Assessment of antiarthritic potential of Asparagus dumosus using formaldehyde and CFA-induced arthritic models in rats via modulation of oxidative stress biomarkers and mRNA expression of IL-1b, IL-6, RANKL, OPG, TNF-α and COX-2.

Medicinal plants play a pivotal role in the prevention of chronic non-communicable diseases including arthritis. Despite the traditional use of Asparagus dumosus in arthritis, it has not been studied yet for its effectiveness in arthritis. This study was aimed to explore the antiarthritic potential of A. dumosus in formaldehyde and complete Freund's adjuvant (CFA)-induced arthritic rats. Body weight, arthritic index, hepatic oxidative stress, hematological, biochemical and inflammatory markers were assessed using ELISA, whilst qRT-PCR studies were carried out for the mRNA expression of IL-1b, IL-6, RANKL, OPG, TNF-α and COX-2 genes. GCMS and HPLC analysis were performed to identify the secondary metabolites of A. dumosus. From day 8 to 28 post-administration of formaldehyde and CFA, oral administration of A. dumosus (600, 300 and 150 mg/kg) showed a noteworthy improvement (p < 0.001) in the body weights, immune organ weights, serum levels of rheumatoid (RA) factor, C-reactive protein, TNF-α and IL-6 levels in arthritic rats similar to the effect of piroxicam and methotrexate. Subsequently, the administration of A. dumosus to formaldehyde and CFA-challenged rats, caused a marked decrease (p < 0.001) in the mRNA expression of IL-1b, IL-6, OPG, RANKL, TNF-α and COX-2 genes in treated rats. Likewise, when assessed for antioxidant potential, A. dumosus produced a pronounced (p < 0.001) reduction in malondialdehyde (MDA) levels and hydrogen peroxide (H2O2) production, whilst a dose-dependent (p < 0.001) increase in catalase (CAT) and superoxide dismutase (SOD) activities was recorded. GCMS profiling of A. dumosus presented benzaldehyde, 3-hydroxy-4-methoxy-, 1-decanol and undecane as plant compositions, whereas HPLC fingerprinting displayed quercetin, benzaldehyde, 3-hydroxy-4-methoxy-, gallic acid and cinnamic acid as plants constituents. These results depict that A. dumosus possesses anti-arthritic effect mediated possibly through attenuation of arthritic indices, chronic inflammatory and oxidative stress biomarkers along with down-regulation in the mRNA expression of arthritic candid genes.

Fabrication, Characterization and Biomedical Evaluation of a Statistically Optimized Gelatin Scaffold Enriched with Co-Drugs Loaded into Controlled-Release Silica Nanoparticles.

The current study focused on the fabrication of a well-designed, biocompatible, physically stable, non-irritating and highly porous gelatin scaffold loaded with controlled-release triamcinolone acetonide (TA) and econazole nitrate (EN) co-loaded into mesoporous silica nanoparticles (EN-TA-loaded MSNs) to provide a better long-lasting antifungal therapeutic effect with minimal unfavorable effects. Optimization of the MSNs-loaded scaffold was performed using central composite rotatable design (CCRD), where the effect of gelatin concentration (X1), plasticizer (X2) and freezing time (X3) on the entrapment of EN (Y1) and TA (Y2) and on the release of EN (Y3) and TA (Y4) from the scaffold were studied. The significant compatibility of all formulation ingredients with both drugs was established from XRD, DSC and FT-IR spectra analyses while SEM and zeta studies represented a very precise unvarying distribution of the loaded MSNs in the porous structure of the scaffold. The stability of the optimized scaffold was confirmed from zeta potential analysis (-16.20 mV), and it exhibited higher entrapment efficiency (94%) and the slower (34%) release of both drugs. During in vitro and in vivo antifungal studies against Candida albicans, the MSNs-loaded scaffold was comparatively superior in the eradication of fungal infections as a greater zone of inhibition was observed for the optimized scaffold (16.91 mm) as compared to the pure drugs suspension (14.10 mm). Similarly, the MSNs-loaded scaffold showed a decreased cytotoxicity because the cell survival rate in the scaffold presence was 89% while the cell survival rate was 85% in the case of the pure drugs, and the MSNs-loaded scaffold did not indicate any grade of erythema on the skin in comparison to the pure medicinal agents. Conclusively, the scaffold-loaded nanoparticles containing the combined therapy appear to possess a strong prospective for enhancing patients' adherence and therapy tolerance by yielding improved synergistic antifungal efficacy at a low dose with abridged toxicity and augmented wound-healing impact.

Role of medicinal herbs and phytochemicals in post burn management.

Burn management is a natural and distinctly programmed process involving overlapping phases of hemostasis, inflammation, proliferation and remodeling. Burn wound healing involves initiation of inflammation, re-epithelialization, granulation, neovascularization and wound contraction. Despite the availability of multiple preparations for management of burn wound, there is dire need for efficacious alternative agents. Current approaches for burn wound management include pharmaceutical agents and antibiotics. However, high cost of synthetic drugs and accelerated resistance to antibiotics is challenging for both developed and developing nations. Among alternative options, medicinal plants have been a biocompatible, safe and affordable source of preventive/curative approaches. Due to cultural acceptance and patient compliance, there has been a focus on the use of botanical drugs and phytochemicals for burn wound healing. Keeping in consideration of medicinal herbs and phytochemicals as suitable therapeutic/adjuvant agents for burn wound management, this review highlights therapeutic potential of 35 medicinal herbs and 10 phytochemicals. Among these, Elaeis guineensis, Ephedra ciliate and Terminalia avicennioides showed better burn wound healing potential with varied mechanisms such as modulation of TNF-alpha, inflammatory cytokines, nitric oxide, eicosanoids, ROS and leukocyte response. Phytochemicals (oleanolic acid, ursolic acid, kirenol) also showed promising role in burn wound management though various pathways involving such as down regulation of TNF-alpha, IL-6 and inflammatory mediators including plasma proteases and arachidonic acid metabolites. This review provides a pavement for therapeutic/adjuvant use of potential botanical drugs and novel druggable phyto-compounds to target skin burn injury with diverse mechanisms, affordability and safety profile.

Anticancer, Cardio-Protective and Anti-Inflammatory Potential of Natural-Sources-Derived Phenolic Acids.

Phenolic acids (PAs) are one of the utmost prevalent classes of plant-derived bioactive chemicals. They have a specific taste and odor, and are found in numerous medicinal and food plants, such as Cynomorium coccineum L., Prunus domestica (L.), and Vitis vinifera L. Their biosynthesis, physical and chemical characteristics and structure-activity relationship are well understood. These phytochemicals and their derivatives exert several bioactivities including but not limited to anticancer, cardioprotective, anti-inflammatory, immune-regulatory and anti-obesity properties. They are strong antioxidants because of hydroxyl groups which play pivotal role in their anticancer, anti-inflammatory and cardioprotective potential. They may play significant role in improving human health owing to anticarcinogenic, anti-arthritis, antihypertensive, anti-stroke, and anti-atherosclerosis activities, as several PAs have demonstrated biological activities against these disease during in vitro and in vivo studies. These PAs exhibited anticancer action by promoting apoptosis, targeting angiogenesis, and reducing abnormal cell growth, while anti-inflammatory activity was attributed to reducing proinflammatory cytokines. Pas exhibited anti-atherosclerotic activity via inhibition of platelets. Moreover, they also reduced cardiovascular complications such as myocardial infarction and stroke by activating Paraoxonase 1. The present review focuses on the plant sources, structure activity relationship, anticancer, anti-inflammatory and cardioprotective actions of PAs that is attributed to modulation of oxidative stress and signal transduction pathways, along with highlighting their mechanism of actions in disease conditions. Further, preclinical and clinical studies must be carried out to evaluate the mechanism of action and drug targets of PAs to understand their therapeutic actions and disease therapy in humans, respectively.

Therapeutic Investigation of Standardized Aqueous Methanolic Extract of Bitter Melon (Momordica charantia L.) for Its Potential against Polycystic Ovarian Syndrome in Experimental Animals' Model: In Vitro and In Vivo Studies.

Polycystic ovarian syndrome (PCOS) is an heterogenous, endocrine, metabolic, and multidisciplinary disorder of reproductive-aged females that aggravates insulin resistance, hyperandrogenism, obesity, menstrual irregularities, and infertility. Bitter melon is consumed as vegetable in various parts of the world. The purpose of this study was to provide the rationale for the folkloric uses of bitter melon (Momordica charantia L.) in reproductive abnormalities. HPLC analysis of standardized aqueous methanolic extract of bitter melon revealed the presence of various phytochemicals such as quercetin, gallic acid, benzoic acid, chlorogenic acid, syringic acid, p-coumaric acid, ferulic acid, and cinnamic acid. Twenty-five Swiss albino adult female rats (120-130 g) were acquired and divided into two groups (5 + 20). Letrozole (1 mg/kg p.o.) was used for four weeks to induce PCOS in twenty rats. Disease induction was confirmed by vaginal smear cytology analysis under the microscope. Animals were further divided into four groups, with one group as PCOS group, and the remaining three are treated with standardized extract of bitter melon (500 mg/kg p.o.), bitter melon plus metformin (500 mg/kg p.o.), and metformin alone for the period of next four weeks. After four weeks, the rats were euthanized at diestrus stage. Ovaries of the experimental animals were removed and fixed in 10% buffered formalin, and blood samples were obtained from direct cardiac puncture and stored. Ovaries histopathological analysis showed cystic follicles (9-10) in PCOS group, while, in all the treatment groups, we found developing and mature follicles. Similarly, hormone analysis showed significant (p < 0.001) reduction of LH surge, insulin, and testosterone levels and improvement in FSH levels. Lipid profile and antioxidant enzymes status were also significantly (p < 0.001) improved. In conclusion, the study validates the bitter melon potential as an insulin sensitizer and ovulation enhancer and authenticates its potential in PCOS management.

Nephroprotective Potential of a Standardized Extract of Bambusa arundinacea: In Vitro and In Vivo Studies.

Bambusa arundinacea (RETZ.) Willd. is distributed in tropical regions of Pakistan, India, and China. It has been used for a long time as a folk remedy for cirrhosis, urinary tract ailments, and various other abdominal cavity disorders. It has antioxidant, free-radical-scavenging, and anti-inflammatory effects. The aims and objectives of this study were to validate the folkloric uses of Bambusa arundinacea and to evaluate its nephroprotective potential on scientific grounds. Gentamycin (G.M, 40 mg/kg) was used to induce nephrotoxicity in the animal model. Two doses of the methanolic extract of Bambusa arundinacea (MEBA; 300 and 500 mg/kg) were utilized in addition to silymarin (200 mg/kg/d). Treatments were administered once daily for 14 days. After 14 days, the blood was collected and the kidneys were removed. The antioxidant potential of the standardized MEBA was evaluated using the total phenolic content, the total flavonoid content, and the DPPH scavenging activity. The plant extract was rich with flavonoid content. The DPPH scavenging activity was 65% as compared to butylated hydroxy toluene (96%), with IC50 values 31.65 and 7.80 µg/mL, respectively. The phytochemical analysis was performed using HPLC, and MEBA was found to contain various phytoconstituents such as quercetin, caffeic acid, vanillic acid, gallic acid, chlorogenic acid, and cinnamic acid. Antioxidant enzymes such as superoxide dismutase and catalase were assayed, and MEBA exhibited significantly improved CAT and SOD levels. The levels of renal function markers such as serum creatinine, serum urea, blood urea nitrogen, serum urea, and serum uric acid levels also evaluated, and a significant retrieval was found in a dose-dependent fashion. Good improvement was also made in various hematological parameters. Statistical analysis was done using analysis of variance to determine the significance of differences among the data. In conclusion, the standardized methanolic extract of Bambusa arundinacea was able to alleviate gentamicin-induced nephrotoxicity by enhancing the antioxidant defensive mechanisms of renal tubular cells.

Promising role of polymeric nanoparticles in the treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory illness caused by an autoimmune disorder of synovial membrane resulting in synovial membrane dysfunction. The available treatment particularly focuses on inhibiting macrophage proliferation and reducing the generation of pro-inflammatory cytokines. However, therapeutic success of current treatment options at targeted site is limited; therefore, development of promising therapeutic strategy is the need of time that may provide better targeted delivery of drug with added safety. In development of precision medicine to manage RA, nanotechnology is a viable option to be considered. Recent research using nanoparticles for the treatment of RA, particularly polymeric nanoparticles, has been discussed in this article. Using polymeric nanoparticles as a therapeutic method has shown considerable promise of enhancing treatment success over standard medications used in routine. It is exclusively evident that the viability of using nanoparticles is mainly owed due to their biocompatibility, chemical stability, controlled drug release, and selective drug delivery to inflamed tissues in RA model animals. The current analysis focuses on the critical design characteristics of RA-targeted nanotechnology-based strategies in quest of better therapeutic strategies for RA, and to identify leading polymer as the most effective medications in RA therapy.

Characterization and in vivo evaluation of nanoformulations in FCA induced rheumatoid arthritis in rats.

Rheumatoid arthritis is an inflammatory arthropathy, autoimmune in nature, leading to disability of joints involving structural destruction of articular bone and cartilage due to inflammation in synovium resulting in joint stiffness, swelling and pain. Nanomedicine has played a crucial role in improving the efficacy of treatment by controlling the release of pharmacologically active ingredients to increase bioavailability and achieve uniform and targeted delivery of drug. In this study, we prepared celecoxib, gingerol and oleanic acid loaded PLGA nanoparticles by solvent evaporation method and nanoparticles were characterized by particle size, zeta potential, polydispersity index, entrapement efficiency and FTIR. FCA is induced in right hand paw of rats for induction of arthritis. Celecoxib, gingerol and oleanic acid loaded PLGA nanoparticles coated with chitosan were given orally to rats for the evaluation of anti-arthritic effect of this nanoformulation in rats. Animals were divided into six groups for 21 days trial. On 21st day blood samples were collected for evaluation of hematological and lipid profile parameters. The data was subjected to statistical analysis by applying one way ANOVA and tukey test. At the end of study it was concluded that PLGA loaded celecoxib, gingerol and oleanic acid coated with chitosan have excellent effects in minimizing the side effects and increasing the therapeutic efficacy of drugs.