Polyhydric Stigmastane-Type Steroids Derivative from Vernonia amygdalina and Their Anti-Neuroinflammatory Activity.

Vernonia amygdalina Del. is a traditional medicinal plant and vegetable originating from tropical Africa. The phytochemical investigation of V. amygdalina led to eight undescribed polyhydric stigmastane-type steroids, vernonin M-T (1-8). Their gross structures and stereochemistry were elucidated by HR-ESI-MS, 1D and 2D NMR spectra, X-ray diffraction, quantum chemical computation of the ECD spectrum, and the in situ dimolybdenum CD method. The anti-neuroinflammatory activity of the isolated compounds was performed in BV-2 microglia cells. As a result, compound 1 displayed a notable anti-neuroinflammatory effect via suppressing the LPS-induced IκB degradation and restricting the activation of the PI3K/AKT and p38 MAPK pathways.

Seco-polyprenylated acylphloroglucinols from Hypericum elodeoides induced cell cycle arrest and apoptosis in MCF-7 cells via oxidative DNA damage.

Four undescribed seco-polyprenylated acylphloroglucinols (seco-PAPs), elodeoidesones A-D (1-4), were characterized from Hypericum elodeoides. Compound 1 represents the 1,6-seco-PAPs with fascinating 5/5 fused ring, while 2-4 possess a 1,2-seco-PAPs skeleton with a five-membered lactone core. Their structures including absolute configurations were established by spectroscopic analyses and quantum chemical computations. A possible biosynthetic pathway of 1-4 from normal PAPs was proposed. All the isolates were investigated for their cytotoxicity against tumor cells. Notably, 1 inhibited the proliferation of MCF-7 cells with the IC50 value of 7.34 µM. Mechanism investigation indicated that 1 induced MCF-7 cells apoptosis by blocking cell cycle at S phase via inducing oxidative DNA damage.

Tautomeric phytosterols from Vernonia amygdalina Delile and their anti-cervical cancer activity.

Vernonia amygdalina Delile is generally used as green vegetables for cuisine in Nigeria and health tea or products in southeast of china. It was also used as folk medicine for the treatment of anti-helminth, febrifuge, digestive tonic and wounds. In this study, eleven undescribed phytosterols (1-2, 4-12) and six known analogues (3, 13-17) were isolated from the stems of V. amygdalina. Their structures including absolute configurations were elucidated by comprehensive spectroscopic methods (1D and 2D NMR, HRESIMS), X-ray diffraction and comparison of their ECD spectra. Besides, the tautomerism of phytosterols (1, 3-6, 12-17) with hemiacetal moiety were analyzed by solution NMR with different deuterated solvent and variable-temperature experiments. In addition, the cytotoxic activities of isolates against HeLa cells were evaluated. As a result, compound 10 exhibited the most potent anti-cervical cancer activity with the IC50 of 22.44 µM. Mechanism studies indicated that 10 triggered HeLa cells apoptosis through activating caspase signaling pathway. Furthermore, 10 could arrest the cell cycle in S phase and suppress the activation of the PI3K/AKT/mTOR pathway, leading to the inhibition of HeLa cells proliferation.

Dysideanones F-G and dysiherbols D-E, unusual sesquiterpene quinones with rearranged skeletons from the marine sponge Dysidea avara.

Four new sesquiterpene quinone meroterpenoids, dysideanones F-G (1-2) and dysiherbols D-E (3-4), were isolated from the marine sponge Dysidea avara collected from the South China Sea. The new structures were elucidated by extensive analysis of spectroscopic data including HR-MS and 1D and 2D NMR spectra, and their absolute configurations were assigned by single-crystal X-ray diffraction and ECD calculations. Anti-inflammatory evaluation showed that dysiherbols D-E (3-4) exhibited moderate inhibitory activity on TNF-α-induced NF-κB activation in human HEK-293T cells with IC50 values of 10.2 and 8.6 µmol·L-1, respectively.

A new phenolic glycoside from Trollius chinensis Bunge with anti-inflammatory and antibacterial activities.

A undescribed phenolic glycoside, trochinenol A (1), was isolated from the flowers of Trollius chinensis Bunge and the structure was identified by spectroscopic methods. Its anti-inflammatory and antibacterial effects were investigated by broth microdilution and NF-κB reporter gene assays. Consequently, compound 1 exhibited an appreciable effect against Staphylococcus aureus with the MIC value of 6.25 µg/mL. Besides, it showed moderate effect against TNFα-induced activation of NF-κB pathway.

Enhanced phytoremediation of uranium-contaminated soils by Indian mustard (Brassica juncea L.) using slow release citric acid.

In this study, a novel slow release carrier for the controlled release of citric acid (CA), hydroxypropyl chitosan-graft-carboxymethyl-ß-cyclodextrin (HPCS-g-CMCD) was synthesized by the grafting reaction of carboxymethyl-ß-cyclodextrin (CMCD) with hydroxypropyl chitosan (HPCS), and the structural characteristics of HPCS-g-CMCD were confirmed by FT-IR, TGA, and NMR. Based on HPCS-g-CMCD and CA, slow release citric acid (SRCA) was prepared by a spray drying method. HPCS-g-CMCD carrier has a better slow release performance for CA compared to HPCS and CMCD, and CA release mechanism was attributed to a Fickian diffusion. Furthermore, the release behavior of uranium in contaminated soil could be effectively controlled by SRCA. The effects of SRCA on improving the phytoremediation capacity in uranium-contaminated soil were investigated using Brassica juncea, which were grown in pots containing soil with uranium at 56 mg kg-1. After 50 days of growth, 5 mmol kg-1 of CA, SRCA I, SRCA II, and SRCA III was applied, respectively. The results showed that slow release citric acid could enhance the uptake of uranium in Indian mustard. Uranium concentration in the root with SRCA I treatment was increased by 80.25% compared to the control, and the uranium removal efficiency of the SRCA I treatment was 1.66-fold greater than that of the control. Simultaneously, the leaching loss of uranium in SRCA I-treated soil was decreased by 37.35% compared to CA-treated soil. As a promising remediation strategy, SRCA-assisted phytoremediation may provide a kind of feasible technology with low leaching risk for remediation of uranium-contaminated soils.

Phosphorus-modified biochar cross-linked Mg-Al layered double-hydroxide composite for immobilizing uranium in mining contaminated soil.

The decommissioning of uranium mill tailings (UMTs) is usually accompanied by uranium (U) contamination in soil, which poses a serious threat to human health and ecological safety. In this study, a novel phosphorus-modified bamboo biochar (PBC) cross-linked Mg-Al layered double-hydroxide (LDH) composite ("PBC@LDH") was successfully prepared by phosphate pre-impregnation and a hydrothermal method with Mg-Al LDH. Physicochemical analysis revealed that phosphorus-containing functional groups and Mg-Al LDH were grafted onto the pristine biochar (BC) matrix. Laboratory-scale incubation and column leaching experiments were performed on the prepared BC, PBC, and PBC@LDH. The results showed that, at a dosage of 10%, the PBC@LDH composite had a commendable ability to immobilize U in soil. After 40 days of incubation with the stabilizer, the more mobile U was converted into immobilized species. Furthermore, during a column leaching experiment with simulated acid rain, the cumulative loss and leaching efficiency of U were remarkably reduced by PBC@LDH treatment compared with the control, reaching 53% and 54%, respectively. Surface complexation, co-precipitation, and reduction described the adsorption and immobilization mechanisms. In conclusion, this research demonstrates that the PBC@LDH composite offers a potentially effective amendment for the remediation of U contaminated soil.

Phenolic glycosides and flavonoids with antioxidant and anticancer activities from Desmodium caudatum.

Descaudatine A (1), an undescribed phenolic glycoside, along with a known analogue (2) and ten flavonoids (3-12), were isolated from the whole plant of Desmodium caudatum. Compounds 1 and 4 exhibited potent antioxidant activities with the IC50 of 58.59 µM and 31.31 µM, respectively, which were approached to that of the positive control Vitamin C (IC50 = 46.32 µM). Meanwhile, 12 showed moderate antioxidant activity with the IC50 of 173.9 µM. Besides, compounds 3 and 6 inhibited the proliferation of HeLa cells with IC50 values of 56.14 µM and 69.04 µM, respectively. Further studies indicated that 3 and 6 could dose-dependently induce PARP cleavage and might trigger caspase-3, 8, 9 activation to induce apoptosis. RXRα is an ideal anticancer target of nuclear receptor. The reporter gene assay of RXRα indicated that 3 and 6 could inhibited the 9-cis-RA induced RXRα transcription in a concentration-dependent manner.

Cytotoxic polyprenylated phloroglucinol derivatives from Hypericum elodeoides Choisy modulating the transactivation of RXRα.

Hyperelodione D (1), an undescribed polyprenylated phloroglucinol derivative possessing 6/6/5/5 fused tetracyclic core, together with hyperelodiones E-F (2-3), two unreported analogues bearing 6/5/5 fused tricyclic structure, were isolated from Hypericum elodeoides Choisy. Their planar structures were elucidated by spectroscopic analysis (HRESIMS, 1D and 2D NMR) and their absolute configurations were determined by comparison of experimental and calculated ECD data. The cytotoxicity and retinoid X receptor-α (RXRα) related activities of the isolates were evaluated and the plausible biogenetic pathways of 1-3 were proposed.

Cytotoxic compound triacremoniate from Marine Fungus Acremonium citrinum. MMF4.

Two new compounds, triacremoniate (1) and dietziamide C (2) along with known compounds ß-Adenosine (3) and acrepyrone A (4) were obtained from the mangrove-derived fungus Acremonium citrinum. MMF4. Their structures were unambiguously determined by extensive spectroscopic methods, including UV, IR, HRESIMS and NMR. Triacremoniate (1) can promote apoptosis of HeLa cells by increasing the PARP cleavage and the phosphorylation of JNK and p38.

Immunomodulatory and Antioxidant Activities of a Polysaccharide from Ligustrum vicaryi L. Fruit.

Ligustrum vicaryi L. is a hybrid of Ligustrum ovalifolium Hassk. var. aureo-marginatum and Ligustrum vulgale L., belonging to the Oleaceae family. It is often used as an ornamental shrub due to its golden leaves. However, its medical value is yet to be discovered. Recently, plant polysaccharides have attracted comprehensive attention owing to their biological properties, including immunomodulatory and antioxidant activities. This study aimed to extract, purify, and characterize the polysaccharide from the Ligustrum vicaryi L. fruit and investigate its immunomodulatory and antioxidant activities. The Ligustrum vicaryi L. fruit polysaccharide (LVFP) was obtained by ultrasonic extraction, ethanol precipitation, macroporous resin separation, and dialysis bag purification. The physicochemical properties of the LVFP were elucidated using Fourier-transform infrared spectrometry, high-performance ion chromatography, and high-performance gel filtration chromatography. The results indicated that the LVFP consisted of rhamnose, arabinose, galactose, and glucose in a ratio of 1.79 : 7.55 : 4.58 : 1.54, and its molecular weight was 88,949 Da. The immunomodulatory and antioxidant activities of the LVFP were investigated using a cyclophosphamide- (Cy-) induced immunosuppressed mouse model. The results demonstrated that the LVFP significantly increased spleen and thymus indexes, enhanced the phagocytic function of neutrophils, activated B and T lymphocytes, and upregulated serum levels of IL-10 and TNF-α. Moreover, we observed that the LVFP relieved Cy-induced liver damage by increasing superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) levels. These results suggested that the LVFP has the immunomodulatory and antioxidant activities, therefore laying a foundation for the application of the LVFP in the pharmaceutical and functional food industries.

Phenolic Glycosides from the Roots of Ficus hirta Vahl. and Their Antineuroinflammatory Activities.

Ficus hirta Vahl. (Wuzhimaotao) is an edible functional food used for the soup cooking and health products. Seven undescribed phenolic glycosides (1-7), along with 20 analogues, were isolated from the roots of Ficus hirta. Their structures were determined by comprehensive spectroscopic methods (UV, IR, HRESIMS, and NMR), while the absolute configuration of 1 was established by comparison of the experimental and calculated ECD data. The antineuroinflammatory effects of all the compounds were examined by Western blot. Compounds 1 and 11 attenuated the phosphorylation of AKT, JNK, and ERK1/2. In addition, compound 11 inhibited the NF-κB p65 phosphorylation. Our results indicated that compounds 1 and 11 decreased the occurrence of neuroinflammation in BV2 microglia cells, which might be regulated by inhibiting the activity of proteins in NF-κB, MAPK (JNK and ERK1/2), or AKT signaling pathways. Thus, 1 and 11 might exhibit antineuroinflammatory activities and show promise in treating neurodegenerative diseases.

Hyperelodiones A-C, monoterpenoid polyprenylated acylphoroglucinols from Hypericum elodeoides, induce cancer cells apoptosis by targeting RXRα.

Hyperelodiones A-C, three undescribed monoterpenoid polyprenylated acylphloroglucinols possessing 6/6/6 fused tricyclic core, were isolated from Hypericum elodeoides Choisy. Their gross structures were elucidated by HRESIMS and NMR data. The absolute configurations of hyperelodiones A-C were assigned by their calculated and compared electronic circular dichroism (ECD) spectra combined with their common biosynthetic origin. A fluorescence quenching assay suggested that hyperelodiones A-C could bind to RXRα-LBD, whereas hyperelodione C showed the strongest interaction with a KD of 12.81 µΜ. In addition, hyperelodiones A-C dose-dependently inhibited RXRα transactivation and the growth of HeLa and MCF-7 cells. Among them, hyperelodione C showed the most potent inhibitory activities and dose-dependent PARP cleavage. Molecular docking results suggested that hyperelodione C showed a different interaction mode compared with hyperelodione A and hyperelodione B. Thus, hyperelodione C can be considered as a promising lead compound for cancer therapy, which can bind to RXRα-LBD and induce HeLa and MCF-7 cell apoptosis.

Identifying the active components of Baihe-Zhimu decoction that ameliorate depressive disease by an effective integrated strategy: a systemic pharmacokinetics study combined with classical depression model tests.

BACKGROUND: Modern pharmacological studies have demonstrated that Baihe-Zhimu decoction (BZD) has antidepressant effects. However, the complex composition and lack of clear evaluation standards for BZD make it less likely to be understood and accepted than evidence-based active natural compounds. METHODS: In this study, an effective method for the identification of antidepressant components was demonstrated and applied to BZD. The first step was to evaluate the efficacy of BZD by the forced swimming test (FST) and the tail suspension test (TST), followed by successive quantitative analyses of the absorbed constituents at different stages, such as before hepatic disposition, liver distribution, after hepatic disposition and brain distribution after the oral administration of BZD. Finally, the compounds detected in the brain were confirmed by activity testing. RESULTS: Our investigation observed that timosaponin BII and timosaponin BIII were accurately determined in the brain after oral administration of BZD, and they were further confirmed to reduce the immobility time in the FST and TST. As described above, timosaponin BII and timosaponin BIII were used to scientifically and reasonably explain the effective chemical basis of the effect of BZD on depression. CONCLUSIONS: This research affords an effective method to discover lead molecules for antidepressants from traditional Chinese medicine.

Preparation of sustainable non-combustion filler substrate from waterworks sludge/aluminum slag/gypsum/silica/maifan stone for phosphorus immobilization in constructed wetlands.

In this study, an artificial wetland filler matrix capable of effectively fixing phosphorus was prepared using a non-combustion process to save energy. To evaluate the adsorption performance of this filler, adsorption experiments were performed and the phosphorus adsorption mechanism characterization was studied. An alkaline environment was found to be conducive to the increase of adsorption capacity, but excessive alkalinity was not conducive to adsorption. Static adsorption experiments showed that the phosphorus removal rate could reach 95% in the simulated phosphorus-containing wastewater after adsorption completion. The adsorption process is closely simulated by the pseudo-second-kinetic adsorption model. The isothermal adsorption experiment data were consistent with the Langmuir and the Freundlich adsorption isotherms. The characterization results showed a large number of micropores and adsorption binding sites inside and on the surface of the filler. Speciation analysis on the adsorbed phosphorus revealed that chemisorption by calcium in this filler was the dominant adsorption mechanism. The research results of this study provide the basis and reference for the development of high-efficiency phosphorus removal filler in constructed wetlands.

Cytotoxic Components from Hypericum elodeoides Targeting RXRα and Inducing HeLa Cell Apoptosis through Caspase-8 Activation and PARP Cleavage.

To find small-molecule regulators of RXRα, a phytochemical study of Hypericum elodeoides was conducted. Fifteen compounds, including the new 1 and 6, were isolated from the whole plant of H. elodeoides. The absolute configuration of 1 was assigned by comparison of experimental and calculated ECD data. Compounds 1 and 6 exhibited concentration-dependent inhibitory effects on RXRα transcription and selectively inhibited the proliferation of HeLa cells. Western blot analysis suggested that 1 and 6 induced apoptosis of HeLa cells with time- and dose-dependent PARP cleavage. A caspase activation assay indicated that these two compounds triggered caspase-8 activation to induce apoptosis by the extrinsic pathway. Molecular docking results suggested that 1 and 6 interacted with the Arg319 moiety of RXRα-LBD. Ligands binding to RXRα have shown promise in the discovery of anticancer drugs. A fluorescence quenching assay indicated the binding of 1 and 6 to the RXRα with the binding constant ( KD) fitted as 68.3 and 14.0 µM, respectively. A preliminary SAR study of the isolates was conducted to enhance the knowledge of the RXRα ligands. Thus, 1 and 6 might act as the small-molecule regulators of RXRα, which target RXRα and mediate HeLa cell apoptosis through the extrinsic pathways.

Secondary metabolites of petri-dish cultured Antrodia camphorata and their hepatoprotective activities against alcohol-induced liver injury in mice.

Antrodia camphorata, a well-known and highly valued edible medicinal mushroom with intriguing activities like liver protection, has been traditionally used for the treatment of alcoholic liver disease. A. camphorata shows highly medicinal and commercial values with the demand far exceeds the available supply. Thus, the petri-dish cultured A. camphorata (PDCA) is expected to develope as a substitute. In this paper, nineteen triterpenes were isolated from PDCA, and thirteen of them were the unique anthroic acids in A. camphorata, including the main content antcin K, which suggested that PDCA produced a large array of the same anthroic acids as the wild one. Furthermore, no obvious acute toxicity was found suggesting the edible safety of PDCA. In mice alcohol-induced liver injury model, triglyceride (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) had been reduced by the PDCA powder as well as the main content antcin K, which indicated that the PDCA could protect alcoholic liver injury in mice model and antcin K could be the effective component responsible for the hepatoprotective activities of PDCA against alcoholic liver diseases.

Stigmastane-type steroids with unique conjugated Δ7,9(11) diene and highly oxygenated side chains from the twigs of Vernonia amygdalina.

Veramyosides A-J, eleven undescribed stigmastane-type steroids, including one aglycone and ten glycosides, along with three known homologues were isolated from the twigs of Vernonia amygdalina Delile (compositae). All compounds featured a stigmastane-type steroid skeleton with a unique conjugated Δ7,9(11) diene segment and highly oxygenated side chains with a γ-lactone or an α, ß-unsaturated five-membered lactone ring. The structures of veramyosides A-J and their absolute configurations were unambiguously elucidated by HR-ESI-MS, extensive NMR spectroscopy, in situ dimolybdenum CD methods, modified Mosher's method, quantum chemical calculation of their ECD curves, and CD comparison methods on basis of their biogenetic pathway. In addition, all isolates were investigated for their effects on RXRα transcription, and their effects on the NF-κB signaling pathway were also evaluated.

Paeoniflorin inhibits mast cell-mediated allergic inflammation in allergic rhinitis.

Paeoniflorin (PF), one of the main effective ingredients from the root of Paeonia lactiflora Pall., was reported to possess antitumor, anti-inflammatory, and antiallergic properties. However, the roles of PF in activated human mast cell line, HMC-1 cells, have not yet been elucidated. Thus, the aim of this study was to examine the antiallergic and anti-inflammatory effects of PF on phorbol-12-myristate 13-acetate plus calcium ionophore (PMACI)-induced human mast cells and to identify the mechanism responsible for these effects. Our results demonstrated that pretreatment with PF effectively attenuated PMACI-induced production of tumor necrosis factor-α and interleukin 1ß in HMC-1 cells. In addition, PF significantly suppressed PMACI-induced histamine release and caspase-1 activation in HMC-1 cells. Furthermore, PF prevented the activation of nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways in activated HMC-1 cells. In conclusion, we showed for the first time that PF attenuated the mast cell-mediated allergic inflammatory response through suppressing the NF-κB and MAPK signaling pathways.

Cytoskyrin C, an unusual asymmetric bisanthraquinone with cage-like skeleton from the endophytic fungus Diaporthe sp.

Cytoskyrin C (1), a new bisanthraquinone with asymmetrically cytoskyrin type skeleton, together with a known symmetrical analogue (+)-epicytoskyrin (2), were isolated from an endophytic fungus ARL-09 (Diaporthe sp.). Cytoskyrin C (1) featured an asymmetrically cage-like structural motif arising from the dimerization of anthraquinone monomers by three carbon­carbon bonds 9a/3', 3/9a' and 1/1'. The structure and absolute configuration of compound 1 were determined by spectroscopic analyses, ECD calculation and exciton chirality methods. Moreover, a plausible biogenetic pathway of 1-2 was predicted. Their cytotoxicities against SMMC-7721 cell as well as effects on NF-κB signaling pathway were evaluated. 2009 Elsevier Ltd. All rights reserved.