A brief review on anti diabetic plants: Global distribution, active ingredients, extraction techniques

Access this article online Quick Response Code: Website: www.phcogrev.com DOI: 10.4103/0973-7847.95854 INTRODUCTION Research on diabetes treatment is gaining ground as the world population with diabetes is rising each year, and is expected to hit 439 million adults by 2030.[1] The awareness on the issue has led to a vast discovery of new medications as well as natural products extracted from herbal plants. Many active ingredients extracted from herbal plants possess therapeutic values, i.e. hypoglycemic activity, antioxidant action, etc and they are yet to be discovered. In view of that, a study has been performed on anti diabetic plant extracts and the focuses are on: the global distribution of the plants; the parts in which therapeutic elements are located; and, also the acting mechanism for diabetic treatment. This study not only provides researchers with the information pertaining to anti diabetic plants, but also to evaluate their related research activities. The papers reviewed in this article are selected from the medicinal journals as tabulated in Table 1 due to their popularity and reliable reputation in medicinal research on herbal plant extract. The research papers were extracted from the selected journals under key words of “Plant extract for diabetes treatment”. The information extracted from the 34 journals listed was compiled and arranged into respective sections as guidance for any interested parties. GLOBAL DISTRIBUTION OF ANTI DIABETIC PLANTS Anti diabetic plants were widely distributed in six continental regions, and some specific regions around the world such as in Caribbean, Mediterranean and Middle East. This section lists the areas of distribution of the anti diabetic plants with the intention to identify and deduce their locations. The worldwide distribution of anti diabetic plants is depicted in Figure 1. This figure shows that Asia (56%) and Africa (17%) dominated the global distribution of the anti diabetic plants. This is not surprising as the two continents are located in the tropic and subtropic regions, and have large coverage of tropical rain forests. Moreover, these regions have their long established traditional medicine systems. As the activity of herbal plant researches in Chan, et al.: Distribution, active ingredients and extraction techniques of anti diabetic plants Pharmacognosy Reviews | January-June 2012 | Vol 6 | Issue 11 23 certain regions is proportional to the plant distribution, American continent has a 10% research performed on the medicinal plants. European countries led by Germany are closely behind with 6%. Besides, some strategic regions such as Caribbean, Mediterranean and Middle East, have individually engaged to around 2 to 4% research on herbal plants, and Australian continent has contributed 1 % to the anti diabetic herbal plants research. Based on the records for 20 years of research on plants possessing anti diabetic properties [Figure 2], Asia and Africa demonstrate an increase in the trends and research activities since 1995, and this rise is further expected to continue. Comparing between these two continents, the increment of the research on herbal plants in Asia is about 40% higher than that in the African continent. On the other hand, North America, South America and Europe show stable increase in the research activity towards the year 2010, whereas Australia remains unchanged in its research activity on anti diabetic plants for the last 20 years. From this figure, it is clear that Asia and Africa which are rich in plants effective for diabetes treatment, have carried out maximum research in the past few years. The distribution in Figure 2 indicates that Asia has the most herbal plants which corresponds to the large numbers of researches conducted in the region. The detail distribution of the antidiabetic herbal plants in this continent is charted in Figure 3. South Asia has a large distribution of 36% followed by East Asia and South East Asia which dominate 27% and 17% respectively. The leading countries for the herbal plant research here are India and China. Many of the research hypotheses have been based on traditional medicine system such as Chinese Herbology and Ayurveda’. These two traditional medicine systems are the foundation for the herbal plant medicinal research in their respective regions. Northern Asia has the least distribution of the herbal plants due to its temperate zone and Siberian influence Table 1: The selected 34 medicinal journals for the study Antiviral Research Asian Pacific Journal of Tropical Medicine Biochemical and Biophysical Research Communication Bioorganic and Medicinal Chemistry Biotechnology Cancer Letters Carbohydrate Polymer Chemico-Biological Interaction Clinical Research and Review Diabetes Research and Clinical Practise Environmental Toxicology and Pharmacology European Journal of Integrative Medicine European Journal of Pharmacology Fitoterapia Food and Chemical Toxicology Food Chemistry Free Radical Biology and Medicine General Pharmacology International Immunopharmacology Journal of Biological Sciences Journal of Controlled Release Journal of Ethnopharmacology Journal of Food Composition and Analysis Journal of Urology Life Sciences Metabolism Neuroscience Letter Nutrition Nutrition Research Nutrition, Metabolism and Cardiovascular Diseases Parasitology International Pharmacological Research Phytomedicine South African Journal of Botany Data was extracted from 1990 up to June 2010. Figure 1: Distribution of plants for diabetes treatment as seen in the study Figure 2: Activity of plant-based research for anti diabetic treatment in the past 20 years as seen in the study Figure 3: The distribution of anti diabetic plants in Asia as seen in the study East asia 27% South asia 36% West asia 14% South east asia 17% North aisa 6% Chan, et al.: Distribution, active ingredients and extraction techniques of anti diabetic plants 24 Pharmacognosy Reviews | January-June 2012 | Vol 6 | Issue 11 whilst, South Asia and East Asia are the potential regions of herbal plants, and so is their intermediate, South East Asia. DISTRIBUTION OF ACTIVE ANTI DIABETIC COMPOUNDS IN PLANTS AND THEIR EXTRACTION TECHNIQUES The parts of plants that possess active compounds for diabetic treatment and various types of extraction techniques applied are presented in this section. In some cases in which the active ingredients are scattered all over the plants, the entire plants were prepared and extracted for the desired ingredient. More than 80 plants with printed records from the 34 related journals reviewed in this manuscript involved the extraction of the whole plant for desired compounds in the last one decade. Generally, leaves are the favorable storage site for desired compounds and more than 35% of the plants extractions for diabetic treatment can be obtained from these parts as illustrated in Figure 4. Besides, fruits contain substantial amount of active ingredients, and thus, in many occasions they are consumed as juice via oral administration to obtain the desired compounds. Other parts of plants that can be extracted for therapeutic compounds are root, aerial parts, flowers, seeds, stem barks, etc. Most of the extractions used in plants extract research are associated with the conventional techniques. The techniques employed in the extraction are tabulated in Table 2. In conventional extraction, the release of the desired compounds traditionally required soaking and maceration in mild solvents. In traditional Chinese medicine practices, decoction in water is broadly employed and is an effective method to be considered in cases where the presence of a chemical solvent is undesired.[2-6] In addition to the soaking/maceration technique, percolations using methanol and ethanol on the stem were also applied.[7-12] Other solvents such as acetone, petroleum ether and hexane have also been used as solvents in the conventional extraction. [13-15] Moreover, extraction by liquid nitrogen was also witnessed in some research works.[16] The soxhlet technique for extracting anti-diabetic ingredient was not popular until 2005, after which the extraction technique was incorporated with ethanol and light petroleum.[17,18] Other than solvent extraction, techniques such as lyophilization [19,20] and sonification[21,22] have also been employed. Furthermore, supercritical fluid extraction and microwave assisted techniques have also been used in recent years. For instances, supercritical fluid extraction on lotus gem were carried out by Taiwanese research teams to investigate the antioxidant activity of the extract,[23] and microwave-assisted extraction was employed to investigate the bioactivity of tea flower polysaccharides.[24] These two advanced, non conventional techniques offer attractive advantages of short extraction time and solvent free active compounds, respectively. The extraction techniques normally used in plant research are lacking in the involvement of the engineering aspect as well, and hence the processes are not optimized. As a result, the therapeutic efficacy of the plants under investigation might be affected. Table 2: Various techniques employed in plant extraction as seen in the study Conventional extraction Non conventional extraction Water Soaking Maceration by water, ethanol, methanol Solvent extraction (ethanol, methanol, pectroleum ether, hexane, acetone,and etc) Percolation by water Soxhlet extraction involved solvents Lyophillization Sonification Supercritical fluid extraction (carbon dioxide) Microwave assisted Extraction Figure 5: The percentage distribution of various anti diabetic acting mechanisms as seen in the study Figure 4: The percentage distribution of anti diabetic ingredients in plant parts as seen in the study THE PLANT EXTRACTS FOR DIABETES TREATMENT AND RELATED ACTING MECHANISM Most of the medicinal researches have aimed to evaluate the therapeutic value of plants and to identify the related active ingredients extracted. The active ingredients from flavonoids (e.g. quercetin and kaempferol), alkaloids such as dieckol, etc which are potential for diabetes treatment have been discovered and their therapeutic functions have been described in Table 3. Besides that, some polysaccharides[25,26] from plants are also beneficial to humans in fighting diabetes. In this study, the anti diabetic acting mechanisms of the active ingredients are categorized into 6 groups for the ease of compilation as shown in Figure 5. The acting mechanisms are namely: alteration of glucose metabolism; hypolipidemic effect; pancreatic effect; antioxidative effect; diabetes complication treatment; and, insulin-like effect. Figure 5 gives an overall picture on the trend of plant research for anti diabetic treatment based on the information gathered for the past 20 years. The figure indicates the percentage distribution of anti diabetic acting Chan, et al.: Distribution, active ingredients and extraction techniques of anti diabetic plants Pharmacognosy Reviews | January-June 2012 | Vol 6 | Issue 11 25 Table 3: Potential anti diabetic active compounds extracted from plants in the study Active ingredients Plants Therapeutic function References Quercetin Euonymus alatus (leaves), Kalanchoe pinnata (leaves), Eucommia ulmoides (leaves) Exhibit hypoglycaemic effect through stimulation of insulin for glucose uptake, regeneration of the pancreatic islets and prevent against dementia associated with vascular and neurodegenerative disorders. [27-31] kaempferol Gynura procumbens (leaves), Euonymus alatus (leaves), Equisetum myriohchaetum (aerial parts) Promote hypoglycaemic effect [27,32,33] 4-hydroxybenzpoc acid Pandanus odorus (roots) Enhance serum insulin level and liver glycogen content [34] 3-hydroxylmethyl xylitol Casearia esculenta (roots) Possess antihyperglycaemic effect [35] Malvidin-3-O-glucoside Vaccinium angustigolium Aiton (fruits) Exhibit hypolgycaemic acitivity [36] Apigenin Tinospora cispa (stems) Improve glucose tolerance and increase plasma insulin level [37] Bassic acid Bumelia sartorum (root bark) Enhance secretion of insulin from the islets of Langerhans, increase glucose uptake process and glycogen synthesis. [38] Catechin Cassia fistula (bark), green tea (leaves) Exhibit hypoglycaemic, glucose oxidizing and insulin mimetic activities [39,40] Chlorogenic acid Cecropia pachystachya (leaves), cecropia obtusifolia (leaves) Possess hypoglycaemic effect [41,42] Comatin Coprinus comatus broth (whole plants) Maintain a low level of blood glucose and improve glucose tolerance [43] Curcumin Curcuma longa (rhizomes) As an adjuvant therapy for the prevention and treatment of diabetic encephalopathy [44] Dieckol Ecklonia cava (whole plants) Potential inhibitor for α-glucosidase and α-amylase [45] Enhydrin Smallanthus sonchifolius (leaves) Exhibit hypoglyacemic effect [46] Eremanthin Costus speciosus (rhizomes) Possess hypoglycaemic and hypolipidemic activities [47] Gensenoside Panax ginseng (roots) Enhance glucose uptake, anti hyperglycaemic and anti obese activities by improving insulin and leptin sensitivity [48,49] Gugulsterone Commiphora mukul (barks) Exhibit hypoglycaemic and hypolipidemic effect [50] Gugulipid Commiphora whighitii (barks) Potential anti dementia drug [51] Gymnemic acid Gymnema sylvestre (leaves) Incease the regeneration of β-cells [52] Lsoorientin Gentiana olivieri (leaves), Cecropia pachystachya (leaves), Cecropia obtusifolia (aerial parts) Exhibit hypolgycaemic and anti hyperglycaemic acitivity [41,42,53] Kinsenoside Anoectochilus roxburghii (wholep plants) Repairing β-cells in pancreatic islet injury and improving its function [54] Anthocyanins (Malvidin, delphinidin, cyanidin, petunidin, peonidin) 3glucoside Vitis vinifera (fruits) Possess inhibitory effect for lens opacity [55] Mangiferin Slacia oblonga (stems) Decrase fasting blood glucose level [56] Naringenin Ajuga iva (whole plants) Reducing lipid peroxidation and enhancing antioxidant Enzymes activities in plasmaerythocytes and tissues [57] Pongamol Pongamia pinnata (fruits) Possess significant anti hyperglycemic acitivity [58] Karangin Pongamia pinnata (fruits) Possess significant anti hyperglycemic acitivity [58] Genistein soy bean Benefial for correcting the hyperglycaemia and preventing diabetic complications [59] Coumarin Hemionitis arifolia (whole plants), Clausena anisata (roots) Exhibit hypoglycaemic effect though stimulation of pancreatic β-cells and subsequent secreation of insulin [60,61] Lignans (isotaxiresinol, secoisolariciresinol and taxiresinol) Taxus yunnanensis (wood) Exhibit blood glucose lowering effect [62] Ursolic acid Leandra lacunosa (aerial parts) Inhibit the increase in blood glucose level [63] mechanisms possessed by herbal plant extracts in descending order. Figure 5 show that 28% of the anti diabetic researches emphasized on the alteration of glucose metabolism. By altering the glucose metabolism, it helps to regulate the blood sugar levels to normal and thus prevent diabetes, whereas other anti diabetic mechanisms assist in treating diabetes and its complications. Several active ingredients belonging to this category are: bassic acid, an active compound isolated from Bumelia sartorum; and, Chan, et al.: Distribution, active ingredients and extraction techniques of anti diabetic plants 26 Pharmacognosy Reviews | January-June 2012 | Vol 6 | Issue 11 natural flavonoids such as quercetin and kaempferol as they can promote hypoglycemia through increase glucose uptake and glycogen synthesis.[27,33,38] Recently, researchers found that dieckol, a compound isolated from Ecklonia cava, is a potential inhibitor for α -glucosidase and α-amylase. It exhibits hypoglycaemia by reducing the impact of carbohydrates on blood sugar and is claimed to be comparable to Acarbose, a medical anti diabetic drug.[45] In addition, the effect of enhancing glucose tolerance and homeostasis have been reported in the root extracts of Berberis aristata and in comatin, an active ingredient extracted from Coprinus comatus broth. Both extracts can prevent diabetes by reducing the severity of insulin resistance.[43,64] The second, third and forth categories of the acting mechanisms respectively focus on hypolipidemic effect, pancreatic effect and antioxidative effect. The interactions among them are important focal points for anti diabetic research; for instance, a common secondary cause of hyperlipidemia is associated with diabetes. On one hand, some herbal plants extract such as guggulsterone isolated from Commiphora mukul and isoorientin obtained from Gentiana olivieri possess hypoglycemic and hypolipidemic properties which are suitable for obese diabetes patients;[50,53] on the other, herbal plants extract with pancreatic effect helps to enhance insulin secretion through insulin sensitizing mechanism. Furthermore, it has been reported that mangiferin and procyanidins, the natural compounds found in several plants like apple, grape and mango, exhibit hypoglycaemic activity through enhancing insulin signaling pathway.[65,66] As for antioxidative effect, plant extracts such as green tea, Ajuga iva aqueous extract and Chlorogenic acid from Cecropia pachystachya are capable of reducing oxidative stress and protecting against tissue damage in diabetes.[41,57,67] Another acting mechanism based on antioxidants such as kinsenoside, gymnemic acid and quercetin are helpful in preventing and treating Type I diabetes as they can regenerate the beta cells in islets of Langerhans in pancreas.[29,52,54,68] The last two acting mechanisms associate with diabetic complication treatment and insulin-like active ingredients administration. There are a lot of diabetic complications; however, only a few are involved in research attributing to their severity. For example, Pterocarpus marsupium extract is more effective compared to Ocimum sanctum extract as it exhibits better anti cataract effect for diabetic complication treatment.[69] Moreover, some extracts, i.e. garlic and ginger extracts, can be used to prevent and attenuate the development of nephropathy. [70] In addition, extracts isolated from Syzigium plants, i.e. S. cumini and S. aromaticum, are potential active ingredients for insulin substitutes.[71,72]