Inflammopharmacology最新文献

Objective: Atopic dermatitis (AD) is a chronic inflammatory skin disease. The JAK/STAT and PDE4/cAMP pathways are pivotal in driving its inflammation. This study aimed to discover natural JAK1 and PDE4 inhibitors from camellia oil to alleviate AD.

Methods: Utilizing the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), we employed a target-based molecular docking approach against key inflammatory targets (JAK1, PDE4B, PDE4D) of AD to screen the compounds in camellia oil. This virtual screening was followed by in vitro enzymatic assays to validate their inhibitory effects. Based on these findings, we employed a DNCB-induced AD mouse model to compare the therapeutic efficacy of (1% and 4%) ( +)-catechin hydrate and (4% and 6%) epicatechin against 1.5% ruxolitinib cream.

Results: Although molecular docking screening predicted seven compounds with potential high binding affinity for PDE4B and PDE4D, respectively, subsequent in vitro enzymatic inhibition assays demonstrated that all of these compounds exhibited low inhibitory rates against the enzymes. In comparison, (+)-catechin hydrate and epicatechin not only exhibited excellent binding affinity with JAK1 but also achieved high inhibition rates. Their IC₅₀ values for JAK1 inhibition were 1125.65 ± 0.56 nM and 3531.24 ± 0.17 nM, respectively. Animal studies have demonstrated that both (+)-catechin hydrate and epicatechin can significantly ameliorate symptoms of AD, including reducing the severity of skin lesions and itching behavior, while also suppressing the expression of inflammatory mediators such as TSLP, IL-4, and IL-13.

Conclusion: In camellia oil, (+)-catechin hydrate and epicatechin are the primary active constituents for the treatment of AD, suggesting that their anti-AD effects were possibly mediated through the suppression of the JAK1-driven inflammatory signaling pathway. This study not only provides a novel utilization strategy for camellia oil, but also offers new insights for the treatment of AD.

Migraine is a prevalent neurovascular disorder strongly associated with neuroinflammation, altered neurotransmitter release, and sensory hypersensitivity. Extracts of Petasites hybridus (butterbur) rootstocks, standardized with eremophilane-type sesquiterpenoids (petasins), have clinically demonstrated efficacy in migraine. However, the pharmacological properties of purified petasins remain insufficiently explored. This study aimed to evaluate their antimigraine and anti-neuroinflammatory potential both in vivo and in vitro. Six sesquiterpenoids were isolated via centrifugal partition chromatography and preparative high-performance liquid chromatography. Male C57BL/6 J mice were subjected to a nitroglycerin model of migraine-like pain, followed by administration of the isolated sesquiterpenoids and mechanical hypersensitivity was evaluated via von Frey filaments. The sesquiterpenoid and neurotransmitter levels in the brain tissues were analyzed via LC‒MS/MS, and the cytokine levels were measured via ELISA. In LPS-stimulated BV-2 microglial cells, anti-inflammatory effects were assessed via Griess assay and a cytokine bead array, and cell viability was measured via MTT assay. Isopetasin significantly attenuated nitroglycerin‒induced mechanical allodynia in both the paw and periorbital regions. These effects may be associated with reduced brain levels of the chemokine CCL2, while LC‒MS/MS confirmed the central bioavailability of isopetasin. In vitro, sesquiterpenoids suppressed LPS‒induced nitric oxide and proinflammatory cytokine release, with isopetasin showing the broadest anti-inflammatory activity. Neurochemical profiling revealed modulation of glutamic acid and GABA associated with the excitatory/inhibitory balance. Purified petasins from butterbur rootstocks, particularly isopetasin, display significant antinociceptive and anti-inflammatory activity in preclinical migraine model. These findings support the importance of well-chemically defined butterbur constituents and provide a foundation for their further investigation as anti-neuroinflammatory agents.

Osteoarthritis (OA) is a degenerative joint disorder marked by chondrocyte metabolic dysfunction and mitochondrial impairment. This study elucidates the role of circHIPK2, a circular RNA downregulated in OA chondrocytes, in regulating glucose metabolism and mitochondrial homeostasis through the miR-206-SIRT3 axis. Clinical samples revealed significant circHIPK2 reduction and miR-206 upregulation in OA chondrocytes, correlating inversely with SIRT3 expression. In vitro LPS-induced injury models demonstrated that circHIPK2 overexpression mitigated chondrocyte apoptosis and metabolic stress, while miR-206 inhibition reversed LPS-driven glycolytic activation and mitochondrial dysfunction. Mechanistically, circHIPK2 directly bound miR-206 via Ago2-dependent interactions, as confirmed by RNA pull-down and luciferase assays, thereby alleviating miR-206-mediated suppression of SIRT3, a key mitochondrial deacetylase. Rescue experiments in chondrocytes showed that SIRT3 restoration rescued miR-206-induced metabolic defects, including impaired oxidative phosphorylation and ATP depletion. In vivo, intra-articular delivery of circHIPK2 in a monosodium iodoacetate (MIA)-induced OA rat model attenuated mechanical allodynia, cartilage degradation, and aberrant miR-206/SIRT3 expression, while improving weight-bearing symmetry; furthermore, similar therapeutic benefits-including pain relief, functional recovery, and cartilage protection-were confirmed in a chronic, post-traumatic destabilization of the medial meniscus (DMM) model, with efficacy demonstrated against appropriate AAV control groups. These findings identify the circHIPK2-miR-206-SIRT3 axis as a critical regulator of chondrocyte bioenergetics and OA progression, offering novel therapeutic targets for modulating non-coding RNA networks in joint degeneration.

A wide variety of acute and chronic respiratory diseases pose a significant disability and mortality worldwide. To date, very few classes of safe and effective therapy are available to effectively manage disease conditions. In recent years, phytochemicals derived from food plants are getting high attention due to their diverse beneficial effects with minimal toxicity. Tannic acid (TA), a water-soluble gallotannin, is present in many plant-based food products. Accumulating experimental evidences indicate that TA possesses numerous health benefits. However, there is no comprehensive review that addresses the beneficial effects of TA on various respiratory diseases. This review provides an overview of the chemical structure, natural sources, bioavailability, toxicity, and beneficial effects of TA against a wide range of respiratory diseases. We have also discussed the mechanistic pathways through which TA offers its beneficial effects. In cancerous cells, it has been reported that TA can help to overcome multidrug resistance by increasing the sensitivity to anti-cancer drugs. Researchers have found that TA-based nanoparticles showed promising results in cancer treatment. Further, as a novel drug nanocarrier, TA has significant potential for the effective delivery of pharmaceutical drugs to lung cancer cells. Yet, clinical applications of TA against respiratory diseases have not been performed. Currently, pharmacokinetic studies of TA are very limited, which may be the reason for the lack of clinical usage. Nevertheless, further studies aimed at implementing appropriate risk and benefit assessment would accelerate the clinical usage of TA for treating common respiratory diseases.

The review has comprehensively examined the therapeutic potential of phytoconstituents in the treatment of arthritis with specific emphasis being given to diosgenin as a promising natural molecule. Arthritis is a significant health concern in the world, with its two most common types; Osteoarthritis and rheumatoid arthritis, becoming the causes of disability, and expensive to manage in the long run. Even though disease-modifying anti-rheumatic drugs and biologics have helped to better the patient outcomes, their side effects, high treatment cost, and inaccessibility demonstrate the necessity of safer and cheaper alternatives. The pharmacological significance of the root steroidal sapogenin, diosgenin, as a derivative of the species Dioscorea, that exhibits strong anti-inflammatory effects with clearly defined, molecular-based, mechanisms, is highlighted in this manuscript. Diosgenin suppresses cartilage destruction because of matrix metalloproteinases, the NF-kB signaling pathway as well as the major pro-inflammatory cytokines, TNF-a, IL-1b, and IL-6. It also has chondroprotective action to maintain the integrity of the extracellular matrix, increase levels of type II collagen and aggrecan, and decrease the expression of MMP-3 and MMP-13 by about 65-85% in the presence of inflammation. The challenges to clinical translation associated with formulation which are discussed in the review include the very low aqueous solubility of diosgenin (0.95 ug/mL) and oral bioavailability (< 7%). It addresses the use of the advanced delivery systems, including lipid nanoparticles, vesicular carriers and amorphous solid dispersions, which have demonstrated a 2.55-fold increase in bioavailability and also have the potential to improve therapeutic efficacy. Crucially, this review uniquely integrates these bioavailability enhancement strategies with diosgenin's underlying molecular mechanisms, illustrating how optimised delivery systems are essential to fully unlock its therapeutic potential. Despite robust preclinical evidence supporting its anti-arthritic and chondroprotective actions, clinical investigations remain scarce, with only a few small studies and none directly evaluating diosgenin for arthritis outcomes. Overall, this review emphasises the need for well-designed clinical trials to validate the therapeutic promise of diosgenin and related phytoconstituents, paving the way for safer, accessible, and multi-targeted natural interventions for arthritis management.

Background: Psoriasis is a chronic, immune-mediated disease with an overabundance of cytokines and aberrant keratinocyte proliferation.

Objective: To assess the therapeutic activity of topical application of 10% sulfasalazine in an imiquimod-induced murine model and to compare its therapeutic activity with that of clobetasol.

Methodology: Thirty-two male mice were randomly assigned into four groups, with each group consisting of eight individuals: normal control group, IMQ + vehicle group, IMQ + clobetasol group, and IMQ + 10% sulfasalazine group. IMQ was administered for 7 days, and then daily topical application was conducted for 14 days. Lesion severity was determined by PASI scores, and histological scores and concentrations of TNF-α and IL-6.

Results: Both sulfasalazine and clobetasol led to significant reduction in PASI scores, compared to IMQ + vehicle (p < 0.05). The regimen of sulfasalazine improved epidermal structure, acanthosis, and inflammation, as well as.

Conclusion: Topical sulfasalazine was found to possess significant anti-inflammatory activity, both clinical and histological, against IMQ-induced inflammation resembling psoriasis.

Helicteres isora L. is widely used in traditional medicine for the treatment of gastrointestinal disorders, diabetes, and inflammatory conditions, yet its anti-arthritic potential has not been systematically explored. Given the limitations of conventional rheumatoid arthritis (RA) therapies, evaluation of this plant may provide scientific validation for its ethnomedicinal use against inflammatory diseases. The present study aimed to investigate the anti-arthritic efficacy and underlying mechanisms of ethanolic extract of Helicteres isora L. (EEHI) in a Complete Freund Adjuvant (CFA) induced arthritis model in rats and to relate these findings to its traditional application in inflammation management. EEHI was prepared and phytochemically profiled using GCMS. Anti-arthritic activity was assessed through in vitro protein denaturation assay and in vivo in CFA induced arthritic rats administered EEHI at 100, 200, and 400 mg/kg for 28 days. Clinical parameters (paw diameter, arthritic score, body weight, and organ weights), hematological and biochemical markers (RF, CRP), oxidative stress indices (SOD, CAT, GSH, MDA), pro-inflammatory gene expression (NF-κB, TNF-α, IL-6, COX-2), and histopathological changes were evaluated. Diclofenac sodium served as the standard drug. EEHI treatment resulted in significant, dose dependent improvements across all evaluated parameters. The 400 mg/kg dose markedly reduced paw swelling and arthritic scores, improved hematological indices, and restored antioxidant enzyme levels. Serum CRP and RF were significantly decreased. Gene expression analysis confirmed downregulation of NF-κB, TNF-α, IL-6, and COX-2, while histopathology showed substantial protection of joint architecture. GCMS identified several bioactive compounds, including dodecanoic acid, 11-octadecenoic acid, and 8, 11-octadecadienoic acid, which may contribute to the observed pharmacological effects. The findings provide scientific evidence supporting the ethnomedicinal use of Helicteres isora L. in inflammatory conditions. EEHI demonstrated potent anti-arthritic, antioxidant, and anti-inflammatory activities through modulation of cytokines and oxidative stress. This work validates traditional knowledge and highlights Helicteres isora L. as a promising natural therapeutic candidate for rheumatoid arthritis, warranting further pharmacological and clinical studies.

Astaxanthin, a xanthophyll carotenoid derived primarily from Hematococcus lacustris, has been proposed as a potent bioactive compound demonstrating wide therapeutic applicability. In addition to its distinct molecular structure, astaxanthin has exceptional antioxidant property, surpassing that of other carotenoids and conventional antioxidants, while also exerting robust anti-inflammatory effects. The present review focuses on the current evidence of the complex multifaceted therapeutic actions of astaxanthin, including cardiovascular protection, neuroprotection, hepatoprotection, renal support, dermatological health, immune modulation, and emerging roles in metabolic disorders, reproductive health, and cancer prevention. Mechanistic insights highlight its potential to control key molecular mechanisms, including the NF-κB, Nrf2, MAPK, and TGF-β/Smad pathways, alongside the enhancement of endogenous antioxidant defenses. Preclinical and clinical findings have demonstrated benefits in conditions such as atherosclerosis, myocardial ischemia, nonalcoholic fatty liver disease, hypertension, Alzheimer's disease, Parkinson's disease, and inflammatory skin diseases. By integrating evidence drawn from molecular, experimental, and clinical studies, this review underscores astaxanthin's potential as a complementary therapeutic agent and functional nutraceutical. The breadth of its bioactivity positions astaxanthin as a promising natural compound for targeted disease prevention and health promotion.

Objective: Trans-Chalcone (TC) is an anti-inflammatory flavonoid that reduces hyperalgesia by targeting nuclear factor κB and inflammasome in gout arthritis model. However, a direct modulation of nociceptors by TC has never been investigated, which was the aim of the present study.

Methods: Experimental models of overt pain-like behaviors were applied as the stimuli-induced behavior depends, at least in part, on nociceptive neuron activation by the stimuli themselves making them suitable to investigate if a drug candidate can inhibit nociceptive neuron activation. The selected models involve transient receptor potential (TRP) vanilloid 1 (V1)⁺ and TRP ankyrin 1 (A1)⁺ nociceptive neuron activation.

Results: TC (10 mg/kg, per oral, 30 min pretreatment) inhibited abdominal contortions induced by acetic acid (58.8%) and phenyl-p-benzoquinone (PBQ-54.6%), and paw flinching (44 and 48%) and licking (38 and 46%) triggered by formalin and complete Freund's adjuvant (CFA-46 and 43%), indicating TC inhibits varied overt pain-like behaviors. Considering TRPV1 and TRPA1 channels are activated in those models, TC activity was also tested in experimental conditions in which capsaicin (a TRPV1 agonist)- and allyl isothiocyanate (AITC, a TRPA1 agonist)-triggered nociceptive behavior. TC inhibited capsaicin (44 and 37.5%) and AITC (35.1 and 52%) paw flinching and licking behavior. TC (3 μM) also reduced the calcium influx caused by capsaicin (30%) and AITC (37.6%) stimulation of primary dorsal root ganglia neurons. Additionally, TC inhibited CFA-induced hyperalgesia, paw inflammation without toxic effects.

Conclusions: TC reduces overt pain-like behavior, at least in part, by inhibiting nociceptive neuron TRPV1 and TRPA1 channels activation.