Search Results (1,790)

Background/Objectives: Metabolic syndrome (MS) is associated with an increased cardiovascular risk. The aim of this study was to reveal the effects of Chaenomeles japonica fruit juice (CJFJ) on energy balance and biochemical and histological parameters in rats with diet-induced MS. Methods: Fifty Wistar rats were allocated into five groups. For ten weeks, the Control group received a standard laboratory diet and tap water, while the other groups were given a high-fat high-fructose (HFHF) diet. The Control and MS groups were treated with distilled water, while the other three groups were treated with CJFJ at increasing doses. Results: Rats on an HFHF diet consumed less food and more liquids and had a higher caloric intake than the Control group. Among the CJFJ-treated animals, an increased food consumption, as well as an increased total caloric intake, and no difference in body weight gain were observed in comparison with the MS group. CJFJ did not affect glucose tolerance or the triglyceride and total cholesterol levels. CJFJ prevented an HFHF-induced decrease in superoxide dismutase and caused a decrease in thiobarbituric acid-reactive substances in serum. The medium CJFJ dose prevented an HFHF-induced increase in adipose tissue indices. Liver and adipose tissue histology revealed a protective effect of CJFJ. Conclusions: CJFJ may exert beneficial effects on visceral adiposity, oxidative status, and histopathological changes in the liver and adipose tissue in rats with diet-induced MS. Full article

Background/Objectives: Non-small-cell lung cancer (NSCLC) involves oxidative stress and inflammation, driving chemoresistance. Paclitaxel (PTX), a first-line chemotherapy, is limited by these factors. Danggui Buxue Tang (DBT), a polyphenolic-rich traditional Chinese herbal formula, was investigated for its ability to potentiate PTX efficacy by inducing ferroptosis via the Nrf2/GPX4 axis. Methods: Effects of DBT + PTX on cell viability, lipid peroxidation, iron accumulation, and Nrf2/GPX4/SLC7A11 expression were evaluated in A549/HCC827 cells with/without ferrostatin-1 (Fer-1). Findings were validated in an A549 xenograft model. Results: DBT significantly enhanced PTX’s anti-tumor effects in vitro and in vivo, an effect reversed by Fer-1. Combination therapy increased ROS, MDA, and iron while suppressing GPX4/SLC7A11 and promoting Nrf2 nuclear translocation. DBT + PTX synergistically reduced tumor volume and proliferation markers (Ki67/PCNA). Crucially, DBT attenuated PTX-induced hepatotoxicity and nephrotoxicity. Conclusions: DBT potentiates PTX efficacy in NSCLC by disrupting the Nrf2/GPX4 axis to induce ferroptosis while mitigating chemotherapy-related toxicity, supporting its potential as an adjuvant strategy targeting oxidative stress pathways. Full article

Background/Objectives: Non-alcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder for which there are limited pharmacotherapies. Sodium rutin (NaR), a soluble flavonoid derivative, has shown beneficial metabolic effects, but its role in NAFLD remains unclear. This study investigates whether NaR ameliorates high-fat diet (HFD)-induced NAFLD and insulin resistance through promoting hepatic lipophagy. Methods: Male mice aged 8 weeks old were fed a HFD for 12 weeks with/without NaR supplementation. Body weight was measured every week. After 12 weeks of treatment, GTT and ITT were performed to assess insulin resistance. Then, the tissues were collected and hepatic histology, serum biochemistry, and markers of autophagy and senescence were assessed. Results: NaR treatment significantly attenuated HFD-induced weight gain, reduced visceral fat and liver weights, and ameliorated hepatic steatosis and vacuolization. NaR improved serum lipid profiles; lowered alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels; and reduced hepatic cellular senescence. NaR enhanced hepatic autophagy, evidenced by decreased p62 levels, increased LC3-II/LC3-I ratio, and enhanced colocalization of lipid droplets with LC3 and LAMP1 in vivo and in vitro. These changes were accompanied by improved glucose tolerance and insulin sensitivity. Conclusions: NaR effectively alleviates HFD-induced NAFLD and insulin resistance by activating hepatic lipophagy. These findings support NaR as a promising multi-targeted therapeutic candidate for NAFLD. Full article

Background/Objectives: EBV is an oncogenic virus linked to NPC and GC, driving cisplatin resistance. Resveratrol has anticancer activity, but its targets and mechanisms against EBV-positive cancers remain unclear. Methods: We assessed resveratrol’s cytotoxicity in EBV-positive cells via functional assays, identified targets by chemical similarity search and molecular docking, and validated PTPN1 via in vitro experiments and nude mouse xenograft models. Results: Resveratrol inhibited EBV-positive cell viability in a time- and concentration- dependent manner, with IC50 values ranging from 35.85 to 145.7 μM across different cell lines at 24–72 h. Apoptosis rates increased by approximately 2- to 4-fold after 80 μM resveratrol treatment for 24 h. Resveratrol directly targeted PTPN1 (docking score = −4.89) and promoted its degradation via the proteasome pathway, as MG132 reversed this effect. Notably, resveratrol synergized with cisplatin (combination index < 1) to reverse cisplatin resistance in both in vitro and in vivo models. Furthermore, resveratrol induced EBV lytic reactivation through ROS production, as evidenced by the increased expression of BZLF1, BMRF1, and BALF2, which was attenuated by the ROS scavenger NAC. Conclusions: Our findings identify PTPN1 as a direct anticancer target of resveratrol in EBV-positive cancers. Resveratrol enhances the therapeutic efficacy of cisplatin via PTPN1 proteasomal degradation and induces EBV lytic reactivation through ROS accumulation. These findings provide a mechanistic basis for the development of novel combination therapies targeting EBV-associated malignancies. Full article

Objectives: To evaluate the long-term effects on retinal structure and visual function of oral bromelain and curcumin supplementation in patients with inherited retinal dystrophies (IRD) complicated by persistent cystoid macular oedema (CMO). Methods: We retrospectively studied 20 eyes with genetically confirmed IRD complicated by CMO, with refractory to systemic or local treatments performed for 6 months. We collected baseline (V1) and follow-up (V2) data from these IRD-CMO patients, who were continuously supplemented with oral bromelain and curcumin for 12 months. Outcome measures were the Snellen best-corrected visual acuity (BCVA) and central macular thickness (CMT) values, collected by spectral-domain optical coherence tomography (OCT). Based on OCT scans, we classified IRD-CMO as microcystic or macrocystic, performing this sub-grouping in two eye cohorts (n = 10). Baseline median BCVA and CMT differences in both groups were verified (Mann–Whitney test). For both CMO groups, changes from V1 to V2 in median BCVA and CMT values were evaluated (Friedman test). Results: At baseline, both the median BCVA and CMT values were significantly different in both groups (p < 0.01 and p < 0.001). Between V1 and V2, in the microcystic CMO group, a slightly improved median BCVA was found, whereas the median CMT was reduced; however, this did not reach statistical significance (p = 0.6 and p = 0.2, respectively). In the macrocystic CMO group, a significant stable median BCVA was found from V1 to V2, with concomitant significant reduction in median CMT (p < 0.05 for both comparisons). Conclusions: Retinal structural improvement and visual function preservation were observed after oral bromelain and curcumin supplementation in macrocystic IRD-CMO. It is likely that the vasogenic component in macrocystic CMO is more responsive to nutraceutical molecules than the degenerative microcystic component. Full article

Background/Objectives: Sexual dysfunction is a prevalent and multifactorial condition affecting a large proportion of the global population, with limited therapeutic options beyond pharmacological approaches primarily targeting erectile dysfunction. This has increased interest in botanical supplements for sexual health, although mechanistic evidence and clear links between phytochemical composition and biological activity remain scarce. The present study provides an integrative evaluation of a commercial Turnera diffusa extract (Liboost^®) formulated to support sexual health by combining detailed phytochemical characterization with targeted in vitro mechanistic assays. Methods: The extract was characterized by HPLC-DAD-HRMS, enabling the identification and semi-quantification of its major constituents. A total of 49 compounds were detected, predominantly flavonoids, including luteolin- and apigenin-derived glycosides, flavonols, methoxyflavones, flavanones, and coumaroyl derivatives, with a total quantified flavonoid content of 15.9 mg·g⁻¹. Biological activity was evaluated in human cell models without cytotoxic effects at the tested concentrations. Results: Liboost^® significantly reduced PDE5 expression, inhibited aromatase activity, and moderately increased nitric oxide production. These complementary effects suggest a multi-target modulation of pathways involved in sexual function, integrating vascular, endocrine, and nitrergic mechanisms. Conclusions: Although limited to in vitro models, the findings provide mechanistic support for the biological activity of T. diffusa extracts and highlight the importance of linking phytochemical composition with functional evidence when evaluating botanical supplements. Full article

Objectives: Periodontitis represents an inflammatory condition affecting the supporting structures of teeth. Basic therapy relies on scaling and root planning, but often fails to eliminate subgingival pathogens. Phytotherapy has emerged as an adjunct due to its antimicrobial, anti-inflammatory, antioxidant, and tissue-protective properties. The aim of this study was to evaluate the effects of the phytotherapeutic product Propoherb G^® as an adjunct to mechanical periodontal therapy. Methods: This study included 90 systemically healthy participants divided into three groups: control, basic therapy, and basic therapy + Propoherb G^®. Periodontal clinical parameters were assessed, alongside the presence of periodontopathogens (A. actinomycetemcomitans, P. gingivalis, and T. denticola) using PCR and cytomorphometric analysis of gingival cells at baseline, first day, and eleven days after therapy. Results: Results showed significant improvements in periodontal clinical parameters in both treatment groups, with the most pronounced effect observed in the Propoherb G^® group (p < 0.001). A marked reduction in periodontopathogenic bacteria was achieved, with Propoherb G^® demonstrating sustained elimination of P. gingivalis and T. denticola, and a significant reduction of A. actinomycetemcomitans compared to standard therapy alone (p < 0.001). The control group showed no significant changes. Cytomorphometric analysis showed a significant decrease in all measured cell parameters after therapy (p < 0.001) in the group with Propoherb G^® preparation. Conclusions: The adjunctive use of Propoherb G^® enhances the clinical, microbiological and cytomorphometric outcomes of basic therapy. These findings support the potential of phytotherapy as a safe and effective supplement to basic treatment, although further studies with larger sample sizes and longer follow-up are necessary to standardize protocols and optimize clinical application. Full article

Background/Objectives: Thymic stromal lymphopoietin (TSLP) is central to the pathogenesis of atopic dermatitis (AD) and a promising therapeutic target. However, developing small-molecule TSLP inhibitors is challenging due to the difficulty in disrupting the TSLP-TSLPR interface. This study aimed to explore naturally sourced blockers of the TSLP-TSLPR interaction and identify novel candidate compounds for AD treatment. Methods: HuT78 cells were stimulated with PMA, ionomycin, and TSLP to establish an AD model. Inflammatory cytokines were measured by qRT-PCR and ELISA. JAK/STAT signaling was analyzed by Western blot. In female BALB/c mice, DNCB-induced AD-like skin lesions were topically treated with test compounds, followed by histopathological and immunohistochemical assessment. Results: Eight compounds were screened, and their key structural features were elucidated via structure–activity relationship (SAR) analysis. Among them, kaempferol-7-O-glucoside (K-7-G) emerged as the most potent candidate. It interfered with the TSLP-TSLPR interaction, selectively inhibited TSLP-mediated JAK2/STAT5 phosphorylation, and significantly downregulated IL-4 (p < 0.0001) and IL-13 (p < 0.001) levels. Topical application of 1% K-7-G significantly alleviated AD-like symptoms in a mouse model, decreasing dorsal skin thickness, dermatitis score, and scratching frequency while restoring the expression of filaggrin, loricrin, and occludin (p < 0.0001). Meanwhile, it significantly reduced key inflammatory mediators in a concentration-dependent manner, including TSLP, IL-4, IL-13, TNF-α, IFN-γ, and IgE. Conclusions: This study demonstrates that K-7-G is a novel natural TSLP inhibitor capable of blocking the TSLP-TSLPR signaling pathway and effectively improving AD symptoms. Further research may explore its therapeutic potential in other inflammatory diseases. Full article

Background/Objectives: Maziren-Wan (MZRW) is a traditional herbal prescription that has been used for the treatment of chronic constipation and is currently available in the form of granules or decoctions. Given its multi-component nature and various dosage forms, evaluating the chemical consistency of MZRW preparations is important for pharmaceutical quality assessment. The aim of the present study was to compare formulation-dependent chemical profiles of different MZRW preparations using a multi-component analytical approach. Methods: An excipient-free reference extract and two commercially available MZRW extract granule products were analyzed using a validated liquid chromatography–tandem mass spectrometry (LC–MS/MS) method operating in multiple reaction monitoring mode. Thirty marker compounds derived from the constituent herbs were simultaneously quantified, and their levels were statistically compared among the preparations. Results: Quantitative analysis revealed formulation-dependent variation in the abundance of several marker compounds. Amygdalin and magnoloside A exhibited markedly higher levels in the excipient-free reference extract than in the commercial granule products, whereas sennoside A showed relatively consistent levels across the preparations. Conclusions: The results indicate that MZRW preparations sharing an identical herbal composition can exhibit formulation-dependent differences in chemical profiles. Comparative evaluation based on multiple marker compounds may provide useful information for assessing chemical consistency and supporting quality assessment of MZRW preparations formulated under different conditions. Full article

Background/Objectives: Salvia chinensis Benth (SJC), as a traditional medicinal plant, has garnered significant attention for its extensive pharmacological activities. However, a systematic investigation of its comprehensive chemical profile and the underlying mechanisms in colorectal cancer (CRC) remains to be elucidated. This study aims to elucidate the active compounds and targets responsible for the anti-colorectal cancer effects of the aqueous extract of SJC. Methods: An integrated strategy was employed. The chemical profile of the SJC aqueous extract was analyzed by UPLC-MS/MS. Its anticancer activities, including effects on cell proliferation, migration, and apoptosis, were evaluated using the HCT-116 CRC cell line. An integrated transcriptomic and bioinformatic approach, followed by protein–protein interaction (PPI) network analysis, was used to identify key molecular pathways and targets. Finally, molecular docking and cellular assays were performed to screen for potential bioactive compounds. Results: A total of 60 natural compounds were tentatively identified in SJC. SJC inhibited the proliferation, migration, and invasion of HCT-116 colorectal cancer cells. Through combined transcriptomic and bioinformatic analysis, four candidate key genes were initially identified. Further PPI network analysis prioritized CXCL8 as a key candidate among the four candidate targets. Molecular docking against CXCL8, together with subsequent cellular experiments, validated naringenin as a potential bioactive constituent contributing to the anti-CRC activity of SJC. Conclusions: This study provides a comprehensive chemical profile of SJC and offers significant insights into its potential anticancer mechanisms in CRC by identifying candidate targets and a potential bioactive constituent. While these findings are preliminary and require further experimental validation through additional CRC cell lines and in vivo models, they establish a solid foundation for future research into the therapeutic applications of SJC for colorectal cancer. These planned studies will help to further elucidate the underlying mechanisms and assess the translational potential of SJC. Full article

Background: Dental caries, primarily caused by Streptococcus mutans (S. mutans), is a prevalent condition with significant global impact. Trans-cinnamaldehyde (TC), a phytochemical derived from the cinnamon plant, has shown promising antibacterial and antibiofilm activity against S. mutans. This study aimed to evaluate the anti-cariogenic effects of TC on S. mutans using an innovative mouse jaw explant model. Methods: TC was diluted in an organic solvent across various concentrations. Initially, cytotoxicity assays were performed at all tested TC concentrations. Sub-minimum bactericidal concentrations were then used to examine the distribution and morphology of S. mutans biofilms. Hemi-mandibles were dissected from euthanized, healthy, seven-week-old female mice to study the impact of TC on the cariogenic activity of S. mutans using stereoscopic analysis. Finally, pH changes during exposure to cariogenic conditions and post-treatment bacterial viability were measured. Results: In vitro data demonstrate that TC doses of ≤625 µg/mL were non-cytotoxic. Treatment groups exposed to TC exhibited altered bacterial morphology, including abnormal and incomplete cell division. In the mouse jaw explant model, TC doses of ≥625 µg/mL showed anti-cariogenic effects, evidenced by the absence of visible carious lesions. Additionally, pH changes and post-treatment viable bacterial counts corresponded with the observed anti-cariogenic activity. TC doses ≤625 µg/mL led to a pH drop over time and the presence of bacterial colonies. Conclusions: TC exhibits significant anti-cariogenic activity against S. mutans in the mouse model. Our findings suggest that 625 µg/mL is the lowest non-toxic concentration of TC that effectively inhibits cariogenic activity. Full article

Background/Objectives: Immunosuppression is a serious side effect of chemotherapeutic agents such as cyclophosphamide (CTX) and significantly increases the risk of infection in patients. Porcupine (Hystrix brachyura) bezoar (PB), a traditional medicine derived from the Hystrix brachyura species of porcupine, is renowned for its antioxidant and anti-inflammatory properties. However, its immunomodulatory potential has not been adequately investigated. This study aimed to systematically evaluate the protective effects of PB against CTX-induced immunosuppression and the underlying mechanisms in a rat model. Methods: An immunosuppression model was established in rats through the injection of CTX. The effects of PB on immune function were evaluated through the measurement of serum immunoglobulin (IgA and IgG) and pro-inflammatory cytokine (IL-6 and TNF-α) levels, as well as through a histopathological examination of immune organs. The mechanisms were further elucidated by analysing changes in serum metabolites and gut microbiota composition using integrated metabolomics and 16S rRNA sequencing. Results: Treatment with PB significantly alleviated CTX-induced immunosuppression, as demonstrated by elevated serum levels of IgA and IgG and reduced concentrations of IL-6 and TNF-α. PB also improved the architecture of spleen and thymus tissues. Metabolomic analysis revealed that PB regulated glycerophospholipid metabolism and steroid hormone biosynthesis, thereby reducing pro-inflammatory metabolites such as prostaglandin F2α. Furthermore, PB modulated the gut microbiota, increasing the abundance of beneficial bacteria (e.g., Bacteroidota and Lachnospiraceae) and decreasing that of harmful bacteria (e.g., Romboutsia and Clostridium sensu stricto). Conclusions: This study demonstrates that PB can effectively counteract CTX-induced immunosuppression in rats. This immunomodulatory effect is linked to changes in the gut microbiota and the regulation of specific metabolic pathways. These findings provide a scientific basis for the potential use of PB as an immunoadjuvant therapy, offering new insights into the mechanisms of traditional medicines. Full article

Background: Psidium guajava L. (Psidium guajava) is an edible plant; its parts are widely used to cure and prevent many health disorders. Psidium guajava leaves contain a wide array of polyphenols that inhibit peroxidation and may play a role in the prevention and treatment of common, degenerative chronic disorders such as diabetes, cardiovascular disease, and cancer. Colon cancer is the third most common type of cancer diagnosed and the second most common cause of cancer-related deaths globally. In contrast, prostate cancer is the second most diagnosed cancer and the fifth leading cause of cancer-related death worldwide. This study aims to evaluate the pharmacological potential of the Psidium guajava plants cultivated in Romania on colon and prostate cancer cell lines. Methods: Phenolic compounds extraction was made using an average sample of all nine Psidium guajava varieties. Analyses were carried out using a HP-1200 liquid chromatograph. The effect of the alcoholic extract of Psidium guajava leaves was tested on two colon cancer and one prostate cancer cell line as in vitro models. Results: The Psidium guajava leaf extract exhibited anticancer activity against the tested cell lines, with decreased proliferation, increased apoptosis, and cell cycle arrest. The extract reduced the cancer cell line’s migration and invasion capacity, demonstrating greater selectivity for the colon cancer cell line than for the prostate cancer cell lines. Conclusions: This study provides further proof of the Psidium guajava plant’s anticancer properties against colon cancer cell lines. Further studies are needed to confirm its use either alone or in conjunction with conventional cancer treatments as an alternate treatment for certain kinds of malignancies. Full article

Background/Objectives: Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disease that primarily affects the joints. Current treatments aim to relieve pain and limit joint damage; however, many are associated with significant side effects or high costs. Neutrophils play a critical role in RA development and progression by driving synovial inflammation and tissue damage, yet no approved therapies directly target neutrophil-mediated pathogenic mechanisms. Cannabinoids have demonstrated anti-inflammatory potential. Although cannabinoids have been studied in RA, the direct modulation of neutrophil-driven mechanisms by purified CBG has not been systematically addressed. To harness the cannabinoid potential, we investigated the effects of the purified cannabinoid Cannabigerol (CBG) on neutrophil-mediated immune responses in RA. Methods: We assessed the effects of CBG on human blood isolated neutrophil cytokine secretion, signal transduction and migration as ex vivo models. In addition, collagen antibody-induced arthritis (CAIA) was applied in C57BL/6 wt mice, and immune-cell recruitment and cytokine secretion were examined after CBG treatment. Results: Ex vivo experiments demonstrated that CBG hampered the secretion of pro-inflammatory cytokines from human neutrophils in a dose-dependent manner (TNF-α and IL-6 by 68% and 72%, respectively). Furthermore, CBG downregulated inflammatory signal transduction, such as P38-MAPK, ERK1/2 and Akt phosphorylationpost neutrophil activation by 41%, 54% and 78%, respectively. Importantly, 60% of the CBG downregulation of IL-6 was consistent with the CB2 receptor axis in a selective way. In addition, CBG attenuated neutrophil migration toward IL-8 by 67%. To further evaluate CBG therapeutic capacity, we used CAIA as an in vivo model. CBG treatment resulted in improving mice arthritis clinical scores and body weight in comparison to RA-diseased mice. Moreover, CBG reduced leukocyte recruitment to the inflamed joints by 48%, primarily through the inhibition of neutrophil and monocyte cells to 27% and 49%, respectively. Additionally, CBG showed its anti-inflammatory effect by decreasing inflammatory cytokines like IL-6 and IL-1β by 98% and 60% in the blood. Also, CBG reduced MCP-1 and IL-1β cytokines in the joints by 22% and 38%, respectively. Conclusions: These results show that CBG has anti-inflammatory capacity and therapeutic potential in regulating neutrophil-mediated immunity in RA. These findings are preclinical and require further validation before therapeutic positioning. Full article

Background/Objectives: Osteoporosis is a progressive systemic skeletal disease, with male osteoporosis emerging as a critical global concern due to high morbidity and mortality from fractures. This study investigated the anti-osteoporotic potential of CGAC—a herbal mixture of Cervus elaphus Linnaeus, Glycine max (L.) Merr., Angelica gigas Nakai, and Cnidium officinale Makino—and its underlying mechanisms in an orchiectomized (ORX) mouse model. Methods: C57BL/6J mice underwent ORX for 8 weeks, followed by CGAC administration (250 and 500 mg/kg) for an additional 8 weeks. Molecular mechanisms were further validated using MG63 osteoblastic and RAW 264.7 osteoclast assays. Results: ORX induced severe osteoporotic phenotypes, including significant reductions in bone mineral density (BMD) and trabecular microarchitecture. Notably, at the time point examined, ORX was associated with a suppressed bone remodeling state, reflected by reductions in both TRAP-positive osteoclasts and ALP-positive osteoblasts, together with lower serum BALP, CTX-1, and Gla/Glu-OC ratio. Conversely, CGAC normalized this stagnant state and restored physiological remodeling. This was accompanied by reduced marrow fat accumulation through the AMPK signaling axis, which upregulated Runx2 and downregulated PPAR-γ. In vitro results confirmed that CGAC promoted osteoblast differentiation and mineralization while suppressing RANKL-induced osteoclastogenesis. These actions suggest that CGAC may be involved in regulating Wnt/β-catenin signaling. Conclusions: Overall, CGAC is a promising therapeutic candidate for male osteoporosis, offering pharmacological benefits particularly relevant to aging populations. Full article