Identification of diverse sesquiterpenoids with anti-fibrotic potential from Inula japonica Thunb.

In the chemical investigation of Inula japonica, a total of 29 sesquiterpenoids (1-29) were obtained, including pseudoguaine-, xanthane-, eudesmane-, and 1,10-secoeudesmane-type compounds, as well as their dimers. Among them, six new dimeric sesquiterpenoids, bisinulains A-F (1-5, 7), characterized by a [4 + 2] biogenetic pathway between different sesquiterpenoid monomers were identified. Additionally, three new monomers named inulaterins A-C (13, 18 and 21) were discovered. The structures of these compounds were determined through analysis of spectroscopic data, X-ray crystallographic data, and ECD experiments. To assess their potential anti-inflammatory activities, the sesquiterpenoid dimers were tested for their ability to inhibit NO production in LPS-stimulated RAW 264.7 cells. Furthermore, the compounds that exhibited anti-inflammatory effects underwent evaluation for their anti-fibrotic potential using a TGF-ß-induced epithelial-mesenchymal transition model in A549 cells. As a result, bisinulain B (2) was screened out to significantly inhibit the production of cytokines involved in pulmonary fibrosis such as NO, α-SMA, collagen I and fibronectin.

Biogenetic and biomimetic synthesis of natural bisditerpenoids: hypothesis and practices.

Covering: up to March 2022Bisditerpenoids, or diterpenoid dimers, are a group of natural products with high structural variance, deriving from homo- or hetero-dimeric coupling of two diterpenoid units. They usually possess complex architectures resulting from the diversity of monomeric diterpenoids as building blocks and the dimerization processes. These compounds have attracted the attention of synthetic and biological scientists owing to the rarity of their natural origin and their significant biological activities. Herein, we provide a review highlighting some of the interesting bisditerpenoids reported since 1961 and showcase the chemical diversity in both their structures and biosynthesis, as well as their biological functions. This review focuses on the biosynthetic dimerization pathways of interesting molecules and their biomimetic synthesis, which may act as useful inspiration for the discovery and synthesis of more bisditerpenoids and further pharmacological investigations.

Unprecedented diterpenoid dimers with soluble epoxide hydrolase inhibitory effect from Euphorbia fischeriana.

Biseuphoids A (1) and B (2), two unprecedented ent-abietane-type diterpenoid dimers linked by monomeric blocks through C-17-C-12' and C-17-C-11', respectively, were isolated from Euphorbia fischeriana, along with their biogenesis related diterpenoid monomers, 17-hydroxyjolkinolide B (3), caudicifolin (4), and fischeriabietane C (5). Their structures were elucidated by extensive spectroscopy assisted by quantum chemical NMR and ECD calculations. The unusual dimeric skeletons are possibly derived from the adduct of diterpenoid monomers through Michael-like reactions. The novel dimers 1 and 2 exhibited inhibitory activities on soluble epoxide hydrolase (sEH) with IC50 values of 8.17 and 5.61 µM, respectively. Molecular dynamics studies illustrated that both 1 and 2 can occupy the catalytic pocket of sEH by forming stable hydrogen bonds with the key amino acid residues including Gln384, Asn378, Pro361, Ala365, Asn366, and Asn472.

Cytotoxic diterpenoid dimer containing an intricately caged core from Euphorbia fischeriana.

Bislangduoids A and B, a novel class of dimeric diterpenoids based on ent-abietanes tethered by C-17-C-15' bridge, were identified as trace components from a traditional Chinese medicine Euphorbia fischeriana (Langdu). Bislangduoid A features a highly oxidized scaffold incorporating a cage-like pentacyclic core. Their structures were elucidated by extensive spectroscopic techniques, electronic circular dichroism, and NMR calculations. The biosynthetic pathway for the dimeric skeleton and the unique caged moiety via Michael and acetal-formation reactions was proposed. Bislangduoid A showed pronounced cytotoxicity against HepG2 cells through the mitochondria-dependent apoptosis pathway.

Bisfischoids A and B, dimeric ent-abietane-type diterpenoids with anti-inflammatory potential from Euphorbia fischeriana Steud.

Two undescribed ent-abietane-type diterpenoid dimers with nonacyclic backbone formed by intermolecular [4 + 2] cycloaddition into a spirocyclic skeleton, bisfischoids A (1) and B (2), along with a known one fischdiabietane A (3), were identified from Euphorbia fischeriana Steud. Their structures were elucidated by extensive spectroscopic analysis, ECD and NMR calculation combined with DP4+ probability analysis, as well as X-ray diffraction. The anti-inflammatory potential of dimers 1-3 were examined using their inhibitory effects on soluble epoxide hydrolase (sEH), which revealed that 1 and 2 exhibited promising activities with inhibition constant (Ki) of 3.20 and 1.95 µM, respectively. Further studies of molecular docking and molecular dynamics indicated that amino acid residue Tyr343 in the catalytic cavity of sEH was the key site for their inhibitory function.

Recent studies on terpenoids in Aspergillus fungi: Chemical diversity, biosynthesis, and bioactivity.

Metabolites from fungi are a major source of natural small molecule drugs in addition to plants, while fungal derived terpenoids have been confirmed to have great potentials in many diseases. Aspergillus fungi are distributed in every corner of the earth, and their terpenoid metabolites exhibit promising diversity in term of both their chemistry and bioactivity. This review attempted to provide timely and comprehensive coverage of chemical, biosynthesis, and biological studies on terpenoids discovered from the genus Aspergillus, including mono-, sesqui-, di-, sester-, tri-, and meroterpenoids, in the last decade. The structural characteristics, biosynthesis, and pharmacological activities of 288 terpenoids were introduced.

Regulation of Vapor Pressure Deficit by Greenhouse Micro-Fog Systems Improved Growth and Productivity of Tomato via Enhancing Photosynthesis during Summer Season.

The role of a proposed micro-fog system in regulating greenhouse environments and enhancing tomato (Solanum lycopersicum L.) productivity during summer season was studied. Experiments were carried out in a multi-span glass greenhouse, which was divided into two identical compartments involving different environments: (1) without environment control and (2) with a micro-fog system operating when the air vapor pressure deficit (VPD) of greenhouse was higher than 0.5 KPa. The micro-fog system effectively alleviated heat stress and evaporative demand in the greenhouse during summer season. The physiologically favourable environment maintained by micro-fog treatment significantly enhanced elongation of leaf and stem, which contributed to a substantial elevation of final leaf area and shoot biomass. These improvements in physiological and morphological traits resulted in around 12.3% increase of marketable tomato yield per plant. Relative growth rate (RGR) of micro-fog treatment was also significantly higher than control plants, which was mainly determined by the substantial elevation in net assimilation rate (NAR), and to a lesser extent caused by leaf area ratio (LAR). Measurement of leaf gas exchange parameters also demonstrated that micro-fog treatment significantly enhanced leaf photosynthesis capacity. Taken together, manipulation of VPD in greenhouses by micro-fog systems effectively enhanced tomato growth and productivity via improving photosynthesis during summer season.

[Effects of sub-low temperature and drought stress on characteristics of photosynthetic and fluorescence kinetics in tomato leaves].

By using tomato as material potted in climatic chamber, the photosynthetic characteristics and allocation of energy and electron flow were studied under sub-low temperature (8-15 °C) and drought (55%-65% of field moisture capacity) conditions. The results showed that the photosynthetic pigment content declined under sub-low temperature stress, but increased under drought stress. Both sub-low temperature stress and drought stress significantly decreased the intercellular CO2 concentration, stomatal conductance and photosynthetic rate, and increased the stomatal limita- tion, which further decreased or increased under simultaneous treatment of sub-low temperature and drought stress. The photorespiration significantly increased under separate treatment of sub-low temperature and drought stress, but decreased under simultaneous treatment. The stress declined the Fo, Fv/Fm and Fv'/Fm', which showed the damage of photosystem. It increased the distribution of energy to PS I and declined the photochemical efficiency, total electron flow and alternating electron flow. Thermal dissipation and the ratio of alternating electron flow were elevated to dissipate the excess energy. Compared with separate treatment of sub-low temperature and drought stress, the simultaneous treatment made thermal dissipation higher, but did not make alternating electrons flow further increase.