Anti-Hyperuricemic, Anti-Arthritic, Hemolytic Activity and Therapeutic Safety of Glycoconjugated Triazole-Phthalimides.

Hyperuricemia, the metabolic alteration that leads to gout or gouty arthritis, is increasing worldwide. Glycoconjugated triazole-phthalimides show potent anti-inflammatory activity. The aim of this study was to evaluate the anti-hyperuricemia effect of glycoconjugated triazole-phthalimides. To develop hyperuricemia, groups of mice received orally potassium oxonate (250 mg/kg) for 7 days, and F2, F3 and F4 glycoconjugated triazole-phthalimides (20 mg/kg), allopurinol (300 mg/kg), and 1% carboxymethylcellulose; indomethacin (2 and 4 mg/kg) was the positive control for anti-arthritic effect. Genotoxic and mutagenic effects were evaluated by the comet and micronucleus assays, respectively. The hemolytic action of the compounds was evaluated. Phthalimides F2, F3 and F4 significantly reduced the levels of serum uric acid, creatinine and urea in hyperuricemic animals. In addition, the compounds were efficient in reducing protein denaturation in a dose-dependent manner. In an interesting way, the histopathological analysis of kidneys from groups treated with F2, F3 and F4 showed a glomerular architecture, with the Bowman's capsule and renal tubules having a normal appearance and without inflammatory changes. Also, F2 and F4 showed a small increase in micronuclei, indicating a low mutagenic effect, whilst by comet assay only, we could infer that F4 affected the frequency and damage index, thus indicating a very small genotoxic action. Similarly, the phthalimides showed a low degree of erythrocyte hemolysis (<3%). Our data demonstrate that the new glycoconjugate triazole-phthalimides have potential to treat hyperuricemia and its secondary complications, such as gouty arthritis, with a low to non-significant rate of erythrocytes hemolysis, genotoxicity and mutagenicity making these molecules strong candidates as pharmaceutical agents for treatment requiring uric-acid-lowering therapy.

Antioxidant, anti-inflammatory and analgesic activity of Mimosa acutistipula (Mart.) Benth.

ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal plants belonging to the genus Mimosa, such as Mimosa tenuiflora, M. caesalpinifolia, and M. verrucosa are known for their popular use for asthma, bronchitis and fever. Ethnopharmacological studies report that Mimosa acutistipula is used to treat alopecia and pharyngitis, conditions that can be related to oxidative stress, inflammatory processes and painful limitations. However, there is no studies on its efficacy and mechanism of action. AIM OF THE STUDY: To elucidate the antioxidant, anti-inflammatory, analgesic and antipyretic activity of M. acutistipula leaves. MATERIALS AND METHODS: Phytochemical profile of M. acutistipula extracts was evaluated by several reaction-specific methods. Secondary metabolites such as tannins, phenols and flavonoids were quantified with colorimetric assays. In vitro antioxidant potential was evaluated using DPPH and ABTS + as free radical scavenging tests, FRAP and phosphomolybdenum as oxide-reduction assays, and anti-hemolytic for lipid peroxidation evaluation. In vivo anti-inflammatory evaluation was performed by paw edema, and peritonitis induced by carrageenan. Analgesic effect and its possible mechanisms were determined by acetic acid-induced abdominal writhing and the formalin test. Antipyretic activity was evaluated by yeast-induced fever. RESULTS: Cyclohexane, chloroform, ethyl acetate and methanol extracts of leaves had presence of tannins, flavonoids, phenol, alkaloids, terpenes (except methanolic extract), and saponins (only for methanolic and chloroformic extracts). In phenols, flavonoids and tannins quantification, methanolic and ethyl acetate extract had higher amounts of this phytocompounds. Ethyl acetate extract, due to its more expressive quantity of phenols and flavonoids, was chosen for carrying out the in vivo tests. Due to the relationship between oxidative stress and inflammation, antioxidant tests were performed, showing that ethyl acetate extract had a high total antioxidant activity (70.18%), moderate activity in DPPH radical scavenging, and a moderate ABTS + radical inhibition (33.61%), and FRAP assay (112.32 µg Fe2+/g). M. acutistipula showed anti-inflammatory activity, with 54.43% of reduction in paw edema (50 mg/kg) when compared to the vehicle. In peritonitis test, a reduction in the concentration of NO could be seen, which is highly involved in the anti-inflammatory activity and is responsible for the increase in permeability. In the analgesic evaluation, most significant results in writhing test were seen at 100 mg/kg, with a 34.7% reduction of writhing. A dual mechanism of action was confirmed with the formalin test, both neurogenic and inflammatory pain were reduced, with a mechanism via opioid route. In the antipyretic test, results were significantly decreased at all concentrations tested. CONCLUSION: M. acutistipula leaves ethyl acetate extract showed expressive concentrations of phenolic compounds and antioxidant activity. It also exhibited anti-inflammatory and analgesic activity, besides its antipyretic effect. Thus, these results provide information regarding its popular use and might help future therapeutics involving this specimen.

Anti-inflammatory, hypoglycemic, hypolipidemic, and analgesic activities of Plinia cauliflora (Mart.) Kausel (Brazilian grape) epicarp.

ETHNOPHARMACOLOGICAL RELEVANCE: Plinia cauliflora (Mart.) Kausel, known in Brazil as jabuticaba or jaboticaba has been used by Brazilian native populations for medicinal purposes, including those related to inflammatory conditions, such as asthma, diarrhea, disorders in female genitourinary tract, and tonsillitis. Inflammation has emerged as a main factor for the oxidative stress, hyperglycemia, and dyslipidemia present in chronic noncommunicable diseases (NCDs). Such disturbances have been a leading cause of death worldwide for decades, despite significant efforts in developing new therapies. Therefore, strengthening the relevance of ethnobotanic approaches, as P. cauliflora has the potential to become a natural, native, and traditional product to prevent and treat inflammation-associated diseases more effectively for more people. AIM OF THE STUDY: Evaluate anti-inflammatory, hypoglycemic, hypolipidemic, and analgesic properties of hydroethanolic extract of P. cauliflora epicarps (PcE). MATERIALS AND METHODS: Phytochemical compound from the PcE were identified through HPLC-DAD-ESI-MSn analysis. Antioxidant activity was determined by measuring 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging. The anti-inflammatory potential was investigated by carrageenan-induced paw edema and peritonitis in mice. Analgesic effect was assessed, in mice, though hot plate test and acetic acid-induced abdominal writhing. Antidiabetic and hypolipidemic potential were evaluated using alloxan-induced diabetic mice. RESULTS: Tannins, phenolic acids, and their derivatives were the predominant phytochemicals found. Overall, PcE showed different properties related to the treatment of clinical conditions associated with chronic diseases as a potent antioxidant activity, demonstrating a radical scavenging action similar to gallic acid. PcE oral administration also significantly reduced inflammation induced by paw edema and partially blocked leukocyte migration. Moreover, PcE produced peripheral and central analgesic effects, as evaluated in the writhing model and hot plate tests. Treatment with PcE significantly improved glucose levels and lipid markers in diabetic mice. CONCLUSIONS: P. cauliflora fruits are rich sources of secondary metabolites, mainly tannins and phenolic acids with high biological potential, which can effectively contribute to the approach of preventing and controlling chronic NCDs.