Identification of Bulbocodin D and C as novel STAT3 inhibitors and their anticancer activities in lung cancer cells.

Cancer stands as one of the predominant causes of mortality globally, necessitating ongoing efforts to develop innovative therapeutics. Historically, natural products have been foundational in the quest for anticancer agents. Bulbocodin D (BD) and Bulbocodin C (BC), two bibenzyls derived from Pleione bulbocodioides (Franch.) Rolfe, have demonstrated notable in vitro anticancer activity. In human lung cancer A549 cells, the IC50s for BD and BC were 11.63 and 11.71 µmol·L-1, respectively. BD triggered apoptosis, as evidenced by an upsurge in Annexin V-positive cells and elevated protein expression of cleaved-PARP in cancer cells. Furthermore, BD and BC markedly inhibited the migratory and invasive potentials of A549 cells. The altered genes identified through RNA-sequencing analysis were integrated into the CMap dataset, suggesting BD's role as a potential signal transducer and activator of transcription 3 (STAT3) inhibitor. SwissDock and MOE analyses further revealed that both BD and BC exhibited a commendable binding affinity with STAT3. Additionally, a surface plasmon resonance assay confirmed the direct binding affinity between these compounds and STAT3. Notably, treatment with either BD or BC led to a significant reduction in p-STAT3 (Tyr 705) protein levels, regardless of interleukin-6 stimulation in A549 cells. In addition, the extracellular signal-regulated kinase (ERK) was activated after BD or BC treatment. An enhancement in cancer cell mortality was observed upon combined treatment of BD and U0126, the MEK1/2 inhibitor. In conclusion, BD and BC emerge as promising novel STAT3 inhibitors with potential implications in cancer therapy.

Two new bibenzyls from Pleione grandiflora (Rolfe) Rolfe and their antioxidant activity.

Two new bibenzyls (1 and 2) were isolated from the pseudobulbs of Pleione grandiflora (Rolfe) Rolfe along with six known compounds, including isoarundinin I (3), isoarundinin II (4), bulbocodin D (5), batatasin III (6), 5,3'-dihydroxy- 4-(p-hydroxybenzyl)-3-methoxybibenzyl (7) and shancigusin F (8). Their structures were established on the basis of spectroscopic methods. These compounds showed potent DPPH free radical scavenging effects with IC50 values ranging from 49.72 ± 0.35 µM to 65.41 ± 0.49 µM.

Discovery of glucosyloxybenzyl 2-hydroxy-2-isobutylsuccinates with anti-inflammatory activities from Pleione grandiflora.

Six new glucosyloxybenzyl 2-hydroxy-2-isobutylsuccinates, pleionesides A-F (1-6), along with two known compounds (7, 8) were obtained from the pseudobulbs of Pleione grandiflora (Rolfe) Rolfe. The structures and absolute configurations of new compounds were established by HRESIMS and NMR data, along with acidic hydrolysis and alkaline hydrolysis experiments. Compounds 1-6 were tested for their anti-inflammatory activities on LPS-induced BV2 microglial cells. Amoung them, 2, 4 and 5 showed moderate activities with IC50 values of 73.4, 32.8 and 57.1 µM, respectively, compared with the positive control quercetin with an IC50 value of 28.3 µM.

[A new lignan from Euscaphis konishii].

The chemical constituents from the extract of the twigs of Euscaphis konishii with anti-hepatoma activity were investigated, twelve compounds by repeated chromatography with silica gel, Sephadex LH-20 and preparative-HPLC. The structures of the chemical components were elucidated by spectroscopy methods, as konilignan(1),(7R, 8S)-dihydrodehydrodico-niferylalcohol-9-O-ß-D-glucopyranoside(2),illiciumlignan B(3),threo-1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]-1,3-panediol(4),erythro-1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]-1,3-panediol(5), matairesinol(6), wikstromol(7), isolariciresinol(8),(+)-lyoniresinol(9), 4-ketopinoresinol(10), syringaresin(11), and vladinol D(12). Among them, compound 1 is a new lignan. Compounds 10 and 12 had moderate inhibitory activity on HepG2 cells, with IC_(50) values of 107.12 µmol·L~(-1) and 183.56 µmol·L~(-1), respectively.