Author: Wang, Ying ; Wang, Qin ; Liu, Lei ; Gao, Mingyou ; He, Ying ; Tan, Chenfeng ; Peng, Yalan ; Zhang, Yonggang ; Dai, Zelei ; Li, Nian ; Song, Ningying ; Wang, Jun

AbstractAs a complementary and alternative therapy, traditional Chinese medicine (TCM) has been playing a significant role in gastric cancer treatment. Data from individual systematic reviews have not been comprehensively summarized, and the relationship between certain interventions and outcomes are ill‐defined. This study aimed to analyze the advantages of TCM interventions for gastric cancer by the method of evidence mapping. We searched PubMed, Embase, Web of Science, China National Knowledge Infrastructure, Chinese Scientific Journals Database, and Wanfang Database for systematic reviews of TCM treating gastric cancer up to December 31, 2023. We used Excel, Endnote 20, and Python software for the analysis of incorporated studies. We assessed the quality of included SRs by AMSTAR‐2 and performed evidence mapping including 89 SRs, 1648 RCTs and 122,902 patients, identifying 47 types of interventions and 39 types of outcomes. From a visual overview, we displayed that most SRs reported beneficial effects in improving short‐ and long‐term survival, myelosuppression, and immune function, even though the quality of evidence was generally low. The benefits of Brucea javanica Oil Emulsion Injection, ShenQiFuZheng Injection, XiaoAiPing, Astragalus‐Containing TCM and Guben Xiaoji Therapy were found the most solid in corresponding aspects. Our findings suggest that although more rigorous clinical trials and SRs are needed to identify the precise effectiveness, integrating such evidence into clinical care of gastric cancer is expected to be beneficial.

06 Oct 2023·Medicine

Efficacy and safety of Xiao-ai-ping injection add-on therapy to chemotherapy in patients with non-small cell lung cancer: A systematic review and meta-analysis

Review

Author: Xu, Jianan ; Lin, Minghao ; Li, Andong ; Li, Zhenyu ; Liu, Shilin ; Yuan, Chengbo ; Zhang, Hui ; Wang, Tan ; Guo, Lijiao

Background:Xiao-ai-ping injection (XAPI) combined with chemotherapy has potential efficacy and less side effects in the treatment of non-small cell lung cancer (NSCLC). At present, there are many clinical studies on XAPI combined with chemotherapy in the treatment of NSCLC, but the results are different. The purpose of this study was to evaluate the efficacy and safety of XAPI combined with chemotherapy in the treatment of NSCLC by meta-analysis system.Methods:The databases to be searched include PubMed, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Wanfang database, Chinese Scientific Journal Database, and so on. In addition, relevant journals and magazines will manually search in various fields as supplements. The search date is set from the establishment of the database until July 8, 2023. The 2 researchers will use Endnote X9 software for literature screening and data extraction and independently evaluate the quality. We then assessed the quality and risk of inclusion in the study and observed outcome indicators.Results:A total of 28 trials were included in this study, 1947 patients with NSCLC (974 receiving XAPI combined chemotherapy and 973 receiving chemotherapy alone). The results of meta-analysis showed that: Objective tumor response rate of NSCLC (P < .00001). Improvement in Karnofsky performance score of NSCLC (P < .00001). Quality of life score of NSCLC (P < .00001). The result of CD3 + (P < .00001). The result of CD4 + (P < .00001). The result of CD8 + (P < .00001). The result of CD4+/CD8 + (P = .0001). Leukopenia (P < .00001). Thrombocytopenia (P < .00001). Hemoglobin decrease (P < .00001). Liver function (P = .04). Nausea and vomiting (P < .00001).Conclusion:Our meta-analyses demonstrated that XAPI adjunct with chemotherapy can improve the patient quality of life, reduce adverse reactions, and enhanced immune function, the treatment is effective and high safety. Which suggests that it might be used for NSCLC. However, a large sample of randomized controlled trials are needed to further study the long-term efficacy of XAPI.

01 Oct 2023·Journal of Ethnopharmacology

Marsdenia tenacissima extract induces endoplasmic reticulum stress-associated immunogenic cell death in non-small cell lung cancer cells through targeting AXL

Article

Author: Han, Shu-Yan ; Yuan, Yuan ; Deng, Xin-Xin ; Guo, Zheng-Wang ; Guo, Yang ; Jiao, Yan-Na ; Hao, Hui-Feng

ETHNOPHARMACOLOGICAL RELEVANCEMarsdenia Tenacissima (Roxb.) Wight et Arn. is a traditional Chinese medicine. Its standardized extract (MTE), with the trade name Xiao-Ai-Ping injection, is widely used for cancer treatment. The pharmacological effects of MTE-inducing cancer cell death have been primarily explored. However, whether MTE triggers tumor endoplasmic reticulum stress (ERS)-associated immunogenic cell death (ICD) is unknown.AIM OF THE STUDYTo determine the potential role of endoplasmic reticulum stress in the anti-cancer effects of MTE, and uncover the possible mechanisms of endoplasmic reticulum stress-associated immunogenic cell death induced by MTE.MATERIAL AND METHODSThe anti-tumor effects of MTE on non-small cell lung cancer (NSCLC) were examined through CCK-8 and wound healing assay. Network pharmacology analysis and RNA-sequencing (RNA seq) were performed to confirm the biological changes of NSCLCs after MTE treatment. Western blot, qRT-PCR, reactive oxygen species (ROS) assay, and mitochondrial membrane potential (MMP) assay were used to explore the occurrence of endoplasmic reticulum stress. Immunogenic cell death-related markers were tested by ELISA and ATP release assay. Salubrinal was used to inhibit the endoplasmic reticulum stress response. SiRNA and bemcentinib (R428) were used to impede the function of AXL. AXL phosphorylation was regained by recombinant human Gas6 protein (rhGas6). The effects of MTE on endoplasmic reticulum stress and immunogenic cell death response were also proved in vivo. The AXL inhibiting compound in MTE was explored by molecular docking and confirmed by Western blot.RESULTSMTE inhibited cell viability and migration of PC-9 and H1975 cells. Enrichment analysis identified that differential genes after MTE treatment were significantly enriched in endoplasmic reticulum stress-related biological processes. MTE decreased mitochondrial membrane potential (MMP) and increased ROS production. Meanwhile, endoplasmic reticulum stress-related proteins (ATF6, GRP-78, ATF4, XBP1s, and CHOP) and immunogenic cell death-related markers (ATP, HMGB1) were upregulated, and the AXL phosphorylation level was suppressed after MTE treatment. However, when salubrinal (an endoplasmic reticulum stress inhibitor) and MTE were co-treated cells, the inhibitory effects of MTE on PC-9 and H1975 cells were impaired. Importantly, inhibition of AXL expression or activity also promotes the expression of endoplasmic reticulum stress and immunogenic cell death-related markers. Mechanistically, MTE induced endoplasmic reticulum stress and immunogenic cell death by suppressing AXL activity, and these effects were attenuated when AXL activity recovered. Moreover, MTE significantly increased the expression of endoplasmic reticulum stress-related markers in LLC tumor-bearing mouse tumor tissues and plasma levels of ATP and HMGB1. Molecular docking illustrated that kaempferol has the strongest binding energy with AXL and suppresses AXL phosphorylation.CONCLUSIONMTE induces endoplasmic reticulum stress-associated immunogenic cell death in NSCLC cells. The anti-tumor effects of MTE are dependent upon endoplasmic reticulum stress. MTE triggers endoplasmic reticulum stress-associated immunogenic cell death by inhibiting AXL activity. Kaempferol is an active component that inhibits AXL activity in MTE. The present research revealed the role of AXL in regulating endoplasmic reticulum stress and enriched the anti-tumor mechanisms of MTE. Moreover, kaempferol may be considered a novel AXL inhibitor.

100 Deals associated with XiaoAiPing

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Indication	Country/Location	Organization	Date
Esophageal Carcinoma	CN	Tonghua Shenyuan Pharmaceutical Co. Ltd.	-
Liver Cancer	CN	Tonghua Shenyuan Pharmaceutical Co. Ltd.	-
Lung Cancer	CN	Tonghua Shenyuan Pharmaceutical Co. Ltd.	-
Stomach Cancer	CN	Tonghua Shenyuan Pharmaceutical Co. Ltd.	-

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