Recent progress on the total synthesis of acetogenins from Annonaceae

To study the antiviral activities of clemastanin B (CB), epigoitrin, phenylpropanoids portion (PEP) and the mixture of phenylpropanoids, alkaloids and organic acid fractions (PEP+ALK+OA) from Banlangen (Radix Isatidis). The experiment consisted of four parts: therapeutic action, prophylaxsis action, inhibition of virus attachment, and direct virucidal action. Cytopathic effect (CPE) and 3-(4,5-Dimethylthiazol-2-yI)-2,5-diphenyltetrazolium (MTT) were used to assess antiviral activity. CB, epigoitrin, PEP and PEP + ALK +OA fractions from Banlangen (Radix Isatidis) extract significantly increased the viability of MDCK cells pre-infected with the virus compared with the virus control group in all the dilutions (P < 0.01). Pretreated with either pure compounds or chemical fractions of Banlangen (Radix Isatidis) extract in all the dilutions significantly improved the viability of MDCK cells (P < 0.01). The inhibition of virus absorption to the host cells by CB, epigoitrin and PEP was in a dose dependent manner. CB, epigoitrin, PEP and PEP+ ALK+ OA exert their anti-influenza activity by inhibiting the virus multiplication, prophylaxsis and blocking the virus attachment. The primary mode of action of PEP and PEP + ALK + OA is the inhibition of virus replication. The inhibitory effects on virus attachment and multiplication are the main modes for epigoitrin.

Multidrug resistance (MDR) is a major obstacle in the effective chemotherapeutic treatment of cancers. Triptolide (TPL) is a diterpenoid isolated from Tripterygium wilfordii Hook. f., a traditional Chinese medicine. It was demonstrated in our previous study that TPL exerts anti‑MDR cancers on various MDR cell lines (including A549/Taxol, MCF‑7/ADR and Bel7402/5‑Fu). The present study was designed to investigate its anti‑proliferative activity on A549/Taxol cells, and explore the underlying mechanism of action. The anti‑proliferative activity of TPL on A549/Taxol cells was assessed by 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide (MTT) assay. Its pro‑apoptosis and cell cycle arrest activities were analyzed by flow cytometry. Western blot assay was employed to investigate the levels of mitogen-activated protein kinases (MAPKs) and apoptosis‑related proteins in cells. TPL efficiently suppressed the proliferation of A549/Taxol cells. Co‑treatment with MAPK inhibitors in the MTT assay indicated that the extracellular signal‑regulated kinase (ERK) and c‑Jun N‑terminal kinase (JNK) pathways were involved in the process. Upregulation of p‑p38, p‑ERK, p‑GSK‑3β, Bax and cleaved caspases‑3 and ‑9, and downregulation of p‑JNK, p‑Akt and Bcl‑2 were observed upon treatment with TPL in the A549/Taxol cells. The results from flow cytometry assay revealed that TPL induced apoptosis and S‑phase arrest in A549/Taxol cells. This occurred as a result of the upregulation of p‑ERK and p‑GSK‑3β, and the downregulation of p‑JNK and p‑Akt, and was responsible for the subsequent anti-proliferative activity.