Evaluation of α-Glucosidase Inhibition and Antihyperglycemic Activity of Extracts Obtained from Leaves and Flowers of Rumex crispus L.

Among antihyperglycemic drugs used for treating diabetes, α-glucosidase inhibitors generate the least adverse effects. This contribution aimed to evaluate the potential antidiabetic activity of Rumex crispus L. by testing its in vitro α-glucosidase inhibition and in vivo antihyperglycemic effects on rats with streptozotocin (STZ)-induced diabetes. Better inhibition of α-glucosidase was found with the methanol extract versus the n-hexane and dichloromethane extracts. The methanol extract of the flowers (RCFM) was more effective than that of the leaves (RCHM), with an IC50 of 7.3 ± 0.17 µg/mL for RCFM and 112.0 ± 1.23 µg/mL for RCHM. A bioactive fraction (F89s) also showed good α-glucosidase inhibition (IC50 = 3.8 ± 0.11 µg/mL). In a preliminary study, RCHM and RCFM at 150 mg/kg and F89s at 75 mg/kg after 30 days showed a significant effect on hyperglycemia, reducing glucose levels (82.2, 80.1, and 84.1%, respectively), and improved the lipid, renal, and hepatic profiles of the rats, comparable with the effects of metformin and acarbose. According to the results, the activity of R. crispus L. may be mediated by a diminished rate of disaccharide hydrolysis, associated with the inhibition of α-glucosidase. Thus, R. crispus L. holds promise for the development of auxiliary drugs to treat diabetes mellitus.

Anti-Inflammatory Effect of Ethanolic Extract from Tabebuia rosea (Bertol.) DC., Quercetin, and Anti-Obesity Drugs in Adipose Tissue in Wistar Rats with Diet-Induced Obesity.

Obesity is characterized by the excessive accumulation of fat, which triggers a low-grade chronic inflammatory process. Currently, the search for compounds with anti-obesogenic effects that help reduce body weight, as well as associated comorbidities, continues. Among this group of compounds are plant extracts and flavonoids with a great diversity of action mechanisms associated with their beneficial effects, such as anti-inflammatory effects and/or as signaling molecules. In the bark of Tabebuia rosea tree, there are different classes of metabolites with anti-inflammatory properties, such as quercetin. Therefore, the present work studied the effect of the ethanolic extract of T. rosea and quercetin on the mRNA of inflammation markers in obesity compared to the drugs currently used. Total RNA was extracted from epididymal adipose tissue of high-fat diet-induced obese Wistar rats treated with orlistat, phentermine, T. rosea extract, and quercetin. The rats treated with T. rosea and quercetin showed 36 and 31% reductions in body weight compared to the obese control, and they likewise inhibited pro-inflammatory molecules: Il6, Il1b, Il18, Lep, Hif1a, and Nfkb1 without modifying the expression of Socs1 and Socs3. Additionally, only T. rosea overexpressed Lipe. Both T. rosea and quercetin led to a reduction in the expression of pro-inflammatory genes, modifying signaling pathways, which led to the regulation of the obesity-inflammation state.

Anti-hyperglycemic activity of aqueous extracts of cells produced in Ibervillea sonorae (S. Watson) Green cell culture on murine model / Actividad anti-hiperglucémica del extracto acuoso de células producidas en cultivo celular de Ibervillea sonorae (S. Watson) Green en un modelo murino

Ibervillea sonorae (S. Watson) Greene, is a plant native to Mexico, where its roots have been used traditionally for treating Diabetes Mellitus. The aim of this work was to establishment of cell cultures of stem explants of I. sonorae and evaluation of the anti-hyperglycemic activity of cell aqueous extract on a murine model of streptozotocin-induced diabetic rats. Cell extracts had 2.29 mg palmitic acid/g extracted, and other compounds with pharmacological activities like palmitoyl ethanolamide and palmitoyl tryptamine were also identified. Diabetic rats treated with aqueous cell extract decreased glucose levels from 350 mg/dL to 145 mg/dL, AST and ALT from 164 U/L to 49 U/L and 99 U/L to 53 U/L, respectively. Additionally, there were no changes in the cellular morphology of the pancreas, liver, kidneys, and spleen. These results revealed that the cell aqueous extract from stem explants has anti-hyperglycemic activity.

Ibervillea sonorae (S. Watson) Greene, es una planta originaria de México, donde sus raíces se han utilizado tradicionalmente para el tratamiento de la Diabetes Mellitus. El objetivo de este trabajo fue el establecimiento de cultivos celulares de explantes de tallo de I. sonorae y la evaluación de la actividad anti-hiperglucémica del extracto acuoso celular en un modelo de ratas diabéticas inducidas con estreptozotocina. El extracto celular contiene 2.29 mg de ácido palmítico/g extracto y se identificaron otros compuestos como palmitoil etanolamida y palmitoil triptamina. Las ratas diabéticas tratadas con extracto celular disminuyeron los niveles de glucosa de 350 mg/dL a 145 mg/dL, AST y ALT de 164 U/L a 49 U/L y 99 U/L a 53 U/L, respectivamente. Además, no hubo cambios en la morfología celular del páncreas, hígado, riñones y bazo. Estos resultados indican que el extracto de células de explantes de tallo de I. sonorae tiene actividad anti-hiperglucémica.

Echinacea Angustifolia DC Extract Induces Apoptosis and Cell Cycle Arrest and Synergizes with Paclitaxel in the MDA-MB-231 and MCF-7 Human Breast Cancer Cell Lines.

BACKGROUND: Echinacea spp. displays different biological activities, such as antiviral, immunomodulatory, and anticancer activities. Currently, high sales of hydroalcoholic extracts of Echinacea have been reported; hence, the importance of studies on Echinacea. AIM: To establish the effects of Echinacea angustifolia DC extract obtained with ethyl acetate (Ea-AcOEt) in breast cancer cell lines. METHODS: Cytotoxicity, cell cycle arrest, and cell death were evaluated. Besides, the safety of the extract, as well as its effect in combination with paclitaxel were investigated. RESULTS: The echinacoside and caffeic acid content in the Ea-AcOEt extract were quantified by HPLC, and its antioxidant activity was assessed. The Ea-AcOEt extract showed cytotoxic activity on breast cancer MDA-MB-231 cells (IC50 28.18 ± 1.14 µg/ml) and MCF-7 cells (19.97 ± 2.31 µg/ml). No effect was observed in normal breast MCF-10 cells. The Ea-AcOEt extract induced cell cycle arrest in the G1 phase and caspase-mediated apoptosis. No genotoxicity was found in vitro or in vivo, and the extract showed no signs of toxicity or death at 2,000 mg/kg in rodents. In vitro, the combination of Ea-AcOEt extract and paclitaxel showed a synergistic effect on both cancer cell lines. CONCLUSION: The Ea-AcOEt extract is a potential candidate for breast cancer treatment.

Cytotoxic effect of Kalanchoe flammea and induction of intrinsic mitochondrial apoptotic signaling in prostate cancer cells.

ETHNOPHARMACOLOGICAL IMPORTANCE: Kalanchoe flammea Stapf (Crassulaceae) is a medicinal plant grown in the South of Mexico (State of Tabasco), which is commonly used in traditional medicine for the treatment of fever, wounds, inflammation, and cancer. AIM OF THE STUDY: To establish the potential of K. flammea for the treatment of prostate cancer, evaluating its cytotoxic activity, its probable mechanism of action, and carrying out some toxicological safety studies. MATERIALS AND METHODS: The cytotoxic activity of the ethyl acetate extract of K. flammea (Kf-EtOAc) was evaluated in several cell lines of prostate cancer by MTT viability assay. The cellular death mechanism was studied by evaluating the translocation of phosphatidylserine (Annexin V); overproduction of reactive oxygen species [2'-7'-Dichlorodihydrofluorescein diacetate (DCFH-DA) assay]; release of Cytochrome C; activation of caspase-3 and -9, and regulation of Bcl-2, XIAP, and PKCε proteins by Western Blot analysis. For the evaluation of the safety of Kf-EtOAc, the Ames test, Micronucleus assay, and acute toxicity study were determined. RESULTS: Kf-EtOAc exhibited selective cytotoxic activity against prostate cell lines as follows: PC-3, LNCaP, and PrEC (IC50 = 1.36 ±â€¯0.05; 2.06 ±â€¯0.02, and 127.05 ±â€¯0.07 µg/mL, respectively). The F82-P2 fraction (rich in coumaric acid and palmitic acid) obtained by bioassay-guided fractionation of Kf-EtOAc also demonstrated selective cytotoxic activity against PC-3 cells (IC50 = 1.05 ±â€¯0.06 µg/mL). Kf-EtOAc induces apoptosis by the intrinsic pathway; this mechanism of cell death was confirmed after observing that the extract produces phosphatidylserine translocation, overproduction of reactive oxygen species, release of Cytochrome C at mitochondrial level, and activation of caspase-3 and -9. It was also observed that Kf-EtOAc produces significant downregulation of apoptosis-related proteins Bcl-2, XIAP, and PKCε and induces DNA fragmentation and cell cycle arrest. In addition, Kf-EtOAc is non-genotoxic in vitro by Ames test and non-genotoxic in vivo by Micronucleus assay, and no signs of toxicity or death were reported after the administration of a single acute exposure of 2000 mg/kg. CONCLUSION: K. flammea is a potential candidate for the development of new drugs for the treatment of prostate cancer. However, to propose their use in clinical trials, additional studies are required to understand their pharmacokinetic behavior, as well as the development of a suitable pharmaceutical form.

Antidiabetic effect, antioxidant activity, and toxicity of 3',4'-Di-O-acetyl-cis-khellactone in Streptozotocin-induced diabetic rats.

Pyranocoumarins are compounds with an important pharmacological profile, such as anti-inflammatory, antioxidant, cytotoxic, antiviral, antibacterial, and hypoglycemic effects. These molecules have a widespread presence as secondary metabolites in medicinal plants used to treat Diabetes Mellitus (DM). The aim of this work was to evaluate antidiabetic activity in Streptozotocin (STZ)-induced diabetic rats and the antioxidant effects of 3',4'-Di-O-acetyl-cis-khellactone (DOAcK), as well as its toxic potential. We obtained DOAcK with an enantiomeric excess of 70% by chemical synthesis. Our results showed that this compound exerts an important antidiabetic effect: blood glucose decreased in groups treated with DOAcK by 60.9% at dose of 15mg/kg (p<0.05) compared with the diabetic control group, and demonstrated a statistically significant increase in weight gain (45.7±9.7 in the group treated with DOAcK vs. -23.0±33.1 in the group with diabetes). In a biochemical profile, DOAcK did not modify lipid metabolism and did not cause damage at the renal level. DOAcK administration increased the activities of Catalase (CAT), Glutathione Peroxidase (GPx), and Super Oxide Dismutase (SOD) to levels near those of the healthy group. Histopathological analysis exhibited morphology similar to that of the healthy group and the group treated with DOAcK. DOAcK is not mutagenic by Ames test for Salmonella typhimurium strains TA98, TA100, or TA102, and is not genotoxic by Micronucleus assay; median lethal dose (LD50) >2000mg/kg and, at this dose, no signs of toxicity or death were reported after 14days of observation. These results indicate that DOAcK can improve glucose metabolism, which may be due to the increased antioxidant activity of CAT, GPx and SOD. In addition, DOAcK is not toxic in the studies tested.

Antihyperglycaemic effect of laser acupuncture treatment at BL20 in diabetic rats.

OBJECTIVE: To investigate the antihyperglycaemic activity of laser acupuncture stimulation at 650 and 980 nm at BL20 in streptozotocin (STZ)-induced diabetic rats. METHODS: Seventy healthy adult male albino Wistar rats weighing 250±50 g were divided into seven groups of 10 animals each. Groups I-III comprised healthy control rats which were untreated (I) or stimulated with laser acupuncture at 650 nm (II) and 980 nm (III), respectively. Groups IV-VII underwent induction of diabetes with a single intraperitoneal administration of STZ at 50 mg/kg. Animals with blood glucose levels of ≥200 mg/dL on the fifth day were used for the experiments and were left untreated (group IV), treated with glibenclamide (group V) or stimulated with laser acupuncture at 650 nm (group VI) and 980 nm (group VII), respectively. Laser acupuncture was applied at BL20 on alternate days for a total of 12 sessions over a 28-day period. RESULTS: After 28 days of treatment, STZ-induced diabetic rats stimulated with laser acupuncture at 650 and 980 nm had significantly lower glucose levels compared with untreated diabetic rats (242.0±65.0 and 129.8±33.2 vs 376.5±10.0 mg/dL, both p≤0.05). Treatment at 980 nm also attenuated the increase in glucose between day 1 and day 28 compared with the glibenclamide-treated diabetic group (41.5±19.6 mg/dL vs 164.1±13.7 g/dL, p<0.05). Laser acupuncture treatment did not affect the blood count or biochemical profile and was not associated with any morphological changes in the pancreas, liver, kidney or spleen. CONCLUSIONS: Stimulation with laser acupuncture at 650 and 980 nm at BL20 in STZ-induced diabetic rats has antihyperglycaemic activity. The results support further evaluation of laser acupuncture as an alternative or complementary treatment for the control of hyperglycaemia.

Anti-hyperglycemic effect, inhibition of inflammatory cytokines expression, and histopathology profile in streptozotocin-induced diabetic rats treated with Arracacia tolucensis aerial-parts extracts.

ETHNOPHARMACOLOGICAL RELEVANCE: Arracacia tolucensis is a medicinal plant used in northeast of Mexico as a remedy to treat people with Diabetes mellitus (DM); however, there are no scientific studies that support this information. Thus, we evaluated the anti-hyperglycemic effect of the hexane, ethyl acetate and ethanol extracts from aerial parts in streptozotocin-induced diabetic rats. MATERIALS AND METHODS: DM was induced in Wistar male rats by single intraperitoneal injection of streptozotocin (STZ 50mg/kg). After STZ-induction, hyperglycemic rats were treated with all three extracts orally at a single dose (250 mg/kg) each 48 h for 21 days. Glibenclamide (1mg/kg) was used as a reference drug. The fasting blood glucose levels, the hematic biometry and biochemical profiles, and the inhibition of inflammatory cytokines expression were estimated. Histopathology analysis of pancreas, liver, spleen, and kidney tissue was carried out. RESULTS: Ours results showed that ethyl acetate extract decreased blood glucose levels significantly (75%, p< 0.05) when compared to diabetic rats and controlled the body weight loss; the lipids level did not change, but the enzyme levels of aspartate aminotransferase and alanine aminotransferase decreased significantly (60.83% and 66.16%, respectively, p< 0.05) and inhibited the expression of inflammatory cytokines,with respect to diabetic rats. Histopathology injury was not observed; by contrast repair of islet of Langerhans was exhibited. CONCLUSION: These results validate the use of Arracacia tolucensis as a treatment against DM and suggests it is suitable to continue studies for its safe therapeutic use.

Ursolic and oleanolic acids as antimicrobial and immunomodulatory compounds for tuberculosis treatment.

BACKGROUND: New alternatives for the treatment of Tuberculosis (TB) are urgently needed and medicinal plants represent a potential option. Chamaedora tepejilote and Lantana hispida are medicinal plants from Mexico and their hexanic extracts have shown antimycobacterial activity. Bioguided investigation of these extracts showed that the active compounds were ursolic acid (UA) and oleanolic acid (OA). METHODS: The activity of UA and OA against Mycobacterium tuberculosis H37Rv, four monoresistant strains, and two drug-resistant clinical isolates were determined by MABA test. The intracellular activity of UA and OA against M. tuberculosis H37Rv and a MDR clinical isolate were evaluated in a macrophage cell line. Finally, the antitubercular activity of UA and OA was tested in BALB/c mice infected with M. tuberculosis H37Rv or a MDR strain, by determining pulmonary bacilli loads, tissue damage by automated histomorphometry, and expression of IFN-γ, TNF-α, and iNOS by quantitative RT-PCR. RESULTS: The in vitro assay showed that the UA/OA mixture has synergistic activity. The intracellular activity of these compounds against M. tuberculosis H37Rv and a MDR clinical isolate in a macrophage cell line showed that both compounds, alone and in combination, were active against intracellular mycobacteria even at low doses. Moreover, when both compounds were used to treat BALB/c mice with TB induced by H37Rv or MDR bacilli, a significant reduction of bacterial loads and pneumonia were observed compared to the control. Interestingly, animals treated with UA and OA showed a higher expression of IFN-γ and TNF-α in their lungs, than control animals. CONCLUSION: UA and OA showed antimicrobial activity plus an immune-stimulatory effect that permitted the control of experimental pulmonary TB.

Antiprotozoal and antimycobacterial activities of Persea americana seeds.

BACKGROUND: Persea americana seeds are widely used in traditional Mexican medicine to treat rheumatism, asthma, infectious processes as well as diarrhea and dysentery caused by intestinal parasites. METHODS: The chloroformic and ethanolic extracts of P. americana seeds were prepared by maceration and their amoebicidal, giardicidal and trichomonicidal activity was evaluated. These extracts were also tested against Mycobacterium tuberculosis H37Rv, four mono-resistant and two multidrug resistant strains of M. tuberculosis as well as five non tuberculosis mycobacterium strains by MABA assay. RESULTS: The chloroformic and ethanolic extracts of P. americana seeds showed significant activity against E. histolytica, G. lamblia and T. vaginalis (IC50 <0.634 µg/ml). The chloroformic extract inhibited the growth of M. tuberculosis H37Rv, M. tuberculosis MDR SIN 4 isolate, three M. tuberculosis H37Rv mono-resistant reference strains and four non tuberculosis mycobacteria (M. fortuitum, M. avium, M. smegmatis and M. absessus) showing MIC values ≤50 µg/ml. Contrariwise, the ethanolic extract affected only the growth of two mono-resistant strains of M. tuberculosis H37Rv and M. smegmatis (MIC ≤50 µg/ml). CONCLUSIONS: The CHCl3 and EtOH seed extracts from P. americana showed amoebicidal and giardicidal activity. Importantly, the CHCl3 extract inhibited the growth of a MDR M. tuberculosis isolate and three out of four mono-resistant reference strains of M. tuberculosis H37Rv, showing a MIC = 50 µg/ml. This extract was also active against the NTM strains, M. fortuitum, M. avium, M. smegmatis and M. abscessus, with MIC values <50 µg/ml.

Microbiological and Pharmacological Evaluation of the Micropropagated Rubus liebmannii Medicinal Plant.

Rubus liebmannii is an endemic species from Mexico used in traditional medicine primarily to treat dysentery and cough. The in vitro activity against Giardia lamblia and Entamoeba histolytica that produces the ethanolic extract of the aerial parts of the plant led us to expand the pharmacological and phytochemical research of this species. Gastrointestinal disorders including amebiasis remain one of the health problems that need to be addressed and it is of interest to find alternatives that improve their treatment. Also, it is important to emphasize that R. liebmannii grows wild in the country and is not found in abundance; therefore, alternatives that avoid overexploitation of the natural resource are mandatory. Ongoing with the evaluation of the potentialities that R. liebmannii possesses for treating infectious gastrointestinal diseases, the aim of the present study was to evaluate the biological effects and the chemical composition of the micropropagated plant.

Acute and subacute toxicity (28 days) of a mixture of ursolic acid and oleanolic acid obtained from Bouvardia ternifolia in mice / Toxicidad aguda y subaguda (28 días) en ratones, de la mezcla de ácido ursólico y ácido oleanólico obtenida de Bouvardia ternifolia

Ursolic acid (UA) and oleanolic acid (OA) are triterpenes that are found in a large number of medicinal plants, one of which is the species Bouvardia ternifolia. These compounds have been shown to have around 120 types of biological activity, especially the hepatoprotective, anti-inflammatory and antimycobacterial effects. Despite having a high therapeutic potential, not much information concerning their toxicity is available. This article describes the results of acute and subacute (28 days) toxicity evaluations in Balb/c mice (both sexes) treated with the mixture of UA/OA obtained from B. ternifolia at doses of 6.5 and 13 mg/kg. The LD50 was >300 mg/kg. During the subacute administration, there was no death of animals and no changes were observed in the growth or weight of the different organs when compared to the control groups. Studies of blood chemistry and blood count showed normal levels in all parameters evaluated. The histopathology of major organs showed no changes or abnormalities. The mixture UA/OA is indeed safe when administered subcutaneously as a single dose of 300 mg/kg or in repeated doses of 13 mg/kg during 28 days.

Los ácidos ursólico (UA) y oleanólico (OA) son triterpenos que se encuentran distribuidos en un gran número de plantas medicinales, una de ellas es la especie Bouvardia ternifolia. Estos compuestos han mostrado alrededor de 120 actividades biológicas, destacando los efectos hepatoprotector, antiinflamatorio y antimicobacteriano. A pesar de ser compuestos con un alto potencial terapéutico, no se han documentado muchos datos acerca de su toxicidad. En este artículo se describen los resultados de la evaluación de toxicidad aguda y subaguda (28 días) en ratones Balb/c de ambos sexos, tratados con la mezcla de AU/AO obtenida de B. ternifolia a dosis de 6.5 y 13 mg/kg. La DL50 fue > 300 mg/kg. Durante la administración subaguda, no hubo muerte de animales, tampoco se observaron alteraciones en su crecimiento ni alteraciones en el peso de los diferentes órganos. Los estudios de biometría hemática y química sanguínea mostraron niveles normales en todos los parámetros evaluados. Los análisis histopatológicos de los principales órganos no presentaron cambios o anormalidades. La mezcla UA/OA es prácticamente inocua cuando se administra subcutáneamente en dosis única de 300 mg/kg y 13 mg/kg en dosis repetida (28 días).