Nerolidol-beta-cyclodextrin inclusion complex enhances anti-inflammatory activity in arthritis model and improves gastric protection.

Rheumatoid arthritis is an autoimmune inflammatory disease with progressive degradation of cartilage and joints. Additionally, gastric ulcer affects many patients who make prolonged use of non-steroidal anti-inflammatory drugs widely used in the symptomatic treatment of rheumatoid arthritis. Nerolidol, a natural sesquiterpene, has several biological activities including anti-inflammatory and antiulcerogenic action. This study aims to develop and characterize a nerolidol ß-cyclodextrin inclusion complex and to evaluate its activity in an experimental arthritis model. Inclusion complex was prepared by the lyophilization method and characterized by NMR, term analysis, XRD and SEM. Neutrophil migration assays and histopathological analysis were performed on zymosan-induced arthritis model using Swiss mice. And the gastroprotective effect was evaluated in two models of gastric ulcers: induced by ethanol and indomethacin. Inclusion complex showed no cytotoxicity and free nerolidol at a dose of 100 mg/kg (p.o.) in the arthritis model reduced neutrophil migration in 56% in relation to vehicle, and this inhibition was more expressive in the inclusion complex (67%) at the same dose. Histopathological analysis of the joint tissue confirmed the reduction of inflammatory signs. In the ethanol-induced gastric ulcer model, free nerolidol reduced the relative ulcer area more expressively (4.64%) than the inclusion complex (21.3%). However, in the indomethacin induction model, the inclusion complex showed better results in gastric protection compared to free nerolidol. The action of nerolidol complexed in beta-cyclodextrin in reducing arthritis inflammation combined with its gastroprotective action make it a potential new drug.

(-)-linalool-Loaded Polymeric Nanocapsules Are a Potential Candidate to Fibromyalgia Treatment.

Fibromyalgia (FM) is a chronic disease that has as main characteristic generalized musculoskeletal pain, which can cause physical and emotional problems to patients. However, pharmacological therapies show side effects that hamper the adhesion to treatment. Given this, (-)-linalool (LIN), a monoterpene with several therapeutic properties already reported in scientific literature as anti-depressive, antinociceptive, anti-inflammatory, and antihyperalgesic also demonstrated therapeutic potential in the treatment of FM. Nevertheless, physicochemical limitations as high volatilization and poor water-solubility make its use difficult. In this perspective, this present research had performed the incorporation of LIN into polymeric nanocapsules (LIN-NC). Size, morphology, encapsulation efficiency, cytotoxicity, and drug release were performed. The antihyperalgesic effect of LIN-NC was evaluated by a chronic non-inflammatory muscle pain model. The results demonstrated that the polymeric nanocapsules showed particle size of 199.1 ± 0.7 nm with a PDI measurement of 0.13 ± 0.01. The drug content and encapsulation efficiency were 13.78 ± 0.05 mg/mL and 80.98 ± 0.003%, respectively. The formulation did not show cytotoxicity on J774 macrophages. The oral treatment with LIN-NC and free-LIN increased the mechanical withdrawal threshold on all days of treatment in comparison with the control group. In conclusion, LIN-NC is a promising proposal in the development of phytotherapy-based nanoformulations for future clinical applications.

Volatile profiling and UHPLC-QqQ-MS/MS polyphenol analysis of Passiflora leschenaultii DC. fruits and its anti-radical and anti-diabetic properties.

Twenty-four phenolic compounds including daidzein, epicatechin and artepillin C were identified in Passiflora leschenaultii DC. fruit by UHPLC-QqQ-MS/MS analysis. The aroma profile has been studied using the HS-SPME/GC-MS which revealed 67 volatile compounds including 13 terpenes, 18 alcoholics, 15 esters, ketones and phenolic acids. Further, the proximate composition, anti-radical and anti-diabetic activities of fruit pulp were also determined. The fresh fruit pulp of P. leschenaultii registered higher total phenolic (691.90 mg GAE/g extract) and tannin (313.81 mg GAE/g extract) contents and it also exhibited maximum DPPH (IC50 of 6.69 µg/ml) and ABTS+ (9760.44 µM trolox equivalent/g extract) scavenging activities. The fresh fruit pulp showed a strong inhibition towards the α-Amylase and α-Glucosidase (IC50 of 32.20 and 19.81 µg/mL, respectively) enzymes. Thus, the work stipulates that phenolic compounds rich P. leschenaultii fruit can serve as a potential nutraceutical, antioxidative and anti-diabetic agent in food and pharmaceutical formulations.

Protective effects of flavonoid composition rich P. subpeltata Ortega. on indomethacin induced experimental ulcerative colitis in rat models of inflammatory bowel diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Polyphenolics (flavonoid and phenolic) rich plants are the effective source for the treatment of acute and chronic degenerative diseases including inflammatory bowel disease. OBJECTIVE: This study was aimed to examine the effects of polyphenolics rich leaf acetone extract of P. subpeltata against the indomethacin induced ulcerative colitis in rats. MATERIALS AND METHODS: Two consecutive days administration of indomethacin produced chronic inflammation in GIT tissues of rats. Further, the plant extract 200 and 400 mg/kg treatment were continued until 11th day. Then hematological, enzymatic antioxidants, MPO and histological evaluations were analyzed. Moreover, the extracts were treated with RAW267.4 cells for the cytotoxicity, NO and TNF-α analysis. RESULTS: The obtained results revealed, that higher dose of the plant extract dropped neutrophil infiltration followed by inhibiting the MPO enzyme levels and controls the enzymatic antioxidants such as SOD, CAT, GSH and LPO. RAW cells study also proved that the plant extract effectively inhibits NO and TNF-α production. CONCLUSIONS: Thus, these results suggest that P. subpeltata extract may have therapeutic potential for the treatment of IBD although further clinical research is still warranted.

UHPLC-QqQ-MS/MS identification, quantification of polyphenols from Passiflora subpeltata fruit pulp and determination of nutritional, antioxidant, α-amylase and α-glucosidase key enzymes inhibition properties.

The diabetic key enzymes inhibition, nutritional, antioxidant activity and bioactive compounds identification of Passiflora subpeltata fruit pulp were investigated. Fifteen polyphenolic compounds including protocatechuic acid, ferulic acid, vanillic acid, epicatechin, p-coumaric acid, cinnamic acid, eriodictyol and quercetin-3-glucoside were identified in the pulp of this species by using UHPLC-QqQ-MS/MS analysis. The total carbohydrates and crude protein contents in fruit pulp were 2.62 mg glucose equivalent/g sample fruit pulp and 8.80 mg BSA equivalent/g sample fruit pulp, respectively. The fresh fruit pulp of P. subpeltata contained high total phenolic (724.76 mg GAE/g sample) content and it revealed very high DPPH• (IC50 of 5.667 µg/mL) and ABTS+• (6794.96 µM trolox equivalent/g sample) scavenging activities. In the key enzymes assays useful for diabetic inhibition the fresh fruit pulp characterized maximum inhibition of α-amylase and α-glucosidase IC50 of 18.69 and 32.63 µg/mL, respectively. Thus, these results lead to conclude that this fruit specie could be very useful source in nutraceutical products preparations for Type 2 diabetic suffering humans.

Polyphenols rich Passiflora leschenaultii leaves modulating Farnesoid X Receptor and Pregnane X Receptor against paracetamol-induced hepatotoxicity in rats.

The hepatoprotective effect of P. leschenaultii. (DC) leaves was investigated in rats under paracetamol induced oxidative stress. Leaf acetone extract (200 and 400mg/kg) were administered daily via gavage for 14days before paracetamol (2000mg/kg, p.o.) treatment. After the experiment, the levels of serum biochemical parameters and enzymatic antioxidant levels were determined. Furthermore, liver tissues were analyzed histopathologically. Additionally, the molecular docking studies of the identified compounds against PXR and FXR proteins were also performed. The assessment revealed that the acetone extract significantly reduced the elevated levels of SGPT, SGOT and ALP in serum. Moreover, the enzymatic antioxidants such as SOD, CAT and LPO were also retained normally by the plant extract. From histopathological analysis, it was clearly evident that the cellular architecture of plant extract treated rat liver tissues were not affected by the paracetamol induction at the higher dose. The results of docking studies also revealed that the identified compounds showed steric interactions (between nonpolar atoms) with amino acid groups. Collectively, the present study suggests that P. leschenaultii leaves extract protects the liver from paracetamol induced hepatic damage.

Hydroalcoholic extract of Brazilian red propolis exerts protective effects on acetic acid-induced ulcerative colitis in a rodent model.

Ulcerative colitis (UC) is a common intestinal inflammatory disease with an etiology that is not well understood. Although the anti-inflammatory and anti-oxidant effects of the hydroalcoholic extract of Brazilian red propolis (HERP) have been reported in various experimental models, its protective effect in models of UC have not been evaluated. The purpose of this study was to investigate the chemopreventive effect of hydroalcoholic extract of Brazilian red propolis (HERP) in acetic acid-induced colitis (AAIC) using a rodent model. The HERP was chemically characterised by HPLC/DAD analyses. Male rats were randomly assigned into four groups: sham, vehicle (with AAIC, treated with vehicle), P10 (with AAIC, treated with 10mg/kg HERP), and P100 (with AAIC, treated with 100mg/kg HERP). Treatments were performed for 7days, and colitis was induced on day seven. Animals were euthanized 24h after colitis induction and body weight, colon length, gross and histological scores, malondialdehyde (MDA) and myeloperoxidase (MPO) concentrations in colon tissue, and the immunohistochemical expression of inducible nitric oxide synthase (iNOS) were assessed. The major compounds found in HERP were liquiritigenin (68.8mg/g), formononetin (54.29mg/g), biochanin A (30.97mg/g), and daidzein (19.90mg/g). Rats treated with 10mg/kg HERP demonstrated significant decreases in MPO concentrations, gross and histological scores of tissue damage, and iNOS expression (p<0.05). Similarly, rats treated with 100mg/kg HERP demonstrated significant decreases in MPO levels (p<0.05) and histological scores of tissue damage (p<0.05). The results of this study indicate that oral administration of HERP attenuates AAIC in rats, which may be due to anti-inflammatory effects related to iNOS inhibition.

Gelatin-based membrane containing usnic acid-loaded liposome improves dermal burn healing in a porcine model.

There are a range of products available which claim to accelerate the healing of burns; these include topical agents, interactive dressings and biomembranes. The aim of this study was to assess the effect of a gelatin-based membrane containing usnic acid/liposomes on the healing of burns in comparison to silver sulfadiazine ointment and duoDerme® dressing, as well as examining its quantification by high performance liquid chromatography. The quantification of the usnic acid/liposomes was examined using high performance liquid chromatography (HPLC) by performing separate in vitro studies of the efficiency of the biomembranes in terms of encapsulation, drug release and transdermal absorption. Then, second-degree 5cm2 burn wounds were created on the dorsum of nine male pigs, assigned into three groups (n=3): SDZ - animals treated with silver sulfadiazine ointment; GDU - animals treated with duoDerme®; UAL - animals treated with a gelatin-based membrane containing usnic acid/liposomes. These groups were treated for 8, 18 and 30days. In the average rate of contraction, there was no difference among the groups (p>0.05). The results of the quantification showed that biomembranes containing usnic acid/liposomes were controlled released systems capable of transdermal absorption by skin layers. A macroscopic assay did not observe any clinical signs of secondary infections. Microscopy after 8days showed hydropic degeneration of the epithelium, with intense neutrophilic infiltration in all three groups. At 18days, although epidermal neo-formation was only partial in all three groups, it was most incipient in the SDZ group. Granulation tissue was more exuberant and cellularized in the UAL and GDU groups. At 30days, observed restricted granulation tissue in the region below the epithelium in the GDU and UAL groups was observed. In the analysis of collagen though picrosirius, the UAL group showed greater collagen density. Therefore, the UAL group displayed development and maturation of granulation tissue and scar repair that was comparable to that produced by duoDerme®, and better than that produced by treatment with sulfadiazine silver ointment In addition, the UAL group showed increased collagen deposition compared to the other two groups.