Amelioration of Rheumatoid Arthritis by Fragaria nubicola (Wild Strawberry) via Attenuation of Inflammatory Mediators in Sprague Dawley Rats.

Background and Objectives: Fragaria nubicola has never been evaluated scientifically for its anti-arthritic potential despite its use in folkloric systems of medicine. The research was conducted to assess the potential of F. nubicola against rheumatoid arthritis. Materials and Methods: The current study provided scientific evidence by evaluating the effects of plants using an in vivo CFA-induced model of arthritic rats and subsequent microscopic histopathological evaluation of ankle joints along with the determination of paw edema using a digital water displacement plethysmometer. The study also gave insight by determining levels of pro-inflammatory cytokines, matrix metalloproteinase enzymes (MMPs), prostaglandin E2 (PGE2), nuclear factor kappa B (NF-κB), vascular endothelial growth factor (VEGF), and biochemical and hematological parameters. GCMS analysis was also conducted for the identification of possible anti-inflammatory plant constituents. Results: The data showed that F. nubicola-treated groups attenuated the progression of arthritis and paw edema. Microscopic histopathological evaluation validated the anti-arthritic potential by showing amelioration of bone erosion, infiltration of inflammatory cells, and pannus formation. RT-PCR analysis displayed that treatment with F. nubicola down-regulated IL1ß, IL6, TNFα, NF-κB, VEGF, MMP2, MMP3, and MMP9 levels. Moreover, ELISA exhibited a reduction in levels of PGE2 levels in treatment groups. The levels of RBCs, platelets, WBCs, and Hb content were found to be nearly similar to negative control in the treated group. Statistically, a non-significant difference was found when all groups were compared for urea, creatinine, ALT, and AST analysis, indicating the safety of plant extract and fractions at test doses. GCMS analysis of extract and fractions showed the existence of many anti-inflammatory and antioxidant phytochemicals. Conclusion: In conclusion, F. nubicola possessed anti-arthritic properties that might be attributed to the amelioration of MMPs and pro-inflammatory cytokines.

In Vitro, In Silico, and In Vivo Studies of Cardamine hirsuta Linn as a Potential Antidiabetic Agent in a Rat Model.

Diabetes mellitus (T2DM) is a multifaceted metabolic disorder with no definite treatment. In silico characterization can help to explain the interaction between molecules and predict 3D structures. The aim of the present study was to evaluate the hypoglycemic activities of the hydro-methanolic extract of Cardamine hirsuta in a rat model. In vitro antioxidant and α-amylase inhibitory assays were evaluated in the present study. Phyto-constituents were quantified using RP-UHPLC-MS analysis. Molecular docking of compounds into the binding site of different molecular targets, i.e., tumor necrosis factor (TNF-α), glycogen synthase kinase 3 ß (GSK-3ß), and AKT, was carried out. Acute toxicity model, in vivo antidiabetic effect, and the influence on biochemical and oxidative stress parameters were also investigated. T2DM was induced in adult male rats by streptozotocin using a high-fat diet model. Three different doses (125, 250, and 500 mg/kg BW) were orally gavaged for 30 days. Mulberrofuran-M and quercetin3-(6″caffeoylsophoroside) have demonstrated remarkable binding affinity toward TNF-α and GSK-3ß, respectively. 2,2-Diphenyl-1-picrylhydrazyl and α-amylase inhibition assay exhibited IC50 values of 75.96 and 73.66 µg/mL, respectively. In vivo findings exhibited that 500 mg/kg body weight (BW) dose of the extract significantly decreased the blood glucose level, improved biochemical parameters as well as oxidative stress by reduction of lipid peroxidation, and increased high-density lipoproteins. Moreover, activities of glutathione-s-transferase, reduced glutathione, superoxide dismutase were enhanced, and cellular architecture in the histopathological examination was restored in treatment groups. The present study affirmed the antidiabetic activities of mulberrofuran-M and quercetin3-(6″caffeoylsophoroside) present in the hydro-methanolic extract of C. hirsuta, possibly due to the reduction in oxidative stress and α-amylase inhibition.

Spasmolytic and Uroprotective Effects of Apigenin by Downregulation of TGF-ß and iNOS Pathways and Upregulation of Antioxidant Mechanisms: In Vitro and In Silico Analysis.

Apigenin is a phytochemical obtained from Chamomilla recutita. Its role in interstitial cystitis is not yet known. The present study is aimed at understanding the uroprotective and spasmolytic effects of apigenin in cyclophosphamide-induced interstitial cystitis. The uroprotective role of apigenin was analyzed by qRT-PCR, macroscopic analysis, Evans blue dye leakage, histological evaluation, and molecular docking. The spasmolytic response was measured by adding cumulative concentrations of apigenin to isolated bladder tissue pre-contracted with KCl (80 mM) and carbachol (10-9-10-4) on non-incubated and pre-incubated tissues with atropine, 4DAMP, methoctramine, glibenclamide, barium chloride, nifedipine, indomethacin, and propranolol. Apigenin inhibited pro-inflammatory cytokines (IL-6, TNF-α and TGF 1-ß) and oxidant enzymes (iNOS) while increasing antioxidant enzymes (SOD, CAT, and GSH) in CYP-treated groups compared to the control. Apigenin restored normal tissue of the bladder by decreasing pain, edema, and hemorrhage. Molecular docking further confirmed the antioxidant and anti-inflammatory properties of apigenin. Apigenin produced relaxation against carbachol-mediated contractions, probably via blockade of M3 receptors, KATP channels, L-type calcium channels, and prostaglandin inhibition. While the blockade of M2 receptors, KIR channels, and ß-adrenergic receptors did not contribute to an apigenin-induced spasmolytic effect, apigenin presented as a possible spasmolytic and uroprotective agent with anti-inflammatory, antioxidant effects by attenuating TGF-ß/iNOS-related tissue damage and bladder muscle overactivity. Thus, it is a potential agent likely to be used in treatment of interstitial cystitis.

Aptamer-conjugated carbon-based nanomaterials for cancer and bacteria theranostics: A review.

Aptamers are single-stranded oligonucleotides that link to various substrates with great affinity and selectivity, including small molecules, peptides, proteins, cells, and tissues. For this reason, they can be used as imaging agents for cancer imaging techniques. Multifunctional nanomaterials combined with imaging probes and drugs are promising cancer diagnosis and treatment candidates. On the other hand, carbon-based nanomaterials (CNMs), including such as fullerene, carbon nanotubes, carbon-based quantum dots, carbon nanohorns, graphene oxide and its derivatives carbon nanodots, and nanodiamonds, are sort of smart materials that can be used in a variety of theranostic applications, including photo-triggered therapies. The remarkable physical characteristics, functionalizable chemistry, biocompatibility, and optical properties of these nanoparticles have enabled their utilization in less-invasive therapies. The theranostic agents that emerged by combining aptamers with CNMs have opened a novel alternative for personified medicine of cancer, target-specific imaging, and label-free diagnosis of a broad range of cancers, as well as pathogens. Aptamer-functionalized CNMs have been used as nanovesicles for targeted delivery of anti-cancer agents (i.e., doxorubicin and 5-fluorouracil) to tumor sites. Furthermore, these CNMs conjugated with aptamers have shown great advantages over standard CNMs to sensitively detect Mycobacterium tuberculosis, Escherichia coli, staphylococcus aureus, Vibrio parahaemolyticus, Salmonella typhimurium, Pseudomonas aeruginosa, and Citrobacter freundii. Regrettably, CNMs can form compounds defined as NOAA (nano-objects, and their aggregates and agglomerates larger than 100 nm), that accumulate in the body and cause toxic effects. Surface modification and pretreatment with albumin avoid agglomeration and increase the dispersibility of CNMs, so it is needed to guarantee the desirable interactions between functionalized CNMs and blood plasma proteins. This preliminary review aimed to comprehensively discuss the features and uses of aptamer-conjugated CNMs to manage cancer and bacterial infections.

Acacia modesta attenuates MnCl2 induced hepatotoxicity, oxidative stress and hepatic inflammation in wistar rats.

Natural Plants are broadly used in treating inflammatory disorders. The current study focused on evaluating the hepato-protective and anti-inflammatory potential of A. modesta in MnCL2 induced hepatotoxicity and liver inflammation. The MnCl2 induce 6.0mg/kg was given for 30 days (p.o) to induced hepatotoxicity and liver inflammation. The ethanolic extract of A. modesta were given orally at the dose of 100mg/kg/day. The in vivo inflammatory manganese induced hepatotoxic model is used for evaluating the acacia heap to-protective effect. Gas chromatography-mass spectrometry analyses were performed to find out compounds responsible for anti-inflammatory properties. Results showed that administration of ethanolic extract (100 mg/kg), altogether diminished inflammation of the liver, expanded liver capacity, oxidative stress and his to-pathological outcomes in the current study compared with disease rats. The beneficial outcomes of A. modesta extract were observed on liver inflammation.

Schiff Bases of Pioglitazone Provide Better Antidiabetic and Potent Antioxidant Effect in a Streptozotocin-Nicotinamide-Induced Diabetic Rodent Model.

Pioglitazone is a Food and Drug Administration-approved thiazolidinedione (TZD) derivative and peroxisome proliferator-activated receptor gamma (PPARγ) agonist and used for the treatment of diabetes mellitus (DM). However, this drug is still associated with many adverse effects. In the present study, four new Schiff bases of pioglitazone (P1-P4) were synthesized and characterized using FTIR, 1HNMR, 13CNMR, mass spectrometry, and elemental analysis. For preliminary screening, the in vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and in vitro alpha-amylase antidiabetic inhibitory assay were performed. Further, P3 was used to investigate in vivo antioxidant and in vivo antidiabetic effects in a streptozotocin-nicotinamide-induced diabetic rat model. Diabetic rats were administered with an i.p dose of pioglitazone 10 mg/kg body weight for 21 days. Moreover, biochemical parameters and antioxidants were quantified from liver and kidney tissues of rodents. In the DPPH assay, compound P3 showed superior antioxidant effects. Using the in vitro α-amylase inhibitory assay, P3 exhibited potent effects as compared to other groups, that is, 93% inhibition, while pioglitazone showed 81% inhibition. Enzymatic and nonenzymatic antioxidants showed significant changes in P3 (10 mg/kg)-treated groups (p < 0.001). Similarly, compound P3 produced significant and better results in comparison to pioglitazone in the rodent model. This study confirmed potent antidiabetic and superior antioxidant potential of the newly synthesized Schiff base (P3), which could ultimately account for insulin sensitization and for cellular protection and hence provide a potential clue for dual therapeutics.