Preparation and structural properties of selenium modified heteropolysaccharide from the fruits of Akebia quinata and in vitro and in vivo antitumor activity.

Cancer is a complex disease, and blocking tumor angiogenesis has become one of the most promising approaches in cancer therapy. Here, an exopoly heteropolysaccharide (AQP70-2B) was firstly isolated from Akebia quinata. Monosaccharide composition indicated that the AQP70-2B was composed of rhamnose, glucose, galactose, and arabinose. The backbone of AQP70-2B consisted of →1)-l-Araf, →3)-l-Araf-(1→, →5)-l-Araf-(1→, →3,5)-l-Araf-(1→, →2,5)-l-Araf-(1→, →4)-d-Glcp-(1→, →6)-d-Galp-(1→, and →1)-d-Rhap residues. Based on the close relationship between selenium and anti-tumor activity, AQP70-2B was modified with selenium to obtain selenized polysaccharide Se-AQP70-2B. Then, a series of methods for analysis and characterization, especially scanning electron microscopy coupled with energy dispersive spectrometry (SEM-EDS), indicated that Se-AQP70-2B was successfully synthesized. Furthermore, zebrafish xenografts and anti-angiogenesis experiments indicated that selenization could improve the antitumor activity by inhibiting tumor cell proliferation and migration and blocking angiogenesis.

Structure features, selenylation modification, and improved anti-tumor activity of a polysaccharide from Eriobotrya japonica.

A homogeneous polysaccharide, EJP90-1, was isolated from the leaves of E. japonica by hot water extraction in this study. EJP90-1 (7702 Da) was a heteropolysaccharide mainly consisting of →5)-linked-α-L-Araf-(1→, →4)-linked-ß-D-Manp-(1→, →2,4)-linked-α-L-Rhap-(1→, →4)-linked-α-D-Xylp-(1→, →4)-linked-ß-D-Galp-(1→, →2)-linked-ß-D-Galp-(1→, →6)-linked-ß-D-Glcp-(1→, α-D-Glcp-(4→, and t-linked-α-L-Araf. EJP90-1 was found to show moderate anti-tumor activity at the cellular level. In order to improve the anti-tumor activity and the potential applications of EJP90-1, a typical sodium selenite-nitric acid (Na2SeO3-HNO3) modification on EJP90-1 was carried out. X-ray photoelectron spectroscopy (XPS) and energy dispersive spectrometer (EDS) analysis confirmed that Se was successfully introduced into the polymer chain of EJP90-1. The subsequent in vitro cytotoxicity evaluation showed the selenylation modification derivative (EJP90-1-Se) possessed significant antiproliferative activity against cancer cells (HepG2 and A549 cells) through inducing cell apoptosis. The anti-tumor activity of EJP90-1-Se was further confirmed by zebrafish models, which inhibited the proliferation and migration of HepG2 cells and the angiogenesis.

Structural properties and in vitro and in vivo immunomodulatory activity of an arabinofuranan from the fruits of Akebia quinata.

In our continuous searching for natural active polysaccharides with immunomodulatory activity, an arabinofuranan (AQP70-3) was isolated and purified from the fruits of Akebia quinata (Houtt.) Decne. by using ion-exchange chromatography and gel permeation chromatography for the first time. AQP70-3 contained both α-l-Araf and ß-l-Araf, and the absolute molecular weight was 1.06 × 104 g/mol. The backbone of AQP70-3 comprised →5)-α-l-Araf-(1→, →3,5)-α-l-Araf-(1→, and →2,5)-α-l-Araf-(1→, with branches of →1)-ß-l-Arafand →3)-α-l-Araf-(1→ residues. Biological assay suggested that AQP70-3 can stimulate phagocytic activity and promote the levels of nitric oxide (NO), interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α (TNF-α) of RAW264.7 cells. Furthermore, AQP70-3 was found to increase the production of reactive oxygen species (ROS) and NO in zebrafish embryo model.

Isolation, structural elucidation, and immunoregulation properties of an arabinofuranan from the rinds of Garcinia mangostana.

In our search for bioactive polysaccharides as immunomodulatory agents, an arabinofuranan (GMP90-1) was purified and characterized from the rinds of Garcinia mangostana L. GMP90-1 (absolute molecular weight: 5.30 × 103 g/mol) was found to be composed of arabinose, galactose, and rhamnose. The backbone of GMP90-1 was determined as (1→5)-linked α-l-Araf, (1→2,3,5)-linked α-l-Araf, (1→3,5)-linked α-l-Araf, (1→6)-linked ß-d-Galp, and (1→2)-linked α-l-Rhap. Conformational analysis revealed GMP90-1 to exist as a rigid rod structure in sodium chloride solution. To explore its potential as immunomodulatory agents, an in vitro cell screening was performed and GMP90-1 was found to significantly enhance the phagocytic uptake of neutral red and improve the secreted level of nitric oxide (NO), interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α (TNF-α) of macrophages. Furthermore, the cellular immunomodulatory activities were confirmed by the in vivo zebrafish experiment, which suggested that GMP90-1 with immunomodulatory effects could be considered as a potential immunomodulatory for immune diseases.

A heteropolysaccharide purified from leaves of Ilex latifolia displaying immunomodulatory activity in vitro and in vivo.

A novel polysaccharide (ILP50-2) was extracted, isolated and purified from the leaves of Ilex latifolia Thunb. Its structure was characterized as a repeating unit consisting of α-L-Araf-(1→, →3)-α-L-Araf-(1→, →5)-α-L-Araf-(1→, →3,5)-α-L-Araf-(1→, →2)-α-L-Rhap-(1→, →2,4)-α-L-Rhap-(1→, ß-D-Galp-(1→, →4)-ß-D-Galp-(1→, →4)-ß-D-Glcp-(1→, →6)-α-D-Manp-(1→, and →3,6)-α-D-Galp-(1→. The absolute molecular weight of ILP50-2 was 1.49 × 105 g/mol, which adapted a compact coil conformation in 0.1 M NaCl solution with Rz of 25.4 nm. Furthermore, ILP50-2 exhibited immunoregulatory activity, mainly through enhancing the phagocytosis ability of macrophages and prompting the release of nitric oxide (NO) and cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß). Simultaneously, ILP50-2 was found to significantly increase the release of ROS and NO in zebrafish embryos, showing immunoregulatory effects in vivo.

Diterpenoids from the leaves of Casearia kurzii showing cytotoxic activities.

A phytochemical investigation to obtain bioactive substances as lead compounds or agents for cancer led to the obtainment of six new and two known clerodane diterpenoids from the leaves of Casearia kurzii. Their structures were elucidated using NMR techniques and electronic circular dichroism (ECD) calculations. The subsequent biological cytotoxicity evaluation of these isolates toward human lung cancer A549, human cervical cancer HeLa, human chronic myeloid leukemia K562, and human hepatocellular carcinoma HepG2 was carried out. The most active compound 4 with an IC50 value of 9.7 µM against HepG2 cells was selected to examine the cytotoxic mechanism, which induced the apoptosis and arrested the HepG2 cell cycle at S stage. The in vivo zebrafish experiments revealed that compound 4 had the property of inhibiting tumor proliferation and migration.

An active heteropolysaccharide from the rinds of Garcinia mangostana Linn.: Structural characterization and immunomodulation activity evaluation.

A previously undescribed polysaccharide, GMP70-1, was isolated from the rinds of Garcinia mangostana Lin. Physicochemical characterization analysis showed that GMP70-1 (absolute molecular weight: 2.01 × 104 g/mol) is a multi-branched acidic heteropolysaccharide with a compact coil chain conformation in sodium chloride solution. The repeated unit of GMP70-1 was mainly composed of (1 → 5)-linked α-L-Araf, (1 → 3, 5)-linked α-L-Araf, (1 → 2, 4)-linked α-L-Rhap, (1 → 4)-linked ß-D-Galp, terminating with t-α-L-Araf, t-α-D-GalpA, and t-ß-D-Galp. To explore the medicinal potential responsible for the bioactivity of G. mangostana, an immunomodulatory assay was performed. The in vitro cell test showed that GMP70-1 possessed a prominent immunoregulatory activity by enhancing the phagocytic uptake of neutral red and promoting the secretion of nitric oxide (NO), reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1ß of macrophages. Furthermore, an in vivo zebrafish evaluation revealed that the production of ROS and NO was significantly increased after treated with GMP70-1.

Clerodane Diterpenoids Isolated from the Leaves of Casearia graveolens.

A phytochemical survey aiming to acquire pharmacologically active substances has resulted in the isolation of nine new clerodane diterpenoids, named graveospenes A-I (1-9), from the leaves of Casearia graveolens. Spectroscopic methods were employed to establish the structures with their absolute configurations being confirmed by ECD data analysis. A biological evaluation was performed, and compound 1 was found to be cytotoxic to both human lung cancer cells (A549) and human hepatocellular carcinoma cells (HepG2). A mechanism-of-action study on 1 revealed this compound to induce apoptosis of A549 cells and impede them at the G0/G1 stage.

A fructan from Anemarrhena asphodeloides Bunge showing neuroprotective and immunoregulatory effects.

A novel polysaccharide, AAP70-1, was isolated from Anemarrhena asphodeloides for the first time. The primary structural analysis revealed that AAP70-1 was composed of glucose and fructose, had an absolute molecular weight of 2720 Da, and contained a (2→6)-linked ß-D-fructofuranose (Fruf) backbone and a (2→1,6)-linked ß-D-Fruf side chain with an internal α-D-glucopyranose (Glcp) in the form of a neokestose. To explore the potential factors responsible for the medicinally relevant bioactivities of A. asphodeloides, a biological assay was performed. Using flow cytometry analysis, AAP70-1 was experimentally shown to have neuroprotective effects, and it can prevent and ameliorate neurological damage via reducing apoptosis. The immunomodulation assay further revealed that AAP70-1 can significantly improve immune function by promoting phagocytic capacity and the secretion of cytokines (IL-6, IL-1ß and TNF-α) in RAW264.7 cells. These results suggest that AAP70-1 has potential as a therapeutic agent for central nervous system diseases or as an immunomodulatory agent.

Cytotoxic diterpenoids as potential anticancer agents from the twigs of Casearia kurzii.

A search for bioactive natural products as anticancer lead compounds has led to the isolation of five new clerodane diterpenoids (1-5) from the twigs of Casearia kurzii. Their structures were elucidated by extensive analysis of their NMR, IR, and HRESIMS data, and the absolute configurations were determined by experimental and calculated electronic circular dichroism (ECD) data analysis. The isolates were biologically evaluated and showed cytotoxic activities toward human lung cancer cells (A549), human cervical cancer cells (HeLa), and human hepatocellular carcinoma cells (HepG2). The most active compound (5) with an IC50 value of 5.3 µM against HeLa cells, was found to induce apoptosis and arrest the HeLa cell cycle at G0/G1 stage to exert cytotoxic effects.

Cytotoxic clerodane diterpenoids from the leaves of Casearia kurzii.

A phytochemical investigation to obtain bioactive substances as lead compounds or agents for cancer led to the obtainment of six new clerodane diterpenoids, designated as kurzipenes A-F (1-6), from the leaves of Casearia kurzii. Their structures were elucidated on the basis of NMR spectroscopic data analysis and the absolute configurations were confirmed by the time-dependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculations. The cytotoxic activities of compounds 1-6 were evaluated against human lung cancer A549 cell line, human cervical cancer Hela cell line, and human hepatocellular carcinoma HepG2 cell line. Most diterpenoids showed potent cytotoxicities against the three selected cancer cell lines. The preliminary mechanism studies revealed that the most active compound 2, with an IC50 value of 5.3 µM against Hela cells, induced apoptosis and arrested the Hela cell cycle at the G0/G1 stage to exert cytotoxic effects.

Bioactive Terpenoids from Salvia plebeia: Structures, NO Inhibitory Activities, and Interactions with iNOS.

A phytochemical investigation to obtain new NO inhibitors resulted in the identification of six new (1-6) and four known (7-10) terpenoids from Salvia plebeia. Compounds 1 and 2 are new diterpenoids, 3-5 are new meroditerpenoids, 6-9 are sesquiterpenoids, and 10 is a known meroditerpenoid. The structures of these isolates were determined by routine NMR experiments and X-ray diffraction, as well as the electronic circular dichroism spectra. Compounds 1-4 are diterpenoids carrying an oxygen bridge, and 6 is a rare copane-type sesquiterpenoid with a bridged tricyclic framework. The isolates inhibited NO generation induced by lipopolysaccharide in BV-2 cells. The possible mechanism of NO inhibition of some bioactive compounds was also investigated using molecular docking, which revealed interactions of bioactive compounds with the iNOS protein.