A systematic review of the active saikosaponins and extracts isolated from Radix Bupleuri and their applications

Yuan, Bochuan; Yang, Rui; Ma, Yongsheng; Zhou, Shiyue; Zhang, Xiaodong; Liu, Ying

doi:10.1080/13880209.2016.1262433

Cited by 159 publications

(122 citation statements)

References 102 publications

Supporting

Mentioning

118

Contrasting

Unclassified

Order By: Relevance

“…Cholestatic liver injury has been reported in the use of OA‐type triterpenoid containing herbal mixtures . Table lists a few examples, Saikosaponins are oleanane‐type triterpenoids and are the major bioactive compounds isolated from Radix Bupleuri .…”

Section: High Doses and Long‐term Use Of Oa And/or Oa Derivatives Promentioning

confidence: 99%

“…Table lists a few examples, Saikosaponins are oleanane‐type triterpenoids and are the major bioactive compounds isolated from Radix Bupleuri . A systemic review of Saikosaponins isolated from Radix Bupleuri showed anti‐inflammatory, antitumor and hepatoprotective effects, similar to OA . Saikosaponin d was effective in protecting against acetaminophen‐induced liver injury .…”

Section: High Doses and Long‐term Use Of Oa And/or Oa Derivatives Promentioning

confidence: 99%

“…Saikosaponin d was effective in protecting against acetaminophen‐induced liver injury . The main side effect of Radix Bupleuri is liver damage with high dosages, indicating that the maximum tolerated dose is critical for clinical use of Radix Bupleuri extract and purified compounds . Total Bupleurum saponins caused serious liver injury and even death in rats, with clear dose and time toxicity relationships .…”

Section: High Doses and Long‐term Use Of Oa And/or Oa Derivatives Promentioning

confidence: 99%

See 2 more Smart Citations

Oleanolic acid reprograms the liver to protect against hepatotoxicants, but is hepatotoxic at high doses

Liu

Lü

et al. 2018

Liver International

View full text Add to dashboard Cite

Oleanolic acid (OA) is a triterpenoid that exists widely in fruits, vegetables and medicinal herbs. OA is included in some dietary supplements and is used as a complementary and alternative medicine (CAM) in China, India, Asia, the USA and European countries. OA is effective in protecting against various hepatotoxicants, and one of the protective mechanisms is reprogramming the liver to activate the nuclear factor erythroid 2-related factor 2 (Nrf2). OA derivatives, such as CDDO-Im and CDDO-Me, are even more potent Nrf2 activators. OA has recently been shown to also activate the Takeda G-protein-coupled receptor (TGR5). However, whereas a low dose of OA is hepatoprotective, higher doses and long-term use of OA can produce liver injury, characterized by cholestasis. This paradoxical hepatotoxic effect occurs not only for OA, but also for other OA-type triterpenoids. Dose and length of time of OA exposure differentiate the ability of OA to produce hepatoprotection vs hepatotoxicity. Hepatotoxicity produced by herbs is increasingly recognized and is of global concern. Given the appealing nature of OA in dietary supplements and its use as an alternative medicine around the world, as well as the development of OA derivatives (CDDO-Im and CDDO-Me) as therapeutics, it is important to understand not only that they program the liver to protect against hepatotoxic chemicals, but also how they produce hepatotoxicity.

show abstract

Section: High Doses and Long‐term Use Of Oa And/or Oa Derivatives Promentioning

confidence: 99%

Section: High Doses and Long‐term Use Of Oa And/or Oa Derivatives Promentioning

confidence: 99%

Section: High Doses and Long‐term Use Of Oa And/or Oa Derivatives Promentioning

confidence: 99%

See 1 more Smart Citation

Oleanolic acid reprograms the liver to protect against hepatotoxicants, but is hepatotoxic at high doses

Liu

Lü

et al. 2018

Liver International

View full text Add to dashboard Cite

show abstract

“…As one of the most widely used herbal treatments, RB is first recorded in Shen Nong Ben Cao Jing, the earliest monograph concerning TCM (Li et al, 2014a), and has been clinically practiced for over past 2000 years to treat fever, chill, tumor, hypochondria, inflammation and uterine prolapsed (Bermejo Benito et al, 1998;Li et al, 2005b;Liu et al, 2003). Recently, RB has been used as a hepatoprotective herb to treat various liver diseases, such as chronic hepatic inflammation, viral hepatitis and even hepatocellular carcinoma in patients with the complication of liver cirrhosis (Hirayama et al, 1989;Oka et al, 1995;Yuan et al, 2017). Clinically, several patented TCMs or traditional in China, including Chai-Hu-Shu-Gan tablets, Xiao- Yao-Wan tablets, Xiao-Chai-Hu-Tang, Da-Chai-Hu-Tang and Chai-Hu-Shu-Gan-San .…”

Section: Introductionmentioning

confidence: 99%

A comprehensive review and perspectives on pharmacology and toxicology of saikosaponins

Huang

et al. 2018

Phytomedicine

145

View full text Add to dashboard Cite

Background: Radix Bupleuri (RB) has been widely used in Chinese Traditional Medicine for over 2000 years and is currently marketed in China as Chai-Hu-Shu-Gan tablets and Xiao-Yao-Wan tablets. Saikosaponins (SSs, especially SSa, SSc and SSd), as the major bioactive compounds in RB, represent anti-inflammatory, anti-tumor, anti-oxidant, anti-viral and hepatoprotective effects. Purpose: To summarize recent findings regarding to the extraction, detection, biosynthesis, metabolism, pharmacological/toxicological effects of SSs. Methods: Online academic databases (including PubMed, Google Scholar, Web of Science and CNKI) were searched using search terms of "Saikosaponin", "Radix Bupleuri", "Bupleurum" and combinations to include published studies of SSs primarily from 2003 to 2018. Several critical previous studies beyond this period were also included. Results: 354 papers were found and 165 papers were reviewed. SSs have drawn great attention for their antiinflammation, anti-viral and anti-cancer effects and contradictory roles in the regulation of cell apoptosis, oxidative stress and liver fibrosis. Meanwhile, increased risks of overdose-induced acute or accumulation-related chronic hepatotoxicity of SSs and RB have also been reported. However, underlying mechanisms of SSs bioactivities, the metabolism of SSs and bioactivities of SSs metabolites are largely unknown. Conclusion: This comprehensive review of SSs provides novel insights and perspectives on the limitations of current studies and the importance of metabolism study and the dose-pharmacological/toxic relationship of SSs for the future discovery of SSs-based therapeutic strategies and clinical safe practice.

show abstract

“…SS exhibits anti-inflammatory, anti-tumor, anti-viral, immunoregulatory and hepatoprotective effects [13]. Our previous study demonstrated that SS contributes to RB-induced chronic and acute hepatotoxic effects on rats and mice [14–17].…”

Section: Introductionmentioning

confidence: 99%

Saikosaponins induced hepatotoxicity in mice via lipid metabolism dysregulation and oxidative stress: a proteomic study

et al. 2017

BMC Complement Altern Med

View full text Add to dashboard Cite

BackgroundRadix Bupleuri (RB) has been popularly used for treating many liver diseases such as chronic hepatic inflammation and viral Hepatitis in China. Increasing clinical and experimental evidence indicates the potential hepatotoxicity of RB or prescriptions containing RB. Recently, Saikosaponins (SS) have been identified as major bioactive compounds isolated from RB, which may be also responsible for RB-induced liver injury.MethodsSerum AST, ALT and LDH levels were determined to evaluate SS-induced liver injury in mice. Serum and liver total triglyceride and cholesterol were used to indicate lipid metabolism homeostasis. Liver ROS, GSH, MDA and iNOS were used to examine the oxidative stress level after SS administration. Western blot was used to detect CYP2E1 expression. A 8-Plex iTRAQ Labeling Coupled with 2D LC - MS/MS technique was applied to analyze the protein expression profiles in livers of mice administered with different doses of SS for different time periods. Gene ontology analysis, cluster and enrichment analysis were employed to elucidate potential mechanism involved. HepG2 cells were used to identify our findings in vitro.ResultsSS dose- and time-dependently induced liver injury in mice, indicated by increased serum AST, ALT and LDH levels. According to proteomic analysis, 487 differentially expressed proteins were identified in mice administrated with different dose of SS for different time periods. Altered proteins were enriched in pathways such as lipid metabolism, protein metabolism, macro molecular transportation, cytoskeleton structure and response to stress. SS enhanced CYP2E1 expression in a time and dose dependent manner, and induced oxidative stress both in vivo and in vitro.ConclusionOur results identified hepatotoxicity and established dose-time course-liver toxicity relationship in mice model of SS administration and suggested potential mechanisms, including impaired lipid and protein metabolism and oxidative stress. The current study provides experimental evidence for clinical safe use of RB, and also new insights into understanding the mechanism by which SS and RB induced liver injury.

show abstract

A systematic review of the active saikosaponins and extracts isolated from Radix Bupleuri and their applications

Cited by 159 publications

References 102 publications

Oleanolic acid reprograms the liver to protect against hepatotoxicants, but is hepatotoxic at high doses

Oleanolic acid reprograms the liver to protect against hepatotoxicants, but is hepatotoxic at high doses

A comprehensive review and perspectives on pharmacology and toxicology of saikosaponins

Saikosaponins induced hepatotoxicity in mice via lipid metabolism dysregulation and oxidative stress: a proteomic study

Contact Info

Product

Resources

About