Pharmacological Effects Research Articles

Pharmacological effects of specialized pro-resolving mediators in sepsis-induced organ dysfunction: a narrative review

Pharmacological effects of specialized pro-resolving mediators in sepsis-induced organ dysfunction: a narrative review

Protective Effects of Crotonis Semen Extract against Sepsis through NF-κB Pathway Inhibition

Sepsis is an inflammatory condition causing organ failure due to an uncontrolled immune response to infection and remains a significant challenge. Crotonis Semen has displayed various pharmacological effects, yet its potential in protecting against sepsis and the mechanisms involved remains largely unclear. Here, we explored the antiseptic properties of Crotons Semen extract (CSE) in both LPS-stimulated J774 macrophages and mice subjected to sepsis through Cecal ligation and Puncture (CLP) or LPS induction. We found that CSE enhanced survival rates in mouse models with acute sepsis induced by CLP operation and LPS injection. Administering CSE also reduced levels of enzymes indicating organ damage, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatine kinase (CK), in septic mice. Furthermore, CSE lowered the serum levels of inflammatory mediators and cytokines, such as NO, TNF-α, IL-1β, and IL-6, in septic mice. In LPS-stimulated J774 macrophages, CSE reduced the expression of pro-inflammatory proteins, including iNOS and COX-2. Moreover, CSE inhibited the phosphorylation of IκBα and IKK, key components of the NF-κB signaling pathway, thereby reducing inflammatory mediators and cytokines. These results demonstrate CSE’s protective effects against sepsis through NF-κB pathway disruption, indicating its potential as a therapeutic option for acute inflammatory conditions.

Mechanism Actions of Coniferyl Alcohol in Improving Cardiac Dysfunction in Renovascular Hypertension Studied by Experimental Verification and Network Pharmacology

Renovascular hypertension (RH), a secondary hypertension, can significantly impact heart health, resulting in heart damage and dysfunction, thereby elevating the risk of cardiovascular diseases. Coniferol (CA), which has vascular relaxation properties, is expected to be able to treat hypertension-related diseases. However, its potential effects on cardiac function after RH remain unclear. In this study, in combination with network pharmacology, the antihypertensive and cardioprotective effects of CA in a two-kidney, one-clip (2K1C) mice model and its ability to mitigate angiotensin II (Ang II)-induced hypertrophy in H9C2 cells were investigated. The findings revealed that CA effectively reduced blood pressure, myocardial tissue damage, and inflammation after RH. The possible targets of CA for RH treatment were screened by network pharmacology. The interleukin-17 (IL-17) and tumor necrosis factor (TNF) signaling pathways were identified using a Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The inflammatory response was identified using a Gene Ontology (GO) enrichment analysis. Western blot analysis confirmed that CA reduced the expression of IL-17, matrix metallopeptidase 9 (MMP9), cyclooxygenase 2 (COX2), and TNF α in heart tissues and the H9C2 cells. In summary, CA inhibited cardiac inflammation and fibrohypertrophy following RH. This effect was closely linked to the expression of MMP9/COX2/TNF α/IL-17. This study sheds light on the therapeutic potential of CA for treating RH-induced myocardial hypertrophy and provides insights into its underlying mechanisms, positioning CA as a promising candidate for future drug development.

Licorice Extract Isoliquiritigenin Protects Endothelial Function in Type 2 Diabetic Mice

Endothelial dysfunction occurs prior to atherosclerosis, which is an independent predictor of cardiovascular diseases (CVDs). Diabetes mellitus impairs endothelial function by triggering oxidative stress and inflammation in vascular tissues. Isoliquiritigenin (ISL), one of the major bioactive ingredients extracted from licorice, has been reported to inhibit inflammation and oxidative stress. However, the therapeutic effects of ISL on ameliorating type 2 diabetes (T2D)-associated endothelial dysfunction remain unknown. In our animal study, db/db male mice were utilized as a model for T2D-associated endothelial dysfunction, while their counterpart, heterozygote db/m+ male mice, served as the control. Mouse brain microvascular endothelial cells (mBMECs) were used for in vitro experiments. Interleukin-1β (IL-1β) was used to induce endothelial cell dysfunction. ISL significantly reversed the impairment of endothelium-dependent relaxations (EDRs) in db/db mouse aortas. ISL treatment decreased ROS (reactive oxygen species) levels in db/db mice aortic sections and IL-1β-treated endothelial cells. Encouragingly, ISL attenuated the overexpression of pro-inflammatory factors MCP-1, TNF-α, and IL-6 in db/db mouse aortas and IL-1β-impaired endothelial cells. The NOX2 (NADPH oxidase 2) overexpression was inhibited by ISL treatment. Notably, ISL treatment restored the expression levels of IL-10, SOD1, Nrf2, and HO-1 in db/db mouse aortas and IL-1β-impaired endothelial cells. This study illustrates, for the first time, that ISL attenuates endothelial dysfunction in T2D mice, offering new insights into the pharmacological effects of ISL. Our findings demonstrate the potential of ISL as a promising therapeutic agent for the treatment of vascular diseases, paving the way for the further exploration of novel vascular therapies.

Research, Development and Pharmacological Activity of Sinomenine and Its Derivatives

Abstract: In this manuscript, the resource distribution, pharmacological activity, pharma-cokinetics of sinomenine and the structure, synthesis, biological activity and mechanism of sinomenine derivatives reported from 2000 to December 2023 were reviewed. The lit-erature was retrieved through Web of Science, PubMed, Science Direct, SciFiner Scholar and other websites. Sinomenine belongs to isoquinoline alkaloids and was extracted from the Chinese herb Sinomenium acutum root. In Asian countries such as China and Japan, it is commonly prescribed as a treatment for rheumatoid arthritis. In addition, sinomenine also has sedative, analgesic, anti-inflammatory, immunosuppressive, neuroprotective, an-ti-drug dependence, anti-tumor and other biological activities. Sinomenine limited its ap-plication prospects because of its large dosage, poor epidermal permeability and short half-life. To overcome these defects, new sinomenine derivatives have been synthesized. Based on the comprehensive analysis of relevant literature at home and abroad, this paper reviews the recent progress in the study of sinomenine's pharmacological effects and structural modifications. Future research on sinomenine will focus on improving its thera-peutic effect, and developing new drug preparations and structural modifications. It is hoped that this review will help to better understand the research progress of sinomenine and provide constructive suggestions for further research of sinomenine.

Bergenin inhibits hepatic fat deposition by activating the AMPK signaling pathway, thereby attenuating alcoholic liver disease

Alcoholic liver disease (ALD) is a prevalent liver condition that arises from prolonged and excessive alcohol intake. Bergenin (BER) is an effective phytotherapeutic agent that exhibits pharmacological properties, including anti-inflammatory and anti-oxidative effects. To establish an in vivo model of ALD, C57BL/6 mice were continuously fed a high-fat diet (HFD) and administered alcohol gavage for 8 weeks, while concurrently administering BER and evaluated for therapeutic effects. After modeling, the therapeutic effects of BER were evaluated by observing histopathological changes and the detection of relevant biochemical indicators in mice. In addition, RNA sequencing of liver tissues was performed to analyze differentially expressed genes and to investigate the associated signaling pathways in order to elucidate the protective mechanisms of BER. These differentially expressed genes were mainly enriched in lipid metabolism pathways and the cytochrome P450 metabolism of exogenous substances. Subsequently, HepG2 was co-treated with sodium oleate (NaOA) and ethanol to establish an in vitro model, and the specific mechanism by which BER ameliorates ALD was further analyzed in depth. AMPK inhibitor, Compound C (CC), was demonstrated to significantly inhibit the regulation of lipid metabolism by BER in vitro. Finally, the differentially expressed genes selected were validated through qRT-PCR and Western blot analysis. Collectively, our findings revealed that BER effectively alleviated liver injury caused by alcohol and HFD in mice, significantly suppressing lipid deposition in ALD, enhancing alcohol metabolism, and mitigating oxidative stress.

Corynoline alleviates hepatic ischemia-reperfusion injury by inhibiting NLRP3 inflammasome activation through enhancing Nrf2/HO-1 signaling.

Corynoline has displayed pharmacological effects in reducing oxidative stress and inflammatory responses in many disorders. However, its effects on hepatic ischemia-reperfusion (I/R) injury remain unclear. This study aimed to investigate the protective effects of corynoline against hepatic I/R injury and the underlying mechanisms. Rat models with hepatic I/R injury and BRL-3A cell models with hypoxia/reoxygenation (H/R) insult were constructed. Models were pretreated with corynoline and/or other inhibitors for functional and mechanistic examination. Corynoline pretreatment effectively mitigated hepatic I/R injury verified by reduced serum transaminase levels, improved histological damage scores, and decreased apoptosis rates. Additionally, corynoline pretreatment significantly inhibited I/R-triggered oxidative stress and inflammatory responses, as indicated by enhanced mitochondrial function, reduced levels of ROS and MDA, reduced neutrophil infiltration and suppressed proinflammatory cytokine release. In vitro experiments further showed that corynoline pretreatment increased cellular viability, decreased LDH activity, reduced cellular apoptosis, and inhibited oxidative stress and inflammatory injury in H/R-induced BRL-3A cells. Mechanistically, corynoline significantly increased Nrf2 nuclear translocation and expression levels of its target gene, HO-1. It also blocked NLRP3 inflammasome activation both in vivo and in vitro. Furthermore, pretreatment with Nrf2 inhibitor ML-385 counteracted the protective effect of corynoline on hepatic I/R injury. Ultimately, in vitro studies revealed that the NLRP3 activator nigericin could also nullified the protective effects of corynoline in BRL-3A cells, but had minimal impact on Nrf2 nuclear translocation. Corynoline can exert protective effects against hepatic I/R injury by inhibiting oxidative stress, inflammatory responses, and apoptosis. These effects may be associated with inhibiting ROS-induced NLRP3 inflammasome activation by enhancing Nrf2/HO-1 signaling. These data provide new understanding about the mechanism of corynoline action, suggesting it is a potential drug applied for the treatment and prevention of hepatic I/R injury.

Galantamine and wedelolactone combined treatment suppresses LPS-induced NLRP3 inflammasome activation in microglial cells

Context Inflammasome NLR family pyrin domain-containing 3 (NLRP3) is associated with neurological disorders. Neuroinflammation can be suppressed by inhibiting NLRP3 inflammasome activation, decreasing neurodegenerative disorder progression. We devised a therapeutic technique that can reduce neuroinflammation induced by microglial activation, avoiding neurodegeneration. We aimed to investigate the mechanisms underlying the pharmacological effects of galantamine and wedelolactone by evaluating the response of the nuclear factor kappa B (NF-κB) signaling pathway and NLRP3 inflammasome in lipopolysaccharide (LPS)-activated N9 microglia. Methods LPS and adenosine triphosphate were used to activate the NLRP3 inflammasome in N9 microglial cells, which were pretreated with galantamine and wedelolactone. Caspase-1, NLRP3, NF-κB, and interleukin (IL)-1β levels were measured using RT-qPCR and immunostaining. Results Combined administration of galantamine and wedelolactone rescued microglial cells from LPS-induced cell death. Furthermore, treatment with galantamine and wedelolactone led to the suppression of NF-κB expression. NLRP3, caspase-1, and IL-1β levels were decreased by the combined treatment. Discussion and Conclusion The concurrent administration of galantamine and wedelolactone effectively suppresses the production of inflammatory cytokines and NLRP3 inflammasome activation in microglia. This inhibitory effect is likely linked to the NF-κB signaling pathway modulation. Therefore, this combined treatment is a potential therapeutic approach for neuroinflammatory diseases.

Studies on the antifungal effects of Hinokitiol on Candida albicans: inhibition of germ tube formation and synergistic pharmacological effects of miconazole.

One of the goals of oral healthcare management is to manage dry mouth. Thus, moisturizers containing antimicrobial ingredients, such as hinokitiol (HT), are applied to the oral mucosa after oral care. In this study, we investigated the preventive effect of HT against the growth of Candida albicans (C. al) and its synergistic effect when combined with miconazole (MCZ), an oral treatment for candidiasis. As the concentration of HT increased, the length and percentage of germ tubes (GT) decreased. Larger inhibition circles were observed for MCZ concentrations of 2.0 and 4.0μg/disc compared to the HT medium without HT. The increased inhibitory effect was observed in both aerobic and anaerobic cultures. This suggests that the production of reactive oxygen species (ROS) by C. al cells increased with the combination of HT and MCZ. The length and percentage of GT increased, whereas the amount of ROS decreased when ROS scavengers were used in combination with the drug. HT led to morphological changes that inhibited the GT associated with pathogenic C. al, exhibited a complementary action against MCZ, and showed a possible association with hydrogen peroxide and superhydroxy anion radicals. These effects suggest that HT is a promising candidate for inhibiting C. al. In conclusion, HT demonstrated a prophylactic effect by inhibiting C. al and a synergistic effect with MCZ, a drug used to treat oral candidiasis. HT may also be useful for suppressing the onset and reducing the severity of oral candidiasis.

Exploring the role of Yuxuebi tablet in neuropathic pain with the method of similarity research of drug pharmacological effects based on unsupervised machine learning

IntroductionHaving multiple pharmacological effects is a characteristic of Traditional Chinese Medicine (TCM). Currently, there is a lack of suitable methods to explore and discover modern diseases suitable for TCM treatment using this characteristic. Unsupervised machine learning technology is an efficient strategy to predict the pharmacological activity of drugs. This study takes Yuxuebi Tablet (YXB) as the research object. Using the unsupervised machine learning technology of drug cell functional fingerprint similarity research, the potential pharmacological effects of YXB were discovered and verified.MethodsLC-MS combined with the in vitro intestinal absorption method was used to identify components of YXB that could be absorbed by the intestinal tract of rats. Unsupervised learning hierarchical clustering was used to calculate the degree of similarity of cellular functional fingerprints between these components and 121 marketed Western drugs whose indications are diseases and symptoms that YXB is commonly used to treat. Then, based on the Library of Integrated Network-based Cellular Signatures database, pathway analysis was performed for selected Western drugs with high similarity in cellular functional fingerprints with the components of YXB to discover the potential pharmacological effects of YXB, which were validated by animal experiments.ResultsWe identified 40 intestinally absorbed components of YXB. Through predictive studies, we found that they have pharmacological effects very similar to non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids. In addition, we found that they have very similar pharmacological effects to anti-neuropathic pain medications (such as gabapentin, duloxetine, and pethidine) and may inhibit the NF-κB signaling pathway and biological processes related to pain perception. Therefore, YXB may have an antinociceptive effect on neuropathic pain. Finally, we demonstrated that YXB significantly reduced neuropathic pain in a rat model of sciatic nerve chronic constriction injury (CCI). Transcriptome analysis further revealed that YXB regulates the expression of multiple genes involved in nerve injury repair, signal transduction, ion channels, and inflammatory response, with key regulatory targets including Sgk1, Sst, Isl1, and Shh.ConclusionThis study successfully identified and confirmed the previously unknown pharmacological activity of YXB against neuropathic pain through unsupervised learning prediction and experimental verification.

Hordenine Alleviates Lipopolysaccharide-Induced Mastitis by Suppressing Inflammation and Oxidative Stress, Modulating Intestinal Microbiota, and Preserving the Blood-Milk Barrier.

Mastitis is a common mammalian disease occurring in the mammary tissue and poses a major threat to agriculture and the dairy industry. Hordenine (HOR), a phenylethylamine alkaloid naturally extracted from malt, has various pharmacological effects, but its role in mastitis is unknown. The aim of this study was to investigate the role of HOR and its underlying mechanism in a lipopolysaccharide (LPS)-induced inflammatory response model of mouse mammary epithelial cells (EpH4-Ev) and mouse mastitis model. The experimental results showed that HOR attenuated LPS-induced mammary tissue damage (from 3.75 ± 0.25 to 1.75 ± 0.25) and restored the integrity of the blood-milk barrier. Further mechanistic studies revealed that HOR inhibited LPS-induced overactivation of the TLR4-MAPK/NF-κB signaling pathway and activated the AMPK/Nrf2/HO-1 signaling pathway. Additionally, HOR altered the composition of the intestinal microbiota in mice, ultimately reducing the extent of inflammatory injury (from 3.33 ± 0.33 to 0.67 ± 0.33) and upregulating the expression of tight junction proteins (ZO-1, occludin, and claudin-3). The findings of this study provide a theoretical basis in the rational use of HOR for the prevention and treatment of mastitis and the maintenance of mammalian mammary gland health.

Sonication-Assisted Self-Assembled Resveratrol Nanoparticles with Enhanced Antiviral and Anti-inflammatory Activity against Respiratory Syncytial Virus-Induced Pneumonia.

Respiratory syncytial virus (RSV)-induced viral pneumonia in children is common worldwide. Its high occurrence and lack of an effective vaccine make it a leading cause of death in children. Severe RSV infection can trigger uncontrolled inflammatory responses in patients, so the development of small molecule drugs with the dual function of "direct antivirus" and "inflammatory response regulation" is welcome. Resveratrol (Res) has been reported to have antiviral and anti-inflammatory pharmacological effects, but its application is limited because of its poor water solubility and oral bioavailability. Based on small-molecule nanotechnology, we developed a sonication-assisted self-assembly method for preparing insoluble Res into highly soluble resveratrol nanoparticles (Res NPs). The obtained Res NPs exhibited a higher water solubility and a faster dissolution rate, which was more conducive to the effectiveness of Res in addressing RSV-induced viral pneumonia. In vitro studies had shown that Res NPs played an antiviral role by inhibiting RSV replication and reducing the production of pro-inflammatory cytokines. Nebulized inhalation administration of Res NPs prolonged the drug's residence time in the lungs, which appears to increase the accumulation and effectiveness of Res NPs. Additionally, in vivo studies had demonstrated significant benefits of Res NPs in inhibiting RSV viral load and improving the pulmonary microenvironment in RSV-infected mice. Both antiviral and anti-inflammatory experiments had confirmed that the pharmacological activity of Res NPs is superior to that of Res. This suggested that nanosizing Res was an effective way to enhance the original pharmacological activity of Res and also offered a new formulation strategy for treating viral pneumonia.

Changes in urinary output due to concomitant administration of sacubitril/valsartan and atrial natriuretic peptide in patients with heart failure: a multicenter retrospective cohort study

BackgroundSacubitril/valsartan is an angiotensin receptor neprilysin inhibitor (ARNI) that inhibits the degradation of endogenous natriuretic peptides. Therefore, ARNIs may increase the efficacy of human atrial natriuretic peptide (hANP), a drug for acute heart failure, by mediating its pharmacological mechanism. This study was aimed at evaluating the effects of ARNIs on the pharmacological effects of hANP by using surrogate marker, such as urinary output, in patients with heart failure.MethodsIn this multicenter retrospective cohort study, adult patients with heart failure who were taking angiotensin II receptor blockers (ARB) or ARNIs combined with hANP were enrolled. Information on basic characteristics, clinical laboratory data, medical history, and severity of cardiac insufficiency were collected from electronic medical records. The primary outcome was the change in adjusted fluid balance, calculated by IN-volume (mL/day) – OUT-volume (mL/day) / daily hANP dosage (μg).ResultsNinety-two and 62 patients in the ARB + hANP and ARNI + hANP groups, respectively, were eligible for analysis. The adjusted fluid balance in the ARNI + hANP group was significantly lower than that in the ARB + hANP group (p = 0.001). After propensity score matching, 27 patients from each group were included. Similarly, there was a significant reduction in adjusted fluid balance in the ARNI + hANP group after propensity score matching (p = 0.026).ConclusionsThese findings suggest that ARNIs may enhance the efficacy of hANP and the combination of the two may be effective in the treatment of heart failure.

A comprehensive analysis of Cestrum nocturnum: Its phytochemical composition, pharmacological applications, and toxicity profile in the context of traditional medicinal practices

According to traditional medicine, the study gives a full look at the phytochemical makeup, pharmacological uses, and toxic profile of Cestrum nocturnum (night-blooming jasmine). The review sought to connect traditional knowledge with scientific evidence, assessing the therapeutic potential and safety concerns linked to this plant. The methods involved conducting a comprehensive search of peer-reviewed literature and ethnobotanical databases. The focus was on studies that examined the chemical composition, pharmacological effects, and toxicological properties of Cestrum nocturnum. The data pertaining to traditional uses, active compounds, therapeutic effects, dosage, and adverse reactions were thoroughly extracted and carefully analyzed. The results indicate that Cestrum nocturnum contains a range of phytochemicals, such as alkaloids, glycosides, flavonoids, and essential oils. Pharmacological studies have extensively documented its various effects, including anti-inflammatory, analgesic, antimicrobial, anticonvulsant, and sedative properties. Common applications involve the treatment of ailments like epilepsy, anxiety, and skin disorders. Nevertheless, there have been some concerns raised about the plant's toxicity, specifically related to the presence of solanine alkaloids. In conclusion, Cestrum nocturnum shows great potential as a source of bioactive compounds that could have valuable therapeutic applications. However, more research is needed, including thorough clinical trials and toxicity assessments, to determine the safety and effectiveness of this treatment for specific conditions. This review highlights the significance of combining traditional knowledge with scientific validation to fully harness the potential of Cestrum nocturnum in modern medicine, while also prioritizing its safe and responsible utilization. Keywords: Cestrum nocturnum, phytochemistry, pharmacology, toxicology, traditional medicine

Adipose stem cell exosomes promote mitochondrial autophagy through the PI3K/AKT/mTOR pathway to alleviate keloids

BackgroundFibrosis with unrelieved chronic inflammation is an important pathological change in keloids. Mitochondrial autophagy plays a crucial role in reducing inflammation and inhibiting fibrosis. Adipose stem cell-derived exosomes, a product of adipose stem cell paracrine secretion, have pharmacological effects, such as anti-inflammatory and antiapoptotic effects, and mediate autophagy. Therefore, this study aims to investigate the function and mechanism of adipose stem cell exosomes in the treatment of keloids.MethodWe isolated adipose stem cell exosomes under normoxic and hypoxic condition to detect their effects on keloid fibroblast proliferation, migration, and collagen synthesis. Meanwhile, 740YPDGFR (PI3K/AKT activator) was applied to detect the changes in autophagic flow levels and mitochondrial morphology and function in keloid fibroblasts. We constructed a human keloid mouse model by transplanting human keloid tissues into six-week-old (20–22 g; female) BALB/c nude mice, meanwhile, we applied adipose stem cell exosomes to treat the mouse model and observed the retention and effect of ADSC exosomes in vivo.ResultsADSC exosomes can inhibit the PI3K/AKT/mTOR signaling pathway. The exosomes of ADSCs decreased the inflammatory level of KFs, enhanced the interaction between P62 and LC3, and restored the mitochondrial membrane potential. In the human keloid mouse model, ADSC exosomes can exist stably, promote mitochondrial autophagy in keloid tissue, improve mitochondrial morphology, reduce inflammatory reaction and fibrosis. Meanwhile, At the same time, the exosomes derived from hypoxic adipose stem cells have played a more effective role in both in vitro and in vivo experiments.ConclusionsAdipose stem cell exosomes inhibited the PI3K/AKT/mTOR pathway, activated mitochondrial autophagy, and alleviated keloid scars.Graphical

Cefotaxime-induced allergic reaction in a 4 years old boy: Case presentation and management strategies

The present case study aims to report and analyze a hypersensitivity reaction to cefotaxime in a 4-year-old boy, highlighting the clinical presentation, diagnostic investigations, management, and classification of the adverse drug reaction using established systems. Cefotaxime, a third-generation cephalosporin, is a semisynthetic antibiotic derived from "cephalosporin-C," produced by the fungus . A 4-year-old boy weighing 15 kg presented with a high-grade fever, cold, loss of appetite, and general weakness. He was admitted with a provisional diagnosis of Acute Febrile Illness (AFI) and initiated on parenteral cefotaxime (750 mg BD), along with paracetamol and febrinil. On the second day of therapy, he developed a hypersensitivity reaction characterized by a rash, prompting the discontinuation of cefotaxime. He was treated with antihistamines and hydrocortisone and switched to intravenous amikacin (100 mg BD). The Widal test was positive for antigen O++, with elevated C-reactive protein levels (1.86 mg/dl). Other tests, including dengue, urine analysis, and complete blood count, were within normal limits except for a slight elevation in white blood cells (8.62×10^9/L). Adverse drug reactions (ADRs) to cefotaxime can be classified using the Rawlins-Thompson and DoTS systems. The Rawlins-Thompson system categorizes ADRs into Type A (predictable pharmacological effects) and Type B (unpredictable and serious). The DoTS system considers dose relatedness, timing, and patient susceptibility, providing a comprehensive framework for understanding drug reactions. This case of cefotaxime-induced hypersensitivity falls under Type B in the Rawlins-Thompson classification and is characterized by the DoTS system. Clinicians should be vigilant for ADRs with cefotaxime, despite its general safety. Prompt recognition and management of hypersensitivity reactions are essential to prevent further complications. Discontinuing the offending agent and providing appropriate supportive care is crucial for patient recovery.

Olanzapine-Induced Hypothermia: A Case Report in an Elderly Black Male Patient Diagnosed with Bipolar 1 Type Disorder

There are few reports that describe incidence of hypothermia in patients treated with olanzapine. We report a case of an elderly 83-year-old black male, readmitted to the state psychiatric hospital December 2023 due to psychiatric exacerbation after 6 months of successful discharge to community, who experienced a fall and profound hypothermia with bradycardia that resulted in a 10-day acute hospitalization in January 2024. Medical workup was unrevealing except for multivessel disease found on CT stroke study of the brain. When patient returned to inpatient psychiatric hospital, his psychiatric medications, including both quetiapine and olanzapine, were restarted at half the dose. The next morning, the patient was again hypotensive, bradycardic and hypothermic. For this patient, only the olanzapine was new upon the most recent admission, and thus this case report supports the other few reports already published, implicating olanzapine in the pharmacologic adverse effect of drug induced hypothermia.

Herbal extracts in hepatoprotection: antioxidant and immunomodulatory effects. A review

The global market for herbal medicines is valued at $83 billion and continues to expand rapidly. Plant extracts, widely used due to their safety and minimal side effects, play a significant role in supporting liver function. The treatment of liver diseases, including hepatitis of various etiologies, alcoholic and non-alcoholic fatty liver disease, and cirrhosis, involves the use of effective hepatoprotective drugs. Plant extracts provide antioxidant and immunomodulatory pharmacological effects that contribute to the maintenance of liver function. The aim of this review was to analyze the mechanisms underlying the hepatoprotective effects of various herbal extracts included in the formulation of DIPANA®, focusing on their antioxidant and immunomodulatory properties. Additionally, the review aimed to present clinical study results supporting their efficacy in treating of various liver diseases. The analysis was based on available literature data and clinical studies on the use of DIPANA®. The reviewed herbal extracts and their combination (DIPANA®) demonstrate efficacy in experimental models of liver damage and clinical studies involving patients with liver diseases, including alcoholic and non-alcoholic steatohepatitis, drug-induced liver injury, and functional disorders of the gallbladder. This drug exhibits hepatoprotective, choleretic, relaxing effects and is well-tolerated by patients.

Asperuloside activates hepatic NRF2 signaling to stimulate mitochondrial metabolism and restore lipid homeostasis in high fat diet-induced MAFLD

BackgroundNutrient overload predisposes the development of metabolic dysfunction-associated fatty liver disease (MAFLD). However, there are no specific pharmacological therapies for MAFLD. Asperuloside (ASP), an iridoid glycoside extracted from Eucommia ulmoides leaves, can alleviate obesity and MAFLD. However, the underlying mechanism and pharmacological effects of ASP on ameliorating MAFLD remain largely investigated. This study aimed to explore the effects of ASP in ameliorating MAFLD and to unravel its underlying mechanism using a high fat diet-induced MAFLD mice model. MethodsSix-week-old C57BL/6 male mice were fed a high fat diet for 12 weeks to induce MAFLD, followed by daily ASP treatment (50 mg/kg via oral gavage) for 7 weeks. HepG2 cells were used for in vitro studies. Nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor, ML385, was employed to explore the mechanisms of ASP's action. ResultsASP stimulated lipolysis and inhibited de novo lipogenesis, contributing to alleviating lipid deposition in obese mice livers and HepG2 cells. ASP restored ATP production and reversed the impairments of mitochondrial energetics and biogenesis in obese mice livers and HepG2 cells. ASP attenuated oxidative stress in obese mice livers and HepG2 cells, exhibiting its antioxidant value. Impressively, ASP significantly promotes Nrf2 nuclear translocation and Nrf2/ARE binding, thereby activating Nrf2/ARE pathway in obese mice livers and HepG2 cells, demonstrating its potential as a hepatic Nrf2 activator. Nrf2 inhibition abolishes the protective effects of ASP against lipid deposition, oxidative stress and mitochondrial dysfunction, emphasizing the critical role of ASP-activated hepatic Nrf2 signaling in ameliorating MAFLD. ConclusionsThis study provides the first line of evidence demonstrating the pivotal role of ASP-stimulated Nrf2 activation in alleviating MAFLD, emphasizing its potential as a hepatic Nrf2 activator targeting fatty liver diseases. These findings offer new evidence of ASP-stimulated mitochondrial metabolism and lipolysis in MAFLD, paving the way for the development of ASP as a therapeutic agent and dietary supplement to attenuate MAFLD progression.

Chemistry, biosynthesis, and theranostics of antioxidant flavonoids and polyphenolics of genus Rhododendron: an overview.

The genus Rhododendron is an ancient and most widely distributed genus of the family Ericaceae consisting of evergreen plant species that have been utilized as traditional medicine since a very long time for the treatment of various ailments including pain, asthma, inflammation, cold, and acute bronchitis. The chemistry of polyphenolics isolated from a number of species of the genus Rhododendron has been investigated. During the currently designed study, an in-depth study on the phytochemistry, natural distribution, biosynthesis, and pharmacological properties including their potential capability as free radical scavengers has been conducted. This work provides structural characteristics of phenolic compounds isolated from the species of Rhododendron with remarkable antioxidant potential. In addition, biosynthesis and theranostic study have also been encompassed with the aims to furnish a wide platform of valuable information for designing of new drug entities. The detailed information including names, structural features, origins, classification, biosynthetic pathways, theranostics, and pharmacological effects of about 171 phenolics and flavonoids isolated from the 36 plant species of the genus Rhododendron with the antioxidant potential has been covered in this manuscript. This study demonstrated that species of Rhododendron genus have excellent antioxidant activities and great potential as a source for natural health products. This comprehensive review might serve as a foundation for more investigation into the Rhododendron genus.