Metabolic profile of Phellodendron amurense Rupr. in vivo of rat and its metabolomic study on intervention in rheumatoid arthritis.

To analyze the metabolites (blood, urine and feces) in normal rats after intragastric administration of the decoction of Phellodendri Amurensis Cortex (PAC) and to map the metabolic profile of PAC in vivo of rat; meanwhile, to evaluate the anti-rheumatoid arthritis (RA) effect of PAC by blood metabolomics technique and to explore its mechanism. Performing on UPLC-Q-TOF-MS technology with a Waters ACQUITY UPLC BEH-C18 column (100 mm × 2.1 mm, 1.7 µm), the mobile phase was acetonitrile-0.1% formic acid aqueous solution (gradient elution). Prior to and following the administration of the decoction of PAC, the samples of blood, urine, and fecal were collected from the rats, in the positive ion mode, pharmacogenic metabolites in each biological sample were identified according to the accurate mass, fragment ions, retention time, metabolic reaction type, comparison of reference substance and retrieval of Pub Med database; The adjuvant-type arthritis (AA) rat model was established, and blood metabonomics method was used to study the improvement effect of rheumatoid arthritis after drug intervention with PAC, and its mechanism was preliminarily explored through analysis of metabolic pathway. A total of 72 exogenous components were identified, including 17 prototype components and 55 metabolites; 14 biomarkers were screened by blood metabolomics techniques combined with multivariate statistical analysis, and PAC significantly improved symptoms of rheumatoid arthritis in rats, and the metabolic pathway analysis mainly involves 5 metabolic pathways. The components in the aqueous decoction of PAC mainly undergo phase I metabolic reactions in rats, such as oxidation, reduction, dehydrogenation, demethylation, and phase II metabolic reactions, such as acetylation, glucuronidation, methylation; PAC has anti-rheumatoid arthritis effects, and its mechanism of action may be related to biosynthesis of aminoacyl-tRNA, metabolism of phenylalanine, metabolism of tryptophan, degradation of valine, leucine and isoleucine and biosynthesis of pantothenic acid and coenzyme A, providing a scientific basis for the study of the pharmacodynamic substances and the action mechanism of PAC against RA.

Antibacterial activity of phellodendron bark against Streptococcus mutans.

Streptococcus mutans is a major cause of tooth decay due to its promotion of biofilm formation and acid production. Several plant extracts have been reported to have multiple biological activities such as anti-inflammation and antibacterial effects. This study investigated the antibacterial activity of three plant extracts, phellodendron bark (PB), yucca, and black ginger, and found that PB had a stronger effect than the other extracts. Then, the minimum inhibitory concentration (MIC) of PB against 100 S. mutans strains was investigated. The MIC range of PB was 9.8-312.5 µg/mL. PB suppressed the growth kinetics of S. mutans in a dose-dependent manner, even at sub-MICs of PB. Then, we investigated the effect of PB on S. mutans virulence. The PB suppressed biofilm formation at high concentrations, although PB did not affect the expression of glucosyltransferase genes. Additionally, PB suppressed the decrease in pH from adding an excess of glucose. The expression of genes responsible for acid production was increased by the addition of excess glucose without PB, whereas their expression levels were not increased in the presence of 1× and 2× MIC of PB. Although PB showed a bacteriostatic effect on planktonic S. mutans cells, it was found that more than 2× MIC of PB showed a partial bactericidal effect on biofilm cells. In conclusion, PB not only showed antibacterial activity against S. mutans but also decreased the cariogenic activity in S. mutans.

[Evaluation for heavy metal pollution of soil and herb from main producing area of Phellodendron amurense in China].

In order to evaluate the heavy metal potential pollution of soil and medicinal materials in main producing area of Phellodendron amurense, we collected 32 soil samples and 32 herb samples from northeast and north of China covering four provinces. In this study, the detection of heavy metal contents was conducted by ICP emission spectroscopy and atomic fluorescence spectrometry. The results showed that the soil from all areas of Ph amurense generally reached the national standard. As, Hg, Cr, Cd, Pb and Cu content of herb samples met the requirtment of the national standard except Hg content exceeding standard slight in a few samples. The reason of excessive Hg was the ability of Hg accumulation in Ph. amurense and atmospheric environment was polluted. So, national standard and Good Agricultural Practice (GAP) must be carried out severely in Ph. amurense resources production.

Phenyl-ß-D-Glucopyranoside Exhibits Anti-inflammatory Activity in Lipopolysaccharide-Activated RAW 264.7 Cells.

Phenyl-ß-D-glucopyranoside is a component of Phellodendron amurense with anti-cancer and anti-inflammatory activities. In the present study, we investigated the role of phenyl-ß-D-glucopyranoside in inflammation using lipopolysaccharide (LPS)-stimulated murine Raw 264.7 macrophages. Phenyl-ß-D-glucopyranoside not only inhibited nitric oxide (NO) production but also significantly inhibited the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) without inducing cytotoxicity. Phenyl-ß-D-glucopyranoside also attenuated proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and other inflammation-related genes, such as IL-6 in a concentration-dependent manner. Furthermore, phenyl-ß-D-glucopyranoside abolished increased adhesion, ninjurin 1 (Ninj1) expression, and matrix metalloproteinase (MMP) activity induced by endotoxin treatment. Finally, phenyl-ß-D-glucopyranoside inhibited the nuclear translocation of nuclear factor-κB (NF-κB), which is one of the most important transcription factors involved in the inflammatory process. Taken together, phenyl-ß-D-glucopyranoside may be beneficial for the prevention and treatment of anti-inflammatory diseases.

Akt-and CREB-mediated prostate cancer cell proliferation inhibition by Nexrutine, a Phellodendron amurense extract.

Evidence from epidemiological studies suggests that plant-based diets can reduce the risk of prostate cancer. However, very little information is available concerning the use of botanicals in preventing prostate cancer. As a first step toward developing botanicals as prostate cancer preventives, we examined the effect of Nexrutine on human prostate cancer cells. Nexrutine is a herbal extract developed from Phellodendron amurense. Phellodendron extracts have been used traditionally in Chinese medicine for hundreds of years as an antidiarrheal, astringent, and anti-inflammatory agent. The present study investigated its potential antitumor effect on human prostate cancer cells. Our results suggest that it inhibits tumor cell proliferation through apoptosis induction and inhibition of cell survival signaling. The results of the present study indicate that Nexrutine treatment 1) inhibits the proliferation of both androgen-responsive and androgen-independent human prostate cancer cells through induction of apoptosis; 2) reduces levels of pAkt, phosphorylated cAMP response-binding protein (pCREB) and CREB DNA-binding activity; and 3) induces apoptosis in prostate cancer cells stably overexpressing Bcl-2. Further, Akt kinase activity was reduced in cells treated with Nexrutine, and ectopic expression of myristoylated Akt protected from Nexrutine induced inhibition of proliferation, implicating a role for Akt signaling.

[Hairy roots induction of Phellodendron chinense and production of its active constituents].

OBJECTIVE: To introduce the hairy roots of Phellodendron chinense and determine the content of its active constituents. METHOD: Transformed hairy roots of P. chinense were obtained by the transformation of Agrobacterium rhizogenes A4, R1600, ATCC15834 and R1000. RESULT AND CONCLUSION: It was clearly demonstrated that T-DNA of A. rhizogenes Ri plasmid was integrated into the cells of hairy roots by PCR. The content of berberine hydrochlodride, which was determined by HPLC, was higher in hairy roots than that in the axenic plantet and callus.