Evaluation of hypoglycemic and antioxidant effects of Brickellia eupatorioides, Citrus limettioides and Gochnatia hypoleuca.

Diabetes is a chronic metabolic condition with a rapidly increasing prevalence. It comes with a rise in the generation of free radicals, potentially leading to additional health issues. Further studies and creative approaches are required to address this. Natural products are potential new antidiabetic drugs that are worth exploring. The aim of the present study is to assess the antihyperglycemic and antioxidant effects of ethanolic extracts of Brickellia eupatorioides, Citrus limettioides and Gochnatia hypoleuca. The antihyperglycemic activity of the extracts was tested on Wistar rats (diabetes induced by alloxan, 150mg/kg), as well as the inhibitory effect on a-glucosidase and a-amylase (in vitro assay). The antioxidant potential was evaluated using DPPH and ABTS assays. The total phenolic and flavonoid contents were also determined. The results indicated that ethanolic extracts of B. eupatorioides induced a powerful hypoglycemic in vivo effect with a significant decrease at 6h after administration, similar to that produced by glibenclamide; the decrease could be related to a-glucosidase inhibition. Moreover, the extract exhibited a potent scavenging activity (IC50 values 33±6mg/mL and 15±2mg/mL in the DPPH and ABTS methods, respectively). The results demonstrated antihyperglycemic and antioxidant activity of ethanolic extracts of B. eupatorioides.

Hepatodamianol as hepatoprotective constituent of Turnera diffusa.

It is well known that liver diseases are a major health problem and that there is a lack of hepatoprotective agents. Turnera diffusa (damiana) is a plant with a widespread distribution in México, which has many traditional uses, including the treatment of hepatic illnesses. Based on the bioassay-guided fractionation of a methanolic extract obtained from the aerial part of T. diffusa, we purified and identified a compound called hepatodamianol (1). This C-glycoside exhibited a four times greater hepatoprotective effect than the widely used hepatoprotective agent silibinin against carbon tetrachloride damage in an in vitro model using HepG2 cells. Hepatodamianol produced no cytotoxic effects and it exhibited a high antioxidant capacity. Therefore, hepatodamianol is a good candidate compound for testing as a hepatoprotective agent in a preclinical trial.

Development of a Hepatoprotective Herbal Drug from Turnera diffusa.

The incidence of liver diseases, such as nonalcoholic fatty liver disease and drug-induced liver injury, continues to rise and is one of the leading causes of acute hepatitis. Current trends suggest that these types of conditions will increase in the coming years. There are few drugs available for the prevention or treatment of hepatic diseases, and there is a growing need for the development of safe hepatoprotective agents. The medicinal plant, Turnera diffusa, has many ethnopharmacological uses, one of which is the production of a flavonoid named hepatodamianol, which is the principal component responsible for this plant's hepatoprotective properties. In the present study, we describe the development and standardization of an active extract obtained from T. diffusa. We conducted nuclear magnetic resonance spectroscopy to identify hepatodamianol unambiguously in each sample. Using this extract, hepatoprotection could be demonstrated in vivo for the first time. The hepatoprotective effect did not display a significant difference in vivo when compared with silymarin used as a positive control at the same doses. Implementation of quality criteria used for standardization, such as flavonoid and hepatodamianol content, hepatoprotective activity, and absence of residual solvents, will allow future preclinical trials with this herbal drug.

Turnera diffusa extract attenuates profibrotic, extracellular matrix and mitochondrial markers in activated human hepatic stellate cells (HSC).

INTRODUCTION AND OBJECTIVES: Hepatic fibrosis is characterized by the accumulation of extracellular matrix which includes the accumulation of α-smooth muscle actin (α-SMA), collagen type I (COL1α1), as well as remodeling induced by metalloproteinases and tissue inhibitor of metalloproteinase (TIMPs), where hepatic stellate cells (HSCs) play a central role. In addition, the transcription factor SNAI1 (which participates in epithelial-mesenchymal transition, EMT) and mitofusin 2 (MFN2, a mitochondrial marker) plays an important role in chronic liver disease. Turnera diffusa (TD), a Mexican endemic plant, has been shown to possess antioxidant and hepatoprotective activity in vitro. We treated human HSC (LX2 cells) with a methanolic extract of Turnera diffusa (METD) to evaluate the mechanism involved in its hepatoprotective effect measured as fibrosis modulation, EMT, and mitochondrial markers. MATERIALS AND METHODS: HSC LX-2 cells were treated with METD (100 and 200ng/mL) alone or combined with TGF-ß (10ng/mL) at different time points (24, 48, and 72h). α-SMA, COL1α1, MMP2, TIMP1, SNAI1, and MFN2 mRNAs and protein levels were determined by real-time quantitative PCR and Western Blot analysis. RESULTS: We found that METD decreases COL1α1-mRNA, α-SMA, and TIMP1 protein expression in LX2 cells treated with and TGF-ß. This treatment also decreases MFN2 and TIMP1 protein expression and induces overexpression of MMP2-mRNA. CONCLUSIONS: Our results suggest that a methanolic extract of Turnera diffusa is associated with an antifibrotic effect by decreasing profibrotic and mitochondrial markers together with the possible induction of apoptosis through SNAI1 expression in activated HSC cells.

Anti-inflammatory and nephroprotective activity of Juglans mollis against renal ischemia-reperfusion damage in a Wistar rat model.

BACKGROUND: Oxidative stress and the inflammatory process are involved in ischemia-reperfusion (I/R) injury. Juglans mollis has been reported as having antioxidant activity, which could attenuate the damage caused by I/R. We evaluated whether a methanolic extract of Juglans mollis (JM) exhibits nephroprotective activity in a Wistar rat model of I/R injury. METHODS: Four groups of six rats were used: Sham, I/R, JM, and JM + I/R. Two groups were dosed with JM (300 mg/kg) for 7 days before I/R. I/R injury was induced by clamping the renal hilums for 45 min and then reperfusing the kidneys for 15 h. Blood samples were taken to evaluate the levels of alanine aminotransferase (ALT), blood urea nitrogen, creatinine, superoxide dismutase (SOD), malondialdehyde (MDA), interleukin 1ß (IL-1ß), IL-6, and tumor necrosis factor α (TNF-α). RESULTS: The levels of creatinine, ALT, MDA, IL-1ß, IL-6, and TNF-α were lower in JM + I/R than in I/R rats, whereas SOD level only was higher in JM + I/R than in Sham rats. No biochemical or histological damage was observed in JM rats compared with Sham rats; however, less histological damage was observed in JM + I/R rats compared with I/R rats. CONCLUSIONS: To our knowledge, this is the first report of nephroprotective activity of J. mollis against damage induced by I/R. This activity may be related to decreased levels of proinflammatory cytokines (IL-1ß, IL-6, and TNF-α) and modulation of oxidative stress markers (SOD and MDA) observed in the present study.

Hypoglycemic Activity of Tilia americana, Borago officinalis, Chenopodium nuttalliae, and Piper sanctum on Wistar Rats.

Diabetes mellitus (DM) is considered the epidemic of the 21st century. Traditional medicine uses plants to treat DM; many of these have hypoglycemic effects in both animal models and diabetic patients. Our objective was to evaluate the hypoglycemic activity of Tilia americana, Borago officinalis, Chenopodium nuttalliae, and Piper sanctum on diabetic rats. The methanolic extracts of the plants under study were obtained by Soxhlet extraction. Toxicity was evaluated on Artemia salina; the antioxidant potential was evaluated using the DPPH technique. Hypoglycemic capacity at doses of 250 and 500 mg/kg was tested on Wistar rats with diabetes induced by alloxan (120 mg/kg). The toxicity on A. salina was null for the extracts of B. officinalis and P. sanctum, moderate for T. americana, and highly toxic for C. nuttalliae. The relevant extract of T. americana var. mexicana showed antioxidant activity. Three plants of the studied plants showed hypoglycemic activity: Tilia Americana (p = 0.0142), Borago officinalis (p = 0.0112), and Piper sanctum (p = 0.0078); P. sanctum was the one that showed the greatest reduction in glucose levels at a lower dose.

Nephroprotective Effect of Sonchus oleraceus Extract against Kidney Injury Induced by Ischemia-Reperfusion in Wistar Rats.

INTRODUCTION: Kidney ischemia-reperfusion (I/R) injury is the main cause of delayed graft function in solid organ transplantation. Sonchus oleraceus is a plant with well-known antioxidant and anti-inflammatory activities; however, its effects on renal I/R are unknown. OBJECTIVE: To evaluate whether S. oleraceus extract (S.O.e.) has nephroprotective activity in an I/R model in Wistar rats. MATERIALS AND METHODS: Animal groups (n = 6): sham, I/R (45 min/15 h), S.O.e (300 mg/kg p.o.), and S.O.e + I/R (300 mg/kg, p.o.; 45 min/15 h). Renal function, proinflammatory cytokines, alanine aminotransferase, markers of oxidative stress, and histology were evaluated. RESULTS: None of the mediators evaluated differed significantly between the S.O.e and sham groups. Levels of blood urea nitrogen (BUN), creatinine, malondialdehyde (MDA), and proinflammatory cytokines were higher, and superoxide dismutase (SOD) was lower in the I/R group than in the sham group. Histology showed tubular epithelial necrosis in the medulla and cortex in the I/R group. In the S.O.e + I/R group, S.O.e pretreatment attenuated the I/R-induced increases in BUN, creatinine, MDA, and proinflammatory cytokines induced, SOD was maintained, and histology showed discontinuous necrosis in the medulla but no necrosis in the cortex. CONCLUSIONS: S.O.e was neither hepatotoxic nor nephrotoxic. S.O.e. pretreatment showed a nephroprotective effect against I/R.

Evaluation of hypocholesterolemic activity of extracts of Bidens odorata and Brickellia eupatorioides.

We sought to evaluate the hypolipidemic activity of extracts of Bidens odorata and Brickellia eupatorioides using a model of hyperlipidemia induced in rats by Triton WR-1339 (300mg/kg intraperitoneally). The rats were divided into 5 groups of 3 rats each: normal control group, hyperlipidemic control group, hyperlipidemic with 20 mg/kg atorvastatin, hyperlipidemic with 300 mg/kg B. odorata extract, and hyperlipidemic with 300mg/kg B. eupatorioides extract, respectively. After 10 d of treatment by intragastric administration, the extract of B. odorata caused a significant decrease of serum total cholesterol and triglyceride levels without altering the liver enzymes aspartate transaminase and alanine aminotransferase. In addition, the extract had antioxidant potential as shown by the 2,2-diphenyl-1-picrylhydrazyl technique. These findings indicate that B. odorata has potential as a hypolipidemic agent and might be beneficial in treatment of hyperlipidemia and atherosclerosis.

Antioxidant and hepatoprotective activity of Hamelia patens extracts.

Hamelia patens is widely used in the traditional medicine of Mexico and Central America for the treatment of illnesses associated with inflammatory processes. In this study, antioxidant and hepatoprotective activity were assayed on the methanolic crude (ME), hexane (HE), ethyl acetate (AE), and butanol (BE) extracts of H. patens. The total phenolic content (TPC) as mg of gallic acid equivalents per g of dry extract was determined by Folin-Ciocalteu's method (ME=141.58±11.99, HE=33.96±1.13, AE=375.18±13.09, BE=132.08±3.62), and antioxidant activity by 2,2-diphenyl-1-picryl-hydrazyl (DPPH) free radical-scavenging method (EC(50) ME=77.87±5.67, HE=236.64±26.32, AE=45.87±2.24, BE=50.97±0.85µg/mL). Hepatoprotective activity was evaluated through AST activity on HepG2 cells subjected to damage with CCl(4) (ME=62.5±3.41, HE=72.25±2.87, AE=63.50±4.20, BE=43.74±4.03). BE showed the greater hepatoprotective activity and a good antioxidant capacity, while HE did not show hepatoprotective or antioxidant activity. Cytotoxicity was evaluated on Vero cells cultures; none showed significant toxicity.

Hepatoprotective effect of commercial herbal extracts on carbon tetrachloride-induced liver damage in Wistar rats.

BACKGROUND: Various hepatoprotective herbal products from plants are available in Mexico, where up to 85% of patients with liver disease use some form of complementary and alternative medicine. However, only few studies have reported on the biological evaluation of these products. OBJECTIVE: Using a model of carbon tetrachloride (CCl4)-induced hepatotoxicity in rats, we evaluated the effects of commercial herbal extracts used most commonly in the metropolitan area of Monterrey, Mexico. MATERIALS AND METHODS: The commercial products were identified through surveys in public areas. The effect of these products given with or without CCl4 in rats was evaluated by measuring the serum concentrations of aspartate amino transferase (AST) and alanine amino transferase (ALT), and histopathological analysis. Legalon(®) was used as the standard drug. RESULTS: The most commonly used herbal products were Hepatisan(®) capsules, Boldo capsules, Hepavida(®) capsules, Boldo infusion, and milk thistle herbal supplement (80% silymarin). None of the products tested was hepatotoxic according to transaminase and histological analyses. AST and ALT activities were significantly lower in the Hepavida+CCl4-treated group as compared with the CCl4-only group. AST and ALT activities in the silymarin, Hepatisan, and Boldo tea groups were similar to those in the CCl4 group. The CCl4 group displayed submassive confluent necrosis and mixed inflammatory infiltration. Both the Hepatisan+CCl4 and Boldo tea+CCl4 groups exhibited ballooning degeneration, inflammatory infiltration, and lytic necrosis. The silymarin+CCl4 group exhibited microvesicular steatosis. The Hepavida+CCl4- and Legalon+CCL4-treated groups had lower percentages of necrotic cells as compared with the CCl4-treated group; this treatment was hepatoprotective against necrosis. CONCLUSION: Only Hepavida had a hepatoprotective effect.

Plants from northeast Mexico with anti-HSV activity.

Based on chemotaxonomic and ethno-pharmacological criteria, three Mexican plants (Jatropha dioica, Salvia texana and S. ballotaeflora) were studied for in vitro activity against HSV-1 and HSV-2. Hydro-methanolic extracts were initially evaluated for their toxicity to Vero cells. Both Salvia species displayed cytotoxicity at the lowest dose (125 microg/mL). The J. dioica extract showed only negligible cytotoxicity (CC50 644 microg/mL). Its anti-HSV activity was evaluated using the plaque reduction assay with HSV-1 and HSV-2 (from clinical isolates) infected Vero cells. The hydro-methanolic extract of J. dioica showed IC50s of 280 and 370 microg/mL against HSV-1 and HSV-2, respectively. The n-hexane liquid-liquid partition of J. dioica extract contained the majority of the active principle(s) with IC50 values of 300 and 270 microg/mL for HSV-1 and HSV-2, respectively. Bioassay-guided isolation led to the known diterpene, riolozatrione.

Protective effect of four Mexican plants against CCl4-induced damage on the Huh7 human hepatoma cell line.

BACKGROUND: Centaurea americana, Krameria ramosissima, Juglans mollis and Turnera diffusa are used by traditional healers in the northeastern region of Mexico to protect against liver damage. However, the hepatoprotective properties of these plants have not been investigated scientifically. This study reports on the protective effects of these plants using an in vitro assay. MATERIAL AND METHODS: Extracts of plants were tested for antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging method. The effects of extracts from these plants on a human hepatoma cell line (Huh7) were evaluated according to cell viability and aspartate aminotransferase and malondialdehyde levels before and after exposure of the cells to carbon tetrachloride (CCl(4)). RESULTS: All extracts reduced DPPH levels by more than 50%. C. americana flower and stem/leaf extracts, the aerial part of T. diffusa, and the nut, leaf and bark of J. mollis extracts were used to assess hepatoprotective activity. The extract of the aerial part of K. ramosissima was toxic. Pretreatment of Huh7 cells with extracts from the flower of C. americana (FCA), the stem/leaf fraction of C. americana (S/LCA), the leaf of J. mollis (LJM) and the bark of J. mollis (BJM) prior to the CCl(4) challenge, protected against CCl(4)-induced liver damage, as evidenced by a significant decrease in the activity of the medium enzyme. The FCA, S/LCA, LJM and BJM extracts showed significant antilipid peroxidant effects in vitro. In conclusion, the hepatoprotective effects of the FCA, S/LCA, LJM and BJM extracts observed in this study may result from their antioxidative properties.