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      Acute toxicity appraisal of Saussurea heteromalla extract and development of its chemotherapeutic herbal dosage form

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          Abstract

          Ethnopharmacological relevance of Saussurea species for anti-cancer compounds instigated us to develop chemotherapeutic herbal tablets. This study was an ongoing part of our previous research based on the scientific evaluation of Saussurea heteromalla ( S. heteromalla) for anti-cancer lead compounds. In the current study, S. heteromalla herbal tablets (500 /800 mg) were designed and evaluated for anti-cancer activity. Arctigenin was found as a bioactive lead molecule with anti-cancer potential for cervical cancer. The in vitro results on the HeLa cell line supported the ethnopharmacological relevance and traditional utilization of S. heteromalla and provided the scientific basis for the management of cervical cancer as proclaimed by traditional practitioners in China. LD50 of the crude extract was established trough oral acute toxicity profiling in mice, wherein the minimum lethal dose was noticed as higher than 1000 mg/kg body weight orally. Chromatographic fingerprint analysis ensured the identity and consistency of S. heteromalla in herbal tablets in terms of standardization of the herbal drug. About 99.15% of the drug ( S. heteromalla crude extract) was recovered in herbal tablets (RSD: 0.45%). In vitro drug release profile was found to be more than 87% within 1 h, which was also correlated with different mathematical kinetic models of drug release (r 2 = 0.992), indicating that drug release from matrix tablets into the blood is constant throughout the delivery. The dosage form was found stable after an accelerated stability parameters study which may be used for anti-cervical cancer therapy in the future, if it qualifies successful preclinical investigation parameters.

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          Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays

          A tetrazolium salt has been used to develop a quantitative colorimetric assay for mammalian cell survival and proliferation. The assay detects living, but not dead cells and the signal generated is dependent on the degree of activation of the cells. This method can therefore be used to measure cytotoxicity, proliferation or activation. The results can be read on a multiwell scanning spectrophotometer (ELISA reader) and show a high degree of precision. No washing steps are used in the assay. The main advantages of the colorimetric assay are its rapidity and precision, and the lack of any radioisotope. We have used the assay to measure proliferative lymphokines, mitogen stimulations and complement-mediated lysis.
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            Cytotoxicity of dietary flavonoids on different human cancer types

            Katrin Sak (2014)
            Flavonoids are ubiquitous in nature. They are also in food, providing an essential link between diet and prevention of chronic diseases including cancer. Anticancer effects of these polyphenols depend on several factors: Their chemical structure and concentration, and also on the type of cancer. Malignant cells from different tissues reveal somewhat different sensitivity toward flavonoids and, therefore, the preferences of the most common dietary flavonoids to various human cancer types are analyzed in this review. While luteolin and kaempferol can be considered as promising candidate agents for treatment of gastric and ovarian cancers, respectively, apigenin, chrysin, and luteolin have good perspectives as potent antitumor agents for cervical cancer; cells from main sites of flavonoid metabolism (colon and liver) reveal rather large fluctuations in anticancer activity probably due to exposure to various metabolites with different activities. Anticancer effect of flavonoids toward blood cancer cells depend on their myeloid, lymphoid, or erythroid origin; cytotoxic effects of flavonoids on breast and prostate cancer cells are highly related to the expression of hormone receptors. Different flavonoids are often preferentially present in certain food items, and knowledge about the malignant tissue-specific anticancer effects of flavonoids could be purposely applied both in chemoprevention as well as in cancer treatment.
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              Kinetic modeling on drug release from controlled drug delivery systems.

              In this paper we review the mathematical models used to determine the kinetics of drug release from drug delivery systems. The quantitative analysis of the values obtained in dissolution/release rates is easier when mathematical formulae are used to describe the process. The mathematical modeling can ultimately help to optimize the design of a therapeutic device to yield information on the efficacy of various release models.
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                Author and article information

                Contributors
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: ValidationRole: Writing – original draft
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: SoftwareRole: ValidationRole: Visualization
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: Validation
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: SoftwareRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: ValidationRole: Visualization
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: Project administrationRole: ResourcesRole: SupervisionRole: Validation
                Role: Data curationRole: Formal analysisRole: SoftwareRole: ValidationRole: Visualization
                Role: Formal analysisRole: InvestigationRole: Project administrationRole: SoftwareRole: SupervisionRole: Writing – review & editing
                Role: InvestigationRole: SoftwareRole: Validation
                Role: Data curationRole: Formal analysisRole: MethodologyRole: ResourcesRole: SoftwareRole: Validation
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – original draft
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLOS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                24 May 2024
                2024
                : 19
                : 5
                : e0302657
                Affiliations
                [1 ] Department of Oncology, The First Affiliated Hospital of Xinxiang Medical University Weihui, Henan Province, P.R. China
                [2 ] Department of Pharmaceutical Chemistry, Hamdard Institute of Pharmaceutical Sciences, Hamdard University, Islamabad, Pakistan
                [3 ] Department of Quality Control, Amson vaccines and Pharma, Islamabad, Pakistan
                [4 ] Faculty of Science, Chemistry Department, University of Hail, Hail, Saudi Arabia
                [5 ] Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka, Aljouf, Saudi Arabia
                [6 ] Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, P.R. China
                [7 ] Faculty of Pharmacy, Capital University of Science and Technology, Islamabad, Pakistan
                [8 ] Department of Pharmaceutics, Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan
                [9 ] Zhongjing Research and Industrialization Institute of Chinese Medicine, Zhongguancun Scientific Park, Meixi, Nanyang, Henan, P.R. China
                [10 ] Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, Lahore, Pakistan
                [11 ] Faculty of Pharmacy, The University of Lahore, Lahore, Pakistan
                University of Agriculture Faisalabad, PAKISTAN
                Author notes

                Competing Interests: All authors declare that they do not have a conflict of interest relating to conduct of the study or publication of this manuscript.

                Author information
                https://orcid.org/0000-0002-7751-1605
                https://orcid.org/0000-0002-2861-0674
                https://orcid.org/0000-0002-2657-9810
                Article
                PONE-D-23-28095
                10.1371/journal.pone.0302657
                11125555
                38787908
                a721e1fe-fa7b-4590-b831-7383c20fb190
                © 2024 Batool et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 14 September 2023
                : 4 April 2024
                Page count
                Figures: 3, Tables: 7, Pages: 18
                Funding
                Funded by: The Joint Fund Project of Henan province
                Award ID: LHGJ20200505
                Award Recipient :
                This work was supported by The Joint Fund Project of Henan province: LHGJ20200505.
                Categories
                Research Article
                Biology and Life Sciences
                Toxicology
                Toxicity
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Toxicology
                Toxicity
                Research and analysis methods
                Biological cultures
                Cell lines
                HeLa cells
                Research and analysis methods
                Biological cultures
                Cell cultures
                Cultured tumor cells
                HeLa cells
                Research and Analysis Methods
                Chromatographic Techniques
                Physical Sciences
                Chemistry
                Phytochemistry
                Phytochemicals
                Biology and Life Sciences
                Biochemistry
                Plant Biochemistry
                Phytochemicals
                Biology and Life Sciences
                Plant Science
                Plant Biochemistry
                Phytochemicals
                Research and Analysis Methods
                Chromatographic Techniques
                Liquid Chromatography
                High Performance Liquid Chromatography
                Medicine and Health Sciences
                Pharmaceutics
                Drug Delivery
                Medicine and Health Sciences
                Pharmacology
                Drug Research and Development
                Biology and Life Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Custom metadata
                All relevant data are within the manuscript.

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