Accepted Manuscript Title: Saponins: Anti-diabetic principles from medicinal plants-A review Author: Elekofehinti Olusola Olalekan PII: DOI: Reference:
S0928-4680(15)00019-X http://dx.doi.org/doi:10.1016/j.pathophys.2015.02.001 PATPHY 832
To appear in:
Pathophysiology
Received date: Revised date: Accepted date:
5-12-2013 25-1-2015 9-2-2015
Please cite this article as: E.O. Olalekan, Saponins: Anti-diabetic principles from medicinal plants-A review, Pathophysiology (2015), http://dx.doi.org/10.1016/j.pathophys.2015.02.001 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Saponins: Anti-diabetic principles from medicinal plants-A review
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Elekofehinti Olusola Olalekan
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Department of Biochemistry, Adekunle Ajasin University, Akungba, Akoko, Ondo State.
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Nigeria.
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*Corresponding Author:
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Elekofehinti Olusola Olalekan
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Department of Biochemistry,
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Adekunle Ajasin University Akungba Akoko.
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P.M.B 001 Akungba Akoko. Ondo State. Nigeria
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e-mail:
[email protected],
[email protected] 14
TEL: +2348034450611
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Abstract
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Diabetes mellitus (DM) represents a global health problem. It is the most common of the
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endocrine disorders and is characterized by chronic hyperglycemia due to relative or absolute
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lack of insulin secretion or insulin actions. According to the World Health Organization
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projections, the diabetes population is likely to increase to 300 million or more by the year 2025.
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Current synthetic agents and insulin used effectively for the treatment of diabetes are scarce
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especially in rural areas, expensive and have prominent adverse effects. Complementary and
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alternative approaches to diabetes management such as isolation of phytochemicals with anti-
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hyperglycemic activities from medicinal plants is therefore imperative. Saponins are
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phytochemical with structural diversity and biological activities. This paper reviews saponins
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and various plants from which they were isolated as well as properties that make them ideal for
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antidiabetic remedy.
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Keyword: Diabetes, Medicinal Plants, Saponin, Hyperglyceamia, Phytochemicals.
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Introduction
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Diabetes mellitus (DM), a common and prevalent disease, is a metabolic disorder affecting the
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citizens of both developed and developing countries [1]. It is one of the five leading causes of
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death in the world. It is projected that about 300 million people will have the disease by the year
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2025 [2-3]. Diabetes is divided into two major categories: Type 1 also known as Insulin-
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dependent diabetes mellitus (IDDM) and type 2 known as non- insulin dependent diabetes
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mellitus (NIDDM). Type 1 (IDDM) is an autoimmune disorder caused by auto aggressive T-
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lymphocytes that infiltrate the pancreas and destroy insulin producing β-cells leading to
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hypoinsulinaemia and thus hyperglycemic condition [4-5]. This develops over a period of time to
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diabetic complications such as nephropathy, retinopathy, neuropathy, and cardiomyopathy [5,6].
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Associated metabolic complications of type-I diabetes are due to insulin deficiency and related
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glucose under-utilization of the insulin-dependent tissue, such as liver, and glucose over-
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utilization in insulin-independent tissue, such as kidney [5,7]. Type 2 diabetes (NIDDM) is
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known to have a strong genetic component with contributing environmental determinants.
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Though the disease is genetically heterogeneous, there appears to be a fairly consistent
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phenotype once the disease is fully manifested [8]. Whatever the pathogenic causes, the early
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stage of type 2 diabetes is characterized by insulin resistance in insulin-targeting tissues, mainly
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the liver, skeletal muscle, and adipocytes. Insulin resistance in these tissues is associated with
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excessive glucose production by the liver and impaired glucose utilization by peripheral tissues
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[9-10].
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Type 2 diabetes can also be influenced by ethnicity, degree of obesity, distribution of body fat,
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sedentary lifestyle, aging, and other concomitant medical conditions [8,11]. Treatment of DM
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takes three main forms: (i) diet and exercise, (ii) insulin replacement therapy and (iii) the
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use of oral hypoglycemic agents (sulfonylureas and biguanides) [12].
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Although, considerable progress in the treatment of diabetes by oral hypoglycemic agent has
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been made, search for newer drugs continues due to the limitation of existing synthetic drugs
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such as hypoglycemia, drug-resistance, dropsy, and weight gain [13]. Thus, there is still a
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challenge in the management of diabetes without any side effects. Reports have shown that about
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80% of the world population is almost entirely dependent on traditional medicines [14-15]. The
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ethnobotanical details, antidiabetic and hypoglycemic potential of several plants have been
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reported [16-18]. Several reports have revealed that the hypoglycaemic activity of most
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antidiabetic medicinal plants has been attributed to the presence of saponins [19-27]. The
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evaluation of saponin constituents of medicinal plants seems to be a logical way of
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searching for new drugs to treat this disease.
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Saponins are naturally occurring surface-active glycosides. They are mainly produced by plants,
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but also by lower marine animals and some bacteria [28-29]. Saponins consist of a sugar moiety
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usually containing glucose, galactose, glucuronic acid, xylose, rhamnose or methylpentose,
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glycosidically linked to a hydrophobic aglycone (sapogenin) which may be triterpenoid or
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steroid in nature [30]. The complex structure of saponin is due (a) to the variation in structure of
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the aglycone, (b) the nature of the side chains and (c) the position of attachment of these moieties
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on the aglycone [30]. Saponin has been reported to have many pharmacological properties.
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The aim of this review is to collate some available data on saponin isolated from medicinal plant
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as the phytochemical in plants with antidiabetic effect. It is hoped that the information collated
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here will provide the reader with information regarding the antidiabetic potential of saponins and
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stimulate further research into these compounds.
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2.0
Saponins with antidiabetic properties
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2.1
Anabasis articulate saponin
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Saponin from areal parts of A. articulate showed potent glycemic control and prevent metabolic
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disorders and liver damage caused by hyperglycemia in streptozotocin-induced diabetic
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hepatopathy in rats. The antihyperglycemic activity was attributed to the ability of saponin to
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induce the release of insulin from the pancreas [31].
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2.2
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Astragalus saponin I , extracted from the root of Astragalus membranaceus (Table 1) has been
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reported to have various biological activities like increase in the secretion of insulin and C-
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peptide on rats [32]. Therapeutic effects on several pharmacological targets, such as oxidative
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stress, advanced glycation end products (AGEs), transforming growth factorβ1 (TGFβ1), in the
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development of diabetic nephropathy (DN) and is a potential drug for prevention of early DN
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[33-34]. Astragaloside IV is a glycoside of cycloartane-type triterpene saponin isolated from the
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Astragalus membranaceus, This saponin has been shown to possess many pharmacological
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activities including antidiabetes [34]. It also showed protective effect against the progression of
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peripheral neuropathy in STZ-induced diabetic rats [35]. The antidiabetic mechanism of this
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Astragalus membranaceus saponin
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compound is through a decrease in blood glucose concentration and an increase in plasma insulin
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levels [35]. In another study, Astragaloside IV at 25 and 50 mg/kg was reported to significantly
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decrease blood glucose, triglyceride and insulin levels, and inhibited the mRNA and protein
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expression as well as enzyme activity of glycogen phosphorylase and glucose 6 phsphatase in
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diabetic mice [36].
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2.3
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A 1%
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male diabetic rats for three weeks significantly decreased plasma glucose and reduced the
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activity of glucose 6 phosphatase in the liver [37].
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2.4
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Diosgenin [25R-spriost-5-en-3β-ol] is a hydrolysate of dioscin contained in the rootstock of yam.
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It is a steroidal saponin, with many biological activities. Consumption of diosgenin demonstrated
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that it possessed hypoglycemic effect. One property of this saponin that is beneficial in diabetes
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is reduction of intestinal disaccharidase activities. Saponin from yam reduced intestinal sucrase
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activity in experimental studies in diabetic male wistar rats. The activity of glucose -6- phosphate
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was also significantly increased [38-39].
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2.5
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Saponin is very abundant in the seed of Entada phaseoloides. Saponin from the seed of E.
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phaseoloides significantly reduced fasted blood glucose, serum insulin levels and alleviates
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hyperglycemia associated oxidative stress in type 2 DM rats. Also, a significantly
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hypolipidemic effect and an improvement in tissue steatosis was observed after saponin
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Dioscorea polygonoides saponin
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Dioscorea rotundata (Yam) saponin
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inclusion of steroidal saponin (Table 1) from Dioscorea polygonoides in the diet of
Entada phaseoloides saponin
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administration. The observed effect of saponin implied that it exhibit its hypoglycemic effect
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through improving peripheral insulin resistance rather than protecting pancreas islet β-cells
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and stimulating insulin secretion [40].
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2.6.
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Garcinia kola is a species of flowering plant in the Clusiaceae or Guttiferae family. Its natural
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habitat is subtropical or tropical moist lowland forests [41]. It has been proved to be one of the
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many non-timber forest products that are of high socio-economic importance(Adebisi, 2004).
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The findings of [42] indicated that administration of saponin from G. kola in alloxan-induced
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diabetic rats caused a significant (P