Effects of Five Coumarins and Standardized Extracts from Tagetes lucida Cav. on Motor Impairment and Neuroinflammation Induced with Cuprizone.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) with no curative treatment, and the available therapies aim to modify the course of the disease. It has been demonstrated that extracts of Tagetes lucida have immunomodulatory and neuroprotective effects. This work induced motor damage and neuroinflammation in male BALB/c mice by oral administration of cuprizone (CPZ) (40 mg/kg) for five weeks. In addition, the extracts and coumarins of Tagetes lucida (25 mg/kg) were used to control these damage variables; during the experiment, animals were subject to behavioral tests, and at the end of 5 weeks, mice from each group were used to measure the integrity of biological barriers (brain, kidneys, and spleen) through the extravasation test with blue Evans dye. In another group of animals, the ELISA method measured the brain concentrations of IL-1ß, IL-4, IL-10, and TNF-α. The results presented here allow us to conclude that the extracts and coumarins IC, HN, PE, DF, and SC of Tagetes lucida exert a neuroprotective effect by controlling the motor damage and neuroinflammation by increasing the expression of IL-4 and IL-10 and decreasing IL-1ß and TNF-α; notably, these treatments also protect organs from vascular permeability increase, mainly the BBB, in mice with CPZ-induced experimental encephalomyelitis (VEH * p < 0.05). However, more studies must be carried out to elucidate the molecular mechanisms of the pharmacological effects of this Mexican medicinal plant.

Coriandrum sativum and Its Utility in Psychiatric Disorders.

The negative impact on worldwide social well-being by the increasing rate of psychiatric diseases has led to a continuous new drug search. Even though the current therapeutic options exert their activity on multiple neurological targets, these have various adverse effects, causing treatment abandonment. Recent research has shown that Coriandrum sativum offers a rich source of metabolites, mainly terpenes and flavonoids, as useful agents against central nervous system disorders, with remarkable in vitro and in vivo activities on models related to these pathologies. Furthermore, studies have revealed that some compounds exhibit a chemical interaction with γ-aminobutyric acid, 5-hydroxytryptamine, and N-methyl-D-aspartate receptors, which are key components in the pathophysiology associated with psychiatric and neurological diseases. The current clinical evaluations of standardized extracts of C. sativum are scarce; however, one or more of its compounds represents an area of opportunity to test the efficacy of the plant as an anxiolytic, antidepressant, antiepileptic, or sleep enhancer. For this, the aim of the review was based on the pharmacological activities offered by the compounds identified and isolated from coriander and the processes involved in achieving their effect. In addition, lines of technological research, like molecular docking and nanoparticles, are proposed for the future development of phytomedicines, based on the bioactive molecules of C. sativum, for the treatment of psychiatric and neurological disorders addressed in the present study.

Chemical Characterization, Antilipidemic Effect and Anti-Obesity Activity of Ludwigia octovalvis in a Murine Model of Metabolic Syndrome.

Ludwigia octovalvis (Jacq.) P.H. Raven is widely used in traditional medicine for different illnesses, including diabetes and hypertension. However, its impact on lipotoxicity and metabolic syndrome in vivo has not been addressed. Therefore, the aim of this study was to evaluate the effects of this plant on the metabolic syndrome parameters in a C57BL6J mouse hypercaloric diet model. L. octovalvis hydroalcoholic extract and its ethyl acetate fraction (25 mg/kg/day) were used for sub-chronic assessment (10 weeks). Additionally, four subfractions (25 mg/kg) were evaluated in the postprandial triglyceridemia test in healthy C57BL6J mice. The hydroalcoholic extract and ethyl acetate fraction significantly decreased body weight gain (-6.9 g and -1.5 g), fasting glycemia (-46.1 and -31.2 mg/dL), systolic (-26.0 and -22.5 mmHg) and diastolic (-8.1 and 16.2 mmHg) blood pressure, free fatty acid concentration (-13.8 and -8.0 µg/mL) and insulin-resistance (measured by TyG index, -0.207 and -0.18), compared to the negative control. A postprandial triglyceridemia test showed that the effects in the sub-chronic model are due, at least in part, to improvement in this parameter. L. octovalvis treatments, particularly the hydroalcoholic extract, improve MS alterations and decrease free fatty acid concentration. These effects are possibly due to high contents of corilagin and ellagic acid.

Dose-Effect Determination of a Neuroprotector Fraction Standardized in Coumarins of Tagetes lucida and Bioavailability.

Neurodegeneration has been associated with chronic inflammation states in the brain. For this reason, attention has been directed to drugs indicated as anti-inflammatory as possible therapies for the treatment of said conditions. Tagetes lucida has been widely used as a folk remedy in illnesses associated with the central nervous system and inflammatory ailments. Among the compounds that stand out in the plant against these conditions are coumarins, such as 7-O-prenyl scopoletin, scoparone, dimethylfraxetin, herniarin, and 7-O-prenylumbelliferone. Therefore, the relationship between the therapeutic effect and the concentration was evaluated through pharmacokinetic and pharmacodynamic studies, including vascular permeability evaluation by blue Evans and pro- and anti-inflammatory cytokines quantification, under a neuroinflammation model induced by lipopolysaccharide by the oral administration of three different doses (5, 10, and 20 mg/kg) of a bioactive fraction of T. lucida. In the present study, it was found that all doses showed a neuroprotective and immunomodulatory effect, although the doses of 10 and 20 mg/kg were able to exert their effect for a longer time and to a greater extent. The protective effects of the fraction may be mainly associated with the DR, HR, and SC coumarins due to their structural profile and plasmatic and brain tissue bioavailability.

Anti-Inflammatory and Neuroprotective Effects of Standardized Fractions in Herniarin and Daphnoretin from Distictis buccinatoria.

Distictis buccinatoria is used for inflammatory-related diseases. From a dichloromethane extract were obtained five different fractions called F1 to F5, and sub-fractions F4-1, F5-1, F5-2, and F5-3; and were evaluated as anti-neuroinflammatory, antioxidant, and nootropic agents in mice exposed to lipopolysaccharide. Also, were isolated herniarin, daphnoretin, and fraction's terpenes with an anti-inflammatory activity using 12-O-tetradecanoylphorbol-13-acetate-induced auricular edema. The inhibition of local edema was: F1 (73.6 %), F2 (57 %), F3 (62.61 %), F4 (87.3 %), and F5 (93.57 %). Terpene fraction inhibited at 89.60 %, herniarin at 86.92 % (Emax 99.01 %, ED50 0.35 mg ear-1 ), and daphnoretin at 86.41 %. Fractions F4-1 and F5-2 (10 mg kg-1 ) enhancer spatial memory acquisition and spontaneous motor activity; reduced IL-1ß, TNF-α, and IL-6; increased IL-10, enhanced the activity of CAT and GR. D. buccinatoria has neuroprotective activity and contains daphnoretin and herniarin, with anti-inflammatory activity.

Fatty-Acid-Rich Agave angustifolia Fraction Shows Antiarthritic and Immunomodulatory Effect.

Agave angustifolia is a xerophytic species widely used in Mexico as an ingredient in sweet food and fermented beverages; it is also used in traditional medicine to treat wound pain and rheumatic damage, and as a remedy for psoriasis. Among the various A. angustifolia extracts and extract fractions that have been evaluated for their anti-inflammatory effects, the acetonic extract (AaAc) and its acetonic (F-Ac) and methanolic (F-MeOH) fractions were the most active in a xylene-induced ear edema model in mice, when orally administered. Four fractions resulting from chemically resolving F-Ac (F1-F4) were locally applied to mice with phorbol 12-myristate 13-acetate (TPA)-induced ear inflammation; F1 inhibited inflammation by 70% and was further evaluated in a carrageenan-induced mono-arthritis model. When administered at doses of 12.5, 25, and 50 mg/kg, F1 reduced articular edema and the spleen index. In addition, it modulated spleen and joint cytokine levels and decreased pain. According to a GC-MS analysis, the main components of F1 are fatty-acid derivatives: palmitic acid methyl ester, palmitic acid ethyl ester, octadecenoic acid methyl ester, linoleic acid ethyl ester, and oleic acid ethyl ester.

Pharmacokinetics and Tissue Distribution of Coumarins from Tagetes lucida in an LPS-Induced Neuroinflammation Model.

Tagetes lucida has been widely used as a folk remedy in illnesses associated with the central nervous system and inflammatory ailments. Among the chemical compounds that stand out in the plant against these conditions are coumarins, such as 7-O-prenylscopoletin (PE), scoparone (SC), dimethylfraxetin (DF), herniarin (HR), and 7-O-prenylumbelliferone (PU), considered potential anti-neuroinflammatory compounds. Therefore, the relationship between the therapeutic effect and the dose can be evaluated through pharmacokinetic-pharmacodynamic (PK-PD) studies under a model of neuroinflammation induced by lipopolysaccharide (LPS). Nonetheless, accomplishing those studies requires an accurate and robust analytical method for the detection of these compounds in different biological matrices of interest. Due to the above, in the present study, a bioanalytical method was established by HPLC-DAD-UV for the simultaneous quantification of the coumarins present in the hexane extract of T. lucida, which was able to determine the temporal concentration profiles of each of the coumarins in the plasma, brain, kidney, and spleen samples of healthy and damaged mice. Coumarins showed an increase in plasma concentrations of up to three times in the neuroinflammation model, compared to healthy mice, so it was possible to quantify the therapeutic agents in the main target organ, the brain. The ability of compounds to cross the blood-brain barrier is an advantage in the treatment of diseases associated with neuroinflammation processes that can be studied in future PK-PD evaluations.

Herniarin, Dimethylfraxetin and Extracts from Tagetes lucida, in Psychosis Secondary to Ketamine and Its Interaction with Haloperidol.

Tagetes lucida Cav., is a medicinal plant used in Mexico to alleviate different disorders related to alterations of the central nervous system, such as behaviors associated with psychosis. The present work evaluated the effect of different extracts separated from this plant, TlHex, TlEA, TlMet, and TlAq, and of two isolated coumarins, herniarin (HN) and dimethylfraxetin (DF), on haloperidol-induced catalepsy (HAL), and psychotic behaviors provoked with a glutamatergic antagonist, ketamine (KET) on ICR mice. The extracts TlEA, TlAq, and the isolated compounds HN and DF, induced an increment of the cataleptic effect of HAL. Schizophrenia-like symptoms caused by KET were analyzed through the behavior of the animals in the open field (OFT), forced swimming (FST), passive avoidance test (PAT), and social interaction test (SIT). Treatments derived from T. lucida could interact with this substance in all tests except for FST, in which only TlMet blocks its activity. Mainly, TlEA, TlAq, HN, and DF, blocked the effects of KET on stereotyped behavior, hyperlocomotion, cognitive impairment, and detriment in the social interaction of rodents. T. lucida interacted with dopaminergic and glutamatergic systems.

Effect of Tecoma stans (L.) Juss. ex Kunth in a Murine Model of Metabolic Syndrome.

Metabolic syndrome is a constellation of abnormalities related to insulin resistance with an unfortunately high prevalence worldwide. Tecoma stans (L.) Juss. Ex Kunth. is a well-known medicinal plant that has been studied in several biological models related to diabetes mellitus. The aim of this study was to evaluate the effects of T. stans on a hypercaloric diet-induced metabolic syndrome model. An organic fraction obtained using liquid-liquid separation from the hydroalcoholic extract of T. stans and four subfractions of this organic fraction were administered for ten weeks to C57BL6J male mice previously fed with a hypercaloric diet. The hypercaloric diet caused changes in glucose levels (from 65.3 to 221.5 mg/dL), body weight (31.3 to 42.2 g), triglycerides (91.4 to 177.7 mg/dL), systolic (89.9 to 110.3 mmHg) and diastolic (61.6 to 73.7 mg/dL) blood pressure, and insulin resistance (4.47 to 5.16). Treatment with T. stans resulted in improvements in triglycerides (83.4-125.0 mg/dL), systolic blood pressure (75.1-91.8 mmHg), and insulin resistance (4.72-4.93). However, the organic fraction and hydroalcoholic extract produced a better response in diastolic blood pressure (52.8-56.4 mmHg). Luteolin, apigenin, and chrysoeriol were the major constituents in the most active subfractions. Treatment with T. stans, particularly a luteolin-rich organic fraction, achieved an improvement in metabolic syndrome alterations.

Anti-arthritic and anti-inflammatory effects of Baccharis conferta Kunth in a kaolin/carrageenan-induced monoarthritis model.

ETHNOPHARMACOLOGICAL RELEVANCE: Popularly known as "escoba" (broom) or "escobilla china" (Chinese brush), Baccharis conferta Kunth (Asteraceae), is a plant widely used in Mexican folk medicine for alleviating muscular and rheumatic pain. A recent study described that dichloromethane extract as well as fractions and isolated compounds, possess anti-inflammatory activity in TPA-induced acute edema. AIM OF THE STUDY: Based on the popular medicinal uses of B. conferta as well as previous studies on its anti-inflammatory activity, the aim of this research was to evaluate the anti-arthritic and anti-inflammatory effects of dichloromethane extract, fractions, and compounds from B. conferta in a monoarthritis model induced with kaolin/carrageenan (K/C). MATERIALS AND METHODS: Aerial parts of B. conferta were collected, dried, and macerated with dichloromethane. The dichloromethane extract (BcD) was separated by open column chromatography to obtain the BcD2 fraction where the diterpene kingidiol (KIN) was isolated and from the BcD3 fraction the flavonoid cirsimaritin (CIR), which are the most active compounds in the TPA model. In addition, the flavonoids acacetin, pectolinaringenin and 6-methoxykaempferide were identified and isolated from the BcD2 fraction. The content of the main compounds was estimated in BcD, BcD2 and BcD3. The anti-arthritic and anti-inflammatory effects of B. conferta were investigated by evaluating ankle joint inflammation, hyperalgesia using the hot plate test, and pro- and anti-inflammatory cytokine levels in the synovial capsule as well as histological changes in ankle joint tissue in a monoarthritis model induced with K/C in Balb/c mice. RESULTS: Oral administration of BcD2 fraction (25 mg/kg) and KIN (10 mg/kg) reduced the ankle thickness induced by K/C and decreased the levels of TNF-α, IL-1ß, IL-6 and IL-17, while BcD2 increased IL-10. In addition, BcD2 and KIN showed significant edema attenuation of the synovial membrane and decreased inflammatory infiltration and cartilage erosion compared to the VEH group. Finally, BcD (50 mg/kg), KIN (10 mg/kg) and CIR (5 mg/kg) decreased hyperalgesia. CONCLUSIONS: B. conferta constitutes a therapeutic or preventive candidate for osteoarthritis, because of decreased articular inflammation and pain accompanied with the modulation of cytokine concentrations, which confirms the anti-arthritic and anti-inflammatory activities of B. conferta and support its popular use.

Agave tequilana Counteracts Chronic Hypertension and Associated Vascular Damage.

Systemic arterial hypertension (SAH) is a health problem of great importance worldwide, and endothelial dysfunction underlies SAH development. This condition's main characteristics include vasoconstriction, inflammation, oxidative stress, and procoagulant and proliferative states. This study's objective was to evaluate the antihypertensive, anti-inflammatory, and antioxidant effects of the whole extract and fractions of Agave tequilana in a murine model of SAH. SAH was induced in male ICR or CD-1 (Strain obtained from animals from Charles River Laboratories, Massachusetts) mice by intraperitoneal administration of angiotensin II (AGII) (0.1 µg/kg) for 4 weeks, and then A. tequilana treatments were co-administered with AGII. At the end of the experiment, systolic and diastolic blood pressure were measured and the kidneys were dissected to quantify interleukin (IL)-1ß, IL-6, tumor necrosis factor-alpha, IL-10, and malondialdehyde (MDA). The whole extract and the fractions of A. tequilana were chemically characterized using gas chromatography-mass spectrometry. The results indicate that the whole extract (At-W) and At-AcOEt fraction treatment are the most efficient in lowering blood pressure, although all the treatments had an immunomodulatory effect on the cytokines evaluated and an antioxidant effect on lipid peroxidation. Finally, the chromatographic profile shows that the integral extract and fractions of A. tequilana contained phytol (M)3,7,11,15-Tetramethyl-2-hexadecen-1-ol; 9,12-octadecadienoic acid; hentriacontane; 9,19-cyclolanost-24-en-3-ol,(3b); t-sitosterol; and stigmasta-3,5-dien-7-one.

Antidiabetic Activity of Xoconostle Fruit from Opuntia matudae Scheivar in Mice.

In Mexico, Cactaceae plants are widely used in folk medicine for the treatment of diabetes. The genus Opuntia spp. Opuntia matudae Sheinvar prickly pears are known as xoconostle and are used in Mexican cuisine for their acidic flavor. Currently there are few reports of pharmacological properties of this plant, which include antioxidant and antimicrobial activities. This study focuses on the chemical characterization of the methanolic (OmMe) and aqueous (OmAq) extracts and the evaluation of the antidiabetic activity of O. matudae fruits in two biological models. For the in vivo model, streptozotocin (STZ)-induced diabetic mice were used, and for the in vitro model, liver sections isolated from healthy mice were used. The OmAq (100 mg/kg, oral pathway [p.o.]) extract decreased postprandial glucose peak at 0.5 h after glucose uptake by 43.1%, similarly, OmMe (100 mg/kg, p.o.) extract reduced postprandial glucose peak at 0.5 h by 34.1% in healthy mice. The effect of the two extracts and the fraction of the mixture of unidentified betalains (OmB) of O. matudae evaluated in the isolated mouse liver slice model showed a concentration-dependent decrease in hepatic glucose output (HGO) with and without insulin administration with the OmMe extract. The OmAq extract, however, showed concentration-dependent increases of HGO with and without insulin, and the OmB fraction generally exhibited an insulin mimetic effect. Moreover, both OmAq and OmMe extracts were tested in mice with STZ-induced diabetes (160 mg/kg, intraperitoneal route), using a semichronic daily administration (2-28 days after diabetes onset) of OmAq extract was able to reduce blood glucose by 34.3%, meanwhile OmMe extract reduced blood glucose by 22.9%, 28 days after diabetes onset. We identified five compounds (1-5) in the two extracts, consisting of two phenolic acids (1, 2), three flavanols (3-5), as well as two unidentified betalains. Therefore, we conclude that the aqueous extract of the xoconostle fruit where betalains are present may be useful for the treatment of diabetes mellitus.

Antidepressant and anxiolytic compounds isolated from Salvia elegans interact with serotonergic drugs.

Salvia elegans belongs to a genus plants with biological activities in central nervous system. In this work, the purpose was to evaluate the anxiolytic and antidepressant effects of fractions and compounds isolated from S. elegans and its interaction with serotoninergic drugs by using behavioral tests in mice. Fractions from aerial parts of S. elegans were obtained by column chromatography, SeF1, SeF2, SeF3, and SeF4. Each of them was administered to 25 mg/k in ICR mice subject to forced swimming test (FST), or elevated plus maze test (EPM), or open field test (OFT). The most active fractions were chemically separated until compounds, which were analyzed as anxiolytic or antidepressant and the coadministration of these treatments with 5-HT1A and 5-HT2 drugs was measured in the different biological tests. All fractions were anxiolytic and antidepressant, oleanolic acid (OA) was found in SeF2, and from SeF3, a mixture of terpenes was found; a GC-MS analysis confirmed the presence of two main compounds: rosifoliol and agaraspirol (TM, mixture of terpenes). TM (doses-response curve, 0.01, 0.1, 0.5, 1.0, and 2.0 mg/kg) and OA (5 mg/kg) were also evaluated demonstrating an antidepressant and anxiolytic effect, respectively. The combination of TM (0.5 mg/kg) with 8-OH (selective 5-HT1A receptor agonist) induced an increment of antidepressant activity, while with the antagonist WAY-100635, the effect diminished. But with DOI (5-HT1c/5-HT2 receptor agonist), there was no change, and with KET (5-HT2 receptor antagonist), the activity was increased. When OA is co-administered with 8-OH or with DOI, the anxiolytic activity of this terpene, diminished; but with the combination with antagonists, the effect of OA shows no change. TM and OA were antidepressant and anxiolytic, respectively, on mice exposed to different tests, and these are able to interact with serotoninergic drugs.

Corneal Healing and Recovery of Ocular Crystallinity with a Dichloromethane Extract of Sedum dendroideum D.C. in a Novel Murine Model of Ocular Pterygium.

Pterygium is a corneal alteration that can cause visual impairment, which has been traditionally treated with the sap of Sedum dendroideum D.C. The pharmacological effect of a dichloromethane extract of S. dendroideum was demonstrated and implemented in a pterygium model on the healing process of corneal damage caused by phorbol esters. In mice of the ICR strain, a corneal lesion was caused by intravitreal injection of tetradecanoylphorbol acetate (TPA). The evolution of the corneal scarring process was monitored with vehicle, dexamethasone, and dichloromethane extract of S. dendroideum treatments by daily ophthalmic administration for fifteen days. The lesions were evaluated in situ with highlighted images of fluorescence of the lesions. Following treatment levels in eyeballs of IL-1α, TNF-α, and IL-10 cytokines were measured. The effective dose of TPA to produce a pterygium-like lesion was determined. The follow-up of the evolution of the scarring process allowed us to define that the treatment with S. dendroideum improved the experimental pterygium and had an immunomodulatory effect by decreasing TNF-α, IL-1α, and maintaining the level of IL-10 expression, without difference with respect to the healthy control. Traditional medical use of S. dendroideum sap to treat pterygium is fully justified by its compound composition.

Effect of Argemone mexicana on Local Edema and LPS-Induced Neuroinflammation.

Argemone mexicana L. is a widely used plant in Mexican traditional medicine to treat inflammatory and nervous medical conditions. It has been subjected to several pharmacological and chemical studies in which acute anti-inflammatory activity is indicated. This work aimed at finding an extract and fraction with anti-inflammatory activity by means of 2-O-tetradecanoylphorbol-13-acetate (TPA)-induced auricular edema. Afterward, the extract and the fraction were tested on neuroinflammation caused by lipopolysaccharides (LPS). Treatments obtained from A. mexicana included the methanolic extract (AmMeOH), a fraction extracted with ethyl acetate (AmAcOEt), and four sub-fractions (AmF-1 to AmF-4), which were evaluated in auricular edema with the TPA assay. Both treatments with the most significant inhibitory effect were employed to test these in the LPS neuroinflammation model. AmAcOEt and AmF-3 induced a higher inhibition of edema (%), and both diminished ear inflammation when viewed under a microscope. These treatments also raised an increase in spleen, but not in brain of mice with neuroinflammation. They were able to decrease the concentration of proinflammatory cytokines (TNF-α, IL-1ß, and IL-6) in both organs. Furthermore, the accumulation of amyloid-ß (Aß) in hippocampus was not visible. AmF-3 contains the flavonoids isoquercetin, luteolin, and rutin, the former being the most concentrated.

Synergism and Subadditivity of Verbascoside-Lignans and -Iridoids Binary Mixtures Isolated from Castilleja tenuiflora Benth. on NF-κB/AP-1 Inhibition Activity.

Pharmacodynamic interactions between plant isolated compounds are important to understand the mode of action of an herbal extract to formulate or create better standardized extracts, phytomedicines, or phytopharmaceuticals. In this work, we propose binary mixtures using a leader compound to found pharmacodynamic interactions in inhibition of the NF-κB/AP-1 pathway using RAW-Blue™ cells. Eight compounds were isolated from Castilleja tenuiflora, four were new furofuran-type lignans for the species magnolin, eudesmin, sesamin, and kobusin. Magnolin (60.97%) was the most effective lignan inhibiting the NF-κB/AP-1 pathway, followed by eudesmin (56.82%), tenuifloroside (52.91%), sesamin (52.63%), and kobusin (45.45%). Verbascoside, a major compound contained in wild C. tenuiflora showed an inhibitory effect on NF-κB/AP-1. This polyphenol was chosen as a leader compound for binary mixtures. Verbacoside-aucubin and verbascoside-kobusin produced synergism, while verbascoside-tenuifloroside had subadditivity in all concentrations. Verbascoside-kobusin is a promising mixture to use on NF-κB/AP-1 related diseases and anti-inflammatory C. tenuiflora-based phytomedicines.

Anti-neuroinflammatory effect of agaves and cantalasaponin-1 in a model of LPS-induced damage.

Chronic neuroinflammation is a key component of many neurodegenerative disorders. Chronic activation of this process produces pro-inflammatory cytokines, prostaglandins and reactive oxygen species that induce brain injury and neuronal dysfunction. Agave species contain saponins, compounds with anti-inflammatory activity. Extracts from A. tequilana (At), A. angustifolia (Aan), A. Americana (Aam) (125 mg/kg) and cantalasaponin-1 (5 and 10 mg/kg, isolated from Aam) were administered to male ICR mice with lipopolysaccharide (LPS)-induced neuroinflammation, after which inflammatory cytokines were measured in brain homogenates by using an enzyme-linked immunoassay (ELISA) test. All agave extracts and cantalasaponin-1, reduced brain concentration of LPS-induced pro-inflammatory cytokines IL-6 and TNF-α. Moreover, Cantalasaponin-1 increased the brain concentration of the anti-inflammatory cytokine IL-10. Agave extracts and derived compounds show promising results in the development of novel drugs for neuroinflammatory disease therapy.

Angiotensin-converting enzyme inhibitors from Salvia elegans Vahl.

Phytochemical research of the acetate and methanol extracts of the aerial parts (flowers, leaves and stems) of Salvia elegans allowed to obtain seventeen known compounds (1-17): three of them (4, 5, 14), had already been described for this species, while the others (1-3, 6-13, 15-17) are described for the first time for S. elegans. All isolated compounds were characterized using spectroscopic techniques and mass spectrometry and were evaluated in the Angiotensin I-converting enzyme (ACE) inhibition model, where the phenolic compounds (13, 14 and 15) had the same inhibitory effect as lisinopril at 0.02 mg/mL. The terpenes showed a moderate inhibitory capacity at a concentration of 0.2 mg/mL.

A mixture of quercetin 4'-O-rhamnoside and isoquercitrin from Tilia americana var. mexicana and its biotransformation products with antidepressant activity in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The aerial parts of Tilia americana var. mexicana (Malvaceae, formerly Tiliaceae) or "sirimo" are used in Mexican traditional medicine for the relief of mild symptoms of mental stress, commonly referred to as "nerve diseases". Individuals use this plant to fall asleep, to calm states of nervous excitement, headaches, mood disorders, and general discomfort. Recent studies indicated that fractions standardized in their flavonoid content possess antidepressant activity in behavioral assays in mice. The present study aims to focus on the evaluation of the antidepressant effect of the mixture of two flavonoids (FMix), and its interaction with serotonergic drugs. Also, the pharmacological effect of the products of the metabolism of aglycone, quercetin, was evaluated in mice subjected to forced swimming test (FST) and open field test (OFT). MATERIALS AND METHODS: A methanol-soluble extract obtained from leaves of Tilia americana was fractionated in an open column chromatographic separation. One of the fractions contained FMix wich is constituted of the mixture of quercetin 4'-O-rhamnoside (1, 47%) y isoquercitrin (2, 53%). The mice were divided into the several following groups: FMix (0.01, 0.1, 0.5, 1.0, and 2 mg/kg); FMix (1.0 mg/kg) and agonist DOI (2.0 mg/kg); FMix (1.0 mg/kg) and antagonist ketanserin (KET, 0.03 mg/kg) of 5-HT2A receptors; FMix (1.0 mg/kg) and selective agonist 8-OH-DPAT (8-OH, 0.01 mg/kg); FMix (1.0 mg/kg) and antagonist WAY100635 (WAY, 0.5 mg/kg) of 5HT1 receptors; Phloroglucinol (PHL); 3,4-dihydroxy-phenyl acid (DOPAC); p-hydroxyphenyl acetic acid (p-HPAA); and m-hydroxyphenyl acetic acid (m-HPAA) were tested in FST or OFT. RESULTS: FMix induced dependent-dose antidepressant activity and, at the highest dose administered, a sedative effect was also observed. The 8-OH-DPAT, or the DOI, or the KET combination with FMix (1.0 mg/kg) induced a higher antidepressant effect than compounds alone; there was no effect exerted with WAY. The activity on OFT increased only with the FMix and KET combination. At the same time, the products of the aglycone metabolism of quercetin, that is, DOPAC and p-HPAA, decreased the immobility time of the mice in FST at 1.0 mg/kg, and a dose-curve was formed for these. CONCLUSION: The antidepressant effect of FMix could depend, at least in part, on the degradation products of quercetin and with a possible action mode through interaction with the serotoninergic system.

Anti-arthritic and anti- inflammatory effects of extract and fractions of Malva parviflora in a mono- arthritis model induced with kaolin/carrageenan.

Malva parviflora is used as food in the gastronomy of some regions of Mexico and, also, in Mexican traditional medicine for inflammation-related conditions like rheumatoid arthritis. The objective of this work was to evaluate its antiarthritic activity in a mice model. In ICR, female mice were tested the dichloromethane extract (MpD) and fractions MpF4 (extracted with a dichoromethane:methanol system) and MpFphy (a precipitate by acetone:methanol) by using the mono-arthritis with kaolin/carrageenan model. During the treatment, joint inflammation was measured daily, and hyperalgesia was measured using the hot plate test. The treatments diminished both joint inflammation and pain. At the end of the evaluation, the left joint and spleen were extracted for determination of pro- and anti-inflammatory cytokines. The results showed that the MpD, MpF4, and MpFphy treatments modulated the concentration of these proteins. Specifically, MpFphy at 1.0 mg/kg increased IL-4 and IL-10 and decreased IL-17, IL-1ß, and TNF-α. GC-MS analysis showed that MpF4 contained a mixture of a total of nine compounds, three of them newly reported for the species. The studies confirmed the presence of five sterols in the MpFphy fraction, including stigmasterol and ß-sitosterol. These results confirm the anti-rheumatoid and anti-inflammatory activities of a fraction rich in sterols from Malva parviflora. Graphical abstract.