Elsevier

Biomedicine & Pharmacotherapy

Volume 84, December 2016, Pages 1067-1077
Biomedicine & Pharmacotherapy

Original article
Structural characterization of a novel derivative of myricetin from Mimosa pudica as an anti-proliferative agent for the treatment of cancer

https://doi.org/10.1016/j.biopha.2016.10.020Get rights and content

Abstract

The study was initiated to determine the anticancer activity of a novel compound isolated from the plant Mimosa pudica. The structure of the compound was identified as a derivative of myricetin having alkyl, hydroxy alkyl and methyl substitutions on the basis of spectral evidences (UV–vis, FT-IR, 1H NMR and Mass spectra). The isolated compound was interpreted as 2-(2′,6′-dimethyl-3′,4′,5′-alkyl or hydroxy alkyl substituted phenyl)-3-oxy-(alkyl or hydoxy alkyl)- 5,7-dihydroxy-chromen-4-one. In vitro evaluation of anticancer activity against human lung adenocarcinoma cell line (A549) and human erythroleukemic cell line (K562) were conducted using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. In vivo anticancer activity was determined against Dalton's Ascites Lymphoma (DAL) in Swiss albino mice. The mice were treated with intraperitoneal administration of the compound at 25 mg/kg and 100 mg/kg body weight and were compared with the normal, DAL control and standard drug cyclophosphamide treated groups. The histology revealed that the compound could protect the cellular architecture of liver and kidney. The results from the in vitro, in vivo and histological examinations confirmed the ethnopharmacological significance of the isolated compound and could be considered further for the development of an effective drug against cancer.

Graphical abstract

2-(2′,6′-dimethyl-3′,4′,5′-alkyl or hydroxy alkyl substituted phenyl)-3-oxy-(alkyl or hydoxy alkyl)- 5,7-dihydroxy-chromen-4-one

A novel derivative of myricetin having alkyl, hydroxy alkyl and methyl substitutions was isolated from the plant mimosa pudica. The structure of the compound was elucidated by means of spectroscopic techniques such as UV–vis, FT-IR, 1H NMR and Mass spectra. The isolated compound was evaluated for its anticancer activity by in vitro and in vivo methods.

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Introduction

Cancer is a major health concern all over the world. It becomes one of the leading causes of mortality worldwide, approximately 7 million deaths every year preceded by cardiovascular and infectious diseases [1]. More than 80% of cancer deaths are due to carcinomas such as lung, breast, prostate, colorectal, and pancreas cancers, which are currently the most lethal cancers [2]. Limited success of clinical therapies for the treatment of cancer including surgery, radiation, chemotherapy, hormone therapy and biological therapy indicate that there is an imperative need of new cancer management [3]. Emerging evidences suggests that a number of naturally occurring compounds are highly useful due to their pharmacological properties including cytotoxic and cancer chemopreventive effects [4], [5]. Naturally obtained compounds are considered safer and more easily biodegradable than synthetic compounds moreover the problem of drug resistance observed in synthetic drugs is also reduced [6]. Plant derived natural products such as flavonoids, terpenoids, and steroids etc have received considerable attention in recent years due to their diverse therapeutic benefits. Some studies have shown positive correlation of the increased uptake of natural antioxidants with the reduced coronary heart disease and cancer mortality [7]. When one could find out the components of the active moiety of the plant, then the importance of the structural elucidation the compound starts. Once the structure of the active compound is identified, the area is opening for researchers in many fields including chemistry and biochemistry as well as pharmaceutical applications in industries for the production as medicine. Structural elucidation of naturally occurring compounds is a highly discussed area of research for the last half a century [8], [9]. The advancement of sophisticated instrumental techniques made the path easier for the researchers to deduce the structure of the isolated compounds.

Mimosa pudica (Family: Leguminosae) is a small or middle sizes diffusely spreading herb with branched stems up to tree about 1 m in height. The leaves are very sensitive, both pinnae and leaflets folding when touched [10], [11]. The plant is useful in vitiated conditions of pitta, leucoderma, vaginopathy, ulcers, dysentery, inflammations, burning sensations, smallpox, strangury, spasmodic, affections and fevers. The leaves are bitter, sudorific and tonic and are useful in hydrocele, hemorrhoids, conjunctivitis, cuts and wounds and hemorrhages [12]. The plant has anti-microbial, anti-convulsant, hyperglycemic, anti-venom, diuretic, anti-cancer, antidiabetic, antiulcer, anti-diarrhoeal, anti-fertility and anti-histamic activities [13], [14], [15]. Phytochemical evaluations on Mimosa pudica have revealed the presence of alkaloids, non-protein amino acid (mimosine), flavonoids, C-glycosides, sterols, terpanoids, tannins and fatty acids [16]. Adrenalin like substance has been identified in its leaf extracts. Ascorbic acid, crocetin, D-glucuronic acid, linoleic acid, linolenic acid, palmitic and stearic acid, D-xylose and b-sitosterols were found the phytochemical analysis of its root. Seeds were reported to yield sitosterol [17], [18]. The roots of Mimosa pudica are useful in diseases arising from blood impurities and bile, bilious fevers, piles, fistula, jaundice, leprosy etc. Aqueous extract of the roots has shown significant neutralizing effects on the lethality of the venom of the monocled cobra. It appears to inhibit the monotoxicity and enzyme activity of cobra venom. All parts of the plant are considered to possess medicinal properties [19], [20].

Flavonoid comprises the largest class of plant secondary metabolites, characterized by a phenyl benzopyrone structure. They occur naturally in fruits, vegetables and plant derived beverages. According to the chemical structure, flavonoids are classifieds into flavonols, flavones, flavanones, isoflavones, catechins, anthocyanidins and chalcones [21]. The flavonoids have aroused considerable interest recently because of their potential beneficial effects on human health. They have been reported to have antiviral, anti-allergic, antiplatelet, anti-inflammatory, antitumor, antithrombotic, hypolipidemic and hypoglycemic activities [22], [23], [24]. Flavonoids have been reported to have potent antioxidant activities. Flavonoid helps to reduce oxidative stress that has been linked to cancer, ageing, atherosclerosis, ischemic injury, inflammation and neuro-degenerative diseases (Parkinson’s and Alzheimer’s) [25], [26], [27]. The role of flavonoids includes the inhibition of activation of pro-carcinogens, inhibition of proliferation of cancer cells, selective death of cancer cells by apoptosis, inhibition of metastasis and angiogenesis, activation of immune response against cancer cells, modulation of the inflammatory cascade and the modulation of drug resistance [28].

In our earlier studies, we have reported the anticancer activity of the flavonoid isolated from Mimosa pudica against human breast cancer cell line (MCF-7) [29] and its radical scavenging and immunomodulatory activities [30]. Here we report the in vitro anticancer activity study of the isolated compound against A549 and K562 cell lines along with in vivo study using Dalton's Ascites Lymphoma (DAL) in Swiss albino mice. The structure of the compound was also elucidated using several spectral techniques such as UV- Visible, FT-IR, 1H NMR and Mass spectra.

Section snippets

Collection of plant materials

The whole plant Mimosa pudica was collected from Kannur district of Kerala, India. After selection, plants were taxonomically identified by Dr. Sujanapal P, Scientist, Kerala Forest Research Institute (KFRI), Thrissur, India. The whole plant Mimosa pudica was thoroughly washed with water. They were chopped into small pieces, dried in shade, grinded into powder form.

Extraction and isolation of flavonoid from Mimosa pudica

The samples were soxhlet extracted in 80% methanol (100 ml/g dry weight) for 24 h. The extracts were concentrated and reconcentrated

2-(2′,6′-dimethyl-3′,4′,5′-alkyl or hydroxy alkyl substituted phenyl)-3-oxy-(alkyl or hydoxy alkyl) 5,7-dihydroxy-chromen-4-one (Fig. 1)

Appearance: yellow solid; UV–vis (Ethanol) ʎmax: 281 nm [phenolic −OH], 319 nm [Cdouble bondO aryl ketone] (Fig. 2 ); FT-IR (KBr) Vmax: 3419 cm−1 [Phenolic Osingle bondH stretching vibrations], 2939 cm−1[Csingle bondH stretching vibrations of alkanes], 1668 cm−1 [Cdouble bondO cyclic ketone stretching vibrations] and 1612 cm−1 [Csingle bondC aromatic ring stretching vibrations] (Fig. 3); 1H NMR (DMSO, δ): 8.80–8.30 ppm (m) [Phenolic Osingle bondH], 7.39–8.04 ppm (m) [aromatic hydrogens adjacent to Phenolic Osingle bondH], 6.90–6.20 ppm (m) [aromatic hydrogens], 6.55 ppm (s), 5.18 

Discussion

Many of the cancer chemotherapeutics are found to have side effects in high and repeated doses. So there has been an increased demand for the development of new effective drugs for the treatment of cancer from natural sources since they are considered to be safe and free from side effects. In this study, we have isolated a novel flavonoid derivative from the plant Mimosa pudica.

The compound isolated from Mimosa pudica has shown potent anticancer activity against tumor cell lines; A549 and K562.

Conclusion

Development of drug having less toxicity and free from side effects is substantially necessary. This creates increase in demand for the naturally occurring compounds having therapeutic properties. Therefore, we focused on phytochemicals and isolated a flavonoid derivative from the plant Mimosa pudica. The structure of the compound was elucidated with the help of different spectroscopic techniques and was found to be a derivative of myricetin having alkyl, hydroxy alkyl and methyl substitutions.

Acknowledgements

The authors are thankful for the financial support provided by the Kannur University, Kerala, India, in the form of Junior Research Fellowship. We are indebted to Dr. Ramadasan Kuttan, Research Director, Amala Cancer Research Centre, Thrissur, Kerala for providing facility for doing in vivo studies. We are also thankful to Dr. C Baby, IIT Madras and Mr. Dineep, MG University, Kerala for their help in Spectroscopic analysis.

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