# Anti-Hyperglycemic Activity of Major Compounds from _Calea terifolia_
## 1 Introduction  
In Mexico some patients manage their diabetic condition with herbal products or combine their allopathic treatments with them. These patients consider that herb preparations are less toxic, more efficacious and less expensive than allopathic products [1]. Among these herbs is _Calea terifolia_ Kunth, locally known as \"prodigiosa\", \"zacachichi\" and \"amula\"; the species is perennial and endemic to Mexico. _Calea terifolia_ has a long history of use in traditional medicine and rituals aimed at dream-based divination [2]. In contemporary Mexico, the infusion prepared from the whole plant, alone or in combination with other herbs, is widely commercialized for treating colics, fever, cough, and diabetes [1; 2; 3]. Furthermore, a tincture made up from this species is marketed in the US for medicinal purposes, including diabetes treatment. Previous pharmacological investigations showed that the plantexhibited antiinflammatory [4; 5], antiplasmodial [6], antileshmanial [7], antimicrobial, antidiarrheal and antinociceptive effects [8]. Recent neuropharmacological evaluation of an aqueous extract of _C. ternifolia_ using the mouse models of convulsion, forced swim, elevated plus-maze, muscular strength in a grip and locomotor tests, revealed that the aqueous extract had not significant effects in these assays [9]. However, an organic extract of this herb displayed significant cytotoxicity against human proximal tubule HK-2 cells and increased the level of nephrotoxicity biomarkers [10]. The first written account about the use of _C. ternifolia_ for treating diabetes appeared at the end of the last century [3]. In addition, an aqueous extract made up from aerial parts of the plant was effective for controlling fasting and postprandial blood glucose levels in normoglycemic and hyperglycemic mice [11; 12]. Bioassay-guided isolation of the active extract using an in vitro enzymatic assay led to the isolation of several flavonoids, chromenes (6-acetyl-5-hydroxy-2,2-dimethyl-2\(H\)-chromene, demethylenccalin (**1**), 6-hydroxyacetyl-5-hydroxy-2,2-dimethyl-2\(H\)-chromene (**2**) and 6-acetyl-5-hydroxy-2-hydroxymethyl-2-methyl-2\(H\)-chromene (**3**)) and sesquiterpene lactones identified as calein A (**4**) and calein C (**5**) (Figure 1) [11; 12; 13]. Some of these compounds showed potent inhibitory activity against yeast \(\alpha\)-glucosidase (\(\alpha\)-YG); altogether, these results revealed the antihyperglycemic potential of _C. ternifolia_ and its secondary metabolites [11; 12]. Other chemical investigations pursued by different groups led to the isolation of several sesquiterpene lactones including caleolactone C and caleins A (**4**) and C (**5**) and analogs; flavonoids; chromenes and chlorogenic acid [7; 10; 14; 15; 16; 17; 18]. Thus, as part of our systematic investigation of Mexican medicinal flora as source of well accepted alternative treatments for type 2 diabetes mellitus and for the discovery of new \(\alpha\)-glucosidase inhibitors [13], the goals of this investigation were: (i) to find out if chromene **1**, lactones **4** and **5** and the essential oil of the plant improved postprandial hyperglycemia in vivo after an oral sucrose tolerance test (OSTT); this was in view of the fact that \(\alpha\)-glucosidase inhibitor agents improved postprandial hyperglycemia; (ii) to develop quality control pharmacopoeic tests for the crude drug of _C. ternifolia_, considering that the quality of herbs represents the foundation of their efficacy and safety. In this case the quality test consisted in determining the volatile profile of the drug by the analyses of the headspace solid phase microextraction (HS-SPME)-adsorbed compounds and those of the essential oil using gas chromatography coupled with mass spectrometry (GC-MS).