Croton campestris A. St.-Hill Methanolic Fraction in a Chlorpyrifos-Induced Toxicity Model in Drosophila melanogaster: Protective Role of Gallic Acid.

Croton campestris A. St-Hill popularly known as "velame do campo" is a native species of the savannah from northeastern Brazil, being used in folk medicine due to its beneficial effects in the treatment of many diseases, inflammation, detoxification, gastritis, and syphilis; however, its potential use as an antidote against organophosphorus compound poisoning has not yet been shown. Here, the protective effect of the methanolic fraction of C. campestris A. St.-Hill (MFCC) in Drosophila melanogaster exposed to chlorpyrifos (CP) was investigated. Flies were exposed to CP and MFCC during 48 h through the diet. Following the treatments, parameters such as mortality, locomotor behavior, and oxidative stress markers were evaluated. Exposure of flies to CP induced significant impairments in survival and locomotor performance. In parallel, increased reactive oxygen species and lipoperoxidation occurred. In addition, the activity of acetylcholinesterase was inhibited by CP, and superoxide dismutase and glutathione S-transferase activity was induced. Treatment with MFCC resulted in a blockage of all CP-induced effects, with the exception of glutathione S-transferase. Among the major compounds found in MFCC, only gallic acid (GA) showed a protective role against CP while quercetin and caffeic acid alone were ineffective. When in combination, these compounds avoided the toxicity of CP at the same level as GA. As far as we know, this is the first study reporting the protective effect of MFCC against organophosphate toxicity in vivo and highlights the biotechnological potential of this fraction attributing a major role in mediating the observed effects to GA. Therefore, MFCC may be considered a promising source for the development of new therapeutic agents for the treatment of organophosphate intoxications.

Molecular mechanism underlying orofacial antinociceptive activity of Vanillosmopsis arborea Baker (Asteraceae) essential oil complexed with ß-cyclodextrin.

BACKGROUND: Vanillosmopsis arborea Baker has recognized economic value owing to the high content of (-)-α-bisabolol (BISA) in the essential oil of its stem (EOVA). The antinociceptive effect of EVOA has already been demonstrated, and ß-cyclodextrin (ßCD) is known to improve the analgesic effect of various substances. PURPOSE: Thus, we aimed to evaluate the orofacial antinociceptive effect of a complex containing EOVA-ßCD in rodents. METHODS: EOVA was obtained by simple hydrodistillation, and the essential oil was complexed with ßCD. The animals (n = 6/group) were treated orally with EOVA-ßCD (10 or 50 mg/kg), or vehicle (control), and subjected to cutaneous orofacial nociception (formalin, capsaicin, acidic saline or glutamate), corneal (hypertonic saline) or temporomandibular (formalin) tests. The expression of FOS protein was analyzed in the spinal cord. Molecular docking was performed using the 5-HT3 and M2 receptors and BISA. RESULTS: The oral administration of EOVA-ßCD reduced nociceptive behaviour. Moreover, EOVA-ßCD decreased FOS expression. The molecular docking study indicates that BISA interacts with 5-HT3 and M2 receptors, indicating the potential mechanism of action of the tested compound. CONCLUSIONS: Our results indicate that EOVA-ßCD possesses orofacial antinociceptive effect, indicating that this complex can be used in analgesic drug development.

Evaluation of gastroprotective and ulcer healing activities of yellow mombin juice from Spondias mombin L.

Spondias mombin L. (yellow mombin) is a tree with a nutritional fruit that is commonly consumed in the North and Northeast of Brazil, as the juice of its pulp is rich in antioxidant compounds. This study aimed to investigate the gastroprotective and ulcer healing activities of yellow mombin juice (YMJ) in Wistar rats, and to elucidate the possible involved mechanisms. Phytochemical characterization of the lyophilized fruit juice was performed by high-performance liquid chromatography (HPLC). The gastroprotective activity of YMJ was investigated in ethanol (25, 50, and 100% YMJ) and indomethacin (100% YMJ) models of acute gastric ulcer in rats. Then, the effect of YMJ on mucus production and gastric secretions, and the involvement of non-protein sulfhydryl groups and prostaglandins in the gastroprotective process were examined. Moreover, the ulcer healing effect of YMJ was investigated in a model of acetic acid-induced chronic ulcer through histological and immunohistochemical analyses. HPLC results identified the presence of epicatechin (7.1 ± 1.6 µg/mL) and quercetin (17.3 ± 2.5 µg/mL) in YMJ. Ethanol-induced gastric lesions were inhibited by YMJ (25, 50, and 100%) by 42.42, 45.09, and 98.21% respectively, and indomethacin-induced lesions were inhibited by YMJ (100%) by 58.96%, compared to control group. Moreover, YMJ reduced gastric content and total acidy by 57.35 and 71.97%, respectively, compared to the control group. Treatment with YMJ also promoted healing of chronic ulcer, regeneration of the gastric mucosa, and restoration of mucus levels in glandular cells, as confirmed by histological analysis. It also increased cellular proliferation, as demonstrated by high reactivity to Ki-67 and bromodeoxyuridine. In conclusion, YMJ was found to possess gastroprotective and ulcer healing activities that are correlated to its antisecretory action. These results support the commercial exploration of YMJ as a functional food.

Evaluation of chemical composition and antiedematogenic activity of the essential oil of Hyptis martiusii Benth.

Evaluations of the therapeutic potential of medicinal plants and their components have been the subject of many studies. Furthermore, the biological activities of various plant species have been reported in various pieces of literature. Hyptis martiusii Benth (Lamiaceae), popularly known as "mad balm" is commonly found in the North, Southeast, and Northeast of Brazil. Its leaves are used ethnobiologically as antiulcerogenic, antimicrobial, antitumor and as insecticide. This study aimed to analyze the chemical composition of the essential oil of H. martiusii Benth (OEHM) by GC/MS as well as its possible topical activity as an antiedematogenic. This is verified by the models of ear edema induced by single (acute edema) and multiple (chronic edema) applications of croton oil topically, and systemically verified through the model of paw edema induced by carrageenan 1%. Doses of 50, 75 and 100 mg/kg OEHM were used in all tests. Chemical analysis of the oil revealed the 1,8-cineole (34.58%) and δ-carene (21:58%) as major components present in the essential oil. On the model of ear edema, acute and chronic OEHM in all the tested doses showed no significant antiedematogenic activity (p < 0.05). The systemic model of paw edema induced by carrageenin showed that a dose of 100 mg/kg effectively reduced swelling by 55.37% in the second hour evaluation when compared to the saline group. The anti-inflammatory systemic effect can give greater bioavailability of the components present in the essential oil and your interference in cytokines and leukotriene, thromboxane and prostaglandin biosynthesis. It is therefore concluded that OEHM presents systemic antiedematogenic activity but not topical activity at these doses.

Oxidant effects and toxicity of Croton campestris in Drosophila melanogaster.

CONTEXT: Croton campestris A.St.-Hil. (Euphorbiaceae) is a species native to Northeast Brazil used by traditional communities for the treatment of a variety of health problems. However, potential toxicological effects of this plant are unknown. OBJECTIVE: The potential toxicity of the hydroalcoholic extract of C. campestris leaves on Drosophila melanogaster insect model, additionally with phytochemical constitution and cellular mechanisms mediating the action of extract were analysed in this study. MATERIALS AND METHODS: Constituents of the extract were evaluated by HPLC. In vitro antioxidant potential of extract was analysed by DPPH, ABTS and FRAP. Flies injected culture medium mixed with extract (0.1-50 mg/mL) for 72 h. After, ROS production was evaluated by DCF-DA oxidation. Phosphorylation of MAPK signalling pathway was investigated by Western blotting method. Activity of antioxidant enzymes was analysed in homogenates. RESULTS: Major components of the extract include quercetin (38.11 ± 0.06 mg/g), caffeic acid (20.06 ± 0.17 mg/g) and kaempferol (15.45 ± 0.05 mg/g). Consumption of the extract impaired locomotor performance and induced fly death of flies (LC50 of 26.51 mg/mL). Augmented ROS formation and SOD, CAT and GST activity were observed from 0.1 mg/mL. JNK and p38 kinases phosphorylation was modulated and Paraquat-induced toxicity was augmented by extract. DISCUSSION AND CONCLUSION: Our data show important toxicological effects of C. campestris leading to increased mortality and impaired locomotor performance accompanied by induction of cell stress markers in flies. The study draws attention to the indiscriminate use of plant extracts.

Protective effects of Croton campestris A. St-Hill in different ulcer models in rodents: evidence for the involvement of nitric oxide and prostaglandins.

ETHNOPHARMACOLOGICAL RELEVANCE: Croton campestris A. St.-Hill., popularly known as "velame do campo", is a species native from savannah area of Northeast Brazil, which is used by traditional communities in folk medicine for a variety of health problems, especially detoxification, inflammation and gastritis. The present study investigates the possible gastric antiulcer activity of Croton campestris root extract (CCRE) and mechanisms of action underlying this effect. MATERIALS AND METHODS: Gastric lesions were induced in mice by ethanol, acidified ethanol and indomethacin. CCRE was previously administered orally in doses ranging from 50 to 750 mg/kg. Stomach lesions were measured. The involvement of Nitric Oxide (NO), prostaglandins (PGEs), ATP-dependent K+ channel and adrenergic receptor was investigated through specific inhibitors. RESULTS: CCRE produced significant antiulcer activity against absolute ethanol, acidified ethanol and indomethacin induced gastric lesions. The pretreatment with L-NAME (10 mg/kg, p.o.), an inhibitor of nitric oxide synthesis and indomethacin (10 mg/kg, s.c.), an inhibitor of prostaglandin production, reversed the antiulcer action of CCRE. CONCLUSION: Taking together, these results suggest that the antiulcer activity of CCRE is dependent of NO and prostaglandin pathways possibly due to its ability to stimulate the synthesis of NO, and activation of endogenous prostaglandin production. Therefore, the use of CCRE in traditional Brazilian medicine against gastric disorders has a scientific basis.

Antiulcerogenic Activity of the Hydroalcoholic Extract of Leaves of Croton campestris A. St.-Hill in Rodents.

Croton campestris A. St.-Hill., popularly known as "velame do campo," is a species native to the savannah area of Northeast Brazil, which is used by traditional communities in folk medicine for variety of health problems, especially detoxification, inflammation, and gastritis. The hydroalcoholic extract of C. campestris leaves (HELCC) was assessed for its antiulcerogenic effect in gastric lesion models and effect on intestinal motility in mice, and possible mechanisms of action were examined. HELCC showed significant gastroprotective action in all models of gastric ulcer evaluated; the results suggest that this action probably involves the nitric oxide pathway. HELCC did not show alteration of intestinal motility in mice. It was also found that C. campestris represents a promising natural source with important biological potential, justifying some of its uses in folk medicine.