Medicinal Plants Used for Eye Conditions in Mexico-A Review.

Medicinal plants have been historically significant for treating common human diseases in Mexico. Although some ethnobotanical research exists, limited ethnomedicinal data has documented medicinal plants employed for eye health. This review focuses on ethnomedicinal information and preclinical and clinical studies regarding medicinal plants used in Mexico for treating symptoms associated with eye conditions. An electronic database search was conducted by consulting scientific articles, books about Mexican herbal medicine, and academic theses. This work recorded 69 plant species belonging to 26 plant families, especially plants from the Crassulaceae family, which are used as remedies for irritation and infections in the eye. Eight of these medicinal plants have been the subject of preclinical studies using ocular models, and one medicinal plant has been tested in clinical trials. The evidence of pharmacological effects indicates the promising therapeutic potential of these medicinal plants for developing new treatments for eye conditions. However, toxicological studies are necessary to ensure safe application to the eye, particularly as traditional medicine continues to be relied upon worldwide. In addition, this review highlights the need to perform ethnobotanical and phytochemical studies in Mexico regarding the medicinal flora used as remedies for eye conditions.

Special Issue "Ethnopharmacology in Latin America".

Latin America is a multicultural region encompassing 43 countries, with 665 million inhabitants with a mean age of 31 years old, 84% of whom live in urban areas [...].

Neuropharmacological Effects of the Dichloromethane Extract from the Stems of Argemone ochroleuca Sweet (Papaveraceae) and Its Active Compound Dihydrosanguinarine.

Argemone ochroleuca Sweet (Papaveraceae) is used in folk medicine as a sedative and hypnotic agent. This study aimed to evaluate the anxiolytic-like, sedative, antidepressant-like, and anticonvulsant activities of a dichloromethane extract of A. ochroleuca stems (AOE), chemically standardized using gas chromatography-mass spectrometry (GC-MS), and its active compound dihydrosanguinarine (DHS). The anxiolytic-like, sedative, antidepressant-like, and anticonvulsant activities of the AOE (0.1-50 mg/kg p.o.) and DHS (0.1-10 mg/kg p.o.) were evaluated using murine models. A possible mechanism for the neurological actions induced by the AOE or DHS was assessed using inhibitors of neurotransmission pathways and molecular docking. Effective dose 50 (ED50) values were calculated by a linear regression analysis. The AOE showed anxiolytic-like activity in the cylinder exploratory test (ED50 = 33 mg/kg), and antidepressant-like effects in the forced swimming test (ED50 = 3 mg/kg) and the tail suspension test (ED50 = 23 mg/kg), whereas DHS showed anxiolytic-like activity (ED50 = 2 mg/kg) in the hole board test. The AOE (1-50 mg/kg) showed no locomotive affectations or sedation in mice. A docking study revealed the affinity of DHS for α2-adrenoreceptors and GABAA receptors. The anxiolytic-like and anticonvulsant effects of the AOE are due to GABAergic participation, whereas the antidepressant-like effects of the AOE are due to the noradrenergic system. The noradrenergic and GABAergic systems are involved in the anxiolytic-like actions of DHS.

Medicinal plants used in rural communities from the municipality of Dolores Hidalgo, Guanajuato, Mexico / Plantas medicinales utilizadas en comunidades rurales del municipio de Dolores Hidalgo, Guanajuato, México

This study recorded the use of medicinal plants in the rural communities from the municipality of Dolores Hidalgo, Guanajuato, Mexico. Data were obtained through open semi-structured interviews with local respondents (n=181), and medicinal plants were recorded and identified in herbariums. The Relative importance (RI) and Informant Consensus Factor (ICF) were calculated to analyze the survey data. In total, 68 plant species belonging to 33 families were reported. Asteraceae had the highest number of species, representing 14. The highest RI was accounted by Chamaemelum nobile (RI=2.0), followed by Thymus vulgaris (RI=1.83),and Moringa oleifera (RI= 1.60). The highest ICF was reported by diseases associated with the respiratory (ICF=0.80), digestive (ICF=0.75), and musculoskeletal systems including connective tissues (ICF= 0.71). Respondents have knowledge about medicinal plant use for primary health care and other chronic diseases. The information obtained here could be extrapolated to different rural areas in Mexico.

Este estudio registró el uso de plantas medicinales en las comunidades rurales del municipio de Dolores Hidalgo, Guanajuato, México. Los datos se obtuvieron a través de entrevistas abiertas semiestructuradas con encuestados locales (n=181), y las plantas medicinales se registraron e identificaron en los herbarios. La importancia relativa (RI) y el factor de consenso del informante (ICF) se calcularon para analizar los datos de la encuesta. En total, se reportaron 68 especies de plantas pertenecientes a 33 familias. Asteraceae tuvo el mayor número de especies, representando 14. El RI más alto fue contabilizado por Chamaemelum nobile (RI = 2.0), seguido por Thymus vulgaris (RI = 1.83) y Moringa oleifera (RI = 1.60). La ICF más alta se informó por enfermedades asociadas con los sistemas respiratorio (ICF = 0,80), digestivo (ICF = 0,75) y musculoesquelético, incluidos los tejidos conectivos (ICF = 0,71). Los encuestados tienen conocimientos sobre el uso de plantas medicinales para la atención primaria de salud y otras enfermedades crónicas. La información aquí obtenida podría extrapolarse a diferentes zonas rurales de México.

In Vivo Neuropharmacological Effects of Neophytadiene.

Neophytadiene (NPT) is a diterpene found in the methanolic extracts of Crataeva nurvala and Blumea lacera, plants reported with anxiolytic-like activity, sedative properties, and antidepressant-like actions; however, the contribution of neophytadiene to these effects is unknown. This study determined the neuropharmacological (anxiolytic-like, antidepressant-like, anticonvulsant, and sedative) effects of neophytadiene (0.1-10 mg/kg p.o.) and determined the mechanisms of action involved in the neuropharmacological actions using inhibitors such as flumazenil and analyzing the possible interaction of neophytadiene with GABA receptors using a molecular docking study. The behavioral tests were evaluated using the light-dark box, elevated plus-maze, open field, hole-board, convulsion, tail suspension, pentobarbital-induced sleeping, and rotarod. The results showed that neophytadiene exhibited anxiolytic-like activity only to the high dose (10 mg/kg) in the elevated plus-maze and hole-board tests, and anticonvulsant actions in the 4-aminopyridine and pentylenetetrazole-induced seizures test. The anxiolytic-like and anticonvulsant effects of neophytadiene were abolished with the pre-treatment with 2 mg/kg flumazenil. In addition, neophytadiene showed low antidepressant effects (about 3-fold lower) compared to fluoxetine. On other hand, neophytadiene had no sedative or locomotor effects. In conclusion, neophytadiene exerts anxiolytic-like and anticonvulsant activities with the probable participation of the GABAergic system.

Concomitant use of allopathic medicine and herbal products for weight-loss among people with overweight or obesity from Central Mexico / Uso concomitante de medicina alopática y productos herbales para bajar de peso en personas con sobrepeso u obesidad del centro de México

This study evaluated the prevalence of concomitant use of herbal products for weight loss (HPWL) and allopathic medicine. Factors associated with the prevalence, adverse reactions, and the alteration of medication adherence with the concomitant use of HPWL alone and in combination with allopathic medicine, were assessed. The study was descriptive and cross-sectional using a questionnaire conducted among people with overweight or obesity (n=662) from five cities of Central Mexico. Adherence to medications was measured using the Morisky Medication Adherence Scale. The prevalence of adverse reactions induced by the concomitant use of HPWL, and allopathic medicine was 25.3%. The use of HPWL affected medication adherence by 68%. There is a high prevalence (45.2%) of concomitant use of HPWL and allopathic medicine in people with overweight or obesity in Central Mexico. The concomitant use of HPWL and allopathic medicine induces adverse reactions, mainly gastrointestinal, and thus, medication adherence is affected.

Este estudio evaluó la prevalencia del uso concomitante de productos a base de hierbas para bajar de peso (HPWL) y medicina alopática. Se evaluaron los factores asociados con la prevalencia, las reacciones adversas y la alteración de la adherencia a la medicación con el uso concomitante de HPWL solo y en combinación con medicina alopática. El estudio fue descriptivo y transversal mediante un cuestionario realizado entre personas con sobrepeso u obesidad (n = 662) de cinco ciudades del centro de México. La adherencia a los medicamentos se midió mediante la Escala de adherencia a la medicación de Morisky. La prevalencia de reacciones adversas inducidas por el uso concomitante de HPWL y medicina alopática fue del 25,3%. El uso de HPWL afectó la adherencia a la medicación en un 68%. Existe una alta prevalencia (45.2%) de uso concomitante de HPWL y medicina alopática en personas con sobrepeso u obesidad en el centro de México. El uso concomitante de HPWL y medicina alopática induce reacciones adversas, principalmente gastrointestinales, y por tanto, afecta la adherencia a la medicación.

Neuropharmacological Activities of Ceiba aesculifolia (Kunth) Britten & Baker f (Malvaceae).

Ceiba aesculifolia (Kunth) Britten & Baker f (Malvaceae) is used for the folk treatment of mood disorders. C. aesculifolia bark was extracted in ethanol, and the extract (CAE) was chemically standardized using gas chromatography-mass spectrometry (GC-MS). This study evaluated the effects of CAE (10-100 mg/kg p.o.) on anxiolytic-like activity, sedation, locomotor activity, depression-like activity, and spatial working memory using in vivo rodent models. A possible mechanism for the anxiolytic-like and antidepressant-like actions induced by CAE was assessed using neurotransmission pathway inhibitors. Myristic acid was one of the compounds found in CAE using GC-MS. This study also evaluated the anxiolytic-like activity and the sedative actions of myristic acid and assessed a possible mechanism of action using neurotransmission pathway inhibitors and an in silico analysis. CAE elicited anxiolytic-like activity and antidepressant-like effects (ED50 = 57 mg/kg). CAE (10-100 mg/kg) did not affect locomotor coordination or induce sedation. The anxiolytic-like and antidepressant-like actions of CAE were reverted by prazosin, suggesting a possible participation of the noradrenergic system. The anxiolytic-like activity of myristic acid was reverted by the co-administration of prazosin and partially reverted by ketanserin. The docking study revealed that myristic acid can form favorable interactions within 5-HT2A and α1A-adrenoreceptor binding pockets.

Factors and Practices Associated with Self-Medicating Children among Mexican Parents.

BACKGROUND: Pediatric self-medication is based on the subjective interpretation of symptoms in children by the mother or an adult, the decision to self-medicate is made by a third party. The objective of this work is to provide information on the factors and practices associated with the self-medication of children among parents in Mexico. METHODS: A cross-sectional and descriptive study was conducted between June 2020 and December 2021 on Mexican parents with children under 12 years of age. Online questionnaires were completed with sections on sociodemographic characteristics, use of medicines or medicinal plants and their treated symptoms, sources of collection, and their recommendation. RESULTS: A total of 9905 online surveys were completed with representation from the 32 states of Mexico, and the prevalence of self-medication was 49.6% (n = 4908). Associated factors were age, having two or more children, children with chronic illnesses, medium educational level, unemployment or employment unrelated to health, medium and high socioeconomic level, and lack of medical security. Respondents self-medicated their children on the recommendation of a family member or friend (55.8%), and own initiative (28%). The most used medication was VapoRub (61.3%), followed by paracetamol (56.9%) and chamomile (33.1%), and the most prevalent symptoms were flu/flow (47.7%) followed by cough (34.2%). The main reasons were perceiving symptoms as not serious (69.9%) and reusing medications (51.9%). CONCLUSIONS: There is a high prevalence of self-medication in children in Mexico, mainly associated with children with chronic diseases and families with three or more children.

Medicinal Plants from Latin America with Wound Healing Activity: Ethnomedicine, Phytochemistry, Preclinical and Clinical Studies-A Review.

Latin America is a multicultural region with ancient traditional medicine. There is extensive knowledge of the use of medicinal plants for wound healing in this region. Nevertheless, many of these medicinal plants lack pharmacological, toxicological, and chemical studies. This review focuses on the ethnomedicinal, phytochemical, and pharmacological (preclinical and clinical) studies of medicinal plants with wound healing activity, from Latin America. An electronic database search was conducted by consulting scientific articles and books. A total of 305 plant species with wound healing activity were recorded, based on traditional medicine. Most medicinal plants used in wound healing in Latin America are topically administered; their methods of preparation are mainly by water infusion from aerial parts. Only thirty-five percent of medicinal plants used in traditional medicine for wound healing have been experimentally validated for their pharmacological effects, and the wound healing activity of five medicinal plants has been studied in clinical trials. In all, 25 compounds (mostly terpenes and flavonoids) have been isolated from medicinal plants with wound healing activity; therefore, extensive work is necessary for a multidisciplinary approach to evaluate the wound healing effects of medicinal plants in Latin America. The mechanism of action of medicinal plants, their toxicological actions on the skin, and their bioactive compounds, have yet to be investigated. This review on the ethnomedicinal, phytochemical, and pharmacological studies, of medicinal plants from Latin America with wound healing activity, offers promising data for further studies, as well as providing new insights into their possible role in wound care.

Antinociceptive effects of Laelia anceps Lindl. and Cyrtopodium macrobulbon (Lex.) G.A. Romero & Carnevali, and comparative evaluation of their metabolomic profiles.

ETHNOPHARMACOLOGICAL RELEVANCE: Laelia anceps and Cyrtopodium macrobulbon are two orchids used in Mexican traditional medicine for treating pain. AIM OF THE STUDY: The individual antinociceptive activity of ethanol extracts from the roots of Laelia anceps (LAE) and Cyrtopodium macrobulbon (CME) was evaluated, and their metabolomic profiles were comparatively evaluated. The antinociceptive activity of CME and naproxen combination (1:1) was also addressed. MATERIALS AND METHODS: The antinociceptive actions of LAE and CME were examined using three nociceptive tests. The combination of CME with naproxen was evaluated in the acetic acid test using isobologram analysis. Metabolomic analysis was performed using capillary reversed phase liquid chromatography-electrospray ionization-high resolution mass spectrometry and the MS-DIAL 4.70 software was used for data analysis and statistics. RESULTS: LAE (ED50 = 48.4 mg/kg) and CME (ED50 = 17.8 mg/kg) showed antinociceptive activity in the acetic acid test. Pre-treatment with L-NAME reverted the antinociceptive effects of LAE and CME in the acetic acid test. LAE (ED50 = 97 mg/kg) and CME (ED50 = 29 mg/kg) also induced antinociceptive activity in the second phase of the formalin test. The combination of CME with naproxen induced synergistic (interaction index = 0.434) antinociceptive effects (ED50 = 10.6 mg/kg). Overall, 156 compounds allocated in 97 different ontologies were found to be differentially expressed in the two orchids; among them, 125 compounds corresponded to LAE and 31 to CME. Three phenanthrene derivatives annotated in CME might be associated with its antinociceptive activity. CONCLUSION: LAE and CME induced antinociceptive activity with the possible participation of the nitric oxide pathway. CME in combination with naproxen synergistically produces antinociceptive effects in the acetic acid test. The untargeted metabolomic analysis allowed for annotation of several compounds potentially involved in the therapeutic potential of two plants; among them, three phenanthrene derivatives might contribute to the observed antinociceptive activity.

Myristic acid reduces skin inflammation and nociception.

This study evaluated the inhibitory effect of myristic acid (MA) on models of inflammation and nociception. The in vitro anti-inflammatory activities of MA were assessed on LPS-stimulated macrophages, membrane stabilization assay, and inhibition of protein denaturation, whereas the inhibitory activity of MA on in vivo inflammation was assessed on TPA-induced ear edema using acute and chronic assays in mice. The inhibitory effect of MA on nociception was assessed using three in vivo models. MA exerted in vitro anti-inflammatory activity by the increase (58%) in the production of IL-10 in LPS-stimulated macrophages. In the in vivo assay, MA showed good anti-inflammatory effects on the acute (ED50 = 62 mg/kg) and chronic (ED50 = 77 mg/kg) TPA-induced ear edema. The antinociceptive activity of MA was related to the participation of the nitrergic system in the formalin-induced paw licking test. PRACTICAL APPLICATIONS: Previous studies with different plant extracts containing MA, as one of their major components, have demonstrated anti-inflammatory and antinociceptive actions. However, the anti-inflammatory and antinociceptive actions of myristic acid have not been previously reported. The results suggest that MA induced anti-inflammatory effects in LPS-stimulated macrophages through the participation of IL-10. The antinociceptive effects of MA are attributed to the participation of the nitrergic system.

Pharmacological activities of Asclepias curassavica L. (Apocynaceae) aerial parts.

ETHNOPHARMACOLOGICAL RELEVANCE: Asclepias curassavica L. (Apocynaceae) is a perennial shrub used in the folk treatment of parasitism, pain, and inflammation. AIM OF THE STUDY: This work assessed the antiparasitic, anti-inflammatory, antinociceptive, and sedative effects of an ethanol extract from the aerial parts of Asclepias curassavica (ACE). MATERIALS AND METHODS: The antiparasitic activity against Trichomonas vaginalis was evaluated using the trypan blue exclusion test. The in vitro anti-inflammatory actions of ACE (1-200 µg/ml) were analyzed using LPS-stimulated primary murine macrophages. The in vivo pharmacological activity of ACE (50-200 mg/kg p.o.) was evaluated using animal models of inflammation (TPA-induced ear edema test and carrageenan-induced paw edema test) and nociception (acetic acid-induced writhing test, formalin-induced licking test, and hot plate test). RESULTS: ACE showed poor antiparasitic effects against Trichomonas vaginalis (IC50 = 302 µg/ml). ACE increased the production of IL-10 in both in vitro assays (EC50 = 3.2 pg/ml) and in vivo assays (ED50 = 111 mg/kg). ACE showed good antinociceptive actions (ED50 = 158 mg/kg in phase 1 and ED50 = 83 mg/kg in phase 2) in the formalin test. Pre-treatment with naloxone blocked the antinociceptive response induced by ACE. In addition, ACE did not induce sedative effects or motor coordination deficits in mice. CONCLUSION: Findings showed that the anti-inflammatory activity of ACE is associated with increasing levels of IL-10 in both in vitro and in vivo assays, whereas the antinociceptive effect is associated with the participation of the opioidergic system, without inducing sedation or motor coordination impairment.

Use of herbal medicine for diabetes mellitus in adults from the central-western region of Mexico.

OBJECTIVE: This study aims to assess the prevalence of herbal medicine (HM) use and factors influencing HM usage including the identification of the main plants consumed by patients with type 2 diabetes mellitus (T2DM) in central-western Mexico. DESIGN: A total of 1862 patients with diabetes were surveyed in public and private hospitals in four states (Guanajuato, Jalisco, Michoacan, and San Luis Potosi) of the central-western region of Mexico. The chi-square test was used to assess associations between HM use and demographic characteristics, such as glucose levels, presence of complications and comorbidities, as well as the selected therapy to treat T2DM. RESULTS: The prevalence of HM use (59.2%) in patients with T2DM was mainly associated with education level (p = 0.001), time of diagnosis of T2DM (p = 0.004), presence of complications (p < 0.001) and comorbidities (p = 0.018) and the use of insulin (p < 0.001). These patients report a higher consumption of herbal medicine compared to those on glycemic control (p < 0.001). The most frequently used medicinal plants to treat T2DM were nopal (54.9%), moringa (26.7%), and aloe (22.1%). CONCLUSION: The prevalence of HM use to treat T2DM in west-central Mexico is high (59.2%) and its consumption is mostly carried out without the recommendation of a health professional (91.9%). The use of HM increases mainly when the patient uses insulin, during complications of the disease or in patients with an inadequate glycemic control.

Use of allopathic and complementary medicine for preventing SARS-CoV-2 infection in Mexican adults: A national survey.

BACKGROUND: The aim of this study was to assess the frequency of allopathic and complementary medicine use for preventing the infection with SARS-CoV-2 in Mexico. A descriptive and cross-sectional study was conducted using an online questionnaire among general adult population (n = 16,724) of the 32 Mexican states from March to November 2020. METHODS: The factors associated with the use, self-medication practice, and adverse reactions due the consumption of allopathic and complementary medicine to prevent infection with SARS-CoV-2 virus were assessed using a structured questionnaire. The suspected adverse reactions associated with the use of drugs or complementary medicine were reported. RESULTS: The prevalence (42.9%) of allopathic and/or complementary medicine use for preventing SARS-CoV-2 infection was mainly associated with unemployment [OR:2.026 (1.722-2.283)]. Acetaminophen (n = 2272) and vitamin C (n = 3252) were the main allopathic and complementary medicine products used to prevent SARS-CoV-2 infection, respectively. The prevalence of self-medication and adverse reactions was 35.3% and 4.8%, respectively. Self-medication [OR:1.930 (1.633-2.282)] and adverse reactions [OR:2.603 (2.015-3.363)] were mainly associated with individuals of low socioeconomic status. Hydroxychloroquine (21.2%) and chloroquine (15.2%) showed the highest prevalence of adverse reactions, which were mainly related to gastrointestinal disorders. CONCLUSION: The use of medications and complementary medicine to prevent SARS-CoV-2 infection is prevalent (almost one-half of the respondents) among Mexican population, and it is mainly associated with unemployment. Self-medication and the adverse reactions derived from self-medication are also prevalent and seem to be influenced by low socioeconomic status.

Self-treatment and adverse reactions with herbal products for treating symptoms associated with anxiety and depression in adults from the central-western region of Mexico during the Covid-19 pandemic.

ETHNOPHARMACOLOGICAL RELEVANCE: There are plant species used in the Mexican traditional medicine for the empirical treatment of anxiety and depression. AIM OF THE STUDY: This work assessed the prevalence of self-medication with medicinal plants and the prevalence of the concomitant use of prescribed psychiatric drugs and medicinal plants for treating symptoms associated with anxiety and depression during the Covid-19 lockdown in Mexico. MATERIALS AND METHODS: The suspected adverse reactions associated with drug-herb interactions were assessed. The factors associated with self-medication, the concomitant use of herb-drug combinations, and the presence of adverse reactions due their combined use is also reported. The study was descriptive and cross-sectional using an online questionnaire conducted among population with symptoms associated with anxiety and depression (n = 2100) from seven states of central-western Mexico. RESULTS: The prevalence of the use of herbs (61.9%) and the concomitant use of drug-herb combinations (25.3%) were associated with being diagnosed with mental illness [OR:2.195 (1.655-2.912)] and the use of psychiatric medications [OR:307.994 (178.609-531.107)], respectively. The presence of adverse reactions (n = 104) by the concomitant use of drug-herb combinations was associated with being unemployed [p = 0.004, OR: 3.017 (1.404-6.486)]. CONCLUSION: Health professionals should be aware if their patients concomitantly use medicinal plants and psychiatric drugs. Public health campaigns should promote the possible adverse reactions that might produce the concomitant use of drug-herb combinations for mental illnesses.

Anti-inflammatory and antitumor activities of the chloroform extract and anti-inflammatory effect of the three diterpenes isolated from Salvia ballotiflora Benth.

BACKGROUND: Drugs used for the treatment of diseases associated with chronic inflammation, such as cancer and rheumatoid arthritis have the potential to cause undesirable side-effects, which might result in patients ending treatment prematurely. However, plants are a viable option for the treatment of inflammatory diseases. In this study, we assessed the in vivo and in vitro anti-inflammatory activity, and the antitumor effects of the chloroform extract of Salvia ballotiflora (ECL). The pro-apoptotic effects of ECL in CT26 cells were also determined. METHODS: The chloroform extract of Salvia ballotiflora (ECL) was standardized using 19-deoxyicetexone (DEOX) as a phytochemical marker. The anti-inflammatory activity of ECL was determined on acute and chronic inflammatory models using the TPA-induced mouse ear edema assay. The antitumor activity of ECL was evaluated by the subcutaneous inoculation of CT26 cells on the back of Balb/c mice. In vitro CT26 cell death induced by ECL was determined by Annexin V/propidium iodide staining assay using flow cytometry. ECL and the diterpenes isolated from the chloroform extract included 19-deoxyicetexone (DEOX), icetexone (ICT), and 7,20-dihydroanastomosine (DAM), which were tested in LPS-stimulated J774A.1 macrophages to quantify pro-inflammatory cytokine levels. The in vitro anti-arthritic activity of ECL was determined using the bovine serum protein (BSP) denaturation assay. RESULTS: ECL exerted anti-inflammatory activities in acute (84% of inhibition, 2 mg/ear) and chronic models (62.71%, at 100 mg/kg). ECL showed antitumor activity at 200 mg/kg and 300 mg/kg, reducing tumor volume by 30 and 40%, respectively. ECL (9.5 µg/mL) induced in vitro apoptosis in CT26 cells by 29.1% (48 h of treatment) and 93.9% (72 h of treatment). ECL (10 µg/ml) decreased levels of NO (53.7%), pro-inflammatory cytokines IL-6 (44.9%), IL-1ß (71.9%), and TNF-α (40.1%), but increased the production of the anti-inflammatory cytokine IL-10 (44%). The diterpenes DEOX, ICT, and DAM decreased levels of NO (38.34, 47.63, 67.15%), IL-6 (57.84, 60.45, 44.26%), and TNF-α (38.90, 31.30, 32.83%), respectively. ECL showed in vitro antiarthritic activity (IC50 = 482.65 µg/mL). CONCLUSIONS: ECL exhibited anti-inflammatory and anti-tumor activities. Furthermore, the diterpenes DEOX, DAM, and ICT showed anti-inflammatory activity by reducing levels of NO, TNF-α, and IL-6.

Antinociceptive and anti-inflammatory effects of Cuphea aequipetala Cav (Lythraceae).

Cuphea aequipetala Cav (Lythraceae) is an herb used in folk treatment for pain and inflammation. The aim of this study was to evaluate the antinociceptive and anti-inflammatory actions of an ethanol extract from the leaves and stem of Cuphea aequipetala (CAE). The antinociceptive actions of CAE (10-200 mg/kg p.o.) were assessed with the acetic acid-induced writhing, hot plate, and formalin tests. The possible mechanism of action of CAE was evaluated using inhibitors. The effects of CAE on motor coordination were assessed by the rotarod test. The in vitro anti-inflammatory actions of CAE were evaluated using LPS-stimulated primary murine macrophages, and the in vivo anti-inflammatory actions were assessed by the TPA-induced ear oedema and the carrageenan-induced paw oedema tests. The production of inflammatory mediators was estimated from both in vitro and in vivo assays. CAE showed antinociception (ED50 = 90 mg/kg) in the acetic acid test and in the second phase of the formalin test (ED50 = 158 mg/kg). Pretreatment with glibenclamide or L-NAME partially reversed the antinociception shown by the plant extract. CAE (50-200 mg/kg) did not affect motor coordination in mice. CAE increased the production of IL-10 in LPS-stimulated macrophages (EC50 = 10 pg/ml) and, in the carrageenan-induced paw oedema test (threefold increase). In conclusion, CAE induced antinociceptive effects without affecting motor coordination, probably due to the involvement of nitric oxide and ATP-sensitive K+ channels. CAE also exerts in vitro and in vivo anti-inflammatory effects by increasing the release of IL-10.

In vitro and in vivo anti-inflammatory effects of an ethanol extract from the aerial parts of Eryngium carlinae F. Delaroche (Apiaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Eryngium carlinae F. Delaroche (Apiaceae) is an herb used in folk medicine as a diuretic, analgesic, and anti-inflammatory agent. AIM OF THE STUDY: This work assessed the diuretic, antinociceptive, and anti-inflammatory actions of an ethanol extract from the leaves and stems of Eryngium carlinae (ECE). These ethnomedicinal properties of ECE were scientifically validated using in vitro and in vivo assays. MATERIALS AND METHODS: The antinociceptive and diuretic actions of ECE (10-200 mg/kg p.o.) were assessed with the acetic acid-induced writhing test and by using metabolic cages to house mice, respectively. The in vitro anti-inflammatory actions of ECE (1-500 µg/ml) were evaluated using LPS-stimulated primary murine macrophages, and the in vivo anti-inflammatory actions were assessed using the TPA-induced ear edema test (2 mg/ear) and carrageenan-induced paw edema test (50-200 mg/kg p.o.). The production of inflammatory mediators was estimated using in vitro and in vivo assays. RESULTS: ECE lacked antinociceptive and diuretic effects. ECE increased the production of IL-10 in LPS-stimulated macrophages (EC50 = 37.8 pg/ml) and the carrageenan-induced paw edema test (ED50 = 82.6 mg/kg). ECE showed similar in vivo anti-inflammatory actions compared to those observed with indomethacin. CONCLUSION: ECE exerts in vitro and in vivo anti-inflammatory effects by increasing the release of IL-10.

Toxicological Screening of Four Bioactive Citroflavonoids: In Vitro, In Vivo, and In Silico Approaches.

Many studies describe different pharmacological effects of flavonoids on experimental animals and humans. Nevertheless, few ones are confirming the safety of these compounds for therapeutic purposes. This study aimed to investigate the preclinical safety of naringenin, naringin, hesperidin, and quercetin by in vivo, in vitro, and in silico approaches. For this, an MTT-based cytotoxicity assay in VERO and MDCK cell lines was performed. In addition, acute toxicity was evaluated on Wistar rats by OECD Guidelines for the Testing of Chemicals (Test No. 423: Acute Oral Toxicity-Class Method). Furthermore, we used the ACD/Tox Suite to predict toxicological parameters such as hERG channel blockade, CYP450 inhibition, and acute toxicity in animals. The results showed that quercetin was slightly more cytotoxic on cell lines (IC50 of 219.44 ± 7.22 mM and 465.41 ± 7.44 mM, respectively) than the other citroflavonoids. All flavonoids exhibited an LD50 value > 2000 mg/kg, which classifies them as low-risk substances as OECD guidelines established. Similarly, predicted LD50 was LD50 > 300 to 2000 mg/kg for all flavonoids as acute toxicity assay estimated. Data suggests that all these flavonoids did not show significant toxicological effects, and they were classified as low-risk, useful substances for drug development.

Anti-inflammatory and antinociceptive effects of an ethanol extract from Senna septemtrionalis.

Senna septemtrionalis (Viv.) H.S. Irwin & Barneby (Fabaceae) is a medicinal plant used as a folk remedy for inflammation and pain. The objective of this study was to evaluate the anti-inflammatory and antinociceptive actions of an ethanol extract of Senna septemtrionalis aerial parts (SSE). The in vitro anti-inflammatory effects of SSE were assessed using LPS-stimulated macrophages and the subsequent quantification of the levels of cytokines (IL-6, IL-1ß, and TNF-α) with ELISA kits, nitric oxide (NO), and hydrogen peroxide (H2O2). The in vivo anti-inflammatory actions of SSE were evaluated with the TPA-induced ear oedema test and the carrageenan-induced paw oedema test. The antinociceptive actions of SSE (10-200 mg/kg p.o.) were assessed using three models: two chemical assays (formalin-induced orofacial pain and acetic acid-induced visceral pain) and one thermal assay (hot plate). SSE showed in vitro anti-inflammatory actions with IC50 values calculated as follows: 163.3 µg/ml (IL-6), 154.7 µg/ml (H2O2) and > 200 µg/ml (IL-1ß, TNF-α, and NO). SSE showed also in vivo anti-inflammatory actions in the TPA test (40% of inhibition of ear oedema) and the carrageenan test (ED50 = 137.8 mg/kg p.o.). SSE induced antinociceptive activity in the formalin orofacial pain test (ED50 = 80.1 mg/kg) and the acetic acid-induced writhing test (ED50 = 110 mg/kg). SSE showed no antinociceptive actions in the hot plate assay. The pre-treatment with glibenclamide abolished the antinociceptive action shown by SSE alone. Overall, SSE exerted in vitro and in vivo anti-inflammatory actions, and in vivo antinociceptive effects by the possible involvement of ATP-sensitive K + channels.