Chemical composition and effects of ethanolic extract and gel of Cochlospermum regium (Schrank) Pilg. Leaves on inflammation, pain, and wounds.

ETHNOPHARMACOLOGICAL RELEVANCE: Cochlospermum regium is well-known as "Algodãozinho do cerrado" in folk Brazilian medicine, and is used to fight infections, inflammation and skin disorders. AIM OF THE STUDY: To identify the phytochemical constituents and the effects of the ethanolic extract of C. regium leaves (EECR) on inflammation and pain, and the effects of C. regium gel (GEECR) on wound healing. MATERIALS AND METHODS: Animals were treated with EECR (30-300 mg/kg) or GEECR (1.25 and 2.5%) and studies were conducted using carrageenan-induced pleurisy and paw edema tests, formalin-induced pain model, and excision wound model. RESULTS: In total, 25 compounds, including quercitrin, methyl gallate, and 1,2,3,4,6-pentagalloylhexose, with highest detectability were identified. The treatments reduced leukocyte migration, nitric oxide production, protein extravasation, edema, mechanical hyperalgesia, pain in both phases (neurogenic and inflammatory), cold hypersensitivity, and improved wound closure and tissue regeneration. CONCLUSIONS: The present findings established the anti-inflammatory, anti-nociceptive, and wound healing potential of the leaves of C. regium, confirming the potential therapeutic effect of this plant.

The Analgesic Dipyrone Affects Pregnancy Outcomes and Endocrine-Sensitive Endpoints in Female and Male Offspring Rats.

Dipyrone is an analgesic and antipyretic drug commonly used in many countries. Although generally not recommended during pregnancy, it is known that many women use dipyrone during the gestational period. In this study, we investigated the endocrine and reproductive effects of dipyrone in female and male offspring rats exposed in utero from gestational days 10-21. Pregnant rats were treated with dipyrone at 25, 75, and 225 mg/kg/day via oral gavage. Developmental landmarks-anogenital index (AGI), number of nipples, vaginal opening, first estrus, and preputial separation-were evaluated in the offspring. Reproductive parameters, including estrous cycle regularity, daily sperm production, weight and histopathology of reproductive organs, steroid hormone levels, and gene expression of selected markers of reproductive function were assessed at adulthood. At the highest dose, dipyrone induced a significant increase in postimplantation losses/fetal death and delayed parturition in dams. Offspring exposed in utero to the highest dose also exhibited significant changes in some early life markers of endocrine disruption, in particular increased AGI in females, indicating a proandrogenic effect, and increased rate of retained nipples in males, indicating an antiandrogenic response. No changes were observed in markers of puberty onset or reproductive parameters at adulthood. These results suggest that exposure to therapeutically relevant doses of dipyrone may induce mild endocrine disruptive effects that can be detected in late pregnancy and early life. Such effects may be relevant considering dipyrone use by pregnant women and the possibility of coexposures with other endocrine disruptors.

Chemical analysis and antioxidant, anti-inflammatory and toxicological evaluations of the hydromethanolic extract of Psidium guineense Swartz leaves.

ETHNOPHARMACOLOGICAL RELEVANCE: Psidium guineense, popularly known as "araçá-do-campo", is used in popular medicine for the treatment of inflammatory diseases. Our research group studied an essential oil obtained from its leaves and reported anti-inflammatory and analgesic properties. However, to date, the anti-inflammatory actions of the leaf extract have not been evaluated although the traditional folk use of this plant has these indications. AIM OF STUDY: The current study was designed to evaluate the antioxidant and anti-inflammatory effects and toxicity of the hydromethanolic extract of the leaves from P. guineense (HME-PG), as well as to investigate the chemical composition. MATERIALS AND METHODS: HME-PG was chemically investigated by Ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). The antioxidant activity was evaluated with 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and malondialdehyde (MDA). Swiss mice were orally (p.o.) pretreated with HME-PG (30, 100 and 300 mg/kg), and after 1 h received carrageenan via paw injection (edema, cold sensitivity and mechanical hyperalgesia were analyzed) or pleural injection (leukocyte migration was analyzed after 4 h) and for nociception using the formalin model. Acute (14 days) and subacute (28 days) toxicity was assessed with female Wistar rats orally treated with 500 and 2000 mg/kg HME-PG. RESULTS: HME-PG showed high levels of phenolic and flavonoid compounds. Six compounds were identified based on UHPLC-MS/MS analysis, including gallic acid, quercetin, 3'-formyl-2',4',6'-trihydroxy-5'-methyldihydrochalcone, vanillic acid, ursolic acid and corilagin. HME-PG exhibited an IC50 of 48.14 µg/mL in the MDA assay and an IC50 of 45.15 µg/mL in the DPPH test. The treatment with HME-PG (100 and 300 mg/kg) significantly inhibited edema at all time points evaluated, mechanical hyperalgesia after 4 h and the response to cold 3 and 4 h after carrageenan injection and anti-nociceptive effects in both phases of formalin nociception. All oral HME-PG treatments significantly inhibited leukocyte migration and plasma extravasation in the pleurisy model. Toxicity tests did not cause signs of toxicity in the treated animals. CONCLUSIONS: The present study showed that HME-PG has antioxidant and anti-inflammatory properties, and no toxicity was detected after acute or subacute treatment with HME-PG, showing the possibility for the safe traditional use of P. guineense.

General and genetic toxicology studies of Aleurites moluccana (L.) Willd. seeds in vitro and in vivo assays.

ETHNOPHARMACOLOGY RELEVANCE: Aleurites moluccana is popularly used for the diseases like ulcers, fever, headache, asthma, conjunctivitis, gonorrhea, inflammation, hepatitis, and rheumatism. The seed, also known as "noz da Índia", has been popularly consumed for weight loss purposes but reports of toxicity have been associated with its ingestion. In the literature, there are not enough studies to elucidate its toxicology, so evaluating the general and genetic toxicological of A. moluccana seeds can provide data to ensure their intake. AIM OF THE STUDY: The objective of the present study was to elucidate the oral toxicity, mutagenicity, genotoxicity and cytotoxicity of A. moluccana seeds in vitro and in vivo assays. MATERIALS AND METHODS: The chemical composition of the aqueous extract of A. moluccana seeds (AEAMS) was analyzed in relation to phenolic compounds, tannins, flavonoids and fatty acid. For the in vitro assays, the cytotoxic potential was assessed by the MTS assay whereas the mutagenic potential was assessed by the Ames test. For in vivo assays, was conducted an acute oral toxicity study, with "Up-and-Down Procedure" and repeated dose toxicity with "Repeated Dose 28-Day Oral Toxicity". To assess genetic damage, mutagenic potential was assessed by the micronucleus test whereas the polychromatic erythrocyte/normochromatic erythrocyte ratio was obtained with bone marrow cells to determine the cytotoxic potential and genotoxic potential was assessed by the comet assay using peripheral blood cells. RESULTS: AEAMS did not show cytotoxic and mutagenic potential in vitro. No clinical signs of toxicity were observed in animals after the acute oral toxicity test, suggesting that the LD50 of aqueous extract of A. moluccana seeds > 2000 mg/kg in a single dose by intragastric route. However, in toxicity at repeated doses for 28 days, the doses initially established (250; 500 and 750 mg/kg/day by intragastric route) caused mortality in the animals and the reestablished doses (25, 50 and 100 mg/kg/day by intragastric route) showed no changes in parameters or clinical signs attributed to toxicity. Furthermore, AEAMS also did not show mutagenic, genotoxic and cytotoxic potential in vivo. CONCLUSIONS: AEAMS did not show cytotoxic, genotoxic and mutagenic potential in vitro and in vivo. And although the AEAMS has an LD50 > 2000 mg/kg, and does not have physiological, biochemical, hematological, histopathological changes or clinical signs related to toxicity when administered in low concentrations and for a short period, in high concentrations and continued use caused toxicity and mortality in Wistar rats. In order to obtain complementary results, is recommended highly that further mid and long-term toxicological studies are investigated, and in no-rodent specie.

Preclinical safety evaluation of the ethanolic extract from guavira fruits (Campomanesia pubescens (D.C.) O. BERG) in experimental models of acute and short-term toxicity in rats.

Campomanesia pubescens is a fruit plant widely distributed in South America and used by the population for medicinal and nutritional purposes, with important economic and cultural value. This study evaluated the toxic potential of the ethanolic extract from C. pubescens (EEFCP) fruits through acute and short-term toxicity tests. For the acute toxicity test, female rats received a single oral dose of 2000 mg/kg body weight of EEFCP and were observed for 14 days. In the short-term toxicity test, male and female rats received repeated oral doses of 125, 250, 500 or 1000 mg/kg of EEFCP, being treated and observed for 28 days, and after the treatment period, a satellite and satellite control group remained under observation for another 14 days. No mortality, clinical and organ weight alterations were observed, indicating that LD50 is greater than 2000 mg/kg body weight. In addition, the doses tested did not produce significant changes in the behavioral, physiological, hematological or histopathological parameters of animals. These results demonstrate the low acute and short-term toxicity of EEFCP in rats. The data obtained are of great relevance since they provide important information about a plant species of great economic, nutritional and ethnopharmacological value.

Oral acute and subchronic toxicity studies of the oil extracted from pequi (Caryocar brasiliense, Camb.) pulp in rats.

The Caryocar brasiliense (pequi) is a Brazilian fruit of important geographic distribution and of broad popular use for nutritional purposes. This study aimed to evaluate the toxicological potential of pequi through the acute and subchronic toxicity tests. For the acute toxicity test, female Wistar rats received, orally, a single dose of 2000 mg/kg/bw of pequi oil and were observed for 14 days. In subchronic toxicity test, Wistar male and female rats received, orally, repeated doses of 125, 250, 500 or 1000 mg/kg/bw of the oil, being treated and observed for 28 days. In the acute toxicity test, no changes as well as no mortality were observed, indicating that the LD50 is higher than 2000 mg/kg/bw. In the subchronic toxicity test, the tested doses produced no significant changes in behavioral, physiological, biochemical or histopathologic parameters in animals. Some hematological abnormalities were found after subchronic exposure and need to be clarified. These results demonstrate the low toxicity of acute and subchronic to the oil of pequi in rats. However, additional studies are required in order to verify if the hematological abnormalities have any relation to the oil exposure and also provide sufficient safety evidence for the use of the oil in humans.