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      Anti- Enterococcus Faecalis, Cytotoxicity, Phytotoxicity, and Anticancer Studies on Clausena excavata Burum. f. (Rutaceae) Leaves

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          Abstract

          Background

          Clausena excavata Burum. f. has long been applied in ethnomedicine for the treatment of various disorders like rhinitis, headache, cough, wound healing, fever, and detoxification. This study is aimed at investigating the antibacterial activity against Enterococcus faecalis ATCC 49532 using AlamarBlue assay and atomic force microscopy (AFM) as well as the cytotoxicity, anticancer, and phytotoxicity of C. excavata.

          Method

          Bacterial cell viability was performed by using microplate AlamarBlue assay. Atomic force microscopy was used to determine morphological changes in the surface of bacterial cells. Cytotoxicity and phytotoxicity were determined by brine shrimp lethality and Lemna minor bioassay. Caco-2 (colorectal adenocarcinoma) cell line was used for the evaluation of the anticancer effects.

          Result

          Among the fractions tested, ethyl acetate (EA) fraction was found to be active with minimum inhibitory concentration (MIC) of 750  μg/mL against E. faecalis, but other fractions were found to be insensitive to bacterial growth. Microscopically, the EA fraction-treated bacteria showed highly damaged cells with their cytoplasmic content scattered all over. The LC 50 value of the EA fraction against brine shrimp was more than 1000  μg/mL showing the nontoxic nature of this fraction. Chloroform (CH), EA, and methanol (MOH) fractions of C. excavata were highly herbicidal at the concentration of 1000  μg/mL. EA inhibited Caco-2 cell line with an IC 50 of 20  μg/mL.

          Conclusions

          This study is the first to reveal anti- E. faecalis property of EA fraction of C. excavata leaves, natural herbicidal, and anticancer agents thus highlight the potential compound present in its leaf which needs to be isolated and tested against multidrug-resistant E. faecalis.

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          Most cited references73

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          Natural phenolic compounds from medicinal herbs and dietary plants: potential use for cancer prevention.

          Natural phenolic compounds play an important role in cancer prevention and treatment. Phenolic compounds from medicinal herbs and dietary plants include phenolic acids, flavonoids, tannins, stilbenes, curcuminoids, coumarins, lignans, quinones, and others. Various bioactivities of phenolic compounds are responsible for their chemopreventive properties (e.g., antioxidant, anticarcinogenic, or antimutagenic and anti-inflammatory effects) and also contribute to their inducing apoptosis by arresting cell cycle, regulating carcinogen metabolism and ontogenesis expression, inhibiting DNA binding and cell adhesion, migration, proliferation or differentiation, and blocking signaling pathways. This review covers the most recent literature to summarize structural categories and molecular anticancer mechanisms of phenolic compounds from medicinal herbs and dietary plants.
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            Astragalin: A Bioactive Phytochemical with Potential Therapeutic Activities

            Natural products, an infinite treasure of bioactive chemical entities, persist as an inexhaustible resource for discovery of drugs. This review article intends to emphasize on one of the naturally occurring flavonoids, astragalin (kaempferol 3-glucoside), which is a bioactive constituent of various traditional medicinal plants such as Cuscuta chinensis. This multifaceted compound is well known for its diversified pharmacological applications such as anti-inflammatory, antioxidant, neuroprotective, cardioprotective, antiobesity, antiosteoporotic, anticancer, antiulcer, and antidiabetic properties. It carries out the aforementioned activities by the regulation and modulation of various molecular targets such as transcription factors (NF-κB, TNF-α, and TGF-β1), enzymes (iNOS, COX-2, PGE2, MMP-1, MMP-3, MIP-1α, COX-2, PGE-2, HK2, AChe, SOD, DRP-1, DDH, PLCγ1, and GPX), kinases (JNK, MAPK, Akt, ERK, SAPK, IκBα, PI3K, and PKCβ2), cell adhesion proteins (E-cadherin, vimentin PAR-2, and NCam), apoptotic and antiapoptotic proteins (Beclin-1, Bcl-2, Bax, Bcl-xL, cytochrome c, LC3A/B, caspase-3, caspase-9, procaspase-3, procaspase-8, and IgE), and inflammatory cytokines (SOCS-3, SOCS-5, IL-1β, IL-4, IL-6, IL-8, IL-13, MCP-1, CXCL-1, CXCL-2, and IFN-γ). Although researchers have reported multiple pharmacological applications of astragalin in various diseased conditions, further experimental investigations are still mandatory to fully understand its mechanism of action. It is contemplated that astragalin could be subjected to structural optimization to ameliorate its chemical accessibility, to optimize its absorption profiles, and to synthesize its more effective analogues which will ultimately lead towards potent drug candidates.
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              Strategies for the Optimization of Natural Leads to Anticancer Drugs or Drug Candidates.

              Natural products have made significant contribution to cancer chemotherapy over the past decades and remain an indispensable source of molecular and mechanistic diversity for anticancer drug discovery. More often than not, natural products may serve as leads for further drug development rather than as effective anticancer drugs by themselves. Generally, optimization of natural leads into anticancer drugs or drug candidates should not only address drug efficacy, but also improve absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles and chemical accessibility associated with the natural leads. Optimization strategies involve direct chemical manipulation of functional groups, structure-activity relationship directed optimization and pharmacophore-oriented molecular design based on the natural templates. Both fundamental medicinal chemistry principles (e.g., bioisosterism) and state-of-the-art computer-aided drug design techniques (e.g., structure-based design) can be applied to facilitate optimization efforts. In this review, the strategies to optimize natural leads to anticancer drugs or drug candidates are illustrated with examples and described according to their purposes. Furthermore, successful case studies on lead optimization of bioactive compounds performed in the Natural Products Research Laboratories at UNC are highlighted.
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                Author and article information

                Contributors
                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi
                2314-6133
                2314-6141
                2021
                23 February 2021
                : 2021
                : 3123476
                Affiliations
                1Department of Biology, College of Science, University of Baghdad, Baghdad, Iraq
                2H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan
                3Department of Veterinary Laboratory Diagnosis, Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia
                4Department of Veterinary Preclinical Sciences, Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia
                Author notes

                Academic Editor: Gail Mahady

                Author information
                https://orcid.org/0000-0002-8168-7048
                https://orcid.org/0000-0002-7597-7364
                https://orcid.org/0000-0001-6625-508X
                https://orcid.org/0000-0003-0762-9242
                Article
                10.1155/2021/3123476
                7954634
                37226248-74f2-4ce8-a3a3-087255e90789
                Copyright © 2021 Shaymaa Fadhel Abbas Albaayit et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 8 June 2020
                : 15 January 2021
                : 27 January 2021
                Funding
                Funded by: University of Karachi
                Categories
                Research Article

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