Insights on in-silico approaches for identifying potential bioactive inhibitors for TNF-α and IL-6 proteins associated with rheumatoid arthritis DOI Creative Commons

Rana M. Aldossari,

Aarif Ali, Summya Rashid

и другие.

Arabian Journal of Chemistry, Год журнала: 2023, Номер 16(11), С. 105200 - 105200

Опубликована: Авг. 15, 2023

Rheumatoid arthritis (RA) is a chronic immunocompromised disorder that primarily affects joints thereby leading to synovial inflammation, pain, stiffness, stress, and affecting the quality of life. The present study aimed determine identify bioactive compounds can be developed as potential inhibitors target human TNF-α IL-6 proteins associated with RA. also physiochemical properties toxicity by ADMET, binding pockets via CASTp server, stereochemical protein PROCHECK, MMGB/SA analysis fastDRH molecular dynamics (WebGro). findings revealed staurosporine was most effective compound against highest affinity -10.8 kcal/mol. Similarly, withanoside L showed -8.2 kcal/mol when docked IL-6. In study, rutin, II, IV did not follow Lipinski's rule five whereas staurosporine, somnifericin, withanolide followed RO5. top pocket had area (SA) 2743.25 Å2 volume 4514.06 Å3 63.54Å2 38.58 respectively. this Ramachandran plot 90.2% 95.2% residues for occupied favored region. rutin complex PB1 score 13.69 12.30 WebGro server estimated dynamic (RMSD, Rg, SASA, RMSF hydrogen bonds) proteins. Bio2Byte tools predicted biophysical behaviour could TNF- α IL-6, however further in-vitro in-vivo studies are required validate these results.

Язык: Английский

Michael Acceptors as Anti-Cancer Compounds: Coincidence or Causality? DOI Open Access
Celia María Curieses Andrés, José Manuel Pérez de la Lastra, Elena Bustamante Munguira

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(11), С. 6099 - 6099

Опубликована: Июнь 1, 2024

Michael acceptors represent a class of compounds with potential anti-cancer properties. They act by binding to nucleophilic sites in biological molecules, thereby disrupting cancer cell function and inducing death. This mode action, as well their ability be modified targeted, makes them promising avenue for advancing therapy. We are investigating the molecular mechanisms underlying interactions cells, particular interfere cellular processes induce apoptosis. The properties not accidental but due chemical structure reactivity. electrophilic nature these allows selectively target residues on disease-associated proteins, resulting significant therapeutic benefits minimal toxicity various diseases. opens up new perspectives development more effective precise drugs. Nevertheless, further studies essential fully understand impact our discoveries translate into clinical practice.

Язык: Английский

Процитировано

14

Immunomodulatory effects of curcumin on macrophage polarization in rheumatoid arthritis DOI Creative Commons
Tingting Deng,

Jiahe Xu,

Qiong Wang

и другие.

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Фев. 28, 2024

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by synovial inflammation, cartilage destruction, pannus formation and bone erosion. Various immune cells, including macrophages, are involved in RA pathogenesis. The heterogeneity plasticity of macrophages render them pivotal regulators both the induction resolution inflammatory response. Predominantly, two different phenotypes have been identified: classically activated M1 exacerbate inflammation via production cytokines, chemokines other mediators, while alternatively M2 inhibit facilitate tissue repair. An imbalance M1/M2 macrophage ratio critical during initiation progression RA. Macrophage polarization modulated various transcription factors, epigenetic elements metabolic reprogramming. Curcumin, an active component turmeric, exhibits potent immunomodulatory effects administered treatment multiple diseases, regulation subsequent cytokine as well migration mechanisms underlying therapeutic effect curcumin on In this review, we summarize which modulates function context to provide evidence for clinical application treatment.

Язык: Английский

Процитировано

12

Curcumin Solubility and Bioactivity Enhancement Through Amorphization with Tryptophan via Supercritical Fluid Technology DOI Open Access
Ewa Garbiec, Natalia Rosiak, Szymon Sip

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(2), С. 855 - 855

Опубликована: Янв. 20, 2025

Curcumin, a compound known for its antioxidant and neuroprotective properties, faces challenges due to low water solubility, which can limit effectiveness. One effective method address this issue is through amorphization. Incorporating curcumin into polymeric matrix form amorphous solid dispersions common approach. Another strategy involves co-amorphous systems, where low-molecular-weight components act as co-formers. A recent innovative approach combines these strategies. This study used tryptophan co-former prepared systems using supercritical fluid technology. The nature of two was confirmed X-ray powder diffraction: one with 10% polymer, another curcumin, tryptophan. Fourier-transform infrared analysis demonstrated molecular interactions among all in the systems. Scanning electron microscopy revealed that amorphization process significantly modified morphology particles. ternary system notably increased solubility by over 300-fold. both exhibited higher dissolution rates compared crystalline form. showed more than threefold improvement permeability according PAMPA test. enhanced led sixfold increase activity 25-fold inhibition enzyme butyrylcholinesterase.

Язык: Английский

Процитировано

2

Electrophilic Compounds in the Human Diet and Their Role in the Induction of the Transcription Factor NRF2 DOI Open Access
Celia María Curieses Andrés, José Manuel Pérez de la Lastra, Elena Bustamante Munguira

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(6), С. 3521 - 3521

Опубликована: Март 20, 2024

The phrase “Let food be thy medicine…” means that can a form of medicine and food; in other words, the diet we eat have significant impact on our health well-being. Today, this is gaining prominence as more scientific evidence suggests one’s help prevent treat disease. A rich fruits, vegetables, whole grains, lean protein reduce risk heart disease, cancer, diabetes, problems and, hand, processed foods, added sugars, saturated fats increase same diseases. Electrophilic compounds health, they are molecules covalently modify cysteine residues present thiol-rich Keap1 protein. These bind to activate NRF2, which promotes its translocation nucleus binding DNA ARE region, triggering antioxidant response protecting against oxidative stress. include polyphenols flavonoids nucleophilic but converted electrophilic quinones by metabolic enzymes such polyphenol oxidases (PPOs) sulfur foods Brassica genus (broccoli, cauliflower, cabbage, Brussel sprouts, etc.) garlic. This review summarizes current knowledge subject.

Язык: Английский

Процитировано

9

Therapeutic Potential of Plant-Derived Compounds and Plant Extracts in Rheumatoid Arthritis—Comprehensive Review DOI Creative Commons
Mateusz Kciuk, Anjali Garg, Manni Rohilla

и другие.

Antioxidants, Год журнала: 2024, Номер 13(7), С. 775 - 775

Опубликована: Июнь 27, 2024

Rheumatoid arthritis (RA) is a persistent autoimmune disorder that characterized by joint inflammation, discomfort, and impairment. Despite the existence of several therapeutic approaches, their effectiveness often restricted may be linked to unfavorable side effects. Consequently, there has been growing interest in investigating naturally derived compounds as plausible agents for RA disease. The objective this review summarize existing preclinical clinical evidence regarding efficacy extracted plant extracts treatment RA, focusing on anti-inflammatory, anti-oxidative, immunomodulatory properties. Some problems with using natural chemicals are uneven quality commercially available preparations poor bioavailability these compounds. Future investigations should focus improving formulations, conducting thorough trials, exploring different techniques fully utilize intrinsic potential treating RA.

Язык: Английский

Процитировано

7

A synergistic effect of triptolide and curcumin on rheumatoid arthritis by improving cell proliferation and inducing cell apoptosis via inhibition of the IL-17/NF-κB signaling pathway DOI Creative Commons
Chaofeng Zhang,

Yiyang Weng,

Haibin Wang

и другие.

International Immunopharmacology, Год журнала: 2024, Номер 142, С. 112953 - 112953

Опубликована: Сен. 2, 2024

Rheumatoid arthritis (RA) is a chronic, progressive, systemic autoimmune disease. While triptolide (TPL) and curcumin (CUR) are known to have multiple beneficial effects on RA, the combined effect of TPL CUR remains unexplored. This study aimed investigate their synergistic cell proliferation apoptosis via IL-17/NF-κB signaling pathway. The collagen-induced (CIA) rat model was established, showing severe joint synovial damage compared normal rats. Treatment with reduced severity RA in CIA alleviated serum inflammatory cytokines, such as rheumatoid factor, IL-17, TNF-α, IL-1β, IL-6. elevated levels IL-17 NF-κB rats were also inhibited, resistant aggravated by CUR. In vitro, improvement induction observed LPS-stimulated MH7A cells treated CUR, associated inhibition Taken together, may involve relieving symptoms, improving excessive proliferation, inducing resistance, inhibiting

Язык: Английский

Процитировано

5

Exploring the Interaction of Lipid Bilayers with Curcumin–Laponite Nanoparticles: Implications for Drug Delivery and Therapeutic Applications DOI Creative Commons

Nisha Pawar,

Miriam Peña‐Figueroa,

Ester Verde‐Sesto

и другие.

Small, Год журнала: 2024, Номер unknown

Опубликована: Окт. 28, 2024

Abstract Curcumin, the active compound in turmeric, is renowned for its anti‐inflammatory, antioxidant, and antimicrobial properties, making it beneficial treating conditions like arthritis, neurodegenerative diseases, various cancers. Despite promising therapeutic potential, curcumin's poor bioavailability—due to rapid metabolism low solubility—limits clinical efficacy. To address this, recent research has focused on enhancing curcumin delivery using nanoparticles, liposomes, novel nanomaterials. Among these, laponite, a synthetic nanoclay, shown promise improving due unique including large surface area, dual charge, stability solution. This study explores use of curcumin–laponite nanoparticles as carrier vehicles controlled vitro model membranes. Utilizing advanced techniques such neutron reflectometry, atomic force microscopy, quartz crystal microbalance with dissipation, infrared spectroscopy, interaction between solid‐supported lipid bilayers monitored, revealing enhanced release across membrane. These findings pave way development curcumin‐based therapies targeting cardiovascular, neurological, oncological leveraging synergistic effects biological activity laponite's capabilities.

Язык: Английский

Процитировано

5

The design of natural hybrid biomaterial to promote osteogenic differentiation, collagen i and II expression and relief of musculoskeletal pains: Bone tissue-engineering applications (in-vitro and clinical studies) DOI Creative Commons
Azadeh Izadyari Aghmiuni, Saeed Heidari Keshel, Ali Aghababai Beni

и другие.

Arabian Journal of Chemistry, Год журнала: 2024, Номер 17(6), С. 105766 - 105766

Опубликована: Апрель 2, 2024

This research aimed to fabricate a natural hybrid biomaterial and assess its physicochemical/biological properties study the role of therapeutic in growth human monocytes, synoviocytes, chondrocytes, expression type-I/II collagen, osteogenic differentiation for bone tissue engineering applications, as well effects bio-ointment derived from this on relief musculoskeletal pains. Hence, an oily formula [turmeric:ginger:chili pepper:rose oils (1:1:1:1w/w)] was mixed with base oil [sesame:black seed:olive (1:0.4:0.6w/w)] 3 wt ratios 1:6(H1), 1.5:5.5(H2), 2:5(H3). Accordingly, H2 indicated better performance cell decrease inflammatory mediators led highest osteoblastic genes RUNX2, OCN, OPN, collagen I II (COL1A1,COL2A) respectively 1.3-fold, 1.7-fold, 1.4-fold, %87 % ∼ 60 higher than H1, 2-fold, 2.1-fold, 3.4-fold, 19 16 H3. A clinical also performed 50 patients H2-based could relieve pain less 10 min 40 after 30 use 35 %. Moreover, analgesia period 36 lasted longer h between 2 h, respectively. 76 stated that possesses stronger other treatments along moderate warming functions. Finally, although 6 reported mild effectiveness relief, 92 users method has resulted more their damaged organ recovery.

Язык: Английский

Процитировано

4

The Role of Mesenchymal Stromal Cells in the Treatment of Rheumatoid Arthritis DOI Creative Commons

Estera Bakinowska,

Aleksandra Wiktoria Bratborska, Kajetan Kiełbowski

и другие.

Cells, Год журнала: 2024, Номер 13(11), С. 915 - 915

Опубликована: Май 25, 2024

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease characterised by the formation of hyperplastic pannus, as well cartilage and bone damage. The pathogenesis RA complex involves broad interactions between various cells present in inflamed synovium, including fibroblast-like synoviocytes (FLSs), macrophages, T cells, among others. Under conditions, these are activated, further enhancing responses angiogenesis promoting degradation. Novel treatment methods for greatly needed, mesenchymal stromal (MSCs) have been suggested promising new regenerative immunomodulatory treatment. In this paper, we MSCs RA-FLSs, macrophages summarise studies examining use preclinical clinical studies.

Язык: Английский

Процитировано

4

Advances in the Medical Treatment of Rheumatoid Arthritis DOI

Stephanie Tancer,

Beth Wallace

Hand Clinics, Год журнала: 2024, Номер 41(1), С. 11 - 23

Опубликована: Окт. 16, 2024

Язык: Английский

Процитировано

3