Efficacy and Safety of Brucea javanica Oil Emulsion Injection in the Treatment of Gastric Cancer: A Systematic Review and Meta-Analysis

Background: Gastric cancer (GC) is one of the most common digestive tract cancers and ranks fifth in the incidence of malignant tumors worldwide. Brucea javanica oil emulsion injection (BJOEI), a Chinese patent medicine extracted from Brucea javanica (Yadanzi in Chinese Pinyin), is widely used as an adjuvant treatment for GC in China. This systematic review and meta-analysis aimed to evaluate the available data on the efficacy and safety of BJOEI in the treatment of GC and assess the quality of the synthesized evidence.Methods: A comprehensive search was performed on PubMed, EMBASE, CENTRAL, Web of Science, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Wanfang database and Chinese Scientific Journals Database (VIP database), and other potential resources, such as the Chinese Clinical Trial Registry (ChiCTR) and ClinicalTrials.gov from their inception to July 31, 2021. Randomized controlled trials (RCTs) comparing the therapeutic effects of BJOEI combined with conventional therapy to those of conventional therapy alone were included. We used RevMan 5.3 for data analysis and quality evaluation of the included studies and assessed the evidence quality based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria.Results: Eighteen RCTs involving 1,210 patients were included, and the meta-analysis results demonstrated that compared with the control group (conventional therapy), the experimental group (BJOEI combined with conventional therapy) showed a significantly improved overall response rate (ORR) (risk ratio [RR] = 1.52, 95% CI: 1.36–1.69, P < 0.00001), clinical benefit rate (CBR) (RR = 1.17, 95% CI: 1.11–1.23, P < 0.00001), performance status (RR = 1.72, 95% CI: 1.46–2.01, P < 0.00001), and reduced incidence of the following adverse drug reactions (ADRs): neutropenia, leukopenia, nausea and vomiting, diarrhea, liver damage, hand-foot syndrome, and peripheral sensory nerve toxicity. Subgroup analysis showed that the BJOEI intervention could significantly improve the ORR and CBR in patients with GC when combined with FOLFOX4, XELOX, and other chemotherapeutics.Conclusion: The evidence presented in this study supports the fact that BJOEI combined with conventional chemotherapy provides a statistically significant and clinically important effect in the improvement of ORR, CBR, performance status, and ADR reduction in patients with GC. To further support this conclusion, more rigorously designed, large-scale, and multicenter RCTs are needed in the future.

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.

Efficacy and Safety of Brucea javanica Oil Emulsion Injection for Treating Gastric Cancer: A Protocol for a Systematic Review and Meta Analysis

Introduction. Brucea javanica oil emulsion injection (BJOEI) is an antitumor drug extracted from the traditional Chinese medicinal plant Brucea javanica, which has broad prospects as an adjuvant treatment for gastric cancer (GC); however, its efficacy and safety are still controversial. We plan to conduct a systematic review and meta-analysis to summarise the clinical efficacy and safety of BJOEI in the treatment of GC and provide credible evidence for the clinical application and subsequent studies of BJOEI. Methods and Analysis. This systematic review will include articles identified by electronically searching the following databases: PubMed, EMBASE, CENTRAL, Web of Science, the Chinese Biomedical Literature Database (CBM), the China National Knowledge Infrastructure (CNKI), Wanfang Database, and Chinese Scientific Journals Database (VIP Database) from inception to 31 July 2021. The primary outcomes of this research will be the clinical total effective rate, performance status, and adverse drug reactions (ADRs). The systematic review will be performed using RevMan 5 software. Finally, we will use the Grading of Recommendations Assessment, Development and Evaluation System (GRADE) to assess the quality of evidence. Ethics and Dissemination. Ethical approval is not required for literature-based studies. The results of this systematic review will be published in a peer-reviewed journal. PROSPERO registration number: CRD42021265646.

The Potential Anti-Inflammatory Effects of Brucea javanica (L.) Merr.

Inflammation is the initial response to acute and chronic tissue damage, which is characterized by redness, swelling, heat, and pain. Natural products derived from plants have specific pharmacological activity and minimal side effects. Brucea javanica is a plant that has an anti-inflammatory effect, this plant contains alkaloid and flavonoid compounds. Flavonoids have the ability to block cyclooxygenase and lipoxygenase while alkaloids as an anti-inflammatory are thought to work by inhibiting prostaglandin H2 PGH2 which is an inflammatory mediator. From the data obtained, there is no complete literature that reviews its use as an anti-inflammatory. The search databases used are as follows: Pubmed, ScienceDirect, and Google Scholar to study the anti-inflammatory activity of Brucea javanica. All recent research articles were published between 2010 to 2021. Based on eligibility, 4 studies were included in this study, consisting of 2 In vivo studies and 2 In vitro and In vivo studies. A series of pharmacological studies have reported that Brucea javanica can block the Nf-kB signaling pathway and decrease the production of inflammatory mediators. It has been reported to be able to inhibit the production of NO, PGE2, TNF-, IL-1β, IL-18IL-23, COX-2, NF-κB, IFN-γ, IL-6, the levels of MPO (Myeloperoxidase), reducing the edema and induce the production of the anti-inflammatory cytokine (IL-4, IL-10 and TGF-β). Brucea javanica also markedly activates Nrf2 expression suppressing the inflammatory response-mediated NLRP3 and NF-κB activation. In addition, the elevated mRNA expression of MMP-1, MMP-3 and RAGE was remarkably inhibited by Brucea javanica, while the mRNA expression of PPAR-γ was significantly enhanced. In vitro and in vivo studies strongly indicate that Brucea javanica has the potential as an anti-inflammatory.

Brusatol-Enriched Brucea javanica Oil Ameliorated Dextran Sulfate Sodium-Induced Colitis in Mice: Involvement of NF-κB and RhoA/ROCK Signaling Pathways

Brucea javanica oil (BJO) is beneficial for the treatment of ulcerative colitis (UC), and that quassinoids in particular brusatol are bioactive components. However, it is still uncertain whether or not other components in BJO, such as oleic acid and fatty acids, have an anti-UC effect. The present study is aimed at comparing the anti-UC effects between brusatol-enriched BJO (BE-BJO) and brusatol-free BJO (BF-BJO) and at exploring the effects and mechanisms of BE-BJO on colon inflammation and intestinal epithelial barrier function. Balb/C mice received 3% (wt/vol) DSS for one week to establish the UC model. Different doses of BE-BJO, BF-BJO, or BJO were treated. The result illustrated that BE-BJO alleviated DSS-induced loss of body weight, an increase of disease activity index (DAI), and a shortening of colon, whereas BF-BJO did not have these protective effects. BE-BJO treatment improved the morphology of colon tissue, inhibited the production and release of TNF-α, IFN-γ, IL-6, and IL-1β in the colon tissue, and reversed the decreased expressions of ZO-1, occludin, claudin-1, and E-cadherin induced by DSS but augmented claudin-2 expression. Mechanistically, BE-BJO repressed phosphorylation of NF-κB subunit p65, suppressed RhoA activation, downregulated ROCK, and prevented phosphorylation of myosin light chain (MLC) in DSS-treated mice, indicating that the protective effect of BE-BJO is attributed to suppression of NF-κB and RhoA/ROCK signaling pathways. These findings confirm that brusatol is an active component from BJO in the treatment of UC.