Rhizoma Paridis Saponins Research Articles

Rhizoma Paridis saponins attenuate Gram-negative bacteria-induced inflammatory acne by binding to KEAP1 and modulating Nrf2 and MAPK pathways.

Acne vulgaris represents a chronic inflammatory condition, the pathogenesis of which is closely associated with the altered skin microbiome. Recent studies have implicated a profound role of Gram-negative bacteria in acne development, but there is a lack of antiacne agents targeting these bacteria. Polyphyllins are major components of Rhizoma Paridis with great anti-inflammatory potential. In this study, we aimed to evaluate the antiacne effects and the underlying mechanisms of PPH and a PPH-enriched Rhizoma Paridis extract (RPE) in treating the Gram-negative bacteria-induced acne. PPH and RPE treatments significantly suppressed the mRNA and protein expressions of interleukin (IL)-1β and IL-6 in lipopolysaccharide (LPS)-induced RAW 264.7 and HaCaT cells, along with the intracellular reactive oxygen species (ROS) generation. Furthermore, PPH and RPE inhibited the nuclear translocation of nuclear factor kappa-B (NF-κB) P65 in LPS-induced RAW 264.7 cells. Based on molecular docking, PPH could bind to kelch-like ECH-associated protein 1 (KEAP1) protein. PPH and RPE treatments could activate nuclear factor erythroid 2-related factor 2 (NRF2) and upregulate haem oxygenase-1 (HO-1). Moreover, RPE suppressed the mitogen-activated protein kinase (MAPK) pathway. Therefore, PPH-enriched RPE showed anti-inflammatory and antioxidative effects invitro, which is promising for alternative antiacne therapeutic.

A new insight into material basis of rhizoma Paridis saponins in alleviating pain

Ethnopharmacological relevanceParis polyphylla, as a traditional Chinese herbal medicine, was often used to relieve inflammation and pain. Rhizoma Paridis saponins (RPS) as the main active components of Paris polyphylla have excellent analgesic effects. Aim of the studyDetermine the analgesic material basis of RPS. Materials and methodsLC-MS/MS was used to analyze RPS, plasma after intravenous injection of RPS, and oral administration of RPS. H22 plantar pain model was established to explore the analgesic material basis of RPS. Moreover, correlation analysis, network pharmacology, RT-PCR and molecular docking were applied in this research. ResultsRPS had dose-dependently analgesic effects in acetic acid- and formalin-induced pain models. LC-MS/MS detection indicated that diosgenin as the metabolite of RPS mainly distributed in brain tissues. The addition of antibiotics increased the anti-tumor effect of RPS, but reduced its analgesic effect. Network pharmacology, RT-PCR and molecular docking showed that diosgenin exerted its analgesic effect through SRC and Rap1 signaling pathway. ConclusionDiosgenin exhibited analgesic effects, while saponins had good anti-tumor effects in RPS. This discovery provided a better indication for the later application of RPS in anti-tumor and analgesic settings.

Rhizoma paridis saponins protected against liver injury in diethylnitrosamine-induced mice

Rhizoma paridis saponins protected against liver injury in diethylnitrosamine-induced mice

Synergy Mechanisms of Rhizoma Paridis Saponins on Non-small Cell Lung Cancer: Segmented Solid Phase Extraction, Bioactivity Screening, and Network Pharmacology.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Rhizoma paridis saponins (RPS), the main bioactive ingredients of Paris polyphylla Smith var. yunnanensis (PPY), have been proved to have remarkable effects on NSCLC cell lines. However, the multi-component synergistic effects and mechanisms of RPS on NSCLC have not been elucidated. To decipher the multi-RPS synergistic effects and mechanisms against NSCLC based on network pharmacology combined with segmented solid-phase extraction (SPE) and bioactivity screening method. Firstly, segmented SPE and cytotoxicity assays were performed to screen the RPS-enrichment fraction of PPY, and the steroidal saponins in it were identified by LC-MS/MS. Then, a network pharmacology analysis was performed to predict the potential therapeutic targets of RPS on NSCLC. Finally, viable cell counting tests and RT-qPCR were utilized to verify the synergistic effects and mechanisms of RPS. 48 potentially active compounds were identified from the 30% MeOH/EtOAc fraction of PPY (30% M/E PPY). The results of the network pharmacology analysis indicated that RPS exerted joint effects by regulating six key targets in the PI3K-AKT signaling pathway. In vitro experiments showed that due to the synergistic effects, 30% M/E PPY at 13.90 μg/mL could exert a stronger inhibitory activity on A549 cells by reducing the overexpression of six hub genes compared with the parallel control groups. This research elaborates on the multi-RPS synergy mechanisms against NSCLC and provides a way to develop new combination medicines for NSCLC.

Rhizoma Paridis saponins suppresses vasculogenic mimicry formation and metastasis in osteosarcoma through regulating miR-520d-3p/MIG-7 axis

Osteosarcoma (OS) is a highly metastatic bone cancer that usually affects children. Rhizoma Paridis saponins (RPS) have been identified to show a broad-spectrum anti-tumor activity. Our previous study has identified vasculogenic mimicry (VM) as an indicator of poor prognosis for OS. Rhizoma Paridis ethanol extract exhibits potent anti-OS property. However, the anti-metastatic effect of RPS on OS and the detailed mechanisms remain unknown. RPS was characterized by liquid chromatography/quadrupole time-of-flight mass spectrometry (LC/Q-TOF/MS) analysis. The anti-OS, anti-metastasis and anti-VM activities of RPS were investigated using in vitro biological assays and a xenograft mouse model. Western blot, qRT-PCR, ELISA, Phalloidin staining and immunohistochemistry assays were conducted to investigate the molecular mechanism of RPS. A total of 34 phytochemicals from RPS were identified by LC/Q-TOF/MS. RPS dose-dependently suppressed the OS cell proliferation, metastasis and VM formation in vitro and in vivo. Mechanically, we found that RPS downregulated migration-inducing gene 7 (MIG-7) expression, resulting in inhibition of the PI3K/MMPs/Ln-5γ2 pathway and cell protrusion formation. Additionally, we confirmed that RPS downregulated MIG-7 by upregulating miR-520d-3p expression. Our results suggests that RPS inhibits the VM formation and metastasis of OS by modulating the miR-520d-3p/MIG-7 signaling axis.

Tissue distribution, metabolism and absorption of Rhizoma Paridis Saponins in the rats

Ethnopharmacological relevanceParis polyphylla var yunnanensis as a traditional Chinese medicine has been used in the treatment of liver disease for thousands of years. Rhizoma Paridis saponins (RPS) were the main active ingredients in Paris polyphylla with an excellent antitumor effect. However, metabolic and distribution of RPS has not been known.Aim of the study: The objective of this study was to research metabolic and distribution of RPS. Materials and methodsIn this study, the separation and simultaneous determination of RPS in rat plasma and tissues were developed and validated by LC–MS/MS. The permeability and recovery of RPS were tested by Caco-2. S9 assay suggested the metabolic mode of RPS in rats. ResultsAfter oral administration of RPS, the metabolic compound like diosgenin was detected in different tissues although there was none in RPS. The concentration of PI, PII, PVI, PVII, PH and gracillin in the spleen was the highest among these organs. The content of diosgenin were the highest in lung and brain. Caco-2 test indicated that PI, PII, PVI and PVII were low permeability and low recovery. Efflux ratio indicated that PVI should be a potential P-gp substrate. Potential P-gp substrate may be PVI. S9 assay suggested that RPS possess slow metabolic and moderate metabolic compounds. ConclusionsIntegrated LC–MS/MS analysis of serum samples, together with Caco-2 and S9 assays provided a theoretical basis for the application of RPS in the future.

PolyphyllinVII induces mitochondrial apoptosis by regulating the PP2A/AKT/DRP1 signaling axis in human ovarian cancer.

Ovarian cancer is a gynecological malignancy with high mortality. Adjuvant therapy such as chemoradiotherapy inevitably leads to side effects and drug resistance. In recent years, traditional Chinese medicine has been widely studied for its safety, effectiveness, and unique pharmacological effects. Polyphyllin VII is an important component of Rhizoma paridis saponins, and has cytotoxic effects on many types of cancer cells. The aim of the present study was to evaluate the anti-tumor activity of polyphyllin VII in human ovarian cancer cells. Recent studies found that polyphyllin VII induces mitochondrial pathway apoptosis by increasing mitochondrial division, but the specific mechanism was unclear. The results of this study revealed that polyphyllin VII could effectively induce mitochondrial dysfunction, including increased mitochondrial division and reactive oxygen species (ROS) production. Notably, the mitochondrial location of dynamin-related protein 1 (DRP1) plays an important role in its function. In addition, polyphyllin VII enhanced the mitochondrial localization of DRP1 which is mediated by increased protein phosphatase 2A (PP2A) activity, and decreased AKT activity. A specific PP2A inhibitor, LB100, attenuated mitochondrial division and apoptosis in cells caused by polyphyllin VII, confirming the function of the PP2A/AKT pathway in polyphyllin VII treatment. Additionally, xenotransplantation experiments have also confirmed the anti-tumor effect of polyphyllin VII in vivo. Therefore, interference of the mitochondrial translocation of DRP1 through PP2A/AKT pathway may be an attractive and effective therapeutic approach by polyphyllin VII in ovarian cancer. This may provide new strategies for polyphyllin VII in the clinical treatment of ovarian cancer.

Paris saponin II-induced paraptosis-associated cell death increased the sensitivity of cisplatin

Paris Saponin II (PSII) has been regarded as an effective and imperative component isolated from Rhizoma Paridis saponins (RPS) and exhibited strong anti-tumor effects on a variety of cancer. Our results revealed that human non-small lung cancer cell lines NCI-H460 and NCI-H520 were exposed to 1 μM of PSII, which inhibited the proliferation of lung cancer cells and activated apoptosis, autophagy and paraptosis. PSII induced paraptosis-associated cell death prior to apoptosis and autophagy. It induced paraptosis based on ER stress through activation of the JNK pathway. Meanwhile, PSII increased the cytotoxicity of cisplatin through paraptosis-associated pathway. All in all, PSII induced paraptosis based on induction of non-apoptotic cell death, which would be a possible approach to suppress the multi-drug resistant to apoptosis.

Anticarcinogenic effect of zinc oxide nanoparticles synthesized from Rhizoma paridis saponins on Molt-4 leukemia cells

Leukemia is considered as a multistep progression by progressively genetic modifications that make the conversion of normal human hematopoietic progenitor/stem cells into leukemic cells. In this current investigation, we optimized the reaction of parameters to control the nanoparticle size that was examined via SEM. A various characterization techniques, for example UV–visible spectroscopy, FTIR and EDX were carried out for the synthesized ZnONPs from Rhizoma paridis saponins plant extract. The RPS-ZnONPs were evaluated to inspect their cytotoxic activity against Molt-4 cells via MTT test. Apoptosis was determined through the ROS, MMP and AO/EtBr fluorescent staining techniques. Moreover, pro and anti-apoptotic signaling protein expression was inspected through RT-PCR method. We observed the fabricated RPS-ZnONPs have a crystalline nature, spherical formand various biomolecules were exist. As well, we detected the cytotoxicity effect of synthesized RPS-ZnONPs at a range of 23.5 μg followed to 24hrs treatment. Apoptosis was triggered via the RPS-ZnONPs along with augmented ROS, decreased MMP and altered dual staining. Moreover, the apoptosis were identified through significant up-regulation of Bax, caspase-9 and caspase-3, but the anti-apoptotic protein expression i.e., Bcl-2 was down regulated. Though, this study, we investigated the synthesis, characterization and anticancer activity of ZnONPs of Rhizoma paridis saponins plant extract (RPS-ZnONPs) were useful for treatments of leukemia.

RhizomaParidis saponins ameliorates hepatic fibrosis in rats by downregulating expression of angiogenesis‑associated growth factors.

Previously, we demonstrated that Rhizoma Paridis saponins (RPS), the major active component of Rhizoma Paridis, may exhibit hepatoprotective effects. The present study aimed to identify the potential mechanism of RPS on hepatic injury and improvement in hepatic fibrosis (HF). A HF model was created in Sprague-Dawley rats by administration of carbon tetrachloride. RPS was administered for treatment following creation of the HF model. The protein and mRNA expression of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), extracellular signal-regulated kinase (ERK)1/2 and α-smooth muscle actin (SMA) was detected by reverse transcription quantitative polymerase chain reaction and western blot analysis. RPS was demonstrated to improve hepatic inflammation and decrease HF severity according to hematoxylin and eosin and Masson trichrome staining. Following RPS treatment, the level of alanine aminotransferase, aspartate aminotransferase and malondialdehyde, and expression levels of the mRNA and protein of VEGF, ERK1/2, PDGF and α-SMA in the model group was decreased. By contrast, the content of glutathione-PX and superoxide dismutase was increased. These data suggest that RPS may treat HF primarily through downregulation of the expression levels of the mRNA and phosphorylated VEGF, ERK1/2, PDGF and α-SMA proteins.

Combinatorial treatment of Rhizoma Paridis saponins and sorafenib overcomes the intolerance of sorafenib

Sorafenib, as a multi-kinase inhibitor, was the first FDA-approved anti- hepatocellular carcinoma (HCC) drug. Rhizoma Paridis saponins (RPS) as natural products have shown antitumor activity through regulation of glycolytic and lipid metabolism which was regarded as the side effect limited the utility of sorafenib. In this research, we tried to use metabolomics to verify the probability of combinatorial treatment of RPS and Sorafenib. As a result, Sorafenib + RPS increased the antitumor effect of sorafenib and RPS in H22 mice. They mitigated the change of liver weight and the increasing levels of AST and ALT in serum, and AFP and MDA in liver tissues, which indicated their liver protective activity. They also up-regulated the activity of NOX and SDH, concentration of ATP, and down-regulated the mRNA and protein levels of HIF-1a and concentration of lactate, which suggested they protected against mitochondria damage and inhibited anaerobic glycolysis. Meanwhile, the combination group remarkably down-regulated the concentration of octadecanoic acid and hexadecanoic acid in serum, and tetradecanoic acid in liver tissues compared with model group (p < 0.05). Relative regulation mechanism included their decreasing mRNA levels of FASN, CPT1, GLUT1, Myc, Akt, mTOR and LDHA, and increasing the protein expression of p53 in tumor and liver tissues (p < 0.05). Furthermore, similar influence can be observed in protein levels of CPT1A, p-PI3K, p-mTOR and p53 in liver tissues and FASN in serum. All of that provided possibility to overcome the intolerance of sorafenib by drug compatibility through protection against mitochondria damage, inhibition of anaerobic glycolysis and suppression of lipid synthesis based on PI3K/Akt/mTOR pathway.

Effect of Rhizoma Paridis saponin on the pain behavior in a mouse model of cancer pain.

Rhizoma Paridis saponins (RPS) as active parts of P. polyphylla Smith var. yunnanensis has been used as an anti-cancer drug in traditional Chinese medicine. In this study, RPS was first found to demonstrate a potent effect on markedly reducing the pain induced by cancer. Therefore, the aim of this study was to further explore the analgesic effect of RPS and its possible reaction pathway on H22 hepatocarcinoma cells inoculated in the hind right paw of mice. Cancer-induced pain model mice were randomly divided into 5 groups (n = 10) and orally administered with RPS (50–200 mg kg−1) for 2 weeks. On the last day of treatment, the pain behavior of mice was measured using hot-plate test and open field test, and brain tissues were sampled for detection of biochemical indices, malondialdehyde (MDA), superoxide dismutase (SOD), prostaglandin E2 (PGE2), serotonin (5-HT) and β-endorphin (β-EP). Moreover, the concentrations of NF-κB and IL-1β in the blood serum were measured by ELISA reagent kits. In addition, naloxone, the non-selective antagonist of opioid receptors, was used to identify the opioid receptors involved in RPS's action. It has been found that RPS alleviates cancer pain mainly via the suppression of inflammatory pain induced by oxidative damage, such as decreasing MDA and PGE2 levels, renewing activity of SOD, as well as increasing 5-HT and β-EP in the brain and suppressing the expression of NF-κB and IL-1β in the serum in a concentration-dependent manner. Overall, the current study highlights that RPS has widespread potential antinociceptive effects on a mouse model of chronic cancer pain, which may be associated with the peripheral nervous system and the central nervous system.

Antitumor and anti-metastatic mechanisms of Rhizoma paridis saponins in Lewis mice.

Lung cancer is one of the most common causes of death in the world. Rhizoma paridis saponins (RPS) have been found to show inhibition of pulmonary adenoma in previous research. However, the detailed mechanisms of RPS from a holistic view have not been established. In this study, Lewis pulmonary adenoma mice were successfully established to analyze the pathways involved in RPS intervening tumor formation and progression. As a result, RPS inhibited levels of cytokines or receptors such as VEGFD, VEGFR3, RAGE, IL6R, IL17BR, and CXCL16 which were regarded as the initiators induced tumor cell proliferation, adhesion, angiogenesis, and invasion. Meanwhile, RPS raised the content of SOD and CAT enzymes and thereby inhibited the aberrantly active NF-κB, and phosphorylation of PI3K/Akt and MAPK (including p38, Erk1/2, and JNK) signaling pathways. Soon after, RPS changed mRNA expression of nuclear factors containing NF-κB, HIF-1A, STAT3, and Jun, and consequentially suppressed the expression of angiogenesis, lymphangiogenesis, adhesion, inflammation, and invasion enzymes. In conclusion, this research provided a holistic view to understand the multi-target antitumor mechanisms of RPS which promoted the application of RPS in the future.

Inhibition of lung cancer in diethylnitrosamine-induced mice by Rhizoma paridis saponins.

Lung cancer is the foremost cause of cancer mortality and a growing economic burden worldwide. Rhizoma paridis saponins (RPS) have been reported to exhibit potential anti-tumor effects on many kinds of tumor models. The present study was designed to investigate the mechanism-based chemopreventive nature of RPS against DEN-induced lung carcinogenesis in Kunming mice. As a result, the treatment with RPS reduced the severity of pulmonary histopathology. The mechanism of its antitumor effect involved in (a) reducing oxidative stress injury through up-regulating activities of CAT and SOD; (b) down-regulating the levels of inflammatory factors, like TNF-α, IL6, COX-2, and PGE2; (c) activation of caspase-3 and up-regulating the pro-apoptotic protein Bax; (d) decreasing the expression of PCNA; (e) depressing the expression of cancer stem cells marker CD133; (f) suppressing aberrant expression of cytokeratin 8 and 18; and (g) inhibiting EGFR/ PI3 K/Akt, EGFR/Ras/Erk and NF-κB pathways. Taken together, RPS would be a potent agent inhibiting lung tumor in the future.

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.

Utilization of metabonomics to identify serum biomarkers in murine H22 hepatocarcinoma and deduce antitumor mechanism of Rhizoma Paridis saponins

Murine H22 hepatocarcinoma model is so popular to be used for the preclinical anticancer candidate’s evaluation. However, the metabolic biomarkers of this model were not identified. Meanwhile, Rhizoma Paridis saponins (RPS) as natural products have been found to show strong antitumor activity, while its anti-cancer mechanism is not clear. To search for potential metabolite biomarkers of this model, serum metabonomics approach was applied to detect the variation of metabolite biomarkers and the related metabolism genes and signaling pathway were used to deduce the antitumor mechanisms of RPS. As a result, ten serum metabolites were identified in twenty-four mice including healthy mice, non-treated cancer mice, RPS-treated cancer mice and RPS-treated healthy mice. RPS significantly decreased tumor weight correlates to down-regulating lactate, acetate, N-acetyl amino acid and glutamine signals (p < 0.05), which were marked metabolites screened according to the very important person (VIP), loading plot and receiver operating characteristic curve (ROC) tests. For the analysis of metabolic enzyme related genes, RPS reversed the aerobic glycolysis through activating tumor suppressor p53 and PTEN, and suppressed FASN to inhibit lipogenesis. What’s more, RPS repressed Myc and GLS expression and decreased glutamine level. The regulating PI3K/Akt/mTOR and HIF-1α/Myc/Ras networks also participated in these metabolic changes. Taken together, RPS suppressed ATP product made the tumor growth slow, which indicated a good anti-cancer effect and new angle for understanding the mechanism of RPS. In conclusion, this study demonstrated that the utility of 1H NMR metabolic profiles taken together with tumor weight and viscera index was a promising screening tool for evaluating the antitumor effect of candidates. In addition, RPS was a potent anticancer agent through inhibiting cancer cellular metabolism to suppress proliferation in hepatoma H22 tumor murine, which promoted the application of RPS in the future.

Metabolic regulatory network alterations reveal different therapeutic effects of cisplatin and Rhizoma paridis saponins in Lewis pulmonary adenoma mice

Metabonomics is used to compare the metabolic profiling of RPS and DDP in Lewis pulmonary adenoma mice; RPS is found to be a potent anticancer agent through inhibiting cancer cellular metabolism to suppress metastases in murine lung adenocarcinoma.

Toxicological risks of Rhizoma paridis saponins in rats involved NF-κB and Nrf2 signaling

The aim of the study is to evaluate the safety of long-term use of Rhizoma paridis saponins (RPS).

Global metabolic profiling for the study of Rhizoma Paridis saponins-induced hepatotoxicity in rats.

Rhizoma Paridis saponins (RPS) is a traditional Chinese medicine (TCM) from the plant Paris polyphylla var. yunnanensis (Fr.) Hand.-Mazz. Despite its potentially clinical utility such as anticancer and anti-inflammation, it has slight side effects and toxicity as previous report. In this work, 90-day administration of RPS induced liver injury. 1 H-NMR- and GC/MS-based metabonomic analyses in conjunction with histopathological examinations, blood biochemistry and hepatic phase I and II enzymes assays were performed to evaluate the toxic mechanisms of RPS induced in rats. As a result, oral administration of RPS possessed certain liver toxicity in SD rats. 1 H-NMR and GC/MS data indicated that RPS inhibited the oxidation of fatty acids, glycolysis, and TCA cycle pathway, and disturbed glycine, serine, and threonine metabolism. Low expression of TG, T-CHO, and LDL-C and high levels of ALT and AST indicated that chronic exposure to RPS caused hepatocyte damage, synthesis dysfunction, and transportation failure of lipoproteins. In addition, RPS downregulated the mRNA levels of CYP1A2, CYP2E1, and UGTs. In conclusion, we used metabonomics approach to study the toxicity of RPS for the first time. This research demonstrated that metabonomics method was a promising tool to study and diagnose TCM-induced toxicity. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 99-108, 2017.

Curcumin alleviated the toxic reaction of Rhizoma Paridis saponins in a 45-day subchronic toxicological assessment of rats.

Rhizoma Paridis saponins (RPS), as steroid saponins, are the main components in Paris polyphylla. Curcumin (diferuloylmethane) is the most important component in the spice turmeric. In our previous research, RPS exhibited side effects such as nausea, vomiting, diarrhea, and so forth. Combination with curcumin not only alleviated the toxicity and gastric stimulus induced by RPS, but also improved the quality life of mice bearing tumor cells and enhanced their anticancer effect. This study evaluated subchronic toxicity of 45th dietary of RPS and curcumin on histopathology, biochemistry, and antioxidant index. As a result, RPS-treatment caused a slight liver injury (the elevation of serum AST, alkaline phosphatase (AKP), alanine transaminase (ALT), and gamma glutamyl transpeptidase (γ-GT), histopathological changes in liver section), oxidative stress (the enhancement of reactive oxygen species (ROS), malondialdehyde (MDA), and 8-hydroxy-2-deoxyguanosine (8-OHdG), separation of thioredoxin (Trx) and thioredoxin-interacting protein (TXNIP), but enhancement of heme oxygenase-1 (HO-1), glutathione S-transferase (GST), and nuclear factor-regulated factor 2 (Nrf2)), and inflammation (up-regulation of cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), and nuclear factor kappaB (NF-κB)). However, these changes were alleviated through co-treatment with curcumin. In conclusion, our work provided useful data for further research and new drug exploration of RPS and curcumin. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1935-1943, 2016.