Реферат
Objective: To investigate bioactive phytochemicals and antioxidant activities of Nymphaea nouchali and to explore its anticancer pathways by a network pharmacology approach.Methods: Using a spectrophotometer and high-performance liquid chromatography-diode array detector (HPLC-DAD), we quantified bioactive phytochemicals in methanolic extract of Nymphaea nouchali tuber. The extracts were investigated for in vitro antioxidant properties. Targets of these bioactive phytochemicals were predicted and anticancer-associated pathways were analyzed by a network pharmacology approach. Moreover, we identified the predicted genes associated with cancer pathways and the hub genes in the protein-protein interaction network of predicted genes. Results: Quantitative results indicated the total phenolics, total flavonoids, and total proanthocyanidins in the methanolic extract of Nymphaea nouchali tuber. HPLC-DAD analysis showed rutin (39.44 mg), catechin (39.20 mg), myricetin (30.77 mg), ellagic acid (11.05 mg), gallic acid (3.67 mg), vanillic acid (0.75 mg), rosmarinic acid (4.81 mg), p-coumaric acid (3.35 mg), and quercetin (0.90 mg) in 1 g of dry extract. The extract showed the radical scavenging activities of 2, 2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) and N,N-dimethyl-p-phenylenediamine. By using network pharmacology, we predicted 130 target genes associated with cancer pathways. The top hub genes (IL6, AKT1, EGFR, JUN, PTGS2, MAPK3, CASP3, and CXCL8) were also identified, which were associated with cancer pathways and interacted with bioactive phytochemicals of the methanolic extract of Nymphaea nouchali tuber. Conclusions: Our study provides insights into the mechanism of anticancer activities of the methanolic extract of Nymphaea nouchali tuber.
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Anthracyclines and vinorelbine have shown good response rates as single agent chemotherapy in metastatic breast cancer. A pahse I study has shown improved results by combining these two drugs. On the basis of this we carried out a phase II study in Oncology Department, Combined Military Hospital, Rawalpindi, in which the efficacy and side effects of epirubicin-vinorelbine as first-line chemotherapy in metastatic breast cancer evaluated. The purpose of this phase II study was to observe the effects of combination of epirubicin and vinorelbine in metastatic breast cancer as first-line chemotherapy in our population. From July 2000 to June 2001, chemo naive patients with metastatic breast cancer were given combination chemotherapy comprising epirubicin 100 mg/m2 i.v. infusion on day 1 and vinorelbine 25 mg/m2 i.v infusion on day 1 and 8. A total of six cycles were given to all patients with 3 weekly intervals. Patients with grade 3 and 4 neutropenia were also given G-CSF support. Seven out of 26 patients were pre menopausal and 73.07% were post menopausal. All patients had WHO performance status of > 3. Four [15.38%] out of 26 patients had complete response [CR] and 53.84% had partial response [PR] making and overall response of 69.22 and. Stable disease was observed in 5[19.23%] patients whereas 3 [11.53%] had progressive disease. Neutropenia was the most common side effect observed which was grade 4 in 6[23.07%] patients and grade 3 in 10 [38.46%] patients. Other side effects were mild to moderate. As first line chemotherapyv in treatment of metastatic breast cancer, the combination of epirubicin and vinorelbine is an active and cost effective regimen, with less side effects and excellent tolerability