Zephyranthes citrina Baker is a bulbous herb, commonly known as yellow rain lily belongs to the family Amaryllidaceae. It is a native of tropical and subtropical America but nowadays it is cultivated as a popular ornamental herb in several parts of the world including India. This herb represents one of the richest sources of phytochemicals, especially alkaloids and possesses great potential for pharmaceutical applications. It shows remarkable antiprotozoal, antimicrobial, anti-Alzheimer, cytotoxic, antioxidant, anti-inflammatory, analgesic, and dye removal activities. This review is an effort to give a detailed study of the literature on the biological activities of Zephyranthes citrina. This review concludes that Zephyranthes citrina has a great potential to treat various diseases and could be used as a source for novel healthcare products in the near future, which requires further experimentation.
BackgroundGlioblastomas arise from multistep tumorigenesis of the glial cells. Despite the current state‐of‐art treatment, tumor recurrence is inevitable. Among the innovations blooming up against glioblastoma, drug repurposing could provide profound premises for treatment enhancement. While considering this strategy, the efficacy of the repurposed drugs as monotherapies were not up to par; hence, the focus has now shifted to investigate the multidrug combinations.AimTo investigate the efficacy of a quadruple‐combinatorial treatment comprising temozolomide along with chloroquine, naringenin, and phloroglucinol in an orthotopic glioma‐induced xenograft model.MethodsAntiproliferative effect of the drugs was assessed by immunostaining. The expression profiles of WNT/β‐catenin and apoptotic markers were evaluated by qRT‐PCR, immunoblotting, and ELISA. Patterns of mitochondrial depolarization was determined by flow cytometry. TUNEL assay was performed to affirm apoptosis induction. In vivo drug detection study was carried out by ESI‐Q‐TOF MS analysis.ResultsThe quadruple‐drug treatment had significantly hampered glioma proliferation and had induced apoptosis by modulating the WNT/β‐catenin signaling. Interestingly, the induction of apoptosis was associated with mitochondrial depolarization. The quadruple‐drug cocktail had breached the blood–brain barrier and was detected in the brain tissue and plasma samples.ConclusionThe quadruple‐drug combination served as a promising adjuvant therapy to combat glioblastoma lethality in vivo and can be probed for translation from bench to bedside.
Background: Glioblastomas arise from multistep tumorigenesis of the glial cells and are associated with poor prognosis. Despite the current state-of-art treatment, tumor recurrence is inevitable. Thus, there exists a desperate need for effective therapeutic alternatives to improve glioblastoma outcome. Among the innovations blooming up, drug repurposing could provide a profound premises for glioblastoma treatment enhancement. While considering this strategy, the efficacy of the repurposed drugs as monotherapies were not up to par; hence, the focus has now shifted to investigate the multi-drug combinations to target glioblastomas. In line with this concept, we investigated the efficacy of a quadruple-combinatorial treatment comprising temozolomide (the benchmark drug) along with chloroquine (a synthetic drug), naringenin (a flavonoid) and phloroglucinol (a marine derivative) in an orthotopic glioma-induced xenograft model. Methods: Anti-proliferative effect of the drugs was assessed by immunostaining. The expression profiles of WNT/β-catenin and apoptotic markers were evaluated by qRT-PCR, immunoblotting and ELISA. Patterns of mitochondrial depolarization was determined by flow cytometry. TUNEL assay was performed to affirm apoptosis induction. In vivo drug detection study was carried out by ESI-Q-TOF MS analysis. Results: The quadruple-drug treatment had significantly hampered GB proliferation and had induced apoptosis by modulating the WNT/β-catenin signalling. Flow cytometric analysis revealed that the induction of apoptosis was associated with mitochondrial depolarization. Further the quadruple-drug cocktail, had breached the blood brain barrier and was detected in the brain tissue and plasma samples from various experimental groups. Conclusion: The quadruple-drug combination served as a promising adjuvant therapy to combat glioma lethality in vivo and can be probed for translation from bench to bedside.
Background: An important hallmark of glioblastoma aggressiveness is its altered metabolism of glucose. This metabolic shift wherein the tumor cells employ aerobic glycolysis regardless of oxygen availability via reprogramming of mitochondrial oxidative phosphorylation is known as the Warburg effect. Previous literatures have linked this metabolic reprograming to tumor progression glioblastoma cell proliferation making it a key target for targeted drug therapy. Objective: To evaluate the anti-Warburg efficacies of the triple-drug combination of temozolomide, metformin and epigallocatechin gallate in preclinical glioblastoma models. Methodology: Based on this lacuna, the current study aimed to explore the therapeutic efficacy of the triple-drug combination of temozolomide, metformin and epigallocatechin gallate in attenuating Warburg effect and glucose uptake in glioblastoma both in vitro and in vivo. Results: Our results showed that the triple-drug combination had significantly reduced glucose uptake and reversed the Warburg effect in glioblastoma cells and in the xenograft-induced glioma rat model. Conclusion: Thus, the triple-drug combination would serve as an effective therapeutic regime to hamper glioblastoma progression via altering glucose metabolism and improve the overall prognosis in patient setting.
Glioma is the most devastating high-grade tumor of the central nervous system, with dismal prognosis. Existing treatment modality does not provide substantial benefit to patients and demands novel strategies. One of the first-line treatments for glioma, temozolomide, provides marginal benefit to glioma patients. Repurposing of existing non-cancer drugs to treat oncology patients is gaining momentum in recent years. In this study, we investigated the therapeutic benefits of combining three repurposed drugs, namely, metformin (anti-diabetic) and epigallocatechin gallate (green tea-derived antioxidant) together with temozolomide in a glioma-induced xenograft rat model. Our triple-drug combination therapy significantly inhibited tumor growth in vivo and increased the survival rate (50%) of rats when compared with individual or dual treatments. Molecular and cellular analyses revealed that our triple-drug cocktail treatment inhibited glioma tumor growth in rat model through ROS-mediated inactivation of PI3K/AKT/mTOR pathway, arrest of the cell cycle at G1 phase and induction of molecular mechanisms of caspases-dependent apoptosis.In addition, the docking analysis and quantum mechanics studies performed here hypothesize that the effect of triple-drug combination could have been attributed by their difference in molecular interactions, that maybe due to varying electrostatic potential. Thus, repurposing metformin and epigallocatechin gallate and concurrent administration with temozolomide would serve as a prospective therapy in glioma patients.
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