Explore the vast range of titles available.

The prevalence of alcohol consumption among the younger generation remains alarmingly high. A hangover is a common short-term consequence observed after consuming alcohol. To effectively study alcohol-induced hangovers, reliable and translational animal models, along with appropriate testing methods, are required. While several testing approaches have been used in hangover-induced mice, they often fail to assess innate behaviors comprehensively and are limited by short observation periods. Although existing studies have developed methods to assess hangover-related behaviors in rodents, few have focused on innate behaviors. This study aimed to establish a model for assessing the innate behaviors of hangover-induced mice using automated home-cage-like behavioral monitoring. Mice were intraperitoneally injected with ethanol at doses of 3, 2, or 1 g/kg, followed by behavioral assessments, including exploratory actions and long-term home-cage-like behaviors during both day and night phases. Results showed a significant reduction in mobile behaviors (climbing, locomotion, rearing), speed, and distance traveled, along with increased immobility in both exploratory and long-term home-cage-like assessments. Furthermore, there was a significant decrease in exploratory behaviors and long-term home-cage-like activities, which were linked to hangover symptoms. This study provides a preliminary approach for assessing hangover behaviors in mice using automated behavioral monitoring, ensuring improved animal welfare, optimised timing, and extended assessment durations. Hence, we propose automated home-cage-like behavioral assessment as an exploratory model for evaluating hangover behaviors in mice, which may serve as a useful tool for future research on the therapeutic efficacy of anti-hangover compounds.

Alkaloid analgesics have been associated with adverse effects on the central nervous system (CNS). Therefore, it is crucial to characterize the effects of alkaloid analgesics. Plants rich in lycorine, an alkaloid, have shown promise as analgesics. However, the exploration of their CNS side effects, and analgesic effectiveness remains incomplete. The aim of the present study was to investigate the CNS safety profiles of lycorine and its potential analgesic efficacy. Lycorine (3, 10, and 30 mg/kg, intraperitoneal) did not affect motor coordination, and doses of 3 and 10 mg/kg of lycorine did not lead to any impairment in spontaneous locomotor activity. However, the highest dose (30 mg/kg) demonstrated a significant impairment in rearing behavior and an increase in immobility. The safety doses were subsequently used to assess the analgesic efficacy of lycorine in a mouse model of inflammatory pain. Lycorine (1, 3, and 10 mg/kg, intraperitoneal) demonstrated a dose-dependent reduction in pain-like behaviors in formalin-induced mice. In the in vitro study, lycorine regulated immune cells, suggesting its involvement as a cellular mechanism underlying the suppression of pain-like behaviors observed in the formalin model. Overall, our findings delineate the CNS safety range of lycorine in mice and suggest its potential use as an analgesic.

Curcumin diglutaric acid (CurDG), an ester prodrug of curcumin, has the potential to be developed as an anti-inflammatory agent due to its improved solubility and stability. In this study, the anti-inflammatory effects of CurDG were evaluated. The effects of CurDG on inflammatory mediators were evaluated in LPS-stimulated RAW 264.7 macrophage cells. CurDG reduced the increased levels of NO, IL-6, and TNF- α, as well as iNOS and COX-2 expression in cells to a greater extent than those of curcumin, along with the potent inhibition of MAPK (ERK1/2, JNK, and p38) activity. The anti-inflammatory effects were assessed in vivo by employing a carrageenan-induced mouse paw edema model. Oral administration of CurDG demonstrated significant anti-inflammatory effects in a dose-dependent manner in mice. The effects were significantly higher compared to those of curcumin at the corresponding doses (p < 0.05). Moreover, 25 mg/kg curcumin did not exert a significant anti-inflammatory effect for the overall time course as indicated by the area under the curve data, while the equimolar dose of CurDG produced significant anti-inflammatory effects comparable with 50, 100, and 200 mg/kg curcumin (p < 0.05). Similarly, CurDG significantly reduced the proinflammatory cytokine expression in paw edema tissues compared to curcumin (p < 0.05). These results provide the first experimental evidence for CurDG as a promising anti-inflammatory agent.

The drug treatment for neuropathic pain remains a challenge due to poor efficacy and patient satisfaction. Curcumin has been reported to alleviate neuropathic pain, but its clinical application is hindered by its low solubility and poor oral bioavailability. Curcumin diglutaric acid (CurDG) is a curcumin prodrug with improved water solubility and in vivo antinociceptive effects. In this study, we investigated the anti-inflammatory mechanisms underlying the analgesic effect of CurDG in the chronic constriction injury (CCI)-induced neuropathy mouse model. Repeated oral administration of CurDG at a low dose equivalent to 25 mg/kg/day produced a significant analgesic effect in this model, both anti-allodynic activity and anti-hyperalgesic activity appearing at day 3 and persisting until day 14 post-CCI surgery (p < 0.001) while having no significant effect on the motor performance. Moreover, the repeated administration of CurDG diminished the increased levels of the pro-inflammatory cytokines: TNF-α and IL-6 in the sciatic nerve and the spinal cord at the lowest tested dose (equimolar to 25 mg/kg curcumin). This study provided pre-clinical evidence to substantiate the potential of pursuing the development of CurDG as an analgesic agent for the treatment of neuropathic pain.

Background Rhizomes of Curcuma wanenlueanga Saensouk, Thomudtha & Boonma have been used in Thai traditional medicine and are included as an ingredient in a Thai traditional liniment formula listed by the Ministry of Public Health of Thailand for treating symptoms related to joints and muscle inflammation. However, anti-inflammatory activity and bioactive constituents of C. wanenlueanga have not yet been investigated. Thus, this study aimed to investigate the anti-inflammatory activity and underlying mechanism of C. wanenlueanga rhizome extract and its responsible bioactive components. Methods The fractionation of bioactive compounds from C. wanenlueanga extract was guided by antioxidant activity on DPPH and Griess assays, and anti-inflammatory activity on LPS-induced RAW 264.7 cells. The biological activities of isolated compounds were first predicted by network pharmacology and further confirmed in cell-based assay with LPS-induced RAW 264.7 cells and enzyme-linked immunosorbent assay (ELISA) of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). Results The ethanolic extract of C. wanenlueanga rhizomes was proved to show anti-inflammatory activity on LPS-induced RAW 264.7 cells. Three curcuminoids including curcumin ( 1 ), demethoxycurcumin ( 2 ), dihydrodemethoxycurcumin ( 3 ), and two sesquiterpenoids, namely curcumenone ( 4 ), and zedoarondiol ( 5 ) were separated from anti-inflammatory fractions of C. wanenlueanga extract. The anti-inflammatory activity of these compounds to attenuate the productions of TNF-α and IL-6 was predicted by pharmacological network. The inflammatory assays, including the Griess assay for NO and ELISA for TNF-α and IL-6, confirmed that all isolated compounds reduced the production of these inflammatory mediators. Conclusion The present study shows the accordance between the results from pharmacological network and cell-based assays, which indicate the anti-inflammatory activity of C. wanenlueanga rhizomes and their bioactive constituents. This suggests the potential of bioactive compounds 1–5 to be used for quality assessment of C. wanenlueanga extract in the development of herbal products.

Analgesic drugs in a combination-form can achieve greater efficacy with lesser side effects compared to either drug alone. The combination of drugs acting at different targets or mechanisms of action has been recognized as an alternative approach for achieving optimal analgesia. In this study, the analgesic effects of pregabalin (30, 60, 100, 200 mg/kg), curcumin (15, 30, 60, 100, 120 mg/kg), and 1:1 fixed-dose ratio of the pregabalin-curcumin combination were assessed using two acute nociceptive pain models, the acetic acid-induced writhing and tail-flick tests in mice. The pregabalin-curcumin combination produced a dose-dependent decrease in mean of writhes and an increase in the percentage of antinociception by the acetic acid-induced writhing test. In the tail-flick test, the combination also showed an improvement in antinociception indicated by the tail-flick latency, % antinociception, and area under the curve (AUC). Isobolographic analysis of interactions demonstrated a significant synergistic interaction effect between pregabalin and curcumin in both acute nociceptive pain models with the experimental ED50 below the predicted additive line and the combination index < 1. These findings demonstrate that the combination of pregabalin and curcumin exhibits a synergistic interaction in mouse models of acute nociceptive pain.

Curcumin is a polyphenol compound that alleviates several neuroinflammation-related diseases including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, epilepsy and cerebral injury. However, the therapeutic efficacy of curcumin is limited by its poor physicochemical properties. The present study aimed to develop a new carrier-linked curcumin prodrug, curcumin diethyl γ-aminobutyrate (CUR-2GE), with improved physicochemical and anti-neuroinflammatory properties. CUR-2GE was designed and synthesized by conjugating curcumin with gamma-aminobutyric acid ethyl ester (GE) via a carbamate linkage. The carbamate linkage was selected to increase stability at acidic pH while GE served as a promoiety for lipophilic enhancement. The synthesized CUR-2GE was investigated for solubility, partition coefficient, stability, and bioconversion. The solubility of CUR-2GE was less than 0.05 μg/mL similar to that of curcumin, while the lipophilicity with log P of 3.57 was significantly increased. CUR-2GE was resistant to chemical hydrolysis at acidic pH (pH 1.2 and 4.5) as anticipated but rapidly hydrolyzed at pH 6.8 and 7.4. The incomplete hydrolysis of CUR-2GE was observed in simulated gastrointestinal fluids which liberated the intermediate curcumin monoethyl γ-aminobutyric acid (CUR-1GE) and the parent curcumin. In plasma, CUR-2GE was sequentially converted to CUR-1GE and curcumin within 1 h. In lipopolysaccharide (LPS)-stimulated BV-2 microglial cells, CUR-2GE effectively attenuated the pro-inflammatory mediators by decreasing the secretion of nitric oxide and cytokines (TNF-α and IL-6) to a greater extent than curcumin due to an increase in cellular uptake. Altogether, the newly developed acid-stable CUR-2GE prodrug is a potential pre-clinical and clinical candidate for further evaluation on neuroprotective and anti-neuroinflammatory effects.

The relocation of Indonesia's capital to Nusantara Capital City (IKN) is expected to accelerate economic transformation in surrounding regions, particularly Samarinda, Balikpapan, North Penajam Paser, and Paser. This study aims to investigate the direct and indirect effects of accounting system implementation, entrepreneurs' accounting literacy, availability of financial information, and accounting knowledge on business information and entrepreneurial growth of small and medium enterprises (SMEs) in these regions. Additionally, this study investigates the mediating role of business information in strengthening these relationships. This research employs a quantitative approach using survey data from 725 SMEs in East Kalimantan. The data is analyzed using Partial Least Squares Structural Equation Modeling to test the proposed relationships. The findings reveal that accounting literacy, financial information availability, and accounting knowledge significantly enhance SME growth and sustainability. Moreover, business information acts as a crucial mediator, reinforcing the positive influence of financial management on entrepreneurial success. These results highlight the importance of financial literacy and access to business information in improving SME resilience and competitiveness in rapidly evolving economic environments.

Folk medicine in Thailand has long made use of Pterocarpus indicus Willd. for treating inflammation-related disorders. However, scientific exploration of isolated compounds from P. indicus for improving inflammation-associated sickness conditions and their impact on central nervous system (CNS) safety remain unexplored. The present study initially screened the anti-neuroinflammatory effects of angolensin, a compound isolated from P. indicus heartwood in vitro. Following substantial findings, the efficacy of angolensin was further evaluated in a mouse model of lipopolysaccharide (LPS)-induced sickness behaviors, alongside an assessment of its CNS safety profiles. The anti-neuroinflammatory effects of angolensin were evaluated in LPS-induced BV-2 microglial cells. The effects of angolensin on sickness behaviors were examined in LPS-induced mice using the Laboratory Animal Behaviors Observation, Registration and Analysis System (LABORAS). Proinflammatory cytokine expression in plasma samples of mice was also determined. LABORAS and rotarod tests were conducted to investigate its impact on the CNS. In vitro assessment of the anti-inflammatory activity of angolensin on BV-2 microglial cells revealed a concentration-dependent reduction in the release of LPS-induced nitric oxide (NO) and proinflammatory cytokines (TNF-α and IL-6). At a concentration of 20 µM, angolensin showed comparable results to the positive control, 20 µM minocycline. In mice, angolensin significantly improved LPS-induced sickness behaviors, as indicated by improved home-cage behaviors. Consistent with the in vitro findings, angolensin attenuated the release of proinflammatory cytokines in the plasma of LPS-induced mice. Importantly, angolensin did not induce any adverse effects on locomotion, motor coordination, or general well-being, indicating a favorable CNS safety profile. Overall, these results highlight the anti-inflammatory potential of angolensin in mitigating sickness behaviors in mice, while demonstrating its CNS safety.

Glioblastoma, a fatal brain cancer with limited treatments and poor prognosis, could benefit from targeting the L-type amino acid transporter I (LAT1). LAT1 is essential for cancer cells to acquire necessary amino acids. Tetrahydrocurcumin (THC), a key curcumin derivative, shows potential for glioblastoma treatment. However, its effectiveness is hindered by poor physicochemical and pharmacokinetic properties. Therefore, this study aims to improve the therapeutic efficacy of THC against glioblastoma by chemically modifying it to target LAT1. A novel series of THC-amino acid conjugates were synthesized by conjugating five amino acids: glycine, leucine, isoleucine, and phenylalanine to THC via carbamate bonds. The therapeutic efficacy of THC-amino acid conjugates was further examined in C6 glioma cells, including the role of LAT1 in their therapeutic effects. Among the conjugates tested, THC conjugated with two phenylalanines (THC-di-Phe) showed remarkably higher cytotoxicity against C6 glioma cells (35.8 μM) compared to THC alone (110.7 μM). THC-di-Phe induced cellular death via necrosis and apoptosis, outperforming THC. Additionally, THC-di-Phe inhibited C6 cell proliferation and migration more effectively than THC. Co-incubation of THC-di-Phe with the LAT1 inhibitor 2-Aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) further increased cellular death. THC-di-Phe also significantly inhibited the P70SK/S6 pathway, regulated by LAT1 inhibitors, more effectively than THC and displayed a similar binding mode with both JX-075 and BCH to the active site of LAT1. Findings suggest the potential role of THC-di-Phe as a LAT1 inhibitor and provide novel insight into its use as a potent antitumor agent in glioma with increased therapeutic efficacy.