Search Results (15)

Mycobacterium avium complex (MAC) infections present significant therapeutic challenges due to their inherent antibiotic resistance, demanding innovative treatment approaches. This study investigated the antimicrobial and antioxidant potential of a novel compound, Fullerene Gallium Phosphonate (FGP), and compared its effects against a previously tested similar compound, Fullerene Disodium Phosphonate (FDSP). Results of experiments using MAC cultures and infected THP-1 macrophages treated with varying FGP and FDSP concentrations (1, 10, 100 µg/mL) revealed that FGP demonstrated greater efficacy than FDSP in reducing M. avium colony-forming units (CFU), achieving a nearly 3-fold reduction by day 8, compared to a 2-fold decrease with FDSP. In infected macrophages, FGP significantly decreased bacterial load at 1 and 10 µg/mL (p < 0.01). FGP also lowered oxidative stress, reflected by a significant reduction in malondialdehyde (MDA) levels on day 4 (p < 0.05) and decreased IL-6 (2-fold) and TNF-α levels (3-fold) by day 8, indicating both antimicrobial and anti-inflammatory effects. However, FGP paradoxically increased MAC burden at its highest concentration and showed no significant difference in efficacy of different concentrations. These findings suggest that FGP may serve as a promising candidate for antimycobacterial therapy with dual antibacterial and antioxidant effects. Further research is crucial to fully elucidate its mechanism of action and find the optimal therapeutic window. Full article

Perilla seed has long been recognized in traditional diets for its health-promoting properties, but its potential role in hair loss prevention remains underexplored. This study compared three extraction methods—maceration (MAC), screw pressing (SC), and supercritical fluid extraction (SFE)—to determine their efficiency in recovering bioactive compounds and their effects on androgenetic alopecia (AGA)-related pathways. The SFE extract contained the highest levels of polyunsaturated fatty acids and tocopherols, while MAC uniquely recovered a broader range of polyphenols. Among all extracts, SFE-derived perilla seed extract showed the most consistent biological effects, promoting proliferation of human hair follicle dermal papilla cells (HFDPCs) by 139.4 ± 1.1% at 72 h (p < 0.05). It also reduced TBARS and nitrite levels in HFDPCs to 66.75 ± 0.62% of control and 0.87 ± 0.01 μM, respectively, indicating strong antioxidant and anti-inflammatory effects. Importantly, the SFE extract significantly downregulated SRD5A1-3 and TGF-β1 expression—key genes involved in androgen-mediated hair follicle regression—outperforming finasteride, dutasteride, and minoxidil in vitro by approximately 1.10-fold, 1.25-fold, and 1.50-fold, respectively (p < 0.05). These findings suggest that perilla seed extract obtained via supercritical fluid extraction may offer potential as a natural candidate to prevent hair loss through multiple biological mechanisms. These in vitro results support its further investigation for potential application in functional food or nutraceutical development targeting scalp and hair health. Full article

Oximes have been reported to exhibit useful pharmaceutical properties, including compounds with anticancer, anti-arthritis, antibacterial, and neuroprotective activities. Many oximes are kinase inhibitors and have been shown to inhibit various kinases. Herein, a panel of oxime derivatives of tricyclic isatins was synthesized and evaluated for inhibition of cellular inflammatory responses and binding affinity to several kinases. Compounds 5a and 5d (a.k.a. NS-102), which have an unsubstituted oxime group, inhibited lipopolysaccharide (LPS)-induced nuclear factor-κB/activating protein 1 (NF-κB/AP-1) transcriptional activity in human THP-1Blue monocytic cells and interleukin-6 (IL-6) production in human MonoMac-6 monocytic cells, with IC₅₀ values in the micromolar range. These compounds also inhibited LPS-induced production of several other proinflammatory cytokines, including IL-1α, IL-1β, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor (TNF) in MonoMac-6 cells. Compounds 5a and 5d exhibited nanomolar/submicromolar binding affinity toward several kinase targets. The most potent inhibitor, 5d (3-(hydroxyimino)-5-nitro-1,3,6,7,8,9-hexahydro-2H-benzo[g]indol-2-one), demonstrated high binding affinity for 12 kinases, including DYRK1A, DYRK1B, PIM1, Haspin, HIPK1-3, IRAK1, NEK10, and DAPK1-3. Molecular modeling suggested modes of binding interaction of selected compounds in the DYRK1A and PIM1 catalytic sites that agreed with the experimental binding data. Our results demonstrate that tricyclic isatin oximes could be potential candidates for developing anti-inflammatory drugs with neuroprotective effects for treating neurodegenerative diseases. Full article

Worldwide, several million people are infected with mycobacteria such as Mycobacterium tuberculosis (M. tb) or non-tuberculous mycobacteria (NTM). In 2023, 10.8 million cases and 1.25 million deaths due to M. tb were recorded. In Europe and North America, the emergence of NTM is tending to outstrip that of M. tb. Among pulmonary NTM, Mycobacterium avium complex (MAC) is the most common, accounting for 80% of NTM infections. First-line treatment requires the combination of at least three antibiotics over a long period and with different mechanisms of action to limit cross-resistance. The challenge is to discover more effective new anti-MAC molecules to reduce the duration of treatment and to overcome resistant strains. The aim of this review is to present an overview of the challenges posed by MAC infection such as side effects, reinfections and resistance mechanisms. The latest therapeutic options such as the optimized combination therapy, drug repurposing and the development of new formulations, as well as new anti-MAC compounds currently in (pre)clinical trials will also be discussed. Full article

Underutilized plant species such as Asteriscus graveolens (Forssk.) Less., Haloxylon scoparium Pomel, and Ruta chalepensis L. have been historically valued in traditional medicine for their potential health benefits. These species present an untapped source of bioactive compounds with significant applications in the food and pharmaceutical industries, including the development of functional foods and additives. Recent advances in food processing have introduced innovative methods, such as pulsed electric fields (PEFs), to enhance the extraction of valuable compounds without compromising their integrity or quality. This study investigates the impact of PEF technology on the recovery of bioactive compounds from these plants, comparing it with conventional maceration (MAC) techniques. Phenolic compound profiles and biological activities, including antioxidant, antimicrobial, anti-inflammatory, and cytotoxic effects, were evaluated. The results demonstrated that for R. chalepensis, PEF extraction achieved comparable phenolic content (58 mg/g) to MAC (72 mg/g). However, MAC generally provided higher phenolic yields for other plants. A. graveolens extracts exhibited significant antitumoral and anti-inflammatory potentials. The antimicrobial results indicated that MAC extracts were more effective against bacterial growth, while PEF extracts outperformed MAC against A. brasiliensis (MIC: 10 mg/mL). Antioxidant potential was observed in both methods, with TBARS IC₅₀ values ranging from 17 to 79.5 µg/mL. While MAC generally yielded superior results, PEF extraction showed great promise as an environmentally sustainable alternative, eliminating the need for organic solvents and aligning with green extraction principles. Full article

Plant botanical extracts are recognized for being a source of biologically active phytochemicals that potentially have diverse applications. The phytochemical composition, potential cytotoxicity, and insecticidal effectiveness of three leaf extracts from the folkloric medicinal plant Mammea americana L. (Calophyllaceae) were investigated. Micro-Soxhlet extraction with chloroform, dichloromethane, and methanol was used, and key phytochemicals were identified via Gas Chromatography-Mass Spectrometry (GC-MS). The extracts were mainly composed of sesquiterpenes, carboxylic acids, coumarins, esters, diterpenes, and other bioactive compounds. Potential cytotoxicity was assessed using brine shrimp lethality tests, where all extracts displayed high toxicity to Artemia salina. The dichloromethane extract (MAD) had the lowest LC₅₀ value (8.39 μg/mL), followed by methanol extract (MAM, 11.66 μg/mL) and chloroform extract (MAC, 12.67 μg/mL). Insecticidal activity was tested against Ferrisia sp. (Hemiptera:Pseudococcidae), demonstrating the highest efficacy with the methanolic extract (LC₅₀ = 5.90 mg/mL after 48 h). These findings provide a basis for further research into the bioactive components of Mammea americana leaves, particularly their antibacterial, anti-inflammatory, and anticancer properties. It also highlights the potential of Mammea americana L. leaf extracts as botanical insecticides due to their high bioactivity against agricultural pests of economic significance. This is the first study that evaluates the insecticidal activity of Mammea americana leaf extracts against Ferrisia sp. insects, offering valuable insights into using plant-based natural products in pest control. Full article

The c-Jun N-terminal kinase (JNK) family includes three proteins (JNK1-3) that regulate many physiological processes, including cell proliferation and differentiation, cell survival, and inflammation. Because of emerging data suggesting that JNK3 may play an important role in neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease, as well as cancer pathogenesis, we sought to identify JNK inhibitors with increased selectivity for JNK3. A panel of 26 novel tryptanthrin-6-oxime analogs was synthesized and evaluated for JNK1-3 binding (K_d) and inhibition of cellular inflammatory responses. Compounds 4d (8-methoxyindolo[2,1-b]quinazolin-6,12-dione oxime) and 4e (8-phenylindolo[2,1-b]quinazolin-6,12-dione oxime) had high selectivity for JNK3 versus JNK1 and JNK2 and inhibited lipopolysaccharide (LPS)-induced nuclear factor-κB/activating protein 1 (NF-κB/AP-1) transcriptional activity in THP-1Blue cells and interleukin-6 (IL-6) production by MonoMac-6 monocytic cells in the low micromolar range. Likewise, compounds 4d, 4e, and pan-JNK inhibitor 4h (9-methylindolo[2,1-b]quinazolin-6,12-dione oxime) decreased LPS-induced c-Jun phosphorylation in MonoMac-6 cells, directly confirming JNK inhibition. Molecular modeling suggested modes of binding interaction of these compounds in the JNK3 catalytic site that were in agreement with the experimental data on JNK3 binding. Our results demonstrate the potential for developing anti-inflammatory drugs based on these nitrogen-containing heterocyclic systems with selectivity for JNK3. Full article

Dairy farming is the most important economic activity in animal husbandry. Mastitis is the most common disease in dairy cattle and has a significant impact on milk quality and yield. The natural extract allicin, which is the main active ingredient of the sulfur-containing organic compounds in garlic, has anti-inflammatory, anticancer, antioxidant, and antibacterial properties; however, the specific mechanism underlying its effect on mastitis in dairy cows needs to be determined. Therefore, in this study, whether allicin can reduce lipopolysaccharide (LPS)-induced inflammation in the mammary epithelium of dairy cows was investigated. A cellular model of mammary inflammation was established by pretreating bovine mammary epithelial cells (MAC-T) with 10 µg/mL LPS, and the cultures were then treated with varying concentrations of allicin (0, 1, 2.5, 5, and 7.5 µM) added to the culture medium. MAC-T cells were examined using RT–qPCR and Western blotting to determine the effect of allicin. Subsequently, the level of phosphorylated nuclear factor kappa-B (NF-κB) was measured to further explore the mechanism underlying the effect of allicin on bovine mammary epithelial cell inflammation. Treatment with 2.5 µM allicin considerably decreased the LPS-induced increase in the levels of the inflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) and inhibited activation of the NOD-like receptor protein 3 (NLRP3) inflammasome in cow mammary epithelial cells. Further research revealed that allicin also inhibited the phosphorylation of inhibitors of nuclear factor kappa-B-α (IκB-α) and NF-κB p65. In mice, LPS-induced mastitis was also ameliorated by allicin. Therefore, we hypothesize that allicin alleviated LPS-induced inflammation in the mammary epithelial cells of cows probably by affecting the TLR4/NF-κB signaling pathway. Allicin will likely become an alternative to antibiotics for the treatment of mastitis in cows. Full article

‘Huahong’ is a popular apple cultivar because of its anti-browning properties and appealing aroma and flavor. It is mainly planted by grafting on dwarf interstocks in Northeast China. We investigated the different aroma profiles of apple fruits grown from six dwarf interstocks (‘CG24’, ‘SH38’, ‘SH3’, ‘MD001’, ‘Mac9’, and ‘CX5’) and from no interstocks (CK). A total of 55 VOCs were detected, including esters (25), aldehydes (14), alcohols (8), ketones (3), alkane hydroxyls (3), and acids (2). Among the VOCs, 48 were detected in the skin and 21 in the pulp. The skin of ‘Huahong’ apples had a strong sweet aroma, and the pulp was green with a subtle aroma. The dominant compounds (>5% of total content) in the skin were 2-methyl butyl acetate, hexyl 2-methyl butyrate, caproic acid butyl ester, hexanal, (Z)-2-heptene aldehyde, and 6-methyl-5-heptene-2-ketone, while in the pulp, they were 2-methyl butyl acetate, methanol, 2-methyl-1-butanol, hexanol, and hexane. Compared with CK, ‘SH38’, ‘MD001’, and ‘SH3’ interstocks had increased total aroma content, and ‘CX5’ and ‘CG24’ had suppressed aroma. The effects of interstocks on aroma were mainly reflected in skin. The VOC content ranged from 3297.52 to 9895.75 µg·kg⁻¹ in skin, and from 748.62 to 1369.21 µg·kg⁻¹ in pulp. PCA revealed that use of interstock ‘SH38’ mainly affected esters. ‘MD001’ affected hexane and 4-pentene-1-acetate; ‘Mac9’ and ‘SH3’ affected octanoic acid-2-methyl butyl ester, hexyl butyrate, and 2-methyl-1-butanol; and ‘CX5’ and ‘CG24’ had a greater impact on isoamyl propionate and 1-pentene-3-ol. Finally, ‘SH38’ had the highest principal comprehensive score. ‘SH38’ and ‘SH3’ interstocks resulted in significantly increased apple VOC content. Full article

The c-Jun N-terminal kinases (JNKs) regulate many physiological processes, including inflammatory responses, morphogenesis, cell proliferation, differentiation, survival, and cell death. Therefore, JNKs represent attractive targets for therapeutic intervention. In an effort to develop improved JNK inhibitors, we synthesized the lithium salt of 11H-indeno[1,2-b]quinoxaline-11-one oxime (IQ-1L) and evaluated its affinity for JNK and biological activity in vitro and in vivo. According to density functional theory (DFT) modeling, the Li⁺ ion stabilizes the six-membered ring with the 11H-indeno[1,2-b]quinoxaline-11-one (IQ-1) oximate better than Na⁺. Molecular docking showed that the Z isomer of the IQ-1 oximate should bind JNK1 and JNK3 better than (E)-IQ-1. Indeed, experimental analysis showed that IQ-1L exhibited higher JNK1-3 binding affinity in comparison with IQ-1S. IQ-1L also was a more effective inhibitor of lipopolysaccharide (LPS)-induced nuclear factor-κB/activating protein 1 (NF-κB/AP-1) transcriptional activity in THP-1Blue monocytes and was a potent inhibitor of proinflammatory cytokine production by MonoMac-6 monocytic cells. In addition, IQ-1L inhibited LPS-induced c-Jun phosphorylation in MonoMac-6 cells, directly confirming JNK inhibition. In a rat model of focal cerebral ischemia (FCI), intraperitoneal injections of 12 mg/kg IQ-1L led to significant neuroprotective effects, decreasing total neurological deficit scores by 28, 29, and 32% at 4, 24, and 48 h after FCI, respectively, and reducing infarct size by 52% at 48 h after FCI. The therapeutic efficacy of 12 mg/kg IQ-1L was comparable to that observed with 25 mg/kg of IQ-1S, indicating that complexation with Li⁺ improved efficacy of this compound. We conclude that IQ-1L is more effective than IQ-1S in treating cerebral ischemia injury and thus represents a promising anti-inflammatory compound. Full article

Persistent inflammation contributes to a number of diseases; therefore, control of the inflammatory response is an important therapeutic goal. In an effort to identify novel anti-inflammatory compounds, we screened a library of pyridazinones and structurally related derivatives that were used previously to identify N-formyl peptide receptor (FPR) agonists. Screening of the compounds for their ability to inhibit lipopolysaccharide (LPS)-induced nuclear factor κB (NF-κB) transcriptional activity in human THP1-Blue monocytic cells identified 48 compounds with anti-inflammatory activity. Interestingly, 34 compounds were FPR agonists, whereas 14 inhibitors of LPS-induced NF-κB activity were not FPR agonists, indicating that they inhibited different signaling pathways. Further analysis of the most potent inhibitors showed that they also inhibited LPS-induced production of interleukin 6 (IL-6) by human MonoMac-6 monocytic cells, again verifying their anti-inflammatory properties. Structure–activity relationship (SAR) classification models based on atom pair descriptors and physicochemical ADME parameters were developed to achieve better insight into the relationships between chemical structures of the compounds and their biological activities, and we found that there was little correlation between FPR agonist activity and inhibition of LPS-induced NF-κB activity. Indeed, Cmpd43, a well-known pyrazolone-based FPR agonist, as well as FPR1 and FPR2 peptide agonists had no effect on the LPS-induced NF-κB activity in THP1-Blue cells. Thus, some FPR agonists reported to have anti-inflammatory activity may actually mediate their effects through FPR-independent pathways, as it is suggested by our results with this series of compounds. This could explain how treatment with some agonists known to be inflammatory (i.e., FPR1 agonists) could result in anti-inflammatory effects. Further research is clearly needed to define the molecular targets of pyridazinones and structurally related compounds with anti-inflammatory activity and to define their relationships (if any) to FPR signaling events. Full article

The edible beans in Fabaceae have been used for foods and medicines since the ancient time, and being used more and more. It is also appeared as a major ingredient in dairy cooking menu in many regions including Thailand, a rich biodiversity country. Many studies reported on health benefits of their flavonoids, but there is no report on the effect of cooking on phytochemical profile and pharmacological potentials. Thus, this present study aims to complete this knowledge, with the 10 most consumed Fabaceae beans in Thailand, by determining the impact of traditional cooking and gastrointestinal digestion on their phytochemicals, their antioxidant and anti-diabetic activities using different in vitro and in cellulo yeast models. The results showed that Vigna unguiculata subsp. sesquipedalis were the richest source of phytochemicals, whereas the population of V. mungo, Phaseolus vulgaris, V. angularis, and V. unguiculata subsp. sesquipedalis were richest in monomeric anthocyanin contents (MAC). Furthermore, the results clearly demonstrated the impact of the plant matrix effect on the preservation of a specific class of phytochemicals. In particular, after cooking and in vitro digestion, total flavonoid contents (TFC) in Glycine max extract was higher than in the uncooked sample. This study is the first report on the influence of cooking and in vitro gastrointestinal digestion on the inhibition capacity toward advanced glycation end products (AGEs). All samples showed a significant capacity to stimulate glucose uptake in yeast model, and V. angularis showed the highest capacity. Interestingly, the increase in glucose uptake after in vitro digestion was higher than in uncooked samples for both P. vulgaris and G. max samples. The current study is the first attempt to investigate at the effects of both processes not only on the natural bioactive compounds but also on antioxidant and anti-diabetic activities of Thailand’s 10 most consumed beans that can be applied for agro-industrial and phytopharmaceutical sectors. Full article

Mycobacteriosis is mainly caused by two groups of species: Mycobacterium tuberculosis and non-tuberculosis mycobacteria (NTM). The pathogens cause not only respiratory infections, but also general diseases. The common problem in these pathogens as of today is drug resistance. Tuberculosis (TB) is a major public health concern. A major challenge in the treatment of TB is anti-mycobacterial drug resistance (AMR), including multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis. Recently, the success rate of the treatment of drug-resistant tuberculosis (DR-TB) has improved significantly with the introduction of new and repurposed drugs, especially in industrialized countries such as Japan. However, long-term treatment and the adverse events associated with the treatment of DR-TB are still problematic. To solve these problems, optimal treatment regimens designed/tailor-made for each patient are necessary, regardless of the location in the world. In contrast to TB, NTM infections are environmentally oriented. Mycobacterium avium-intracellulare complex (MAC) and Mycobacterium abscessus species (MABS) are the major causes of NTM infections in Japan. These bacteria are naturally resistant to a wide variation of antimicrobial agents. Macrolides, represented by clarithromycin (CLR) and amikacin (AMK), show relatively good correlation with treatment success. However, the efficacies of potential drugs for the treatment of macrolide-resistant MAC and MABS are currently under evaluation. Thus, it is particularly difficult to construct an effective treatment regimen for macrolide-resistant MAC and MABS. AMR in NTM infections are rather serious in Japan, even when compared with challenges associated with DR-TB. Given the AMR problems in TB and NTM, the appropriate use of drugs based on accurate drug susceptibility testing and the development of new compounds/regimens that are strongly bactericidal in a short-time course will be highly expected. Full article

c-Jun N-terminal kinase (JNK) plays a central role in stress signaling pathways implicated in important pathological processes, including rheumatoid arthritis and ischemia-reperfusion injury. Therefore, inhibition of JNK is of interest for molecular targeted therapy to treat various diseases. We synthesized 13 derivatives of our reported JNK inhibitor 11H-indeno[1,2-b]quinoxalin-11-one oxime and evaluated their binding to the three JNK isoforms and their biological effects. Eight compounds exhibited submicromolar binding affinity for at least one JNK isoform. Most of these compounds also inhibited lipopolysaccharide (LPS)-induced nuclear factor-κB/activating protein 1 (NF-κB/AP-1) activation and interleukin-6 (IL-6) production in human monocytic THP1-Blue cells and human MonoMac-6 cells, respectively. Selected compounds (4f and 4m) also inhibited LPS-induced c-Jun phosphorylation in MonoMac-6 cells, directly confirming JNK inhibition. We conclude that indenoquinoxaline-based oximes can serve as specific small-molecule modulators for mechanistic studies of JNKs, as well as potential leads for the development of anti-inflammatory drugs. Full article

Lipopolysaccharide (LPS) is an endotoxin, which may cause immune response and inflammation of bovine mammary glands. Mastitis impairs animal health and results in economic loss. Curcumin (CUR) is a naturally occurring diketone compound, which has attracted widespread attention as a potential anti-inflammatory antioxidant. The purpose of this study is to investigate whether CUR can reduce the damage of bovine mammary epithelial cells (MAC-T) induced by LPS and its underlying molecular mechanism. The MAC-T cell line was treated with different concentrations of LPS and CUR for 24 h. The results showed that CUR rescued the decrease of MAC-T cell viability and cell damage induced by LPS. At the same time, 10 µM CUR and 100 µg/mL LPS were used to treat the cells in the follow-up study. The results showed CUR treatment reduced the accumulation of reactive oxygen species (ROS), the expression of inflammatory cytokines (tumor necrosis factor-a (TNF-α), interleukin-8 (IL-8), IL-6 and IL-1β) and the rate of apoptosis induced by LPS. These effects were associated with the activation of the nuclear factor E2-related factor 2 (NFE2L2)-antioxidant response element (ARE) pathway coupled with inactivation of the nuclear factor-κB (NF-κB) inflammatory and caspase/Bcl2 apoptotic pathways. Full article