Sumatriptan mitigates bleomycin-induced lung fibrosis in male rats: Involvement of inflammation, oxidative stress and α-SMA.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung condition that produces symptoms including coughing which may cause by excessive accumulation of scar tissue inflammatory and oxidative stress exacerbation. Sumatriptan, utilized for migraine treatment as a selective 5-HT1B/1D receptor agonist, has demonstrated significant anti-inflammatory and antioxidant properties in multiple preclinical investigations. Operating primarily on serotonin receptors, sumatriptan leverages the diverse physiological functions of serotonin, playing a pivotal role in regulating both inflammation and oxidative stress which is particularly relevant in the context of IPF. MATERIALS & METHODS: Thirty-five male Wistar rats were divided to five group, including: Sham (without IPF induction), control (BLM 5 mg/kg, intraperitoneally), and three fibrosis group with sumatriptan (0.5, 1, and 3 mg/kg, i.p. for 2 weeks) administration. IPF was induced by injection of BLM (single dose, 5 mg/kg intratracheally). Lung tissues were separated for measurement of myeloperoxidase (MPO) as an oxidative stress hallmark, and tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-ß), and transforming growth factor-ß (TGF-ß) as inflammatory markers as well as alpha smooth muscle actin (α-SMA). Also, for histological investigations, tissue damages were assessed by Hematoxylin-eosin (H&E) and Masson's trichrome staining method. RESULTS: BLM-induced fibrosis could increase α-SMA, MPO, TNF-α, IL-1ß, and TGF-ß, while treatment with sumatriptan has reversed the α-SMA, MPO, and IL-1ß levels. Moreover, the results of H&E and Masson's trichrome staining indicated that sumatriptan (1 and 3 mg/kg) reduced tissue damages, alveolar wall thickness, collagen accumulation, and pulmonary fibrosis induced by BLM. CONCLUSION: According to the data achieved from this study, Sumatriptan appears to have therapeutic benefits in IPF, possibly via reducing α-SMA as well as inflammation and the toxicity caused by oxidative stress.

Anti-psoriatic characteristics of ROCEN (topical Arthrocen) in comparison with Cyclosporine A in a murine model.

Topical ROCEN (Roc), liposomal arthrocen hydrogel, is a robust anti-inflammatory formulation which has been developed for skin diseases such as eczema. Therefore, we aimed to evaluate the efficacy of Roc 2% on the healing of imiquimod (Imiq)-induced psoriasis in a mouse model. Psoriasis was induced by applying Imiq topically to the mice's back skin once daily for five consecutive days. Moreover, a group of animal experiments was treated with Cyclosporine A (CsA), as a standard drug, for comparison with Roc treated group. The efficacy of Roc on skin lesions was evaluated by employing Psoriasis Area and Severity Index (PASI) scores. Subsequently, the skin samples were assessed using Baker's scoring system and Masson's trichrome staining, immunohistochemistry, and real-time PCR analysis. The observational and histopathological results indicated that topical application of Roc significantly reduced the PASI and Baker's scores in the plaque-type psoriasis model. Moreover, biochemical assessments showed that Roc suppressed significantly the increase of IL-17, IL-23, and TNF-α cytokines gene expression in the lesion site of psoriatic animals. In conclusion topical Roc 2% could significantly alleviate major pathological aspects of Imiq-induced psoriasis through inflammation inhibition which was comparable to the CsA drug. The beneficial outcomes of Roc application in the psoriasis model suggest its potential usage in complementary medicine.

Phosphatidylserine accelerates wound healing and reduces necrosis in the rats: Growth factor activation.

To examine the effect of topical phosphatidylserine (PS) on wound healing factors and tissue necrosis in in vivo models. Topical PS was applied to evaluate aspects of the wound healing process and growth factors production of vascular endothelial growth factors (VEGF) as well a necrosis reduction in the skin flap of rat models. Moreover, phenytoin (PHT) and cyclosporine A (CsA) were used topically as positive control treatments in wound and necrosis models, respectively. Immunohistochemistry (IHC) VEGF, transforming growth factor-ß (TGF-ß), fibroblast growth factor (FGF) and histopathology were analysed on the wounds of rats. In the necrosis assessment, necrotic areas were determined on photography taken from the back skin of rats. Results indicated that PS topically enhanced significantly (P < 0.05) numbers of fibroblasts and endothelium while inhibiting the neutrophils and macrophages during the 14 days of wound treatment. Moreover, higher values of collagen deposition and epithelialization scores as well as wound recovery percentage (near 80%) were determined significantly (P < 0.05) in the PS group compared with the control. IHC analysis determined that FGF and VEGF cytokine factors were elevated in the wound site by topical PS. Moreover, the necrotic area was significantly (P < 0.05) improved in the PS group. Our experiment indicated that wound improvement and flap survival values in PS treatments were superior to PHT and CsA control groups, respectively. In conclusion, these findings suggest the potential of PS application in the healing of wounds and control of necrosis development after surgery or skin injuries.

The role of bacterial infections in rheumatoid arthritis development and novel therapeutic interventions: Focus on oral infections.

BACKGROUND: Rheumatoid arthritis (RA) represents a primary public health challenge, which is a major source of pain, disability, and socioeconomic effects worldwide. Several factors contribute to its pathogenesis. Infections are an important concern in RA patients, which play a key role in mortality risk. Despite major advances in the clinical treatment of RA, long-term use of disease-modifying anti-rheumatic drugs can cause serious adverse effects. Therefore, effective strategies for developing novel prevention and RA-modifying therapeutic interventions are sorely needed. OBJECTIVE: This review investigates the available evidence on the interplay between various bacterial infections, particularly oral infections and RA, and focuses on some potential interventions such as probiotics, photodynamic therapy, nanotechnology, and siRNA that can have therapeutic effects.

Beneficial effects of arthrocen on neuroinflammation and behavior like depression in stroke in a murine model.

Stroke is a considerable reason for death, disability, socioeconomic loss, and depression in the world. Notably, many attempts to the reduction of the complications of poststroke injuries like depression have failed so far. In this study, we aimed to evaluate the anti-inflammatory effect of arthrocen, avocado/soybean unsaponifiables (ASU), in the poststroke injuries like depression improvement in a mice model. We examined the antidepressant-like effect of arthrocen using the forced swimming test and tail suspension test in mice subjected to stroke. Furthermore, immunohistochemistry of proinflammatory cytokines, IL-10 and TNF-α, and neural cell count were performed in the ischemic brain hippocampus of mice. Oral arthrocen reduced significantly (p < .001) the immobility time in the forced swimming test and tail suspension test in the stroke animals. Also, immunohistochemistry analysis of the hippocampus indicated significantly (p < .01) the reduction of IL-10 and TNF-α cytokines production. Nissl staining showed a significant (p < .0001) increase in the number of viable neurons in stroke mice receiving arthrocen. In conclusion, our data revealed the antidepressant activity of arthrocen in the stroke mice which may be the result of its anti-inflammatory and neuroprotective role.

Nanomedicine and regenerative medicine approaches in osteoarthritis therapy.

Osteoarthritis (OA), the most common chronic joint disease, is a degenerative disease that affects 7% of the worldwide population, more than 500 million people all over the world. OA is the main factor of disability in elderly people which decreases the quality of life of patients. It is characterized by joint pain, low bone density, and deterioration of the joint structure. Despite ongoing novel advances in drug discovery and drug delivery, OA therapy is still a big challenge since there is no available effective treatment and the existing therapies mainly focus on pain and symptomatic management rather than improving and/or suppressing its progression. This review aims to summarize the currently available and novel emerging therapies for OA including regenerative medicine and nanotechnology-based materials and formulations at the clinical and experimental levels. Applications of regenerative medicine and novel technologies such as nanotechnology in OA treatments have opened a new window to support OA patients by offering treatments that could halt or delay OA progression satisfactorily or provide an effective cure in near future. Nanomedicine and regenerative medicine suggest novel alternatives in the regeneration of cartilage, repair of bone damage, and control of chronic pain in OA therapy.

The Potential Application of Natural Photosensitizers Used in Antimicrobial Photodynamic Therapy against Oral Infections.

Oral health problems and the emergence of antimicrobial resistance among pathogenic bacterial strains have become major global challenges and are essential elements that negatively affect general well-being. Antimicrobial photodynamic therapy (APDT) is based on a light source and oxygen that activates a nontoxic photosensitizer, resulting in microbial destruction. Synthetic and natural products can be used to help the APDT against oral microorganisms. The undesirable consequences of conventional photosensitizers, including toxicity, and cost encourage researchers to explore new promising photosensitizers based on natural compounds such as curcumin, chlorella, chlorophyllin, phycocyanin, 5-aminolevulinic acid, and riboflavin. In this review, we summarize in vitro studies describing the potential use of APDT therapy conjugated with some natural products against selected microorganisms that are considered to be responsible for oral infections.

Phosphatidylserine liposomes containing curcumin inhibit bone loss in osteoporotic rats: A possible synergy through a common signaling pathway.

The present study aimed to investigate the effect of phosphatidylserine liposomes containing curcumin (PSLs-Cur) on the development of osteoporosis induced by glucocorticoids (GCs) in the rat model. PSL-Cur, phosphatidylserine (PSL), curcumin (Cur), and alendronate (AL) drugs as a positive control were administrated orally to evaluate the beneficial effects of 3-week treatments on osteoporotic rats. The biochemical and biomechanical properties of bone parameters as well as gene expression were evaluated in treated rats. Moreover, histomorphometric examinations were performed on the bone tissues of the animals. The results revealed that PSL-Cur oral administration caused a significant improvement in serum markers, mechanical strength, and OPG gene expression rather than PSL or Cur administration in osteoporotic rats. Also, PSL-Cur significantly increased the thickness and volume of cortical and trabecular bone mass in comparison with the untreated osteoporotic group. The results of this study indicated that PSL-Cur had a more inhibitory effect on bone loss induced by GCs compared to AL standard drug. Our findings suggested that PSL-loaded Cur may be an appropriate alternative therapy for glucocorticoid-induced osteoporosis. PRACTICAL APPLICATIONS: Osteoporosis is one of the most serious metabolic chronic diseases that causes fragile bone due to decreased mineral density and microarchitectural deterioration in humans. The osteoprotective effects of curcumin and phosphatidylserine, as a food spice and supplementary diet, respectively, have been shown, previously. However, the low bioavailability of curcumin (Cur) due to its poor absorption, rapid metabolism, and fast systemic elimination, limits its benefits. This deficit can be modified with phosphatidylserine liposome (PSL) formulation that facilitates the gastrointestinal delivery of Cur. Moreover, PSL is known as an osteoprotective agent that may make synergy effect with Cur against GC-induced osteoporosis. In this study, daily oral administration of phosphatidylserine liposomes containing curcumin (PSL-Cur) for 3 weeks, considerably improved biochemical, biomechanical, and gene expression of bone parameters in the treated animals subjected to osteoporosis. PSL-Cur can significantly increase the thickness and volume of cortical and trabecular bone mass as well as the mechanical bone strength in animals. Experimental findings proposed PSL-Cur consumption as a proper and safe supplementary medication in the controlling of bone loss in patients with a high risk of osteoporosis.

Joint Dysfunctionality Alleviation along with Systemic Inflammation Reduction Following Arthrocen Treatment in Patients with Knee Osteoarthritis: A Randomized Double-Blind Placebo-Controlled Clinical Trial.

Background and objectives: Many mediators and cytokines are involved in the pathogenesis of osteoarthritis (OA). Some of these cytokines are spontaneously expressed by cultured fibroblast-like synoviocytes. Therefore, using serum samples, the efficacy and the effects of avocado/soy unsaponifiables, ASU, (Arthrocen) on cytokine changes were assessed in patients with knee OA (KOA). Materials and Methods: Experimental procedure: A randomized, double-blind, placebo-controlled clinical trial was conducted on patients with a diagnosis of mild to moderate OA who received either Arthrocen 300 mg/day (n = 61) or placebo (n = 58) for 3 months. Data collection was performed using questionnaires including the Western Ontario and McMaster Universities osteoarthritis index (WOMAC), 20-item short form survey (SF-20), Lequesne index of severity for osteoarthritis of the knee (LISOK), and three visual analog scales (VASs) as pain quality indices. The serum levels of interleukins 2 (IL-2), IL-4, IL-10, IL-17α, and TNF-α were measured using an ELISA reader. Results: Both quality of life indices, pain sensation and scored by specialists (as VASs), respectively, including WOMAC and SF-20, as well as joint dysfunctionality symptoms assessed by physicians were significantly improved (p < 0.05) in OA patients receiving Arthrocen. The serum levels of anti-inflammatory interleukins 4 and 10 were also augmented, while levels of inflammatory IL-17 and TNF-ɑ cytokines were decreased significantly (p < 0.05) compared with the control groups during the 3- and 6-month treatment. Conclusions: Arthrocen consumption may increase the quality of life in OA patients through amelioration of inflammation and improvement of functional activities without any adverse effects in the long term.

Nanostructures as Targeted Therapeutics for Combating Oral Bacterial Diseases.

Pathogenic oral biofilms are now recognized as a key virulence factor in many microorganisms that cause the heavy burden of oral infectious diseases. Recently, new investigations in the nanotechnology field have propelled the development of novel biomaterials and approaches to control bacterial biofilms, either independently or in combination with other substances such as drugs, bioactive molecules, and photosensitizers used in antimicrobial photodynamic therapy (aPDT) to target different cells. Moreover, nanoparticles (NPs) showed some interesting capacity to reverse microbial dysbiosis, which is a major problem in oral biofilm formation. This review provides a perspective on oral bacterial biofilms targeted with NP-mediated treatment approaches. The first section aims to investigate the effect of NPs targeting oral bacterial biofilms. The second part of this review focuses on the application of NPs in aPDT and drug delivery systems.

Beneficial effects of ROCEN (Topical Nano-arthrocen) on atopic dermatitis in mice.

OBJECTIVE: Atopic dermatitis (AD) is a chronic inflammatory skin disease mainly caused by immune stimuli. The current study was conducted to investigate the effects of ROCEN and to compare it with betamethasone (Beta) on mice subjected to AD. METHODS: First, the safety of topical ROCEN was tested to determine possible sensitization induction in vivo. Then, the mice were subjected to oxazolone (Oxa) to induce chronic AD. Consequently, they underwent treatment with ROCEN and Beta. Scratching and wiping behaviors related to dermatitis were evaluated in treated animals for 35 days. The histopathology and immunohistochemistry (IHC) analysis of interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) cytokines were performed on the dorsal skin of the treated mice. RESULTS: Topical administration of ROCEN and Beta to the dorsum of sensitized mice for 5 weeks significantly alleviated scratching and wiping symptoms and reduced erythema, scaling, and edema in the skin of the mice with AD. Moreover, histological indices showed that ROCEN effectively reduced leucocyte infiltration and improved skin healing parameters in treated AD mice. Application of ROCEN or Beta reduced IHC markers including IL-8 and TNF-α significantly. CONCLUSION: ROCEN alleviated the AD symptoms similar to betamethasone in an experimental animal model.

Neuroprotective phosphatidylserine liposomes alleviate depressive-like behavior related to stroke through neuroinflammation attenuation in the mouse hippocampus.

OBJECTIVE: To investigate the protective effect of phosphatidylserine liposomes (PSL) on post-stroke (ST) injuries such as neuroinflammation and depression in mice. METHODS: Brain ischemia was induced via the right unilateral common carotid artery occlusion model. Then, behavioral assessments including the forced swimming test (FST) and tail suspension test (TST) were used to evaluate the antidepressant-like effect of PSL. Moreover, inflammatory cytokines changes in the hippocampus including TNF-α and IL-10 levels as well as the number of survived neurons were evaluated in ST mice using immunohistochemistry (IHC). RESULTS: A significant reduction of the immobility time in both behavioral tests indicated the antidepressant activity of PSL. Moreover, the number of viable neurons increased significantly with PSL treatment, which was similar to control group, compared to the untreated ST group. IHC analysis of ST mice receiving PSL showed a significant reduction in TNF-α and IL-10 levels in the inflamed hippocampus of mice. CONCLUSION: Oral PSL may improve post-stroke depression (PSD) through its anti-inflammatory properties.

Evaluation of ROCEN on Burn Wound Healing and Thermal Pain: Transforming Growth Factor-ß1 Activation.

The present study aimed to evaluate the effect of liposomal arthrocen 2% (ROCEN) on the healing of burn wound and pain alleviation of thermal stimuli in a rat model of the second-degree burn. The results showed that ROCEN formulation significantly improved the main parameters of burn wound healing in a short period of time (7 days). The percentage of wound surface was also reduced significantly compared with the control group following once daily application of ROCEN for 14 days. The level of TGF (transforming growth factor)-ß1 cytokine was also elevated significantly in the burn tissue treated with ROCEN almost the same as zinc oxide cream. Also, ROCEN showed a significant analgesic effect evaluated by 2 models of acute thermal pain, tail-flick and hotplate tests, which suggested that the formulation may act as a pain reliever in burn injuries. In conclusion, the application of the topical formulation of ROCEN may have benefits in the acceleration of the wound healing process and alleviation of the pain due to burn injuries.

Combination therapy of phosphatidylserine liposome with cyclosporine A improves nephrotoxicity and attenuates delayed-type hypersensitivity response.

This study aimed to evaluate the antioxidant capacity of phosphatidylserine liposome (PS) against oxidative stress due to cyclosporine A (CsA) and concurrent administration of PS and CsA on the attenuation of immune response. The effect of oral PS was evaluated on biochemical and oxidative renal markers and histopathology of nephrotic rats receiving CsA. The effect of co-administration of PS with CsA was also assessed on DTH (delayed-type hypersensitivity) reaction of immunized rats. The cytokines production level of IL-2 (Interleukin-2) and IFN-γ (Interferon gamma) was measured in immunized rat's splenocytes. PS treatment significantly (P < 0.05) reduced Cr and BUN of serum and MDA (malondialdehyde) in kidney tissue, and increased SOD (superoxide dismutase) and CAT (Catalase) of kidney tissue in CsA-nephrotic rats. Histopathology data indicated significantly (P < 0.05) nephrotoxicity improvement after 25-day treatment with PS. Furthermore, CsA plus PS administration significantly reduced DTH response and cytokines production of IL-2 and IFN-γ in immunized rats. In conclusion, coadministration of CsA plus PS may overcome oxidative stress and improve the performance of organ transplantation or autoimmune therapy.

Novel osteoprotective nanocochleate formulation: A dual combination therapy-codelivery system against glucocorticoid induced osteoporosis.

Phosphatidylserine nanocochleates (Nanocochs) are novel delivery systems that may play a prominent osteoprotective role with their cargo, vitamin D3 (Vit-D3), against osteoporosis. Therefore, this study was conducted to characterize a Nanococh containing vitamin D3 (Nanococh-D3) and investigate its potential role in improving GIO in a rat model. Roll-shaped Nanococh-D3 particles were obtained in a size range of 320 nm with a sustained release performance. Oral Nanococh-D3 significantly increased the bioavailability of Vit-D3, enhanced bone mechanical strength, and improved osteogenic biomarkers including B-ALP, osteocalcin, Ca, and OPG in GIO rats. This formulation markedly suppressed gene expression of RANK and RANKL in treated rats. Histomorphometric analysis showed significant repairs in bone tissues and TRAP staining indicated a significant decrease in osteoclasts using Nanococh-D3 in osteoporotic rats. Nanococh alone similar to Nanococh-D3 acted better than AL as a standard anti-osteoporotic drug in the improvement of bone strength. In conclusion, our results established the potential role of Nanococh-D3 against osteoporosis in rats.

Phosphatidylserine nanoliposomes inhibit glucocorticoid-induced osteoporosis: A potential combination therapy with alendronate.

The present study aimed to investigate the effects of phosphatidylserine liposomes (PSLs) and phosphatidylserine liposomes containing alendronate (AL-PSLs) on the improvement of methylprednisolone (MP) induced osteoporosis in a rat model. AL-PSLs formulation was prepared, characterized, and evaluated in different pH media to simulate gastrointestinal condition. Osteoporosis was induced by 3 weeks oral administration of MP (10 mg/kg) and then treatment by PSLs, AL-PSLs, and alendronate (AL). Bone metabolic and biomechanical markers were measured in treated rat groups. Also, Tartrate-resistant acid phosphatase (TRAP) staining and histomorphometry were evaluated on bone tissues of treated rats. AL-PSLs were obtained in a size range of 155 nm and negatively surface charge with an entrapment efficiency of 42%. The AL leakage from AL-PSLs did not exhibit a significant difference in acidic or basic media in comparison with the neutral condition. The concentrations of calcium, osteocalcin, bone alkaline phosphatase, and osteoprotegerin (OPG) of serum were significantly increased in PSLs and AL-PSLs treated groups compared to the MP group. Also, PSLs and AL-PSLs significantly improved the thickness and volume of the cortical and trabecular bone mass in treated groups. In addition, TRAP staining indicated a significant decrease of osteoclast number in osteoporotic rats treated with AL-PSLs and PSLs. In this study, AL-PSLs and even PSLs alone made a potential bone mechanical strength in glucocorticoid-induced bone loss more than AL in rats. In conclusion, our findings suggest that PSLs consumption with or without an anti-osteoporotic drug might be an applicable choice in control of osteoporosis.

Arthrocen, an avocado-soy unsaponifiable agent, improves acetic acid-induced colitis in rat by inhibition of NF-kB signaling pathway.

The goal of the current study was to evaluate the anti-inflammatory effect of Arthrocen against acetic acid-induced colitis in rats. Acute inflammation was produced through intrarectal administration of 2 ml diluted acetic acid (4%) solution. All interventions were carried out for 5 days after colitis induction. Arthrocen was administered orally at doses of 30, 60, and 120 mg kg-1  day-1 . Then, macroscopic and microscopic studies were performed. Myeloperoxidase (MPO) activity and tumor necrosis factor-α (TNF-α) activity were measured by biochemical and ELISA methods, respectively. Immunohistochemistry was done to investigate the expression of pNF-κB. The results of this study demonstrated that Arthrocen reduced macroscopic and microscopic damage compared to the acetic acid group. Furthermore, Arthrocen decreased the activity of MPO and TNF-α as well as the protein expression of pNF-kB in rat colon tissue. The results of the current study revealed the anti-inflammatory activity of Arthrocen in acetic acid mediated colon inflammation through suppressing the NF-κB pathway. PRACTICAL APPLICATIONS: Inflammatory bowel disease (IBD) is an immune-mediated chronic relapsing disorder affecting the gastrointestinal tract (GIT) characterized by chronic bowel inflammation. A plant-based dietary supplement containing avocado and soy unsaponifiable extracts in a ratio of 1:2 is known as Arthrocen. Arthrocen can be used as a complementary drug beside current drugs in clinical trials for the treatment of IBD.

Novel effect of Arthrocen (avocado/soy unsaponifiables) on pentylenetetrazole-induced seizure threshold in mice: Role of GABAergic pathway.

Arthrocen, an avocado/soy unsaponifiable (ASU)-containing agent, is now used in the clinic and has potentially to decrease joint inflammation and pain associated with mild to severe osteoarthritis. Phytosterols are the major component of Arthrocen with documented anti-inflammatory properties, antioxidant, and analgesic effects. Here, we evaluated ASU anticonvulsant effect by its oral administration in pentylenetetrazole (PTZ)-induced seizure threshold and Maximal Electroshock Seizure (MES) Models. Also, the involvement of N-methyl-d-aspartate (NMDA) receptor, benzodiazepine receptor, and nitric oxide (NO) pathway were studied in anticonvulsant effect of ASU in male NMRI mice. Acute administration of Arthrocen (150, 75, 30, 10 mg/kg) by oral gavage significantly (p < 0.001) increased the clonic seizure threshold induced by intravenous administration of PTZ. Nonspecific inducible NO synthase (NOS) inhibitor L-NAME (10 mg/kg) and a specific NMDA receptor antagonist MK-801 (0.05 mg/kg) did not affect the anticonvulsant effect of Arthrocen, while pretreatment with flumazenil (0.25 mg/kg), a selective benzodiazepine receptor antagonist, reversed this effect (p < 0.01). Also, Arthrocen treated mice did not affect tonic hindlimb extension in the MES model. The data showed that Arthrocen might produce its anticonvulsant effect by enhancing GABAergic neurotransmission and/or action in the brain.

Estimation of Anti-inflammatory and Analgesic Effects of Topical NANOCEN (Nanoliposomal Arthrocen) on Mice.

The purpose of this study was to evaluate the effect of topical application of nanoliposomal avocado/soybean unsaponifiables (NANOCEN) on inflammation inhibition and pain relief in mice. NANOCEN was prepared by the injection method and characterized for vesicle size, charge, entrapment efficiency, in vitro release, and 1-month vesicle stability. The analysis of ASU formulation showed that liposomes had an average size of around 146 nm with a surface charge of - 43 mV. SEM and TEM imaging confirmed the spherical shape of the nanovesicles in ASU formulation. Moreover, ASU nanoliposomes had a high entrapment efficiency (96%) and exhibited significantly (p < 0.0001) sustained release of the drug in vitro model. The topical NANOCEN (ASU 2%) showed robust anti-inflammatory (p < 0.01) and analgesic effect (p < 0.01) superior to ibuprofen 5%. The histopathology of the inflamed tissues confirmed that the topical ASU formulation potentially (p < 0.001) inhibited infiltration of inflammatory cells. Our findings suggest that the topical formulation of NANOCEN may have local applications for pain relief in medicine.

Evaluation of the novel avocado/soybean unsaponifiable Arthrocen to alter joint pain and inflammation in a rat model of osteoarthritis.

BACKGROUND: Avocado/soybean unsaponifiables such as Arthrocen have been reported to reduce cartilage catabolism and chondrocytic synthesis of inflammatory mediators associated with osteoarthritis (OA). While there is some clinical evidence that avocado/soybean unsaponifiables can reduce OA pain, no preclinical studies have corroborated this observation. The present study determined whether addition of an avocado/soybean unsaponifiable (Arthrocen) to the drinking water of OA rats reduced direct and referred joint pain. METHODS: OA was induced in male Wistar rats by intra-articular injection of sodium monoiodoacetate (MIA: 0.3mg) and animals were allowed to recover for 14 days. Arthrocen was added to the drinking water which was available to animals ad libitum. On day 30, joint pain was assessed by dynamic incapacitance while referred pain was determined by von Frey hair algesiometry. RESULTS: The joint damage induced by MIA injection was severe and was consistent with end-stage OA. Arthrocen consumption (approximately 35 mg/day) attenuated the joint oedema associated with MIA injection. Hindlimb weight bearing also significantly improved in Arthrocen-treated rats (P<0.05); however, von Frey hair mechanosensitivity was unaffected by this treatment. CONCLUSIONS: These data indicate that Arthrocen has the potential to reduce joint inflammation and pain associated with end-stage OA.