Pharmacological Activities Research Articles

Healing and Hallucinations: A Comprehensive Look at Datura

The Solanaceae plant family is a large clade that includes Datura, a genus of plants with many species recognized for their severe pharmacological effects via tropane alkaloids like atropine, hyoscyamine and scopolamine. These alkaloids act as antagonists of muscarinic acetylcholine receptors with leading to a truly diverse pharmacological action, ranging from anticholinergic effects all the way through hallucinogenic properties. Datura plants have been used historically in traditional medicine and rituals worldwide but are infamous for poisoning due to the risk of severe anticholinergic toxicity, including death. Nevertheless, their pharmacology has become of interest for research due to potential therapeutic applications: specifically in controlling nauseousness and perhaps neurological disorders. In this review, we provide a summary of the botanical description and cultivation methods in addition to those on traditional use practices concerning phytochemistry, pharmacology and toxicology as compared with evidence-based information together emphasizing cautions against availability without stringent regulatory consideration for its modern medical uses or ritualistic purposes.

An Assessment of Antidepressant Activity of Etlingera elatior Alone and in Combination with Fluoxetine

Aim: Present study deals to access the antidepressant activity of Etlingera elatior leaves extract in rodent. Background: Etlingera elatior is a species of herbaceous perennial plant in the family Zingiberaceae; native to Indonesia, Thailand, Malaysia and New Guinea. Depression is one of the most common mental disorders affecting humans, pathological basis of which is not fully understood. The current antidepressant drugs have several adverse effects including their effects on cognition. Therefore, natural product are being evaluated for their antidepressant activities. Objective: In this study, Etlingera elatior leaf extracts are being evaluated for antidepressant activity in rodent models. A wide range of synthetic medicines that can be used to treat depression which may exerts various side effects such as dry mouth, gastrointestinal problems, nausea, respiratory problems, cardiac arrhythmias, drowsiness, anxiety etc. Hence, it becomes essential to discover new anti-depressant drug with more potency, efficacy and safety profile than those of marketed synthetic drugs. Methods: Using the forced swimming test, the tail suspension test, mouse 5-HTP-induced head twitches and estimation of brain lipid peroxidation modelsthe antidepressant efficacy of Etlingera elatior ethanolic extract was examined. Imipramine was used as reference standards. result: According to our study, Etlingera elatior significantly (p0.01) reduced immobility in tail suspension, forced swimming, and 5-HTP-induced head twitches in mice with depression that were comparable to imipramine. Results: According to our study, Etlingera elatior significantly (p 0.01) reduced immobility in tail suspension, forced swimming, and 5-HTP-induced head twitches in mice with depression that were comparable to imipramine. Conclusion: Based on the results obtained we can conclude that Etlingera elatior leaves extract possess significant antidepressant activity. The antidepressant effectiveness of Etlingera elatior leaves extract can be confirmed in the future by adding more models, and attempts can also be made to isolate and characterise the phytoconstituents responsible for the pharmacological action.

Targeted isolation of barrigenol-like triterpenoids from the husks of Xanthoceras sorbifolia Bunge based on feature-based molecular networking and their antitumor activities

The husks of Xanthoceras sorbifolia Bunge have gradually attracted widespread attention in recent years due to the abundant resources and ideal pharmacological activities, with barrigenol-like triterpenoid saponins being its biological constituents. In this study, a feature-based molecular networking (FBMN) was utilized to perform the targeted isolation of triterpenoids. As a result, six undescribed barrigenol-type saponins (1–6) along with fourteen known analogues (7–22) were isolated from the extract of X. sorbifolia husk. Their structures were determined through a comprehensive analysis of NMR and HRMS spectroscopic data. Among them, compounds 1–3 are a specific type of saponin featuring a fucose moiety attached at C-21. The antitumor activities of isolated compounds were evaluated and compounds 7, 9 and 10 showed significant inhibitory activities against A549 and HepG2 cell lines in a dose-dependent manner.

Recent Advances in Phenazine Natural Products: Chemical Structures and Biological Activities.

Phenazine natural products are a class of colored nitrogen-containing heterocycles produced by various microorganisms mainly originating from marine and terrestrial sources. The tricyclic ring molecules show various chemical structures and the decorating groups dedicate extensive pharmacological activities, including antimicrobial, anticancer, antiparasitic, anti-inflammatory, and insecticidal. These secondary metabolites provide natural materials for screening and developing medicinal compounds in the field of medicine and agriculture due to biological activities. The review presents a systematic summary of the literature on natural phenazines in the past decade, including over 150 compounds, such as hydroxylated, O-methylated, N-methylated, N-oxide, terpenoid, halogenated, glycosylated phenazines, saphenic acid derivatives, and other phenazine derivatives, along with their characterized antimicrobial and anticancer activities. This review may provide guidance for the investigation of phenazines in the future.

Innovative Synthesis of 3,5-Disubstituted Pyrazoline with Heterocyclic System for Hybrid Development

The synthesis of 3,5-disubstituted pyrazolines, integrated with heterocyclic systems, represents a crucial area of chemical research due to their pharmacological and biological significance. This article reviews various synthetic methods used to prepare 3,5-disubstituted pyrazolines with different heterocyclic groups. The methodology employed in this study entails a multi-step synthesis, where readily available starting materials are transformed into complex pyrazoline derivatives through strategic reaction sequences. Incorporating heterocyclic systems not only enhances the structural diversity but also imparts unique chemical and biological properties to these compounds. Various heterocyclic groups, such as furans, thiophenes, and pyridines, are introduced at the 3,5-positions of the pyrazoline ring, yielding a versatile library of compounds. This study highlights the potential applications of these novel compounds in medicinal chemistry and drug discovery, emphasizing their bioactivity against specific targets. Preliminary data suggests that certain derivatives possess promising pharmacological activities, making them potential candidates for further development as therapeutic agents. In summary, this review provides a valuable contribution to the field of organic synthesis, offering a novel and efficient route to synthesize 3,5-disubstituted pyrazolines with heterocyclic systems. Furthermore, the structural activity relationship of the compounds is also discussed. The structural diversity and potential pharmacological properties of these compounds make them valuable candidates for further exploration and development in drug discovery and related areas.

RNA m6A methyltransferase activator affects anxiety-related behaviours, monoamines and striatal gene expression in the rat.

Modification of mRNA by methylation is involved in post-transcriptional regulation of gene expression by affecting the splicing, transport, stability and translation of mRNA. Methylation of adenosine at N6 (m6A) is one of the most common and important cellular modification occurring in the mRNA of eukaryotes. Evidence that m6A mRNA methylation is involved in regulation of stress response and that its dysregulation may contribute to the pathogenesis of neuropsychiatric disorders is accumulating. We have examined the acute and subchronic (up to 18 days once per day intraperitoneally) effect of the first METTL3/METTL14 activator compound CHMA1004 (methyl-piperazine-2-carboxylate) at two doses (1 and 5 mg/kg) in male and female rats. CHMA1004 had a locomotor activating and anxiolytic-like profile in open field and elevated zero-maze tests. In female rats sucrose consumption and swimming in Porsolt's test were increased. Nevertheless, CHMA1004 did not exhibit strong psychostimulant-like properties: CHMA1004 had no effect on 50-kHz ultrasonic vocalizations except that it reduced the baseline difference between male and female animals, and acute drug treatment had no effect on extracellular dopamine levels in striatum. Subchronic CHMA1004 altered ex vivo catecholamine levels in several brain regions. RNA sequencing of female rat striata after subchronic CHMA1004 treatment revealed changes in the expression of a number of genes linked to dopamine neuron viability, neurodegeneration, depression, anxiety and stress response. Conclusively, the first-in-class METTL3/METTL14 activator compound CHMA1004 increased locomotor activity and elicited anxiolytic-like effects after systemic administration, demonstrating that pharmacological activation of RNA m6A methylation has potential for neuropsychiatric drug development.

Isoliquiritigenin as a modulator of the Nrf2 signaling pathway: potential therapeutic implications.

Nuclear factor erythroid-2-related factor 2 (Nrf2), a transcription factor responsible for cytoprotection, plays a crucial role in regulating the expression of numerous antioxidant genes, thereby reducing reactive oxygen species (ROS) levels and safeguarding cells against oxidative stress. Extensive research has demonstrated the involvement of Nrf2 in various diseases, prompting the exploration of Nrf2 activation as a potential therapeutic approach for a variety of diseases. Consequently, there has been a surge of interest in investigating the Nrf2 signaling pathway and developing compounds that can modulate its activity. Isoliquiritigenin (ISL) (PubChem CID:638278) exhibits a diverse range of pharmacological activities, including antioxidant, anticancer, and anti-tumor properties. Notably, its robust antioxidant activity has garnered significant attention. Furthermore, ISL has been found to possess therapeutic effects on various diseases, such as diabetes, cardiovascular diseases, kidney diseases, and cancer, through the activation of the Nrf2 pathway. This review aims to evaluate the potential of ISL in modulating the Nrf2 signaling pathway and summarize the role of ISL in diverse diseases prevention and treatment through modulating the Nrf2 signaling pathway.

Synthesis and characterization of activated carbon-supported magnetic nanocomposite (MNPs-OLAC) obtained from okra leaves as a nanocarrier for targeted delivery of morin hydrate.

The method of encapsulating the drug molecule in a carrier, such as a magnetic nanoparticle, is a promising development that has the potential to deliver the medicine to the site where it is intended to be administered. Morin is a pentahydroxyflavone obtained from the leaves, stems, and fruits of various plantsmainly from the Moraceae family exhibiting diverse pharmacological activities such as anti-inflammatory, anti-oxidant, and free radical scavenging and helps treat diseases such as diabetes, myocardial infarction and cancer. In this study, we conducted the synthesis of a nanocomposite with magnetic properties by coating biocompatible activated carbon obtained from okra plant leaves with magnetic nanoparticles. Characterization of the synthesized activated carbon-coated magnetic nanocomposite was confirmed by Fourier transform infrared, scanning electron microscopy, dynamic light scattering, and zeta potential. The cytotoxic effects of the drug-loaded magnetic nanocomposite were examined in HT-29 (Colorectal), MCF-7 (breast), U373 (brain), T98-G (Glioblastoma) cancer cell lines, and human umbilical vein endothelial cells healthy cell line. We studied the loading and release behavior of morin hydrate in the activated carbon-coated magnetic nanocomposite. Activated carbon-coated magnetic nanocomposite carriers can show promising results for the delivery of Morin hydrate drugs to the targeted site.

In Vitro Anticancer Potential of Eugenol on Oral Cancer Cell Lines: A Systematic Review.

Oral cancer is one of the most common types of cancer and has become a global health concern. Oral squamous cell carcinoma (OSCC) is the most prevalent form of oral cancer worldwide. Eugenol, an aromatic phenolic compound, exhibits various pharmacological activities, including anticancer effects. Several studies have reported the anticancer activity of eugenol against OSCC via different pathways. However, no current review has discussed the extent of eugenol anticancer research on oral cancer cell lines using in vitro studies. This systematic review aimed to discuss the anticancer potential of eugenol against oral cancer cell lines in vitro. Articles were selected from PubMed, ScienceDirect, SpringerLink and EBSCOhost databases based on specified inclusion and exclusion criteria. Additional articles were identified through manual hand searching. The selection process followed PRISMA guidelines. A risk-of-bias assessment was performed to evaluate the reliability and relevance of the in vitro studies. Thirteen articles with high-quality results were assessed and analysed for further investigation. These studies investigated the ability of eugenol to induce cell death through apoptotic and non-apoptotic pathways, inhibit cell proliferation and affect oxidative stress, contributing to cell death in several oral cancer cell lines. Therefore, eugenol is a potential anticancer agent for OSCC, as it exhibited anticancer activity in oral cancer cell lines in vitro studies.

Sesquiterpenoids in Agarwood: Biosynthesis, Microbial Induction, and Pharmacological Activities.

Agarwood, derived from the Aquilaria genus, is widely utilized in perfumery, traditional medicine, and cultural practices throughout Asia. Agarwood is rich in terpenes, especially sesquiterpenes, which are considered to be the source of its rare and exquisite fragrance. This Review consolidates recent research on sesquiterpene biosynthesis in agarwood and the influence of fungi on these processes, alongside a discussion of the potential medicinal value of agarwood sesquiterpenes. This Review commences by elucidating the general biosynthesis of sesquiterpenes and identifying the main enzymes and transcription factors involved in the production of agarwood sesquiterpenes. This Review also summarizes the fungi associated with agarwood and highlights how commensal fungi stimulate agarwood and sesquiterpene production. We then scrutinize the pharmacological properties of sesquiterpenes, underscoring their anti-inflammatory and antimicrobial effects, which are closely linked to cellular signaling pathways, such as the NF-κB and MAPK pathways. Additionally, we review the potential therapeutic benefits of agarwood essential oil for its antidepressant properties, which are linked to the regulation of stress-related neurochemical and hormonal pathways. This Review also addresses the challenges of sustainable agarwood production, highlighting issues such as overharvesting and habitat loss while discussing the potential strategy of harnessing microbes in agarwood production to support the ecological preservation of wild resources. By advancing our knowledge of agarwood and sesquiterpene characteristics, we propose potential directions for the future application and sustainable development of agarwood research.

Nerium oleander Cultivation in Tamil Nadu, India: An Exploratory Study

In Indian traditional medicine, Nerium oleander is a significant medicinal herb. This plant has the potential to be fatal in many situations; poisoning cases have been documented in tropical and subtropical regions of the world, and suicide cases are common in South Asian nations, particularly in India and Sri Lanka. The plant is hazardous in all sections and contains a range of cardiac glycosides, such as gentiobiosyl, neriin, oleandrin, cardenolides, and odoroside. Additionally, this plant species produces secondary metabolites with medicinal uses, including steroids, flavonoids, and alkaloids. Antibacterial, anthelmintic, anti-inflammatory, hepatoprotective, immunopotential, anti-pyretic, antioxidant, antifungal, anticancer, and anti-HIV activity are among the significant pharmacological activities. Nerium indicum is also highly well-liked for its traditional medical applications, which include treating inflammation, wound healing, cancer, asthma, corns, heart disease, and epilepsy. Its bloom is the source of a green dye that is used to cure skin conditions, promote wound healing, and have anti-inflammatory properties. Both ultrasonic transesterification and the magnetic stirrer method have been utilized to produce biodiesel from nerium oleander oil. When administered topically, Nerium oleander's special qualities also have a notable age-defying effect. Nerium oleander to acquire several C and N compounds as well as heavy metals that are frequently produced by cars, including as Pb, Cd, Ni, and Zn. Based on the significance of nerium, the study was conducted in the Kanyakumari district of Tamil Nadu, where there is a greater area dedicated to nerium plant cultivation. The study's focus was on the factors that influence nerium cultivation, the factors that contribute to the volatility of nerium prices, and the challenges that farmers face in terms of production and marketing.

Biofortification of Mushrooms: A Promising Approach

Mushrooms exhibit a broad spectrum of pharmacological activities and are widely used for medical purposes and in nutrition. Numerous bioactive metabolites are responsible for these activities. Their distribution and biological effects differ depending on the fungal species and their chemical composition. Biofortification is a sustainable process that aims to improve the nutritional profile of food crops, as most of them are low in key nutrients. This review aims to delve into the process of fungal biofortification and review the most commonly used elements and species. Through biofortification, it is possible to combat hidden hunger, which affects as many as 2 billion people worldwide. “Hidden hunger” is a phenomenon in which the organism lacks the minerals and vitamins needed for development, growth, and good overall health. Mushrooms are increasingly being considered for biofortification due to their ability to accumulate various elements (both micro- and macroelements).

Hyaluronic Acid-Modified Luteolin-Copper Complex Nanodelivery System for Bacterial Prostatitis.

Bacterial prostatitis is a common disease of the male genitourinary system, which seriously affects the normal life and health of male patients. Antibiotics are commonly used in the clinical treatment of bacterial prostatitis, but the efficacy of fluoroquinolones is gradually declining due to the increasing drug resistance of bacteria. Hence, it is necessary to find new antibacterial drugs to treat bacterial prostatitis. Luteolin is a natural flavonoid compound with many pharmacological activities such as antibacterial and anti-inflammatory activities, but its poor water solubility and low structural stability seriously limit its clinical application. In this study, we designed a targeting drug delivery system via a luteolin-copper complex grafted with hyaluronic acid. The results of the characterization proved the successful synthesis of the system. The results of the in vitro performance test show that the system has a good antibacterial effect and excellent blood compatibility and can be effectively released under different pH conditions. The prepared nanodrug delivery system not only provides a new idea for the treatment of bacterial prostatitis but also lays a theoretical and practical foundation for the wide application of luteolin in clinical practice.

Simultaneous estimation of catechin hydrate and vanillic acid by HPTLC from Alternanthera sessilis plant extract and evaluating their pharmacological activity

Objective: The aim of this study was to identify and quantify catechin hydrate and vanillic acid from plant Alternanthera sessile and determine their antimicrobial and antioxidant activity. Method: By using toluene: ethyl acetate: formic acid (5:5:1v/v) as a mobile phase combination, separation of catechin hydrate and vanillic acid were carried out at 254 nm. Parameters validation of developed method were performed for linearity, precision, robustness, LOD and LOQ. Microorganism’s zone of inhibition determine by using agar well diffusion method and antimicrobial activity of these two phytoconstituents were evaluated. DPPH assay method was used for determination of antioxidant activity. Result: The Rf values for catechin hydrate and vanillic acid were found to be 0.49 and 0.75 respectively and validation of parameters showed linear and accurate method for analysis. The zone of inhibition was found immensely significant for S.aureus, B.subtillis and C. albicans which when compared to standard antimicrobial agents and gave promising results. Catechin hydrate and vanillic acid also shows significant antioxidant activity. Conclusion: The optimised method was found to be efficient, precise, accurate, specific and economic. Therefore, the method would be useful for qualitative and quantitative routine analysis in pharmaceutical industry. Also, the antimicrobial and antioxidant effect of these two phytochemicals shows excellent result which is useful in many pharmaceuticals and disease conditions.

Synergistic Phytochemical and Pharmacological Actions of Hair RiseTM Microemulsion: A Novel Herbal Formulation for Androgenetic Alopecia and Hair Growth Stimulation.

Androgenetic alopecia (AGA) is a genetic condition characterized by an excessive response to androgens, leading to hairline regression in men and hair thinning at the vertex in women, which can negatively impact self-esteem. Conventional synthetic treatments for AGA are often limited by their side effects. In contrast, Thai medicinal plants offer a promising alternative with fewer adverse effects. This study investigates the synergistic phytochemical and pharmacological effects of a novel Hair RiseTM microemulsion, formulated with bioactive extracts from rice bran (Oryza sativa), shallot bulb (Allium ascalonicum), licorice root (Glycyrrhiza glabra), and corn kernels (Zea mays), for the treatment of hair loss. The microemulsion, in concentrations of 50%, 75%, and 100% (v/v), significantly enhanced the proliferation of human hair follicle dermal papilla cells (HFDPCs) compared to minoxidil. Additionally, it upregulated critical hair growth signaling pathways, including Wnt/β-catenin (CTNNB1), Sonic Hedgehog (SHH, SMO, GLI1), and vascular endothelial growth factor (VEGF), surpassing standard controls such as minoxidil and purmorphamine. The microemulsion also demonstrated potent anti-inflammatory and antioxidant properties by reducing nitric oxide production and oxidative stress, factors that contribute to inflammation and follicular damage in AGA. Furthermore, Hair RiseTM inhibited 5α-reductase (types 1-3), a key enzyme involved in androgen metabolism, in both human prostate cancer cells (DU-145) and HFDPCs. These findings suggest that Hair RiseTM microemulsion presents a promising natural therapy for promoting hair growth and reducing hair loss via multiple synergistic mechanisms, offering a potent, plant-based alternative to synthetic treatments.

Metabolomics analysis of (Geo)propolis from Brazilian stingless bees by FIA and UHPLC-HRMS (Orbitrap)

Native stingless bees (Meliponini) from Brazil make (geo)propolis which is largely used in folk medicine, specially by indigenous and quilombos communities and beekeepers´ families but are progressively being recognized for their pharmacological activities. In this study, the ethanolic extracts of (geo)propolis (EEGs) from Melipona marginata, M. quadrifasciata, M. scutellaris, and Tetragonisca angustula were analysed by Flow injection analysis (FIA) and Ultra-high performance liquid chromatography (UHPLC) in a high resolution Orbitrap mass analyser (HRMS) to investigate and compare their chemical profile. Untargeted metabolomic approach based on UHPLC-HRMS experiments, and bioinformatic tools, allowed to annotate 59 compounds from diverse classes such as: flavonoids, phenolic compounds, sugars, terpenoids, and lipids. In addition, using multivariate tools and Flow injection- high resolution mass spectrometry (FIA-HRMS), it was possible to classify samples and identify marker ions related to the bee species or genus and to the geographical origin as a proof of concept.

6827 Pharmacological PPARα Activation In Combination With Ketogenic Nutrition Aggravated Muscle Weakness By Metabolic Failure In Septic Mice

Abstract Disclosure: C. Lauwers: None. M.P. Casaer: None. W. Vankrunkelsven: None. S. Derde: None. I. Derese: None. S. Vander Perre: None. P. Vermeersch: None. G.H. Van Den Berghe: None. L. Langouche: None. Introduction: In septic mice, infusion of ketone bodies (beta-hydroxybutyrate (BHB)) attenuated muscle weakness, a debilitating complication of critical illness. Interestingly, in critically ill children, fasting-induced ketosis also improved outcomes, but in adults ketosis upon fasting was impaired, likely due to suppression of PPARα, a key transcriptional regulator of ketogenesis. In septic mice, pharmacological induction of PPARα by pemafibrate (PF) alone, however, was ineffective in promoting ketosis. Therefore, we here hypothesized that PPARα activation by PF combined with ketogenic nutrition can more effectively induce ketosis and hereby reduce muscle weakness in sepsis. Methods: In a fluid-resuscitated and antibiotic-treated mouse model of prolonged (5 days) sepsis (male C57BL/6J), the impact of PF (1mg/kg/d) combined with 4 types of parenteral nutrition (PN) was studied. Mice were either allocated to PF + total PN (composed of glucose, long-chain triglycerides (LCTs) and amino acids) (TPN, n = 18), PF + TPN with an extra LCT emulsion (TPN + LCTs, n = 18), PF + a pure low dose LCT emulsion (Low LCT, n = 16) or PF + a pure high dose LCT emulsion (High LCT n = 18). Healthy control mice on standard chow served as a reference (HC, n=19). After 5 days of sepsis, ex vivo muscle force (aurora scientific®), plasma BHB and lipids (TG, FFA, LDL- and HDL-cholesterol; commercial assays), and liver gene expression levels were measured. Metabolomics of muscle tissue was assessed by LC-MS and plasma acylcarnitines by LC-MS-MS. Results: Liver PPARα gene expression was higher in all PF-treated mice than in HCs. Compared to HCs, specific muscle force was reduced in all septic mice, but mostly so in both PF + LCT groups (PF + Low LCT: 10.7%, PF + High LCT: 25.0%, PF+TPN + LCTs: 44.6%, PF+TPN: 58.4% of HC: 124.7 mN/mm²; p = 0.0001). PF + TPN + LCTs did not induce ketosis, whereas BHB plasma levels increased 95-fold in the PF + High LCT and 10-fold in the PF + Low LCT group (p < 0.0001 vs. other groups). Glycemia was lower in both PF + LCT groups relative to the other septic mice (PF + Low LCT: 52 mg/dl; PF + High LCT: 80 mg/dl; PF + TPN + LCTs: 108 mg/dl; PF + TPN: 102 mg/dl; p < 0.0001). Compared to the PF + TPN group, plasma lipids and long-chain acylcarnitines were increased in all other septic mice with the highest levels in the PF + High LCT group. Muscular glycolytic intermediates and ATP levels were depleted in both PF + LCT groups in comparison with all other septic mice and HCs. Conclusion: In septic mice, PF-induced PPARα activation combined with TPN, irrespective of the amount of LCTs, was unable to induce ketosis and did not attenuate muscle weakness. By contrast, PF-induced PPARα activation in combination with pure LCTs resulted in ketosis, but aggravated rather than improved muscle weakness, irrespective of the dose. In these groups, metabolic analyses suggested a bioenergetic failure of muscle fibers with an accumulation of plasma lipids. Presentation: 6/1/2024

Qiwei Jinggan Ling regulates oxidative stress and lipid metabolism in alcoholic liver disease by activating AMPK

BackgroundAlcoholic liver disease (ALD) is a severe public health concern worldwide and there is still a lack of effective treatments. Qiwei Jinggan Ling (QJL) has protective effects against various liver injuries, but its pharmacological action on ALD has received little attention. PurposeTo investigate the effect and mechanism of QJL on ALD in vivo and in vitro. MethodsIn vivo, an ALD mouse model was established by alcohol combined with a high-fat diet (HFD) and treated with QJL. Biochemical indicators, HE staining, and Oil Red O staining were employed to assess hepatic oxidative stress, steatosis, and alcohol metabolism. RNA sequencing analysis was performed, and the results were verified by qRT-PCR and Western blot to elucidate the hepatoprotective mechanism of QJL. In vitro, HepG2 cells were co-stimulated with NaOA (sodium oleate) and EtOH (ethanol), followed by intervention with Compound C (CC, AMPK inhibitor) and QJL-containing serum. Oil Red O, BODIPY (boron-dipyrromethene), and ROS (reactive oxygen species) staining were applied to validate the efficacy and mechanism of QJL-containing serum. The expression of AMP-activated protein kinase (AMPK) pathway-related factors was analyzed through qRT-PCR and Western blot for additional corroboration. Moreover, the key pharmacodynamic components of QJL were identified by UPLC-MS/MS and molecular docking. ResultsIn vivo, QJL ameliorated liver structural disorders, steatosis, oxidative stress, and impaired alcohol metabolism, as indicated by biochemical indicators and histopathological assays. RNA sequencing analysis revealed that QJL reversed the expression of genes related to alcohol metabolism, fatty acid metabolism, and cholesterol metabolism. The results of qRT-PCR and Western blot were in line with those of RNA sequencing. Furthermore, it was discovered that QJL significantly upregulated the expression of p-AMPK and downregulated the expression of sterol regulatory element binding transcription factor 1 (SREBP-1c). In vitro, biochemical indicators and staining assays demonstrated that QJL-containing serum inhibited lipid accumulation and oxidative stress. The qRT-PCR and Western blot analysis revealed that QJL-containing serum markedly enhanced the expression of p-AMPK and carnitine palmitoyltransferase 1a (Cpt1a), while suppressing the expression of SREBP-1c, fatty acid synthase (Fasn), and acetyl-coenzyme A carboxylase 1 (ACC-1). However, CC inhibited the above pharmacological activities of QJL-containing serum. Additionally, (2S)-Liquiritigenin, Glycyrrhetinate, Isovitexin, Taxifolin, and Yohimbine were proved to be the key active components of QJL. ConclusionQJL had the potential to be a therapeutic drug for ALD by activating the AMPK pathway, thereby regulating lipid metabolism and inhibiting oxidative stress.

Lubiprostone Improves Distal Segment-Specific Colonic Contractions through TRPC4 Activation Stimulated by EP3 Prostanoid Receptor

Background: Prokinetic agents are effective in increasing gastrointestinal (GI) contractility and alleviating constipation, often caused by slow intestinal motility. Lubiprostone (LUB), known for activating CLC-2 chloride channels, increases the chloride ion concentration in the GI tract, supporting water retention and stool movement. Despite its therapeutic efficacy, the exact mechanisms underlying its pharmacological action are poorly understood. Here, we investigated whether LUB activates the canonical transient receptor potential cation channel type 4 (TRPC4) through stimulation with E-type prostaglandin receptor (EP) type 3. Methods: Using isotonic tension recordings on mouse colon strips, we examined LUB-induced contractility in both proximal and distal colon segments. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to determine mRNA levels of EP1-4 receptor subtypes in distal colonic muscular strips and isolated myocytes. The effects of a TRPC4 blocker and EP3 antagonist on LUB-stimulated contractions were also evaluated. Results: LUB showed significant contraction in the distal segment compared to the proximal segment. EP3 receptor mRNA levels were highly expressed in the distal colon tissue, which correlated with the observed enhanced contraction. Furthermore, LUB-induced spontaneous contractions in distal colon muscles were reduced by a TRPC4 blocker or EP3 antagonist, indicating that LUB-stimulated EP3 receptor activation may lead to TRPC4 activation and increased intracellular calcium in colonic smooth muscle. Conclusions: These findings suggest that LUB improves mass movement through indirect activation of the TRPC4 channel in the distal colon. The segment-specific action of prokinetic agents like LUB provides compelling evidence for a personalized approach to symptom management, supporting the defecation reflex.

Identification and functional analysis of GmPsaL regulating pod color in vegetable soybean

BackgroundVegetable soybean is rich in nutrients and has a unique flavor. It is highly preferred by people because of its pharmacological activities, including those that regulate the intestines and lower blood pressure. The pod color of vegetable soybeans is an important quality that indicates their freshness and has a significant impact on their commercialization.ResultsIn this study, pod color was evaluated in 301 vegetable soybean accessions collected from various regions. Genome-wide association analysis was carried out using the Mixed linear model (MLM), a total of 18 quantitative trait loci including 117 SNPs were detected. Two significant QTLs located on chromosomes 6 (qGPCL4 /qGPCa1/qGPCb2) and 18 (qGPCL10/qGPCb3) were consistently detected across different variables. Based on gene functional annotation, 30 candidate genes were identified in these two candidate intervals. Combined with transcriptome analysis, Glyma.18g241700 has been identified as a candidate gene for regulating pod color in vegetable soybeans. Glyma.18g241700 encodes a chlorophyll photosystem I subunit XI. which localizes to the chloroplast named GmPsaL, qRT-PCR analysis showed that GmPsaL was specifically highly expressed in developing pods. Furthermore, overexpression of GmPsaL in transgenetic Arabidopsis plants produced dark green pods.ConclusionsThese findings may be useful for clarifying the genetic basis of the pod color of vegetable soybeans. The identified candidate genes may be useful for the genetic improvement of the appearance quality of vegetable soybeans.