Curative effects of traditional Chinese medicine on liver fibrosis: A protocol for a systematic review and meta-analysis.

BACKGROUND: Assessing the effectiveness and safety of traditional Chinese medicine on liver fibrosis is the main purpose of this systematic review protocol. METHODS: The following electronic databases will be searched from their respective inception dates to 1st December 2021: PubMed, MEDLINE, the Cochrane Library, Embase, WorldSciNet, Ovid, the Allied and Complementary Medicine Database, the Web of Science, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, the Chongqing VIP Chinese Science and Technology Periodical Database, the Wanfang Database, and the China Biology Medicine Disc. All published randomized controlled trials in English or Chinese related to curative effects of Traditional Chinese medicine on liver fibrosis will be included. The primary outcome is the levels of serum hyaluronic acid, laminin, type III procollagen, and type IV procollagen. There is no secondary outcomes. Two reviewers will conduct the study selection, data extraction, and assessment independently. The assessment of risk of bias and data synthesis will be conducted with Review Manager Software V.5.2. RESULTS: The results will provide a high-quality synthesis of current evidence for researchers in this subject area. CONCLUSION: The conclusion of our study will provide an evidence to judge whether traditional Chinese medicine is an effective intervention for patients with liver fibrosis. REGISTRATION NUMBER: INPLASY202110017.

Effects of different therapeutic modalities for postacne scars on circulating collagen III.

BACKGROUND: Therapies for postacne scarring act through modulation of elastin and collagen, and collagen III might therefore represent a biomarker of treatment effectiveness. PATIENTS AND METHODS: Patients (n = 70) with postacne scars and individuals without scars (n = 56) were included in this case-control study. Patients were treated with Dermaroller microneedling, trichloroacetic acid chemical reconstruction, punch excision, or scar subcision. Scar severity was graded immediately before and after treatment with a photographic quartile scale and the ECCA scale. Serum levels of collagen III were measured in control individuals and in patients, before treatment, 1 month after the first treatment session, and 4 months after the final session. RESULTS: Circulating levels of collagen III were significantly higher in patients with postacne scarring (24.1 ± 12.5) before treatment than in control individuals (2.6 ± 0.8). Circulating levels of collagen in patients were significantly lower 4 months posttreatment (14.3 ± 8.1) than at baseline. The mean percentage change in serum collagen III was positively correlated with both the mean percentage improvement by photographic evaluation (r = .530, P < .000) and the mean percentage change in the ECCA scale (r = .632, P < .000). CONCLUSION: Circulating collagen III is a biomarker for improvement of postacne scarring following different therapies.

[Effects of Corbrin Shugan capsule on dimethylnitrosamine-induced hepatic fibrosis in rats].

OBJECTIVE: To investigate the effects of Corbrin Shugan capsule on dimethylnitrosamine (DMN)-induced hepatic fibrosis in rats. METHODS: Hepatic fibrosis was induced by DMN in AD rats. The serum concentrations of III pro-collagen (III PC),laminin (LN) and tissue inhibitor of metalloproteinase-1(TIMP-1) were determined with ELISA. The concentration of albumin (ALB) in sera and the content of hydroxyproline (Hyp) in liver tissues were determined with chemical colorimetric and HPLC, respectively. The fibrosis area was measured with Motic Med 6.0 digital medical image analysis system. RESULTS: Compared to model group the high-dose (450 mg kg(-1)),mid-dose (270 mg kg(-1)) and low-dose (90 mg kg(-1)) groups of Corbrin Shugan capsule had significantly lower serum content of III PC [34.46 ± 13.95),(36.15 ± 9.46), and (40.58 ± 7.72)ng ml(-1) compared with (49.38 ± 10.95)ng ml(-1),P<0.05 or P<0.01],TIMP-1 [(16.65 ± 4.24),(16.66 ± 4.34),and (18.99 ± 6.05)ng ml(-1) compared with (30.84 ± 14.48)ng ml(-1), P<0.05 or P<0.01], LN [(12.94 ± 4.29), (12.96 ± 3.21),and (15.32 ± 8.00)ng ml(-1) compared with (30.22 ± 17.00)ng ml(-1),P<0.05 or P<0.01] and smaller hepatic fibrosis area [(0.02240 ± 0.01337), (0.02176 ± 0.01460) and (0.02384 ± 0.01405)µm(2) compared with vs (0.03929 ± 0.01732)µm2, P<0.05 or P<0.01]; the high-dose and mid-dose groups of Corbrin Shugan capsule had significantly lower content of Hyp in liver tissues [(0.77 ± 0.09) and (0.81 ± 0.09)µg µmg(-1) compared with (1.06 ± 0.33)µg mg(-1),P<0.05 or P<0.01]; and the high-dose group of Corbrin Shugan capsule significantly increased the content of ALB in sera [(34.02 ± 4.17)g L(-1) compared with (30.25 ± 4.21)g L(-1),P<0.05]. CONCLUSION: Corbrin Shugan capsule is effective in treatment of DMN-induced hepatic fibrosis in rats.

Effects of Fufang Biejia Ruangan pills on hepatic fibrosis in vivo and in vitro.

AIM: To explore the protective effect and the relevant mechanisms of Fufang Biejia Ruangan Pills (FFBJRGP) on hepatic fibrosis in vivo and in vitro. METHODS: Hepatic fibrosis was induced by carbon tetrachloride composite factors. Adult Wistar rats were randomly divided into four groups: normal control group; hepatic fibrosis model group; FFBJRGP-treated group at a daily dose of 0.55 g/kg; and colchicine-treated group at a daily dose of 0.1 g/kg. The effects of FFBJRGP on liver function, serum levels of hyaluronic acid (HA), type IV collagen (CIV), type III procollagen (PC III), laminin (LN), histopathology, and expression of transforming growth factor (TGF-ß1) and Smad3 in hepatic fibrosis were evaluated in vivo. The effects of FFBJRGP on survival rate, hydroxyproline content and cell cycle distribution were further detected in vitro. RESULTS: Compared with the hepatic fibrosis model group, rats treated with FFBJRGP showed a reduction in hepatic collagen deposition and improvement in hepatic lesions. Compared with those of the model group, the activities of alanine aminotransferase (62.0 ± 23.7 U/L) and aspartate aminotransferase (98.8 ± 40.0 U/L) in the FFBJRGP-treated group were decreased (50.02 ± 3.7 U/L and 57.2 ± 30.0 U/L, respectively, P < 0.01). Compared with those in the model group, the levels of PCIII (35.73 ± 17.90 µg/mL), HA (563.82 ± 335.54 ng/mL), LN (89.57 ± 7.59 ng/mL) and CIV (29.20 ± 6.17 ng/mL) were decreased to 30.18 ± 9.41, 456.18 ± 410.83, 85.46 ± 7.51 and 28.02 ± 9.45 ng/mL, respectively. Reverse-transcriptase polymerase chain reaction and Western blotting also revealed that expression of TGF-ß1 and Smad3 were down-regulated in vivo. Cell proliferation was inhibited, the level of hydroxyproline was decreased compared with the control group (P < 0.01), and the cell cycle was redistributed when exposed to FFBJRGP in vitro. CONCLUSION: FFBJRGP inhibits hepatic fibrosis in vivo and in vitro, which is probably associated with downregulation of fibrogenic signal transduction of the TGF-ß-Smad pathway.

Impact of low versus conventional doses of chemotherapy during transcatheter arterial chemo-embolization on serum fibrosis indicators and survival of liver cancer patients.

OBJECTIVES: To explore the impact of low- vs conventional-dose chemotherapy via transcatheter arterial chemo-embolization (TACE) on serum fibrosis indicators and treatment efficacy of hepatocellular cancer patients (HCC). MATERIALS AND METHODS: Patients fulfilling the eligibility criteria were assigned to TACE in Group A (with low-dose chemotherapy) or Group B (conventional-dose chemotherapy). Four serum fibrosis related indicators, hyaluronic acid(HA), human pro-collagen type-III (hPC-III), laminin (LN), and collagen type-IV(IV-C) before TACE were compared with the values 7 days after TACE. The response rate and survival time were also compared between the two groups. RESULTS: Fifty patients with HCC were enrolled in this study, including 25 in Group A and 25 in Group B. No significant differences were detected between the two groups in the four indicators before TACE. After TACE, the value of the four serum indicators increased significantly in Group B. However, no significant differences regarding these four indicators were found in Group A after TACE. Significant differences were demonstrated between the two groups after TACE, but median survival time and 1 or 2 year overall survival rates did not differ (P>0.05). CONCLUSIONS: Low-, compared with conventional-dose chemotherapy exerts the same impact on the variation of fibrosis related indicators and has no influence on median survival time and survival rate after TACE in HCC patients.

Effect and mechanism of methyl helicterate isolated from Helicteres angustifolia (Sterculiaceae) on hepatic fibrosis induced by carbon tetrachloride in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Methyl helicterate is a triterpenoid isolated from Helicteres angustifolia (Sterculiaceae), one of the valuable traditional Chinese herbs. Antifibrotic activities of H. angustifolia have been extensively proved. AIM OF THE STUDY: The purpose of this study was to investigate the effect of methyl helicterate (MH) on liver fibrosis in rats induced by carbon tetrachloride (CCl(4)) and to explore its underlying mechanism. MATERIALS AND METHODS: Hepatic fibrosis was induced in male Sprague-Dawley (SD) rats by intragastric administration with 2 ml/kg CCl(4) (mixed 1:1 in peanut oil) twice a week for 12 weeks. To evaluate the effect of MH (16.72, 33.45, 66.90 mg/kg) on hepatic fibrosis, liver function, histological study and hepatic fibrosis evaluation were performed. Liver function was assessed by determining the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (Alb) and total protein (TP). The biomarkers such as hydroxyproline (Hyp), hyaluronic acid (HA), type III precollagen (PCIII) and laminin (LN) were examined for the evaluation of hepatic fibrosis. The underlying mechanism was investigated by measuring oxidative stress level and detecting the expression of TGF-ß1 mRNA and Smad3 protein. RESULTS: MH (33.45, 66.90 mg/kg) treatment significantly inhibited the loss of body weight and the increase of liver index in rats induced by CCl(4). MH also improved the liver function as indicated by decreasing serum enzymatic activities of ALT, AST, TP and Alb (P<0.05). Histological results indicated that MH alleviated liver damage and reduced the formation of fibrous septa. Moreover, MH significantly decreased liver Hyp, HA, LN and PCIII (P<0.05). Research on mechanism showed that MH could markedly reduce liver malondialdehyde (MDA) concentration, increase activities of liver superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and inhibit the expression of TGF-ß1 mRNA and Smad3 protein (P<0.05). CONCLUSIONS: Our findings indicated that MH can inhibit CCl(4)-induced hepatic fibrosis, which may be ascribed to its radical scavenging action, antioxidant activity, and modulation of TGF-ß-Smad3 signaling pathway.

Liver fibrosis and five year survival of hepatocellular cancer cases undergoing transcatheter arterial chemo embolization using small doses.

OBJECTIVE: To investigate liver fibrosis, TGF-?1 levels and curative effects on hepatocellular carcinoma (HCC) with small and conventional dose perfusion chemotherapy by transcatheter arterial chemo embolization (TACE). METHODS: Thirty-six hepatocellular carcinoma patients not indicated for surgical resection underwent super- selective transcatheter arterial chemoembolization, divided into small dose (n=15) and conventional dose (n=21) chemotherapy groups. RESULTS: With conventional doses, four indices of liver fibrosis focusing on hyaluronate acide (HA), human procollagen type-III (hPC-III), collagen type-IV (IV-C) and transforming growth factor-ßl (TGF-ß1) were obviously increased postoperative compared with preoperative (P<0.01); in contrast, with small doses there were no significant differences except for TGF-ß1. Five year survival demonstrated no significant differences between the two groups (P>0.05). CONCLUSION: To hepatocellular carcinoma patients treated by TACE, reducing doses of chemotherapy drugs can reduce progress of liver fibrosis, without impacting on five year survival.

Total glucosides of Danggui Buxue Tang attenuates bleomycin-induced pulmonary fibrosis via inhibition of extracellular matrix remodelling.

OBJECTIVES: This study was designed to investigate the antifibrosis effects and possible mechanism of action of total glucosides of Danggui Buxue Tang (DBTG) on bleomycin-induced pulmonary fibrosis in rats. METHODS: DBTG was extracted from Radix Astragali and Radix Angelicae Sinensis. Pulmonary fibrosis was induced by intratracheal instillation of bleomycin (5 mg/kg) in Wistar rats. Subsequently, the rats received daily intragastric administration of DBTG (16, 32 or 64 mg/kg per day) or cortisone (3 mg/kg) 1 day after bleomycin instillation for 4 weeks. Histological changes in the lung were evaluated by hematoxylin and eosin and Masson's trichrome staining. Markers of fibrosis in serum were determined by radioimmunoassay. The mRNA expression of metalloproteinases 1 and 9 (MMP-1, MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) in lung tissue were detected by reverse transcription PCR. KEY FINDINGS: DBTG administration attenuated the degree of alveolitis and lung fibrosis, and markedly reduced the elevated levels of hyaluronic acid, laminin, type III procollagen and type IV collagen in serum. DBTG decreased the mRNA levels of MMP-9 and TIMP-1. MMP-1 expression was only moderately decreased by DBTG. CONCLUSIONS: DBTG had an inhibitory effect on bleomycin-induced pulmonary fibrosis and its effect may be associated with the ability of DBTG to inhibit the synthesis of extracellular matrix and balance the MMP/TIMP-1 system.

Vitamin E reduces hepatic fibrosis in mice with Schistosoma japonicum infection.

To investigate whether vitamin E protects against hepatic fibrosis in mice with Schistosoma japonicum infection, 24 pathogen-free Kunming mice were selected and randomly divided into four groups: control (uninfected, untreated), model (infected, untreated), low-dose intervention (infected, vitamin E-treated, 30 mg/g bodyweight/day) and high-dose intervention (infected, vitamin E-treated, 60 mg/g bodyweight/day). Mice were infected with Schistosoma japonicum by inoculating abdominal skin with snail hosts. The activities of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) were detected in hepatic tissue by colorimetry. The expression levels of laminin (LN), hyaluronic acid (HA), procollagen type Ⅲ (PC-III) and type Ⅳ collagen (IV-C) were detected in the serum by radioimmunoassay. Finally, areas and numbers of granulomas were assessed through histopathology 42 days following treatment. The results revealed that mean areas of granulomas were smaller in the low- and high-dose intervention groups compared to those in the model group. Furthermore, the higher dose of vitamin E resulted in smaller granulomas than the low dose. The levels of LN, HA, PC-III and IV-C in the serum were lower following vitamin E treatment than in the model group. By contrast, activity of SOD, GPx and CAT in hepatic tissue was higher following vitamin E treatment compared to the model group. The activity of MDA was lower in hepatic tissue following vitamin E treatment compared to the model group, but was higher compared to controls. In general, the higher dose of vitamin E affected measurements to a greater extent than the lower dose. In conclusion, vitamin E treatment may reduce the growth of granulomas, slowing the process of hepatic fibrosis, and this effect may be the result of the altered activity of the oxidation-reduction enzyme system.

Glutamine supplementation prevents collagen expression damage in healthy urinary bladder caused by radiotherapy.

OBJECTIVE: Patients who have had pelvic radiotherapy as part of their cancer therapy may develop subsequent urinary bladder effects such as hyperactive bladder, incontinence, and dysuria. Therefore, the goal of this study was to evaluate whether glutamine supplementation could prevent collagen expression damage in healthy urinary bladder caused by radiotherapy. METHODS: Fifteen adult Wistar rats were separated into a control group that received food and water ad libitum (C group), an irradiated group that received a single pelvic radiation dose of 1164 cGy (I group), and an irradiated group supplemented with l-glutamine every day during the entire experimental period (0.65 g/kg of body weight; I+G group). All animals were sacrificed 15 d after irradiation. The extracellular matrix and muscle were quantified by a morphometric method. Picro Sirius Red was used to visualize the different collagen types. Reverse transcription-polymerase chain reaction and immunohistochemistry were used to determine collagen type I and III expressions. RESULTS: The extracellular matrix (C group 36.84±4.37, I group 31.64±5.00, I+G group 35.53±2.60, P=0.0001), muscle (C group 36.43±6.15, I group 29.39±7.08, I+G group 31.38±3.14, P=0.0001), and gene expressions of collagen type I (C group 1.067±0.31, I group 0.579±0.17, I+G group 1.816±0.66, P=0.0009) and type III (C group 0.99±0.28, I group 0.54±0.13, I+G group 1.07±0.28, P=0.0080) were decreased in the I group. Apart from muscle, glutamine supplementation prevented these alterations. Immunohistochemistry and Picro Sirius Red showed similar results. CONCLUSION: Supplementation with l-glutamine seems to prevent bladder wall damage in relation to extracellular matrix volumetric density and collagen expression. These results suggest that glutamine supplementation could be efficient in protecting healthy tissues from the adverse effects of radiotherapy.

[Therapeutic effect of Haobieyangyinruanjianfang on the mouse liver fibrosis caused by schistosomiasis].

OBJECTIVE: To explore therapeutic effect of Haobieyangyinruanjianfang (HBYYRJ) on mouse liver fibrosis by schistosomiasis. METHODS: Mice except for normal control were infected with Japanese schistosome cercarias, after 12 weeks, infected mice were divided into 7 groups: low HBYYRJ group, middle HBYYRJ group, high HBYYRJ group, Fufangbiejiaruangan tablet (FFBJRG) group, colchicine group, 3 months infection group and 6 months infection group. Hepatic fibrosis was found in 3 months infection group. Liver hydroxyproline (Hyp) was determined, matrix metalloproteinase-2 and 9 (MMP-2, MMP-9) were detected with gelatin zymography, serum hyaluronic acid (HA) and precollagen III (PC-III) were detected using RIA. RESULTS: HBYYRJ obviously reduced hepatic fibrosis (probability value less than 0.01). Collagen and HA in 3 months infection group and 6 months infection group were higher than that in normal group (probability value less than 0.01), collagen in high and middle HBYYRJ groups and HA in middle and low HBYYRJ groups were lower than that in 6 months infection group (P less than 0.01, probability value less than 0.05). The expression of MMP-9 and MMP-2 in 3 months infection group and 6 months infection group was higher than that in normal group (probability value less than 0.01), The expression of MMP-9 in three HBYYRJ groups and the expression of MMP-2 in high HBYYRJ group were lower than that in 6 months infection group (probability value less than 0.05). CONCLUSION: HBYYRJ can reduce liver fibrosis caused by schistosomiasis.

Effects of Haobie Yangyin Ruanjian decoction on hepatic fibrosis induced by carbon tetrachloride in rats.

AIM: To explore the anti-fibrotic effect of Haobie Yangyin Ruanjian decoction (HYRD) on CCl(4)-induced hepatic fibrosis in rats and its modulation on the transforming growth factor (TGF) beta-Smad signaling pathway. METHODS: Fifty-six healthy Wistar rats were randomly divided into five groups: normal control group (n = 6), CCl(4)-induced hepatic fibrosis group (n = 14) and three treatment groups (the treated rats received HYRD via oral administration at daily dosages of 8.2, 2.5 and 0.82 g/kg, respectively) of HYRD (n = 12, respectively). Experimental hepatic fibrosis was induced by subcutaneous injection of carbon tetrachloride solution (CCl(4) dissolved in peanut oil, 4:6, V/V) with 0.5 mL/100 g body weight for the first time, and then 0.3 mL/100 g body weight twice a week for 8 wk. In the former 2 wk, rats were raised by feedstuff I (80% corn meal, 20% lard, 0.5% cholesterol). After 2 wk, they were raised by feedstuff II (corn meal and 0.5% cholesterol). Except for the control group, 30% alcohol solution was given orally to each rat every other day from the beginning, 1 mL for each rat. Liver function parameters and hepatic hydroxyproline content were detected by chromatometry. Serum levels of hyaluronic acid (HA), type IV collagen (CIV), type III precollagen (PCIII) and laminin (LN) were assayed with radioimmunoassay. Deposition of collagen was observed with hematoxylin-eosin staining and collagen staining. Gene expression of TGFbeta1 and Smad3 were detected with real-time reverse transcriptase-polymerase chain reaction and Western blotting, respectively. RESULTS: The serum levels of alanine transaminase and aspartate transaminase were increased in the model group compared with the control group (P < 0.01), and they were decreased in the three treatment groups compared with the model group. The serum levels of total protein and albumin were decreased in the model group and increased in the three treatment groups. The hepatic hydroxyproline content and serum levels of PCIII, HA, LN and CIV were markedly increased in the model group compared with the control group, and decreased in the treatment groups. The gene expression of TGFbeta1 and Smad3 was enhanced in the model group compared with the control group, and HYRD could down regulate their expression. CONCLUSION: HYRD can inhibit hepatic fibrosis induced by CCl(4) in rats, which is probably associated with its down-regulation on fibrogenic signal transduction of TGFbeta-Smad pathway.

Protective effects of astragaloside IV on porcine-serum-induced hepatic fibrosis in rats and in vitro effects on hepatic stellate cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Astragaloside IV is the primary pure saponin isolated from Astragalus membranaceus, one of the valuable traditional medical herbs. Antifibrotic activities of Astragalus membranaceus have been extensively proved. AIM OF THE STUDY: To investigate the effects of astragaloside IV on hepatic stellate cells (HSCs) and hepatic fibrosis in rats induced by porcine-serum (PS). MATERIALS AND METHODS: Liver fibrosis was induced by PS injection (0.5 ml, twice a week) for 12 weeks. Astragaloside IV (2.0, 4.0 mg kg(-1)) was administered intragastrically. Liver samples were subjected to histological and immunohistochemical studies. In vitro effects of astragaloside IV on primary cultured HSCs were detected by incorporation assays. RESULTS: Astragaloside IV delayed the formation of liver fibrosis and decrease the serum levels of hyaluronic acid (HA), procollagen type III (PCIII) and hydroxyproline (Hyp) content in liver. The levels of transforming growth factor-beta(1) (TGF-beta(1)) in serum and expression in liver were significantly decreased by astragaloside IV. Collagen synthesis and proliferation were significantly inhibited by astragaloside IV (1.5, 3.0, 6.0, 12.0 and 24.0 mg L(-1)) in HSCs. CONCLUSION: The results showed that astragaloside IV displays antifibrotic effects in rats induced by PS, the mechanism by which might be associated with its inhibitory effects on collagen synthesis and proliferation in HSCs.

[Prevention and treatment of experimental liver fibrosis in rats by Semen Hoveniae extracts].

OBJECTIVE: To investigate the prevention and treatment of experimental liver fibrosis in rats by Semen Hoveniae extracts (SHE). METHODS: Rats liver fiborsis model was induced by carbon tetrachloride (CCl4). SD rats were randomly divided into six groups: the normal control group, the model control group, the positive control group and the SHE groups. The level of serum procollgan type-III (PC-III), hyaluronic acid (HA), laminin (LN) and liver function were measured, respectively. Liver histological examination was made. RESULTS: SHE could ameliorate CCl4-induced liver fibrosis significantly. The lever of serum PC-III, HA, LN decreased and liver function was improved. The histological examination also demonstrated its anti-fibrotic effect. CONCLUSION: SHE have anti-fibrotic effect on liver in vivo, and may have potential value for clinical use.

[The clinical study on decompensatory cirrhotic patients treated by Bie Jia Jian].

OBJECTIVE: To observe the clinical curative effect on decompensatory cirrhotic patients treated by Bie Jia Jian. METHODS: 98 decompensatory cirrhotic patients were randomly divided into two groups: 49 patients in treatment group and 49 in control group. Both groups were treated with the same western medicine of protecting and supporting liver. Except that, treatment group were treated by Bie Jia Jian. RESULTS: The Contents of AST, ALT, total bilirubin (TB), direct bilirubin (DB), hyaluronic acid (HA), Laminin (LN) , procollagen III (pc III), and type IV collagen (IV.C) in both groups decreased after treatment, and prothrombin time activity (PTA) increased. Among them, the decrease of TB, DB, HA, LN, PC-III and IV-C, and the increase of PTA in treatment group were more obvious than those in control group (P < 0. 05). CONCLUSION: Bie Jia Jian is effective in treating decompesatory cirrhotic patients.

Effects and mechanisms of extract from Paeonia lactiflora and Astragalus membranaceus on liver fibrosis induced by carbon tetrachloride in rats.

Paeonia lactiflora and Astragalus membranaceus are two popular traditional Chinese medicines, commonly used in Chinese herb prescription to treat liver disease. The extract prepared from the roots of Paeonia lactiflora and Astragalus membranaceus (PAE) demonstrated more excellent hepato-protective activity than the single herbs used individually as indicated in our preliminary studies. The present study was carried out to investigate the effects of PAE on liver fibrosis in rats induced by carbon tetrachloride (CCl(4)) and to explore its possible mechanisms. Liver fibrosis was induced in male Sprague-Dawley rats by injection with 50% CCl(4) subcutaneously twice a week for 8 weeks. At the same time, PAE (40, 80 and 160 mg/kg) was administered intragastrically. Upon pathological examination, the PAE-treated rats significantly reduced the liver damage and the symptoms of liver fibrosis. Administration of PAE decreased CCl(4)-induced elevation of serum transaminase activities, hyaluronic acid, laminin and procollagen type III levels, and contents of hydroxyproline in liver tissue by approximately 30-60%. It also restored the decrease in SOD and GSH-Px activities and inhibited the formation of lipid peroxidative products during CCl(4) treatment. Moreover, PAE (80, 160 mg/kg, ig) decreased the elevation of TGF-beta1 by 47.7% and 53.1%, respectively. In the primary cultured hepatic stellate cells (HSCs), PAE also significantly decreased [(3)H] thymidine incorporation in cells stimulated with platelet-derived growth factor-B subunit homodimer (PDGF-BB) and suppressed [(3)H] proline incorporation. These results suggested that PAE significantly inhibited the progression of hepatic fibrosis induced by CCl(4), and the inhibitory effect of PAE on hepatic fibrosis might be associated with its ability to scavenge free radicals, decrease the level of TGF-beta1 and inhibit collagen synthesis and proliferation in HSCs.

[Therapeutic effect of Hongbeiyegen on alcohol-induced rat hepatic fibrosis].

OBJECTIVE: To observe the therapeutic effect of Hongbeiyegen [the root of Alchornea trewioides(Benth.) Muell.-Arg.] on alcohol-induced liver fibrosis (AF) in rats and explore its mechanism. METHODS: In rats with AF, the serum levels of transforming growth factor beta1 (TGFbeta1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were detected along with examination of the changes in serum hyaluronic acid (HA), laminin (LN), procolagen type III (PC III), collagen type IV (C IV), glutamic-pyruvic transaminase (ALT) and glutamic-oxalacetic transaminase (AST) levels. RESULTS: Compared with the control group, Hongbeiyegen could significantly reduce the levels of TGFbeta1, TIMP-1, HA, LN, PC III, CIV, ALT and AST in rats with AF. CONCLUSION: Hongbeiyegen can relieve and ameliorate liver fibrosis possibly by inhibiting the expression of TGFbeta1 and TIMP-1.

[Experimental study on protective effects of curcumin on exaggerated extracellular matrix accumulation of pulmonary fibrosis rats].

OBJECTIVE: To study the protective effects of curcumin on exaggerated extracellular matrix accumulation of pulmonary fibrosis rats. METHOD: One hundred and forty-four male Sprague-Dawley rats were randomly divided into 6 groups (24 rats in each group). Rats in the model control group, positive medicine group, and high, moderate and low curcumin groups were injected with a single dose of bleomycin by trachea, and rats in sham-model control group with same volume normal saline. One day after the injection, curcumin solution of different dosages (200, 100, 50 mg x kg(-1) x d(-1)) was respectively given to rats in the high, moderate and low curcumin group daily by gastrogavage, while equal volume of normal saline was given to those in the sham-model control group and model control group, and an equal volume of prednisone (0.56 mg x kg(-1) x d(-1)) was given to those in positive medicine control group. On the 7, 14, 28 days, 8 rats per treatment group were randomly killed, the levels of III-collagen, IV-collagen, laminin and hyaluronic acid in the serum were determined, the determination of hydroxyproline in lung homogenates was analyzed, and the lung was incised to make pathological sections which were stained with HE and Mallory. RESULT: Curcumin could decreas the levels of III-collagen, IV-collagen, laminin and hyaluronic acid in the serum, and inhihit the proliferation of fibrous tissue. CONCLUSION: Curcumin may play its therapetuic role by leveling down the content of extracellular matrix in rats with pulmonary fibrosis induced by bleomycin.

Effects of extract from Ginkgo biloba on carbon tetrachloride-induced liver injury in rats.

AIM: To study the effects of extract from Ginkgo biloba (EGb) containing 22% flavonoid and 5% terpenoid on chronic liver injury and liver fibrosis of rats induced by carbon tetrachloride (CCl(4)). METHODS: All rats were randomly divided into control group, CCl(4)-treated group, colchicine-treated group and EGb-protected group. Chronic liver injury was induced in experimental groups by subcutaneous injection of CCl(4) and fed with chows premixed with 79.5% corn powder, 20% lard and 0.5% cholesterol (v/v). EGb-protected group was treated with EGb (0.5 g/kg body weight per day) for 7 wk. At the end of wk 8, all the rats were killed. Liver function, liver fibrosis, oxidative stress and expression of transforming growth factor beta1 (TGF-beta1), a-smooth muscle actin (alpha-SMA) and type I collagens in liver were determined. In addition, pathology changes of liver tissue were observed under light microscope. RESULTS: The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and albumin (Alb) in EGb-protected group were notably improved as compared with the CCl(4)-treated group (P < 0.01). The contents of serum hyaluronic acid (HA), type III procollagen (PCIII), type IV collagen (CIV) and the expression of hepatic tissue TGF-beta1, alpha-SMA and type I collagen in EGb-protected group were significantly lower than those in CCl(4)-treated groups (P < 0.05, P < 0.01). The degrees of liver fibrosis in EGb-protected groups were lower than those in CCl(4)-treated groups (6.58 +/- 1.25 vs 9.52 +/- 2.06, P < 0.05). Compared to the CCl(4)-treated group, the levels of plasma glutathoine peroxidase (Se-GSH-Px), superoxide dismutase (SOD) and malondialdehyde (MDA) were strikingly improved also in EGb-protected group (P < 0.05, P < 0.01). CONCLUSION: EGb resists oxidative stress and thereby reduces chronic liver injury and liver fibrosis in rats with liver injury induced by CCl(4).

Effect of Astragalus complanatus flavonoid on anti-liver fibrosis in rats.

AIM: To observe the anti-liver fibrosis effect of Astragalus complanatus flavonoids (ACF) in rats. METHODS: The liver fibrosis model in rats was established by injecting interperitoneally 0.2 mL/100 g 0.5% dimethylnitrosamine, thrice a week. Meanwhile, the rats were administered ACF (30, 60, 120 mg/kg) or colchicine (0.1 mg/kg) once a day for 1 mo. Serum N-propeptide of type I procollagen (PINP) and type III procollagen (PIIINP) were measured using ELISA. Malondialdehyde (MDA) and superoxide dismutase (SOD) in hepatic tissue were evaluated. Matrix metal protease-1 (MMP-1) mRNA expression was assayed by RT-PCR and the protein expression of tissue inhibitor of metal protease-1 (TIMP-1) was analyzed by immunohistochemistry. RESULTS: In the ACF groups, SOD activity increased and MDA content decreased in comparison to the liver fibrosis model group. The serum PINP and PIIINP contents in ACF-2 and -3 group decreased compared to those in model group. In ACF-2 and -3 group, the expression of MMP-1 mRNA increased significantly and the protein expression of TIMP-1 decreased compared to that in model group. CONCLUSION: The antifibrotic mechanisms of ACF are associated with its influence on lipid peroxidation and collagen synthesis and degradation.