Therapeutic Efficacy of Wuzhi Tablet (<i>Schisandra sphenanthera</i> Extract) on Acetaminophen-Induced Hepatotoxicity through a Mechanism Distinct from <i>N</i>-Acetylcysteine

Fan, Xiaomei; Chen, Pan; Jiang, Yiming; Wang, Ying; Tan, Huasen; Zeng, Hang; Wang, Yongtao; Qu, Aijuan; Gonzalez, Frank J.; Huang, Min; Bi, Huichang

doi:10.1124/dmd.114.062067

Cited by 37 publications

(24 citation statements)

References 34 publications

(41 reference statements)

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“…The patient was consuming the supplement Green Tea Fat Burner ® , whose components, other than green tea, are not known as causing hepatotoxicity; on the contrary, some of them are considered to possess hepatoprotective effects (Fan et al 2015;Huang et al 2011). However, the young man was consuming also other supplements such as Nopal ® , an extract from cactus of Opuntia genus, used as source of dietary fibers in the management of overweight (Grube et al 2013), GNC Mega Men Sport ® , a complex mixture containing numerous vitamins, minerals among which are chromium, branched chain amino acids, l-carnitine, lycopene, choline, zeaxanthin, astaxanthin, alpha-lipoic acid and others and, finally, whey protein.…”

Section: Discussionmentioning

confidence: 99%

Hepatotoxicity of green tea: an update

2015

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Green tea (GT), obtained from the leaves of Camellia sinensis (L.) Kuntze (Fam. Theaceae), is largely used for its potential health benefits such as reduction in risk of cardiovascular diseases and weight loss. Nevertheless, it is suspected to induce liver damage. Present work reviews the hepatic adverse reactions associated with GT-based herbal supplements, published by the end of 2008 to March 2015. A systematic research was carried out on PubMed, MedlinePlus, Scopus and Google Scholar databases, without any language restriction. Moreover, some accessible databases on pharmacovigilance or phytovigilance were consulted. The causality assessment was performed using the CIOMS/RUCAM score. Nineteen cases of hepatotoxicity related to the consumption of herbal products containing GT were identified. The hepatic reactions involved mostly women (16/19); the kind of liver damage was generally classified as hepatocellular (16/19). The causality assessment between consumption of herbal preparation and hepatic reaction resulted as probable in eight cases and as possible in eleven cases. In seven cases, patients used preparations containing only GT, while twelve reactions involved patients who took multicomponent preparations (MC). The reactions induced by GT had a generally long latency (179.1 ± 58.95 days), and the outcome was always resolution, with recovery time of 64.6 ± 17.78 days. On the contrary, liver injury associated with MC had a shorter latency (44.7 ± 13.85 days) and was more serious in four cases that required liver transplantation and, when resolution occurred, the recovery time was longer (118.9 ± 38.79). MC preparations contained numerous other components, many of which are suspected to induce liver damage, so it is difficult to ascribe the toxicity to one specific component, e.g., GT. Present data confirm a certain safety concern with GT, even if the number of hepatic reactions reported is low considering the great extent of use of this supplement. The mechanism of GT hepatotoxicity remains unclear, but factors related to the patient are becoming predominant. A major safety concern exists when GT is associated with other ingredients that can interact between them and with GT, enhancing the risk of liver damage. Patients should be discouraged from using herbal or dietary supplements containing complex mixtures and should be encouraged to use herbal and dietary supplement possibly under supervision of healthcare professionals.

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Section: Discussionmentioning

confidence: 99%

Hepatotoxicity of green tea: an update

2015

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“…proliferation-related genes and may promote compensatory liver regeneration to prevent hepatic failure, suggesting that WZ may act as a therapy drug to limit liver injury (Fan et al, 2015). However, whether WZ can directly facilitate liver regeneration after liver resection and what related mechanisms are involved remain unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, we reported that WZ exerts significant hepatoprotective effects against acetaminophen-induced acute liver injury (Bi et al, 2013;Fan et al, 2015). This hepatoprotection, in large part, contributes to the ability of WZ to induce the expression of hepatocyte dmd.aspetjournals.org…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, our previous study found that 350 mg/kg WZ possessed therapeutic potential in acetaminophen hepatotoxicity through promoting liver regeneration after acute liver injury (Fan et al, 2015). Thus, we chose a dose of 350 mg/kg WZ to study the effect of WZ on liver regeneration after PHX.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, we reported that WZ exerted significant hepatoprotection against acetaminophen-induced liver injury and may promote compensatory liver regeneration, as it induced the expression of hepatocyte proliferation-related genes (Bi et al, 2013;Fan et al, 2015). However, the effects of WZ on liver regeneration after a two-thirds partial hepatectomy have not been determined.…”

Section: Introductionmentioning

confidence: 93%

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Schisandra sphenanthera Extract Facilitates Liver Regeneration after Partial Hepatectomy in Mice

Fan

et al. 2016

Drug Metabolism and Disposition

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Liver regeneration after surgical liver resection is crucial for the restoration of liver mass and the recovery of liver function. Schisandra sphenanthera extract (Wuzhi tablet, WZ) is a preparation of an extract from the dried ripe fruit of Schisandra sphenanthera Rehd. et Wils, a traditional hepatoprotective herb. Previously, we found that WZ could induce liver regeneration-related genes against acetaminopheninduced liver injury. However, whether WZ can directly facilitate liver regeneration after liver resection remains unknown. We investigated whether WZ has potential in promoting liver regeneration after a partial hepatectomy (PHX) in mice. Remnant livers were collected 1, 1.5, 2, 3, 5, 7, and 10 days after PHX. Hepatocyte proliferation was assessed using the Ki-67 labeling index. Western blot analysis was performed on proteins known to be involved in liver regeneration. The results demonstrated that WZ significantly increased the liver-to-body weight ratio of mice after PHX but had no effect on that of mice after a sham operation. Additionally, the peak hepatocyte proliferation was observed at 1.5 days in PHX/WZ-treated mice but at 2 days in PHX/saline-treated mice, as evidenced by the Ki-67 positive ratio. Furthermore, WZ significantly increased the protein expression of ligand-induced phosphorylation of epidermal growth factor receptor and up-regulated cyclin D1, cyclin D-dependent kinase 4, phosphorylated retinoblastoma, and proliferating cell nuclear antigen protein expression and down-regulated the expression of cell cycle inhibitors p21 and p27 in the regenerative process after PHX. These results demonstrate that WZ significantly facilitates hepatocyte proliferation and liver regeneration after PHX.

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Population pharmacokinetics of tacrolimus in Chinese adult liver transplant patients

Teng

Zhang

Wang

et al. 2022

Biopharm & Drug Disp

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Tacrolimus is widely used in organ transplantation to prevent rejection. However, the narrow therapeutic window and the large inter-and intra-individual variability in the pharmacokinetics (PK) of tacrolimus make it difficult for individualization of dosing. This study aimed at developing a population pharmacokinetic model for estimating the oral clearance of tacrolimus in Chinese liver transplant patients, and identifying factors that contribute to the PK variability of tacrolimus. Data of 151 liver transplant patients who received tacrolimus were analyzed in this study. The population PK model was analyzed and the covariates including population demographic and biochemical characteristics, drug combination, and genetic polymorphism were explored using non-linear mixed-effects modeling approach. A single-compartment population PK model was developed, and the final model was CL/F = (14.6-2.38 � cytochrome P450 (CYP) 3A5−3.72 � WZC+1.04 � (POD/9) +2.48 � COR) � Exp(η i ), where CYP3A5 was 1 for CYP3A5*3/*3, Wuzhi Capsule (WZC) was 1 when patients took tacrolimus combined with WZC, otherwise it was 0, corticosteroids (COR) was 1 when patients take tacrolimus combined with COR, otherwise, it was 0, POD was the post-operative day. Visual inspection and bootstrap indicated that the final model was stable and robust. In this study, we developed the first tacrolimus population PK model in Chinese adult liver transplant patients. We first determined the influence of WZC on tacrolimus in these people, which could provide useful PK information for the drug combination of tacrolimus and WZC. We also revealed the influence of genetic polymorphism of CYP3A5, POD, and a combination of COR on tacrolimus PK. Therefore, these significant factors should be taken into consideration in optimizing dosage regimens.

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Therapeutic Efficacy of Wuzhi Tablet (Schisandra sphenanthera Extract) on Acetaminophen-Induced Hepatotoxicity through a Mechanism Distinct from N-Acetylcysteine

Cited by 37 publications

References 34 publications

Hepatotoxicity of green tea: an update

Hepatotoxicity of green tea: an update

Schisandra sphenanthera Extract Facilitates Liver Regeneration after Partial Hepatectomy in Mice

Population pharmacokinetics of tacrolimus in Chinese adult liver transplant patients

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