A class of geranylquinol-derived polycyclic meroterpenoids from Arnebia euchroma against heart failure by reducing excessive autophagy and apoptosis in cardiomyocytes.

Ten new B-ring aromatized 6/6/6-tricyclic dearomatized benzocogeijerene-based meroterpenoids with unusual methyl 1,2-shift or demethylation (2-9b), and two new geranylquinol derivatives (1 and 10), together with two known compounds (11 and 12), were isolated from the roots of Arnebia euchroma. Their structures were elucidated by extensive spectroscopic methods, X-ray diffraction crystallography, and ECD calculations. The plausible biosynthetic pathways including the unusual methyl 1,2-shfit and demethylation for B-ring aromatized 6/6/6-tricyclic meroterpenoids were discussed. Compounds 1, 2, 5, 6, 11, and 12 showed significant cardioprotective activities comparable to diltiazem against isoprenaline (ISO)-induced H9C2 cell damage in vitro. Compound 11 probably exerted heart-protective effect on ISO-induced H9C2 cells by modulating the PI3K-AKT-mTOR pathway, reducing excessive autophagy, and decreasing myocardial apoptosis.

Fourteen new 2-benzylbenzofuran glycosides with cardioprotective activity from Heterosmilax yunnanensis.

Fourteen new 2-benzylbenzofuran O-glycosides (1-13, 15) and one new key precursor, diarylacetone (14) were isolated from the roots of Heterosmilax yunnanensis Gagnep, which all have characteristic 2,3,4-O-trisubstituted benzyl. Their structures were elucidated by 1D and 2D NMR, HRESIMS, UV and IR. The isolated compounds were assessed for their cardioprotective activities and compounds 1, 3 and 6 could significantly improve cardiomyocytes viability. Moreover, the mechanistic study revealed that these three compounds could significantly decrease intracellular ROS levels and maintain mitochondrial homeostasis upon hypoxia inducement. Consequently, 1, 3 and 6 might serve as potential lead compounds to prevent myocardial ischemia.

Heteryunine A, an amidated tryptophan-catechin-spiroketal hybrid with antifibrotic activity from Heterosmilax yunnanensis.

An unprecedented spiro-C-glycoside adduct, heteryunine A (1), along with two uncommon alkaloids featuring a 2,3-diketopiperazine skeleton, heterpyrazines A (2) and B (3), were discovered in the roots of Heterosmilax yunnanensis. The detailed spectroscopic analysis helped to clarify the planar structures of these compounds. Compound 1, containing 7 chiral centers, features a catechin fused with a spiroketal and connects with a tryptophan derivative by a CC bond. Its complex absolute configuration was elucidated by rotating frame overhauser enhancement spectroscopy (ROESY), specific rotation, and the 13C nuclear magnetic resonance (NMR) and electronic circular dichroism (ECD) calculation. The possible biosynthetic routes for 1 were deduced. Compounds 1 and 2 showed significant antifibrotic effects and further research revealed that they inhibited the activation, migration and proliferation of hepatic stellate cells (HSCs) through suppressing the activity of Ras homolog family member A (RhoA).

Two new cucurbitane-type triterpenoid saponins from the fruit of Citrullus colocynthis.

Two new cucurbitane-type triterpenoid saponins, 2,20ß,22ß-trihydroxy-16α,23(R)-epoxycucurbita-1,5,24-triene-3,11-dione 2-O-ß-D-glucopyranoside (1), 2,20ß,22α-trihydroxy-16α,23(S)-epoxycucurbita-1,5,11,24-tetraene-3-one 2-O-ß-D-glucopyranoside (2) were isolated from the fruit of Citrullus colocynthis (L.) Schrad. Their structures were elucidated by mass spectrometry, IR, 1D, and 2D NMR spectroscopy, etc. Besides, both of the compounds showed significant hepatoprotective activities at 10 µM against paracetamol-induced HepG2 cell damage.

Six new iridoid glycosides from the whole plants of Hedyotis diffusa.

Six new iridoid glycosides were isolated from the ethyl acetate fraction of the whole plants of Hedyotis diffusa Willd. They were identified as E-6-O-p-methoxycinnamoyl-10-O-acetyl scandoside acid methyl ester (1), Z-6-O-p-methoxycinnamoyl-10-O-acetyl scandoside acid methyl ester (2), E-6-O-caffeoyl scandoside methyl ester (3), E-6-O-p-coumaroyl-6'-O-acetyl scandoside methyl ester (4), Z-6-O-p-coumaroyl-6'-O-acetyl scandoside methyl ester (5), and E-6-O-p-coumaroyl-4'-O-acetyl scandoside methyl ester (6). The structures of them were elucidated based on unambiguous spectroscopic data (UV, IR, HRESIMS, and NMR). They were screened for anti-inflammatory effect, antioxidant effect, antitumor effect, and neuroprotective effect and did not show potent activities.

Three new flavonoids from the roots of Sophora tonkinensis.

Three new flavonoids including two isoflavanones sophortones A and B (1 and 2), and one chalcone sophortone C (3) were isolated from the roots of Sophora tonkinensis. Their structures were established by UV, IR, HRESIMS, and NMR data. The absolute configurations of 1 and 2 were determined by electronic circular dichroism (ECD) calculations.

Eight new arnebinol B-based meroterpenoids with planar chirality in the constrained 6/10/5 tricyclic skeleton from Arnebia euchroma and their cytotoxicities.

Eight new arnebinol B-based meroterpenoids ((-)-1, 2, 3, (-)-5, and 7-10) with a constrained 6/10/5 tricyclic backbone were isolated from the roots of Arnebia euchroma. The planar and steric structures of these new compounds were unambiguously elucidated by extensive spectroscopic analyses, X-ray diffraction crystallography, and ECD calculations. The predominant relative orientation between H-7 and the Z double bond with a methyl substituent in the rigid 10-membered carbocycle, along with the planar chirality of the Z double bond was analyzed and discussed for the first time. The illustration of the planar chirality derived from the Z double bond should be paid great importance during the structure elucidation on these homologous meroterpenoids. All the isolated meroterpenoids were screened for their cytotoxicities against the HCT-8, PANC-1, HGC-27, HepG2, and PC9 cell lines, and compounds (+)-5 and (-)-5 exhibited the most potent cytotoxicity.

Two dimers generated by lithospermic decarboxylation coupling from Danshen.

To further reveal the active ingredients of Danshen, we systematically studied its chemical components and obtained two new lithospermic acid derivatives (compounds 1 and 2) together with five known phenylpropionic acids (compounds 3-7) from the dried rhizomes of Salvia miltiorrhiza. The structures of the two new compounds were determined by multiple spectral analyses (UV, IR, HR-ESI-MS, NMR, and ECD). In addition, the absolute configurations were established by chiral analysis and calculated and experimental circular dichroism spectra. Biological research indicated that compound 1 could significantly inhibit the proliferation of isoproterenol (ISO)-treated cardiac fibroblasts (AC16 cells), and MMP9 was found to be the most likely target of compound 1. The protein expression and mRNA levels of MMP9 were increased in ISO-induced AC16 cells, which could be reversed by treatment with compound 1. Furthermore, this treatment could alleviate the migration and activation of ISO-induced cardiac fibroblasts.

Photoinduced Irreversible Intramolecular Proton Transfer of Arnebinones B, D, and E: The Case of Photoenolization at the p-Benzoquinone-CH2/CH-π System.

Arnebinones B, E, and D (1-3) have been found to be sensitive to light, generating complex and diverse proton transfer products when triggered by light. A unique two-step irreversible intramolecular proton transfer of 1 produced five scalemic mixtures, of which four possessed intriguing dual planar chirality. The unprecedented orientation epimerization equilibrium of the intra-annular double bond was first observed and researched in the homologous meroterpenoids by HPLC monitoring and DFT calculations. A "p-benzoquinone-CH2/CH-π" moiety in the structure was the common key feature for the occurrence of this type of photoenolization reaction. The product transformation processes and universality of this photoinduced irreversible proton transfer reaction were analyzed together with the cytotoxic activities of arnebinones B, D, and E, and their photoreaction products.

New dimeric phloroglucinol derivatives from Agrimonia pilosa and their hepatoprotective activities.

Five new dimeric phloroglucinol derivatives, agrimones A - E (1-5), were isolated from the whole plant of Agrimonia pilosa. Their structures including absolute configurations were determined by a series of spectroscopic data (UV, IR, HR-ESI-MS, 1D and 2D NMR), complemented with the comparison of the experimental and calculated ECD spectra, and gauge-independent atomic orbital (GIAO) NMR calculations. Notably, compounds 1 and 2 represent a highly oxidized 6/6/6 tricyclic ring skeleton based on the cis-fused paraquinone and chroman. Compounds 1a, 4, and 5 exhibited moderate hepatoprotective activities against APAP-induced HepG2 cell injury at 10 µM.