Search

Realgar and indigo naturalis are clinically combined to treat varieties of leukemia. Exploring the drug-drug interactions might be beneficial to find active substances and develop new targeted drugs. This study aimed at exploring the change of arsenic concentration in mice and across MDCK-MDR1 cells and the cytotoxicity on K562 cells when realgar and indigo naturalis were combined. In the presence or absence of indigo naturalis, pharmacokinetics and cell-based permeability assays were used to evaluate the change of arsenic concentration, and K562 cell line was applied to evaluate the change of cytotoxicity. The drug concentration-time profiles exhibited that the combination medication group generated higher AUC, thalf, and longer MRT for arsenic, compared with the single administration of realgar. The apparent permeability coefficients (Papp) of bidirectional transport in MDCK-MDR1 cell permeability experiments showed that arsenic permeability obviously went up when indigo naturalis was incubated together. The combination medication significantly decreased the cell viability of K562 cells when both the concentration of realgar and the concentration of indigo naturalis were nontoxic. The pharmacokinetic research, the MDCK-MDR1 based permeability study, and the K562 cytotoxicity study were united together to verify the combination medication of realgar and indigo naturalis enhanced the absorption and the permeability across cells for arsenic and effectively inhibited the proliferation of K562 cell line. The molecular binding of As4S4 and indirubin was analyzed by computational study. It is predicted that the formation of the complex [As4S4…Indirubin] involves noncovalent interaction that changes the concentration of arsenic. [ABSTRACT FROM AUTHOR]

Liver regeneration after partial hepatectomy (PHx) is a physiological response for maintaining homeostasis. The aim of this study is to investigate effects of Elephantopus scaber L.- (ESL-) induced liver regeneration on growth factors (HGF and IGF-1), cell cycle regulation, and apoptosis suppressed. In this study, we fed five Chinese medicinal herbs (1 g/kg/day), Codonopsis pilosula (CP, Dangshen), Salvia miltiorrhiza Bunge (SMB, Danshen,), Bupleurum kasi (BK, Chaihu), Elephantopus scaber L. (ESL, Teng-Khia-U), and Silymarin (Sm, 25 mg/kg) for 7 days to male Spraue-Dawley rats. Then surgical 2/3 PHx was conducted and liver regeneration mechanisms were estimated on the following 24 hrs and 72 hrs. The activities of growth factors (HGF and IGF-I) and cell cycle proteins were measured by Western blot and RT-PCR. Histological analysis and apoptosis were detected by H&E stain and TUNEL. The results showed that extraction of Elephantopus scaber L. (ESL) and Silymarin (Sm, positive control) were increased protein expression levels of HGF and IGF-1 which leads into cell cycle. These results suggest that the ESL plays a crucial role in cell cycle-induced liver regeneration and apoptosis. These results suggested that the ESL plays a crucial role in cell cycle-induced liver regeneration and suppressed hepatocytes apoptosis. [ABSTRACT FROM AUTHOR]

We tested the effect of Astragalus membranaceus (AM) on acute hemorrhagic stroke. Seventy-eight patients were randomly assigned to Group A (3 g of AM three times/day for 14 days); or Group B (3 g of placebo herb). A total of 68 patients (Group A 36, Group B 32) completed the trial. The increase of functional independence measure scale score between baseline and week 4 was 24.53 ± 23.40, and between baseline and week 12 was 34.69 ± 28.89, in the Group A was greater than 11.97 ± 11.48 and 23.94 ± 14.8 in the Group B (both P ⩽ 0.05). The increase of Glasgow outcome scale score between baseline and week 12 was 0.75 ± 0.77 in the Group A was greater than 0.41 ± 0.50 in the Group B (P < 0.05). The results are preliminary and need a larger study to assess the efficacy of AM after stroke. [ABSTRACT FROM AUTHOR]

We used the carbon tetrachloride (CCl4) induced liver cirrhosis model to test the molecular mechanism of action involved in cirrhosis-associated cardiac hypertrophy and the effectiveness of Ocimum gratissimum extract (OGE) and silymarin against cardiac hypertrophy.We treated male wistar rats with CCl4 and either OGE (0.02 g/kg B.W. or 0.04 g/kg B.W.) or silymarin (0.2 g/kg B.W.). Cardiac eccentric hypertrophy was induced by CCl4 along with cirrhosis and increased expression of cardiac hypertrophy related genes NFAT, TAGA4, and NBP, and the interleukin-6 (IL-6) signaling pathway related genes MEK5, ERK5, JAK, and STAT3. OGE or silymarin co-treatment attenuated CCl4-induced cardiac abnormalities, and lowered expression of genes which were elevated by this hepatotoxin. Our results suggest that the IL-6 signaling pathway may be related to CCl4-induced cardiac hypertrophy. OGE and silymarin were able to lower liver fibrosis, which reduces the chance of cardiac hypertrophy perhaps by lowering the expressions of IL-6 signaling pathway related genes. We conclude that treatment of cirrhosis using herbal supplements is a viable option for protecting cardiac tissues against cirrhosis-related cardiac hypertrophy. [ABSTRACT FROM AUTHOR]

Garlic oil has been reported to protect the cardiovascular system; however, the effects andmechanisms behind the cardioprotection of garlic oil on diabetes-induced cardiaomyopathy are unclear. In this study, we used streptozotocin (STZ)-induced diabetic rats to investigate whether garlic oil could protect the heart from diabetes-induced cardiomyopathy. Wistar STZ-induced diabetic rats received garlic oil (0, 10, 50 or 100 mg kg-1 body weight) by gastric gavage every 2 days for 16 days. Normal rats without diabetes were used as control. Cardiac contractile dysfunction and cardiac pathologic hypertrophy responses were observed in diabetic rat hearts. Cardiac function was examined using echocardiography. In addition to cardiac hypertrophy-related mitogen-activated protein kinases (MAPK) pathways (e.g., p38, c-Jun N-terminal kinases (JNK) and extracellularly responsive kinase (ERK1/2)), the IL-6/MEK5/ERK5 signaling pathway was greatly activated in the diabetic rat hearts, which contributes to the up-regulation of cardiac pathologic hypertrophy markers including atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), and leads to cardiac contractile dysfunction. Garlic oil treatment significantly inhibited the up-regulation in MAPK (e.g., p38, JNK and ERK1/2) and IL-6/MEK5/ERK5 signaling pathways in the diabetic rat hearts, reducing the levels of cardiac pathologic hypertrophy markers such as ANP and BNP, and improving the cardiac contractile function. Collectively, data from these studies demonstrate that garlic oil shows the potential cardioprotective effects for protecting heart from diabetic cardiomyopathy. [ABSTRACT FROM AUTHOR]

Apoptosis involves in the pathogenesis of various cardiac abnormalities. This study intends to evaluate the effects of Li-Fu formula on cardiac apoptosis induced by hyper-cholesterol diet. Twenty-four male Golden Syrian hamsters were randomly divided into Control, Cholesterol and Li-Fu formula groups. Histopathological analysis, western blotting and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were performed to measure the effects of Li-Fu formula on left ventricle. Significantly reduced TUNEL-positive cells andmitochondria- dependent apoptosis were observed in the left ventricle of hamsters from Li-Fu formula group compared to the Cholesterol group. Additionally, induced cardiac insulin like growth factor I receptor (IGFIR)-dependent survival pathway was detected in the Li-Fu formula group compared to the Cholesterol group. Besides, minor fibrosis, increased collagen deposition, and myofibril disarray was detected in the Cholesterol group, whereas the reductions of collagen deposition and myofibril disarray were observed in the Li-Fu formula group. This study demonstrated that Li-Fu formula not only reduced the mitochondria-dependent apoptosis and fibrosis, but also enhanced the IGF-I survival pathway in the left ventricle from high cholesterol-fed hamsters. We suggest the protective effects of Li-Fu formula on cardiac apoptosis and therapeutic potentials against cardiovascular disease. [ABSTRACT FROM AUTHOR]

Hypercholesterolemia diets are considered as major sources to cause cardiac hypertrophy. This study intends to evaluate the effects of Li-Fu formula on cardiac hypertrophy induced by hypercholesterolemia diet. Twenty-four male Golden Syrian hamsters were randomly divided into control, cholesterol and Li-Fu formula groups and fed with different experimental diets for 2 months. Histopathological analysis and western blotting were performed to measure the myocardial architecture, and various cardiac hypertrophy-associated molecules in the excised left ventricle from hamsters. The ratios of whole heart weight/body weight (BW) and left ventricle weight/BWwere significantly higher in the cholesterol group but significantly lower in the Li-Fu formula group. The protein levels of both atrial natriuretic peptide and brain natriuretic peptide were significantly increased in the cholesterol group but significantly reduced in the Li-Fu formula group. Additionally, significantly increased interleukin-6, STAT3, MEK5, p- ERK5 and non-cardiomyocyte proliferate signal molecules such as p-MEK and p-ERK, were detected in the cholesterol group but significantly reduced in the Li-Fu formula group. Notably, no significant variations of inflammatory signalingmolecules, including p-P38 and p-JNK, were detected in all groups. Our experimental results demonstrated the significant reductions of cardiac hypertrophy and related eccentric hypertrophy signaling, non-cardiomyocyte proliferate signaling in the excised left ventricle of hamsters from the Li-Fu formula.We suggested the protective effects of Li-Fu formula on cardiac hypertrophy that may be useful in prevention or treatment of hypertrophy-associated cardiovascular diseases. [ABSTRACT FROM AUTHOR]

The earthworm, which has stasis removal and wound-healing functions, is a widely used Chinese herbal medicine in China. Schwann cell migration is critical for the regeneration of injured nerves. Schwann cells provide an essentially supportive activity for neuron regeneration. However, the molecular migration mechanisms induced by earthworms in Schwann cells remain unclear. Here, we investigate the roles of MAPK (ERK1/2, JNK and p38) pathways for earthworm-induced matrix-degrading proteolytic enzyme (PAs and MMP2/9) production in Schwann cells.Moreover, earthworm induced phosphorylation of ERK1/2 and p38, but not JNK, activate the downstream signaling expression of PAs and MMPs in a time-dependent manner. Earthworm-stimulated ERK1/2 and p38 phosphorylation was attenuated by pretreatment with U0126 and SB203580, resulting in migration and uPArelated signal pathway inhibition. The results were confirmed using small interfering ERK1/2 and p38 RNA. These results demonstrated that earthworms can stimulate Schwann cell migration and up-regulate PAs and MMP2/9 expression mediated through the MAPK pathways, ERK1/2 and p38. Taken together, our data suggests the MAPKs (ERK1/2, p38)-, PAs (uPA, tPA)-, MMP (MMP2, MMP9) signaling pathway of Schwann cells regulated by earthworms might play a major role in Schwann cell migration and nerve regeneration. [ABSTRACT FROM AUTHOR]

Dilong, also known as earthworm, has been widely used in traditional Chinese medicine (TCM) for thousands of years. Schwann cell migration and proliferation are critical for the regeneration of injured nerves and Schwann cells provide an essentially supportive role for neuron regeneration. However, the molecular mechanisms of migration and proliferation induced by dilongs in Schwann cells remain unclear. Here, we discuss the molecular mechanisms that includes (i) migration signaling, MAPKs (mitogen-activated protein kinases), mediated PAs and MMP2/9 pathway; (ii) survival and proliferative signaling, IGF-I (insulinlike growth factor-I)-mediated PI3K/Akt pathways and (iii) cell cycle regulation. Dilong stimulate RSC96 cell proliferation and migration. It can induce phosphorylation of ERK1/2 and p38, but not JNK, and activate the downstream signaling expression of PAs (plasminogen activators) andMMPs (matrixmetalloproteinases) in a time-dependent manner. In addition, Dilong stimulated ERK1/2 and p38 phosphorylation was attenuated by pretreatment with chemical inhibitors (U0126 and SB203580), and small interfering ERK1/2 and p38 RNA, resulting in migration and uPA-related signal pathway inhibition. Dilong also induces the phosphorylation of IGF-I-mediated PI3K/Akt pathway, activates protein expression of PCNA (proliferating cell nuclear antigen) and cell cycle regulatory proteins (cyclin D1, cyclin E and cyclin A) in a time-dependent manner. In addition, it accelerates G1- phase progression with earlier S-phase entry and significant numbers of cells entered the S-phase. The siRNA-mediated knockdown of PI3K that significantly reduces PI3K protein expression levels, resulting in Bcl2 survival factor reduction, revealing a marked blockage of G1 to S transition in proliferating cells. These results reveal the unknown RSC96 cell migration and proliferation mechanism induced by dilong, which find use as a new medicine for nerve regeneration. [ABSTRACT FROM AUTHOR]

Schwann cell proliferation is critical for the regeneration of injured nerves. Dilongs are widely used in Chinese herbal medicine to remove stasis and stimulate wound-healing functions. Exactly how this Chinese herbal medicine promotes tissue survival remains unclear. The aim of the present study was to investigate the molecular mechanisms by which Dilong promote neuron regeneration. Our results show that treatment with extract of Dilong induces the phosphorylation of the insulin-like growth factor-I (IGFI)- mediated phosphatidylinositol 3-kinase/serine-threonine kinase (PI3K/Akt) pathway, and activates protein expression of cell nuclear antigen (PCNA) in a time-dependent manner. Cell cycle analysis showed that G1 transits into the S phase in 12–16 h, and S transits into the G2 phase 20 h after exposure to earthworm extract. Strong expression of cyclin D1, cyclin E and cyclin A occurs in a time-dependent manner. Small interfering RNA (siRNA)-mediated knockdown of PI3K significantly reduced PI3K protein expression levels, resulting in Bcl2 survival factor reduction and a marked blockage of G1 to S transition in proliferating cells. These results demonstrate that Dilong promotes the proliferation and survival of RSC96 cells via IGF-I signaling. The mechanism is mainly dependent on the PI3K protein. [ABSTRACT FROM AUTHOR]