Mechanism of action of Daqinjiao decoction in treating cerebral small vessel disease explored using network pharmacology and molecular docking technology.

BACKGROUND AND PURPOSE: Cerebral small vessel disease (CSVD) is a clinically commonly-seen slow-progressing cerebral vascular disease. As a classic Chinese formula for the treatment of stroke, Daqinjiao Decoction (DQJD) is now used to treat CSVD with desirable effect. Since the mechanism of action is still unclear, this article will explore the therapeutic effect and mechanism of action of the formula using network pharmacology technology. METHODS: The major chemical components and potential target genes of DQJD were screened by bioinformatics. The key targets in CSVD were identified based on network modules. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. Pharmacodynamics of the decoction was evaluated by establishing a rat model with bilateral common carotid artery occlusion in the brain. Molecular docking, Western blot analysis and quantitative real-time polymerase chain reaction (QRT-PCR) were performed to confirm the effectiveness of targets in related pathways. RESULTS: Network pharmacology showed that 16 targets and 30 pathways were involved in the DQJD-targeted pathway network. Results revealed that DQJD might play a role by targeting the key targets including Caspse3 and P53 and regulating the P53 signaling pathway. Cognitive function and neuronal cell changes of rats were evaluated using Morris water maze, open field test and HE staining. It was indicated that DQJD could keep the nerve cells intact and neatly arranged. The decoction could improve the memory and learning ability of rats compared with the model group. It decreased the protein and mRNA expression levels of Caspse3 and P53 significantly (p<0.01). CONCLUSION: The study shows that baicalein, quercetin and wogonin, the effective components of DQJD, may regulate multiple signaling pathways by targeting the targets like Caspse3 and P53 and treat CSVD by reducing the damage to brain nerve cells.

[Baimai Ointment relieves chronic pain induced by chronic compression of dorsal root ganglion in rats by regulating neuroactive ligand-receptor interaction and HIF-1 signaling pathway].

The Baimai Ointment with the effect of relaxing sinew and activating collaterals demonstrates a definite effect on Baimai disease with pain, spasm, stiffness and other symptoms, while the pharmacodynamic characteristics and mechanism of this agent remain unclear. In this study, a rat model of chronic compression of L4 dorsal root ganglion(CCD) was established by lumbar disc herniation, and the efficacy and mechanism of Baimai Ointment in the treatment of CCD were preliminarily explored by behavioral tests, side effect evaluation, network analysis, antagonist and molecular biology verification. The pharmacodynamic experiment indicated that Baimai Ointment significantly improved the pain thresholds(mechanical pain, thermal pain, and cold pain) and gait behavior of CCD model rats without causing tolerance or obvious toxic and side effects. Baimai Ointment inhibited the second-phase nociceptive response of mice in the formalin test, increased the hot plate threshold of normal mice, and down-regulated the expression of inflammatory cytokines in the spinal cord. Network analysis showed that Baimai Ointment had synergistic effect in the treatment of CCD and was related to descending inhibition/facilitation system and neuroinflammation. Furthermore, behavioral tests, Western blot, and immunofluorescence assay revealed that the pain-relieving effect of Baimai Ointment on CCD may be related to the regulation of the interaction between neuroactive ligand and receptors(neuroligands) such as CHRNA7, ADRA2A, and ADRB2, and the down-regulation of the expression of NOS2/pERK/PI3K, the core regulatory element of HIF-1 signaling pathway in spinal microglia. The findings preliminarily reveal the mechanism of relaxing sinew and activating collaterals of Baimai Ointment in the treatment of Baimai disease, providing a reference for the rational drug use and further research of this agent.

Antioxidative and immunological effects of Cyclocarya paliurus polysaccharides on the spleen injury of diabetic rat.

OBJEVTIVE: To investigate the effects of Cyclocarya paliurus (C. paliurus) polysaccharides on the spleen injury of diabetic rats. METHODS: Animals were divided into 6 groups, including normal group, model group, control group, low-dose group of C. paliurus polysaccharides treatment, middle-dose group of C. paliurus polysaccharides treatment and high-dose group of C. paliurus polysaccharides treatment. Histological analysis of spleen was analyzed using hematoxilin and eosin. Levels of biological parameters and anti-oxidative enzymes were determined by spectrophotometry. Interleukin-7 (IL-7) and IL-10 were measured by enzyme-linked immunosorbent assay. RESULTS: Compared with that of model group, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase level increased 78.63% (P < 0.05), 51.76% (P < 0.05), 2.95 times (P < 0.01) and 41.11% (P < 0.05) in the high-dose group of C. paliurus polysaccharides treatment, respectively. IL-7 and IL-10 increase 1.66 (P < 0.01) and 1.21 times (P < 0.01) in the high-dose group of C. paliurus polysaccharides treatment, respectively. CONCLUSION: It is suggested that C. paliurus polysaccharides may play a protecting role for spleen injury of diabetic rats by enhancing the antioxidative ability and evaluating the immunity.

Effect of Cyclocarya paliurus polysaccharides on streptozotocin-induced diabetic nephropathy in rats.

OBJEVTIVE: To investigate the efficacy of Cyclocarya paliurus (C. paliurus) polysaccharides on stre- ptozotocin-induced diabetic nephropathy in rats. METHODS: Rats were divided into 6 groups, including group of normal control, group of diabetic control, group of metformin treatment, low-dose group of C. paliurus polysaccharides treatment, middle-dose group of C. paliurus polysaccharides treatment and high-dose group of C. paliurus polysaccharides treatment. Histological analysis of kidney was analyzed using hematoxilin and eosin. Levels of blood glucose, creatinine, urea, uric acid were determined by spectrophotometry. Anti-oxidative enzymes were measured by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Advanced glycation end products (AGEs) and transforming growth factor-ß1 (TGF-ß1) level was measured by ELISA. RESULTS: Abnormal changes were observed in the group of diabetic control characterized by atrophy of the renal glomeruli with hypercellularity, congestion of glomerular tufts, dilation of the renal spaces, and degeneration of renal tubule. Compared with that of normal group, blood glucose, creatinine, urea, uric acid level was significantly increased in the group of diabetic control. Superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase level was significantly decreased, but AGEs and TGF-ß1 level was significantly increased. By contrast, administration of C. paliurus polysaccharides and metformin could reverse the above-mentioned results of the group of diabetic control, especially in the high-dose group of C. paliurus polysaccharides. CONCLUSION: Our findings suggest that C. paliurus polysaccharides may play a protecting role for nephropathy of diabetic rats by lowering glucose, creatinine, urea, uric acid level, enhancing the antioxidative ability, and reducing AGEs and TGF-ß1 expression.

A new understanding of prescription.

To promote the development of Traditional Chinese Medicine (TCM), it is necessary to innovate the traditional prescription. It is feasible to use one or several components to substitute TCM, which can be regarded as a process of discarding the dregs and preserving the essential components. In this way, traditional prescription can be converted into various combinations of pharmacological ingredients deriving from several TCMs. Furthermore, some of pharmacological ingredients should be modified to increase their efficacy. It is practical to select the main structural unit with specific substituents having strong pharmacological activity. After the innovation mentioned above, the prescription will evolve into a variety of modified components having distinct pharmacological activity, and this is the novel integration of active ingredients.

Wenyang Huazhuo Tongluo formula inhibits fibrosis via suppressing Wnt/ß-catenin signaling pathway in a Bleomycin-induced systemic sclerosis mouse model.

BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs. So far, no Western medicine treatment can completely inhibit or reverse the progress of SSc, while at the same time, our previous series of studies have shown that the treatment of SSc by the Wenyang Huazhuo Tongluo formula (WYHZTL), a Chinese herbal decoction, shows a delightful prospect. The aim of this study is to further investigate the mechanism of anti-fibrosis of WYHZTL formula in SSc mouse model. METHODS: The Bleomycin-induced SSc mouse model was treated with saline (BLM), high-dosage of WYHZTL formula (WYHZTL-H), medium-dosage of WYHZTL formula (WYHZTL-M), low-dosage of WYHZTL formula (WYHZTL-L) and XAV-939, a small molecule inhibitor of Wnt/ß-catenin signaling pathway, by the intragastric administration and intraperitoneal injection, respectively. The mRNA and protein levels of Wnt/ß-catenin signaling pathway associated genes, fibrosis markers and histopathology were detected by reverse transcription-quantitative polymerase chain reaction, Western blotting and hematoxylin/eosin-staining. The levels of Wnt1, CTGF and DKK1 protein in serum were detected by enzyme-linked immunosorbent assay. RESULTS: Compared with BLM group, the WYHZTL formula and XAV-939 could significantly inhibit the thickness of the skin tissue of the SSc mouse model. The mRNA expression levels of GSK3ß and DKK1 in the WYHZTL formula and XAV-939-treated group were significantly higher than those in the BLM group, while Wnt1, ß-catenin, TCF4, cyclin D1, survivin, VEGF, CTGF, FN1, collagen I/III were decreased. Compared with BLM group, the protein expression levels of GSK3ß and DKK1 in the WYHZTL formula and XAV-939-treated group were upregulated, while Wnt1, ß-catenin, cyclin D1, survivin, CTGF, FN1, collagen I/III were downregulated. WYHZTL formula and XAV-939 could inhibit expression of Wnt1 and CTGF, but promoted DKK1 in serum. Furthermore, WYHZTL-H seemed more effective than WYHZTL-M and/or XAV-939 on regulating Wnt1, ß-catenin, TCF4, GSK3ß, DKK1, cyclin D1, survivin, VEGF, CTGF, FN1 and collagen I/III. CONCLUSION: This present study demonstrates that WYHZTL formula has anti-fibrosis effect in Bleomycin-induced SSc mouse model in a dosage-dependent manner, and the molecular mechanism may be related to the inhibition of Wnt/ß-catenin signaling pathway.

[Analgesic effect and central mechanisms of CQ prescription on cancer invasion induced mirror image pain in model mice].

This study aimed to analyze the analgesic effect and related central mechanisms of CQ prescription on cancer invasion induced mirror image pain (CIIMIP)in model mice.In the study, male BALB/c mice were randomly divided into normal group, operation control group (injected with 0.2 mL inactivated S180 sarcoma cell sap), model group (injected with 0.2 mL S180 sarcoma cell sap on the right leg near the greater trochanter of femur) and CQ prescription low dose group (intraperitoneally injected with CQ prescription 100 mg•kg⁻¹ on the basis of model mice), CQ prescription middle dose group (intraperitoneally injected with CQ prescription 150 mg•kg⁻¹ on the basis of model mice), and CQ prescription high dose group (intraperitoneally injected with CQ prescription 200 mg•kg⁻¹ on the basis of model mice). Mechanical withdraw threshold (MWT) of the mirror image lateral hind paws were evaluated by Von Frey hairs before modeling and after surgery. The levels of glutamate (Glu), gamma aminobutyric acid (GABA), glycine (Gly), and taurine (Tau) in the L3-L5 spinal cord were measured by the high performance liquid chromatography-fluorescence detector (HPLC-FLD); AimPlex detection technology with multiple factors was used to detect the levels of regulated on activation in normal T-cell expressed and secreted (RANTES), monocyte chemoattractant protein (MCP-3) in the L3-L5 spinal cord. Then we observed the influence of GABAa receptor antagonist (Bicuculline) on analgesic effect of CQ prescription.The results indicated that CQ prescription could remarkably increase MWT of model mice(P<0.01, P<0.05), decrease the level of Glu(P<0.01, P<0.05), improve the levels of GABA, Gly, Tau(P<0.01, P<0.05), lower the ratio of Glu/GABA(P<0.01, P<0.05), and reduce the levels of RANTES, MCP-3(P<0.05) in the L3-L5 spinal cord, and GABAa receptor antagonist significantly blocked the analgesic effect of CQ prescription at two time points(P<0.05).This study showed that CQ prescription had significant analgesic effect on CIIMIP model mice, and its mechanism was associated with regulating the balance between excitability amino acid(EAA) and inhibitory amino acid (IAA) transmitters in central nervous system, partially activating GABAa receptor, and reducing the release of RANTES and MCP-3 in the spinal cord.

Velvet antler polypeptide is able to induce differentiation of neural stem cells towards neurons in vitro.

OBJECTIVE: To investigate the neural differentiation capacity of water extraction of velvet antler. METHODS: Velvet antler (Cervus Nippon Temminck) polypeptide (VAP) was used to differentiate neural stem cells (NSCs) towards neurons in the study. Firstly, we obtain the polypeptides of VAP by water extraction. Secondly, we observed the morphology, assayed the factors in the media by enzyme-linked immunosorbent assay, and detected the special neural molecules by immunfluorescence staining. NSCs were cultured on the cell climbing film. After neuronal differentiation, differentiated NSCs were mounted for immunocytochemistry with immunofluorescence technique. RESULTS: The differentiating cells look like neuron, some special factors, such as Glial cell line-derived neurotrophic factor, nerve growth factor, in the media can be detected while differentiated neuron-like cells can express the special neural molecules. CONCLUSION: Differentiation of NSCs towards neurons can be induced by velvet antler polypeptide.

Efficacy of Bushenjianpi prescription on autoimmune premature ovarian failure in mice.

OBJECTIVE: To assess the efficacy of Bushenjianpi prescription (BSJPP), a formula from Traditional Chinese Medicine, on a mouse model of autoimmune premature ovarian failure (POF) induced by mouse zona pellucida (ZP3) and to investigate the mechanisms underlying the action. METHODS: After randomization, POF was induced in the model mice by immunization with ZP3. One week later, mice received low (8.1 mg/kg), moderate (16.2 mg/kg) and high (32.4 mg/kg) doses of BSJPP by gastrogavage once daily for 90 days. Premarin (0.03 mg/kg) served as the positive group. Serum samples were collected 1 week after the last dose and stored at -20 for analysis. After cervical dislocation, the uterus and ovaries were collected aseptically for evaluation by histological assessment, scanning electron microscopy, immunohistochemical staining, and Western blot and reverse transcription-polymerase chain reaction analyses. RESULTS: Serum E2 levels in POF model mice were decreased, whereas follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were dramatically increased. Serum levels of E2, LH and FSH were reduced in POF model mice treated with BSJPP (moderate and high doses) and premarin. Anti-bone morphogenetic protein 15 (BMP-15) and connexin 43 (Cx43) were repressed in autoimmune POF model mice, whereas high expression was observed in control mice and those treated with BSJPP (moderate and high doses) and premarin. CONCLUSION: BSJPP is effective in treating ZP3-induced POF in mice and the increase in the expression of BMP-15 and Cx43 may be implicated in the mechanism underpinning the action.

Wenyang Huazhuo Tongluo formula, a Chinese herbal decoction, improves skin fibrosis by promoting apoptosis and inhibiting proliferation through down-regulation of survivin and cyclin D1 in systemic sclerosis.

BACKGROUND: Fibrosis is a major contributor to systemic sclerosis (SSc)-related morbidity, and rapid, progressive skin involvement predicts later mortality. Western medicine therapies for SSc cannot produce satisfactory effects currently, while Traditional Chinese Medicine (TCM), such as the Wenyang Huazhuo Tongluo (WYHZTL) formula, a Chinese herbal decoction, has shown amazing anti-fibrosis efficacy on SSc in clinical applications. This study is aiming to investigate the anti-fibrotic mechanism of WYHZTL formula for the treatment of SSc. METHODS: Fibroblasts from primary culture of skin lesions of SSc patients were exposed to rat medicated sera containing WYHZTL or XAV939, a small-molecule inhibitor of both tankyrase 1/2 and Wnt/ß-catenin pathway. Cell counting kit-8 assay and Annexin V FITC/PI apoptosis kit were used to analyze cell proliferation and apoptosis in fibroblasts, respectively. Reverse transcription-polymerase chain reaction (RT-PCR) and western blotting were used to detect the mRNA and protein levels of cyclin D1 and survivin. RESULTS: After 28, 48 and 72 h of incubation, the proliferative ability of the fibroblasts cells was obviously reduced by the sera containing WYHZTL compared with that in the control group; the percentage of apoptotic cell population in the sera containing WYHZTL treated fibroblasts cells was significantly higher than that in those treated with the control sera, and was about similar to that in those treated with XAV939. The sera containing WYHZTL could down-regulate both mRNA and protein levels of cyclin D1 and survivin, compared with the control group. CONCLUSIONS: The present study demonstrates the antiproliferative and pro-apoptotic actions of WYHZTL formula against fibroblasts and the effect may be related to the down-regulation of mRNA and protein levels of cyclin D1 and survivin in SSc.

Generation of insulin-producing cells from rat mesenchymal stem cells using an aminopyrrole derivative XW4.4.

Type 1 diabetes mellitus (T1DM), a multisystem disease with both biochemical and anatomical/structural consequences, is a major health concern worldwide. Pancreatic islet transplantation provides a promising treatment for T1DM. However, the limited availability of islet tissue or new sources of insulin producing cells (IPCs) that are responsive to glucose hinder this promising approach. Though slow, the development of pancreatic beta-cell lines from rodent or human origin has been steadily progressing. Bone marrow-derived mesenchymal stem cells (MSCs) are multipotent, culture-expanded, non-hematopoietic cells that are currently being investigated as a novel cellular therapy. The in vitro differentiation potential of IPCs has raised hopes for a treatment of clinical diseases associated with autoimmunity. We screened for small molecules that induce pancreatic differentiation of IPCs. There are some compounds which showed positive effects on the DTZ staining. The aminopyrrole derivative compound XW4.4 which shows the best activity among them was found to induce pancreatic differentiation of rat MSCs (rMSCs). The in vitro studies indicated that treatment of rMSCs with compound XW4.4 resulted in differentiated cells with characteristics of IPCs including islet-like clusters, spherical, grape-like morphology, insulin secretion, positive for dithizone, glucose stimulation and expression of pancreatic endocrine cell marker genes. The data has also suggested that hepatocyte nuclear factor 3ß (HNF 3ß) may be involved in pancreatic differentiation of rMSCs when treated with XW4.4. Results indicate that XW4.4 induced rMSCs support the efforts to derive functional IPCs and serve as a means to alleviate limitations surrounding islet cell transplantation in the treatment of T1DM.

Hepatic differentiation of rat mesenchymal stem cells by a small molecule.

Mesenchymal stem cells (MSCs) are capable of self-renewal and multilineage differentiation. A periodic acid-Schiff (PAS) stain-based assay was developed to screen for small-molecule inducers of hepatic differentiation of bone marrow MSCs. 2-(4-Bromophenyl)-N-(4-fluorophenyl)-3-propyl-3H-imidazo[4,5-b]pyridin-5-amine (SJA710-6) was identified as a novel small molecule able to induce the differentiation of rat MSCs (rMSCs) toward hepatocyte-like cells in vitro, where rMSCs treated with SJA710-6 have typical morphological and functional characteristics of hepatic cells, including glycogen storage, urea secretion, uptake of low density lipoprotein (LDL) and expression of hepatocyte-specific genes and proteins. Expression of FoxH1 (FAST1/2) induces the differentiation of rMSCs towards hepatocyte-like cells, suggesting that this gene plays an important role in the hepatic fate specification of rMSCs.

Synthesis of berbamine acetyl glycosides and evaluation of antitumor activity.

A series of berbamine glycosides was designed, synthesized and evaluated as a new class of antitumor agents. An efficient glycosylation route was developed for berbamide derivatives. The newly synthesized glycosides were evaluated for their cytotoxic activity in vitro against a human leukemia cell line K562, a human lung adenocarcinoma cell line A549 and mouse lymphocytic leukemia cells L1210. In contrast to berbamine most of its glycosides manifested potent cytotoxic activities. The acetyl glycosyl berbamine 5a, 5d caused distinct improvement against K562, A549 and L1210. It is suggested that the acetyl D-glucose residue has affinity to these cancer cells.

Synthesis and biological evaluation of 2-indolinone derivatives as potential antitumor agents.

Three series of 3-substituted-indolin-2-ones and azaindolin-2-ones have been synthesized and showed potential antiproliferative activity to cancer cell lines. The inhibition activities on VEGF-induced VEGFR phosphorylation were observed for selected 2-indolinones. Among the compounds synthesized, 5-fluoroindolin-2-one derivative 23 with a pyridone unit showed the most significant enzymatic and cellular activities. Flow cytometric analysis indicates that 23 plays a role in suppressing HCT-116 cell proliferation via G1 phase arrest and apoptosis in a dose dependent manner. The binding mode of compound 23 complexed with VEGFR-2 was predicted using FlexX algorithm. Described here are the chemistry and biological testing for these series which will guide the design and optimization of novel 2-indolione antitumor agents.

A novel therapeutic regimen for hepatic fibrosis using the combination of mesenchymal stem cells and baicalin.

Baicalin, isolated from the root of Scutellaria baicalensis Georgi, has shown anti-inflammatory and antioxidant activities, while mesenchymal stem cells (MSCs) have the capability of self-renewal and multilineage differentiation. In the present study, we found that baicalin could promote differentiation of bone marrow-derived MSCs into hepatocytes in vitro. We then compared the therapeutic effects of five therapeutic regimens for hepatic fibrosis induced by carbon tetrachloride in vivo by analysis of serum enzymes, morphological characteristics, cytokines and cell engraftment. Transplantation of MSCs alone was able to promote partial recovery of liver function and suppression of liver inflammation, but showed little effect on reducing the fibrotic area; transplantation with baicalin-treated MSCs gave an improved therapeutic effect; MSC transplantation and baicalin administration showed a synergistic effect; transplantation with baicalin-treated MSCs in combination with baicalin administration had the best therapeutic effect for hepatic fibrosis. Therefore, we conclude that transplantation of pre-differentiated MSC together with baicalin administration may serve as an effective therapeutic regimen for severe liver diseases.

Synergistic effects of rMSCs and salidroside on the experimental hepatic fibrosis.

Rat mesenchymal stem cells (rMSCs) and salidroside have been applied in the treatment of hepatic fibrosis. The present study aimed to investigate the mechanism of hepatic differentiation of rMSCs in vitro and synergistic effects of rMSCs and salidroside on the experimental hepatic fibrosis in rats. rMSCs treated with 10 microg/mL, 20 microg/mL and 50 microg/mL salidroside were taken at 14 days and the proteins were subjected to western blot analysis. Hepatic fibrosis was induced in rats by administration of porcine serum for 8 weeks. Then, rats were randomly divided into 6 groups: control group, hepatic fibrosis group (model), salidroside group, rMSCs group and rMSCs plus salidroside group. Four weeks later, the localization and differentiation of rMSCs were determined. To evaluate the improvement of liver injury, the pathology of hepatocytes (or liver) and serum transforming growth factor-beta1 (TGF-beta1) were assessed. Induced rMSCs expressed alpha-fetoprotein (AFP) and albumin (ALB), which suggested rMSCs differentiated towards hepatocytes; moreover, E-adherin and beta-catenin were involved in the hepatic differentiation of rMSCs. In experiments of rMSCs transplantation, the amount of collagen in the liver of rMSCs plus salidroside treated rats was significantly lowered accompanied by reduced expression of TGF-beta1, when compared to the control group and rMSCs group. These findings suggested the synergistic effects of rMSCs transplantation and salidroside on hepatic fibrosis. Salidroside could differentiate rMSCs towards hepatocytes and E-adherin and beta-catenin were involved in the hepatic differentiation of rMSCs. Treatment with rMSCs transplantation and salidroside exerted synergistic effects on the experimental hepatic fibrosis via suppressing the expression of TGF-beta1.

In-vitro promoted differentiation of mesenchymal stem cells towards hepatocytes induced by salidroside.

OBJECTIVES: The present study aimed to investigate whether salidroside can induce differentiation of rat mesenchymal stem cells (rMSCs) towards hepatocytes in vitro and the mechanism of hepatic differentiation of rMSCs. METHODS: rMSCs were subject to hepatic differentiation. One, two and three weeks later, the expression of alpha fetoprotein (AFP) and albumin (ALB), cytochrome P450 (CYP450)-dependent activity and inducibility, cellular uptake of low density lipoprotein (LDL) and urea synthesis were assessed and the hepatic differentiation of rMSCs was evaluated. In order to unravel the mechanism of hepatic differentiation of rMSCs in vitro, inhibitors of extracellular regulated kinase1/2 (ERK1/2), phosphatidylinositol 3-kinase (PI3K) and p38 were applied. When the process of hepatic differentiation was completed, special proteins of hepatic differentiation were detected and blocking of inhibitors was evaluated. KEY FINDINGS: Salidroside significantly induce differentiation of rMSCs towards hepatocytes. Differentiated rMSCs have typical functional hepatic characteristics. The results also showed that the ERK1/2 and PI3K signalling pathways play important roles in the regulatory effects of salidroside on hepatic differentiation of rMSCs and are involved in cell fate determinations, while the p38 signalling pathway does not. CONCLUSIONS: Salidroside can induce differentiation of rMSCs towards hepatocytes in vivo, and the ERK1/2 or PI3K signalling pathway underlie the process of hepatic differentiation.