Anti-inflammatory Research Articles

A Review of the Ethnomedicine, Phytochemistry and Biological Activities of the Genus Parinari

Parinari is a genus of woody medicinal plants with expansive ethnomedicinal uses. While extensive data are available for several members of this genus, this information is generally scattered. This review therefore crystallizes major reports relating to the ethnomedicinal uses, phytochemistry, and biological activities of this genus for easy accessibility. The rich therapeutic applications of this genus include their use as antimalarial, antidiabetic, anti-inflammatory, antimicrobial, anti-snake venom, and anticancer agents. However, the overarching biological theme for this genus appears to be their application in treating infection and infection-related diseases. These bioactivities have largely been attributed to molecules isolated from this genus and categorized under; kaurene-type diterpenoids, triterpenoids (ursane, oleanane, and lupane types), flavonoids, steroids, and phenolic compounds. While data is available for most parts of the plants, the stem appears to be the most used part. Given the varied medicinal uses of this genus, and yet the scarcity of information on many Parinari species, studies on the ethnomedicine, phytochemistry, and biological activities that fully explore the medicinal potential of this genus for drug discovery are critical. These include the need for comprehensive phytochemical profiling to uncover novel compounds, detailed studies on mechanisms of action, and translational research to validate clinical efficacy. Additionally, comparative ethnobotanical studies, standardization of extraction methods, and sustainable harvesting practices are critical to fully realizing the medicinal potential of Parinari species.

Phenolic Content, Antioxidant Activity and In Vitro Anti-Inflammatory and Antitumor Potential of Selected Bulgarian Propolis Samples

Background/objectives: Propolis (bee glue) is a valuable bee product widely used as a natural remedy, a cosmetic ingredient, a nutritional value enhancer and a food biopreservative. The present research aims to investigate the phenolic content, antioxidant activity and in vitro anti-inflammatory and antitumor potential of six propolis samples from three regions of Bulgaria (Vidin, Gabrovo and Lovech). Methods: the analysis of propolis phenolic compounds was determined by high-performance liquid chromatography (HPLC); the antioxidant activity of ethanolic propolis extracts was assessed by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and ferric-reducing antioxidant power (FRAP) assay; the in vitro anti-inflammatory activity was assessed by the inhibition of albumin denaturation method; the in vitro antitumor activity was determined in human metastatic breast cancer cell line MDA-MB-231 using 3-(4,5-Dimethyl -2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Results: The ethanolic propolis extracts exhibited the total phenolic content from 190.4 to 317.0 mg GAE/g, total flavonoid content from 53.4 to 79.3 mg QE/g and total caffeic acid derivatives content from 5.9 to 12.1 mg CAE/g. The studied propolis extracts showed significant antioxidant capacity (between 1000.3 and 1606.0 mM TE/g determined by the DPPH assay, and between 634.1 and 1134.5 mM TE/g determined by the FRAP assay). The chemical composition analysis indicated high concentrations of caffeic acid benzyl ester, chrysin, pinocembrin and pinobanksin-3-O-propionate, predominantly in three of the propolis samples originating from Gabrovo and Lovech regions. All propolis samples demonstrated promising in vitro anti-inflammatory activity, expressed as the inhibition of thermally induced albumin denaturation by 73.59% to 78.44%, which was higher than that of the conventional anti-inflammatory drugs Aspirin (58.44%) and Prednisolone Cortico (57.34%). The propolis samples exhibited high in vitro cytotoxicity against cancer cells MDA-MB-231 with IC50 values ranging between 9.24 and 13.62 µg/mL as determined by MTT assay. Conclusions: Overall, we can suggest that the high phenolic content of Bulgarian propolis from respective areas contributes to its enhanced antioxidant, anti-inflammatory and antitumor activity. Taken together, our results support the beneficial properties of Bulgarian propolis, with potential application as a promising therapeutic agent.

Correction: Dogs receiving cyclooxygenase-2-sparing nonsteroidal anti-inflammatory drugs and/or nonphysiologic steroids are at risk of severe gastrointestinal ulceration

Correction: Dogs receiving cyclooxygenase-2-sparing nonsteroidal anti-inflammatory drugs and/or nonphysiologic steroids are at risk of severe gastrointestinal ulceration

The Anticonvulsant Effect of Nonsteroidal Anti-Inflammatory Drug, Fenoprofen, in Pentylenetetrazole-Induced Epileptic Rats: Behavioral, Histological, and Biochemical Evidence.

This study aimed to evaluate the anticonvulsant properties of fenoprofen on the experimental model of pentylenetetrazole (PTZ)-induced epilepsy. Male Wistar rats were randomly grouped into five, and the kindling model was induced by intraperitoneal injection of PTZ 35 (mg/kg) every other day for 1 month. Aside from the control and PTZ groups, three groups received intraperitoneal injections of fenoprofen at doses of 10, 20, and 40 (mg/kg) before each PTZ injection. Rats were challenged with PTZ 70 (mg/kg) 1 week after kindling development. Then rats were subjected to deep anesthesia, and serum and brain samples were prepared. Oxidative stress (OS) markers (malondialdehyde, superoxide dismutase, and glutathione peroxidase) were measured in serum samples. Hippocampal tissue was used to investigate the relative expression of OS-related genes (nuclear factor [erythroid-derived 2]-like 2 (Nrf2)/heme oxygenase 1 (Hmox1)) and histological studies. Seizure behavior was assessed based on Lüttjohann's score. In treated groups, the number of myoclonic jerks and generalized tonic-clonic seizure (GTCS) duration decreased significantly, while myoclonic jerks and GTCS latency increased compared with the PTZ group. The biochemical evaluation revealed the antioxidative effects of fenoprofen. The decreased expression of Nrf2/HO-1 genes in the PTZ group was reversed after fenoprofen administration. The results of the histological study obtained from Nissl staining in the hippocampal tissue also confirmed the protective effect of fenoprofen. The anticonvulsant effects of fenoprofen seem to be through inhibition of OS-related markers, induction of protective effect in hippocampal tissue, and activation of the Nrf2/HO-1 signaling pathway.

Significance of non-steroidal anti-inflammatory drugs in the prevention and treatment of cervical cancer

Significance of non-steroidal anti-inflammatory drugs in the prevention and treatment of cervical cancer

Structural and theoretical studies of amantadinium fenamates.

Two new crystals of amantadinium salts were obtained from fenamic and tolfenamic acid. The salt of fenamic acid is a model compound for interaction analysis, while amantadinium tolfenamate is a composition of a drug used in the treatment of symptoms of Parkinsonism and as a nonsteroidal anti-inflammatory drug. The crystal structures were studied and a theoretical analysis of the hydrogen bonds and weak interactions was carried out using quantum theory of atoms in molecules (QTAIM) and non-covalent interaction (NCI) methods.

Current research status, applications and challenges of ketorolac-based sustained-release and controlled-release formulations.

Ketorolac, a nonsteroidal anti-inflammatory drug, exhibits moderate antipyretic and anti-inflammatory properties, as well as potent analgesic effects. It is widely used in clinical practice for pain relief in cases of mild and severe pain such as postoperative pain, fractures, sprains, toothaches and cancer pain. Due to its relatively short half-life, patients experiencing pain often need frequent injections or oral medications, leading to poor patient compliance. Thus, it is crucial to create long-acting sustained-release formulations of ketorolac. This paper provides an overview of the research, applications, and challenges associated with ketorolac sustained-release formulations over the past decade, based on a comprehensive review of the literature. The aim is to provide fresh insights for the research and development of long-acting, sustained-release, and controlled-release formulations of ketorolac.

Development of novel bis(2-ethylhexyl) phosphate-based magnetic deep eutectic solvent for the highly efficient enrichment of non-steroidal anti-inflammatory drugs from environmental water and milk samples

Development of novel bis(2-ethylhexyl) phosphate-based magnetic deep eutectic solvent for the highly efficient enrichment of non-steroidal anti-inflammatory drugs from environmental water and milk samples

Fishroesomes show intrinsic anti-inflammatory bioactivity and ability as celecoxib carriers in vivo.

According to the World Health Organization (WHO), chronic inflammatory-related diseases represent the greatest threat to human health. Indeed, failure in the resolution of inflammation leads to serious pathological conditions, such as cardiovascular diseases, arthritis, cancer, diabetes, autoimmune diseases, and neurodegenerative disorders that are often associated with extremely high human suffering and societal and economic burdens. Despite the number and efficacy of available therapeutic agents have been increased, the serious side effects associated with some of them often create a very high risk/benefit ratio for patients. Therefore, herein, a drug delivery system was engineered to overcome important drawbacks of conventional therapies and to have a synergistic action with the incorporated drug. Indeed, it will have an added beneficial role in controlling inflammation. For that, sardine (Sardina pilchardus) roe was used as the lipidic source to produce bioactive liposomes, namely fishroesomes. These spherical vesicles with ≈326 nm in size and a significant negative surface charge (≈-31 mV) were able to encapsulate and control the release of the anti-inflammatory drug celecoxib. Moreover, fishroesomes were cytocompatible for different cell types (chondrocytes and macrophages), at concentrations in which they present anti-inflammatory properties. Importantly, fishroesomes were more effective in reducing pro-inflammatory mediators than the free drug. We also demonstrated that a single intra-articular injection of the fishroesomes encapsulating or not celecoxib in an experimental rat model of inflammatory arthritis was safe and more effective in controlling the pain and reducing the synovial inflammation compared to the free drug. Notably, as the celecoxib concentration in the sardine roe-derived liposomes was less than half of the amount of free drug, this study demonstrates the value of fishroesomes in counteracting inflammation. Therefore, the developed formulations may be considered a promising therapeutic option for inflammatory conditions.

Best Practices for Reducing Pain Associated with Intrauterine Device Placement.

Intrauterine devices are highly effective, long-acting, reversible forms of contraception. Despite their benefits, limited uptake persists, particularly among underserved populations, adolescents, and young adults. While most intrauterine device placement procedures are uncomplicated, pain is commonly reported, with more severe pain reported in certain groups. No current standard of care has been established specifically to manage pain with intrauterine device placement, resulting in wide variation in clinical practice. This article aims to provide practical, evidence-based, and expert-informed guidelines for managing pain during intrauterine device placement. The authors (a group of board-certified obstetrician-gynecologists, pediatricians, and a family physician) conducted a virtual expert meeting to develop consensus-based recommendations for pain management. The meeting covered environmental considerations, non-pharmacological, and pharmacological options. Key strategies include using a person-centered care model that focuses on patient values, needs, and preferences to promote shared decision-making around pain relief. Clinicians should assist patients in setting realistic expectations, including a discussion of the placement procedure, anticipated pain, and all options for pain relief, to allow for a comprehensive informed consent process. Non-pharmacological interventions, such as the use of therapeutic language and comforting environmental, complementary and integrative, and mind-body elements, are recommended to reduce patient anxiety and discomfort. In terms of pharmacological options, clinicians may offer pre-procedural specific nonsteroidal anti-inflammatory drugs (e.g., naproxen and ketorolac) and anxiolytics to patients with significant anxiety, as well as intra-procedural application of topical anesthesia and paracervical or intracervical blocks. Finally, additional techniques, such as using appropriately sized instruments and ensuring gradual and gentle procedural steps, can also help enhance patient comfort during insertion. These expert guidelines emphasize the importance of personalized, trauma-informed, and evidence-based care, prioritizing patient autonomy and preferences to facilitate a safe and acceptable insertion experience. They are critical to reducing barriers to intrauterine device uptake and improving overall patient outcomes.

Uterine stromal but not epithelial PTGS2 is critical for murine pregnancy success.

Use of non-steroidal anti-inflammatory drugs that target prostaglandin synthase (PTGS) enzymes have been implicated in miscarriage. Further, PTGS2-derived prostaglandins are reduced in the endometrium of patients with a history of implantation failure. However, in the mouse model of pregnancy, peri-implantation PTGS2 function is controversial. Some studies suggest that Ptgs2-/- mice display deficits in ovulation, fertilization, and implantation, while other studies suggest a role for PTGS2 only in ovulation but not implantation. Further, the uterine cell type responsible for PTGS2 function and role of PTGS2 in regulating implantation chamber formation is not known. To address this, we generated tissue-specific deletion models of Ptgs2. We observed that PTGS2 ablation from the epithelium alone in Ltfcre/+; Ptgs2f/f mice and in both the epithelium and endothelium of the Pax2cre/+; Ptgs2f/f mice does not affect embryo implantation. Further, deletion of PTGS2 in the ovary, oviduct, and the uterus using Pgrcre/+; Ptgs2f/f does not disrupt pre-implantation events but instead interferes with post-implantation chamber formation, vascular remodeling, and decidualization. While all embryos initiate chamber formation, more than half of the embryos fail to transition from blastocyst to epiblast stage, resulting in embryo death and resorbing decidual sites at mid-gestation. Thus, our results suggest no role for uterine epithelial PTGS2 in early pregnancy but instead highlight a role for uterine stromal PTGS2 in modulating post-implantation embryo and implantation chamber growth. Overall, our study provides clarity on the compartment-specific role of PTGS2 and provides a valuable model for further investigating the role of stromal PTGS2 in post-implantation embryo development.

Stigmasterol from Prunella vulgaris L. Alleviates LPS-induced mammary gland injury by inhibiting inflammation and ferroptosis.

Dairy mastitis, a prevalent condition affecting dairy cattle, represents a significant challenge to both animal welfare and the quality of dairy products. However, current treatment options remain limited. Stigmasterol (ST) is a bioactive component of Prunella vulgaris L. (PV) with various pharmacological functions such as anti-inflammatory and anti-oxidation. At present, the specific effects and underlying mechanisms of PV and ST on dairy mastitis are still not fully understood. The aim of this research was to evaluate the pharmacological effects of PV and its active component ST on lipopolysaccharide (LPS) -stimulated bovine mammary epithelial cells (BMECs) and a mouse mastitis model, and to elucidate the possible mechanisms of action. UPLC-Q-TOF-MS/MS was employed to identify the constituents of PV. BMECs and mice were used to establish in vitro and in vivo models of mastitis. Western Blotting, RT-qPCR, immunofluorescence and other techniques were used to explore the effects of PV and ST on inflammatory factors, blood-milk barrier integrity, ferroptosis related indicators and their potential molecular mechanisms. PV significantly attenuated the production of inflammatory mediators by LPS-stimulated BMECs. Subsequently, ST was found to be a potent anti-inflammatory agent in PV by inhibiting TLR4/NF-κB signaling pathway. This inhibition inhibits the myosin light chain (MLC)/MLC kinase signaling cascade and alleviates blood-milk barrier (BMB) disruption in BMECs. In addition, ferroptosis occurred in BMECs after LPS stimulation, and ST inhibited ferroptosis by stimulating Nrf2/GPX4 signaling pathway. Treatment of BMECs with the Nrf2 inhibitor ML385 significantly attenuated the therapeutic effect of ST. In vivo experiments further confirmed that both PV and ST attenuated LPS-induced breast tissue damage while reducing ferroptosis levels and restoring BMB. ST from PV exhibits substantial anti-inflammatory properties and is a promising candidate for the treatment of dairy mastitis.

The Utility of Prolonged Chronic Unpredictable Stress to Study the Effects of Chronic Fluoxetine, Eicosapentaenoic Acid, and Lipopolysaccharide on Anxiety-Like Behavior and Hippocampal Transcriptomic Responses in Male Rats.

Chronic stress is a common trigger of multiple neuropsychiatric illnesses. Animal models are widely used to study stress-induced brain disorders and their interplay with neuroinflammation and other neuroimmune processes. Here, we apply the prolonged 12-week chronic unpredictable stress (PCUS) model to examine rat behavioral and hippocampal transcriptomic responses to stress and to chronic 4-week treatment with a classical antidepressant fluoxetine, an anti-inflammatory agent eicosapentaenoic acid (EPA), a pro-inflammatory agent lipopolysaccharide and their combinations. Overall, PCUS evoked anxiety-like behavioral phenotype in rats, corrected by chronic fluoxetine (alone or combined with other drugs), and EPA. PCUS also evoked pronounced transcriptomic responses in rat hippocampi, involving > 200 differentially expressed genes. While pharmacological manipulations did not affect hippocampal gene expression markedly, Gpr6, Drd2 and Adora2a were downregulated in stressed rats treated with fluoxetine, EPA and fluoxetine + EPA, suggesting their respective protein products (G protein-coupled receptor 6, dopamine D2 receptor and adenosine A2A receptor) as potential evolutionarily conserved targets under chronic stress. Overall, these findings support the validity of rat PCUS paradigm as a useful model to study stress-related anxiety pathogenesis, and call for further research probing how various conventional and novel drugs may (co)modulate behavioral and neurotranscriptomic biomarkers of chronic stress.

Anti-Inflammatory Resveratrol Protects Mice From Early Mortality After Haematopoietic Stem Cell Transplantation.

The occurrence of inflammation subsequent to haematopoietic stem cell transplantation is associated with an elevated risk of transplant-related mortality (TRM). However, the duration of inflammation and the potential efficacy of anti-inflammatory agents in reducing TRM remain uncertain. We performed a comprehensive investigation to examine the post-transplantation alterations of inflammatory mediators and to ascertain the correlation between inflammation level and TRM through the neutrophil-lymphocyte ratio, ELISAs and cytometric bead array. The findings revealed that the 30-day interval following transplantation is characterised by the most pronounced inflammatory response in both human and murine subjects, thereby elevating the risk of TRM. The inflammation is primarily caused by myeloid bias during haematopoietic reconstitution, which is a commonly overlooked aspect in clinical transplantation, additionally, a lesser extent of irradiation-induced injury. The administration of the anti-inflammatory agent resveratrol has the potential to reduce systemic inflammation and TRM by suppressing the NOD-like receptor signalling pathway and slowing down granulocyte implantation in HSCT mice. This approach did not impair the differentiation potential of haematopoietic stem cells. These findings demonstrate that the 30-day post-transplant period represents an opportunity to facilitate HSCT colonisation, mitigate transplant-related adverse effects, and potentially reap the benefits of anti-inflammatory treatments.

Ultrasonographic evaluation of acute idiopathic scrotal wall oedema in adults

Acute idiopathic scrotal wall oedema is an uncommon cause of acute scrotal oedema that usually affects the paediatric population and is rarely encountered in adults. It frequently goes away without the need for surgery, presenting as sudden scrotal oedema and erythema. Acute idiopathic scrotal wall oedema is diagnosed and distinguished from other scrotal disorders by clinical examination and ultrasonography, which includes the distinctive ‘fountain sign’. A variety of clinical and radiological variables are included in the differential diagnosis and were carefully ruled out in this instance. Antibiotics and non-steroidal anti-inflammatory medications are used to treat acute idiopathic scrotal oedema conservatively; full recovery usually happens within a week. Though inadvertently discovered in this case, epididymal cysts may or may not be relevant in acute idiopathic scrotal wall oedema. When assessing acute scrotal oedema, especially in uncommon circumstances, acute idiopathic scrotal wall oedema should be considered in order to avoid unnecessary surgical intervention and associated risks.

Carbon dots derived from organic drug molecules with improved therapeutic effects and new functions.

Carbon dots (CDs) are new types of fluorescent nanomaterials with particle diameters of 1∼10 nm and have excellent photoluminescence (PL) properties, good biocompatibility, simple preparation methods and numerous raw materials; consequently, they are promising in the biomedical field. In recent years, to overcome drug resistance and toxic side effects of traditional organic drugs, the synthesis of CDs from drug molecules has become an effective strategy, which produces CDs with the same therapeutic effects as the raw drugs and even possessing new properties. At present, many CDs derived from organic drugs have been developed, which can be classified according to their sources such as antibiotics, anti-inflammatory drugs, and guanidine drugs. This article focuses on the progress of the above-mentioned drug-derived CDs compared with their drug precursors in terms of therapeutic efficacy, enhanced performance and new additional functions, with special attention to the structure-activity relationship between the drug precursors and the CD-based therapeutic agents. It demonstrates the feasibility of designing new drug-derived CDs for clinical applications, summarizes the shortcomings and research gaps of the existing work, and provides a reference for related work in the future.

The Anti-inflammatory Potential of Tricyclic Antidepressants (TCAs): A Novel Therapeutic Approach to Atherosclerosis Pathophysiology

Atherosclerosis, a chronic inflammatory disease, is driven by complex molecular mechanisms involving inflammatory cytokines and immune pathways. According to recent research, tricyclic antidepressants (TCAs), which are typically prescribed to treat depressive disorders, have strong anti-inflammatory effects. TCAs, including imipramine and amitriptyline, alter inflammatory signaling cascades, which include lowering the levels pro-inflammatory cytokines like TNF-α, IL-1β, and IL-6 and inhibiting NF-κB activation. By inhibiting the NLRP3 inflammasome and suppressing pathways including JAK/STAT, MAPK, and PI3K, these effects are produced, improving endothelial function and reducing oxidative stress. The intricacy of TCAs’ anti-inflammatory actions has demonstrated by the existence of contradictory findings about how they alter IL-6 levels. The dependence of the heterogeneity of the reaction on the use of particular TCAs and experimental settings is shown by the fact that some studies show reduced IL-6 production, while others indicate increases or no changes. This review explores the multifaceted mechanisms through which TCAs modulate inflammatory pathways. TCAs inhibit NF-κB activation, reduce oxidative stress, and suppress the production of key inflammatory mediators, including IL-6 and TNF-α. They also regulate Toll-like receptor (TLR) signaling and NOD-, LRR-, and NLR family pyrin domain-containing protein 3 (NLRP3) inflammasome activation, reducing the release of IL-1β and IL-18, critical drivers of endothelial dysfunction and plaque instability. Given their capacity to target critical inflammatory molecules and pathways, TCAs provide great potential in the therapy of atherosclerosis, particularly for individuals with associated depression and cardiovascular risk factors. Nevertheless, further research is essential to clarify the precise molecular mechanisms, resolve inconsistencies in current findings, and establish the clinical applicability of TCAs as anti-inflammatory agents in atherosclerosis management.

Perspectives on Berberine and the Regulation of Gut Microbiota: As an Anti-Inflammatory Agent

Perspectives on Berberine and the Regulation of Gut Microbiota: As an Anti-Inflammatory Agent

Nandrolone decanoate induces heart injury via oxidative damage and mitochondrial apoptotic pathway by regulation of TLR4/NF-κB/NLRP3 axis in male rats: The rescue effect of N-acetylcysteine.

Myocardial apoptosis is a leading cause of damage in cardiac tissues of nandrolone (ND) treatment. However, its molecular mechanism is not fully understood. This study aims to investigate the effect of ND with or without N -acetylcysteine (NAC) treatment on oxidative damage and TLR4/NF-κB /NLRP3 signaling pathway in the heart of male rats. Eighteen male Wistar rats with a weight range of 220 ± 10 g were selected. They were divided into three groups (n = 6): control (C) group, ND group, NAC + ND group. After six weeks of treatment, the TUNEL staining indicated that ND increased the number of apoptotic cells in the hearts of male rats. The molecular analysis demonstrated that ND exposure resulted in increased protein levels of cytochrome c, c-Caspase-3/p-Caspase-3 ratio, p53, TLR4, NF-κB, NLRP3, and 8-OHdG with a concomitant up-regulation of LDH and CK-MB enzymes activity in the heart tissue compared to the C group. Our findings suggested that ND can cause damage to heart tissue via induction of DNA damage, apoptosis, and probably TLR4/NF-κB/NLRP3 signaling pathway plays a crucial role in this process. It also demonstrates that these negative effects of ND can be reduced by using NAC treatment as an antioxidant and anti-inflammatory agent.

Sudden Cardiac Arrest Associated With Widespread Coronary Vasospasm After Oral Amoxicillin/Clavulanic Acid Intake (A Rare Case Of Kounis Syndrome)

Kounis syndrome is known as a type of acute coronary syndrome that occurs secondary to hypersensitivity reactions and constitutes a life-threatening medical emergency. Although multiple etiologies of KS have been elucidated, pharmacological agents are the most prevalent. Antimicrobial agents and nonsteroidal anti-inflammatory drugs (NSAIDs) are the most frequently utilized medications. KS is not rare, and its frequency has been reported to increase since it was first described in 1950. However, it is often underdiagnosed owing to its wide range of clinical manifestations. Diagnostic evaluation should encompass laboratory, electrocardiographic, echocardiographic, and angiographic evidence in addition to clinical symptoms and signs. In this case study, we presented a 56 year old patient without any chronic disease who presented with sudden cardiac arrest after taking oral amoxicillin/clavulanic acid.