Effect of Dioscorea villosa extract and the phytoestrogen diosgenin on ovariectomized mice with zymosan-induced arthritis

Abstract Humans are exposed to natural compounds such as phytoestrogens primarily through diet and supplements. These compounds promote health by alleviating the symptoms and illnesses associated with menopause and arthritis. Diosgenin (DSG) occurs naturally in plants such as Dioscorea villosa (DV) and binds to estrogen receptors, so it may have similar effects to this hormone, including against arthritis. Thus, we investigated the effect of chronic treatment with dry extract of DV and its phytoestrogen DSG on ovariectomized mice with arthritis. We found that dry extract of Dioscorea villosa (DV) contains the phytoestrogen diosgenin (DSG) in its composition. Furthermore, arthritic mice treated with DV and DSG showed reduced neutrophil accumulation in the articular cartilage. Also, the dry extract of DV administered orally (v.o) did not alter the leukocyte count in the joints or promote changes in the reproductive tract. However, DSG altered these parameters, with possible beneficial effects by reducing symptoms related to reproductive aging. Thus, oral treatment with dry extract of DV and subcutaneous (s.c) treatment with DSG showed promise by acting against inflammation caused by arthritis and reducing symptoms in the reproductive tract due to menopause.

Enhancement of the functionality of women with knee osteoarthritis by a gel formulation with Caryocar coriaceum Wittm ("Pequi") nanoencapsulated pulp fixed oil.

Osteoarthritis (OA) is a degenerative joint disease that occurs when there is a change in the mechanical and biological properties of the articular cartilage and the subchondral bone; The condition is more prevalent in women than in men. Pequi oil (PO), which is extracted from the fruits of the pequi tree (Caryocar coriaceum Wittm), is widely used in traditional medicine in the Brazilian northeast for the management of inflammation and joint pain. The aim of this study was to develop a pharmaceutical formulation containing Carbopol® hydrogel nanoencapsulated with pequi pulp fixed oil (PeONC) and evaluate its therapeutic effect on functionality and pain in women with knee osteoarthritis. The study was divided into two stages: Stage 1 - preparation and physico-chemical characterization of the pharmaceutical formulation containing PeONC, cell viability assays and skin irritability testing. Step 2 - A double-blind randomized clinical trial evaluating knee symptoms, quality of life, pressure pain, function, muscle strength and range of motion. The nanoformulation was in a gel form, with a particle size of 209.5 ± 1.06 nm, a pH of 6.23 ± 0.45, a zeta potential of - 23.1 ± 0.4 mV, a polydispersity index of 0.137 ± 0.52, and containing nanocapsules with a spherical shape a polymeric wall and an oily nucleus. The gel showed no cytotoxicity and was not irritating to human skin. The treatment with PeONC increased the strength of the knee flexor and extensor muscles and the total motion range of the knee. In addition, the treatment reduced knee instability, pain, swelling, and locking; There was also an improvement in some items of the SF-36 quality of life questionnaire such as in respect of functional capacity and social aspects. In conclusion, PeONC was found to be a stable, safe formulation with no toxicity in respect of topical use in humans. Additionally, the treatment produced an increase in muscle strength and functionality that was associated with reduced knee symptoms and improved quality of life. Our findings showed that in a group of women treated with PeONC mitigated the symptoms of knee osteoarthritis.

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.

Evaluation of the Use of Compressive Stockings Impregnated With Hesperetin-Based Nanocapsules in the Healing of Venous Ulcers: A Case Report.

Venous ulcers are a more severe complication of chronic venous insufficiency, significantly compromising patient quality of life (QoL). Compressive stockings are still the gold standard treatment method with alternative therapies currently being evaluated. In this perspective, we investigate the influence of compressive stockings impregnated with hesperetin-based nanocapsules in the healing process of venous ulcers. Compressive stockings impregnated with hesperetin-based nanocapsules were applied to a consenting patient for 6 months following all relevant ethical principles for patient studies. The patient was evaluated at baseline (T0), 3 months (T3), and 6 months (T6), using photographic register (healing) probes to measure skin melanin, erythema and hydration parameters, and venous diameters, followed by questionnaires regarding QoL and pain perception. Healing was observed at the 3-month time point and with 91.6% and 93.1% of retraction area in larger ulcers of the right leg and lateral portion of the left leg, respectively. The deepest ulcer in a medial portion of the left leg healed 47.3%. A reduction of all measured skin parameters was observed, indicating a possible hesperetin effect. The scores of QoL and pain were, respectively, in the ranges of 91.6 to 31.2 and 7 to 0. Reduction in venous diameters also indicates healing function. These preliminary findings suggest that compressive stockings impregnated with hesperetin nanocapsules enhance venous ulcer healing. Further clinical trial controlled by placebo, involving a greater number of patients, is required to confirm the findings of this case report.

Bioassay-guided evaluation of Dioscorea villosa - an acute and subchronic toxicity, antinociceptive and anti-inflammatory approach.

BACKGROUND: Dioscorea villosa (DV) has been used in Brazil as an alternative medicine to attenuate menopause symptoms, as well as for the treatment of joint pain and rheumatoid arthritis. In spite of the popular use of DV for the treatment of various disorders, there are limited scientific data regarding safety aspects of this herb. In this regard, we carried out to evaluated both antinociceptive and anti-inflammatory activities in experimental models and assess the toxic effects of the acute (single dose) and subchronic (30 days) oral administration of dry extract of Dioscorea villosa in rodents. METHODS: The LC analyses were performed to assess the presence of the diosgenin in samples of DV. The antinociceptive study of DV was performed using models of acetic acid-induced writhing and formalin-induced pain in mice. The anti-inflammatory study was accomplished by leukocyte migration to the peritoneal cavity. A dry extract of DV was tested at doses of 100, 200 and 400 mg/kg (per os or p.o.). The toxicological properties of the dry extract were evaluated by toxicity assays of acute (5 g/kg, single dose) and subchronic (1 g/kg/day, 30 days) treatment. Haematological, biochemical, and histopathological parameters were studied. The results are expressed as mean ± S.D., and statistical analysis of the data were performed with the Student's t-test or one-way analysis of variance (ANOVA) followed by Tukey's test. In all cases differences were considered significant if p < 0.05. RESULTS: HPLC-DAD analysis of the extract from DV revealed the presence of diosgenin as the major compound. Doses of 200 and 400 mg/kg significantly reduced the amount of acetic acid-induced writhing in relation to the vehicle (p < 0.0001). In the first phase, using the formalin-induced neurogenic pain test, only the 400 mg/kg dose of DV showed significant inhibition of neurogenic pain (p < 0.001). In the second phase, 200 and 400 mg/kg of DV showed significant inhibition of inflammatory pain (p < 0.0001). Significant inhibition of leukocyte migration was observed with doses of 100 (p < 0.001), 200 (p < 0.01) and 400 mg/kg (p < 0.01). Haematological, biochemical and histopathological data obtained in both acute and subchronic toxicological assays revealed only unremarkable changes, which are unlikely to indicate DV toxicity with oral administration. CONCLUSION: We found that DV possesses antinociceptive and anti-inflammatory properties in rodent models. In addition, no acute or subchronic toxicity was evident when the herbal extract was administered orally. These results supporting the folkloric usage of the plant to treat various inflammatory diseases.

Tratamento cirúrgico em dois tempos do aneurisma toracoabdominal roto com prótese intraluminal sem sutura / Two-stage surgical management of ruptured thoracoabdominal aneurysm by intraluminal prosthesis without suture

The surgical management of thoracoabdominal aneurysms requires thoracophrenic laparotomy, prolonged periods of aortic clamping with visceral ischemia, profuse bleeding leading to a difficult postoperative course with pulmonary, renal, neurological complications, coagulation disturbances and others. All this resulting in an elevated morbidity/mortality very often contraindicating it for the very elderly or those with prior respiratory, renal or cardiac symptoms. Rupture of this aneurysm greatly increases the already high rate of morbidity/mortality. Crawford and Borst have described a two-stage surgery with good results, for aneurysms that affect more than one segment of aorta. The objective of our report is to demonstrate a two-stage operation, employing an intraluminal prosthesis without suture. This procedure results in a less agressive surgery since it approaches only the ruptured segment of aorta, therefore, only one cavity is manipulated (thorax or abdomen). The anastomosis with intraluminal prosthesis greatly decreases the time necessary for clamping the aorta and consequently visceral ischemia and also reduces bleeding. The reduction of surgical aggression on these already severely ill patients yielded very good surgical results.