Hypoglycemic activity of Thai medicinal plants selected from the Thai/Lanna Medicinal Recipe Database MANOSROI II

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Abstract

Ethnopharmacological relevance

Five medicinal plants including Anogeissus acuminata (Roxb. ex DC.) Gills. & Perr. (Combretaceae), Catunaregam tormentosa (Bl. ex DC.) Tirveng (Rubiaceae), Dioecrescis erythroclada (Kurz) Tirveng. (Rubiaceae), Mimosa pudica Linn. var. hispida Bren. (Fabaceae), and Rauwolfia serpentina (L). Benth. ex Kurz. (Apocyanaceae), which have been traditionally used for the treatment of diabetes mellitus and other diseases for several generations by the Thai-Lanna people in the Northern part of Thailand were investigated for their hypoglycemic activity in normoglycemic and alloxan, induced diabetic mice.

Materials and methods

The aqueous extracts of the selected five medicinal plants were tested for their phytochemicals, free radical scavenging activity and hypoglycemic activity on 18 h fasted normoglycemic and alloxan induced diabetic mice over a period of 4 h comparing with the standard anti-diabetic drugs (insulin and glibenclamide) using two way analysis of variance (ANOVA) as analytical tool. Phytochemical analysis was performed using the standard methods while 2,2-diphenyl-1-picrylhydrazine (DPPH) was used to test for free radical scavenging activities of the medicinal plant extracts.

Results

Phytochemicals detected in the extracts were glycosides, xanthones, tannins, alkaloids and saponins. Anogeissus acuminata showed the highest free radical scavenging activity with the IC50 value of 11.00 μg/mL which was 4 folds of the standard ascorbic acid. Significant reduction in fasting blood glucose (FBG) levels of the normoglycemic mice was observed at 4 and 3 h with the extracts of Mimosa pudica (200 mg/kg bw) and Rauwolfia serpentina (100 mg/kg bw), and percentage decreases of 46.15 and 27.94% which were 0.76 and 1.47; 0.53 and 0.91 folds of insulin and glibenclamide, respectively. In alloxan induced diabetic mice, all extracts showed significant (p < 0.05) hypoglycemic activity, with the maximum FBG reduction of 78.96 at 100 mg/kg bw shown by Anogeissus acuminata at the 4 h. The hypoglycemic activity of Anogeissus acuminata was comparable to insulin (1.1 fold), but more potent than glibenclamide (1.76 folds).

Conclusions

Medicinal plants selected from the Thai/Lanna Medicinal Plant Recipe Database MANOSROI II showed hypoglycemic activity in normoglycemic and alloxan induced diabetic mice. This study confirmed the traditional use of these medicinal plants for the treatment of diabetes mellitus and the thiazolidiendiones mimic hypoglycemic effects of the medicinal plants was suggested.

Graphical abstract

Hypoglycemic activity of Thai medicinal plants selected for the Thai/Lanna Medicinal Recipe Database MANOSROI II.

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Introduction

Diabetes mellitus is one of the chronic diseases that causes problem not only to the patient but also to the health care system. Diabetes mellitus is divided into two main groups namely, type I diabetes which results from the body's failure to produce insulin and requires the person to inject insulin, and type II which results from insulin resistance and a gradual beta-cell dysfunction. Although this disease can be controlled by nutrition and exercise (Shaw et al., 2010), most patients need oral hypoglycemic drugs to control their blood glucose levels. In Thai traditional medical practice, diabetes mellitus (Bao wan) is diagnosed by symptoms such as internal body heat (Khang hont), which leads to the voiding of high volume of urine, body weakness, weight loss (Salguero, 2003), and what may be termed as “ants hill test” in which the patient is asked to urinate beside an ant hill or hole and to observe the activity of the ants on the urine spot after a few minutes. If the ants are seen to besiege the spot on which the urine was voided, it is indicative of diabetes which results from high concentration of glucose in the urine and assumed likewise for the blood. The long term use of hypoglycemic drugs, such as sulphonylureas, metformin and others which are the main stay for diabetes management have been observed to have wide range of side effects (Nissen and Wolski, 2007, Nissen, 2010) including a progressive decline in effectiveness, termed “secondary failure” (Groop et al., 1986). This condition occurs as a result of “increased loss of beta-cell function and insulin sensitivity due to disease progression (Spoelstra et al., 2003). Other problems observed are the high cost and long term use of drugs by the patients, leading to non compliance and hence worsening of the conditions. The generation of reactive oxygen species (ROS) or free radicals and consequently the induction of several chain reactions, such as lipid peroxidation (Cross et al., 1987) are among the most common complications in the diabetic patients. These free radicals are known to be extremely reactive and therefore interact with some vital macromolecules including lipids, nucleic acids and proteins (Nia et al., 2003). Diabetes mellitus induces changes in the tissue content and the activity of the antioxidant enzymes (Genet et al., 2002). Synthetic antioxidants such as butylated hydroxyanisole (BHA) to human health (Safer and Al-Nughamish, 1999), causes deleterious side effects. Hence, novel antioxidants from natural sources have been searched (Thomes and Wade, 2007). Diabetic patients often seek complementary or alternative therapies such as herbal medicines. In Thailand, several herbal medicines have been documented as anti-diabetic. These recipes were collected in the traditional Thai/Lanna Medicinal Plants/Recipe Database “MANOSROI II” (Manosroi et al., 2006) of the Natural Product Research and Development Center (NPRDC), Faculty of Pharmacy, Chiang Mai University, Thailand.

The recipes written in Lanna alphabets were collected from all regions of Thailand, selected and translated from classical Lanna or native Thai language to a modern understandable Thai language. At present, MANOSROI II contains 7467 medicinal plants, 50,000 out of expected 200,000 recipes and 3613 diseases/symptoms covering several diseases and symptoms such as cancer, hypertension, diabetes, fever, pain, wound and abscess. Moreover, the database also included the recipes for cosmetics and food supplements. The advantage of the database is that, all of the recipes in the MANOSROI II have been directly used by humans for several generations. Only the effective recipes will be recorded hence, circumventing the huge cost in conventional drug development protocol and cost of research. The MANOSROI II is a convenient source for the searching and ranking of potential recipes and medicinal plants for further studies.

The medicinal plants from many Thai/Lanna anti-diabetic recipes selected for this study, were as follows: Anogeissus acuminata (Roxb. ex DC.) Gills. & Per. (Combretaceae) (Ta Khian Nu), Catunaregam tormentosa (Bl. ex DC.) Tirveng (Rubiaceae) (Nam Taeng), Dioecrescis erythroclada (Kurz) Tirveng (Rubiaceae) (Ma Khang Daeng), Mimosa pudica Linn. var. hispida Bren. (Fabaceae) (Mai Ya Rab) and Rauwolfia serpentina (L). Benth. ex Kurz. (Apocynaceae) (Yom Teen Mha).

These medicinal plants are also used for the treatment of other ailments. Anogeissus acuminata is indicated in the traditional treatment of diarrhea. It is also used externally in sprain and to cure burns without leaving any scar (Sharma et al., 2001). Other studies show that Anogeissus acuminata can be used in the management of human immune virus (HIV) infection. New lignans have been isolated from Anogeissus acuminata which has shown significant HIV-1 reverse transcriptase inhibitory activity (Rimando et al., 1994). Catunaregam tormentosa is used in the treatment of several infections in early childhood care, in the form of decoction (Chuakul et al., 2002). Dioecrescis erythroclada is used in the treatment of bodily discomfort, stomach ache and as an antipyretic medicine (Kaewkrud et al., 2007). In India, Mimosa pudica is used for the treatment of cuts or fresh wounds, diarrhea, amoebic dysentery, bleeding piles, bronchitis and for sexual potency (Rajkumar et al., 2011). Rauwolfia serpentina is used in the Ayurvedic treatment of epilepsy, insomnia, hysteria, eclampsia and hypertension (Wilkins and Judson, 1953) and presently in treating cardiovascular disease (Nick et al., 1998).

For antidiabetic activity, these medicinal plants have never been investigated. In this study, the phytochemical contents and free radical scavenging activities was assayed. The aqueous extracts of the medicinal plants were screened for their hypoglycemic effects in normoglycemic and alloxan induced diabetic mice comparing with the standard antidiabetic drugs (insulin and glibenclamide).

Section snippets

Materials

Human insulin (molecular weight 5807 Da, 98% purity, Boehringer Ingelheim, Germany), glibenclamide (Government Pharmaceutical Organization, Bangkok, Thailand), ascorbic acid (Carlo Erba, Italy). alloxan monohydrate (Aldrich, Germany). Anthraquinones, flavone, tannin, xanthones and quinine sulphate were from Sigma–Aldrich Company, Germany. All other chemicals were of analytical grade and obtained commercially. Finetest Glucometer (Infopia Co., Ltd., Korea) was used to determine the blood glucose.

Collection of plant materials

Phytochemistry

The phytochemistry of all plant extracts. The high contents of glycosides, xanthones, tannins and alkaloids were observed in Anogeissus acuminata, whereas Catunaregam tormentosa and Rauwolfia serpentina showed high alkaloid and flavone content but low in other phytochemicals. The other medicinal plant extracts showed lower contents of phytochemicals.

Free radical scavenging activity

The Anogeissus acuminata extract showed the highest free radical scavenging activity with IC50 value of 11.00 μg/ml which was 4 folds of ascorbic

Discussion

The hypoglycemic activities of the medicinal plant extracts were compared to the standard hypoglycemic drugs, insulin and glibenclamide in order to validate their effect. The results of phytochemical analysis of the medicinal plant extracts showed that Anogeissus acuminata had high contents of glycosides, xanthones, tannins and alkaloids. These phytochemicals have previously been observed to possess significant hypoglycemic activities (Dineshkumar et al., 2010, Khan et al., 2010). Free radical

Conclusion

The results from this study have confirmed the hypoglycemic activities of the aqueous extracts of Anogeissus acuminata, Rauwolfia serpentina, Catunaregam tormentosa, Dioecrescis erythroclada and Mimosa pudica which supported the folkloric uses of the medicinal herbs in the control or management of diabetes mellitus among people of the Thai Lanna community in the Northern part of Thailand. Anogeissus acuminata extract showed strong free radical scavenging activity and highest hypoglycemic

Competing interest

The authors declare that they have no competing interests.

Role of funding source

Funding for this research was provided by the Natural Products Research and Development Center (NPRDC), Faculty of Pharmacy, Chiang Mai University, Thailand. Information on the Thai-Lanna traditional medicine was sourced from NPRDC database (MANOSROI II). Some of the medicinal plants were provided by the center while others were obtained within the vicinity of the Lanna home stead.

Acknowledgements

Appreciation goes to the Natural Product Research and Development Center (NPRDC), Institute of Science and Technology (IST), Chiang Mai University, Dr. Panee Sirisa-ard of the Faculty of Pharmacy at Chiang Mai University, Thailand and the Management, Adamawa State University, Mubi in Nigeria.

References (47)

  • C. Cross et al.

    Oxygen radical and human diseases

    Annal Internal Medicine

    (1987)
  • R.A. Defronzo

    Pharmacologic therapy for type 2 diabetes mellitus

    Annals of Internal Medicine

    (1999)
  • B. Dineshkumar et al.

    Antidiabetic and hypolipidermic effect of Mahanimbine (Carbazole alkaloid) from Murraya Koenigii (Rutaceae) leaves

    International Journal of Phytomedicine

    (2010)
  • D.J. Drucker

    The role of gut hormones in glucose homeostasis

    Journal of Clinical Investigation

    (2007)
  • S. Genet et al.

    Alteration on antioxidant enzymes and oxidative damage in experimental diabetic rat tissue: effect of vanadate and fenugreek (Trigonella faenum graecum)

    Molecular and Cellular Biochemistry

    (2002)
  • B. Gidwani et al.

    Pharmacognostic standardization and physico-chemical evaluation of Psoralea corylifolia Linn seeds

    Imperial Journal of Pharmacognosy and Natural Products

    (2011)
  • L.C. Groop et al.

    Secondary failure to treatment with oral antidiabetic agents in non insulin dependent diabetes

    Diabetes Care

    (1986)
  • S.H. Jo et al.

    In vitro and in vivo anti-hyperglycemic effects of Omija (Schizandra chinensis) fruit

    International Journal of Molecular Science

    (2011)
  • A.S. Kamba et al.

    Phytochemical screening and antimicrobial activities of Euphorbia balasamifera leaves, stems and root against some pathogenic microorganisms

    African Journal of Pharmaceutical Sciences and Pharmacy

    (2010)
  • W. Kaewkrud et al.

    Chemical constituents of the Thai medicinal plant Dioecrescis erythroclada (Kurz) Tirveng

    Journal of Natural Medicine

    (2007)
  • M.R.I. Khan et al.

    Antidiabetic effects of the different fraction of ethanolic extracts of Ocimum sanctum in normal and alloxan induced diabetic rats

    Journal of Scientific Research

    (2010)
  • W.J. Malaisse et al.

    Determinants of the selective toxicity of alloxan to the pancreatic B cell

    Proceedings of the National Academy of Science of United States of America

    (1982)
  • J. Manosroi et al.

    Collection/Translation and interpretation of Thai/Lanna Medicinal Plant Recipes for Research and Development of Modern Pharmaceuticals (Database – MANOSROI II)

    (2006)
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