ABSTRACT
Objectives: To evaluate the effects of Amburana cearensis leaf extract against cisplatin-induced ovarian toxicity in mice and involvement of p-PTEN and p-Akt proteins. Materials and Methods: A. cearensis ethanolic leaf extract was analyzed by high-performance liquid chromatography (HPLC). Mice were pretreated once daily for 3 days as follows: (1) the control group was pretreated with oral administration (o.p.) of saline solution, followed by intraperitoneal (IP) injection of saline solution. The other groups were pretreated (o.p.) with (2) saline solution (cisplatin group), (3) N-acetylcysteine (positive control), with (4) 50, or (5) 200 mg/kg body weight of A. cearensis extract, followed by injection of 5 mg/kg body weight (IP) of cisplatin. The ovaries were harvested and destined for histological (follicular morphology), immunohistochemistry (apoptosis and cell proliferation), and fluorescence (reactive oxygen species [ROS], glutathione concentrations [GSH], and active mitochondria) analyses. Furthermore, immunoexpression of p-PTEN and p-Akt was evaluated to elucidate a potential mechanism by which A. cearensis extract could prevent cisplatin-induced ovarian damage. Results: After HPLC analysis, protocatechuic acid was detected in the extract. The pretreatment with N-acetylcysteine or A. cearensis extract maintained the percentage of normal follicles and cell proliferation, reduced apoptosis and ROS concentrations, and increased GSH concentrations and mitochondrial activity compared with cisplatin treatment. Furthermore, pretreatment with A. cearensis extract regulated p-PTEN and p-Akt immunoexpression after cisplatin exposure. Conclusion: Pretreatment with A. cearensis extract prevented cisplatin-induced ovarian damage through its anti-oxidant actions and by modulating the expression of phosphorylated PTEN and Akt proteins.
ABSTRACT
Syzygium cumini L. Skeels belongs to Myrtaceae family. This species has been recognized by its antidiabetic, anti-inflammatory, and antimicrobial activities. Despite ever-increasing scientific interest for this species there is no pharmacopeia method for characterization and standardization of S. cumini yet. So, toward this aim, the objective of this work was to develop an efficient analytical methodology able to determine polyphenols and tannins content from leaves hydroethanolic extract of S. cumini using Folin-Ciocalteu method by ultraviolet absorption spectrophotometry (UV-Vis). The analytical methodology was developed for the first time in the literature for leaves of this specie shown to be fast and low-cost with results expressed through tannic acid equivalent (TAE). Moreover, the methodology presented selectivity with maximum absorption at 706 nm wavelength, linearity with R2>0.99; limit of detection 0.275 µg TAE mL-1 and 0.102 µg TAE mL-1; limit of quantification 1.046 µg TAE mL-1 and 0.912 µg TAE mL-1 for total polyphenols and total tannins, respectively. Furthermore, the methodology was accurate with recover value greater than 98%, as well as exact, reproductive, and robust with coefficient of variation values less than 15% for both compounds. All the results are found within the fixed limits according to RDC 166/2017.
Subject(s)
Syzygium , Antioxidants , Plant Extracts , Plant Leaves , Polyphenols , TanninsABSTRACT
The present study consisted in optimizing the extractive method of polyphenols and total tannins of leaves of Syzygium cumini (L) Skeels assisted by microwaves to potentiate the antimicrobial activity of the dried extract of S. cumini against sensitive and resistant strains. A Box-Behnken design that consisted of 27 experimental runs coupled with a desirability function for multiple response optimization was employed to optimize the total polyphenols content and total tannins content. Antimicrobial sensitivity tests were evaluated by obtaining the minimum inhibitory concentration, minimum fungicidal concentration and minimum bactericidal concentration in 96-well petri dishes. The optimal extraction conditions were found to be 8 min of extraction, under 300 w of microwave power, using a 1:34 g/mL solid/solvent ratio and 38% of ethanol concentration as extraction solvent. The parameter with the greatest influence in the extraction was primarily the time, followed by the potency and proportion solid/solvent. This yielded a total polyphenol content of 87.37 ± 1.85 mg TAE g-1ext and a total tannin content of 79.68 ± 1.64 mg TAE g-1 ext. All tested microorganisms were sensitive to the extract, evidencing the effectiveness of the extraction method optimization.
Subject(s)
Polyphenols , Syzygium , Antioxidants , Microwaves , Plant Extracts/pharmacology , Plant Leaves , Research Design , TanninsABSTRACT
The frequent use of acaricides against the tick Rhipicephalus microplus increases the risk of development of resistance. Recent studies have revealed that Neoglaziovia variegata, an indigenous plant species known in Brazil as 'caroá', has a deleterious effect against R. microplus. In the current study, extracts of N. variegata were studied for their possible acaricidal properties. A hexane extract of N. variegata leaves was fractionated in a chromatography column and the fractions were tested in adult tick immersion tests in triplicate using three concentrations (5, 10 and 25 mg/ml). All the fractions had harmful effects on the ticks. However, three fractions were more efficaceous. Phytochemical analysis indicated that stigmast-5-en-3-ol and stigmastanol were most abundant; they might be responsible for the acaricidal effects, making them potentially useful as alternative agents to control the tick R. microplus.
Subject(s)
Acaricides , Bromeliaceae , Rhipicephalus , Tick Infestations , Animals , Brazil , Hexanes , Larva , Plant Extracts/pharmacology , Plant LeavesABSTRACT
Triplaris gardneriana is used by traditional medicine. The objective of this work was the leaves chemical study with isolate, identify and quantify the chemical constituent, validate the analytical method and evaluate the antibacterial activity. The ethyl acetate and chloroform fractions were subjected to column chromatography for isolation of the compounds quercetin and lupeol, respectively. For the identification, quantification of quercetin in the samples and validation of method were performed using HPLC-DAD. The antibacterial activity was evaluated by the microdilution method. The isolated phytochemicals are being reported for the first time in the species. The ethyl acetate fraction showed a higher content of quercetin with 9.967 ± 1.01 mg.g-1. The method was validated. The samples showed good antibacterial activity. In this study, quercetin was isolated and quantified in the species being a great alternative as a producer of this secondary metabolite, which can be safely applied in the quality control analysis.
Subject(s)
Anti-Bacterial Agents/pharmacology , Polygonaceae/chemistry , Quercetin , Anti-Bacterial Agents/isolation & purification , Chromatography, High Pressure Liquid , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , Plant Extracts , Plant Leaves/chemistry , Quercetin/isolation & purification , Quercetin/pharmacologyABSTRACT
BACKGROUND: The health area in its most diverse fields has progressively incorporated nanotechnology into its products, such as in dermatology. In this sector, nanoparticles are one of the strategies that allow improvements, both in terms of value-added, as well as the efficacy, safety and stability of products for cosmetic or therapeutic purposes. OBJECTIVE: To understand the scenario of development and innovation of dermatological products with nanoparticles, through a patent prospection, evaluating the annual evolution, the main technology investors countries, the profile of the depositors, besides the uses and purposes of the products. METHODS: The Espacenet® database was used for consultation, using the search term "nanoparticle and skin". A total of 285 patents were found, of which 208 were available and 89 were based on the scope. RESULTS: There was a progressive evolution in the number of patents after the year 2000, with South Korea, the United States, China and Japan as the main depositor countries. Private companies and Education and Research Institutions were the entities with the largest amount of deposits. The cosmetic purpose was the predominant use compared to the therapeutic one. The most prominent nanoparticles were polymeric, metallic and lipid, while the therapeutic area presented a larger number of the functionalized ones. CONCLUSION: The market for dermatological products has been innovating and growing over the years through the use of nanoparticles, evidencing a prominent development of nanotechnology-based cosmetics. Countries investing in nanotechnology and major developers of innovative products are highlighted in this scenario.
Subject(s)
Dermatology , Inventions , Nanoparticles/chemistry , Patents as Topic , Cosmetics , HumansABSTRACT
Alternanthera brasiliana is popularly known as 'penicillin' and used as an anti-inflammatory and for wound healing. The objective of this work was the phytochemical study of the species by analytical techniques such as LC-MS/MS and GC-MS. Twenty-seven compounds were identified, five by LC-MS and 22 by GC-MS analysis. All compounds identified by LC-MS are flavonoids. However, several classes were found in GC-MS analysis, such as hydrocarbons, diterpenes, monoterpenes, vitamin and carotenoid derivatives, phytosterols and triterpenes. In the analysis, it is suggested the presence of 27 substances, of which 23 are unpublished for the species, that reaffirms the importance of this study and the contribution to chemical knowledge.
Subject(s)
Amaranthaceae/chemistry , Phytochemicals/analysis , Anti-Inflammatory Agents , Carotenoids/analysis , Chromatography, Liquid/methods , Flavonoids/analysis , Gas Chromatography-Mass Spectrometry/methods , Phytochemicals/isolation & purification , Phytosterols/analysis , Plant Extracts/chemistry , Tandem Mass Spectrometry/methods , Terpenes/analysis , Wound HealingABSTRACT
Ethnomedicinal studies in the Amazon community and in the Northeast region of Brazil highlight the use of Libidibia ferrea fruits for the treatment of gastric problems. However, there are no data in the literature of this pharmacological activity. Thus, the aim of this paper is to provide a scientific basis for the use of the dry extract of L. ferrea pods (DELfp) for the treatment of peptic ulcers. Phytochemical characterization was performed by HPLC/MS. In vitro antioxidant activity was assessed using DPPH, ABTS, phosphomolybdenum, and superoxide radical scavenging activity. The gastroprotective activity, the ability to stimulate mucus production, the antisecretory activity, and the influence of -SH and NO compounds on the antiulcerogenic activity of DELfp were evaluated. The healing activity was determined by the acetic acid-induced chronic ulcer model. Anti-Helicobacter pylori activity was investigated. HPLC/MS results identified the presence of phenolic compounds, gallic acid and ellagic acid, in DELfp. The extract showed antioxidant activity in vitro. In ulcers induced by absolute ethanol and acidified ethanol, the ED50 values of DELfp were 113 and 185.7 mg/kg, respectively. DELfp (100, 200, and 400 mg/kg) inhibited indomethacin-induced lesions by 66.7, 69.6, and 65.8%, respectively. DELfp (200 mg/kg) reduced gastric secretion and H+ concentration in the gastric contents and showed to be independent of nitric oxide (NO) and dependent on sulfhydryl (-SH) compounds in the protection of the gastric mucosa. In the chronic ulcer model, DELfp reduced the area of the gastric lesion. DELfp also showed anti-H. pylori activity. In conclusion, DELfp showed antioxidant, gastroprotective, healing, and antiulcerogenic activities. The mechanism of these actions seems to be mediated by different pathways and involves the reduction of gastric secretion and H+ concentration, dependence on sulfhydryl compounds, and anti-H. pylori activity. All these actions support the medicinal use of this species in the management of peptic ulcers.
Subject(s)
Anti-Ulcer Agents/chemistry , Antioxidants/chemistry , Fabaceae/chemistry , Plant Extracts/chemistry , Acetic Acid/toxicity , Animals , Anti-Ulcer Agents/pharmacology , Anti-Ulcer Agents/therapeutic use , Chromatography, High Pressure Liquid , Fabaceae/metabolism , Female , Gastric Mucosa/drug effects , Gastric Mucosa/pathology , Helicobacter pylori/drug effects , Mass Spectrometry , Nitric Oxide/chemistry , Nitric Oxide/metabolism , Phenols/analysis , Plant Extracts/pharmacology , Rats , Rats, Wistar , Stomach Ulcer/chemically induced , Stomach Ulcer/drug therapy , Stomach Ulcer/pathology , Sulfhydryl Compounds/chemistry , Sulfhydryl Compounds/metabolismABSTRACT
Cirsiliol is a flavone found in many Lamiaceae species with high cytotoxic activity against tumor cell lines. Although cirsiliol is being used in cancer therapy, its pharmacological potential is limited by its low solubility and bioavailability. In this paper, a cirsiliol-ß-cyclodextrin inclusion complex was developed in order to increase its solubility and bioavailability. The formation of inclusion complex was proved by scanning electron microscopy, Fourier-transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) and solubility increment was verified through the ultraviolet-visible (UV-Vis) method. The cytotoxic effect against tumor cells (PC3, HCT-116 and HL-60 human cell lines, and S-180 murine cell line) and the antitumor activity in mice bearing sarcoma S-180 were also investigated. The inclusion complex was obtained with 71.45% of total recovery and solubility 2.1 times higher compared to the compound in its free form. This increment in solubility was responsible by a tumor growth inhibition potentiation (1.5 times greater compared to compound in its free form). In addition, this study showed that cirsiliol and its inclusion complex in ß-cyclodextrin have strong antitumor potential at low doses without promoting side effects commonly observed for conventional drugs as doxorubicin.
ABSTRACT
This study aimed to verify the chelating, antioxidant and cytoprotective activities of Psidium brownianum Mart. Ex DC against mercury and aluminum. The ethanolic extract, as well as the tannic and flavonoid fractions, were prepared and subjected to liquid chromatography-mass spectrometry analysis. Ferric ion reduction and antioxidant activity measurement using the FRAP method were performed with P. brownianum. After determining the sub-allelopathic doses, germination tests using Lactuca sativa (lettuce) seeds were performed. The main compounds identified in the extract and fractions were: quercetin and its derivatives; myricetin and its derivatives; gallic acid; ellagic acid; quinic acid and gallocatechin. The Minimum Inhibitory Concentration (MIC) for all samples wereâ¯≥â¯1024⯵g/mL. The flavonoid fraction in association with mercury chloride demonstrated cytoprotection (pâ¯<â¯0.001). The sub-allelopathic concentration used was 64⯵g/mL. The extract and fractions were cytoprotective for radicles and caulicles when assayed in association with mercury and against aluminum for radicles. This suggests that the P. brownianum extract and its fractions present cytoprotective activity, possibly related to the antioxidant effect of secondary metabolites, especially flavonoids.
Subject(s)
Aluminum Chloride/toxicity , Antioxidants/pharmacology , Chelating Agents/pharmacology , Mercuric Chloride/toxicity , Plant Extracts/pharmacology , Psidium , Allelopathy , Antioxidants/chemistry , Candida albicans/drug effects , Candida albicans/growth & development , Chelating Agents/chemistry , Chromatography, Liquid , Cytoprotection , Escherichia coli/drug effects , Escherichia coli/growth & development , Flavonoids/analysis , Flavonoids/pharmacology , Germination/drug effects , Iron/chemistry , Lactuca/drug effects , Lactuca/growth & development , Mass Spectrometry , Plant Extracts/chemistryABSTRACT
The present study had as its objective to verify the Psidium guajava var. Pomifera L. chelating, antioxidant and cytoprotective effects against mercury and aluminum. The ethanolic extract, tannic and flavonoid fractions were subjected to LC-MS analysis. The Ferric Reducing Antioxidant Power (FRAP) and ferric ion reduction demonstrated a present antioxidant activity. The fungicidal and bactericidal activity of these metals were established. After determining the sub-allelopathic doses, germination tests using Lactuca sativa were performed. Quercetin and its derivatives were the main compounds identified in the extract and the fractions. Mercury chloride significantly reduced the bactericidal effect of the flavonoid fraction (pâ¯<â¯0.001). None of the fractions were cytoprotective against mercury or aluminum in the fungal model assays. Using a sub-allelopathic concentration (64⯵g/mL), the ethanolic extract, flavonoid and tannic fractions were found to be cytoprotective against aluminum for radicles, however only the tannic fraction was cytoprotective for caulicles. These data suggest that natural P. guajava products are promising cytoprotective compound sources. This activity may be related to the antioxidant effect of secondary metabolites, mainly flavonoids. Our results point to a potential for environmental intervention product and technique development aimed at mitigating contamination by toxic metals such as mercury and aluminum.
Subject(s)
Antioxidants/chemistry , Flavonoids/chemistry , Metals, Heavy/toxicity , Psidium/chemistry , Antioxidants/analysis , Metals, Heavy/analysisABSTRACT
The objective of this work was to evaluate the antioxidant, metal chelating and cytoprotective activity of the Eugenia jambolana Lam. extract, as well as of its flavonoid and tannic fractions, against the action of Mercury Chloride (HgCl2). Flavonoids were quantified and an LC-MS chromatographic analysis was performed to identify secondary metabolites. Fe2+ and Fe3+ chelation tests and antioxidant activity were carried out using the FRAP method. Microbiological tests were performed by microdilution to determine the Minimum Inhibitory Concentration (MIC). From these results the Minimum Bactericidal (MBC) and Minimum Fungicide Concentration (MFC) were evaluated. The allelopathy and cytoprotection assays were performed using eukaryotic and prokaryotic models. The results revealed the presence of phenolic acids and flavonoids in the E. jambolana extract and fractions. The sub-allelopathic concentration (64⯵g/mL) was used and the results demonstrated the E. jambolana potential cytoprotective effect against mercury chloride.
Subject(s)
Biological Products/chemistry , Mercuric Chloride/toxicity , Syzygium/chemistry , Allelopathy , Anti-Infective Agents/chemistry , Antioxidants/chemistry , Cytoprotection , Flavonoids/chemistry , Lactuca/drug effects , Microbial Sensitivity Tests , Plant Extracts/chemistryABSTRACT
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.
Subject(s)
Anacardiaceae , Fruit and Vegetable Juices , Gastric Mucosa , Stomach Ulcer , Animals , Drug Evaluation, Preclinical , Ethanol/adverse effects , Ethanol/pharmacology , Female , Gastric Mucosa/metabolism , Gastric Mucosa/pathology , Male , Rats , Rats, Wistar , Stomach Ulcer/chemically induced , Stomach Ulcer/drug therapy , Stomach Ulcer/metabolism , Stomach Ulcer/pathologyABSTRACT
We prepared a number of di- and trifunctionalized quinolines by selective metalation of chloro-substituted quinolines with metal amides followed by reaction with different electrophiles. Metalation of the C-3 position of the quinolinic ring with lithium diisopropylamide at -70 °C is easy to achieve, whereas reaction with lithium-magnesium and lithium-zinc amides affords C-2 or C-8 functionalized derivatives in a regioselective fashion. These complementary methods could be rationalized by DFT calculations and are convenient strategies toward the synthesis of bioactive quinoline derivatives such as chloroquine analogues.
ABSTRACT
Neglected diseases are those that are prevalent in developing countries, even with a rich biodiversity. These diseases still persist because of the lack of scientific studies, government negligence or failures of the public health system. This study aims to identify the composition of extracts and fractions from Psidium brownianum and Psidium guajava through LC-MS, to evaluate its in vitro anti-parasitic and cytotoxic activity against Trypanosoma cruzi, Leishmania brasiliensis and L. infantum epismastigote and promastigote forms, as well as mammalian cells. The results showed the presence of chemical constituents in the two Psidium species as quercetin, myricetin and gallic acid derivatives. The P. brownianum extract and fractions showed low toxicity at all tested concentrations and all samples were effective at the concentration of 1000µg/mL against the parasites, with the extract being the most efficient against the L. infantum promastigote form. The ethanolic extract, and the flavonoid and tannic fractions, from P. guajava showed low toxicity for the fibroblasts. All samples showed effectiveness at the highest concentration tested and the extract was more effective against the promastigote forms tested. The results showed that the species Psidium brownianum and Psidium guajava demonstrated an anti-parasitic activity against the T. cruzi, L. brasiliensis and L. infantum parasite cell lines indicating these species as an alternative therapy given their efficacy in the in vitro assays performed, opening the possibility for new biological studies to further this knowledge through in vivo assays.
Subject(s)
Leishmania braziliensis/drug effects , Leishmania infantum/drug effects , Plant Extracts/analysis , Plant Extracts/pharmacology , Psidium , Trypanosoma cruzi/drug effects , Animals , Biological Products/analysis , Biological Products/pharmacology , Chromatography, Liquid , Cytotoxins/pharmacology , Fibroblasts/drug effects , Flavonoids/pharmacology , Gallic Acid/analogs & derivatives , Gallic Acid/pharmacology , Mass Spectrometry , Plant Leaves , Quercetin/analogs & derivatives , Quercetin/pharmacologyABSTRACT
Morus nigra has been used popularly for several proposes, including diabetic. In an attempt to support medicinal value, the acute hypoglycemic, hypolipidemic, and antioxidant effects of the ethanolic extract of Morus nigra (EEMn 200 or 400 mg/kg b.w.) were evaluated in normal and alloxan-induced diabetic treated for 14 days. Serum biochemical and antioxidant analysis were performed at the end of experiment. Oral glucose tolerance test was performed at 10th and 15th days. Chromatographic analysis by HPLC-DAD of EEMn was performed. Insulin was used as positive control to glycemic metabolism as well as fenofibrate to lipid metabolism. EEMn (400 mg/kg/day) reduced fasting and postprandial glycaemia, improved oral glucose tolerance, and reduced lipolysis and proteolysis in diabetic rats. EEMn decreased the blood levels of total cholesterol and increased HDL level when compared to the diabetic control rats. At higher levels, EEMn reduced triglycerides and VLDL levels in diabetic rats. Also, EEMn reduced malondialdehyde and increased the reduced glutathione levels in liver of diabetic rats. Chromatographic analysis identified the presence of the flavonoids rutin, isoquercetin, and kaempferitrin. Acute EEMn treatment reduced hyperglycemia, improved oral glucose tolerance, and minimized dyslipidemia and oxidative stress leading to a reduction in atherogenic index in alloxan-induced diabetic rats.
Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Dyslipidemias/drug therapy , Hyperglycemia/drug therapy , Hypoglycemic Agents/pharmacology , Morus/chemistry , Plant Extracts/pharmacology , Alloxan , Animals , Blood Glucose/analysis , Brazil , Glucose Tolerance Test , Liver/metabolism , Rats , Rats, WistarABSTRACT
Hyptis umbrosa (syn. Mesosphaerum sidifolium) (Lamiaceae Family) has been used to treat several conditions such as gastrointestinal disorders, skin infections, nasal congestion, fever and cramps. The objective of this study was to evaluate the chemical composition, analgesic and anti-inflammatory profiles of ethanol extract from leaves of Hyptis umbrosa (EEB). HPLC-DAD was used to determine the fingerprint chromatogram of the extract. Male Swiss mice were orally pretreated with EEB (100, 200 or 400 mg/kg; 60 min before initiating algesic stimulation) and antinociceptive activity was assessed using the acetic acid-induced writhing model, formalin test and hyperalgesia induced by glutamate or capsaicin. Also, peritonitis was induced by the intrathoracic injection of carrageenan to quantify the total number of leukocytes. The presence of phenolic compounds in the extract was confirmed using HPLC-DAD. The treatment with EEB, at all doses, produced a significant analgesic effect against acetic acid-induced antinociceptive activity. In the formalin test, only the 400-mg/kg-dose of EEB had a significant effect in the first phase. However, all doses tested were able to reverse nociception in the second phase. The effect of all doses of EEB also showed a significant antinociceptive effect in the glutamate and capsaicin tests and inhibited the carrageenan-induced leukocyte migration to the peritoneal cavity. The present study suggests that the EEB possesses peripheral analgesic action and showed potential in reducing the spreading of the inflammatory processes. Also, it seems to be related with vanilloid and glutamate receptors.
ABSTRACT
UNLABELLED: Abstract Context: Benznidazole (BNZ) is an antiparasitic with trypanocidal properties for the etiological treatment of Chagas disease since 1973. Monitoring the stability of this drug is one of the most effective methods of assessment, forecasting and prevention of problems related to quality product. OBJECTIVE: To investigate the direct and indirect photodegradation of BNZ and to evaluate the interference of the excipients used in the forms dosage solid as well as to shed light on the chemical structure of the degradation products obtained. MATERIALS AND METHODS: To perform this work we adopted the "ICH Harmonised Tripartite Guideline: Photostability Testing of New Drug Substances and Products Q1B" (Guideline Q1B). We used benzonidazole (BNZ) (N-benzil-2-(2-nitroimidazol-1-il) acetamide) (LAFEPE®, Recife, Brazil) and various excipients; beyond high-performance liquid chromatography (HPLC), differential scanning calorimetry (DSC), infrared spectroscopy (IR) and mass spectrometry/mass spectrometry (MS/MS). The indirect photodegradation of BNZ was carried out using physical mixtures with 13 pharmaceutical excipients commonly used in the preparation of solid dosage forms. RESULTS: HPLC and MS/MS techniques were selected for the identification of two photoproducts (PPs) and photoreactions found in direct and indirect tests with the microcrystalline cellulose, considered a critical excipient. DISCUSSION: Despite variations in the infrared spectrometry, differential scanning calorimetry and differential thermogravimetry curves, these techniques are not conclusive since the study of photodegradation of the drug caused decay of 30%, according to the ICH. CONCLUSIONS: The results show that BNZ only undergoes direct photodegradation, since no new PPs were found for a combination of the drug and excipients.
Subject(s)
Chemistry, Pharmaceutical/methods , Excipients/chemistry , Nitroimidazoles/chemistry , Photolysis , Trypanocidal Agents/chemistry , Chagas Disease/drug therapy , Drug Stability , Excipients/radiation effects , Excipients/therapeutic use , Nitroimidazoles/radiation effects , Nitroimidazoles/therapeutic use , Photolysis/radiation effects , Trypanocidal Agents/radiation effects , Trypanocidal Agents/therapeutic useABSTRACT
Simarouba amara stem bark decoction has been traditionally used in Brazil to treat malaria, inflammation, fever, abdominal pain, diarrhea, wounds and as a tonic. In this study, we investigate the hepatoprotective effects of the aqueous extract of S. amara stem bark (SAAE) on CCl4-induced hepatic damage in rats. SAAE was evaluated by high performance liquid chromatography. The animals were divided into six groups (n = 6/group). Groups I (vehicle-corn oil), II (control-CCl4), III, IV, V and VI were pretreated during 10 consecutive days, once a day p.o, with Legalon® 50 mg/kg b.w, SAAE at doses 100, 250 and 500 mg/kg b.w, respectively. The hepatotoxicity was induced on 11th day with 2 mL/kg of 20% CCl4 solution. 24 h after injury, the blood samples were collected and their livers were removed to biochemical and immunohistochemical analyzes. The SAAE decreased the levels of liver markers and lipid peroxidation in all doses and increased the catalase levels at doses 250 and 500 mg/kg. Immunohistochemical results suggested hepatocyte proliferation in all doses. These results may be related to catechins present in SAAE. Thus, SAAE prevented the oxidative damage at the same time that increased regenerative and reparative capacities of the liver.
Subject(s)
Carbon Tetrachloride/adverse effects , Chemical and Drug Induced Liver Injury/drug therapy , Plant Bark/chemistry , Plant Extracts/pharmacology , Plant Stems/chemistry , Protective Agents/pharmacology , Simarouba/chemistry , Animals , Liver/drug effects , Male , Plant Extracts/chemistry , Protective Agents/chemistry , Rats , Rats, WistarABSTRACT
Spectrophotometric determinations (direct dilution or after acid hydrolysis) of flavonoid content in leaves of Bauhinia forficata Link, Fabaceae, from two different regions from Brazil were compared with contents of kaempferitrin quantified by HPLC analysis. The absence of kaempferitrin peak in one sample denotes the risk of LC-method failure. On the other hand, the both spectrophotometric assays showed satisfactory performance and do not underwent influence from absence of kaempferitrin. Since several flavonoids are present in the herbal material, different content of flavonoids were observed for each analytical procedure. However, a strong positive association could be detected among methods (R²>0.99). Although a conversion factor should be adopted to compare procedures, the data showed that the spectrophotometric methods remain as an important tool for analysis of complex matrices such herbal drugs, notably when there aren't any pharmacological or chemical marker established for the species. Moreover, it's possible to suggest that the techniques studied in this work exhibit similar performance under the conditions employed. Nevertheless, before the adoption of kaempferitrin as an analytical marker by HPLC for Bauhinia species, the pharmacological knowledge should be better developed. In this cases, the use of spectrophotometric assay provide higher assurance of the reproducibility of the efficacy and safety.