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 elucidation and immunomodulatory evaluation of a polysaccharide from Stevia rebaudiana leaves.

Stevia rebaudiana, a sweetener with medicinal functions, has attracted extensive attention due to its application in food and pharmaceutical fields. However, a few studies were performed to explore polysaccharides in this plant. Herein, SRP70-1 was derived from S. rebaudiana. Structural analysis (monosaccharide composition analysis, high-performance liquid chromatography-multi-angle light scattering detection, gas chromatography-mass spectrometry, and nuclear magnetic resonance spectroscopy) revealed that SRP70-1 was composed of mannose, glucose, galactose, and arabinose at the molar ratio of 1.35:1.00:3.23:3.47, with an absolute molecular weight of 7698 Da. SRP70-1 was found to contain â†’ 5)-α-l-Araf-(1→, →2,3,5)-α-l-Araf-(1→, →4)-ß-l-Arap-(1→, →4)-ß-d-Galp-(1→, →6)-ß-d-Galp-(1→, →4)-ß-d-Manp-(1→, →6)-ß-d-Manp-(1→, and terminal α-l-Araf, ß-d-Galp, and ß-d-Glcp residues. Cell experiments showed that SRP70-1 could significantly promote phagocytosis and increase the release of nitric oxide and cytokines including IL-1ß, IL-6, and TNF-α. Further zebrafish experiments confirmed the immunological enhancement effects of SRP70-1. This study revealed that SRP70-1 may be useful for the development of functional foods.

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.

Anti-Inflammatory ent-Kaurane Diterpenoids from Isodon serra.

Ten new ent-kaurane diterpenoids, including two pairs of epimers 1/2 and 4/5 and a 6,7-seco-ent-kauranoid 10, were obtained from the aerial parts of Isodon serra. The structures of the new compounds were confirmed by extensive spectroscopic methods and electronic circular dichroism (ECD) data analysis. An anti-inflammatory assay was applied to evaluate their nitric oxide (NO) inhibitory activities by using LPS-stimulated BV-2 cells. Compounds 1 and 9 exhibited notable NO production inhibition with IC50 values of 15.6 and 7.3 µM, respectively. Moreover, the interactions of some bioactive diterpenoids with inducible nitric oxide synthase (iNOS) were explored by employing molecular docking studies.

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.

Bioactive triterpenoids from Lantana camara showing anti-inflammatory activities in vitro and in vivo.

Bioactive natural products play an important role in the research and development of new drugs. In our search for bioactive natural substances as potential lead compounds for inflammation, four new (1-4) and six known (6-10) triterpenoids were acquired from Lantana camara. Using NMR and MS techniques and electronic circular dichroism (ECD) calculations, these isolates were characterized and the new compounds (1-4) were found to be euphane-type triterpenoids. The in vitro anti-inflammatory effects of all the isolates were evaluated and the more bioactive compounds were selected for the investigation of preliminary mechanism using molecular docking and Western blotting experiments, as well as the in vivo anti-inflammatory evaluation using a zebrafish model.

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 as potential anti-inflammatory agents from Ajuga pantantha.

A phytochemical survey to obtain bioactive natural products from Ajuga pantantha afforded five new neo-clerodane diterpenoids (1-5). The structures were established by analysis of their NMR spectroscopic data, and electronic circular dichroism calculations were applied to define their absolute configurations. Compounds 2 and 5 were found to have the property of inhibiting NO production (IC50 values < 40 µM). Molecular docking and Western blotting were used to study the mechanism of anti-inflammatory action. Furthermore, compound 5 with the highest activity was tested for its in vivo anti-inflammatory effects using a zebrafish model.

Nitric oxide inhibitory iridoids as potential anti-inflammatory agents from Valeriana jatamansi.

Five new iridoids, jatadomins A-E (1-5), together with six known analogues (6-11) and one known sesquiterpenoid (12), were isolated from the roots of Valeriana jatamansi Jones. Their structures were determined by analysis of their NMR, HRESIMS, and electronic circular dichroism calculations (ECD) data. The biological evaluation revealed that compounds 1-6 had anti-inflammatory activities by inhibiting nitric oxide (NO) release in LPS-induced murine microglial BV-2 cells, with IC50 values of 24.4, 9.2, 21.2, 25.9, 30.6, and 0.4 µM, respectively. Further molecular docking studies revealed a potential mechanism for NO inhibition by the bioactive compounds.

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.

Caseahomopene A, a ring-expanded homotriterpenoid from Casearia kurzii showing anti-inflammatory activities in vitro and in vivo.

Caseahomopene A (1), a rare natural product with a ring-expanded homotriterpenoid skeleton, was isolated from the leaves of Casearia kurzii. The structure including the absolute configuration was determined by spectroscopic data and X-ray crystallography analysis. Compound 1 showed anti-inflammatory effects in vitro and in vivo using LPS-stimulated cell and zebrafish model. As a potential anti-inflammatory agent, the anti-inflammatory mechanism of 1 was also investigated.

Anti-inflammatory neo-Clerodane Diterpenoids from Ajuga pantantha.

Eight new neo-clerodane diterpenoids (1-8) were acquired from the aerial parts of Ajuga pantantha. Spectroscopic data analysis permitted the definition of their structures, and experimental and calculated electronic circular dichroism data were used to define their absolute configurations. Compounds 2 and 4-8 were found to have NO inhibitory effects with IC50 values of 20.2, 45.5, 34.0, 27.0, 45.0, and 25.8 µM, respectively. The more potent compounds 2, 6, and 8 were analyzed to establish their anti-inflammatory mechanism, including regulation of the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins as well as their binding interactions with the two proteins.

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.

NO inhibitory diterpenoids as potential anti-inflammatory agents from Euphorbia antiquorum.

Two new ent-atisane-type diterpenoids (1 and 2), three new lathyrane-type diterpenoids (3-5), and seven known analogues (6-12) were isolated from Euphorbia antiquorum. The structures of these diterpenoids were established by analysis of their NMR, MS, and electronic circular dichroism data. The anti-inflammatory activities were evaluated biologically and compounds 1, 4, 7, 8, and 10 displayed strong NO inhibitory effects with IC50 values less than 40 µM. The potential anti-inflammatory mechanism was also investigated using molecular docking and Western blotting.

Bioactive Diterpenoids from the Stems of Euphorbia antiquorum.

A total of 18 diterpenoids, including 10 new analogues (1-10), were isolated from Euphorbia antiquorum. The structures were characterized by spectroscopic techniques, and circular dichroism data analysis was adopted to confirm the absolute configurations of 1-10. Compounds 1-9 were classified as ent-atisane diterpenoids, and 10 was assigned as an ent-kaurane diterpenoid. The biological evaluation of nitric oxide (NO) production inhibition was conducted, and all of these isolates showed the property of inhibiting NO generation in lipopolysaccharide-induced BV-2 cells. Further research on molecular docking disclosed the affinities between the diterpenoids obtained and inducible nitric oxide synthase.

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.

Withanolides from Physalis peruviana showing nitric oxide inhibitory effects and affinities with iNOS.

A phytochemical study to obtain new nitric oxide (NO) inhibitors resulted in the isolation of five new withanolides from the whole plants of Physalis peruviana. The structures were determined on the basis of extensive NMR spectroscopic data analysis as well as the time-dependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculations. The NO inhibitory effects were examined by inhibiting NO release in lipopolysaccharide-stimulated murine microglial BV-2 cells. Molecular docking studies showed the strong interactions of bioactive compounds with the inducible nitric oxide synthase (iNOS) protein, revealing the potential mechanism of NO inhibition of bioactive compounds.