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Objective: To investigate the mechanism of induction of ferroptosis by brazilin in breast cancer cells. Methods: Breast cancer 4T1 cells were divided into 6 groups: control, brazilin 1/2 half maximal inhibitory concentration (IC50), IC50, 2×IC50, erastin (10 µg/mL) and capecitabine (10 µg/mL) groups. The effect of brazilin on the proliferation of 4T1 cells was detected by cell counting kit-8 assay, and the treatment dose of brazilin was screened. The effect of brazilin on the mitochondrial morphology of 4T1 cells, and the mitochondrial damage was evaluated under electron microscopy. The levels of Fe2+, reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH) and glutathione peroxidase 4 (GPX4) were estimated using various detection kits. The invasion and migration abilities of 4T1 cells were detected by scratch assay and transwell assay. The expressions levels of tumor protein p53, solute carrier family 7 member 11 (SLC7A11), GPX4 and acyl-CoA synthetase long-chain family member 4 (ACSL4) proteins were quantified by Western blot assay. Results: Compared to the control group, the 10 (1/2 IC50), 20 (IC50) and 40 (2×IC50) µg/mL brazilin, erastin, and capecitabine groups showed a significant decrease in the cell survival rate, invasion and migration abilities, GSH, SLC7A11 and GPX4 protein expression levels, and mitochondrial volume and ridge (P<0.05), and a significant increase in the mitochondria membrane density, Fe2+, ROS and MDA levels, and p53 and ACSL4 protein expression levels (P<0.05). Conclusions: Brazilin actuated ferroptosis in breast cancer cells, and the underlying mechanism is mainly associated with the p53/SLC7A11/GPX4 signaling pathway. [ABSTRACT FROM AUTHOR]

Caesalpinia sappan L. has generally been used in Asian folk medicines for disease treatment. C. sappan heartwood is commonly utilized as a dyeing agent in food items, beverages, cosmetics, and clothing. The effects of three extraction techniques (maceration, reflux, and ultrasonic-assisted extraction) of C. sappan heartwood extract (CSE) on the brazilin content and potential of biological activities were investigated. The brazilin content was determined using high-performance liquid chromatography (HPLC). Quantifications of the antioxidant properties (DPPH and ABTS), the total phenolic contents, and the antimicrobial activity were also examined. Additionally, the effect of CSE on pro-inflammatory cytokine and mediator production was investigated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. The results showed that the CSE from the maceration and reflux methods produced high levels of brazilin and total phenolic contents, as well as having excellent antioxidant and antimicrobial activities. The macerated extract showed significant antioxidant activities with IC50 values of 2.88 ± 0.01 and 0.32 ± 0.01 mg/mL from DPPH and ABTS assays, respectively. Furthermore, the CSE from the maceration method which was rich in brazilin had an anti-inflammatory response by decreasing the levels of nitric oxide (NO), interleukin (IL)-6, and tumor necrosis factor (TNF)-α on LPS-stimulated RAW 264.7 macrophage cells. These results confirmed CSE as a potential source of biological components. Antioxidant and anti-inflammatory assays proved maceration was the best extraction method.Article Highlights: Three extraction methods (maceration, reflux, and ultrasonic-assisted extraction) were applied to study the brazilin content and biological activities of Caesalpinia sappan L. The maceration method is illustrated as the most efficient extraction technique. The heartwood extract of C. sappan from maceration contained a high level of brazilin and exhibited antioxidant and anti-inflammatory properties. [ABSTRACT FROM AUTHOR]

Abstract Caesalpinia sappan L. has generally been used in Asian folk medicines for disease treatment. C. sappan heartwood is commonly utilized as a dyeing agent in food items, beverages, cosmetics, and clothing. The effects of three extraction techniques (maceration, reflux, and ultrasonic-assisted extraction) of C. sappan heartwood extract (CSE) on the brazilin content and potential of biological activities were investigated. The brazilin content was determined using high-performance liquid chromatography (HPLC). Quantifications of the antioxidant properties (DPPH and ABTS), the total phenolic contents, and the antimicrobial activity were also examined. Additionally, the effect of CSE on pro-inflammatory cytokine and mediator production was investigated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. The results showed that the CSE from the maceration and reflux methods produced high levels of brazilin and total phenolic contents, as well as having excellent antioxidant and antimicrobial activities. The macerated extract showed significant antioxidant activities with IC50 values of 2.88 ± 0.01 and 0.32 ± 0.01 mg/mL from DPPH and ABTS assays, respectively. Furthermore, the CSE from the maceration method which was rich in brazilin had an anti-inflammatory response by decreasing the levels of nitric oxide (NO), interleukin (IL)-6, and tumor necrosis factor (TNF)-α on LPS-stimulated RAW 264.7 macrophage cells. These results confirmed CSE as a potential source of biological components. Antioxidant and anti-inflammatory assays proved maceration was the best extraction method.

Caesalpinia sappan L (CS) heartwood is used as a natural red colorant in several Asian ethnic traditional drinks both as sole ingredient or mixed with other herbs. However, the pigment is unstable and easily degraded during storage which affects consumer acceptance. This research aimed to investigate the effect of different blanching and drying methods on the color stability, brazilin content, and antioxidant activity of CS heartwood drinks. Steam blanching, water blanching, sun drying and cabinet drying were examined in this study. The most common method applied in traditional production, without blanching and sun drying, was used as a control. The experimental design used was complete randomized design with triplicates. Data are presented as mean ± standard deviation and analyzed by SPSS statistics version 20. The results showed that blanching and drying methods affected the color intensity. For a pure CS heartwood herbal drink, the sample prepared with water blanching and cabinet drying (BCD) showed the highest red value, leading to a 48 % improvement compared to the control. This red value is in accordance with the brazilin content. Sample BCD showed the highest brazilin content, which was 376 % higher than that of the control. Similarly, the BCD sample had the highest antioxidant activity and total phenolic content, with IC50 values of 98.99 ppm and 213.12 mg GAE g-1, respectively. This result revealed that brazilin might act as an antioxidant. Similar to the pure CS drink, the highest quality of mixed herbal drink was obtained by BCD sample. The results suggest that the combination of water blanching and cabinet drying (BCD) was the best method to improves the quality of CS heartwood drink both in pure and mixed herbal drinks as a functional drink. [ABSTRACT FROM AUTHOR]

To reveal the anti-protein aggregation ability of brazilin (Bra), hematoxylin (Hto) and hematein (Hte) under physiological crowding environment, the macromolecular crowding reagent (polyethylene glycol) was used to construct a simulated crowding environment. Then the inhibition mechanisms of these three structurally similar polyphenol compounds on the aggregation behavior of human serum albumin (HSA) were investigated by fluorescence spectroscopy, UV-vis absorption spectroscopy, dynamic light scattering (DLS) and atomic force (AFM) microscope assay. The results showed that they could maintain the stability of the HSA structure, decrease the number of amyloid fibrils and shorten the length of aggregates in crowding environment. Therefore, they inhibited the aggregation process of HSA, and the sequence of the inhibition ability was in the order of Hto>Bra>Hte. Moreover, the presence of crowding reagents could lead to a decrease in the inhibitory activity of these three inhibitors compared to in vitro dilute solution. In conclusion, this study suggested that Hto could be used as a potential protein aggregation inhibitor and a functional food ingredient for the treatment and intervention of amyloid-related diseases.

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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. [ABSTRACT FROM AUTHOR]

Background: Iron overload and inflammation are severe conditions that can lead to various chronic diseases. However, the current iron chelator drugs have their limitations. The phytochemical compounds from herbals, such as brazilin, the major active compound in Caesalpinia sappan Linn., have significant therapeutic potential in various chronic diseases. Our study was designed to examine the effect of brazilin on iron chelating properties, antioxidant activity in hepatocytes, and anti-inflammatory potential in macrophages. Methods: This study focused on the isolation, purification, and evaluation of brazilin, the principal bioactive constituent found in C. sappan wood. Brazilin was extracted via methanol maceration followed by column chromatography purification. The purified compound was characterized using high-performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR) spectroscopy, and mass spectrometry (MS). The antioxidant potential of brazilin was assessed by in vitro assays, including 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azinobis-(3-ethylbenzthiazolin-6-sulfonic acid (ABTS), and ferric-reducing antioxidant power (FRAP). Furthermore, its cellular antioxidant activity was evaluated using hydrogen peroxide-induced oxidative stress in the hepatocellular carcinoma cell line (Huh-7). The iron-chelating capacity of brazilin was determined spectrophotometrically, and Job's plot method was used to elucidated the stoichiometry of the iron-brazilin complex formation. The anti-inflammatory properties of brazilin were investigated in lipopolysaccharide (LPS)-stimulated macrophages (RAW 264.7). Nitric oxide (NO) inhibition was quantified using the Griess reagent, while the expression levels of pro-inflammatory cytokines, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), were evaluated by RT-qPCR. Results: The results demonstrated that brazilin exhibited potent antioxidant activity in vitro and hepatocytes in a concentration-dependent manner. It also showed anti-inflammatory activity, in which NO production was significantly reduced and IL-6 and TNF-α expression in LPS-induced macrophages were repressed. Furthermore, it can bind ferric and ferrous ions. Brazilin acts as a bidentate iron chelator that forms a complex with iron in a 2:1 ratio, and two water molecules are used as additional chelators in this complex. Conclusions: Our findings have significant implications. Brazilin can potentially alleviate the harmful effects of iron-induced oxidative stress and inflammatory disorders.

Abstract A catalytic diastereoselective Prins reaction for hydroxymethylation and hydroxylation of 1,3-diarylpropene was successfully utilized to prepare various 1,3-dioxanes 7 in 14–88% yields. Take advantage of the synthetic intermediate 7h, the key B/C rings in brazilin core could be constructed by the sequential of Friedel–Crafts/Ullmann-Ma rather than Ullmann-Ma/Friedel–Crafts reactions. Graphical Abstract

A catalytic diastereoselective Prins reaction for hydroxymethylation and hydroxylation of 1,3-diarylpropene was successfully utilized to prepare various 1,3-dioxanes 7 in 14–88% yields. Take advantage of the synthetic intermediate 7h, the key B/C rings in brazilin core could be constructed by the sequential of Friedel–Crafts/Ullmann-Ma rather than Ullmann-Ma/Friedel–Crafts reactions. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common invasive neoplasm and the leading cause of cancer death in women worldwide. The main cause of mortality in cancer patients is invasion and metastasis, where the epithelial-mesenchymal transition (EMT) is a crucial player in these processes. Pharmacological therapy has plants as its primary source, including isoflavonoids. Brazilin is an isoflavonoid isolated from Haematoxilum brasiletto that has shown antiproliferative activity in several cancer cell lines. In this study, we evaluated the effect of Brazilin on canonical markers of EMT such as E-cadherin, vimentin, Twist, and matrix metalloproteases (MMPs). By Western blot, we evaluated E-cadherin, vimentin, and Twist expression and the subcellular localization by immunofluorescence. Using gelatin zymography, we determined the levels of secretion of MMPs. We used Transwell chambers coated with matrigel to determine the in vitro invasion of breast cancer cells treated with Brazilin. Interestingly, our results show that Brazilin increases 50% in E-cadherin expression and decreases 50% in vimentin and Twist expression, MMPs, and cell invasion in triple-negative breast cancer (TNBC) MDA-MB-231 and to a lesser extend in MCF7 ER+ breast cancer cells. Together, these findings position Brazilin as a new molecule with great potential for use as complementary or alternative treatment in breast cancer therapy in the future. [ABSTRACT FROM AUTHOR]

Brazilin is the main compound in Caesalpinia sappan and Haematoxylum braziletto, which is identified as a homoisoflavonoid based on its molecular structure. These plants are traditionally used as an anti-inflammatory to treat fever, hemorrhage, rheumatism, skin problems, diabetes, and cardiovascular diseases. Recently, brazilin has increased its interest in cancer studies. Several findings have shown that brazilin has cytotoxic effects on colorectal cancer, breast cancer, lung cancer, multiple myeloma, osteosarcoma, cervical cancer, bladder carcinoma, also other cancers, along with numerous facts about its possible mechanisms that will be discussed. Besides its flavonoid content, brazilin is able to chelate metal ions. A study has proved that brazilin could be used as an antituberculosis agent based on its ability to chelate iron. This possible ironchelating of brazilin and all the studies discussed in this review will lead us to the statement that, in the future, brazilin has the potency to be a chemo-preventive and anticancer agent. The article review aimed to determine the brazilin mechanism and pathogenesis of cancer. [ABSTRACT FROM AUTHOR]

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.

The main components of Caesalpinia sappan L. (CS) are brazilin and brazilein, which show high potential in pharmacologic applications. However, these have been drastically limited by the poor water solubility and stability. The present study investigates the formation of inclusion complexes F1, F2, and F3 between CS and β-cyclodextrin (βCD), hydroxypropyl-β-cyclodextrin (HPβCD), and methyl-β-cyclodextrin (MβCD), respectively. These complexes were characterized by Fourier transform infrared spectroscopy (FT-IR). The results showed that the highest encapsulation efficiency and loading capacity of CS extract were 44.24% and 9.67%, respectively. The solubility and stability of CS extract were significantly increased through complexation in phase solubility and stability studies. The complexes F1–F3 showed mainly significant antibacterial activities on gram-positive bacteria pathogens causing mastitis. Moreover, the expression levels of COX-2 and iNOS were significantly decreased in LPS-induced inflammatory cells at concentrations of 50 and 100 µg/mL. In addition, treatment of complex F3 (CS/MβCD) in bovine endothelial cells remarkably increased the chemokine gene expression of CXCL3 and CXCL8, which were responsible for immune cell recruitment (9.92 to 11.17 and 8.23 to 9.51–fold relative to that of the LPS-treated group, respectively). This study provides a complete characterization of inclusion complexes between CS extract and βCD, HPβCD, and MβCD for the first time, highlighting the impact of complex formation on the pharmacologic activities of bovine mastitis. [ABSTRACT FROM AUTHOR]

Brazilin is the main compound in Caesalpinia sappan and Haematoxylum braziletto, which is identified as a homoisoflavonoid based on its molecular structure. These plants are traditionally used as an anti-inflammatory to treat fever, hemorrhage, rheumatism, skin problems, diabetes, and cardiovascular diseases. Recently, brazilin has increased its interest in cancer studies. Several findings have shown that brazilin has cytotoxic effects on colorectal cancer, breast cancer, lung cancer, multiple myeloma, osteosarcoma, cervical cancer, bladder carcinoma, also other cancers, along with numerous facts about its possible mechanisms that will be discussed. Besides its flavonoid content, brazilin is able to chelate metal ions. A study has proved that brazilin could be used as an antituberculosis agent based on its ability to chelate iron. This possible iron-chelating of brazilin and all the studies discussed in this review will lead us to the statement that, in the future, brazilin has the potency to be a chemo-preventive and anticancer agent. The article review aimed to determine the brazilin mechanism and pathogenesis of cancer.

The major problem leading to substantial waste in the food industry is the spoilage of food products during transportation and storage periods. Consequently, the scope of this research focuses on the development and preparation a pH responsive monitoring films based on biodegradable materials of poly(vinyl alcohol) (PVA) and natural colorant extract from Caesalpinia sappan L. heartwood (SP). These monitoring films were prepared by a solution casting method and the film stability was improved by crosslinking with citric acid (CA). The red tone of monitoring film without CA was observed, while the crosslinked monitoring film showed a yellow color, which occurs from the structural change of brazilin (structure presenting in SP) to brazilein under acidic conditions. From the SEM and FTIR results, the monitoring film showed high compatibility between phases, improvements in light barrier properties and good WVTR performance. The tensile strength and elongation at break were slightly increased. For pH responsive properties, the monitoring films showed a high response with NH3 gas detection with the change in color from a yellow tone to a red tone. These results indicated that the monitoring films have potential to be applied as food packaging for meat, fish, pork, chicken, and other foods that generate ammonium gas during spoilage. Therefore, these high stable, and non-toxic biodegradable PVA films that incorporated with SP extract and crosslinked by CA have the potential to be used for food spoilage detection in packaging.

Lip cream is a semi-solid lipstick preparation. One of the important ingredients in lipcream preparations is a variety of colorants. Secang wood contains the active compound brazilin which gives it a yellow to purple color which can be used as a natural dye. The conventional lip cream preparations from extracts have low homogeneity and unstable, so it is necessary to increase the stability of the preparation by making a nanoemulsion of secang wood extract which is incorporated into the lip cream preparation. The preparation of 10% secang wood extract nanoemulsion preparation using Tween 80, Virgin Coconut Oil (VCO), and PEG 400 with particle size reduction using a bath sonicator. The concentration of the nanoemulsion preparation was 1% (F3) and 3% (F4) incorporated into the lip cream base and conventional lip cream preparations with the same concentration (F1 and F2). The test results for the size of the 10% secang wood extract nanoemulsion globules were 127.54 ± 0.45 nm (PI: 0.3 ± 0.013). The test results for the F3 and F4 nanoemulsion lipcream preparations had a pink to purple color, pH 6-6.4, spreadability of 5.9-6.8 cm, adhesion of 5.5-6 seconds, the preparation was homogeneous and non-irritating, compared with conventional lip cream preparations F1 and F2 are not homogeneous, the color of the lip cream is paler, and the irritating properties are very mild in both formulas. The conclusion of this research is that secang wood extract can be formulated into a nanoemulsion preparation and incorporated into a lip cream preparation. [ABSTRACT FROM AUTHOR]

Brazilin possesses anticancer effects, but the mechanisms are poorly understood. This study investigated the mechanisms of brazilin‐induced cell death in the T24 human bladder cancer cell line. Low serum cell culture and the lactate dehydrogenase assay were used to confirm the antitumor effect of brazilin. Annexin V and propidium iodide double staining, transmission electron microscopy, fluo‐3‐AM assay for Ca2+ mobilization and caspase activity assay were performed to identify the type of cell death after brazilin treatment. Mitochondria membrane potentials were measured using JC‐1. Quantitative real‐time polymerase chain reaction and western blot analyses were performed to verify the expression of the necroptosis‐related genes and proteins receptor interacting protein 1 (RIP1), RIP3 and mixed lineage kinase domain‐like (MLKL). The results showed that brazilin induced necrosis in T24 cells and upregulated the mRNA and protein levels of RIP1, RIP3 and MLKL and Ca2+ influx. The necroptosis‐mediated cell death was rescued by the necroptosis inhibitor necrostatin‐1 (Nec‐1), but not by the apoptosis inhibitor z‐VAD‐fmk. Brazilin repressed caspase 8 expression and decreased the mitochondrial membrane potentials; both effects were partially reversed by Nec‐1. Brazilin induced physiological and morphological changes in T24 cells and RIP1/RIP3/MLKL‐mediated necroptosis might be involved. In conclusion, the results confirm the involvement of necroptosis in brazilin‐induced cell death and suggest that brazilin could be explored as an anticancer agent against bladder cancer. [ABSTRACT FROM AUTHOR]

• Brazilin is a promising natural red dye, isolated from Caesalpinia sappan. • It exhibited anti-inflammatory, antioxidant, anti-depressant, and anxiolytic. • Anti-diabetic, anticancer, antibacterial, and vasorelaxant are reported. • It is an effective drug candidate for management of different disorders. Brazilin is a promising natural red dye, extracted from the wood of Caesalpinia sappan L. It exhibits several pharmacological activities including anti-inflammatory, antioxidant, anti-depressant and anxiolytic, anti-diabetic, anticancer, antibacterial, and vasorelaxant. Moreover, bioavailability studies demonstrated that brazilin is quickly absorbed into the bloodstream. The data were collected from several databases as ScienceDirect, Web of Science, Pubmed and Proquest. This review is designed to conduct an in-depth search on its pharmacological activities, as well as the underlying cell signaling pathways and mechanism of actions. In addition, we have addressed the bioavailability and structural analysis of brazilin and its close derivatives, safety and quality profiles, and toxicological status. Brazilin with its safety characteristics and acceptable bioavailability, has the potential to touch numerous natural grids, thus, it is possible that this medicinally effective molecule will assist as a promising principal for the development of drug in management of different disorders. [ABSTRACT FROM AUTHOR]

After accelerated solvent extraction using ethanol-water solvent (at a weight ratio of 3 to 1) at extraction temperatures of 60°C, 120°C, and 180°C for 5 min under 1500 psi extraction pressure, the brazilin content in the extracts was determined and also the obtained sappan heartwood extracts (SHE) were used to inhibit some pathogenic bacteria in food, including B. cereus, E. coli, S. aureus, and S. Typhimurium, using agar disc diffusion method. According to the findings of this study, the average yield of SHE using ethanol-water solvent at different extraction temperatures of 60°C, 120°C, and 180°C was 9.16, 13.64 and 16.81%, respectively, providing that the brazilin compound was found in the extracts to be approximately 3.36, 2.69 and 2.68%, respectively. SHE samples were found to be antibacterial against all bacteria tested. These extracts' minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) at 37°C for E. coli were 3.91 and 5.64-6.51 mg/ml, respectively; S. aureus, 3.69-3.91 and 3.69-3.91 mg/ml, respectively; B. cereus, 0.15-0.16 and 0.20 mg/ml, respectively, and S. Typhimurium, 0.96 and 1.31-1.96 mg/ml, respectively. SHE obtained at 120°C extraction temperature were suitable and selected for addition into beetroot juice stored at 4°C for 7 days and 37°C for 24 hr, with the lowest SHE concentrations found to completely and simultaneously kill B. cereus, E. coli, S. aureus, and S. Typhimurium in beetroot juice being 11.73 and 3.91 mg/ml, respectively. [ABSTRACT FROM AUTHOR]

Background: Ultraviolet (UV) radiation is a well‐known factor that causes skin aging. Recently, with the development of technology, the skin has been exposed to not only the UV radiation but also the blue light from electronic devices. Blue light is a high‐energy visible light that penetrates deep into the dermal layer, producing reactive oxygen species (ROS) and resulting in skin aging. In this study, we searched for candidate materials that can inhibit blue light–induced skin aging and found Caesalpinia sappan extract (CSE) to be effective. Methods: Human dermal fibroblasts (HDFs) were treated with various concentrations of CSE and brazilin and exposed to blue light. We measured that antioxidant activity, MMP‐1 levels using MMP‐1 ELISA, changes in collagen type 1, collagen type 3, MMP‐1, and MMP‐3 mRNA expressions, and ROS generation. Results: We confirmed that CSE has high absorption of blue light and antioxidant activity. Blue light irradiation at 30 J/cm2 decreased the expression of collagen types 1 and 3, increased the expression of matrix metalloproteinase (MMP)‐1 and 3, and decreased the production of ROS in human dermal fibroblasts as compared to those of the nonirradiated group. However, pretreatment with CSE protected against the damage caused by the blue light. Brazilin, a major constituent of C. sappan, had high absorbance in the blue light region and antioxidant activities. Pretreatment with brazilin also inhibited the damage caused by the blue light in the cells. Conclusion: CSE and brazilin are potential agents for inhibiting skin aging caused by blue light–induced damage. [ABSTRACT FROM AUTHOR]

Background: Iron overload and inflammation are severe conditions that can lead to various chronic diseases. However, the current iron chelator drugs have their limitations. The phytochemical compounds from herbals, such as brazilin, the major active compound in Caesalpinia sappan Linn., have significant therapeutic potential in various chronic diseases. Our study was designed to examine the effect of brazilin on iron chelating properties, antioxidant activity in hepatocytes, and anti-inflammatory potential in macrophages., Methods: This study focused on the isolation, purification, and evaluation of brazilin, the principal bioactive constituent found in C. sappan wood. Brazilin was extracted via methanol maceration followed by column chromatography purification. The purified compound was characterized using high-performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR) spectroscopy, and mass spectrometry (MS). The antioxidant potential of brazilin was assessed by in vitro assays, including 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azinobis-(3-ethylbenzthiazolin-6-sulfonic acid (ABTS), and ferric-reducing antioxidant power (FRAP). Furthermore, its cellular antioxidant activity was evaluated using hydrogen peroxide-induced oxidative stress in the hepatocellular carcinoma cell line (Huh-7). The iron-chelating capacity of brazilin was determined spectrophotometrically, and Job's plot method was used to elucidated the stoichiometry of the iron-brazilin complex formation. The anti-inflammatory properties of brazilin were investigated in lipopolysaccharide (LPS)-stimulated macrophages (RAW 264.7). Nitric oxide (NO) inhibition was quantified using the Griess reagent, while the expression levels of pro-inflammatory cytokines, interleukin-6 ( IL-6 ) and tumor necrosis factor-alpha ( TNF-α ), were evaluated by RT-qPCR., Results: The results demonstrated that brazilin exhibited potent antioxidant activity in vitro and hepatocytes in a concentration-dependent manner. It also showed anti-inflammatory activity, in which NO production was significantly reduced and IL-6 and TNF-α expression in LPS-induced macrophages were repressed. Furthermore, it can bind ferric and ferrous ions. Brazilin acts as a bidentate iron chelator that forms a complex with iron in a 2:1 ratio, and two water molecules are used as additional chelators in this complex., Conclusions: Our findings have significant implications. Brazilin can potentially alleviate the harmful effects of iron-induced oxidative stress and inflammatory disorders., Competing Interests: 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 manuscript., (© 2024 The Authors.)

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. Sappanwood-derived polyphenolic antidote (brazilin) achieved detoxification of PSMα3 toxins via inhibition/reversion of amyloidal fibrillation, and thus alleviated their cytotoxicity and accelerated the infectious wound healing. [Display omitted] • This study provides a new antidote aiming at neutralizing PSMα3 toxins, termed brazilin. • This work confirms the feasibility of the assembly-regulation strategy in development of antidotes against fibrillation-dependent toxins. • This work emphasizes the importance of plant-derived natural polyphenolic compounds in the research and development of antidotes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Caesalpinia sappan L. heartwood was collected from Mae Chaem District, Chiang Mai Province, Thailand. Crude extracts were prepared by Soxhlet's extraction using 50, 60, and 70% of ethanol (EtOH) at 50, 60, and 70 °C, and the brazilin content was measured using reversed-phase high performance liquid chromatography (RP-HPLC). The antibacterial activity against foodborne pathogens and anti-inflammatory aspects were investigated. C. sappan, prepared from 70% EtOH at 70 °C (E70T70), significantly (p < 0.05) exhibited the highest amount of brazilin (7.90 ± 0.50% w/w). All extracts were investigated for anti-inflammatory activity through an inhibition effect on nitric oxide (NO) and inducible nitric oxide synthase (iNOS) production in RAW264.7 mouse macrophage cells. The inhibitory effect on cyclooxygenase-2 (COX-2) production in HT-29 and HCT116 was also studied. All the extracts inhibited NO, iNOS, and COX-2 production induced by combined lipopolysaccharide and interferon-γ, especially E70T70, indicating the highest inhibition effect among other extracts. Additionally, E70T70 was selected to determine the antibacterial activity against foodborne pathogens, including Staphylococcus aureus, Escherichia coli, Salmonella enteritidis, and Vibrio parahaemolyticus. The result showed that 200 µg/mL extract reduced all test pathogens 100% at 24 h. These results suggested the potential of using C. sappan L. extract as a natural preservative in food and a natural active pharmaceutical ingredient. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Brazilin, structurally composed of a chroman skeleton cis-fused with a 2,3-dihydro-1H-indene unit, is an important active component of the famous traditional Chinese medicine, Caesalpinia sappan L., which belongs to homoisoflavonoid natural products. Brazilin possesses a series of outstanding bioactivities, such as antitumor, anti-inflammatory, hypoglycemic, antibacterial, hepatoprotective activities, which attracts the great interest of synthetic chemists and medicinal chemists. In almost all of the recently published approaches to brazilin, dihydroxylation using highly toxic osmium reagents was employed to construct chiral hydroxyl at C-3 position. Herein, we described a total synthesis of (+)-brazilin from 3,4-dimethoxybenzyl alcohol via overall nine steps, including oxidation using air to prepare hydroxyl at C-3 position, a lipase-catalyzed desymmetrization to establish chiral hydroxyl at the C-3 position, and a trifluoroacetic acid-catalyzed one-pot intramolecular tandem Prins/Friedel-Crafts reaction to construct the cis-fused chromane and indane framework. [ABSTRACT FROM AUTHOR]

The mTOR pathway is a crucial biological regulatory mechanism of cell growth, proliferation and cell death, and its inhibitors were new candidates of anticancer drugs through regulation of energy balance and metabolism. In the present study, whether brazilin and mTOR inhibitor (Torin1) exerts anti-cancer effects was evaluated and the mechanism of its regulation in colorectal cancer cells investigated. Brazilin showed dose- and time-dependent cytotoxicity of colorectal cancer cells (SW480 cells) through apoptosis pathways such as Bcl-2, Bax, as well as cleavage of caspase 3, caspase 9, and PARP1. In addition, brazilin reduced mammalian target of rapamycin (mTOR) phosphorylation in a dose- and time-dependent manner, and the mTOR inhibitor torin 1 blocked this phosphorylation. Brazilin also decreased heme oxygenase-1 (HO-1) expression in a dose- and time-dependent manner; however, hemin, a specific HO-1 substrate, markedly increased HO-1 expression. Torin 1 reduced hemin-induced HO-1 expression and increased colorectal cell death in a dose-dependent manner in the presence and absence of hemin. Moreover, nuclear factor erythroid 2–related factor 2 (Nrf2) translocation into nucleus fraction was crucial role in brazilin-mediated apoptosis of colorectal cancer cells. These results showed that brazilin and torin1 might regulate the mTOR signaling pathway by decreasing mTOR phosphorylation. Furthermore, mTOR signaling was associated with brazilin-regulated HO-1 expression, which induced apoptosis in colorectal cancer cells. These results suggest that synthetic and/or natural mTOR inhibitors were useful candidate for treatment of colorectal cancer cells.

Caesalpinia sappan L. is a medicinal plant generally used to promote blood circulation and as an anti-thirst remedy. Fifteen samples were collected from different locations in Thailand. The aim was to identify parameters including the anatomical and histological characters as well as the thin layer chromatography (TLC) fingerprint. The quality parameter results of total ash, acid insoluble ash, ethanol and water soluble extractive values, loss on drying, and water content were 0.87±0.14, 0.44±0.14, 2.94±0.57, 3.77±0.64, 8.50±0.37, and 8.52±0.43% by weight, respectively. TLC-densitometry and TLC-image analysis were performed to detect brazilin using silica gel 60 GF254 as the stationary phase and chloroform, ethyl acetate, and formic acid (10:8:2) as the mobile phase. The results of brazilin from the TLC-densitometry and TLC-image analysis were 1.259±0.285 g/100 g and 1.256±0.266 g/100 g of dried heartwood, respectively. The result showed that both techniques were not statistically significantly different.

Indonesia is a country with fertile soil and rich in plant species. Currently in society the use of medicinal plants as herbal treatment has increased. Elderly people often experience Rheumatoid Arthritis, which is inflammation of the synovial lining of the joints. One of the plants used by the community is red betel leaf (Piper crocatum). However, scientific information related to the potential of red betel as an anti-inflammatory in Rheumatoid Arthritis is still not widely known by the public. This study was conducted to explore the potential of P. crocatum leaves to treat Rheumatoid Arthritis which can be used as references regarding Rheumatoid Arthritis therapy. This study uses a narrative review method from previous studies that were collected related to the topic which was then discussed systematically. By using keywords in the search for Piper crocatum, anti-inflammatory activity, red betel bioactivity, secondary compounds in red betel leaf, and Rheumatoid Arthritis. P. crocatum leaves contain various bioactive compounds. Flavonoids have activity as primary and secondary antioxidants. Flavonoid compounds such as brazilien, brazilin, taxifolin, procyanidin found in red betel have anti-inflammatory activity in rheumatoid arthritis. Brazilin is one of the flavonoid compounds from P. crocatum leaves that has the potential as an anti-inflammatory in rheumatoid arthritis by regulating the transcription factor nuclear factor kappa B (NF-kB) for TNF- expression against inflammation.

Brazilin, a constituent of the Chinese medicine heartwood, exhibits pronounced anti-tumor effects. To date, brazilin quantification mostly relies on high-performance liquid chromatography (HPLC), which is not accurate enough because of an easily oxidizable structure. Herein, a thin-layer chromatography (TLC)-based method was developed for the quantitative analysis of brazilin. A water solution of purified brazilin was spotted on a GF254 silica gel plate and developed using a mixture of chloroform‒acetone‒formic acid (8:4:1, V/V). After ammonia vaporing, AlCl3 solution (90 mg/mL) was sprayed to form a stable compound. Detection was performed at 508 nm using a dual-beam TLC scanner, and brazilin was quantitatively analyzed by using an external standard. The optimal time for ammonia vaporing was 6 min. Sample stability remained for 10‒200 min. At 508 nm, brazilin absorbance showed a good linear relationship in the range of 0‒6 μg (R2 = 0.9962). Precision RSD was no more than 3.40%, and recovery was between 100 and 105%. This novel TLC-based method has great potential for the quantitative assessment of brazilin. It is simpler, more reliable, and faster than HPLC-based analysis. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases are the leading cause of death worldwide. The long-term aim of cardiovascular disease therapy is to reduce the mortality rate and decelerate the progression of cardiovascular organ damage. Current therapies focus on recovering heart function and reducing risk factors such as hyperglycemia and dyslipidemia. However, oxidative stress and inflammation are important causes of further damage to cardiovascular organs. Caesalpinia sappan Linn. (Fabaceae), a flowering tree native to tropical Asia, has antioxidant and anti-inflammatory properties. It is used as a natural dye to color food and beverages and as a traditional treatment for diarrhea, diabetes, and blood stasis. The phytochemical compounds in C. sappan , mainly the homoisoflavonoids brazilin, sappanone A, protosappanin, and hematoxylin, can potentially be used to protect cardiovascular organs. This review aims to provide updates on recent developments in research on C. sappan in relation to treatment of cardiovascular diseases. Many studies have reported protective effects of the plant's bioactive compounds that reduce cardiac damage and enhance vasorelaxation. For example, brazilin and sappanone A have an impact on molecular and cellular changes in cardiovascular disease pathogenesis, mainly by modulating oxidative, inflammatory, and apoptotic signaling pathways. Therefore, bioactive compounds of C. sappan have the potential to be developed as therapeutic agents to combat cardiovascular diseases like myocardial infarction and vascular disease. This review could help further the understanding of the possible modulatory role of the compounds in cardiovascular diseases, thereby facilitating future studies. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases are the leading cause of death worldwide. The long-term aim of cardiovascular disease therapy is to reduce the mortality rate and decelerate the progression of cardiovascular organ damage. Current therapies focus on recovering heart function and reducing risk factors such as hyperglycemia and dyslipidemia. However, oxidative stress and inflammation are important causes of further damage to cardiovascular organs. Caesalpinia sappan Linn. (Fabaceae), a flowering tree native to tropical Asia, has antioxidant and anti-inflammatory properties. It is used as a natural dye to color food and beverages and as a traditional treatment for diarrhea, diabetes, and blood stasis. The phytochemical compounds in C. sappan, mainly the homoisoflavonoids brazilin, sappanone A, protosappanin, and hematoxylin, can potentially be used to protect cardiovascular organs. This review aims to provide updates on recent developments in research on C. sappan in relation to treatment of cardiovascular diseases. Many studies have reported protective effects of the plant’s bioactive compounds that reduce cardiac damage and enhance vasorelaxation. For example, brazilin and sappanone A have an impact on molecular and cellular changes in cardiovascular disease pathogenesis, mainly by modulating oxidative, inflammatory, and apoptotic signaling pathways. Therefore, bioactive compounds of C. sappan have the potential to be developed as therapeutic agents to combat cardiovascular diseases like myocardial infarction and vascular disease. This review could help further the understanding of the possible modulatory role of the compounds in cardiovascular diseases, thereby facilitating future studies.

Memory is an essential aspect of human cognition. A decrease in this aspect is well associated with Alzheimer's disease (AD). The development of a novel cognitive enhancer (CE) may help overcome AD-related problems. In this study, we evaluated the CE effect of Caesalpinia sappan L. (CS) in memory deficit mice. Administration of its ethanolic extract (250 and 500 mg/kg body weight (BW)) and brazilin (5 and 10 mg/kg BW) ameliorated the scopolamine-amnesic effect, as evidenced by significant decreases (p < 0.01, p < 0.05) in the escape latency time and increases (p < 0.01) in the percentage of time spent in the target quadrant of the Morris water maze test. We also examined the cyclic adenosine monophosphate (cAMP) level, protein kinase A (PKA) activity, and protein expression levels of phosphorylated cAMP response element binding (pCREB) and brainderived neurotrophic factor (BDNF) in hippocampal tissues to elucidate the underlying molecular mechanism. Results showed that CS wood ethanolic extract and brazilin not only significantly increase (p < 0.01, p < 0.05) cAMP levels and PKA activity but also significantly enhance (p < 0.01, p < 0.05) the expression level of pCREB and BDNF in the hippocampus. These findings indicate that CS activates the cAMP/PKA/CREB/BDNF pathway. Taken together, our results demonstrate that CS is a promising herb that could be developed as a CE agent. [ABSTRACT FROM AUTHOR]

Dye-sensitized solar cells (DSSCs) are promising third-generation photovoltaic cell technology owing to their easy fabrication, flexibility and better performance under diffuse light conditions. Natural pigment sensitizers are abundantly available and environmentally friendliness. However, narrow absorption spectra of natural pigments result in low efficiencies of the DSSCs. Therefore, combining two or more pigments with complementary absorption spectra is considered an appropriate method to broaden the absorption band and boost efficiency. This study reports three complex molecules: brazilin-betanidin-oxane (Braz-Bd-oxane), brazilin-betanidin-ether (Braz-Bd-ether) and brazilein-betanidin-ether (Braze-Bd-ether), obtained from the etherification and bi-etherification reactions of brazilin dye and brazilein dye with betanidin dye. The equilibrium geometrical structure properties, frontier molecular orbital, electrostatic surface potential, reorganization energy, chemical reactivities, and non-linear optical properties of the studied dyes were investigated using density functional theory (DFT)/B3LYP methods, with 6-31+G(d,p) basis sets and LANL2DZ for light atom and heavy atoms respectively. The optical-electronic properties were calculated using TD-DFT/B3LYP/6-31+G(d,p) for isolated dye and TD-DFT/CAM-B3LYP/6-31G(d,p)/LANL2DZ for dyes@(TiO 2) 9 H 4. The results reveal that spectra for Braz-Bd-oxane and Braze-Bd-ether complexes red-shifted compared to the individually selected dyes. The simulated absorption spectra of the adsorbed dyes on (TiO 2) 9 H 4 are red-shifted compared to the free dye. Moreover, Braz-Bd-oxane and Braz-Bd-ether exhibit better charge transfer and photovoltaic properties than the selected natural dyes forming these complexes. Based on the dyes' optoelectronic properties and photovoltaic properties, the designed molecules Braz-Bd-oxane and Braze-Bd-ether are considered better candidates to be used as photosensitizers in dye solar cells. [Display omitted] • Designed complex via etherification and bi-etherification of brazilein and brazilin with betanidin dye. • The stability of the dye@cluster and its optical properties were analyzed. • Designed complex dyes were observed to have lower energy gaps with broadened absorption spectra than individual dyes. • The combination of brazilin and brazilein with betanidin enhances the optoelectronic and photovoltaic properties of the dye. • The Braz-Bd-ether and Braz-Bd-oxane are anlyzed as best candidates to be used as a photosensitizer in DSSCs. [ABSTRACT FROM AUTHOR]

Caesalpinia sappan L. heartwood was collected from Mae Chaem District, Chiang Mai Province, Thailand. Crude extracts were prepared by Soxhlet’s extraction using 50, 60, and 70% of ethanol (EtOH) at 50, 60, and 70 °C, and the brazilin content was measured using reversed-phase high performance liquid chromatography (RP-HPLC). The antibacterial activity against foodborne pathogens and anti-inflammatory aspects were investigated. C. sappan, prepared from 70% EtOH at 70 °C (E70T70), significantly (p < 0.05) exhibited the highest amount of brazilin (7.90 ± 0.50% w/w). All extracts were investigated for anti-inflammatory activity through an inhibition effect on nitric oxide (NO) and inducible nitric oxide synthase (iNOS) production in RAW264.7 mouse macrophage cells. The inhibitory effect on cyclooxygenase-2 (COX-2) production in HT-29 and HCT116 was also studied. All the extracts inhibited NO, iNOS, and COX-2 production induced by combined lipopolysaccharide and interferon-γ, especially E70T70, indicating the highest inhibition effect among other extracts. Additionally, E70T70 was selected to determine the antibacterial activity against foodborne pathogens, including Staphylococcus aureus, Escherichia coli, Salmonella enteritidis, and Vibrio parahaemolyticus. The result showed that 200 µg/mL extract reduced all test pathogens 100% at 24 h. These results suggested the potential of using C. sappan L. extract as a natural preservative in food and a natural active pharmaceutical ingredient.

Increased reactive oxygen species and advanced glycation end products are often associated with human ageing and degenerative diseases. Biancaea sappan L serves as a medicinal plant and a healthy drinks ingredient in Java. However, the pharmacological investigation of the plant native to this island is still lacking in depth. In the current study, DNA barcoding using the marker gene maturase K ( matK ), evaluation of the chemical composition, total phenolic content (TPC) and antioxidant properties, antiglycation, anti-β-amyloid, anti-inflammatory, and selective cytotoxic activities were performed . B. sappan shares well-known phytoconstituents with other members of the genus Biancaea . The heartwood ethanol extract possesses the most prominent antioxidant, anti-inflammatory, and anti-β-amyloid effects. The aqueous extract demonstrated a most substantial anti-glycation activity and was rich in phenolics. The ethanol extract from heartwood exhibited the highest cytotoxicity against SW-48, indicating B. sappan heartwood from Java holds promise as antioxidants and may selectively inhibit colorectal cancer.

Purpose: Breast cancer cells with overexpression of HER2 are known to be more aggressive, invasive, and resistant to chemotherapeutic agent. Brazilin, the major compound in the Caesalpinia sappan L. (CS) heartwood, has been studied for it's anticancer activity. The purpose of this study was to investigate the cytotoxic and antimigratory activity of brazilin (Bi) in combination with doxorubicin (Dox) on MCF-7/HER2 cells. Methods: Cytotoxic activities of Bi individually and in combination with Dox were examined by MTT assay. Synergistic effects were analyzed by combination index (CI). Apoptosis and cell cycle profiles were observed by using flow cytometry. Migrating and invading cells were observed by using a Boyden chamber assay. Levels of MMP2 and MMP9 activity were observed by using a gelatin zymography assay. Levels of HER2, Bcl-2, Rac1, and p120 protein expression were observed by using an immunoblotting assay. Results: The results of the MTT assay showed that Bi inhibited MCF-7/HER2 cell growth in a dose-dependent manner with an IC50 of 54 ± 3.7 µM. Furthermore, the combination of Bi and Dox showed a synergistic effect (CI

Introduction: A decrease in cAMP and cGMP levels in the brain is linked to human cognitive problems. The degradation of cellular cAMP and cGMP is attributed to phosphodiesterases (PDEs), which constitute a superfamily of enzymes. The inhibition of PDE1 is a promising mechanism to increase cAMP and cGMP levels associated with cognitive disorders. Caesalpinia sappan L. (CS) wood is a natural coloring agent usually consumed as a traditional refreshment or drink by people in Yogyakarta, Indonesia. However, scientific evidence regarding the inhibitory activity of CS wood against PDE1 has yet to be obtained. This study aimed to investigate the potency of CS wood as a PDE1 inhibitor. Methods: The ethanol extract of CS wood and its fractions were evaluated in vitro by using a cyclic nucleotide phosphodiesterase assay kit. The presence of brazilin in the extract and fractions was analyzed by thin-layer chromatography. In silico assay was performed using MOE software to obtain insights into the interaction between compounds in the CS wood and the enzyme. Results: Ethanol extract and ethyl acetate soluble fraction effectively inhibited the PDE1 activity. Interestingly, brazilin, the major compound in CS wood, also exhibited a potent inhibitory effect on the enzyme. The in silico assay revealed that the interaction between tetraacetylbrazilin and brazilin with the PDE1B active site involved hydrogen bonding and p-p interactions. Conclusion: Ethanol extract, ethyl acetate soluble fraction, and brazilin inhibited the PDE1 activity. CS wood and its chemical constituent could be developed as natural cognitive enhancers. [ABSTRACT FROM AUTHOR]

Some natural deep eutectic solvents (NADES) can replace organic solvents that are toxic and harmful to the environment. The main flavonoid in sappan wood (Caesalpinia sappan L.) is brazilin. The aims of this study were to extract brazilin from sappan wood by using NADES and to evaluate the effect of the extract on inhibition of dipeptidyl peptidase IV (DPP IV) activity. The selected NADES compositions used choline chloride and betaine as hydrogen bond acceptors (HBA) with glycerol, xylitol, sorbitol, lactic acid, malic acid, and citric acid as various hydrogen bond donors (HBD). Ultrasound-assisted NADES extraction of brazilin was performed, and the content was measured by highperformance liquid chromatography (HPLC). Between selected NADES, betain-lactic acid gave the highest brazilin content of 4.49 mg/g. This result was comparable to conventional methods by a reflux using 96% ethanol that gave brazilin content of 5.43 mg/g. However, the reflux required 3 hours for three extraction cycle, while optimal extraction conditions by betain-lactic acid were 30 min. The sappan wood extract using choline chloride-lactic acid had a percent inhibition of 5.72% (2.03 ppm), and that using betaine-lactic acid had a percent inhibition of 7.74% (2.08 ppm) for DPP IV activity. These inhibitory activities were comparable to the brazilin standard which was 8.93% (2.2 ppm). Our results showed that two NADES compositions could extract brazilin from sappan wood and it showed potential DPP IV inhibitory activity. [ABSTRACT FROM AUTHOR]

Ethanolic extract and brazilein-containing fraction of Caesalpinia sappan L., has been reported to inhibit cell proliferation on T47D (estrogen receptor positive, luminal A subtype model). The luminal A subtype is the most prevalent subtype of breast cancer in Indonesian females. In this study, we explored the activity of the reduced form of brazilein, brazilin, on T47D cells proliferation and the mechanism that involved. The cytotoxicity activity of brazilin was observed using the MTT assay. The cell cycle profile was analyzed by using flow cytometry, and the cells senescent was observed using S-A-ß-galactosidase assay. The results showed that brazilin was cytotoxic to T47D with an IC50 value of 50µM (14.3µg/mL). Cell cycle profile showed that after treated with brazilin, the cells were accumulated at the G2/M phase. Furthermore, cells treated with a combination of brazilin and doxorubicin were accumulated at the G2/M and sub G1 phase. Cells accumulation at sub G1 phase indicates that the cells underwent apoptosis. Our data of S-A-ß- galactosidase assay showed that cells treated with ?IC50, ½IC50, and IC50 brazilin had lower senescent cells than the untreated cells. The morphology of cells treated with IC50 (50µM) brazilin was changed. The cells shape became rounded, cells were shrink and detached from the well plate, indicating that cells may undergo apoptosis. These results suggested that brazilin cytotoxic towards T47D cells, decreased cell senescence, and may induce apoptosis. Therefore, we believe that brazilin is potential to be further examined for its mechanism of action in inhibiting the proliferation of T47D cells. [ABSTRACT FROM AUTHOR]

Background: Urinary bladder carcinoma is characterized by high post-operative recurrence rates. Sufu'ning lotion, prepared with Lignum Sappan, can reduce the recurrence of urinary bladder carcinoma. Objectives: The present study describes a methodology for extracting and obtaining high purity brazilin from Lignum sappan and evaluates its effects on urinary bladder carcinoma, in vitro and in vivo. Materials and Methods: The brazilin was extracted from Lignum sappan, purified and identified. The purified brazilin was assessed in vitro for its effects on tumor cell viability and growth using human (T24) and mouse urinary bladder (BTT) cancer cell lines. The role of brazilin in the inhibition of the cell cycle was determined by flow cytometry. The in vivo activity of brazilin was assessed based on the survival of tumor-bearing mice. Results: Brazilin was purified of 99.10% purity and was bioactive as it significantly (P < 0.05) inhibited the growth of T24 and BTT cells. The IC50was 10.08 μg/ml for T24 cells and 8.76 μg/ml for BTT cells after 48 h of treatment. Brazilin blocked the cell cycle progression in the G2 phase. Brazilin (100, 200 and 300 mg/kg) significantly (P < 0.05) increased the survival of BTT tumor-bearing T739 mice and T24 tumor-bearing BALB/c nude mice. Conclusion: The methodology described for the extraction of brazilin from Lignum sappan yields high purity and bioactive brazilin. The extracted brazilin exerts marked inhibitory effects on urinary bladder cancer cells in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Dye from Sappang Tree has been isolated using ethanol as a solvent. Braziline is one of the chemical compound found in the ethanol extract. The Compound can be used as anion calorimethric due to their active sites of hydroxyl and chromophore groups. Dyes from sappang tree has been tested on 10 g of several types of saturated anions (carbonate, sulfate, phosphate, cyanide, acetate, borax, nitrite, chloride, bromide, and iodide). The results of the tests show that the color of the dye from changes in carbonate, phosphate, cyanide, acetate, nitrite, and hydroxyl. Spectrophotometer UV/Vis is used to detect the limit of cyanide anion. Metanol and acetone show positive results on the dye in cyanide anion. Detection limit of braziline is 3x10-4 M. By addition of cyanide anion, the dye has detection limit at 1x10-4 M.

Introduction: Prostate cancer, primarily originating from the prostate gland, manifests as prostate adenocarcinoma. Characterized by symptoms related to urination difficulties, this form of cancer is commonly diagnosed in individuals aged 65 and above. Prostate cancer also tends to progress slowly. Current research highlights the anticancer potential of natural compounds and their secondary metabolites in inhibiting the proliferation of various cancer cell types. One such compound that merits further exploration for its anticancer potential is brazilin. Brazilin is an isoflavonoid obtained from the Caesalpinia sappan heartwood. Methods: Acute toxicity of brazilin was assessed using the fix dose procedure method. In vitro cytotoxicity was performed on prostate cancer cell line using the WST-8 method. Syngeneic cancer animal model was used to study in vivo anticancer activity. Histopathological analyses of liver and kidneys were performed through the hematoxylin-eosin staining method. Results: The results confirmed the absence of heavy metal contamination (Cd, Cu, Pb, As, and Hg) in brazilin. The total plate count and mold/yeast count on brazilin adhered to established requirements, with values = 10 and = 103, respectively. Brazilin exhibited a favourable lethal dose 50 (LD50) above 5,000 mg/kg bodyweight, categorizing it as practically non-toxic. The IC50 value of brazilin against DU prostate cancer cell line was determined to be 145 ± 17.25 mg/L. Histopathological examinations revealed no observable changes in the kidneys and liver. No metastatic developments were observed. In vivo studies demonstrated brazilin's prostate tumour inhibitory activity in C57BL/6 mice. Conclusion: Based on present data, brazilin demonstrated potential as a promising candidate for an anticancer drug. However, further research is required to unveil a comprehensive profile of its anticancer activity and underlying mechanisms. [ABSTRACT FROM AUTHOR]

Abstract The conditions of heating, ionic liquid-based ultrasonic-assisted extraction combined with reverse-phase high performance liquid chromatography were optimized to simultaneously isolate and determinate brazilin and protosappanin B in Caesalpinia sappan. Ionic liquids, including [BMIM]Br, [BMIM]BF4, [BMIM]PF6 and [HMIM]PF6, were selected as extraction solvents while methanol, acetone, acetonitrile, ethanol and water were selected as dispersants. The chromatographic column was Purospher star RP-C18 (250 mm × 4.6 mm, 5 μm), a mixture of methanol and 0.2% phosphoric acid–water was used as mobile phase at a flow rate 0.65 mL/min. The result displayed that the extraction yields of brazilin and protosappanin B were highest when the concentration of [BMIM]Br methanol solution as extraction solvent was 0.5 mol/L and the solid–liquid ratio was 1:50 (g/mL). Under the optimal extraction conditions, the contents of brazilin showed a good linearity (r = 1.0000) within the range of 1.25–7.50 μg with the average recovery of 99.33%, the contents of protosappanin B also showed a good linearity (r = 0.9999) within the range of 0.50–3.00 μg with the average recovery of 98.31%. This experiment, which adopted environmentally friendly reagent as extraction solvent, not only improved the extraction efficiency, but also avoided the environmental pollution caused by organic solvent. Moreover, it was simple and reliable, and can be of important significance in the study of Traditional Chinese Medicine active ingredient extraction methods. The antibacterial activities of the ionic liquids and methanol extracts were determined using the paper disc diffusion method. The ionic liquid extract was found to possess antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureus (MIC value of 37.5 mg crude drug/mL), β-Lactamase producing S. aureus (MIC values of 18.8 mg crude drug/mL), but not against E. coli, Extended spectrum β-Lactamases E. coli and P. aeruginosa. Compared with the ionic liquid extract, the methanol extract was found to have antibacterial activity against S. aureus and methicillin-resistant S. aureus (MIC value of 75.0 mg crude drug/mL), β-Lactamase producing S. aureus (MIC values of 150.0 mg crude drug/mL). However, the same, the methanol extract did not have antibacterial activity against E. coli, Extended spectrum β-Lactamases E. coli and P. aeruginosa.

Purpose: The aim of this study is to observe the synergistic effect of two active compounds of secang, brazilin and brazilein, combined with cisplatin on WiDr colon cancer cells. Methods: Cytotoxic activities of brazilin (Bi) and brazilein (Be) in single and in combination with cisplatin (Cisp) were examined by MTT assay. Synergistic effect was analyzed by combination index (CI) parameter. Apoptosis and cell cycle profiles were observed by using flow cytometry. Results: The result of MTT assay showed that IC50 value of brazilin and brazilein on WiDr cancer cells were 41 µM and 52 µM respectively. The combination of ½ IC50 of Bi-Cisp reduced cells viability up to 64% and showed synergistic effect with CI value less than 1 (CI = 0.8). The combinations of ½ IC50 of Be-Cisp also reduced cells viability up to 78% and showed synergistic effect (CI=0.65). Combination of Bi-Cisp and Be-Cisp induced apoptosis higher than the single treatments. Further analysis on the cell cycle progression showed that single treatment of ½ IC50 of Be and Bi induced S-phase and G2/M-phase accumulation, while combination of Be-Cisp and Bi-Cisp enhanced S-phase accumulation. Conclusion: Both combination of Bi-Cisp and Be-Cisp showed synergistic effect on WiDr cells through induction of apoptosis and halted the cell cycle progression, thus, WiDr cells growth were significantly reduced.

We have synthesized a series of cis-6a,7,8,12b-tetrahydro-6H-naphtho[2,1-c]chromen-6a-ols as B-ring-modified analogues of (±)-brazilin. A completely regio- and cis-diastereoselective intramolecular Friedel–Crafts epoxy–arene cyclization of 1-tetralone-derived glycidyl ethers catalyzed by Brønsted acids was used as the key step. Our worries concerning the formation of cis–trans product mixtures and their probable conversion to naphthopyran derivatives via dehydration of the tertiary hydroxy group were laid to rest. Additionally, the angular hydroxy group of one of the synthesized products has been reductively removed by a diastereoselective method which should be useful in future for preparing libraries of chroman-fused tetralins with trans-stereochemistry at the ring junction.