Bulbocodin D

Identification of Bulbocodin D and C as novel STAT3 inhibitors and their anticancer activities in lung cancer cells.[Pubmed:38035939]

Chin J Nat Med. 2023 Nov;21(11):842-851.

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 IC(50s) for BD and BC were 11.63 and 11.71 mumol.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.[Pubmed:35289695]

Nat Prod Res. 2023 Jul-Aug;37(15):2486-2492.

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 IC(50) values ranging from 49.72 +/- 0.35 muM to 65.41 +/- 0.49 muM.

Bulbocodin D ameliorate cognitive impairment in APP/PS1 transgenic mice by modulating amyloid-beta burden, oxidative status and neuroinflammation.[Pubmed:33811504]

Psychopharmacology (Berl). 2021 Aug;238(8):2073-2082.

RATIONALE: Amyloid beta peptide (Abeta) triggers a series of pathological events including microglial activation, oxidative stress, and inflammation-causing neuronal death and typical pathological changes in Alzheimer's disease (AD). OBJECTIVES: This study aimed to investigate the therapeutic effects and mechanism of Bulbocodin D for AD in vivo. METHODS: In this study, Morris water maze (MWM) analysis was used to detect the cognitive ability of APP/PS1 mice after gavage with Bulbocodin D for 2 months. Levels of Abeta40, Abeta42, IL-1beta, and TNF-alpha were evaluated by ELISA. Abeta plaques and biomarkers of neuroinflammation were also investigated through histological analysis. RESULTS: We established that Bulbocodin D significantly improved cognitive deficits in APP/PS1 transgenic mice and reduced the levels of amyloid plaque, Abeta40, and Abeta42. Bulbocodin D also reduced levels of microglial markers IbA1, GFAP, and antioxidant enzymes and reduced the products of lipid peroxidation and proinflammatory cytokines. CONCLUSION: In summary, the present study provides preclinical evidence that oral Bulbocodin D can reduce AD pathology.

Biological evaluation of naturally occurring bulbocodin D as a potential multi-target agent for Alzheimer's disease.[Pubmed:32991975]

Brain Res Bull. 2020 Dec;165:48-55.

In recent years, with the in-depth understanding of the pathogenesis of Alzheimer's disease (AD) and the development of advanced pharmacological technology, "multi-target" strategy has recently attracted the wide interest of scientists. The purpose of this study was to investigate the protective effect and mechanism of Bulbocodin D for AD in vitro. In this study, we established the oxidative stress model of SH-SY5Y cells mediated by H(2)O(2) and the inflammatory model of BV2 cells stimulated by LPS. Western blot was used to analysis the expression of mitochondrial apoptosis and inflammation related proteins. Moreover, predicted binding modes of Bulbocodin D with AChE and GSK3beta were performed by molecular docking analysis. We found that Bulbocodin D could reduce cell apoptosis, reduce ROS production in SH-SY5Y cell, and inhibit the secretion of inflammatory cytokines in BV2 cell. Furthermore, western blot results showed that Bulbocodin D could regulate mitochondrial apoptotic pathway and MAPKs pathway. In addition, Bulbocodin D can reduce the aggregation of Abeta. We also found that Bulbocodin D had a good inhibitory effect on AChE and GSK3beta. In summary, Bulbocodin D might be a potential multi-target agent for Alzheimer's disease.

[Chemical Constituents from Cremastra appendiculata].[Pubmed:26415404]

Zhong Yao Cai. 2015 Feb;38(2):298-301.

OBJECTIVE: To study the chemical constituents of Cremastra appendiculata. METHODS: The compounds were isolated by repeated column chromatography with silica gel, Sephadex LH-20 and ODS-HPLC. The structures were elucidated by analysis of spectroscopic data(1H-NMR and 13C-NMR). RESULTS: Ten compounds were isolated from the EtOAc extract in the tuber of Cremastra appendiculata. Their structures were identified as shancigusin I (I), 4-O-beta-D-glucopyranosyl cinnamate (II), Bulbocodin D (III), blestriarene A (IV), 7-hydroxy-2,4-dimethoxy phenanthrene (V), coelonin (VI), militarine (VII), gastrodine (VIII), 3-hydroxyphenylpropionic acid (IX) and cinnamic acid (X). CONCLUSION: Compounds I-III, IX and X are isolated from Cremastra appendiculata for the first time.

Bulbocodin D (CAS 211229-85-5) is a natural product offered by BioCrick for research applications. Customers can buy or order Bulbocodin D from BioCrick, a supplier and manufacturer of research chemicals, with product specifications, purity, packaging, and pricing information available upon request.