Plants and their active constituents from South, Central, and North America with hypoglycemic activity

REVISÃO

Plants and their active constituents from South, Central, and North America with hypoglycemic activity

José M. Barbosa-Filho^*; Tereza H.C. Vasconcelos; Adriana A. Alencar; Leônia M. Batista; Rinalda A.G. Oliveira; Diego N. Guedes; Heloina de S. Falcão; Marcelo D. Moura; Margareth F.F.M. Diniz; João Modesto-Filho

Laboratório de Tecnologia Farmacêutica "Delby Fernandes de Medeiros", Universidade Federal da Paraíba, Caixa Postal 5009, 58051-970, João Pessoa, PB, Brazil

ABSTRACT

There has been marked interest in recent years in the use of plants for the treatment of diabetes. Plants have been found in many countries which have been indicated as having hypoglycemic activity. The present work is an up-to-date review with 178 references of crude plant extracts and chemically defined molecules with hypoglycemic activity from South, Central and North America. The review refers to 224 plants with their families, parts used and type of extract, organism tested and activity. It also includes 40 compounds isolated from those plants. Some aspects of recent research with natural products from plants directed to the treatment of diabetes are discussed.

Keywords: Diabetes, hypoglycemic activity, medicinal plants, natural products.

INTRODUCTION

Diabetes is a disease in which the body does not produce insulin or use it properly. Insulin is a hormone needed to convert sugar, starch and other food into energy needed for daily life. The cause of diabetes continues to be a mystery, althought both genetic and environmental factors such as obesity and lack of exercise appear to play a part.

Worldwide 177 million people suffer from diabetes. This figure is likely to more than double by 2030 (See Table 1). The greater part of the increase is likely to occur in developing countries, which can least afford it.

The annual number of deaths in 2000 caused by diabetes mellitus in Latin America and the Caribbean has been estimated as 339035. This represents a loss of 757096 years of productive life among persons younger than 65 years (Barceló et al 2003). Diabetes is the third leading cause of death in the United States after heart disease and cancer (Acessed from http://www.medicinenet.com/Diabetes_Mellitus/article.htm in 01/21/2004).

Plants have always been an important source of drugs and many of the currently available drugs have been derived directly or indirectly from them. Ethnobotanical reports indicate about 1200 plants in the world with anti-diabetic potential (Alarcon-Aguilara et al 2002c), of which more than three hundred have been reported in the literature (Perez et al 1984; Almeida et al 1986; Bailey et al 1989; Handa et al 1989; Ivorra et al 1989; Oliveira et al 1989; Rahman et al 1989; Marles et al 1995; Ernest 1997; Pereira 1997; Perez et al 1998b; Volpato et al 2002; Grover et al 2002), referring to a large variety of identified chemical substances (Ivorra et al 1989; Rahman et al 1989; Marles et al 1995; Perez et al 1998b; Lamba et al 2000). The discovery of the widely used hypoglycemic drug, metformin (N,N-dimethylguanylguanidine) came from the traditional approach through the use of Galega officinalis (Grover et al 2002).

In a previous paper this research group has reviewed crude plant extracts and chemically defined molecules with potential antitumor activity for mammary (Moura et al 2001), cervical (Moura et al, 2002) and ovarian neoplasias (Silva et al 2003), as inhibitors of HMG CoA reductase (Gonçalves et al, 2000), central analgesic activity (Almeida et al, 2001), employed in prevention of osteoporosis (Pereira et al, 2002), for the treatment of Parkinson's disease (Morais, 2004) and antileishmanial activity (Rocha et al, 2005).

The present work reviews the literature on plants and plant-derived compounds from South, Central, and North America with hypoglycemic activity. Those plants which are used in the indigenous system of medicine have not been included, except for those whose hypoglycemic activity has been scientifically established.

The search was carred out on Chemical Abstracts, Biological Abstracts, Web of Sciences, LILACS (Latin American and Caribbean literature in Health Sciences) and the data bank of The University of Illinois in Chicago - NAPRALERT (Acronym for Natural Products ALERT), updated to December 2003, using hypoglycemic activity plus anti-diabetic as search terms. The references found in the search were consulted.

The search for data from different sources led to the elaboration of a list of natural products, evaluated specifically for hypoglycemic effect, of several plants and plant-derived compounds, used as anti-diabetic remedies from South, Central and North America (Tables 2-4). It should be noted that most of the references cited are not first hand observations, but compilations copied from other sources. The original references should be consulted for details on the models or mechanism based bioassays used for testing plant extracts and pure compounds for hypoglycemic activity.

Plants and plant-derived compounds with hypoglicemic activity

In the Americas many plants are used popularly to control diabetes mellitus. This has caused an increase in the number of experimental and clinical investigations directed toward the validation of the anti-diabetic properties, which have been empirically attributed to these remedies.

In Brazil, around 200 plants are used empirically to control diabetes mellitus. Of these, fifty two have been experimentally studied and hypoglycaemic activity detected in most of them (See Table 2). Bauhinia forficata known popularly as "pata-de-vaca" (cows hoof) is the most studied species. Some studies confirm the activity and others do not. This controversy may be related to the model employed in the experiments. More recently, Pepato et al. (2002) analysed the effects of a leaf decoction as a driking-water substitute for about 1 month on streptozotocin-diabetes (STZ-diabetes) in male Wistar rats. The STZ-diabetic rats treated with the decoction showed a significant reduction in serum and urinary glucose as compared with the STZ-diabetic control, no difference being seen between decoction-treated and -untreated non-diabetic rats.

In Venezuela, the aqueous extract of B. megalandra has been used for diabetes mellitus. It was shown to inhibit intestinal glucose absorption in a concentration-dependent way and additive to phlorizine (Gonzalez-Mujica et al., 2003). In addition, the Chilean species B. candicans also used for diabetes, presented a significant decrease of glycaemia in alloxan diabetic rats (Lemus et al., 1999).

Phyllanthus sellowianus is a plant used in folk medicine in Argentina as a hypoglycemic and diuretic agent. The aqueous and butanolic extract of this plant, administered at a dose of 200 mg/kg p.o., caused a significant reduction in blood glucose concentration after 6 and 9 h in mice, similar to that observed with glibenclamide (10 mg/kg) which was used as a reference, while the dichloromethane extract of the same plant was ineffective (Hnatyszyn et al., 2002).

Aproximately 150 plants are used in traditional folk medicine in the treatment of diabetes in Mexico (Alarcon-Aguilar et al., 1998). However, only a small number of them have been studied scientifically. The plants most extensively studied are "nopal" Opuntia streptacantha, "tronadora" Tecoma stans, "Guarumbo" Cecropia obtusifolia and "Matarique" Psacalium decompositum, (see Table 3). The aqueous extract of the latter species significantly reduced blood glucose in a dose-dependent manner in normal mice after intraperitoneal administration (P < 0.05) (Alarcon-Aguilar et al., 2000).

A menu which includes common culinary herbs and spices with hypoglycemic activity for the control and prevention of diabetes mellitus was utilized by Broadhurst et al. (2000). To evaluate the possible effects on insulin function, 49 herb, spice, and medicinal plant extracts were tested in the insulin-dependent utilization of glucose using the rat epididymal adipocyte assay. "Cinnamon" Cinnamomum cassia was the most bioactive product followed by witch hazel Hamamelis virginiana, green and black teas Camellia sinensis, allspice Pimenta officinalis, bay leaves Laurus nobilis, nutmeg Myristica fragans, and cloves Syzigium aromaticum (see Table 4).

A survey of the literature has shown that a large variety of compounds obtained from several plants of South, Central and North America were found to possess hypoglycemic action. For instance, the triterpenes oleanolic acid (1) and bassic acid (2) from Bouvardia terniflora (Perez et al., 1998) and Bumelia sartorum (Naik et al., 1991) respectively lowered blood sugar in test animals. Similarly the diterpenes trans-dehydrocrotonin (3) from Croton cajucara (Farias et al., 1997) and steviol (4) from Stevia rebaudiana (Ishii; Bracht, 1985) exhibited similar activity. Certain flavonoids eg. 5,7,3-trihydroxy-3,6-4'-trimethoxyflavone (5) from Brickellia veronicaefolia (Perez et al., 2000a) and the glycoside isoorientin (6) from Cecropia obtusifolia (Andrade-Cetto et al., 2001) also showed hypoglycaemic effects. A number of alkaloids isolated from Vinca rosea (Catharanthus rosea) with antitumor activity (Svoboda et al., 1964) were submitted for assay for hypoglycemic effects. The results indicated that catharantine, leurosine (7), lochnerine, tetrahydroalstonine, vindoline and vindolinine (8) produce varying degrees of blood-sugar reduction. For Otholobium pubescens this property was attributed to a phenolic compound bakuchiol (9). The amino acid hypoglycine A (10) isolated from Blighia sapida was particularly effective against diabetes (Kean, 1975; Mills et al., 1987) (Figure 1). The great variety of chemical classes indicate that a variety of mechanisms of action are involved in reduction of the glucose level in blood.

The information recorded in Tables 2-4, has been assembled by continent (South, Central and North America), with the name of the country, plant in alphabetical order, scientific name, family, part used, organism tested, activity and reference. This study has enumerated 224 plants and 40 compounds for which hypoglycemic activity has been reported, as a result of pharmacological studies carried out in various research centers in Argentina, Brazil, Canada, Chile Colombia, Cuba, Jamaica, Mexico, Panama, Paraguay, Peru, Puerto Rico Trinidad and the USA. The ten principal families in which such activity has been reported are Fabaceae (25), Asteraceae (25), Myrtaceae (11), Labiatae (10), Cucurbitaceae (8), Solanaceae (7), Anacardiaceae (6), Euphorbiaceae (6), Rubiaceae (6), and Liliaceae (5).

CONCLUSION

This literature review adds more data to that previously published, since there are many plants in South, Central and North America, which present hypoglycemic effects.

The number of plants described in the literature as having hypoglycemic activity is more or less the same in the three continents. Among the 224 plants studied 73 (33%) are found in South America, 77 (34%) in Central America and 74 (33%) in North America. The countries in each continent with the largest contribution are: Brazil with 52 (23%) of the plants studied, Mexico with 54 (24%) and the USA with 70 (31%). None of the plants with hypoglycemic activity was found in all three continents. The following species stood out for the number of citations reported in the scientific literature in each continent: Bauhinia forficata with 8 citations (Brazil), Opuntia streptacantha with 5 citations (Mexico) and, Avena sativa (USA) with 3 citations.

Of an estimated 250.000 higher plants, less than 1% have been screened pharmacologycally and very few in regard to diabetes mellitus. Therefore, it is prudent to look for options in herbal medicine for diabetes mainly in developing countries because it is a pathological condition associated with high morbidity, mortality and economic impact. None of the plants used in traditional medicine, should be used until safety studies have been completed.

ACKNOWLEDGEMENTS

The authors wish to express their sincere thanks to the College of Pharmacy of the University of Illinois at Chicago, Chicago, Illinois 60612-7231, U.S.A., for helping with the computer aided NAPRALERT and CNPq/FAPESQ-PB/Brazil for financial support.

Received 08/22/05

Accepted 11/25/05

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Publication Dates

• Publication in this collection
  05 May 2008
• Date of issue
  Dec 2005

History

• Accepted
  25 Nov 2005
• Received
  22 Aug 2005