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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 CO 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 IC50 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.

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BACKGROUND: Ardisia gigantifolia Stapf. (AGS), a Chinese folk medicine widely grows in the south of China and several studies reported that AGS could inhibit the proliferation of breast cancer, liver cancer, and bladder cancer cell lines. However, little is known about its anti-colorectal cancer (CRC) efficiency. METHODS: In the present study, a combination of MTT assay, network pharmacological analysis, bioinformatics, molecular docking, and molecular dynamics simulation study was used to investigate the active ingredients, and targets of AGS against CRC, as well as the potential mechanism. RESULTS: MTT assay showed that three kinds of fractions from AGS, including the n-butanol extract (NBAGS), ethyl acetate fraction (EAAGS), and petroleum ether fraction (PEAGS) significantly inhibited the proliferation of CRC cells, with the IC50 values of 197.24, 264.85, 15.45 µg/mL on HCT116 cells, and 523.6, 323.59, 150.31 µg/mL on SW620 cells, respectively. Eleven active ingredients, including, 11-O-galloylbergenin, 11-O-protocatechuoylbergenin, 11-O-syringylbergenin, ardisiacrispin B, bergenin, epicatechin-3-gallate, gallic acid, quercetin, stigmasterol, stigmasterol-3-o-ß-D-glucopyranoside were identified. A total of 173 targets related to the bioactive components and 21,572 targets related to CRC were picked out through database searching. Based on the crossover targets of AGS and CRC, a protein-protein interaction network was built up by the String database, from which it was concluded that the core targets would be SRC, MAPK1, ESR1, HSP90AA1, MAPK8. Besides, GO analysis showed that the numbers of biological process, cellular component, and molecular function of AGS against CRC were 1079, 44, and 132, respectively, and KEGG pathway enrichment indicated that 96 signaling pathways in all would probably be involved in AGS against CRC, among which MAPK signaling pathway, lipid, and atherosclerosis, proteoglycans in cancer, prostate cancer, adherens junction would probably be the major pathways. The docking study verified that AGS had multiple ingredients and multiple targets against CRC. Molecular dynamics (MD) simulation analysis showed that the binding would be stable via forming hydrogen bonds. CONCLUSION: Our study showed that AGS had good anti-CRC potency with the characteristics of multi-ingredients, -targets, and -signaling pathways.

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ETHNOPHARMACOLOGICAL RELEVANCE: Ardisia gigantifolia Stapf, known as Zou-ma-tai (in Chinese), is a traditional folk medicine, which was commonly used by Dong, Jing, Li, Maonan, Miao, Mulam, Yao, and Zhuang people. The main use of A. gigantifolia is the treatment of rheumatoid arthritis, gouty arthritis, fractures, osteoproliferation, traumatic injuries, gynecological, and neurological diseases. Current studies have shown that the plant has various bioactive components, especially gigantifolinol, which has anti-tumor, anti-inflammatory, anti-tuberculosis, and neuroprotective activities. However, to date, few reviews have been made to summarize A. gigantifolia's related studies. AIMS OF THE REVIEW: This review aimed to summarize the traditional use, phytochemistry, pharmacology, clinical applications, and toxicity of A. gigantifolia, which expect to provide theoretical support for future utilization and highlight the further investigation of this vital plant. MATERIALS AND METHODS: The information related to A. gigantifolia were collated by surveying the traditional medicine books, ethnomedicinal publications, and searching academic resource databases including Web of Science, SciFinder, Springer Link, Pub Med, Science Direct, CNKI, and CQVIP database. RESULTS: A. gigantifolia has been used as a traditional folk medicine for more than 400 years in China. Different parts of the plant, including the aerial part, root, rhizome, and leaf, are mainly used as herbal medicine to treat rheumatoid arthritis, traumatic injuries, gynecological, etc. Currently, 165 compounds have been identified from the plant, including triterpenes, phenolics, coumarins, quinones, volatile oil, and sterols, 137 of which were identified from the rhizome parts. Pharmacological research showed that A. gigantifolia has various bioactivities, such as anti-tumor, anti-inflammatory, anti-oxidant, anti-thrombus, anti-tuberculosis, cough expectorant, and neuroprotective activities. Clinical studies have shown that the plant has no toxic side effects. In vivo administration at the maximum dose was not lethal, indicating the plant's safety. CONCLUSION: To date, most bioactive compounds are identified from the rhizomes of A. gigantifolia, which pharmacological activity and clinical observational studies have validated the plant's traditional use as a treatment for rheumatoid arthritis. It would be helpful to verify the mechanism of some components in vivo, such as gigantifolinol. Moreover, the plant's triterpenoid saponins demonstrated valid anti-tumor effects, especially the AG4 and AG36 compounds, which were shown to have anti-breast cancer effects both in vitro and in vivo. Further research on these components, including molecular mechanisms and in vivo metabolic regulation, needs to be confirmed.

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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.

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Objective: To study the chemical constituents of transformed products by Sphingomonas yabuuchiae GTC 868T (AB071955) and Pectinex Ultra AFP from the saponin of Ardisia gigantifolia. Methods: Transformation products separated by the process of silica gel column, compounds were identified and elucidated by spectral and chemical methods. Their cytotoxicity activities were tested by Cell Counting Kit 8 colorimetric assay. Results: Five triterpenoid saponins were obtained, including 3β-O-{α-L-rhamnopyranosyl-(1→3)-[β-D-xylopyranosyl-(1→2)]-β-D-glucopyranosyl-(1→4)-α-L-arabinopyranosyl}-cyclamiretin A (1), 3β-O-{β-D-glucopyranosyl-(1→4)-[β-D-glucopyranosyl-(1→2)]-α-L-arabinopyranoside}-cyclamiretin A (2), 3β-O-{β-D-glucopyranosyl-(1→2)-α-L-arabinopyranoside}-cyclamiretin A (3), 3-O-α-L-arabinopyranosyl cyclamiretin A (4), and cyclamiretin A (5). Conclusion: Compounds 2-5 are obtained by biotransformation for the first time. Some of the compounds showed certain antitumor activity, among them, compound 2 shows more cytotoxicity activity than Ag3 and positive control.

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Objective: To clarify the species composition, structural characteristics, age-class structure, and floristic diversity of the community where a precious medicinal plant Ardisia gigantifolia inhabited, and to provide a scientific basis for species conservation and large-scale-breeding management. Methods: Eleven plots of 10 m × 10 m were set up. Complete enumeration survey method was employed to study the species composition, diameter at breast height, tree height, and crown width. Data were analyzed using species diversity index. Results: There were 213 species of vascular plant belonging to 153 genera and 78 families in the 1 100 m2 plot; The flora were dominated by tropical-subtropical elements; Dominant tree species were Schima superba, Alniphyllum fortune, Liquidambar formosana, and Pinus massoniana, while dominant shrub species were A. gigantifolia, Itea chinensis, and Mussaenda pubescens; A. gigantifolia occurred in both shrub layer and herbal layer, possessing abundant age-class I seedlings, however scanty age-class IV Shannon-individuals show pyramid-type age-class structure of the population; The species richness of the community was 30.04, the Wienner index was 3.79, the Simpson index was 0.88, and the evenness Pielou index was 0.71; The species richness index of the community ranged as herb layer > shrub layer > tree layer > liana layer, while the Simpson index varied as liana layer > shrub layer > tree layer > herb layer, and the Shannon-Wienner index ranged as liana layer > shrub layer > tree layer > herb layer, when the evenness index turned out as liana layer > shrub layer > tree layer > herb layer. It indicated that the herb layer has the highest species richness but the most uneven distribution, and the predominant species stand out prominently. Conclusion: A. gigantifolia show gathering distribution in the lower layer of the community, and grown well as dominant species in shrub and herbal layer. The shade enduring species needs scattered light, prefers warm and humid environment with acid and porous soils.

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AG36 is the biotransformation product of triterpenoid saponin from Ardisia gigantifolia stapf. In this study, the antitumor activity and underlying molecular mechanisms of AG36 against human breast MCF-7, MDA-MB-231, and SK-BR-3 cancer cells were investigated. AG36 inhibited the viability of MCF-7, MDA-MB-231, and SK-BR-3 cells in a dose and time-dependent manner, with an IC50 of approximately 0.73, 18.1, and 23.4 µM at 48 h, respectively. AG36 obviously induced apoptosis and G2/M arrest of all the three breast cancer cells. Moreover, AG36 decreased the protein expression of cycle regulatory proteins cyclin B1 or cyclin D1. In MCF-7 and MDA-MB-231 cells, AG36 strongly increased the cleaved caspase-3 and -8 protein expressions, while in SK-BR-3 cells, AG36 only increased the protein expression of cleaved caspase-3. In all the three breast cancer cells, the ratio of Bax/Bcl-2 and cytosolic cytochrome c content increased significantly compared with control group. The death receptor-related proteins Fas/FasL, TNFR1, and DR5 were detected by Western blot, it showed that different breast cancer cells activated the death receptor-mediated extrinsic caspase-8 pathway through different receptors. In addition, the caspase-8 inhibitor z-IETD-fmk could significantly block AG36-triggered MCF-7 cells apoptosis. The in vivo studies showed that AG36 significantly inhibited the growth of MCF-7 xenograft tumors in BALB/c nude mice comparing with control. In conclusion, AG36 inhibited MCF-7, MDA-MB-231, and SK-BR-3 cells proliferation by the intrinsic mitochondrial and the extrinsic death receptor pathways and AG36 might be a potential breast cancer therapeutic agent.

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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-(8Z-heptadecenyl) resorcinol (1) and 5-(8Z-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 µm in MABA assay, respectively, and 91.7 and 168.3 µm 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 µm in MABA assay and 100.2 µm 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.

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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).

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Compound 1, a triterpenoid saponin from Ardisia gigantifolia Stapf showing potential anti-tumour activity, was hydrolysed into two deglycosyl derivatives (2 and 3) by Alternaria alternata AS 3.6872. Both these derivatives are new compounds. Their structures were elucidated on the basis of 1D, 2D NMR, HR-ESI-MS and optical rotation spectral data. Compounds 1-3 were evaluated for their cytotoxicity against human hepatocellular carcinoma and normal liver cells by Cell Counting Kit 8 colorimetric assay.

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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 R(5) 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. 3ß-O-α-L-rhamnopyranosyl-(1→3)-[ß-D-xylopyranosyl-(1→2)]-ß-D-glucopyranosyl-(1→4)-[ß-D-glucopyranosyl-(1→2)]-α-l-arabinopyranoside-16α-hydroxy-13,28-epoxy-oleanane (2) showed better inhibitory activity to Bel-7402 (IC50 0.86 µM) than that of 5-FU (IC50 8.30 µM), 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.

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