Codonopis bulleynana Forest ex Diels (cbFeD) effectively attenuates hepatic fibrosis in CCl4-induced fibrotic mice model.

The root of Codonopis bulleynana Forest ex Diels (cbFeD), a tonic food widely used in Yunnan Province of China, was found to have a wide range of pharmacological effects. The present study was designed to investigate the anti-fibrotic effect of water extracts of cbFeD in chronic liver injury mice model induced by carbon tetrachloride (CCl4) and to explore its underlying mechanisms. Phytochemical analysis revealed multiple components were present in the water extract of cbFeD and the compounds were mostly enriched in organic acid and its derivatives, flavone, amino acid derivatives, nucleotide and its derivatives, carbohydrates etc. Treatment with cbFeD significantly attenuated liver injury and fibrosis in CCl4-administered mice evidenced by improved liver histology, ameliorated apoptosis of hepatocytes, and decreased transaminase levels in the serum. Decreased activities of superoxide dismutase (SOD) and catalase (CAT) were markedly reversed upon treatment with cbFeD while levels of malondialdehyde (MDA) and glutathione (GSH) were significantly restored towards normal values. cbFeD also suppressed intrahepatic inflammatory cell infiltration and Kupffer cell activation. Furthermore, our study revealed an inhibitory effect of cbFeD on hepatic stellate cells (HSCs) activation both in vitro and in vivo. In conclusion, cbFeD could exert a protective role against liver fibrosis in mice model induced by CCl4 that is comparable to the positive control silymarin and might be developed into a promising anti-fibrotic drug.

Codonopis bulleynana Forest ex Diels inhibits autophagy and induces apoptosis of colon cancer cells by activating the NF-κB signaling pathway.

Despite its favorable clinical efficacy, oxaliplatin­based chemotherapy frequently results in treatment withdrawal and induces liver damage in colon cancer. Therefore, it is important to develop novel drugs, which can safely and effectively complement or replace the therapeutic effects of oxaliplatin. Codonopis bulleynana Forest ex Diels (cbFeD) has wide range of pharmacological effects, including anticancer effects. In the present study, the anticancer activity of cbFeD and its potential molecular mechanisms were investigated. In vitro, cell counting kit­8 assays and flow cytometry were used to assess the anti­proliferation and apoptosis­promoting activities of cbFeD. Transmission electron microscopy was used to monitor the autophagic vesicles. Immunofluorescence staining was performed to observe the nuclear translocation of p65 and the fluorescence of microtubule­associated protein 1 light chain 3 (LC3) B­II. The protein expression levels of p65, inhibitor of nuclear factor (NF)­κB (IκB) a, LC3B­I, LC3B­II and Beclin­1 were detected using western blot analysis. In vivo, the antitumor effect of cbFeD was assessed in colon cancer­bearing nude mice as a model. H&E staining and immunohistochemistry (IHC) were performed, with oxaliplatin set as a positive control. The results showed that cbFeD inhibited cell proliferation and promoted cell apoptosis in a dose­dependent manner. The effects of a high dose of cbFeD on colon cancer cells were similar to those of oxaliplatin. In HCT116 and SW480 cells, cbFeD inhibited the expression of IκBα, LC3B­I/II and Beclin­1, and the results of western blot analysis and immunofluorescence showed that, in the cells treated with cbFeD, p65 gradually entered nuclei in a dose­dependent manner, and the expression of LC3B­II was gradually reduced. The results of the acridine orangestaining and electron microscopy demonstrated fewer autophagic vesicles in the high­dose cbFeD group and the oxaliplatin group. The high dose of cbFeD reversed the effect of pyrrolidine dithiocarbamate, a p65­inhibitor, on the expression of p65, LC3B­I, LC3B­II and Beclin­1, and on the production of autophagic vacuoles. The high dose of cbFeD and oxaliplatin also suppressed tumorigenicity in vivo. The results of the H&E and IHC staining confirmed the inhibition of autophagy (LC3 and Beclin­1) and activation of p65 by treatment with the high dose of cbFeD and oxaliplatin. Taken together, cbFeD exhibited an antitumor effect in colon cancer cells by inhibiting autophagy through activation of the NF­κB pathway. Therefore, cbFeD may be a promising Chinese herbal compound for development for use in cancer therapy.

[The production of gastrodin through biotransformation of p-hydroxybenzaldehyde by cell suspension culture of Datura stramonium].

AIM: To investigate the production of p-hydroxymethylphenol-beta-D-glucoside (gastrodin) through biotransformation by plant cell suspension cultures. METHODS: Using cell suspension cultures of Datura stramonium to convert the exogenous p-hydroxybenzaldehyde into gastrodin was conducted and the converted compounds were separated with a combination of multi-chromatography. Their chemical structures were determined on the basis of spectral analysis and chemical evidence. RESULTS: The conversion procedure of p-hydroxybenzaldehyde into gastrodin by Datura stramonium cell suspension cultures was established. The synthesized gastrodin (II) was isolated from the fermental liquor and identified by spectral analysis. At the same time, the p-hydroxybenzyl alcohol (I) converted through biotransformation of p-hydroxybenzaldehyde by cell suspension cultures of Datura stramonium was also isolated and identified. Two compounds were also isolated from the cell cultures and they were identified as beta-D-furanoallulose (III) and n-butyloxystyryl-beta-D-pyranoallulose (IV). CONCLUSION: Datura stramonium grown in suspension cultures can convert exogenous p-hydroxybenzaldehyde into the corresponding gastrodin.

[Production of gastrodin through biotransformation of p-hydroxybenzaldehyde by cell suspension cultures of Datura tatula L].

The conversion of exogenous p-hydroxybenzaldehyde to p-hydroxy-methyl-phenol-beta-D-glucoside (gastrodin) was studied by using cell suspension culture of Datura tatula L. The chemical structure of this synthesized gastrodin was identified based on the spectral analysis and chemical evidence. The conversion procedure of p-hydroxybenzaldehyde into gastrodin by D. tatula L. cell suspension cultures was established. The synthesized gastrodin (II) was isolated from the ferment liquor and identified by spectral analysis. At the same time, the p-hydroxybenzyl alcohol (I) converted through biotransformation of p-hydroxybenzaldehyde by cell suspension cultures of D. tatula L. was also isolated and identified. The efficiency of glucosylation of p-hydroxybenzaldehyde was remarkably enhanced by adding salicylic acid (0.1 mg/L) and keeping the lower pressure (0.001MPa) in 25L airlift loop bioreactor. The biotransformation of exogenous p-hydroxybenzaldehyde to gastrodin by cell suspension culture of D. tatula L. is a promising approach.