Two new chemical constituents from the aerial parts of Tripterygium wilfordii.

Tripterygium wilfordii has been historically employed as a conventional botanical insecticide and a plant of medicinal significance. A new dihydroagarofuran sesquiterpene (1) and a new acyclic compound (2), along with seven known compounds (3-9), have been isolated from the aerial parts of Tripterygium wilfordii. The identification of the structures of novel compounds were accomplished through comprehensive spectroscopic analyses, encompassing HRESIMS, NMR, UV, IR, and a comparative analysis with spectroscopic data from compounds previously characterised. In in-vitro bioassay, compound 8 exhibited significant inhibitory activity for NO release in LPS-induced RAW 264.7 cells, with an IC50 value of 15.7 µM.

Phenolic and flavonoid compounds from the fruit shell of Camellia oleifera.

A new phenolic compound oleiphenol (1), and a new dihydrochalcone oleifechalcone (2) along with seven known compounds (3-9) were isolated from the fruit shell of Camellia oleifera Abel. The planar structures of compounds 1 and 2 were determined on the basis of extensive spectroscopic analyses (IR, UV, NMR, and HR-ESI-MS) and comparison with literature data. The absolute configurations of the new structures were determined by ECD calculations and chemical methods. In addition, compounds 1-9 underwent a series of pharmacological activity tests, including cytotoxic, anti-inflammatory, anti-RSV and antioxidant activities.

Two new pregnane glycosides from the root of Cynanchum auriculatum.

Two new pregnane glycosides (1 and 2), together with four known ones (3- 6), were isolated from the roots of Cynanchum auriculatum Royle ex Wight (Asclepiadaceae). On the basis of detailed spectroscopic analysis and chemical method, the structures of new compounds were characterized to be metaplexigenin 3-O-ß-D-cymaropyranosyl- (1→4)-α-L-diginopyranosyl-(1→4)-ß-D-cymaropyranoside (1), metaplexigenin 3-O-α-L-diginopyranosyl-(1→4)-ß-D-cymaropyranoside (2). All the isolated compounds (1-6) were tested for their in vitro inhibitory activity against the growth of human colon cancer cell lines HCT-116. Compounds 5 and 6 showed significant cytoxicities with IC50 values of 43.58 µM and 52.21 µM.

Two new aryltetralin-type lignans from Camellia oleifera husk.

Two new aryltetralin-type lignans (1-2) were isolated from the dichloromethane fraction of 95% ethanol extract of Camellia oleifera fruit husk. Their structures were elucidated on the basis of spectroscopic analysis, and the absolute configurations of compounds 1-2 were determined by the comparison of measured ECD curves with the quantum chemical calculated ones. The new compounds were tested for their antioxidant activities and cytotoxicity against three human cancer cell lines (Huh-7, H460 and MCF-7). While compounds 1 and 2 only showed slight DPPH radical scavenging activities with the IC50 values of 38.68 ± 5.02 and 56.62 ± 1.49 µM, respectively.

Two new chemical constituents from the stem and branch of Tripterygium wilfordii.

A chemical investigation of 95% ethanol extract from the stem and branch of Tripterygium wilfordii has resulted in the isolation and characterization of two new compounds, one neolignan (1) and one phenylalanine derivative (2), as well as four known compounds (3-6). The structures of the new compounds were determined based on extensive spectroscopic analyses. The absolute configuration of compound 1 was defined by X-ray crystallographic analyses and electronic circular dichroism calculation. In addition, compounds 2 and 4-6 exhibited inhibitory effects against NO production in LPS-induced RAW 264.7 macrophages with the IC50 value ranging from 3.51 µM to 30.40 µM.

Bixasteroid, a new compound from the fruits of Bixa orellana and its anti-inflammatory activity.

Bixasteroid (1), one new steroid together with five known compounds (2-6), were isolated from the ethyl acetate fraction of ethanol extract of Bixa orellana fruits. All of these known compounds were isolated from the plant for the first time. Their structures were elucidated on the basis of spectroscopic analysis, and the absolute configuration of compound 1 was determined by X-ray crystallographic data analysis as well as by the quantum chemical ECD calculations. All the isolated compounds were tested for their anti-inflammatory activities. Compounds 1 and 2 showed inhibiting NO release activities in LPS-induced RAW 264.7 macrophages with the IC50 values of 4.72 ± 0.28 and 5.48 ± 1.48 µM, respectively.

Undescribed abietane-type diterpenoids and oleanane-type triterpenoids from the stem and branch of Tripterygium wilfordii.

Six undescribed abietane-type diterpenoids (tripterydinoids A-F) and five undescribed oleanane-type triterpenoids (tripterytrinoids A-E) were obtained and determined from the stem and branch of Tripterygium wilfordii Hook. f. (Celastraceae). Tripterydinoids A-C possessed the abietane-type diterpenoid skeleton with rare 8, 9-epoxy ring. The structures of undescribed compounds were established by extensive spectroscopic studies [HRESIMS, 1D/2D-NMR and electronic circular dichroism (ECD) calculation]. The absolute configurations of tripterydinoids A, B, E and tripterytrinoid A were defined by X-ray crystallographic analyses. Bioactivity screening indicated that tripterydinoids A-C exhibited potent inhibitory effects against NO release in LPS-activated RAW 264.7 macrophages with IC50 values of 6.93, 4.46 and 2.98 µM, respectively. Meanwhile, tripterydinoids A-D and tripterytrinoids B, C showed moderate and selective cytotoxicities against five human tumor cell lines (A375, Huh7, MCF-7, HCT-116 and NCI-H460).

Diverse dihydroagarofuran sesquiterpene derivatives from the stem and branch of Tripterygium wilfordii.

Ten new dihydroagarofuran sesquiterpene polyol esters, tripterdines A-J (1-10) were isolated from the stem and branch of Tripterygium wilfordii. The structures of new compounds were elucidated on the basis of extensive spectroscopic analyses, including UV, IR, HRESIMS, NMR, and CD exciton chirality method. The structures of compounds 1, 3, and 6 were confirmed by X-ray crystallographic analyses. The anti-inflammatory and cytotoxic activities were assessed for all the compounds (1-10). Compounds 3, 5 and 10 exhibited potent anti-inflammatory activities with the secretion level of TNF-α ranging from 43.86% to 51.27%, and the IL-6 ranging from 32.44% to 50.64%. In addition, compounds 1, 3, 7 and 9 showed weak cytotoxicities against three human tumor cell lines (Huh7, MCF-7 and HCT-116).

New phenylpropanoids from the fruits of Xanthium sibiricum and their anti-inflammatory activity.

Seven new phenylpropanoids, including two pairs of enantiomers of 8-O-4'-type neolignans, named (±)-xanthiifructins A-B (1a/1b-2a/2b), a pair of simple phenylpropanoid derivatives (±)-xanthiifructins C (3a/3b), and a racemic phenylpropanoid derivative xanthiifructin D (4), together with four known analogues (5-8) were isolated from the fruits of Xanthium sibiricum. Racemic xanthiifructins A-C were separated on chiral HPLC columns. Their structures were elucidated by comprehensive spectroscopic data analysis and comparison with the literatures. The anti-inflammatory and cytotoxic activities were evaluated for all isolates. Among them, (-)-xanthiifructin C (3b) exhibited potent inhibitory effect against nitric oxide production in lipopolysaccharide-activated RAW 264.7 mouse macrophage cells with an IC50 value of 9.94 ± 0.57 µM. All compounds obviously were inactive for three human tumor cell lines (MCF-7, HepG2, and A549) with IC50 values much more than 10 µM.

One pair of new enantiomeric trinorsesquiterpenes from the aerial parts of Justicia gendarussa.

A pair of new enantiomeric trinorsesquiterpenes, (+)-genpenterpene A (1a) and (-)-genpenterpene A (1b), together with seven known compounds (2-8), were isolated from the aerial parts of Justicia gendarussa Burm.f.. All of these known compounds were isolated from this plant for the first time. Racemic genpenterpene A was separated by chiral HPLC column. Their chemical structures were elucidated based on extensive spectroscopic analysis, single crystal X-ray diffraction, and ECD calculations. (+)-genpenterpene A (1a) exhibited potent inhibitory effect against nitric oxide production in lipopolysaccharide-activated RAW 264.7 mouse macrophage cells with an IC50 value of 9.54 ± 1.02 µM.

Lyciyunin, a new dimer of feruloyltyramine and five bioactive tyramines from the root of Lycium yunnanense Kuang.

Lyciyunin, a new dimer of feruloyltyramine (1), together with five known tyramines (2-6), was isolated from the water-soluble fraction of an EtOH extract of the root of L. yunnanense. Based on HR-TOF-MS, NMR spectral data and quantum chemistry ECD calculations, the structure of this new compound was determined, including its absolute configuration. Compounds (1-6) were tested for their antioxidant activity using in vitro DPPH radical scavenging assay, and 1-6 showed the moderate antioxidant activities with IC50 values of 12.44 ± 0.39, 21.29 ± 0.75, 24.44 ± 1.63, 21.15 ± 0.66, 21.15 ± 0.66 and 45.15 ± 0.56 µM, respectively. Compounds (5-6) showed anti-inflammatory activity in LPS-induced RAW 264.7 macrophages with the IC50 values of 43.95 ± 6.11 and 33.50 ± 2.04 µM, respectively.

New compounds from the aerial parts of Justicia gendarussa Burm.f. and their antioxidant and anti-inflammatory activities.

Three new compounds (1-3), together with six known compounds (4-9), were isolated from the ethyl acetate fraction of ethanol extract of the aerial parts of Justicia gendarussa Burm.f. All of these known compounds were isolated from the plant for the first time. Their structures including absolute configurations were elucidated on the basis of HR-ESI-MS, NMR spectroscopic analyses, single crystal X-ray diffraction and comparison with the literatures. Compounds 1-9 were tested for their antioxidant and anti-inflammatory activities. Compounds 5 and 8 showed the antioxidant activities with IC50 values of 28.61 ± 1.56 and 22.55 ± 1.38 µM, respectively. Compounds 2 and 3 showed anti-inflammatory activity in LPS-induced RAW 264.7 macrophages with the IC50 values of 20.95 ± 1.11 and 16.50 ± 1.04 µM, respectively.

Barbaram, a bicyclic neolactam from the root and stem of Lycium barbarum.

Barbaram (1), a neolactam together with other five known compunds (2-6) was isolated from the EtOAc-soluble fraction of an EtOH extract of the root and stem of Lycium barbarum by using silica gel, Sephadex LH-20 column chromatography and semi-preparative RP-C18 HPLC. Based on HR-TOF-MS, NMR spectral data, quantum chemistry ECD calculations and referencing to the data reported earlier, the structures of these compounds (1-6) were determined, specially including the absolute configuration of the neolactam (1). Compounds 2 and 4 showed significant anti-inflammatory activity in LPS-induced RAW 264.7 macrophages with the IC50 values of 8.98 ± 0.57 µM, 6.68 ± 0.77 µM.

Lyciiterpenoids A-D, four new rearranged eudesmane sesquiterpenoids from Lycii Cortex.

Four new rearranged eudesmane sesquiterpenoids, Lyciiterpenoids A-D (1-4), together with four known compounds (5-8) were isolated from the aqueous extract of Lycii Cortex. Their structures were elucidated by spectroscopic analysis, and the absolute configurations of compounds 1-4 were determined by the quantum chemical ECD calculations. The absolute configuration of 1 was further confirmed by X-ray crystallographic data analysis. All the isolated compounds were evaluated for their cytotoxicity against three human cancer cell lines (MCF-7, HepG2, and A549). However, no significant activities were detected even with a concentration up to 100 µM.

[Chemical constituents from Xanthii Fructus].

This study was carried out to investigate the chemical constituents from Xanthii Fructus(the fruits of Xanthium sibiricum). The compounds were separated and purified by silica gel column chromatography, Sephadex LH-20 and ODS chromatography and semi-preparative HPLC. Base on HR-ESI-MS, NMR and other spectral data, their structures were identified. The anti-inflammatory activity of the isolated compounds was evaluated by lipopolysaccharide(LPS)-induced macrophage RAW264.7 as a screening model. A total of twenty-one compounds were isolated from the EtOAc fraction of 95% ethanol extract and identified as uracil(1), thymine(2), uridine(3), indole-3-carbaldehyde(4), indole-3-carboxylic acid(5), 2'-O-methyluridine(6), guanosine(7), 2,4(1H,3H)-quinazolinedione(8), 3-hydroxy-3-(2-hydroxyethyl)indolin-2-one(9), nicotinamide(10), N-acetyl-L-phenylalaninol(11), heliolactam(12), terresoxazine(13), caudatin(14), qingyangshengenin(15), caudatin-3-O-ß-D-oleandropyranosyl-(1→4)-ß-D-cymaropyranosyl-(1→4)-ß-D-cymaropyranoside(16), caudatin-3-O-ß-D-cymaropyranosyl-(1→4)-ß-D-oleandropyranosyl-(1→4)-ß-D-cymaropyranosyl-(1→4)-ß-D-cymaropyranoside(17), caudatin-3-O-α-L-cymaropyranosyl-(1→4)-ß-D-cymaropyranosyl-(1→4)-ß-D-cymaropyranosyl-(1→4)-α-L-cymaropyranosyl-(1→4)-ß-D-oleandropyranosyl-(1→4)-ß-D-cymaropyranoside(18), qinyangshengenin-3-O-ß-D-oleandropyranosyl-(1→4)-ß-D-oleandropyranosyl-(1→4)-ß-D-cymaropyranoside(19), qinyangshengenin-3-O-ß-D-oleandropyranosyl-(1→4)-ß-D-cymaropyranosyl-(1→4)-ß-D-digitoxopyranoside(20), rostratamine-3-O-ß-D-oleandropyranosyl-(1→4)-ß-D-cymaropyranosyl-(1→4)-ß-D-cymaropyranoside(21). Compounds 5-21 are obtained from genus Xanthium for the first time. Compounds 12 and 13 indirectly exhibited anti-inflammatory activity by suppressing LPS-induced NO production in RAW264.7 cells with IC_(50) values of(15.45±0.56) and(20.14±0.78) µmol·L~(-1), respectively.

Bioactive sulfur-containing compounds from Xanthium sibiricum, including a revision of the structure of xanthiazinone.

Seven previously undescribed sulfur-containing compounds, (+)- and (-)-xanthiazinone A, (+)- and (-)-xanthiazinone B, (+)- and (-)-xanthiazinone C and xanthiazinone D, and four known thiazinedione derivatives, together with three thiophene derivatives were isolated from the fruits of Xanthium sibiricum. Racemic xanthiazinones A-C were separated by chiral HPLC columns. Their chemical structures were elucidated based on extensive spectroscopic analyses, ECD calculations, and single crystal X-ray diffractions. The X-ray crystallographic analyses for xanthiazinones A-C represent the first example described for the structure elucidation of the thiazinedione with the five-membered lactone ring attached via an oxygen atom. Accordingly, the previously proposed structure for xanthiazinone was revised. The anti-inflammatory and cytotoxic activities were evaluated for all the isolated compounds. (+)-xanthiazinone B and 2-hydroxy-xanthiazone exhibited potent inhibitory effects against nitric oxide production in lipopolysaccharide-activated RAW 264.7 mouse macrophage cells with IC50 values of 8.75 and 10.90 µM, respectively. All compounds obviously were inactive for three human tumor cell lines (HepG2, MCF-7, and A549) with IC50 values more than 10 µM.

Anticandidal Potential of Stem Bark Extract from Schima superba and the Identification of Its Major Anticandidal Compound.

Plant-derived extracts are a promising source of new drugs. Schima superba is traditionally used in China for heat clearing, detoxification, and treatment of furuncles. In this study, the anticandidal properties and mechanism of action of S. superba (SSE) were explored using a stem bark extract. SSE possessed high polyphenol and saponin contents of 256.6 ± 5.1 and 357.8 ± 31.5 µg/mg, respectively. A clear inhibition zone was observed for C. albicans growth through the disc diffusion method and the 50% inhibition of C. albicans by SSE was 415.2 µg/mL. Transcriptomic analysis in C. albicans treated with different doses of SSE was conducted through RNA-seq. Average values of 6068 genes and 20,842,500 clean reads were identified from each sample. Among these samples, 1680 and 1956 genes were differentially expressed genes (DEGs) from the SSE treatments of 0.2 and 0.4 mg/mL, respectively. C. albicans growth was inhibited by the changes in gene expression associated with the cell wall and membrane composition including the regulation of chitin degradation and ergosterol biosynthesis. This result could be reflected in the irregularly wrinkled morphology of the ruptured cell as revealed through SEM analysis. ESI-MS and NMR analyses revealed that the major compound purified from SSE was sasanquasaponin III and the 50% inhibition of C. albicans was 93.1 µg/mL. In summary, the traditional Chinese medicine S. superba can be applied as an anticandidal agent in complementary and alternative medicine.

Sasanquasaponin ΙΙΙ from Schima crenata Korth induces autophagy through Akt/mTOR/p70S6K pathway and promotes apoptosis in human melanoma A375 cells.

BACKGROUND: Melanoma is a high fatality skin cancer which lacks effective drugs. Sasanquasaponin, an important sort of constituents in theaceae, has been demonstrated to have potent anti-tumor effect in breast cancer and hepatocellular carcinoma. As a sasanquasaponin, we speculate that Sasanquasaponin III (SQS III) isolated from Schima crenata Korth may also have anti-tumor activity. PURPOSE: This study aims to investigate whether SQS III has anti-melanoma activity and examine the underlying mechanisms of SQS III against melanoma. METHODS/STUDY DESIGNS: The anti-proliferative effect of SQS III was assessed by cells viability assay. Annexin V-FITC/PI double staining assay was utilized for detection of apoptosis. Mitochondrial membrane potential and reactive oxygen species (ROS) production were detected using JC-1 and DCFH-DA assay, respectively. Autophagy was monitored using transmission electron microscopy (TEM) and GFP-LC3 transfection fluorescence analysis. Autophagosome-lysosome fusion and lysosomal degradation were determined using a GFP-LC3 & LAMP1 co-localization assay and DQ-BSA staining. Proteins related to apoptosis and autophagy were analyzed by Western blotting. RESULTS: Our results demonstrated that the SQS III exhibited potent anti-cancer activity in A375 cells by inducing both apoptosis and autophagy. In melanoma cells treated with SQS III, caspases were activated and PARP was cleaved, proving the occurrence of apoptosis. Mechanistic studies indicated that the pro-apoptosis activity of SQS III was mediated by death receptor pathway and mitochondrial dysfunction which was induced by ROS accumulation and reversed by the ROS inhibitor N-acetyl-cysteine (NAC). In addition to triggering apoptosis, SQS III may also cause autophagy in melanoma cells. Our results demonstrated that SQS III induced up-regulated expression of GFP-LC3, autophagosome-lysosomal fusion and lysosomal degradation. Additionally, the ROS accumulation was also involved in the activation of autophagy. Meanwhile, it was also found that after SQS III treatment, the expression of LC3-II was up-regulated and the AKT/mTOR signaling pathway was inhibited. The autophagy inhibitor 3-MA converted cytotoxicity and apoptosis of SQS III in A375 cells, which indicated that autophagy promoted the SQS III-induced apoptosis. CONCLUSION: SQS III showed potent anti-cancer activity by inducing apoptosis and autophagy, which provides insights into its possible use as a therapy for melanoma.

Dihydrosanguinarine suppresses pancreatic cancer cells via regulation of mut-p53/WT-p53 and the Ras/Raf/Mek/Erk pathway.

BACKGROUND: There have been some reports implicating the pharmacologic action of Dihydrosanguinarine (DHSA), but little research including the effects of it on cancer cells. PANC-1 cells have mutations in K-Ras and TP53, which respectively express mutant K-Ras and p53 protein, and the mutations in Ras/p53 have been believed with closely relationship to the occurrence of various tumors. PURPOSE: To reveal the inhibition of Dihydrosanguinarine on pancreatic cancer cells (PANC-1 and SW1990) proliferation by inducing G0/G1 and G2/M phase arrest via the downregulation of mut-p53 protein, inducing apoptosis and inhibiting invasiveness through the Ras/Mek/Erk signaling pathway. METHODS: Human pancreatic cancer cell lines were cultured with cisplatin and DHSA. Then, cell proliferation, the cell cycle and apoptosis were measured by CCK-8 and flow cytometry. The migratory and invasive abilities of pancreatic cancer cells were evaluated by transwell assay. The expression levels of mRNA and protein were measured by RT-PCR and western blotting. RESULTS: The results showed that DHSA treatment inhibited cell proliferation, migration and invasion in a time- and dose-dependent manner and led to induction of cell cycle arrest and apoptosis. G0/G1 and G2/M phase arrest inhibited the viability of PANC-1 cells by downregulating the expression of mut-p53 protein. Decreased levels of C-Raf and Erk phosphorylation in DHSA-treated PANC-1 and SW1990 cells were observed in a time- and dose-dependent manner. However, the total expression of p53 and Ras proteins had a different change in PANC-1 and SW1990 cells. CONCLUSIONS: Our findings offer the novel perspective that DHSA inhibits pancreatic cancer cells through a bidirectional regulation between mut-p53/-Ras and WT-p53/-Ras to restore the dynamic balance by Ras and p53 proteins.

Three new lignanamides from the root of Lycium chinense with anti-inflammatory activity.

Three new lignanamides, that is, a new lignanamide (1), and a pair of enantiomers (2a and 2b) were isolated from the EtOAc-soluble fraction of an EtOH extract of the root of Lycium chinense. The structures of these new compounds, including their absolute configuration, were established on the basis of HR-ESI-MS, NMR spectroscopic data and quantum chemical ECD calculations. Compound 2a showed significant anti-inflammatory activity in LPS-induced RAW 264.7 macrophages with the IC50 value of 10.77 ± 2.14 µM, comparing to that of positive control quercetin (17.21 ± 0.50 µM).