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BACKGROUND: Stomach diseases have become global health concerns. Protoberberine alkaloids (PBAs) are a group of quaternary isoquinoline alkaloids from abundant natural sources and have been shown to improve gastric disorders in preclinical and clinical studies. The finding that PBAs exhibit low oral bioavailability but potent pharmacological activity has attracted great interest. PURPOSE: This review aims to provide a systematic review of the molecular mechanisms of PBAs in the treatment of gastric disorders and to discuss the current understanding of the pharmacokinetics and toxicity of PBAs. METHODS: The articles related to PBAs were collected from the Web of Science, Pubmed, and China National Knowledge Infrastructure databases using relevant keywords. The collected articles were screened and categorized according to their research content to focus on the gastroprotective effects, pharmacokinetics, and toxicity of PBAs. RESULTS: Based on the results of preclinical studies, PBAs have demonstrated therapeutic effects on chronic atrophic gastritis and gastric cancer by activating interleukin-4 (IL-4)/signal transducer and activator of transcription 6 (STAT6) pathway and suppressing transforming growth factor-beta 1 (TGF-β1)/phosphoinositide 3-kinase (PI3K), Janus kinase-2 (JAK2)/signal transducers and activators of transcription 3 (STAT3), and mitogen-activated protein kinase (MAPK) pathways. The major PBAs exhibit similar pharmacokinetic properties, including rapid absorption, slow elimination, and low bioavailability. Notably, the natural organ-targeting property of PBAs may account for the finding of their low blood levels and high pharmacological activity. PBAs interact with other compounds, including conventional drugs and natural products, by modulation of metabolic enzymes and transporters. The potential tissue toxicity of PBAs should be emphasized due to their high tissue accumulation. CONCLUSION: This review highlights the gastroprotective effects, pharmacokinetics, and toxicity of PBAs and will contribute to the evaluation of drug properties and clinical translational studies of PBAs, accelerating their transfer from the laboratory to the bedside.

BACKGROUND: Berberine is a nutraceutical that can improve lipid metabolism. Berberine may also affect sex hormones and exert sex-specific lipid-modifying effects, which have been overlooked. This study aimed to comprehensively review the efficacy and safety of berberine in adults for the treatment of dyslipidemia with consideration of potential sex disparity. Data Sources We searched Medline, Embase, Wanfang, CNKI, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform from inception to 13 December 2022. No language restrictions were applied. This study was registered in PROSPERO (CRD42021293218) prior to completing the literature search. Study Selection Two blinded reviewers assessed studies for inclusion. Eligible studies were randomized controlled trials in adults that compared berberine versus placebo, and measured blood lipids or lipoproteins. Data Extraction and Synthesis Data extraction was performed by two blinded reviewers using a structured form in Covidence. Risk of bias was assessed using the Cochrane risk of bias tool for randomized trials. Mean differences (MD) were estimated using inverse variance weighting with random effects models for lipid outcomes using R. Adverse events (AEs) were described narratively. Main Outcomes Primary outcomes were low-density lipoprotein (LDL) cholesterol, total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and apolipoprotein B. Secondary outcomes were gastrointestinal and muscle-related AEs. RESULTS: Eighteen studies (n = 1788 participants), conducted mainly in mainland China and Hong Kong (15 studies [83%]), were included with treatment durations ranging from 4 to 24 weeks. Berberine reduced LDL cholesterol (- 0.46 mmol/L, 95% CI - 0.62 to - 0.30, 14 studies, n = 1447), total cholesterol (- 0.48 mmol/L, 95% CI - 0.63 to - 0.33, 17 studies, n = 1637), triglycerides (- 0.34 mmol/L, 95% CI - 0.46 to - 0.23, 18 studies, n = 1661) and apolipoprotein B (- 0.25 g/L, 95% CI - 0.40 to - 0.11, 2 studies, n = 127). Berberine increased HDL cholesterol by 0.06 mmol/L (95% CI 0.00 to 0.11, 15 studies, n = 1471). Notably, the effect on HDL cholesterol was different in women (0.11

BACKGROUND: The blockade of the progression or onset of pathological events is essential for the homeostasis of an organism. Some common pathological mechanisms involving a wide range of diseases are the uncontrolled inflammatory reactions that promote fibrosis, oxidative reactions, and other alterations. Natural plant compounds (NPCs) are bioactive elements obtained from natural sources that can regulate physiological processes. Inflammation is recognized as an important factor in the development and evolution of chronic renal damage. Consequently, any compound able to modulate inflammation or inflammation-related processes can be thought of as a renal protective agent and/or a potential treatment tool for controlling renal damage. The objective of this research was to review the beneficial effects of bioactive natural compounds on kidney damage to reveal their efficacy as demonstrated in clinical studies. METHODS: This systematic review is based on relevant studies focused on the impact of NPCs with therapeutic potential for kidney disease treatment in humans. RESULTS: Clinical studies have evaluated NPCs as a different way to treat or prevent renal damage and appear to show some benefits in improving OS, inflammation, and antioxidant capacity, therefore making them promising therapeutic tools to reduce or prevent the onset and progression of KD pathogenesis. CONCLUSIONS: This review shows the promising clinical properties of NPC in KD therapy. However, more robust clinical trials are needed to establish their safety and therapeutic effects in the area of renal damage.

The primary objectives of these studies were to determine the clinical efficacy and safety of the potential antisecretory and antimicrobial drugs in the treatment of diarrhoea due to Vibrio cholerae and enterotoxigenic Escherichia coli (ETEC). The drugs evaluated were chlorpromazine (CPZ), nicotinic acid, berberine, indomethacin, chloroquine, tetracycline, furazolidone, and bioflorin. Additionally, the role of prostaglandins (PGs) in the pathogenesis of cholera diarrhoea has been studied. The drug studies were carried out as placebo-controlled, randomized clinical trials in patients with active diarrhoea due to vibrio cholerae and ETEC. All patients received intravenous (i.v.) or oral rehydration solutions (ORS), but no other medications except the study drugs. Results indicate that CPZ (1 mg/kg or 4 mg/kg), berberine (200 mg), and nicotinic acid (2 g) all reduced stool volumes from 30% to more than 50% in diarrhoeal patients without significant side effects. It appeared that berberine was more effective in ETEC diarrhoea than in cholera. However, chloroquine, indomethacin, clonidine, and bioflorin had no clinically useful effects. Among the antimicrobial agents, a single dose of tetracycline was found to be effective in cholera, because the drug significantly (p < 0.05) reduced the total stool volume from 20.9 +/- 15.9 to 10.5 +/- 8.6 (liters in 6-days, mean +/- SD) compared to furazolidone. Drugs other than antimicrobial and antisecretory agents were also evaluated in the treatment of cholera. It has been shown that treatment with bioflorin, which is a bacterial preparation of lyophilized Streptococcus faecium, did not significantly (p > 0.05) reduce fluid-loss in cholera. Additional studies in animals indicated that treatment with short chain glucose polymers, alone or in combination with a chloride blocking agent, anthracene-9-carboxylic acid (A9C), significantly reduced intestinal secretion in a rat model of secretory diarrhoea. For the first time it was demonstrated that jejunal prostaglandin (PG) E2 concentrations were significantly increased during acute cholera and correlated with the volumes of stool and duration of diarrhoea. Furthermore, it was shown

Pharmaceutical co-crystals could modulate the physio-chemical properties of active pharmaceutical ingredients (APIs) and co-crystal formations (CCFs) via non-covalent interactions, including hydrogen bonds, π-π stacking and hydrophobic effects, which may generate synergistic pharmacological effects. Aiming to the antibiotic resistance and drug residues in aquaculture resulting from antibiotic overuse, in this study, we chose the key bioactive ingredients from traditional Chinese medicine (TCM), namely berberine (BBR), gallic acid (GA), and resveratrol (RSV), sourced from Coptis chinensis, Galla chinensis, and Polygonum cuspidatum, respectively. Through mixed-solution crystallization, two novel co-crystals of berberine and polyphenols (BBR-GA and BBR-RSV) were synthesized. Structural characterization using single crystal X-ray diffraction, Fourier infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR), and Hirshfeld surface analysis verified that both BBR-GA and BBR-RSV are predominantly stabilized by hydrogen bonds and hydrophobic interactions. Thermogravimetric analysis indicated that both BBR-GA and BBR-RSV display thermal stability, with decomposition temperatures higher than 200 °C. In vitro antibacterial tests against three typical aquatic pathogens revealed that both BBR-GA and BBR-RSV retained the broad-spectrum antibacterial activity of their respective API monomers. Specifically, BBR-RSV exhibited significant inhibitory effects against Aeromonas veronii and Citrobacter freundii, with minimum inhibitory concentration (MIC) of 0.125 mg/mL and 0.25 mg/mL, respectively. This study gives the first investigation on the potential application of the co-crystals from the active ingredients of TCM in the antibacterial field of aquaculture. It suggests that the co-crystals of berberine with natural polyphenols hold promise for development as new green veterinary drugs to substitute veterinary antibiotics.

We aim to estimate and compare the cost-effectiveness of statins, berberine, and their combined use for primary cardiovascular disease (CVD) prevention. The Scottish CVD Policy Model was used to predict long-term health and cost outcomes in Scottish adults aged 40 years or older without pre-existing CVD. Intervention and cost inputs were sourced from published literature and health service cost data. The primary outcome measure was the lifetime incremental cost-effectiveness ratio (ICER), evaluated as cost per quality-adjusted life year (QALY) gained. Five strategies were analyzed for individuals with ASSIGN risk scores ≥20% and ≥10%: no intervention, atorvastatin 20 mg/day, berberine 1000 mg/day, simvastatin 20 mg plus berberine 1500 mg/day, and simvastatin 20 mg plus berberine 900 mg/day. All intervention strategies were cost-effective, compared to no intervention, at the threshold of ICER of £20,000 per QALY. Compared to statins, berberine was less cost-effective, but the combined interventions remained cost-effective. Notably, when using drug costs from China (reflecting lower berberine prices), berberine and the combined interventions were preferable to statins alone. Statins, berberine, and combined interventions are all cost-effective options for primary CVD prevention. Berberine could be considered a valuable alternative or complementary therapy, particularly if its price decreases below that of statins. © 2026. The Author(s).

Background Mycobacterium tuberculosis ( Mtb), the causative agent of tuberculosis (TB), is the leading cause of death due to a single infectious pathogen globally. The increasing prevalence of drug-resistant Mtb strains underscores the pressing need for the development of new antimycobacterial drugs with novel mechanisms of action. Targeting pathogen drug efflux, a key antimycobacterial drug resistance mechanism, is an attractive, viable strategy for the development of new TB therapeutics. Methods In this study, we utilised Mycobacterium smegmatis ( Msm), a non-pathogenic Mtb surrogate, to delineate the ability of natural-product based compounds to augment the efficacy of bedaquiline (BDQ), clofazimine (CFZ) and doxycycline (DOX), probably via efflux inhibition (EI). Literature reporting the plant sources of the known efflux inhibitors (EIs) reserpine (RES), berberine (BER) and piperine (PIP) was scoped and additional compounds, (+)-lyoniresinol-3-Alpha-O-Beta-D-glucopyranoside (LYO-3) and lyoniresinol (LYO), isolated from the same plant species were chosen for testing. In vitro screening of the selected compounds was performed using the two-dimensional (2-D) checkerboard assay in which each likely efflux disruptor was tested in combination with BDQ, CFZ and DOX against Msm and the effect of the combinations ascertained. Thereafter, compounds that exhibited probable EI activity were docked onto potential targets namely MSMEG_5187, a Msm homologue of Mtb Rv1258c efflux pump (EP) and MmpL5. Results Molecular docking revealed that the EIs avidly bound to the EPs with docking scores of <-7 kcal/mol while the checkerboard combination assays demonstrated strong synergistic interactions for BDQ plus BER, LYO-3 and LYO. Conclusion These results point to a probable disruption of the Msm efflux system by Berberis species derivatives. Copyright: © 2026 Chacha R et al.

Antimicrobial resistance (AMR) poses a significant global health threat, with multidrug-resistant pathogens undermining the effectiveness of conventional antibiotics. Natural alkaloids, a diverse group of nitrogen-containing compounds mainly derived from plants, are gaining attention as potential antimicrobial agents due to their broad-spectrum activity, structural variety, and unique mechanisms of action. This review examines the antimicrobial properties of natural alkaloids, classifying them by chemical structure (e.g., quinoline, isoquinoline, pyridine, indole, and imidazole alkaloids). Their antibacterial, antifungal, and antiviral activities are discussed, along with the mechanisms by which they target pathogenic microorganisms, including disruption of cell walls and membranes, inhibition of protein synthesis, interference with DNA replication, and viral assembly. The review also explores the synergistic effects of alkaloids when combined with conventional antimicrobial agents. Alkaloids demonstrate potent antimicrobial activity against various pathogens. Quinoline alkaloids, such as quinine, inhibit DNA replication and damage cell membranes. Isoquinoline alkaloids like berberine and sanguinarine exhibit broad-spectrum antibacterial effects. Pyridine alkaloids, including nicotine, disrupt bacterial membranes. In fungi, alkaloids such as sanguinarine and indole derivatives prevent cell wall synthesis and spore germination. Antiviral alkaloids like lycorine target viral RNA polymerases. Additionally, alkaloids enhance the activity of traditional antibiotics by overcoming resistance. Natural alkaloids represent a promising source of antimicrobial agents with diverse mechanisms to combat AMR. Future research should focus on optimizing alkaloid structures, ensuring safety and efficacy, and exploring combination therapies to address the escalating AMR challenge.

Alzheimer's disease (AD) remains a significant global health challenge, highlighting the need for novel dual inhibitors targeting acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). This study investigated the trunk bark of Terminalia triptera Stapf. as a potential source of bioactive secondary metabolites for AD management. Bioassay-guided isolation led to the identification of two flavan-3-ol derivatives, epicatechin-(4β→8)-ent-catechin (1) and (-)-catechin (2), reported here for the first time from this species. In vitro assays demonstrated that the dimeric compound 1 exhibited stronger dual inhibitory activity against AChE and BChE, with IC50 values of 4.41 × 10-4 and 4.75 × 10-4 mol/L, respectively, surpassing the reference compound berberine chloride. Molecular docking analysis revealed that compound 1 formed extensive interactions within both catalytic and peripheral anionic sites of the enzymes. Density Functional Theory (DFT) calculations indicated high kinetic stability, reflected by large HOMO-LUMO energy gaps (6.66-6.97 eV), while global reactivity descriptors suggested lower electrophilicity (ω = 2.19-2.34 eV), supporting a potentially favorable safety profile. Furthermore, 100 ns molecular dynamics simulations confirmed stable ligand-protein complexes stabilized by hydrogen-bond networks and deep binding within catalytic pockets. Overall, these findings highlight T. triptera and its dimeric proanthocyanidins as promising multi-target candidates for anti-Alzheimer drug development.

Gastrointestinal malignancies remain among the leading causes of cancer-related morbidity and mortality worldwide, largely due to late diagnosis, aggressive tumor progression, and resistance to conventional therapies. Tumor angiogenesis and the tumor microenvironment (TME) play crucial roles in the initiation, growth, and metastatic dissemination of gastrointestinal cancers. Hypoxia-driven signaling pathways, including hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), and inflammatory mediators such as NF-κB and MAPK, are key regulators of these processes. Increasing evidence suggests that natural products derived from medicinal plants and other biological sources may modulate these pathways and exhibit anti-angiogenic, anti-inflammatory, and anti-fibrotic properties. This review summarizes recent findings on natural compounds that influence angiogenesis and tumor microenvironment dynamics through the regulation of molecular pathways involved in hypoxia signaling, extracellular matrix remodeling, fibroblast activation, and inflammatory responses. Compounds such as neotuberostemonine, aloperine, silymarin derivatives, tanshinone IIA, berberine, asiatic acid, and phloretin demonstrate promising biological activities in experimental models by targeting pathways including HIF-1α, PI3K/AKT/mTOR, TGF-β/Smad, and NF-κB signaling. However, further studies focusing on gastrointestinal cancer models and clinical validation are required to translate these preclinical observations into effective therapeutic strategies.

Argemone mexicana (Linn.), commonly known as prickly poppy, is a well-documented medicinal plant in Indian Ayurvedic literature, recognized for its diverse pharmacological properties. It has been investigated for its potential applications in the treatment of cancer, inflammation, and wound healing, thereby highlighting its pharmacological significance. Traditionally, it has been used successfully to treat skin diseases, ulcers, tumors, boils, and snake venom poisoning. The therapeutic potential of this plant has been further validated by recent studies, which also demonstrated its safety in clinical trials for antimalarial activity. Berberine, argemonine, argenaxine, and chelerythrine are among the bioactive alkaloids abundant in Argemone mexicana, shown to possess significant anticancer, antibacterial, anti-inflammatory, and antimalarial properties. These compounds exert cytotoxic effects against various cancer cell lines by modulating key oncogenic pathways and preventing the acquisition of cancer hallmark characteristics, such as uncontrolled proliferation, apoptosis evasion, inflammation, invasion, angiogenesis, and drug resistance. Preclinical studies have further explored the role of Argemone mexicana in cancer treatment and wound healing, expanding its pharmacological relevance. This review systematically compiles evidence from in vitro and in vivo studies, elucidating the mechanisms through which Argemone mexicana and its derived compounds exhibit anticancer activity. By highlighting its potential as a natural source of anticancer agents, this review aims to provide a foundation for future research and the development of novel plant-based cancer therapeutics.

Type 2 diabetes mellitus (T2DM) is a complex systemic metabolic disease driven by insulin resistance, β-cell dysfunction, chronic low-grade inflammation, oxidative stress, and neuro-immune dysregulation. It frequently progresses to multi-organ complications affecting the kidneys, retina, heart, and central nervous system. This review synthesizes mechanistic and translational evidence on Traditional Chinese Medicine (TCM)-related botanical drugs and botanical preparations (formula-based interventions), along with representative plant metabolites that are frequently investigated in the TCM research context (e.g., berberine, baicalin, and tanshinone IIA, which are not unique to TCM). For formula-based preparations, we extracted and reported intervention identity elements (dosage form, complete composition, and processing/standardization as described in primary studies); missing identity items were recorded as not reported (NR) and not inferred. We organized findings across shared T2DM-relevant pathogenic modules, including PI3K/Akt and AMPK signaling, inflammatory outputs (NF-κB/NLRP3), redox regulation (NRF2/ROS), angiogenic signaling (VEGF), and gut-liver-brain-immune network interactions, emphasizing studies in which pathway modulation is accompanied by metabolic or complication-relevant endpoints. To strengthen interpretability and reproducibility, we conducted a structured literature search (2000-2025) and applied evidence grading (human/RCT vs. animal vs. in vitro/in silico), and we critically appraised reporting quality using the GA-online Best Practice in Research - ConPhyMP tool. All source organisms were taxonomically validated using authoritative resources, and full scientific names (including author citation and family) were standardized. We caution that compound-target links, particularly those derived from in silico predictions or single-assay readouts, may be vulnerable to assay interference liabilities (including PAINS) and should be supported by orthogonal validation and outcome-linked readouts before strong mechanistic claims are made. Finally, we outline translational priorities, including rigorous standardization and quality control (distinguish

Berberine, an isoquinoline quaternary alkaloid, is a molecule with significant therapeutic adaptability. It has been identified, isolated, and measured in a wide range of plant families and species. Of these, Berberis stands out as a significant natural source of berberine, with Berberis vulgaris (B. vulgaris) bark being one of the most notable. The numerous health benefits associated with berberine include its potential use in the treatment of diseases, such as cancer, cardiovascular diseases, diabetes, and neurological disorders. The principal use of berberine has been for its antidiarrheal properties, which may have several modes of action. Its potent antioxidant and anti-inflammatory effects are responsible for its preventive action against stomach ulcers, and it has been found to kill dangerous gut bacteria while boosting the species and numbers of health-promoting bacteria. It protects the colon by influencing the production of several immune factors in addition to upregulating the Wnt-β creatinine signaling cascade. Berberine has shown its potential in regulating cholesterol metabolism by elevating the levels of low-density lipoprotein receptor in the liver. This review comprehensively examines the pharmacokinetics, multifaceted bioactivities, and gut-protective roles of berberine, providing a detailed analysis of its diverse physiological functions and potential clinical applications to advance the understanding and management of gastrointestinal diseases.

Melanoma, the most lethal form of skin cancer, poses significant therapeutic challenges despite advances in immunotherapy. Natural compounds have emerged as promising adjuncts for modulating immune checkpoint pathways, including PD-1/PD-L1, CTLA-4, and LAG-3. A systematic review was conducted from inception to July 2025, searching the Web of Science, PubMed/MEDLINE, and Scopus. MeSH terms and keywords encompassed immune checkpoints, natural compounds (e.g., phytochemicals), and melanoma. We included original studies investigating natural compounds in melanoma models that reported outcomes related to immune checkpoint modulation. Nineteen preclinical studies met the inclusion criteria. Flavonoids (quercetin, apigenin, and luteolin) inhibited PD-L1 via JAK2/STAT3 and IFN-γ/STAT1 suppression. Emerging bioactive sources such as Polygonum minus and drimenol were identified as multi-target agents capable of reprogramming the tumor microenvironment. Alkaloids such as berberine promoted PD-L1 degradation through the CSN5-ubiquitin-proteasome axis. Nanocarrier-based delivery systems, particularly calcium carbonate nanoparticles, enhanced bioavailability and achieved synergistic efficacy with reduced systemic toxicity, highlighting a key strategy for clinical translation. Natural compounds offer a multi-targeted strategy to overcome melanoma resistance. While current preclinical evidence is promising, it remains hypothesis-generating. The findings suggest that phytochemicals can modulate multiple checkpoints with a favorable safety profile. Future research must focus on rigorous clinical trials to establish standardized dosing and validate safety margins for translating these agents into effective personalized melanoma immunotherapies. © 2026. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Subcellular disorders are linked with several diseases, specifically mitochondrial dysfunction linked to age, metabolic disorders, cancer, cardiovascular disease, and other mitochondrial diseases (MDs). Intracellular medication delivery is a promising option for effective therapy. This study aims to highlight subcellular delivery with focus on mitochondrial pharmacology, gene therapy, transplantation, and drug targeting. PubMed, Google Scholar, Scopus, and other scholarly sources were leveraged to prepare this narrative review. According to current studies, intermittent fasting, consistent exercise, well-balanced diets, and proper sleep can all help to increase mitochondrial quality. Molecular therapies improve mitochondrial bioenergetics, redox status, biogenesis, dynamics, mitophagy, bioenergetic, and sirtuins. The antioxidant supplementation restores endogenous antioxidants such as alpha-lipoic acid, tocopherols, L-carnitine, and coenzyme Q10 to prevent mitochondrial damage. Mdivi-1, melatonin, resveratrol, PGC-1α agonists, metformin, and Opa1 activators modify the dynamics and biogenesis of mitochondria. Bioactive phytochemicals, including curcumin, berberine, quercetin, and capsaicin, affect OXPHOS and mitochondrial sirtuins. These agents affect gene expression, antioxidant defenses, inflammation, and mitochondrion functions. Therefore, bioactive phytochemicals limit oxidative damage, increase insulin sensitivity, and improve extended cell longevity. Mitochondrial transplantation and gene therapy using mRNA and gene editing technologies are promising treatment options for MDs. Mitoquidone, triphenylphosphine, mitochondrial-targeting peptides, and nanocarriers localize medicines within mitochondrial compartments. In conclusion, a good lifestyle and bioactive materials, alongside mitochondrial medications, gene therapy, transplantation, and drug targeting, could restore overall cellular health.

With changing lifestyles, non-alcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease worldwide. A substantial increase in the incidence, mortality, and associated burden of NAFLD-related advanced liver disease is expected. Currently, the initial diagnosis of NAFLD is still based on ultrasound and there is no approved treatment method. Lipid-lowering drugs, vitamin supplementation, and lifestyle improvement treatments are commonly used in clinical practice. However, most lipid-lowering drugs can produce poor patient compliance and specific adverse effects. Therefore, the exploration of bio-diagnostic markers and active lead compounds for the development of innovative drugs is urgently needed. More and more studies have reported the anti-NAFLD effects and mechanisms of natural products (NPs), which have become an important source for new drug development to treat NAFLD due to their high activity and low side effects. At present, berberine and silymarin have been approved by the US FDA to enter clinical phase IV studies, demonstrating the potential of NPs against NAFLD. Studies have found that the regulation of lipid metabolism, insulin resistance, oxidative stress, and inflammation-related pathways may play important roles in the process. With the continuous updating of technical means and scientific theories, in-depth research on the targets and mechanisms of NPs against NAFLD can provide new possibilities to find bio-diagnostic markers and innovative drugs. As we know, FXR agonists, PPARα agonists, and dual CCR2/5 inhibitors are gradually coming on stage for the treatment of NAFLD. Whether NPs can exert anti-NAFLD effects by regulating these targets or some unknown targets remains to be further studied. Therefore, the study reviewed the potential anti-NAFLD NPs and their targets. Some works on the discovery of new targets and the docking of active lead compounds were also discussed. It is hoped that this review can provide some reference values for the development of non-invasive diagnostic markers and new drugs against NAFLD in the clinic.

Many types of mycotoxins are found in food sources contaminated with fungi, and if these are ingested in large quantities or over a long period, they can affect the health of humans and domestic animals. Berberine (BBR) is a plant alkaloid with multiple pharmacological functions. This study aimed to investigate the effect of different levels of the plant alkaloid BBR on reducing toxic effects of aflatoxin B1 (AFB) and ochratoxin A (OTA) in broilers by examining performance characteristics, blood biochemistry, antioxidant systems, ileum morphology, and histopathology of the liver. The experiment was performed with 288 Ross 308 broilers reared in floor pens for 42 d in a randomized design with 9 treatments. Each treatment was replicated 4 times, and each replicate contained 8 chicks. Experimental treatments included (1) negative control diet with no additives (NC); (2) NC + 2 ppm AFB (positive control AFB; PCAFB); (3) NC + 2 ppm OTA (positive control OTA; PCOTA); (4) PCAFB + 200 mg/kg BBR; (5) PCAFB + 400 mg/kg BBR; (6) PCAFB + 600 mg/kg BBR; (7) PCOTA + 200 mg/kg BBR; (8) PCOTA + 400 mg/kg BBR; and (9) PCOTA + 600 mg/kg BBR. Compared with NC, feeding PCAFB and PCOTA diets reduced average daily feed intake, weight gain, serum concentrations of superoxide dismutase, glutathione peroxidase, and the length and width of ileum villi (P < 0.05). At the same time, these parameters increased in birds fed PCAFB or PCOTA diets supplemented with 600 mg/kg of BBR (P < 0.05). Feeding PCAFB and PCOTA diets increased feed conversion ratio (FCR), serum aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT) activities, serum urea, and liver lesions compared with NC. By contrast, compared with PCAFB and PCOTA, adding 600 mg/kg BBR decreased FCR, AST, LDH, ALT, and GGT activities, urea, and liver lesions (P < 0.05). Overall, supplementation with 600 mg/kg BBR may improve growth performance, liver function, and antioxidant status of broilers fed diets contaminated with AFB and OTA.

Sulforaphane (SFN) is an active component extracted from vegetables like cauliflower and broccoli. Activation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling is a common mechanism for the anti-oxidative and anti-inflammatory activity of some herb-derived compounds, such as icariin and berberine. However, due to its peculiar ability in Nrf2 activation, SFN is recognized as an activator of Nrf2 and recommended as a supplementation for prevention and/or treatment of disorders like neoplasm and heart failure. In the central nervous system (CNS), the prophylactic and/or therapeutic effects of SFN have been revealed in recent years. For example, it has been reported to prevent the progression of Alzheimer's disease, Parkinson's disease, cerebral ischemia, Huntington's disease, multiple sclerosis, epilepsy, and psychiatric disorders via promotion of neurogenesis or inhibition of oxidative stress and neuroinflammation. SFN is also implicated in reversing cognition, learning, and memory impairment in rodents induced by scopolamine, lipopolysaccharide, okadaic acid, and diabetes. In models of neurotoxicity, SFN has been shown to suppress neurotoxicity induced by a wide range of toxic factors, such as hydrogen peroxide, prion protein, hyperammonemia, and methamphetamine. To date, no consolidated source of knowledge about the pharmacological effects of SFN in the CNS has been presented in the literature. In this review, we summarize and discuss the pharmacological effects of SFN as well as their possible mechanisms in prevention and/or therapy of disorders afflicting the CNS, aiming to get a further insight into how SFN affects the pathophysiological process of CNS disorders.

INTRODUCTION: The German cockroach (Blattella germanica) is a notorious urban pest with significant health impacts, owing in part to its highly sophisticated gustatory system that enables precise food discrimination and toxin avoidance. Odorant-binding proteins (OBPs) are known to play critical roles in insect chemoreception, yet their specific contributions to sweet and bitter compound recognition remain poorly understood. METHODS: We investigated the function of three maxillary palp-enriched OBPs (BgerOBP10, BgerOBP44, and BgerOBP91) using fluorescence competitive binding assays, RNA interference (RNAi), bitter selection behavioral assays, analytical ultracentrifugation, and structural modeling with AlphaFold-3 followed by molecular docking. RESULTS: Binding assays identified Berberine chloride hydrate and Vanillin as potential bitter ligands of the three OBPs. RNAi efficiently suppressed their expression in both male and female maxillary palps, leading to loss of bitter discrimination: while control cockroaches avoided bitter sources, OBP-deficient individuals failed to distinguish them from water. Analytical ultracentrifugation revealed that recombinant BgerOBP91 forms dimers, and structural predictions showed distinct 3D conformations and unique ligand-interacting residues among the three OBPs. Taken together, the present study demonstrates, for the first time, that maxillary palp OBPs mediate bitter perception in B. germanica. By uncovering novel molecular mechanisms of gustation, our findings not only expand the functional repertoire of insect OBPs but also provide promising molecular targets for the development of innovative strategies to disrupt cockroach feeding behavior and pest management.

Background/Objectives: Extracellular vesicles (EVs) are nanosized carriers with high biocompatibility, low immunogenicity, and the ability to cross biological barriers, making them attractive for drug delivery. Despite growing interest, the clinical translation of drug-loaded EVs remains limited. This systematic review aimed to summarize current evidence on EV sources, loading strategies, therapeutic applications, and translational challenges. Methods: Following PRISMA 2020 guidelines, a systematic search was conducted in Embase, PubMed, Reaxys, and Scopus for the period 2020-2025. Eligible studies included original articles on drug-loaded EVs from human, animal, plant, or other sources. Data on EV source, drug type, particle size, loading method, administration route, and therapeutic application were extracted. Clinical trials were identified through ClinicalTrials.gov. Results: A total of 65 studies were included after screening 5316 records, along with two clinical trials. Human mesenchymal stem cell (MSC)-derived EVs were the most frequent source in oncology, while plant-derived EVs predominated in non-oncology applications. Anti-cancer drugs such as doxorubicin, gemcitabine, and docetaxel were most frequently loaded, alongside curcumin, berberine, and atorvastatin. EV sizes generally ranged from 50 to 200 nm, with larger vesicles reported for plant-derived EVs. Intravenous administration predominated, with most studies demonstrating sustained release and enhanced therapeutic efficacy. Passive loading was most common, especially for hydrophobic drugs, whereas active methods such as electroporation and sonication were preferred for hydrophilic cargo. Two clinical trials showed preliminary therapeutic benefits with favorable safety. Conclusions: Drug-loaded EVs represent a promising and versatile drug delivery platform, yet their clinical translation is hindered by variability in isolation and loading methods, production scalability, and safety evaluation. Further standardization and large-scale studies are needed to advance EV-based therapeutics toward clinical use.

This study aims to investigate the moistening mechanism of Phellodendri Chinensis Cortex via multiple characterization methods and characterize the moistening process and determine the endpoint based on multi-source data fusion. Low-field nuclear magnetic resonance(LF-NMR) was employed to investigate water migration and distribution patterns during the moistening process of Phellodendri Chinensis Cortex. The texture analysis was performed to monitor the hardness variations, and near-infrared spectroscopy(NIRS) was adopted to collect spectral data throughout the moistening process. The results showed that during the moistening process of Phellodendri Chinensis Cortex, water penetrated from the outer to the inner, and the content of semi-free water increased from 16.68% to 81.63% in the first 5 h. Meanwhile, the hardness decreased and gradually became stable after 5 h. The contents of berberine hydrochloride and phellodendrine hydrochloride changed mildly during the moistening process. The correlation analysis of LF-NMR parameters, hardness, water content, and chemical components demonstrated that total water content and semi-free water content exhibited correlations with hardness(P&lt;0.05). Prediction models for water content and hardness were established based on near-infrared spectroscopy(NIRS). The models exhibited strong linear correlations(R~2&gt;0.90), with root mean square errors of the calibration set and prediction set being closely aligned, indicating good robustness of the models. By integrating LF-NMR, texture analysis, and near-infrared spectral data, a prediction model for the moistening process and endpoint determination of Phellodendri Chinensis Cortex was established, providing a reference for non-destructive monitoring and endpoint determination in the moistening process of Chinese medicinal materials.

Breast cancer (BC) is the most common cancer and a major cause of cancer-related deaths in women worldwide. Its significant molecular heterogeneity leads to different response rates, leaving standard therapy approaches comparatively ineffective. Recent evidence highlights the promise of natural compound-based therapies in modulating oncogenic signaling, regulating epigenetic mechanisms, and reshaping the tumor microenvironment. This review systematically explores the anticancer potential of bioactive phytochemicals, including curcumin, resveratrol, thymoquinone, and berberine, in BC. These agents exhibit pleiotropic mechanisms such as promoting apoptosis (e.g., via p53 activation), suppressing angiogenesis (e.g., through VEGF downregulation), and reversing chemoresistance (e.g., by inhibiting the PI3K/AKT/mTOR axis). The role of epigenetic regulation is explored, focusing on DNA methylation, histone modifications, and non-coding RNAs. Compounds like EGCG and ellagic acid have been shown to restore the expression of tumor suppressor genes. Special attention is given to different types of breast cancer, especially triple-negative breast cancer (TNBC), which currently has limited treatment options and poor outcomes. Laboratory studies suggest that plant-based compounds can enhance the sensitivity of TNBC cells to standard chemotherapy, while also impacting immune and metabolic functions. Advances in nanotechnology, such as liposome-encapsulated curcumin, gold nanoparticles containing berberine, and nano-delivery systems for resveratrol, have improved the absorption and effectiveness of these substances. In conclusion, natural compounds represent a valuable source of novel therapeutics for breast cancer management, bridging molecular insights with translational potential.

BACKGROUND: The management of small intestinal bacterial overgrowth (SIBO) involves a range of therapeutic options such as antibiotics, probiotics, and prokinetic agents, yet their comparative clinical efficacy remains poorly characterized. OBJECTIVE: To address this critical evidence gap, we systematically evaluated all empirically used treatment regimens through a network meta-analysis (NMA) of published randomized controlled trials (RCTs), with the goal of providing clearer guidance for therapeutic selection. DESIGN: We conducted a systematic review and NMA following established methodological standards for evidence synthesis. DATA SOURCES AND METHODS: Our comprehensive literature search covered PubMed/MEDLINE, Embase, and Web of Science from their inception through December 31, 2024. We included RCTs examining SIBO treatments in adult populations. The extracted data from qualifying RCTs were subjected to Bayesian NMA to (1) conduct pairwise comparisons of empirical SIBO treatment regimens and (2) determine their hierarchical efficacy ranking. The ranking probability for each regimen was evaluated by means of the surfaces under cumulative ranking values. RESULTS: Our NMA incorporated 30 eligible RCTs, involving a total of 1552 participants and evaluating 12 distinct interventions. Based on comparative efficacy rankings, berberine was associated with the highest surface under the cumulative ranking curve (SUCRA) value, positioning it as a potentially favorable option for SIBO eradication. In the subgroup of patients with concurrent functional gastrointestinal disorders (FGIDs), the combination of rifaximin and a gastrointestinal motility drug also showed a high SUCRA value (89%), suggesting it may represent a particularly effective regimen in this clinical context. Furthermore, among SIBO patients with chronic liver disease, the gastrointestinal motility drug alone exhibited the most favorable ranking trend (SUCRA: 79.6%). While three of the included studies were assessed as having a high risk of bias (RoB), meta-regression analysis indicated that the RoB did not significantly influence the model outcomes. The confidence in network estimates was generally rate

44. Ther Adv Gastroenterol. 2025 Dec 11;18:17562848251399033. doi: 10.1177/17562848251399033. eCollection 2025. Comparative efficacy of diverse therapeutic regimens for small intestinal bacterial overgrowth: a systematic network meta-analysis. Zhang Q(1), Li H(2), Chen C(2), Li M(2), Song J(2),

Type 2 diabetes mellitus (T2DM) is a global health challenge that requires new therapeutic approaches. Natural compounds from botanical sources offer promise as alternative treatments due to their multifaceted bioactivity and favourable safety profiles. This study employs an in-silico methodology to evaluate their therapeutic potential by targeting genes associated with T2DM. Bioactive natural compounds were screened and sourced from Natural Product Activity and Species Source Database (NPASS) and ZINC12 databases against 14 T2DM-associated genes (GPD2, IRS1, PPARG, IAPP, GCK, ABCC8, MAPK8, MTNR1B, AKT2, PTPN1, INSR, AMPK, GAA, and SLC2A4). Molecular docking assessed binding affinities, while pharmacokinetic and ADMET profiles were predicted. Comparative analyses with approved drugs from DrugBank, network pharmacology approaches, and molecular dynamics simulations further evaluated their therapeutic potential. 72 natural compounds exhibited superior or comparable binding affinities to standard drugs of which, 17 ligands -Moracin D, Moracin P, Plantagineoside A, Pyrene (carcinogenic), Curcumin, Rohitukine, Berberine Chloride, Berberrubine, Apigenin, Emodin, Chelerythrine, Alvocidib, A-443,654, Xambioona, Altertoxin I, Ursolic Acid, and Oleanolic Acid -were selected as top candidates for further analysis. ADME/T analyses highlighted Pyrene, Guggulsterone, Melatonin, Gefitinib, Apigenin, Rotenone, Curcumin, Bavachinin A, Bavachinin, and Quinidine as particularly promising in terms of superior ADME and oral bioavailability. Four ligands-2-Tert-Butyl-6-[(3-Tert-Butyl-2-Hydroxy-5-Methylphenyl)Methyl]-4-Methylphenol, 4-(2-Phenylpropan-2-Yl)Phenol, Phenothiazine, and 2-Naphthalen-1-Ylacetic Acid- showed notable minimal toxicity. Chelerythrine, Emodin, Rohitukine, A-443,654, and Alvocidib demonstrated multi-target networking interactions. Molecular dynamics simulations of the 17 highest-ranked complexes (500 ns) demonstrated stable RMSD values (4.39-5.33 Å), strong hydrogen bonding, and favorable energetic profiles. Particularly, Moracin P, Moracin D, Plantagineoside A, Chelerythrine, Alvocidib, and Ursolic Acid showed the most stable MD trajectories and highly favorable