Research Article - International Research Journal of Plant Science ( 2022) Volume 13, Issue 5
Received: 01-Oct-2022, Manuscript No. IRJPS-22- 78830; Editor assigned: 03-Oct-2022, Pre QC No. IRJPS-22- 78830; Reviewed: 17-Oct-2022, QC No. IRJPS-22- 78830; Revised: 21-Oct-2022, Manuscript No. IRJPS-22- 78830; Published: 28-Oct-2022, DOI: http:/dx.doi.org/10.14303/irjps.2022.034
Background: The world is demanding an increased commercial requirement of various secondary metabolites to cure numerous ailments. Anthraquinones (AQs), is one among them, responsible for the pigmentation of heartwood and bark of many economically valuable plants. It is a natural red dye having an outstanding curative application, used from time immemorial.
Main body of the abstract: AQs have been identified from various plants, animals and even from microbes. In addition to their use in various pharmacopoeias, it is used in the textile industry, cosmetics, food etc. AQs have always been a fascinating molecule for chemists to synthesize and access diversely substituted derivatives as therapeutic agents. Its curative efficiency is well utilized in the treatment of various modern diseases and even to Covid 19. Moreover, the AQs exhibit a unique anticancer activity in various cell lines.
Short conclusion: The present work overviews the various effective uses of AQs and highlight its importance in cancer therapy
In plants, the production of secondary metabolites (SMs) is a part of their defense mechanism. Of the variety of SMs, phenolics are placed as the major dyestuff group produced either through the shikimate pathway or phenylpropanoid pathway. Plant phenolics including simple phenols, phenolic acids, flavonoids, coumarins, stilbenes, hydrolyzable and condensed tannins, lignans, and lignins are the most abundant secondary metabolites (Kumar and Pruthi, 2014, Li Y, 2009, Li Y and Jiang, 2018). Typically, they are present in a bound form such as amides, esters, or glycosides and rarely in free form (Pereira et al., 2009). Even though phenols do not have hydrogen at their a-carbon atoms, they do undergo oxidation. The most common oxidation products of phenols are quinones, a pervasive biological pigment found in a wide range of organisms. Naturally occurring quininesinclude benzoquinones, naphthoquinones, benzanthreno phenanthrenoquinones, anthraquinones, anthracyclinones, etc (Korulkin and Muzychkin, 2014). AQ (anthracenedione or dioxoanthracene) represents the largest phenolic group, found in their free form (aglycone) or as AQ glycosides (Derksen et al., 2003, Deshkar et al., 2008).AQs are yellow whereas the AQ glycosides are orange-red or brown-red.
Over 200 AQ compounds are identified in flowering plants, bacteria, molds, fungi, lichen, and insects. These pigments are often responsible for the pigmentation of colored heartwood and bark of many economically valuable plants. In intact powdered form, it exhibits different shades of colors (Priya and Siril, 2013, Samatha and Vasudevan 1996, Mishra et al.,) and an array of different colored dyes was also derived (Patel and Patel, 2016) from it. AQs show restricted distributional plant kingdom, found only in families such as Amaranthaceae, Convolvulaceae, Ericaceae, Euphorbiaceae, Gesneriaceae, Hypericaceae, Leguminosae, Lythraceae, Nyctaginaceae, Polygonaceae, Rhamnaceae, Rubiaceae, Saxifragaceae, Scrophulariaceae, Verbenaceae, Liliaceae etc (Teuscher and Lindequist, 1994). In fungi, it is represented in Aspergillus, Penicillium, and Trichoderma species (Betina et al., 1986). It is also found in some marine invertebrates (Bandaranayake 2006). Furthermore, a few insect species contain AQ either sequestered (Eisner et al., 1994) or not sequestered (Blum and Hilker 2002) from their food plants.
For the present review work the published scientific literature indexed in various databases, peer-reviewed studies were collected and arranged systematically. The central concept is partitioned in various heads each one is discussed and evaluated.
General Uses of Anthraquinones
The tinctorial property of this dye is described in ancient scripts and evidence was gathered from various civilizations. These organic compounds are used to color natural fibers like wool, cotton, and silk with very good fastness to washing and light. Since this is largely employed in textile dyeing, the palatability of this dyestuff was under suspicion. But now it has been used as a food colorant and hair dye (Samantha and Vasudevan, 1996). It is used as a seed dressing or in seed treatments. It can also be employed as a pesticide, to offer bird repellence (Linz and Homan, 2012) also as a gas generator in satellite balloons (Yadav et al., 2019). In addition to the dyeing property, AQ has a significant role in commercial applications. It is used as a catalyst in the production of wood pulp and paper (Sturgeoff and Pitil, 1997). AQs are used in gel preparations of sun protection cream (Dweck, 2002). 2-ethylAQ, an AQ derivative, is utilized in the manufacture of hydrogen peroxide (Goor et al., 2000). The persuasive antioxidant activity of AQ is effectively exploited in the food industry as a chemo-preventive agent. It is a well-documented medical compound and promotes intestinal muscle contraction and speeds up bowel movements (Li 2009). Hydroxy AQs are used as an intermediate in dyes and drug production (Imaki and Fukumoto, 1988). These are stored in plants in the form of glycosides, due to glycosylation (van der Plas et al., 1998), which can improve the solubility of these metabolites and facilitate in better metabolism and distribution (Pandey et al., 2014). Medically, AQs are used as a laxative, which irritate the upper as well as the lower parts of our gastrointestinal tract (Portalatin and Winstead, 2012). AQs also exhibit laxative, diuretic, estrogenic, and immune-modulatory effects. Numerous therapeutic effects like cancer growth inhibition by inducing apoptosis, ease bowel movement, relieve constipation (Khan,2019, Kirtikar and Basu, 1980) and possess antibacterial, antiparasitic, insecticidal, fungicidal, and antiviral properties (Yadav et al., 2019). Reports revealed that the AQ glycosides in plants gradually increase with time. These are mainly absorbed in the intestines and are mostly distributed in blood flowrich tissues and organs and its transformation produce improved pharmacological and/or toxicological outcomes (Wang et al., 2021). The curative properties of AQs have been successfully practicing to bring about constipation relief through their laxative effects and to stimulate colon contractions (Portalatin and Winstead, 2012). The AQ ring and AQ glycosides have significant anticancer activity and anti-constipation activity, while alizarin has significant antioxidant activity and antibacterial activities (Li and Jiang, 2018).
Uses of AQ in Modern Time
In modern medicine, plant-derived chemicals are offered prime importance and AQ is the secret to the medicinal potency of many medicinal plants. A series of bicyclic peptides (RA-series) has been elucidated from various spectroscopic and chemical methods using various solvent systems in various Rubiaceae members and were noted for its cytotoxic and antitumor competence (Itokawa et al., 1984c, Kato et al., 1987, Hamanaka et al., 1987, Itokawa et al., 1993) and are used against various carcinoma, melanoma, and leukemia. According to Tian et al. (2020), AQ compounds have been considered to have anticancer activity mainly through DNA damage, cycle arrest, and apoptosis and also through paraptosis, autophagy, radio-sensitizing, overcoming chemo-resistance, and other methods. Mechanistically, most of the AQ-based compounds inhibit cancer progression by targeting essential cellular proteins (Malik et al., 2021).
The AQ showed cytotoxicity toward human carcinoma cell lines like colon carcinoma (HT-29), breast carcinoma [(MCF- 7), liver carcinoma (HepG2), cervical cancer (Tiwari et al., 2012), MDA-MB-231 (Barlow et al., 2016), human larynx carcinoma and human cervical cancer (Tiwari et al., 2012). It was found to have inhibitions against human cervical cancer cell line (HeLa) and larynx carcinoma (HEp-2) cell lines (Patel et al., 2010). The prominent AQ-based drugs doxorubicin, mitoxantrone as well as more recent epirubicin, idarubicin, and valrubicin are successfully used in chemotherapy of hematological malignancies and solid tumors (Tikhomirov et al., 2018). Nano structured AQ active molecule showed the absence of cytotoxicity and improved cell uptake of photo-sensitizer resulting in increased cell death compared to free AQ (Amantino et al., 2020). The liposomal AQ-based molecule has excellent promise for Triple Negative Breast Cancer therapy (George et al., 2022). Natural anthraquinone (AQ) equivalents extend their antitumor activity on different targets including telomerase, topoisomerases, kinases, matrix metalloproteinases, DNA and different phases of cell lines (Siddamurthi et al., 2020). Moreover, emodin and artinemol may be effective antiviral drugs for the treatment of patients with COVID-19 (Prathiviraj et al., 2021).
Due to the long-term use of AQs the lining of the colon takes on a dark brownish-black hue. This condition in term may, cause short-term side effects but the melanosis of coli can be reverted when the anthraquinone use was discontinued. However, the presence of the quinone moiety in AQs raises safety concerns, and its laxative has therefore been under critical reassessment (Malik and Müller 2016). Moreover, the transformation of one form of AQ into another may increase the blood concentration of the latter, leading to an increased pharmacological and/or toxicological effect (Wang et al., 2021).
Since the world is looking forward to nano-particles for effective drug delivery more attention should be given to those metabolites like AQs and their derivatives, which have proven their potency in controlling many dreadful diseases especially tumor cell lines with minimum drug leakage. There is plenty of opportunity for utilizing AQ-based anticancer drugs in combination therapies with newly approved anticancer drugs targeting different biological receptors, which can be achieved through a detailed understanding of the mechanistic pathways of the intended combination. Recently, Polymer enzyme liposome therapy (PELT), triple block nanocarrier (TBN) platforms and amphiphilic core cross-linked star (CCS) polymers were reported to perform excellent pharmacokinetic profile in in vivo models. Similarly, selective drug delivery, computational techniques like ligand-based drug designing and scaffold hopping, drug repurposing, the in-silico drug designing tools for the diversification of targets and drug repurposing techniques.
Amantino CF, de Baptista-Neto Á, Badino AC, Siqueira-Moura MP, Tedesco AC et al. (2020). Anthraquinone encapsulation into polymeric nanocapsules as a new drug from biotechnological origin designed for photodynamic therapy. Photodiagnosis Photodyn Ther. 3: 101815.
Indexed at, Google Scholar, Cross Ref
Bandaranayake WM. (2006). The nature and role of pigments of marine invertebrates. NPR. 23: 223-255.
Indexed at, Google Scholar, Cross Ref
Barlow R, Barnes DA, Campbell AM, Nigam PS, Owusu-Apenten RK (2015). Antioxidant, anticancer and antimicrobial, effects of Rubia cordifolia aqueous root extract. J Adv Biol Biotechnol. 5: 1-8.
Indexed at, Google Scholar, Cross Ref
Betina V, Sedmera P, Vokoun J, Podojil M (1986). Anthraquinone pigments from a conidiating mutant ofTrichoderma viride. Experientia. 42: 196-197.
Indexed at, Google Scholar, Cross Ref
Blum MS, Hilker M (2003). Chemical protection of insect eggs. Chemoecology of insect eggs and egg deposition. 61-90.
Indexed at, Google Scholar, Cross Ref
Derksen GC, Naayer M, van Beek TA, Capelle A, Haaksman IK et al. (2003). Chemical and enzymatic hydrolysis of anthraquinone glycosides from madder roots. Phytochemical Analysis IJCBS. 14: 137-144.
Indexed at, Google Scholar, Cross Ref
Deshkar N, Tilloo S, Pande VA (2008) Comprehensive Review of Drug Invention Today 2:244-246.
Dweck A. (2002). Herbal medicine for the skin. Their chemistry and effects on skin and mucous membranes. J Appl Cosmetol. 20: 83-83.
Eisner T, Ziegler R, McCormick JL, Eisner M, Hoebeke ER et al. (1994). Herbal medicine for the skin. Their chemistry and effects on skin and mucous membranes. J Appl Cosmetol. Experientia. 50: 610-615.
George TA, Chen MM, Czosseck A, Chen HP, Huang HS et al. (2022). Liposome-encapsulated anthraquinone improves efficacy and safety in triple negative breast cancer. JCR. 342: 31-43.
Indexed at, Google Scholar, Cross Ref
Goor G, Glenneber J, Jacobi S (2000) Hydrogen peroxide. In: Ullmann’s Encyclopedia of Industrial Chemistry, Wiley-VCH Verlag GmbH &CoKGzA
Hamanaka T, Ohgoshi M, Kawahara K, Yamakawa K, Tsuruo T et al. (1987). A novel antitumor cyclic hexapeptide (RA-700) obtained from Rubiae radix. J Pharmacobio-dyn. 10: 616-623.
Indexed at, Google Scholar, Cross Ref
Imaki S, Fukumoto Y (1988) Process for the preparation of hydroxyanthraquinone derivatives as intermediates for dyes and drugs (Patent No JP 63091347) Jpn, Kokai Tokkyo Koho (in Japanese)
Itokawa H, Ibraheim ZZ, Qiao YF, Takeya K (1993). Anthraquinones, naphthohydroquinones and naphthohydroquinone dimers from Rubia cordifolia and their cytotoxic activity. Chem Pharm Bull. 41: 1869-1872.
Indexed at, Google Scholar, Cross Ref
Itokawa H, Takeya K, Mori N, Takanashi M, Yamamoto H et al. (1984). Cell growth-inhibitory effects of derivatives of antitumor cyclic hexapeptide RA-V obtained from Rubiae radix (V). GANN J Cancer Res. 75: 929-936.
Indexed at, Google Scholar, Cross Ref
Kato T, Suzumura Y, Takamoto S, Ota K (1987). Antitumor activity and toxicity in mice of RA-700, a cyclic hexapeptide. Anticancer Res. 7: 329-334.
Khan NT (2019) Anthraquinones-A Naturopathic Compound. JNDC. 2: 25-28.
Indexed at, Google Scholar, Cross Ref
Kirtikar KR, Basu BD (1980) Indian Medicinal Plants vol II,
Kumar N, Pruthi V (2014). Potential applications of ferulic acid from natural sources. Biotechnol Rep. 4: 86-93.
Indexed at, Google Scholar, Cross Ref
Li Y (2009). The health efficacy of aloe and its development and utilization. Asia Social Sci. 5: 151-154.
Li Y, Jiang JG (2018). Health functions and structure–activity relationships of natural anthraquinones from plants. Food Funct. 9: 6063-6080.
Indexed at, Google Scholar, Cross Ref
Linz GM, Homan HJ (2012). Preliminary evaluation of 9, 10 anthraquinone bird repellent for managing blackbird damage to ripening sunflower. USDA National Wild life Research Center- Staff Publications. 1160-1165.
Malik MS, Alsantali RI, Jassas RS, Alsimaree AA, Syed R et al. (2021). Journey of anthraquinones as anticancer agents–a systematic review of recent literature. RSC Advances. 11: 35806-35827.
Indexed at, Google Scholar, Cross Ref
Mishra D, Mishra D, Awasthi A, Arnold R. Science Secure Journal of Biotechnology.
Pandey RP, Parajuli P, Koirala N, Lee JH, Park YI et al (2014). Glucosylation of isoflavonoids in engineered Escherichia coli. Mol Cells. 37: 172-177.
Indexed at, Google Scholar, Cross Ref
Patel PR, Nagar AA, Patel RC, Rathod DK, Patel VR (2010). In-vitro anticancer activity of Rubia cordifolia against Hela and Hep-2 cell lines. Phytomedicine. 2: 44-46.
Patel V, Patel R (2016). The active constituents of herbs and their plant chemistry, extraction and identification methods. J Chem Pharm. 8: 1423-1443.
Pereira DM, Valentão P, Pereira JA, Andrade PB (2009). Phenolics: From chemistry to biology. Molecules. 14: 2202-2211.
Portalatin M, Winstead N (2012). Medical management of constipation. Clinics in colon and rectal surgery. 25: 012-019.
Prathiviraj R, Saranya S, Bharathi M, Chellapandi P (2021). A hijack mechanism of Indian SARS-CoV-2 isolates for relapsing contemporary antiviral therapeutics. CBM. 132: 104315.
Indexed at, Google Scholar, Cross Ref
Priya MD, Siril EA (2013) Pharmacognostic Studies on Indian Madder (Rubia cordifolia L.). RJPP. 1: 112-119.
Samatha S, Vasudevan TN (1996). Natural hair dyes. JSIR. 55: 885-887.
Siddamurthi S, Gutti G, Jana S, Kumar A, Singh SK (20202) Anthraquinone: a promising scaffold for the discovery and development of therapeutic agents in cancer therapy. Future Med Chem. 12: 1037-1069.
Indexed at, Google Scholar, Cross Ref
Sturgeoff LG, Pitil Y (1997) Low Kappa Pulping without Capital Investment. In: Goyal JC (ed.), Anthraquinone Pulping, TAPPI Press, London. 3-9.
Teuscher E (1994). Lindequist U. U.(eds): Biogene Gifte-Biologie, Chemie, Pharmakologie: Gustav Fischer Verlag. Stuttgart, Jena, New York. 159-175.
Tian W, Wang C, Li D, Hou H (2020). Novel anthraquinone compounds as anticancer agents and their potential mechanism. Future Med Chem. 12: 627-644.
Indexed at, Google Scholar, Cross Ref
Tikhomirov AS, Shtil AA, Shchekotikhin AE (2018). Advances in the discovery of anthraquinone-based anticancer agents. Recent Pat Anticancer Drug Discov. 13: 159-183.
Indexed at, Google Scholar, Cross Ref
Tiwari S, Upadhyaya R, Shroti R, Upadhyaya ST (2012). Rubia cordifolia root extract induces apoptosis in cancer cell line. Sci Secure J. 1: 39-42.
Van der Plas LH, Hagendoorn MJ, Jamar DC (1998). Anthraquinone glycosylation and hydrolysis in Morinda citrifolia cell suspensions: regulation and function. J Plant Physiol. 152: 235-241.
Indexed at, Google Scholar, Cross Ref
Wang D, Wang XH, Yu X, Cao F, Cai X et al. (2021). Pharmacokinetics of anthraquinones from medicinal plants. Front Pharmacol. 12: 306.
Indexed at, Google Scholar, Cross Ref
Yadav AN, Kour D, Rana KL, Yadav N, Singh B et al. (2019). Metabolic engineering to synthetic biology of secondary metabolites production. In New and Future Developments in Microbial Biotechnology and Bioengineering. 279-320.
Indexed at, Google Scholar, Cross Ref
Citation: Devi Priya M (2022). A critical review on the drug molecule: Anthraquinone. IRJPS. 13: 034.
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