Anti-epileptic activity, toxicity and teratogenicity in CD1 mice of a novel valproic acid arylamide derivative, N-(2-hydroxyphenyl)-2-propylpentanamide.

N-(2-hydroxyphenyl)-2-propylpentamide (HO-AAVPA) is a novel arylamide derivative of valproic acid (VPA) designed in silico, with better antioxidant and antiproliferative effect on cancer cell lines than VPA. This study was aimed to evaluate the anticonvulsant activity, the toxicity and teratogenicity produced in HO-AAVPA-treated CD1 mice using VPA as positive control. With the maximal electroshock (MES)- and pentylenetetrazole (PTZ)-induced seizure models, HO-AAVPA reduced the time of hind limb extension, stupor and recovery, the number of clonic and tonic seizures and the mortality rate in a dose-dependent manner, obtaining an ED50 of 370 and 348 mg/kg for MES and PTZ, respectively. On the rotarod test, mice administered with 600 mg/kg HO-AAVPA manifested reduced locomotor activity (2.78%); while HO-AAVPA at 300 mg/kg and VPA at 500 mg/kg gave a similar outcome (∼60%). The LD50 of 936.80 mg/kg herein found for HO-AAVPA reflects moderate toxicity. Concerning teratogenicity, the administration of HO-AAVPA to pregnant females at 300 and 600 mg/kg on gestation day (GD) 8.5 generated less visceral and skeletal alterations in the fetuses, as well as, minor rate of modifications in the expression pattern of the neuronal marker Tuj1 and endothelial marker PECAM1 in embryos, that those induced by VPA administration. Altered embryonic development occurred with less frequency and severity with HO-AAVPA at 600 mg/kg than VPA at 500 mg/kg. In conclusion, the protective effect against convulsions provided by HO-AAVPA was comparable to that of VPA in the MES and PZT seizure models, showed lower toxicity and less damage to embryonic and fetal development.

Synthesis and highly potent anti-inflammatory activity of licofelone- and ketorolac-based 1-arylpyrrolizin-3-ones.

Since NSAIDs are commonly used anti-inflammatory agents that produce adverse effects, there have been ongoing efforts to develop more effective and less toxic compounds. Based on the structure of the anti-inflammatory pyrrolizines licofelone and ketorolac, a series of 1-arylpyrrolizin-3-ones was synthesized. Also prepared was a series of substituted pyrroles, mimicking similar known anti-inflammatory agents. The anti-inflammatory activity of the test compounds was determined with a phorbol ester (TPA)-induced murine ear edema protocol. For the most active derivatives, 19b-c/20b-c, the anti-inflammatory effect was the same as that of the reference compound (indomethacin) and was dose-dependent. These compounds have an aryl ring at the C-1 position and a methoxycarbonyl group at the C-2 position of the pyrrolizine framework, which represent plausible pharmacophore groups with anti-inflammatory activity. The anti-inflammatory activity of 1-substituted analogs containing a five- or six-membered heterocycles was lower but still good, while that of the pyrroles was only moderate. Although the docking studies suggests that the effect of analogs 19a-c/20a-c is associated with the inhibition of cyclooxygenase-2, experimental assays did not corroborate this idea. Indeed, a significant inhibition of NO was found experimentally as a plausible mechanism of action.

Resveratrol partially prevents oxidative stress and metabolic dysfunction in pregnant rats fed a low protein diet and their offspring.

Protein restriction in pregnancy produces maternal and offspring metabolic dysfunction potentially as a result of oxidative stress. Data are lacking on the effects of inhibition of oxidative stress. We hypothesized that maternal resveratrol administration decreases oxidative stress, preventing, at least partially, maternal low protein-induced maternal and offspring metabolic dysfunction. In the present study, pregnant wistar rats ate control (C) (20% casein) or a protein-restricted (R) (10% casein) isocaloric diet. Half of each group received resveratrol orally, 20 mg kg(-1) day(-1), throughout pregnancy. Post-delivery, mothers and offspring ate C. Oxidative stress biomarkers and anti-oxidant enzymes were measured in placenta, maternal and fetal liver, and maternal serum corticosterone at 19 days of gestation (dG). Maternal (19 dG) and offspring (postnatal day 110) glucose, insulin, triglycerides, cholesterol, fat and leptin were determined. R mothers showed metabolic dysfunction, increased corticosterone and oxidative stress and reduced anti-oxidant enzyme activity vs. C. R placental and fetal liver oxidative stress biomarkers and anti-oxidant enzyme activity increased. R offspring showed higher male and female leptin, insulin and corticosterone, male triglycerides and female fat than C. Resveratrol decreased maternal leptin and improved maternal, fetal and placental oxidative stress markers. R induced offspring insulin and leptin increases were prevented and other R changes were offspring sex-dependent. Resveratrol partially prevents low protein diet-induced maternal, placental and sex-specific offspring oxidative stress and metabolic dysfunction. Oxidative stress is one mechanism programming offspring metabolic outcomes. These studies provide mechanistic evidence to guide human pregnancy interventions when fetal nutrition is impaired by poor maternal nutrition or placental function.

Structural and Physicochemical Characterization of Spirulina (Arthrospira maxima) Nanoparticles by High-Resolution Electron Microscopic Techniques.

The objective of this work was to obtain Spirulina (Arthrospira maxima) nanoparticles (SNPs) by using high-impact mechanical milling and to characterize them by electron microscopy and spectroscopy techniques. The milling products were analyzed after various processing times (1-4 h), and particle size distribution and number mean size (NMS) were determined by analysis of high-resolution scanning electron microscopic images. The smallest particles are synthesized after 3 h of milling, had an NMS of 55.6±3.6 nm, with 95% of the particles being smaller than 100 nm. High-resolution transmission electron microscopy showed lattice spacing of ~0.27±0.015 nm for SNPs. The corresponding chemical composition was obtained by energy-dispersive X-ray spectroscopy, and showed the presence of Ca, Fe, K, Mg, Na, and Zn. The powder flow properties showed that the powder density was higher when the average nanoparticle size is smaller. They showed free flowability and an increase in their specific surface area (6.89±0.23 m2/g) up to 12-14 times larger than the original material (0.45±0.02 m2/g). Fourier transform infrared spectroscopy suggested that chemical damage related to the milling is not significant.

Synthesis and highly potent hypolipidemic activity of alpha-asarone- and fibrate-based 2-acyl and 2-alkyl phenols as HMG-CoA reductase inhibitors.

In the search for new potential hypolipidemic agents, the present study focused on the synthesis of 2-acyl phenols (6a-c and 7a-c) and their saturated side-chain alkyl phenols (4a-c and 5a-c), and on the evaluation of their hypolipidemic activity using a murine Tyloxapol-induced hyperlipidemic protocol. The whole series of compounds 4-7 greatly and significantly reduced elevated serum levels of total cholesterol, LDL-cholesterol, and triglycerides, with series 6 and 7 showing the greatest potency ever found in our laboratory. At the minimum dose (25mg/kg/day), the latter compounds lowered cholesterol by 68-81%, LDL by 72-86%, and triglycerides by 59-80%. This represents a comparable performance than that shown by simvastatin. Experimental evidence and docking studies suggest that the activity of these derivatives is associated with the inhibition of HMG-CoA reductase.

Reduced-calorie avocado paste attenuates metabolic factors associated with a hypercholesterolemic-high fructose diet in rats.

The objective of this study was to evaluate the effect of reduced-calorie avocado paste on lipid serum profile, insulin sensitivity, and hepatic steatosis in rats fed a hypercholesterolemic-high fructose diet. Thirty five male Wistar rats were randomly separated in five groups: Control group (ground commercial diet); hypercholesterolemic diet plus 60% fructose solution (HHF group); hypercholesterolemic diet plus 60% fructose solution supplemented with avocado pulp (HHF+A group); hypercholesterolemic diet plus 60% fructose solution supplemented with reduced-calorie avocado paste (HHF+P group); and hypercholesterolemic diet plus 60% fructose solution supplemented with a reduced-calorie avocado paste plus fiber (HHF+FP group). The A, P, and FP were supplemented at 2 g/kg/d. The study was carried out for seven weeks. Rats belonging to the HHF group exhibited significantly (P ≤ 0.05) higher total cholesterol, triglycerides, and insulin levels in serum as well as lower insulin sensitivity than the control group. Supplementation with reduced-calorie avocado paste showed a significant (P ≤ 0.05) decrease in total cholesterol (43.1%), low-density lipoprotein (45.4%), and triglycerides (32.8%) in plasma as well as elevated insulin sensitivity compared to the HHF group. Additionally, the liver enzymes alanine aminotransferase and aspartate aminotransferase decreased significantly in the HHF-P group (39.8 and 35.1%, respectively). These results are likely due to biocompounds present in the reduced-calorie avocado paste, such as polyphenols, carotenoids, chlorophylls, and dietary fibre, which are capable of reducing oxidative stress. Therefore, reduced-calorie avocado paste attenuates the effects of a hypercholesterolemic-high fructose diet in rats.

Phytochemicals and Their Usefulness in the Maintenance of Health.

Inflammation is the immune system's first biological response to infection, injury, or irritation. Evidence suggests that the anti-inflammatory effect is mediated by the regulation of various inflammatory cytokines, such as nitric oxide, interleukins, tumor necrosis factor alpha-α, interferon gamma-γ, as well as the non-cytokine mediator, prostaglandin E2. Currently, the mechanism of action and clinical usefulness of phytochemicals is known; their action on the activity of cytokines, free radicals, and oxidative stress. The latter are of great relevance in the development of diseases, such that the evidence collected demonstrates the beneficial effects of phytochemicals in maintaining health. Epidemiological evidence indicates that regular consumption of fruits and vegetables is related to a low risk of developing cancer and other chronic diseases.

Developmental Toxicity Study of DL-4-Hydroxy-4-Phenylhexanamide (DL-HEPB) in Rats.

Antiepileptic drugs affect embryonic development when administered during pregnancy, generating severe alterations, such as as cleft lip, spina bifida, heart abnormalities, or neuronal alterations. The compound DL-4-hydroxy-4-phenylhexanamide (DL-HEPB), a phenyl alcohol amide structurally different from known anticonvulsants, has shown good anticonvulsant effects in previous studies. However, its effects on intrauterine development are unknown. So, the purpose of this study was to determine the potential of DL-HEPB to produce alterations in conceptus. Pregnant Wistar rats were orally exposed to 0, 50, 100, and 200 mg/kg of DL-HEPB during organogenesis, and their food consumption and weight gain were measured. On gestation day 21, pregnant females were euthanized to analyze the fetuses for external, visceral, and skeletal malformations. A significant decrease in food consumption and body weight was observed in mothers, without any other manifestation of toxicity. In fetuses, no external malformations, visceral, or skeletal abnormalities, were observed under the dose of 100 mg/kg, while the dose of 200 mg/kg caused malformations in low frequency in brain and kidneys. In view of the results obtained, DL-HEPB could be a good starting point for the design of new highly effective anticonvulsant agents, with much lower developmental toxicity than that shown by commercial anticonvulsants.

C-Phycocyanin: A Phycobiliprotein from Spirulina with Metabolic Syndrome and Oxidative Stress Effects.

Spirulina maxima is a cyanobacterium considered a "superfood" due to its metabolites and nutrient content. These include a complex mixture of minerals, vitamins, fatty acids, proteins, and accessory pigments. In recent years, it has positioned itself as a promising source of bioactive molecules for the treatment of several diseases, including metabolic syndrome, coronary diseases, cancer, and the improvement of health modulating oxidative stress. C-Phycocyanin (C-PC) is a photosynthetic pigment from green-blue cyanobacterium and the most abundant phycobiliprotein in the Spirulina genus with various pharmacological properties attributed due to its antioxidant capacity but has no specific cellular target. This has made it a molecule of great interest in biomedical research. This review focuses on the pharmacological effects and the benefits on metabolic syndrome and oxidative stress of C-PC.

Spirulina (Arthrospira maxima) mitigates the toxicity induced by a mixture of metal and NSAID in Xenopus laevis.

Cadmium (Cd) is often detected in the environment due to its wide use in industry; also, NSAIDs are one of the most consumed pharmaceuticals, particularly diclofenac (DCF). Several studies have reported the presence of both contaminants in water bodies at concentrations ranging from ng L-1 to µg L-1; in addition, they have shown that they can induce oxidative stress in aquatic species and disturb signal transduction, cell proliferation, and intercellular communication, which could lead to teratogenesis. Spirulina has been consumed as a dietary supplement; its antioxidant, anti-inflammatory, neuroprotective, and nutritional properties are well documented. This work aimed to evaluate if Spirulina reduces the damage induced by Cd and DCF mixture in Xenopus laevis at early life stages. FETAX assay was carried out: 20 fertilized oocytes were exposed to seven different treatments on triplicate, control, Cd (24.5 µg L-1), DCF (149 µg L-1), Cd + DCF, Cd+DCF+Spirulina (2 mg L-1), Cd+DCF+Spirulina (4 mg L-1), Cd+DCF+Spirulina (10 mg L-1), malformations, mortality, and growth were evaluated after 96 h, also lipid peroxidation, superoxide dismutase and catalase activity were determined after 192 h. Cd increased DCF mortality, Cd and DCF mixture increased the incidence of malformations as well as oxidative damage; on the other hand, the results obtained show that Spirulina can be used to reduce the damage caused by the mixture of Cd and DCF since it promotes growth, reduce mortality, malformations, and oxidative stress in X. laevis.

Polyamines modulate mouse sperm motility.

Polyamines are polycationic molecules which contains two or more amino groups (-NH3+) highly charged at physiological pH, and among them we found spermine, spermidine, putrescine, and cadaverine. They interact with proteins, nucleic acids, modulate Ca2+, K+, and Na+ channels, and protect sperm from oxidative stress. In this work, we evaluate the effect of spermine, spermidine, and putrescine on the total, progressive and kinematic parameters of motility, capacitation, acrosome reaction, also in presence and absence of the dbcAMP, an analogue of the cAMP, and the IBMX, a phosphodiesterase inhibitor. In addition, we evaluated the intracellular concentrations of cAMP [cAMP]i, and performed an in silico analysis between polyamines and the sAC from mouse to predict the possible interaction among them. Our results showed that all polyamines decrease drastically the total, progressive and the kinetic parameters of sperm motility, decrease the capacitation, and only spermidine and putrescine impeded the acquisition of acrosome reaction. Moreover, the effect of polyamines was attenuated but not countered by the addition of db-cAMP and IBMX, suggesting a possible inhibition of the sAC. Also, the presence of polyamines induced a decrease of the [cAMP]i, and the in silico analysis predicted a strong interaction among polyamines and the sAC. Overall, the evidence suggests that probably the polyamines interact and inhibit the activity of the sAC.

Protective Effect of the Phycobiliproteins from Arthrospira maxima on Indomethacin-Induced Gastric Ulcer in a Rat Model.

Gastric ulcers (GU) constitute a disease with a global prevalence ≈ 8.09 million. Of their causes, non-steroidal anti-inflammatory drugs (NSAIDs) such as indomethacin (IND) rank as the second most frequent etiologic agent. The pathogenic process of gastric lesions is given by the overproduction of oxidative stress, promotion of inflammatory processes, and inhibition of prostaglandin synthesis. Spirulina Arthrospira maxima (SP) is a cyanobacterium with a wide variety of substances with high nutritional and health values such as phycobiliproteins (PBPs) that have outstanding antioxidant activity, anti-inflammatories effects, and accelerate the wound healing process. This study aimed to determine the protective effect of PBPs in GU induced by IND 40 mg/kg. Our results show that the PBPs protected against IND-induced damage with a dose-dependent effect. At a dose of 400 mg/kg, a marked decrease in the number of lesions is observed, as well as the recovery of the main markers of oxidative stress damage (MDA) and antioxidant species (SOD, CAT, GPx) at close to baseline levels. The evidence derived from the present investigation suggests that the antioxidant effect of PBPs, together with their reported anti-inflammatory effects to accelerate the wound healing process, is the most reliable cause of their antiulcerogenic activity in this GU model.

Chiranthodendron pentadactylon Larreat (Sterculiaceae), a Potential Nephroprotector against Oxidative Damage Provoked by STZ-Induced Hyperglycemia in Rats.

BACKGROUND: Chiranthodendron pentadactylon, known in Mexico as the "tree of the little hands", flower's infusion is used to treat kidney failure associated with diseases such as diabetes. The aim of this work is to evaluate the antioxidant effect of the methanolic extract of its flowers on oxidative damage in kidneys caused by streptozotocin in rats. METHODS: The extract phytochemical profile was performed with HPLC. Antioxidant potential in vitro was determined with DPPH and total phenolic tests; antioxidant evaluation in vivo was performed in diabetic rats administered daily via the intragastric route (100 and 200 mg/kg) for 6 weeks; serum glucose/creatinine, food/water consumption, and urinary volume were measured. Relative weight, protein/DNA ratios and oxidative stress were measured in renal tissue. RESULTS: The extract showed 20.53% of total phenolic content and IC50 of 18.05 µg/mL in DPPH, and this was associated with ferulic acid, phloretin and α-amyrin. Both doses showed a moderate decrease in the protein/DNA ratio in renal tissue, and the same behavior was observed for total urinary protein loss and serum creatinine, while the best antioxidant effect was exerted by a lower dose, which increased catalase activity and decreased lipid peroxidation in the kidneys. CONCLUSIONS: Results demonstrated that C. pentadactylon methanolic flower's extract improves renal function through antioxidant mechanisms during experimental diabetes.

Effects of Spirulina maxima on a Model of Sexual Dysfunction in Streptozotocin-Induced Diabetic Male Rats.

Arthrospira (Spirulina) maxima (SM) is a cyanobacterium that has a long history of being used as human food. In recent years, several investigations have shown its beneficial biological effects, among which its antioxidant capacity has been highlighted. The purpose of this study was to evaluate the effects of SM on body weight, glycemia, sexual behavior, sperm quality, testosterone levels, sex organ weights, and the activity of antioxidant enzymes in diabetic male rats (a disease characterized by an increase in reactive oxygen species). The experiment consisted of six groups of sexually expert adult males (n = 6): (1) control (vehicle); (2) streptozotocin (STZ)-65 mg/kg; (3) SM-400 mg/kg; (4) STZ + SM-100 mg/kg; (5) STZ + SM-200 mg/kg; and (6) STZ + SM-400 mg/kg. Sexual behavior tests were performed during the first 3 h of the dark period under dim red illumination. Our results showed that SM significantly improved sexual behavior and sperm quality vs. diabetic animals. Likewise, while the enzymatic activities of SOD and GPx increased, TBARS lipoperoxidation decreased and testosterone levels increased. In view of the findings, it is suggested that SM may potentially be used as a nutraceutical for the treatment of diabetic male sexual dysfunction due to its antioxidant property.

Antioxidant, antinociceptive, and anti-inflammatory effects of carotenoids extracted from dried pepper (Capsicum annuum L.).

Carotenoids extracted from dried peppers were evaluated for their antioxidant, analgesic, and anti-inflammatory activities. Peppers had a substantial carotenoid content: guajillo 3406 ± 4 µg/g, pasilla 2933 ± 1 µg/g, and ancho 1437 ± 6 µg/g of sample in dry weight basis. A complex mixture of carotenoids was discovered in each pepper extract. The TLC analysis revealed the presence of chlorophylls in the pigment extract from pasilla and ancho peppers. Guajillo pepper carotenoid extracts exhibited good antioxidant activity and had the best scavenging capacity for the DPPH(+) cation (24.2%). They also exhibited significant peripheral analgesic activity at 5, 20, and 80 mg/kg and induced central analgesia at 80 mg/kg. The results suggest that the carotenoids in dried guajillo peppers have significant analgesic and anti-inflammatory benefits and could be useful for pain and inflammation relief.

The effect of cocoa, soy, oats and fish oil on metabolic syndrome in rats.

BACKGROUND: The effect of functional foods alone or in combination (cocoa + soy + oats + fish oil) on hepatic damage in rats affected with metabolic syndrome was investigated. RESULTS: Rats that were given cocoa showed a decrease in the levels of triglycerides (TGs) and glucose (63 and 32% respectively) as well as a decrease in blood pressure (15%). Animals fed with soy showed a reduction of 21% in total cholesterol, 15% in blood pressure and 44% in TGs, while feeding oats reduced the concentration of TGs by 53% (P < 0.5). Fish oil caused a reduction in TGs (56%) and glucose (26%). The effect on blood pressure was statistically significant for the groups supplemented with cocoa, soy, cocoa + oats and the total mix. The main finding was a reduction in liver steatosis in animals supplemented with cocoa + oats (from 30 to 4.7% steatosis). Cocoa or fish oil alone did not protect the liver from damage, while cocoa + fish oil did. CONCLUSION: The most relevant effects were that the cocoa + oats mix decreased steatosis by a very large percentage, as did the cocoa + fish oil mix and the mix of all four functional foods.

Hypolipidemic effect of avocado (Persea americana Mill) seed in a hypercholesterolemic mouse model.

Avocado seed contains elevated levels of phenolic compounds and exhibits antioxidant properties. We investigated the effect of Avocado Seed Flour (ASF) on the lipid levels in mice on a hyperlipidemic diet. The concentration of phenols was determined by high-performance liquid chromatography, antioxidant activity was evaluated using the Trolox equivalent antioxidant capacity method, and dietary fiber was measured using the Association of Official Analytical Chemists (AOAC) method. The LD50 of ASF was determined using Lorke's method and hypolipidemic activity was evaluated in a hypercholesterolemic model in mice. Protocatechuic acid was the main phenolic compound found in ASF, followed by kaempferide and vanillic acid. The total phenolic content in the methanolic extract of ASF was 292.00 ± 9.81 mg gallic acid equivalents/g seed dry weight and the antioxidant activity resulted in 173.3 µmol Trolox equivalents/g DW. In addition, a high content of dietary fiber was found (34.8%). The oral LD50 for ASF was 1767 mg/kg body weight, and treatment with ASF significantly reduced the levels of total cholesterol, LDL-C, and prediction of the atherogenic index. Therefore, the antioxidant activity of phenolic compounds and dietary fiber in ASF may be responsible for the hypocholesterolemic activity of ASF in a hyperlipidemic model of mice.

Phycobiliproteins extract from Spirulina protects against single-dose cadmium-induced reproductive toxicity in male mice.

Cadmium (Cd) is known for its many toxic effects on male population such as hypogonadism and fertility difficulties, which are oftenly associated with oxidative stress. As beneficial food, Spirulina(Sp) has been proved efficient against the heavy metal toxicity. This capacity can be associated with its phycobiliproteins (PBP). In this study, the capability of PBP and Sp to treat Cd-induced oxidative damage on the testes and spermatozoa was considered. CD-1 strain mice were orally treated with either Sp or PBP for 10 days prior to single-dose Cd challenge. Sperm quality determinations and testicle histology analysis were performed. Testosterone on serum was measured using enzyme-linked immunosorbent assay (ELISA). Oxidative damage was determined. Antioxidant enzyme activity was analyzed by measuring the activity of super oxide dismutase (SOD), catalase (Cat), and glutathione peroxidase (GpX). The motility and viability of sperm decrease with Cd and improve with PBP and Sp, as the acrosomal reaction (AR) is diminished by PBPs. Testosterone levels decrease due to Cd, and only Sp maintains elevated levels. Cd increases the production of malondialdehyde in the spermatozoa, but not in testes; this production of malondialdehyde in the spermatozoa decreases in the presence of PBP. ROS only decreases with Cd, FBP, and Sp at high concentrations. Advanced oxidative protein products (AOPP) decrease with Cd and PBPs. Cat and GpX increase their activity with Cd and are altered by FBP. Cd produces vascular alterations testes. Within the seminiferous tubule, it produces areas of necrosis and apoptosis, which improve with PBPs and Sp. PBPs have a strong antioxidant activity as they show protective properties against Cd oxidative-induced toxicity on testes and sperm.

A Complete Review of Mexican Plants with Teratogenic Effects.

In Mexico, the use of medicinal plants is the first alternative to treat the diseases of the most economically vulnerable population. Therefore, this review offers a list of Mexican plants (native and introduced) with teratogenic effects and describes their main alterations, teratogenic compounds, and the models and doses used. Our results identified 63 species with teratogenic effects (19 native) and the main alterations that were found in the nervous system and axial skeleton, induced by compounds such as alkaloids, terpenes, and flavonoids. Additionally, a group of hallucinogenic plants rich in alkaloids employed by indigenous groups without teratogenic studies were identified. Our conclusion shows that several of the identified species are employed in Mexican traditional medicine and that the teratogenic species most distributed in Mexico are Astragalus mollissimus, Astragalus lentiginosus, and Lupinus formosus. Considering the total number of plants in Mexico (≈29,000 total vascular plants), to date, existing research in the area shows that Mexican plants with teratogenic effects represent ≈0.22% of the total species of these in the country. This indicates a clear need to intensify the evaluation of the teratogenic effect of Mexican plants.