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α-Glucosidase and tyrosinase inhibitory effects of an abietane type diterpenoid taxoquinone from Metasequoia glyptostroboides
© Bajpai et al.; licensee BioMed Central. 2015
Received: 1 October 2014
Accepted: 18 March 2015
Published: 26 March 2015
Nowadays plant derived natural compounds have gained huge amount of research attention especially in food and medicine industries due to their multitude of biological and therapeutic properties as alternative medicines.
In this study, a diterpenoid compound taxoquinone, isolated from Metasequoia glyptostroboides was evaluated for its α–glucosidase and tyrosinase inhibitory efficacy in terms of its potent anti-diabetic and depigmentation potential, respectively.
As a result, taxoquinone at the concentration range of 100–3,000 μg/mL and 200–1,000 μg/mL showed potent efficacy on inhibiting α-glucosidase and tyrosinase enzymes by 9.24-51.32% and 11.14-52.32%, respectively.
The findings of this study clearly evident potent therapeutic efficacy of an abietane diterpenoid taxoquinone isolated from M. glyptostroboides with a possibility for using it as a novel candidate in food and medicine industry as a natural alternative medicine to prevent diabetes mellitus type-2 related disorders and as a depigmentation agent.
Diabetes mellitus is a metabolic disorder caused by a lack of insulin characterized by hyperglycemia . Diabetes mellitus type 2 is also known as non-insulin-dependent diabetes mellitus which is caused by insulin dysfunction, especially after food intake. The effective treatment for type 2 is to inhibit or delay intestinal carbohydrate digestion. Carbohydrates which are the major components of our daily foods, for instance polysaccharides, are transformed into simple sugars, and then absorbed through the intestine. α-Glucosidase, an enzyme located in the small intestine epithelium, catalyzes the cleavage of disaccharides and oligosaccharides to glucose. Glucosidase inhibitors reduce the rate of carbohydrate digestion and delay the carbohydrate absorption from the digestive tract. Therefore, they have a potential to prevent the development of type 2 diabetes mellitus by lowering the after-meal glucose levels .
Human skin contains four major chromophores including haemoglobin, oxyhaemoglobin, carotenoids and melanin(s) where melanin acts as a dominant component of normal skin color and pigmentation . The epidermis cells in the innermost layer of skin produce melanin upon exposure of ultraviolet radiation leading to tyrosinase mediated melanogenesis . Tyrosinase is a multifunctional copper-containing enzyme, widely distributed in plants and animals which catalyzes the initial step in the formation of the pigment melanin from tyrosine . Hence, tyrosinase is known to be a key enzyme for melanin biosynthesis in plants and animals. Although use of tyrosinase inhibitors such as kojic acid and hydroquinone is gaining increasing attention in the cosmetic industry due to their anti-pigmenting effects, they have found to exert severe causes of skin inflammations. Hence, use of natural plant based secondary metabolite to cure skin diseases especially for cosmetic purposes could be a safe and alternative therapy in cosmetic industry to provide lead compounds to serve as natural anti-pigmentation compounds .
Phytochemicals confer various health benefits, among them, α-glucosidase and tyrosinase inhibitory activities have particularly received intensive attention due to the increasing number of patients suffering from diabetes type 2 and skin disorders. Though synthetic α-glucosidase and tyrosinase inhibitors have been used effectively, many doubts have been raised on their safety such as increased toxicity and adverse side effects. Hence, attention has been focused on the effective use of plant based compounds which are less toxic and natural in origin.
Although biological and therapeutic potential of M. glyptostroboides derived compounds has been reported previously [6-8], no report is available on α-glucosidase and tyrosinase inhibitory effects of taxoquinone, a diterpenoid from M. glyptostroboides. Hence, the aim of this research is to confirm the therapeutic potential of taxoquinone as a potent α-glucosidase and tyrosinase inhibitor.
Chemicals and instrument
Kojic acid, acarbose, sodium azide (NaN3) bovine serum albumin, P-Nitrophenyl-α-D-glucopyranoside, yeast α-glucosidase, mushroom tyrosinase, and 3,4-dihydroxy-L-phenylalanine (DOPA) were purchased from (Sigma-Aldrich, St. Louis, MO, USA). All other reagents used were of high analytical grade. Spectrophotometric measurements were done by using a 96-well micro-plate ELISA reader (Infinite M200, Tecan, Switzerland).
The mature cones (16 ~ 22 months old) of M. glyptostroboides were collected from Pohang city, Korea, and identified by the morphological features and the database present in the library at the Department of Biotechnology, Daegu University, Korea. A voucher specimen of M. glyptostroboides cone (DUB-0038) was deposited in the herbarium of College of Engineering, Department of Biotechnology, Daegu University, Korea.
Extraction and isolation of taxoquinone
Dried cones of M. glyptostroboides (2 kg) were milled into powder and then extracted with ethyl acetate at room temperature for 12 days. The extract was evaporated under reduced pressure using a rotary evaporator (EYELA N1000, Japan). The dried ethyl acetate extract (7 g) was subjected to column chromatography over silica gel (mesh 230–400 mesh, Merck, Darmstadt, Germany) and was eluted with hexane-ethyl acetate-methanol solvent system to give 20 fractions. Of the fractions obtained, fraction-12 was further purified by preparative TLC over silica gel GF254 using hexane-ethyl acetate (1:2) as a mobile phase to give one compound (152 mg) which on the basis of spectral data analysis was characterized as a taxoquinone .
Assay of α-glucosidase inhibition
Assay of tyrosinase inhibition
All the data were expressed as mean ± standard deviation of three replicates. Tests of significant differences were determined by one way ANOVA followed by Duncan’s test using SAS software (SAS 9.2, SAS), and the values were considered to be significant (p < 0.05).
Results and discussion
Identification of taxoquinone
Inhibition of α-glucosidase
Phytochemicals efficiently contribute human being with health beneficial therapeutic agents of natural origin for their use in developing novel diabetes therapies or bio-therapeutic agents . Although there is a huge ongoing interest in the application of plant-based compounds for alleviating chronic diseases due to their potent therapeutic and biomedicinal efficacy, the use of phytochemicals within the context of diabetes remains largely unexplored. This has urged the scientists to provide scientific evidences on the development of more effective agents conferring inhibitory effects on intestinal glucosidases. In this regard, inhibition of intestinal α-glucosidase to control hyperglycemia is an established strategy [11,12]. Hence, to overcome the adversary effects of clinical available synthetic α-glucosidase inhibitors, there is still need to develop alternative therapies to inhibit this key enzyme in order to minimize side effects and drug cost efficacy. A number of plant-based natural compounds have been screened for their enzymatic inhibitory activities [9,11,12].
Inhibition of tyrosinase
Melanin is a polymerized natural coloring determinant widely distributed in plants, animals and microorganisms. A number of melanins are produced by multi-stepped enzymatic and non-enzymatic oxidation and polymerization processes. The mechanism of tyrosinase inhibition activity may be an important factor in the skin whitening of a cosmetic composition . Melanin biosynthesis steps in the body include L-DOPA by tyrosine as a substrate, followed by its conversion to L-dopaquinone by the successive enzymatic oxidations, leading to take place a reaction of polymerization .
In this research, a diterpenoid compound taxoquinone isolated from M. glyptostroboides demonstrated a considerable amount of α-glucosidase and tyrosinase inhibitory effects in vitro which may have potential to reduce after meal blood glucose levels and to maintain healthy skin by serving as a skin depigmentation agent. Based on the finding of this study, it can be concluded that taxoquinone in terms of its potent hypoglycemic and skin-whiting efficacy makes it to be a molecule of choice for using in health-care and drug therapies in the treatment of infectious diseases. However, further studies are needed to demonstrate a precise mode of action of taxoquinone to confirm its in vivo anti-diabetic and depigmentation potential.
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