Croton stipulaceus Kunth, a native Mexican medicinal plant with antioxidant and anti-inflammatory activities / Croton stipulaceus Kunth, planta medicinal mexicana con actividad antioxidante y antiinflamatoria

Leaves of Croton stipulaceuswere extracted (EHex, ECHCl3and EEtOH extracts) to assesstheir antioxidant potential, anti-inflammatory activity in murine models and acute toxicity. EEtOH showed the highest effect in DPPH (37.80% inhibition), FRAP (1065.00 ± 55.30 µmolFe2+) and total polyphenols (231.24 ± 9.05 meq AG/gM). EHex was the most active, ~ 50% inhibition of TPA-induced ear edema; while EEtOH (dose of 2 mg/ear) showed the highest inhibition in the chronic model (97% inhibition), and inhibited MPO activity (48%). In carrageenan-induced edema, ECHCl3(dose 500 mg/kg) was the most active. None of the extracts showed acute toxicity (LD50) at 2 g/kg (p.o.). This work is the first report that supports the traditional use of C. stipulaceusas an anti-inflammatory.

De las hojas de Croton stipulaceusse obtuvieron diferentes extractos (EHex, ECHCl3y EEtOH) evaluando el potencial antioxidante y la actividad antiinflamatoria en modelos murinos y la toxicidad aguda. El EEtOH mostró mayor efecto en DPPH (37.80% inhibición), FRAP (1065.00 ± 55.30 µmolFe2+) y polifenolestotales (231.24 ± 9.05 meq AG/gM). El EHex fue el más activo, cercano al 50% de inhibición del edema auricular inducido con TPA; mientras que el EEtOH (dosis de 2 mg/oreja) mostró la mayor inhibición en el modelo crónico (97% inhibición), e inhibió la actividad de la MPO (48%). En el edema inducido con carragenina, el ECHCl3(dosis 500 mg/kg) fue el más activo. Ninguno de los extractos mostró una toxicidad aguda (DL50) mayor a 2 g/kg (p.o). Este trabajo es el primer reporte que sustenta el uso tradicional de C. stipulaceuscomo antiinflamatorio.

Comprehensive In-vitro Evaluation of Indigofera hochstetteri Baker Extract: Effect of chemicals in Antimicrobial, Anticancer, Anti-Inflammatory, and Anti-diabetic activities.

The study aimed to analyze the pharmacological properties of medicinal plant Indigofera hochstetteri Baker extracts. Preliminary phytochemical analysis revealed a diverse range of secondary metabolites present in it. TLC analysis detected numerous phytochemicals with varying Rf values, aiding in different solvent systems. GC-MS analysis revealed the presence of 29 bioactive compounds with diverse pharmacological activities, including anti-inflammatory, antioxidant, analgesic and antimicrobial properties. Antimicrobial effect of I. hochstetteri Baker methanolic extract showed significant inhibitory effects against E. coli, E. aerogenes, S. flexneri, P. aeruginosa, S. aureus, E. faecalis, B. cereus, and fungal strain C. albicans. The methanol extract also showed significant antifungal activity by inhibiting the growth of Sclerotium rolfsii in food poisoning method. MTT assays revealed significant cytotoxic activity of methanolic extract against human leukemia HL-60 cancer cells with IC50 of 116.01 µg/mL. In apoptotic study, I. hochstetteri Baker methanolic extract showed 28.84% viable cells, 30.2% early apoptosis, 35.54% late apoptosis, and 5.86% necrosis comparatively similar with standard used. The extract showed significant anti-inflammatory effect on HRBC stabilization, and protein denaturation of BSA and egg albumin denaturation with IC50 of 193.62 µg/mL, 113.94 µg/mL respectively. In anti-diabetic assays like α-amylase, α-glucosidase, and Glucose uptake assay, I. hochstetteri extract showed good anti-diabetic effect with IC50 of 60.64 µg/mL, 169.34 µg/mL, and 205.63 µg/mL respectively. In conclusion I. hochstetteri Baker have promising bioactive metabolites with significant biological activities, it can be good substitute for the chemical drugs after successful clinical studies.

Therapeutic properties of Inonotus obliquus (Chaga mushroom): A review.

Inonotus obliquus, also known as Chaga, is a medicinal mushroom that has been used for therapeutic purposes since the sixteenth century. Collections of folk medicine record the application of Chaga for the treatment of diseases such as gastrointestinal cancer, diabetes, bacterial infection, and liver diseases. Modern research provides scientific evidence of the therapeutic properties of I. obliquus extracts, including anti-inflammatory, antioxidant, anticancer, anti-diabetic, anti-obesity, hepatoprotective, renoprotective, anti-fatigue, antibacterial, and antiviral activities. Various bioactive compounds, including polysaccharides, triterpenoids, polyphenols, and lignin metabolites have been found to be responsible for the health-benefiting properties of I. obliquus. Furthermore, some studies have elucidated the underlying mechanisms of the mushroom's medicinal effects, revealing the compounds' interactions with enzymes or proteins of important pathways. Thus, this review aims to explore available information on the therapeutic potentials of Inonotus obliquus for the development of an effective naturally sourced treatment option.

Reactive oxygen species induced by indomethacin enhance accumulation of heme carrier protein 1 and hematoporphyrin accumulation in vitro and in vivo in a brain tumor model.

Photodynamic therapy (PDT) is useful for various cancers such as high-grade glioma and cancers of other organs. However, the mechanism of tumor-specific accumulation of porphyrin is not clear. The authors previously reported that heme carrier protein 1 (HCP1) contributes to the transport of porphyrins; specifically, we showed that the production of cancer-specific reactive oxygen species from mitochondria (mitROS) leads in turn to enhanced HCP1 expression. Indomethacin (IND), a non-steroidal anti-inflammatory drug, increases ROS production by affecting mitochondrial electron transfer system. In the present work, the authors investigated the effect of pretreatment with IND on cancer-specific porphyrin accumulation, using both a glioma cell line and a rat brain tumor model. This work demonstrated that exposure of a rat glioma cell to IND results in increased generation of cancer-specific mitROS and accumulation of HCP1 expression and porphyrin concentration. Additionally, systemic dosing of a brain tumor animal model with IND resulted in elevated cellular accumulation of porphyrin in tumor cell. This is an effect not seen with normal brain tissue. Thus, the administration of IND increases intracellular porphyrin concentrations in tumor cell without exerting harmful effects on normal brain tissue, and increased porphyrin concentration in tumor cell may lead to improved PDT effect.

Inflammation and cancer: friend or foe?

Chronic inflammation plays a crucial role in the onset and progression of pathologies like neurodegenerative and cardiovascular diseases, diabetes, and cancer, since tumor development and chronic inflammation are linked, sharing common signaling pathways. At least 20% of breast and colorectal cancers are associated with chronic inflammation triggered by infections, irritants, or autoimmune diseases. Obesity, chronic inflammation, and cancer interconnection underscore the importance of population-based interventions in maintaining healthy body weight, to disrupt this axis. Given that the dietary inflammatory index is correlated with an increased risk of cancer, adopting an anti-inflammatory diet supplemented with nutraceuticals may be useful for cancer prevention. Natural products and their derivatives offer promising antitumor activity with favorable adverse effect profiles; however, the development of natural bioactive drugs is challenging due to their variability and complexity, requiring rigorous research processes. It has been shown that combining anti-inflammatory products, such as non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and statins, with plant-derived products demonstrate clinical utility as accessible adjuvants to traditional therapeutic approaches, with known safety profiles. Pharmacological approaches targeting multiple proteins involved in inflammation and cancer pathogenesis emerge as a particularly promising option. Given the systemic and multifactorial nature of inflammation, comprehensive strategies are essential for long term success in cancer therapy. To gain insights into carcinogenic phenomena and discover diagnostic or clinically relevant biomarkers, is pivotal to understand genetic variability, environmental exposure, dietary habits, and TME composition, to establish therapeutic approaches based on molecular and genetic analysis. Furthermore, the use of endocannabinoid, cannabinoid, and prostamide-type compounds as potential therapeutic targets or biomarkers requires further investigation. This review aims to elucidate the role of specific etiological agents and mediators contributing to persistent inflammatory reactions in tumor development. It explores potential therapeutic strategies for cancer treatment, emphasizing the urgent need for cost-effective approaches to address cancer-associated inflammation.

Design and Synthesis of MarinePolybrominated Diphenyl Ether Derivatives as Potential Anti-inflammatory Agents.

Natural polybrominated diphenyl ethers are generally isolated from sponges and possess a broad range of biological activities. Through screening of our marine natural product library, we discovered that polybrominated diphenyl ethers 5 and 6 exhibit considerable anti-inflammatory activity. In order to expand our repertoire of derivatives for further biological activity studies, we designed and synthesized a series of 5-related polybrominated diphenyl ethers. Importantly, compound 5a showed comparable anti-inflammatory activity while much lower cytotoxicity on lipopolysaccharide (LPS)-induced RAW264.7 cells. Additionally, western blotting analysis showed that 5a reduced the expression of phosphorylated extracellular signal-regulated kinase (p-ERK). Besides, molecular docking experiments were conducted to predict and elucidate the potential mechanisms underlying the varying anti-inflammatory activities exhibited by compounds 5a, 5, and 6.

Anti-Inflammatory and Anti-Arthritis Activity of Quercetin: A Comprehensive Review.

This comprehensive exploration delves into the multifaceted attributes of quercetin, a flavonoid with extensive health-promoting potential. The review navigates through its fundamental properties, encompassing its chemical structure, classification as a flavonoid, and its natural prevalence in various sources. Addressing solubility, stability, and bioavailability challenges, the investigation delves into innovative isolation techniques, including solvent extraction, solid-phase extraction, natural deep eutectic solvents, supercritical fluid extraction, microwave-assisted extraction, column chromatography, and high-performance thin-layer chromatography. Transitioning into pharmacological implications, the study unveils quercetin's roles in anti-inflammatory pathways, antioxidant effects, and immune modulation, reflecting its versatile significance in health management. The review highlights its impact on wound healing processes and its potential to mitigate arthritis, elucidating its holistic contributions. Culminating in an exploration of recent studies, the analysis underscores quercetin's remarkable anti-inflammatory and anti-arthritis activities, reflecting its substantial potential across various ailments. The review concludes by projecting future trajectories, emphasizing prospects for an advanced understanding of quercetin's mechanisms, sustainable extraction techniques, clinical integration, and exploration of synergistic combinations. Collectively, this review investigation underscores quercetin's dynamic role at the intersection of natural compounds and medicinal applications, offering profound implications for well- being and health enhancement.

Unveiling the anti-vitiligo, anti-inflammatory, and antitumor activities of sesquiterpene coumarins isolated from Ferula kuhistanica.

Six undescribed bicyclic sesquiterpene coumarins, kuhistanin A, ferukrin isovalerate, 9'ß,12'α - ferukrin isovalerate, (17'E)- 9'α, 12'ß - isomarcandin, (17'Z)- 9'α, 12'ß - isomarcandin and (17'E) - isomarcandin, together with nine known ones were isolated from the roots of Ferula kuhistanica Korovin. The structures of them were elucidated using NMR and HRESIMS data analysis. The relative configurations of the isolates were confirmed by NOE correlations and NMR calculation. The absolute configurations of them were confirmed by X-ray diffraction analysis and ECD calculation. Anti-vitiligo, anti-inflammatory and cytotoxicity of the isolates were tested. Acetyl feselol, feselol, ferusingensine I and farnesiferol A significantly increased the melanin content at the concentration of 10 µM. (17'E) - 9'α, 12'ß - isomarcandin exhibited strong cytotoxicity against HT-29 cell line with IC50 values of 8.94 ± 0.47 µM, and (17'E) - isomarcandin demonstrated strong cytotoxicity against Hela, A549 and HT-29 cell lines with IC50 values of 5.29 ± 0.25, 4.01 ± 0.20, and 4.16 ± 0.21 µM, respectively. This study concluded that, isolated compounds from F. kuhistanica demonstrated strong bioactivity towards anti-vitiligo and cytotoxicity and active compounds are suggested as anti-vitiligo and cytotoxicity agent for future drug development.

Anti-inflammatory Fucoidan-ConA oral insulin nanosystems for smart blood glucose regulation.

The smart oral administration Insulin device has the potential to improve glycemic management. It can reduce the risk of hypoglycemia associated with exogenous Insulin (INS) therapy while also avoiding many of the disadvantages associated with subcutaneous injections. Furthermore, diabetes mellitus (DM) is an endocrine illness characterized by inflammation, and it is critical to minimize the amount of inflammatory markers in diabetic patients while maintaining average blood glucose. In this study, a responsive nanosystem vitamin B12-Fucoidan-Concanavalin A (VB12-FU-ConA NPs) with anti-inflammatory action was developed for smart oral delivery of Insulin. Con A has high sensitivity and strong specificity as a glucose-responsive material. Fucoidan has anti-inflammatory, immunomodulatory, and hypoglycemic functions, and it can bind to Con A to form a reversible complex. Under high glucose conditions, free glucose competitively binds to Con A, which swells the nanocarrier and promotes Insulin release. Furthermore, in the low pH environment of the gastrointestinal tract, positively charged VB12 and anionic fucoidan bind tightly to protect the Insulin wrapped in the carrier, and VB12 can also bind to intestinal epithelial factors to improve transit rate, thereby promoting INS absorption. In vitro tests showed that the release of nanoparticles in hyperglycemic solutions was significantly higher than the drug release in normoglycemic conditions. Oral delivery of the nanosystems dramatically lowered blood glucose levels in type I diabetic mice (T1DM) during in vivo pharmacodynamics, minimizing the risk of hypoglycemia. Blood glucose levels reached a minimum of 8.1 ± 0.4 mmol/L after 8 h. Administering the nanosystem orally notably decreased the serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in diabetic mice. The nano delivery system can be degraded and metabolized in the intestinal tract after being taken orally, demonstrating good biodegradability and biosafety. In conclusion, the present study showed that VB12-FU-ConA nanocarriers are expected to be a novel system for rationalizing blood glucose.

Conversion of gingerols to shogaols in ginger (Zingiber officinale roscoe) by puffing.

Effect of puffing on conversion of gingerols to shogaols, physicochemical properties as well as antioxidant and anti-inflammatory activities of puffed ginger was investigated. Puffing significantly increased extraction yield and the highest value was 12.52% at 980 kPa. The significant decrease in gingerols and increase in shogaols were occurred after puffing, respectively. Especially, 6-shogaol was dramatically increased from 4.84 to 99.10 mg/g dried ginger. Puffed ginger exhibited the higher antioxidant activities (analyzed by DPPH, ABTS, TPC, and TFC) than those of control, and they were significantly increased with increasing puffing pressure. In case of anti-inflammatory activity, puffed ginger did not inhibit NO production, but significantly inhibited TNF-α and IL-6 productions. Among gingerols and shogaols, 6-shogaol showed significantly strong correlations with both antioxidant and anti-inflammatory activities. Consequently, puffed ginger can be applied to functional food industry, which dramatically increased the contents of 6, 8, 10-shogaols, the main bioactive compounds in ginger.

Oleanolic acid and its analogues: promising therapeutics for kidney disease.

Kidney diseases pose a significant threat to human health due to their high prevalence and mortality rates. Worryingly, the clinical use of drugs for kidney diseases is associated with more side effects, so more effective and safer treatments are urgently needed. Oleanolic acid (OA) is a common pentacyclic triterpenoid that is widely available in nature and has been shown to have protective effects in kidney disease. However, comprehensive studies on its role in kidney diseases are still lacking. Therefore, this article first explores the botanical sources, pharmacokinetics, derivatives, and safety of OA, followed by a summary of the anti-inflammatory, immunomodulatory, anti-oxidative stress, autophagy-enhancing, and antifibrotic effects of OA and its analogues in renal diseases, and an analysis of the molecular mechanisms, aiming to provide further insights for the development of novel drugs for the treatment of kidney diseases.

ADVANCES AND CHALLENGES IN SERRATIOPEPTIDASE TOPICAL FORMULATION.

Enzymes are a key part of most metabolic processes and are required for the correct functioning of the human body, either directly or indirectly. Proteolytic enzymes aid in the digestion of proteins in the body. Proteolytic enzymes are created in the pancreas naturally, but they can also be found in certain diets. Serratiopeptidase is an enzyme found in the stomach wall of silkworms and produced from S. marcescens strain. Less Solubility, toxicity, instability, incompatibility, and less penetration are all common issues with Serratiopeptidase drug delivery. Because of its proteinaceous nature, serratiopeptidase is susceptible to enzymatic breakdown in the gastrointestinal system. It also has a low permeability through the intestinal barrier due to its hydrophilic nature. Depending on the features of the medicine, a suitable delivery mechanism is required. Topical formulation may eliminate the risk of gastric degradation of drug and increase direct permeation through skin and show effects. Topical SRP may effectively lower inflammatory markers, as it has been found to have superior anti-inflammatory effects than topical NSAIDs. Serratiopeptidase topical formulations could be more effective than nonsteroidal anti-inflammatory medications in treating local inflammation. This article reviews studies on various topical formulations.

Tropane Alkaloid Isolated from Erythroxylum bezerrae Exhibits Neuropharmacological Potential in an Adult Zebrafish (Danio rerio) Model.

This study carried out to investigate the anti-inflammatory and antinociceptive effect of tropane alkaloid (EB7) isolated from E. bezerrae. It evaluated the toxicity and possible involvement of ion channels in the antinociceptive effect of EB7, as well as its anti-inflammatory effect in adult zebrafish (Zfa). Docking studies with EB7 and COX-1 and 2 were also performed. The tested doses of EB7 (4, 20 and 40 mg/kg) did not show any toxic effect on Zfa during the 96h of analysis (LD50 > 40 mg/kg). They did not produce any alteration in the locomotor behavior of the animals. Furthermore, EB7 showed promising pharmacological effects as it prevented the nociceptive behavior induced by hypertonic saline, capsaicin, formalin and acid saline. EB7 had its analgesic effect blocked by amiloride involving the neuromodulation of ASICs in Zfa. In evaluating the anti-inflammatory activity, the edema induced by κ-carrageenan 3.5% was reduced by the dose of 40 mg/kg of EB7 observed after the fourth hour of analysis, indicating an effect similar to that of ibuprofen. Molecular docking results indicated that EB7 exhibited better affinity energy when compared to ibuprofen control against the two evaluated targets binding at different sites in the cocrystallized COX-1 and 2 inhibitors.

Deferoxamine-Loaded Injectable Chitosan-Grafted Chlorogenic Acid/Oxidized Hyaluronic Acid Hybrid Hydrogel with Antibacterial, Anti-inflammatory, and Angiogenesis-Promoting Properties for Diabetic Wound Repair.

Diabetic chronic wounds are notoriously difficult to heal as a result of their susceptibility to infection. To address this issue, we constructed an innovated and adaptable solution in the form of injectable chitosan (CS) hydrogel, denoted as CCOD, with enhanced antibacterial and anti-inflammatory properties. This hydrogel is created through a Schiff base reaction that combines chitosan-grafted chlorogenic acid (CS-CGA) and oxidized hyaluronic acid (OHA) with deferoxamine (DFO) as a model drug. The combination of CS and CGA has demonstrated excellent antibacterial and anti-inflammatory properties, while grafting played a pivotal role in making these positive effects stable. These unique features make it possible to customize injectable hydrogel and fit any wound shape, allowing for more effective and personalized treatment of complex bacterial infections. Furthermore, the hydrogel system is not only effective against inflammation and bacterial infections but also possesses antioxidant and angiogenic abilities, making it an ideal solution for the repair of chronic wounds that have been previously thought of as unmanageable.

[Radiotherapy for non-tumoral disorders : a brief history and indications in 2024]. / La radiothérapie des pathologies non tumorales : un bref historique et possibilités en 2024.

Radiotherapy for non-tumoral disorders has a long history. Lack of high-level evidence, therapeutic alternatives and fear of side effects (particularly radiation-induced cancer) reduced some indications to a trickle during the second half of the 20th century. Others were logically abandoned. There are two exceptions to this trend. On the one hand, some Central European countries (Germany in particular) still use radiotherapy regularly for diseases such as osteoarthritis, plantar fasciitis, chronic tendinopathies, Dupuytren's disease, etc. On the other hand, the development of stereotactic ablative radiotherapy has opened up new indications, whether cerebral (arteriovenous malformations, trigeminal neuralgia, obsessive-compulsive disorders) or cardiac (ventricular tachycardia). In this article, we present a non-exhaustive list of some indications (or rather possibilities) for radiotherapy in non-tumoral disorders in 2024.

La radiothérapie des pathologies non tumorales possède une longue histoire. L'absence de preuves d'un niveau élevé, les alternatives thérapeutiques et la peur d'effets secondaires (en particulier le cancer radio-induit) ont réduit certaines indications à peau de chagrin durant la seconde moitié du 20ème siècle. D'autres ont logiquement été abandonnées. Deux exceptions existent concernant cette diminution. D'une part, certains pays d'Europe centrale (l'Allemagne en particulier) continuent d'utiliser régulièrement la radiothérapie dans des pathologies telles que l'arthrose, la fasciite plantaire, les tendinopathies chroniques, la maladie de Dupuytren ... D'autre part, le développement de la radiothérapie stéréotaxique ablative a permis d'envisager de nouvelles indications qu'elles soient cérébrales (malformations artério-veineuses, névralgie du trijumeau, troubles obsessionnels compulsifs) ou cardiaques (tachycardie ventriculaire). Nous présentons, de façon non exhaustive, quelques indications (ou plutôt possibilités) de radiothérapie dans les pathologies non tumorales utilisées en 2024.

Anti-inflammatory, anti-oxidant and anti-ulcer activities of aqueous lyophilizate of Markhamia lutea (Bignoniaceae).

OBJECTIVES: This work was carried out with a view to determining the antioxidant, anti-inflammatory and anti-ulcer properties of the aqueous lyophilized extract of Markhamia lutea. METHODS: In vitro proteinases inhibition, albumin denaturation, hemolysis of red blood cells by heat, inhibition of the proton pump H+/K+ATPase, FRAP (Ferric reducing antioxidant power) and DPPH (1,1-diphenyl-2-picrylhydrazyl) assays were performed. In vivo, cold water immersion-induced ulceration and methylene blue-induced ulceration was used to determine the anti-ulcer properties of the lyophilizate (100, 200 and 300 mg/kg). RESULTS: In vitro, the lyophilizate (400 µg/mL) significantly inhibited protein denaturation (66.65 %), hemolysis of red blood cells (56.54 %), proteinase activity (69.22 %); then the IC50 was 26.31 µg/mL on proton pump activity. It has also developed a strong ferric reducing antioxidant power (EC50=52.96 mmol FeSO4/g) as well as free radicals scavenging activity (EC50=22.38 µg/mL). In vivo, the aqueous lyophilizate (200 and 300 mg/kg) protected the gastric mucosa (70.68 and 79.00 % protection respectively) and reduced (p<0.05) acetylcholine, calcium and corticosterone concentrations. A decrease in malondialdehyde level, an increased glutathione level and an increased in catalase and SOD activities were recorded. In the methylene blue test, it significantly increased gastric fluid pH, while reducing gastric volume and improving hematological parameters in ulcer animals. In addition, the histological sections show that the aqueous lyophilizate of M. lutea protected the gastric mucosa from the deleterious effects of stress. CONCLUSIONS: The aqueous lyophilizate of M. lutea has anti-ulcer properties thanks to its anti-inflammatory, antioxidant and anti-secretory properties.

How to Define and Manage Low-Risk Drug Allergy Labels.

Risk stratification in drug allergy implies that specific risk categories (eg, low, moderate, and high) classify historical drug hypersensitivity reactions. These risk categories can be based on reaction phenotypic characteristics, the timing of the reaction and evaluation, the required reaction management, and individual characteristics. Although a multitude of frameworks have been described in the literature, particularly for penicillin allergy labels, there has yet to be a global consensus, and approaches continue to vary between allergy centers. Immune-mediated drug allergies can sometimes be confirmed using skin testing, but a negative drug challenge is required to demonstrate tolerance and remove the allergy from the electronic health record ("delabel" the allergy). Even for quintessential IgE-mediated drug allergy, penicillin allergy, recent data reveal that a direct oral challenge, without prior skin testing, is an appropriate diagnostic strategy in those who are considered low-risk. Drug allergy pathogenesis and clinical manifestations may vary depending on the culprit drug, and as such, the optimal approach should be based on risk stratification that considers individual patient and reaction characteristics, the likely hypersensitivity reaction phenotype, the drug class, and the patient's clinical needs. This article will describe low-risk drug allergy labels, focusing on ß-lactam and sulfonamide antibiotics, nonsteroidal anti-inflammatory drugs, iodinated contrast media, and common chemotherapeutics. This review will also address practical management approaches using currently available risk stratification and clinical decision tools.

Real-World Bleeding Risk of Anticoagulant and Nonsteroidal Anti-inflammatory Drugs Combotherapy versus Anticoagulant Monotherapy.

Background/Aims: The incidence of acute gastrointestinal bleeding (GIB) increases with the utilization of anticoagulant and nonsteroidal anti-inflammatory drugs (NSAIDs). This study aimed to compare the risk of GIB between anticoagulant and NSAIDs combotherapy and anticoagulant monotherapy in real-world practice. Methods: We investigated the relative risk of GIB in individuals newly prescribed anticoagulant and NSAIDs combination therapy and that in individuals newly prescribed anticoagulant monotherapy at three hospitals using "common data model." Cox proportional hazard models and Kaplan-Meier estimation were employed for risk comparison after propensity score matching. Results: A comprehensive analysis of 2,951 matched pairs showed that patients who received anticoagulant and NSAIDs combousers exhibited a significantly higher risk of GIB than those who received anticoagulant monousers (hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.30 to 2.12; p<0.001). The risk of GIB associated with anticoagulant and NSAIDs combination therapy was also significantly higher than that associated with anticoagulant monotherapy in patients aged >65 years (HR, 1.53; 95% CI, 1.15 to 2.03; p=0.003) and >75 years (HR, 1.89; 95% CI, 1.23 to 2.90; p=0.003). We also found that the risk of GIB was significantly higher in the patients who received anticoagulant and NSAIDs combousers than that in patients who received anticoagulant monousers in both male (p=0.016) and female cohorts (p=0.010). Conclusions: The risk of GIB is significantly higher in patients who receive anticoagulant and NSAIDs combotherapy than that in patients who receive anticoagulant monotherapy. In addition, the risk of GIB associated with anticoagulant and NSAIDs combotherapy was much higher in individuals aged >75 years. Therefore, physicians should be more aware of pay more attention to the risk of GIB when they prescribe anticoagulant and NSAIDs.

Association Between Statin Use and the Incidence of Clinically Diagnosed Osteoarthritis: A Nationwide Retrospective Cohort Study in Taiwan.

OBJECTIVE: To investigate the effect of higher cumulative defined daily dose per year (cDDD/y) compared with lower cDDD/y of statin use in the incidence of any joint osteoarthritis (OA). DESIGN: In this population-based retrospective cohort study, patients who were aged ≥40 years were newly initiated on statin therapy between 2002 and 2011, and had a statin prescription for ≥90 days in the first year of treatment were identified from the 2000 Longitudinal Generation Tracking Database. All patients were separated into groups with higher cDDD/y (>120 cDDD/y) and lower cDDD/y (≤120 cDDD/y; as an active comparator) values. Propensity score matching was performed to balance potential confounders. All recruited patients were followed up for 8 years. Marginal Cox proportional hazard models were used to estimate time-to-event outcomes of OA. RESULTS: Compared with lower cDDD/y use, higher cDDD/y use did not reduce the risk of any joint OA (adjusted hazard ratio, 1.07; 95% confidence interval, 0.99-1.14). Dose-related analysis did not reveal any dose-dependent association. A series of sensitivity analyses showed similar results. Joint-specific analyses revealed that statin did not reduce the incidence of knee, hand, hip, and weight-bearing (knee or hip) OA. CONCLUSIONS: Higher cDDD/y statin use did not reduce the risk of OA in this Taiwanese nationwide cohort study. The complexity of OA pathogenesis might contribute to the ineffectiveness of statin. Repurposing statin with its anti-inflammation properties might be ineffective for OA development, and balancing the catabolism and anabolism of cartilage might be a major strategy for OA prevention.

Biological Potential and Therapeutic Effectiveness of Phytoproduct 'Fargesin' in Medicine: Focus on the Potential of an Active Phytochemical of Magnolia fargesii.

Flos Magnoliae is one of the important medicinal plants in different traditional medicine, including Chinese herbal medicine. Lignans and neolignans, including tetrahydrofurofuran, tetrahydrofuran, and aryltetralin, are present in the Flos Magnoliae species. A wide range of pharmacological activity of Flos Magnoliae has been reported in medicine. Fargesin has been isolated from Magnolia fargesii and is a lignan-class phytochemical. Fargesin has numerous pharmacological activities in medicine, including its effectiveness on lipid and glucose metabolism, oxidative stress, myocardial apoptosis, etc. In the present work, we have summarized the detailed scientific information of fargesin concerning its medicinal properties and pharmacological activities. Numerous biological and chemical aspects of fargesin are discussed here, including the detailed pharmacological activities and analytical aspects of fargesin. In this review, we have also compiled analytical data on fargesin based on available scientific literature. Ethnopharmacological information on fargesin was gathered by a literature survey on Pubmed, Science Direct, Google, and Scopus using the terms fargesin, Flos Magnoliae, phytochemical, and herbal medicine. The present review paper compiled the scientific data on fargesin in medicine for its pharmacological activities and analytical aspects in a very concise manner with proper citations. The present work signified the biological importance of fargesin in medicine due to its significant impact on bone disorders, lung injury, colon cancer, atherosclerosis, neurological disorders, ischemia, sars-cov-2, allergy, lipid and glucose metabolism, melanin synthesis, and different classes of enzymes. Furthermore, fargesin also has anti-inflammatory, antihypertensive, antiprotozoal, antimycobacterial, and antifeedant activity. However, analytical methods used for the separation, identification and isolation of fargesin in different biological and non-biological samples were also covered in the present review. The present work revealed the pharmacological activities and analytical aspects of fargesin in medicine and other allied health sectors.