The discovery of bioactive compounds from medicinal plants has played a crucial role in drug discovery. In this study, a simple and efficient method utilizing affinity-based ultrafiltration (UF) ...coupled with high-performance liquid chromatography (HPLC) was developed for the rapid screening and targeted separation of α-glucosidase inhibitors from
roots. First, an active fraction of
roots (SGR2) was prepared, and 17 potential α-glucosidase inhibitors were identified based on UF-HPLC analysis. Second, guided by UF-HPLC, a combination of MCI gel CHP-20P column chromatography, high-speed counter-current countercurrent chromatography, and preparative HPLC were conducted to isolate the compounds producing active peaks. Sixteen compounds were successfully isolated from SGR2, including two lignans and fourteen cucurbitane-type triterpenoids. The structures of the novel compounds (
,
,
,
,
, and
) were elucidated using spectroscopic methods, including one- and two-dimensional nuclear magnetic resonance spectroscopy and high-resolution electrospray ionization mass spectrometry. Finally, the α-glucosidase inhibitory activities of the isolated compounds were verified via enzyme inhibition assays and molecular docking analysis, all of which were found to exhibit certain inhibitory activity. Compound
exhibited the strongest inhibitory activity, with an IC
value of 430.13 ± 13.33 μM, which was superior to that of acarbose (1332.50 ± 58.53 μM). The relationships between the structures of the compounds and their inhibitory activities were also investigated. Molecular docking showed that the highly active inhibitors interacted with α-glucosidase through hydrogen bonds and hydrophobic interactions. Our results demonstrate the beneficial effects of
roots and their constituents on α-glucosidase inhibition.
Six new tirucallane-type triterpenoids, named munropenes A–F (1–6), were extracted from the whole plants of Munronia pinnata using a water extraction method. Their chemical structures were determined ...based on detailed spectroscopic data. The relative configurations of the acyclic structures at C-17 of munropenes A–F (1–6) were established using carbon–proton spin-coupling constants (2,3JC,H) and inter-proton spin-coupling constants (3JH,H). Furthermore, the absolute configurations of munropenes A–F (1–6) were determined through high-performance liquid chromatography (HPLC), single-crystal X-ray diffraction, and electronic circular dichroism (ECD) analyses. The antiproliferative effects of munropenes A–F were evaluated in five tumor cell lines: HCT116, A549, HepG2, MCF7, and MDAMB. Munropenes A, B, D, and F (1, 2, 4, and 6) inhibited proliferation in the HCT116 cell line with IC50 values of 40.90, 19.13, 17.66, and 32.62 µM, respectively.
The incidence of pancreatitis (AP) is increasing and there is no specific treatment available. Intracellular digestive enzyme activation is a key event in the pathogenesis of AP downstream of ...cytosolic calcium overload and impaired autophagy.
Siraitia grosvenorii
(Swingle) was used in Traditional Chinese Medicine to reduce inflammation and facilitate bowel movement. The bioactive components of this plant show hypolipedimic, antidiabetic, antifibrotic activity and have been used against pancreatic cancer. Here, we examined whether mogroside II
E
, a major bioactive component of unripe
S. grosvenorii
fruit, can protect against AP. We found that mogroside II
E
decreased the activity of trypsin and cathepsin B induced by cerulein plus lipopolysaccharide (LPS) in the pancreatic acinar cell line AR42J and primary acinar cells in a dose- and time-dependent manner. Mogroside II
E
treatment decreased the levels of serum lipase and serum amylase in mice injected with cerulein plus LPS without influencing inflammation significantly. A multi-cytokine array revealed that mogroside II
E
decreased the level of interleukin 9 (IL-9) in AP mice. Exogenous IL-9 eliminated the mogroside II
E
induced reduction of trypsin and cathepsin B activity and reversed the inhibition of cytosolic calcium and modulation of autophagy mediated by mogroside II
E
. An IL-9 receptor antibody neutralized the effect of IL-9, restoring mogroside II
E
activity. The mogroside II
E
targeted IL-9 may partially arise from Th9 cells. Taken together, we provide experimental evidence that mogroside II
E
ameliorates AP in cell models and mice through downregulation of the IL-9/IL-9 receptor pathway.
The accumulation of heavy metals (HMs) in lakes can pose a serious risk to aquatic ecosystems. Caohai Lake is the largest plateau freshwater lake in Guizhou Province, China. However, the spatial and ...temporal dynamics and ecological risks of HM contamination in Caohai sediments in recent years remain unclear. Here, we analyzed the HM content of sediments in Caohai Lake in 2022 and collected historical (2011–2021) data from published articles to explore the spatiotemporal distribution characteristics, toxicity risks and potential sources of HMs. The mean concentrations (2011–2022) of Ni, As, Cd, Zn, Hg and Pb in the Caohai Lake sediments were all higher than the background values, and the values of As (32.0 mg/kg), Cd (14.19 mg/kg), Pb (87.6 mg/kg) and Zn (406.2 mg/kg) were 1.9, 4.0, 2.4 and 1.3 times their probable effect level (PEL) values, respectively. Sediment As and Cd concentrations in Caohai Lake showed significant decreasing and increasing trends from 2011 to 2022, with mutation points occurring in 2018 and 2020, respectively. The Caohai Lake sediment aquatic life risk index (TRI) for HMs showed a gradual increase until 2019, when it reached a sudden change point, leading to a very high toxicity risk in 2020, with Cd contributing the most to the TRI (43.66). Cd, Pb and Zn, the main pollutants in the sediments of Caohai Lake, originate from traffic, mining and agricultural sources. Our integrated results demonstrated the severity of HM pollution in Caohai Lake and can be helpful for formulating reasonable pollution prevention and control measures.
Litchi pericarp is rich in polyphenols, and demonstrates significant biological activity. This study assessed the therapeutic effects of litchi pericarp extract (LPE) on type 2 diabetes mellitus in ...db/db mice. The results showed that LPE ameliorated symptoms of glucose metabolism disorder, oxidative stress, inflammatory response, and insulin resistance in db/db mice. The mechanistic studies indicated that LPE activates adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and suppresses the protein expression of phosphoenolpyruvate carboxykinase (PEPCK), thereby reducing hepatic gluconeogenesis. Additionally, LPE facilitates the translocation of nuclear factor erythroid2-related factor 2 (Nrf2) into the cell nucleus, initiating the transcription of antioxidant factors superoxide dismutase (SOD) and NAD(P)H: quinone oxidoreductase 1 (NQO1), which alleviate oxidative stress and reduce oxidative damage. Furthermore, LPE blocks nuclear factor kappa-B (NF-κB) nuclear translocation and subsequent inflammatory response initiation, thereby reducing inflammation. These findings indicate that LPE addresses type 2 diabetes mellitus by activating the AMPK energy metabolic pathway and regulating the Nrf2 oxidative stress and NF-κB inflammatory signaling pathways.
blooms are an intractable global environmental problem that pollute water and compromise ecosystem functioning. Closed-lake management practices keep lakes free of sewage and harmful algae invasions ...and have succeeded in controlling local
blooms; however, there is little understanding of how the bacterioplankton communities associated with
have changed. Here, based on metagenomic sequencing, the phyla, genera, functional genes and metabolic functions of the bacterioplankton communities were compared between open lakes (underlying
blooms) and closed lakes (no
blooms). Water properties and zooplankton density were investigated and measured as factors influencing blooms. The results showed that (1) the water quality of closed lakes was improved, and the nitrogen and phosphorus concentrations were significantly reduced. (2) The stability of open vs. closed-managed lakes differed notably at the species and genus levels (
< 0.01), but no significant variations were identified at the phylum and functional genes levels (
> 0.05). (3) The relative abundance of
(Cyanobacteria) increased dramatically in the open lakes (proportions from 1.44 to 41.76%), whereas the relative abundance of several other dominant genera of Cyanobacteria experienced a trade-off and decreased with increasing
relative abundance. (4) The main functions of the bacterioplankton communities were primarily related to dominant genera of Proteobacteria and had no significant relationship with
. Overall, the closed-lake management practices significantly reduced nutrients and prevented
blooms, but the taxonomic and functional structures of bacterioplankton communities remained stable overall.
Prain (
) is an important legume species of the Dalbergia family, due to the use of its trunk and root heart in traditional Chinese medicine (TCM). In the present study, we reported the isolation, ...characterization and pharmacological activities of robustic acid (RA) from the ethyl acetate extract of
Prain. The SwissADME prediction showed that the RA satisfied the Lipinski's rule of five (molecule weight (MW): 380.39 g/mol, lipid-water partition coefficient (log P): 3.72, hydrogen bond donors (Hdon): 1, hydrogen bond acceptors (Hacc): 6, rotatable bonds (Rbon): 3. Other chemical and pharmacological properties of this RA were also evaluated, including topological polar surface area (TPSA) = 78.13 Å and solubility (Log S) = -4.8. The probability values of the antineoplastic, anti-free radical activities and topoisomerase I (TopoⅠ) inhibitory activity were found to be 0.784, 0.644 and 0.379, respectively. The molecular docking experiment using the Surflex-Dock showed that the Total Score and C Score of RNA binding with the human DNA-Topo I complex were 7.80 and 4. The MTS assay experiment showed that the inhibitory rates of RA on HL-60, MT4, Hela, HepG2, SK-OV-3 and MCF-7 cells were 37.37%, 97.41%, 81.22%, 34.4%, 32.68% and 51.4%, respectively. In addition, RA exhibited an inhibitory effect on the angiogenesis of zebrafish embryo, a good TopoⅠ inhibitory activity at a 10 mM concentration and in a dose-dependent manner, excellent radical scavenging in the DPPH and ABTS assays, and the free radical scavenging rate was close to the positive control (BHT) at different concentrations (0.5-2.0 mg/mL). Furthermore, 18 potential targets were found for this RA by PharmMapper, including ANXA3, SRC, FGFR2, GSK3B, CSNK2B, YARS, LCK, EPHA2, MAPK14, RORA, CRABP2, PPP1CC, METAP2, MME, TTR, MET and KDR. The GO and KEGG pathway analysis revealed that the "protein tyrosine kinase activity", "rap1 signaling pathway" and "PI3K-Akt signaling pathway" were significantly enriched by the RA target genes. Our results will provide new insights into the pharmaceutical use of this species. More importantly, our data will expand our understanding of the molecular mechanisms of RA functions.
Five new chlamydosporol derivatives, named pleospyrones A-E (1-5), together with one known congener (6), were isolated from the culture of the endophytic fungus Pleosporales sp. Sigrf05, obtained ...from the medicinal plant Siraitia grosvenorii. The structures of the new compounds were elucidated mainly by analysis of the HRESIMS, and (1D, 2D) NMR data, while ECD and optical rotation calculations were used to assign the absolute configurations. The plausible biosynthetic pathway of these compounds were proposed. The isolated compounds were evaluated for their cytotoxicity, antifungal and antibacterial activities. Compounds 1, and 4-6 were cytotoxic against the tested cancer cells with IC
values of 1.26~47.5 μM. Compounds 1-3 showed moderate antifungal activities against Magnaporthe oryzae, while compound 5 displayed weak antibacterial activity.
The genus Ormosia comprises approximately 130 species, which are found in tropical regions all over the world. The taxonomy and evolutionary history are still ambiguous due to the lack of a solid ...phylogeny at the species level. Due to the fast advancement of high-throughput sequencing technology, it is now possible to retrieve the full chloroplast (cp) genome sequence, providing a molecular basis for phylogenetic analysis. Five species of Ormosia were used in this work, and their whole cp genomes were sequenced. One circular, quadripartite-structured molecule, ranging from 169,797 to 173,946 base pairs in length, was present in all five Ormosia species. The cp genomes of the five newly sequenced Ormosia species were further compared with the published cp genomes of O. pinnata. Ten hypervariable regions (Pi > 0.025) were uncovered in the Ormosia chloroplast genomes, among which petN-psbM showed the highest Pi value. Phylogenetic analysis revealed that O. microphylla and O. olivacea clustered with strong support. O. balansae was resolved as a sister to O. pinnata, and they were further found to be sisters to the remaining 13 Ormosia species. The cp genes of O. elliptica showed a close relationship to O. hosiei, and O. semicastrata clustered with O. emarginata. Taken together, the comprehensive analysis of the complete cp genomes of five Ormosia species offers valuable insight and information for reconstructing their phylogeny and sheds light on the evolutionary dynamics of the chloroplast genome in Ormosia.
PDF
