Polygonum multiflorum-Induced Liver Injury: Clinical Characteristics, Risk Factors, Material Basis, Action Mechanism and Current Challenges

Abstract

Polygonum multiflorum Thunb. (PM), called Heshouwu in China, is a popular Chinese medicine in clinical practice. Several clinical studies have been conducted to evaluate the traditional therapeutic claims and to study the potential therapeutic activity of PM in dyslipidemia and neurodegenerative diseases, highlighting available clinical evidence. In recent years, reports on clinical adverse reactions of Raw Radix P. multiflorum (RPM) and P. multiflorum Praeparata (PMP) have been on the increase, especially with respect to liver injury. Most liver injury cases had been assessed for causality using RUCAM (Roussel Uclaf Causality Assessment Method) in this paper. However, the components of PM responsible for the reported hepatotoxic effects have not yet been identified. Moreover, many of the reports are contradictory, while studies on the mechanism involved in PM-induced liver damage are not comprehensive. This study was aimed at reviewing the status of research on liver injury due to PM, including clinical characteristics, risk factors, material basis research and mechanism of action, with a view to understanding PM-induced hepatotoxicity, and taking reasonable and effective measures to prevent it. In short, quality control is still one of the major safety problems in TCM drug safety concerns. The model of safety monitoring and risk management of PM drugs is not yet developed. Indeed, the characteristics and risk factors associated with PM require both proper understanding and control of the risk by strengthening standardization of clinical applications, basic science research, quality control in manufacturing, active monitoring methodology and enhancement of international communication and cooperation. Measures should also be encouraged and implemented to promote healthy development of the TCM industry.

Overview of Pharmacokinetics and Liver Toxicities of Radix Polygoni Multiflori

“…So far, there are several retrospective analysis studies investigating the clinical cases on RPM induced liver injury [ 59 , 60 , 61 ]. According to these studies, the common reasons for consuming RPM products included treating grey hair, hair loss, using it as a health supplement, or for the treatment of hypertension, coronary heart disease, hyperlipidemia, etc.…”

“…Most of the liver injuries induced by RPM were diagnosed as hepatocellular injury followed by mixed liver injury and cholestatic liver injury with jaundice, fatigue, anorexia as the major symptoms of RPM induced liver injury. Although RPM can induce liver injury in different degrees and even lead to death, the majority of RPM associated liver damage was found to be reversible after discontinuing RPM products and conservative care [ 59 , 60 , 61 ].…”

Herb-induced Liver Injury in Asia and Current Role of RUCAM for Causality Assessment in 11,160 Published Cases

“…As outlined in the report of Chau et al, 20 the interrater agreement between experts and RUCAM was 81%, facilitating evaluations and exclusion of cases with alternative causes or unclear herbal product identification. In general, RUCAM-based HILI series are preferred that cover in more detail a single herb, such as Gynura segetum and other pyrrolizidine alkaloids (PAs)-containing herbs like in the reports of Lin et al 21 and Gao et al, 22,25 or Psoralea corylifolia like in the reports of Cheung et al 19 and Li et al, 34 or Polygonum multiflorum (PM), as shown in the reports of Dong et al, 23 Wang et al, 27 Zhu et al, 28 Li et al, 31 Jing et al, 33 and Liu et al 35 For instance, Li et al 31 presented a perfect case report on HILI caused by PM, using the updated RUCAM of 2016. 15 Similarly, the case series of Dong et al 23 focuses on PM on a single herb causing HILI in 18 patients, with each having received an individual causality grading of probable or highly probable.…”

“…Occasionally, RUCAM-based causality gradings, classified initially as possible, had afterwards been upgraded to a probable level through a non-transparent maneuver 36 -an overall highly questionable and disputable approach as also discussed previously. 11 In rare instances, causality gradings were not reported 35 or RUCAM was used for causality grading but the respective publication remained unquoted, 26,34 even if the updated RUCAM was mentioned in the text. 34 Similar omissions of RUCAM quotation have been observed in some publications related to DILI.…”

Kupffer Cells in Non-alcoholic Fatty Liver Disease: Friend or Foe?

“…The stilbene component of Polygonum multiflorum improves the function of damaged fatty livers in rats and reduces lipid peroxide contents in the liver. Moreover, P. multiflorum is rich in phospholipids that promote cholesterol and lipids metabolism in the liver, thereby reducing intrahepatic fat accumulation [116,117]. Perhaps further in-depth research will determine whether the aforementioned herbs slow the inflammatory response by regulating Kupffer cells and other macrophages to achieve anti-oxidant and anti-liver fibrosis effects.…”