Rearranged neoclerodane diterpenoids from the aerial parts of Salvia hispanica L.

Six new rearranged neoclerodane diterpenoids (1-6), as well as three known ones, were obtained from the aerial part of Salvia hispanica L. Their structures were elucidated by extensive analysis of spectroscopic data (1D, 2D NMR, and HRESIMS) and Mosher's method. The absolute configurations of 1, 2, and 4 were determined by single-crystal X-ray diffraction analysis. All isolated compounds were evaluated for their cardioprotective effects against H2O2-induced cardiomyocytes injury, and compound 5 showed statistically significant cardioprotective effect in vitro assays.

Phytochemical constituents of the pericarps of Illicium difengpi and their anti-inflammatory activity.

Phytochemical investigation on the pericarps of Illicium difengpi lead to the isolation and structure elucidation of a new sesquiterpene, sesquicaranoic acid C (1), a new neolignan, difengpiol C (2), and 10 known compounds. The structures and absolute configurations of two new compounds were determined by a combination of NMR and CD spectroscopic analyses. All isolates were evaluated for their inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 cells.

[Effect of electrical stimulation at auricular points combined with sound masking on the expression of CREB, BDNF and TrkB in the auditory cortex of tinnitus rats].

OBJECTIVE: To explore the effect of electrical stimulation at auricular points (EAS) combined with sound masking on the expression of cAMP-response element binding protein (CREB), brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB) in the auditory cortex of tinnitus rats. METHODS: A total of 27 adult male SD rats were randomly divided into a control group, a model group and an EAS group. The rats in the model group and the EAS group were intervened with intraperitoneal injection of sodium salicylate to induce tinnitus model, while the rats in the control group were intervened with injection of 0.9% NaCl solution. After the model was successfully established, the rats in the EAS group were treated with electrical stimulation at "Shenmen" (TF4) and "Yidan" (CO11), combined with sound masking; the treatment was given once a day for 15 days. The gap prepulse inhibition of acoustic startle (GPIAS) and prepulse inhibition (PPI) testing were performed using the acoustic startle reflex starter package for rats. The expression of BDNF, TrkB, CREB and p-CREB in the auditory cortex of each group were measured with Western Blot analysis. RESULTS: ① Compared with the control group, the GPIAS values in 12 kHz, 16 kHz, 20 kHz and 28 kHz were significantly decreased in the model group (all P<0.05); compared with the model group, GPIAS values in 12 kHz, 16 kHz, 20 kHz and 28 kHz were significantly increased in the EAS group (all P<0.05). ② Compared with the control group, the expression of BDNF and p-CREB in the model group was significantly increased (P<0.01), and the expression of TrkB in the model group was significantly increased (P<0.05); the differences of expression of BDNF, TrkB, CREB and p-CREB between the model group and the EAS group had no statistics significance (all P>0.05). CONCLUSION: EAS could improve the GPIAS values of high-frequency background sound in tinnitus rats, which may be related with the upregulation of the BDNF/TrkB/CREB signaling pathway in the auditory cortex, leading to the reversion of the maladaptive plasticity.

Protostane-Type Triterpenoids from Alisma orientale.

Twenty-eight protostane triterpenoids, including a new degraded one (1), nine new ones (2 - 10), and two new natural ones (11 and 12), have been isolated from the dried rhizomes of Alisma orientale. Alisol R (1) was the first 20,21,22,23,24,25,26,27-octanorprotostane triterpenoid. The absolute configurations of 25-methoxyalisol F (2) and 16ß-hydroperoxyalisol B 23-acetate (3) were determined by X-ray diffraction analysis. In addition, alismaketone-B 23-acetate (28) showed potent vasorelaxant activity on endothelium-intact thoracic aorta rings precontracted with KCl.

Sauruchinenols A and B, unprecedented monocyclic diterpenes with new carbon skeleton from the aerial parts of Saururus chinensis.

Sauruchinenols A (1) and B (2), two novel monocyclic diterpenes with unique carbon skeleton, as well as two new structurally related diterpenes, sauruchinenols C (3) and D (4), were isolated from the aerial part of Saururus chinensis. Their structures were elucidated based on the analysis of spectroscopic data. A hypothetical biogenetic pathway for sauruchinenols A and B was proposed.

Sesquiterpenoids from the twigs and leaves of Fokienia hodginsii.

A rare carotane-type sesquiterpenoid, forkienin A (1), a new eudesmane-type sesquiterpenoid, forkienin B (2), and a new natural eudesmane-type sesquiterpenoid, forkienin C (3), were isolated from the twigs and leaves of Fokienia hodginsii, along with eight known sesquiterpenoids. The structures of the new compounds were elucidated on the basis of their spectroscopic analysis, including 1D and 2D NMR methods. All compounds were evaluated for cytotoxicity against HL-60, SMMC-7721, A-549, MCF-7, and SW480 cell lines.

Five new Lycopodium alkaloids from the aerial parts of Phlegmariurus henryi.

A series of new Lycopodium alkaloids, namely 1-epi-malycorin A (1), 1-epi-17S-hydroxymalycorin A (2), 6α-hydroxyphlegmariurine A (3), 2S,4R-dihydroxyfawcettimine (4), and 16-hydroxylycodine (5), together with 24 known ones, have been isolated from the club moss Phlegmariurus henryi. The structures of the new compounds were determined by extensive spectroscopic analysis, including 1D and 2D NMR, as well as X-ray crystallographic analysis. Among them, the absolute configurations of 1, 2, and 4 and the structure of 3 were confirmed on the basis of the single-crystal X-ray diffraction analysis. 1-Epi-17S-hydroxymalycorin A (2) was a unique C19N-type Lycopodium alkaloid consisting of a serratinine skeleton with 1,2-propanediol unit. 2S,4R-dihydroxyfawcettimine (4) was a 2,4-dihydroxy derivative of fawcettimine. 16-Hydroxylycodine (5) was the oxidative product of lycodine with an unusual hydroxymethyl group at C-15. All new compounds were evaluated for in vitro acetylcholinesterase (AChE) inhibitory activity and cytotoxicity against four human cancer cell lines.

Bioactive sesquiterpenoids from the flowers of Inula japonica.

Phytochemical investigation of the flowers of Inula japonica led to isolation of nine sesquiterpenoids, inujaponins A-I, as well as eighteen known ones. These sesquiterpenoids belong to six skeletal-types, including eudesmane, 1,10-seco-eudesmane, germacrane, guaiane, 4,5-seco-guaiane, and pseudoguaiane sesquiterpenoids. Their structures were established by extensive spectroscopic analysis. The absolute configurations of inujaponin A, eupatolide, and deacetylovatifolin were determined by Cu-Kα X-ray crystallographic analysis. Most of the isolated compounds exhibited potent cytotoxicity against HL-60, SMMC-7721, A-549, MCF-7, and SW-480 cancer cell lines, with IC50 values ranging from 1.57 to 22.58 µM. Some selected compounds also possessed significant inhibitory activity against LPS-induced NO production in RAW264.7 macrophages with IC50 values ranging from 1.42 to 8.99 µM.

Lignan Glucosides from the Stem Barks of Illicium difengpi.

In this study, four new lignan glucosides, named difengpiosides A-D (1-4), were isolated from the stem barks of Illicium difengpi, together with seven known compounds 5-11. Their structures were identified on the basis of spectroscopic analyses (1D and 2D NMR, HRESIMS, CD) and a comparison with literature data. All the compounds were evaluated for their inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 cells.

Obscurumines H-P, new Lycopodium alkaloids from the club moss Lycopodium obscurum.

Seven new fawcettimine-type (1-7) and two new lycopodine-type (8 and 9) Lycopodium alkaloids, as well as 10 known compounds, were isolated from the club moss, Lycopodium obscurum L. The structures of obscurumines H-P (1-9) were determined based on high-resolution MS and 1D and 2D NMR data. Compounds 1 and 2 include a new skeleton that is formed via the linkage of C-9-N-2', which is rarely present in Lycopodium alkaloids. The in vitro acetylcholinesterase (AChE) inhibitory activity assay showed that 5 exhibited weak anti-AChE activity with an IC50 value of 81.0 µM. Compound 8 exhibited inhibition of the secretion of IL-2 in phytohemagglutinin (PHA) and phorbol myristate acetate (PMA) stimulated Jurkat cells, and the IC50 value was 17.2 µM.

Vibsane-type diterpenes from leaves and twigs of Viburnum odoratissimum.

Seven new vibsane-type diterpenes, vibsanols C-H (1-6) and vibsanin X (7), together with seven analogues, were isolated from the leaves and twigs of Viburnum odoratissimum. The structures of the new compounds were elucidated by extensive spectroscopic methods. All the new compounds were detected for their cytotoxicity. Compound 1 showed significant cytotoxicity against all the tested cell lines (HL-60, SMMC-7721, A-594, MCF-7, and SW-480), with IC50 values of 3.35, 4.41, 5.18, 11.30, and 3.70 µM, respectively. Compounds 4 and 5 also displayed significant cytotoxicity against hepatocellular carcinoma SMMC-7721 cell line, with IC50 values of 3.69 and 3.52 µM, respectively.

Nor-lupane triterpenoid and guaiane sesquiterpenoids from Schefflera venulosa.

A novel nor-lupane triterpenoid, 3-oxo-29α-hydroxy-17ß,20-epoxy-28-norlupane (1), and two new guaiane sesquiterpenoids, schvenols A-B (2-3), has been isolated from leaves of Schefflera venulosa. Structures of the new compounds were elucidated on the basis of their spectroscopic methods, including 1D and 2D NMR techniques. And the structure of 1 was further confirmed by the X-ray diffraction analysis. None of the compounds showed inhibitory effects on NO release in LPS-stimulated RAW 264.7 macrophage cell line.

Hupehenols A-E, selective 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) inhibitors from Viburnum hupehense.

Five selective 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) competitive inhibitors, hupehenols A-E (1-5), were isolated from Viburnum hupehense. The structure elucidation indicated that compounds 1-5 are new 20,21,22,23,24,25,26,27-octanordammarane triterpenoids. Their structures were established on the basis of NMR spectroscopic and mass spectrometric analysis. Hupehenols A-E (1-5) showed inhibition against human 11ß-HSD1, with hupehenols B (2) and E (5) having IC50 values of 15.3 and 34.0 nM, respectively. Moreover, hupehenols C (3) and D (4) are highly selective inhibitors of human 11ß-HSD1 when compared to murine 11ß-HSD1.

Huperserines A-E, Lycopodium alkaloids from Huperzia serrata.

A phytochemical study on Huperzia serrata led to the isolation of four new 5-deoxyfawcettimine-related Lycopodium alkaloids, huperserines A-D (1-4), and one new lycodine-type alkaloid, huperserine E (5). Their structures were elucidated based on spectroscopic data, including 1D and 2D NMR techniques. 5-Carbonyl or 5-hydroxyl group is a typical characteristic of lycopodine- and fawcettimine-type alkaloids. This is the first report of the 5-deoxyfawcettimine type Lycopodium alkaloids. In vitro acetylcholinesterase (AChE) inhibitory activity assay showed that huperserine E exhibited moderate anti-AChE activity with an IC50 value of 6.71 µM.

Sesquiterpenoids from Tussilago farfara and their inhibitory effects on nitric oxide production.

Tussilagone (TSL) and its allied sesquiterpenoids were considered as the main active principles of the flower buds of Tussilago farfara, which has been widely used in China as an antitussive herbal medicine. Six new bisabolane-type sesquiterpenoids, tussfararins A-F (1-6), along with 12 known sesquiterpenoids, were isolated from the flower buds of T. farfara. Structures of the new compounds were elucidated by extensive spectroscopic analysis. The biological analysis showed that compounds 1, 3, 6, and 7 inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells with IC50 values of 13.6-24.4 µM.

New Lycopodium alkaloids from Phlegmariurus squarrosus.

Four new Lycopodium alkaloids (1-4), together with 15 known ones, were isolated from club moss Phlegmariurus squarrosus. Notably, 8α-hydroxylycojapodine A (1) was the first derivative of lycojapodine A (5) which was a novel C16N-type Lycopodium alkaloid with an unprecedented 6/6/6/7 tetracyclic ring system. Their structures were elucidated based on the spectroscopic data, including 1D and 2D NMR techniques.

Further lignans from Saururus chinensis.

Three new sauchinone analogues, sauchinones B-D (1-3), together with sauchinone (4), were isolated from the aerial part of Saururus chinensis. Structures of the new compounds were determined by extensive spectroscopic data as well as X-ray analysis. Compounds 3 and 4 inhibited nitric oxide production in lipopolysaccharide stimulated RAW 264.7 cells with IC50 values of 13.0 and 14.2 µM, respectively.

The relationships between chemical and genetic differentiation and environmental factors across the distribution of Erigeron breviscapus (Asteraceae).

AIMS: Erigeron breviscapus (Vant.) Hand.-Mazz. is an important, widely used Chinese herb with scutellarin, 1,5-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid and erigoster B being its major active compounds. We aimed to resolve the influence of biotic and abiotic factors on the concentrations of these compounds and to determine appropriate cultivation methods to improve the yields of the four compounds in this herb. METHODS: In order to detect the major genetic and natural environmental factors affecting the yields of these four compounds, we applied AFLP markers to investigate the population genetic differentiation and HPLC to measure the concentrations of four major active compounds among 23 wild populations which were located across almost the entire distribution of this species in China. The meteorological data including annual average temperature, annual average precipitation and annual average hours of sunshine were collected. The relationships among the concentrations of four compounds and environmental factors and genetic differentiation were studied. IMPORTANT FINDINGS: Low intraspecific genetic differentiation is detected, and there is no obvious correlation between the genetic differentiation and the contents of the chemical compounds. We investigated the correlation between the concentrationsof four compounds (scutellarin, 1,5-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid and erigoster B) and environmental factors. Concentrations of two compounds (1,5-dicaffeoylquinic acid and 3,5-dicaffeoylquinic acid) were correlated with environmental factors. The concentration of 1,5-dicaffeoylquinic acid is positively correlated with latitude, and is negatively correlated with the annual average temperature. The concentration of 3,5-dicaffeoylquinic acid is positively correlated with annual average precipitation. Therefore, changing cultivation conditions may significantly improve the yields of these two compounds. We found the concentration of scutellarin positively correlated with that of erigoster B and 3,5-dicaffeoylquinic acid, respectively. We inferred that the synthesis of these two pairs of compounds may share similar triggering mechanism as they synthesized in a common pathway.

Triterpenoids and steroids with cytotoxic activity from Emmenopterys henryi.

Two new ursane-type triterpenoids, 3ß,19α,23-trihydroxyurs-12-en-24-al-28-oic acid (1) and 3ß,19α,24-trihydroxy-23-norurs-12-en-28-oic acid (2), two new pregnane derivatives, 3ß,12ß-dihydroxy-5α-pregnane-14,16-dien-20-one (9) and 12ß-hydroxy-5α-pregnane-14,16-dien-3,20-dione (10), and eight known compounds were isolated from the twigs and leaves of Emmenopterys henryi. The structures of the new compounds were elucidated on the basis of extensive spectroscopic analysis, including 1D and 2D NMR experiments. Compounds 4, 11, and 12 showed cytotoxicity against HL-60, SMMC-7721, A-549, MCF-7, and SW-480 cell lines with IC50 values in the range of 3.11-20.12 µM.

Diterpenoids from the twigs and leaves of Fokienia hodginsii.

Five new isopimarane diterpenoids, fokihodgins A-E (1-5), four new labdane diterpenoids, fokihodgins F-I (6-9), and one new icetexane diterpenoid, fokihodgin J (10), as well as 18 known diterpenoids were isolated from Fokienia hodginsii. The structures of the new compounds were determined on the basis of their spectroscopic analysis, and the absolute configurations of 1 and 6 were established by X-ray crystallographic analysis. Compound 9 showed moderate cytotoxicity against HL-60 and SMMC-7721 cell lines, with IC50 values of 9.10 and 7.50 µM, respectively.