Effect of Brucea javanica Oil on the Toxicity of ß-Cypermethrin Emulsifiable Concentrate Formulation.

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% ß-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 ß-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% ß-cypermethrin EC (ß-CYP EC-1), 4.5% ß-cypermethrin EC with BJO (ß-CYP EC-2), and 4.5% ß-cypermethrin EC without BJO (ß-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. ß-CYP EC-2 demonstrated superior wetting properties on cabbage leaves (the wetting performance of ß-CYP EC-2 emulsion on cabbage leaves is 2.60 times that of the ß-CYP EC-1 emulsion), heightened insecticidal activity against the third larvae of Plutella xylostella [diamondback moth (DBM)] [the insecticidal activity of the ß-CYP EC-2 emulsion against the third larvae of DBM is 1.93 times that of the ß-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.

Brucea javanica derived exosome-like nanovesicles deliver miRNAs for cancer therapy.

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.

Intrapleural injection of brucea javanica oil emulsion provided a long-term benefits in patient with malignant pleural effusion from pleural mesothelioma: A case report.

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.

Exploring the Mechanism of Brucea Javanica against Ovarian Cancer based on Network Pharmacology and the Influence of Luteolin on the PI3K/AKT Pathway.

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, ß-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.

Inhibition of Hepatitis B Virus (HBV) replication and antigen expression by Brucea javanica (L.) Merr. oil emulsion.

Introduction: The seeds of Brucea javanica (L.) Merr. (BJ) have been traditionally used to treat various types of cancers for many years in China. In this study, we systematically investigated a BJ oil emulsion (BJOE) produced from BJ seeds with the purpose of evaluating its antiviral effect against hepatitis B virus (HBV). Methods: HepG2.215 (a wild-type HBV cell line), HepG2, and Huh7, transfected with wildtype (WT) or lamivudine-resistance mutant (LMV-MT) HBV replicon plasmids, were treated with different doses of BJOE and then used for pharmacodynamic evaluation. Cell viability was determined using CCK8 assay. The levels of HBsAg/HBeAg in cell cultured supernatant, HBcAg in cell lysis solution, and HBV DNA in both were evaluated. Results: BJOE at ≤5 mg/ml was nontoxic to carcinoma cell lines, but could significantly inhibit WT/LMV-MT HBV replication and HBs/e/c antigen expression in a dose-dependent manner by upregulating interleukin-6 (IL-6), demonstrating that it possesses moderate anti-HBV activity. As one of the major components of BJOE, bruceine B was found to play a dominant role in IL-6 induction and HBV inhibition. Discussion: Our results demonstrated that BJOE suppressed HBV replication by stimulating IL-6, indicating that it has promising clinical therapeutic potential for both WT and LMV-MT HBV.

Brucea javanica oil inhibits tongue squamous cell invasion and metastasis by regulating miR-138-EZH2 pathway.

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.

Brusatol: A potential sensitizing agent for cancer therapy from Brucea javanica.

Cancer is currently the most important problem endangering human health. As antitumor drugs have always been the most common methods for treating cancers, searching for new antitumor agents is of great significance. Brusatol, a quassinoid from the seeds of Brucea javanica, exhibits a potent tumor-suppressing effect with improved disease outcome. Studies have shown that brusatol not only shows potential tumor inhibition through multiple pharmacological effects, such as promoting apoptosis and inhibiting metastasis but also exhibits significant synergistic antitumor effects in combination with chemotherapeutic agents and overcoming chemical resistance in a wide range of cancer types. In this paper, the antitumor effects and mechanisms of brusatol were reviewed to provide evidence that brusatol has the exact antitumor efficacy of chemotherapeutic agents and show the potential of brusatol to be developed as a promising antitumor drug.

Hyperthermia-sensitive Liposomes Containing Brucea Javanica Oil for Synergistic Photothermal-/Chemo-Therapy in Breast Cancer Treatment.

INTRODUCTION: High mortality and limited therapeutic efficacy of clinical treatment make breast cancer a stubborn disease in women. The hypovascular issue is the main challenge needed to be overcome in breast cancer treatment. METHODS: For this purpose, hyperthermia-sensitive liposomes containing indocyanine green (ICG) and brucea javanica oil (BJO) (LP(BJO/ICG)) were constructed for near-infrared (NIR) laser-induced photothermal- /chemo-antitumor therapy. ICG, an FDA-approved photothermal agent, was employed in this study to perform photothermal therapy (PTT) effect as well as relieve hypovascular conditions in breast cancer tissue. RESULTS: BJO triggered release from the hyperthermia-sensitive LP (BJO/ICG) due to disassembly of liposomes under the PTT effect caused by ICG under NIR laser irradiation. It was found that mice in LP (BJO/ICG) group showed the slowest tumor growth under NIR laser irradiation, illustrating the strongest antitumor effect among all groups. CONCLUSION: This responsive-release drug delivery platform can be a promising candidate for the treatment of breast cancer.

Brucea javanica oil emulsion significantly improved the effect of anti-programmed cell death protein-1 immunotherapy.

BACKGROUND: Brucea javanica oil (BJO) is the active substance extracted from the dry and mature fruit of Brucea javanica. Its pharmaceutical preparation, BJO emulsion (BJOE), is one of the most widely studied traditional Chinese medicine preparations for the treatment of malignancy. However, the unrevealed anti-tumor mechanism immensely limits further development of BJOE. PURPOSE: In this study, we delved into the anti-tumor mechanism of commercial BJOE, including its influence on the tumor microenvironment (TME) and the treatment effect when combined with anti-programmed cell death protein-1 (PD-1) therapy. METHODS: The cytotoxicity of BJOE was tested in different cells in vitro, and a Förster resonance energy transfer system was also constructed to predict the release behavior of BJOE in vivo. Then, a B16 melanoma mouse model was used to explore the combination of BJOE and anti-mouse PD-1 antibody therapy. In addition, mass cytometry was used to test the impact of both drugs on the TME. RESULTS: Out data revealed that BJOE did not directly kill tumor cells in vitro. However, BJOE was mainly released at the tumor site, converting an immunosuppressive TME into an immune-activated state, and its combination with anti-PD-1 therapy significantly inhibited the growth of melanoma and prolonged the survival time of the mice due to an increase in cytotoxic T lymph (CD8+ T) and helper/inducible T lymph (CD4+ T) cells in lymph nodes and tumors. CONCLUSIONS: Our work explored the anti-tumor mechanism of commercial BJOE and the regulation of cytokines by BJOE when it was combined with anti-PD-1 therapy in vivo. The combination of these therapies could increase the numbers of CD4+ T-cells, CD8+ T-cells, and effective natural killer cells and the ratio of MI/M2 macrophages in tumor tissues, promoting inflammatory activity and enhancing the anti-tumor effect. This study provides a theoretical basis for advancing the modern development of traditional Chinese medicine preparations and stands as a reference for clinically improving the efficacy of PD-1 antibodies.

Brujavanoids A-U, structurally diverse apotirucallane-type triterpenoids from Brucea javanica and their anti-inflammatory effects.

Extensive phytochemical investigation on the methanol extract of the inflorescences, twigs, and leaves of Brucea javanica led to the isolation and identification of 27 triterpenoids, including 21 previously undescribed ones, named brujavanoids A-U (1-21). Their structures were determined based on comprehensive spectroscopic analysis and single-crystal X-ray diffraction. Of these compounds, brujavanoid A (1) represents the first apotirucallane-type triterpenoid with a novel 19(10 â†’ 9)abeo motif, and brujavanoids B and C (2-3) are the first apotirucallane-type triterpenoids with a rarely occurring 14-hydorxy-15,16-epoxy fragment. All the isolates were evaluated for their anti-inflammatory effect in an LPS-activated RAW264.7 cells model. Furthermore, the most active one, brujavanoid E (5), can suppress the transcriptional expression of typical pro-inflammatory mediators and inhibit the nuclear translocation of NF-κB p65 in the LPS- activated RAW264.7 cells.

A New C22-Quassinoid with Anti-Pancreatic Adenocarcinoma Activity from Seeds of Brucea javanica.

An undescribed C22-quassinoid named sergeolide A (1) and fifteen known quassinoids (2-16) were obtained from the seeds of Brucea javanica (Simaroubaceae). All chemical structures were established based on spectroscopic data and X-ray diffraction analysis. Sergeolide A (1) is the first example of a naturally occurring C22-quassinoid bearing a butenolide group fused the A ring of the bruceolide skeleton from Brucea genus. And this is the first report of the NMR data for desmethyl-bruceines B (2) and C (3) and the crystal structure for bruceolide (11). In addition, all isolates were evaluated for their anti-pancreatic adenocarcinoma activity by measuring the growth inhibitory of the MIA PaCa-2 cell lines. Consequently, compounds 1, 7-10, and 12-16 exhibited potent anti-pancreatic cancer activity in vitro (IC50 =0.054∼0.357 µM).

Efficacy and safety of Brucea javanica oil emulsion injection as adjuvant therapy for cancer: An overview of systematic reviews and meta-analyses.

BACKGROUND: In China, Brucea javanica oil emulsion injection (BJOEI) has been used as adjuvant therapy to treat cancer for many years. Many systematic reviews (SRs) or meta-analyses (MAs) were published to evaluate its efficacy and safety. Nevertheless, uneven quality made it difficult to reach a consensus and there has been no specific review to integrate the evidence of BJOEI for cancer at present. Therefore, a comprehensive evidence map is needed to guide clinicians. PURPOSE: We, for the first time, conducted an overview to assess the SRs/MAs of BJOEI, and provided a comprehensive evidence map to guide clinicians. Besides, this study provided a promising direction for future research to promote the generation of advanced evidence. STUDY DESIGN: An overview of SRs or MAs. METHODS: The pre-defined search strategies were applied to 8 databases. Suitable SRs/MAs were included according to the inclusion and exclusion criteria. Methodological quality, reporting quality, and risk of bias were assessed. An evidence map was conducted to show the situation of clinical evidence. RESULTS: 27 SRs/MAs in 7 cancer types were included in this overview. The main problems of SRs/MAs were concentrated on the following aspects: without registration or protocol, lacking gray literature retrieval and a list of excluded studies, incomplete description in the literature retrieval strategy or the methods of merging results, the bias of each synthetic result, less exploration in heterogeneity or publication bias, deficiencies in assessing evidence quality and less description in conflict, funding or access to relevant information. Based on the rules of GRADE, the evidence quality of 154 items in 27 SRs/MAs was defined as moderate quality (103 items), low-quality (44 items), and very low-quality (7 items). Especially, risk of bias (154 items), imprecision (27 items), inconsistency (20 items), and publication bias (9 items) were the main downgrading factors. CONCLUSION: BJOEI may be a promising adjuvant therapy for treating cancer, especially in the digestive system. However, high-quality SRs/MAs are expected to be carried out to improve the reliability of the above conclusion in the future.

Brusatol inhibits the growth of renal cell carcinoma by regulating the PTEN/PI3K/AKT pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Brucea javanica (L.) Merr. is a medicinal herb used in China for the prevention and treatment of diseases such as cancer and malaria. Brusatol was isolated from the seeds of Brucea javanica (L.) Merr, brusatol has a wide range of pharmacological effects, including anti-inflammation and anti-cancer effects. AIM OF THE STUDY: Renal cell carcinoma is one of the most common urinary system tumours and seriously threatens the lives of patients. We aimed to study the mechanism by which brusatol regulates the growth of renal cancer cells through the PTEN/PI3K/AKT signalling pathway. MATERIALS AND METHODS: We chose the A498, ACHN, and OSRC-2 cell lines as experimental models. After intervention with brusatol, CCK-8 experiments and plate cloning experiments were used to detect the cell proliferation ability; flow cytometry was used to detect the cell apoptosis rate; scratch and transwell invasion assays were used to detect the cell migration and invasion ability; qRT-PCR and Western blotting was used to detect PTEN, p-PI3K/PI3K, p-AKT/AKT, Bax, Bcl2, E-cadherin, N-cadherin, and vimentin relative expression. Then, we knocked down the PTEN gene in the three cell lines and again tested the proliferation, apoptosis, migration, and invasion capabilities of each group of cells. RESULTS: Brusatol significantly inhibited the proliferation, migration and invasion and increased the rate of apoptosis of the A498, ACHN, and OSRC-2 cell lines, and brusatol significantly increased the expression of PTEN mRNA and protein, and inhibited the expression of p-PI3K and p-AKT. Moreover, knockdown of PTEN significantly reduced the inhibitory effect of brusatol on the growth of renal cancer cells. CONCLUSION: Our research results show that brusatol has an effective inhibitory effect on the growth of A498, ACHN, and OSRC-2 renal cancer cell lines, and this effect is likely to be produced by regulating the PTEN/PI3K/AKT signalling pathway.

Isolation, screening and identification of key components having intense insect repellent activity against Plodia interpunctella from four different medicinal plant materials.

BACKGROUND: Global warming and the indiscriminate use of pesticides have increased the propagation of the stored-product insect pests, leading to enormous losses in the agriculture and food industries. The most used insect repellents are synthetic derivatives; however, these have an adverse effect on human health as well as on the environment. Therefore, we attempted to find materials with insect repellent activity in natural products. The present study aimed to identify the single chemical component with intense insect repellent activity in extracts from four different Oriental medicinal plant materials: (i) Anethum graveolens L. (dill) seeds; (ii) Artemisia capillaris Thunb. (capillary wormwood) leaves; (iii) smoked Prunus mume Siebold & Zucc. (mume) fruits; and (iv) Rhus javanica L. (galls). RESULTS: As a result of the bioassay-guided fractionation of each extract against the Plodia interpunctella, stored-product insect, the n-hexane fraction of dill seeds extract was confirmed as the optimal fraction between all of the fractions. In total, 32 chemical components were identified from the n-hexane fraction of dill seeds by gas chromatography-mass spectrometry analysis, and the two main components were dillapiole (47.51%) and carvone (26.76%). Of the two components, dillapiole was confirmed as the key component playing an essential role in insect repellent activity. CONCLUSION: Our study suggests that dillapiole has the potential to be used as a natural insect repellent for the control of P. interpunctella infestation in agricultural and food products during distribution and storage. © 2021 Society of Chemical Industry.

Efficacy of Aidi Injection and Brucea javanica Oil Emulsion Injection in Rectal Cancer during CapeOX Adjuvant Chemotherapy.

BACKGROUND: Adjuvant chemotherapy with CapeOX regimen is widely used in resected rectal cancer, which brings benefits to patients. But drug-related toxicities are severe during this process; thus, survival outcomes may potentially be affected. This study explored the efficacy of two Chinese herbal injections, Aidi injection (ADI) and Brucea javanica oil emulsion injection (BJOEI), as adjuvant drugs in CapeOX adjuvant chemotherapy on rectal cancer patients. METHODS: A total of 240 cases were enrolled in this retrospective study. 80 cases received CapeOX with ADI (the ADI group), 80 cases received CapeOX with BJOEI (the BJOEI group), and the rest 80 cases received CapeOX alone (the control group). After four cycles' chemotherapy, adverse reactions (ADRs) and quality of life (QOL) were analyzed. Then, patients received follow-up for at least one year, and the endpoint was disease-free survival (DFS). RESULTS: All patients completed at least four cycles' adjuvant chemotherapy. The incidence of leukopenia and thrombocytopenia was significantly lower in the ADI group; the incidence of nausea was significantly lower in the BJOEI group; the incidence of hand-foot syndrome was significantly lower in both the ADI group and BJOEI group. Significant difference was found in the control group regarding the Karnofsky Performance Status (KPS) scores prior and posttreatment. No difference was found among three groups regarding one-year DFS. CONCLUSION: As adjuvant drugs for rectal cancer during CapeOX chemotherapy, ADI shows advantages in decreasing leukopenia and thrombocytopenia, while BJOEI results better in remitting nausea. Both two CHIs had positive impacts on decreasing hand-foot syndrome and the maintenance of patients' QOL. It is worthy of further study and promotion for CHIs.

Bruceine D ameliorates the balance of Th1/Th2 in a mouse model of ovalbumin-induced allergic asthma via inhibiting the NOTCH pathway.

Allergic asthma is a heterogeneous inflammatory disorder triggered by inhaled allergens, leading to airflow obstruction, bronchial inflammation, and airway hyperresponsiveness (AHR). T helper (Th) 2 cell-mediated immune response and airway inflammation are the key features of allergic asthma. Bruceine D (BD) is a bioactive compound extracted from the seeds of Brucea javanica. The present study aimed to investigate the effects of increased doses of BD on AHR, secretion of Th1-/Th2-associated cytokines, and inflammatory cell infiltration in ovalbumin (OVA)-induced allergic asthma mice. The results showed that BD reduced OVA-induced inflammatory cell infiltration and bronchial hyperresponsiveness into the peribronchial tissues and perivascular areas. Mice treated with BD also showed significantly decreased expressions of Th2-associated cytokines (i.e., interleukin (IL)-4, IL-5, and IL-13) and elevated production of Th1-associated cytokines (i.e., interferon gamma and IL-2) following OVA stimulation. BD treatment dose-dependently inhibited OVA-induced accumulation of inflammatory cells in asthmatic mice. Further analysis revealed that OVA exposure upregulated pulmonary expressions of NOTCH signaling receptors, a group of transmembrane proteins that communicate signals upon binding to transmembrane ligands expressed on adjacent cells, while BD treatment significantly abolished OVA-induced activation of the NOTCH pathway. In conclusion, BD protected mice against OVA-induced allergic asthma by reducing AHR and restoring the Th1/Th2 balance through the NOTCH signaling pathway. Our findings highlighted the potential of BD as a therapeutic agent for allergic asthma.

Normalisation of human chorionic gonadotrophin (hCG) levels in a patient with partial molar pregnancy with a uterine mass without chemotherapy: impact of using herbal remedies.

OBJECTIVES: Level of ßhCG and the presence of any uterine mass of hydatidiform mole need a careful review or monitoring in order to prevent metastasis, provide an early treatment and avoid unnecessary chemotherapy. CASE PRESENTATION: A 36-year old fifth gravida patient who had a missed abortion was diagnosed as having a molar pregnancy with beta human chorionic gonadotrophin (ßhCG) level of 509,921 IU/L. Her lung field was clear and she underwent suction and curettage (S & C) procedure. However, after six weeks, AA presented to the emergency department with a massive bleeding, although her ßhCG level had decreased to 65,770 IU/L. A trans-abdominal ultrasound indicated the presence of an intra-uterine mass (3.0 × 4.4 cm). Nevertheless, her ßhCG continued to show a declining trend (8,426 IU/L). AA was advised to undergo a chemotherapy but she refused, citing preference for alternative medicine like herbs instead. She opted for an "at own risk" (AOR) discharge with scheduled follow up. Subsequently, her condition improved with her ßhCG showing a downward trend. Surprisingly, at six months post S & C, her ßhCG ameliorated to 0 IU/L with no mass detected by ultrasound. CONCLUSIONS: Brucea javanica fruits, Pereskia bleo and Annona muricata leaves can potentially be useful alternatives to chemotherapy and need further studies.

Pharmacokinetic study on bruceoside A revealed the potential role of quassinoid glycosides for the anticancer properties of Fructus Bruceae.

Bruceoside A, an abundant quassinoid glycoside in Fructus Bruceae, was chosen for the pharmacokinetic study. It is the first case report on the pharmacokinetic study of quassinoid glycosides so far. A sensitive, accurate, and repeatable UHPLC-MS/MS method was developed for the determination of bruceoside A and its major metabolite. The results showed bruceoside A could be transformed into the potent anticancer component brusatol in vivo, rather than its direct deglycosylated metabolite bruceosin. And the intestinal bacteria were proposed to take a potential role during such transformation. Based on the present study, it could be concluded that the quassinoid glycosides possessing weak activities in vitro could do contribution to the anticancer properties of Fructus Bruceae in vivo via transforming into more active metabolites.

Improved delivery of natural alkaloids into lung cancer through woody oil-based emulsive nanosystems.

Most antitumor ingredients found in nature have poor solubility. These ingredients are expected to have much better absorption and higher bioavailability than synthetic antitumor agents. Woody oil emulsive nanosystems carrying poorly soluble natural alkaloids were fabricated (evodiamine (EA) carried by fructus bruceae oil-based emulsive nanosystems, or EFEN). Fructus bruceae oil has two excipient-like properties (oil phase and stabilizer) that contribute to the formulation and one drug-like property (antitumor effects) that synergizes with the antitumor effect of EA. The properties of EFEN were compared with free EA, a blank nanoemulsion, an EA-loaded emulsive nanosystem, and a fructus bruceae oil-loaded emulsive nanosystem. For the first time, this suggests that increases in the sensitivity of lung cancer cells to poorly soluble natural alkaloids can be achieved by delivering drugs using woody oil-based emulsive nanosystems. In this study, woody oil-based emulsive nanosystems efficiently deliver poorly soluble natural alkaloids.

Simultaneous determination of aflatoxins B1, B2, G1, G2 in Fructus Bruceae by high-performance liquid chromatography with online postcolumn photochemical derivatization.

A simple, reliable, and highly sensitive method for the simultaneous determination of aflatoxin B1 , B2 , G1 , G2 in Fructus Bruceae was developed using high-performance liquid chromatography coupled to online postcolumn photochemical derivatization and fluorescence detection. Aflatoxins were first extracted by a methanol/water mixture and then cleaned up with an AflaTest™ immunoaffinity column. Different clean-up and derivatization methods were compared and optimized. The established method was extensively validated to show satisfactory performance of linearity (R(2) ≥ 0.9997), recovery (74.3-100.8%), and precision (RSDs ≤ 2.8%) for the investigated aflatoxins. This proposed method was also applied to 11 F. Bruceae samples and the results showed that 10 out of 11 were contaminated with aflatoxins ranging from 0.26 to 27.52 µg/kg and the occurrence of aflatoxin B1 , the most toxic one, was as high as 91% in all the samples, highlighting the severe contamination and the necessity to set legal limits for aflatoxins in F. Bruceae.