• Boron compounds
• Foreskin-derived mesenchymal stem cells
• Liver fibrosis
• Scratch assay
• Smooth muscle sctin
• Three lineage differentiation

• Male
• Rats
• Animals
• Carcinoma, Hepatocellular/complications
• Carcinoma, Hepatocellular/pathology
• Thioacetamide/adverse effects
• Foreskin/pathology
• Liver Neoplasms
• Liver Cirrhosis/chemically induced
• Liver Cirrhosis/drug therapy
• Liver
• Fibrosis
• Mesenchymal Stem Cells/pathology

• cardiac fibrosis
• circulating lipidomic profile
• pharmacology network
• total alkaloids of Plumula nelumbinis

An environment-friendly and efficient method for simultaneous determination of five alkaloids (nunciferine, O-nornuciferin, liriodenine, armepavine, and pronuciferine) in rat plasma was established by HPLC-MS/MS associated with micro-solid phase extraction (micro-SPE). The plasma sample was pretreated by using micro-SPE columns filled with polymer materials PEP-2 and eluted by little organic solvent (400 µl acetonitrile). The five alkaloids were separated with acetonitrile and 0.1% formic acid aqueous solution on Eclipse plus C₁₈ column. The mode of positive electrospray ionization was used to measure the analytes in multiple-reaction monitoring (MRM). The determination coefficients (R²) of the five alkaloids were greater than 0.99. The lower limit of quantification (LLOQ) of O-nornuciferin, liriodenine, and armepavine was 0.5 ng·ml⁻¹, and that of nunciferine and pronuciferine was 1 ng·ml⁻¹. The validated method was effectively used for the pharmacokinetics of the five orally administrated alkaloids of lotus leaf extract in rat plasma.

• HPLC-MS/MS
• PEP-2
• lotus leaf
• micro-solid phase extraction
• pharmacokinetics

Liver fibrosis is a dynamic pathological condition which can be slowed down in its initial phases. Without proper clinical management of fibrosis, progressive liver damage may lead to cirrhosis and ultimately to liver failure or primary liver cancer, which are irreversible conditions. Therefore, in order to cure fibrotic damage to liver, its early stages should be the centre of attention. In this context, some supplements and ‘complementary and alternative medicine (CAM)’ deserve specific mention, because of their already recognized natural way of healing and long lasting curative effects. Moreover, CAM display negligible side effects and hence it is gaining worldwide importance in clinical practices. In particular, herbal medicines are now replacing synthetic pharmaceuticals and looked upon as the sources of novel bioactive substances. To develop satisfactory herbal combinations for treating liver fibrosis, phytoproducts need to be systematically evaluated for their potency as anti-fibrotic, anti-hepatotoxic and antioxidant agents. More importantly, the identified herb/agent should have the remarkable tendency to stimulate hepatocytes regeneration. The present review is a systematic account of at least fifty medicinal herbs and their products which in experimental models have demonstrated antifibrotic activity and thus, most likely candidates to offer therapeutic protection to liver. Nevertheless, much additional work is still needed to explore molecular pathways to discover potential applications of these medicines so as to open up new vistas in biomedical research.

• Complementary and alternative medicine
• Hepatoprotection
• Herbal medicine
• Liver fibrosis
• Phytoproducts

The hepatic stellate cells in the liver are stimulated sustainably by chronic injury of the hepatocytes, activating myofibroblasts, which produce abundant collagen. Myofibroblasts are the major source of extracellular proteins during fibrogenesis, and may directly, or secreted products, contribute to carcinogenesis and tumor progression. Cancer-associated fibroblasts (CAFs) are one of the components of the tumor microenvironment that promote the proliferation and invasion of cancer cells by secreting various growth factors and cytokines. CAFs crosstalk with cancer cells stimulates tumor progression by creating a favorable microenvironment for progression, invasion, and metastasis through the epithelial-mesenchymal transition. Basic studies on CAFs have advanced, and the role of CAFs in tumors has been elucidated. In particular, for hepatocellular carcinoma, carcinogenesis from cirrhosis is a known fact, and participation of CAFs in carcinogenesis is supported. In this review, we discuss the current literature on the role of CAFs and CAF-related signaling in carcinogenesis, crosstalk with cancer cells, immunosuppressive effects, angiogenesis, therapeutic targets, and resistance to chemotherapy. The role of CAFs is important in cancer initiation and progression. CAFtargeted therapy may be effective for suppression not only of fibrosis but also cancer progression.

• Cancer associated fibroblast
• Hepatic stellate cell
• Hepatocellular carcinoma
• Immunosuppression
• Therapeutic target

• Cancer-Associated Fibroblasts/physiology
• Carcinoma, Hepatocellular/etiology
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/therapy
• Cell Communication
• Hepatic Stellate Cells/physiology
• Humans
• Liver Neoplasms/etiology
• Liver Neoplasms/pathology
• Liver Neoplasms/therapy
• Tumor Microenvironment/physiology

Anti-inflammation via inhibition of NF-κB pathways in hepatic stellate cells (HSCs) is one therapeutic approach to hepatic fibrosis. Tanshinone IIA (C₁₉H₁₈O₃, Tan IIA) is a lipophilic diterpene isolated from Salvia miltiorrhiza Bunge, with reported anti-inflammatory activity. We tested whether Tan IIA could inhibit HSC activation.

The cell line of rat hepatic stellate cells (HSC-T6) was stimulated with lipopolysaccharide (LPS) (100 ng/ml). Cytotoxicity was assessed by MTT assay. HSC-T6 cells were pretreated with Tan IIA (1, 3 and 10 µM), then induced by LPS (100 ng/ml). NF-κB activity was evaluated by the luciferase reporter gene assay. Western blotting analysis was performed to measure NF-κB-p65, and phosphorylations of MAPKs (ERK, JNK, p38). Cell chemotaxis was assessed by both wound-healing assay and trans-well invasion assay. Quantitative real-time PCR was used to detect gene expression in HSC-T6 cells.

All concentrations of drugs showed no cytotoxicity against HSC-T6 cells. LPS stimulated NF-κB luciferase activities, nuclear translocation of NF-κB-p65, and phosphorylations of ERK, JNK and p38, all of which were suppressed by Tan IIA. In addition, Tan IIA significantly inhibited LPS-induced HSCs chemotaxis, in both wound-healing and trans-well invasion assays. Moreover, Tan IIA attenuated LPS-induced mRNA expressions of CCL2, CCL3, CCL5, IL-1β, TNF-α, IL-6, ICAM-1, iNOS, and α-SMA in HSC-T6 cells.

Our results demonstrated that Tan IIA decreased LPS-induced HSC activation.

• Abietanes/pharmacology
• Actins/metabolism
• Animals
• Anti-Inflammatory Agents, Non-Steroidal/pharmacology
• Cell Line, Transformed
• Chemotaxis/drug effects
• Enzyme Activation/drug effects
• Hepatic Stellate Cells/drug effects
• Hepatic Stellate Cells/metabolism
• Lipopolysaccharides/pharmacology
• MAP Kinase Signaling System/drug effects
• Mitogen-Activated Protein Kinases/metabolism
• NF-kappa B/metabolism
• Phosphorylation
• Rats