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      Pharmacological Properties, Molecular Mechanisms, and Pharmaceutical Development of Asiatic Acid: A Pentacyclic Triterpenoid of Therapeutic Promise

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          Abstract

          Asiatic acid (AA) is a naturally occurring aglycone of ursane type pentacyclic triterpenoids. It is abundantly present in many edible and medicinal plants including Centella asiatica that is a reputed herb in many traditional medicine formulations for wound healing and neuropsychiatric diseases. AA possesses numerous pharmacological activities such as antioxidant and anti-inflammatory and regulates apoptosis that attributes its therapeutic effects in numerous diseases. AA showed potent antihypertensive, nootropic, neuroprotective, cardioprotective, antimicrobial, and antitumor activities in preclinical studies. In various in vitro and in vivo studies, AA found to affect many enzymes, receptors, growth factors, transcription factors, apoptotic proteins, and cell signaling cascades. This review aims to represent the available reports on therapeutic potential and the underlying pharmacological and molecular mechanisms of AA. The review also also discusses the challenges and prospects on the pharmaceutical development of AA such as pharmacokinetics, physicochemical properties, analysis and structural modifications, and drug delivery. AA showed favorable pharmacokinetics and found bioavailable following oral or interaperitoneal administration. The studies demonstrate the polypharmacological properties, therapeutic potential and molecular mechanisms of AA in numerous diseases. Taken together the evidences from available studies, AA appears one of the important multitargeted polypharmacological agents of natural origin for further pharmaceutical development and clinical application. Provided the favorable pharmacokinetics, safety, and efficacy, AA can be a promising agent or adjuvant along with currently used modern medicines with a pharmacological basis of its use in therapeutics.

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          Mesoporous silica nanoparticles for drug and gene delivery

          Mesoporous silica nanoparticles (MSNs) are attracting increasing interest for potential biomedical applications. With tailored mesoporous structure, huge surface area and pore volume, selective surface functionality, as well as morphology control, MSNs exhibit high loading capacity for therapeutic agents and controlled release properties if modified with stimuli-responsive groups, polymers or proteins. In this review article, the applications of MSNs in pharmaceutics to improve drug bioavailability, reduce drug toxicity, and deliver with cellular targetability are summarized. Particularly, the exciting progress in the development of MSNs-based effective delivery systems for poorly soluble drugs, anticancer agents, and therapeutic genes are highlighted.
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            Natural products in cancer chemotherapy: past, present and future.

            John Mann (2002)
            Natural products have been the mainstay of cancer chemotherapy for the past 30 years. However, the quickening pace of (aberrant) gene identification, and the new technologies of combinatorial chemistry and high-throughput screening, should provide access to a wide range of new, totally synthetic drugs. Will these new approaches sound the death knell for therapies based on natural products? In reality, natural products are likely to provide many of the lead structures, and these will be used as templates for the construction of novel compounds with enhanced biological properties.
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              Angiogenesis and invasion in glioma.

              Despite advances in surgical and medical therapy, glioblastoma consistently remains a fatal disease. Over the last 20 years, no significant increase in survival has been achieved for patients with this disease. The formation of abnormal tumor vasculature and glioma cell invasion along white matter tracts are believed to be the major factors responsible for the resistance of these tumors to treatment. Therefore, investigation of angiogenesis and invasion in glioblastoma is essential for the development of a curative therapy. In our report, we first reviewed certain histopathological studies that focus on angiogenesis and invasion of human malignant gliomas. Second, we considered several animal models of glioma available for studying angiogenesis and invasion, including our novel animal models. Third, we focused on the molecular aspects of glioma angiogenesis and invasion, and the key mediators of these processes. Finally, we discussed the recent and ongoing clinical trials targeting tumor angiogenesis and invasion in glioma patients. A better understanding of the mechanism of glioma angiogenesis and invasion will lead to the development of new treatment methods.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                04 September 2018
                2018
                : 9
                : 892
                Affiliations
                [1] 1Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University , Al Ain, United Arab Emirates
                [2] 2SVKM's Institute of Pharmacy , Dhule, India
                [3] 3Department of Pharmacology, R. C. Patel Institute of Pharmaceutical Education and Research , Shirpur, India
                [4] 4Department of Internal Meicine, College of Medicine and Health Sciences, United Arab Emirates University , Al Ain, United Arab Emirates
                Author notes

                Edited by: Marcello Locatelli, Università degli Studi G. d'Annunzio Chieti e Pescara, Italy

                Reviewed by: Felisa Cilurzo, Università degli Studi G. d'Annunzio Chieti e Pescara, Italy; Stefania Cesa, Sapienza Università di Roma, Italy

                *Correspondence: Shreesh K. Ojha shreeshojha@ 123456uaeu.ac.ae

                This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology

                Article
                10.3389/fphar.2018.00892
                6131672
                30233358
                2b6e4877-1ee9-4136-afb9-a483068a2249
                Copyright © 2018 Nagoor Meeran, Goyal, Suchal, Sharma, Patil and Ojha.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 28 April 2018
                : 23 July 2018
                Page count
                Figures: 3, Tables: 7, Equations: 0, References: 267, Pages: 35, Words: 29813
                Funding
                Funded by: United Arab Emirates University 10.13039/501100006013
                Award ID: 31M195
                Categories
                Pharmacology
                Review

                Pharmacology & Pharmaceutical medicine
                asiatic acid,pharmacological properties,phytochemicals,triterpenoids,small molecule,c. asiatica

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