Suffruticosol A

A dual recognition-based strategy employing Ni-modified metal-organic framework for in situ screening of SIRT1 inhibitors from Chinese herbs.[Pubmed:38599114]

Talanta. 2024 Mar 27;274:125975.

Sirtuin1 (SIRT1), an NAD(+)-dependent histone deacetylase, plays a crucial role in regulating molecular signaling pathways. Recently, inhibition of SIRT1 rather than its activation shows the therapeutic potential for central nervous system disorder, however, the discovered SIRT1 inhibitors remains limited. In this work, a dual recognition-based strategy was developed to screen SIRT1 inhibitors from natural resources in situ. This approach utilized a Ni-modified metal-organic framework (Ni@Tyr@UiO-66-NH(2)) along with cell lysate containing an engineered His-tagged SIRT1 protein, eliminating the need for purified proteins, pure compounds, and protein immobilization. The high-performance Ni@Tyr@UiO-66-NH(2) was synthesized by modifying the surface of UiO-66-NH(2) with Ni(2+) ions to specifically capture His-tagged SIRT1 while persevering its enzyme activity. By employing dual recognition, in which Ni@Tyr@UiO-66-NH(2) recognized SIRT1 and SIRT1 recognized its ligands, the process of identifying SIRT1 inhibitors from complex matrix was vastly streamlined. The developed method allowed the efficient discovery of 16 natural SIRT1 inhibitors from Chinese herbs. Among them, 6 compounds were fully characterized, and Suffruticosol A was found to have an excellent IC(50) value of 0.95 +/- 0.12 muM. Overall, an innovative dual recognition-based strategy was proposed to efficiently identify SIRT1 inhibitors in this study, offering scientific clues for the development of drugs targeting CNS disorders.

Enhanced neuronal activity by suffruticosol A extracted from Paeonia lactiflora via partly BDNF signaling in scopolamine-induced memory-impaired mice.[Pubmed:37474737]

Sci Rep. 2023 Jul 20;13(1):11731.

Neurodegenerative diseases are explained by progressive defects of cognitive function and memory. These defects of cognition and memory dysfunction can be induced by the loss of brain-derived neurotrophic factors (BDNF) signaling. Paeonia lactiflora is a traditionally used medicinal herb in Asian countries and some beneficial effects have been reported, including anti-oxidative, anti-inflammatory, anti-cancer activity, and potential neuroprotective effects recently. In this study, we found that Suffruticosol A is a major compound in seeds of Paeonia lactiflora. When treated in a SH-SY5 cell line for measuring cell viability and cell survival, Suffruticosol A increased cell viability (at 20 microM) and recovered scopolamine-induced neurodegenerative characteristics in the cells. To further confirm its neural amelioration effects in the animals, Suffruticosol A (4 or 15 ng, twice a week) was administered into the third ventricle beside the brain of C57BL/6 mice for one month then the scopolamine was intraperitoneally injected into these mice to induce impairments of cognition and memory before conducting behavioral experiments. Central administration of Suffruticosol A into the brain restored the memory and cognition behaviors in mice that received the scopolamine. Consistently, the central treatments of Suffruticosol A showed rescued cholinergic deficits and BDNF signaling in the hippocampus of mice. Finally, we measured the long-term potentiation (LTP) in the hippocampal CA3-CA1 synapse to figure out the restoration of the synaptic mechanism of learning and memory. Bath application of Suffruticosol A (40 microM) improved LTP impairment induced by scopolamine in hippocampal slices. In conclusion, the central administration of Suffruticosol A ameliorated neuronal effects partly through elevated BDNF signaling.

Inhibitory Effect of Monoterpenoid Glycosides Extracts from Peony Seed Meal on Streptococcus suis LuxS/AI-2 Quorum Sensing System and Biofilm.[Pubmed:36498098]

Int J Environ Res Public Health. 2022 Nov 30;19(23):16024.

Streptococcus suis LuxS/AI-2 quorum sensing system regulates biofilm formation, resulting in increased pathogenicity and drug resistance, and diminished efficacy of antibiotic treatment. The remaining peony seed cake after oil extraction is rich in monoterpenoid glycosides, which can inhibit the formation of bacterial biofilm. In this study, we investigated the effect of seven major monocomponents (Suffruticosol A, suffruticosol B, suffruticosol C, paeonifloin, albiflorin, trans-epsilon-viniferin, gnetin H) of peony seed meal on minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of S. suis. The results showed that the MICs of the seven single components were all greater than 200 mug/mL, with no significant bacteriostatic and bactericidal advantages. Crystal violet staining and scanning electron microscope observation showed that the seven single components had a certain inhibitory effect on the biofilm formation ability of S. suis at sub-MIC concentration. Among them, the ability of paeoniflorin to inhibit biofilm was significantly higher than that of the other six single components. AI-2 signaling molecules were detected by bioreporter strain Vibrio harvey BB170. The detection results of AI-2 signal molecules found that at 1/2 MIC concentration, paeoniflorin significantly inhibited the production of S. suis AI-2 signal, and the inhibitory effect was better than that of the other six single components. In addition, molecular docking analysis revealed that paeoniflorin had a significant binding activity with LuxS protein compared with the other six single components. The present study provides evidence that paeoniflorin plays a key role in the regulation of the inhibition of S. suis LuxS/AI-2 system and biofilm formation in peony seed meal.

Efficient discovery of potent alpha-glucosidase inhibitors from Paeoniae lactiflora using enzyme-MOF nanocomposites and competitive indicators.[Pubmed:36477546]

Food Funct. 2023 Jan 3;14(1):171-180.

A great deal of attention has been paid to the seeds of Paeoniae lactiflora pall., an underutilized food resource, since its extract exhibits excellent alpha-glucosidase (GAA) inhibitory activity. In the present study, to gain further insight into this plant and find out potent GAA inhibitors, we established a novel ligand fishing strategy by introducing a competitive inhibitor as an indicator. After the successful establishment of this approach was verified by a series of methods, including kinetic assay, fluorescence determination, and HPLC, the newly developed ligand fishing method was applied to acquire potent GAA inhibitors from P. lactiflora seeds. Nine bioactive compounds were captured, and seven of them were identified as Suffruticosol A, suffruticosol B, resveratrol, vitisin E, luteolin, trans-delta-viniferin, and ampelopsin E. The data of their GAA inhibitory activity demonstrated that these constituents were vigorously active against GAA with IC(50) values of 1.67-30.47 muM, while such value of 1-DNJ was 228.77 muM. Among them, vitisin E and ampelopsin E were reported to show such inhibitory activity for the first time. Collectively, our findings provide valuable clues for the further utilization of P. lactiflora seeds as a functional food, and offer a new avenue for acquiring potent inhibitors from natural resources.

Suffruticosol A elevates osteoblast differentiation targeting BMP2-Smad/1/5/8-RUNX2 in pre-osteoblasts.[Pubmed:35852295]

Biofactors. 2023 Jan;49(1):127-139.

The Paeonia suffruticosa ANDR. (P. suffruticosa) is commonly used in traditional medicine for various purposes. Suffruticosol A (Suf-A), isolated from P. suffruticosa, is a beneficial compound with antibiofilm, antivirulence, and anti-inflammatory properties. The aim of the present study was to investigate the biological effects of Suf-A on osteogenic processes in pre-osteoblasts. It was determined here in that Suf-A (>98.02%), isolated from P. suffruticosa, showed no cytotoxicity at 0.1-30 muM; however, it induced cytotoxicity at 50-100 muM in pre-osteoblasts. Suf-A increased osteogenic alkaline phosphatase activity and expression levels of noncollagenous proteins. Adhesion and trans-migration on the extracellular matrix were potentiated by Suf-A, but not by wound-healing migration. Suf-A did not affect autophagy or necroptosis during osteoblast differentiation. We found that Suf-A increased runt-related transcription factor 2 (RUNX2) levels and mineralized matrix formation. RUNX2 expression was mediated by Suf-A-induced BMP2-Smad1/5/8 and mitogen-activated protein kinase signaling, as demonstrated by Noggin, a BMP2 inhibitor. These results suggest that Suf-A is a potential natural osteogenic compound.

[Simultaneous rapid detection of ten stilbenes in serum of mice by UPLC-MS/MS].[Pubmed:32495569]

Zhongguo Zhong Yao Za Zhi. 2020 May;45(9):2180-2185.

Stilbenes is a class of natural polyphenols with 1,2-diphenylethylene as the skeleton structure which have structural and active diversity. However, there are fewer studies on their metabolic process, which limits the in-depth research and development of such components. An UPLC-MS/MS method simultaneously determining contents of ten stilbenes was firstly established in this study and applied to study the ten stilbenes of peony seed coats in the serum of C57 mice.Piceatannol was the internal standard, and methanol was used for protein precipitation, UPLC-MS/MS with negative ion mode was used for analysis, and the method was validated.The serum samples were collected and detected after mice being oral administered with 800 mg.kg~(-1) peony seed coat extracts for 8 weeks. The results showed that Suffruticosol A, suffruticosol B, suffruticosol C, trans-epsilon-viniferin, cis-gnetin H, trans-suffruticosol D and trans-gnetin H were detected in serum samples, and the highest is Suffruticosol A. The method is simple and quick with high specificity and sensitivity, and it is suitable for quantitative determination of ten stilbenes in the serum of mice.

The anti-biofilm and anti-virulence activities of trans-resveratrol and oxyresveratrol against uropathogenic Escherichia coli.[Pubmed:31505984]

Biofouling. 2019 Aug;35(7):758-767.

Uropathogenic Escherichia coli (UPEC) is the primary causative agent of urinary tract infections, which are one of the most common infectious disease types in humans. UPEC infections involve bacterial cell adhesion to bladder epithelial cells, and UPEC can also form biofilms on indwelling catheters that are often tolerant to common antibiotics. In this study, the anti-biofilm activities of t-stilbene, stilbestrol, t-resveratrol, oxyresveratrol, epsilon-viniferin, Suffruticosol A, and vitisin A were investigated against UPEC. t-Resveratrol, oxyresveratrol, and epsilon-viniferin, Suffruticosol A, and vitisin A significantly inhibited UPEC biofilm formation at subinhibitory concentrations (10-50 mug ml(-1)). These findings were supported by observations that t-resveratrol and oxyresveratrol reduced fimbriae production and the swarming motility in UPEC. Furthermore, t-resveratrol and oxyresveratrol markedly diminished the hemagglutinating ability of UPEC, and enhanced UPEC killing by human whole blood. The findings show that t-resveratrol, oxyresveratrol, and resveratrol oligomers warrant further attention as antivirulence strategies against persistent UPEC infections.

A Fragmentation Study on Four Oligostilbenes by Electrospray Tandem Mass Spectrometry.[Pubmed:31119499]

Nat Prod Bioprospect. 2019 Aug;9(4):279-286.

Oligostilbenes have attracted much interest due to their intricate structures and diverse bioactivities. In this study, two stilbene dimers, (-)-7,8-cis-epsilon-viniferin (1) and carasiphenol A (2), and two trimers, Suffruticosol A (3) and suffruticosol C (4), were investigated by electrospray ionization ion-trap time-of-flight multistage mass spectrometry (ESI-IT-TOF-MS(n)). Based on the MS(n) study, the fragmentation pathways and diagnostic ions of four oligostilbenes in both positive and negative modes were proposed. The consecutive elimination of phenol (C(6)H(6)O) and resorcinol (C(6)H(6)O(2)) moieties were the particular dissociation for oligostilbenes due to the presence of 1,2-diphenylethylene nucleus. The present MS(n) fragmentation study will provide valuable information for the fast characterization of oligostilbenes from complicated natural mixtures.