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In this study, a composite cell model for evaluation of idiosyncratic drug-induced liver injury (IDILI) was established in vitro from the perspective of immune inflammation. And this model was used to evaluate the risk of IDILI for 2,3,5,4'-tetrahydroxy-cis-stilbene-2-O-β-glucoside (Cis-SG) and 2,3,5,4'-tetrahydroxy-trans-stilbene-2-O-β-glucoside (Trans-SG). To determine the low, medium, and high dosage of Cis-SG and Trans-SG, CellTiter-Glo® 3D Cell Viability Assay was used to detect the effects of Cis-SG and Trans-SG on cell viability of HepG2 cells in three dimensional (3D) culture, and MTT assay was used to detect the effects of Cis-SG and Trans-SG on cell viability of THP-1 derived macrophages. THP-1 derived macrophages were incubated by Cis-SG and Trans-SG directly or supernatants from HepG2 cells incubated with them. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of interleukin-1β (IL-1β) in the supernatants of the THP-1 derived macrophages. Western blot and reverse transcription-polymerase chain reaction (RT-PCR) were used to determine the expression of apoptosis-associated speck-like protein (ASC), Nod-like receptor protein 3 (NLRP3), cysteinyl aspartate specific proteinase-1 (caspase-1), and IL-1β in THP-1 derived macrophages. The results showed that there was no effect on the secretion of IL-1β in THP-1 derived macrophages incubated by Cis-SG and Trans-SG directly. However, the secretion of IL-1β, the protein and mRNA expression of ASC, NLRP3, caspase-1, and IL-1β significantly increased in THP-1 derived macrophages incubated by supernatants from HepG2 cells incubated with 1, 5, and 25 μmol·L-1 Cis-SG or 25 μmol·L-1 Trans-SG. In summary, the composite cell model for evaluation of IDILI established in vitro has been successfully applied in testing Cis-SG and Trans-SG. This composite cell model is helpful to evaluate and screen drugs with IDILI risk in vitro preliminarily, which provides methods for predicting and solving the idiosyncratic liver toxicity of drugs.
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Objective: To isolate the phenolic compounds obtained from the dried roots of Polygonum multiflorum and investigate their pharmacological activities. Methods: The chemical constituents were isolated and purified by combining them with a macroporous resin (DM-8), MCI gel, and Sephadex LH-20 and by performing ODS column chromatography. Their structures were elucidated by 1D and 2D NMR analyses, as well as mass spectrometry. The isolated compounds were evaluated to determine their hepatoprotective and α-glucosidase inhibitory activities in vitro. Results: Two phenolic compounds, namely, polygonimitin E (1) and polygonimitin F (2), were isolated from the dried roots of P. multiflorum. Compound 2 (10 µmol/L) only showed moderate hepatoprotective activity against N-acetyl-p-aminophenol (APAP)-induced HepG2 cell damage. Unfortunately, these two compounds exhibited no α-glucosidase inhibitory activity. Conclusion: Compounds 1 and 2 were new compounds. Compound 2 could be one of the potential hepatoprotective constituents of P. multiflorum.
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Objective: To extract and separate a polysaccharide from Polygonum multiflorum, characterize its structural features and study its immunomodulatory activity. Methods The polysaccharide from P. multiflorum (PMT) was isolated and purified by water extraction and ethanol precipitation following Q-Sepharose Fast Flow ion exchange chromatography column. Molecular weight of PMT was determined by high performance gel permeation chromatography-multiple angle laser light scattering (HPGPC-MALLS), and monosaccharide composition was analyzed by HPLC with PMP (1-phenyl-3-methyl-5-pyrazolone) pre-column derivatization, respectively. The structure of PMT was characterized by proton nuclear magnetic resonance spectrum (2D-NMR). The immunomodulatory activities were tested by MTT, neutral red colorimetric assay and Griess method. Results: PMT was a kind of α-1,4-glucan, and its molecular mass was 3.96 × 105. PMT promoted the proliferation and phagocytosis of RAW 264.7 cells, and significantly induced the increase of NO production in a dose-dependent manner. Conclusion: The polysaccharide from P. multiflorum is a linear α-1,4-glucan with potent immunomodulatory activity, which would be potentially developed as an effective drug.
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Objective: To study the mechanism that TSG can reduce plasma glucose level by inhibiting sodium-dependent glucose cotransporters 2 (SGLT2) and α-glucosidase in vitro and in vivo. Methods: Molecular docking method was used to study the binding affinities of TSG and diabetes related targets. The structures of targets were taken from Protein Data Bank or references. 1-NBDG and PNPG were used as the substrates for the inhibition assays of TSG against SGLT2 and α-glucosidase respectively in vitro. The antihyperglycemic activity of TSG was operated by oral glucose tolerance test (OGTT) and urinary glucose excretion (UGE) test in rats. Results: TSG was identified as the inhibitors of SGLT2 with the docking score of -9.35 less than -9.79 of dapagliflozin as the positive control and α-glucosidase with the docking score of -5.44 compared to -5.58 of acarbose as the positive control. TSG showed the inhibitory rate of 21.6% at the dose of 10 μmol/L against SGLT2 and 32.5% at the dose of 100 μmol/L in vitro test. Compared with model group, the group of 120 mg/kg dose had significant difference (P < 0.05) but the overall effect was not as strong as dapagliflozin in OGTT and UGE test. The result of rat in vivo test showed that glucose inhibition rate of TSG (120 mg/kg) was (9.3 ± 1.0)%, urinary glucose content was (435.5 ± 84.0) mg/kg, which showed certain hypoglycemic effect. Conclusion: TSG exhibited antiglycemic activity through inhibiting SGLT2 and α-glucosidase, which was considered to be a new lead compound of dual target inhibitors.
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Objective: The molecular identification method of Polygonum multiflorum from different producing areas was explored by using the sequencing of intergenic region of chloroplast genes psbA-trnH. Methods: A total of 116 samples of P. multiflorum were collected from 15 populations in seven provinces and autonomous regions. The total DNA was extracted and the sequences of psbA-trnH were amplified by PCR. The purified PCR products were sequenced and analyzed by MEGA 6.06 software. Results: The genetic distances among the populations of P.multiflorum are 0.001—0.187. In the maximum likelihood phylogenetic tree, 15 populations of P. multiflorum were clustered into two blanches. Conclusion: The genetic variation of P. multiflorum is significant and the psbA-trnH sequences of P. multiflorum can be used as germplasm source for molecular identification between Deqing regarded as geo-authentic habitat and other producing areas.
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Objective:To optimize the high pressure steaming processing technology for Polygonum multiflorum Thunb.by Box-Behnken response surface methodology , and compare with the traditional processing .Methods:The effects of factors such as steaming temperature, steaming time and drying temperature on polysaccharide content , stilbene glucoside content and normalized value in Po-lygonum multiflorumThunb.were studied by Box-Behnken response surface methodology .The content differences of polysaccharides and stilbene glucoside between the high pressure steaming processed product and the traditional processed product were evaluated .Re-sul ts:The best high pressure steaming processing conditions for Poyl gonumm luitlfo urm Thunb .were as follows:the steaming tempera -ture was 1254.℃ , the steaming time was3.1 h, and the drying temperature was 52℃.The contents of polysaccharides and stilbene glycosides in Polygonum multiflorum Thunb.processed by the high pressure steaming method were 1.24-fold and 5.26-fold higher than those processed by the traditional method .Conclusion:Box-Behnken response surface method can be used to optimize the high pres-sure steaming processing for Polygonum multiflorum Thunb., and the method is simple and predictable .
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OBJECTIVE This study investigated transcriptional regulation of the main chemical con-stituents of Polygonum multiflorum Thunb. including Stilbene Glucoside (THSG) and anthraquinone constituents (Emodin, Rhein, Aloeemodin, Chrysophanol and Physcion) and six potential liver injury constituents(gallic acid,quercetin,luteolin,kaempferol,resveratrol)on mediated by PXR CYP3A4.Early establishment of pregnane X receptor mediated CYP3A4 drug induced rapid screening technique was used to determine the effects of these constituents. METHODS First,effect of constituents on the cell activity was detected by MTS cell viability assay. IC50was calculated. Second, the expression vector and reporter vector were co-transfected into Hep G2 cells,10 μmol·L-1Rifampicin as a positive control, 10 μmol·L-1Ketoconazole as a negative control. After treated with different concentrations of (the an-thraquinone constituents concentrations were 2.5,5 and 10 μmol·L-1;the concentrations of Gallic Acid, Quercetin,Luteolin,Kaempferol,Apigenin,Resveratrol concentrations were 5,10 and 20 μmol·L-1)for 24 h,the cells were tested for dual luciferase activity.RESULTS The results show that the inhibitory ef-fect of THSG,Chrysophanol,Emodin,Rhein and Aloeemodin on CYP3A4 was inhibited by co-transfec-tion of pcDNA3.1 and pGL4.17-CYP3A4. The expression of pcDNA3.14-PXR and pGL4.17-CYP3A4 was induced by the four constituents. Besides, Emodin has a directly inducing effect. Four anthraqui-none constituentscan induce the effect of CYP3A4 by PXR, but Emodin can directly induce CYP3A4. THSG can inhibit CYP3A4,but in the presence of PXR plasmid can induce CYP3A4.For the six poten-tial liver injury constituents, results show that the plasmid pcDNA3.1 was cotransfected with pGL4.17-CYP3A4 regulation of Gallic Acid and Resveratrol on CYP3A4 inhibitory effects of Quercetin,Luteolin, Kaempferol have an induce effect; after pcDNA3.14-PXR and pGL4.17-CYP3A4 cotransfected, Quercetin, Luteolin, Kaempferol, Apigenin, Resveratrol have induced effect, three constituents'induc-tion effect had significant difference.CONCLUSION 12 kinds of Polygonum multiflorum Thunb.constit-uents have inhibitory or activating effects on CYP3A4, after the participation of PXR, 9 components have induced effects on CYP3A4, and the induction effect of 6 components has significant difference. The results suggested that we should pay attention to potential drug interactions when combined with Polygonum multiflorum Thunb.,and improve safety and efficacy.
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Objective: To investigate the protective effect of Liuweiwuling Tablets of Polygonum multiflorum (PM)-induced idiosyncratic hepatotoxicity. Methods: Eighty Sprague-Dawley (SD) rats were randomly divided into control group, LPS group, PM group, LPS + PM group, LPS + PM + Liuweiwuling Tablets low, medium, and high dose (0.4, 0.8, and1.6 g/kg) groups, and LPS + PM + positive drug Biphenyl group (2 mg/kg). All groups were orally given Liuweiwuling Tablets and Biphenyl once daily for consecutive 2 d according to the different dosages. On day 3, except the normal group and LPS group oral administration of distilled water, all groups were given PM (crude drug 2.16 g/kg), 3 h after the group by the tail vein injection LPS (2.8 mg/kg) according to the different dosage; After 7 h, the rats were anesthetized with sodium pentobarbital, and the inferior vena cava was used to collect blood and liver tissue samples were collected. HE staining was used to observe the pathological changes of liver tissue, and the contents of ALT, AST, TNF-α, IL-1β, IL-6, and IFN-γ in rat plasma were determined. TUNEL assay analyzed hepatocyte apoptosis, and immunohistochemical staining was performed to detect the liver tissue expression activity of NF-κB p65. Results: Liuweiwuling Tablets could decrease ALT and AST levels of PM-induced idiosyncratic liver injury rat plasma, reduce liver pathological injury and hepatocyte apoptosis, inhibit the expression of NF-κB p65, and decrease plasma TNF-α and other inflammatory cytokines. Conclusion: Liuweiwuling Tablets can reduce inflammation through the inhibition of NF-κB signaling pathway, and prevent of PM induced idiosyncratic liver injury.
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Objective: To study the chemical constituents from Polygonum multiflorum. Methods: The constituents were isolated and purified by macroporous adsorbent resin (DM-8), gel chromatography, silica chromatography, and other modern separation methods, and the structures were identified by spectral analyses. Results: Ten compounds were isolated and identified as thunberginol C 6-O-β-D-glucopyranoside (1), p-hydroxybenzaldehyde (2), trans-N-caffeoyltyramine (3), (Z)-2,3,5,4'-tetrahydroxy-stilbene-2-O-β-D- glucoside (4), (E)-2,3,5,4'-tetrahydroxy-stilbene-2-O-β-D-glucoside (5), pieceid-2″-O-gallate (6), (E)-2,3,5,4'-tetrahydroxystilbene-2-O-β-D-(3″-galloyl)-glucoside (7), tricin-7-O-β-D-glucoside (8), torachrysone-8-O-β-D-glucoside (9), and emodin-8-O-β-D-glucoside (10). Conclusion: Compound 1 is a new compound named as polygonimitin D. Compounds 3 and 8 are isolated from this plant for the first time.
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In this study, the three dimensional(3D)organoid culture system was established by liquid overlay method, and applied as an effective model to evaluate the hepatic injury of susceptible compounds in Polygonum multiflorum Thunb. Compared with the ordinary two dimensional(2D)culture of liver cells, the albumin expression of L02 cells and HepG2 cells were increased by 2.5 and 6.7 times in the 3D organoid culture system, respectively. After the cultivation of 21 days, urea generation levels of 3D culture were increased by 8.3 and 15.5 times. More importantly, HepG2 cells were more suitable to development of organoids than L02 cells. The gene expressions of phase I and II drug metabolism enzymes of HepG2 cells cultured as 3D organoids were significantly increased than that in 2D culture, such as the fold changes of CYP2C9 was up to 381.9, CYP3A4 to 87.0, CYP2D6 to 312.6. In addition, drug transporter relative genes were also up-regulated. The results demonstrated that the liver synthesis and metabolic function of the 3D model were better than that of the 2D cultured hepatocytes. The results of hepatotoxicity evaluation showed this developed model can be used to assess the hepatotoxicity of acetaminophen and other positive control drugs, which were considered with defined hepatotoxicity. On the 3D culture model, the IC50 value of repeated drug dose administration was significantly lower than that of single dose administration. However, the IC50 of 2,3,5,4'-tetrahydroxy-cis-stilbene-2-O-β-glucoside(cis-SG), which is the susceptible compound in Polygonum multiflorum Thunb., could not be detected in 2D cultured model. With the treatment of a single dose administration in organ 3D culture model, the IC50 of cis-SG was 1.9 times than that of cyclosporine A, and the IC50 of 2,3,5,4'-tetrahydroxy-trans-stilbene-2-O-β-glucoside(trans-SG)was 4.1 times than cis-SG. The hepatotoxicity results of cis-SG and trans-SG on the 3D cultures were similar to in vivo toxicity results obtained in previous work. On organ 3D culture model, the IC50 of cis-SG with repeat of administration decreased compared with that with single dose administration, suggesting that long-term medication may increase the risk of liver injury. In summary, the 3D organoid culture system can be used for a long period to preserve the capacity of liver synthesis and metabolism. The organoids were a model suitable for evaluation of mechanism of the drugs with low toxicity.
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OBJECTIVE To investigate the hepatotoxicity mechanisms of ethanol extract of Radix Polygoni Multiflori (RPM) and Radix Polygoni Multiflori Praeparata (RPMP) by high-content screen assay.METHODS HepG2 cells were treated with RPM (10,25,50,100,200 and 300 mg·L-1) and RPMP (10,50,100,300,600 and 1200 mg· L-1) for 3-24 h,respectively.The cell viability was detected by a CellTiter-GloTM luminescent cell viability assay kit.Cell count,reactive oxygen species (ROS),mitochondrial membrane potential (MMP),glutathione (GSH),superoxide dismutase 2 (SOD2),activating transcription factor 4 (ATF4),apoptosis,and cell cycles were investigated by high-content screen assay.Besides,SOD2 and ATF4 levels were confirmed by Western blotting.RESULTS RPM 300 mg· L-1 showed nearly 48 ％ reduction in cell viability compared with cell control (P＜0.01),while RPMP had no significant effect at the same concentration.Both RPM and RPMP decreased the level of MMP (P＜0.05) but incresed levels of GSH,ROS,SOD2 and ATF4 significantly (P＜0.05).Besides,RPM 200 mg· L-1 significantly increased the expression of SOD2 (P＜0.05) at 3 h by high-content screen assay,and the enhanced expression of ATF4 was shown at 6 h (P＜0.05).RPMP 300 mg· L-1 markedly increased the expression of ATF4 at 6 h (P＜0.05),while the expression of SOD2 significantly increased at 24 h (P＜0.05).CONCLUSION Both RPM and RPMP have some cytotoxicity,and the cytotoxicity of RPM is stronger than that of RPMP.The hepatotoxicity mechanisms of RPM and RPMP may be related to cell apoptosis caused by long-term oxidative stress and endoplasmic reticulum stress.
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Aim To study the effect of emodin in Po-lygonum multiflorum on the expression of CYP450 isoenzymes in L02 hepatocytes and explore its mecha-nism of cytotoxicity. Methods L02 cells were treated with different concentrations of emodin. Cell viability was examined by MTS assay kit, and cell membrane injury was examined by detecting the release rate of lactate dehydrogenase( LDH) . The expression of cyto-chrome P450 mRNA was detected by real time PCR. Results The result of MTS assay showed that L02 cells viability was significantly reduced following expo-sure to emodin in a concentration and time dependent manner. The LDH release rate of L02 cells significant-ly increased after exposure to emodin for 48 h com-pared with the control group. On the mRNA level, compared with the control group,emodin had inductive effects on mRNA of each CYP450 enzyme, while had significant inductive effects on mRNA of CYP1 A1 and CYP1 B1 in a concentration and time dependent man-ner. Conclusion Emodin in Polygonum multiflorum may generate significant liver injury in L02 cells and has inductive effects on CYP450 enzyme activity.
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Objective To research the toxicity of ethanol extracts from Poylgonum multiflorum Thunb (PMT) induced by endotoxin of Gram-negative bacteria lipopolysaccharide (LPS) in rat liver, and then investigate the hepatotoxicity mechanisms of PMT on immune inflammatory signal pathway Toll-Like receptor 4 (TLR4) -interferon regulated factor3 (IRF-3). Methods SD rats were randomly assigned into normal control, LPS (4 mg/kg), acetaminophen APAP (625 mg/kg), PMT 6 g/kg (PMT- L), PMT 12 g/kg (PMT-H), LPS+APAP and LPS+PMT-L/-H groups. The 4 groups later were injected LPS 4 mg/kg by caudal vein, after 2 h, the corresponding drugs were administered once a day for 7 consecutive days, respectively. The changes of weight of rats were observed every day. The tissue morphology of liver tissue of rats on 2 h, 14 h, 5 d, 8 d after administration were detected by hematoxylin-eosin staining respectively. Real time quantitative PCR (RT-qPCR) method and Western blotting were used to detect the expression of TLR4, TRIF and IRF3 in the TLR4 signaling pathway in liver cells. Results Two hours after the rat tail vein injection of LPS, the liver tiny granulomas of rats could be observed in LPS-induced groups, and then, the liver injury of rats in LPS group was gradually recovered. Eight Days after LPS induction, the liver tissue structure of rats in LPS group was clear and complete, but in LPS + APAP group and LPS + PMT 6 or 12 g/kg groups, the focal necrosis of hepatocytes, with inflammatory cell infiltration could be observed. The results of RT-qPCR and Western blotting showed that in oral administration of PMT groups, the expression of TLR4, TRIF and IRF-3 mRNA and protein in the liver cells had no significant change compared with the normal control group. But in 4 groups induced with LPS, the expression of TLR4, TRIF and IRF- 3 mRNA and protein in the liver cells were significantly higher than that of the normal control group and LPS group (P<0.05). Conclusion PMT can cause liver damage induced by LPS, the hepatotoxicity is related to the positive regulation of TLR4/IRF-3 signaling pathways, which is not related to the dosage of PMT. The results show that activating TLR4/IRF3 signaling pathway is one of the mechanisms of liver injury of PMT in rats induced by LPS.
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Objective To research the toxicity of ethanol extracts from Poylgonum multiflorum Thunb(PMT)induced by en?dotoxin of Gram-negative bacteria lipopolysaccharide(LPS)in rat liver,and then investigate the hepatotoxicity mechanisms of PMT on immune inflammatory signal pathway Toll-Like receptor 4(TLR4)-interferon regulated factor3(IRF-3). Methods SD rats were randomly assigned into normal control,LPS(4 mg/kg),acetaminophen APAP(625 mg/kg),PMT 6 g/kg(PMT-L),PMT 12 g/kg (PMT-H),LPS+APAP and LPS+PMT-L/-H groups. The 4 groups later were injected LPS 4 mg/kg by caudal vein,after 2 h,the corre?sponding drugs were administered once a day for 7 consecutive days,respectively. The changes of weight of rats were observed every day. The tissue morphology of liver tissue of rats on 2 h,14 h,5 d,8 d after administration were detected by hematoxylin-eosin stain? ing respectively. Real time quantitative PCR(RT-qPCR)method and Western blotting were used to detect the expression of TLR4, TRIF and IRF3 in the TLR4 signaling pathway in liver cells. Results Two hours after the rat tail vein injection of LPS,the liver tiny granulomas of rats could be observed in LPS-induced groups,and then,the liver injury of rats in LPS group was gradually recovered. Eight Days after LPS induction,the liver tissue structure of rats in LPS group was clear and complete,but in LPS+APAP group and LPS+PMT 6 or 12 g/kg groups,the focal necrosis of hepatocytes,with inflammatory cell infiltration could be observed. The results of RT-qPCR and Western blotting showed that in oral administration of PMT groups,the expression of TLR4,TRIF and IRF-3 mRNA and protein in the liver cells had no significant change compared with the normal control group. But in 4 groups induced with LPS,the expression of TLR4, TRIF and IRF-3 mRNA and protein in the liver cells were significantly higher than that of the normal control group and LPS group(P<0.05). Conclusion PMT can cause liver damage induced by LPS,the hepatotoxicity is related to the positive regulation of TLR4/IRF-3 signaling pathways,which is not related to the dosage of PMT. The results show that activating TLR4/IRF3 signaling pathway is one of the mechanisms of liver injury of PMT in rats induced by LPS.
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Objective: To investigate the effects of crude and prepared Polygonum multiflorum (PM) to liver injury based on idiosyncratic hepatotoxicity model co-treated with lipopolysaccharide (LPS) at a non-hepatotoxic dose, aiming to compare the difference between them. Methods: The Sprague-Dawley (SD) rats were used by ig administration, respectively with 50% alcohol extracts from crude or prepared PM alone or co-treated noninjurious dose of bacterial lipopolysaccharide (LPS, 2.8 mg/kg) via tail vein injection. Blood was collected from the inferior vena cava into a sodium citrate-anticoagulant tube, and the liver was removed. The plasma samples separated from the collected blood were used for analysis on ALT and AST activities and the isolated livers were used for histopathological assessment. Results: Both crude and prepared PM were nontoxic on normal SD rats under the dose of 17.28 g/kg, when co-treated with LPS, the liver injury was found at the dose of 1.08 g/kg of crude PM, however, 8.64 g/kg of prepared PM. Conclusion: When processed, the maximum safe therapeutic dosage of PM would be enlarged from 1.08 g/kg of crude PM that is close to clinical dosage to 8.64 g/kg of prepared PM, which is four times larger than the crude one in LPS model. It shows that toxicity of PM could be reduced by processing.
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Objective To screen and clone the genes related to stilbene glucosides biosynthesis in Polygonum multiflorum Thunb. Methods The differentially expressed genes in the root, stem and leaf of Polygonum multiflorum which have different contents of stilbene glucosides were screened by differential display reverse transcription polymerase chain reaction (DDRT-PCR). After pMD19-T carrier was inserted into the obtained differential genes for sequencing and comparison, the gene function was analyzed. Results Fifty-one differentially expressed cDNA fragments were found. Of them, 9 were used for the identification by semi-quantitative PCR. The identification results presented 3 positive fragments, one fragment was specifically expressed in the stem and leaf of Polygon-um multiflorum Thunb., sharing high homology with glycine dehydrogenase, and 2 were specifically expressed in the root of Polygonum multiflorum Thunb., having high homology with enoyl-CoA hydratase and aminopeptidase N, respectively. Conclusion Three homologous gene sequences obtained through DDRT-PCR provide a basis for the further study of biosynthetic pathway of stilbene glucoside from Polygonum multiflorum Thunb..
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[Objective] To sum up researches on components, pharmacological actions and toxicity of Polygonum multiflorum Thunb(Heshouwu). [Method] The research reference about Heshouwu in CNKI, VIP and PUBMAD database is col ected and calssified to three aspects on components, pharmacological actions and toxicity.[Result]①On components:Heshouwu contains stilbene, lecithin, anthraquinone, flavonoids, tannin and trace elements. The stilbene and anthraquinone are the mainly active components. Producing area, growth years, harvest time and processing methods are factors affecting the content of the components such as TSG in Heshouwu; Macroporous adsorption resin is the main separation method for preconcentration of TSG and anthraquinone constituents; ② On pharmacological actions and toxicity: Heshouwu has effects of hypolipidemic and liver protection, antioxidative, anti-osteoporosi, hpyerglycemic, antidepressive and antibiosis, the hypolipidemic and liver protection are the main effects which have been studied more. A reversible liver injury which displays as abnormal liver function parameter and bile metabolic disorder would be induced if the Heshouwu is administrated with a large dosage for long term. The possible components which would induce the toxicity in Heshouwu are tannin and anthraquinone, and the anthraquinone is the component with double effects of toxicity and therapy which should be considered in clinical application. [Conclusion]Reducing lipid and protecting liver is the main pharmaceutical function of the herb. As a commonly used Chinese herb for liver protection, the studies on alcoholic hepatic injury protection of Heshouwu may be a point for the researchers to focus on. The comparison studies on hypolipidemic and liver protection between Hesouwu and its processing products, and the correlations between components and pharmacological actions are worth study further.
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BACKGROUND/AIMS: Complementary medicines, including herbal preparations and nutritional supplements, are widely used without prescriptions. As a result, there has been growing interest in the risk of hepatotoxicity with these agents. It is difficult to determine causal relationships between these herbal preparations and hepatotoxicity. We report on 25 patients diagnosed with toxic hepatitis following ingestion of Polygonum multiflorum Thunb. METHODS: Twenty-five patients (median age, 48 years [24 to 65 years]; M:F=18:7) with suspected P. multiflorum Thunb-induced liver injury were admitted to our hospital between 2007 and 2009. We analyzed clinical and histological data, including the types and the duration of P. multiflorum Thunb intake and the duration of hospital care. We also determined the type of liver injury using the R ratio (serum activity of ALT/serum activity of ALP). RESULTS: The types of complementary medicine used included tea (n=16), liquor (n=5), tea and liquor (n=2), powder (n=1), and honeyed pudding (n=1). The most common presenting sign was jaundice (76%), and 18 patients (72%) had evidence of hepatocellular liver injury. Histological findings were consistent with acute hepatitis in all cases (n=10) for which liver biopsy was performed. Twenty-three patients (91.6%) recovered with conservative management, 1 patient (4%) had a liver transplant, and 1 patient (4%) died of hepatic failure. CONCLUSIONS: In our cases, we found that P. multiflorum Thunb could be hepatotoxic and could lead to severe drug-induced liver injury, and even death.
Subject(s)
Humans , Biopsy , Complementary Therapies , Chemical and Drug Induced Liver Injury , Eating , Hepatitis , Jaundice , Liver , Plant Preparations , Polygonum , Prescriptions , Tea , TransplantsABSTRACT
The desire to maintain youth and beauty has led to an increase in the use of health foods and herbs. Because Polygonum multiflorum Thunb. is thought to prevent hair loss and maintain black hair, this herb in particular has captured public interest in Korea and China. Although there have been many reports regarding the toxic effects of herbs and health foods, the potential toxicity of this herb has not yet been reported. Here, we discuss two cases of toxic hepatitis due to Polygonum multiflorum ingestion and present a review of the relevant literature.
Subject(s)
Adolescent , Humans , Beauty , China , Chemical and Drug Induced Liver Injury , Eating , Hair , Food, Organic , Korea , PolygonumABSTRACT
Several cases of Polygonum multiflorum Thunb-induced hepatitis have been reported worldwide. Anthraquinone is an active ingredient of P. multiflorum Thunb. that has been thought to play a role in its hepatotoxicity. Here we report the case of a 34-year-old Korean man who had P. multiflorum Thunb-induced hepatitis and reactivation of pulmonary tuberculosis caused by bone marrow suppression, which developed simultaneously. He was admitted to our hospital with recently developed fatigue and aggravated jaundice. He was a previously healthy man except for the sequelae of pulmonary tuberculosis seen on chest X-ray. He had a 30-day history of ingesting the root of P. multiflorum as a form of liquor and tea. The patient was diagnosed with P. multiflorum Thunb-induced hepatitis after excluding all other potential causes of acute hepatitis. Liver function gradually improved following the total cessation of the consumption of the material. However, he suffered from spiking fever with progressive pancytopenia during the hospital stay. A bone marrow biopsy showed markedly hypocellular marrow, suggesting transient bone marrow suppression, which was probably caused by extrinsic factors such as drugs, toxins, and viral infection. Although he began to complain of a dry cough, repeated sputum investigations revealed positive acid-fast bacillus staining. The fever subsided and pancytopenia improved after treatment for pulmonary tuberculosis. These observations suggest that P. multiflorum Thunb induces both bone marrow suppression and hepatotoxicity.