Brazilin cream from Caesalpinia sappan inhibit periodontal disease: in vivo study.

Background: Gingivitis is an inflammation of the gums that is the initial cause of the development of periodontal disease by the activity of Nuclear Factor-kappa B (NF-κB), Interleukin-1ß (IL-1ß), Interleukin-6 (IL-6), p38, and Tumor Necrosis Factor-α (TNF-α). Unaddressed chronic inflammation can lead to persistent disturbances in other parts of the body. Brazilin is a naturally occurring plant chemical that may have antibacterial and anti-inflammatory effects. Treatment based on the natural plant compound, brazilin, is developed in the form of a topical cream for easy application. Objective: The aim is to develop the natural compound brazilin in the form of a topical cream as an anti-inflammatory agent to reduce NF-κB expression through Imunohistochemistry (IHC) methods, and the expression of pro-inflammatory genes IL-1ß, IL-6, p38, and TNF-α. Methods: Male Sprague-Dawley rats were induced with gingivitis using P. gingivalis bacteria. The observed groups included rats treated with a single application of brazilin cream and rats treated with two applications of brazilin cream. The treatment was administered for 15 days. On days 3, 6, 9, 12, and 15, anatomical wound observations and wound histology using hematoxylin-eosin and Masson's Trichrome staining were performed. NF-κB protein expression was analyzed using the IHC method. Gingival inflammation gene expression of NF-κB, IL-1ß, IL-6, p38, and TNF-α was measured using q-RTPCR. Results: Single and double applications of brazilin cream increased angiogenesis and decreased NF-κB protein expression, in addition to the IL-1ß, IL-6, p38, and TNF-α gene expressions. Conclusion: In a rat gingivitis model, Brazilin cream may function as an anti-inflammatory agent in the gingival tissue.

Structurally diverse diterpenoids from the seeds of Caesalpinia minax Hance and their bioactivities.

Eight previously undescribed diterpenoids, caesamins A-H (1-8), were separated and identified from the seeds of Caesalpinia minax Hance. Their structures were characterized by extensive spectroscopic data and X-ray crystallographic analysis. Structurally, caesamin A (1) is the first cassane-type diterpenoid with a C23 carbon skeleton containing an unusual isopropyl. Caesamin F (6) represents the first example of cleistanthane diterpenoid from the genus Caesalpinia. Caesamins B (2) and F (6) exhibited inhibitory activity against LPS-induced nitric oxide production in RAW 264.7 macrophages with IC50 values of 45.67 ± 0.92 and 42.99 ± 0.24 µM, comparable to positive control 43.69 ± 2.62 µM of NG-Monomethyl-L-arginine. Furthermore, the chemotaxonomic significance of the isolates was discussed.

Antioxidant, antiglycation, and antibacterial of copper oxide nanoparticles synthesized using Caesalpinia Sappan extract.

Synthesis of metal nanoparticles using plant extracts is environmentally friendly and of increasing interest. However, not all plant extracts can meet successfully on the synthesis. Therefore, searching for the high potential extracts that can reduce the metal salt precursor in the synthesis reaction is essential. The present study explores the synthesis of copper oxide nanoparticles (CuONPs) using Caesalpinia sappan heartwood extract. Phytochemical analysis and determination of the total phenolic content of the extract were performed before use as a reducing agent. Under the suitable synthesized condition, a color change in the color of the solutions to brown confirmed the formation of CuONPs. The obtained CuONPs were confirmed using ultraviolet-visible spectroscopy, photon correlation spectroscopy, X-ray diffraction, scanning electron microscope, energy dispersive X-ray, and Fourier transform infrared analysis. The synthesized CuONPs investigated for antioxidant, antiglycation, and antibacterial activities. CuONPs possessed antioxidant activities by quenching free radicals with an IC50 value of 63.35 µg/mL and reducing activity with an EC range of 3.19-10.27 mM/mg. CuONPs also inhibited the formation of advanced glycation end products in the bovine serum albumin/ribose model with an IC50 value of 17.05 µg/mL. In addition, CuONPs showed inhibition of human pathogens, including Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli, and prevention of biofilm formation and biofilm eradication, with maximum inhibition of approx. 75%. Our findings suggest that C. sappan extract can be used to obtain highly bioactive CuONPs for the development of certain medical devices and therapeutic agents.

Pharmaceutical activity of sappan wood extract (Caesalpinia sappan L.) for treating Escherichia coli infection in piglets.

Background: Escherichia coli infection is one of the major diarrheal diseases resulting in the loss of pigs at a young age. Aim: This research investigated the antimicrobial activity of Caesalpinia sappan wood extract against E. coli infection as an antibiotic replacement. Methods: E. coli was cultured from diarrheal piglets and then used to find the minimal inhibition concentration (MIC). Caesalpinia sappan wood extract (500 mg/kg) was used for the treatment of diarrheal piglets compared to antibiotics (enrofloxacin 5 mg/kg) by oral administration. Another three groups of diarrheal piglets were used supplemented feed with 1% and 2% extract compared with commercial feed. Subsequently, E. coli enumeration, fecal shape, fecal color, and growth rate were recorded from day 1 to 7. Results: Based on the results, C. sappan wood extract could inhibit E. coli growth at a MIC of 16-34 mg/ml. The number of colonies did not significantly differ between C. sappan wood extract and enrofloxacin treatment groups. A supplemented feed with 1% and 2% C. sappan wood extract could improve the fecal shape and fecal score compared to the control group, albeit only in suckling pigs. There were significant differences from the control group on days 4, 5, 6, and 7 (p < 0.05). However, the average daily gain did not significantly differ among the three groups. Conclusion: The results indicate that C. sappan wood extract could improve diarrheal signs in suckling pigs and can be used as a replacement for antibiotics for organic pig production.

Strawberries treated with biodegradable film containing plant extracts.

Strawberry (Fragaria x ananassa Duch.) is a highly perishable fruit whose characteristics make it susceptible to developing microorganisms. Plant extracts have been studied as an alternative to pesticides to control spoilage microorganisms, responding to the expectation of the population seeking a healthier way of life. The fungus Botrytis cinerea is a facultative pathogen of vegetables, which can affect all stages of the development of several fruits, such as the strawberry, where it causes gray rot. Trichilia catigua (catuaba), Paullinia cupana (guarana), Stryphnodendron barbatiman (barbatimão), and Caesalpinia peltophoroides (sibipiruna) are planted in the Brazilian flora and have demonstrated pharmacological properties in their extracts. This work aimed to treat strawberries with a biodegradable film containing extracts of these species to evaluate strawberry conservation. There were notable distinctions in mass loss between the extract-treated and control samples. The pH, total acidity (TA), and soluble solids parameters exhibited consistently significant means across both sets of samples. Luminosity increased over the course of days in the color parameters, with the exception of strawberries coated with guarana. The red color showed greater intensity, except for those coated with barbatimão extract. Considering the results, it is possible to conclude that the coatings used can become an alternative to enhance the conservation of strawberries.

Anti-pancreatic cancer activity of cassane diterpenoids isolated from the seeds of Caesalpinia sappan mediated by autophagy activation via ROS/AMPK/mTORC1 pathway.

Three undescribed cassane diterpenoids, caesalpanins D-F (1-3), and seven known ones were isolated from the seeds of Caesalpinia sappan. Structures and absolute configurations of 1-3 were elucidated based on the extensive spectroscopic analysis, single-crystal X-ray diffraction analysis, and ECD calculations. Structurally, compound 1 was the first example of 18-norcassane diterpenoid and 2 was a rare 20-norcassane diterpenoid having an unusual five-membered oxygen bridge between C-10/C-18. The anti-proliferative activity of 1, 3, and 4-10 against PANC-1 cells (pancreatic ductal adenocarcinoma cell line) was evaluated, and phanginin H (4) was found to exhibit anti-cancer activity with IC50 value of 18.13 ± 0.63 µM. Compound 4 inhibited PANC-1 cell growth by arresting the cell cycle at G2/M phase via regulation of cyclin-dependent kinases, and the self-renewal and metastasis of PANC-1 cells by suppressing cancer cell stemness. Furthermore, compound 4 induced ROS generation and subsequently activated autophagy, which was demonstrated by the formation of autophagic vacuoles and dynamic change of autophagic flux. The induced ROS accumulation resulted in AMPK activation and subsequently regulation of mTORC1 activity and ULK phosphorylation, indicating that 4 triggered autophagy through ROS/AMPK/mTORC1 pathway. These findings suggested that 4 might potentially be an autophagy inducer for the therapy of pancreatic cancer.

New cassane-type alkaloids and diterpenoids from the pericarps of Caesalpinia bonduc.

The phytochemical investigation of the pericarps of Caesalpinia bonduc led to the isolation and identification of five new cassane-type alkaloids: caesalminines C - G (1-5) and six new diterpenoids: caesalbonducin K - P (6-11), along with seven known compounds (12-18). Compounds 1-5 were identified as a group of rare alkaloids possessing a tetracyclic cassane-type diterpenoid skeleton with a lactam D-ring instead of a typical furan or lactone moiety. The structures of 1-11 were elucidated on the basis of 1D and 2D NMR including HSQC, HMBC, COSY and NOESY, and other spectroscopic analyses. The cytotoxic activities of the isolated compounds were evaluated in the A431, A549 and U87MG cancer cell lines.

Caesalpinflavans D-F and caesalpinnone B, hybrid flavan-chalcones and normonoterpene-chalcone heterodimer from Caesalpinia digyna.

Three undescribed hybrid flavan-chalcones, caesalpinflavans D-F, and an unreported normonoterpene-chalcone heterodimer, caesalpinnone B, along with three known biflavonoids were isolated from the twigs and leaves of Caesalpinia digyna. Their structures were elucidated based on extensive spectroscopic analysis and quantum chemical calculations. Caesalpinflavan F was identified as a bis-(hybrid flavan-chalcone), its natural occurrence was supported by HPLC-IT-TOF-MS analysis. The condensation of caesalpinflavan B with acetone was possibly a key step in the biosynthesis of caesalpinflavan F. Caesalpinnone B represents an unprecedented meroterpenoid featuring a cyclobutane central framework, which was derived from chalcone and normonoterpenoid via a key [2 + 2] cyclization reaction. Biological evaluation revealed that compounds caesalpinflavan D, oxytrodiflavanone A, and caesalpinnone B exhibited moderate cytotoxicity against HL-60, SMMC-7721, SW480, A-549 and/or MDA-MB-231 cell lines with IC50 values ranging from 8.051 ± 0.673 to 24.26 ± 0.61 µM. This study provided evidence for further research and possible utilization of C. digyna in the future.

Molecular characterization of a galactomannan extracted from Tara (Caesalpinia spinosa) seeds.

Tara gum (TG) is a polysaccharide extracted from the seeds of a South American tree called Tara (Caesalpinia spinosa). TG is a galactomannan with many applications in the food industry, mainly as an emulsifier and stabilizer agent. In addition, it is also used in the paper and cosmetic industries. In the present study, we performed a molecular characterization based on chemical composition and physicochemical properties to understand the properties behind TG applications. TG was extracted and purified from Tara seeds distributed in different ecoregions of Bolivia. The monosaccharide composition analysis was determined by high-performance anion-exchange chromatography/pulsed amperometric detection (HPAEC-PAD). At the same time, their molecular characteristics, such as molar mass, root-mean-square radius, hydrodynamic radius, conformation, and densities, were studied by asymmetrical flow field-flow fractionation coupled to multi-angle light scattering refractive index (AF4-MALS-dRI), also the specific refractive index increment (dn/dc) was determined for the first time using AF4 for TG. The results revealed that the gum samples are galactomannans composed of mannose (Man) and galactose (Gal) in a ratio of 3.37 (Man/Gal), with an average molar mass range from 2.460 × 107 to 3.699 × 107 Da, distributed in a single population. The root-mean-square radius range from 260.4 to 281.6 nm, and dn/dc is 0.1454. The Kratky plots based on 14 scattering angles indicated that the conformation of all samples corresponds to random coil monodisperse, while their gyration radius/hydrodynamic radius ratio (ρ) is high. All these results suggest that the chains have a low branched density, consistent with the Gal/Man composition. To the best of our knowledge, we report for the first time an integrated physicochemical study of TG relevant to developing emulsifier and stabilizer formulations.

Mechanistic study on the anti-proinflammatory activity of Kunitz type inhibitor from Caesalpinia decapetala seeds.

The study reports the biochemical characterization and mechanism of action of a novel 19.6 kDa protease inhibitor (PIs) isolated from the seeds of Caesalpinia decapetala belonging to the Fabaceae family. A systematic study was performed to ascertain the purity, specificity, biochemical and structural characterization, and its potential in curbing inflammation in vitro conditions. A two-step chromatography technique was used to purify the PIs. Sodium dodecyl sulfate polyacrylamide gel electrophoresis and matrix-assisted laser desorption ionization time of flight were employed to detect the molecular mass of the protein. N-terminal sequence analysis of the inhibitor showed sequence similarity with the Kunitz family PIs. The in vitro test tube assay was performed for determining the anti-inflammatory activity and the inhibitor is antiproliferative against macrophage (RAW264.7) and lung cancer cell lines (A549). An effective decrease in the release of inflammatory mediators (NO, IL-6, TNF-α) and on the activity of elastase was observed in macrophage cell lines (RAW264.7) which were treated with PIs. The purified inhibitor shows promising results against inflammation.

Diversified cassane family diterpenoids from the leaves of Caesalpinia minax exerting anti-neuroinflammatory activity through suppressing MAPK and NF-κB pathways in BV-2 microglia.

ETHNOPHARMACOLOGICAL RELEVANCE: Caesalpinia minax Hance, whose seeds are known as "Ku-shi-lian" in China, have been used in Chinese folk medicine for treatment of rheumatism, dysentery, and skin itching. However, the anti-neuroinflammatory constituents of its leaves and their mechanism are rarely reported. AIM OF THE STUDY: To search for new anti-neuro-inflammatory compounds from the leaves of C. minax and elucidate their mechanism on anti-neuroinflammatory effect. MATERIALS AND METHODS: The main metabolites of the ethyl acetate fraction from C. minax were analyzed and purified via HPLC and various column chromatography techniques. Their structures were elucidated on the basis of 1D and 2D NMR, HR-ESI-MS, and single crystal X-ray diffraction analysis. Anti-neuroinflammatory activity was evaluated in BV-2 microglia cells induced by LPS. The expression levels of molecules in NF-κB and MAPK signaling pathways were analyzed through western blotting. Meanwhile, the time- and dose-dependent expression of associated proteins such as iNOS and COX-2 were detected by western blotting. Furthermore, Compounds 1 and 3 were performed on the NF-κB p65 active site using molecular docking simulation to elucidate the molecular level inhibition mechanism. RESULTS: 20 cassane diterpenoids, including two novel ones (caeminaxins A and B) were isolated from the leaves of C. minax Hance. Caeminaxins A and B possessed a rare unsaturated carbonyl moiety in their structures. Most of the metabolites exhibited potent inhibition effects with IC50 values ranging from 10.86 ± 0.82 to 32.55 ± 0.47 µM. Among them, caeminaxin A inhibited seriously the expression of iNOS and COX-2 proteins and restrained the phosphorylation of MAPK and the activation of NF-κB signaling pathways in BV-2 cells. The anti-neuro-inflammatory mechanism of caeminaxin A has been studied systematically for the first time. Furthermore, biosynthesis pathways for compounds 1-20 were discussed. CONCLUSIONS: The new cassane diterpenoid, caeminaxin A, alleviated the expression of iNOS and COX-2 protein and down-regulated of intracellular MAPK and NF-κB signaling pathways. The results implied that cassane diterpenoids had potential to be developed into therapeutic agents for neurodegenerative disorders such as Alzheimer's disease.

Guided Isolation of New Cytotoxic Cassane Diterpenoids from Caesalpinia sappan.

Guided by an MS/MS-based molecular networking, six undescribed cassane diterpenoids and three known ones were isolated and identified from the seeds of Caesalpinia sappan. Their structures were unequivocally elucidated by extensive spectroscopic analyses and electronic circular dichroism (ECD) calculations. Cytotoxic evaluation showed that phanginin JA exhibited significant antiproliferative activities against human non-small cell lung cancer (A549) cells with IC50 values of 16.79±0.83 µM. Further flow cytometry analysis revealed that phanginin JA could exert apoptotic effect of A549 cells by arresting cell cycle in G0/G1 phase.

An efficient method for identifying natural common homoisoflavonoid by 1H-NMR.

Homoisoflavone contains 16 carbon atoms in the skeleton. The homoisoflavonoid skeleton from natural products can be roughly divided into 13 kinds, among which 5 kinds of common skeletons contain a large amount of compounds and 8 kinds of abnormal skeletons comprise a small amount of compounds. In this article, the structure identification experience of homoisoflavonoids found in Caesalpinia mimosoides was used as references and an efficient 1H NMR spectroscopic method for identifying homoisoflavonoid structure has been established. Using the chemical shift differences of H-2, 3, 4 and 9, the common natural homoisoflavonoids can be quickly and conveniently determined.

Discovery of diversified cassane diterpenoids as potent antibacterial agents from Caesaplinia pulcherrima and their mechanisms.

BACKGROUND: Natural products play a significant role in the development of novel bactericide candidates. Caesalpinia pulcherrima, a traditional medicine, had anti-inflammatory, antimicrobial, and antifeedant activities, therefore the previous bioassay results of C. pulcherrima implied that its main active ingredients may have potential to be used as botanical bactericides. RESULTS: Bio-guided isolation of C. pulcherrima was conducted to obtain 11 novel cassane diterpenoids (capulchemins A-K) and 10 known sesquiterpenes. Their structures were established by extensive spectroscopic methods and single-crystal X-ray diffraction analyses. Capulchemins A-F possess a rare aromatic C ring, while capulchemin K with a 15,16-degradative carbon skeleton represents a rare group of cassane diterpenes. Capulchemin A exhibited remarkable antibacterial activity against four phytopathogenic bacteria, particularly against Pseudomonas syringae pv. actinidae and Bacillus cereus, with minimal inhibitory concentration values of 3.13 µM. Meanwhile, capulchemin A showed significant control effect on kiwifruit canker in vivo. Further investigation of its mechanism of antibacterial activity revealed that compound 1 was closely related to destroy cell membrane to cause cell death. Additionally, some of those cassane diterpenoids showed potential antifeedant against Mythimna separate walker and Plutella xylostella. Consequently, capulchemin A could have the potential to be used as a template for the development for new eco-friendly NP-based bactericides. CONCLUSION: These data contribute to a better understanding of the antibacterial activity of cassane diterpenes. Cassane diterpenes have been discovered to be leading to broad application prospects in the development as novel botanical bactericides. © 2023 Society of Chemical Industry.

Brazilin from Caesalpinia sappan inhibits viral infection against PRRSV via CD163ΔSRCR5 MARC-145 cells: an in silico and in vitro studies.

This research aimed to identify bioactive compounds from Caesalpinia sappan extract that function as novel porcine reproductive and respiratory syndrome virus (PRRSV) infection inhibitors by computational molecular screening. We obtained a set of small-molecule compounds predicted to target the scavenger receptor cysteine-rich domain 5 (SRCR5) of CD163. In addition, the functions of positive hits were assessed and verified utilizing an in vitro antiviral activity assay with PRRSV-infected MARC-145 cells. Combining molecular docking with the results of binding affinity and ligand conformation, it was found that brazilin had the highest binding energy with the SRCR5 receptor compared to catechin and epicatechin (- 5.8, - 5.5, and - 5.1 kcal/mol, respectively). In terms of molecular mechanics, the binding free energy between the SRCR5 receptor was - 15.71 kcal/mol based on the Poisson-Boltzmann surface area of brazilin. In addition, PRRSV infection in MARC-145 cells was significantly inhibited by brazilin compared to the control (virus titer, 4.10 vs. 9.25 TCID50/mL, respectively). Moreover, brazilin successfully limited the number of PRRSV RNA copies in MARC-145 cells as determined by RT-qPCR. By inhibiting the PRRSV-CD163 interaction with brazilin from Caesalpinia sappan, it may be possible to prevent PRRSV infection in pigs, as suggested by this research.

Ethyl acetate extract of Caesalpinia sappan L. for the treatment of atherosclerosis in ApoE-/- mice and its mechanism.

The ethyl acetate extract of Caesalpinia sappan L. is a traditional Chinese medicine extract commonly used in the treatment of atherosclerosis. However, the mechanism of its use in the treatment of AS is not yet clear, which seriously affects the wide-scale application of this drug. In this study, a combination of metabolomics and lipidomics was used to analyze cardiac tissue to obtain differential metabolites and differential lipid molecules, bioinformatic analysis was performed on the significantly different metabolites and subclass analysis, cluster analysis, and chain length and chain saturation analyses were performed on screened lipid molecules showing significant differences. A correlation network diagram of the screened differential metabolites and differential lipid molecules was constructed. Hematoxylin and eosin staining of thoracic aorta in rats confirmed its therapeutic effect. This study found that the ethyl acetate extract of C. sappan L. upregulates D-mannose through the lysosome pathway, enhances lysosomal function, mediates autophagy, and indirectly regulates the levels of lipid subtypes such as lysophosphatidylinositol and phosphatidylserine, thereby improving AS.

New polyphenolic glycosides from the stems of Caesalpinia cucullata and their inhibitory effect on methicillin-resistant Staphylococcus aureus with different ways.

Anti-virulence strategy represents an emerging alternative strategy in the war against increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) due to its milder selection pressure on bacterial resistance. Sortase A (SrtA), as an important virulence factor, is a membrane-localized cysteine transpeptidase which anchors cell surface proteins to the cell wall. Natural products in medicinal plants are the source of targeting bacterial virulence factors. Here, we found polyphenolic glycosides (1-15), including thirteen new derivatives isolated from the stems of Caesalpinia cucullata, exhibited weak to moderate SrtA inhibitory activity without affecting the growth of MRSA, and compound 7 (53.7 % inhibition at 100 µM) was superior to the positive control curcumin. Meanwhile, compounds 2, 4 and 8 could effectively reduce the dose of ceftiofur in combination in vitro with fractional inhibitory concentration index (FICI) ranging from 0.188 to 0.375, which meant polyphenolic glycosides have got antibacterial activity with different ways. Here, we reported all new compounds structures determined by spectroscopy methods and their antibacterial activities, together, the relationship between structures with the inhibitory efficiency. The results indicated that polyphenolic glycosides could be used as promising therapeutic agents to prevent resistance development for S. aureus infections.

Identification of Protosappanoside D from Caesalpinia decapetala and Evaluation of Its Pharmacokinetic, Metabolism and Pharmacological Activity.

Protosappanoside D (PTD) is a new component isolated from the extract of Caesalpinia decapetala for the first time. Its structure was identified as protosappanin B-3-O-ß-D-glucoside by 1H-NMR, 13C-NMR, 2D-NMR and MS techniques. To date, the pharmacological activities, metabolism or pharmacokinetics of PTD has not been reported. Therefore, this research to study the anti-inflammatory activity of PTD was investigated via the LPS-induced RAW264.7 cells model. At the same time, we also used the UHPLC/Q Exactive Plus MS and UPLC-MS/MS methods to study the metabolites and pharmacokinetics of PTD, to calculate its bioavailability for the first time. The results showed that PTD could downregulate secretion of the pro-inflammatory cytokines. In the metabolic study, four metabolites were identified, and the primary degradative pathways in vivo involved the desaturation, oxidation, methylation, alkylation, dehydration, degradation and desugarization. In the pharmacokinetic study, PTD and its main metabolite protosappanin B (PTB) were measured after oral and intravenous administration. After oral administration of PTD, its Tmax was 0.49 h, t1/2z and MRT(0-t) were 3.47 ± 0.78 h and 3.06 ± 0.63 h, respectively. It shows that PTD was quickly absorbed into plasma and it may be eliminated quickly in the body, and its bioavailability is about 0.65%.

Two new C-benzylated chalcones and one new mimosin-type homoisoflavonoid from the twigs and leaves of Caesalpinia digyna.

Two new C-benzylated chalcones, 2',4'-dihydroxy-3'-(2-hydroxylbenzyl) chalcone (1) and 2',4'-dihydroxy-5'-(2-hydroxybenzyl) chalcone (2), one new and one known mimosin-type homoisoflavonoid, mimosol H (7) and mimosol G (8), together with four known chalcones (3-6) and four known sappanin-type homoisoflavonoids (9-12), were isolated from the twigs and leaves of Caesalpinia digyna. Their structures were characterized by comprehensive spectroscopic analyses (including NMR and HRESIMS). Compounds 1, 2 and 8 exhibited moderate cytotoxicity against SMMC-7721, A-549 and/or MDA-MB-231 cell lines with IC50 values ranging from 11.41 ± 0.88 to 30.01 ± 1.56 µM. Notably, C-benzyl chalcones (1 and 2) were isolated from species of the genus Caesalpinia for the first time. Homoisoflavonoids 7 and 8 are the first examples of mimosin-type homoisoflavonoids reported in Caesalpinia digyna.

Sappanwood-derived polyphenolic antidote of amyloidal toxins achieved detoxification via inhibition/reversion of amyloidal fibrillation.

The formidable virulence of methicillin-resistant staphylococcus aureus (MRSA) have thrown great challenges to biomedicine, which mainly derives from their autocrine phenol-soluble modulins (PSMs) toxins, especially the most toxic member termed phenol-soluble modulins α3 (PSMα3). PSMα3 cytotoxicity is attributed to its amyloidal fibrillation and subsequent formation of cross-α sheet fibrils. Inspired by the multiple biological activity of Sappanwood, herein, we adopted brazilin, a natural polyphenolic compound originated from Caesalpinia sappan, as a potential antidote of PSMα3 toxins, and attempted to prove that the regulation of PSMα3 fibrillation was an effective alexipharmic way for MRSA infections. In vitro results revealed that brazilin suppressed PSMα3 fibrillation and disassembled preformed amyloidal fibrils in a dose-dependent manner, in which molar ratio (brazilin: PSMα3) of efficient inhibition and disassembly were both 1:1. These desired regulations dominated by brazilin benefited from its bonding to core fibrils-forming residues of PSMα3 monomers urged by hydrogen bonding and pi-pi stacking, and such binding modes facilitated brazilin-mediated inhibition or disruption of interactions between neighboring PSMα3 monomers. In this context, these inhibited and disassembled PSMα3 assemblies could not easily insert into cell membrane and subsequent penetration, and thus alleviating the membrane disruption, cytoplasmic leakage, and reactive oxygen species (ROS) generation in normal cells. As such, brazilin dramatically decreased the cytotoxicity borne by toxic PSMα3 fibrils. In addition, in vivo experiments affirmed that brazilin relieved the toxicity of PSMα3 toxins and thus promoted the skin wound healing of mice. This study provides a new antidote of PSMα3 toxins, and also confirms the feasibility of the assembly-regulation strategy in development of antidotes against supramolecular fibrillation-dependent toxins.