Immune response enhancement by dietary supplementation with Caesalpinia sappan extract in weaned pigs challenged with porcine reproductive and respiratory syndrome virus.

BACKGROUND: At present, porcine reproductive and respiratory syndrome (PRRS) caused by the PRRS virus (PRRSV) is one of the most severe epidemics impacting pig farming globally. Despite the fact that a number of studies have been conducted on potential solutions to this problem, none have proven effective. The focus of problem solving is the use of natural ingredients such as plant extracts. Popular throughout Asia, Caesalpinia sappan (CS) is a therapeutic plant that inhibits PRRSV in vitro. Therefore, this study was performed to determine the efficacy of CS extract dietary supplementation on the productive performance, antibody levels, immunological indicators, and lung pathology of PRRSV-challenged weaned pigs. A total of 32 weaned piglets (28 days old) were randomized into 4 groups and kept separately for 14 days. The treatments were organized in a 2 × 2 factorial design involving two factors: PRRSV challenge and supplementation with 1 mg/kg CS extract. The pigs in the PRRSV-challenged groups were intranasally inoculated with 2 mL of PRRSV (VR2332) containing 104 TCID50/mL, while those in the groups not challenged with PRRSV were inoculated with 2 mL of normal saline. RESULTS: In the PRRSV-challenged group (CS + PRRSV), supplementation with CS extract led to an increase in white blood cells (WBCs) on Day 7 post infection (p < 0.05) and particularly in lymphocytes on Days 7 and 14. The antibody titer was significantly greater in the CS + PRRSV group than in the PRRSV-challenged group not administered CS (PRRSV group) on Day 14 postinfection (S/P = 1.19 vs. 0.78). In addition, CS extract administration decreased the prevalence of pulmonary lesions, which were more prevalent in the PRRSV-challenged pigs that did not receive the CS extract. CONCLUSION: The findings of this study suggest that supplementation with CS extract is beneficial for increasing WBC counts, especially lymphocytes, increasing the levels of antibodies and reducing the prevalence of lung lesions in PRRSV-infected pigs.

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

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

A Comprehensive Review on Bioactive Compounds Found in Caesalpinia sappan.

Sappan wood (Caesalpinia sappan) is a tropical hardwood tree found in Southeast Asia. Sappan wood contains a water-soluble compound, which imparts a red color named brazilin. Sappan wood is utilized to produce dye for fabric and coloring agents for food and beverages, such as wine and meat. As a valuable medicinal plant, the tree is also known for its antioxidant, anti-inflammatory, and anticancer properties. It has been observed that sappan wood contains various bioactive compounds, including brazilin, brazilein, sappan chalcone, and protosappanin A. It has also been discovered that these substances have various health advantages; they lower inflammation, enhance blood circulation, and are anti-oxidative in nature. Sappan wood has been used as a medicine to address a range of illnesses, such as gastrointestinal problems, respiratory infections, and skin conditions. Studies have also suggested that sappan wood may have anticarcinogenic potential as it possesses cytotoxic activity against cancer cells. Based on this, the present review emphasized the different medicinal properties, the role of phytochemicals, their health benefits, and several food and nonfood applications of sappan wood. Overall, sappan wood has demonstrated promising medicinal properties and is an important resource in traditional medicine. The present review has explored the potential role of sappan wood as an essential source of bioactive compounds for drug development.

Safety and efficacy of P2Et extract from Caesalpinia spinosa in breast cancer patients: study protocol for a randomized double blind phase II clinical trial (CS003-BC).

BACKGROUND: Chemotherapy in breast cancer is effective but can generate significant toxicity and lead to tumor resistance. Joint treatment with standardized plant extracts can be an alternative to improve the response and allow an effective activation of the antitumor immune response that favors recovery in the short and long term. The P2Et extract of Caesalpinia spinosa presents antitumor activity in cells and animal models of breast cancer, improves the tumor microenvironment, and induces activation of the specific immune response against the tumor and is synergistic when used together with anthracyclines, which makes it a good candidate for evaluation in patients. METHODS: Conducted at a single center, this phase II study is a randomized, double-blind, placebo-controlled trial aimed at assessing the safety and efficacy of P2Et extract in patients diagnosed with stage II and III breast cancer, who are eligible for neoadjuvant treatment. The study aims to determine the safety profile at the previously established optimal biological dose from phase I trial while investigating various efficacy outcomes. These outcomes include improvements in quality of life, immunomodulation, metabolic profile, microbiome, as well as clinical indicators such as tumor reduction, disease-free survival, and pathological response, assessed at different stages of the treatment regimen. DISCUSSION: Treatment with the P2Et extract in breast cancer patients is hypothesized to enhance overall well-being, positively influencing their quality of life, while also triggering an antitumor immune response and enhancing immune infiltration. These combined effects have the potential to contribute to improved long-term survival outcomes for patients receiving the phytomedicine alongside neoadjuvant chemotherapy treatment. TRIAL REGISTRATION: This trial was registered in the US National Library of Medicine with identifier NCT05007444. First Registered August 16th, 2021. Last Updated: August 9th, 2022.

Biosynthesis of copper oxide nanoparticles using Caesalpinia sappan extract: In vitro evaluation of antifungal and antibiofilm activities against Candida albicans.

Synthesis of nanoparticles using natural organic substances has attracted more attention due to avoiding inorganic toxicity. This work aimed to synthesize copper oxide nanoparticles (CuONPs) using Caesalpinia sappan heartwood extract as a reducing agent. The effects of pH of synthesis reaction were investigated. The obtained CuONPs were characterized using UV-visible spectroscopy, Fourier transform infrared spectroscopy, scanning electron microscopy, and energy dispersive X-ray spectroscopy. Their particle size, size distribution, and zeta potential were determined using photon correlation spectrophotometry. Candida albicans is a major cause of chronic fungal infections due to its biofilms leading to severe drug resistance problems. In this study, in vitro antifungal and antibiofilm activities as well as killing kinetics of the synthesized CuONPs against C. albicans were investigated. Additionally, fungal biofilm was observed by using confocal laser scanning microscopy. The results showed that the pH of the synthesis reaction played an important role in the physicochemical properties and antifungal activities of the obtained CuONPs. CuONPs synthesized at pH 10 and 12 showed the relatively small and narrow size distribution with high negative zeta potential and time-dependent killing kinetics. Confocal laser scanning microscopy confirms obvious fungal biofilm reduction and increased fungal cell death after exposure to CuONPs. These findings suggest the optimal pH of CuONPs synthesis using C. sappan extract as a reducing agent. The results on antifungal and antibiofilm activities indicate that the obtained CuONPs can be a promising agent for treating fungal infection.

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

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

Antioxidant, antiglycation, and anti-inflammatory activities of Caesalpinia mimosoides.

Oxidative stress, glycation and inflammation are the main causes of many severe diseases. To date, no single extract has been shown to simultaneously inhibit these three reactions. In this study, the antioxidant, antiglycation and anti-inflammatory activities of ethanol extracts from four edible plants that are commonly used as Thai folk medicine were compared. Among these extracts, Caesalpinia mimosoides extract (CME) showed the highest antioxidant potential with Trolox equivalent antioxidant activity (TEAC) of 5.9 ± 0.1 mM/mg followed closely by Zingiber officinale extract (ZOE) with a TEAC value of 5.4 ± 0.2 mM/mg. However, CME showed no cytotoxicity, whereas ZOE greater than 60 µg/mL showed cytotoxicity to normal human cells. Antiglycation assay using bovine serum albumin-ribose showed comparable potency between CME and Spondias dulcis extract (SDE). However, CME exhibited a high anti-inflammatory activity, significantly higher than SDE and activity depending on the dose. At a concentration of 60 µg/mL, approximately 85% of the interleukin-6 pro-inflammatory cytokine produced from human monocytes, induced by lipopolysaccharides, was completely inhibited by CME whereas SDE showed no inhibition. In summary, CME is the most potential extract with simultaneously activity of these three reactions. CME has the highest total phenolic content expressed as gallic acid equivalent to 301 ± 8 mg/g. Identification using high-performance liquid chromatography revealed the presence of at least four phenolic compounds, gallic acid, syringic acid, p-coumaric acid, and ellagic acid are existed in CME. Our finding suggests that CME is a promising natural source for inhibition of oxidative stress, glycation, and inflammation.

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

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

Isolation, Characterization, and In Silico Interaction Studies of Bioactive Compounds from Caesalpinia bonducella with Target Proteins Involved in Alzheimer's Disease.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by memory loss, cognitive deterioration, and neuropsychiatric symptoms. Various drug targets implicated in AD are amyloid beta peptides, cholinesterase enzymes, and anti-amylogenic protein. Medicinal plants derived phytochemical constituents provide a vast pool of diverse compounds as a source of novel drugs. In view of this, the Caesalpinia bonducella seed extract and its active phytoconstituents were used to study the disease-modifying effects in Alzheimer's disease. The present study successfully demonstrated the therapeutic potential of various phytochemicals as it binds to multiple drug targets, resulting in inhibition of acetylcholinesterase (AChE) enzyme, butyrylcholinesterase (BuChE), BACE-1 enzyme, and anti-amylogenic protein as indicated by docking analysis. In conclusion, phytochemicals identified can be used as a suitable lead to developing a molecule that might have multi-targeted directed ligand (MTDL) potential and disease amelioration effects in Alzheimer's disease.

Protease inhibitor from Libidibia ferrea seeds attenuates inflammatory and nociceptive responses in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Libidibia ferrea (Mart. ex. Tul.) L.P. Queiroz is a Brazilian native tree locally known as jucá and pau-ferro, and it has been used in folk medicine for relieving, asthma, bronchitis, sore throat, rheumatism, enterocolitis and fever. The anti-inflammatory properties of L. ferrea were confirmed for its stem, fruit, leaves, bark and seeds extracts, however little is known about the natural compounds that may be associated with that response. AIM OF THIS STUDY: In a normal physiological condition, many enzymes play an important role in catalyzing biological functions. Among them, proteases are of great interest. Although they take part of many biological systems, as the inflammatory process, when deregulated, proteases may cause system malfunctions, such as under- or overproduction of cytokines, or immune cells activation. Thus, protease inhibitors prevent these immune responses by regulating proteases. The objective of this study was to evaluate the anti-inflammatory and anti-nociceptive response of a protease inhibitor purified from L. ferrea seeds (LfTI). MATERIALS AND METHODS: In vitro (5, 50 and 250 µg/mL of LfTI) and in vivo (0.6, 3 e 15 mg/kg of LfTI) assays were performed. Male Swiss mice weighing 18-25 g were used for cell harvesting and for the in vivo assays. The anti-inflammatory activity was analyzed in vitro by macrophage cytotoxicity, hydrogen peroxide (H2O2) production, and cell adhesion assays; and in vivo by leukocyte recruitment, nitric oxide (NO) production, vascular permeability, paw edema and mast cell degranulation assays. The anti-nociceptive activity was evaluated through abdominal writhing test induced by acetic acid and formalin sensitization. RESULTS: Our results showed that, in vitro, LfTI is not cytotoxic. Also, LfTI (50 µg/mL) inhibited macrophage H2O2 production (48.2%), and adhesion (48.4%). LfTI (0.6, 3 e 15 mg/kg) decreased polymorphonuclear cell recruitment dose-dependently, and it inhibited NO production (53%), vascular permeability (40.7%) and paw edema at 3 mg/kg at different time, but it did not inhibit mast cell degranulation. Besides, LfTI did not inhibit either the number of writhing or the licking time in the formalin test in the second phase (inflammatory). However, LfTI (3 mg/kg) inhibited licking time at the first phase (neurogenic) in the formalin sensitization (46.1%). CONCLUSIONS: Our results show that LfTI has anti-inflammatory and antinociceptive (neurogenic pain) effects, and these effects might be associated with the inhibition of inflammatory proteases and/or protease-activated receptors activation hindering.

Caesalpinia palmeri: First Report on the Phenolic Compounds Profile, Antioxidant and Cytotoxicity Effect.

This study aimed to determine the phenolic compounds profile, antioxidant potential and cytotoxicity of extracts and fractions of Caesalpinia palmeri. Methanolic extracts were generated from C. palmeri berries, stems and flowers. The latter was subjected to liquid-liquid partition, obtaining hexane, ethyl acetate and residues fractions. Results showed that the flower extract and ethyl acetate fraction had a larger concentration of phenolic compounds (148.9 and 307.9 mg GAE/g, respectively), being ellagic acid (6233.57 and 19550.08 µg/g, respectively), quercetin-3-ß-glycoside (3023.85 and 8952.55 µg/g, respectively) and gallic acid (2212.98 and 8422.34 µg/g, respectively) the most abundant compounds. Flower extract and ethyl acetate fraction also presented the highest antioxidant capacity on all tested methods (DPPH, ABTS, ORAC and FRAP) and low cytotoxicity against ARPE-19 cells (IC50 >170 µg/mL). C. palmeri possessed high antioxidant potential, associated with the presence of phenolic compounds and low cytotoxicity, suggesting that they could represent an option to counter oxidative stress.

Sappanone A: A natural PDE4 inhibitor with dual anti-inflammatory and antioxidant activities from the heartwood of Caesalpinia sappan L.

ETHNOPHARMACOLOGICAL RELEVANCE: Sumu (Lignum sappan), the dry heartwood of Caesalpinia sappan L., is a traditional Chinese medicine used as an analgesic and anti-inflammatory agent. AIM OF THE STUDY: The study aspired to discover natural phosphodiesterase 4 (PDE4) inhibitors with dual anti-inflammatory and antioxidant activities from Sumu for the treatment of chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: To accurately and efficiently identify natural PDE4 inhibitors from Sumu, molecular docking and molecular dynamics (MD) analysis methods were used for structure-based virtual screening of a self-built database of primary polyphenols in Sumu. According to the previous studies of Sumu and the free radical scavenging mechanism of polyphenols, the reported antioxidant components from Sumu and the potential antioxidants with the antioxidant pharmacophore of catechol and π-conjugated moieties were selected from the potential PDE4 inhibitors predicted by docking. Sappanone A, a potential PDE4 inhibitor with antioxidant activity from Sumu, was selected, calculated and synthesized to evaluate its dual anti-inflammatory and antioxidant functions in vitro and in vivo studies. Herein sappanone A was assayed for its inhibitory effects against PDE4 enzyme activity, tumor necrosis factor-alpha (TNF-α) production induced by lipopolysaccharide (LPS) in RAW264.7 macrophages and malondialdehyde (MDA) production induced by Fe2+ in mouse lung homogenate; sappanone A was also assayed for its abilities of radical (DPPH) scavenging, reducing Fe3+ and complexing Fe2+ in vitro. Additionally, LPS-induced acute lung injury (ALI) in mice was used to evaluate its anti-inflammatory activity as a PDE4 inhibitor in vivo, and the levels of TNF-α and total protein in bronchoalveolar lavage fluid (BALF) and myeloperoxidase (MPO) activity in the lung were assayed. RESULTS: The present study predicted and validated that sappanone A was a promising PDE4 inhibitor from Sumu with dual anti-inflammation and antioxidant activities from Sumu. In vitro, sappanone A remarkably inhibited PDE4 enzyme activity and reduced TNF-α production induced by LPS in RAW264.7 macrophages and MDA production induced by Fe2+ in mouse lung homogenate. Meanwhile, it showed outstanding abilities of scavenging DPPH radicals, reducing Fe3+ and complexing Fe2+. In vivo, sappanone A (25 mg/kg and 50 mg/kg, i.p., twice daily for 7 days) distinctly prevented LPS-induced ALI in mice by reducing the levels of TNF-α and total protein in BALF and MPO activity in the lung. CONCLUSION: Sappanone A is a natural PDE4 inhibitor with dual anti-inflammatory and antioxidant activities from the traditional Chinese medicine Sumu, which may be a promising therapeutic agent to prevent the vicious cycle of COPD inflammation and oxidative stress.

Gastroprotective effect methanol extract of Caesalpinia coriaria pods against indomethacin- and ethanol-induced gastric lesions in Wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Caesalpinia coriaria (Jacq.) Willd is widely used as a traditional medinal plant in Mexico for protective and healing purposes and the treatment of gastrointestinal diseases. AIM OF THE STUDY: To investigate the gastroprotective effect of extract of Caesalpinia coriaria pods against ethanol-induced and indomethacin-induced gastric lesion models, its anti-inflammatory and antioxidative activities, and its main compounds through LC-MS analysis. MATERIALS AND METHODS: Male Wistar rats were orally administered a methanol extract obtained from the pods of C. coriaria at doses of 10, 30, 100, and 300 mg/kg prior to inducing gastric lesions with ethanol or indomethacin. Gastric mucosal lesions were evaluated by macroscopic and histopathological alterations. Determination of prostaglandin E2 (PGE2), alpha tumor necrosis factor (TNF-α), leukotriene B4 (LTB4), nitrites/nitrates, superoxide dismutase (SOD), and H2S gastric levels were investigated. Its main compounds of the active extract through LC-MS analysis. RESULTS: Phenolic compounds were identified as major components of methanol extract. LC-MS analysis identified 15 constituents, and the significant compounds were gallic acid, 3-O-galloylquinic acid, digalloylglucose, tetragalloylglucose, valoneic acid dilactone, pentagalloylglucose, digalloylshikimic acid, and ellagic acid. Pretreatment with the extract at doses of 100 and 300 mg/kg significantly reduced gastric ulcer lesions in both models. Compared with the reference drugs (omeprazole or ranitidine, respectively), no significant difference was found (p < 0.05). The extract's gastroprotective effect was accompanied by significant decreases in leukocyte recruitment, and gastric levels of TNF-α and LTB4 by two to fourfold (p < 0.05). Also, gastric levels of PGE2 gastric levels were maintained and the antioxidant enzyme activities of SOD and nitrate/nitrite in the gastric tissue were improved (p < 0.05). The LC-MS analysis indicated the presence of hydrolyzable tannins (mainly gallic acid derivatives). CONCLUSION: The results suggest that the gastroprotective effect of the methanol extract of C. coriaria pods occurs through anti-inflammatory, antioxidant, and NO modulation properties, and gallic acid derivatives may be the main possible compounds responsible for its actions.

Investigation of antioxidant activity of ethanolic extract of the bark of Caesalpinia ferrea in Swiss mice exposed to paracetamol / Investigação da atividade antioxidante do extrato etanólico da casca de Caesalpinia ferrea em camundongos Swiss expostos ao paracetamol

Aims: it was evaluated the antioxidant effect of the ethanolic extract of Caesal-pinia ferrea bark in a model of oxidative stress induced by paracetamol (PCM). Methods: male Swiss mice were subdivided into four groups (control; PCM; PCM+extract; extract; n=8) in which a dose of paracetamol (250 mg.kg-1) was administered and after 3 hours the treatment with the extract (100 mg.kg-1/day) was administered for seven days, via gavage. Oxidative stress biomarkers were determined, such as catalase, glutathione-S-transferase, reduced gluta-thione, ascorbic acid, thiobarbituric acid reactive substances and carbonylated proteins of liver, kidneys and brain and plasma parameters through the dosage of glucose, cholesterol, triglycerides, aspartate aminotransferase and alanine aminotransferase. Results: the Caesalpinia ferrea extract was able to reverse the lipid and protein damage caused by the drug in the liver tissue and caused the same effect in the renal and brain tissues in the carbonylated proteins. The extract alone decreased liver glutathione-S-transferase and increased catalase and brain glutathione-S-transferase activity, in addition to lowering glucose and cholesterol, but without altering the triglycerides. Conclusions: it was possible to conclude that the ethanolic extract of the bark of Caesalpinia ferrea has a good antioxidant activity, probably due to dose of paracetamol in the samples investigated. However, more studies are needed for a better understanding of the effects of this extract compared to the effects found in this research

Objetivos: foi avaliado o efeito antioxidante do extrato etanólico da casca de Caesalpinia ferrea em modelo de estresse oxidativo induzido por paracetamol (acetaminofeno, PCM). Métodos: camundongos Swiss machos foram subdivididos em quatro grupos (controle; PCM; PCM+extrato; extrato; n=8) nos quais foi administrada uma dose de paracetamol (250 mg.kg-1) e após três horas foi administrado o tratamento com o extrato (100 mg.kg-1/ dia) por sete dias, via gavagem. Foram determinados biomarcadores de estresse oxidativo, como catalase, glutationa-S-transferase, glutationa reduzida, ácido ascórbico, substâncias reativas ao ácido tiobarbitúrico e proteínas carboniladas do fígado, rins e cérebro, além de parâmetros plasmáticos através da dosagem de glicose, colesterol, triglicerídeos, aspartato aminotransferase e alanina aminotransferase. Resultados: o extrato de Caesalpinia ferrea foi capaz de reverter os danos lipídicos e proteicos causados pela droga no tecido hepático, e também causou o mesmo efeito nos tecidos renal e cerebral nas proteínas carboniladas. O extrato sozinho diminuiu a atividade da glutationa-S-transferase hepática e aumentou a da catalase e glutationa-S-transferase cerebral, além de diminuir a glicose e o colesterol, mas sem alterar os triglicerídeos. Conclusões: foi possível concluir que o extrato etanólico da casca de Caesalpinia ferrea apresenta uma boa atividade antioxidante, provavelmente devido à presença de taninos, tendo em vista os danos causados pela alta dose de paracetamol nas amostras investigadas. Entretanto, mais estudos são necessários para um melhor entendimento dos efeitos deste extrato frente aos efeitos encontrados nesta pesquisa

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

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

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

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

In vitro and in vivo anthelmintic properties of Caesalpinia coriaria fruits against Haemonchus contortus.

The purpose of the present study was to assay the in vitro and in vivo anthelmintic activity (AA) of Caesalpinia coriaria (Cc) mature fruits against the nematode Haemonchus contortus (Hc). The Hc infective larvae were used to assess the in vitro AA through larval mortality assay. The exposure of larvae to the different treatments was performed in 96-well microtitration plates. The treatments were as follows: hydroalcoholic extract (HA-E, at 25-100 mg/mL), aqueous fraction (Aq-F, at 12.5-50 mg/mL), organic fraction (EtOAc-F at 12.5-50 mg/mL), compounds (1, methyl gallate and 2, gallic acid at 1.25-10 mg/mL), positive control (ivermectin at 5 mg/mL) and two negative controls (distilled water and 4% methanol). After exposure, dead and live larvae were quantified and results were compared to their controls. The in vivo assay was carried out by a faecal egg count reduction test (FECRT); artificially infected goat kids (F1: Boer x Nubia) were treated with Cc ground dried fruits to assess the AA. The treatments were established as follows: G1-untreated goats (negative control), G2-goats dewormed with ivermectin (positive control), G3-goats fed with Cc mature fruits (10% of their diet). Results in both in vitro and in vivo assays were analysed using an ANOVA through random design, applying a general linear model and mixed models. The in vitro results showed an evident larvicidal effect of the HA-E, EtOAc-F from Cc, indicating that the compound responsible for the AA was gallic acid. The results of the in vivo study corroborated the anthelmintic properties of Cc, reaching 78.6% reduction in the elimination of Hc eggs per gram of faeces. This plant represents a potential natural anthelmintic for the control of haemonchosis in goats under grazing conditions. Future studies should standardise the Cc extract or dried fruits for use in the management of nematodiasis in goat herds.

Anticancer activity of Caesalpinia sappan by downregulating mitochondrial genes in A549 lung cancer cell line.

Background: The standardization and mechanism of action of  Caesalpinia sappan as an anticancer agent are still lacking. This study aimed to understand the mechanism of action of  C,sappan extract as an anticancer agent. Methods: This study was conducted using the A549 lung cancer cell line to understand the mechanism of action of  C. sappan extract as an anticancer agent. The cytotoxicity activity, cell cycle progression, apoptosis, protein-related apoptosis (i.e., BCL-2and BAX protein) assays, and RNA sequencing were performed level were measured. Moreover, the antioxidant activity, total flavonoids, and phenolics of C.sappan were also assessed. Results: C.sappan has strong antioxidant activity (22.14 ± 0.93 ppm) total flavonoid content of (529.3 ± 4.56 mgQE/g), and phenolics content of (923.37 ± 5 mgGAE/g). The C.sappan ethanol extract inhibited cancer cell growth and arrested at G0/G1 phase of cell cycle, inducing apoptosis by increasing BAX/BCL-2 protein ratio in A549 lung cancer cell line. Furthermore, results from RNA sequencing analysis showed that C.sappan ethanol extract caused downregulation of genes acting on mitochondrial function including adenosine triphosphate (ATP) production and respiration. Conclusions: This study demonstrated that C.sappan has the ability to inhibit cancer cell growth by inducing apoptosis and mitochondrial dysfunction in A549 cells.

Ethanolic extract of Caesalpinia bonduc seeds triggers yeast metacaspase-dependent apoptotic pathway mediated by mitochondrial dysfunction through enhanced production of calcium and reactive oxygen species (ROS) in Candida albicans.

Candida albicans is a widespread disease-causing yeast affecting humankind, which leads to urinary tract, cutaneous and various lethal systemic infections. As this infection rate steadily increases, it is becoming a significant public health problem. Recently, Caesalpinia bonduc has received much attention from researchers due to its diverse pharmacological properties, including antimicrobial effects. Accordingly, we first planned to explore the in-vitro anticandidal potential of three extracts obtained from C. bonduc seeds against four Candida species. Initially, the anticandidal activity of the seed extracts was checked by the microdilution technique. Out of three seed extracts tested, ethanolic extract of C. bonduc seed (EECS) recorded the best activity against C. albicans. Hence, we next aimed to find out the anticandidal mechanism of EECS in C. albicans. The liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) analysis showed that the major compounds present in the EECS were tocopherols, fucosterol, linoleic acid, ß-amyrin, ß-sitosterol, campesterol, cassane furanoditerpene, Norcassane furanoditerpene and other diterpenes. To evaluate the cell death mechanism in C. albicans, a series of parameters related to apoptosis, viz., reactive oxygen species (ROS) production, membrane permeability, mitochondrial membrane potential, release of cytochrome c, DNA fragmentation, nuclear condensation, increased Ca2+ level in cytosolic and mitochondrial and activation of metacaspase, were analyzed. The results showed that EECS treatment resulted in the elevation of ROS, which leads to plasma membrane permeability in C. albicans. Annexin V staining further confirms the early stage of apoptosis through phosphatidylserine (PS) externalization. We further inspected the late apoptotic stage using DAPI and TUNEL staining assays. From the results, it can be concluded that EECS triggered mitochondrial dysfunction by releasing high levels of ROS, cytochrome c and Ca2+resulting in the activation of metacaspase mediated apoptosis, which is the central mechanism behind the cell death of C. albicans. Finally, a Galleria mellonella-C. albicans infection system was employed to assess the in-vivo potential of EECS. The outcomes displayed that the EECS considerably enhanced the recovery rate of G. mellonella larvae from infection after the treatment. Additionally, EECS also recorded low hemolytic activity. This study thus spotlights the anticandidal potential and mechanism of action of EECS against C. albicans and thus delivers a promising treatment approach to manage C. albicans infection in the future.

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

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