Active Ingredients and Action Mechanisms of Yi Guan Jian Decoction in Chronic Hepatitis B Patients with Liver Fibrosis.

BACKGROUND AND AIM: The progression of liver fibrosis in chronic hepatitis B (CHB) patients is currently insufficiently controlled worldwide. The Yi Guan Jian decoction (YGJD) has been widely used in the treatment of liver fibrosis in CHB cases. Although animal studies have reported the antifibrotic effects of the decoction, the active ingredients of the YGJD remain unknown. This study aimed at identifying the potential active ingredients and exploring the mechanisms of action (MOA) of the decoction when treating CHB patients with fibrosis. METHODS: Using data mining techniques and a structural clustering analysis, the potential active ingredients were determined. A network analysis of the differentially expressed genes was conducted to identify the potential targets. Selected compounds were docked to the potential targets for the compound-target interaction simulation. In vitro validation, including a cell proliferation assay and Western blot analysis, was conducted to evaluate the prediction results. RESULTS: In the microarray data, 224 differentially expressed genes related to liver fibrosis were considered to be potential targets. Thirty active ingredients of the YGJD and 15 main targets and relevant pathways were identified. Among them, two active ingredients, methylophiopogonone A and 8-geranyloxypsoralen, were validated as exhibiting antifibrotic effects on hepatic stellate cells. CONCLUSIONS: We identified the potential active ingredients of the YGJD and proposed the possible explanation for the MOA in the treatment of CHB patients with liver fibrosis. Moreover, this study provides a methodological reference for the systematic investigation of the bioactive compounds and related MOA of a traditional Chinese medicine formula in a clinical context.

Tanshinone IIA attenuates demyelination and promotes remyelination in A. cantonensis-infected BALB/c mice.

BACKGROUND: Angiostrongylus cantonensis infection can cause demyelination in the central nervous system, and there is no effective treatment. METHODS: We used dexamethasone, Tanshinone IIA (TSIIA) and Cryptotanshinone(Two traditional Chinese medicine monomers) in combination with albendazole (AB, a standard anti-helminthic compound) to observe their therapeutic effect on demyelination in A. cantonensis-infected mice. Luxol fast blue staining and electron microscope of myelin sheath, Oligodendrocyte (OL) number and myelin basic protein (MBP) expression in brain was detected in above groups. RESULTS: TSIIA+AB facilitated OL proliferation and significantly increased both myelin sheath thickness and the population of small-diameter axons. In addition, TSIIA treatment inhibited the expression of inflammation-related factors (interleukin [IL]-6, IL-1ß, tumor necrosis factor [TNF]-α, inducible nitric oxide synthase [iNOS]) rather than inhibiting eosinophil infiltration in brain. TSIIA also decreased microglial activation and shifted their phenotype from M1 to M2. CONCLUSIONS: Taken together, these results provide evidence that TSIIA combined with AB may be an effective treatment for demyelination caused by A. cantonensis infection and other demyelinating diseases.

A cross-sectional survey comparing a free treatment program for advanced schistosomiasis japonica to a general assistance program.

The prevalence and intensity of schistosomiasis has dropped dramatically in China due to an effective integrated control program. However, advanced schistosomiasis is becoming a key challenge on the road to elimination. The aims of this study were to compare the disease condition between advanced cases under the general assistance program (GAP) and free treatment program (FTP) and to determine whether the FTP should be popularized to provide an objective reference for policymakers in China's advanced schistosomiasis control program. One hundred and ninety-four patients with schistosomiasis japonica who were enrolled in the GAP or FTP participated in this study. Little significant difference was observed in the potential confounders, including general characteristics, comorbidities, and lifestyle, indicating a similar effect on the pathology of liver damage caused by schistosome infection. There was no apparent difference in the incidence of common clinical symptoms. Furthermore, no significant difference was observed in the ultrasound findings, implying that the GAP and FTP groups shared a similar degree of liver lesion. With the exception of the abnormal rates of aspartate aminotransferase (AST), alkaline phosphatase (ALP), and hyaluronic acid (HA), the other serological indicators were comparable between the groups. Overall, the FTP is not a better option for controlling advanced schistosomiasis in China. It is important to reveal the precise mechanism underlying the pathogenesis of advanced schistosomiasis so that specific approaches to treating and preventing the development of advanced schistosomiasis can be developed and schistosomiasis can be eliminated in China.

Effects of albendazole combined with TSII-A (a Chinese herb compound) on optic neuritis caused by Angiostrongylus cantonensis in BALB/c mice.

BACKGROUND: Angiostrongylus cantonensis (A. cantonensis) infection can lead to optic neuritis, retinal inflammation, damage to ganglion cells, demyelination of optic nerve and visual impairment. Combined therapy of albendazole and dexamethasone is a common treatment for the disease in the clinic, but it plays no role in vision recovery. Therefore, it has been necessary to explore alternative therapies to treat this disease. Previous studies reported the neuro-productive effects of two constituents of Danshen (a Chinese herb)-tanshinone II-A (TSII-A) and cryptotanshinone (CPT), and this study aims to evaluate the impacts of TSII-A or CPT combined with albendazole on optic neuritis caused by A. cantonensis infection in a murine model. METHODS: To assess the effects of TSII-A or CPT combined with albendazole on optic neuritis due to the infection, mice were divided into six groups, including the normal control group, infection group and four treatment groups (albendazole group, albendazole combined with dexamethasone group, albendazole combined with CPT group and albendazole combined with TSII-A group). The infection group and treatment groups were infected with A. cantonensis and the treatment groups received interventions from 14 dpi (days post infection), respectively. At 21 dpi, the visual acuity of mice in each group was examined by visual evoked potential (VEP). The pathologic alteration of the retina and optic nerve were observed by hematoxylin and eosin (H&E) staining and transmission electronic microscopy (TEM). RESULTS: Infection of A. cantonensis caused prolonged VEP latency, obvious inflammatory cell infiltration in the retina, damaged retinal ganglions and retinal swelling, followed by optic nerve fibre demyelination and a decreasing number of axons at 21 dpi. In treatment groups, albendazole could not alleviate the above symptoms; albendazole combined with dexamethasone lessened the inflammation of the retina, but was futile for the other changes; however, albendazole combined with CPT and albendazole combined with TSII-A showed obvious effects on the recovery of prolonged VEP latency, destruction and reduction of ganglion cells, optic nerve demyelination and axon loss. Compared with albendazole-CPT compound, albendazole combined with TSII-A was more effective. CONCLUSIONS: The current study demonstrates that albendazole combined with TSII-A plays a more effective role in treating optic neuritis caused by A. cantonensis in mice than with dexamethasone, as applied in conventional treatment, indicating that albendazole combined with TSII-A might be an alternate therapy for this parasitic disease in the clinic.

Efficacy of combined treatment with albendazole and baicalein against eosinophilic meningitis induced by Angiostrongylus cantonensis in mice.

Angiostrongylus cantonensis infection causes eosinophilic meningitis in humans. Baicalein is a flavonoid originally isolated from the roots of Scutellaria baicalensis Georgi. In this study we evaluated the efficacy of the combination of albendazole and baicalein for treating eosinophilic meningitis in BALB/c mice. Therapeutic efficacy included the survival time, body weight, neurological function, leucocyte and eosinophil counts, eotaxin concentration, matrix metalloproteinase-9 (MMP-9) activity, larval recovery and histopathological examination. The results showed that the combination of albendazole and baicalein was more effective than either drug administered singly. Combination therapy increased the survival time, decreased body weight loss, neurological dysfunction, leucocyte response, eotaxin concentration and MMP-9 activity. Our results suggest that the combination of albendazole and baicalein may exhibit synergistic beneficial effects in the treatment of eosinophilic meningitis induced by A. cantonensis.

Expression profile, localization of an 8-kDa calcium-binding protein from Schistosoma japonicum (SjCa8), and vaccine potential of recombinant SjCa8 (rSjCa8) against infections in mice.

Researches on genes expressed in a cercarial stage-specific manner may help us understand the molecular events and functions during schistosome invasion of skin. A genomic clone encoding 8-kDa calcium-binding protein (SjCa8) specifically expressed in cercariae and skin-stage schistosomulum (transformed within 3 h) was obtained from cercariae. Recombinant protein was expressed in vector pET32a (+) and purified using a Ni-NTA purification system. The target protein SjCa8 was determined by matrix-assisted laser desorption/ionization time-of-flight (TOF)/TOF mass spectrometer after thrombin digestion and dialysis. Reverse transcriptase polymerase chain reaction and Western blot revealed SjCa8 can be detected in cercaria and skin-stage schistosomulum but not lung-stage schistosomulum, adult, or egg and was localized to head gland, penetration gland tubes, and penetration glands where Ca(2+) was abundant, and the cercarial tegument (but not tegument of tail) and body-tail junction. Furthermore, SjCa8 was interestingly detected in cercarial secretions. The characterization of SjCa8 indicated that it may undergo structural and physiological modifications, including repair of the surface membrane, changes in permeability that account for the loss of water tolerance, activities of calcium-depending enzymes, and immune signaling, etc. Furthermore, vaccination with rSjCa8 plus adjuvant induced protective effect with 50.39% worm reduction rate and significantly high hepatic and intestine egg reduction rates (54.16%, 50.63%, respectively), which is possibly mediated through an apparent induction of Th1-type immune response for strikingly high level of IgG2a and IgG2b developed in immunized C57BL/6 mice.

A novel tegumental protein 31.8 kDa of Clonorchis sinensis: sequence analysis, expression, and immunolocalization.

The complementary DNA (cDNA) plasmid libraries of adult worm, metacercariae and egg of Clonorchis sinensis (C. sinensis) were constructed for researches on genomics and proteomics of C. sinensis. The full-length cDNA sequence encoding tegumental protein 31.8 kDa (CsTP31.8) was identified from the adult cDNA library. The cDNA sequence has been submitted to the GeneBank Database with accession number ABK60086. This novel cDNA sequence contains 828 bp with a putative open reading frame of 275 amino acids. The deduced amino acid sequence shows identity to membrane-associate antigens or tegumental antigens of other species. There were conserved calcium-binding EF hand and dynein light chain type 1 in the sequence. CsTP31.8 transcripts were detected in cDNA libraries of adult worm and metacercariae but not in that of egg. Recombinant CsTP31.8 was expressed and purified from Escherichia coli BL21 (DE3). CsTP31.8 was immunolocalized at the tegument of adult C. sinensis by using antirecombinant CsTP31.8 sera.