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This review examines advances in the metabolites, pharmacological research, and therapeutic applications of the medicinal fruit of Brucea javanica (L.) Merr. Brucea javanica (BJ) is derived from the fruit of the Brucea javanica (L.) Merr. There are nearly 200 metabolites present in BJ, and due to the diversity of its metabolites, BJ has a wide range of pharmacological effects. The traditional pharmacological effects of BJ include anti-dysentery, anti-malaria, etc. The research investigating the contemporary pharmacological impacts of BJ mainly focuses on its anti-tumor properties. In the article, the strong monomeric metabolites among these pharmacological effects were preliminarily screened. Regarding the pharmacological mechanism of action, current research has initially explored BJ's pharmacological agent and molecular signaling pathways. However, a comprehensive system has yet to be established. BJ preparations have been utilized in clinical settings and have demonstrated effectiveness. Nevertheless, clinical research is primarily limited to observational studies, and there is a need for higher-quality research evidence to support its clinical application. There are still many difficulties and obstacles in studying BJ. However, it is indisputable that BJ is a botanical drugs with significant potential for application, and it is expected to have broader global usage. [ABSTRACT FROM AUTHOR]

This article presents two types of phytochemical data obtained from Brucea javanica (L.) Merr. roots, a medicinal plant belonging to the Simaroubaceae family. The high-resolution LC–MS dataset comprised the chemical profile of dichloromethane extract, which was utilised to annotate 35 chemical constituents. For annotations, the measured spectral data were compared with the in-silico spectral data generated from 920 molecular structures previously reported in Simaroubaceae. Indole alkaloids, quassinoids, aliphatics and lignan were the chemical groups identified in the root extract. The second dataset provides NMR spectra (1H, 13C, COSY, HMQC and HMBC) for the six indole alkaloids previously detected in LC–MS analysis and isolated through centrifugal partition chromatography. The chemical structures of all compounds were confirmed based on NMR data as bruceolline J (compound 7), canthin-6-one-N-oxide (compound 10), bruceolline E (compound 15), 5-methoxycanthin-6-one (compound 16), canthin-6-one (compound 20), and 1‑hydroxy-11-methoxycanthin-6-one (compound 22). This phytochemical data was generated to support an ongoing anti-cancer and anti-dengue study.

Background: Currently Mycobacterium tuberculosis is found to be resistant to the treatment of tuberculosis with rifampin and isoniazid (INH) and often stated as multi-drug resistance (MDR). Knowledge and determination of biological properties of plant extracts is a source of drug candidates in various health fields. Therefore, natural products are important in the discovery of new drugs, especially in disease therapy, particularly for tropical diseases, tuberculosis. Brucea javanica, known as Buah Makasar, is found in many Asian countries including Indonesia. This plant fruit has a very bitter taste so it cannot be directly consumed and is often used as a traditional medicine to prevent some diseases, especially malaria. There has been no research on the effectiveness of Buah Makasar in tuberculosis. Objective: This study aims to identify compounds contained in Brucea javanica, namely bruceines, bruceosides and yadanziosides in inhibiting the InhA enzyme found in the wall of Mycobacterium tuberculosis. Methods: This in-silico study is using Molegro Virtual Docker (MVD) Ver. 5.5. We compared it to the native ligand, namely N-(4-Methylbenzoyl)-4-Benzylpiperidine (code: 4PI) and the reference drug standard, INH. Results: In-silico results show that yadanziosides found in Brucea javanica have the potential to inhibit the InhA enzyme. Bruceoside F (-190.76 Kcal/mol) has the lowest MolDock score among the 27 other compounds. It is also having lower MolDock score than the native ligand 4PI (-120.61 Kcal/mol) and INH (- 54.44 Kcal/mol). Conclusion: Brucea javanica can be considered as source of drug development for againts tuberculosis. [ABSTRACT FROM AUTHOR]

A phytochemical study of the roots of Brucea javanica was conducted and four alkaloids and three quassinoids were isolated. The structures of the compounds were verified using physical and spectroscopic data, which were compared to the literature. The cytotoxicity of the compounds was evaluated against KB (oral cavity carcinoma), NCI-H187 (small cell lung cancer), and MCF-7 (breast adenocarcinoma) cell lines. The results showed that the quassinoid, Bruceine A, exhibited very strong cytotoxicity against KB, and high potency against NCI-H187, with both being 581- and 100-fold more active than ellipticine, and 99- and 10-fold more active than doxorubicin, respectively. These results suggest the potential use of bruceine A as an anticancer agent. [ABSTRACT FROM AUTHOR]

Background: Currently Mycobacterium tuberculosis is found to be resistant to the treatment of tuberculosis with rifampin and isoniazid (INH) and often stated as multi-drug resistance (MDR). Knowledge and determination of biological properties of plant extracts is a source of drug candidates in various health fields. Therefore, natural products are important in the discovery of new drugs, especially in disease therapy, particularly for tropical dis- eases, tuberculosis. Brucea javanica, known as Buah Makasar, is found in many Asian countries including Indonesia. This plant fruit has a very bitter taste so it cannot be directly consumed and is often used as a traditional medicine to prevent some diseases, especially malaria. There has been no research on the effectiveness of Buah Makasar in tuberculosis. Objective: This study aims to identify compounds contained in Brucea javanica, namely bruceines, bruceosides and yadanzio-sides in inhibiting the InhA enzyme found in the wall of Mycobacterium tuberculosis. Methods: This in-silico study is using Molegro Virtual Docker (MVD) Ver. 5.5. We compared it to the native ligand, namely N-(4- Methylbenzoyl)-4-Benzylpiperidine (code: 4PI) and the reference drug standard, INH. Results: In-silico results show that yadanziosides found in Brucea javanica have the potential to inhibit the InhA enzyme. Bruceoside F (-190.76 Kcal/mol) has the lowest MolDock score among the 27 other compounds. It is also having lower MolDock score than the native ligand 4PI (-120.61 Kcal/mol) and INH (- 54.44 Kcal/mol). Conclusions: Brucea javanica can be considered as source of drug development for againts tuberculosis.

Background: Breast cancer is the most common malignancy in women worldwide, so it is imperative to find new medications for this disease. The dry seeds of Brucea javanica have been extensively used in Traditional Chinese Medicine (TCM) for the treatment of tumor. Objectives: To isolate antitumor peptides from B. javanica seeds and research their antitumor activity with MCF-7 cells. Materials and Methods: Globulin of B. javanica was extracted and enzymatically hydrolyzed by pepsin. Then ultrafiltration, gel filtration chromatography (GFC), and reverse-phase high-performance liquid chromatography (RP-HPLC) were employed to purify the peptides. Anticancer activity was studied in humans in human breast cancer MCF-7 cells, MTT (3- [4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide)-assessed cell viability, Giemmsa staining determined whether the cells should undergo apoptosis, and apoptosis and cycle assays assessed the antitumor mechanism of the cells. Real time quantitative polymerase chain reaction (RT-qPCR) was used to study the alterations of oncogenes and cancer metastasis suppressor genes in MCF-7 cells treated with peptide extracts. Results: The fraction F9-9 extracted from B. javanica significantly inhibited the proliferation of MCF-7 cells with the IC50 of 0.124 ± 0.004 μg/mL. The possible mechanisms of this fraction were further explored. F9-9 obviously induced cell cycle arrest at G0/G1 phase and promoted apoptosis of MCF-7 cells. The underlying molecular mechanisms were explored by RT-qPCR and results showed that in B. javanica small molecular peptides upregulated the expression of tumor suppressor genes P53 and PTEN as well as tumor metastasis suppressor gene NM23H-1. Conclusion: This study suggests that B. javanica peptides have therapeutic activity and mechanisms for antibreast cancer, encouraging further isolation and purification to obtain monomeric peptides of this extract for anticancer use. [ABSTRACT FROM AUTHOR]

Objective: Inflammation plays a crucial role in the progression of many diseases, excessive inflammation increases immune cell activation, which can destroy tissues and body health. When inflammation occurs, multiple pro-inflammatory mediators are overproduced, leading to a variety of diseases such as rheumatism, diabetes, and cardiovascular problems. Brucea javanica has been used as traditional medicine as a therapy for anti-tumor, amebic dysentery, diarrhea, malaria, and intestinal inflammation. Therefore, in this study, we explored the effect of ethanol extract Brucea javanica Fruit on anti-inflammation activity in carrageenan-induced rat paw edema and the COX-2 inhibitory effect in vivo. Methods: In vivo anti-inflammatory activity of the ethanolic extracts was evaluated using the carrageenan-induced rat paws edema method at doses of 50, 100, and 200mg/kg and further investigated the effect of Cyclooxygenase-2 inhibitory using ELISA readers. Results: The ethanolic extract of Brucea javanica Fruit exhibited anti-inflammatory activity by oral intake of 50 mg/kg of the ethanolic extract and Brucea javanica inhibited rat paw edema by 50.91% significantly compared to Celecoxib by 58.52%. Moreover, Brucea javanica showed COX-2 inhibition by 16,40% compared to Celecoxib by 20,50%. Conclusions: These findings indicate that Brucae javanica Fruit extracts have promising antiinflammatory activity directed against COX-2 enzymatic activity. [ABSTRACT FROM AUTHOR]

As a widely used Traditional Chinese Medicine in China, the extract of Brucea javanica has a variety of pharmacological effects, especially has been shown to have potent anti-cancer effects. Studies have found that Brucea javanica can play an anti-cancer role by inhibiting tumor cell growth, affecting tumor cell apoptosis, autophagy, migration and invasion processes, and activating immunity. In this paper, we summarize the anti-cancer effects and mechanisms of Brucea javanica, including NF-κB, phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT), p38-mitogen-activated protein kinase (MAPK), Wnt/β-catenin, and signal transducer and activator of transcription 3 (STAT3) pathways. We discuss Brucea javanica in combination with other anti-cancer drugs to enhance anticancer effects or mitigate adverse effects. The inhibitory effect of Brucea javanica on tumor cell lines is also summarized. The anti-cancer material basis and toxic components of BJO are discussed here. These data suggest that Brucea javanica is a promising anti-tumor reagent which is expected to open a broader application market.

Brucea javanica (Ya-dan-zi in Chinese) is a well-known Chinese herbal medicine, which is traditionally used in Chinese medicine for the treatment of intestinal inflammation, diarrhea, malaria, and cancer. The formulation of the oil (Brucea javanica oil) has been widely used to treat various types of cancer. It has also been found that B. javanica is rich in chemical constituents, including quassinoids, triterpenes, alkaloids and flavonoids. Pharmacological studies have revealed that chemical compounds derived from B. javanica exhibit multiple bioactivities, such as anti-cancer, anti-bacterial, anti-diabetic, and others. This review provides a comprehensive summary on the pharmacological properties of the main chemical constituents presented in B. javanica and their underlying molecular mechanisms. Moreover, the review will also provide scientific references for further research and development of B. javanica and its chemical constituents into novel pharmaceutical products for disease management. [ABSTRACT FROM AUTHOR]

Brucea javanica (Ya-dan-zi in Chinese) is a well-known Chinese herbal medicine, which is traditionally used in Chinese medicine for the treatment of intestinal inflammation, diarrhea, malaria, and cancer. The formulation of the oil (Brucea javanica oil) has been widely used to treat various types of cancer. It has also been found that B. javanica is rich in chemical constituents, including quassinoids, triterpenes, alkaloids and flavonoids. Pharmacological studies have revealed that chemical compounds derived from B. javanica exhibit multiple bioactivities, such as anti-cancer, anti-bacterial, anti-diabetic, and others. This review provides a comprehensive summary on the pharmacological properties of the main chemical constituents presented in B. javanica and their underlying molecular mechanisms. Moreover, the review will also provide scientific references for further research and development of B. javanica and its chemical constituents into novel pharmaceutical products for disease management.

A new quassinoid, dehydrobruceantinol B (1), was isolated from the seeds of Brucea javanica, together with two known compounds, bruceantinol (2) and bruceine A (3). The structure of the new compound 1 was elucidated by advanced spectrometric methods, including HR-MS, UV, IR, 1D and 2D NMR experiments. The inhibitory effects of 1–3 on nitric oxide production in lipopolysaccharide-activated macrophages were also investigated in this study. [ABSTRACT FROM AUTHOR]

Tumbuhan racun ayam adalah salah satu tumbuhan yang buahnya memiliki beberapa aktivitas salah satunya adalah sebagai antibakteri. Penelitian ini bertujuan untuk menetapkan aktivitas antibakteri ekstrak etanol daun racun ayam. Ekstraksi dilakukan dengan metode maserasi menggunakan pelarut etanol. Uji aktivitas antibakteri dilakukan terhadap bakteri S. aureus, E. coli, dan P. aeruginosa dengan metode difusi cakram pada konsentrasi 80, 100, dan 120 ppm. Hasil penelitian diperoleh ekstrak etanol daun B. javanica memiliki zona hambat paling besar pada E. coli dengan nilai diameter zona hambat pada 80, 100, 120 ppm yaitu 11,7mm, 14,5 mm dan 19,67 mm. Zona hambat pada S. aureushanya terlihat pada konsentrasi 100 dan 120 ppm dengan diameter zona hambat 1,17 mm dan 2,17 mm, sedangkan pada P. aeruginosa tidak memiliki nilai zona hambat. Hasil analisis statistik yaitu menunjukkan signifikansi nilai diameter zona hambat pada bakteri E. coli mulai 80 ppm dengan nilai sig 0,034 karena sig 0,05 yaitu tidak berbeda signifikan terhadap semua konsentrasi.

Triple-negative breast cancer (TNBC) is an aggressive disease with worst prognosis than other subtypes of breast cancer. Owing to the lack of hormone receptors and HER2 expression on TNBC cells, patients do not have targeted therapy options available with other breast cancer subtypes. Extensive efforts have been made to identify novel therapeutics against TNBC. Interestingly, recent studies had shown that plant-derived natural products could modulate the autophagy and induce the breast cancer cells death. Seed of Brucea javanica has been used as an important traditional Chinese medicine against cancers. In the present study, the anti-breast cancer potential of ethanol crude extracts from B. javanica seed (BJE) was explored. Data demonstrated that BJE could inhibit the TNBC cell line MDA-MB-231 proliferation and induced apoptosis. In the cells exposed to BJE, protein expressions of UNC-51-like kinase-1 (ULK1) and Beclin-1 and the ratio of light chain 3 II/I (LC3 II/I) were reduced, while the expression of p62 was increased, indicating an inhibition on autophagy. Moreover, BJE promoted the phosphorylation of mammalian target of rapamycin (mTOR), phosphatidylinositol 3-kinase (PI3K), and Akt in MDA-MB-231. BJE also suppressed the MDA-MB-231 tumor growth in vivo. Coincide with the results in vitro, autophagy in the tumor tissue was weakened as indicated by decreased ratio of LC 3 II/I and Beclin-1 accompanied by enhanced phosphorylation of mTOR, which confirmed that autophagy restraint via the PI3K/Akt/mTOR signaling pathway contributes to the suppression by BJE. Notably, no noticeable toxicity in non-targeted organs was found, including small intestine, liver, and kidney. Taken together, this study revealed anti-breast cancer activity of BJE based on autophagy restraint, highlighting its clinical importance as a novel natural agent against TNBC.

Elham Bagheri,1 Fatemeh Hajiaghaalipour,2 Shaik Nyamathulla,1 Nur’Ain Salehen3 1Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 2Institute of Biological Science, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia; 3Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia Background: Brucea javanica (L.) Merr. is a plant from the genus Brucea, which is used in local traditional medicine to treat various diseases. Recent studies revealed an impressive anticancer efficiency of B. javanica extract in different types of cancer cells.Purpose: In this study, we have investigated the cytotoxic effects of the B. javanica hexane, ethanolic extracts against colon cancer cells. HT29 colon cells were selected as an in vitro cancer model to evaluate the anticancer activity of B. javanica ethanolic extract (BJEE) and the possible mechanisms of action that induced apoptosis.Methods: 3-(4,5-dimethylthiazol-2-yl)-2, 5,-diphenyltetrazolium bromide (MTT), lactate dehydrogenase, acridine orange/propidium iodide, and annexin-V-fluorescein isothiocyanate assays were performed to determine the antiproliferative and apoptosis validation of BJEE on cancer cells. Measurement of reactive oxygen species (ROS) production, caspase activities, nucleus factor-κB activity, and gene expression experiments was done to investigate the potential mechanisms of action in the apoptotic process.Results: The results obtained from this study illustrated the significant antiproliferative effect of BJEE on colorectal cancer cells, with a concentration value that inhibits 50% of the cell growth of 25±3.1 µg/mL after 72 h of treatment. MTT assay demonstrated that the BJEE is selectively toxic to cancer cells, and BJEE induced cell apoptosis via activation of caspase-8 along with modulation of apoptosis-related proteins such as Fas, CD40, tumor necrosis factor-related apoptosis-inducing ligands, and tumor necrosis factor receptors, which confirmed the contribution of extrinsic pathway. Meanwhile, increased ROS production in treated cells subsequently activated caspase-9 production, which triggered the intrinsic pathways. In addition, overexpression of cytochrome-c, Bax, and Bad proteins along with suppression of Bcl-2 illustrated that mitochondrial-dependent pathway also contributed to BJEE-induced cell death. Consistent with the findings from this study, BJEE-induced cancer cell death proceeds via extrinsic and intrinsic mitochondrial-dependent and -independent events.Conclusion: From the evidence obtained from this study, it is concluded that the BJEE is a promising natural extract to combat colorectal cancer cells (HT29 cells) via induction of apoptosis through activation of extrinsic and intrinsic pathways. Keywords: Brucea javanica, apoptosis, cancer, HT29, mitochondrial pathway, apoptosis protein array

Two novel norquassinoids possessing a unique ketal skeleton, designated quassilactones A (1) and B (2), were isolated from the fruits of Brucea javanica (Simaroubaceae). Their structures were established by extensive NMR and HR-ESI-MS spectroscopic analysis. The absolute configuration of 1 was determined through single-crystal X-ray crystallography, and that of 2 was assigned by comparing the calculated electronic and experimental circular dichroism with compound 1. In addition, their cytotoxic activities against three human cancer cell lines and their antimicrobial activities were evaluated. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is an aggressive disease with worst prognosis than other subtypes of breast cancer. Owing to the lack of hormone receptors and HER2 expression on TNBC cells, patients do not have targeted therapy options available with other breast cancer subtypes. Extensive efforts have been made to identify novel therapeutics against TNBC. Interestingly, recent studies had shown that plant-derived natural products could modulate the autophagy and induce the breast cancer cells death. Seed of Brucea javanica has been used as an important traditional Chinese medicine against cancers. In the present study, the anti-breast cancer potential of ethanol crude extracts from B. javanica seed (BJE) was explored. Data demonstrated that BJE could inhibit the TNBC cell line MDA-MB-231 proliferation and induced apoptosis. In the cells exposed to BJE, protein expressions of UNC-51-like kinase-1 (ULK1) and Beclin-1 and the ratio of light chain 3 II/I (LC3 II/I) were reduced, while the expression of p62 was increased, indicating an inhibition on autophagy. Moreover, BJE promoted the phosphorylation of mammalian target of rapamycin (mTOR), phosphatidylinositol 3-kinase (PI3K), and Akt in MDA-MB-231. BJE also suppressed the MDA-MB-231 tumor growth in vivo. Coincide with the results in vitro , autophagy in the tumor tissue was weakened as indicated by decreased ratio of LC 3 II/I and Beclin-1 accompanied by enhanced phosphorylation of mTOR, which confirmed that autophagy restraint via the PI3K/Akt/mTOR signaling pathway contributes to the suppression by BJE. Notably, no noticeable toxicity in non-targeted organs was found, including small intestine, liver, and kidney. Taken together, this study revealed anti-breast cancer activity of BJE based on autophagy restraint, highlighting its clinical importance as a novel natural agent against TNBC. [ABSTRACT FROM AUTHOR]

An investigation on seeds of Brucea javanica led to the acquisition of a new quassinoid, 20-hydroxyyadanzigan (1), along with five known quassinoids (2–6). The structure of the new compound was elucidated on the basis of extensive spectral analysis. All of the compounds were assayed for their anticomplement activities through classical and alternative pathways. Compounds 1–6 exhibited potent anticomplement activity with CH50 and AP50 values of 0.032–0.075 mg/mL and 0.061–0.118 mg/mL, respectively. Moreover, the structure-activity relationships of these compounds are discussed. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is characterized by complex heterogeneity, high recurrence and metastasis rates, and short overall survival, owing to the lack of endocrine and targeted receptors, which necessitates chemotherapy as the major treatment regimen. Exosome-like nanovesicles derived from medicinal plants have shown great potential as novel biotherapeutics for cancer therapy by delivering their incorporated nucleic acids, especially microRNAs (miRNAs), to mammalian cells. In this study, we isolated exosome-like nanovesicles derived from B. javanica (BF-Exos) and investigated their influence and underlying molecular mechanisms in TNBC. We found that BF-Exos delivered 10 functional miRNAs to 4T1 cells, significantly retarding the growth and metastasis of 4T1 cells by regulating the PI3K/Akt/mTOR signaling pathway and promoting ROS/caspase-mediated apoptosis. Moreover, BF-Exos were shown to inhibit the secretion of vascular endothelial growth factor, contributing to anti-angiogenesis in the tumor microenvironment. In vivo, BF-Exos inhibited tumor growth, metastasis, and angiogenesis in breast tumor mouse models, while maintaining high biosafety. Overall, BF-Exos are considered promising nanoplatforms for the delivery of medicinal plant-derived nucleic acids, with great potential to be developed into novel biotherapeutics for the treatment of TNBC., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Objective: Brucein D (BrD), a quassinoid isolated from Brucea javanica fruit, reportedly demonstrates anti-cancer activity. This study's objective is to evaluate the cytotoxicity of Brucein D and its ability to induce apoptosis in T24 bladder cancer cells., Methods: We investigated the cytotoxic activity of BrD against the T24 cell through the induction of apoptosis in vitro. This cytotoxic activity was evaluated with ΜΤΤ assay and followed by Calcein-AM/PI viability staining. Apoptotic activity was determined with Hoechst 33342 nuclear staining and DNA fragmentation. Doxorubicin and docetaxel were used as a positive control. Evaluation of apoptotic-related gene expression, Bax, Bak, Bcl2, and p53 was also performed using semi-quantitative PCR analysis. Statistical analysis was conducted using One-way ANOVA followed by post hoc test Turkey's HSD (Honestly Significance Difference)., Results: Results show that BrD had high toxicity against T24 bladder cancer cells with an IC50 value of 7.65 ± 1.2 µg/mL but relatively less toxic to 1BR3 normal skin fibroblast cells compared to the doxorubicin and docetaxel treated cells. The viability assay shows that BrD significantly increases the percentage of dead cells relative to control in a dose-dependent manner. Furthermore, the percentage of cells with apoptotic appearance was significantly higher in group treated with BrD IC50 (56.04±3.09%) compared to control (9.42±2.88). The result was similar to doxorubicin IC50 (58.97±12.31) but lower than docetaxel IC50 (74.42±9.79). DNA fragmentation in gel electrophoresis was also observed in T24 cells treated with BrD. Apoptosis was also verified by an alteration in the expression of apoptosis-related genes, upregulation of Bax, Bak, and p53, and downregulation of Bcl-2., Conclusion: BrD has shown a cytotoxic effect against T24 bladder cancer cells. Hence, it is a promising natural compound for the management of bladder cancer by induction of apoptosis through activation of the intrinsic pathway, with low toxicity to normal cells.

Enhancing the performance of traditional pesticide formulations by improving their leaf surface wetting capabilities is a crucial approach for maximizing the pesticide efficiency. This study develops an emulsifiable concentrate (EC) of 4.5% β-cypermethrin containing Brucea javanica oil (BJO). The incorporation of BJO aims to improve the leaf-wetting properties of the EC formulation and enhance its insecticidal effectiveness. The droplet size and emulsion characteristics of β-CYP EC emulsion with varying concentrations of the emulsifier were evaluated, and changes after incorporating BJO were assessed to develop the optimal formulation. A comprehensive comparison was conducted among commercial 4.5% β-cypermethrin EC (β-CYP EC-1), 4.5% β-cypermethrin EC with BJO (β-CYP EC-2), and 4.5% β-cypermethrin EC without BJO (β-CYP EC-3). This comparison encompassed various factors including storage stability, insecticidal activity, cytotoxicity, and wetting performance on cabbage leaves. The results indicated that the ideal emulsifier concentration was 15% emulsifier 0201B. β-CYP EC-2 demonstrated superior wetting properties on cabbage leaves (the wetting performance of β-CYP EC-2 emulsion on cabbage leaves is 2.60 times that of the β-CYP EC-1 emulsion), heightened insecticidal activity against the third larvae of Plutella xylostella [diamondback moth (DBM)] [the insecticidal activity of the β-CYP EC-2 emulsion against the third larvae of DBM is 1.93 times that of the β-CYP EC-1 emulsion (12 h)], and more obvious inhibitory effects on the proliferation of DBM embryo cells than the other tested formulations. These findings have significant implications for advancing pest control strategies and promoting sustainable and effective agricultural practices.

This review examines advances in the metabolites, pharmacological research, and therapeutic applications of the medicinal fruit of Brucea javanica (L.) Merr. Brucea javanica (BJ) is derived from the fruit of the Brucea javanica (L.) Merr. There are nearly 200 metabolites present in BJ, and due to the diversity of its metabolites, BJ has a wide range of pharmacological effects. The traditional pharmacological effects of BJ include anti-dysentery, anti-malaria, etc. The research investigating the contemporary pharmacological impacts of BJ mainly focuses on its anti-tumor properties. In the article, the strong monomeric metabolites among these pharmacological effects were preliminarily screened. Regarding the pharmacological mechanism of action, current research has initially explored BJ's pharmacological agent and molecular signaling pathways. However, a comprehensive system has yet to be established. BJ preparations have been utilized in clinical settings and have demonstrated effectiveness. Nevertheless, clinical research is primarily limited to observational studies, and there is a need for higher-quality research evidence to support its clinical application. There are still many difficulties and obstacles in studying BJ. However, it is indisputable that BJ is a botanical drugs with significant potential for application, and it is expected to have broader global usage., Competing Interests: Author HY was employed by Power China Chengdu Engineering Corporation Limited. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor RS declared a parent affiliation with the author(s) at the time of review., (Copyright © 2024 Chen, Yu, Li, Deng, Yang, Chen and Bai.)

A novel alkaloid with a hexa-tetra-hexa-cyclic skeleton, Bi-4-methoxycarbonyl-2-quinolone ( 1 ), was discovered during the investigation of Brucea javanica . Additionally, six known alkaloids ( 2 - 7 ) were also found. The chemical structures of these compounds were identified using HRESIMS and 1D and 2D NMR spectroscopic analysis. Additionally, the absolute configuration of the new compound 1 was determined through X-ray single crystal diffraction. Compound 1 exhibited significant anti-inflammatory activity in RAW264.7 cells and demonstrated promising anti-cancer effects in Lewis cells.

Bioactivity-guided purification obtained polysaccharide BP-S1 from seeds of Brucea javanica . The results showed that BP-S1 was a homogenous polysaccharide with molecular weight of 45.7 kDa, mainly composed of arabinose and glucose in the ratio of 1.0:1.0 and the backbone of BP-S1 was deduced to be →3,4)-α-Glu p -(1→ with branches of →2)-α-Ara p -(1→and α-Ara p -(1→, and the possible repetitive units were speculated according to result of methylation and 2D-NMR. Moreover, BP-S1 is a periodic rope-like structure. Functional analysis revealed that BP-S1 inhibited complement activation on the classic and alternative pathways with values of CH 50 0.073 ± 0.012 mg/mL and AP 50 0.097 ± 0.004 mg/mL, respectively. In mechanism study, using complement component depleted-sera methods indicated that BP-S1 selectively interacted with C3 and C4 components.

Malignant pleural mesothelioma (MPM) is a severe form of cancer that originates from mesothelium cells. Around 54-90% of mesotheliomas are associated with pleural effusions. Brucea Javanica Oil Emulsion (BJOE) is the processed oil derived from the seeds of Brucea javanica, which has shown potential as a treatment option for several types of cancer. Here, we present a case study of a MPM patient with malignant pleural effusion who received intrapleural injection of BJOE. The treatment resulted in the complete response of pleural effusion and chest tightness. While the precise mechanisms underlying the therapeutic effects of BJOE for pleural effusion are not yet fully understood, it has demonstrated a satisfactory clinical response without significant adverse effects., (Copyright © 2023. Published by Elsevier Inc.)

Background: Ovarian cancer (OC) is a commonly diagnosed female cancer around the world. The Chinese herbal medicine Brucea Javanica has an anti-cancer effect. However, there is no relevant report on whether Brucea Javanica is effective in treating OC, and the corresponding mechanism is also unknown., Objective: This study was projected to excavate the active components and underpinned molecular mechanisms of Brucea Javanica in treating ovarian cancer (OC) through network pharmacology combined with in vitro experiments., Methods: The essential active components of Brucea Javanica were selected using the TCMSP database. The OC-related targets were selected by GeneCards, intersecting targets were obtained by Venn Diagram. The core targets were obtained through the PPI network and Cytoscape, and the key pathway was gained through GO and KEGG enrichment analyses. Meanwhile, docking conformation was observed as reflected by molecular docking. MTT, colony formation assay and flow cytometer (FCM) analysis were performed to determine cell proliferation and apoptosis, respectively. Finally, Levels of various signaling proteins were evaluated by western blotting., Results: Luteolin, β-sitosterol and their corresponding targets were selected as the essential active components of Brucea Javanica . 76 intersecting targets were obtained by Venn Diagram. TP53, AKT1, and TNF were obtained through the PPI network and Cytoscape, and the key pathway PI3K/AKT was gained through GO and KEGG enrichment analyses. A good docking conformation was observed between luteolin and AKT1. Luteolin could hinder A2780 cell proliferation, induce cell apoptosis and enhance the inhibition of the PI3K/AKT pathway., Conclusion: It was verified in vitro that luteolin could hinder OC cell proliferation and activate the PI3K/AKT pathway to lead to apoptosis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: The seeds of B. javanica are known as herbal material for anticancer, antimalaria and antiamoeba. Limited report is available on their antidiabetic and antibacterial properties. Methods: Methanol (ME) and Ethyl acetate extracts (EAE) were studied for their inhibition activities on α-glucosidase in vitro, including combination of ME with acarbose and inhibition mechanism. Antibacterial activity was tested by well diffusion and microdilution methods. The extracts were evaluated for their in vitro antioxidant property by DPPH assay, as well as their phenolic and flavonoid contents. Results: ME exhibited a strong α-glucosidase inhibition activity (IC50 271.97 μg/ml) compared to EAE and acarbose (IC50 of 1745.05 and 823.99 μg/ml, respectively). A low dose of ME gave an additive inhibition on α-glucosidase when combined with acarbose. By a kinetic analysis, ME was found to inhibit α-glucosidase in a mixed-type inhibition. Both ME and EAE showed strong antibacterial activities against gram negative and positive bacteria. The strongest inhibition was observed against C. violaceum and S. mutans for ME (MIC of both 0.387 mg/ml) and P. aeruginosa for EAE (MIC 2.938 mg/ml). Both extracts showed weaker antioxidant activities than standards; IC50 664.73 and 4225.40 μg/ml, respectively. ME was rich in phenolics (277.54 mg GAE/100 g DW), unlike EAE (1.86 mg GAE/100 g DW). Conclusion: This study can recommend B. javanica seeds as a source for antidiabetic and antibacterial agents. Combination with acarbose may have important role for the treatment of diabetes mellitus. [ABSTRACT FROM AUTHOR]

Seung-Hun Kim,1,* Chun-Yen Liu,1,* Po-Wei Fan,1 Chang-Heng Hsieh,1 Hsuan-Yuan Lin,1 Ming-Chung Lee,2 Kang Fang1 1Department of Life Science, National Taiwan Normal University, Taipei, 2Brion Research Institute of Taiwan, New Taipei City, Taiwan *These authors contributed equally to this work Abstract: As a practical and safe herbal medicine, the seeds of Brucea javanica (L.) Merr., were used to cure patients suffering from infectious diseases such as malaria. Recent advances revealed that the herb could also be a useful cancer therapy agent. The study demonstrated that aqueous B. javanica (BJ) extract attenuated the growth of human non-small-lung cancer cells bearing mutant L858R/T790M epidermal growth factor receptor (EGFR). The reduced cell viability in H1975 cells was attributed to apoptosis. Transfection of EGFR small hairpin RNA reverted the sensitivities. When nude mice were fed BJ extract, the growth of xenograft tumors, as established by H1975 cells, was suppressed. Additional histological examination and fluorescence analysis of the resected tissues proved that the induced apoptosis mitigated tumor growth. The work proved that the BJ extract exerted its effectiveness by targeting lung cancer cells carrying mutated EGFR while alleviating tumorigenesis. Aqueous BJ extract is a good candidate to overcome drug resistance in patients undergoing target therapy. Keywords: Brucea javanica, target therapy, epidermal growth factor receptor, human lung, herbal medicine, apoptosis

Jian-He Chen,* Seung-Hun Kim,* Po-Wei Fan, Chun-Yen Liu, Chang-Hung Hsieh, Kang Fang Department of Life Science, National Taiwan Normal University, Taipei, Taiwan *These authors contributed equally to this work Abstract: Being effective and relatively safe, the traditional Chinese medicinal herb Brucea javanica (BJ) has been valuable in curing patients in East Asia and its nearby regions for years. Recent reports suggested that the medicinal herb possesses broad antitumor activity against various cancer cells. This study evaluated whether low concentrations of BJ aqueous extract inhibited the growth of liver cancer cells. Experiments including flow cytometry and Western blot analysis established the development of apoptotic cell death after treatment. Further experiments evaluated the growth of the enriched spheroids. BJ not only reduced the expression of stem cell markers but also eliminated tumor spheroids by apoptotic death. The findings suggest BJ is a promising supplement to the current therapy regimen and highlight the opportunity of BJ as a practical avenue to suppress the growth of the stem cells in liver cancer. Keywords: Brucea javanica, apoptosis, stem cells, human liver cancer cells

Breast cancer is currenly the number one cancer of all cancers attacking women, especially those who live in developing countries including Indonesia. Therefore, the pursuit of drugs for breast cancer is still needed. The aim of this study was to determine the anti proliferative activity of brucein-A against breast cancer T47D cells in vitro. Bruceine-A was isolated from “buah makasar” (Brucea javanica (L.) Merr) and the structure of the isolated compound was elucidated by spectral data. The activities of anticancer were evaluated from the antiproliferative effects on T47D breast cancer cell line . The antiproliferative effects were examined in cultured cells stained with sulforhodamin B. Each well contained 30,000 cells, which was treated with bruceine-A in 10 concentration variations of 0.04 µg/mL, 0.08 µg/mL, 0.16 µg/mL, 0.31 µg/mL, 0.63 µg/mL, 1.25 µg/mL, 2.5 µg/mL, 5 µg/mL, 10 µg/mL, and 20 µg/mL for 72 hours. The experiment was replicated twice and the inhibitory percentage of cells was then calculated. The results showed that the IC50 value of bruceine-A on T47D cells as anantiproliferative effect was0.54 µg/mL with cisplatin 0.43 µg/mL as the positive control. In conclusion, bruceine-A has an antiproliferative activity on T47D breast cancer cell line.

This article presents two types of phytochemical data obtained from Brucea javanica (L.) Merr. roots, a medicinal plant belonging to the Simaroubaceae family. The high-resolution LC-MS dataset comprised the chemical profile of dichloromethane extract, which was utilised to annotate 35 chemical constituents. For annotations, the measured spectral data were compared with the in-silico spectral data generated from 920 molecular structures previously reported in Simaroubaceae. Indole alkaloids, quassinoids, aliphatics and lignan were the chemical groups identified in the root extract. The second dataset provides NMR spectra ( 1 H, 13 C, COSY, HMQC and HMBC) for the six indole alkaloids previously detected in LC-MS analysis and isolated through centrifugal partition chromatography. The chemical structures of all compounds were confirmed based on NMR data as bruceolline J (compound 7 ), canthin-6-one- N -oxide (compound 10 ), bruceolline E (compound 15 ), 5-methoxycanthin-6-one (compound 16 ), canthin-6-one (compound 20 ), and 1‑hydroxy-11-methoxycanthin-6-one (compound 22 ). This phytochemical data was generated to support an ongoing anti-cancer and anti-dengue study., (© 2023 The Author(s).)

Tongue squamous cell carcinoma (TSCC) is one of the most common malignant tumors of head and neck. Its incidence is on the rise, and the proportion of young patients is gradually increasing, which is prone to tumor recurrence and metastasis. At present, there is no effective method to completely treat TSCC. Studies have shown that brucea javanica oil (BJO) has good antitumor activity against lung cancer and gastrointestinal tumors, but its therapeutic effect on TSCC is not clear. We have previously confirmed that oleic acid, the main component of BJO, can induce apoptosis of TSCC and reduce its invasion and metastasis ability. However, the anticancer effect and mechanism of BJO in TSCC remain unclear. In order to further explore the effects of BJO on the biological characteristics of TSCC cells, we studied the effects of different concentrations of BJO on the migration, invasion ability and epithelial mesenchymal transition (EMT) progression of TSCC cells and the possible mechanisms through in vitro experiments. We found that BJO could inhibit the invasion and metastasis of TSCC and up-regulate miR-138. After BJO treatment, the expression of E-cad was significantly increased, while the expression of EZH2, Slug, p-ERK1/2 and Vimentin was significantly decreased. EZH2 is a miR-138 target gene involved in TSCC. BJO inhibits TSCC invasion and metastasis by regulating the miR-138-EZH2 pathway. In vivo experiments have also well demonstrated the targeting effect of this pathway. This study provides a new therapeutic strategy for the treatment of TSCC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Ethnopharmacological relevance The seeds of Brucea javanica and its aqueous decoction is a traditional medicine consumed by diabetic patients in Malaysia. The daily consumption of B. javanica seeds and it's aqueous decoction causes much concern as the quassinoids and its glycosides from the seeds exhibited various pharmacological activity at low doses. Aims of study The aim of the present study is to evaluate the repeated dose toxicity of the standardized aqueous extract administered daily for 30 days through oral administration at its effective hypoglycemia doses. Materials and methods The seeds were dried, ground and extracted in deionized water. A HPLC-photodiode array method was developed and validated for the standardization of both the hypoglycemia agents, namely bruceine D and E in aqueous extract. Both normoglycemia and streptozotocin (STZ)-induced diabetic rats were fed orally with 15, 30 and 60 mg/kg body weight of standardized aqueous extract. The blood glucose was measured at 0–8 h. In repeated dose toxicity, similar doses were administered orally to rats for 30 days. At the end of 30 days, the blood was withdrawn and subjected to biochemical and haematology analysis while organs were harvested for histology analysis. Results Oral administration of standardized aqueous extract exhibited a dose-response relationship in both the normoglycemia and STZ-induced diabetic rats. Daily oral administration of 15, 30 and 60 mg/kg standardized aqueous extract for 30 days to rats did not show signs to toxicity in its biochemical, haematology and histology analysis. Conclusion In conclusion, although the seeds were reported to contain compounds with various pharmacological activity, the daily oral administration to rats for 30 days do not showed signs of toxicity at its effective hypoglycemia doses. [ABSTRACT FROM AUTHOR]

Brucea javanica (L.) Merr, belonging to Simaroubaceae family, is one species of the genus Brucea. The seeds, roots, leaves, fruits, stems and twigs of this plant had been used as a folk medicine for the treatment of various types of diseases. It is reported that there are kinds of chemical components in B. javanica. The main chemical components of this plant include quassinoids, triterpenoids and alkaloids. In this review, we summarized the researches on the chemical components and listed the main compounds isolated from the B. javanica. [ABSTRACT FROM AUTHOR]

Phytochemical investigation of the stems from Brucea javanica led to the isolation of two new quassinoids, brujavanol C ( 1) and brujavanol D ( 2), together with six known compounds ( 3- 8). The chemical structures were elucidated by means of various spectroscopic methods. All the isolated compounds were evaluated for antimalarial activity against Plasmodium falciparum and compounds 6 and 7 exhibited the most potent activity against the K1 strain, with IC values of 1.41 and 1.06 μM, respectively. [ABSTRACT FROM AUTHOR]

Two new quassinoids, brujavanol A (1) and brujavanol B (2), along with five known quassinoids (3–7), were isolated from the roots ofBrucea javanica.Their structures were elucidated by spectroscopic methods. The antimalarial and cytotoxic activities of the isolated compounds were also assessed. Compounds1and2exhibited significantin vitrocytotoxicity against human oral cavity cancer (KB) cells with IC50values of 1.30 and 2.36 μg/ml, respectively, whereas compound3showed excellent antiplasmodial activity against thePlasmodium falciparumstrains, K1 (IC50 = 0.58 μg/ml). [ABSTRACT FROM PUBLISHER]

Background: Brucea javanica (B. javanica) seeds, also known as "Melada pahit" in Indo-Malay region are traditionally used to treat diabetes. The objective of this study was to determine antidiabetic, antioxidant and anti-inflammatory effects of B. javanica seeds on nicotinamide (NA)-streptozotocin (STZ) induced type 2 diabetic (T2D) rats and to analyze its chemical composition that correlate with their pharmacological activities. Methods: A hydroethanolic extract of B. javanica seeds was fractionated with n-hexane, chloroform and ethyl acetate. An active fraction was selected after screening for its ability to inhibit α-glucosidase and glycogen phosphorylase α (GP-α). Isolation and characterization were carried out by using column chromatography, NMR and LCMS/MS. All isolates were assayed for inhibition of GP-α and α-glucosidase. Antidiabetic effect of active fraction was further evaluated in T2D rat model. Blood glucose and body weight were measured weekly. Serum insulin, lipid profile, renal function, liver glycogen and biomarkers of oxidative stress and inflammation were analyzed after 4-week treatment and compared with standard drug glibenclamide. Results: Ethyl acetate fraction (EAF) exerted good inhibitory potential for α-glucosidase and GP-α compared with other fractions. Chromatographic isolation of the EAF led to the identification of seven compounds: vanillic acid (1), bruceine D (2), bruceine E (3), parahydroxybenzoic acid (4), luteolin (5), protocatechuic acid (6), and gallic acid (7). Among them, Compound (5) was identified as the most potent inhibitor of GP-α and α-glucosidase and its GP-α inhibitory activity (IC50 = 45.08 µM) was 10-fold higher than that of caffeine (IC50 = 457.34 µM), and α-glucosidase inhibitory activity (IC50 = 26.41 µM) was 5.5-fold higher than that of acarbose (IC50 = 145.83 µM), respectively. Compounds (4), (6), and (7) inhibited GP-α activity in a concentration-dependent manner with IC50 values of 357.88, 297.37, and 214.38 µM, and their inhibitory effect was higher than that of caffeine. These compounds exhibited weak potency on α-glucosidase compared with acarbose. Compounds (1), (2), and (3) showed no inhibition on both GP-α and α-glucosidase. In vivo study showed that EAF treatment significantly reduced blood glucose level, increased insulin and glycogen contents, decreased markers of oxidative stress and inflammation, and lipid levels in T2D rats compared with untreated group. Conclusions: The EAF has potential therapeutic value for the treatment of T2D via acting as GP-α and α-glucosidase inhibitors by improving hepatic glucose and carbohydrate metabolism, suppressing oxidative stress, and preventing inflammation in T2D rats. According to the results, the efficacy of EAF could be due to the presence of luteolin along with synergistic effect of multiple compounds such as parahydroxybenzoic acid, protocatechuic acid, and gallic acid in B. javanica seeds. [ABSTRACT FROM AUTHOR]

Brucea javanica, a Chinese herbal medicine, combined with conventional anticancer modalities, has been widely used for treatment of various cancers. Based on researches over the last decades, authors briefly summarized its active constituents, molecular mechanisms and clinical application for cancer treatment. [ABSTRACT FROM AUTHOR]

A green fluorescent protein (GFP)-tagged pepper mottle virus (PepMoV) based leaf-disc method and systemic host method were developed to identify antiviral agents. Preliminary experiments using a PepMoV-GFP based leaf-disc method led to the isolation of five quassinoids, including brusatol ( 1 ), bruceantin ( 2 ), brucein A ( 3 ), bruceantinol ( 4 ), and brucein B ( 5 ), from the CH 3 OH extract of Brucea javanica . All isolated compounds exhibited inactivation effects in systemic host plants, and compounds 3 and 4 were potent, with a minimum inhibitory concentration of 10 μ M. Furthermore, compound 3 was found to have a protective effect at the tested concentration of 40 μ M. [ABSTRACT FROM AUTHOR]