Search Results (348)

Berberine, a natural isoquinoline alkaloid, has been shown to improve glycemic control, lipid metabolism, and blood pressure regulation. However, its poor bioavailability has limited widespread clinical use. ToBeRock^® is a self-emulsifying formulation designed to enhance the bioaccessibility of berberine. This retrospective, real-world pilot study conducted through community pharmacies with pharmaceutical care services aimed to evaluate the metabolic and hemodynamic effects of ToBeRock^® in adults with impaired fasting glucose (IFG). Sixty adults with IFG (FPG 100–125 mg/dL) were enrolled through territorial pharmacies offering pharmaceutical services. Patients were retrospectively grouped into two cohorts: a Low-Dose Group (ToBeRock^® 1 capsule/day) and a High-Dose Group (ToBeRock^® 2 capsules/day). Capillary blood sampling and in-pharmacy blood pressure measurements were recorded at baseline (T0), 4 weeks (T1), and 8 weeks (T2). Evaluated parameters included fasting glucose, HbA1c, lipid profile (total cholesterol, LDL, HDL, triglycerides), systolic and diastolic blood pressure (SBP/DBP), and oxidative stress markers (FORT, FORD). Both cohorts showed statistically significant reductions in fasting glucose (p < 0.001), LDL (p = 0.036 Low-Dose/p = 0.039 High-Dose), and triglycerides (p = 0.012/0.009) after 8 weeks of treatment. The High-Dose Group experienced a greater improvement in HbA1c (−0.26%, p = 0.041) and a mild but statistically significant increase in HDL (p = 0.049). Improvements in oxidative balance were observed with significant reductions in FORT (p = 0.019/0.011), increases in FORD (p = 0.033/0.008), and a favorable shift in the REDOX index (p = 0.012/0.006). Systolic blood pressure decreased by −6.3 mmHg in the Low-Dose Group (p = 0.031) and −7.6 mmHg in the High-Dose Group (p = 0.048), while diastolic pressure dropped by −3.9 mmHg (p = 0.044) and −4.2 mmHg (p = 0.051), respectively. This real-world, retrospective analysis highlights the potential clinical benefit of ToBeRock^® in improving glycemic, lipid, oxidative, and hemodynamic profiles. The High-Dose Group demonstrated more consistent and significant results, supporting the dose-responsive efficacy of the bioavailable formulation and the value of pharmacy-based monitoring of nutraceutical interventions. Full article

Dickeya solani causes soft rot in potato (Solanum tuberosum L.) tubers. We used bulk RNA-seq to compare the early transcriptional responses of the diploid F₁ genotypes from the mapping population that varied in tuber resistance to D. solani. RNA was collected from wounded tubers inoculated with D. solani (B), wounded tubers treated with sterile water (W), and non-treated tubers (NT) at 8, 24, and 48 hours post-inoculation (hpi). The largest transcriptional divergence between resistant (R) and susceptible (S) genotypes occurred at 8 hpi, with R tubers showing stronger induction of phenylpropanoid biosynthesis, phenylalanine and tyrosine metabolism, amino sugar and nucleotide sugar metabolism, isoquinoline alkaloid biosynthesis, and glutathione metabolism. Phenylpropanoid biosynthesis was dominant in R tubers, in 17 differentially expressed genes (DEGs), consistent with rapid suberin and lignin deposition as a physical barrier. RT-qPCR of nine defence-related genes corroborated the RNA-seq trends. The suberisation-associated anionic peroxidase POPA was located within a QTL for D. solani resistance on chromosome II, supporting its role as a candidate for future functional studies. This is the first transcriptome-based comparison of R and S potato genotypes challenged with D. solani, providing candidate pathways and genes that may guide future molecular breeding once their roles are validated. Full article

Phytochemistry serves as a vital bridge between traditional medicinal knowledge and modern scientific research, with important implications for pharmaceutical and industrial applications. This review offers an updated and integrated perspective on Chelidonium majus (greater celandine), focusing on its isoquinoline alkaloids—the principal bioactive constituents—alongside emerging phytochemicals (e.g., lignanamides, polyphenols). Detailed biosynthetic pathways of isoquinoline alkaloids are described, tracing their formation from the shikimate pathway to multiple structural subclasses. Reported biological activities include anticancer, antioxidant, anti-inflammatory, antimicrobial, antiviral, and immunomodulatory effects. A bibliometric analysis was conducted using VOSviewer software (Scopus dataset, 2015–2025), enabling the identification of major research themes and temporal trends. These research tools supported a structured and data-driven overview of the current scientific landscape. However, additional studies are needed to optimize its therapeutic use while ensuring efficacy and safety. Full article

Weaning is one of the most challenging stages in a piglet’s life, with multiple stressors contributing to poor gut health. For several years, zinc oxide (ZnO) was the preferred means of promoting a healthy gut and preventing post-weaning diarrhea (PWD). However, with the banning of its use at medicinal levels in the EU since 2022, alternatives are needed. Berberine (BBR), an isoquinoline alkaloid, has been used for centuries in Chinese medicine to treat diarrhea and has pharmacological properties that could make this molecule an attractive alternative to ZnO. The aim of this study was to investigate how berberine is metabolized in the intestinal tract and liver of weaned piglets; determine which metabolites are detected in intestinal contents and plasma; and whether a low dose can alter histomorphological parameters, short-chain fatty acid (SCFA) production, and gut microbiota composition. A total of 60 piglets weaned at 4 weeks were divided into two groups (Control and BBR), each consisting of six pens of five animals. After two weeks of feeding with a normal diet or a berberine-supplemented diet (30 mg berberine/kg feed), berberine and its metabolites were quantified in intestinal contents and plasma by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) on 12 animals per group (2 male piglets per pen). Moreover, villus length and crypt depth were measured in small-intestinal tissue, and 16S rRNA gene sequencing was performed to examine jejunal, cecal, and colonic gut microbiota composition. Our findings show that piglets metabolize berberine into phase I and II metabolites; however, a low dose does not affect their histomorphology, microbiota composition, or SCFA production. Full article

Background/Objectives: Sweet potato is a tropical and subtropical crop and its growth and yield are susceptible to low-temperature stress. However, the molecular mechanisms underlying the low temperature stress of sweetpotato are unknown. Methods: In this work, combined transcriptome and metabolism analysis was employed to investigate the low-temperature responses of two sweet potato cultivars, namely, the low-temperature-resistant cultivar “X33” and the low-temperature-sensitive cultivar “W7”. Results: The differentially expressed metabolites (DEMs) of X33 at different time stages clustered in five profiles, while they clustered in four profiles of W7 with significant differences. Differentially expressed genes (DEGs) in X33 and W7 at different time points clustered in five profiles. More DEGs exhibited continuous or persistent positive responses to low-temperature stress in X33 than in W7. There were 1918 continuously upregulated genes and 6410 persistent upregulated genes in X33, whereas 1781 and 5804 were found in W7, respectively. Core genes involved in Ca²⁺ signaling, MAPK cascades, the reactive oxygen species (ROS) signaling pathway, and transcription factor families (including bHLH, NAC, and WRKY) may play significant roles in response to low temperature in sweet potato. Thirty-one common differentially expressed metabolites (DEMs) were identified in the two cultivars in response to low temperature. The KEGG analysis of these common DEMs mainly belonged to isoquinoline alkaloid biosynthesis, phosphonate and phosphinate metabolism, flavonoid biosynthesis, cysteine and methionine metabolism, glycine, serine, and threonine metabolism, ABC transporters, and glycerophospholipid metabolism. Five DEMs with identified Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were selected for correlation analysis. KEGG enrichment analysis showed that the carbohydrate metabolism, phenylpropanoid metabolism, and glutathione metabolism pathways were significantly enriched and played vital roles in low-temperature resistance in sweet potato. Conclusions: These findings contribute to a deeper understanding of the molecular mechanisms underlying plant cold tolerance and offer targets for molecular breeding efforts to enhance low-temperature resistance. Full article

The sorghum aphid (Melanaphis sacchari (Zehntner, 1897)), a globally destructive pest, severely compromises sorghum yield and quality. This study compared aphid-resistant (HX133) and aphid-susceptible (HX37) sorghum (Sorghum bicolor (L.) Moench) cultivars, revealing that HX133 significantly suppressed aphid proliferation through repellent and antibiotic effects, while aphid populations increased continuously in HX37. Transcriptome analysis identified 2802 differentially expressed genes (DEGs, 45.9% upregulated) in HX133 at 24 h post-infestation, in contrast with only 732 DEGs (21% upregulated) in HX37. Pathway enrichment highlighted shikimate-mediated phenylpropanoid/flavonoid biosynthesis and glutathione metabolism as central to HX133’s defense response, alongside photosynthesis-related pathways common to both cultivars. qRT-PCR validation confirmed activation of the shikimate pathway in HX133, driving the synthesis of dhurrin—a cyanogenic glycoside critical for aphid resistance—and other tyrosine-derived metabolites (e.g., benzyl isoquinoline alkaloids, tocopherol). These findings demonstrate that HX133 employs multi-layered metabolic regulation, particularly dhurrin accumulation, to counteract aphid infestation, whereas susceptible cultivars exhibit limited defense induction. This work provides molecular targets for enhancing aphid resistance in sorghum breeding programs. Full article

Berberine, a bioactive isoquinoline alkaloid derived from medicinal plants such as Berberis and Coptis species, shows significant promise for managing obesity and associated metabolic disorders. This review synthesizes evidence on its modulation of AMP-activated protein kinase (AMPK) signaling, gut microbiota composition, lipid metabolism, and adipokine networks, elucidating how these actions converge to suppress adipogenesis and improve insulin sensitivity. Metabolomic profiling reveals critical shifts in bile acid metabolism, short-chain fatty acid production, and mitochondrial function. Recent studies also highlight berberine’s anti-inflammatory effects and regulatory influence on glucose homeostasis. Despite its promise, challenges in oral bioavailability and drug interactions necessitate the development of advanced delivery strategies. We further discuss nanoformulations and multi-omics approaches, which integrate data from genomics, transcriptomics, proteomics, and metabolomics, provide new insights into berberine’s mechanisms, and may guide personalized therapeutic applications. While promising, further studies are needed to validate these findings in humans and translate them into effective clinical strategies. Full article

In this study, on the basis of a previous report, a pyrene-anchored nickel complex was designed and synthesized via five steps. The NMR spectra of the synthesized complex were found to exhibit significant proton and carbon chemical shift anisotropy. Cyclic voltammetry spectra showed that the introduction of pyrene slightly influenced the onset potential of CO₂ reduction. Lastly, controlled-potential electrolysis experiments disclosed that a pyrene-anchored nickel carbene–isoquinoline (Ni−2) complex selectively converted CO₂ into CH₄ with a TON value of 2.3 h⁻¹. Full article

Skin cancers are associated with a significant psychological burden across all age groups, particularly as their global incidence continues to rise. Ultraviolet (UV) radiation—primarily UVA and UVB—remains the leading etiological factor, inducing DNA mutations in key genes such as TP53 and BRAF. Among skin cancers, basal cell carcinoma (BCC) is the most prevalent and typically indolent. In contrast, squamous cell carcinoma (SCC) tends to be more invasive, while melanoma is the most aggressive and prone to metastasis. Melanoma is especially concerning due to its rapid dissemination and its occurrence not only on the skin but also in ocular, mucosal, and nail tissues. These challenges, along with rising treatment resistance and mortality, underscore the urgent need for novel anticancer agents. Berberine—a plant-derived isoquinoline alkaloid—has attracted increasing attention for its broad-spectrum anticancer potential, including against skin cancers. In this review, we summarize current evidence regarding berberine’s mechanisms of action in melanoma and SCC, emphasizing both its preventive and therapeutic effects. We further explore its potential as an adjuvant agent in combination with conventional treatments, offering a promising avenue for enhancing the clinical outcomes of skin cancer therapy. Full article

Various metabolic modulators have been widely used in recent years to increase the accumulation of desired secondary metabolites in medicinal plants, although most studies to date have focused on in vitro systems. Although simpler and cheaper, their potential application in vivo is still limited. Therefore, the aim of this study was to compare the effect of three chemically different elicitors (150 mg/L chitosan lactate—ChL; 10 mg/L selenium as selenite—Se; 100 mg/L salicylic acid—SA) applied to the soil substrate on some aspects of the secondary metabolism and physiological responses of Chelidonium majus L. Using HPLC-DAD, six isoquinoline alkaloids were identified and quantified in shoot extracts. LC-ESI-TOF-MS analysis confirmed the molecular identity of all target alkaloids, supporting the identification. The strongest stimulatory effect on the accumulation of protopine, berberine, and allocryptopine was observed with the Se and SA treatment, whereas ChL was less effective. In turn, the dominant alkaloids (coptisine and chelidonine) remained unaffected. There was also an increase in total phenolic compounds, but not in soluble flavonols. The elicitor treatments caused an increase in the antioxidant activity of the plant extracts obtained. Regardless of the metabolic modulator type, the strongest effect was generally observed on days 7 and 10 after application. No visual signs of toxicity and no effect on shoot biomass were found, although some elicitor-induced changes in the oxidative status (increased H₂O₂ accumulation and enhanced lipid peroxidation) and free proline levels in leaves were observed. We suggest that Se or SA can be applied to C. majus grown in a controlled pot culture to obtain high-quality raw material and extracts with increased contents of valuable specialized metabolites and enhanced antioxidant capacity. Full article

In recent years, one of the most important issues in public health is the rapid growth of antibiotic resistance among pathogens. Multidrug-resistant (MDR) strains (mainly Enterobacteriaceae and non-fermenting bacilli) cause severe infections, against which commonly used pharmaceuticals are ineffective. Therefore, there is an urgent need for new treatment options and drugs with innovative mechanisms of action. Natural compounds, especially alkaloids, are showing promising potential in this area. This review focuses on the ability of the isoquinoline alkaloid berberine (BRB) to overcome various resistance mechanisms against conventional antimicrobial agents. BRB has demonstrated significant activity in inhibiting efflux pumps of the RND (Resistance-Nodulation-Cell Division) family, such as MexAB-OprM (P. aeruginosa) and AdeABC (A. baumannii). Moreover, BRB was able to decrease quorum sensing activity in both Gram-positive and Gram-negative pathogens, resulting in reduced biofilm formation and lower bacterial virulence. Additionally, BRB has been identified as a potential inhibitor of FtsZ, a key protein responsible for bacterial cell division. Particularly noteworthy, though requiring further investigation, are reports suggesting that BRB might inhibit β-lactamase enzymes, including NDM, AmpC, and ESβL types. The pleiotropic antibacterial actions of BRB, distinct from the mechanisms of traditional antibiotics, offer hope for breaking bacterial resistance. However, more extensive studies, especially in vivo, are necessary to fully evaluate the clinical potential of BRB and determine its practical applicability in combating antibiotic-resistant infections. Full article

Sinomenium acutum is the main raw material for sinomenine. Empirical evidence indicates a marked disparity in sinomenine content among S. acutum plants with different genders, resulting in varying medicinal potential of the processing products. However, the mechanism underlying gender-determined differences in sinomenine accumulation is still elusive. In this study, untargeted metabolomics was performed among female, male, and undifferentiated S. acutum plants. In total, 1213 metabolites were identified, and most of them vary in the roots but not in the leaves among the different genders. Integrated correlation analysis on the DAMs (differentially accumulated metabolites) enriched in the isoquinoline alkaloid biosynthesis pathway suggests coclaurine as an intermediate determining gender-dependent sinomenine variation. Furthermore, hormonal profiling revealed 34 endogenous phytohormones exhibiting significant gender-based discrepancy in the roots. Among these, ABA (abscisic acid) and 5-DS (5-deoxystrigol) show significant positive correlation with sinomenine content. Then, exogenous ABA with gradient concentration was applied on S. acutum plants, and the sinomenine content in the roots increased from 31% to 166% under treatment. Our findings demonstrate that coclaurine might serve as a pivotal intermediate during sinomenine biosynthesis in S. acutum. Meanwhile, it is speculated that ABA is a key factor regulating different sinomenine accumulation, which provide a potential method to improve the yield of sinomenine. Full article

Aromathecin compounds—which contain the same indolizine core structure as camptothecin-like compounds—are expected to show anticancer activity. Among them, 22-hydroxyacuminatine—which has a substituent on the E-ring of the pentacyclic scaffold—exhibits topoisomerase 1 inhibitory activity; therefore, the development of efficient methods for its synthesis has been actively pursued. Herein, we report a versatile synthetic methodology for introducing various substituents on the E-ring, leading to the total synthesis of 22-hydroxyacuminatine as a model compound of the aromathecin family. The synthesis comprises the following key steps: the synthesis of an isoquinoline N-oxide via the thermal cyclization of 2-alkynylbenzaldehyde oxime, the subsequent Reissert–Henze-type reaction to yield an isoquinolone, and the construction of the indolizine moiety (CD-ring) through C–N bond formation via the Mitsunobu reaction. Consequently, a pentacyclic benz[6,7]indolizino[1,2-b]quinolin-11(13H)-one framework is obtained. Using this methodology, the total synthesis of the natural products norketoyobyrine and naucleficine and an intermediate of the latter, which are indoloquinolizidine-type alkaloids, was achieved, and their antiproliferative activity against HCT-116 human colon cancer cells and HepG2 human liver cancer cells was assessed. Naucleficine and its intermediate exhibited moderate antiproliferative activity against HCT-116 cells, with IC₅₀ values of 55.58 and 41.40 μM, respectively. Full article

Acute lung injury (ALI) is a fatal respiratory disease caused by excessive inflammation. Chelerythrine chloride (CH), an isoquinoline alkaloid, exhibits diverse biological activities. The research focused on assessing CH’s therapeutic effects against LPS-mediated ALI in mice and its underlying mechanisms. The anti-inflammatory effects of CH were evaluated both in LPS-induced RAW264.7 cells and ALI mouse model. An amount of 2.5 μM CH significantly inhibited the secretion of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1β in RAW264.7 cells. CH treatment notably mitigated the thickened alveolar septa and reduced edema in LPS-induced ALI in mice. Activity-based protein profiling (ABPP) technology was employed to identify the targets of CH. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was one of the direct targets of CH identified by ABPP. CH could downregulate the production of pyruvate. Furthermore, CH reduced the extracellular acidification rate (ECAR) while increasing the oxygen consumption rate (OCR) in LPS-stimulated RAW264.7 cells. All results suggest that CH mitigates LPS-induced ALI by targeting GAPDH and inhibiting glycolysis. This study reveals preliminary anti-inflammatory mechanisms of CH and its therapeutic potential for ALI. Full article