Chrozophora plicata has been extensively utilized in India for the management of numerous disorders. The effective Phytoconstituents derived from the Ethyl Acetate Fraction of Chrozophora plicata [EAFCP] have been identified as Camptothecin Agathisflavone, Rutin, Procynidine B, and Apigenin. These Phytoconstituents have been detected in the EAFCP through qualitative analysis using LC-Q-TOF-MS/MS. The anti-inflammatory properties of Chrozophora plicata are yet to be determined. Therefore, the aim of this study was to utilize a network pharmacology-based methodology to predict potential therapeutic targets of EAFCP in the setting of inflammation. The identification of inflammation targets was followed by the acquisition of verified targets of EAFCP. The key therapeutic targets of EAFCP against inflammation were found by creating a target-functional PPI network, GO studies were conducted on the core therapeutic targets in order to assess the essential signalling pathways involved in the anti-inflammatory effects of EAFCP. A total of 38 significant hub targets associated with EAFCP's anti-inflammatory effects were identified. The key proteins were retrieved for the docking investigation based on the findings, which aided in anticipating the potential interaction between components and targets. The in vivo study revealed that EAFCP had a notable efficiency in decreasing paw edema induced by carrageenan in rats. The evidence we have gathered collectively offers clarification about the anti-inflammatory activity of EAFCP, which is predominantly linked to the suppression of the Cox 1, 2 pathway. The aforementioned findings highlight potential therapeutic targets that could be utilized for the anti-inflammatory activity of EAFCP.

29 Jun 2023·Journal of translational medicine

A novel camptothecin derivative, ZBH-01, exhibits superior antitumor efficacy than irinotecan by regulating the cell cycle.

Article

Author: Zhang, Wenqiu ; Wu, Di ; Shi, Weiguo ; Yu, Hong ; Guo, Zhen ; Yang, Miaomiao ; Zhao, Dawei ; Lan, Shijie ; Wu, Zhihui ; Li, Yongqi

BACKGROUNDIrinotecan (CPT-11) is a classic chemotherapeutic agent that plays an important role in the clinical treatment of metastatic colon cancer and other malignant tumors. We previously designed a series of novel irinotecan derivatives. In this study, we select one representative, ZBH-01, to investigate its sophisticated antitumor mechanism in colon tumor cells.METHODSThe cytotoxic activity of ZBH-01 on colon cancer cells was evaluate by MTT or Cell Counting Kit-8 (CCK8) assay, 3D and xenograft model. The inhibitory effect of ZBH-01 on TOP1 was detected by DNA relaxation assay and Immuno Complex of Ezyme (ICE) bioassay. The molecular mechanism of ZBH-01 was explored by Next-Generation Sequencing (NGS), bioinformatics analyses, flow cytometry, qRT-PCR, and western blot etc. RESULTS: ZBH-01 can induce obvious DNA damage and has superior antitumor activity against colon cancer cells compared to CPT-11 and SN38 (7-Ethyl-10-hydroxy camptothecin, the in vivo active form of CPT-11) both in vivo and in vitro. Its inhibitory effect on topoisomerase I (TOP1) was also comparable with these two control drugs. There are a much larger number of 842 downregulated and 927 upregulated mRNAs in ZBH-01 treatment group than that in the controls. The most significantly enriched KEGG pathways for these dysregulated mRNAs were DNA replication, the p53 signaling pathway, and the cell cycle. After constructing a protein-protein interaction (PPI) network and screening out a prominent cluster, 14 involved in the cell cycle process was identified. Consistently, ZBH-01 induced G₀/G₁ phase arrest in colon cancer cells, while CPT-11/SN38 caused S phase arrest. The initiation of apoptosis by ZBH-01 was also superior to CPT-11/SN38, followed by the increased expression of Bax, active caspase 3, and cleaved-PARP, and decreased expression of Bcl-2. Additionally, CCNA2 (cyclin A2), CDK2 (cyclin-dependent kinase 2), and MYBL2 (MYB proto-oncogene like 2) might be involved in the G₀/G₁ cell cycle arrest induced by ZBH-01.CONCLUSIONSZBH-01 can be an antitumor candidate drug for preclinical study in the future.

02 Oct 2021·Journal of Liposome ResearchQ4 · MEDICINE

Engineered liposomes bearing camptothecin analogue for tumour targeting: in vitro and ex-vivo studies

Q4 · MEDICINE

Article

Author: Tiwari, Ankita ; Saraf, Shivani ; Jain, Ankit ; Jain, Sanjay K. ; Verma, Amit

Topotecan (TPT) is a semi-synthetic, water-soluble derivative of camptothecin, which inhibits the action of topoisomerase I in the S-phase of the cell cycle leading to cell death. For the effective delivery of TPT to cancer cells, pH-sensitive sialic acid modified liposomes were developed. These liposomes were prepared by the thin-film hydration method using the active loading technique. Vesicle size, polydispersity index (PDI), zeta potential, and percentage entrapment efficiency were determined to be 167 ± 3.78 nm, 0.243, -8.39 mV, and 79.88 ± 1.67%, respectively. The pH-sensitive sialic acid (SA) conjugated liposomes enhanced the drug release at acidic pH 4 (92.33 ± 4.21%) as compared to physiological pH 7.4 (63.11 ± 4.51%). A Sulforhodamine B (SRB) cytotoxicity assay was performed in Murine sarcoma S180 cell lines and the GI₅₀ value of free TPT, Lipo, P-Lipo, SA-P-Lipo, and Adriamycin (ADR) were determined to be 10.07 ± 0.15, 27.33 ± 1.01, 28.76 ± 0.87, 15.7 ± 0.45, and 11.5 ± 0.21 µg/mL, respectively. Results obtained from the apoptosis study revealed that cell death by a combination of early apoptosis and apoptosis caused by SA-P-Lipo was ∼24 fold higher than the control. These results demonstrated that pH-sensitive sialic acid conjugated liposomes will be a potential formulation for improving the antitumor efficacy of TPT. However, further research is necessitated to expedite its applicability in clinical regimen in order to ascertain its safety and efficacy.

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Indication	Highest Phase	Country/Location	Organization	Date
Colonic Cancer	Preclinical	CN	Chinese Academy of Sciences	-

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