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

Ahsan, Fatima; Shabbir, Arham; Shahzad, Muhammad; Mobashar, Aisha; Sharif, Marriam; Basheer, Muhammad Irfan; Tareen, Rasool Baksh; Syed, Nawazish-i-Husain

doi:10.1016/j.resp.2019.04.005

Cited by 13 publications

(6 citation statements)

References 62 publications

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“…IL-4’s inhibitory effects are also extended to the osteoclasts, which play a critical role in cartilage destruction and bone erosion. Recombinant IL-4 therapy has shown promising results in RA patients by suppressing cytokine production and inflammatory processes . In our study, Ct significantly augmented the expression of IL-4 in all of the treatment groups.…”

Section: Discussionsupporting

confidence: 59%

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

Dar,

Mobashar,

Shabbir

et al. 2023

ACS Omega

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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-1β, 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-1β, 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.

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Section: Discussionsupporting

confidence: 59%

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

Dar,

Mobashar,

Shabbir

et al. 2023

ACS Omega

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“…Moreover, it is responsible for negative regulation of NF- κ B by increasing I κ B. IL-4 inhibits osteoclasts which are responsible for the destruction of cartilage and bone erosion in arthritic patients. Recombinant IL-4 therapy has resulted in the inhibition of cytokine production in patients suffering from RA [ 44 ]. J. regia significantly increased the levels of IL-4 in the treatment groups when compared to the positive arthritis control group.…”

Section: Discussionmentioning

confidence: 99%

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

Mobashar

Shabbir

Shahzad

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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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-1β, 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.

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“…These alterations of transcriptomes may have mediated the mechanisms underlying the correlation between AQP1 methylation and the prognosis of elderly CN-AML. While there are no novel drugs targeting AQP1 DNA methylation-related genes, there are demethylation drugs such as DNA methyltransferase inhibitors [5-azacytidine (52) and 5-aza-2 ′ -deoxycytidine (53)], second-generation DNMT inhibitors [Zebularine (54) and Guadecitabine (55)], and lysine demethylase inhibitors (56), and drugs that affect the expression level of AQP1 like Ziziphora clinopodioides which upregulates aquaporin 1 (57). It is worth noting that drugs affecting AQP1 expression are not currently used for cancer treatment.…”

Section: Discussionmentioning

confidence: 99%

A Novel Scoring System for Risk Assessment of Elderly Patients With Cytogenetically Normal Acute Myeloid Leukemia Based on Expression of Three AQP1 DNA Methylation-Associated Genes

Yin

Huang

et al. 2020

Front. Oncol.

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Background: Aquaporin 1 (AQP-1), a transmembrane water channel protein, has been proven to involve in many diseases' progression and prognosis. This research aims to explore the prognostic value of AQP-1 in elderly cytogenetically normal acute myeloid leukemia (CN-AML).Methods: Complete clinical and expression data of 226 elderly patients (aged > 60) with cytogenetically normal acute myeloid leukemia (CN-AML) were downloaded from the databases of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). We have explored prognostic significance of AQP-1, investigated the underlying mechanism, and developed a novel scoring system for the risk assessment of elderly patients with AML based on AQP1 methylation. Results:In the first and second independent group, AQP1 shows lower expression in CN-AML than normal people, while high AQP1 expression and AQP1 promoter hypomethylation were related to better overall survival (OS; P < 0.05). To understand the underlying mechanisms, we investigated differentially expressed genes (DEGs), miRNA and lncRNA associated with AQP1 methylation. A three-gene prognostic signature based on AQP1 methylation which was highly correlated with OS was established, and the performance was validated by Permutation Test and Leave-one-out Cross Validation method. Furthermore, an independent cohort was used to verify the prognostic value of this model.Conclusions: AQP1 methylation could serve as an independent prognostic biomarker in elderly CN-AML, and may provide new insights for the diagnosis and treatment for elderly CN-AML patients.

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

Cited by 13 publications

References 62 publications

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

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

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

A Novel Scoring System for Risk Assessment of Elderly Patients With Cytogenetically Normal Acute Myeloid Leukemia Based on Expression of Three AQP1 DNA Methylation-Associated Genes

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