Three new phenols and one new lignan from Clematis terniflora var. manshurica (Rupr.) Ohwi with their anti-inflammatory activity.

Three undescribed phenols, mandshusica C-E (1-3) and a new lignan, mandshusica F (5), along with six known compounds (4, 6-10) were isolated from the roots and rhizomes of Clematis terniflora var. manshurica (Rupr.) Ohwi. Their structures were elucidated by extensive spectroscopic analysis as well as NMR and ECD calculations. Moreover, the possible biosynthetic pathways of compounds 1-3 were also discussed. All compounds were evaluated for their anti-inflammatory activities in LPS-induced RAW 264.7 cells. Compounds 1, 3, 4 significantly reduced the levels of NO and TNF-α, while compounds 2 and 8 significantly inhibited NO production in LPS-induced RAW264.7 cells.

Mono-ADP-ribosylation, a MARylationmultifaced modification of protein, DNA and RNA: characterizations, functions and mechanisms.

The functional alterations of proteins and nucleic acids mainly rely on their modifications. ADP-ribosylation is a NAD+-dependent modification of proteins and, in some cases, of nucleic acids. This modification is broadly categorized as Mono(ADP-ribosyl)ation (MARylation) or poly(ADP-ribosyl)ation (PARylation). MARylation catalyzed by mono(ADP-ribosyl) transferases (MARTs) is more common in cells and the number of MARTs is much larger than poly(ADP-ribosyl) transferases. Unlike PARylation is well-characterized, research on MARylation is at the starting stage. However, growing evidence demonstrate the cellular functions of MARylation, supporting its potential roles in human health and diseases. In this review, we outlined MARylation-associated proteins including MARTs, the ADP-ribosyl hydrolyses and ADP-ribose binding domains. We summarized up-to-date findings about MARylation onto newly identified substrates including protein, DNA and RNA, and focused on the functions of these reactions in pathophysiological conditions as well as speculated the potential mechanisms. Furthermore, new strategies of MARylation detection and the current state of MARTs inhibitors were discussed. We also provided an outlook for future study, aiming to revealing the unknown biological properties of MARylation and its relevant mechanisms, and establish a novel therapeutic perspective in human diseases.

Two new anti-inflammatory compounds from the roots and rhizomes of Clematis terniflora var. manshurica (Rupr.) Ohwi.

Two new compounds named mandshurica A (1) and mandshurica B (2), together with four known lignans (3-6) were isolated from the roots and rhizomes of Clematis terniflora var. manshurica (Rupr.) Ohwi. The structures of the new compounds were elucidated by HR-ESI-MS, 1D and 2D NMR spectroscopy. Moreover, the anti-inflammatory activity of compounds 1 and 2 were evaluated against lipopolysaccharide-induced mouse macrophage RAW264.7 cells. Compounds 1 and 2 displayed significant inhibitory effect on NO production, and compound 2 exhibited obvious inhibition on the pro-inflammatory cytokines TNF-α. Both new compounds showed potential anti-inflammatory activity.

Two new neolignans and an indole alkaloid from the stems of Nauclea officinalis and their biological activities.

A pair of new diastereoisomers neolignans (1-2) and a new alkaloid (7) were isolated from the stems of Nauclea officinalis: naucleaoxyneolignoside A (1), naucleaoxyneolignoside B (2), (2S,3S)-javaniside (7), together with nine known compounds, 2S-3,3-di-(4-hydroxy-3-methoxyphenyl)-propane-1,2-diol (3), threo-1,2-bis-(4-hydroxy-3-methoxyphenyl)-propane-1,3-diol (4), nauclefine (5), angustidine (6), naucleoxoside A (8), naucleoxoside B (9), angustoline (10), (3S,19S)-3,14-dihydroangustoline (11), and (3S,19R)-3,14-dihydroangustoline (12).The structures of 1, 2 and 7 were elucidated by extensive spectroscopic methods and the known compounds were identified by comparison of their data with those reported in the literature. The absolution configurations of 1, 2, 7,11 and 12 were confirmed by the quantum chemical CD calculation method. Compounds 1-9 showed weak to moderate inhibitory activity on nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells in vitro with IC50 values comparable to that of dexamethasone. In addition, compounds 1-9 were evaluated for the antibacterial and cytotoxic effects, and the results revealed that these compounds showed no anti-bacterial activity, and compounds 3-6 showed modest cytotoxic activity.

Cephalotaxine-type alkaloids with antiproliferation effects from the branches and leaves of Cephalotaxus fortunei var. alpina.

Eight cephalotaxine-type alkaloids (1-8), including two new compounds cephafortunines A and B (1-2), were isolated from the branches and leaves of Cephalotaxus fortunei var. alpina. Their structures were identified by a series of spectroscopic methods (MS, UV, IR, 1D, and 2D NMR) and comparison with the reported data of known analogs. The absolute configurations of 1 and 2 were determined by electronic circular dichroism (ECD) calculations. 1-8 were evaluated for their in vitro antiproliferation effects against two human leukemia cell lines (U937 and HL-60). All compounds showed different levels of antiproliferation effects against U937 cells with GI50 values of 4.21-23.70 µM. 4 and 5 were the most active against U937 cells with GI50 values of 4.21 and 6.58 µM and against HL-60 cells with GI50 values of 6.66 and 6.70 µM, respectively. 4 and 5 arrested HL-60 cell cycle in G0/G1 phase.

Therapeutic effects of Caesalpinia minax Hance on complete Freund's adjuvant (CFA)-induced arthritis and the anti-inflammatory activity of cassane diterpenes as main active components.

ETHNOPHARMACOLOGICAL RELEVANCE: Seeds of Caesalpinia minax Hance called 'Ku-Shi-Lian' (KSL) in China have been used as Zhuang or Dai folk medicines for treatment of common cold, fever, rheumatoid arthritis and dysentery for hundred years. AIM OF THE STUDY: This study aimed to investigate therapeutic efficacy of KSL extract using complete Freund's adjuvant (CFA) induced arthritis in a rat model and the anti-inflammatory activity of cassane diterpenes as the main active material basis of this herb. MATERIALS AND METHODS: Arthritis was induced in male Wistar rats (200-220 g) by immunization with CFA. Dexamethasone (DXMS) and Tripterygium glycosides (TG) were chosen as the positive drugs. Water soluble fraction (CMW, 1000 and 2000 mg/kg) and chloroform soluble fraction (CMC, 400 and 800 mg/kg) of KSL were orally administered from day 1 and continued for 21 days. Change of paw swelling perimeter, arthritics score, body weight growth, were observed, and the production of TNF-α, IL-1ß and IL-6 in serum were measured by enzyme-linked immunosorbent assay (ELISA). The histological changes in the ankle joint were analyzed in adjuvant induced arthritis rats. Moreover, the inhibitory effect on mRNA expression of proinflammatory cytokine IL-1ß, IL-6 and TNF-α of fourteen cassane diterpenes obtained from CMC extract were valued using the RAW 264.7 macrophages cell stimulated by lipopolysaccharide (LPS) assay. RESULTS: The chloroform soluble fraction (CMC) showed the significantly suppressed change of paw swelling perimeter, arthritics score and increased body weight loss. The overproduction of TNF-α, IL-1ß and IL-6 were remarkably suppressed in the serum. Fourteen cassane derivatives as the main constituents of CMC extract showed the promising activity on the expression mRNA of cytokine IL-1ß, IL-6 and TNF-α produced by macrophages cells. CONCLUSIONS: In this study, the chloroform soluble fraction of 'KSL' (seeds of C. minax) was found to exert an anti-RA activity significantly in vivo for the first time, which indicted this fraction might be used as a powerful therapeutic agent for arthritis treatments. Cassane diterpenes, as the main constituents in this fraction, showed the anti-inflammation activity through the regulation of cytokine expression, which might be developed as target-agents for this national herb further developing.

Simultaneous identification and analysis of cassane diterpenoids in Caesalpinia minax Hance by high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry.

Cassane diterpenoids were successfully and simultaneously identified in Caesalpinia minax Hance by high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. A total of 59 peaks were detected, and among them 51 compounds, including 41 furanocassane diterpenoids, 10 furanolactone cassane diterpenoids were simultaneously identified and characterized on the basis of the protonated molecule, retention behavior, and fragments in MS(2) . Ten compounds, including seven novel compounds, were identified or tentatively identified for the first time in C. minax. In a positive ion mode, the fragmentation pathways of cassane diterpenoids were also analyzed for the first time. The relative amounts of the five main diterpenoids (caesalpinin L, caesalpinin F2 , bondcellpin C, caesalpinin E, and ξ-caesalmin) were simultaneously quantified by high-performance liquid chromatography. Results showed that the newly discovered and known components of C. minax can be used to determine the material basis of bioactivity; this method can also be applied to analyze cassane diterpenoids in herbal medicines from the genus Caesalpinia belonging to the family Fabaceae.

Two new diterpenes from the seeds of Caesalpinia minax Hance.

Molecules with diterpene skeletons often possess valuable medicinal properties. Two new diterpenes 1α,6α,7ß-triacetoxy-5α-hydroxy-14ß-ethyl-O-vouacapane (1) and 2α-acetoxy-14,15-cyclopimara-7ß,16-diol (2) were isolated from the seeds of Caesalpinia minax Hance. Their structures were established on the basis of extensive spectroscopic analyses, including HR-ESI-MS, UV, IR, 1D, and 2D NMR (HSQC, HMBC, NOESY) methods. The stereochemical structure of 1 was confirmed via the circular dichroism spectrum and calculated ECD experiment. The inhibitory activity of nitric oxide production of RAW264.7 macrophages stimulated by lipopolysaccharide of compounds 1 and 2 was evaluated, and compound 1 was found to show significant inhibitory effect.

Anti-inflammation furanoditerpenoids from Caesalpinia minax Hance.

Cassane skeletons are rare in nature, but often possess valuable medicinal properties. A furanoditerpenoid with an unusual A-seco-rearranged cassane skeleton, neocaesalminin A, and five furanoditerpenoids were isolated from seeds of Caesalpinia minax Hance, along with six known cassane derivatives, 7-O-acetyl-bonducellpin C, caesalmin F, caesalmin C, ζ-caesalmin, caesalmin E1 and caesalpinin K. Compound structures were determined by spectroscopy (HR-ESI-MS, UV, IR, 1D NMR, 2D NMR), X-ray crystallography and quantum chemical computation of electronic circular dichroism). Three of the previously known compounds exhibited significant inhibition of nitric oxide production of RAW264.7 macrophages stimulated by lipopolysaccharide (LPS).

[Studies on chemical constituents from Rhizoma Heterosmilacis Japonicae].

Six compounds were isolated from Rhizoma Heterosmilacis Japonicae. They were identified as beta-sitosterol (I) dau-costerol (II),3,3',5,5'-tetrahydroxy-4'-methoxystilbene (III), naringenin (IV), alpha-L-butylsorbopyranoside (V) and macrozamin (VI). The compounds III, IV, V and VI were isolated from this genus for the first time.

New diterpenoids from Semiaquilegia adoxoides.

Two new ent-kaurane-type diterpenoids, E-semiaquilegin (1) and Z-semiaquilegin (2), together with eight known compounds (3-10) were isolated from the dried roots of Semiaquilegia adoxoides (DC.) Makino. The structures of compounds 1 and 2 were elucidated mainly by 2D NMR techniques including 1H-1H COSY, HSQC, HMBC, NOESY as 16alpha-hydroxy-ent-kaurane-17,20-di-(3,4-dihydroxy-E-cinnamoyl) ester and its (Z)-isomer.

[Studies on dihydroflavonol glycosides from rhizome of Smilax glabra].

OBJECTIVE: To investigate the chemical constituents from the rhizomes of Smilax glabra. METHOD: The compounds were isolated by column chromatography with silica gel, Diaion HP-20 and ODS as packing materials, and HPLC. Their structures were determined on the basis of their spectral evidence. RESULT: 5 dihydro-flavonol glycosides were identified as: astilbin (1), neoastilbin (2), isoastilbin (3), neoisoastilbin (4), (2R, 3R)-taxifolin-3'-O-beta-D-pyranglucoside (5). CONCLUSION: Compounds 2, 4, 5 were isolated from this plant for the first time.