The impact of seasonal variation on the composition of the volatile oil of Polyalthia suberosa (Roxb.) Thwaites leaves and evaluation of its acetylcholinesterase inhibitory activity.

BACKGROUND: Polyalthia suberosa (Roxb.) Thwaites (Annonaceae) is a medicinal plant that has been reported for its various pharmacological potentials, such as its anti-inflammatory, analgesic, antioxidant, and neuropharmacological activities. This study aimed to analyze the leaf essential oils of P. suberosa (PSLO) collected in different seasons, to evaluate the acetylcholinesterase inhibitory activity, and to corroborate the obtained results via in-silico molecular docking studies. METHODS: The leaf essential oils of P. suberosa collected in different seasons were analyzed separately by GC/MS. The acetylcholinesterase inhibitory activity of the leaves oil was assessed via colorimetric assay. In-silico molecular docking studies were elucidated by virtual docking of the main compounds identified in P. suberosa leaf essential oil to the active sites in human acetylcholinesterase crystal structure. RESULTS: A total of 125 compounds were identified where D-limonene (0.07 - 24.7%), α-copaene (2.25 - 15.49%), E-ß-caryophyllene (5.17 - 14.42%), 24-noroleana-3,12-diene (12.92%), ß-pinene (0.14 - 8.59%), and α-humulene (2.49-6.9%) were the most abundant components. Results showed a noteworthy influence of the collection season on the chemical composition and yield of the volatile oils. The tested oil adequately inhibited acetylcholinesterase enzyme with an IC50 value of 91.94 µg/mL. Additionally, in-silico molecular docking unveiled that palmitic acid, phytol, p-cymene, and caryophyllene oxide demonstrated the highest fitting scores within the active sites of human acetylcholinesterase enzyme. CONCLUSIONS: From these findings, it is concluded that P. suberosa leaf oil should be evaluated as a food supplement for enhancing memory.

Anti-Inflammatory, Analgesic, Functional Improvement, and Chondroprotective Effects of Erigeron breviscapus (Vant.) Hand.-Mazz. Extract in Osteoarthritis: An In Vivo and In Vitro Study.

Osteoarthritis (OA) is a degenerative bone disease characterized by inflammation as a primary pathology and currently lacks therapeutic interventions to impede its progression. Erigeron breviscapus (Vant.) Hand.-Mazz. (EB) is an east Asian herbal medicine with a long history of use and a wide range of confirmed efficacy against cardiovascular and central nervous system diseases. The purpose of this study is to evaluate whether EB is worthy of further investigation as a treatment for OA based on anti-inflammatory activity. This study aims to assess the potential of EB as a treatment for OA, focusing on its anti-inflammatory properties. Analgesic effects, functional improvements, and inhibition of cartilage destruction induced by EB were evaluated in acetic acid-induced peripheral pain mice and monosodium iodoacetate-induced OA rat models. Additionally, the anti-inflammatory effect of EB was assessed in serum and cartilage tissue in vivo, as well as in lipopolysaccharide-induced RAW 264.7 cells. EB demonstrated a significant alleviation of pain, functional impairment, and cartilage degradation in OA along with a notable inhibition of pro-inflammatory cytokines, including interleukin-1ß, interleukin-6, matrix metalloproteinases 13, and nitric oxide synthase 2, both in vitro and in vivo, in a dose-dependent manner compared to the active control. Accordingly, EB merits further exploration as a potential disease-modifying drug for OA, capable of mitigating the multifaceted pathology of osteoarthritis through its anti-inflammatory properties. Nonetheless, additional validation through a broader experimental design is essential to substantiate the findings of this study.

Chronic Low Back Pain in Adults: Evaluation and Management.

Chronic low back pain, defined as lumbar pain persisting for 12 weeks or more, occurs in about 13% of U.S. adults. Patients with chronic low back pain should have a history and physical examination to identify red flags that may indicate serious conditions that warrant immediate intervention or yellow flags (i.e., psychological, environmental, and social factors) that indicate risk of disability. The examination should include an evaluation for radicular symptoms. Routine imaging is not recommended but is indicated when red flags are present, there is a neuromuscular deficit, or if pain does not resolve with conservative therapy. Patients should avoid bed rest. Nonpharmacologic treatment is first-line management and may include therapies with varying evidence of support, such as counseling, exercise therapy, spinal manipulation, massage, heat, dry needling, acupuncture, transcutaneous electrical nerve stimulation, and physical therapy. Pharmacologic interventions are second-line treatment. Nonsteroidal anti-inflammatory drugs are the initial medication of choice; duloxetine may also be beneficial. Evidence is inconclusive to recommend the use of benzodiazepines, muscle relaxants, antidepressants, corticosteroids, insomnia agents, anticonvulsants, cannabis, acetaminophen, or long-term opioids. Epidural corticosteroid injections are not recommended except for short-term symptom relief in patients with radicular pain. Most patients with chronic low back pain will not require surgery; evaluation for surgery may be considered in those with persistent functional disabilities and pain from progressive spinal stenosis, worsening spondylolisthesis, or herniated disk. Physicians should consider prevention of chronic low back pain when patients present with acute back pain. Screening tools are available to predict the progression from acute to chronic low back pain, and targeted treatment strategies are beneficial for preventing progression.

Synthesis and in†vitro Anti-Inflammatory Activity of Novel Dendrobine Amide/Sulfonamide Derivatives.

A traditional Chinese medicine ingredient, dendrobine, has been demonstrated to have anti-inflammatory properties. However, due to its poor anti-inflammatory properties, its clinical use is limited. Consequently, we have designed and synthesized 32 new amide/sulfonamide dendrobine derivatives and screened their anti-inflammatory activities in vitro. Experiments showed that nitric oxide (NO) generation in lipopolysaccharide (LPS)-induced RAW264.7 cells was strongly reduced by derivative 14, with an IC50 of 2.96 µM. Western blot research revealed that 14 decreased the concentration-dependent expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (INOS). Molecular docking was used to predict the binding of the inflammation-associated proteins COX-2 and INOS to compound 14.

An Evaluation of the Effects of Pineapple-Extract and Bromelain-Based Treatment after Mandibular Third Molar Surgery: A Randomized Three-Arm Clinical Study.

A three-arm, randomized, placebo-controlled clinical study was conducted to assess the impact of lyophilized pineapple extract with titrated bromelain (Brome-Inf®) and purified bromelain on pain, swelling, trismus, and quality of life (QoL) following the surgical extraction of the mandibular third molars. Furthermore, this study examined the need for Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) by comparing their effects with a placebo group. This study enrolled 42 individuals requiring the extraction of a single mandibular third molar under local anesthesia. The patients were randomly assigned to receive Brome-Inf®, purified bromelain, or a placebo orally, initiating treatment on the day of surgery and continuing for the next 7 days. The primary outcome measured was the requirement for NSAIDs in the three groups. Pain, swelling, and trismus were secondary outcome variables, evaluated postoperatively at 1, 3, and 7 days. This study also assessed the comparative efficacy of freeze-dried pineapple extract and single-component bromelain. Ultimately, the placebo group showed a statistically higher need for ibuprofen (from days 1 to 7) at the study's conclusion (p < 0.0001). In addition, reductions in pain and swelling were significantly higher in both the bromelain and pineapple groups (p < 0.0001 for almost all patients, at all intervals) than in the placebo group. The active groups also demonstrated a significant difference in QoL compared to the placebo group (p < 0.001). A non-significant reduction in trismus occurred in the treatment groups compared to the placebo group. Therefore, the administration of pineapple extract titrated in bromelain showed significant analgesic and anti-edema effects in addition to improving QoL in the postoperative period for patients who had undergone mandibular third molar surgery. Moreover, both bromelain and Brome-Inf® supplementation reduced the need for ibuprofen to comparable extents, proving that they are good alternatives to NSAIDs in making the postoperative course more comfortable for these patients. A further investigation with larger samples is necessary to assess the pain-relieving and anti-inflammatory impacts of the entire pineapple phytocomplex in surgical procedures aside from mandibular third molar surgery.

Clinical pharmacokinetics and pharmacodynamics of topical non-biological therapies for psoriasis patients.

INTRODUCTION: Psoriasis is a chronic inflammatory cutaneous disease that causes patients psychosocial distress. Topical therapies are utilized for mild-to-moderate disease and for more severe disease in conjunction with systemic therapies. Topical corticosteroids are a cornerstone of treatment for psoriasis, but long-term use can cause stria and cutaneous atrophy and as well as systemic side effects such as topical steroid withdrawal. Non-steroidal topical therapies tend to be safer than topical corticosteroids for long-term use. AREAS COVERED: We conducted a literature review on the pharmacokinetic (PK) and pharmacodynamic (PD) properties of topical therapies for psoriasis. We discuss how the PK and PD characteristics of these therapies inform clinicians on efficacy and toxicity when prescribing for patients. EXPERT OPINION: Topical corticosteroids, used intermittently, are very safe and effective. Long-term, continuous use of topical corticosteroids can cause systemic side effects. Several generic and newly approved non-steroidal options are available, but no head-to-head studies compare the effectiveness of the generics (vitamin D analogs, tacrolimus, pimecrolimus) against the newer therapies (roflumilast, tapinarof). Patients often do not respond to topical therapies due to poor adherence to treatment regimens. For patients resistant to topical treatment, phototherapy or systemic therapy may be an option.

Changes in pharmacist's recommendations of over-the-counter treatments for the common cold during the COVID-19 pandemic.

BACKGROUND: The common cold is one of the most frequently occurring illnesses worldwide. The aim of this study was to determine which OTC anti-common cold medications were most often recommended by pharmacists and if the COVID-19 pandemic affected such recommendations. METHODS: Non-interventional, observational research trial using a self-developed questionnaire to collect data on pharmacists' recommendations for anti-common cold OTC treatment. The data were collected during the COVID-19 pandemic (December 2021-February 2022) in four large community network pharmacies in Lodz (Poland) and then compared with an analogue period of time before the pandemic (December 2019-February 2020). RESULTS: During COVID-19 pandemic there was a significant (p < 0.05) reduction in paracetamol, acetylsalicylic acid, metamizole magnesium, inosines, alpha-mimetics, mucolytics, homeopathics, and sore throat products and an increase in other tablets/capsules and add-on product recommendations. There was a significant relationship (p < 0.05, OR > 1) between the recommended frequency of paracetamol, inosines, sore throat products (each symptom), metamizole magnesium (headache, fever), acetylsalicylic acid (headache, fever, fatigue), NSAIDs, alpha-mimetics (headache, rhinorrhea), pseudoephedrine (rhinorrhea), homeopathics (headache), herbal products (fatigue), antihistamines (rhinorrhea, cough), and mucolytics (headache, fever, cough). CONCLUSIONS: Favorable prices (before COVID-19 pandemic) and reports on common NSAIDs side effects (beginning of the pandemic) led to high sale of paracetamol. Increased awareness of clinical effectiveness of some medications or their reduced availability influenced their limited recommendations.

Comprehensive review of the phytochemistry, pharmacology, pharmacokinetics, and toxicology of alkamides (2016-2022).

Alkamides refer to a class of natural active small-molecule products composed of fatty acids and amine groups. These compounds are widely distributed in plants, and their unique structures and various pharmacological activities have caught the attention of scholars. This review provides a collection of literatures related to the phytochemistry, pharmacological effects, pharmacokinetics, and toxicity of alkamides published in 2016-2022 and their summary to provide references for further development of this class of ingredients. A total of 234 components (including chiral isomers) were summarized, pharmacological activities, such as anti-inflammatory, antitumor, antidiabetic, analgesic, neuroprotective, insecticidal, antioxidant, and antibacterial, and miscellaneous properties of alkamides were discussed. In addition, the pharmacokinetic characteristics and toxicity of alkamides were reviewed. However, information on the pharmacological mechanisms of the action, drug safety, and pharmacokinetics of alkamides is limited and thus requires further investigation and evaluation.

Short-term effects of cupping and scraping therapy for chronic nonspecific low-back pain: A prospective, multicenter randomized trial.

BACKGROUND: As one of the most common musculoskeletal ailments, chronic nonspecific low-back pain (CNLBP) causes persistent disability and substantial medical expenses. Epidemiological evidence shows that the incidence rate of CNLBP in young and middle-aged people who are demanded rapidly recovery and social contribution is rising. Recent guidelines indicate a reduced role for medicines in the management of CNLBP. OBJECTIVE: The present study investigates the short-term effects of cupping and scraping therapy using a medicated balm, compared to nonsteroidal anti-inflammatory drug (NSAID) with a capsaicin plaster, in the treatment of CNLBP. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: We designed a prospective multicenter randomized clinical trial enrolling patients from January 1, 2022 to December 31, 2022. A total of 156 patients with CNLBP were randomized into two parallel groups. Diclofenac sodium-sustained release tablets were administered orally to participants in the control group for one week while a capsaicin plaster was applied externally. Patients in the test group were treated with cupping and scraping using a medical device and medicated balm. MAIN OUTCOME MEASURES: Primary outcome was pain recorded using the visual analogue scale (VAS). Two secondary outcomes were recorded using the Japanese Orthopedic Association low-back pain scale (JOA) and the traditional Chinese medicine (TCM) syndrome integral scale (TCMS) as assessment tools. RESULTS: Between baseline and postintervention, all changes in outcome metric scales were statistically significant (P < 0.001). Compared to the control group, patients in the test group had a significantly greater treatment effect in all outcome variables, as indicated by lower VAS and TCMS scores and higher JOA scores, after the one-week intervention period (P < 0.001). Further, according to the findings of multivariate linear regression analysis, the participants' pain (VAS score) was related to their marital status, age, smoking habits and body mass index. No adverse reactions were reported for any participants in this trial. CONCLUSION: The effectiveness of TCM combined with the new physiotherapy tool is superior to that of NSAID combined with topical plasters, regarding to pain intensity, TCM symptoms and quality of life. The TCM plus physiotherapy also showed more stable and long-lasting therapeutic effects. TRIAL REGISTRATION: This study was registered at Chinese Clinical Trial Registry (ChiCTR2200055655). Please cite this article as: He JY, Tu XY, Yin ZF, Mu H, Luo MJ, Chen XY, Cai WB, Zhao X, Peng C, Fang FF, Lü C, Li B. Short-term effects of cupping and scraping therapy for chronic nonspecific low-back pain: A prospective, multicenter randomized trial. J Integr Med. 2024; 22(1): 39-45.

Exploration of the anti-inflammatory, analgesic, and wound healing activities of Bletilla Striata polysaccharide.

Bletilla Striata (BS) Polysaccharide (BSP) is one of the main components of the traditional Chinese medicinal plant Bletilla striata Rchb. F. BSP has been widely used in antimicrobial and hemostasis treatments in clinics. Despite its use in skin disease treatment and cosmetology, the effects of BSP on wound healing remain unclear. Here we investigated the anti-inflammatory, antioxidant, and analgesic effects of BSP and explored its impact on morphological changes and inflammatory mediators during wound healing. A carrageenan-induced mouse paw edema model was established to evaluate the anti-inflammatory effect of BSP. Antioxidant indicators, including NO, SOD, and MDA, were measured in the blood and liver. The increased pain threshold induced by BSP was also determined using the hot plate test. A mouse excisional wound model was applied to evaluate the wound healing rate, and HE staining and Masson staining were used to detect tissue structure changes. In addition, ELISA was employed to detect the expression of pro-inflammatory cytokines TNF-α, IL-6, and IL-1ß in serum. BSP significantly decreased the concentration of NO and MDA in serum and liver while increasing SOD activity. It exhibited a notable improvement in mouse paw edema induced by carrageenan. BSP dose-dependently delayed the appearance of licking behavior in mice, indicating its analgesic effect. Compared to the control group, the wound healing rate was significantly improved in the BSP treatment group. HE and Masson staining results showed that the BSP and 'Jingwanhong' ointment groups had slightly milder inflammatory responses and significantly promoted more new granulation tissue formation. The levels of serum inflammatory mediators TNF-α, IL-1ß, and IL-6 were reduced to varying degrees. The results demonstrated that BSP possesses anti-inflammatory, antioxidant, analgesic, and wound healing properties, and it may promote wound healing through inhibition of inflammatory cytokine synthesis and release.

Plants with Anti-Ulcer Activity and Mechanism: A Review of Preclinical and Clinical Studies.

Ulcer disorders including the oral mucosa, large intestine, and stomach mucosa, cause significant global health burdens. Conventional treatments such as non-steroid anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), histamine H2 receptor antagonists (H2RAs), and cytoprotective agents have drawbacks like mucosal injury, diminish gastric acid secretion, and interact with concurrent medications. Therefore, alternative therapeutic approaches are needed to tackle this health concern. Plants are rich in active metabolites in the bark, roots, leaves, fruits, and seeds, and have been utilized for medicinal purposes since ancient times. The use of herbal therapy is crucial, and regulations are necessary to ensure the quality of products, particularly in randomized studies, to assess their efficacy and safety in treating ulcer disorders. This study aims to explore the anti-ulcer activity of medicinal plants in treating peptic ulcer disease, ulcerative colitis, and aphthous ulcers. Articles were searched in Scopus and PubMed, and filtered for publication from 2013 to 2023, resulting in a total of 460 from Scopus and 239 from PubMed. The articles were further screened by title and abstract and resulted in 55 articles. Natural products, rich in active metabolites, were described to manage ulcer disease by protecting the mucosa, reducing ulcer effects, inhibiting pro-inflammatory factors, and reducing bacterial load, thus improving patients' quality of life. Natural extracts have proven effective in managing other health problems, including ulcers by reducing pain and decreasing lesions. This review provides an overview of preclinical and clinical studies on medicinal plants, focusing on their effectiveness in treating conditions like peptic ulcers, ulcerative colitis, and aphthous ulcers.

Isolation, invitro, invivo anti-inflammatory, analgesic and antioxidant potential of Habenaria plantegania Lindl.

Habenaira plantaginea belong to orchid family which is native to Asia. Members of this family are commonly famous for the cure of pain and inflammation. To date, no research was found on isolation of compounds from this plant for the treatment of inflammation and analgesia nor has been published to our knowledge. The purpose of this study was to evaluate an analgesic, anti-inflammatory and anti-oxidant activity of the isolated compound from the most potent chloroform sub-fraction and the isolated compounds form the habenaria plantaginea. Anti-inflammatory analgesic and antioxidant potential of the various chloroform sub-fractions and isolated compounds from the most potent sub-fraction (HP-1 & HP-1) were screened for their in vitro enzymatic assays. Furthermore, prior to in-vivo investigation, the isolated compounds were subjected for their toxicity study. The potent compound was then examined for acetic acid-induced writhing, hot plate test, carrageenan-induced inflammation assays. Further various phlogistic agents were used for the evaluation of mechanism. In the COX-2 inhibitory assay the chloroform sub fraction Cf-4 demonstrated excellent activity as compared to the other sub-fraction with 92.15% inhibition. The COX-2 enzyme make prostaglandins which are directly involved in inflammation. Likewise against 5-LOX the Cf-4 was the most potent sub-fraction with IC50 3.77 µg/mL. The 5-LOX catalyzes the biosynthesis of leukotrienes which is a group of lipid mediators of inflammation derived from arachidonic acid. Free radicals can induce inflammation through cellular damage while chronic inflammation generates a large number of free radicals, whose eventually lead to inflammation. In antioxidant assays the Cf-4 fraction was displayed excellent results against ABTS, DPPH and H2O2 free radical with 88.88, 77.44, and 65.52% inhibition at highest concentration. Likewise, the compound HP-1 demonstrated 88.81, 89.34 and 80.43% inhibition while compound HP-2 displayed 84.34, 91.52 and 82.34% inhibition against ABTS, DPPH and H2O2 free radical which were comparable to the standard drug ascorbic acid respectively. This study's findings validate the use of this species as traditional use.

Formulation Studies with Cyclodextrins for Novel Selenium NSAID Derivatives.

Commercial cyclodextrins (CDs) are commonly used to form inclusion complexes (ICs) with different molecules in order to enhance their water solubility, stability, and bioavailability. Nowadays, there is strong, convincing evidence of the anticancer effect of selenium (Se)-containing compounds. However, pharmaceutical limitations, such as an unpleasant taste or poor aqueous solubility, impede their further evaluation and clinical use. In this work, we study the enhancement of solubility with CD complexes for a set of different nonsteroidal anti-inflammatory drug (NSAID) derivatives with Se as selenoester or diacyl diselenide chemical forms, with demonstrated antitumoral activity. The CD complexes were analyzed via nuclear magnetic resonance (NMR) spectroscopic techniques. In order to obtain additional data that could help explain the experimental results obtained, 3D models of the theoretical CD-compound complexes were constructed using molecular modeling techniques. Among all the compounds, I.3e and II.5 showed a remarkable increase in their water solubility, which could be ascribed to the formation of the most stable interactions with the CDs used, in agreement with the in silico studies performed. Thus, the preliminary results obtained in this work led us to confirm the selection of ß and γ-CD as the most suitable for overcoming the pharmaceutical drawbacks of these Se derivatives.

Efficacy of topical curcumin on mild to moderate carpal tunnel syndrome: a randomized double-blind, placebo-controlled clinical trial.

OBJECTIVES: Recently, there has been a renewed interest in traditional medicine for carpal tunnel syndrome (CTS). Curcumin has been reported as an agent with antioxidant, anti-inflammatory, analgesic, and neuroprotective attributes. This study is one of the first investigations to assess the effect of curcumin gel on CTS. METHODS: This study is a prospective, 8-week, randomized, placebo-controlled, parallel-group clinical trial. A total of 70 patients with CTS were analyzed. The intervention group (n = 35) received a topical curcumin gel and a night wrist splint and the control group (n = 35) received a placebo gel and a night wrist splint for 8 weeks. The primary outcome was the assessment of the symptom severity scale (SSS) and functional status scale (FSS) of the participants using the Boston Carpal Tunnel Questionnaire (BCTQ) after 8 weeks. In addition, all participants were evaluated by electrodiagnostic (EDX) test at baseline and after 8 weeks. RESULTS: The mean scores of SSS demonstrated a significant decrease in the curcumin group compared to the placebo group; P-value= 0.021. The mean change score of SSS after the intervention was 12.45 ± 8.18 in curcumin and 3.28 ± 7.06 in the placebo group; P-value = 0.0001 and the mean change score of FSS were 6.24 ± 4.91 and 2.31 ± 4.95 in curcumin and placebo groups, respectively; P-value = 0.002. However, the EDX study showed no significant changes in both groups. CONCLUSIONS: It seems that curcumin gel could be effective in the improvement of the symptom severity and daily activity of patients with CTS.

Anti-inflammatory, analgesic, antitussive and antipyretic activities of polyphenol-enriched fraction from Nymphaea candida.

ETHNOPHARMACOLOGICAL RELEVANCE: "Snow-white waterlily" (Nymphaea candida) dried flower possesses various efficacy in Uighur medicine such as reducing fever and nourishing the liver, anti-inflammatory and cough relieving, moistening the throat and quenching thirst. AIM OF THE STUDY: Polyphenols are characteristic component of N. candida as well as its quality markers, and the purpose of this study was to conduct investigations into anti-inflammatory, antitussive, antipyretic, and analgesic activities of the polyphenol-enriched fraction from N. candida (NCTP) in order to validate the traditional efficacy of this plant. MATERIALS AND METHODS: The polyphenols in NCTP were analyzed by HPLC, and an acute oral toxicity study was conducted for NCTP. The anti-inflammatory activities of NCTP were evaluated using xylene induced ear edema, capillary permeability, cotton pellet granuloma, and carrageenan-induced rat paw edema, of which multiple biochemical indices were measured in carrageenan-induced rat paw edema such as prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2),5-lipoxygenase (5-LOX), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) activities; the analgesic activities were investigated using acetic acid writhing, hot plate test, and formalin test; the anti-tussive and antipyretic effects were tested by ammonia induced cough in mice and yeast-induced fever respectively. RESULTS: NCTP with LD50 of 5222 mg/kg was low toxicity and safety. NCTP (200 mg/kg) could significantly reduce ear swelling and capillary permeability by 30.63% and 31.37%, respectively. NCTP revealed 15.76% inhibiting activities in cotton pellet granuloma in mice at a dosage of 200 mg/kg. Furthermore, NCTP (50, 100, and 200 mg/kg) substantially decreased carrageenin-induced paw edema in rats between 1 and 5 h, and NCTP could decrease PGE2, 5-LOX, COX-2 levels as well as IL-6, IL-1ß, TNF-α activities compared with the control group; NCTP could decrease MDA contents in carrageenin-induced rise, and increase SOD and GSH activities. Furthermore, the dose-dependent inhibition effect of NCTP on pain was revealed in the hot plate experiment. In addition to reducing the amount of writhes brought on by acetic acid, NCTP (50, 100, and 200 mg/kg) significantly inhibited pain latency against both stages of the formalin test. Moreover, NCTP (50, 100, 200 mg/kg) showed the better antitussive activities in mice in a dose-dependent manner. In the yeast-induced pyrexia test, dosages of 50, 100, and 200 mg/kg resulted in a statistically significant drop in rectal temperature. CONCLUSION: The experimental results proved the analgesic, anti-inflammatory, anti-tussive and antipyretic activities of the polyphenol-enriched fraction from N. candida, and supported the traditional use of this plant as well.

Guarea microcarpa C. DC. extract inhibits NLRP3 inflammasome by suppressing its ATPase activity.

ETHNOPHARMACOLOGICAL RELEVANCE: Guarea genus comprises tropical and subtropical terrestrial herbs inhabiting Central and South America. These plants, including Guarea guidonia (L.) Sleumer, have anti-inflammatory, analgesic, antibacterial, antiviral, and immune-enhancing properties. AIM OF THE STUDY: Although various species of the Guarea genus are known for their medicinal properties, comprehensive data on their anti-inflammatory effects remain limited. Therefore, we investigated the NLRP3 inflammasome-inhibiting effects of the Guarea genus in this study. MATERIALS AND METHODS: To evaluate the anti-inflammatory activities of 18 members of the Guarea genus, we treated NLRP3 inflammasome activators with their extracts in LPS-primed J774A.1 and THP-1 cells. Cell viability was determined by water soluble tetrazolium salt (WST) and cytokine production, protein expression, and nuclear fractionation were determined by western blotting. Reactive oxygen species (ROS) production and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) oligomerization were measured using confocal microscopic analysis. Inflammation-induced zebrafish was used in the in vivo experiments. RESULTS: Among the 18 Guarea members tested, Guarea microcarpa C. DC. extract (GM) exhibited no cytotoxicity and specifically suppressed the activation of the NLRP3 inflammasome, but not of the AIM2 or NLRC4 inflammasomes, by inhibiting the ATPase activity of NLRP3. This was achieved without affecting NF-κB signaling, potassium efflux, or intracellular ROS production, all of which are involved in NLRP3 activation. The reduced ATPase activity of NLRP3 led to decreased ASC oligomerization. Furthermore, GM exhibited anti-inflammatory effects in vivo. Additionally, GM treatment alleviated inflammation at the organismal level in an LPS-induced inflammation model using zebrafish embryos. CONCLUSION: Our results demonstrate the anti-inflammatory effects of GM via suppressing the NLRP3 inflammasome. Therefore, GM can be a potential therapeutic candidate for various inflammatory diseases caused by aberrant NLRP3 inflammasome activation.

Sinomenine ameliorates fibroblast-like synoviocytes dysfunction by promoting phosphorylation and nuclear translocation of CRMP2.

ETHNOPHARMACOLOGICAL RELEVANCE: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and arthritic pain. Sinomenine (SIN), derived from the rhizome of Chinese medical herb Qing Teng (scientific name: Sinomenium acutum (Thunb.) Rehd. Et Wils), has a longstanding use in Chinese traditional medicine for treating rheumatoid arthritis. It has been shown to possess anti-inflammatory, analgesic, and immunosuppressive effects with minimal side-effects clinically. However, the mechanisms governing its effects in treatment of joint pathology, especially on fibroblast-like synoviocytes (FLSs) dysfunction, and arthritic pain remains unclear. AIM: This study aimed to investigate the effect and underlying mechanism of SIN on arthritic joint inflammation and joint FLSs dysfunctions. MATERIALS AND METHODS: Collagen-induced arthritis (CIA) was induced in rats and the therapeutic effects of SIN on joint pathology were evaluated histopathologically. Next, we conducted a series of experiments using LPS-induced FLSs, which were divided into five groups (Naïve, LPS, SIN 10, 20, 50 µg/ml). The expression of inflammatory factors was measured by qPCR and ELISA. The invasive ability of cells was detected by modified Transwell assay and qPCR. Transwell migration and cell scratch assays were used to assess the migration ability of cells. The distribution and content of relevant proteins were observed by immunofluorescence and laser confocal microscopy, as well as Western Blot and qPCR. FLSs were transfected with plasmids (CRMP2 T514A/D) to directly modulate the post-translational modification of CRMP2 protein and downstream effects on FLSs function was monitored. RESULTS: SIN alleviated joint inflammation in rats with CIA, as evidenced by improvement of synovial hyperplasia, inflammatory cell infiltration and cartilage damage, as well as inhibition of pro-inflammatory cytokines release from FLSs induced by LPS. In vitro studies revealed a concentration-dependent suppression of SIN on the invasion and migration of FLSs induced by LPS. In addition, SIN downregulated the expression of cellular CRMP2 that was induced by LPS in FLSs, but increased its phosphorylation at residue T514. Moreover, regulation of pCRMP2 T514 by plasmids transfection (CRMP2 T514A/D) significantly influenced the migration and invasion of FLSs. Finally, SIN promoted nuclear translocation of pCRMP2 T514 in FLSs. CONCLUSIONS: SIN may exert its anti-inflammatory and analgesic effects by modulating CRMP2 T514 phosphorylation and its nuclear translocation of FLSs, inhibiting pro-inflammatory cytokine release, and suppressing abnormal invasion and migration. Phosphorylation of CRMP2 at the T514 site in FLSs may present a new therapeutic target for treating inflammatory joint's destruction and arthritic pain in RA.

Iatrogenic rectal perforation due to application of topical treatment in a patient with ulcerative colitis: a rare complication.

Rectal perforations due to topical treatments (enemas or foams) are unusual complications and they have been mostly reported in the use of barium enemas or in elderly patients with constipation. Very little has been reported about perforations secondary to topical treatment in patients with ulcerative colitis. We present the case of a patient with ulcerative colitis who suffered a rectal perforation complicated with a superinfected collection after the application of topical mesalazine foam.

A systematic strategy for investigating the pharmacological effects and mechanism of traditional Chinese medicinal formula: Guilin Xiguashuang as a case.

BACKGROUND: Traditional Chinese medicinal formula (TCMF) has specific advantages in treating diseases. However, the pharmacological effects and mechanism of TCMF composed of traditional Chinese medicines (TCM) with unclear active components or targets have not yet been fully elucidated. OBJECTIVES: This research proposed a strategy for elucidating the pharmacological effects and mechanism to address this issue systematically. METHODS: With Guilin Xiguashuang (GLXGS) taken as a case, this study newly provided the multi-level assays, which decomposes TCMF into components, TCM, and TCMF levels. The main pharmacological effects were acquired through a comprehensive analysis based on the active components, pharmacological effects of TCM, and clinical efficacy of TCMF, respectively. The core targets and pathways were further identified and verified to elucidate the mechanism. RESULTS: The main pharmacological effects of GLXGS were anti-inflammatory, analgesic, antibacterial, immunoregulatory, and wound healing. Moreover, the mechanism analysis demonstrated that GLXGS was involved in the regulation of NF-κB and VEGF signaling pathways and core targets, such as IL-6 and TNF-α. Finally, unproven immunomodulatory and anti-inflammatory mechanism were verified using RAW264.7 and THP-1 cells. GLXGS was verified to down-regulate IL-6, IL-1ß, TNF-α, and CD86 in lipopolysaccharides-stimulated RAW264.7 cells, while enhancing polarization in both RAW264.7 and THP-1 cells, which were consistent with analysis results. CONCLUSION: The present research provides a systematic strategy for the pharmacological effect prediction and mechanism analysis of TCMF, which is of great significance for studying complex TCMF.

Nonsteroidal anti-inflammatory drug "allergy" labeling is associated with increased postpartum opioid utilization.

BACKGROUND: Current guidelines recommend a stepwise approach to postpartum pain management, beginning with acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), with opioids added only if needed. Report of a prior NSAID-induced adverse drug reaction (ADR) may preclude use of first-line analgesics, despite evidence that many patients with this allergy label may safely tolerate NSAIDs. OBJECTIVE: We assessed the association between reported NSAID ADRs and postpartum opioid utilization. METHODS: We performed a retrospective cohort study of birthing people who delivered within an integrated health system (January 1, 2017, to December 31, 2020). Study outcomes were postpartum inpatient opioid administrations and opioid prescriptions at discharge. Statistical analysis was performed on a propensity score-matched sample, which was generated with the goal of matching to the covariate distributions from individuals with NSAID ADRs. RESULTS: Of 38,927 eligible participants, there were 883 (2.3%) with an NSAID ADR. Among individuals with reported NSAID ADRs, 49.5% received inpatient opioids in the postpartum period, compared to 34.5% of those with no NSAID ADRs (difference = 15.0%, 95% confidence interval 11.4-18.6%). For patients who received postpartum inpatient opioids, those with NSAID ADRs received a higher total cumulative dose between delivery and hospital discharge (median 30.0 vs 22.5 morphine milligram equivalents [MME] for vaginal deliveries; median 104.4 vs 75.0 MME for cesarean deliveries). The overall proportion of patients receiving an opioid prescription at the time of hospital discharge was higher for patients with NSAID ADRs compared to patients with no NSAID ADRs (39.3% vs 27.2%; difference = 12.1%, 95% confidence interval 8.6-15.6%). CONCLUSION: Patients with reported NSAID ADRs had higher postpartum inpatient opioid utilization and more frequently received opioid prescriptions at hospital discharge compared to those without NSAID ADRs, regardless of mode of delivery.