Alpinia hainanensis Rhizome Extract Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis: Active Ingredient Investigation and Evaluation.

Alpinia hainanensis is an important food spice and ethnic medicine in Southwest China. In this study, we found that the EtOAc-soluble fraction (AHE) of the A. hainanensis rhizome ethanol extract could ameliorate dextran sulfate sodium-induced ulcerative colitis (UC). To explore active constituents, five pairs of previously unreported enantiomers (1-5), together with nine known ones (6-14), were obtained. Structural characterization was achieved by comprehensive spectroscopic methods. Compounds 1 and 2 were new curcumin-butyrovanillone hybrids featuring a rare structural fragment of 2,3-dihyrofuran. The anti-inflammatory activities of isolates were evaluated, and the results indicated that compounds (-)-1, (-)-3, 6, 9, 11, and 12 significantly inhibited the nuclear factor-κB signaling pathway. These findings indicate the major active fraction of the A. hainanensis rhizome ethanol extract enriched with diarylheptanoids, flavonoids, phenolics, and their hybrid mixtures, which could be developed as a nutritional and dietary supplement for treating UC.

Geranyl phenyl ethers from Illicium micranthum and their anti-HBV activity.

Fourteen new geranyl phenyl ethers (1-14) along with three known compounds (15-17) were isolated from Illicium micranthum, and their structures were elucidated by comprehensive spectroscopic methods. Illimicranins A-H (1-8) were characterized as geranyl vanillin ethers, while 9 and 10 were dimethyl acetal derivatives. Illimicranins I and J (11 and 12) were rare geranyl isoeugenol ethers. Illimicranins K and L (13 and 14) represented the first example of geranyl guaiacylacetone ether and geranyl zingerone ether, respectively. Compounds 1, 2 and 15 exhibited anti-HBV (hepatitis B virus) activity against HBsAg (hepatitis B surface antigen) and HBeAg (hepatitis B e antigen) secretion, and HBV DNA replication.

Engineering the Surface of Ti3C2 MXene Nanosheets for High Stability and Multimodal Anticancer Therapy.

The surface of Ti3C2 MXene nanosheets (TC NSs) was first modified with the antioxidants sodium ascorbate (SA) and dopamine (DA) (DSTC NS) to improve their stability in oxidative and hydration environments and thereby improve their bioapplications. This novel approach not only improved MXene stability by arresting oxidation but also increased the available functional groups for further functionalization with various biomolecules. The DSTC NSs were then sequentially conjugated with enzyme glucose oxidase (GOx) and photosensitizer Ce6 to render the obtained CGDSTC NSs with glucose starvation and photodynamic therapeutic properties and thus attain high efficiency in killing cancer cells through the cooperative effect. The as-synthesized CGDSTC NSs demonstrated tremendous photothermal effect with conversion efficiency of 45.1% and photodynamic (ROS generation) properties upon irradiation with 808 and 671 nm lasers. Furthermore, it was observed that the enzymatic activity of CGDSTC NSs increased upon laser irradiation due to enhanced solution temperature. During in vitro studies, the CGDSTC NSs exhibited cytocompatability to HePG2 and HeLa cells under nonstimulus conditions. However, they elicited more than 90% cell-killing efficiency in the presence of glucose and laser irradiation via the cooperative effect between starvation therapy and phototherapy. These results indicate that CGDSTC NSs could be used as potential therapeutic agents to eradicate cancers with no or few adverse effects. This surface modification approach is also simple and facile to adopt in MXene-based research.

Structurally diverse limonoids and bio-active evaluation from Trichilia connaroides.

Four new limonoids, named as trichiconlide G (1), 2-hydroxyltrijugin F (2), 23-oxo-21-hydroxyltrijugin F (3), 21-oxo-23-hydroxyltrijugin F (4), along with sixteen known analogues (5-20) were isolated from the leaves and twigs of Trichilia connaroides. Their structures and absolute configurations were determined by spectroscopic analyses, X-ray diffraction analysis, and TD-DFT-ECD calculations. Trichiconlide G (1) is one rare naturally occurring 1,2-seco phragmalin-type limonoid bearing a C-7/28 δ-lactone ring. Additionally, 2-hydroxyltrijugin F (2), 23-oxo-21-hydroxyltrijugin F (3), and 21-oxo-23-hydroxyltrijugin F (4) are three naturally occurring limonoids with a rare C-16/8 δ-lactone ring. All isolates were evaluated for their cytotoxic and anti-inflammatory activities. None of compounds exhibited cytotoxicity against five human cancer cell lines A-549, HepG2, 5-8F, Siha, and SCC-4 at the concentration of 40 µM. Compounds 16 and 17 showed moderate anti-inflammatory activity with IC50 values of 28.45 ± 2.51 and 22.66 ± 2.01 µM, respectively.

Calcitriol promotes the maturation of hepatocyte-like cells derived from human pluripotent stem cells.

Human hepatocyte-like cells (HLCs) derived from human pluripotent stem cells (hPSCs) represent a promising cell source for the assessment of hepatotoxicity and pharmaceutical safety testing. However, the hepatic functionality of HLCs remains significantly inferior to primary human hepatocytes. The bioactive vitamin D (VD), calcitriol, promotes the differentiation of many types of cells, and its deficiency is correlated to the severity of liver diseases. Whether calcitriol contributes to the differentiation of HLCs needs to be explored. Here, we found that the supplementation of calcitriol improved the functionalities of hPSCs-derived HLCs in P450 activities, urea production, and albumin secretion. Moreover, calcitriol also enhanced mitochondrial respiratory function with increased protein expression levels of the subunit of respiratory enzyme complexes in HLCs. Further analyses showed that the mitochondrial biogenesis regulators and mitophagy were increased by calcitriol, thus improving the mitochondrial quality. These improvements in functionality and mitochondrial condition were dependent on vitamin D receptor (VDR) because the improvements were abolished under VDR-deficient conditions. Our finding provides a cost-effective chemical process for HLC maturation to meet the demand for basic research and potential clinic applications.

Two new steroids with NO inhibitory effects from lansium domesticum.

Chemical investigation of Lansium domesticum has led to the isolation of two undescribed compounds, namely 17(20)E-dyscusin B (1) and 17(20)Z-dyscusin B (2), as well as three known ones (3 - 5). Structural elucidation was accomplished by the analysis of NMR, MS and IR data. Compounds 1 and 2 were a pair of Δ17(20) geometric isomers of pregnane steroids and showed the significant nitric oxide (NO) inhibitory activities.

Lignans and Neolignans with Antioxidant and Human Cancer Cell Proliferation Inhibitory Activities from Cinnamomum bejolghota Confirm Its Functional Food Property.

In the aim to evaluate the functional food property of Cinnamomum bejolghota, seven new lignans and neolignans, bejolghotins A-G (1-4 and 9-11), along with 14 known ones (5-8 and 12-21), were isolated and their structures including absolute configurations were elucidated by extensive spectroscopic data and electronic circular dichroism (ECD) analyses. All of the isolates were tested for antioxidant and human cancer cell proliferation inhibitory activities. Twenty compounds showed comparable antioxidant activity to the positive controls, and three significantly inhibited the growth of three cancer cell lines HCT-116, A549, and MDA-MB-231 with IC50 values of 0.78-2.93 µM, which confirmed its health benefits.

Four new steroids from the leaves and twigs of Dysoxylum pallens and their cytotoxic activities.

Four previously undescribed steroids, identified as (3S,7S,8S,9S,10R,13S,14S,16S,17R,20S)-7α-methoxy-ergosta-5,24(28)-dien-3ß,16ß,20-triol (1), ergosta-5,24(28)-dien-3ß,7α,16ß-triol (2), ergosta-5,25-dien-3ß,7α,16ß,20-tetrol (3) and 7α,16ß,24α-trihydroxy-varninasterol (4), as well as five known analogues (5-9), were isolated from the leaves and twigs of Dysoxylum pallens Hiern (Meliaceae). Their structures were elucidated based on extensive spectroscopic analysis such as HR-ESI-MS, 1D and 2D NMR, UV, and IR. The absolute configuration of compound 1 was determined by X-ray diffraction analysis. Selected compounds were evaluated for their cytotoxic activities. Compounds 1, 2, and 8 exhibited moderate cytotoxic activity against HL-60, Hela, and HepG2 tumor cell lines with IC50 ranged from 11.09 to 17.51 µM.

Aspidoptoids A-D: Four New Diterpenoids from Aspidopterys obcordata Vine.

Four new diterpenoids, named aspidoptoids A-D (1-4), together with two known analogues (5-6) were isolated from Aspidopterys obcordata vine. Aspidoptoids A-B (1-2) are the first examples of phenylethylene-bearing 20-nor-diterpenoids of which aspidoptoid B (2) possesses a rare 3,10-oxybridge. Their structures and absolute configuration were determined by extensive spectroscopic analyses (IR, HRESIMS, 1D and 2D NMR) and electronic circular dichroism (ECD) calculation. In addition, all the isolates were evaluated for their cytotoxic activities and inhibitory effects on the nitric oxide (NO) production.

New cadinane sesquiterpenoids from Mikania micrantha.

Chemical investigation of the aerial parts of Mikania micrantha led to the isolation of eight sesquiterpenoids and ten diterpenoids, including five cadinane sesquiterpenoids (1-5), three bisabolene sesquiterpenoids (6 - 8), nine ent-kaurane diterpenoids (9-17), and an abietane diterpenoid (18). Among them, 1 - 3 are new and feature a rare lactone or furan ring derived from C-6 isopropyl group side chain. Compound 18 was isolated from genus Mikania for the first time, and was also the first example of abietane-type diterpenoids from this plant. Their structures were elucidated on the basis of extensive spectroscopic analyses (1D and 2D NMR, HRESIMS, and ECD). All compounds were examined for their inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 macrophage cells, and compound 18 exhibited pronounced inhibition on NO production (IC50 = 11.04 µM), being comparable to the positive control, quercetin (IC50 = 11.15 µM).

Proximal Tubular Development Is Impaired with Downregulation of MAPK/ERK Signaling, HIF-1α, and Catalase by Hyperoxia Exposure in Neonatal Rats.

Supplemental oxygen therapy (hyperoxia) is a widely used treatment for alveolar hypoxia in preterm infants. Despite being closely monitored, hyperoxia exposure is believed to undermine neonatal nephrogenesis and renal function caused by elevated oxidative stress. Previous studies have mostly focused on the hyperoxia-induced impairment of glomerular development, while the long-term impact of neonatal hyperoxia on tubular development and the regulatory component involved in this process remain to be clarified. Here, we examined tubular histology and apoptosis, along with the expression profile of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling, hypoxia-inducible factor 1α (HIF-1α), and catalase, following hyperoxia exposure in neonatal rats. Hematoxylin and eosin (H&E) staining revealed the early disappearance of the nephrogenic zone, as well as dilated lumens and reduced epithelial cells, of mature proximal tubules following neonatal hyperoxia. A robust increase in tubular cell apoptosis caused by neonatal hyperoxia was found using a TUNEL assay. Moreover, neonatal hyperoxia altered renal MAPK/ERK signaling activity and downregulated the expression of HIF-1α and catalase in the proximal tubules throughout nephrogenesis from S-shaped bodies to mature proximal tubules. Cell apoptosis in the proximal tubules was positively correlated with HIF-1α expression on the 14th postnatal day. Our data indicates that proximal tubular development is impaired by neonatal hyperoxia, which is accompanied by altered MAPK/ERK signaling as well as downregulated HIF-1α and catalase. Therapeutic management that targets MAPK/ERK signaling, HIF-1α, or catalase may serve as a protective agent against hyperoxia-induced oxidative damage to neonatal proximal tubules.

(±)-Meliviticines A and B: Rearranged prenylated acetophenone derivatives from Melicope viticina and their antimicrobial activity.

Two new prenylated acetophenone derivatives racemates, meliviticines A (1) and B (2) with unprecedented rearranged skeletons, were isolated from Melicope viticina. Subsequent chiral resolution led to the separation of two pairs of enantiomers, (±)-meliviticines A (1a/1b) and (±)-meliviticines B (2a/2b). Their structures including absolute configurations were elucidated by extensive spectroscopic data, electronic circular dichroism analysis, and X-ray crystallography. A plausible biosynthetic pathway of 1 and 2, involving ring cleavage and rearrangement of the prenylated acetophenone backbone was proposed. All the isolates showed moderate antimicrobial activities with MIC values of 25-50 µg/mL against several bacterial and fungal strains.

Cytotoxic arylalkenyl α,ß-unsaturated δ-lactones from Cryptocarya brachythyrsa.

Three new arylalkenyl α,ß-unsaturated δ-lactones, cryptobrachytones A-C (1-3), together with one known analogue kurzilactone (4), were isolated from the leaves and twigs of Cryptocarya brachythyrsa. Their structures were elucidated based on extensive spectroscopic data and electronic circular dichroism (ECD) analysis. All the isolates were evaluated in vitro for anti-proliferative activity against a panel of five human cancer cell lines and one human normal cell, respectively, and the results showed 1, 2 and 4 possessing significant selective cytotoxicity toward the human cancer cell lines with IC50 values from 5.41 to 15.43 µM. This is the first study for C. brachythyrsa.

Two spiroketal derivatives with an unprecedented amino group and their cytotoxicity evaluation from the endophytic fungus Pestalotiopsis flavidula.

Two new spiroketal derivatives with an unprecedented amino group, 2'-aminodechloromaldoxin (1) and 2'-aminodechlorogeodoxin (2), along with one known analogue dechloromaldoxin (3), were isolated from the plant endophytic fungus Pestalotiopsis flavidula. Their structures were elucidated on the basis of extensive spectroscopic analysis. The purification was cytotoxicity-guided which indicated the extract, fractions and compounds were evaluated in vitro for anti-proliferative activity against a panel of human cancer cell lines. The results showed compounds 1 and 2 with moderate cytotoxicity while 3 was inactive, which suggested -NH2 group might play a very important role for their cytotoxicity. This is the first study for P. flavidula and the first time to report the spiroketal derivatives as alkaloids from the Pestalotiopsis genus.

Anti-inflammatory sesquiterpenoids from the Traditional Chinese Medicine Salvia plebeia: Regulates pro-inflammatory mediators through inhibition of NF-κB and Erk1/2 signaling pathways in LPS-induced Raw264.7 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia plebeia R. Brown, a traditional Chinese medicinal herb, has been used to treat inflammatory diseases such as cough, hepatitis, and diarrhea for a long history. AIM OF THE STUDY: The aim of the present study was to isolate and identify potential anti-inflammatory agents from the herb of S. plebeia, which may have contributed to its folk pharmacological use in the treatment of inflammatory diseases. MATERIAL AND METHODS: The aerial parts of S. plebeia were extracted with 95% ethanol and separated by silica gel, RP-C18, Sephadex LH-20, and HPLC. The structures of the isolated compounds were elucidated by extensive spectroscopic analysis (MS, NMR, and X-ray). Anti-inflammatory activities of all compounds were evaluated by the model of LPS-induced up-regulated of NO in Raw264.7 macrophages. The expression levels of cytokine (TNF-α) and proteins (iNOS and COX-2) were assessed by ELISA kit and Western blotting analysis, respectively. Furthermore, the influences of salviplenoid A (1) on NF-κB and MAPK signaling pathways were determined by Western blotting analysis and immunofluorescence assay. RESULTS: Six new (1-6, salviplenoids A-F) and ten known (7-16) sesquiterpenoids were isolated from the herb of S. plebeia. The absolute configurations of compounds 1, 2, and 7 were determined by X-ray diffraction. The new eudesmane-type sesquiterpenoid, salviplenoid A (1), significantly decreased the release of NO and TNF-α and the expression of proteins iNOS and COX-2. In addition, the biochemical mechanistic study indicated that 1 regulated the NF-κB dependent transcriptional activity through inhibiting the nuclear translocation of p50/p65 dimer and decreasing the phosphorylation of IκB and Erk1/2. CONCLUSIONS: Among all sesquiterpenoids isolated from S. plebeian, the new salviplenoid A (1) exhibited the most potent anti-inflammatory activity in LPS-induced Raw264.7 cells via inhibition of NF-κB and Erk1/2 signaling pathways.

Protective effect of the essential oil of Zanthoxylum myriacanthum var. pubescens against dextran sulfate sodium-induced intestinal inflammation in mice.

BACKGROUND: Zanthoxylum myriacanthum var. pubescens is an ethnic medicine for digestive disease known as Maqian. A previous report showed that the Maqian fruits essential oil (MQEO) exhibited an NO inhibitory effect on RAW 264.7 cells, but the effect on inflammatory disease in vivo remains unknown. PURPOSE: To investigate the anti-inflammatory effect of Z. myriacanthum var. pubescens as potential candidate for the treatment of intestinal inflammation. STUDY DESIGN: Evaluation of anti-inflammatory effect of MQEO using dextran sulfate sodium (DSS)-induced intestinal inflammation in mice and exploration of the mechanisms with THP-1 cells. METHODS: C57BL/6 mice were provided drinking water containing 3% DSS for 10 days followed by normal drinking water for 3 days. MQEO (35 and 70mg/kg) were given 5 days before experiments and continued for another 13 days. At the end of experiments, mice were euthanized and colonic tissue was collected to be analyzed by H&E staining, RT-PCR and immunohistochemistry for evaluating the damage of colons, the mRNA levels of IL-1ß, IL-6, IL-12p35 and TNF-α, and the expressions of myeloperoxidase (MPO) and matrix metalloproteinase-9 (MMP-9). The LPS-stimulated THP-1 cell line was used for exploring the role of inflammatory markers using ELISA, western blot and flow cytometry methods. RESULTS: Oral administration of MQEO (35 and 70mg/kg) markedly attenuated the symptoms of intestinal inflammation, including diarrhea, rectal bleeding, and loss of body weight. It also reduced the shortening of colon length and histopathological damage. The expressions of MPO and MMP-9 and the mRNA levels of pro-inflammatory cytokines (IL-1ß, IL-6 and IL-12p35) in colonic tissue significantly decreased after MQEQ treatment. The activation of NF-κB p65 in colonic mucosa was also markedly suppressed. In addition, MQEO significantly suppressed LPS-stimulated production of TNF-α and IL-1ß, effectively blocked phosphorylation of IKK and IκB, and dose-dependently reduced LPS-stimulated expression of TLR4 in THP-1 cells at concentrations ranging from 0.01‰ to 0.05‰ (v/v). CONCLUSION: MQEO exhibited protective effect against DSS-induced intestinal inflammation and the anti-inflammatory activity may be associated with TLR4 mediated NF-κB signaling pathway, suggesting it might be used as an anti-inflammatory agent.

Cytotoxicity and Synergistic Effect of the Constituents from Roots of Aglaia odorata (Meliaceae).

Twelve compounds were isolated from the roots of Aglaia odorata. Their structures were established on the basis of NMR and MS data as rocaglaol (1), rocaglamide (2), eichlerialactone (3), sapelins A (4), isofouquierone (5), eichlerianic acid (6), shoreic acid (7), agladupol E (8), 3-epimeliantriol (9), cleomiscosins B (10), 2ß,3ß-dihydroxy-5α-pregnane-16-one (11) and ß-D-glucopyranos-1-yl N-methylpyrrole-2-carboxylate (12). Among them, compounds 1 and 2 showed significant cytotoxicity against human cancer cell (HL-60, SMMC-7721, A-549, MCF-7 and SW480) with IC50 values of 0.007-0.095 µM, while compounds 3-5 and 10 and 11 showed moderate to no cytotoxicity (IC50 0.43 to values >40 µM). Compound 6 showed only weak cytotoxicity (IC50 6.87 to >40 µM) and its epmier 7 was completely inactivite (IC50>40 µM) in the assay. However, potent synergistic effect was observed when the molar ratio of 6 to 7 is between 4:1 and 1:1.

Koumine, Humantenine, and Yohimbane Alkaloids from Gelsemium elegans.

Nine new alkaloids of the koumine (1-4), humantenine (5-7), and yohimbane (8, 9) types as well as 12 known analogues were isolated from the leaves and vine stems of Gelsemium elegans. Compound 1 is the first N-4-demethyl alkaloid of the koumine type, compound 7 is the first nor-humantenine alkaloid, and compounds 8 and 9 are the first N-1-oxide and the first seco-E-ring alkaloids, respectively, of the yohimbane type. Compounds 1 and 7 exhibited moderate cytotoxicity against five human tumor cell lines with IC50 values in the range 4.6-9.3 µM.

Chemical composition, antimicrobial and anti-inflammatory activities of the essential oil from Maqian (Zanthoxylum myriacanthum var. pubescens) in Xishuangbanna, SW China.

ETHNOPHARMACOLOGICAL RELEVANCE: Maqian (Zanthoxylum myriacanthum var. pubescens Huang) is widely consumed as an indigenous remedy for digestive disorders, detoxification, detumescence and analgesia by the ethnic groups in Xishuangbanna, SW China. A related species, Huajiao (Zanthoxylum schinifolium Sieb. et Zucc.), has similar uses in traditional Chinese medicine. We aimed to scientifically validate the traditional uses by investigating and comparing the chemical composition, antimicrobial and anti-inflammatory activities of the essential oils of Maqian and Huajiao. MATERIALS AND METHODS: Essential oils were collected from the fruits of Maqian and Huajiao by simultaneous distillation extraction and identified by gas chromatography-mass spectrometry (GC-MS) analysis. To assess antimicrobial activity, the minimum inhibitory and bactericidal concentrations (MIC and MBC) against 7 microbial strains, including 5 food-borne pathogens, were evaluated by serial dilution with a standardized microdilution broth methodology. For anti-inflammatory activity, the cell viability and nitric oxide (NO) production were determined on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells by MTS assay and the Griess reagent system, respectively. RESULTS: The essential oil from Maqian is rich in limonene (67.06%) and has strong antimicrobial activity against the tested pathogens and spoilage organisms, with MIC ranging from 64 to1024µg/ml and MBC ranging from 64 to 2048µg/ml. It also showed anti-inflammatory activity by significantly inhibiting nitric oxide (NO) production induced by LPS in RAW 264.7 cells at 0.04‰ without effects on cell viability. Furthermore, it showed relatively stronger antimicrobial and anti-inflammatory activities than the essential oil from Huajiao. CONCLUSIONS: Our findings not only justify the use of Maqian as an indigenous remedy for digestive disorders, detoxification, detumescence and analgesia, but also suggest that it could be promoted as a preferred substitute for Huajiao.

Limonoids from the Leaves and Twigs of Walsura yunnanensis.

Nine new cedrelone limonoids, namely, walsuranolide B (1), 11ß-hydroxy-23-O-methylwalsuranolide (2), yunnanolide A (3), yunnanol A (4), 11ß-hydroxyisowalsuranolide (5), 11ß-hydroxy-1,2-dihydroisowalsuranolide (6), 1α,11ß-dihydroxy-1,2-dihydroisowalsuranolide (7), 11ß-hydroxy-1α-methoxy-1,2-dihydroisowalsuranolide (8), and yunnanolide B (9), together with a new cycloartane triterpenoid, (24S*,25R*)-cycloartane-3ß,24,25,26-tetrol (10), were isolated from the leaves and twigs of Walsura yunnanensis. Their structures were elucidated on the basis of spectroscopic analysis and by comparison with literature data. Compounds 3 and 5 exhibited potent cytotoxicity against five human tumor cell lines with IC50 values in the range 2.2-4.2 µM.