Background: Chiranthodendron pentadactylon Larreat. (Sterculiaceae) is a Mexican plant used in traditional medicine for the treatment of heart disease symptoms and infectious diarrhea. Objective: To evaluate in vitro antiprotozoal and antibacterial activities and in vivo antidiarrheal activity from the flowers of C. pentadactylon using the extract, fractions, and major isolated flavonoids. Materials and methods: Bioassay-guided fractionation of the methanol extract of C. pentadactylon (MECP) led to the isolation of five flavonoids, tiliroside, astragalin, isoquercitrin, (+)-catechin, and (-)-epicatechin. Antimicrobial activities were tested on two protozoa (Entamoeba histolytica and Giardia lamblia) and nine bacterial enteropathogens (two Escherichia coli strains, two Shigella sonnei strains, two Shigella flexneri strains, two Salmonella sp. strains, and Vibrio cholerae) isolated from feces of children with acute diarrhea or dysentery and resistant to chloramphenicol. Also, antidiarrheal activity was tested on cholera toxin-induced diarrhea in male Balb-c mice. Results: Epicatechin was the most potent antiamoebic and antigiardial compound with IC₅₀ values of 1.9 μg/mL for E. histolytica and 1.6 μg/mL for G. lamblia; tiliroside showed moderate antiprotozoal activity against both protozoan. In contrast, in the antibacterial activity, tiliroside was the most potent compound on all microorganisms with minimum inhibitory concentration values less than 0.7 mg/mL. In the case of cholera toxin-induced diarrhea, epicatechin was the most potent flavonoid with IC₅₀ of 14.7 mg/kg. Conclusion: Epicatechin and tiliroside were the flavonoids responsible for antimicrobial andantidiarrheal activities of C. pentadactylon. Its antiprotozoal, antibacterial, and antidiarrheal properties are in good agreement with the traditional medicinal use of C. pentadactylon for the treatment of infectious diarrhea. Abbreviations used: MECP: Methanol extract of C. pentadactylon

Twelve terpenoids were evaluated in the treatment of type 2 diabetes mellitus: seven monoterpenes (geranyl acetate (1), geranic acid (2), citral (3), geraniol (4), methyl geranate (5), nerol (6), and citronellic acid (7)), three sesquiterpenes (farnesal (8), farnesol (9), and farnesyl acetate (10)), one diterpene (geranylgeraniol (11)), and one triterpene (squalene (12)) were selected to carry out a study on normoglycemic and streptozotocin-induced diabetic mice. Among these, 2, 3, 7, 8, 9, and 10 showed antihyperglycemic activity in streptozotocin-induced diabetic mice. They were then selected for evaluation in oral sucrose and lactose tolerance tests (OSTT and OLTT) as well as in an oral glucose tolerance test (OGTT). In the OSTT and OLTT, compounds 3, 7, 8, 9, and 10 showed a reduction in postprandial glucose peaks 2 h after a sucrose or lactose load (comparable to acarbose). In the case of the OGTT, 2, 7, 8, 9, and 10 showed a reduction in postprandial glucose peaks 2 h after a glucose load (comparable to canagliflozin). Our results suggest that the control of postprandial hyperglycemia may be mediated by the inhibition of disaccharide digestion, such as sucrose and lactose, and the regulation of the absorption of glucose. The first case could be associated with an $\propto$ -glucosidase inhibitory effect and the second with an inhibition of the sodium–glucose type 1 (SGLT-1) cotransporter. Finally, five acyclic terpenes may be candidates for the development and search for new α-glucosidase and SGLT-1 cotransporter inhibitors.

Annona diversifolia Safford and two acyclic terpenoids were evaluated to determine their antihyperglycemic activity as potential α-glucosidase and selective SGLT-1 inhibitiors. Ethanolic extract (EEAd), chloroformic (CHCl₃Fr), ethyl acetate (EtOAcFr), aqueous residual (AcRFr), secondary 5 (Fr5) fractions, farnesal (1), and farnesol (2) were evaluated on normoglycemic and streptozocin-induced diabetic mice. EEAd, CHCl₃Fr, Fr5, (1) and (2) showed antihyperglycemic activity. The potential as α-glucosidase inhibitors of products was evaluated with oral sucrose and lactose tolerance (OSTT and OLTT, respectively) and intestinal sucrose hydrolysis (ISH) tests; the potential as SGLT-1 inhibitors was evaluated using oral glucose tolerance (OGTT), intestinal glucose absorption (IGA), and urinary glucose excretion (UGE) tests. In OSTT and OLTT, all treatments showed significant activity at two and four hours. In ISH, half maximal effective concentrations (CE₅₀) of 565, 662 and 590 μg/mL, 682 and 802 μM were calculated, respectively. In OGTT, all treatments showed significant activity at two hours. In IGA, CE₅₀ values of 1059, 783 and 539 μg/mL, 1211 and 327 μM were calculated, respectively. In UGE Fr5, (1) and (2) showed significant reduction of the glucose excreted compared with canagliflozin. These results suggest that the antihyperglycemic activity is mediated by α-glucosidase and selective SGLT-1 inhibition.

The antihyperglycemic and antilipidemic effects of the tea infusion extracts of leaves from Annona cherimola Miller (IELAc-0.5, IELAc-1.5, and IELAc-3.0) were evaluated on normoglycemic (NG) and streptozocin-induced diabetic (STID) mice. In the acute test, IELAc-1.5 at 300 mg/kg bodyweight (bw) exhibited antihyperglycemic activity on STID mice since the first hour of treatment. Then, its antidiabetic potential was analyzed in a subchronic evaluation. IELAc-1.5 was able to reduce the blood glucose level, glycated hemoglobin (HbA1c), cholesterol (CHO), and triglycerides (TG); high-density lipoprotein (HDL) showed an increase at the end of treatment. IELAc-1.5 did not modify the urine profile at the end of the evaluation, and neither toxicity nor macroscopic organ damage were observed in acute and subchronic assays. In addition, a major flavonol glycoside present in the tea infusion extracts was identified using high-performance liquid chromatography with diode array detection (HPLC-DAD). The analysis of the tea infusion extracts by HPLC revealed that rutin was the major component. This study supports the use of tea infusions from Annona cherimola for the treatment of diabetes and suggests that rutin could be responsible, at least in part, for their antidiabetic properties.

Background: Schinus molle Linn. (Anacardiaceae) is a medicinal plant used by traditional healers in Mexican traditional medicine as antitumoral. Objective: This study was undertaken to obtain information that support the traditional use of the leaves from S. molle as antitumoral. Material and Methods: Antilymphoma properties of the ethanol extract of the leaves from S. molle (EELSm) and rutin were made on athymic CD-1 nu/nu and CD-1 mice inoculated with U-937 cell line (human leukemic monocyte lymphoma [HLML]), and for their antiproliferative effects on U-937 cell line by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Furthermore, the extract and rutin were tested for brine shrimp (BS) toxicity test. In addition, HPLC analysis was realized to known the content of rutin in the leaves from S. molle. Results: An EELSm and rutin exhibited important cytotoxic effects on U-937 cells line (IC₅₀from 172.0 μg/mL and 9.6 μg/mL, respectively) and showed in vivo antitumoral properties on HLML in two murine models (EC₅₀from 52.2 and 9.5 mg/kg to CD-1 nu/nu mice; EC₅₀from 99.4 mg/kg and 6.8 mg/kg to CD-1 mice, respectively). In addition, both showed strong lethality on BS larvae (LC₅₀≤ 22.2 μg/mL). The result of HPLC showed that rutin was the major constituent of EELSm. Conclusions: These test results support traditional medicinal use of S. molle as antitumoral and also suggest that both rutin and EELSm possess antitumor effect on HLML in murine models. Finally, rutin may play an important role in anticancer properties of S. molle. Abbreviations used: EELSm: Ethanol extract of the leaves from S. molle, HLML: Human leukemic monocyte lymphoma, HPLC: High pressure liquid chromatography, BS: Brine shrimp, BSLT: BS lethality test, DMSO: Dimethyl sulfoxide, MTT: 3 (4,5 dimethylthiazol 2 yl) 2,5 diphenyltetrazolium bromide.

The Annona genus contains some species used in Mexican traditional medicine for the treatment cancer, including Annona macroprophyllata (A. macroprophyllata). The present study aimed to investigate the anticancer activity of caryophyllene oxide (CO) isolated from A. macroprophyllata using in vivo, in vitro, and in silico approaches. The identification of CO was performed using gas chromatography-mass spectroscopy and NMR methods. Antilymphoma activity was evaluated in male and female Balb/c mice inoculated with U-937 cells. Cytotoxic activity was evaluated using the WST method and flow cytometry was used to determine the type of cell death. Acute oral toxicity was determined, and a molecular docking study was performed using target proteins associated with cancer, including, HMG-CoA, Bcl-2, Mcl-1, and VEGFR-2. Results showed that CO exhibited significant antilymphoma and cytotoxic activities, and its effects were comparable to MTX. In addition, flow cytometry showed that the anticancer activity of CO could be mediated by the induction of late apoptosis and necrosis. The result for the acute oral toxicity of CO was classified in category 4, suggesting it is low risk. Finally, molecular coupling studies showed that CO had more affinity for the enzymes HMG-CoA reductase and Bcl-2. Our study provides evidences that CO is a potential anticancer agent for the treatment of histiocytic lymphoma.