Fúlvio Rieli Mendes

Antinociceptive peripheral effect of Achillea millefolium L. and Artemisia vulgaris L.: both plants known popularly by brand names of analgesic drugs.

The hydroalcohol extracts of Achillea millefolium L. (AM) and Artemisia vulgaris L. (AV), both belonging to the Asteraceae family, were evaluated by the hot plate, writhing, formalin and intestinal transit tests in an attempt to confirm their folk use as analgesic, antiinflammatory and antispasmodic agents. AM 500 and 1000 mg/kg significantly inhibited abdominal contortions by 65% and 23%, respectively, whereas AV 500 and 1000 mg/kg inhibited them by 48% and 59%, respectively. None of the extracts produced differences in the intestinal transit in mice, nor in the response time in the hot plate or in the immediate or late responses in the formalin test. In HPLC/DAD analyses ‘fingerprint’, monitored at 360 and 270 nm, both hydroalcohol extracts showed the same flavonoid glycoside as a principal constituent, which was identified as rutin. A high content of caffeic acid derivatives were also found in both extracts. The main differences were observed at 240 nm: AM had a higher content of rutin, while in AV the hydroxybenzoic acid derivative was the major component. Copyright

Activity of Hypericum brasiliense and Hypericum cordatum on the central nervous system in rodents.

Hydroalcoholic extracts from species Hypericum brasiliense Choisy (HB) and Hypericum cordatum (Vell. Conc.) N. Robson (HC), were evaluated on the central nervous system (CNS) in some pharmacological tests. Signs of toxicity were observed for both species during the initial screening when high doses of up to 100 mg/kg (i.p.) and 1000 mg/kg (oral) were utilized. HC presented greater toxicity, with LD(50) of 269 mg/kg, as compared to HB (537 mg/kg). Alterations in sleeping time and in motor coordination were not observed both for HB and for HC. On the other hand, both species showed signs of general depressant action on the CNS, verified by decreased motor activity. Furthermore, animals treated with HB presented an increase in response time to thermal stimulus with doses of 50 mg/kg (i.p.) and 500 mg/kg (oral) suggesting possible analgesic action. Both HB and HC were tested in animal models to verify antidepressant action (forced swimming and hypothermy induced by apomorphine). In these tests, neither of the plants inhibited hypothermy, nor did they reduce immobility time in forced swimming.

α1-Adrenoceptor Subtypes in Rat Epididymis and the Effects of Sexual Maturation

Abstract We have characterized the expression of α1-adrenoceptor in epididymis from rats in different stages of sexual maturation: 40 (immature), 60 (young adult), and 120 (adult) days of age. Plasma testosterone levels were low in the immature animals but increased significantly in the 60- and 120-day-old animals. These changes were followed by a progressive increase in rat body weight and in caput and cauda epididymis relative weight. Reverse transcription polymerase chain reaction assay indicated that α1a-, α1b-, and α1d-adrenoceptor transcripts were present in both caput and cauda epididymis from adult rats. Ribonuclease protection assays further indicated that the expression of these α1-adrenoceptor transcripts differed with age and epididymal region analyzed. Prazosin (nonselective α1 antagonist), 5-methyl urapidil (α1A-selective), and BMY 7378 (α1D-selective) displaced [3H]prazosin binding curves in caput and cauda epididymis from 40- and 120-day-old rats. The potency order for these antagonists, as calculated from the negative logarithm of the inhibition constant (pKi) values for the high-affinity sites, indicated a predominant population of α1A-adrenoceptor subtype in caput and cauda epididymis from adult animals. Differences in pKi values in caput and cauda epididymis from immature and adult animals also suggested that the relative amount of α1-adrenoceptors, at the protein level, is modulated by sexual maturation. Taken together, the changes in α1-adrenoceptor expression during sexual maturation may suggest specific roles for these receptors in epididymal function.

Comparison of the chemical composition and biological effects of the roots, branches and leaves of Heteropterys tomentosa A. Juss

ETHNOPHARMACOLOGICAL RELEVANCE HETEROPTERYS TOMENTOSA: A. Juss (Malpighiaceae), commonly mistaken as Heteropterys aphrodisiaca, is chronically used by the Brazilian population to improve general health due to its claimed protective effects against a wide range of medical conditions. AIM OF THE STUDY This study in rodents aimed to verify the adaptogenic potential of the hydroalcoholic extracts of the roots (the most commonly used portion), branches and leaves of the plant. MATERIALS AND METHODS The phytochemical constitution of the extracts was analyzed through thin-layer chromatography and high-performance liquid chromatography. Restriction- and cold-induced stress in rats treated for 14 days with 100 or 300 mg/kg of the extracts were used to evaluate parameters such as ulceration, adrenals, thymus and spleen weights, as well as ACTH and corticosterone plasmatic levels. The stress response also was evaluated in mice by self-analgesia induced by restraint stress, after 7 days of treatment at doses of 100 and 300 mg/kg. The learning and memory of aged rats treated with extracts of root or branches at the dose of 50 mg/kg for 80 days were evaluated in the elevated T-maze test. RESULTS The chemical constituents of the three parts of the plant were relatively similar in the presence of saponins, hydrolysable tannins, flavonoids, polyphenols and triterpenes. None of the three extracts were capable of protecting the stomach from ulcerations in rats submitted to cold restraint stress or protecting from alterations in adrenal or spleen weight (p>0.05). Furthermore, the extracts did not inhibit increases in plasma levels of corticosterone and adrenocorticotropic hormone. Moreover, the extracts did not inhibit self-analgesia induced by restraint stress in mice and did not improve the performance of aged rats in the T-maze test (p>0.05). CONCLUSION The tests employed in this study did not show evidence of adaptogenic activity in the three extracts of Heteropterys tomentosa.

Antinociceptive activity of the HPLC- and MS-standardized hydroethanolic extract of Pterodon emarginatus Vogel leaves

Several studies have demonstrated the analgesic and anti-inflammatory effects of fruit and seed extracts from Pterodon emarginatus Vogel (Fabaceae). The objective of this study was to evaluate the antinociceptive activity of the hydroethanolic extract of P. emarginatus leaves in mice and characterize its chemical composition using HPLC coupled to UV-vis diode array detection and mass spectrometry with electrospray ionization. Our results showed that the doses of 500 and 1000 mg/kg produced an antinociceptive effect, as observed in the hot plate test and writhing induced by acetic acid. The chromatographic profile and spectral mass data suggest the presence of di-C-glycosylflavones (e.g., vicenin-2 and schaftoside), C,O-glycosylflavones (e.g., chrysoeriol-8-C-glucosyl-2″-O-glucuronide-6-C-arabinoside) and luteolin-7-O-rutinoside as the main constituents. Lower levels of oleanane-type saponins, such as soyasaponin Bb and Be, and the saponin derivatives hederagenin and aglycone B, which are typical of Fabaceae family, were also found. From this study, it is suggested that the analgesic effect observed is not due to the terpenoids previously reported from fruit and seed extracts, but could be attributed to flavones and the hederagenin derivatives that were identified as main constituents of the hydroethanolic extract from the leaves.

Effects of a hydroalcoholic extract of Turnera diffusa Willd. ex Schult., Turneraceae, in tests for adaptogenic activity

The objective of the present study was to assess whether Turnera diffusa Willd. ex Schult., Turneraceae, (TD), plant known in popular medicine as tonic and aphrodisiac, has other effects that are characteristic of an adaptogen substance, such as improvement of the memory and reduction of the damage caused by stress. We carried out an initial screening to detect a possible toxicity of the plant. In that phase of the study we used tests of observational screening; evaluation of acute toxicity; measurement of motor activity and motor coordination, and sleeping time induced by pentobarbital, and observed that the extract presented low toxicity and no stimulant or depressant effect on the animals. We then performed specific tests for the evaluation of an adaptogen effect. TD did not protect the stomach of the animals from the formation of ulcers, neither did it alter the plasmatic levels of adrenocorticotropic hormone (ACTH) and corticosterone of the animals submitted to immobilization and cold. As regards the evaluation of memory in passive avoidance, TD did not inhibit scopolamine-induced amnesia. Additionally, the hydroalcoholic extract presented low antioxidant activity in vitro. In the models used, TD produced no changes in relation to a possible adaptogen effect.

Plants Indicated by Brazilian Indians for Disturbances of the Central Nervous System: A Bibliographical Survey

Brazil possesses great biological and cultural diversity, above all, in view of the great number of indigenous ethnic groups - 218 in all - that inhabit the five main biomas in Brazil. The purpose of this review is to analyze the relationship between chemical constituents of species utilized by several groups of Brazilian Indians and the uses/indications made of the species by these same groups using ethnopharmacological surveys by different researchers, as from the seventies. The 34 publications selected, involving 26 indigenous ethnic groups, showed a total of 307 species utilized for 67 different diseases or effects possibly related to the Central Nervous System (CNS). These plants belong to 85 taxonomic families, mostly Fabaceae, Asteraceae, Rubiaceae, Poaceae, Apocynaceae, Bignoniaceae, Euphorbiaceae, and Solanaceae. The chemical constitution of these plants was researched as from the Pubmed and Web of Science and the information obtained was crossed with different indigenous uses, grouped in 12 categories according to similarities between their expected effects on the CNS: analgesics, to counteract fever, tonics and/or adaptogens, hallucinogens, anxiolytics, anticonvulsants, head illnesses, hypnotics, stimulants, weight control, memory enhancers, and others. Some phytochemical classes were observed to be more common among plants utilized for certain purposes: flavonoids (analgesia, fever, anxiety, hypnotic, weight control, and as a stimulant), alkaloids (hallucinogens, head illnesses, and as a stimulant), essential oils (fever and anxiety), lignans (hallucinogen), tannins (anxiety), triterpenes and saponins (hypnotic). These data suggest that these phytochemical classes possibly possess a greater number of chemical constituents that perform the effects described or that, in some way, assist in determining the use of the plant by the Indians.

Preliminary investigation of the central nervous system effects of 'Tira-capeta' (Removing the Devil), a cigarette used by some Quilombolas living in Pantanal Wetlands of Brazil.

During an ethnopharmacological survey carried out among some Quilombolas living in Brazil, 48 plants with possible central nervous system (CNS) action were cited. A mixture of nine plants, known as ‘Tira‐capeta’ (Removing the Devil) cigarette, has been utilized for years as a tonic for the brain. The effects observed after consuming this cigarette are: dizziness, lightness sensation, humor changes, yawns, heavy eyes, hunger, sleep and relaxation. This study aimed to verify the effects of a hydroalcohol extract of ‘Tira‐capeta’ cigarette (ETC), as well as to evaluate the phytochemical profile. The phytochemical screening carried out through characterization reactions, thin layer chromatography and high efficiency liquid chromatography indicated the presence of tannins, phenolic acids, flavonoids, saponins and alkaloids; tannins and phenolic acids being the principal constituents. The pharmacological tests showed that ETC induced a biphasic effect, with intense initial stimulation of the CNS, followed by a general depressor state; decreased the latency for sleeping and increased the total sleeping time (50, 100 and 500 mg/kg), without causing prejudice in motor coordination (doses up to 200 mg/kg); induced catalepsy in mice, verified 10 and 50 min after drug administration (500 mg/kg). Also, no anxiolytic or anxiogenic effects were verified in rats submitted to the elevated plus‐maze. Copyright

Memory retrieval improvement by Heteropterys aphrodisiaca in aging rats

Few data exists about the pharmacological properties of Heteropterys aphrodisiaca O. Mach. (Malpighiaceae), which is native to the scrubland regions of Brazil. The present study investigated the effects of oral treatment with H. aphrodisiaca extract (BST0298) on the learning and memory of young (3-6 months) and aged (21-23 months) rats, and compared the in vitro antioxidant activity of three lots collected in different years. An improvement in the number of sessions to learn the task was observed in the left/right discrimination test in aged rats treated for 45 days with 25 mg/kg (7.0 ± 0.5; p=0.005) or 50 mg/kg (7.6 ± 0.6; p=0.012) compared with control old rats (11.0 ± 1.6). On the other hand, pre-treatment did not improve the performance of scopolamine-treated mice in the passive avoidance test. The in vitro malondialdehyde test showed that all three different extracts presented similar antioxidant activity. The flavonoids astilbin, isoastilbin and neoastilbin were isolated from the extract and may contribute to the biological activity. These results suggest that repeated treatment with H. aphrodisiaca improves learning and memory, probably by a non-muscarinic mechanism.

Heteropterys tomentosa A. Juss.

Heteropterys tomentosa A. Juss. (Syn. Heteropterys aphrodisiaca, Malpighiaceae) is a species that occurs in Brazilian Cerrado, where it is known as no-de-cachorro and used as a tonic, aphrodisiac, depurative, a treatment for nervous debility, and other uses. Preparations in traditional medicine use the leaves and, mainly, the roots, as a decoction or macerated in alcoholic beverages. The roots of H. tomentosa are obtained mainly by extractivism, which has contributed to the decline of populations of the plant. Agronomic studies indicate that the species is easy to cultivate. There are reports indicating the sale of botanical material from other species as no-de-cachorro, which indicates the importance of quality control studies. The H. tomentosa roots have flavonoids, tannins, saponins, terpenoids, and other phytochemical classes. The flavonoids astilbin, neoastilbin, and isoastilbin were identified in the plant and an aliphatic nitro compound with antimicrobial activity suggested as a possible marker. Pharmacological tests indicate that the hydroalcoholic extract of H. tomentosa has antioxidant activity and a beneficial effect on memory, especially in aged rats. The aqueous infusion produced positive effects on spermatogenesis and on the reproductive tract of male rats. Preclinical toxicological data are conflicting, indicating that the toxicity depends on the route of administration, dose, and animal species used.