Flavonoids from the Roots of Sophora flavescens and Their Potential Anti-Inflammatory and Antiproliferative Activities.

The phytochemical investigation of the roots of the traditional Chinese medicinal plant Sophora flavescens led to the isolation of two novel prenylflavonoids with an unusual cyclohexyl substituent instead of the common aromatic ring B, named 4',4'-dimethoxy-sophvein (17) and sophvein-4'-one (18), and 34 known compounds (1-16, 19-36). The structures of these chemical compounds were determined by spectroscopic techniques, including 1D-, 2D-NMR, and HRESIMS data. Furthermore, evaluations of nitric oxide (NO) production inhibitory activity against lipopolysaccharide (LPS)-treated RAW264.7 cells indicated that some compounds exhibited obvious inhibition effects, with IC50 ranged from 4.6 ± 1.1 to 14.4 ± 0.4 µM. Moreover, additional research demonstrated that some compounds inhibited the growth of HepG2 cells, with an IC50 ranging from 0.46 ± 0.1 to 48.6 ± 0.8 µM. These results suggest that flavonoid derivatives from the roots of S. flavescens can be used as a latent source of antiproliferative or anti-inflammatory agents.

Two new iridoid glycosides from Hedyotis diffusa.

Two new iridoid glycosides, named productasperulosidic acid butyl ester (1) and E-6-O-3-hydroxy-p-methoxycinnamoyl scandoside methyl ester (2), along with nine known ones (3-11), were isolated from Hedyotis diffusa Willd. The structures of them were elucidated by extensive 1D, 2D NMR and HR-ESI-MS spectral data. Compounds 1-11 showed no significant cytotoxic activity against HeLa cells.

Gansui-Banxia Decoction extraction inhibits MDSCs accumulation via AKT /STAT3/ERK signaling pathways to regulate antitumor immunity in C57bl/6 mice.

BACKGROUND: Gansui-Banxia Decoction (GSBXD) is a classic formula of traditional Chinese medical (TCM) sage Zhang Zhongjing to treat stagnation of evil heat and obstruction of qi. At present GSBXD is wildly used to treat cancerous ascites, pleural effusion, peritoneal effusion, pericardial effusion, cranial cavity effusion and several types of cancers, such as hepatocellular carcinoma (HCC) and esophageal cancer. Myeloid-derived suppressor cells (MDSCs) are a kind of immature and heterogeneous cells which can suppress lymphocytes activation by forming a suppressive environment. MDSCs accumulation in peripheral blood and tumors are closely related to the cancer stage and low survival rate of clinical patients. The antitumor immune effect of GSBXD has not received widespread attention. PURPOSE: To investigate the effects of GSBXD on MDSCs accumulation and the mediators including AKT/STAT3/ERK signaling pathways. METHODS: The chemical components of GSBXD were analyzed by UHPLC-MS, and the putative pathways of GSBXD based on Network pharmacology were predicted. Mice were vaccinated with Hepatoma 22 (H22) to establish tumor growth model, which were then administrated with GSBXD ethanol extraction (0.49 mg/kg/day, 1.75 mg/kg/day), sorafenib (60 mg/kg) or saline for 14 days. The cell morphology was evaluated by hematoxylin and eosin (H&E) staining, and immunity cells were determined through flowcytometry analysis. The levels of cytokines production in blood were evaluated by using ELISA kits. STAT3, ERK and AKT/mTOR signaling transduction associated proteins were determined by Western blot. RESULTS: GSBXD could inhibit tumor growth and splenomegaly in H22 tumor model mice. Importantly, GSBXD reduced MDSCs accumulation and differentiation, and inhibited proliferation of F4/80+ CD11b+ macrophages and apoptosis of T cells and B cells, and increased the percentage of CD 3- NK1.1+ NK cells. To better understand the active component of GSBXD, the ethanol-extraction powdered GSBXD was prepared and analyzed by UHPLC-MS. Combined with these main chemical compounds, we predicted that the anti-tumor effect of GSBXD mainly mediated PI3K-AKT and RAS-MAPK signal pathways based on Network Pharmacology. Western blot analysis of tumor tissues and MDSCs cells demonstrated that phosphorylation of AKT, ERK and STAT3 were significantly reduced, specially the activation of ERK. The levels of IL-1ß and IFN-γ were significantly decreased by ELISA analysis. CONCLUSION: GSBXD exhibited antitumor immune activity by reducing the accumulation of MDSCs in vivo, which is possible via down-regulation of AKT/STAT3/ERK signaling pathway and suppression of IL-1ß and IFN-γ.

neo-Clerodane Diterpenoids from the Aerial Parts of Scutellaria barbata with Anti-Inflammatory Activity.

The bioactivity-guided isolation on the Scutellaria barbata extract resulted in the purification of four undescribed neo-clerodane diterpenoids, scuttenlines A-D (1-4), alone with 20 known diterpenoids (5-24). The chemical structures of them were elaborated by extensive spectroscopic means, including 1D, 2D-NMR and HR-MS. The anti-inflammatory potential ability of 1-24 was screened in lipopolysaccharide-stimulated mouse RAW 264.7 cells. Scuttenline C (IC50 =1.9 µM) and 18 (IC50 =3.7 µM) exhibited potent activity to inhibit NO production.

Matrine-Type Alkaloids from the Seeds of Sophora alopecuroides and Their Potential Anti-inflammatory Activities.

Three new matrine-type alkaloids, 8ß-hydroxyoxysophoridine (1), 9ß-hydroxysophoridine (2), 9ß-hydroxyisosophocarpine (3), together with one known analog, 11,12-dehydromatrine (4), were isolated from the seeds of Sophora alopecuroides L. The structures of new compounds were elucidated using extensive spectroscopic techniques including the experimental and calculated ECD data. The anti-inflammatory activities of all the isolates on NO production in RAW 264.7 cells stimulated by lipopolysaccharide were evaluated. Among them, 8ß-hydroxyoxysophoridine (1) showed a significant inhibitory effect with an IC50 value of 18.26 µM.

New Terpenoids And Lignans From The Twigs Of Tripterygium Hypoglaucum.

Six new compounds, including three terpenoids (1-3) and three lignans (4-6), were isolated from the 95% EtOH extract of the twigs of Tripterygium hypoglaucum. Their structures were determined on the basis of extensive spectroscopic analysis. 9'-O-benzoyl-lariciresinol (4) showed weak cytotoxicity against HepG2/Adr cells, with an IC50 value of 30.1 µM in vitro.

Anti-inflammatory and Anti-HIV Compounds from Swertia bimaculata.

Three new compounds (1 - 3), including a sesterterpenoid, aspterpenacid C (1), with an unusual 5/3/7/6/5 pentacyclic skeleton, together with seven known ones (4 - 10), were isolated from the ethanol extract of the traditional Chinese medicinal plant Swertia bimaculata. Their structures were elucidated on the basis of the methods of spectroscopic NMR, MS, and computational chemistry. The structure of 1 was further confirmed by single-crystal X-ray diffraction analysis. Compounds 1 - 10 were tested for activities on the inhibition of nitric oxide production and HIV-1 replication in vitro. Compound 1 exhibited moderate activity in inhibiting nitric oxide production (IC50 = 16.1 µM) and HIV-1 replication (EC50 = 1.35 µM).

Highly Oxygenated Grayanane Diterpenoids from Flowers of Pieris japonica and Structure-Activity Relationships of Antifeedant Activity against Pieris brassicae.

Six new highly oxygenated grayanane diterpenoids, neopierisoids G-L, 1-6, together with 10 known related compounds, 7-16, were identified from the flowers of the poisonous plant Pieris japonica. The structures were elucidated on the basis of comprehensive NMR spectroscopy and mass analysis. The relative configurations of 1-6 were elucidated by analysis of ROESY spectra and comparison of NMR data with the analogues. The absolute configurations of 1-6 were established by the X-ray diffraction analysis of 1 and comparison of the CD spectra of 1-6. Compared with the skeleton of the normal grayanane diterpenoids, compounds 1-6 shared an unusual seco A ring moiety. The antifeedant activities of compounds 1-16 against Pieris brassicae were evaluated by using a dual-choice bioassay, and compounds 1-10 with a normal grayanane skeleton showed potent antifeedant activity against P. brassicae. The structure-activity relationships of antifeedant activities of 1-16 against P. brassicae are discussed.

Naphthoquinones from Onosma paniculatum with Potential Anti-inflammatory Activity.

Four new naphthoquinones (1-4), including a dimeric one, shikometabolin G (1), together with six known ones (6-10), were isolated from the methanol extract of Onosma paniculatum. Their structures were established based on the analysis of NMR and MS spectroscopic data. All of the compounds were evaluated for inhibitory effects on NO production in murine macrophage RAW 264.7 cells. Compounds 2, 3, 5, 6, 7, 8, and 10 displayed good activity on the inhibition of NO production (IC50 = 0.4-16.5 µM), suggesting the potential property of anti-inflammation.

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.

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.

Polycyclic polyprenylated acylphloroglucinols and cytotoxic constituents of Hypericum androsaemum.

Two new polycyclic polyprenylated acylphloroglucinols (PPAPs), androforin A and hyperandrone A, together with twelve known compounds, were isolated from the aerial parts of Hypericum androsaemum. Their structures were established by detailed spectral analysis. In the cytotoxic assay, 1,4-O-diferuloylsecoisolariciresinol showed activities comparable with those of cisplatin, and acetyloleanolic acid exhibited moderate inhibitory effects against HL-60, SMMC-7721, A-549, MCF-7, and SW480 cancer cell lines.

Norditerpenoids from Salvia castanea Diels f. pubescens.

Three new norditerpenoids, castanol A-C (1-3), along with eighteen known diterpenoids, were isolated from Salvia castanea Diels f. pubescens. Their structures were elucidated by extensive spectroscopic analysis. All compounds were evaluated for their cytotoxic activities against five human cancer cell lines. The known compounds neo-tanshinlactone (12) and methyltanshinoate (17) exhibited significant cytotoxic activities against some cells.

Spirocyclic acylphloroglucinol derivatives from Hypericum beanii.

Four new acylphloroglucinols with an unusual 6/6/5 spirocyclic skeleton, hyperbeanols A-D (1-4), were isolated from the methanol extract of Hypericum beanii along with 16 known compounds. Their structures were established on the basis of spectroscopic and X-ray diffraction analysis. Hyperbeanols A-C were three stereoisomers different only at the relative configuration of C-4 and C-13, which were distinguished by the nuclear Overhauser effect spectroscopy (NOESY) spectroscopic data in combination with the single X-ray analysis of hyperbeanol A (1). The cytotoxic activity of hyperbeanols A-D against the cancer cell lines SK-BR-3, HL-60, SMMC-7721, PANC-1, MCF-7, and K562 was also evaluated.

Triterpenoids from Viburnum betulifolium.

Two new triterpenoids, ursa-12-sene-3ß,11ß-diol 3-O-palmitate (1) and ursa-12-sene-1ß,3ß,11α-triol 3-O-palmitate (2), were isolated from the 70% aqueous acetone extract of the aerial parts of Viburnum betulifolium, together with the artificial diene derivative of 2, ursa-12-dien-1ß,3ß-diol 3-O-palmitate (2a). Their structures were characterized by various spectroscopic methods, including 1D NMR, 2D NMR, and HR-ESI-MS.

Polycyclic polyprenylated acylphloroglucinols and chromone O-glucosides from Hypericum henryi subsp. uraloides.

Two new C(30)-epimeric polycyclic polyprenylated acylphloroglucinols (PPAPs), named uralodins B and C (1 and 2, resp.), were isolated from the aerial parts of Hypericum henryi subsp. uraloides together with two new chromone glucosides, urachromones A and B (3 and 4, resp.), as well as 16 known compounds. Their structures were established by extensive NMR techniques and MS analysis. The epimers 1 and 2 always behaved like a single compound when examined by TLC, and were separated by HPLC. Their configuration was distinguished by comparative analysis of the NMR data with known analogues together with the ROESY experiment. All the isolated PPAPs were evaluated for their cytotoxic activities against HepG2, SGC7901, HL-60, and K562 cell lines. Compound 1 showed modest cytotoxic activities against SGC7901 and HL-60 cell lines, and 2 showed modest cytotoxic activities against HepG2, SGC7901, HL-60, and K562 cell lines.

Four new lignans from Viburnum foetidum var. foedidum.

The 70% aqueous acetone extract of the aerial part of Viburnum foetidum var. foedidum afforded four new lignans (1-4) together with six known ones. The structures of the four new compounds were elucidated on the basis of 1D (dimensional), 2D-NMR, and mass spectral analysis. The structure of compound 1, with a novel spirocyclic moiety, was also confirmed by X-ray diffraction analysis. Compounds 1-10 were evaluated for their cytotoxic activity. However, none of the compounds showed significant cytotoxic activity.

Lycojapodine A, a novel alkaloid from Lycopodium japonicum.

Lycojapodine A, a novel C(16)N-type Lycopodium alkaloid with an unprecedented 6/6/6/7 tetracyclic ring system, was isolated from the club moss Lycopodium japonicum. The structure and relative stereochemistry were elucidated on the basis of spectroscopic data and were further confirmed by X-ray analysis. A possible biosynthetic pathway for 1 was proposed. Its inhibitory activity on acetylcholinestrease and anti-HIV-1 activity were also evaluated.