Prostaglandin Synthesis Research Articles

Usage of COX-1 and COX-2 Nanomedicines in Nanotechnology

Nanomedicine is the branch of medical applications in nanotechnology. Nanomedicine ranges from medical applications of nanomaterials, biological devices to nanoelectronic biosensors, molecular nanotechnology such as biological machines. It utilizes knowledge and tools of nanotechnology to prevention and treatment of disease. Nanomedicine involves use of nanoscale materials such as biocompatible nanoparticles for delivery, sensing or actuation in a living organism. COX inhibitors are a class of pharmaceutical compounds that selectively target and inhibit the activity of the enzymes cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). These enzymes are key players in the synthesis of prostaglandins, which are important mediators of inflammation, pain, and fever in the body. By modulating prostaglandin production, COX inhibitors have significant therapeutic implications in the management of various inflammatory conditions, pain relief, and fever reduction. COX-1 is constitutively expressed in many tissues and is involved in maintaining normal physiological functions, including the protection of the stomach lining and platelet aggregation. In contrast, COX-2 is induced at sites of inflammation and is primarily responsible for producing prostaglandins involved in the inflammatory response. The selective inhibition of COX-2 allows for targeted suppression of inflammation while preserving the beneficial functions of COX-1. Moreover, recent research has shed light on the complex interplay between COX-1 and COX-2 in health and disease. Emerging evidence suggests that the balance between COX-1 and COX-2 inhibition may have implications beyond pain and inflammation. Investigating the diverse roles of these enzymes in different tissues and pathologies may open up new avenues for drug development and personalized medicine. COX inhibitors represent an important therapeutic class with a profound impact on managing pain, inflammation, and related disorders. Understanding the differential regulation and functions of COX-1 and COX-2 is crucial for optimizing the clinical use of COX inhibitors and developing novel strategies for targeted and safer anti-inflammatory therapies.

Investigation of Novel Urinary Biomarkers in Hepatocellular Carcinoma Risk in a Predominantly African American Population: A Case-Control Study

Introduction: African Americans are at increased risk of hepatocellular carcinoma (HCC) compared to other racial and ethnic groups. We investigated the associations of four urinary biomarkers of prostaglandin E2 (PGE-M), prostacyclin (PGI-M), and thromboxane (11dTxB2) synthesis and the ratio of PGI-M to 11dTXB2 with HCC risk in a cohort of predominantly African American populations. Methods: We conducted a nested case-control study (50 cases; 43 with HCC, 151 controls) in the Southern Community Cohort Study (SCCS), a large prospective cohort study including over 80,000 study participants, of whom two-thirds are African Americans. Urine samples were collected at enrollment and subsequently analyzed to assess biomarker levels. Multivariable regression models adjusted for age, race, sex, BMI, smoking status, NSAID use, education level, income, and alcohol consumption were used to assess the relationship between the biomarker and HCC risk. Results: Only 11dTxB2 (OR = 11.50; 95% CI [2.34–56.47] for highest tertile vs. lowest tertile, p = 0.004) and the PGI-M/11dTXB2 ratio of the second quartile (0.25–0.49) (OR = 5.16; 95% CI [1.44–18.47]; p = 0.01) were significantly associated with increased risk of liver cancer. Conclusion: 11dTXB2 and PGI-M/11dTXB2 ratio may be urinary markers of HCC risk, particularly among African Americans, and future prospective studies are needed to evaluate this finding further and to develop accessible methods.

The impact of propolis on clinical manifestations and specific IgE levels against salsola in perennial-allergic rhinitis patients.

Objectives: Propolis has an anti-inflammatory effect induced by inhibiting cyclooxygenase, subsequent inhibition of prostaglandin and nitric oxide synthesis, reduction of inflammatory cytokines, and eventually immunosuppressive activity [1-3]. This study aims to evaluate the impact of propolis on clinical features and specific IgE levels against salsola in perennial allergic rhinitis patients. Methods: Thirty patients diagnosed with perennial allergic rhinitis with salsola-positive skin prick test were enrolled in this randomized controlled clinical trial and divided into two groups. The intervention group received the propolis (200 mg per day), and the control group received a placebo for four months, besides intranasal corticosteroids. At baseline and the end of the intervention, the level of Salsola-specific IgE was measured by the RAST method. To assess the propolis effect on the quality of life and disease severity, miniRQLQ and SNOT22 questionnaires were completed by patients before and after the intervention. Results: According to Table 1, Serum IgE level showed decreasing changes (-0.057) despite increasing changes in the control group (1.039). However, these differences were not statistically significant (P = 0.967). Based on the miniRQLQ questionnaire, quality of life improved in both groups without any significant difference (P = 0.930). According to the SNOT-22 questionnaire, both groups' nasal and sinus problems decreased significantly. However, the intervention type did not affect this decrease and was observed over time in both groups (P> 0.05). Conclusion: Propolis supplementation did not significantly affect various laboratory parameters, clinical symptoms, and quality of life of patients with allergic rhinitis.

Lysophosphatidic acid stimulates rat uterine contraction in vitro.

Lysophosphatidic acid (LPA) has been implicated in the uterine endometrial functions of implantation and decidualization; however, not much is known about its myometrial contractile function. Herein we characterized the uterotonic effects of LPA in non-pregnant (estrus) and peri-parturient rats in vitro. LPA dose-dependently (0.01-10 μM) stimulated the amplitude and integral, but not the frequency, of the uterine strip contraction of estrous rats. The stimulatory effect of LPA was enhanced 1 day before parturition but was lost 1 day postpartum. LPA did not cause the de novo synthesis of prostaglandin (PG) F2α but stimulated contractions cooperatively with the PG. LPA-induced contractions were significantly inhibited by an LPA1/2/3 antagonist in the uteri of estrous rats but not in term rats. This study characterized the uterotonic effect of a natural LPA that occurs at physiological concentrations, changes with reproductive states, and is independent of mediation by the newly synthesized PG.

Aspirina en Prevención Primaria Cardiovascular

Willow bark and leaves have been used for thousands of years for their analgesic and anti-inflammatory effect, and Aspirin was synthesized from them at the end of the 19th century. From the 70s of the 20th century, we know its mechanisms of action well. Through the blockade it exerts on the synthesis of prostaglandins derived from arachidonic acid, both in the vascular endothelium and in platelets. We understand the mechanism of action on the formation of platelet thrombus and we know from multiple clinical trials which are its indications in the prevention of complications of cardiovascular disease. With a precise indication in secondary prevention in patients who have suffered a coronary or ischemic stroke, but with more controversial data in the case of primary prevention, which is the reason for this updated review of the action of Aspirin. In these cases, the decision to start treatment should be shared between the clinician and the patient, and risk tables and calculators should be used to help determine the level of CVD and bleeding risk.

Different Medicinal Treatment Modalities in the Management of Patent Ductus Arteriosus in Paediatric Population- A Narrative Review of Available Drug Approaches

Regardless of the size of a patient’s Patent Ductus Arteriosus (PDA), it is crucial for paediatric and adult cardiologists to have a thorough understanding of the condition’s origin, clinical ramifications, and treatment options. Possessing a PDA, no matter how little, might cause complications. Ibuprofen and indomethacin, both cyclo-oxygenase (COX) inhibitors, are used as the gold standard pharmacologic therapy for closing a PDA that has been produced surgically. These non selective COX inhibitors bring about ductal constriction, in addition to lowering the synthesis of prostaglandin. However, these drugs may also have a broad array of unintended consequences. Interest in paracetamol for PDA constriction has recently increased due to fewer adverse effects than indomethacin or ibuprofen. Evidence that paracetamol is now a topic of intense study lends credence to this hypothesis. Information on the long term effects of paracetamol is scarce in paediatric population.

Tubular Elabela-APJ axis attenuates ischemia-reperfusion induced acute kidney injury and the following AKI-CKD transition by protecting renal microcirculation.

Rationale: Ischemia-reperfusion injury (I/R) is a common cause of acute kidney injury (AKI). Post-ischemic recovery of renal blood supply plays an important role in attenuating injury. Exogenous application of elabela (ELA) peptides has been demonstrated by us and others to alleviate AKI, partly through its receptor APJ. However, the endogenous role of ELA in renal I/R remains unclear. Methods: Renal tubule specific ELA knockout (ApelaKsp KO) mice challenged with bilateral or unilateral I/R were used to investigate the role of endogenous ELA in renal I/R. RNA-sequencing analysis was performed to unbiasedly investigate altered genes in kidneys of ApelaKsp KO mice. Injured mice were treated with ELA32 peptide, Nω-hydroxy-nor-L-arginine (nor-NOHA), prostaglandin E2 (PGE2), Paricalcitol, ML221 or respective vehicles, individually or in combination. Results: ELA is mostly expressed in renal tubules. Aggravated pathological injury and further reduction of renal microvascular blood flow were observed in ApelaKsp KO mice during AKI and the following transition to chronic kidney disease (AKI-CKD). RNA-seq analysis suggested that two blood flow regulators, arginine metabolizing enzyme arginase 2 (ARG2) and PGE2 metabolizing enzyme carbonyl reductases 1 and 3 (CBR1/3), were altered in injured ApelaKsp KO mice. Notably, combination application of an ARG2 inhibitor nor-NOHA, and Paricalcitol, a clinically used activator for PGE2 synthesis, alleviated injury-induced AKI/AKI-CKD stages and eliminated the worst outcomes observed in ApelaKsp KO mice. Moreover, while the APJ inhibitor ML221 blocked the beneficial effects of ELA32 peptide on AKI, it showed no effect on combination treatment of nor-NOHA and Paricalcitol. Conclusions: An endogenous tubular ELA-APJ axis regulates renal microvascular blood flow that plays a pivotal role in I/R-induced AKI. Furthermore, improving renal blood flow by inhibiting ARG2 and activating PGE2 is an effective treatment for AKI and prevents the subsequent AKI-CKD transition.

Aspirin for the primary prevention of breast cancer: an unforeseen advantage

Aspirin for the primary prevention of breast cancer: an unforeseen advantage

Selective modification of diclofenac to reduce the adverse effects; A computer-aided drug design approach

Diclofenac (DCF) is a non-steroidal anti-inflammatory drug (NSAID), commonly used for the treatment of pain. It can inhibit prostaglandin synthesis by blocking cyclooxygenase (COX). It shows some crucial side effects like gastrointestinal, cardiovascular, renal, and liver injury. The gastrointestinal injury occurred due to the presence of a carboxylic (COOH) group at the core of DCF. The hydroxyl (OH) portion of COOH was replaced by inserting some new functional groups (CH3, OCH3, CH2NH2, NH2, NHCOCH3, NHCONH2, Cl, CF3) considering the retrosynthetic strategy which reduces gastrointestinal side effects with improved chemical and biological activity. Herein, we have investigated the physicochemical, spectral, molecular dynamics, biological and pharmacokinetic properties of the mentioned analogues. Density functional theory (DFT) and time-dependent DFT along with the B3LYP/6-31g (d,p) basis set have been utilized to calculate their geometrical, chemical, and spectral properties. Molecular docking and non-bonding interactions have been performed against human prostaglandin synthase protein (PDB ID: 5F1A) to investigate their binding affinities, modes, and stability. ADMET and PASS prediction studies were performed to investigate their microbial inhibition and toxicological profile. Quantum chemical calculations and spectral characterization support the geometry of newly designed analogues. From the molecular docking simulation, most of the analogues exhibited better binding affinity than the parent drug except for DCF-2. ADMET calculations predict the improved pharmacokinetic and non-carcinogenic properties of all DCF analogues. Biological activities and drug-likeness indicate that all the analogues of DCF have been exposed to comparatively lower action of the gastrointestinal hemorrhage than DCF and exhibit antipyretic, analgesic, and anti-inflammatory actions as well as performed to overcome the poor absorption or permeation of drugs. Finally, based on the above investigation, this study can be helpful to design a potential drug candidate with improved medicinal action and reduced selective adverse effects.

Modulation of prostaglandin synthesis to improve farm animal reproduction

Modulation of prostaglandin synthesis to improve farm animal reproduction

PS-BPB03-2: VASORELAXANT-MEDIATED ANTIHYPERTENSIVE EFFECT OF THE SEED AQUEOUS EXTRACT OF AFRAMOMUM PRUINOSUM GAGNEP. (ZINGIBERACEAE)

Objective: Despite the existing therapies, arterial hypertension is still a prevalent and a worldwide major public health concern, prompting the search for new therapeutic alternatives. The present study investigated the antihypertensive and the related mechanisms of action of the seed aqueous extract of Aframomum pruinosum (AEAP), a plant used in Cameroon traditional medicine against cardiovascular ailments. Design and method: Male Wistar rats were rendered hypertensive by chronic oral administration of L-NAME (30 mg/kg/day) for three consecutive weeks, and hypertensive rats were selected and treated with L-NAME alone or in combination with AEAP at doses of 75 or 150 mg/kg/day for an additional 3 consecutive weeks. Captopril (25 mg/kg/day, p.o) was used as reference drug. Blood pressure and heart rate were monitored weekly. At the end of the experiment, the heart was harvested, weighed, and sections of cardiac tissue were stained with hematoxylin and eosin for histological analysis. Cumulative concentrations of the aqueous extract (3, 10, 30, 100, and 300 μg/mL) were tested on intact or endothelium-denuded aorta rings precontracted with norepinephrine (NE; 1 μM) or KCl (90 mM) in absence or presence of L-NAME (a nitric oxide synthase inhibitor, 100 μM), indomethacin (a prostaglandin synthesis inhibitor; 10 μM), methylene blue (a guanylate cyclase inhibitor, 1 μM), tetraethylammonium (TEA; a non-specific potassium channel blocker; 5 μM) or glibenclamide (an ATP-sensitive potassium channel blocker; 10 μM). The contractile response to NE, or CaCl2 was also assessed in the presence or absence of the plant extract. Results: AEAP completely reversed (p < 0.001) L-NAME-induced elevated systolic and diastolic blood pressure, and increased heart rate. AEAP partially reversed cardiac hypertrophy, leucocyte infiltration, and prevent cardiac necrosis. AEAP induced a concentration-dependent vasorelaxant effect on NE- and KCl-evoked contraction with EC50 values of 13.46 and 49.37 μg/mL, respectively. Removal of the endothelium and the preincubation of aorta rings with L-NAME significantly (p < 0.05) reduced the vasorelaxant effect of the plant extract, while indomethacin and methylene blue had no effect (p > 0.05). Glibenclamide, similar to TEA, significantly (p < 0.001) inhibited the vasorelaxant response to AEAP. Also, the extract significantly (p < 0.01 and p < 0.001) inhibited NE- and CaCl2-induced contraction. Conclusion: AEAP possesses antihypertensive effects that are at least partially mediated by its vasorelaxant activity. Nitric oxide release, opening of KATP channels, blockade of alpha-1 receptors, and inhibition of Ca2+ influx account for this vasorelaxant activity.

Spectrochemical, medicinal, and toxicological studies of ketoprofen and its newly designed analogs; quantum chemical, and drug discovery approach

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used as analgesics, antipyretics, anti-clotting, and anti-inflammatory agents. One such NSAID, ketoprofen (KTP), is prescribed to treat pain, sprains, menstrual irregularities, osteoarthritis (OA), and rheumatoid arthritis (RA). By inhibiting cyclooxygenase, it halts prostaglandin synthesis. However, it exhibits significant side effects in humans and other living things. Herein, the chemical structure of KTP has been modified to search for improved chemical and medicinal effects. Density functional theory (DFT) has been employed for geometry optimization. Molecular docking and molecular dynamics (MD) simulations were conducted to investigate the binding affinity and stability of the protein-drug complex with prostaglandin synthase protein. ADMET predictions were carried out to calculate and compare the pharmacokinetic behavior of KTP and its new analogs. Spectral and chemical results support the structural conformation of the new analogs, all of which exhibit improved physicochemical, and binding properties compared to the parent drug. After a 100 ns MD simulation, the drugs remained tightly bound to the binding site of the receptor protein, showing significant interactions with shorter distances among the new analogs. The ADMET predictions confirmed better pharmacokinetic properties of novel analogs compared to KTP. The study compares several KTP metabolites using thermo-chemical, spectral, biological, and toxicological analysis. Results showed the reactivity and stability, with spectral data evaluating all KTP analogs. ADMET predicts that all KTP derivatives are less toxic and have better pharmacokinetic features than KTP. Most KTP analogs exhibit excellent oral bioavailability and significant analgesic, antipyretic, and anti-inflammatory functions. These findings support the potential use of these drugs in the future drugs.

Development of an Intrauterine Device Releasing Both Indomethacin and Levonorgestrel During the First Months of Use: Pharmacokinetic Characterization in Healthy Women.

Post-placement menstrual bleeding pattern changes with intrauterine contraceptives (IUCs), including levonorgestrel-releasing intrauterine systems (LNG-IUS), can be a reason for avoidance or early discontinuation. Prostaglandins play an important role in menstrual bleeding and pain. The key drivers of prostaglandin synthesis are cyclooxygenase (COX) enzymes, which are inhibited by non-steroidal anti-inflammatory drugs. In this study, we report the findings from pharmacokinetic (PK) analyses undertaken with an LNG-IUS (LNG-IUS8) modified with an additional reservoir containing indomethacin (IND). The IND/LNG-IUS8 is a proof-of-concept device studied in a phase II proof-of-concept/dose-finding study. IND/LNG-IUS8 contains the same LNG content as the unmodified LNG-IUS8 (13.5 mg) but was prepared with three different IND doses (low, 6.5 mg; middle, 12.5 mg; and high, 15.4 mg), resulting in different daily release rates. Overall, 174 healthy, premenopausal women were randomized to one of the four treatment arms (low-, middle-, high-dose IND/LNG-IUS8 or LNG-IUS 8). Initial and residual IND and LNG content were collected and the amount of IND and LNG released in vivo over the period of use was calculated. A subset of 62 participants underwent dense blood sampling for PK analysis. Concentrations of IND and LNG in plasma were determined by validated liquid chromatography-tandem mass spectrometry methods and plotted over time. Descriptive statistics were calculated for plasma drug concentrations and PK parameters. High-dose IND/LNG-IUS8 initially released much higher levels of IND than expected based on in vitro release data, followed by a steep decline, with the reservoir emptied by 4.5 months. Middle- and low-dose IND/LNG-IUS8 demonstrated steady sustained release of IND over time, emptying after 7.4 and 8.4 months, respectively. Peak plasma concentrations of IND for low- and middle-dose IND/LNG-IUS8 remained below the 20% maximal inhibitory concentration (IC20) values for COX enzymes. The average daily IND release rate in vivo was 49 µg/day for low-dose and 112 µg/day for middle-dose IND/LNG-IUS8. The IND release rate profile and IND plasma concentrations in vitro both decreased steadily over time with low- and middle-dose IND/LNG-IUS8. The LNG release rate profile was comparable for all IND/LNG-IUS8 dose groups and LNG-IUS8. This PK study demonstrates that two different drugs can be released at different rates from an IUS designed with two drug reservoirs. Inclusion of IND does not impact the LNG PK profile. Low- and middle-dose IND/LNG-IUS8 were associated with a systemic IND exposure that should preclude the occurrence of adverse events typically observed after oral IND dosing. ClinicalTrials.gov identifier number: NCT03562624.

Nutrients in Pharmaceutical

Nutraceutical is any substance that might be categorized as food or a component of food that are beneficial in the prevention and treatment of diseases. Categories of nutraceuticals are dietary fiber, prebiotics, probiotics, fatty acids, polyphenols, antioxidants etc. Dietary fiber is made up of lignins and non-digestible carbohydrates that are intrinsic in plants. Probiotics are beneficial live bacteria and yeasts for our digestive system. Prebiotics are substances that stimulate the activity or growth of microorganisms that improve the health of their host. Omega-3 polyunsaturated fatty acids have a significant anti-inflammatory function. The synthesis of proinflammatory cytokines such prostaglandins, leukotrienes, and tumor necrosis factor-alpha, interferon-gamma, and interleukins-6 and 12 is inhibited by alpha-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid. The anti-inflammatory characteristics of curcumin are demonstrated by its capacity to inhibit pro-inflammatory cytokines. Epigallocatechin Gallate is a tea polyphenols decrease DNA damage caused by UV radiation, prevent lipid peroxidation, and lessen the production of ROS and free radicals in the skin. Antioxidants are also essential for maintenance of health and wellness since they act as our body's first line of defense against free radical damage. Antioxidants like N-acetyl cysteine, lycopene, beta-carotene, lutein and zeaxanthin, vitamin C and vitamin E are used as a nutraceuticals. For the prevention and treatment of CVD, it is also advised to combine physical activity with nutraceuticals such as antioxidants, dietary fiber, omega-3 PUFA, vitamins, and minerals. Nutraceuticals like flavonoids, resveratrol, saponins, are used to cure cancer.

Development and Validation of UV-Visible spectroscopic method for estimation of Nimesulide in bulk and its pharmaceutical formulation

The aim of the present work was to develop and validate a simple UV Spectroscopic method for the determination of Nimesulide, which is the inhibitor of prostaglandin synthesis from arachidonic acid and platelet aggregation. It has the ability to exert analgesic and anti-inflammatory actions through various mechanisms (ie, COX independent pathways) and also it inhibits the release of tumour necrosis factor (TNFα) and interleukins, and stops the release of histamine from mast cells and reduce the synthesis of platelet activating factor (PAF) from the basophil cells. The UV visible Spectrophotometric analysis was performed using systronics UV-Spectrophotometer 2704 X visible double beam by using solvent KOH. Detection was performed at a wavelength of 395nm. Method validation was carried out according to ICH Q2R1 guidelines by taking the parameters such as accuracy, linearity, precision, ruggedness, and robustness, LOD and LOQ. The UV spectrophotometric was found linear in the range 5- 25µg/ml. The method was rugged and robust with % relative standard deviation less than 2. The extraction recoveries was found to be higher than 99.19% in all experimental conditions. Based upon the performance characteristics, the proposed method was found accurate, precise, rapid and suitable for the determination of nimesulide for routine analysis. The aim of the present work was to develop and validate a simple UV Spectroscopic method for the determination of Nimesulide, which is the inhibitor of prostaglandin synthesis from arachidonic acid and platelet aggregation. It has the ability to exert analgesic and anti-inflammatory actions through various mechanisms (ie, COX independent pathways) and also it inhibits the release of tumour necrosis factor (TNFα) and interleukins, and stops the release of histamine from mast cells and reduce the synthesis of platelet activating factor (PAF) from the basophil cells. The UV visible Spectrophotometric analysis was performed using systronics UV-Spectrophotometer 2704 X visible double beam by using solvent KOH. Detection was performed at a wavelength of 395nm. Method validation was carried out according to ICH Q2R1 guidelines by taking the parameters such as accuracy, linearity, precision, ruggedness, and robustness, LOD and LOQ. The UV spectrophotometric was found linear in the range 5- 25µg/ml. The method was rugged and robust with % relative standard deviation less than 2. The extraction recoveries was found to be higher than 99.19% in all experimental conditions. Based upon the performance characteristics, the proposed method was found accurate, precise, rapid and suitable for the determination of nimesulide for routine analysis.

Prostaglandin F2α drives female pheromone signaling in cichlids, revealing a basis for evolutionary divergence in olfactory signaling

Pheromones play essential roles in reproduction in many species. Prostaglandin F2α (PGF2α) acts as a female reproductive hormone and as a sex pheromone in some species. An olfactory receptor (OR) for PGF2α was recently discovered in zebrafish, but this signaling pathway is evolutionarily labile. To understand the evolution of signals that attract males to fertile females, we used the African cichlid Astatotilapia burtoni and found that adult males strongly prefer fertile female odors. Injection of a prostaglandin synthesis inhibitor abolishes this attractivity of fertile females, indicating these hormones are necessary for pheromonal signaling. Unlike zebrafish, A. burtoni males are insensitive to PGF2α, but they do exhibit strong preference for females injected with PGF2α. This attractiveness is independent of the PGF2α hormonal receptor Ptgfr, indicating that this pheromone signaling derives from PGF2α metabolization into a yet-undiscovered pheromone. We further discovered that fish that are insensitive to PGF2α lack an ortholog for the OR Or114 that zebrafish use to detect PGF2α. These results indicate that PGF2α itself does not directly induce male preference in cichlids. Rather, it plays a vital role that primes females to become attractive via an alternative male OR.

Trihydroxyxanthones from the heartwood of Maclura cochinchinensis modulate M1/M2 macrophage polarisation and enhance surface TLR4.

The anti-inflammatory actions of phytochemicals have attracted much attention due to the current state of numerous inflammatory disorders. Thai traditional medicine uses Maclura cochinchinensis (Lour.) Corner to treat chronic fever and various inflammatory diseases, as well as to maintain normal lymphatic function. Five flavonoids and five xanthones were isolated from the heartwood of M. cochinchinensis and we investigated the anti-inflammatory properties of the isolated compounds. All isolated compounds possessed an anti-inflammatory effect by decreasing prostaglandin E2 (PGE2) synthesis in lipopolysaccharide (LPS)-activated murine macrophages with varying degrees of potency. The greatest decrease in M1 inflammatory mediators, nitric oxide, PGE2, and proinflammatory cytokines was observed with 1,3,7-trihydroxyxanthone and 1,3,5-trihydroxyxanthone treatment of LPS-activated macrophages. The anti-inflammatory mechanism of the two xanthones is mediated by the suppression of inducible nitric oxide synthase, cyclooxygenase-2, and phosphatidylinositol 3-kinase/protein kinase B expression and the upregulation of M2 anti-inflammatory signalling proteins phosphorylated signal transducer and activator of transcription 6 and peroxisome proliferator-activated receptors-γ. 1,3,7-Trihydroxyxanthone exhibits superior induction of anti-inflammatory M2 mediator of LPS-activated macrophages by upregulating arginase1 expression. Following the resolution of inflammation, the two xanthones enhanced surface TLR4 expression compared to LPS-stimulated cells, possibly preserving macrophage function. Our research highlights the role of the two xanthones in modulating the M1/M2 macrophage polarisation to reduce inflammation and retain surface TLR4 once inflammation has been resolved. These findings support the use of xanthones for their anti-inflammatory effects in treating inflammatory dysregulation.

AMPK integrates metabolite and kinase-based immunometabolic control in macrophages

ObjectivePrevious mechanistic studies on immunometabolism have focused on metabolite-based paradigms of regulation, such as itaconate. Here, we, demonstrate integration of metabolite and kinase-based immunometabolic control by AMP kinase. MethodsWe combined whole cell quantitative proteomics with gene knockout of AMPKα1. ResultsComparing macrophages with AMPKα1 catalytic subunit deletion with wild-type, inflammatory markers are largely unchanged in unstimulated cells, but with an LPS stimulus, AMPKα1 knockout leads to a striking M1 hyperpolarisation. Deletion of AMPKα1 also resulted in increased expression of rate-limiting enzymes involved in itaconate synthesis, metabolism of glucose, arginine, prostaglandins and cholesterol. Consistent with this, we observed functional changes in prostaglandin synthesis and arginine metabolism. Selective AMPKα1 activation also unlocks additional regulation of IL-6 and IL-12 in M1 macrophages. ConclusionsTogether, our results validate AMPK as a pivotal immunometabolic regulator in macrophages.

The phytochemical profiles and growth of Prunus africana in Kenya

Abstract. Nyamai DW, Burugu MW, Ng’ang’a MM, Muchugi AN. 2022. The phytochemical profiles and growth of Prunus africana in Kenya. Asian J Nat Prod Biochem 20: 63-74. African mountain ranges are home to the evergreen tree Prunus africana (Hook.f.) Kalkman. Benign prostate hyperplasia can be treated with the bark or extracts from the bark of this plant. The primary goal of this research was to compare the domesticated stand at Muguga (Kenya) to samples taken from a wild stand in Kobujoi and a remnant on-farm stand in Karuri in terms of their growth characteristics and phytochemical profile. Various solvents, including water, hexane, dichloromethane, and methanol, were used in the compound extraction process. The phytochemical analysis was performed with Liquid Chromatography and Gas Chromatography-mass spectrometry. The GC Chemstation version 11 program was used to examine the data from the GC-MS. The trees in the Muguga tamed stand varied in height from 3 meters to 14 meters, with a corresponding range in circumference at breast height from 0.9 centimeters to 104.5 centimeters. A total of 273 trees were planted in the orchard, and 92 (33%) produced fruit when the data was collected. When comparing the raw organic extract yields of the three groups, there was no statistically significant difference (p>0.05). Myristic acid, linoleic acid, lauric acid, methyl myristate, methyl laurate, and methyl linoleate made up the bulk of the essential oils in the bark samples across all three sources. For men with benign prostatic hyperplasia (BPH), these substances reduce cholesterol in the prostate. It was shown that dichloromethane and hexane extracts of the three populations included Campesterol, ?-sitosterol, lup-20(29)-en- 3-one, palmitic acid, ?-sitostenone, (3.?., 5.?)- stigmast-7-en-3-ol, stigmastan-3,5-diene, and ?-tocopherol. Increased urine output and decreased prostaglandin synthesis in the prostate are effects of (3.?., 5.?)-stigmast-7-en-3-ol, ?-sitosterol, and ?-sitostenone. Cyanidin-o-galactoside, cyanidin-3-o-rutinoside, procyanidin B5, and robinetinidol-(4-?-8) catechin-(6,4-?) robinetinol are thought to have anticancer effects by inhibiting cell proliferation and scavenging free radicals in cancer cells. Evidence suggests that ursolic acid can reduce inflammation, prevent cell damage, and slow the growth of BPH. The essential oils of the Karuri people had noticeably (p<0.05) more myristic and lauric acids than any other population. Myristic acid, linoleic acid, methyl myristate, and ?-tocopherol concentrations all varied significantly (p<0.05) between the Muguga population and the Karuri and Kobujoi populations. The findings show that the phytochemical composition of P. africana is not significantly changed by domestication (p>0.05), allowing for its cultivation in agricultural settings. Strategies for the sustainable collection, management, and conservation of this species through cultivation can be derived from the morphological and phytochemical data, which has crucial significance for these areas.

A Green Synthesis of Acetyl Eugenol by Sonochemical Method and Potential as Anti-Inflammatory In-Vitro

<p>Clove oil is an essential oil from the clove plant (<em>Syzygium aromaticum</em>) containing eugenol compounds. One of the properties of eugenol is as an anti-inflammatory with a mechanism of inhibition of prostaglandin synthesis and neutrophil chemotaxis. Several derivatives of eugenol have active compounds that have been developed into new drug compounds as anti-inflammatory such as acetyl eugenol (4-allyl-2-methoxyphenyl acetate). This study aims to determine the % yield of acetyl eugenol produced from synthesis using ultrasonic 0.0323 mol of eugenol added to Erlenmeyer, and 0.25 mol of 10% sodium hydroxide was added. The mixture was put in a sonicator for 15 minutes and heated at 60<sup>0</sup>C. Then, 0.0974 mol acetic anhydride was reacted with DCC, added to the mix and sonicated with time variations (60, 80, and 100 minutes). The chemical structure was elucidated using FTIR, ATR, and GC-MS. The synthesized % yield is 32.75%. Based on the interpretation data from FTIR, 3405 cm<sup>-1</sup> is an O-H group (free phenol), 1405 cm<sup>-1 </sup>is an alkene group (C=C) aliphatic, and 1560 cm<sup>-1</sup> is an aromatic compound with the presence of a C=C aromatic bond. The presence of the (C-O) ether group is indicated in the wave number at 1301 cm<sup>-1</sup>. The C=O ester bond in the ester group is shown at 1700 cm<sup>-1</sup>. GC-MS shows that the synthesized compound has a molecular ion with m/z = 206. According to the molecular weight of acetyl eugenol of 206 g/mol, it can be concluded that acetyl eugenol was successfully synthesized. The most stable ionic fragment, 37, has a molecular weight of m/z = 164. The activities of anti-inflammatory, acetyl eugenol compounds at 400 concentration ppm get % inhibition of 32.20%.</p><p class="Standard"><strong><em> </em></strong></p>