Protective Effect of Alcohol Extract of Phyllanthi Fructus on Silicosis Mice and Its Correlation with Nrf2/ARE Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the effect and underlying mechanism of alcohol extract of Phyllanthi Fructus on silicosis mice induced by silicon dioxide （SiO2）. MethodThirty-six male Kunming mice of SPF grade were randomly divided into a blank group，a model group，high-， medium， and low-dose Phyllanthi Fructus groups （800， 400， 200 mg·kg-1），and a tetrandrine group （0.039 mg·kg-1），with six mice in each group. The silicosis model was induced by static SiO2 exposure in mice except for those in the blank group. After 28 days of administration by gavage，the lung tissues were collected and the organ coefficient was calculated. Hematoxylin-eosin（HE）staining and Masson staining were used to detect the morphology of lung tissues. The content of hydroxyproline （HYP），superoxide dismutase （SOD），malondialdehyde （MDA）， and catalase （CAT） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. Western blot and Real-time polymerase chain reaction（Real-time PCR） were used to detect the protein and mRNA expression of nuclear factor E2-related factor 2 （Nrf2），heme oxygenase-1 （HO-1），NAD（P）H：quinone oxidoreductase 1 （NQO1），and Kelch-like ECH-associated protein 1 （Keap1）， respectively. ResultCompared with the blank group，the model group showed seriously damaged morphological structure of lung tissues with inflammatory cell infiltration and fibrous tissue proliferation， reduced serum content of SOD and CAT（P<0.01），increased content of HYP and MDA（P<0.01）， down-regulated protein and mRNA expression of Nrf2，HO-1， and NQO1（P<0.01），and up-regulated protein and mRNA expression of Keap1 （P<0.05，P<0.01）. Compared with the model group，the high- and medium-dose Phyllanthi Fructus groups showed significantly restored morphological structure of lung tissues with reduced collagen deposition， increased serum content of SOD and CAT（P<0.05，P<0.01），decreased content of HYP and MDA（P<0.01）， up-regulated protein and mRNA expression of Nrf2，HO-1， and NQO1 （P<0.05，P<0.01），and down-regulated protein and mRNA expression of Keap1（P<0.05，P<0.01）. ConclusionThe alcohol extract of Phyllanthi Fructus can inhibit pulmonary fibrosis in silicosis mice，and the underlying mechanism may be related to the regulation of the Nrf2/antioxidant response element （ARE） signaling pathway.

Clinical research progress on drugs for non-alcoholic steatohepatitis treatment / 药学学报

Nonalcoholic steatohepatitis (NASH) is the leading chronic liver disease worldwide. NASH is commonly associated with metabolic risk factors, including obesity, hypertension, and diabetes. Hepatic glucose and lipid metabolism disorder, bile acid toxicity, oxidative stress, inflammation, fibrosis, intestinal dysbacteriosis, and susceptibility gene variation are involved in the pathogenesis of NASH. Drug development for NASH has been slow, this article focuses on the clinical research and development of several promising NASH drugs and their mechanisms, such as drugs targeting gut-liver axis, improving metabolism, inhibiting inflammation and fibrosis.

Effects of Nintedanib associated with Shenfu Injection on paraquat-induced lung injury in rats / 中华劳动卫生职业病杂志

Objective: To study the effects of Nintedanib associated with Shenfu Injection on lung injury induced by paraquat (PQ) intoxication. Methods: In September 2021, a total of 90 SD rats were divided into 5 groups in random, namely control group, PQ poisoning group, Shenfu Injection group, Nintedanib group and associated group, 18 rats in each group. Normal saline was given by gavage route to rats of control group, 20% PQ (80 mg/kg) was administered by gavage route to rats of other four groups. 6 hours after PQ gavage, Shenfu Injection group (12 ml/kg Shenfu Injection), Nintedanib group (60 mg/kg Nintedanib) and associated group (12 ml/kg Shenfu Injection and 60 mg/kg Nintedanib) were administered with medicine once a day. The levels of serum transforming growth factor beta1 (TGF-β1), interleukin-1 beta (IL-1β) were determined at 1, 3 and 7 d, respectively. The pathological changes of lung tissue, the ratio of wet weight and dry weight (W/D) of lung tissue, the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in lung tissue were observed and determined after 7 d. Western blot was used to analyse the expression levels of fibroblast growth factor receptor 1 (FGFR1), platelet derivation growth factor receptor alpha (PDGFRα), vascular endothelial growth factor receptor 2 (VEGFR2) in lung tissue after 7 d. Results: The levels of TGF-β1, IL-1β in all poisoning groups went up first and then went down. The levels of TGF-β1, IL-1β in associated group at 1, 3, 7 d were lower than that of PQ poisoning group, Shenfu Injection group and Nintedanib group at the same point (P<0.05). Pathological changes of lung tissue under the light microscopes showed that the degrees of hemorrhage, effusion and infiltration of inflammatory cells inside the alveolar space of Shenfu Injection group, Nintedanib group and associated group were milder than that of PQ poisoning group, and the midest in associated group. Compared with control group, the W/D of lung tissue was higher, the level of MDA in lung tissue was higher, while the level of SOD was lower, the expressions of FGFR1, PDGFRα and VEGFR2 in lung tissue were higher in PQ poisoning group (P<0.05). Compared with PQ poisoning group, Shenfu Injection group and Nintedanib group, the W/D of lung tissue was lower, the level of MDA in lung tissue was lower, while the level of SOD was higher, the expressions of FGFR1, PDGFRα and VEGFR2 in lung tissue were lower in associated group (P<0.05) . Conclusion: Nintedanib associated with Shenfu Injection can relieve lung injury of rats induced by PQ, which may be related to Nintedanib associated with Shenfu Injection can inhibit the activation of TGF-β1 and the expressions of FGFR1, PDGFRα, VEGFR2 in lung tissue of rats.

Traditional Chinese Medicine Treats Hepatic Fibrosis via NF-κB Signaling Pathway： A Review / 中国实验方剂学杂志

Hepatic fibrosis is a common complication of chronic liver disease， seriously affecting patients' quality of life and leading to severe consequences such as cirrhosis and liver cancer. Modern medicine has made progress in the treatment of hepatic fibrosis， while it still faces certain challenges and limitations. Therefore， seeking new therapeutic strategies is of great clinical significance. The nuclear factor-κB （NF-κB） signaling pathway plays a role in regulating inflammation and immune responses. Recent studies have shown that the NF-κB signaling pathway plays a key role in the occurrence and development of hepatic fibrosis. The abnormal activation of the NF-κB signaling pathway leads to the overexpression of genes related to liver inflammation and fibrosis， thereby promoting the development of hepatic fibrosis. Traditional Chinese medicine （TCM） is a traditional treatment method with unique advantages and potential. In recent years， increasing studies have proved that TCM can treat hepatic fibrosis by regulating the NF-κB signaling pathway. The active ingredients in Chinese herbal medicines can intervene in the activation of the NF-κB signaling pathway to inhibit inflammatory responses， thereby reducing the severity of hepatic fibrosis. This article reviews the mechanisms of TCM in treating hepatic fibrosis via the NF-κB signaling pathway and evaluates the efficacy and discusses the clinical application prospects of relevant Chinese herbs and formulae， aiming to provide references for further research and clinical practice.

An adjuvant effect of Metformin as an anti-fibrotic agent when administered with the anti-schistosomal Praziquantel in Schistosoma mansoni infected mice

@#Schistosomiasis is the second most common parasitic disease post Malaria around the world. Praziquantel (PZQ) is known as the most efficient anti- schistosomal drug but has no anti-fibrotic effect. Metformin (Met) is a well-known drug for type 2 diabetes. This study aimed to evaluate the role of Met as anti-schistosomal and anti-fibrotic agents alone or in combination with PZQ treatment. Forty male CD1 mice were divided into four groups (n=10 mice) as following; the first group (Gp1) was served as a negative control. Gp2, Gp3, Gp4, and Gp5 were infected with (60-80) S. mansoni cercariae. After a month of infection, Gp3 was administered orally with PZQ (500 mg/Kg) for 2 consecutive days. Gp4 was administered orally with Met (150 mg/Kg) for 15 consecutive days, and Gp5 was orally administered with PZQ followed by Met for 15 consecutive days at the same doses as in Gp 3 and 4. The results showed that PZQ had potent worms and egg reduction in liver and intestine tissues with no anti-fibrotic effect of the granuloma formation. However, Met or PZQ/Met treatment postinfection led to a reduction in egg count in both liver and intestine tissues with a significant reduction in granuloma site. Treatment of S. mansoni-infected mice with Met or PZQ/Met ameliorated the hematological and biochemical alterations induced by S. mansoni infection. Collectively, Met has no anti-schistosomal activity but led to a reduction in egg deposition and showed an anti-fibrotic effect on granulomatous development either when used alone or in combination with PZQ treatment. This study shed light on the possible role of Met as an anti-fibrotic agent when administered with PZQ for S. mansoni infected humans.

Research Progress of Anti-fibrosis Pharmacological Effect and Mechanisms of Chemical Components in Salviae Miltiorrhizae Radix et Rhizoma / 中国实验方剂学杂志

Fibrosis is a pathological feature of most chronic inflammatory diseases， which is pathologically characterized by activation of fibroblasts and deposition of extracellular matrix components. Fibrosis affects nearly every tissue in the body. If highly progressive， the fibrotic process eventually leads to organ malfunction and even death. Due to the complexity of the pathological mechanism of fibrosis， there is still a lack of effective therapeutic drugs. Salviae Miltiorrhizae Radix et Rhizoma， dry roots and rhizomes of Salvia miltiorrhiza， is a kind of traditional Chinese medicines for activating blood and removing stasis. Modern pharmacological studies have shown that the tanshinones and salvianolic acids in Salviae Miltiorrhizae Radix et Rhizoma have a wide range of anti-fibrosis effects， such as inhibiting the production of collagen fibers， promoting the degradation of fibrin， and inhibiting cell proliferation. In this review， pharmacological actions and mechanisms of active ingredients of Salviae Miltiorrhizae Radix et Rhizoma were summarized to provide references for the further development and utilization of Salviae Miltiorrhizae Radix et Rhizoma.

Inhibitory effect of rapamycin on proliferation, migration and fibrosis of human pterygium fibroblasts in vitro / 中华实验眼科杂志

Objective To investigate the inhibitory effect of rapamycin,an mammalian target of rapamycin (mTOR) pathway inhibitor,on the proliferation,migration and fibrosis of human pterygium fibroblasts (PFBs).Methods Pterygium tissues were collected from patients with primary pterygium who underwent surgical excision in Shenyang Fourth People's Hospital from May to July 2015.The tissues were cultured in vitro and the PFBs were identified by anti-human vimentin immunofluorescence assay.The 3 to 5 generation cells were used for the experiments.The viability of cells treated with different concentrations of rapamycin was detected by methyl thiazolyl tetrazolium (MTT).The cells were divided into normal control group and rapamycin group,and the scratch wound healing test was used to evaluate migration of the PFBs.The expressions of MKI67,α-smooth muscle actin (α-SMA),fibronectin,caspase3,mammalian target of rapamycin (mTOR) and LC3B mRNA were detected by real-time quantitative PCR.Results The cultured cells showed morphology of long spindle and were vimentin immunopositive.The cell viability in rapamycin treated PFBs demonstrated a dose-dependent decrease.At 24 hours after culture,The cell viability in 30 μmol/L rapamycin group was (76.67±8.84)％ of that in 0 μmol/L rapamycin group (P＜0.001).The relative residual scratch width in 30 μ mol/L rapamycin group was (35.40±11.62) ％ 48 hours after scratch,which was significantly greater than (2.45±0.76) ％ in the normal control group (P＜0.05).Real-time quantitative PCR showed that the mRNA expressions of MKI67,α-SMA,fibronectin and mTOR in rapamycin group were significantly decreased when compared with those in normal control group (all at P＜0.05).The expression of LC3B mRNA in rapamycin group was significantly higher than that in normal control group (P＜0.05).The mRNA expression of caspase3 was not significantly different between the two groups (P=0.861).Conclusions Rapamycin can effectively inhibit the proliferation,migration and fibrosis of PFBs without affecting the cell survival.Detailed mechanism remains to be further studied.Rapamycin may serve as an anti-fibrosis agent to prevent the progression and recurrence of pterygium in the future.

Phenotypic and functional characteristics of natural killer cells in HBV cirrhotic patients / 解放军医学杂志

Objective To analyze the phenotypic and functional characteristics of hepatic and peripheral natural killer (NK) cells in HBV cirrhotic patients, and further confirm the key role of NK cells in the immunopathogenesis of liver fibrosis. Methods Thirty HBV cirrhotic patients were recruited for this study in the First People's Hospital of Zhengzhou and Fifth Medical Center of Chinese PLA General Hospital from January 2015 to January 2017, meanwhile thirty age-and sex-matched healthy individuals were enrolled as health controls. Liver biopsies were collected from 10 HBV cirrhotic patients, and 8 healthy liver tissue samples were obtained from the healthy donors whose livers were used for liver transplantation. The frequency, phenotypic and functional characteristics of hepatic and peripheral NK cells from the two groups were analyzed by using multicolor flow cytometry. The killing activities of NK cells against HSCs were explored using LX-2 cell model (a cell line of HSCs) in vitro. Results Compared with health controls, the percentages of hepatic and peripheral NK cells were reduced significantly in cirrhotic patients (U=8.5, P=0.006; U=184.0, P<0.001, respectively); the expression levels of activation markers CD69 (U=102.0, P=0.009), HLA-DR (U=82.5, P<0.001) and CD38 (U=0.0, P=0.029) were increased; the expressions of functional molecule granzyme B (U=0.0,P=0.004) was decreased in peripheral NK cells, and perforin and Granzymes were also decreased in hepatic NK cells except TRAIL that was up-regulated (U=4.0, P=0.026), especially the change of perforin (U=4.0, P=0.034); the functional decrease in IFN-γ production (U=2.0, P=0.032) was observed in vitro in hepatic NK cells and the reduction of CD107a degranulation and IFN-γ production were both observed in hepatic and peripheral NK cells (U=88.0, P=0.018; U=13.0, P<0.001, respectively); purified NK cells from peripheral blood of HBV cirrhotic patients could induce less 7AAD– Annexin V+ early apoptotic LX2 cells and 7AAD+ Annexin V+ late apoptotic LX2 cells compared with those from health controls (U=6.5, P=0.025; U=2.0, P=0.002, respectively). Conclusions NK cells from HBV cirrhotic patients displayed a decreased frequency, activation increase, functional decrease in CD107a degranulation and IFN-γ production, and cytolytic activities decrease against HSCs in response to various stimulators in vitro compared with those from health controls. These findings demonstrate an impaired anti-fibrotic function of NK cells' in HBV cirrhotic patients and further clarify the immunopathogenesis of liver fibrosis.

Antiviral and antifibrotic therapies reduce occurrence of hepatocellular carcinoma in patients with chronic hepatitis B and liver fibrosis: a 144-week prospective cohort study / 南方医科大学学报

OBJECTIVE@#To compare the efficacy and safety of different antiviral and antifibrotic regimens in patients with chronic hepatitis B (CHB) and hepatic fibrosis and the incidence of hepatocellular carcinoma (HCC) associated with these therapies.@*METHODS@#A total of 840 patients with CHB and concurrent hepatic fibrosis, who received antiviral therapy in Nanfang Hospital between June, 2010 and June, 2018, were enrolled in this follow-up cohort study. The patients were assigned to 3 cohorts matched for gender, age (difference≤5 years), HBeAg status and liver stiffness measurement (LSM) for treatment with one of the 3 antiviral drugs, namely entecavir, tenofovir dipivoxil and adefovir dipivoxil; each cohort was divided into 2 groups, with one of the groups having a combined treatment with Fufang Biejiaruangan tablet. The cumulative negative conversion rate of HBV DNA, normalization rate of ALT, hepatic fibrosis regression and the incidence of HCC were compared among the 3 cohorts and across the 6 groups at 144 weeks.@*RESULTS@#A total of 749 patients were available to follow-up at 144 weeks. Compared with the baseline data, the cumulative negative conversion rate of HBV DNA increased gradually and the abnormal rate of ALT decreased significantly over time during the treatment in all the 6 groups (all < 0.001). Compared with the any of the antiviral drugs used alone, the combined treatments all resulted in significantly better antifibrotic effects (χ=11.345, χ=10.160, χ=6.358; all < 0.05). At 144 weeks, the incidence of HCC were 2.2%, 1.7%, 1.7% and 3.3% in enecavir group, enecavir with Biejiaruangan tablet group, adefovir group, and adefovir with Biejiaruangan tablet group, respectively, showing no significant difference between the two cohorts (4 groups; χ=6.813, =0.138). None of the patients in the 2 groups with tenofovir treatment had HCC by the end of the observation.@*CONCLUSIONS@#Antiviral therapy combined with antifibrotic therapy can effectively reverse hepatic fibrosis and reduce the incidence of HCC in patients with CHB; among the 3 antiviral drugs, tenofovir dipivoxil can be a better option for reducing the incidence of HCC in these patients.

Inhibitory effect of rapamycin on proliferation,migration and fibrosis of human pterygium fibroblasts in vitro / 中华实验眼科杂志

Objective To investigate the inhibitory effect of rapamycin,an mammalian target of rapamycin (mTOR) pathway inhibitor,on the proliferation,migration and fibrosis of human pterygium fibroblasts (PFBs). Methods Pterygium tissues were collected from patients with primary pterygium who underwent surgical excision in Shenyang Fourth People's Hospital from May to July 2015. The tissues were cultured in vitro and the PFBs were identified by anti.human vimentin immunofluorescence assay. The 3 to 5 generation cells were used for the experiments. The viability of cells treated with different concentrations of rapamycin was detected by methyl thiazolyl tetrazolium ( MTT) . The cells were divided into normal control group and rapamycin group, and the scratch wound healing test was used to evaluate migration of the PFBs. The expressions of MKI67,α.smooth muscle actin (α.SMA), fibronectin,caspase3, mammalian target of rapamycin ( mTOR ) and LC3B mRNA were detected by real.time quantitative PCR. Results The cultured cells showed morphology of long spindle and were vimentin immunopositive. The cell viability in rapamycin treated PFBs demonstrated a dose.dependent decrease. At 24 hours after culture,The cell viability in 30μmol/L rapamycin group was (76. 67±8. 84)％ of that in 0μmol/L rapamycin group ( P<0. 001 ) . The relative residual scratch width in 30μmol/L rapamycin group was ( 35. 40 ± 11. 62 )％ 48 hours after scratch,which was significantly greater than (2. 45±0. 76)％ in the normal control group (P<0. 05). Real.time quantitative PCR showed that the mRNA expressions of MKI67,α.SMA,fibronectin and mTOR in rapamycin group were significantly decreased when compared with those in normal control group (all at P<0. 05). The expression of LC3B mRNA in rapamycin group was significantly higher than that in normal control group (P<0. 05). The mRNA expression of caspase3 was not significantly different between the two groups (P=0. 861). Conclusions Rapamycin can effectively inhibit the proliferation, migration and fibrosis of PFBs without affecting the cell survival. Detailed mechanism remains to be further studied. Rapamycin may serve as an anti.fibrosis agent to prevent the progression and recurrence of pterygium in the future.

Advances in drug delivery systems for the treatment of liver fibrosis / 中国药科大学学报

Liver fibrosis is a major disease that affects human health. Currently,drugs used for the treatment of hepatic fibrosis have such problems as low drug solubility,lack of liver specificity and possible occurrence of side-effects. In order to improve the anti-fibrosis therapeutic efficacy,various nano-drug delivery systems and targeting strategies are explored in liver fibrosis therapy. This review summarizes the drug delivery systems and targeting strategies that have been applied to liver fibrosis therapy in recent years from the types of carriers and modified ligands,which serve as a basis of designing safe and effective drug delivery systems for liver fibrosis therapy.

Research of the anti-fibrosis factors affecting liver regeneration after partial hepatectomy for hepatic cellular carcinoma with liver cirrhosis / 国际外科学杂志

Hepatic cellular carcinoma is the third most common cause of cancer deaths in China.Partial hepatectomy is still the most effective treatment for hepatic cellular carcinoma.The liver is an organ with strong regenerative ability,and its regenerative mechanism is very complex.Majority of patients with hepatic cellular carcinoma are accompanied by cirrhosis,and cirrhosis is an important factor affecting the regeneration of the remaining liver after surgery.Liver regeneration is obviously impaired under this condition.However,the anti-liver fibrosis mechanisms behind these processes have not been completely elucidated,the current treatment of fibrosis is merely supportive care,and thus further definition of the antiliver fibrosis related factors such as keratinocyte growth factor,hepatocyte growth factor,milk fat globule epidermal growth factor 8,collagen-binding vascular endothelial growth factor,ex vivo expansion of circulating CD34+ cells has far-reaching significance for improving their prognosis.This article mainly introduces some relevant factors associated with anti liver fibrosis,for later use of single factor or a combination of multifarious factors to resist liver fibrosis,to provide reference for improving the ability of remained liver regeneration after partial hepatectomy.

Effect of Alpha2-macroglobulin on Anti-Oxidation and Anti-Fibrosis in Human Skin Fibroblasts after X-ray Irradiation / 中山大学学报(医学科学版)

[Objective]To explore the effect of alpha2-macroglobulin(α2M)on superoxide anion(.O2-)content, superoxide dismutase(SOD)activity and the process of cell-to-myofibroblast transformation in human skin fibroblasts (HSF)after X-ray irradiation.[Methods]HSF cells were irradiated with 0,5,10,15 and 20 Gy X-ray.The change of. O2- content and SOD activity in the supernatant of cell culture medium were measured on the first day after irradiation. The protein expression of alpha-smooth muscle actin(α-SMA)was detected by Western blot on the fifth day after irradia-tion.The most sensitive radiation dose is selected.HSF cells were irradiated with the above sensitive dose.Respectively, 1h before irradiation,1 h after irradiation,the experimental group cell culture medium was added to a final concentration of 0.25 mg/mL,0.5 mg/mL of α2M.The change of.O2-content,SOD activity and the protein expression of α-SMA were detected.[Results]HSF cells were irradiated with 5~20 Gy doses of X-ray..O2- content increased,SOD activity de-creased and α-SMA protein expression increased gradually(P<0.05).The addition of α2M at 1 h after 10Gy X-ray irradi-ation reduced the.O2- content,increased the SOD activity and downregulated the protein expression of α-SMA in HSF cells(P<0.05). There was no significant change in the administration at 1 h before irradiation.[Conclusion]HSF cells increased.O2-content significantly,while SOD activity decreased,and the tendency to transform myofibroblasts after X-ray irradiation.α2M can reduce the.O2-content,increase the SOD activity in HSF cells and inhibit the transformation of fibroblasts into myofibroblasts after irradiation.Indicating that α2M can play a role in radiation protection by anti-oxida-tion and anti-fibrosis.

Investigations on secondary metabolites of endophyte Diaporthe sp. hosted in Tylophora ovata / 中国中药杂志

One new compound ()-2,3-dihydroxybutyl 2-hydroxy-3,5,6-trimethylbenzoate (1) and six known compounds xylariphthalide A (2), convolvulol (3), cis-4-hydroxy-6-deoxytalone (4), phomoxydienes B (5), 5,6-dihydroxy-2,3,6-trimethylcyclohex-2-enone (6), trans-cyclo-(D-tryptophanyl-L-tyrosyl) (7) were isolated from Diaporthe sp., an endophytic fungus hosted in the leaves of the toxic Chinese folk medicine Tylophora ouata, using the combination methods of silica gel column chromatography, medium-pressure ODS column chromatography and RP-preparative HPLC. The structure of compound 1 was elucidated by NMR and MS data analyses. The absolute configurations were established according to the ¹H-NMR data and exciton chirality method. Compound 1 inhibited the activation of human lung fibroblasts MRC-5 cells by 64.0% at 10 μmol·L⁻¹. The MTT assay showed that compounds 2 and 4 displayed cytotoxic activity against human tumor cell lines BGC-823 cells with IC₅₀ values of 1.5 and 8.6 μmol·L⁻¹, respectively.

Research advances on baicalin and baicalein as potential therapeutic agents for fibrotic disease / 中国中药杂志

Tissue and organ fibrosis is the major cause for disability and death related to a variety of diseases worldwide. As specific therapies to halt, or even to reverse the existing tissue fibrosis are not yet available, it is of great significance to find new anti-fibrosis therapeutic agents. Tissue and organ fibrosis is a nonphysiological scarring process, associated with excessive deposition of extracellular matrix, and leads to impairment of organ function. Fibrotic lesions of all organs show similar histological abnormalities. In recent years, plenty of studies showed that Baicalin and baicalein had anti-fibrosis effects in different tissues or organs. In this paper, the effects and mechanisms of baicalin and baicalein on different organ fibrosis were reviewed. Baicalin and its aglycone baicalein had similarity in structural and pharmacological characteristics, with broad biotransformation effect within the body. The research suggested that baicalin and baicalein can suppress different tissue and organ fibrosis occurrence and development via various mechanisms, including down-regulating expression of promote-fibrosis cytokines, inhibiting pro-fibrogenic signaling pathways, anti-inflammatory and anti-oxidant effects. Though baicalin and baicalein are promising anti-fibrosis agents, there is still a long way to go before being approved as specific anti-fibrotic drugs.

Research progress of prevention and cue effects of caffeoylquinic acids from Erigeron breviscapus on ischemic stroke / 中草药

This paper summarized the chemical structures and amounts of caffeoylquinic acids in Erigeron breviscapus, as well as its prevention and cure effects on ischemic stroke in clinical and possible pharmacological mechanism. The results showed 22 caffeoylquinic acids reported from E. breviscapus, accounting for 29% of all compounds from this herb; The average content of total polyphenols was 36.93%, and more than 95% of components in Erigeron Breviscapus Injection are caffeoylquinic acids, higher than that of scutellarin. Several high quality clinical studies confirmed that Erigeron Breviscapus Injection enhanced treatment performance and improve the neurological score in the treatment after ischemic stroke and had good safety. In pharmacological research, caffeoylquinic acid compounds display anti-oxidant, anti-free radical, anticoagulation, and anti-fibrosis effects, which can protect neuro, vascular endothelial cells, glial cells, and astrocytes. They are also able to inhibit inflammatory, suppress cytokines IL-1, TNF-α, and enhance SOD & GSH-Px, which play a role in different treatment stages of ischemic stroke. So, caffeoylquinic acid is a kind of important chemical in E. breviscapus.

Study on characteristic spectrum of ingredients from different species Cordyceps and its anti-fibrotic activity on human embryonic fibroblasts / 中国中药杂志

In this study, 10 samples of parasites, cursive, and the whole from six different species of Cordyceps were determined and compared by HPLC and LC-MS methods. Uridine, adenosine, and cordycepin were selected as the main evaluation index. The anti-fibrotic activity of different species Cordyceps extracts was observed using in vitro TGF-β1-induced ECM accumulation in human embryonic fibroblasts CCC-ESF-1. The results demonstrated that the number of atoms and hyphae ingredients of different species showed little difference, however, the content distribution of each component has obvious significance. The in vitro anti-fibrotic activities of different species were as follow： Cordyceps flower > Cicada Cordyceps (Cicada flower)> Silkworm Cordyceps> Tussah Cordyceps>natural Cordyceps. Our preliminary data could serve as reference for the discovery of artificial alternatives of natural Cordyceps.

Research advances in molecular mechanism of pharmacological actions of oxymatrine / 中国药理学通报

Oxymatrine is the main effective monomer of Radix Sophorae flavescentis( Kushen) , which has a variety of pharma-cological actions and valuable clinical applications. Recently, there are many reports about molecular mechanisms of oxymatrine pharmacological actions, giving highly attention to the anti-in-flammatory, anti-fibrosis and antineoplastic effects. These effects are achieved through resisting of oxidation and free radical, anti- ＜br> virus, and affecting the secretion of inflammatory factor and ap-optosis and so on. This article summarizes the reports on the mo-lecular mechanism of the protection on liver, cardiovascular sys-tem, endocrine system and nervous system, hoping to provide theoretical basis for the practical application.

Direct intercellular communications dominate the interaction between adipose-derived MSCs and myofibroblasts against cardiac fibrosis

The onset of cardiac fibrosis post myocardial infarction greatly impairs the function of heart. Recent advances of cell transplantation showed great benefits to restore myocardial function, among which the mesenchymal stem cells (MSCs) has gained much attention. However, the underlying cellular mechanisms of MSC therapy are still not fully understood. Although paracrine effects of MSCs on residual cardiomyocytes have been discussed, the amelioration of fibrosis was rarely studied as the hostile environment cannot support the survival of most cell populations and impairs the diffusion of soluble factors. Here in order to decipher the potential mechanism of MSC therapy for cardiac fibrosis, we investigated the interplay between MSCs and cardiac myofibroblasts (mFBs) using interactive co-culture method, with comparison to paracrine approaches, namely treatment by MSC conditioned medium and gap co-culture method. Various fibrotic features of mFBs were analyzed and the most prominent anti-fibrosis effects were always obtained using direct co-culture that allowed cell-to-cell contacts. Hepatocyte growth factor (HGF), a well-known anti-fibrosis factor, was demonstrated to be a major contributor for MSCs' anti-fibrosis function. Moreover, physical contacts and tube-like structures between MSCs and mFBs were observed by live cell imaging and TEM which demonstrate the direct cellular interactions.

Mesenchymal stem cell therapy for liver fibrosis

Currently, the most effective treatment for end-stage liver fibrosis is liver transplantation; however, transplantation is limited by a shortage of donor organs, surgical complications, immunological rejection, and high medical costs. Recently, mesenchymal stem cell (MSC) therapy has been suggested as an effective alternate approach for the treatment of hepatic diseases. MSCs have the potential to differentiate into hepatocytes, and therapeutic value exists in their immune-modulatory properties and secretion of trophic factors, such as growth factors and cytokines. In addition, MSCs can suppress inflammatory responses, reduce hepatocyte apoptosis, increase hepatocyte regeneration, regress liver fibrosis and enhance liver functionality. Despite these advantages, issues remain; MSCs also have fibrogenic potential and the capacity to promote tumor cell growth and oncogenicity. This paper summarizes the properties of MSCs for regenerative medicine and their therapeutic mechanisms and clinical application in the treatment of liver fibrosis. We also present several outstanding risks, including their fibrogenic potential and their capacity to promote pre-existing tumor cell growth and oncogenicity.