The complementary and alternative roles of elemene injection in cancer: An umbrella review.

BACKGROUND: In the past, many meta-analyses (MAs) suggested that elemene injection (EI) played a complementary and alternative role in cancer treatment. However, some results were contradictory and a lot of evidences weren't classified. Thus, their clinical guidance effect was very limited. METHODS: Two reviewers independently retrieved 8 databases from their origin to May 19, 2023 and appropriate MAs were taken into consideration. A pooled analysis was conducted to merge results extracted from trials of included MAs. The methodological quality of MAs and the evidence certainty of pooled results were assessed. RESULTS: 31 MAs were taken into analysis with poor methodological quality. The main weaknesses were in the areas of heterogeneity analysis, bias risk, and literature selection. According to the present evidence, on the one hand, compared with conventional treatment (CT) alone, EI combined with CT may significantly enhance short-term or long-term efficacy and reduce adverse reactions caused by CT in multiple cancers. On the other hand, using EI alone also can improve ORR in the malignant (pleural) effusion and lessen the recurrence rate in bladder cancer obviously with fewer adverse reactions compared with CT alone. However, this evidence was rated as moderate to very low certainty mainly due to the risk of bias in clinical trials. CONCLUSION: EI may be a viable medication for the treatment of cancer although more convincing trials are still required to demonstrate its alternative and complementary benefits. Besides, it seems to have a broad potential for further development in immunotherapy, drug delivery technique, and predictive factor.

Prevalence of inappropriateness of elemene injection for hospitalized cancer patients: a multicenter retrospective study.

Background: Elemene injection could provide clinical benefit for the treatment of various cancers, but the clinical evidence is weak. Thus, its wide use in China has raised concerns about the appropriateness of its use. Methods: This was a multicenter retrospective study to evaluate the prevalence of inappropriateness of elemene injection for hospitalized cancer patients. Patients who met the inclusion criteria were retrospectively included, and demographic characteristics were extracted from the hospital information systems. The inappropriateness of elemene injection use was assessed using the preset criteria, and the prevalence was calculated. Multivariate logistic analysis was applied to identify any factors associated with inappropriate use. Results: A total of 275 patients were included in the analysis. The median age was 62 years, and 30.9% were females. The most common cancer was lung cancer (24.0%), and 68.2% of the patients were receiving chemotherapy. The overall prevalence of inappropriateness was 61.8%. The most common reason for inappropriateness was inappropriate indications, and the second was inappropriate doses. Age and oncological department were significant risk factors associated with inappropriate use, while lung cancer, liver cancer and admission to cardiothoracic surgery were associated with a low risk of inappropriate use. Conclusion: The prevalence of inappropriateness among hospitalized elemene injection users was high. More efforts, especially those to improve the appropriateness of indications, should be made to improve the rational use of elemene, as well as other complementary medicines. Physicians should take caution to avoid inappropriate use when prescribing drugs with limited clinical evidence.

Elemene Injection Overcomes Paclitaxel Resistance in Breast Cancer through AR/RUNX1 Signal: Network Pharmacology and Experimental Validation.

BACKGROUND: Paclitaxel (PTX) is a cornerstone chemotherapy for Breast Cancer (BC), yet its impact is limited by emerging resistance. Elemene Injection (EI) has shown potential in overcoming chemotherapy resistance. However, the efficacy by which EI restores PTX sensitivity in BC and the implicated molecular mechanism remain uncharted. METHODS: Network pharmacology and bioinformatic analysis were conducted to investigate the targets and mechanisms of EI in overcoming PTX resistance. A paclitaxel-resistant MCF-7 cell line (MCF-7PR) was established. The efficacy of EI and/or PTX in inhibiting cell viability was evaluated using sulforhodamine B assay, while cell proliferation was assessed using EdU staining. Furthermore, protein and gene expression analysis was performed through Western blotting and qPCR. RESULTS: The EI containing three active components exhibited a multifaceted impact by targeting an extensive repertoire of 122 potential molecular targets. By intersecting with 761 differentially expressed genes, we successfully identified 9 genes that displayed a direct association with resistance to PTX in BC, presenting promising potential as therapeutic targets for the EI to effectively counteract PTX resistance. Enrichment analysis indicated a significant correlation between these identified targets and critical biological processes, particularly DNA damage response and cell cycle regulation. This correlation was further substantiated through meticulous analysis of single-cell datasets. Molecular docking analysis revealed robust binding affinities between the active components of the EI and the identified molecular targets. Subsequently, in vitro experiments unequivocally demonstrated the dose- and time-dependent inhibitory effects of the EI on both PTX-resistant and sensitive BC cell lines, effectively mitigating the resistance phenotype associated with PTX administration. Furthermore, our findings have indicated EI to effectively suppress the protein expression levels of AR and RUNX1 in MCF-7 and MCF-7PR cells under PTX treatment, as well as downregulate the mRNA expression levels of stem-like properties' markers, KLF4 and OCT4, in these cell lines. CONCLUSION: Elemene Injection (EI) application has exhibited a significant capability to mitigate PTX resistance in BC, which has been achieved through targeted suppression of the AR/RUNX1 axis, revealing a key strategy to overcome chemotherapeutic resistance.

The effect of beta-elemene on alpha-tubulin polymerization in human hepatoma HepG2 cells.

OBJECTIVE: To investigate the impact of beta-elemene injection on the growth and alpha-tubule of human hepatocarcinoma HepG2 cells. METHODS: Cell proliferation was assessed by MTT assay. Cell cycle distribution was detected by flow cytometry (FCM). The mRNA expression of alpha-tubulin was measured by RT-PCR. Western blot analysis was used to determine protein expression of alpha-tubulin and the polymerization of tubulin. RESULTS: Beta-elemene injection inhibited HepG2 cells proliferation in a dose- and time-dependent manner; FCM analysis indicated beta-elemene injection induced cell cycle arrested at S phase. RT-PCR and western-blot analysis showed that beta-elemene injection down-regulated alpha-tublin at both mRNA and protein levels, presenting a dose-dependent manner. Moreover, beta-elemene injection reduced the polymerization of microtubules in a dose-dependent manner. CONCLUSIONS: Beta-elemene injection can inhibit the proliferation of hepatoma HepG2 cells and induce cell apoptosis, the mechanism might be partly related to the down-regulation of alpha-tubulin and inhibition of microtubular polymerization.

Effect of Network-Based Positive Psychological Nursing Model Combined With Elemene Injection on Negative Emotions, Immune Function and Quality of Life in Lung Cancer Patients Undergoing Chemotherapy in the Era of Big Data.

Background: With the development of big data, big data interpenetrate in every person's life. Health care is no exception to this trend, especially in regard to nursing analytics. The data that is analyzed and leveraged in this field is gathered from a variety of sources, including electronic health records (EHRs), medical histories, provider notes and mobile applications, creating an accumulation of personalized health information around each individual. Objective: To explore the effect of the network-based positive psychological nursing model combined with elemene injection on negative emotions, immune function and quality of life (QOL) in patients with lung cancer (LC) undergoing chemotherapy. Methods: The clinical data of 90 LC patients who underwent chemotherapy in our hospital from December 2020 to December 2021 were retrospectively analyzed, and the patients were equally split into experimental group (EG) and control group (CG) according to the order of enrollment. The patients in CG received routine nursing intervention during chemotherapy, while those in EG received the network-based positive psychological nursing model combined with elemene injection to compare negative emotions, immune function and quality of life (QOL) between the two groups. Results: Compared with CG, EG had notably higher immune function indexes (P < 0.001), lower serum VEGF and MMP-2 levels (P < 0.001), lower HAMA and HAMD scores (P < 0.05), and higher scores of PTGI, physiological function, psychological function, social function and physical function (P < 0.001). Conclusion: The network-based positive psychological nursing model combined with elemene injection is a reliable method to enhance the immune function and QOL of LC patients undergoing chemotherapy and alleviate their negative emotions, which has a high clinical application value.

Beta-Elemene Reduces the Malignancy of Non-Small Cell Lung Cancer by Enhancing C3orf21 Expression.

BACKGROUND: Beta-elemene has potent anti-tumor effect, but its anti-tumor mechanism remains unclear. Chromosome 3 open reading frame 21 (C3orf21) acts as a tumor suppressor. This study tested whether the anti-tumor effect of beta-elemene was associated with modulating C3orf21 expression in non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: The impact of beta-elemene on C3orf21 expression in NSCLC cells was quantified. The stable C3orf21 silencing A549 and over-expressing PC-9 cells were established and their effects on the beta-elemene-attenuated proliferation, wound healing and invasion of NSCLC cells as well as the expression of key regulators and signal events were determined. RESULTS: Beta-elemene significantly up-regulated C3orf21 expression in NSCLC cells. Beta-elemene treatment significantly attenuated the proliferation, wound healing and invasion of NSCLC cells, which were significantly mitigated by C3orf21 silencing, but enhanced by C3orf21 over-expression. Similar patterns of beta-elemene-modulated cyclinD1, c-Myc, COX2, MMP2, MMP9, VEGF, PTEN and Notch1 expression were detected in NSCLC cells. CONCLUSIONS: Such data indicated that beta-elemene treatment attenuated the malignancy of NSCLC cells by up-regulating C3orf21 expression. Our findings may provide new mechanisms underlying the pharmacological action of beta-elemene.

Elemene injection as adjunctive treatment to platinum-based chemotherapy in patients with stage III/IV non-small cell lung cancer: A meta-analysis following the PRISMA guidelines.

BACKGROUND: Elemene injection is an anticancer Chinese patent medicine that is widely used for the treatment of advanced lung cancer. Its active ingredients are ß-, γ- and δ-elemene, which are extracted from Curcumaaromatica Salisb. (Curcumawenyujin Y.H. Chen & C. Ling). PURPOSE: To evaluate the effects of Elemene injection as adjunctive treatment to platinum-based chemotherapy (PBC) in patients with stage III/IV non-small cell lung cancer. STUDY DESIGN: A systematic review and meta-analysis of randomized clinical trials (RCTs). MATERIALS AND METHODS: A systematic review and meta-analysis were conducted following the PRISMA (Preferred Reported Items for Systematic Review and Meta-analysis) guidelines. Analyses were performed using Review Manager 5.3, Comprehensive Meta-Analysis 3.0 and Trial Sequential Analysis software. All RCTs comparing Elemene injection combined with PBC vs. PBC alone were selected and assessed for inclusion. The disease control rate (DCR) was defined as the primary endpoint, and the objective Response rate (ORR), survival rate, quality of life (QOL), cellular immune function and toxicities were the secondary outcomes. RESULTS: 15 RCTs recruiting 1,410 patients with stage III/IV NSCLC were included. The methodological quality of most included trials was low to moderate. Compared with PBC alone, Elemene injection plus PBC can improve DCR (RR = 1.23, 95% CI 1.16 to 1.31, p < 0.00001), ORR (RR = 1.62, 95% CI 1.44 to 1.82, p < 0.00001), 1- and 2-year survival rates (RR = 1.33, 95% CI 1.11 to 1.59, p = 0.002; RR = 1.73, 95% CI 1.21 to 2.46, p = 0.002, respectively), QOL (RR = 1.91, 95% CI 1.58 to 2.32, p < 0.00001), CD4+T cell counts (WMD = 10.43, 95% CI 8.25 to 12.62, p < 0.00001), and the CD4+/CD8+ratio (WMD = 0.78, 95% CI 0.42 to 1.14, p < 0.0001) and can reduce severe toxicities by 58% (RR = 0.42, 95% CI 0.34 to 0.52, p < 0.00001). CONCLUSION: Elemene injection is a safe and effective adjunctive treatment to platinum-based chemotherapy in patients with stage III/IV NSCLC. Elemene injection can improve clinical efficacy, enhance cellular immune function and alleviate the toxicity of chemotherapy. High-quality RCTs with significant survival outcomes and longer follow-ups are warranted to confirm the results further.

[Severe Adverse Reactions Induced by the Chest Injection of Elemene: 
An Analysis of 7 Cases].

BACKGROUND: Malignant pleural effusion (MPE) refers to pleural effusion which arises from primary malignant tumor of pleura or other pleural metastatic tumors. Injection of elemene in chest makes good effect on the treatment of MPE, and is widely used in clinic. Adverse effects also exist, but the severe adverse effects and relevant managements are rarely reported. The aim of this study is to observe the adverse reactions induced by the treatment of malignant pleural effusion through elemene injection and to explore the solutions. METHODS: A retrospective analysis was made on 14 cases of patients receiving intra-pleural injections with elemene, and the incidence of severe adverse reactions of 7 cases were disscussed in detail. RESULTS: Most of the severe adverse reactions caused by elemene were severe chest pain, dyspnea, wheezing, clouding of consciousness and coagulopathy. CONCLUSIONS: Strict screening, full preprocessing and close monitoring are necessary to prevent serious adverse reactions caused by elemene injection in the treatment of malignant pleural effusion.

Severe Adverse Reactions Induced by the Chest Injection of Elemene: An Analysis of 7 Cases / 中国肺癌杂志

BACKGROUND@#Malignant pleural effusion (MPE) refers to pleural effusion which arises from primary malignant tumor of pleura or other pleural metastatic tumors. Injection of elemene in chest makes good effect on the treatment of MPE, and is widely used in clinic. Adverse effects also exist, but the severe adverse effects and relevant managements are rarely reported. The aim of this study is to observe the adverse reactions induced by the treatment of malignant pleural effusion through elemene injection and to explore the solutions.@*METHODS@#A retrospective analysis was made on 14 cases of patients receiving intra-pleural injections with elemene, and the incidence of severe adverse reactions of 7 cases were disscussed in detail.@*RESULTS@#Most of the severe adverse reactions caused by elemene were severe chest pain, dyspnea, wheezing, clouding of consciousness and coagulopathy.@*CONCLUSIONS@#Strict screening, full preprocessing and close monitoring are necessary to prevent serious adverse reactions caused by elemene injection in the treatment of malignant pleural effusion.

Efficacy and Safety of Elemene Injection Combined with Chemotherapy in the Treatment of Gastric Carcino-ma:A Meta-analysis / 中国药房

OBJECTIVE:To systematically review the efficacy and safety of Elemene injection combined with chemotherapy in the treatment of gastric carcinoma,and provide evidence-based reference for clinical treatment. METHODS:Retrieved from CBM, CJFD,VIP Database,Wanfang Database,Medline,EMBase,Cochrane Library and American Medical Association Database,ran-domized clinical trials(RCT)about Elemene injection combined with chemotherapy in the treatment of gastric carcinoma were col-lected,Meta-analysis was performed by using Rev Man 5.3 software after data extracting and quality evaluating by Cochrane 5.1.0. RESULTS:Totally 7 RCTs were enrolled,involving 434 patients. Results of Meta-analysis showed recent efficacy [RR=1.38,95%CI(1.14,1.67),P=0.001] and improvement rate of life quality [RR=1.36,95% CI(1.15,1.60),P<0.001] of Elemene injection combined with chemotherapy in the treatment of gastric carcinoma were significantly higher than only chemotherapy. The incidence of Ⅲ-Ⅳ leukemia inhibition [RR=0.58,95%CI(0.37,0.91),P=0.02],incidence of Ⅰ-Ⅳ hemoglobin inhibition [RR=0.76,95%CI(0.60,0.95),P=0.02],incidence of Ⅰ-Ⅳ platelet inhibition [RR=0.69,95%CI(0.52,0.91),P<0.001] and Ⅲ-Ⅳ[RR=0.53, 95%CI(0.30,0.93),P=0.03] and incidence of Ⅰ-Ⅳ neurotoxicity[RR=0.69,95%CI(0.52,0.93),P=0.01] in test group were sig-nificantly lower than control group,the differences were statistically significant. CONCLUSIONS:Both efficacy and safety of El-emene injection combined with chemotherapy in the treatment of gastric carcinoma are good.

Review of Elemene Injection in Treating Malignant Pleural Effusions and Ascites / 中国中医药信息杂志

Malignant pleural effusions and ascites are common complications in various cancers, which are difficulties in clinical treatment. Elemene injection, with the main ingredient ofβ-elemene, extracted from Chinese herbal medicine Curcumae Rhizoma, has broad-spectrum antitumor activity by inhibiting proliferation and inducing apoptosis in several types of solid tumor cells. This article reviewed the clinical experience of Chinese scholars in treating malignant pleural effusions and ascites with elemene injection.