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.

Association of a high-fat diet with I-FABP as a biomarker of intestinal barrier dysfunction driven by metabolic changes in Wistar rats.

BACKGROUND: The epithelial lining of the gut expresses intestinal fatty-acid binding proteins (I-FABPs), which increase in circulation and in plasma concentration during intestinal damage. From the perspective of obesity, the consumption of a diet rich in fat causes a disruption in the integrity of the gut barrier and an increase in its permeability. HYPOTHESIS: There is an association between the expression of I-FABP in the gut and various metabolic changes induced by a high-fat (HF) diet. METHODS: Wistar albino rats (n = 90) were divided into three groups (n = 30 per group), viz. One control and two HF diet groups (15 and 30%, respectively) were maintained for 6 weeks. Blood samples were thus collected to evaluate the lipid profile, blood glucose level and other biochemical tests. Tissue sampling was conducted to perform fat staining and immunohistochemistry. RESULTS: HF diet-fed rats developed adiposity, insulin resistance, leptin resistance, dyslipidemia, and increased expression of I-FABP in the small intestine compared to the control group. Increased I-FABP expression in the ileal region of the intestine is correlated significantly with higher fat contents in the diet, indicating that higher I-FABP expression occurs due to increased demand of enterocytes to transport lipids, leading to metabolic alterations. CONCLUSION: In summary, there is an association between the expression of I-FABP and HF diet-induced metabolic alterations, indicating that I-FABP can be used as a biomarker for intestinal barrier dysfunction.

Anti-arthritic effects of geranium essential oil loaded chitosan nanoparticles in Freund's complete adjuvant induced arthritic rats through down-regulation of inflammatory cytokines.

Geranium essential oil (GEO) has been widely used in aromatherapy and traditional medicines. Nanoencapsulation, a novel technique has emerged to overcome the environmental degradation and less oral bioavailability of essential oils. This work was undertaken to encapsulate geranium essential oil in chitosan nanoparticles (GEO-CNPs) by ionic gelation technique and to explore anti-arthritic and anti-inflammatory potential in FCA-induced arthritic model in rats. The GEO was characterized by gas chromatography flame ionization detector (GCFID) and the nanosuspension was characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and X-rays diffraction (XRD). The Wistar albino rats (n = 32) were separated into four groups; Group 1 and 2 were considered as normal and arthritic controls. Group 3 was positive control that received oral celecoxib for 21 days while Group 4 was treated with oral GEO-CNPs after the induction of arthritis. Hind paw ankle joints diameters were weekly measured throughout the study and significant decrease (5.5 ± 0.5 mm) was observed in GEO-CNPs treatment group in comparison to arthritic group (9.17 ± 0.52 mm). Blood samples were drawn at end for evaluation of hematological, biochemical and inflammatory biomarkers. A significant upregulation of red blood cells and hemoglobin while downregulation of white blood cells, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP) and rheumatoid factor (RF) was observed. Ankles were transected for the histopathological and radiographic examination after animals were sacrificed which confirmed the alleviation of necrosis along cellular infiltration. It was concluded that GEO-CNPs were found to possess excellent therapeutic potential and promising candidates to reduce FCA-induced arthritis.

Phytochemical analysis and gastroprotective effect of Stellaria media (L.) Vill. methanolic extract on piroxicam-induced gastric ulcer in Wistar rats.

Stellaria media L. has traditionally been used to treat inflammatory and gastrointestinal ailments. This study aimed to phytochemically characterize the S. media extract and explore its anti-ulcer efficacy against piroxicam-induced stomach lesions in Wistar rats. Phytochemical analysis was performed and antioxidant capacity of extract was determined using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. In vivo, piroxicam (30mg/kg) was administered to induce gastric ulceration. Gastro protective effect of S. media extract was observed at 150, 300 and 450mg/kg, respectively. While omeprazole (20mg/kg) was used as a conventional anti-ulcer drug. After oral treatment for 14 days, stomach acidic secretions, ulcerogenic indices, hematological markers and oxidative stress parameters were assessed along with histological examination. The existence of polyphenol contents in S. media extract was confirmed in correlation to a marked DPPH inhibition (IC50 27.94µg/mL). S. media extract resulted in a dose-dependent elevation in gastric pH while a decrease in acid volume, acidity and ulceration. Also, S. media extract administration restored the impaired hematological markers (RBCs, Hb, WBCs and PLTs) and decreased oxidative stress by reducing oxidants (TOS and MDA) while raising antioxidants (TAC and CAT). Furthermore, gastric histological results corroborated the aforementioned findings. Conclusively, S. media could provide a promising protective effect against drug-induced gastric ulceration.

Therapeutic potential of quinoa seed extract as regenerative and hepatoprotective agent in induced liver injury wistar rat model.

The liver is a fundamental metabolic organ that performs many essential functions including the detoxification of toxic substances present in the body. Exposure to various toxicants leads the liver towards hepatic injury. This study was planned to estimate the hepatoprotective and regenerative efficacy of Quinoa seeds (Chenopodium quinoa) extract against carbon tetrachloride (CCl4) induced liver damage. At a dose of 1ml/kg (153.8mg/kg) body weight carbon tetrachloride (CCl4) was used intraperitoneally to induce hepatic injury in Wistar rats. Silymarin (30mg/kg body weight, p.o.), an antioxidant was used as a reference standard drug. Subsequently, ethanolic extract of Quinoa seeds (QEE) was administered at 400 and 600mg/kg body weight through oral gavage. Various biochemical and regenerative biomarkers were assessed to evaluate the potential efficacy of QEE in liver tissue regeneration. Results revealed that QEE administration significantly reduced the CCl4-induced raised quantities of alanine transaminase (ALT), aspartate transaminase (AST), and total oxidative stress (TOS) while, significantly improved the level of triiodothyronine (T3), thyroxine (T4), albumin and total protein concentration in QEE treated groups. The expression level of IGF-1, FOXA-2, Stmn-2, SPP-1 was found significantly down-expressed. It is concluded that QEE treatment has the regenerative and hepatoprotective effect.

Detection of Paracetamol as substrate of the gut microbiome.

Gut microbiome, a new organ; represent targets to alter pharmacokinetics of orally administered drugs. Recently, in vitro trials endorsed the idea that orally administered drugs interact and some of their quantity may be taken up by normal microbiome during transit through gut. Such transport mechanisms in microbiome may compete for drug with the host itself. Currently, no data confirms specific transport system for paracetamol uptake by gut microbiome. In vivo trial was conducted in normal healthy male rats (n=36). Paracetamol was administered orally in a single dose of 75mg/kg to isolate microbial mass after transit of 2, 3, 4, 5 and 6 hours post drug administration. Paracetamol absorbance by microbiome was pursued by injecting extracted microbial lysate in RP-HPLC-UV with C18 column under isocratic conditions at 207nm using acetonitrile and water (25:75 v/v) pH 2.50 as mobile phase. Paracetamol absorbance (14.10±0.75µg/mg of microbial mass) and percent dose recovery (13.16±0.55%) seen at transit of 4 hours was significantly higher (P<0.05) compared to other groups. Study confirms the hypothesis of homology between membrane transporters of the gut microbiome and intestinal epithelium. Orally administered drugs can be absorbed by gut microbes competitively during transit in small intestine and it varies at various transit times.

Haematopoietic effects of Angelica sinensis root cap polysaccharides against lisinopril-induced anaemia in albino rats.

CONTEXT: Angelica sinensis L. (Umbelliferae) has medicinal properties. OBJECTIVES: The present study evaluates the haematopoietic effects of A. sinensis polysaccharides (ASP) against lisinopril-induced anaemia. MATERIALS AND METHODS: Thirty healthy adult male albino rats were randomly divided into five groups (n = 6). Group I was control group. Group II was treated with angiotensin-converting enzyme inhibitor (ACEI, 20 mg/kg/day) to induce anaemia. In group III, erythropoietin (EPO, 100 IU/kg/each) was administered in combination with ACEI. Group IV was treated with ASP (1 g/kg/day), extracted from A. sinensis root caps. In Group V, ASP (1 g/kg/day) was treated with ACEI. After 28 days, blood and tissue samples were collected for haematological and histopathological analysis, respectively. RESULTS: The results showed that ACEI significantly reduced the haemoglobin (Hb, 10.0 g/dL), packed cell volume (PCV, 39.5%), red blood cells (RBCs, 6.2 million/mm3), mean corpuscular volume (MCV, 53.5 fL) and mean corpuscular haemoglobin (MCH, 16.2 pg/cell) values. In the group treated with ASP, the Hb (13.7 g/dL) and RBCs (7.8 million/mm3) increased significantly (p < 0.05). The combination of ASP and ACEI led to the significant (p < 0.05) reduction in Hb (10.7 g/dL), PCV (33.3%), RBCs (6.0 million/mm3), MCV (54.42 fL) and MCH (16.44 pg/cell) values. While histopathological examination of the liver and kidney cells showed a mild degree of toxicity in the ASP-treated group. CONCLUSION: ASP has a potentiating effect on haematological parameters when given alone. However, when administered simultaneously with lisinopril, it showed an unfavourable effect with more complicated anaemia so it should not be used with ACEIs.

Polyherbal extract improves glycometabolic control in alloxan-induced diabetic rats via down-regulating the MAPK/JNK pathway, modulating Nrf-2/Keap-1 expression, and stimulating insulin signaling.

Objectives: This study focused on the evaluation of antioxidant and antidiabetic activities of polyherbal extract (PHE), containing Cassia absus (L.), Gymnema sylvestre (R. Br.), Nigella sativa (L.), and Piper nigrum (L.), in alloxan-induced diabetes model. Materials and Methods: In vitro, HPLC characterization, DPPH scavenging assay, and α-amylase inhibition test were conducted. In vivo, acute oral toxicity of PHE was assessed. Alloxan-induced diabetic Wistar rats (n=6) were orally treated with PHE (200, 400, and 600 mg/kg/day) and glibenclamide (GLB; 10 mg/kg/day) for six consecutive weeks. Then, biochemical biomarkers, oxidative stress parameters, histopathological examination, and mRNA expression levels (RT-qPCR) were determined. Results: The presence of polyphenols in PHE was confirmed in correlation to marked DPPH scavenging (IC50: 1.60 mg/ml) and α-amylase inhibition (IC50: 0.82 mg/ml). PHE demonstrated no toxicity in rats up to a dose of 2000 mg/kg. In diabetic rats, PHE dose-dependently ameliorated the serum levels of glucose, insulin, glycated hemoglobin A1c (HbA1c), leptin, and glucokinase (GCK). Also, PHE substantially alleviated serum inflammatory markers (TNF-α and CRP) and oxidative stress indicators (MDA, SOD, and CAT) in pancreatic tissues. PHE, particularly at 600 mg/kg, attenuated cellular oxidative stress via modulating the mRNA expression levels of genes regulating MAPK/JNK (Mapk-8, Traf-4, and Traf-6) and Nrf-2/Keap-1 pathways and promoted insulin signaling through up-regulating insulin signaling cascade (Pdx-1, Ins-1, and Ins-2), as compared to GLB. Furthermore, histopathological findings supported the aforementioned results. Conclusion: Our study suggests that polyherbal extract has promising antioxidant and antidiabetic activities by modulating the MAPK/JNK, Nrf-2/Keap-1, and insulin signaling pathways.

Fumaria indica (Hausskn.) Pugsley Hydromethanolic Extract: Bioactive Compounds Identification, Hypotensive Mechanism, and Cardioprotective Potential Exploration.

Fumaria indica (Hausskn.) Pugsley (FIP), a member of the Papaveraceae family, has a documented history of use in traditional medicine to treat cardiovascular ailments, particularly hypertension, and has shown substantial therapeutic efficacy among native cultures worldwide. However, the identification of bioactive compounds and the mechanism of hypotensive effect with the cardioprotective potential investigations are yet to be determined. The study aimed to identify bioactive compounds, explore the hypotensive mechanism and cardioprotective potential, and assess the safety of Fumaria indica (Hausskn.) Pugsley hydromethanolic extract (Fip.Cr). LC ESI-MS/MS analysis was performed to identify the bioactive compounds. In vitro experiments were conducted on isolated rat aorta and atria, and an in vivo invasive BP measurement model was used. Acute and subacute toxicities were assessed for 14 and 28 days, respectively. Isoproterenol (ISO) was used to develop the rats' myocardial infarction damage model. The mRNA levels of NLRP3 inflammasome and the abundance level of Firmicutes and Lactobacillus were measured by qRT-PCR. The hypotensive effect of FIP bioactive compounds was also investigated using in silico methods. Fip. Cr LC ESI-MS/MS analysis discovered 33 bioactive compounds, including alkaloids and flavonoids. In isolated rat aorta, Fip.Cr reversed contractions induced by K+ (80 mM), demonstrating a calcium entry-blocking function, and had a vasorelaxant impact on phenylephrine (PE) (1 µM)-induced contractions unaffected by L-NAME, ruling out endothelial NO participation. Fip.Cr caused negative chronotropic and inotropic effects in isolated rat atria unaffected by atropine pretreatment, eliminating cardiac muscarinic receptor involvement. Safety evaluation showed no major adverse effects. In vivo, invasive BP measurement demonstrated a hypotensive effect comparable to verapamil. Fip.Cr protected the rats from ISO-induced MI interventions significantly in biometrical and cardiac serum biochemical indicators and histological examinations by reducing inflammation via inhibiting NLRP3 inflammasome and elevating Firmicutes and Lactobacillus levels. The network pharmacology study revealed that the FIP hypotensive mechanism might involve MMP9, JAK2, HMOX1, NOS2, NOS3, TEK, SERPINE1, CCL2, and VEGFA. The molecular docking study revealed that FIP bioactive compounds docked better with CAC1C_ HUMAN than verapamil. These findings demonstrated that Fip.Cr's hypotensive mechanism may include calcium channel blocker activity. Fip.Cr ameliorated ISO-induced myocardial infarction in rats by attenuating inflammation, which might be via inhibiting NLRP3 inflammasome and may prove beneficial for treating MI.

Therapeutic efficacy of spirulina against ovalbumin and cigarette smoke-induced asthma-specific stress biomarkers in Sprague-Dawley rats.

Due to the high prevalence of allergies and asthma, awareness about allergens and therapeutic use of functional foods and nutraceuticals have gained immense attention. Spirulina powder is being used as health-boosting and antioxidant agent against several ailments owing to its unique nutritional profile. Considering its antioxidant role, the current study was focused on exploring therapeutic role of spirulina against stress biomarkers in asthmatic model. To assess the therapeutic efficacy of spirulina against allergic asthma-specific oxidative stress biomarkers, a model feed trial was conducted and rats were divided into four groups (n = 10). G0-I (negative control), G0-II (positive control), whereas GI (spirulina) and G2 (salbutamol) served as treatment groups. Salbutamol is a chemical compound which is used in several antiallergic medicines because it works as bronchodilator. G2 group was given salbutamol for comparison of results. For asthma induction, rats were given intraperitoneal injection of ovalbumin on 7th, 14th, and 21st day. Treatment groups were given spirulina powder (500 mg/kg body weight) and salbutamol (1 mg/kg), respectively, after the induction of asthma. All three asthmatic groups were also exposed to cigarette smoke daily along with respective treatment for 4 weeks. Asthma induction caused an increase in total cell count in bronchioalveolar fluid (BALF), while spirulina treatment reduced total cells in BALF by 33.50% and salbutamol by 41.7%. Level of interleukins (IL) like IL-4 decreased by 33.32% & 48.56% in G1 and G2. Similarly, IL-5 and IL-13 levels reduced by 40.9% & 49.9% and 18.62% & 38.02%, respectively, in G1 and G2. Serum levels of Immunoglobin-E (Ig-E) declined by 29.70% and 52.82%, while histamine levels were 26.23% & 45.58% less at the end of study in comparison to positive control. Moreover, histological analysis of lung tissue revealed that both spirulina and salbutamol effectively reduced ovalbumin and cigarette smoke-induced moderate to severe necrosis, architectural changes, and congestion. It was concluded that salbutamol showed better results however, spirulina also effectively reduced mild to moderate allergic symptoms in dose-dependent manner. Nutraceutical and functional foods are considered helpful in mitigating oxidative stress-mediated health problems. Spirulina has its unique nutritional profile including phycobiliproteins, phytochemicals, and antioxidant vitamins which make it useful against several ailments. Considering its antioxidant role, current study was focused on exploring therapeutic efficacy of spirulina against stress biomarkers in asthmatic model. Outcomes of present research also demonstrated beneficial effect of spirulina in modulating allergic symptoms. In this regard, ancient concept of "medicine food homology" can be implemented and spirulina can be incorporated in food for additional benefits. However, further research regarding safety aspects is needed for its use in clinical practice for humans.

Effect of iron-fortified jamun leather on the Asunra-induced anemia in Sprague Dawley rats.

Introduction: Micronutrients such as minerals and vitamins are required in a minute quantity but play a pivotal role in the functioning of the body. Therefore, deficiency in one of them can lead to lethal health conditions. Iron deficiency anaemia is one of the most common micronutrient deficiencies across the world and is affecting women and children. Methods: The present study aimed to investigate the anti-anaemic effect of fortified jamun leather on anaemia biomarkers and haematology in anaemic female Sprague Dawley rats. A total of 40 Sprague Dawley rats were used in 4 groups. Iron deficiency anaemia was induced by oral administration of the Asunra drug. The treatments were fed at two dosage levels i.e., 40 and 60% iron-fortified leather. All animals were treated for 60 days and the parameters including biochemical, and histopathology of the kidney and liver were examined. Results: The experiment's findings showed that the group fed with iron-fortified leather (G3) succeeded significantly (P < 0.05) in restoring the serum iron (98.68 ± 2.88 µg/dL), haemoglobin (12.41 ± 0.32 g/dL), ferritin (24.54 ± 1.98 ng/mL) and haematocrit levels (39.30 ± 1.66%) at the end of the 60 days period. Additionally, the treated group's mean values for transferrin and total iron binding capacity were lower than those of the anaemic rats, indicating an improvement in iron levels. The microscopic analysis revealed that treatments had no toxic effects on the kidney and liver tissues, except in the diseased group, which had necrosis and irregular cell structure. Conclusion: Conclusively, iron-fortified jamun leather helped improve iron deficiency biomarkers and imparted a non-toxic effect on tissues in rats.

Phytochemical screening of Prunus avium for its antioxidative and anti-mutagenic potential against DMBA-induced hepatocarcinogenesis.

Scope: Prunus avium fruit is the richer source of phenolics known to exert anticancer and anti-invasive activities. The study aimed at elucidating antiproliferative and chemo-preventive potential of sweet cherries (P. avium) against the in vivo hepatocarcinoma model. Methods and results: The quantification of ultrasound-assisted extract (UAE) of P. avium depicted anthocyanins, ferulic acid, gallic acid, quercetin, syringic acid and p- and m-coumaric acids as major phytochemicals. The hepatocarcinoma (HCC) was induced in rats through intraperitoneal administration of DMBA (20 mg/kg B.W) once a week for the period of eight weeks. The intragastric administration of P. avium UAE, as cotreatment (500 mg/Kg B.W) to treatment group, significantly (p < 0.01) attenuated the raised serum alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) as well as total oxidative stress (TOS) and enhanced total antioxidant capacity TAOC in contrast to diseased rats. Moreover, microscopic examination of hepatic tissues confirmed the pleomorphism, nests of neoplastic hepatocytes and necrosis in HCC-bearing rats as compared to extract-fed rats, where these necrotic changes were suppressed. Besides, qRT-PCR analysis of hepatic tissues demonstrated the higher mRNA expression of CHEK1, CHEK2 and P21/CDKN1α genes, while downexpression of ATM gene in extract fed rats, further denoting the anti-mutagenic potential. Conclusion: Consequently, the polyphenol-rich sweet cherries UAE exhibited antiproliferative and chemo-preventive potential by reducing tumor biomarkers, serum transaminases and oxidative stress, as well as enhancing antioxidant status. It further upregulated the downstream targets of ATM signaling cascade.

Development and bioassessment of high nutria-omega 5 cookies through animal modeling.

The food industry generates a diverse range of waste byproducts during fruit processing, which can be repurposed to create functional foods and other valuable commodities. In this particular study, leftover agro-waste from pomegranate juice was valorized to obtain pomegranate seed oil (PSO), while utilizing sunflower oilseed cake to produce sunflower meal protein concentrate (SMPC). These two extracted components were then combined as ingredients to produce High Nutria Omega 5 (HNO5) cookies. To ensure the quality and viability of pomegranate seed oil, a comprehensive set of laboratory analytical procedures were employed to evaluate its characteristics. Subsequently, different ratios of pomegranate seed oil and sunflower meal protein concentrate were utilized to develop the HNO5 cookie products. These cookies underwent thorough sensory, physicochemical, storage, and proximate evaluations as well as efficacy studies to assess their overall nutritional quality and shelf-life properties. As compared to the control feed, the findings of the renal and liver functional tests indicated a favorable effect on ALT, AST, ALP, serum urea, creatinine, albumin, globulins, total proteins, and A/G ratio. The results revealed that PSO and SMPC cookies containing 15% PSO and 15% SMPC exhibited stability in numerous physicochemical and sensory assessments. The punicic acid in HNO5 cookies significantly reduced the effects of starvation in rats and progressively improved several metabolic processes and overall health profiles. Graphical Abstract.

Analyzing cross-talk of EPO and EGF genes along with evaluating therapeutic potential of Cinnamomum verum in cigarette-smoke-induced lung pathophysiology in rat model.

The integrity of the distal alveolar epithelium is crucial for lung regeneration following an injury. The present study aimed to evaluate the effect of Cinnamomum verum extract; cross-talk of epidermal growth factor (EGF) and erythropoietin (EPO) genes in a smoke-induced lung injury rat model. For experimentation (n = 27), albino rats were divided equally into three groups, i.e., negative control (NC), positive control (PC), and treatment group (TG). Cigarette smoke was exposed to PC and TG (4 CG/day). C. verum was given orally (350 mg/kg body weight) for 21 days. Decapitation (n = 3) was done on 14th, 18th, and 21st days, respectively. Analyses (hematology, biochemical, high performance liquid chromatography [HPLC], histology, and gene expression) were carried out and results were statistically analyzed by two-way analysis of variance. HPLC analysis of ethanolic extract of C. verum was done to identify the presence of phenolic constituents which showed high concentrations of quercetin and P-coumaric acid. Serum oxidative parameters such as total oxidant status, malondialdehyde, and hematological parameters such as red blood cells, hemoglobin, hematocrit, and white blood cells were significantly (p < .05) elevated in the PC group; however, these parameters were significantly (p < .05) improved in TG. While total antioxidant capacity and serum parameters such as total protein, albumin, and globulin were significantly (p < .05) reduced in the PC group but significantly improved (p < .05) in TG. Histological analysis revealed that smoke exposure resulted in a measurable increase in alveolar septal thickening while ethanolic extract of C. verum greatly ameliorated the histopathological changes in the lung alveoli. The gene expression analysis of EGF and EPO genes showed a significant upregulation (p < .05) of both genes in PC group while in TG, the level of both genes downregulated, in which lung damage was ameliorated due to cytoprotective effects of ethanolic extract of C. verum.

Curcumin Co-Encapsulation Potentiates Anti-Arthritic Efficacy of Meloxicam Biodegradable Nanoparticles in Adjuvant-Induced Arthritis Animal Model.

This study aimed to evaluate the anti-arthritic activity of curcumin and meloxicam co-loaded PLGA nanoparticles in adjuvant-induced arthritic rats. PLGA nanoparticles encapsulating curcumin (nCur) and meloxicam (nMlx) alone and in combination (nCur/Mlx) were used to characterize zeta size and potential, polydispersity index, encapsulation efficiency (%), compound-polymer interactions (FT-IR analysis), and surface morphology (SEM imaging). In vivo, Complete Freund's adjuvant-induced arthritic rats were intraperitoneally (i.p.) administered with curcumin, meloxicam, curcumin plus meloxicam, nCur, nMlx, and nCur/Mlx for 28 consecutive days. Results showed that nCur, nMlx, and nCur/Mlx significantly (p ≤ 0.05) reduced paw swelling and arthritic score, restored body weight and the immune organ index (thymus and spleen), as well as attenuated serum inflammatory markers (RF, CRP, and PGE2) and oxidative stress parameters (MDA, SOD, and CAT) in adjuvant-induced arthritic rats compared to free compounds. In addition, mono- and dual-compound-loaded nanoparticles significantly (p ≤ 0.05) down-regulated pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6), up-regulated anti-inflammatory cytokines (IL-4, IL-10, and IFN-γ), and modulated OPG and RANKL expressions in paw tissue. The aforementioned results were further confirmed through radiological and histopathological examinations. Furthermore, the anti-arthritic effect of nCur/Mlx was notably (p ≤ 0.05) enhanced compared to nCur or nMlx alone. In conclusion, the co-nanoencapsulation of curcumin could potentiate the anti-arthritic activity of meloxicam and could provide a novel therapeutic approach for the formulation of nanocarrier pharmaceutical products for the management of arthritis.

Anti-Pyretic, Analgesic, and Anti-Inflammatory Activities of Meloxicam and Curcumin Co-Encapsulated PLGA Nanoparticles in Acute Experimental Models.

Herein, we evaluated the in vivo effects of meloxicam and curcumin co-encapsulated PLGA nanoparticles in experimental acute models of pyrexia, nociception, and inflammation. Seven groups (n = 6) were designed for each investigation and pretreated intraperitoneally (i.p.): the control group, meloxicam (4 mg/kg b.w.), curcumin (15 mg/kg b.w.), and equivalent content containing PLGA capped nanoparticles of meloxicam (Mlx-NP) and curcumin (Cur-NP) alone and in combination (Mlx-Cur-NP; at two doses). The results showed that PLGA encapsulation significantly (p ≤ 0.05) improved the in vivo activities of each compound. Furthermore, co-encapsulation of meloxicam and curcumin potentiated the anti-pyretic effect on yeast-induced pyretic rats, anti-nociceptive effect on nociception induced in rats by formalin and heat, and anti-edematogenic activity in xylene-induced ear edema in rats in a dose-dependent manner. In carrageenan-induced paw inflammation in rats, meloxicam and curcumin co-loading (Mlx-Cur-NP) resulted in significant (p ≤ 0.05) inhibition of paw inflammation, reduction in TNF-α and PGE2 levels, downregulation of expressions of pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6), as well as a decrease in histopathological changes and TNF-α immunoexpression in paw tissues. Moreover, Mlx-Cur-NP demonstrated noteworthy potentiation in pharmacological effects compared to free compounds and mono-compound-loaded nanoparticles. Thus, the association of meloxicam with curcumin in a biodegradable nanocarrier system could provide a promising anti-pyretic, anti-nociceptive, and anti-inflammatory therapeutic approach for acute conditions.

Acacia jacquemontii ethyl acetate extract reduces hyperglycemia and pro-inflammatory markers while increasing endogenous antioxidant potential in alloxan-induced diabetic rats.

Acacia jacquemontii possess has numerous traditional therapeutic uses. The rationale of this study was to investigate the role of Acacia jacquemontii ethyl acetate extract (AJEAE) in the downregulation of hyperglycemia. The current study was performed in two parts, in vitro, through characterization (high-performance liquid chromatography), estimation of total phenolic content, total flavonoid content, antioxidant (2,2-diphenyl-1-picrylhydrazylassay), and α-amylase inhibitory activities of the studied extract, and in vivo using Wistar rats in which animals were divided into five groups NC, DC, GL, AJEAE 250 mg/kg, and AJEAE 500 mg/kg. The effects of AJEAE on fasting plasma glucose, plasma insulin, HOMA-IR, oral glucose tolerance test, glycated hemoglobin (HBA1c), lipid profile, inflammatory cytokines (Interleukin-6, tumor necrosis factor-alpha), and oxidative stress markers (lipid peroxidation, nitic oxide, superoxide dismutase, catalase, glutathione peroxidase) were evaluated. Our findings confirmed the presence of quercetin, kaempferol, gallic acid, vanillic acid, syringic acid, M-coumaric acid, sinapic acid, chlorogenic acid, cinnamic acid, and ferulic acid in AJEAE. Total flavonoid and phenolic contents in AJEAE were 83.83 mg GAE/g and 77.06 mg QE/g, respectively. Significant inhibition of DPPH (69.470%/1 mg/ml) and α-amylase (71.8%/1 mg/ml) activities were exhibited by AJEAE. Alloxan-injected rats showed marked hyperglycemia and hypoinsulinemia, and increased inflammatory marker levels as compared to normal control (p < 0.001). Additionally, raised levels of triglyceride (139.7 ± 2.771), total cholesterol (198.7 ± 1.856), very low-density lipoprotein (33.43 ± 0.2728), low-density lipoprotein (155.5 ± 2.754), lipid peroxidation, and nitric oxide (p < 0.001) and decreased levels of high-density lipoprotein (17.20 ± 0.1732), superoxide dismutase, catalase, and glutathione peroxidase were observed in diabetic rats (p < 0.001). AJEAE significantly (p < 0.05) improved the aforementioned parameters and the protective efficacy was comparable to glibenclamide. Histopathological findings also evidenced the anti-hyperglycemic properties of AJEAE through regeneration of pancreatic ß cells. Conclusively, our findings demonstrated the antihyperglycemic, antihyperlipidemic, antioxidant, anti-inflammatory, and pancreatic beta ß cell regenerative properties of AJEAE against alloxan-induced diabetes.

Phytochemical characterization of Morus nigra fruit ultrasound-assisted ethanolic extract for its cardioprotective potential.

The current work investigated the phytochemical profile of ultrasound-assisted ethanolic extract of Morus nigra (M. nigra) fruit. FTIR analysis of M. nigra fruit extract revealed the presence of alcohols (O-H), alkanes (C-H stretch), alkenes (C=C), and alkynes (C≡C). The HPLC analysis quantified the quercetin, gallic acid, vanillic acid, chlorogenic acid, syringic acid, cinnamic acid, sinapic acid, and kaempferol. Furthermore, the cardioprotective activity of ethanolic extract of M. nigra fruit was investigated. Cholesterol supplementation (2%) in the daily diet and exposure to cigarette smoke (2 cigarettes twice a day) were to induce hypertension in rats. The experimental animals were categorized into four groups: G0 (negative control), G1 (positive control), G2 (standard drug), and G3 (M. nigra fruit). The fruit extract administration at 300 mg/kg BW/day orally for 2 months significantly (p < .001) enhanced the activities of serum and cardiac tissue antioxidants in hypertensive rats. Meanwhile, the fruit extract reduced the elevated serum lipid profile while significantly increasing the high-density lipoproteins in G3 than G1 and G2. The increase in blood pressure, liver transaminases, and serum lactate dehydrogenase also reduced significantly in M. nigra fruit extract-treated rats. Histopathological findings revealed mild normalization of cardiac myocytes with central nuclei, branching, and cross-striations. Consequently, the M. nigra fruit extract exerted the cardioprotective potential via increasing the antioxidant enzymes and reducing the lipids, lactate dehydrogenase, liver transaminases, and blood pressure. The therapeutic potential of M. nigra fruit can be due to flavonols and phenolic acids. PRACTICAL APPLICATIONS: The present work quantified the Morus nigra fruit phytochemicals and its significant role in reducing lipid markers and blood pressure and improving antioxidant status in rats fed a hypercholesterolemic diet and exposed to cigarette smoke. Conclusively, the inclusion of M. nigra fruit in daily diet could improve the cardiac health of the individuals. Furthermore, the therapeutic potential of M. nigra fruit and its isolated constituents in modulating the gene expression against cardiac problems can explore after clinical trials and standardization in higher animals.

Probing the antioxidant potential of Juglans regia (walnut) against arthritis-induced oxidative stress in Sprague Dawley rats.

Oxidative stress is the underlying cause of various chronic diseases and can contribute to its progression. Plant-based therapeutics are effective in the prevention of various chronic diseases through the management of underlying causes. Walnuts owing to their rich phytochemistry possess antioxidative potential. In this context, the present research was designed to explore the therapeutic potential of walnut against arthritis-induced oxidative stress in rat model. Purposely, 50 Sprague Dawley rats were separated into five groups of 10 rats each. The rats were categorized as G0 (negative control), G1 (positive control), G2 (methotrexate), G3 (walnut feed), and G4 (walnut extract). Walnut feed and extract significantly reduced oxidative stress by improving the antioxidant enzymes in arthritic rats. Total oxidative stress was reduced by 41.44% and 21.52% in G3 while 52.81% and 36.76% in G4 when compared with G1 and G2 , respectively. Antioxidant enzyme levels in serum were significantly improved after the walnut-based interventions. Evidently, superoxide dismutase level improved by 74.5% in G3 and 83.40% in G4 , while catalase level increased by 51.99% in G3 and 61.34% in G4 , respectively, when compared with G1 . Liver function biomarkers, that is, ALP and AST, were decreased in G3 and G4 when compared with G1 and G2 . The histopathological examination illustrated the promising role of walnut-based interventions in conserving the structural integrity of hepatic and renal tissues. Meanwhile, gene expression analysis revealed that walnut treatments protected from oxidative damage by the downregulation of Dual-oxidases expression. Conclusively, walnut feed and extract might serve as potent antioxidant intervention with no potential side effects. PRACTICAL APPLICATIONS: The present work was aimed to evaluate the efficacy of walnut-based interventions against arthritis-induced oxidative stress. The walnut-based interventions positively modulated the antioxidant enzymes, liver, and kidney functions, while downregulating the gene associated with oxidative stress in animal model. Consequently, the current findings suggest wider applications of walnuts to avoid free radical induced damage during arthritis; however, human intervention studies may be carried out to further understand the mechanism of their bioefficacy.

Prophylactic role of olive fruit extract against cigarette smoke-induced oxidative stress in Sprague-Dawley rats.

Cigarette smoke exposure increases the production of free radicals leading to initiation of several pathological conditions by triggering the oxidative stress and inflammatory cascade. Olive fruit owing to its unique phytochemical composition possesses antioxidant, immune modulatory, and anti-inflammatory potential. Considering the compositional alterations in olive fruits during ripening, the current experimental trail was designed to investigate the prophylactic role of green and black olives against the oxidative stress induced by cigarette smoke exposure in rats. Purposely, rats were divided into five different groups: NC (negative control; normal diet), PC [positive control; normal diet + smoke exposure (SE)], drug (normal diet + SE + citalopram), GO (normal diet + SE + green olive extract), and BO (normal diet + SE + black olive extract). Rats of all groups were exposed to cigarette smoke except "NC" and were sacrificed for collection of blood and organs after 28 days of experimental trial. The percent reduction in total oxidative stress by citalopram and green and black olive extracts in serum was 29.72, 58.69, and 57.97%, respectively, while the total antioxidant capacity increased by 30.78, 53.94, and 43.98%, accordingly in comparison to PC. Moreover, malondialdehyde (MDA) was reduced by 29.63, 42.59, and 45.70% in drug, GO, and BO groups, respectively. Likewise, green and black olive extracts reduced the leakage of hepatic enzymes in sera, alkaline phosphatase (ALP) by 23.44 and 25.80% and 35.62 and 37.61%, alanine transaminase (ALT) by 42.68 and 24.39% and 51.04 and 35.41%, and aspartate transaminase (AST) by 31.51 and 16.07% and 40.50 and 27.09% from PC and drug group, respectively. Additionally, olive extracts also maintained the antioxidant pool, i.e., superoxide dismutase, catalase, and glutathione in serum. Furthermore, histological examination revealed that olive extracts prevented the cigarette smoke-induced necrosis, pyknotic alterations, and congestion in the lung, hepatic, and renal parenchyma. Besides, gene expression analysis revealed that olive extracts and citalopram decreased the brain and lung damage caused by stress-induced upregulation of NRF-2 and MAPK signaling pathways. Hence, it can be concluded that olives (both green and black) can act as promising antioxidant in alleviating the cigarette smoke-induced oxidative stress.