Zhen Liu

Inhibition of pulmonary adenoma in diethylnitrosamine-induced rats by Rhizoma paridis saponins

Nowadays, people pay more and more attention to the natural products based on their multiple targets in the antitumor treatment. In our previous research, Rhizoma paridis saponins (RPS) were regarded as potent anticancer agent that elicits programmed cell death and inhibits metastases in murine lung adenocarcinoma in vivo. In the present study, we set up a rat model of diethylnitrosamine (DEN) induced pulmonary adenoma to evaluate the antitumor effects of RPS again. After 20 weeks treatment, rats were sacrificed in order to perform histopathological examinations, blood biochemistry, immunohistochemistry, western blot, PCR and metabonomics. As a result, DEN induced pulmonary adenoma generation in the lungs and damaged hepatocytes and hepatoma formation in the livers. RPS effectively attenuated hepatotoxic and inhibited pulmonary adenoma through down-regulating expression of MMP-9 and up-regulating level of TIMP-2 in DEN-induced rats. Meanwhile, RPS remarkably decreased energy metabolism, and glycine, serine and threonine metabolism to block the tumor growth. In conclusion, RPS would be a potent anticancer agent used in the prospective application.

Chemosensitizing effect of Paris Saponin I on Camptothecin and 10-hydroxycamptothecin in lung cancer cells via p38 MAPK, ERK, and Akt signaling pathways.

Paris Saponin I (PSI), a steroidal sponins isolated from plant, has been exhibited antitumor and many other biological activities. In this study, we investigated the role and underlying mechanisms of PSI in the synergistic regulation of antitumor activity of Camptothecin (CPT) and 10-hydroxycamptothecin (HCPT) in four types of lung cancer cells. The inhibitory evaluation showed that PSI could significantly reduce the CPT/HCPT-mediated cell proliferation and enhance the sensitivities of H1299, H460 and H446 lung cancer cells to CPT/HCPT. Mechanism study indicated that PSI improved the CPT/HCPT induced apoptosis in lung cancer cells through mitochondria pathway including cytochrome C release and activation of caspase-9 and -3 cascades. Furthermore, PSI plus CPT/HCPT also increased the up-regulation of Bax and down-regulation of Bcl-2 and Bcl-XL in H460 and H446xa0cells. Moreover, PSI enhanced CPT/HCPT-mediated inhibition of p38 MAPK and activation of phosphorylation of p38 MAPK in H1299xa0cells, and suppression of Akt and ERK pathways activation in H460xa0cells as well as in H446xa0cells. Collectively, our results demonstrated that PSI functions as a chemosensitizer by enhancing apoptosis through influencing p38 MAPK, ERK, and Akt pathways in lung cancer cells, and the combination with CPT/HCPT might be a promising strategy for the development of new therapeutic agents.

Analysis of bioactive components and pharmacokinetic study of herb-herb interactions in the traditional Chinese patent medicine Tongmai Yangxin Pill.

Tongmai Yangxin (TMYX) Pill is a traditional Chinese patent medicine, composed of eleven Chinese medicinal herbs. It has been used to treat coronary heart disease for several decades. In this study, six male Sprague-Dawley rats were dosed orally with TMYX methanol extract, and a serum pharmacochemistry technique was used to screen absorbed bioactive compounds by UPLC/Q-TOF-MS. By comparing MS spectra to the published literature data, 40 bioactive components were identified. The results indicated that almost 45% of the absorbed compounds were from Radix Glycyrrhizae (GC). Subsequently, a reliable HPLC method was used to determine the concentrations of liquiritin, liquiritigenin, isoliquiritigenin, glycyrrhizic acid, and glycyrrhetinic acid in rat plasma following oral administration of GC or the combination of GC and Ramulus Cinnamomi (GZ). The results showed that GZ enhanced the absorption of four bioactive components: liquiritigenin, isoliquiritigenin, glycyrrhizic acid, and glycyrrhetinic acid. The data demonstrate that herb combination in TMYX Pill exhibit a synergistic action.

Curcumin-cyclodextrin complexes enhanced the anti-cancer effects of curcumin.

Curcumin (CUR), as a yellow pigment in the spice turmeric (Curcuma longa), possessed a pleiotropic application containing cancer therapy. Due to its poor oral bioavailability, the objective of this study was to investigate the use of curcumin-cyclodextrin complexes (CD15) as an approach to cancer chemoprevention. In this study, CUR encapsulation into the β-cyclodextrin (CD) cavity was achieved by the saturated aqueous solution method. CD15 was characterized by Fourier transform infrared (FTIR) and UV spectra analyses. An optimized CD15 was evaluated by cellular uptake and anti-cancer activity. As a result, CD15 enhanced curcumin delivery and improved its therapeutic efficacy compared with free curcumin in vivo and in vitro. Therefore, through regulation of MAPK/NF-κB pathway, CD15 up-regulated p53/p21 pathway, down-regulated CyclinE-CDK2 combination and increased Bax/caspase 3 expression to induce cellar apoptosis and G1-phase arrest. In conclusion, these results suggested that CD15 formulation should be used as a system for improving curcumin delivery and its therapeutic efficacy in lung cancer.

A synergistic antitumor effect of polyphyllin I and formosanin C on hepatocarcinoma cells

Polyphyllin I (PPI) and formosanin C (FC) were regarded as effective and imperative components isolated from Rhizoma Paridis saponins (RPS) and exhibited strong anti-tumor effects on a variety of cancers. With the wide application of complex mixtures in clinics, synergistic interactions are of vital importance in phytomedicine. Therefore, it is of inherent importance to study whether there is a synergistic anti-tumor effect on PPI and FC from one herb. In this study, the viability was detected by MTT assay. The combination index (CI) analysis was used to assess their synergistic effect. Consequently, there was a synergistic anti-tumor effect between PPI and FC at a ratio of 1:1. The CI value was less than 1.0. Their combination significantly increased their single G1 phase arrest and mitochondria-dependent apoptotic pathway. Meanwhile, PPI and FC reduced the ability of cell migration. In conclusion, polyphyllin I and formosanin C showed a synergistic anti-tumor effect on hepatocarcinoma cells. The findings would provide the foundation for the use of RPS in the future.

Inhibition of urethane-induced lung carcinogenesis in mice by a Rhizoma paridis saponin involved EGFR/PI3K/Akt pathway

Lung cancer is one of the most common cancers in the world. Due to a lack of successful treatments for lung cancer, there is a need to evaluate new and effective agents for lung cancer treatment. Rhizoma Paridis saponins (RPS) were deemed effective for the treatment of cancer disease. In the present study, we evaluated the role of RPS on urethane-induced lung carcinogenesis in C57BL/6 mice. As a result, the treatment with RPS reduced the severity of the histopathology on urethane-induced lung tumorigenesis in mice. The mechanisms of its antitumor effect involved in (i) reducing oxidative stress injury through up-regulation of Nrf2 and HO-1, (ii) decreasing the level of inflammatory factors, like COX-2 and PGE2, (iii) activation of caspase-3 through the down-regulation of anti-apoptotic protein (Bcl2) and up-regulation of pro-apoptotic protein (Bax), (iv) decreasing the expression of PCNA, and (v) inhibiting the epidermal growth factor receptor (EGFR)/PI3K/Akt pathway. In conclusion, RPS would be a potent agent inhibiting lung cancer in the future.

Paris Saponin II induced apoptosis via activation of autophagy in human lung cancer cells.

Paris Saponin II (PSII) has been shown anticancer activity against several cancer lines through the pro-apoptotic pathway. The aim of the study was to investigate the relationship between apoptosis and autophagy taking part in the anti-cancer mechanisms of PSII. In this study, PSII induced autophagy and apoptosis in dose- and time-dependent manners. Meanwhile, it induced autophagy as early as 2xa0h after exposure to 1xa0μM of PSII accompanying with apoptosis. Blockade of autophagy with chloroquine (CQ) attenuated apoptosis, while regulation of reactive oxygen species (ROS) by N-acetyl cysteine (NAC), gallic acid (GA) and H2O2 could not influence autophagy. In addition, PSII induced apoptosis via activation of autophagy, which might be associated with the activation of JNK and inhibition of PI3K/AKT/mTOR pathway. All in all, our research increased the understanding of the role of PSII regulating autophagy and apoptosis, which would hopefully provide prospective strategies for cancer therapy.

Turmeric enhancing anti-tumor effect of Rhizoma paridis saponins by influencing their metabolic profiling in tumors of H22 hepatocarcinoma mice

Rhizoma Paridis saponins combined with turmeric (RT) showed well anti-hepatocarcinoma activities in our previous research. The aim of this study was to investigate the progression of the biochemical response to RT and capture metabolic variations during intragastric administration of their compatibility. In the experiment, histopathological examination and (1)H NMR method were developed and validated for the metabolic profiling of RT intervention in H22 tumor growth. Data were analyzed with principal components analysis (PCA) and partial least-squares discrimination analysis (PLS-DA). As a result, Rhizoma paridis saponins (RPS) or RT induced inflammatory cell infiltration in tumors. RT also mediated the tumor microenvironment to promote anti-tumor immunity of mice. RT significantly inhibited tumor growth rate through suppressing levels of amino acids containing alanine, asparagine, glutamine, putrescine, and sarcosine, lipid compounds, and carbohydrates like myo-inositol and arabinose in the tumor tissues. In conclusion, these results uncovered unexpectedly poor nutritional conditions in the RT-treated tumor tissues whose effect was stronger than RPSs. Therefore, RT could be a novel anticancer agent that targets on cancer metabolism through starving tumors reducing viability of cancer cells.

Evaluation of the anti-cancer activity of the triterpenoidal saponin fraction isolated from the traditional Chinese medicine Conyza blinii H. Lév.

Conyza blinii H. Lev. is traditionally used in China as a medicinal plant to treat inflammation. We show here that the active fraction of this plant, Conyza blinii saponin (CBS), also has potent anti-cancer activity both in vitro and in vivo. Cell-based experiments showed that CBS suppresses the growth of cancer cells in a number of ways. CBS induces apoptosis in a dose-dependent manner. The mitochondrial membrane potential (ΔΨm) can be disrupted by CBS, which indicates activation of the mitochondrial apoptosis pathway. This was confirmed by an increase in the number of apoptotic bodies seen with scanning electron microscopy. CBS is capable of inhibiting cancer cell migration and invasion. Flow cytometry experiments demonstrated that CBS causes S phase arrest in cancer cells. These effects collectively led to an inhibitory activity against HeLa cells. In vivo animal experiments were carried and showed that 15 mg kg−1 CBS is a tolerable dose and reduced the tumour weight by 70% in a 10 day administration regimen.

Saponin fraction isolated from Conyza blinii H.Lév. demonstrates strong anti-cancer activity that is due to its NF-κB inhibition

CBS (Conyza blinii saponin) is the total triterpenoidal saponins of Conyza blinii H.Lév which is a type of traditional Chinese medicine (TCM). We have discovered that CBS has a profound cytostatic activity against a range of solid tumour cells in a time- and dose-dependent manner. We also confirm that the cytostatic activity of CBS originates from its apoptosis induction effect. Additionally, we use immunoblot to find out that the apoptosis induction effect of CBS is attributable to the activation of mitochondrial pathway. Mechanistic study demonstrates that CBS is an effective NF-κB inhibitor. It inhibits p65 nuclear translocation and NF-κB downstream gene expression, including XIAP, survivin, Bcl-xL, COX-2, cyclin D1, MMP-2, MMP-9 in HeLa cells. Tumour xenografted animal models verify the anti-cancer efficacy inxa0vivo. Tumour growth is significantly repressed in two CBS-treated groups compared with the controls (Pxa0<xa00.001). CBS treatment (i.g.) leads to a 48.5% and 57.0% reduction in terms of tumour weight for the 10 and 20xa0mg/kg dosed groups respectively. Also no apparent observable adverse effects can be seen. These results suggest that CBS obliterate tumour, at least in part due to its NF-κB inhibition, which creates potential for CBS to be developed as a practical cancer treatment.