Inflammopharmacology最新文献

Gamma-oryzanol, a potent nutraceutical derived from Oryza sativa and primarily extracted as rice bran oil, has gained significant interest due to its antioxidant, anti-inflammatory, and neurorestorative properties. This review explores its potential as a promising alternative for managing neuropathic pain, especially considering the limitations and adverse effects associated with conventional pharmacological treatments. A comprehensive literature search was conducted using databases such as PubMed, ScienceDirect, Google Scholar, Taylor and Francis, and Scopus, focusing on studies published from 2010 onward. These studies highlighted gamma-oryzanol's multifaceted pharmacodynamic actions that target the complex mechanisms underlying neuropathic pain. Its natural origin and favourable safety profile further support its potential as a phytotherapeutic agent. In the evolving field of phyto-based neuroprotective therapies, gamma-oryzanol represents a compelling intersection between pharmacology and nutrition. Preclinical and clinical studies evaluating γ-oryzanol's effects on neuropathic-pain-related mechanisms were systematically reviewed. Nonetheless, to fully realise its therapeutic potential, further translational research and clinical trials are essential.

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.

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.

Polycystic ovary syndrome (PCOS) is a common gynaecological disorder, clinically characterized by chronic anovulation and hyperandrogenism. Despite its high prevalence, no curative treatment exists, and managing the syndrome remains challenging. A strong association between PCOS and metabolic syndrome, particularly insulin resistance, adversely influences fertility, leading to an increased worldwide demand for advanced treatment options. Although the exact aetiology and pathophysiology of the syndrome remain unclear, an intricate interaction of ovarian, endocrine, and metabolic factors is highly likely. During the last two decades, several pathophysiological factors have been identified, and growing evidence suggests that PCOS is not solely a reproductive endocrinologic disorder but a multisystem syndrome with reproductive, endocrine, metabolic, and psychiatric manifestations. Diagnostic criteria such as the Rotterdam criteria, the NIH-NIHCD criteria, and the Androgen Excess Society (AES) criteria have uncovered a wide spectrum of clinical manifestations. Lifestyle modification and insulin sensitizers remain the gold standard for management in obese PCOS women. Emerging therapeutics include novel insulin-sensitizing agents, such as glucagon-like peptide 1 receptor agonists, sodium-glucose co-transporter 2 inhibitors, and dipeptidyl peptidase-4 inhibitors. Nutraceuticals and herbal remedies, surgical interventions, which have undergone modifications and refinements over time, facilitate follicle growth by increasing endogenous gonadotropin secretion as an alternative to ovulation induction in clomiphene-resistant PCOS women. Treatment of infertility resulting from PCOS is demanding, and current approaches are neither uniformly successful nor universally accepted. Future directions involve exploring the potential of vaginal microbiota and photothermogenesis for comprehensive management.

Dry eye disease (DED), a disorder with multiple contributing factors, is marked by instability in the tear film, increased osmolarity, and inflammatory responses. This research investigates the therapeutic potential of essential oil derived from wild chrysanthemum essential oil (CHEO) in treating DED. GC-MS analysis identified 121 bioactive compounds in CHEO, including L-borneol (6.00%) and β-sitosterol (4.60%), compounds with established anti-inflammatory properties. In human corneal epithelial cells subjected to hyperosmotic stress, CHEO treatment significantly improved cell viability and lowered inflammatory cytokines (IL-1β, IL-6, TNF-α) secretion. CHEO administration was demonstrated to restore tear production, improve corneal epithelial integrity, and increase conjunctival goblet cell density in scopolamine-induced DED mice. Notably, the ocular tissues demonstrated suppression of mitogen-activated protein kinases (MAPK) and NF-κB pathway activation by CHEO. The collective evidence indicates that CHEO alleviates DED through multimodal mechanisms involving anti-inflammatory action and ocular surface protection, highlighting its promise as a new phytotherapeutic option for managing DED.

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.