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

Man, Shuli; Qiu, Peiyu; Li, Jing; Zhang, Liming; Gao, Wenyuan

doi:10.1002/tox.22215

Cited by 16 publications

(10 citation statements)

References 15 publications

(16 reference statements)

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“…Lists of herbs and concoctions that were hepatotoxic or hepatoprotective, their respective causality levels, and number of cases are compiled in Tables 1 to 5. 9,13-46…”

Section: Resultsmentioning

confidence: 99%

Literature Review of Traditional Chinese Medicine Herbs–Induced Liver Injury From an Oncological Perspective With RUCAM

Chow

Choi

et al. 2019

Integr Cancer Ther

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Traditional Chinese medicine (TCM) herbs are commonly regarded to be safe with minimal toxicities in Chinese communities. Cancer patients who are receiving Western oncology therapy often concurrently take TCM herbs for anticancer and symptom relief purposes. We performed a literature review for current evidence on TCM herb–induced liver injury from an oncological perspective. A literature search on PubMed was performed to identify publications regarding TCM herbs and concoctions with hepatoprotective or hepatotoxic properties. Lists of commonly used herbs and their causality levels were compiled. In view of the wide range of evidence available, cases assessed by the well-established RUCAM (Roussel Uclaf Causality Assessment Method) algorithm were categorized as the highest level of evidence. More than one case of TCM herb–induced liver injury was confirmed by RUCAM in the following herbs and concoctions: Lu Cha ( Camellia sinensis), Bai Xian Pi ( Dictamnus dasycarpus), Tu San Qi ( Gynura segetum), Jin Bu Huan ( Lycopodium serratum), He Shou Wu ( Polygoni multiflora), Ge Gen ( Pueraria lobata), Dan Lu Tong Du tablet, Shou Wu Pian, Xiao Chai Hu Tang, Xiao Yin pill, and Yang Xue Sheng Fa capsule. Finally, TCM with anticancer or symptom relief uses were discussed in detail with regard to their hepatotoxic or hepatoprotective properties.

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“…Lists of herbs and concoctions that were hepatotoxic or hepatoprotective, their respective causality levels, and number of cases are compiled in Tables 1 to 5. 9,13-46…”

Section: Resultsmentioning

confidence: 99%

Literature Review of Traditional Chinese Medicine Herbs–Induced Liver Injury From an Oncological Perspective With RUCAM

Chow

Choi

et al. 2019

Integr Cancer Ther

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“…The saponins in Paris saponins have many pharmacological properties, such as anti-tumor [40,41], hemostatic [42], anti-bacterial [43], anti-inflammatory [44], angiogenesis-inhibitory [45] and immune-regulatory [46] effects. However, in recent years, some studies have reported the in vivo hepatotoxicity of Paris saponins [3,4,5,6,7]. The purpose of the present study was to investigate the hepatotoxicity of the four main saponins from Rhizoma paridis in vitro and to unravel the cellular and molecular mechanisms involved.…”

Section: Discussionmentioning

confidence: 97%

“…Rhizoma paridis, a liliaceous plant of the Yunnan Paris or the dried rhizome of the seven-leaf flower, is a frequently used traditional Chinese medicine in clinics due to its numerous pharmacological effects [1,2]. Recently, some studies reported that an excess dose of Rhizoma paridis produced liver injury due to its saponin components [3,4,5,6,7]. However, the hepatotoxicity of various saponins in Rhizoma paridis and their mechanism of action have not been studied.…”

Section: Introductionmentioning

confidence: 99%

Hepatocellular Toxicity of Paris Saponins I, II, VI and VII on Two Kinds of Hepatocytes-HL-7702 and HepaRG Cells, and the Underlying Mechanisms

Wang

Liu

Sun

et al. 2019

Cells

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Rhizoma paridis is a popularly-used Chinese medicine in clinics, based on the pharmacodynamic properties of its saponin components. The four main saponins in Rhizoma paridis are designated saponins I, II, VI, and VII. At present, much attention is focused on the anticancer effect of Rhizoma paridis which is manifested in its cytotoxicity to various cancer cells. The purpose of this study was to investigate the hepatocellular toxicities of the four saponins in Rhizoma paridis and the relative intensities of their cytotoxic effects. It was found that the four saponins were cytotoxic to two types of hepatocytes-HL-7702 and HepaRG cells. The cytotoxicities of the four saponins to the two cell models were compared. One of the most cytotoxic saponins was Rhizoma paridis saponin I (PSI). This was used to determine the mechanism of hepatocellular toxicity. Results from MTT assays demonstrated that the four saponins induced apoptosis of the two hepatocyte models in a dose-dependent and time-dependent manner. In addition, fluorescent 4′,6-diamidino-2-phenylindole (DAPI) staining was used to observe the morphological changes of HepaRG cells after saponin administration. Further, as the concentration increased, PSI-induced lactate dehydrogenase (LDH) release from HepaRG cells increased gradually. In addition, PSI enhanced the levels of reactive oxygen species (ROS) and blocked the S and G2 phases of the cell cycle in HepaRG cells. A western blot indicated that PSI upregulated the protein expression levels of p53, p21, and Fas. Furthermore, the PSI-induced changes in the p53 protein increased the Bax/bcl-2 ratio, resulting in enhancement of the release of mitochondrial cytochrome c, activation of caspases-3, -8, and -9, poly-ADP ribose polymerase (PARP), and ultimately apoptosis. Increased Fas protein activated caspase-8, which led to the activation of caspase-3 and its downstream PARP protein, resulting in cell apoptosis. These results indicate that PSI induced apoptosis in HepaRG cells through activation of ROS and death receptor pathways. The results obtained in this study suggest that the hepatocellular toxicity of saponins in Rhizoma paridis should be considered during the clinical application of this drug. In addition, they provide a reference for future anti-cancer studies on Rhizoma paridis.

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“…For thousands of years, Paridis saponin (PS) and its components have always been used as hemostatic regulatory, antifungal, anti-inflammatory, antimicrobial, and antibacterial medications in China ( White et al, 2015 ; Moldogazieva et al, 2018 ). Recent studies have reported promising roles of PS in the regulation of glycolytic and lipid metabolism ( Man et al, 2017 ; Man et al, 2020 ). In addition, the PSII extract has been approved as an antitumor agent for many years in China, but its mechanism of action is not well understood.…”

Section: Discussionmentioning

confidence: 99%

“…yunnanensis used as an anticancer drug in traditional Chinese medicine (TCM) which is also an active component of Paris saponin II (PSII), has shown a strong antitumor power in various cancers, such as hepatocellular carcinoma (HCC) ( Cheng et al, 2008 ), lung cancer ( Man et al, 2015 ), and ovarian cancer ( Xiao et al, 2009 ). Recent studies have reported promising roles of PS in the regulation of glycolytic and lipid metabolism ( Man et al, 2017 ; Man et al, 2020 ). All these results indicate that PSII may be a valuable anti-HNSCC agent.…”

Section: Introductionmentioning

confidence: 99%

The Antitumoral Effect of Paris Saponin II on Head and Neck Squamous Cell Carcinomas Mediated via the Nitric Oxide Metabolic Pathway

Zhu

Wang

et al. 2022

Front. Cell Dev. Biol.

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Paris saponin has shown great therapeutic value in cancer therapy. We used isolated Paris saponin II (PSII), an active component of Paris saponin, and demonstrated its antitumor effect on human head and neck squamous cell carcinoma cell lines. Additionally, we investigated its mechanisms of action in vivo by establishing a xenograft mouse model. The results showed that PSII had presented strong anticancer effects on both hypopharyngeal malignant tumor cell lines (FaDu) and laryngeal carcinoma cell lines (Tu212 and Tu686). In addition, we successfully isolated and cultured the head and neck squamous stem cells and the primary fibroblasts to perform metabonomics studies. The results showed that RPII remarkably decreased energy metabolism, and type III nitric oxide synthase 3 (NOS3) may be a target to block tumor growth. Furthermore, we found that PSII inhibited HNSCC proliferation and metastasis by inhibiting the nitric oxide metabolic pathway. Overall, these results demonstrated that PSII is a potent anticancer agent, and the metabonomics analysis is a valuable tool to investigate and establish the antitumor effects of traditional Chinese medicines.

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

Cited by 16 publications

References 15 publications

Literature Review of Traditional Chinese Medicine Herbs–Induced Liver Injury From an Oncological Perspective With RUCAM

Literature Review of Traditional Chinese Medicine Herbs–Induced Liver Injury From an Oncological Perspective With RUCAM

Hepatocellular Toxicity of Paris Saponins I, II, VI and VII on Two Kinds of Hepatocytes-HL-7702 and HepaRG Cells, and the Underlying Mechanisms

The Antitumoral Effect of Paris Saponin II on Head and Neck Squamous Cell Carcinomas Mediated via the Nitric Oxide Metabolic Pathway

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