard. The plasma sample pre-treatment consisted of a liquid-liquid extraction. Chromatographic separation was achieved on a C18 column with linear gradient elution using water and methanol, which were both acidified with 0.1% formic acid, at a flow rate of 0.7 mL/min. A tandem mass spectrometric detection was conducted using multiple reaction monitoring (MRM) via an electrospray ionization (ESI) source. A novel multi-determination-periods program was executed to achieve a higher sensitivity by setting five scanning periods. The method presented here utilizes a novel determination strategy, enabling the application of positive and negative ESI-MS in a single run. The optimized mass transition ion-pairs (m/z) for quantitation were 361.2/287.1 for epinodosin, 382.3/347.3 for Epinodosinol, 363.3/281.2 for nodosin, 365.3/347.3 for oridonin, 407.3/329.1 for lasiokariurinol, 405.2/59.0 for lasiokaurin, 363.2/283.1 for rabdoternin A and 254.1/156.0 for IS. The total run time was 20.50 min (including 5 min equilibration time) between injections. The specificity, linearity, accuracy, precision, recovery, matrix effect and several validation results demonstrate that this method is sensitive, specific and reliable. The proposed method was further applied to investigate the pharmacokinetics of all analytes after a single oral administration of Isodon serra extract to rats.

Comparison of cytotoxicity and DNA damage potential induced by ent-kaurene diterpenoids from Isodon plant.[Pubmed:19606380]

Nat Prod Res. 2011 Sep;25(15):1402-11.

The cytotoxicity of six ent-kaurene diterpenoids isolated from the leaves of Isodon japonica (Burm.f.) Hara var. galaucocalyx (maxin) Hara was evaluated against three human tumour HepG2, GLC-82 and HL-60 cell lines through SRB assay, and their DNA damage potential (against HepG2 cell line) was assessed by comet assay. Among the six ent-kaurene diterpenoids, Rabdosin B was most cytotoxic, followed by Oridonin, Epinodosin, Rabdosinate, Lasiokaurin and Epinodosinol. All of the six ent-kaurene diterpenoids induced significant DNA damage (p < 0.05) to HepG2 cells in a time- and dose-dependent manner except Lasiokaurin and Eponodosinol at 6 micromol L(-)(1) for 24 h. The structure-activity relationships (SARs) were discussed and it was found that exo-methylene cyclopentanone in the molecular structure was important for maintaining the cytotoxicity and DNA damage potential of the compounds.-OAc group at site C-1 in Lasiokaurin had a higher stereospecific blockade, which made the compound have less cytotoxicity and DNA damage potential than Oridonin (-OH at C-1).

Two novel ent-kauranoid diterpenoids from Isodon japonica leaves.[Pubmed:16142643]

Planta Med. 2005 Aug;71(8):764-9.

Two novel ent-kaurane diterpenoids, taihangjaponicain A (1), and taihangjaponicain B ( 2), and nine known diterpenoids, epinodosin (3), oridonin (4), Epinodosinol (5), lasiokaurin ( 6), 1alpha- O-beta- D-glucopyranosylenmenol (7), lasiodonin (8), rabdosichuanin D ( 9), shikokianin (10) and rabdoternin A (11) were isolated from I. japonica leaves. The structures of the two new compounds were elucidated using 1-D and 2-D NMR spectroscopy. Compounds 1 and 3 - 11 were tested against HL-60, HO-8910 and A-549 human tumor cells. Compounds 4, 6 and 10 showed significant cytotoxicity against HL-60 cells with IC (50) values of 4.6, 2.0 and 3.4 microM, respectively, and against A-549 cells with IC (50) values of 17.5, 11.4 and 18.8 microM, respectively. Compound 6 exhibited moderate cytotoxicity against HO-8910 cells with an IC (50) value of 17.9 microM.

[Chemical constituents of Isodon parvifolia (Batalin) Hara].[Pubmed:2390167]

Zhongguo Zhong Yao Za Zhi. 1990 Feb;15(2):101-3, 127.

Twelve compounds were isolated from the leaves and stems of Isodon parvifolia. This paper deals with the isolation and identification of two diterpenes Epinodosinol (I), lasiodonin (II) and two triterpenes alpha-amyrin (XI a) and beta-amyrin (XI b).