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Objective: To evaluate the effects of ethanol extract from Ardisia gigantifolia leaves on cell proliferation and cancer stem cell (CSC) number in gastric cancer. Methods: The inhibitory effect of Ardisia gigantifolia extract on the proliferation of MKN45 and MKN74 gastric cancer cells was assessed using 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay. Non-adherent culture (3D) model was used to evaluate the effect of the extract on tumorsphere size and number. Moreover, the expression of CD44, ALDH, and p21 was determined by immunofluorescence analysis. Flow cytometric analysis was performed to evaluate cell cycle arrest and the expression of gastric CSC markers CD44 and ALDH. Real-time PCR analysis was also carried out to assess the effect of the extract on the expression of cell cycle-regulated genes. Results: Ardisia gigantifolia extract effectively inhibited cell proliferation with an IC50 of 55.7 µg/mL in MKN45 cells and 123.6 µg/mL in MKN74 cells. The extract also arrested cell cycle in the G0/G1 phase as well as significantly reduced the size and number of tumorspheres. The markedly increased expression of p21 was observed at both mRNA and protein levels in the extract-treated adherent cells and tumorspheres. In addition, Ardisia gigantifolia extract significantly reduced the number of CD44- and/or ALDH-expressing gastric CSC. Conclusions: The development of gastric CSC can be inhibited by the ethanol extract of Ardisia gigantifolia.

Using extracts from herbs for silver nanoparticle synthesis is attracting attention for its anticancer activity. Ardisia gigantifolia is a herb used in traditional Chinese medicine for treating stomach ailments, and some compounds isolated from this plant exhibit the inhibitory activity against different cancer cells. However, the synthesis of silver nanoparticle using extract of Ardisia gigantiflia leaves and their anti-cancer activity was not reported. In this report, the green synthesized silver nanoparticles using Ardisia gigantiflia extract (Arg-AgNPs) has average diameter of 6 nm with functional groups including O–H, C–H, and C O founded on the surface of these nanoparticles. The viability assays results revealed Arg-AgNPs reduced gastric cancer cell proliferation in a dose-dependent manner, with IC 50 values of 1.37 and 0.65 μg/mL for AGS cells and 1.03 and 0.96 μg/mL for MKN45 cells. Arg-AgNPs caused cell cycle arrest at the G0/G1 phase and suppressed cell migration. Additionally, Arg-AgNPs significantly increased the percentage of senescent cells and promoted overproduction of reactive oxygen species (ROS) compared to the control. Thus, this study indicates that Arg-AgNPs can be considered as a promising candidate against human gastric cancer cells. • Arg-AgNPs were characterized by UV-Vis, XRD, TEM and FTIR. • Arg-AgNPs reduce cell viability and cause cell cycle arrest at G0/G1 phase in gastric cancer. • Arg-AgNPs reduce cell migration ability and induce cellular senescence in gastric cancer. • Arg-AgNPs promote overproduction of ROS in gastric cancer. [ABSTRACT FROM AUTHOR]

Ardisia gigantifolia is a medicinal plant; its herbal medicinal product has played important roles in the ways of life of people in China. However, commercial products of this herbal medicine are frequently adulterated with Rhododendron molle root and Clerodendrum cyrtophyllum stem. In fact, R. molle has hepatotoxic effects which could pose health issues to the end user. In this study, we applied DNA barcoding coupled with high resolution melting (Bar-HRM) to distinguish A. gigantifolia and adulterant products. Two DNA barcode loci (ITS2 and psbA-trnH) were chosen for Bar-HRM analysis. We found that ITS2 and psbA-trnH regions contain some inter-species variability, which showed enough discrimination capability for Bar-HRM analysis. We applied the Bar-HRM method to test the method, and found that some products labelled as “A. gigantifolia” collected from local markets in China were identified to contain C. cyrtophyllum. Our study demonstrated that DNA barcoding coupled with high resolution melting can be used as a routine test to guarantee the quality of A. gigantifolia herbal products.

Ardisia gigantifolia is a medicinal plant; its herbal medicinal product has played important roles in the ways of life of people in China. However, commercial products of this herbal medicine are frequently adulterated with Rhododendron molle root and Clerodendrum cyrtophyllum stem. In fact, R. molle has hepatotoxic effects which could pose health issues to the end user. In this study, we applied DNA barcoding coupled with high resolution melting (Bar-HRM) to distinguish A. gigantifolia and adulterant products. Two DNA barcode loci (ITS2 and psbA-trnH) were chosen for Bar-HRM analysis. We found that ITS2 and psbA-trnH regions contain some inter-species variability, which showed enough discrimination capability for Bar-HRM analysis. We applied the Bar-HRM method to test the method, and found that some products labelled as "A. gigantifolia" collected from local markets in China were identified to contain C. cyrtophyllum. Our study demonstrated that DNA barcoding coupled with high resolution melting can be used as a routine test to guarantee the quality of A. gigantifolia herbal products. [ABSTRACT FROM AUTHOR]

AG36 is a triterpenoid saponin from Ardisia gigantifolia stapf. Our recent studies proved that AG36 displayed prominent cytotoxicity against breast cancer cells both in vitro and in vivo. However, whether AG36 has antiangiogenic properties is unknown. Therefore, in the present study, we evaluated the antiangiogenic effect of AG36 and the underlying mechanism. The results indicated that AG36 could significantly inhibit the proliferation, migration and invasion of human umbilical vein endothelial cells (HUVEC). Further antiangiogenic molecular mechanism investigation showed that AG36 significantly suppressed phosphorylated FAK and AKT, and downregulated the expressions of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR2) in HUVECs. PI3K inhibitor (LY294002) and FAK inhibitor (PF562271) pretreatment could markedly enhance AG36-induced inhibition of HUVEC proliferation and p-FAK suppression, respectively. In addition, AG36 inhibited the tumor growth in xenograft model and expressions of p–VEGFR2 and p–Akt in vivo. Molecular docking simulation indicated that AG36 formed hydrogen bonds and hydrophobic interactions within the ATP binding pocket of VEGFR2 kinase domain. The present study firstly revealed the high antiangiogenic potency and related underlying molecular of AG36, demonstrating that AG36 maybe a potential antiangiogenic cancer therapy agent or lead candidate. [ABSTRACT FROM AUTHOR]

Ardisia gigantifolia is a medicinal plant that belongs to genus Ardisia. This plant has been an important traditional Chinese medicine in China for thousands of years. Now, with the development of pharmacological research, A. gigantifolia is not only used as a clinical medicine, but also plays a role in diet and health aspects. The pharmacological validity of its medicinal value has extended in an enlarged market. At present, the wild A. gigantifolia in our country is rare, and the cultivars become the new important source. However, the quality and efficacy of cultivars often suffer from intraspecific variation, unstable quality and other issues. Moreover, the cultivars were also affected by origin, age and environmental conditions. In order to efficiently utilize and conserve this medicinal plant resource, ISSR analysis was employed to reveal genetic diversity of 36 A. gigantifolia germplasm which were collected from different places of Guangxi Zhuang Autonomous Region in China. Data were analyzed by POPGENE32, and a cluster diagram was presented by UPGMA. The results indicated that fourteen ISSR primers generated a total of 136 bands among which 112 (82.35%) were polymorphic bands. Nei's genetic diversity index (H) was 0.296 5, Shannon diversity index (I) was 0.441 7, and the coefficient of gene differentiation (Gst) was 0.855 8. The genetic similarity coefficient among the populations ranged from 0.667 8 to 0.838 2 in an average of 0.739 1. Based on the clustering analysis, all accessions were clustered into five groups with UPGMA method. Most of the accessions from the same or adjacent regions were clustered into the same group or subgroups. A few accessions, however, were greatly different from the majority of all accessions. The results suggested that ISSR marker was an effective tool for the study of genetic variation in Chinese natural A. gigantifolia germplasm resources. These results can also be used for germplasm characterization and plant breeding. [ABSTRACT FROM AUTHOR]

Tuberculosis ( TB) is a highly contagious disease mainly caused by Mycobacterium tuberculosis H37 RV. Antitubercular (anti- TB) bioassay-guided isolation of the CHCl3 extract of the leaves and stems of the medicinal plant Ardisia gigantifolia led to the isolation of two anti- TB 5-alkylresorcinols, 5-(8 Z-heptadecenyl) resorcinol ( 1) and 5-(8 Z-pentadecenyl) resorcinol ( 2). We further synthesized 15 derivatives based on these two natural products. These compounds (natural and synthetic) were evaluated for their anti- TB activity against Mycobacterium tuberculosis H37 RV. Resorcinols 1 and 2 exhibited anti- TB activity with MIC values at 34.4 and 79.2 μ m in MABA assay, respectively, and 91.7 and 168.3 μ m in LORA assay, respectively. Among these derivatives, compound 8 was found to show improved anti- TB activity than its synthetic precursor ( 2) with MIC values at 42.0 μ m in MABA assay and 100.2 μ m in LORA assay. The active compounds should be regarded as new hits for further study as a novel class of anti- TB agents. The distinct structure-activity correlations of the parent compound were elucidated based on these derivatives. [ABSTRACT FROM AUTHOR]

Compound 1, a triterpenoid saponin from Ardisia gigantifolia Stapf. showing potential anti-tumor activity, was transformed into three derivatives (2–4) by Aspergillus avenaceus 3.4454. Among them, compounds 2 and 3 are new compounds. Their structures were elucidated on the basis of 1D NMR, 2D NMR, HR-ESI-MS, and optical rotation data. Compounds 1–3 were evaluated for their cytotoxicity against human hepatocellular carcinoma and normal liver cells by cell counting kit 8 colorimetric assay. Compound 3 displayed better cytotoxicity against Bel-7402 and HepG2 cell lines and much weaker cytotoxicity against normal liver L02 cell than that of positive control (epirubicin hydrochloride). [ABSTRACT FROM AUTHOR]

Abstract: Thirteen 13,28-epoxy triterpenoid saponins were isolated from Ardisia gigantifolia stapf. and one potential anti-tumor saponin was methanolysised by H2SO4 to afford four new compounds. The seventeen compounds were evaluated for their anti-proliferative activity on A549, HCT-8 and Bel-7402 cells. The structure–activity relationship analysis indicated that the incorporation of O group at C-16, l-rhamnose at R5 and acetyl group at OH-6 of the d-glucose lead to a significant increase of the cytotoxic activity on A549 and HCT-8 but significant reduction of the cytotoxic activity on Bel-7402 cells. The synthesized saponins losing 13,28-epoxy and CHO at C-30, losed their cytotoxicities on A549 and HCT-8 cells, suggesting that the two moieties play an essential role for activity. 3β-O-α-l-rhamnopyranosyl-(1→3)-[β-d-xylopyranosyl-(1→2)]-β-d-glucopyranosyl-(1→4)-[β-d-glucopyranosyl-(1→2)]-α-l-arabinopyranoside-16α-hydroxy-13,28-epoxy-oleanane (2) showed better inhibitory activity to Bel-7402 (IC50 0.86μM) than that of 5-FU (IC50 8.30μM), which indicate that five saccharide and methyl moiety at C-30 are important for anti-proliferative activity. The activities of saponins 15 > 14, 17 > 16, suggested that the configuration of 28,30-epoxy is preferable to be 30(R) rather than 30(S) on Bel-7402 cells. Further molecular mechanism studies of saponins 1 and 2 were carried out on the cell cycle distribution of Bel-7402 cells. [Copyright &y& Elsevier]

One new bergenin derivative, named 11-O-veratroylbergenin (1) along with five known bergenin derivatives, 11-O-(3′-O-methylgalloyl) bergenin (2), 11-O-syringylbergenin (3), 11-O-Galloylbergenin (4), 4-O-Galloylbergenin (5) and bergenin (6) were isolated from Ardisia gigantifolia Stapf. Their structures were established on the basis of spectroscopic analysis, especially by means of 1D, 2D-NMR and HR–ESIMS analyses. Compounds 2, 4 and 5 showed significant 2,2-diphenyl-1-picrylhydrazyl (DPPH) free-radical scavenging activity with EC50 9.7, 9.0 and 7.8 µmol L−1, respectively. They showed more antioxidant activity than the positive control vitamin C (EC50 = 28.3 µmol L−1). [ABSTRACT FROM AUTHOR]

A new triterpenoid saponin, named 3-O-β-d-glucopyranosyl-(1 → 3)-β-d-xylopyranosyl-(1 → 2)-[α-l-rhamnopyranosyl-(1 → 3)]-β-d-glucopyranosyl-(1 → 4)-[β-d-glucopyranosyl-(1 → 2)]-α-l-arabinopyranosyl-3β,16α,28,30-tetrahydroxy-olean-12-ene (1), along with four known triterpenoids (2–5), was isolated from the rhizomes ofArdisia gigantifolia. Their structures were elucidated by spectroscopic methods. Compounds1–4showed cytotoxic activity against Hela, EJ, BCG, and HepG-2 cell lines. The percentage of early apoptotic cells after treatment with1was significantly increased compared with control cells (p < 0.05). [ABSTRACT FROM PUBLISHER]

Abstract: Naturally occurring dimeric 1,4-benzoquinone derivatives, belamcandaquinones F, G, H, and I, as well as one resorcinol derivative and four known compounds, were isolated from rhizomes of Ardisia gigantifolia. Their structures were established by means of spectroscopic analyses. All compounds were tested against cell lines PC-3, EMT6, A549, Hela, RM-1, and SGC7901 for cytotoxicity in vitro. In comparison with cisplatin, compounds 5 and 6 showed a strong cytotoxicity with IC50 values less than 30μM for most cell lines tested. [Copyright &y& Elsevier]