In Vitro Antiviral Activity of Nordihydroguaiaretic Acid against SARS-CoV-2.

The coronavirus infectious disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has been spreading rapidly worldwide, creating a pandemic. This article describes the evaluation of the antiviral activity of nordihydroguaiaretic acid (NDGA), a molecule found in Creosote bush (Larrea tridentata) leaves, against SARS-CoV-2 in vitro. A 35 µM concentration of NDGA was not toxic to Vero cells and exhibited a remarkable inhibitory effect on the SARS-CoV-2 cytopathic effect, viral plaque formation, RNA replication, and expression of the SARS-CoV-2 spike glycoprotein. The 50% effective concentration for NDGA was as low as 16.97 µM. Our results show that NDGA could be a promising therapeutic candidate against SARS-CoV-2.

Phytochemical Compounds and Pharmacological Properties of Larrea tridentata.

For centuries, traditional medicine from plants (phytotherapy) was the only treatment for infectious and non-infectious diseases. Although it is still practiced in several countries with excellent therapeutic results, it is frequently underestimated because, unlike Western medicine, it is not based on an empirical scientific foundation. However, interest in the search for plant-based therapeutic resources has been stimulated by disciplines such as phytochemistry and the side effects of conventional pharmacological therapies. For example, Larrea tridentata is a perennial shrub used in traditional medicine in northern Mexico and the southern United States to treat infertility, rheumatism, arthritis, colds, diarrhea, skin problems, pain, inflammation and excess body weight. Scientific research has revealed its beneficial effects-antioxidant, antitumor, neuroprotective, regenerative, antibacterial, antiviral, antifungal, anthelmintic, antiprotozoal and insecticidal-although reports indicate that some compounds in Larrea tridentata may be hepatotoxic and nephrotoxic. Therefore, the aim of this review was to highlight the updates regarding phytochemical compounds and the pharmacological properties of Larrea tridentata.

nor 3'-Demethoxyisoguaiacin from Larrea tridentata Is a Potential Alternative against Multidrug-Resistant Bacteria Associated with Bovine Mastitis.

Bovine mastitis is one of the most common diseases in dairy cows, and it causes significant economic losses in dairy industries worldwide. Gram-positive and Gram-negative bacteria can cause bovine mastitis, and many of them have developed antimicrobial resistance. There is an urgent need for novel therapeutic options to treat the disease. Larrea tridentata-derived compounds represent an important potential alternative treatment. The aim of the present study was to isolate and characterize antibacterial compounds from Larrea tridentata against multidrug-resistant bacteria associated with bovine mastitis. The L. tridentata hydroalcoholic extract (LTHE) exhibited antibacterial activity. The extract was subjected to a bipartition, giving an aqueous fraction (moderate antibacterial activity) and an organic fraction (higher antibacterial activity). Chromatographic separation of the organic fraction enabled us to obtain four active sub-fractions. Chemical analyses through HPLC techniques were conducted for the LTHE, fractions, and sub-fraction Ltc1-F3, from which we isolated two compounds, characterized by 1H and 13C NMR analyses. Compound nor-3 demethoxyisoguaiacin exhibited the best antibacterial activity against the evaluated bacteria (MIC: 0.01-3.12 mg/mL; MBC: 0.02-3.12 mg/mL). The results indicated that nor-3 demethoxyisoguaiacin can be used as an alternative treatment for multidrug-resistant bacteria associated with mastitis.

Larrea tridentata and its Biological Activities.

BACKGROUND: Larrea tridentata is a dominant shrub in the deserts of North America and is recognized for its various traditional uses. More than 50 traditional uses have been recorded. Regarding its chemical composition, the products of the mevalonate, shikimate, and malonate pathways are predominant. L. tridentata has nordihydroguaiaretic acid (NDGA), one of its most studied secondary metabolites that exhibited remarkable different biological activities: sequestration of reactive oxygen species, inhibition of lipoxygenases (LOX) and activation of the endogenous antioxidant response mediated by nuclear factor erythroid 2-related factor 2 (NRF2). OBJECTIVE AND METHODS: This review seeks to draw attention to metabolites other than NDGA and which also contribute to the various biological activities of L. tridentata. Therefore, the present review includes those reports focused on the pharmacological properties of the organic extracts of L. tridentata and its natural products with promising values. RESULTS AND CONCLUSION: Among the most promising and widely reported metabolites from L. tridentata, are: 3'-demethoxy-6-O-demethylisoguaiacin, 3'-O-methyldihydroguaiaretic acid, meso-dihydroguaiaretic acid, and tetra-O-methylnordihydroguaiaretic acid. These have been reported to exhibit antibacterial, antiprotozoal, anthelmintic, antifungal, antiviral, anticancer, and antioxidant activities.

Creosote Bush (Larrea tridentata) Extract Assessment as a Green Antioxidant for Biodiesel.

In this work, the antioxidant properties of methanolic extract of Larrea tridentata were assessed through the free radical scavenging method, ferric reducing antioxidant power and oxygen radical absorbance capacity. The phenolic acids content in the extract was quantified by high-performance liquid chromatography (HPLC) and the total phenol content by the Folin-Ciocalteu method. The extract was used as an antioxidant in biodiesel from canola oil composed mostly by fatty acid methyl esters identified and quantified by gas chromatography-mass spectrophotometry (GC-MS). The performance of the extract as an antioxidant was assessed by the oxidative stability index (OSI) with a Rancimat equipment at 100, 110, 120 and 130 °C. Additionally, the change of the peroxide value (PV) and the higher heating value under conditions of oxidative stress at 100 °C and air injection were measured. The antioxidant capacity of the extract reached 50,000 TAEC (micromole of Trolox antioxidant equivalent capacity per gram). The biodiesel was constituted by more than 70% of unsaturated fatty acid methyl esters (FAME), mainly methyl oleate. The time needed to reach a PV of 100 meqO2/kg was almost four times longer with an antioxidant concentration of 250 mg/L than the blank. The biodiesel showed an OSI time of 1.25 h at 110 °C, while it increased to 8.8, 15.89 and 32.27 h with the antioxidant at concentrations of 250, 500 and 1000 mg/L, respectively. The methanolic Larrea tridentata extract proved to have an antioxidant capacity and it is a green antioxidant in biodiesel to increase its oxidative stability. According to the results obtained, the L. tridentata methanolic extract is an alternative to the commercial synthetic antioxidants used in biodiesel nowadays.

Dinámica de la diversidad temporal de los hongos micorrícicos arbusculares de Larrea tridentata (Sesse & Mocino ex DC) Coville en un ecosistema semiárido / Temporal diversity dynamics of the arbuscular mycorrhizal fungi of Larrea tridentata (Sesse & Mocino ex DC) Coville in a semi-arid ecosystem

Los hongos micorrícicos arbusculares (HMA) de los ambientes áridos y semiáridos son importantes para el desarrollo de las plantas que crecen bajo estrés biótico y abiótico en áreas naturales o en agroecosistemas. Existe poca información sobre la diversidad temporal de los HMA en plantas perennes de ecosistemas áridos en el norte de México. En este estudiose evaluaron la colonización micorrícica y la diversidad temporal de los HMA en la rizosfera de Larrea tridentata, planta perenne de amplia distribución en el Desierto Chihuahuense. Se obtuvieron muestras de la rizosfera y de raíces de 15 plantas, en 3 fechas de muestreo del año 2015. Se encontró un total de 17 especies de HMA, distribuidas en 12 géneros y 7 familias dentro del phylum Glomeromycota. La especie más abundante fue Funneliformis geosporum. Esta especie pertenece a la familia Glomeraceae, la única que estuvo representada con varios géneros en L. tridentata. El mayor porcentaje de micorrización se presentó en febrero, con un 83,22%, en septiembre fue del 75,27% y en mayo del 65,27%. El muestreo realizado en febrero presentó el mayor número de especies (16), seguido por el de mayo (15) y el de septiembre (12). El análisis estadístico mostró diferencias significativas en el número de esporas entre los muestreos de febrero y los de mayo y septiembre.

Arbuscular mycorrhizal fungi (AMF) of arid and semiarid ecosystems are important for the development of plants that grow under biotic stress in wild or in agro-ecosystems. There is little information on the temporal diversity of these organisms in perennial plants from arid ecosystems in northern Mexico. On this study, the mycorrhizal colonization and the temporal diversity of AMF in the rhizosphere of Larrea tridentata, perennial plant abundant in the Chihuahuan Desert region were explored. Samples of the rhizosphere and roots of fifteen plants in each of the three sampling dates during the 2015 year were obtained. A total of 17 species of HMA belonging to 12 genera and 7 families within the phylum Glomeromycota in all three sampling dates were found. Funneliformis geosporum was the dominant species belonging to the family Glomeraceae which possess the highest genera number on L. tridentata.The highest mycorrhization percentage was in February with 83.22, followed by September and May with 75.27 and 65.27%, respectively. A maximum of 16 AM fungal species were isolated and identified from L. tridentata rhizosphere in February, 15 species in May and 12 species in September. Statistical analysis showed significant differences between sampling dates in the spores number.

[Temporal diversity dynamics of the arbuscular mycorrhizal fungi of Larrea tridentata (Sesse & Mocino ex DC) Coville in a semi-arid ecosystem]. / Dinámica de la diversidad temporal de los hongos micorrícicos arbusculares de Larrea tridentata (Sesse & Mocino ex DC) Coville en un ecosistema semiárido.

Arbuscular mycorrhizal fungi (AMF) of arid and semiarid ecosystems are important for the development of plants that grow under biotic stress in wild or in agro-ecosystems. There is little information on the temporal diversity of these organisms in perennial plants from arid ecosystems in northern Mexico. On this study, the mycorrhizal colonization and the temporal diversity of AMF in the rhizosphere of Larrea tridentata, perennial plant abundant in the Chihuahuan Desert region were explored. Samples of the rhizosphere and roots of fifteen plants in each of the three sampling dates during the 2015 year were obtained. A total of 17 species of HMA belonging to 12 genera and 7 families within the phylum Glomeromycota in all three sampling dates were found. Funneliformis geosporum was the dominant species belonging to the family Glomeraceae which possess the highest genera number on L. tridentata. The highest mycorrhization percentage was in February with 83.22, followed by September and May with 75.27 and 65.27%, respectively. A maximum of 16 AM fungal species were isolated and identified from L. tridentata rhizosphere in February, 15 species in May and 12 species in September. Statistical analysis showed significant differences between sampling dates in the spores number.

Creosote Bush (Larrea tridentata) Improves Insulin Sensitivity and Reduces Plasma and Hepatic Lipids in Hamsters Fed a High Fat and Cholesterol Diet.

Creosote bush, Larrea tridentata (Sesse y Moc. Ex DC, Zygophyllaceae) is a shrub found in the deserts of Northern Mexico and Southwestern United States. In traditional medicine, it is used to treat a variety of illnesses including type 2 diabetes. The present study aims to investigate the effects of creosote bush ethanolic extract on plasma and liver parameters associated with the metabolic syndrome in hamsters fed a high fat and cholesterol diet (HFD), comparing them with those induced by ezetimibe (EZ). Seven groups of six hamsters each were formed. Six groups were fed HFD for 2 weeks. The following 2 weeks, the HFD groups received: (1) only HFD, (2) HFD + 3 mg% EZ, (3) HFD + 0.2% creosote bush ethanolic extract, (4) only standard diet (Std Diet), (5) Std Diet + 3 mg% EZ, (6) Std Diet + 0.2% creosote bush ethanolic extract. The beneficial effects of creosote bush ethanolic extract in the HFD hamster model were a reduction of insulin resistance, associated with lower serum insulin and leptin, lower hepatic lipid peroxidation and higher liver antioxidant capacity. Plasma and liver lipids tended or were reduced to values closer to those of animals fed standard diet. A similar effect on lipids was induced by EZ, although with even lower hepatic cholesterol and total lipids concentrations. In general, the change from HFD to standard diet plus ethanolic extract induced the same but deeper changes, including a reduction in plasma glucose and an increase in the percentage of HDL cholesterol. Unlike creosote bush extract, EZ increased food consumption and neutral fecal steroids, with no significant effect on body weight, epididymal fat pads, liver peroxidation or antioxidant capacity. Also EZ did not modify serum insulin and leptin. However, insulin sensitivity improved to values similar to those induced by the extract. This suggests that the mechanism of action of creosote bush ethanolic extract is different to inhibition of cholesterol absorption or increase excretion. The ethanolic extract of L. tridentata could be useful in the treatment of the metabolic syndrome.

Potential Mechanism of Action of 3'-Demethoxy-6-O-demethyl-isoguaiacin on Methicillin Resistant Staphylococcus aureus.

Bacterial infections represent one of the main threats to global public health. One of the major causative agents associated with high morbidity and mortality infections in hospitals worldwide is methicillin-resistant Staphylococcus aureus. Therefore, there is a need to develop new antibacterial agents to treat these infections, and natural products are a rich source of them. In previous studies, we reported that lignan 3'-demethoxy-6-O-demethylisoguaiacin, isolated and characterized from Larrea tridentate, showed the best activity towards methicillin-resistant S. aureus. Thus, the aim of this study was to determine the potential molecular mechanism of the antibacterial activity of 3'-demethoxy-6-O-demethylisoguaiacin against methicillin-resistant S. aureus using microarray technology. Results of microarray genome expression were validated by real-time polymerase chain reaction (RT-PCR). The genetic profile expression results showed that lignan 3'-demethoxy-6-O-demethylisoguaiacin had activity on cell membrane affecting proteins of the ATP-binding cassette (ABC) transport system causing bacteria death. This molecular mechanism is not present in any antibacterial commercial drug and could be a new target for the development of novel antibacterial agents.

Competition intensity as a function of resource availability in a semiarid ecosystem.

Two field experiments were conducted using three dominant perennial species of the Chihuahuan Desert: Hilaria mutica (a tussock grass), Larrea tridentata (a microphyllous shrub) and Opuntia rastrera (a flat-stemmed succulent cactus). Two hypotheses concerning competition in arid plant communities were tested. (1) Marked resource partitioning with no interspecific competition could be expected since the three species belong to different life-forms, and that plant growth in deserts is basically limited by harsh environmental conditions. (2) Alternatively, resource scarcity (particularly water) will result in strong plant competition. In a 1-year removal experiment, water status and plant growth of the three species were monitored in twelve 10 m × 10 m plots randomized in three blocks and assigned to the following treatments: (a) removal of all species, except H. mutica; (b) removal of all species, except L. tridentata; (c) removal of all species, except O. rastrera, and (d) control without any manipulation. In a watering experiment, under two neighbourhood conditions (growing isolated or in associations of plants of the three species in plots of 20 m2), the water status of the three species and the growth of H.mutica and L.tridentata were studied for 32 days after an irrigation equivalent to 30 mm of rain, similar to a strong storm event at the site. In the removal experiment, where plants were free to capture water, no evidence of competition was observed. However, during the watering experiment, in which water was forced into the soil, competitive effects were observed. Associated individuals of L. tridentata had lower xylem water potentials and osmotic potentials (OPs) and produced shorter twigs and less leaves and nodes. Although less pronounced, neighbours also had a negative effect on the OP in O. rastrera. According to these results, the intensity of the interspecific competition for water seems to depend on the level of resource availability in the soil. Thus, the validity of the two hypotheses tested in this study also depends on the level of resources. Competition could be absent or very low in years of low precipitation, as in the year of this study (173 mm against a 25-year average of 264 mm). However, when soil water availability is high, e.g. following heavy rain, the negative interactions between species could be more intense.

Effects of plant size and water relations on gas exchange and growth of the desert shrub Larrea tridentata.

Larrea tridentata is a xerophytic evergreen shrub, dominant in the arid regions of the southwestern United States. We examined relationships between gasexchange characteristics, plant and soil water relations, and growth responses of large versus small shrubs of L. tridentata over the course of a summer growing season in the Chihuahuan Desert of southern New Mexico, USA. The soil wetting front did not reach 0.6 m, and soils at depths of 0.6 and 0.9 m remained dry throughout the summer, suggesting that L. tridentata extracts water largely from soil near the surface. Surface soil layers (<0.3 m) were drier under large plants, but predawn xylem water potentials were similar for both plant sizes suggesting some access to deeper soil moisture reserves by large plants. Stem elongation rates were about 40% less in large, reproductively active shrubs than in small, reproductively inactive shrubs. Maximal net photosynthetic rates (Pmax) occurred in early summer (21.3 µ mol m-2 s-1), when pre-dawn xylem water potential (XWP) reached ca. -1 MPa. Although both shrub sizes exhibited similar responses to environmental factors, small shrubs recovered faster from short-term drought, when pre-dawn XWP reached about -4.5 MPa and Pmax decreased to only ca. 20% of unstressed levels. Gas exchange measurements yielded a strong relationship between stomatal conductance and photosynthesis, and the relationship between leaf-to-air vapor pressure deficit and stomatal conductance was found to be influenced by pre-dawn XWP. Our results indicate that stomatal responses to water stress and vapor pressure deficit are important in determining rates of carbon gain and water loss in L. tridentata.

Foliole movement and canopy architecture of Larrea tridentata (DC.) Cov. in Mexican deserts.

The creosote bush (Larrea tridentata) is a common desert perennial with bifoliate, amphistomatic, divaricate leaves. The leaves can vertically close their folioles and vary their profile with respect to direct solar radiation. Field data from different Mexican deserts showed a significant correlation between foliole aperture and mean foliole inclination: in plants in which folioles were more open, the foliole surfaces were less vertical. In a series of field experiments in the Chihuahuan Desert, foliole aperture varied significantly with the water-status of the plant and the hour of the day. In moist plants, folioles opened in the early morning and closed in the afternoon. Water-stressed plants showed significantly lower foliole apertures. A simulation of the light interception patterns of the plants showed that foliole closure in water-stressed individuals reduces direct radiation interception by around 24%. Most (64%) of the reduction in interception was due to the vertical inclination of the photosynthetic surfaces induced by foliole closure in the water-stressed plants. The rest (36%) of the reduction in interception was due to differential self-shading between foliole pairs, which was higher in the closed folioles of the water-stressed plants, but operated more towards the early hours of the day.