Lignans with NO inhibitory activity from Tinospora sinensis.

Two new lignan glucosides, tinsinlignans A and B (1 and 2), two new oxyneolignans, tinsinlignans C and D (3 and 4), along with one known analogue (5), were isolated from the stems of Tinospora sinensis. The structures of the new compounds were elucidated based on analysis of spectroscopic data, and the absolute configuration of 1 was determined through electronic circular dichroism (ECD) calculation based on the time-dependent density functional theory (TD-DFT). Compounds 1-4 were evaluated for their inhibitory effects on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in murine RAW264.7 macrophage cells and compounds 1 and 2 exhibited moderate inhibitory activities with IC50 values of 18.5 ± 2.0 and 28.8 ± 1.2 µmol·L-1, respectively.

Chemical constituents from Tinospora sagittata and their biological activities.

Six undescribed low-polarity compounds including three rare 14-methylergostane steroids (1-3), one euphane triterpenoid (4) and two octadecanoic acid ethyl esters (5 and 6), along with ten previously reported terpenyl cometabolites (7-16), were isolated from the stems of Tinospora sagittata. Their structures were determined by detailed spectroscopic analyses and comparison with structurally related known compounds, and all of them have been reported from T. sagittata for the first time. Compounds 4-6 and 16 showed potent in vitro inhibitory activity against the diabetes target α-glucosidase, while compounds 10 and 14 displayed promising antibacterial effect toward Staphylococcus aureus ATCC 25923.

Bioactive aromatic butenolides from a mangrove sediment originated fungal species, Aspergillus terreus SCAU011.

Seven new compounds including five aromatic butenolide analogues (1-5), one quinazolinone alkaloid (6) and one benzoic acid derivative (7), along with eleven known co-metabolites (8-18), were isolated from Aspergillus terreus SCAU011, a fungus from the rhizosphere sediment of a mangrove plant Rhizophora stylosa. The structures of these isolates were established by a combination of MS, NMR and ECD data analyses, as well as chemical method. Compound 3 is a rare ring-open aromatic butenolide, while 6 represents the first natural ring-open benzomalvin-type quinazolinone alkaloid. Also, the previously reported structures for asperlides A-C were proposed to be revised in the present work. The COX-2 inhibitory, α-glucosidase inhibitory, antioxidant and antibacterial activities of all the compounds were assessed. While compounds 4, 6, 11 and 18 exhibited better COX-2 inhibitory activity than the positive control celecoxib, compounds 9 and 10 showed significant α-glucosidase inhibitory activity with IC50 values of 56.1 and 12.9 µM, respectively. Meanwhile, half of the tested samples (1, 8-11 and 15-17) exerted similar or better antioxidant activity compared with the reference drug curcumin, and compounds 3, 9, 17 and 18 displayed moderate antibacterial effect against Staphylococcus aureus.

New antibacterial thiophenes from Eclipta prostrata.

Three new thiophene derivatives, ecliprostins A-C (1-3), have been isolated from the aerial parts of a Compositae medicinal plant Eclipta prostrata, and structures of them have been elucidated by comprehensive spectroscopic analyses. Both ecliprostins A (1) and B (2) feature an acetylenic bithiophenyl backbone and also incorporate an isovalerate moiety, while ecliprostin C (3) is a symmetrical dimer of compound 1 and represents the first example bonded via an ether bridge among the very limited natural dimers. All three compounds show antibacterial activity against Staphylococcus aureus.

New e:b-Friedo-Hopane Type Triterpenoids from Euphorbia peplus with Simiarendiol Possessing Significant Cytostatic Activity against HeLa Cells by Induction of Apoptosis and S/G2 Cell Cycle Arrest.

Seven rare e:b-friedo-hopane-type triterpenoids including four new (1-4) and three known (5-7) ones with 5 being first reported as a natural product, together with five other known triterpenoids (8-12), were isolated from the nonpolar fractions of the ethanolic extract of Euphorbia peplus. Structural assignments for these compounds were based on spectroscopic analyses and quantum chemical computation method. The structural variations for the C-21 isopropyl group, including dehydrogenation (1 and 3) and hydroxylation at C-22 (simiarendiol, 2), were the first cases among e:b-friedo-hopane-type triterpenoids. Simiarendiol (2) bearing a 22-OH showed significant cytostatic activity against HeLa and A549 human tumor cell lines with IC50 values of 3.93 ± 0.10 and 7.90 ± 0.31 µM, respectively. The DAPI staining and flow cytometric analysis revealed that simiarendiol (2) effectively induced cell apoptosis and arrested cell cycle at the S/G2 phases in a dose-dependent manner in HeLa cells.

Secondary metabolites from the mangrove sediment-derived fungus Penicillium pinophilum SCAU037.

Five new funicone derivatives, pinophilones A-E (1a/1b and 2-4), along with 18 biosynthetically related known analogues (5-22), were obtained from the culture of a mangrove sediment-derived fungus Penicillium pinophilum SCAU037. Their structures were established by analysis of 1D/2D NMR and MS data, while the absolute configurations of the new compounds were determined by ECD calculation based on time-dependent density functional theory (TD-DFT). The dihydrofuran moiety in 1a and 1b was first reported for funicone derivatives. Compound 22 exhibited antibacterial activity against Mycobacterium smegmatis and Staphylococcus aureus with IC50 of 23.5 and 2.6 µM, respectively, while 16, 18 and 22 showed significant α-glucosidase inhibitory activity with IC50 of 51.9, 78.4 and 33.8 µM, respectively.

Absolute structure assignment of an iridoid-monoterpenoid indole alkaloid hybrid from Dipsacus asper.

Iridoid-monoterpenoid indole alkaloid hybrids (IMIAHs) represent a rare class of natural products reported from only several plants of Rubiaceae and Dipsacaceae families, while their structural assignments remain a very challenging work due to complexity and flexibility. In the current study, a new IMIAH (1) was isolated from the roots of Dipsacus asper and its structure with absolute configuration was unambiguously established by a combination of spectroscopic analyses, chemical degradation and ECD calculation. A new oleanane-type triterpenoid saponin (2) and 15 known co-metabolites were also obtained and structurally characterized. Our biological evaluations showed that compound 2 exhibited moderate inhibition against acetylcholine esterase (AChE) with an IC50 value of 15.8 ±â€¯0.56 µM, and compound 15 displayed potent cytotoxicity selectively against human A549 and H157 lung cancer cells with IC50 values of 6.94 ±â€¯0.24 and 9.06 ±â€¯0.12 µM, respectively.

Network pharmacological mechanisms of Vernonia anthelmintica (L.) in the treatment of vitiligo: Isorhamnetin induction of melanogenesis via up-regulation of melanin-biosynthetic genes.

BACKGROUND: Vitiligo is a long-term skin disease characterized by the loss of pigment in the skin. The current therapeutic approaches are limited. Although the anti-vitiligo mechanisms of Vernonia anthelmintica (L.) remain ambiguous, the herb has been broadly used in Uyghur hospitals to treat vitiligo. The overall objective of the present study aims to identify the potential lead compounds from Vernonia anthelmintica (L.) in the treatment of vitiligo via an oral route as well as the melanogenic mechanisms in the systematic approaches in silico of admetSAR and substructure-drug-target network-based inference (SDTNBI). RESULTS: The results showed that the top 5 active compounds with a relatively higher bioavailability that interacted with 23 therapeutic targets were identified in Vernonia anthelmintica (L.) using admetSAR and SDTNBI methods. Among these compounds, Isorhamnetin and Kaempferide, which are methyl-flavonoids, performed 1st and 2nd. Isorhamnetin and Kaempferide significantly increased the expression of melanin-biosynthetic genes (MC1R, MITF, TYR, TYRP1 and DCT) and the tyrosinase activity in B16F10 cells. Isorhamnetin and Kaempferide significantly increased the mRNA-expression of melanin-biosynthetic genes (MC1R, MITF, TYR, TYRP1 and DCT), the protein level of MITF and the tyrosinase activity. Based on the SDTNBI method and experimental verification, Isorhamnetin and Kaempferide effectively increased melanogenesis by targeting the MC1R-MITF signaling pathway, MAPK signaling pathway, PPAR signaling pathway (PPARA, PPARD, PPARG), arachidonic acid metabolism pathway (ALOX12, ALOX15, CBR1) and serotonergic synapses (ALOX12, ALOX15) in the treatment of vitiligo from a network perspective. CONCLUSION: We identified the melanogenic activity of the methyl-flavonoids Isorhamnetin and Kaempferide, which were successfully predicted in a network pharmacological analysis of Vernonia anthelmintica (L.) by admetSAR and SDTNBI methods.

[Clinical characteristics and therapy of pan-drug resistant Acinetobacter baumannii infection].

OBJECTIVE: To analyze clinical characteristics and therapy of pan-resistant Acinetobacter baumannii (PDRAB) infection and explore the methods for effective therapy and prevention of this infection. METHODS: Nine hospitalized patients with PDRAB infection confirmed by pathogen and susceptibility testing were analyzed for the risk factors and the treatment outcomes were assessed by case analysis. RESULTS: PDRAB infections occurred mainly in patients with severe complications, most of whom had complications by diabetes or hypertension or damaged mucosal integrity due to mechanical ventilation, surgery and catheterization. The polymyxin sensitivity were 100% for these infections, but all the bacteria identified showed a antimicrobial resistance rates of 100%. The majority of the infections were acquired during hospitalization occurring mainly in the lungs; all the patients had prolonged hospitalization and received antibiotic treatments with high proportions of broad-spectrum antimicrobial agents especially third-generation cephalosporins and quinolones. Exclusive or sequential use of carbapenems and sulbactam in combination with quinolone or aminoglycoside produced favorable effects. CONCLUSIONS: The prevalence of hospital-acquired pan-resistance of PDRAB infections increased significantly in recent years, particularly in patients with high risk factors. The widespread use of broad-spectrum antibiotics may have some relevance to drug resistant occurrence. The application of carbapenems or sulbactam, or their sequential use, in combination with other agents may produce good effects.

[Establishment of high-throughput drug screening cell models based on JAK-STAT signal pathway].

AIM: To discover new drugs which may be applied to diseases of the immune system, hemogenesis system diseases and tumors, several high-throughput drug screening cell models based on JAK-STAT signal pathway have been established. METHODS: Four repeats of STAT DNA binding conserved sequences were synthesized, subcloned into pGL-Luc reporter vector and stably transfected into cell lines in vitro. Cell clones with high copy numbers of STAT binding sites and reporter genes were chosen as high-throughput drug screening cell models. The cell models were tested with known anti-allergic drugs and anti-tumor drugs by determining luciferase activity. The reaction was performed in 96 well micro-plates with a final volume of 50 microL. RESULTS: The cell models by performing rapid fluorescence assay were shown to be highly sensitive and stable after testing with cytokine and drugs. The modification of the expression plasmid simplified this method and made it more practical. It also provided good linear correlation, wide range of assay, highly sensitive and good reproducibility. CONCLUSION: The method can be performed by high-throughput drug screening for effective extraction of Chinese traditional herbs.