The effects of BuYang HuanWu Decoction and its effective components on proliferation-related factors and ERK1/2 signal transduction pathway in cultured vascular smooth muscle cells

Buyang Huanwu Decoction (BYHWD) was a commonly used traditional Chinese medicine for the treatment and prevention of ischemic cardiovascular and cerebral disease. Previous studies had shown that BYHWD alkaloids and glycosides could inhibit intimal hyperplasia and vascular smooth muscle cell (VSMC) proliferation after injury caused by balloon catheter. The present study aims to explore the mechanisms by which cell cycle was affected by BYHWD and its components. Primary rat VSMC was treated with platelet-derived growth factor (PDGF) and cell cycle phase and extracellular-signal regulated protein kinase (ERK) transduction pathway factors were measured. PDGF-treated cells were associated with a significant increase in the number of cells in the G₂/M phase and S phase, and in the expression of P-ERK1/2, proliferating cell nuclear antigen (PCNA), c-fos, cyclinD₁ and cyclin-dependent kinase-4, as well as a decrease in the number of cells in the G₀/G₁ phase, and in the expression of cyclin-dependent kinase inhibitor P21 protein and mitogen-activated protein kinase phosphatase-1 (MKP-1). Treatment with plasma of rats fed seven doses of BYHWD crude extract (22.2 g/kg), BYHWD alkaloids (1.66 g/kg), BYHWD glycosides (14.2 g/kg) or the negative control atorvastatin (20 mg/kg) inhibited these changes. All drug-containing plasma had similar activity to the mitogen activated protein kinase (MAPK)/ERK antagonist PD098059 which inhibited PDGF-induced expression of P-ERK1/2 and enhanced MKP-1. These suggest that BYHWD and its components may prevent VSMC proliferation by interfering with the ERK transduction pathway.     

The inhibitory effect of Houttuynia cordata extract on stem cell factor-induced HMC-1 cell migration

Hottuynia cordata Thunb (Saururaceae; HC) is known as a therapeutic drug that has been used in traditional oriental medicine for the treatment of allergy. Mast cells play an important role in a variety of inflammatory diseases, and specifically asthma and atopy. In the present study, we investigated the effect of HC extracts on the migration of the human mast cell line, HMC-1, in response to stem cell factor (SCF). Treatment with HC extracts at a concentration of 10mug/ml for 24h showed no significant decrease in the survival rate of the HMC-1 cells. SCF showed the typical bell-shape curve for the HMC-1 cell chemoattraction with the peak of the curve at the SCF concentration of 100ng/ml. HC-1, which was the whole plant (Houttuynia cordata) extracted with 80% EtOH, and HC-3, which was the residue successively partitioned with EtOAc, both had inhibitory effects on HMC-1 cell movement. After the treatment with 10mug/ml HC-1 extract for 6 and 24h, the chemotactic index (CI) of HMC-1 cells decreased up to 74 and 63%, respectively. HC-3 extract treatment for 6 and 24h lowered the CI to 72 and 44%, respectively. The HC-1 and HC-3 extracts had no inhibitory effect on the mRNA and surface protein expressions of c-kit, SCF receptor. SCF mediated the chemotaxis signaling via NF-kappaB activation, and both extracts inhibited the activation. Therefore, our results indicate that HC-1 and HC-3 extracts decrease the chemotactic ability of HMC-1 cells in response to SCF by inhibiting the NF-kappaB activation, and these substances may be useful for treating mast cell-induced inflammatory diseases.     

Chemopreventive and anti-cancer properties of the aqueous extract of flowers of Butea monosperma

Ethnopharmacological relevance

Butea monosperma (Lam.) (Fabaceae) popularly known as ‘flame of the forest’ has been widely used in the traditional Indian medical system of ‘Ayurveda’ for the treatment of a variety of ailments including liver disorders.

Aim of the study

To evaluate the antioxidative, anti-inflammatory, hepatoprotective and anti-cancer activities of the aqueous extract of Butea monosperma flowers.

Materials and methods

Dried flowers of Butea monosperma were extracted with water. The extract was tested for its anti-proliferative, pro-apoptotic and anti-carcinogenic effects in hepatoma cell lines. The chemopreventive and anti-angiogenic effects of the extract were evaluated by its daily oral administration in a HBV-related X15-myc mouse model of hepatocellular carcinoma (HCC).

Results

Treatment with the aqueous extract inhibited cell proliferation and accumulation of cells in G1 phase. This was accompanied by a marked reduction in the levels of activated Erk1/2 and SAPK/JNK and induction of apoptotic cell death. Oral administration of the extract in transgenic mice conferred hepatoprotection as is evident from normal serum ALT levels and improved liver histopathology and lowered serum VEGF level.

Conclusions

The ability of aqueous extract of Butea monosperma flowers to impose growth arrest and trigger pro-apoptotic death in cell culture strongly correlated with its strong chemopreventive effect in vivo when given orally.     

Eucommia ulmoides Oliv. Bark. protects against hydrogen peroxide-induced neuronal cell death in SH-SY5Y cells

Ethnopharmacological relevance

Eucommia ulmoides Oliv. Bark. (EUE), has commonly been used to fortify the muscles and lungs, lower blood pressure, prevent miscarriage, improve the tone of liver and kidneys, and promote longevity the traditional tonic medicines of Korea, China, and Japan.

Aim of the study

In this study, we investigated that the neuroprotective activities and possible mechanisms of EUE aqueous extract in hydrogen peroxide (H₂O₂)-induced neuronal cell death in human SH-SY5Y neuroblastoma cells.

Material and method

We examined the effects of EUE against H₂O₂-induced cytotoxicity, DNA condensation, the production of reactive oxygen species (ROS), loss of mitochondria membrane potential (MMP), the proteolysis of cleaved poly-ADP-ribose polymerase (PARP), and the expression of Bcl-2, Bcl-xL, cleaved caspase-3, and release of cytochrome c. Moreover, we attempted to determine whether EUE suppressed the phosphorylation of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase 1/2 (ERK 1/2), and phosphoinositide 3-kinase (PI3K)/Akt.

Results

Pretreatment with EUE increased cell viability and inhibited cytotoxicity and DNA condensation. EUE also attenuated the increase in ROS production and MMP reduction. Western blot data revealed that EUE inhibited H₂O₂-induced up- or down-regulation of cleaved PARP, cleaved caspase-3, Bcl-2, and Bcl-xL. The EUE inhibited release of cytochrome c from mitochondria to the cytosol, and significantly attenuated H₂O₂-induced phosphorylation of JNK, p38 MAPK, ERK 1/2, and PI3K/Akt.

Conclusion

The potent neuroprotective capacity of EUE, shown in these experiments, may potentially be applied in the prevention or treatment of neurodegenerative diseases such as Alzheimer's disease (AD).     

Triptolide: Progress on research in pharmacodynamics and toxicology

Ethnopharmacological relevance

Tripterygium wilfordii Hook. f. (Tripterygium wilfordii), also known as Huangteng and gelsemium elegan, is a traditional Chinese medicine that has been marketed in China as Tripterygium wilfordii glycoside tablets. Triptolide (TP), an active component in Tripterygium wilfordii extracts, has been used to treat various diseases, including lupus, cancer, rheumatoid arthritis and nephritic syndrome. This review summarizes recent developments in the research on the pharmacodynamics, pharmacokinetics, pharmacy and toxicology of TP, with a focus on its novel mechanism of reducing toxicity. This review provides insight for future studies on traditional Chinese medicine, a field that is both historically and currently important.

Materials and methods

We included studies published primarily within the last five years that were available in online academic databases (e.g., PubMed, Google Scholar, CNKI, SciFinder and Web of Science).

Results

TP has a long history of use in China because it displays multiple pharmacological activities, including anti-rheumatism, anti-inflammatory, anti-tumor and neuroprotective properties. It has been widely used for the treatment of various diseases, such as rheumatoid arthritis, nephritic syndrome, lupus, Behcet?s disease and central nervous system diseases. Recently, numerous breakthroughs have been made in our understanding of the pharmacological efficacy of TP. Although TP has been marketed as a traditional Chinese medicine, its multi-organ toxicity prevents it from being widely used in clinical practice.

Conclusions

Triptolide, a biologically active natural product extracted from the root of Tripterygium wilfordii, has shown promising pharmacological effects, particularly as an anti-tumor agent. Currently, in anti-cancer research, more effort should be devoted to investigating effective anti-tumor targets and confirming the anti-tumor spectrum and clinical indications of novel anti-tumor pro-drugs. To apply TP appropriately, with high efficacy and low toxicity, the safety and non-toxic dose range for specific target organs and diseases should be determined, the altered pathways and mechanisms of exposure need to be clarified, and an early warning system for toxicity needs to be established. With further in-depth study of the efficacy and toxicity of TP, we believe that TP will become a promising multi-use drug with improved clinical efficacy and safety in the future.