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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 IC 50 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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 IC 50 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 IC 50 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.

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-1β (IL-1β), 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-1β, 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-1β, 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-1β, 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., Competing Interests: The authors declare there are no competing interests., (©2024 Sugiaman et al.)

Background: Medical manifestations in the form of incisions, burns, and trauma will trigger a natural wound-healing process that involves complex interactions between cells. Brazilin and other secondary metabolites found in Sappan wood have numerous bioactive qualities, including anti-inflammatory, anti-cancer, and antioxidant properties., Aim: This study aimed to investigate the efficacy of Sappan wood ( Caesalpinia Sappan L.) ethanol extract topically on the incision wound healing of albino rats., Methods: Twenty male rats were randomly assigned into five groups with four replications, i.e., (C-) was treated ointment-based, (C+) was treated with 10% povidone-iodine, (T1, T2, and T3 groups) were treated with Sappan wood extract concentration for 6.5%, 15%, and 30%, respectively. The treatment was topically administered to wounded areas twice a day for 15 days. Wound healing was evaluated histologically as the following parameters collagen deposition, polymorphonuclear neutrophils (PMN), angiogenesis, and fibrosis degree using H&E staining. IL-2 level was evaluated using the enzyme-linked immunosorbent assay (ELISA) method. Wound length reduction was calculated on days 8 and 15., Results: As a result, the 6.5% (T1), 15% (T2), and 30% (T3) Sappan wood extract groups were improved significantly ( p < 0.05) compared to ointment-based (C-) and povidone-iodine (C+) groups on the collagen deposition, PMN, angiogenesis, fibrosis degree, and IL-2 level. In particular, the 6.5% (T1) Sappan wood extract group was highlighted significantly ( p < 0.05) compared to other groups, evidenced by the improvisation of wound healing parameters and reduction of wound length on days 8 and 15., Conclusion: In conclusion, a 6.5% Sappan wood extract revealed its applicability to improve incision wound healing in albino rats., Competing Interests: The authors declare that they have no competing interests.

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 IC 50 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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.

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., Competing Interests: The authors declare that there is no conflict of interest.

This research aimed to evaluate atmospheric pressure immersion (API) and vacuum impregnation (VI) of non-hydrolyzed and hydrolyzed tara gallotannins (TE and THE) extracts and the purification process by leaching with ethyl acetate (TE-L and THE-L) and absorption chromatography on the acrylamide (AA) mitigation in potato chips. Better results were obtained with THE-L at hydrolysis degrees of 48.5 and 99.8 % and API with AA reduction of 57.9 and 61.7 %, respectively (p > 0.05), while with TE-L, AA reduction was 29.2 %. Instead, THE-L and TE-L with VI reduced AA by 70.3 and 66.4 %, respectively. In potato chips subjected to THE-L treatment, phenolic compounds and ABTS AC increased in 86.5-91.0 % and 71.0-103.2 %, respectively compared to the control. The main antioxidants were identified in the extracts and in potato chips. Tara gallotannins are an interesting alternative to mitigate AA formation and to enhance the antioxidant power of potato chips., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors of the present manuscript have declared that no competing interests exist., (Copyright © 2024. Published by Elsevier B.V.)

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 IC 50 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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 × 10 7 to 3.699 × 10 7  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., (© 2023. The Author(s).)

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., (© 2023 John Wiley & Sons Ltd.)

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 IC 50 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., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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 1 H 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.

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., (© 2023 Society of Chemical Industry.)

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 IC 50 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., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

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 TCID 50 /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., (© 2022. The Author(s).)

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.

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Three new cassane-type diterpenoids, namely, (4 S )-6 β ,12 α ,19-trihydroxy-cass-13(15)-en-16,12-olide ( 1 ), cass-13(15)-en-​16,12-olide ( 2 ), and 12 α -hydroxy-cass-13(15)-en-16,12-olide ( 3 ), were isolated from the seeds of Caesalpinia sinensis. The structures of 1 - 3 were established by extensive spectroscopic analysis, and their absolute configurations were assigned by electronic circular dichroism (ECD) calculations. The inhibitory activities against PTP1B of the isolated compounds were evaluated. The results showed that compound 2 possessed PTP1B inhibitory activity with an IC 50 value of 217.45 ± 36.4 μM.

Five compounds were isolated from the methanolic extract of Caesalpinia sinensis stems and leaves including a new cassane-type butenolide norditerpenoid compound ( 1 ) and a new type of biphenyl compound ( 2 ); the compounds were identified as Norcaesalpin-one ( 1 ), 4'-hexyl 3-methyl 6-methoxy-[1,1'-biphenyl]-3,4'-dicarboxylate ( 2 ), rhapontigenin ( 3 ), 3-deoxysappanchalcone ( 4 ), isoliquiritigenin ( 5 ). Compounds 1 - 5 were first isolated from C. sinensis . Their structures were elucidaded on the basis of MS, IR, NMR spectroscopic, X-ray diffraction data analyses. The NGF-induced PC12 differentiation assay was performed on compound 1 , and the results showed that compound 1 had a promotive effect on PC12 cell differentiation, with a differentiation rate of 12.32%. In addition, compounds 1 - 5 were evaluated for their cytotoxic activities against four human cancer cell lines (including A-549, BGC-823, MDA-MB-231, HepG2), and the results showed that compounds 3 - 5 showed inhibitory activity against these cancer cell lines with IC 50 values ranging from 22.96 to 74.92 μmol/L, compound 4 showing the best activity against human malignant melanoma cells A375 with an IC 50 value of 22.96 μmol/L.

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 IC 50 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., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Two new cassane-type derivatives ( 1 - 2 ), together with three known compounds ( 3 - 5 ), were isolated from the seed kernels of Caesalpinia sinensis . Their structures were elucidated on the basis of interpretation of comprehensive spectroscopic data, including HRESIMS and 1D/2D NMR spectroscopy, and the absolute configuration were established by means of ECD calculation. Compound 2 , possessing a 16-degradative cassane skeleton, was rarely encountered in cassane diterpenoids isolated from the genus Caesalpinia . All compounds were evaluated for their anti-inflammatory activities against the overproduction of NO in LPS-stimulated RAW 264.7 macrophages, and compounds 1-5 could inhibit production of NO at the concentration of 50 μM.

The first investigation of chemical composition in seed kernels of Caesalpinia cucullata Roxb. resulted in the separation of four new cassane diterpenes, including three furanoditerpenes ( 1 , 2 and 4 ) and one tricyclic type ( 3 ). It was the first found cassane diterpenoids from this plant. Their gross structures were elucidated by means of comprehensive spectroscopic analysis (UV, IR, NMR, HRESIMS) as well as electronic circular dichroism (ECD) calculation. The compound 1 possess a rare isomerized dihydrofuran ring in structure framework. In bioassay, compounds 1 - 4 exhibited moderate anti-inflammatory activity by inhibiting production of NO in LPS-induced RAW 264.7 cells.

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 - β -D-glucoside by 1 H-NMR, 13 C-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 T max was 0.49 h, t 1/2z 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%.

Three undescribed cassane-type diterpenoids (CAs), caesalpulcherrins K-M ( 1 - 3 ), together with three known ones ( 4 - 6 ) were isolated from the aerial parts of Caesalpinia pulcherrima (L.) Sw (Fabaceae). Their structures were elucidated via analysis of NMR (1 D and 2 D) and HRESIMS data. The character for caesalpulcherrin K possessing the olefin bond at C-11 and C-12 in its cassane skeleton was observed, which belonged to a small group among more than 450 CAs. That is, only fifteen derivatives have been reported up to now, to our knowledge. Biological evaluation revealed that compounds 1 - 6 exhibited moderate anti-inflammatory activity, with an IC 50 value from 6.04 ± 0.34 to 8.92 ± 0.65 μM. Furthermore, compounds 5 and 6 exhibited significant α -glucosidase inhibitory activity at 10 μM.

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., (Copyright © 2022. Published by Elsevier B.V.)

In this study, phytochemical investigation on the chloroform soluble fraction of seed kernels of Caesalpinia bonduc led to the isolation of two new cassane-type diterpenoids, norcaesalpinin Q ( 1 ) and caesalpinin MR ( 2 ), together with seven known compounds ( 3 - 9 ). The structures of the new compounds were elucidated on the basis of extensive NMR spectroscopic and mass spectrometric analyses, and their absolute configurations were determined by electronic circular dichroism (ECD) calculations. All compounds were evaluated for inhibitory effects against NO production of RAW264.7 cells induced by LPS, and compounds 5 , 7 and 8 could inhibited the production of NO at the concentration of 50 µM.

The aim of this work was to identify the main chemical constituents and to evaluate the antilithiatic activity of the aqueous and hydroalcoholic extracts of stems of Caesalpinia bahamensis Lam. Fractionation and isolation of constituents from the hydroalcoholic extract was carried out by flash chromatography and semi-preparative liquid chromatography. The antilithiatic activity of the aqueous and hydroalcoholic extracts was evaluated in Wistar rats, where kidney stones were induced by ethylene glycol and ammonium chloride. Creatinine, calcium, and oxalate levels were evaluated and histological analysis was carried out. The homoisoflavonoids protosappanin B, 10-methyl-protosappanin B and brazilin were isolated and the antilithiatic activity of the aqueous and hydroalcoholic extracts was demonstrated by the reduction of the concentration of calcium and oxalate in urine compared to the lithiasis group. It was corroborated by histological analysis. Brazilin and protosappanin B were proposed as chemical markers for this plant species.

Two undescribed nitrogen bridged cassane alkaloids (caesanamides A-B) and five undescribed oxygen bridged cassane diterpenoids (caesalpinins JA-JE), together with six known analogs, were isolated and identified from the seeds of Caesalpinia sappan. Their structures, including the absolute configurations, were unequivocally elucidated by the analysis of comprehensive spectroscopic data, ECD calculations, single-crystal X-ray diffraction and the CASE algorithm. Among them, caesanamides A and B represent the first examples of cassane alkaloids bearing unique ring systems of an amide bridge between C-19/C-20 incorporating a 1,3-oxazolidine (6/6/6/5/6/5) or a 7-one-1,3-oxazepine (6/6/6/5/6/7). Caesalpinin JA is an A/B cis-20-norcassane diterpenoid with a rare five-membered oxygen bridge between C-10/C-18. Biological evaluation showed that cassane alkaloids exhibited significant cytotoxicity against HepG2 cells with IC 50 values of 13.48 ± 1.07 μM (caesanamide A), 18.91 ± 0.98 μM (caesanamide B), and 7.82 ± 0.65 μM (caesanine B). Further flow cytometry analysis revealed that caesanine B could cause G0G1 cell cycle arrest and promote apoptosis in a dose- and time-dependent manner in HepG2 cells., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The tetracyclic phenolic compound brazilin, derived from the wood of Caesalpinia sappan, has been shown to bind to the chromatin protein BAF1 (barrier-to-autointegration factor 1), a protein essential to maintain integrity of the nuclear envelope in cells. BAF1 plays a role in cancer development. Using molecular docking, we have located the binding site for brazilin on the surface of the BAF1 monomer and compared its binding to that of four analogs. The oxidized product brazilein (ΔE = -57.7 kcal/mol) exhibits a higher affinity for BAF1 compared to the reduced form brazilin (ΔE = -38.2 kcal/mol). Incorporation of a 4-hydroxyl substituent on the indenochromene unit affords hematoxylin and hematein. In silico analysis predicts that the oxidized form hematein (ΔE = -66.2 kcal/mol) displays a higher affinity for BAF1 than the reduced form hematoxylin (ΔE = -42.2 kcal/mol). In contrast, the atypical bis-lactone product brazilide A cannot form good complexes with BAF1. The analysis points to the formation of more stable BAF1 complexes with the oxidized molecules compared to the reduced ones, but the position of the binding site on the protein cavity is different for brazilin/hematoxylin compared to brazilein/hematein. Our study may be useful to guide the design of BAF1 ligands., (© 2022 New York Academy of Sciences.)

A new cassane diterpenoid, caesappine A ( 1 ), and a new natural cassane diterpenoid, caesappine B ( 2 ) were isolated from the seeds of Caesalpinia sappan . The new structures of compounds 1 and 2 were elucidated by analysing their 1D NMR, 2D NMR and HR-ESI-MS spectra. Compounds 1 and 2 were evaluated for the cytotoxic activities on Hela and HepG-2 human cancer cell lines.

Eight undescribed cassane diterpenes, pterolobirins C-J, together with two known analogs, were isolated from the roots of Pterolobium macropterum. Their structures were characterized by extensive spectroscopic techniques including NMR, MS, ECD and X-ray crystallographic spectroscopy. The absolute configuration of pterolobirin J was confirmed by single-crystal X-ray diffraction data. The compounds were screened for their anti-inflammatory activity on the lipopolysaccharide (LPS) induced nitric oxide (NO) production in J774. A1 macrophage cells. Pterolobirin E and sucutinirane C displayed good NO inhibition with IC 50 values of 24.44 ± 1.34 and 19.16 ± 1.22 μM, respectively., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Sixteen cassane diterpenoids (CAs), including four undescribed lactam-type, four unreported lactone-type, along with eight known ones, were isolated from the aerial parts of Caesalpinia pulcherrima (L.) Sw. Their structures were characterized by comprehensive spectroscopic analyses (including NMR and HRESIMS). The absolute configuration of pulcherritam A was finally established by single-crystal X-ray diffraction with Cu Kα radiation. Notably, pulcherritam s A-D were elucidated as a group of rare CAs bearing an α, β-unsaturated γ-lactam ring rather than a typical lactone moiety. Almost all compounds were examined for their antibacterial. The results reveal that pulcherritam H exhibited significant antibacterial activities against Bacillus cereus, Staphylococcus aureus, as well as Pseudomonas syringae pv. actinidae (Psa) with the MIC from 6.25 to 12.5 μM, while pulcherritams A and C displayed potent antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA). Then, all isolates were evaluated for their anti-glioblastoma activities. Pulcherritam A and Pulcherrimin G illustrated moderate inhibitory activity against glioblastoma multiforme (GBM) U87MG cell, and the other compounds did not show obvious inhibitory activity against GBM U87MG cell. Furthermore, the preliminary structure-activity relationship and their biosynthetic pathway were also discussed., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The seeds of Caesalpinia minax Hance have shown anti-tumor potential, while the chemical principle is still unknown. In a search for anti-tumor compounds, six new cassane-type diterpenoids, 12-demethylcaesalpin G ( 1 ), caesalpinolide H ( 2 ), 12-demethylcaesalpin H ( 3 ), caesalpinolide J ( 4 ), 12- O -ethyl neocaesalpin B ( 5 ), and 3-deacetyldecapetpene B ( 6 ), were isolated from the seeds of C. minax Hance, along with fifteen known analogues. The structures of the new compounds were established by means of spectroscopic techniques (NMR, HRESIMS and IR). The absolute configurations of the new compounds were determined by their ECD spectra. All of the new compounds were tested for their anti-proliferative activity against human lung cancer A549 cells, breast cancer MCF-7 cells, and ovarian cancer HEY cells. The results indicated that only compound 6 displayed moderate cytotoxicity against three cancer cell lines. Thus, the opening of furan ring in cassane-type diterpenoids might enhance the cytotoxic activity.

Objective: To evaluate the anti-cancer properties of Caesalpinia sappan and Ficus septica in combination with doxorubicin on 4T1 cells, confirm their nephroprotective activities, and predict the molecular targets of the underlying mechanisms., Methods: The cytotoxic activities of all extracts and doxorubicin were determined by MTT assay followed by cell cycle and apoptosis analysis using flow cytometry. Immunoblotting was used to determine the protein expressions. The proteins involved in the cell proliferation and migration were analyzed through bioinformatics approaches, whereas, the interaction between compounds and protein targets was observed through molecular docking. Furthermore, the effect of the extracts on cell migration was analyzed by scratch wound healing assay. The intracellular ROS after treatment with extracts was observed using DCFDA staining flow cytometry., Results: Both ECS and EFS performed cytotoxic properties and significantly enhanced doxorubicin's cytotoxic effects against 4T1 cells. However, these cytotoxic activities did not correlate with the cell cycle progression. On the contrary, the combination treatment caused apoptosis that may correlate with the decreasing of IκBα phosphorylation, indicating that all agents targeted the inhibition of NF-κB activation. The combination treatments also inhibited cell migration and decreased MMP-9 expression. TNBC proliferation and metastasis needed at least 54 proteins to be activated, some of them are related to NF-κB activation. The inhibitory effect of ECS correlated with the interaction of brazilin and brazilein to IKK, a kinase protein that plays a role in IκBα phosphorylation. In addition, ECS and EFS reduced ROS expression in Vero cells caused by doxorubicin., Conclusion: In conclusion, ECS and EFS effectively enhanced the cytotoxic effect of doxorubicin and inhibit cell migration on 4T1 cells and these activities may correlate to the inhibitory effect of NF-κB activation. ECS and EFS also exhibit ROS suppressing effect on Vero cells that may be beneficent to reduce nephrotoxicity of chemotherapeutic treatment.

A novel cassane-type diterpenoid, caesalpinaxin (1), was isolated from the seeds of Caesalpinia minax Hance. The structure of caesalpinaxin was established by means of spectroscopic techniques (NMR, HR-ESIMS, UV and IR). The absolute configuration of caesalpinaxin was determined by quantum chemical calculations of its theoretical electronic circular dichroism (ECD) spectrum. Caesalpinaxin is the first cassane-type diterpenoid with 21 carbons core skeleton, containing an unusual δ-lactone ring. A plausible biosynthetic pathway was proposed for compound 1. Furthermore, caesalpinaxin was tested for the pro-angiogenetic activity on human umbilical vein endothelial cells(HUVECs). The results indicated that this compound significantly stimulated migration and tuber formation through enhancing the level of vascular endothelial growth factor (VEGF). Thus, caesalpinaxin might be applied in accelerating wound healing., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Caesalpinia bonduc (L.) Roxb. [Family: Fabaceae (Caesalpiniaceae)], known as bonduc nut or fever nut, has been used in India for many years to treat fever, inflammation, diabetes, cardiovascular disorder, cancer and also for birth control. In recent years, the seeds of this plant are consumed to regulate the menstrual disorders in PCOS. Poly cystic ovary syndrome (PCOS) is one of the most common endocrinological disorders faced by women of reproductive-age in several countries., Aim of the Review: This review is aimed at providing the updates on the potential of Caesalpinia bonducella in treating the major symptoms of PCOS and also highlights the future research needs., Materials and Methods: All the data pertaining to the plant was collected from multiple databases like Google, Science Direct, Springer, PubMed, Reaxys, Sci Finder, Wiley Online library and Taylor and Francis without any language restrictions. Moreover, information related to PCOS treatment was obtained from native medicine practitioners and from Ayurvedic pharmacopeia of India., Results: More than 50 compounds have been identified in the seed kernels of C. bonducella so far. Seed kernel extracts rich in active compounds like bonducellin, caesalpinin, cassane furanoditerpenes, terpernoids, flavonoids and sterols are studied for their anti-diabetic, anti-hyperlipidemic, anti-cancer, anti-pyretic, and anti-oxidant properties. Recent literature has also attributed anti-androgenic and anti-estrogenic potential to this plant which might be helpful in regulating hyperandrogenism, the major predisposing factor contributing to various other clinical symptoms of PCOS., Conclusion: Phytochemicals in C. bonducella are effective against several ailments attributed to PCOS. However, there are no experiments done in PCOS animal models to claim the direct application of C. bonducella in PCOS treatment. Hence, further dose dependent toxicity studies are warranted in animal PCOS models and in PCOS patients to support the traditional evidence of the plants' potential to treat PCOS., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Ten new cassane-type diterpenoids were isolated from the seeds of Caesalpinia bonduc (L.) Roxb., including 6α-hydroxycaesalpinin P (1), 14-epi-caesalpinin E1 (2), 6-deacetylcaesalmin Z (3), 14-epi-caesalmin Z (4), caesalpinolides I (5), K (6), L (7), M (9) and N (10), and 14-epi-neocaesalpin L (8). Their planar structures and absolute configurations were fully determined by comprehensive spectroscopic methods, including 2D NMR and electronic circular dichroism spectra. Compounds 1-4 are tetracyclic cassane diterpenoids possessing a furan ring, and compounds 5-10 are tetracyclic cassane diterpenoids possessing a fused butenolide moiety. The anti-inflammatory and cytotoxic activities of the isolates were evaluated, while none of them showed obvious effects. The current study identified ten new cassane-type diterpenoids from the seeds of C. bonduc (L.) Roxb., which enriched the chemical diversity of the titled herbal medicine., (© 2021 Wiley-VHCA AG, Zurich, Switzerland.)

The first investigation of phytochemistry on the seed kernels of Caesalpinia sinensis led to the isolation and characterization of six new compounds including three tricyclic-type cassane diterpenoids (1--3) and three norcassane-type diterpenoids (4-6), together with three know compounds (7-9). Compounds 1-9 represented the first discovery of cassane-type diterpenoids from C. sinensis. Their structures were elucidated by a combination of spectroscopic analysis, single-crystal X-ray diffraction experiment and ECD calculation. The characters for compounds 4 and 5 possessing the 15,16-degradative cassane skeleton were observed, which was extremely rare structural type in the genus Caesalpinia. The anti-inflammatory activities of all isolates were evaluated via examining their inhibitory effects against NO production in LPS-simulated RAW 264.7 cells. The results demonstrated that compound 1 exhibited the most significantly inhibitory efficacy with inhibition rate 67.3% at 10 μM. The iNOS enzyme activity assay further revealed that compound 1 showed potent NO inhibitory effect by reducing the enzymatic activity of iNOS., (Copyright © 2021. Published by Elsevier B.V.)

Eighteen cassane diterpenoids, including five new lactam-type ( 4 - 8 ), 12 new lactone-type ( 1 - 3 and 9 - 17 ), and one known compound ( 18 ), were isolated from Caesalpinia sinensis . To our knowledge, this is the first study on the seed kernels of C. sinensis , and cassane derivatives were discovered in this plant for the first time. Their structures including absolute configurations were established by extensive spectroscopic methods complemented with single-crystal X-ray diffraction analyses and ECD calculations. Compounds 4 - 8 were identified as a group of rare cassane diterpenoids possessing a lactam D-ring instead of a typical lactone moiety. Biological evaluation revealed that compounds 4 - 6 exhibited effective inhibitory effects on NO production in the LPS-induced RAW 264.7 macrophages, with IC 50 values in the range 8.2-11.2 μM. Compound 4 suppressed the excessive production of NO by down-regulating the expression of inducible nitric oxide synthase enzymes (iNOS) and reducing the enzymatic activity of iNOS. Moreover, the intermolecular interaction and binding mode between compound 4 and iNOS were elaborated by conducting a molecular docking study.

The in vivo hepatoprotective potential of methanolic extract of Ceasalpinia bonduc (CBLM) has been explored against carbon tetrachloride (CCl 4 ) induced acute liver injury in rats. Treatment of plant extract on CCl 4 intoxicated liver significantly reduced the hepatoxicity, along with serum enzymes GPT and GOT. To explore the chemical constituents from CBLM extract, it was fractionated into non-polar to moderately polar fractions (CBLM-H, CBLM-HEt, CBLM-Et, CBLM-EtM, CBLM-M) and subjected to GC/GC-MS analysis. Altogether twenty seven (~71%) phytochemicals were identified from different fractions by using Electronic Mass Spectral Library GC-MS (NIST 20). Out of which twenty one are first time reported from Ceasalpinia bonduc, fourteen from genus Caesalpinia and ten from family Fabaceae. The identified phytochemicals 2-ethyl-2-hydroxy-1,3-dimethylcyclopentanecarboxylic acid, ethyl ester (21) and 1,3,5-triazine-2,4-diamine,6-hydroxy-N,N-dicyclohexyl (23) are first time identified as plant metabolites. To explore the antimicrobial potential four strains of Gram-positive and eight strains of Gram-negative bacteria were used along with pure cultures of five saprophytic fungus (molds) and two strains of yeast were utilized. CBLM-H and CBLM-HEt were exhibited praiseworthy antimicrobial potential. CBLM-H showed complete growth inhibition of P. mirabilis and V. cholerae at the concentration of 0.1g/mL while CBLM-HEt at 0.05g/mL halted the growth of S. aureus.

Ethnopharmacological Relevance: Stem barks of Caesalpinia ferrea Mart. Ex Tul. (Caesalpiniaceae), also known as pau-ferro jucá or jucaína, are popularly used to treat contusions, diabetes, rheumatism and other inflammatory conditions in the form of tea, lick or decoction., Objective: To evaluate the effect of the polysaccharide-rich extract obtained from C. ferrea stem barks (PE-Cf) in mice models of acute inflammation induced by zymosan and the involvement of oxidative stress biomarkers., Materials and Methods: Mice were treated with PE-Cf (0.001, 0.01, 0.1, 1 mg/kg) by endovenous route (i.v.) or per oral (p.o.) 30 or 60 min before injection of the inflammatory stimuli zymosan (0.5 mg; intraperitoneal or subcutaneous intraplantar). The inflammatory parameters (edema, nociception, leukocyte migration) and oxidative stress markers (myeloperoxidase-MPO, malondialdehyde-MDA, nitrite, reduced glutathione-GSH, glutathione peroxidase-GPx) were evaluated in the models of paw edema (hidropletysmometry/expressed as ml or area under curve-AUC) and peritonitis (optical microscopy/expressed as n° of cells/mm 3 of peritoneal fluid). Statistical analysis was performed by ANOVA, followed by Bonferroni test., Results: PE-Cf (0.1, 0.01 and 1 mg/kg) dose-dependently inhibited paw edema, showing maximal effect (74%) at 1 mg/kg in the 5th (52 ± 9.6 μl vs. zymosan: 204 ± 3.6 μl). PE-Cf (1 mg/kg) also inhibited by 43% MPO activity in the paw tissues (17 ± 1 vs. zymosan: 30 ± 2.6 U/mg). Besides, 4 h after peritonitis induction, PE-Cf (1 mg/kg) reduced neutrophil migration by 84% (432 ± 45 vs. zymosan: 2651 ± 643 cells/mm 3 ); visceral nociception by 76% (3 ± 0.6 vs. zymosan: 16 ± 4 writhes); nitric oxide by 73% (0.131 ± 0.033 vs. zymosan: 0.578 ± 0.185 NO 2 - /NO 3 - ml); MDA (98 ± 10 vs. zymosan:156 ± 21 U/ml), and increased GSH by 65% (736 ± 65 vs. zymosan: 259 ± 58 μmol/ml) and GPx by 72% (0.037 ± 0.007 vs. zymosan: 0.010 ± 0.005 U/mg protein)., Conclusion: The polysaccharide-rich extract of Caesalpinia ferrea stem barks present anti-inflammatory and antioxidant effects in mice models of acute inflammation induced by zymosan., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Brazilein is among the main chemical constituents of Caesalpinia sappan . It has diverse pharmacological activities. Modern pharmacological studies have shown that the compound has antitumor, anti-inflammatory, antibacterial, antioxidant, immunomodulatory, and other pharmacological activities. Brazilein is often used as a stain in various industries. The separation of brazilein by traditional column chromatography will not only result in contamination of the chromatographic column materials, but also lead to loss of the active ingredient. Countercurrent chromatography is an advanced liquid-liquid chromatographic separation technique. It has been widely used for natural product separation and isolation as it offers several advantages, such as low solvent consumption, a highly selective solvent system, and high recoveries. Typical countercurrent chromatography techniques include centrifugal partition chromatography (CPC), high-speed countercurrent chromatography (HSCCC), and high performance countercurrent chromatography (HPCCC). It is well known that choosing a suitable solvent system is vital in countercurrent separation. Therefore, two methods were introduced for choosing a suitable solvent system. One is the generally useful estimation of solvent systems (GUESS) method, which employs thin-layer chromatography (TLC) to identify a suitable solvent system with minimal labor for the rapid purification of target compounds, and another is the Shake-Flash method. The solvent system could be determined by observing the distribution of the sample in the upper and lower phases. Two kinds of solvent systems were screened using the TLC-GUESS and Shake-Flash methods, and tested through the analysis mode of the HPCCC instrument. The results showed that chloroform-methanol-water (4:3:2, v/v/v) was the optimal solvent system for HPCCC separation. A total of 15.2 mg of brazilein and 5.7 mg of caesappanin C were obtained from an ethyl acetate extract with high purities (95.6% and 89.0%, analyzed by HPLC) in one step using the preparation mode of HPCCC, the reversed-phase liquid chromatography mode with the apparatus rotated at 1600 r/min, a flow rate of 10 mL/min, separation temperature of 25℃, and detection wavelength of 285 nm. Their structures were determined by spectroscopic and spectrometric analyses. Brazilein stained the solid packing material in the column and was difficult to elute. The results showed that the use of HPCCC for the separation of brazilein can not only prevent the loss of target active ingredients in Caesalpinia sappan , but also shorten the separation and purification times and improve the operating efficiency. Therefore, HPCCC can be used for the separation and preparation of other pigment compounds in Caesalpinia sappan and other dye plants.

P2Et extract obtained from the Caesalpinia spinosa plant is abundant in phenolic compounds such as gallic acid and ethyl gallate and can generate signals to activate the immune response by inducing a mechanism known as immunogenic cell death in murine models of breast cancer and melanoma. Immunogenic cell death involves mechanisms such as autophagy, which can be modulated by various natural compounds, including phenolic compounds with a structure similar to those found in P2Et extract. Here, we determine the role of autophagy in apoptosis and the generation of immunogenic signals using murine wild-type B16-F10 melanoma cells and cells with beclin-1 gene knockout. We show that P2Et extract and ethyl gallate induced autophagy, partially protecting tumor cells from death and promoting calreticulin exposure and the release of ATP. Although ethyl gallate showed a mechanism similar to that of P2Et, the induction of apoptosis and immunogenic signals was significantly weaker. In contrast, gallic acid-induced autophagy acted by blocking autophagic flux, which was associated with increased cell death. However, this compound did not induce any of the immunogenic death signals evaluated. Therefore, the complex extract has greater antitumor potential than isolated compounds. Here, we show that inducing autophagic flux with P2Et protects cancer cells from cell death and that this delay in cell death is required for the generation of immunogenic signals.

The main cause of death by cancer is metastasis rather than local complications of primary tumors. Recent studies suggest that breast cancer stem cells (BCSCs), retains the ability to self-renew and differentiate to repopulate the entire tumor, also, they have been associated with resistance to chemotherapy and tumor recurrence, even after tumor resection. Chemotherapy has been implicated in the induction of resistant phenotypes with highly metastatic potential. Naturally occurring compounds, especially phytochemicals such as P2Et, can target different populations of cancer cells as well as BCSC, favoring the activation of immune response via immunogenic tumor death. Here, we evaluated the presence of BCSC as well as markers related to drug resistance in tumors obtained from 78 patients who had received (or not) chemotherapy before surgery. We evaluated the ex vivo response of patient tumor-derived organoids (or mammospheres) to chemotherapy alone or in combination with P2Et. A xenotransplant model engrafted with MDA-MB-468 was used to evaluate in vivo the activity of P2Et, in this model P2Et delay tumor growth. We show that patients with luminal and TNBC, and those who received neoadjuvant therapy before surgery have a higher frequency of BCSC. Further, the treatment with P2Et in mammospheres and human breast cancer cell lines improve the in vitro tumor death and decrease its viability and proliferation together with the release of immunogenic signals. P2Et could be a good co-adjuvant in antitumor therapy in patients, retarding the tumor growth by enabling the activation of the immune response.

Caesalpinia pulcherrima is a shrub with worldwide distribution used as an ornamental plant. In this study, we extracted a lignin from the C. pulcherrima leaves and investigated its biological functions. The lignin was characterized by FT-IR, UV-Vis, GPC, TGA and nuclear magnetic resonance ( 1 H and 13 C). The antioxidant activity was evaluated using phosphomolybdenum complexation methods (TAA), sequestration of DPPH and ABTS radicals, reducing power, formation of nitrite radical and iron chelating activity (Fe 2 + ). Antifungal activity was made using Candida spp., Aspergillus spp. and Cryptococcus neoformans strains. Cytotoxicity, oxidative stress, and cytokine production were performed using mouse splenocytes. The lignin showed maximal UV-Vis at ~280 nm, 22.27 L/g·cm of absorptivity and, 2,503 kDa of molecular weight. Phenolic compounds (41.33 ± 0.65 mg GAE/g) and indications of a guaiacyl-syringyl-hydroxyphenyl (GSH)-type composition were found. Antioxidant activities of lignin to TAA (40±1.2%) and to DPPH (16.9±0.2%) was high and showed antifungal potential, especially against Candida spp. (IC 50  = 31.3 μg/mL) and C. neoformans (15.6 μg/mL). In mouse splenocytes, the lignin was not cytotoxic and stimulated the cell proliferation and cytokine release. These results indicate that C. pulcherrima lignin has the potential to be used as antifungal and immunostimulant compound., Competing Interests: Declaration of competing interest The authors have no conflict of interest with this work., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Caesalpinia pulcherima (CP) is a traditional herb used for the treatment of asthma, bronchitis, cancer, anti-bacterial, anti-fungal and as abortifacient. In the present study, bioactive components and potential targets in the treatment of breast cancer validated through in silico, in vitro and in vivo approach. The results for the analysis were as among 29 components, only four components were found active for further study which proved the use of CP as a multi-target herb for betterment of clinical uses. The results found by PPI states that our network has significant interactions which include the ESR-1, ESR-2, ESRRA, MET, VEGF, FGF, PI3K, PDK-1, MAPK, PLK-1, NEK-2, and GRK. Compound-target network involves 4 active compound and 150 target genes which elucidate the mechanisms of drug action in breast cancer treatment. Furthermore, on the basis of the above results the important proteins were fetched for the docking study which helps in predicting the possible interaction between components and targets. The results of the western blotting showed that CP regulates ER and EGFR expression in MCF-7 cell. In addition to this animal experimentation showed that CP significantly improved immunohistological status in MNU induced carcinoma rats. Network pharmacology approach not only helps us to confirm the study of the chosen target but also gave an idea of compound-target network as well as pathways associated to the CP for treating the complex metabolic condition as breast cancer and they importance for experimental verification.

Protein-tyrosine phosphatase 1B (PTP1B) has been considered as a promising target for treating insulin resistance. In searching for naturally occurring PTB1B antagonists, two new pimarane diterpenoids, named 2α-hydroxy-7-oxo-pimara-8(9),15-diene ( 1 ) and 19-hydroxy-2α-acetoxy-7-oxo-pimara-8(9),15-diene ( 2 ), were isolated from the seeds of Caesalpinia minax . Their structures were determined by extensive analysis of NMR and HR-ESIMS data, and their absolute configurations were determined by electronic circular dichroism (ECD) spectra. Compound 1 was disclosed as a competitive inhibitor of PTP1B with an IC 50 (the half-maximal inhibitory concentration) value of 19.44 ± 2.39 µM and a K i (inhibition constant) value of 13.69 ± 2.72 μM. Moreover, compound 1 dose-dependently promoted insulin-stimulated glucose uptake in C2C12 myotubes through activating insulin signaling pathway. Compound 1 might be further developed as an insulin sensitizer.