Therapeutic potential of d-limonene in rheumatoid arthritis: Modulation of inflammatory, anti-inflammatory cytokines, and prostaglandin E2.

Rheumatoid arthritis (RA) is a persistent autoimmune disorder predominantly affecting the joint structures, eliciting inflammatory responses, and ultimately leading to degenerative changes without proper medical intervention. Ultimately, this can severely impair joint function and impact the patient's quality of life. Current treatment approaches include disease-modifying anti-rheumatic drugs, non-steroidal anti-inflammatory drug, corticosteroids, and biologic therapies for RA management. The current study contributes to the ongoing advancements in RA treatment. d-Limonene is a monocyclic monoterpene. It is present in essential oils of various aromatic plants, such as Lippia alba and Artemisia dracunculus, and in citrus fruits such as lemon and orange. It has reported anti-inflammatory and anti-nociceptive properties and was selected for the current study as a potential anti-arthritic candidate. It was administered at three dosages (25, 50, 100 mg/kg, b.w., p.o) in Complete Freund's adjuvant-induced arthritic rats over 28 days. The efficacy of the compound was compared to piroxicam, a widely used standard drug for treating RA. The anti-arthritic activity of the compound was assessed by measuring arthritic scoring and plethysmometry at both baseline and post-intervention stages. Additional confirmation of the investigation was sought by performing biochemical and hematological activities. Moreover, quantitative polymerase chain reaction was employed to determine the levels of messenger RNA expression for transcription factors such as tumor necrosis factor-α, interleukin (IL)-1ß, nuclear factor-κB, matrix metalloproteinase-3, IL-6, and IL-4 in the blood. The levels of PGE2 were evaluated by enzyme-linked immunosorbent assay. The histopathological and radiographic studies were also carried out for further confirmation. The results of these findings supported our assertion regarding the anti-arthritic potential of the compound.

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.

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.

Protective effect of Heliotropium strigosum 70% aqueous methanolic extract against paracetamol induced hepatotoxicity in mice.

The study was carried out to evaluate the hepatoprotective potential of aqueous methanolic extract of Heliotropium strigosum (HSME) against paracetamol induced hepatotoxicity in Swiss albino mice. The plant powder (1.5Kg) was macerated in aqueous methanol (30:70) for 7 days. The extract was evaluated for the presence of different phytochemicals and High-performance liquid chromatography (HPLC) analysis. HSME was orally administered to mice at 125, 250 and 500mg/kg for 8 days followed by paracetamol intoxication (500mg/kg orally) on the 8th day using silymarin as standard control. All the therapy was administered by oral gavage. The liver biochemical parameters and histopathological evaluation were carried out to assess changes in liver function and histology. HPLC analysis confirmed the presence of quercetin, kaempferol, and other phenolic compounds. Treatment with the extract resulted in notable (p<0.05) reduction in liver parameters in dose dependent manner. The action of HSME 500mg/kg dose was comparable to silymarin. The effect of HSME against paracetamol induced hepatotoxicity was demonstrated by protective changes in the liver histopathological which proved the traditional uses of the plant.

Anti-inflammatory effects of Trigonella gharuensis: Comparative analysis in BALB/C mouse model.

Plants are extensively used in treating inflammatory disorders. The current study focused on evaluating anti-inflammatory potential of Trigonella gharuensis. The ethanolic and n-hexane extracts of T. gharuensis were given orally at the dose of 400mg/kg/day. Various in vivo inflammatory models such as carrageenan-, histamine-, dextran- and serotonin-induced paw edemas; xylene-induced ear edema, and castor oil-induced diarrhea models were used for validation of different mechanisms of autacoid inhibition. Gas chromatography-mass spectrometry analyses were performed to find out compounds responsible for anti-inflammatory properties. Both extracts significantly inhibited (P<0.05) carrageenan-, histamine-, dextran- and serotonin-induced paw edema in early and late acute inflammation phases. Suppression of xylene-induced ear edema supported suggested inhibition of autacoids. Attenuation of castor oil-induced diarrhea suggested prostaglandin inhibition by both extracts and supported inhibition of carrageenan-induced inflammation in the late phase. GC-MS analysis indicated constituents with considerable biological activities such as, saturated and unsaturated fatty acid esters, coumarins, terpenes, and aromatic and aliphatic compounds in the extracts. In conclusion, extracts of T. gharuensis possess significant anti-inflammatory activity which might be ascribed to the inhibition of autacoids.

Effectiveness of clobazam on perception, creativity, intelligence, selective and visual memory.

Clobazam belongs to benzodiazepine class and is preferably used against anti-epileptic disorders. However, when used in reduced doses, its ability for improving cognitive functions becomes explicitly evident. This study objectively undertook the task of using the reduced doses of clobazam for proving potentials effects on cognitive functions. The drug, clobazam was administered in "active group" which contained 15 young healthy volunteers. The "placebo group" also entailed 15 subjects and each was administered with placebo drug. The controlled group? also included 15 subjects. All these 45 young healthy subjects were subjected to tests for perceptual learning, creativity, selective memory, visual memory and intelligence. Results clearly demonstrated significant impact of clobazam at the dose of 5mg/day on perceptual learning (P=0.0380), creativity (P=0.0787), memory function (P=0.4920), visual memory (P=0.4816) and intelligence of the subject (P=0.4920). The outcomes highlighted in the studies reviled the positive effects of clobazam when used at reduced doses.

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.

Mechanistic evaluation of antiarthritic and anti-inflammatory effect of campesterol ester derivatives in complete Freund's adjuvant-induced arthritic rats.

Background: Current therapies for RA have limitations and side effects, leading to a growing need for safer treatment options. Natural compounds from plants are gaining attention for their therapeutic benefits and fewer side effects. One such compound is the campesterol derivative, a steroid derivative occurring in plants. Studies have shown that this derivative has anti-inflammatory properties and can impact the expression of pro-inflammatory factors. The primary objective of this study was to explore and assess the potential therapeutic effects of Campesterol Ester Derivatives (CED) utilizing a rat model of arthritis induced by Complete Freund's Adjuvant (CFA). Method: The rats were divided into specific experimental groups and treated with either CED or piroxicam (as a positive control) for a duration of 28 days. We determined the effects of CED on various parameters including paw edema, thermal hyperalgesia, and mechanical allodynia at different time points. Furthermore, serum levels of inflammatory cytokines, oxidative stress markers and histological analyses were performed. Additionally, mRNA expression levels of inflammatory markers, both pro-inflammatory (such as TNF-α, NF-κB, IL-6, COX-1, COX-2, and IL-4) and anti-inflammatory were analyzed. Results: In the arthritic rat model, CED exhibited significant anti-inflammatory effects and resulted in a notable reduction in paw edema levels compared to the control group. Histopathological examination of the treated rats' paws confirmed a decrease in inflammation and tissue damage, including reduced pannus formation and bone erosion. Importantly, there were no observable signs of damage to the liver and kidneys following CED treatment, indicating its safety profile and potential for organ protection. At the molecular level, CED treatment downregulated mRNA expression levels of pro-inflammatory markers, indicating its ability to suppress inflammation. Conversely, certain anti-inflammatory markers were upregulated following CED treatment, suggesting a positive influence on the immune response. The positive effects of CED were not limited to joint inflammation; it also showed systemic benefits by positively influencing hematological and biochemical parameters. Conclusion: CED demonstrated promising therapeutic potential as an anti-inflammatory intervention for arthritis in the experimental rat model. Its ability to reduce inflammation, protect tissues, and improve organ function indicates its multifaceted benefits.

Mechanistic Evaluation of Antiarthritic Effects of Citronellol in CFA-Induced Arthritic Rats.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by systemic inflammation, joint tissue damage, pain, and synovitis. It leads to deformity of joints, disability, and even premature death. Markers of inflammation are highly expressed in synovium fluid and serum of arthritic patients and play an important role in the pathophysiology of RA. These transcription factors promote the fabrication of type I interferons and inflammatory cytokines. In RA, degradation of synovial cartilage and bone results from stimulation of proinflammatory cytokines. Citronellol (Ct), a monoterpene alcohol, is found in citrus fruits and essential oils of many aromatic plants. It possesses numerous pharmacological properties such as antioxidant activity and potential antinociceptive and anti-inflammatory effects. Keeping in view the significant anti-inflammatory role of Ct, a trial of 28 days was conducted. Ct was administered orally at three different doses (25, 50, and 100) mg/kg in Freund's adjuvant-induced arthritic rats, and the results were compared with piroxicam, chosen as the standard drug. The antiarthritic activity of the compound was evaluated through measurements of arthritic scoring and plethysmometry before and after treatment. The blood biochemical and hematological parameters and histopathological analyses were performed. Additionally, qPCR was conducted to analyze the mRNA expression levels of TNF-α, IL-1ß, NF-κB, MMP3, IL-6, and IL-4 in the blood. ELISA was performed to evaluate the levels of PGE2. The results demonstrated that Ct showed significant results at all doses, but the highest dose proved to be most significant in terms of decreasing arthritic scoring and paw edema, indicating the antiarthritic potential of Ct. Furthermore, the compound was found to downregulate all the proinflammatory cytokines (TNF-α, IL-1ß, NF-κB, MMP3, and IL-6) and upregulate the anti-inflammatory cytokine (IL-4). The levels of PGE2 were also reduced which further supported the antiarthritic effects of Ct and validated it as a potential antiarthritic candidate.

Evaluation of anti-inflammatory and immunomodulatory potential of Lawsone (2-hydroxy-1,4-naphthoquinone) using pre-clinical rodent model of rheumatoid arthritis.

Background: Lawsone (2-hydroxy-1,4-naphthoquinone) is naturally present in Lawsonia Inermis and flowers of Eicchornia crassipes. This study assessed the anti-arthritic potential of Lawsone, using FCA-induced Sprague-Dawley rats. Methods: Arthritic progress was analyzed through a macroscopic scoring scale, measurement of paw edema, and histopathological changes. Effects of Lawsone on mRNA expression levels of inflammatory markers were examined using the reverse transcription PCR technique. ELISA technique was used to evaluate the PGE2 levels. Moreover, levels of biochemical and hematological parameters were also analyzed. Results: The research elucidated that Lawsone showed an inhibitory potential towards arthritic progress and ameliorated the paw edema. The histopathological analysis also validated the inhibition in arthritic development. Treatment with Lawosne reduced the expression levels of inflammatory markers in rats i.e., VEGF, TNF-α, MMP-2, MMP-3, NF-κB, IL-1ß, and IL-6. PGE2 levels (all p < 0.001) were also found reduced in treatment groups. Lab investigations showed improved results of hematological and hepatic parameters in the treated groups as compared to the positive control. This study found no hepatotoxic or nephrotoxic effects of Lawsone in the test doses. Conclusion: Lawsone possesses an anti-arthritic property which could be ascribed to its immunomodulatory and anti-inflammatory effects.

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.

Anti-Arthritic and Immunomodulatory Potential of Methanolic, n-Hexane, and Ethyl Acetate Fractions of Bark of Acacia modesta on Complete Freund's Adjuvant-Induced Arthritis in Rats.

Rheumatoid arthritis is an autoimmune disorder and topic of interest for researchers due to its increasing frequency and limited treatment. Acacia modesta Wall is known to treat rheumatic disorders in the traditional system of medicinal plants. Traditional medicines are still required for the treatment of this disease due to the large number of side-effects caused by commercial medicines. In the current study, the antiarthritic potential of methanolic extract (AM-metha), n-hexane (AM-hexa) fraction, and ethyl acetate (AM-etha) fraction of the bark of A. modesta against a complete Freund's adjuvant rat model was evaluated. Evaluation using a digital plethysmometer, macroscopic evaluation, and histopathological evaluation were conducted to determine the paw volume and arthritic scoring. ELISA was performed to assess the PGE2 levels. RT-PCR was used to evaluate the expression levels of MMP2, MMP3, MMP9, NF-κB, IL6, IL1ß, TNFα, and VEGF. Biochemical and hematological analyses were also conducted. GC/MS was also carried out to analyze the presence of medicinal compounds. The data revealed a marked reduction in the paw volume, arthritic scoring, and histopathological parameters, indicating the anti-arthritic potential of the plant. Treatment with plant extracts and fractions markedly down-regulated MMP2, MMP3, MMP9, NF-κB, IL6, IL1ß, TNFα, and VEGF levels. Similarly, PGE2 levels were also found to be ameliorated in the treatment groups, indicating the immunomodulatory property of plant bark. Plant treatment nearly normalized hematological parameters such as counts of WBCs, RBCs, and platelets, along with Hb content, thereby validating the anti-arthritic activity. GC/MS analysis disclosed the presence of strong anti-inflammatory compounds such as lupeol, oleic acid, and squalene. The study showed that A. modesta possesses anti-arthritic and immunomodulatory potential linked to significant down-regulation of pro-inflammatory and inflammatory biomarkers.

Preclinical Rodent Models of Arthritis and Acute Inflammation Indicate Immunomodulatory and Anti-Inflammatory Properties of Juglans regia Extracts.

Juglans regia has been used to treat inflammatory and arthritic disorders in traditional medicine. The present study aimed to investigate the antiarthritic and anti-inflammatory potential of ethanolic leaves extract of J. regia. Arthritis was induced in rodents with Freund's complete adjuvant. J. regia treatment was started on 8th day of arthritis induction and sustained for 20 days. Acute inflammatory models were developed using carrageenan, histamine, serotonin, and dextran. Qualitative and GC-MS analyses were also performed. Arthritis was determined using an arthritis scoring index and histopathological examination of ankle joints. RT-PCR was performed to determine the expression of pro-inflammatory markers (TNF-α, NF-κB, IL-6, IL-1ß, and COX-2) and anti-inflammatory IL-4. PGE2 levels were evaluated using an ELISA. Blood and biochemical parameters were also determined. Paw edema was measured using a digital plethysmometer. Treatment with extracts inhibited arthritic development and attenuated paw edema along with all histopathological parameters. The expression levels of pro-inflammatory cytokines and COX-2 were downregulated, while IL-4 was upregulated. PGE2 levels were also reduced in extract-treated groups. Blood and biochemical parameters were nearly normalized in the treatment groups. Both extracts significantly inhibited carrageenan, histamine, serotonin, and dextran-induced paw edema. Qualitative phytochemical screening and GC-MS analysis confirmed that extracts possessed potential medicinal compounds. In conclusion, ethanol and n-hexane extracts of J. regia leaves have immunomodulatory and anti-inflammatory effects that ameliorate experimentally induced arthritis and edema. The inhibition of autacoids may also be one of the mechanisms inducing the immunomodulatory effect.

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.

Phyllanthus reticulatus Prevents Ethanol-Induced Gastric Ulcer via Downregulation of IL-8 and TNF-α Levels.

The current study aimed to determine the protective effect of P. reticulatus on ethanol-induced gastric ulcer. For this purpose, thirty-six Sprague-Dawley rats were divided into six groups. The first group served as normal control, while, in other five groups, absolute ethanol was used to induce gastric ulcer. Group II served as a diseased group, while groups III, IV, and V were treated with methanol extract, ethyl acetate fraction, and n-hexane fraction, respectively, in a dose of 400 mg/kg bodyweight. Group VI was given omeprazole in a dose 20 mg/kg bodyweight. The stomachs were removed, ulcer score was evaluated, and histopathological examination of gastric lumen was conducted. Total acidity and pH values were determined in gastric juice. TNF-α and IL-8 mRNA expressions levels were determined using the reverse transcription real-time PCR method. The data indicated that P. reticulatus protected against gastric ulcer, which was evident by attenuation of ulcer score. The pretreatment with P. reticulatus raised the gastric pH and improved all evaluated histopathological parameters such as ulcer score, erosion score, hemorrhage score, fibrinoid necrosis score, inflammatory infiltrate score, and edema score. P. reticulatus significantly reduced mRNA expression levels of TNF-α and IL-8. In conclusion, P. reticulatus possess antiulcer property which might be attributed to downregulation of TNF-α and IL-8 expression levels.

Amelioration of airway inflammation and pulmonary edema by Teucrium stocksianum via attenuation of pro-inflammatory cytokines and up-regulation of AQP1 and AQP5.

Current study investigates the immunomodulatory effects of T. stocksianum using mouse model of ovalbumin (OVA)-induced allergic asthma. The mice were treated with methanolic extract, n-hexane, and ethyl acetate fractions for consecutive 7 days along with intranasal challenge. The mRNA expression levels of interleukin-4 (IL-4), IL-5, Aquaporin-1 (AQP1) and Aquaporin-5 (AQP5) were evaluated using reverse transcription polymerase chain reaction. The data showed that T. stocksianum significantly reduced airway inflammation as indicated by reduced inflammatory cell infiltration in lungs, and attenuated total and differential leukocyte counts both in blood and BALF. Expression levels of pro-inflammatory IL-4 and IL-5 in lungs were also found significantly reduced. T. stocksianum significantly reduced pulmonary edema as indicated by reduced lung wet/dry ratio and goblet cell hyperplasia. AQP1 and AQP5 expression levels were also found elevated in treatment groups. In conclusion, T. stocksianum possesses anti-asthmatic activity which may be attributed to reduction in IL-4 and IL-5 expression levels, and elevation in AQP1 and AQP5 expression levels.

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.

Evaluation of Immunomodulatory and Antiarthritic Potential of Trigonella gharuensis Extracts.

The genus of Trigonella has long been used for the treatment of arthritis and inflammatory disorders. This study was aimed to investigate the immunomodulatory activities of ethanol and n-hexane extracts of T. gharuensis in the rat model of rheumatoid arthritis. Freund's complete adjuvant (FCA) model was used to induce arthritis in rats. Arthritis was induced on day 0, while treatment which was started on day 8 continued for twenty days. Arthritic development and paw edema were determined using an arthritic scoring index and plethysmometer, respectively. Histopathology was evaluated using H&E staining. RNA extraction, reverse transcription, and polymerase chain reaction (RT-PCR) were performed to determine expression levels of proinflammatory markers such as TNF-α, NF-ĸB, IL-6, IL-1ß, COX2, and anti-inflammatory cytokine IL-4. Prostaglandin E2 level (PGE2) was evaluated using ELISA. Blood analysis and biochemical parameters were also determined. The significance level was set as P < 0.05. Treatment with extracts reduced paw edema, arthritic progression, and histopathological parameters. Expression levels of abovementioned proinflammatory cytokines and COX2 were downregulated, while IL-4 was upregulated. PGE2 levels were found reduced with extract treatment. Blood parameters were nearly normalized in treatment groups. Extract treatment did not alter biochemical parameters. Both extracts had effects comparable with piroxicam. In conclusion, extracts of T. gharuensis ameliorated experimentally induced arthritis that may be ascribed to its immunomodulatory effects.

Amelioration of allergic asthma by Ziziphora clinopodioides via upregulation of aquaporins and downregulation of IL4 and IL5.

Ziziphora clinopodioides has been frequently used as an anti asthmatic plant in traditional medication. Recent work explores the anti-asthmatic activity of Z. clinopodioides in allergen-induced asthmatic mice. Intraperitoneal sensitization followed by intranasal challenge were given with ovalbumin (allergen) to develop allergic asthma. Investigational groups of animals were administered with drug methylprednisolone (MP) (15 mg/kg body weight), n-hexane fraction, ethylacetate fraction, and methanolic extract of Z. clinopodioides extract (500 mg/kg b.w.) for successive 07 days. Hematoxyline and eosin (H&E) and periodic acid-Schiff (PAS) stains were used to evaluate histopathological parameters on lung tissues. As an index of lungs tissues edema, wet/dry weight ratio of lungs was determined. Evaluation of expression levels of AQP1, AQP5, IL4, and IL5 was conducted by using RT-PCR. The data exhibited that both Z. clinopodioides and MP attenuated differential and total leukocyte counts in hematological examination i.e. in BALF and blood. Treatment with Z. clinopodioides also caused suppression of inflammatory cell infiltration and expression levels of IL4 and IL5, the later could have caused attenuation of pulmonary inflammation. The study also found decline in lung wet/dry ratio and goblet cellh hyperplasia in treated groups which indicates amelioration of lung edema. Treatment with Z. clinopodioides significantly increased the expression levels of aquaporin-1 and -5, which could have led to reduction in lung edema. The treatment with MP showed comparable results to Z. clinopodioides. Current investigation revealed that Z. clinopodioides possessed anti-asthmatic property which might be accredited to upregulagted AQP1 and AQP5 levels and downregulated IL4 and IL5 levels.