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Öğe 6-Phosphogluconate dehydrogenase fuels multiple aspects of cancer cells: From cancer initiation to metastasis and chemoresistance(Wiley, 2020) Sarfraz, Iqra; Rasul, Azhar; Hussain, Ghulam; Shah, Muhammad Ajmal; Zahoor, Ameer Fawad; Asrar, Muhammad; Selamoglu, ZelihaReprogrammed metabolism is key biochemical characteristic of malignant cells, which represents one of the emerging hallmarks of cancer. Currently, there is rising contemplation on oxidative pentose phosphate pathway (PPP) enzymes as potential therapeutic hits due to their affiliation with tumor metabolism. 6-Phosphogluconate dehydrogenase (6PGD), third oxidative decarboxylase of PPP, has received a great deal of attention during recent years due to its critical role in tumorigenesis and redox homeostasis. 6PGD has been reported to overexpress in number of cancer types and its hyperactivation is mediated through post-transcriptional and post-translational modifications by YTH domain family 2 (YTHDF2), Nrf2 (nuclear factor erythroid 2-related factor 2), EGFR (epidermal growth factor receptor) and via direct structural interactions with ME1 (malic enzyme 1). Upregulated expression of 6PGD provides metabolic as well as defensive advantage to cancer cells, thus, promoting their proliferative and metastatic potential. Moreover, enhanced 6PGD expression also performs key role in development of chemoresistance as well as radiation resistance in cancer. This review aims to discuss the historical timeline and cancer-specific role of 6PGD, pharmacological and genetic inhibitors of 6PGD and 6PGD as prognostic biomarker in order to explore its potential for therapeutic interventions. We anticipate that targeting this imperative supplier of NADPH might serve as tempting avenue to combat the deadly disease like cancer.Öğe A Review on Phyto-pharmacology of Oxalis corniculata(Bentham Science Publ Ltd, 2022) Sarfraz, Iqra; Rasul, Azhar; Hussain, Ghulam; Shah, Muhammad Ajmal; Nageen, Bushra; Jabeen, Farhat; Selamoglu, ZelihaOxalis corniculata (Oxalidaceae) is a small decumbent and delicate appearing medicinal herb flourishing in warm temperate and tropical domains such as Pakistan and India. Main bioactive chemical constituents of Oxalis plant include several alkaloids, flavonoids, terpenoids, cardiac glycosides, saponins, and phlobatannins, along with steroids. Due to its polyphenolic, glycosides and flavonoid profile, it is proved to be protective in numerous ailments and exhibit various biological activities such as anti-fungal, anti-cancer, anti-oxidant, anti-bacterial, anti-diabetic, and cardioprotective. Moreover, bioactive phytochemicals from this plant possess significant wound healing potential. Our current effort intends to emphasize on the immense significance of this plant species, which have not been the subject matter of clinical trials and effective pharmacological studies, even though its favored usage has been stated. This review proposes that Oxalis corniculata possess a potential for the cure of various diseases. However, further researches on isolation and characterization of bioactive compounds along with pre-clinical trials are compulsory to figure out its pharmacological applications.Öğe Alkaloids in the treatment of gastrointestinal tract cancer(Bentham Science Publishers, 2023) Riaz, Ammara; Rasul, Azhar; Batool, Rabia; Kanwal, Lubna; Hussain, Ghulam; Sarfraz, Iqra; Shah, Muhammad AjmalAlkaloids, nitrogen-containing compounds, are found in living organisms ranging from microbes to seed-producing plants all over the world. About more than 20,000 alkaloids have been discovered, mostly occurring in higher plants of the families Ranunculaceae, Papaveraceae, Leguminosae, Loganiaceae and Menispermaceae. These compounds are able to inhibit cancer proliferation, especially gastrointestinal cancer, which constitutes the highest incidence rate all over the world. The most diversified group of phytochemicals, alkaloids offer a mighty series of chemical scaffolds and moieties which can be harnessed to ameliorate the devastating consequences underlying cancer. Gastrointestinal (GIT) cancers constitute the malignancies of esophageal, gastric, pancreatic, colorectal and anal tumors, which possess aberrant metabolic signals giving rise to uncontrolled cell proliferation. These cancers are the most frequent of all cancers and account for the high mortality rates worldwide. Conventional therapeutic options carry the risks like being non-economical as well as they possess severe side effects. Natural products offer a wide spectrum of pharmacological properties which can overcome these risk factors by providing cheaper products and are reliable regarding their bio-safety profiles. Alkaloids can be investigated in detail to investigate their pharmacological potential against GIT cancers. Several alkaloids are known to modulate the cell signaling pathways by inducing cell cycle arrest at G0/G1, S and G2/M phases in addition to being the apoptosis inducers. In addition to that, they are also known to target various metabolic pathways, such as p53, B-catenin, MAPK and PIM3. The chapter intends to investigate the biological as well as pharmacological profiles of various alkaloids with special reference to GIT cancers in order to update scientists and researchers about the pharmaceutical potential of these compounds. © 2023 Bentham Science Publishers. All rights reserved.Öğe Cardamonin: A new player to fight cancer via multiple cancer signaling pathways(Pergamon-Elsevier Science Ltd, 2020) Nawaz, Javaria; Rasul, Azhar; Shah, Muhammad Ajmal; Hussain, Ghulam; Riaz, Ammara; Sarfraz, Iqra; Zafar, SabaNature's pharmacy has undoubtedly served humans as an affordable and safer health-care regime for a long times. Cardamonin, a chalconoid present in several plants has been known for a longtime to have beneficial properties towards human health. In this review, we aimed to highlight the recent advances achieved in discovering the pharmacological properties of cardamonin. Cardamonin is cardamom-derived chalcone, which plays a role in cancer treatment, immune system modulation, inflammation and pathogens killing. Through the modulation of cellular signaling pathways, cardamonin activates cell death signal to induce apoptosis in malignant cells that results in the inhibition of cancer development. Moreover, cardamonin arrests cell cycle by altering the expression of regulatory proteins during malignant cells division. Due to its relatively selective cytotoxic potential against host malignant cells, cardamonin is emerging as a promising novel experimental anticancer agent. The potential of cardamonin to target various signaling molecules, transcriptional factors, cytokines and enzymes, such as mTOR, NF-kappa B, Akt, STAT3, Wnt/beta-catenin and COX-2 enhances the opportunity to explore it as a new multi-target therapeutic agent. The pharmacokinetic and biosafety profile of cardamonin favor it as a potentially safe biomolecule for pharmaceutical drug development.Öğe Ginkgetin: A natural biflavone with versatile pharmacological activities(Pergamon-Elsevier Science Ltd, 2020) Adnan, Muhammad; Rasul, Azhar; Hussain, Ghulam; Shah, Muhammad Ajmal; Zahoor, Muhammad Kashif; Anwar, Haseeb; Sarfraz, IqraNatural products, being richly endowed with curative powers, have become spotlight for biomedical and pharmaceutical research to develop novel therapeutics during recent years. Ginkgetin (GK), a natural non-toxic biflavone, has been shown to exhibit anti-cancer, anti-inflammatory, anti-microbial, anti-adipogenic, and neuroprotective activities. GK combats cancer progression by arresting cell cycle, inducing apoptosis, stimulating autophagy, and targeting many deregulated signaling pathways such as JAK/STAT and MAPKs. GKhalts inflammation mediators like interleukins, iNOS, COX-2, PGE2, NF-0, and acts as an inhibitor of PLA2. GK shows strong neuroprotection against oxidative stress-promoted cell death, inhibits cerebral micro -hemorrhage, decreases neurologic deficits, and halts apoptosis of neurons. GK also acts as anti-fungal, anti-viral, anti-bacterial, leishmanicidal and anti-plasmodial agent. GK shows substantial preventive or therapeutic effects in in vivo models of many diseases including atherosclerosis, cancer, neumdegenerative, hepatic, influenza, and inflammatory diseases. Based on various computational, in vitro and in vivo evidences, this article demonstrates the potential of ginkgetin for development of therapeutics against various diseases. Although GK has been systematically studied from pharmacological point of view, a vast field of pharmacokinetics, pre-clinical and clinical studies is still open for the researchers to fully validate its potential for the treatment of various diseases.Öğe Nutrition and nutraceuticals for brain cancer(Nova Science Publishers, Inc., 2021) Sadiqa, Ayesha; Rasul, Azhar; Hussain, Ghulam; Shah, Muhammad Ajmal; Sarfraz, Iqra; Riaz, Ammara; Sarfraz, AyeshaBrain cancers are highly lethal and fatal human cancers due to various hurdles imposed by the brain's physiology and anatomy on therapeutic implications. Higher relapse rates and poor prognosis in brain cancers complicate the situation, leading to high mortalities. Therefore, it is the need of the hour to develop efficient therapeutic strategies against brain cancers. The exploitation of nutraceuticals is an emerging approach for the cure of cancers due to their safety, efficacy, and cost-effectiveness. This chapter focuses on the significance and mechanism of anti-brain cancer nutraceuticals such as juglone, formononetin, eugenol, curcumin, and biochanin. The anti-brain cancer activity of nutraceuticals is governed by the modulation of various cell signaling molecules such as apoptosis-related factors (caspase-3, caspase-9, Bax, Bid, Reactive oxygen species), cell cycle regulators (Cyclin D1, p53), protein kinases (FAK, p-ERK, p38 MAPK), enzymes (MMP-2, MMP-9), transcriptional factors (c-myc, Wnt, ?-catenin), and cytokines (TGF-?). The reported data recommend multitarget activity of nutraceuticals which might play an essential role in developing nutraceuticals to novel pharmacological drugs shortly. © 2021 Nova Science Publishers, Inc. All rights reserved.Öğe Oleandrin: A bioactive phytochemical and potential cancer killer via multiple cellular signaling pathways(Pergamon-Elsevier Science Ltd, 2020) Kanwal, Nazia; Rasul, Azhar; Hussain, Ghulam; Anwar, Haseeb; Shah, Muhammad Ajmal; Sarfraz, Iqra; Riaz, AmmaraNerium oleander, a member of family Apocynaceae, is commonly known as Kaner in various countries of Asia and Mediterranean region. This plant has been renowned to possess significant therapeutic potential due to its various bioactive compounds which have been isolated from this plant e.g., cardiac glycosides, oleandrin, a-tocopherol, digitoxingenin, umsolic acid, quercetin, odorosides, and adigoside. Oleandrin, a saponin glycoside is one of the most potent and pharmacologically active phytochemicals of N. oleander. Its remarkable pharmacotherapeutic potential have been interpreted as anticancer, anti-inflammatory, anti-HIV, neuropmtective, antimicrobial and antioxidant. This particular bioactive entity is known to target the multiple deregulated signaling cascades of cancer such as NF-kappa B, MAPK, and PI3K/Akt. The main focus of the current study is to comprehend the action mechanisms of oleandrin against various pathological conditions. The current review is a comprehensive summary to facilitate the researchers to understand the pharmacological position of the oleandrin in the arena of drug discovery, representing this compound as a new drug candidate for further researches. Moreover, in vivo and in silico based studies are required to explore the mechanistic approaches regarding the pharmacokinetics and biosafety profiling of this compound to completely track its candidature status in natural drug discovery.Öğe Osthole: A Multifunctional Natural Compound with Potential Anticancer, Antioxidant and Anti-inflammatory Activities(Bentham Science Publ Ltd, 2021) Zafar, Saba; Sarfraz, Iqra; Rasul, Azhar; Shah, Muhammad Ajmal; Hussain, Ghulam; Zahoor, Muhammad Kashif; Shafiq, NusratNature has always proved to be a significant reservoir of bioactive scaffolds that have been used for the discovery of drugs since times. Medicinal plants continue to be a solid niche for biologi-cally active and therapeutically effective chemical entities, opening up new avenues for the successful treatment of several human diseases. The contribution of plant-derived compounds to drug discovery, either in their original or in the semi-synthetic derivative form, extends far back in time. This review aims to focus on the sources, biological, and pharmacological profile of a pharmacologically active plant-derived coumarin, osthole, which is an important component of numerous remedial plants such as Cnidium monnieri. Several studies have revealed that osthole possess pharmacological properties such as anticancer, antioxidant, anti-hyperglycemic, neuroprotective, and antiplatelet. Osthole has been reported to regulate various signaling pathways, which in turn modulate several apoptosis-related pro-teins, cell cycle regulators, protein kinases, transcriptional factors, cytokines, and growth receptors affiliated with inflammation, proliferation and several other ailments. Osthole is known to halt prolif-eration and metastasis of cancerous cells by arresting the cell cycle and inducing apoptosis. The data in this review paper supports the pharmacological potential of osthole but further experimentation, biosafety profiling and synergistic effects of this compound need to be focused by the researchers to understand the full spectrum of pharmacological potential of this therapeutically potent compound.Öğe Physcion and Physcion 8-O-?-D-glucopyranoside: Natural Anthraquinones with Potential Anticancer Activities(Bentham Science Publ Ltd, 2021) Adnan, Muhammad; Rasul, Azhar; Hussain, Ghulam; Shah, Muhammad Ajmal; Sarfraz, Iqra; Nageen, Bushra; Riaz, AmmaraNature has provided prodigious reservoirs of pharmacologically active compounds for drug development since times. Physcion and physcion 8-O-beta-D-glucopyranoside (PG) are bioactive natural anthraquinones which exert anti-inflammatory and anticancer properties with minimum or no adverse effects. Moreover, physcion also exhibits anti-microbial and hepatoprotective properties, while PG is known to have anti-sepsis as well as ameliorative activities against dementia. This review aims to highlight the natural sources and anticancer activities of physcion and PG, along with associated mechanisms of actions. On the basis of the literature, physcion and PG regulate multitudinous cell signaling pathways through the modulation of various regulators of cell cycle, protein kinases, microRNAs, transcriptional factors, and apoptosis linked proteins resulting in the effective killing of cancerous cells in vitro as well as in vivo. Both compounds effectively suppress metastasis, furthermore, physcion acts as an inhibitor of 6PGD and also plays an important role in chemosensitization. This review article suggests that physcion and PG are potent anticancer drug candidates, but further investigations on their mechanism of action and pre-clinical trials are mandatory in order to comprehend the full potential of these natural cancer killers in anticancer remedies.