Huanglian (HL) is a member of the Ranunculaceae family, including Coptis chinensis Franch., Coptis deltoidea C. Y. Cheng et Hsiao, or Coptis teeta Wall. The dried rhizomes are highly esteemed herbal medicine in Chinese pharmacopeia. However, the composition of HL is complex, and current identification technologies are insufficient for conducting a comprehensive analysis of HL, leading to major obstacles in quality control. Therefore, an in-depth exploration of the influence of species diversity and geographic provenance on the chemical profile of HL is imperative for its rational application and quality assurance. To comprehensively analyze compounds in HL samples from diverse geographical regions, this study employed an integrated approach combining offline two-dimensional ultra-high-performance liquid chromatography coupled with quadrupole-Orbitrap mass spectrometry (2D-LC-MS/MS) with online 2D-LC-MS/MS. This dual-platform strategy enabled detailed characterization of complex compound profiles. Additionally, the retention time prediction (RT-Ensemble Pred) models were utilized to predict and identify the retention times of unknown compounds, which particularly facilitated the differentiation of isomers. The comprehensive research resulted in the identification of 150 chemical constituents in HL, including 72 isomers. Furthermore, the compounds were analyzed and categorized according to mathematical classification models, allowing for distinction between various geographical origins. Based on unexposed data, the model demonstrated robust predictive capability, enabling the selection of 20 distinctive characteristic compounds with prominent features for use in geographical origin discrimination. Overall, this multidimensional investigation significantly enhanced our understanding of the chemical composition and inherent variability of HL plant resources, providing crucial technical underpinnings and methodological insights for the comprehensive exploitation and utilization of HL in biomedical and pharmaceutical applications.

The flavor evolution of unsweetened green tea beverage (USGTB) under actual storage is critical for quality control yet remains unclear. Unlike previous studies conducted by accelerated shelf-life testing, this research investigated sensory-chemical changes in naturally stored USGTB (0-7 months) through multi-omics integrating metabolomics and sensomics. Results identified the 5-month as a critical point for flavor preservation. The EC-EGCG dimer emerged as a novel aging marker, contrasting with freshness indicators (ascorbic acid and other antioxidants). Protocatechuic acid and 2-furoic acid served as multi-flavor contributors (yellowish, sweetness and astringency), whereas L-tartaric acid and malic acid enhanced sourness. Concurrently, aroma deterioration was driven by the diminished (E)-β-ionone and accumulated methyl salicylate. Mechanistically, oxidations of ascorbic acid, catechins, and fresh aroma-related volatiles, flavonoid glycosylation, and oligosaccharides hydrolysis collectively drove color darkening, astringency enhancement, sweetness intensification, and cooked-off flavor development. These findings provided targeted quality control points for USGTB during actual shelf-life.

Depression seriously affects people's quality of life, and there is an urgent need to find novel drugs to cure treatment-resistant depression. Berberine (BBR), extracted from Coptis chinensis Franch., Phellodendron bark, Berberis vulgaris, and Berberis petiolaris, could be a potential multi-target drug for depression. To summarize the effects of BBR on depression in terms of in vitro or in vivo experiments, we searched electronic databases, such as PubMed, Web of Science, Google Scholar, Wanfang Database, and China National Knowledge Infrastructure, from inception until May 2024. Then, we summarize that BBR has indirect antidepressant properties to improve depressive symptoms, manifesting in modulating the gut microbial community, strengthening the intestinal barrier, increasing the abundance of short-chain fatty acid-producing bacteria, and regulating tryptophan metabolism. BBR also exerts antidepressant-like effects via remodulating nuclear factor-erythroid 2-related factor 2/antioxidant response element pathway, hypothalamic-pituitary-adrenal axis, and peroxisome proliferators-activated receptor-delta. Nevertheless, further clinical trials and more high-quality animal studies are needed to show the actual clinical value of BBR for depression.

Given the high recurrence rate, elevated risk of metastasis, and drug resistance associated with oral squamous cell carcinoma (OSCC), the development of low - toxicity and highly efficient therapeutic agents has emerged as a top research priority. In this study, we conducted an in-depth investigation into the efficacy and underlying mechanism of berberine (BBR), a compound renowned for its broad anticancer activity, in the context of OSCC. Using network pharmacology, we identified 91 potential targets of BBR in OSCC, with SRC, PIK3CA, and CDC42 ranking among the top. KEGG pathway analysis indicated that the cross-targets were predominantly concentrated in signaling pathways such as PI3K/AKT, AGE-RAGE, and Ras. Molecular docking assays demonstrated that the binding energies between BBR and the core targets were all below -5 kcal/mol, signifying favorable binding interactions. Bioinformatics studies unveiled that SRC, PIK3CA, and CDC42 were highly expressed in OSCC patients and correlated with a poorer prognosis. In vitro, experiments further substantiated that BBR impeded the proliferation and migration of OSCC cells and reduced the intracellular expression levels of RAGE, p-PI3K, p-AKT, and p-mTOR proteins. Our results suggest that BBR effectively facilitates apoptosis and curbs the proliferation and migration of OSCC, potentially by suppressing the RAGE/PI3K/AKT/mTOR pathway. In summary, these findings underscore the potential of BBR as a single agent capable of exerting multi-target and multi-pathway synergistic effects on cancer cells.

The present research was designed to explore the epigenetic mechanism by which dietary berberine (BBR) affects glucose metabolism in fish. Blunt snout bream (Megalobrama amblycephala) is susceptible to disturbances in glucose metabolism when subjected to prolonged high-carbohydrate diets. This study aimed to elucidate whether BBR can enhance glucose regulation in M. amblycephala via modulating DNA methylation levels. Fish (average weight of 20.36 ± 1.44 g) were administered a normal-carbohydrate diet (NC, 30 % carbohydrate), a high-carbohydrate diet (HC, 43 % carbohydrate), or a high-carbohydrate diet supplemented with 50 mg/kg berberine (HB) for 10 weeks. Subsequently, global DNA methylation level, whole-genome bisulfite sequencing (WGBS), RNA-seq, bisulfite sequencing PCR, and real-time quantitative PCR were employed to analyze the DNA methylation patterns and transcription results of the liver genome. The findings indicated that high carbohydrate diets induced glucose metabolism disorders in M. amblycephala, whereas BBR mitigated these metabolic disturbances by reducing methylation levels. WGBS results revealed that CG-type cytosine methylation predominated, and that DNA methylation mainly occurred in promoter, intron, and exon regions. Furthermore, analyses demonstrated a negative correlation between DNA methylation around the transcriptional start site and gene expression levels for 47 genes. Functional enrichment analysis revealed that these genes were associated with 60 KEGG pathways, including 12 genes implicated in the amelioration of insulin resistance, reduction of gluconeogenesis, and maintenance of glucose homeostasis. Consequently, we generated a comprehensive catalog of liver DNA methylation in M. amblycephala, which provides a foundational framework for future investigations into the epigenetic regulation of glucose metabolism by BBR.

This research focused on fabricating a new type of wound dressing made from nanofibers infused with strontium-doped berberine carbon quantum dots (Str-Ber-CQD) to speed up healing and improve the quality of healed tissue. We applied a hydrothermal method using berberine as the carbon source to synthesize Str-Ber-CQD and then blended it into nanofibers made from scleroglucan/polyvinyl alcohol at different concentrations. The results showed that the CQDs have spherical morphology with a size of 3.6 ± 0.9 nm, an average hydrodynamic diameter of 53.2 ± 2.1 nm, and a PDI of 0.350. The XPS and EDX analysis showed that CQDs were composed of C, O, N, and Sr. The fabricated nanofibers have a uniform morphology with promising mechanical strength, swelling capacity, biodegradation, water vapor transmittance rate, and microbial barrier potential. The in vitro biological evaluations confirmed potent antioxidant and antibacterial activities and excellent hemocompatibility/cytocompatibility. The animal studies showed that the optimum structure (nanofibers/ Str-Ber-CQD 5 %) showed impressive results in animal tests involving full-thickness skin wounds. In summary, this study demonstrates that nanofibers/Str-CQD exhibited promising physical, chemical, and biological properties and can be considered a multifunctional wound dressing.

Acne vulgaris is an immune-mediated inflammatory skin condition. It is the 8th most treated skin condition, affecting over 80% of teenagers globally. The pathophysiology of the disease is intricate and involves the interaction of multiple factors, including hyperactivation of sebaceous glands, abnormal hyperkeratinization of pilosebaceous follicles, dysbiosis of microflora, and, subsequently, immune-mediated inflammation. Due to the multifaceted nature of the disorder, a combination of different anti-acne agents is preferred. However, synthetic topical anti-acne agents such as retinol derivatives and benzoyl peroxide are often associated with common side effects such as redness, dryness, peeling, irritation, and eczema. Also, increasing cases of multidrug resistance against commonly used antibiotics further reduce the therapeutic effectiveness of the treatment and upsurge the overall expense. Many studies validate using plant extracts and secondary metabolites for treating acne. Alongside synergistic formulations, the co-delivery of synthetic and herbal agents is emerging as the latest target for developing novel and efficient acne treatments. This article summarizes the comprehensive pathophysiology of the disease, classification, and grading system evolution, along with detailed information on different FDA-approved synthetic topical and systemic anti-acne agents (retinoids, antibiotics, and diverse medications). In addition, we highlight the new investigation on several phytoconstituents and secondary metabolites for treating acne vulgaris. Finally, we have attached the details of all the ongoing clinical trials on acne therapy.

The overuse of antibiotics has increased the prevalence of drug-resistant bacteria in periodontitis. "Sentinel" gingival fibroblasts, stimulated by pathogenic bacteria, continue to release signaling factors that affect stem cell repair and recruit immune cells, resulting in persistent inflammation in periodontal tissues, eventually leading to the loosening and loss of teeth. Periodontal pathogenic bacteria cause surface hypoxia, and gingival fibroblasts in the inflammatory microenvironment express HIF-1α, promoting hypoxic areas in periodontal pockets. No drug delivery system is available for the hypoxic region of periodontal pockets. We synthesized BI NPs via berberine (BBR) and indocyanine green (ICG) and formed BIP NPs by wrapping BI NPs with polydopamine (PDA), and the BIP NPs were delivered to the hypoxic region of the periodontal pocket by hitchhiking with the anaerobic probiotic Bifidobacterium bifidum (Bif). The BIP NPs released berberin (BBR) under near-infrared (NIR) irradiation, which inhibited the sulfur metabolism of Porphyromonas gingivalis via mild photothermal action and BBR-targeted serine acetyltransferase, resulting in a decrease in resistance to oxidative stress, thus exerting a nonantibiotic bacteriostatic effect. This mild photothermal effect facilitated the uptake of BIP NPs bygingival fibroblasts. Moreover, BBR targeted nuclear factor-erythroid 2-related factor 2 (NRF2) to reduce ferroptosis, and the gingival fibroblast supernatant modulated macrophage polarization through the NF-κB pathway. In the periodontitis rat model, Bif@BIP+NIR treatment carried the drug to deep periodontal pockets, decreasing local gingival ferroptosis and alleviating periodontitis symptoms. To summarize, engineered probiotics target low-oxygen periodontal pockets for drug delivery, P. gingivalis for nonantibiotic bacterial inhibition, and gingival fibroblasts to mitigate ferroptosis, thus alleviating periodontitis to reduce periodontitis.

Childhood obesity is a growing global health issue. Its rising prevalence is linked to genetic, environmental, and lifestyle factors. Obesity in children could lead to different comorbidities and complications with an increased risk of metabolic disorders, such as insulin resistance, dyslipidemia, type 2 diabetes mellitus (T2DM), and metabolic dysfunction-associated steatotic liver disease (MASLD). First-line treatment involves dietary modifications and lifestyle changes; however, adherence is often poor and remains a significant challenge. Pharmacotherapy, while a potential option, has limitations in availability and can cause side effects, leading to growing interest in alternative treatments, such as nutraceutical compounds. Derived from natural sources, these compounds have different anti-inflammatory, antiallergic, antioxidant, antibacterial, antifungal, neuroprotective, antiaging, antitumor, insulin-sensitizing, glucose, and lipid-lowering effects. This review describes commonly used nutraceutical compounds, such as omega-3 fatty acids, vitamin D, polyphenols (such as resveratrol and curcumin), berberine, white mulberry leaves and others, and pre- and probiotics in the management of obesity, evaluating the evidence on their mechanisms of action and efficacy in metabolic comorbidities. The evidence suggests that the integration of nutraceuticals into the diet may positively influence body mass index, glucose metabolism, lipid profiles, and gut microbiota composition and reduce inflammation in obese individuals. These effects may provide future practical guidance for clinical practice, contribute to metabolic health improvement, and potentially prevent obesity-related complications. In this first part, we discuss the effects of nutraceutical compounds on insulin sensitivity and insulin resistance, T2DM, dyslipidemia, and MASLD in addition to diet and lifestyle interventions.

Glucocorticoids (GCs) are widely used anti-inflammatory agents that inhibit growth in children. However, their mechanisms and effect on the growth hormone (GH)/insulin-like growth factor (IGF)-1 axis remain unclear.

This study, we aimed to establish a mouse model of GC-induced growth retardation during the critical growth period and explore the underlying mechanisms. Additionally, we aimed to identify novel biomarkers and potential therapeutic agents for GC-induced growth impairment.

Four-week-old mice were treated with GCs for two weeks and subsequently assessed for body length, weight, and body composition. Immunohistochemical analysis of the growth plate in the proximal tibia and biochemical assays of blood were performed to evaluate changes in growth plate length and GH/IGF-1 axis. KMT1A expression and its effects on Ghr expression were examined, and the impact of berberine on GC-induced growth retardation was assessed.

GCs significantly reduced growth by impairing growth plate expansion, disrupting the GH/IGF-1 axis, and downregulation of the GH receptor (Ghr) and Igf-1 levels in the liver. These changes were attributed to the upregulation of the H3K9 trimethyltransferase KMT1A, which decreased Ghr transcription in the liver. In vitro screening of natural compounds revealed that berberine chloride hydrate decreased the KMT1A levels and increased GHR levels. Berberine chloride hydrate also effectively ameliorated GC-induced growth retardation by restoring Ghr expression via KMT1A inhibition, thereby enhancing the circulating IGF-1 levels.

Overall, our findings highlight the potential of targeting KMT1A using berberine chloride hydrate as an epigenetic modifier to treat GC-induced growth impairment.

Berberine hydrochloride (Ber), a bioactive compound widely found in the roots, rhizomes, stems and barks of Coptis chinensis, has demonstrated efficacy in treating many diseases, such as cancer, congestive heart failure, Alzheimer's disease, especially inflammatory caused by bacteria. The molecularly imprinted microspheres based on chitosan were fabricated to adsorb selectively, release and anti-bacteria of Ber. The Ber surface molecularly imprinted microspheres (Ber-PSSS@GCS-MIPs) were synthesized using crosslinked chitosan as matrix, Ber as template, and sodium 4-styrene sulfonate (SSS) as functional monomer via a redox surface-initiating system -NH2/-S2O82-. The microspheres were characterized by fourier transform infrared reflection (FTIR), scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). Adsorption kinetics, isotherms and imprinting factor were investigated, and the drug release performance and antibacterial activity were evaluated. As a result, via electrostatic interaction and "lock-key" imprinted cavities, the adsorption capacity of Ber-PSSS@GCS-MIPs reaches 185 mg/g at 2 h, significantly higher than 51 mg/g observed for non-imprinted microspheres. The adsorption of Ber-PSSS@GCS-MIPs. follows pseudo-second-order kinetics, with adsorption amount decreasing as temperature increases and salt concentration rises. Ber-PSSS@GCS-MIPs show excellent recognition and selectivity with an imprinting factor of 3.07, a selectivity factor exceeding to 2. The adsorption capacity remains at 82.4 % of three times cycles. The Ber-PSSS@GCS-MIPs loaded drug microspheres attain slow and sustained release for 70 % at 139 h. The relative antibacterial rate of Ber-PSSS@GCS-MIPs loaded Ber is higher than non-imprinted microsphere and control against S. aureus and E. coli.

Berberine (BBR), an isoquinoline alkaloid from Coptidis Rhizoma, possesses powerful activities against diverse human malignancies, including non-small cell lung cancer (NSCLC). Nevertheless, the underlying anti-tumor mechanisms of BBR in NSCLC remain poorly understood.

NSCLC cells were cultured and treated with various doses (0, 15, 30, and 45 μM) of BBR for 48 h. Cell viability, proliferation, apoptosis, migration, and invasion were detected using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, transwell, and wound healing assays. Cell division cycle-associated protein 5 (CDCA5) and Cyclin A2 (CCNA2) mRNA level and protein level were measured using real-time quantitative polymerase chain reaction (RT-qPCR) and western blot assays. After STRING databases prediction, the possible interaction between CDCA5 and CCNA2 was identified using Co-Immunoprecipitation (IP) assays. The biological role of BBR treatment on NSCLC tumor growth was assessed using the xenograft tumor model in vivo.

BBR treatment blocked NSCLC cell proliferation, migration, invasion, and promoted apoptosis. CDCA5 and CCNA2 levels were increased in NSCLC tissues, whereas their expression was decreased in BBR-induced NSCLC cells. CDCA5 or CCNA2 overexpression might attenuate the inhibitory role of BBR on NSCLC cell malignant behaviors. CDCA5 interacted with CCNA2 to regulate its expression in NSCLC cells. BBR administration blocked NSCLC xenograft growth in vivo.

BBR hindered NSCLC cell malignant progression partly by modulating CDCA5 and CCNA2, providing a promising therapeutic target for NSCLC treatment.

Natural products, characterized by their structural diversity, broad spectrum of biological activities, and safe yet effective therapeutic potential, have become pivotal resources in drug research and development. However, the target proteins of many natural products remain unidentified, a significant challenge that impedes their development into viable drug candidates. Therefore, the target identification is crucial for elucidating the pharmacological mechanisms of natural products and facilitating their therapeutic applications. In this review, we present a comprehensive overview of recent advancements in methodologies for target identification of natural products. Additionally, we predict future developments in new technologies for target discovery. Collectively, this review establishes a methodological framework for uncovering the cellular targets and pharmacological mechanisms of natural products, thereby advancing the development of innovative natural product-based drugs.

Chinese herbal medicine constitutes a substantial cultural and scientific resource for the Chinese nation, attracting considerable scholarly interest due to its intrinsic characteristics of "multi-component, multi-target, and multi-pathway" interactions. Simultaneously, it aligns accurately with the intricate and continuously evolving progression of non-small cell lung cancer (NSCLC). Furthermore, contemporary pharmacological studies indicate that natural herbaceous plants and their bioactive compounds exhibit a diverse array of biological activities, including antioxidant, anti-inflammatory, and anti-tumor effects, among others. Additionally, these substances have been demonstrated to possess a degree of safety, particularly in terms of exhibiting comparatively lower levels of toxicity to the liver and kidneys when contrasted with conventional Western medicine. Thus, the development of herbal plants, which includes both single herbs and composite formulations, as well as their bioactive constituents, through the targeted regulation of ferroptosis and mitophagy, presents substantial potential and instills considerable hope for individuals diagnosed with NSCLC.

This review aims to conduct a critical analysis of the ethnopharmacological applications of natural herbaceous plants in relation to ferroptosis and mitophagy in NSCLC. The objective is to evaluate the potential advantages of prioritizing specific phytochemical constituents found in these plants, which may serve as novel therapeutic candidates informed by ethnobotanical knowledge. Additionally, this study seeks to enhance the current pharmacological applications of natural herbaceous plants.

An investigation into natural herbal remedies for NSCLC was conducted, with a particular emphasis on the ferroptosis and mitophagy pathways. This study utilized traditional medical texts and ethnomedicinal literature as primary sources. Furthermore, relevant information related to ethnobotany, phytochemistry, and pharmacology is obtained from online databases, including PubMed and the China National Knowledge Infrastructure (CNKI), among others. "Traditional Chinese medicine compound preparations", "single herb extracts", "active compounds", "NSCLC", "ferroptosis", and "mitophagy" were used as keywords when searching the databases. Consequently, pertinent articles published in recent years were collected and analyzed.

Given the complex etiology of NSCLC, treatment strategies that concentrate exclusively on ferroptosis or mitophagy often demonstrate limitations. In this regard, the utilization of herbal plants offers unique benefits in the management of NSCLC. The rationale can be summarized within the following two dimensions: Firstly, due to the molecular mechanisms of ferroptosis and mitophagy involving multiple signaling pathways (including PINK1/Parkin, HMGB1, system Xc-/GPX4/GSH, FSP1/CoQ10/NAD (P) H, and so on), sometimes drugs with a single target are difficult to involve multiple pathways. Fortunately, there is an expanding body of evidence suggesting that various herbaceous plants and their bioactive compounds can affect multiple biological targets. Moreover, these compounds seem to interact with several targets associated with ferroptosis and mitophagy in NSCLC (such as NIX, BNIP3, FUNDC1, GPX4, FSP1, P53, Nrf2, LncRNA, and so on). Secondly, Herbaceous plants and their bioactive compounds have been shown to possess a favorable safety profile, particularly with respect to reduced hepatotoxicity and nephrotoxicity in comparison to conventional Western medicine. For example, Numerous compound formulations, such as Fangji Huangqi decoction, Mufangji decoction, Qiyu Sanlong decoction, and Fuzheng Kangai decoction, have been employed in China for millennia, and their clinical efficacy appears to be quite promising. Notably, In recent years, numerous researchers have sought to isolate active constituents from clinically effective compound formulations through the application of chemical methodologies. This endeavor has been driven by the necessity to tackle challenges related to complex ingredient compositions and sophisticated processing. These active compounds have been employed in cellular and animal studies to elucidate the molecular mechanisms underlying these formulations.

The Asian region has a long-standing historical tradition of employing natural herbaceous plants for traditional medicinal purposes. Phytochemical and pharmacological studies have shown that various compound preparations derived from traditional Chinese medicine, along with individual herb extracts and their active constituents, display a range of bioactive effects. These effects encompass anti-tumor, anti-inflammatory, antibacterial, and antioxidant properties, among others. Numerous traditional compound formulations originating from China have emerged as promising candidates for the development of pharmacological agents targeting NSCLC. It is noteworthy that a variety of compound formulations aimed at the ferroptosis and mitophagy pathways, which demonstrate unique therapeutic effects on NSCLC, are presently under extensive investigation by an increasing number of researchers. Therefore, it is imperative to consider in vitro mechanistic studies, in vivo pharmacological evaluations, and assessments of clinical efficacy. Furthermore, it is essential to conduct a comprehensive assessment of plant resources, implement quality control measures, and engage in toxicological research to ensure that the data is appropriate for further examination.

Berberine is an isoquinoline alkaloid isolated from Chinese herb coptis chinensis and other berberis plants which can be used to treat a wide range of chronic diseases. However, the current research evidence on the therapeutic effects of berberine has not been summarized. We aimed to synthesize the current evidence on the systematic review (SRs) of berberine for the treatment of diverse conditions.

A comprehensive search of the Cochrane Library, PubMed, EMBASE, Web of Science, CNKI, Wanfang, VIP, and SinoMed was performed from the database inception to April 11, 2024. SRs on berberine were included and evaluated. The methodological quality and the reporting quality of each SR were assessed using the AMSTAR-2 tool and PRISMA checklist, respectively. The quality of evidence was appraised based on the GRADE.

Fifty-four SRs were included and analyzed. Overall, associations were found between berberine and 70 health outcomes concerned with 9 diseases. Berberine has improved most outcomes of these diseases: 78% (25/32) cardiovascular disease outcomes, 92.59% (25/27) type 2 diabetes mellitus outcomes, 94.74% (18/19) gastrointestinal disorders outcomes, 72.22% (13/18) polycystic ovary syndrome (PCOS) outcomes, 86.67% (13/15) non-alcoholic fatty liver disease (NAFLD) outcomes, 92.31% (12/13) schizophrenia outcomes, 90.91% (10/11) metabolic syndrome outcomes, 57.14% (4/7) obesity outcomes, and 100.00% (6/6) dyslipidemia outcomes. There was a high overlap of primary studies (CCA > 15%) in the SRs of PCOS, NAFLD, obesity, and schizophrenia. Only one SR was rated as high quality while eight SRs were rated as low quality and forty-five SRs as very low quality according to AMSTAR-2. Regarding the reporting quality, Item 14, 15, 21, and 22 were poorly reported for the included SRs in terms of PRSMA assessment. For GRADE, eight outcomes were rated as high quality evidence, twenty-two outcomes were rated as moderate quality, and 110 outcomes were rated as low quality.

Current evidence suggests that berberine has beneficial effects on a range of health outcomes for people with chronic diseases. Specifically, berberine significantly improves type 2 diabetes, gastrointestinal disorders, schizophrenia, metabolic syndrome, and dyslipidemia outcomes. However, caution is needed considering the shortcomings in the quality of the relevant system reviews included.

Parkinson's disease is a progressive neurodegenerative disorder characterized by motor symptoms such as tremors, rigidity, and bradykinesia. Although the exact etiology is unknown, the nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome-induced inflammation, plays a crucial role in the pathogenesis of Parkinson's disease. Many NLRP3 inhibitors are recognized for their role as potential therapeutic interventions for Parkinson's disease.

A systematic literature search was performed in PubMed, Embase, and Science Direct databases for papers published during the 10 years prior to May 2023. All animal interventional studies assessing the effects of NLRP3 inhibitors on Parkinson's disease animal models were included. Primary outcomes included NLRP3 inflammasome inhibition, microglial activation reduction, oxidative stress, and anti-inflammatory marker reduction. The secondary outcomes included dopaminergic neuron loss alleviation and behavioral motor function attenuation. Quality assessment and narrative synthesis of the studies were performed.

Twenty-four studies out of 796 papers initially identified met the inclusion criteria. All the included studies, except one, found a reduction in NLRP3 inflammasome activation and anti-inflammatory markers in Parkinson's disease animal models after treatment with various NLRP3 inhibitors compared to control groups without inhibitors. Additionally, eighteen out of twenty-four inhibitors decreased microglial activation and behavioral deficits. Moreover, ten inhibitors attenuated oxidative stress, and twenty-two out of twenty-four alleviated dopaminergic neuron loss. The inhibitors utilized different mechanisms and pathways to exert their effects, including the NLRP3/Caspase-1 pathway, the NF-κB/NLRP3 pathway, inhibition of ROS and/or pyroptosis, as well as autophagy and mitophagy.

NLRP3 inhibitors represent a prospective therapy for Parkinson's disease, demonstrating efficacy in lowering neuroinflammation and protecting against dopaminergic loss. However, constraints, such as a male animal focus, apparent regional bias from China-centric studies, and diversity in induction models, entail the results presented herein require cautious interpretation. Further research, including preclinical and clinical studies, is required to thoroughly examine the safety, effectiveness, and generalizability of NLRP3 inhibitors in Parkinson's disease.

Cancer continues to be among the most substantial health challenges globally. Among various natural compounds, berberine, an isoquinoline alkaloid obtained from Coptidis Rhizoma, has garnered considerable attention for its broad-spectrum biological activities, including anti-inflammatory, antioxidant, anti-diabetic, anti-obesity, and anti-microbial activities. Furthermore, berberine exhibits a broad spectrum of anti-cancer efficacy against various malignancies, such as ovarian, breast, lung, gastric, hepatic, colorectal, cervical, and prostate cancers. Its anti-cancer mechanisms are multifaceted, encompassing the inhibition of cancer cell proliferation, the prevention of metastasis, the induction of apoptosis, the facilitation of autophagy, the modulation of the tumor microenvironment and gut microbiota, and the enhancement of the efficacy of conventional therapeutic strategies. This paper offers an exhaustive overview of the cancer-fighting characteristics of Coptidis Rhizoma and berberine, while also exploring recent developments in nanotechnology aimed at enhancing the bioavailability of berberine. Furthermore, the side effects and safety of berberine are addressed as well. The potential role of artificial intelligence in optimizing berberine's therapeutic applications is also highlighted. This paper provides precious perspectives on the prospective application of Coptidis Rhizoma and berberine in the prevention and management of cancer.

Medicinal plants, recognized as significant natural resources, have gained prominence in response to the increasing global demand for herbal medicines, necessitating the large-scale production of these plants and their derivatives. Medicinal plants are exposed to a variety of internal and external factors that interact to influence the biosynthesis and accumulation of secondary metabolites. With the rapid development of omics technologies such as genomics, transcriptomics, proteomics, and metabolomics, multi-omics technologies have become important tools for revealing the complexity and functionality of organisms. They are conducive to further uncovering the biological activities of secondary metabolites in medicinal plants and clarifying the molecular mechanisms underlying the production of secondary metabolites. Also, artificial intelligence (AI) technology accelerates the comprehensive utilization of high-dimensional datasets and offers transformative potential for multi-omics analysis. However, there is currently no systematic review summarizing the genomic mechanisms of secondary metabolite biosynthesis in medicinal plants. Safflower (Carthamus tinctorius L.) has rich and diverse bioactive flavonoids, among of which Hydroxysafflor yellow A (HSYA) is specific to safflower and emerging as a potential medication for treating a wide range of diseases. Hence, significant progress has been made in the study of safflower as an excellent example for the regulation of secondary metabolites in medicinal plants in recent years. Here, we review the progress on the understanding of the regulation of main secondary metabolites at the multi-omics level, and summarize the influence of various factors on their types and contents, with a particular focus on safflower flavonoids. This review aims to provide a comprehensive insight into the regulatory mechanisms of secondary metabolite biosynthesis from the perspective of genomics.

Diabetes mellitus (DM) is a chronic endocrine and metabolic disorder characterized by persistent hyperglycemia that poses serious threats to human health and quality of life. The morbidity, disability, and mortality rates of cardiovascular complications stemming from chronic hyperglycemia are primary factors affecting the lifespan of patients with diabetes. Currently, there is no cure for DM. Standard biomedical treatments mostly control the symptoms using insulin injections or oral hypoglycemic drugs. Although the effect of standard biomedical therapy is remarkable, its long-term use is prone to toxic side effects. Numerous studies have recently found that Traditional Chinese Medicine (TCM) has strong advantages in the prevention and treatment of DM and cardiovascular complications (DACC). The collection, processing, preparation and clinical use of TCM are guided by the theory of TCM and follow the "holistic concept." Multiple components, pathways, and targets form the basis for the use of TCM in treating multiple parts and organs of the body simultaneously. TCM is mainly derived from natural medicines and their processed products and has fewer side effects. TCM is clinically used as compound prescriptions, botanical drugs, and monomers. TCM, either independently or in combination with standard biomedical treatments, has shown unique therapeutic advantages. This review aimed to explore the recently reported mechanisms of action of TCM in the prevention and treatment of DACC. These findings will aid the optimization of the current therapy or formation of a therapeutic schedule for integrated TCM and standard biomedical treatments.

Infection with influenza A virus (IAV) may trigger excessive inflammatory responses, leading to severe viral pneumonia and accelerating disease progression. Therefore, controlling these excessive inflammatory responses is crucial for the prevention and treatment of pneumonia caused by IAV. Berberine (BBR), an isoquinoline alkaloid extracted from traditional Chinese medicine, possesses extensive pharmacological activities. However, its immunoregulatory effects and molecular mechanisms in the context of IAV infection require further investigation. This study explored the impact of BBR on macrophage pyroptosis and inflammatory responses induced by IAV infection. Our findings revealed that BBR effectively inhibits the release of IL-1β and TNF-α induced by IAV infection and suppresses gasdermin D (GSDMD)-mediated pyroptosis in a dose-dependent manner. Further research indicates that BBR alleviates macrophage pyroptosis and inflammatory responses in IAV-infected cells by reducing the release of mitochondrial reactive oxygen species (mtROS), inhibiting mitochondrial antiviral signaling protein (MAVS) expression and blocking the activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome. Experiments using siRNA to knockdown MAVS further confirmed the pivotal role of MAVS in BBR's inhibition of IAV-induced macrophage pyroptosis. This study provides a scientific basis for the application of BBR as an anti-inflammatory drug in the treatment of inflammatory diseases caused by IAV infection and directs future research endeavors.

Endometrial cancer (EC) is a common malignant disease in women, originating from the endometrial tissue. Over the past few decades, the global incidence rate of EC has gradually increased, and the affected population has become progressively younger. Traditional treatment methods, such as surgery and adjuvant therapy, have considerable toxic side effects. Furthermore, their therapeutic effectiveness is significantly very uncertain. Therefore, the search for a new type of treatment for EC is a top priority. Natural products are a class of compounds found in nature that have a wide range of biological functions; their derivatives have chemical structures that show great potential for developing new drugs. The latest studies have found that certain natural products, such as flavonoids, plant polyphenols, terpenoids and alkaloids, have inhibitory effects on EC cells in non-clinical models and animal studies. Despite challenges, including low extraction and bioavail ability, the potential of natural products for treating EC is still highly regarded by the scientific community. In the future, as research on natural products deepens and is combined with modern drug design and delivery technologies, it is hoped that more efficient and less toxic anti-cancer drugs will be developed, thereby offering EC patients more treatment options and hope. This article summarises the possible molecular mechanisms of various natural products and their bioactive components with regard to EC cells, as well as the latest research, to provide new ideas for further research and drug development.

Cardiovascular disease poses a significant risk to human health and remains the leading cause of illness and death globally, with its incidence continuing to rise. The intricate pathophysiological mechanisms of CVDs include inflammation, oxidative stress, autophagy, and myocardial fibrosis. In light of these underlying mechanisms, traditional Chinese medicine (TCM) and its constituents have demonstrated distinct advantages in managing CVDs. By exerting synergistic effects across multiple components and targets, traditional Chinese medicine can modulate the inflammatory response, mitigate oxidative stress, regulate excessive autophagy, and enhance myocardial fibrosis repair. This article reviews the latest advancements in understanding how TCM compounds regulate signaling pathways involved in the treatment of CVDs.

Rhizoma Coptidis (RC) is an edible and medicinal herb with anti-hyperglycemia, which has potential application in the prevention of diabetic encephalopathy (DE). However, its efficacy and underlying mechanism in DE prevention have not been elucidated yet. The objective of the current study is to investigate the preventive effect of RC on DE, thereby focusing on the target through the method of network pharmacology and molecular docking.

Sixty 4-week-old, male C57BL/6 mice were randomly allocated to six groups: control, model, metformin (200 mg/kg), RCL (0.75 g/kg), RCM (1.5 g/kg), and RCH (3 g/kg). The DE-model mice were induced by streptozocin combined with a high-fat diet. In addition, the neuroprotective effect of RC was determined both in vivo and in vitro. Network pharmacology analysis was used to screen the potential mechanism of RC. Thereafter, the underlying mechanism of action of RC was explored by molecular docking prediction and Western blot analysis. An analysis of patients with DE was performed to validate it from another perspective.

The results showed that the cognitive state of DE model mice was improved and neuronal injury was ameliorated after RC administration. Active compounds in RC, berberine and coptisine, were found to ameliorate HT22 injury induced by high glucose. Network pharmacology results suggest that voltage-gated sodium channel subtypes (Nav1.1, Nav1.2, and Nav1.6) may be the targets for RC prevention of DE. Furthermore, the Western blot analysis revealed that RC significantly upregulated Nav1.1 and Nav1.2, while Nav1.6 could not. In addition, serum sodium was related to the cognitive status of DE patients, which can be used as a diagnostic index for mild and moderate-severe DE.

RC has the potential to be a functional food or adjuvant drug for DE prevention, and Nav1.1 and Nav1.2 are promising DE intervention targets.

Vascular cognitive impairment (VCI) is a prevalent cognitive disorder resulting from cerebrovascular disease and encompasses a spectrum of cognitive deficits, ranging from mild impairment to vascular dementia (VD). VCI is responsible for a minimum of 20% to 40% of all cases of dementia, with its prevalence ranking second only to Alzheimer's disease on a global scale. The pathogenesis of VCI is complex and includes a lack of cholinergic nerve cells, inflammation, oxidative stress, alterations in the blood-brain barrier, and cell apoptosis. Current guideline-recommended drugs have unsatisfactory therapeutic effects. However, traditional Chinese medicine (TCM) has long been associated with treating dementia, and numerous studies regarding treating dementia with TCM have been conducted. The etiology and pathogenesis of VaD are linked to deficiencies in the spleen and kidney, as well as phlegm turbidity. Treatment involves benefiting the spleen and kidney, improving blood circulation, removing blood stasis, and dispelling phlegm. Moreover, TCM presents benefits such as few adverse effects, low cost, long-term use suitability, and preventive effects. This review outlines the pathogenesis of VCI in both modern medicine and TCM, examines traditional prescriptions and single-agent ingredients with their pharmacological effects, emphasizes TCM's unique features, and explores its multi-targeted approach to treating VCI.

Chronic atrophic gastritis (CAG) is an important stage of precancerous lesions of gastric cancer. Effective treatment and regulation of CAG are essential to prevent its progression to malignancy. Traditional Chinese medicine (TCM) has shown multi-targeted efficacy in CAG treatment, with advantages in enhancing gastric mucosal barrier defense, improving microcirculation, modulating inflammatory and immune responses, and promoting lesion healing, etc. Clinical studies and meta-analyses indicate that TCM provides significant benefits, with specific Chinese herbal compounds and monomers demonstrating protective effects on the gastric mucosa through mechanisms including anti-inflammation, anti-oxidation, and regulation of cellular proliferation and apoptosis, etc. Finally, it is pointed out that the efficacy of TCM in the treatment of CAG requires standardized research and unified standards, and constantly clarifies and improves the evaluation criteria of each dimension of gastric mucosal barrier function.

Diabetes is a serious global health issue and increases the risk of several chronic diseases. However, if hyperglycemia and other metabolic abnormalities related to diabetes are controlled, fewer micro- and macrovascular complications may occur.

To investigate whether daily supplementation with berberine in combination with cinnamon could have effect on cardiometabolic risk factors, such as impaired glucose regulation, dyslipidemia, and hypertension in patients with diabetes.

Patients with type 2 diabetes were recruited to participate in a parallel, double-blind, placebo-controlled, randomized study. Participants were randomized into berberine in combination with cinnamon supplementation or placebo group. Participants were then asked to take a divided daily dose of 1200 mg berberine and 600 mg cinnamon or placebo for 12 weeks. ANCOVA was then performed to evaluate the differences between the two groups, controlling for the respective baseline values.

At the end of study, fasting blood sugar (FBS) (P = 0.031) and hemoglobin A1C (HbA1c) (P = 0.013) were significantly lower in participants taking berberine plus cinnamon than those taking the placebo capsules. The results of the serum lipid profile also indicated a significant difference in the level of low density lipoprotein cholesterol (LDL-C) (P = 0.039), while no difference was observed in the levels of total cholesterol, high density lipoprotein cholesterol (HDL-C), and triglycerides between the study groups. In addition, there was no difference in other measured metabolic and anthropometric parameters between the two groups.

Twelve weeks of berberine plus cinnamon consumption reduced blood FBS, HbA1c and LDL-C concentration in patients with diabetes.

Polycystic ovary syndrome (PCOS) is a prevalent gynecological endocrine and metabolic disorder in women, with an incidence rate of 10-13%. The etiology of PCOS is multifaceted, involving genetic predisposition, environmental influences, lifestyle factors, and endocrine metabolic dysregulation. Iron, a critical mineral, not only plays a role in regulating female physiological functions and the progression of PCOS but also requires careful management to avoid deficiency. However, excess iron can trigger ferroptosis, a form of nonapoptotic cell death characterized by the accumulation of lipid peroxides. While numerous studies have explored ferroptosis in patients with PCOS and animal models, the precise mechanisms and therapeutic implications remain inadequately understood. This review seeks to elucidate the pathophysiology of PCOS and the contributory factors of ferroptosis. Additionally, we examine the diverse manifestations of ferroptosis in PCOS and evaluate its role. Furthermore, we introduce ferroptosis-related traditional Chinese medicines that may enhance the understanding of PCOS pathogenesis and aid in the development of targeted therapies for ferroptosis in PCOS.

Streptococcus suis (S. suis) is a major swine pathogen throughout the world as well as an emerging zoonotic agent. Among the symptoms caused by S. suis, including septicemia, pneumonia, endo-carditis, arthritis, and meningitis, the latter is the most overlooked. In the present study, we explored the mechanism of action of berberine against S. suis meningitis by obtaining berberine-related action targets, porcine S. suis meningitis targets, and human S. suis meningitis targets from open databases. We constructed a protein-protein interaction (PPI) network by using the STRING database and employed Cytoscape 3.8.0 to screen for core targets. We performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses through DAVID. We identified 31 potential targets of berberine, of which Toll-like receptor 4 (TLR4), fibronectin 1 (FN1), superoxide dismutase (SOD1), and catalase (CAT) were the four most critical targets. GO analysis revealed the enrichment of terms related to the response to oxidative stress and the inflammatory response. KEGG analysis revealed the enrichment of the interleukin 17 (IL-17), phosphoinositide 3-kinase (PI3K)-Akt, TLR, tumor necrosis factor (TNF), and mitogen-activated protein kinase (MAPK) signaling pathways. In addition, the admetSAR results showed that berberine can cross the blood-brain barrier. The molecular docking results indicated key binding activity between TLR4-berberine and FN1-berberine. In summary, berberine protects against Streptococcus suis meningitis by regulating inflammatory response and oxidative stress in humans and pigs. Our study updates the current knowledge of the targets of S. suis meningitis to exploit new drugs in humans and pigs, to develop environmentally friendly and antibiotic-free animal-derived food products, and to improve the farming industry and economic development.

Hyperthyroidism is a prevalent clinical endocrine disorder. Danggui Liuhuang Decoction (DGLHD), a traditional Chinese herbal medicine formula, has shown potential benefits for patients with hyperthyroidism in recent studies. However, the clinical efficacy and safety of DGLHD have not been systematically evaluated. To address this, a systematic review and meta-analysis are necessary to comprehensively evaluate its efficacy and safety in treating hyperthyroidism.

To evaluate the efficacy and safety of DGLHD in treating hyperthyroidism.

A comprehensive search of eight databases was conducted from their inception to November 2023 to identify randomized controlled trials (RCTs) comparing DGLHD combined with antithyroid drugs (ATDs) to ATDs alone. The quality of the included studies was assessed using the Cochrane Risk of Bias Assessment Tool. A meta-analysis was conducted using Revman 5.3 software, while publication bias was evaluated with Stata 16.0 software. The certainty of the evidence was assessed using the GRADE system.

Overall, 20 RCTs involving 1757 patients with hyperthyroidism were included in this analysis. The methodological quality was generally low. The meta-analysis revealed that, compared to ATDs alone, the combination of DGLHD with ATDs was more effective in reducing free triiodothyronine (FT3) [standardized mean difference (SMD) = -0.80, 95% confidence interval (CI): -1.31 to -0.28, P = 0.002], free thyroxine (FT4) [SMD = -1.47, 95% CI: -1.99 to -0.94, P < 0.00001], Traditional Chinese Medicine (TCM) syndrome scores [mean difference (MD) = -3.65, 95% CI: -4.68 to -2.62, P < 0.00001], and adverse events [relative risk (RR) = 0.23, 95% CI: 0.15 to 0.36, P < 0.00001]. Additionally, combining DGLHD with ATDs led to an improvement in thyroid-stimulating hormone (TSH) levels [SMD = 2.75, 95% CI: 1.37 to 4.13, P < 0.0001] and increased the effectiveness rate of TCM syndrome [RR = 1.20, 95% CI: 1.08 to 1.34, P = 0.001]. However, other outcomes, such as recurrence rates and quality of life scores, could not be analyzed through meta-analysis owing to the limited number of included studies.

Combining DGLHD with ATDs may alleviate clinical symptoms, enhance thyroid function, and reduce adverse events in patients with hyperthyroidism. Moreover, this treatment appears to be safe for clinical use. However, owing to the limited quantity and quality of the included studies, these conclusions require further validation through more large-sample, multicenter, high-quality RCTs.

Obesity has become a global pandemic. The approaches researched to prevent it include decreasing energy intake and/or enhancing energy expenditure. Therefore, research on brown adipose tissue is of great importance. Brown adipose tissue is characterized by its high mitochondrial content. Mitochondrial uncoupling protein 1 (UCP1) releases energy as heat instead of chemical energy. Thermogenesis increases energy expenditure. Berberine, a phytochemical widely used in Asian countries, has positive effects on body weight control. While the precise mechanisms behind this effect remain unclear, the adenosine monophosphate-activated protein kinase (AMPK) pathway is known to play a crucial role. Berberine activates AMPK through phosphorylation, significantly impacting brown adipose tissue by enhancing lipolytic activity and increasing the expression of UCP1, peroxisome proliferator-activated receptor γ-co-activator-1α (PGC1α), and PR domain containing 16 (PRDM16). While investigating the mechanism of action of berberine, both the AMPK pathway is being examined in more detail and alternative pathways are being explored. One such pathway is growth differentiation factor 15 (GDF15), known for its appetite-suppressing effect. Berberine's low stability and bioavailability, which are the main obstacles to its clinical use, have been improved through the development of nanotechnological methods. This review examines the potential mechanisms of berberine on browning and summarizes the methods developed to enhance its effect.

Metabolic syndrome (MS) refers to a cluster of metabolic disorders characterized by systemic chronic inflammation. Er Miao San (EMS) is a classic traditional Chinese medicine compound containing Phellodendron amurense and Atractylodis rhizome at a ratio of 1:1, proven to be effective against inflammatory diseases in clinical practice. Nevertheless, the precise functions of EMS in treating MS and its underlying mechanism have yet to be elucidated.

This study focuses on the intervention effects of EMS on high humidity exposure and high sugar-fat diet (HHSF)-induced MS in pigs.

Blood biochemical indices and metabolome analysis were employed to confirm the successful establishment of the MS model, and the preliminary evaluation of the intervention effect of EMS was conducted. Subsequently, a parallel microbiota analysis of the tongue and cecum was combined with metabolomic analysis, histopathologic examination, and other molecular biological detection to further assess the administration mechanism of EMS.

The results demonstrated that EMS significantly reduced the excessive weight gain rate, fat accumulation, hyperlipidemia, hyperglycemia, and systemic inflammation while improving serum metabolic disorder in MS pigs. Moreover, microbiota analysis indicates that EMS restored the diversity and composition of oral-gut microbiota by increasing the proportions of Lactobacillus (gut), Roseburia (gut), Faecalibacterium (gut), CF231 (gut), Streptococcus (gut), Prevotella (gut), while decreasing those of Chryseobacterium (oral), Corynebacterium (oral), Clostridium (oral), Oscillospira (gut), and Turicibacter (oral, gut). Subsequently, EMS up-regulated the concentrations of acetic acid, butyric acid, propionic acid, while down-regulated isobutyric acid and isovaleric acid. This resulted in a suppression of HDAC3 expression and an increase of SCL16A1 expression in the colon. Notably, the changes in acetic acid and butyric acid showed a strong correlation with gut microbiota. Additionally, EMS reduced the serum level of lipopolysaccharide (LPS) and enhanced epithelial barrier integrity by inhibiting the LPS-TLR4/MyD88/NF-κB pathways.

EMS was found to ameliorate MS by alleviating the dysbiosis of the oral-gut microbiota and serum metabolome, thereby improving gut barrier and reducing systemic inflammation. These findings suggest that EMS holds promise as a therapeutic agent for MS.

Dengue virus (DENV) continues to pose a significant global health challenge, causing diseases such as dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. While efforts in vaccine development and antiviral drug discovery are ongoing, effective therapeutic options remain limited. In this review, we highlight natural compounds and the analogs that demonstrated antiviral activity against DENV in in vitro and in vivo studies. Specifically, these studies examine alkaloids, phenolic acids, phenols, flavonoids, terpenoids, and glycosides which have shown potential in inhibiting DENV entry, replication, and reducing the cytokine storm. By focusing on these bioactive compounds and the analogs, a comprehensive overview of their promising roles is provided to advance therapeutic strategies for combating DENV infection.

Herbal medicines are widely used as alternative or complementary therapies to treat and prevent chronic diseases. However, these can lead to drug-drug interactions (DDIs) that affect the glucuronidation reaction of UDP glucuronosyltransferases (UGTs), which convert drugs into metabolites. Plant extracts derived from medicinal herbs contain a diverse array of compounds categorized into different functional groups. While numerous studies have examined the inhibition of UGT enzymes by various herbal compounds, it remains unclear which group of compounds exerts the most significant impact on DDIs in the glucuronidation reaction. Recently, alkaloids derived from medicinal herbs, including kratom (Mitragyna speciosa), have gained attention due to their diverse pharmacological properties. This review primarily focuses on the DDIs of plant alkaloids from medicinal herbs, including kratom on the phase II UGT enzymes. Kratom is a new emerging herbal product in Western countries that is often used to self-treat chronic pain, opioid withdrawal, or as a replacement for prescription and non-prescription opioids. Kratom is well-known for its psychoactive alkaloids, which have a variety of psychopharmacological effects. However, the metabolism mechanism of kratom alkaloids, particularly on the phase II pathway, is still poorly understood. Simultaneously using kratom or other herbal products containing alkaloids with prescribed medicines may have an impact on the drug metabolism involving the phase II UGT enzymes. To ensure the safety and efficacy of treatments, gaining a better understanding of the DDIs when using herbal products with conventional medicine is crucial.

Berberine is a promising agent for modulating the intestinal microbiota, playing a crucial role in human health homeostasis. This natural compound promotes the growth of beneficial bacteria such as Bacteroides, Bifidobacterium, and Lactobacillus while reducing harmful bacteria such as Escherichia coli. Clinical and preclinical studies demonstrate that Berberine helps regulate T2D and metabolic disorders, improves blood glucose levels during T2D, and reduces lipid profile and chronic inflammation, especially when combined with probiotics. Berberine represents a promising adjuvant therapy for inflammatory diseases, particularly intestinal disorders, due to its multifaceted actions of inhibiting proinflammatory cytokines and pathways during IBS, IBD, and UC and its modulation of gut microbiota and/or enhancement of the integrity of the intestinal epithelial barrier. This review establishes the basis for future treatment protocols with berberine and fully elucidates its mechanisms.

This article reviews the synergistic effects of antioxidant-enriched functional foods and exercise in improving metabolic health, focusing on the underlying molecular mechanisms. The review incorporates evidence from PubMed, SCOPUS, Web of Science, PsycINFO, and reference lists of relevant reviews up to 20 December 2024, highlighting the central role of the Nrf2 pathway. As a critical regulator of oxidative stress and metabolic adaptation, Nrf2 mediates the benefits of these interventions. This article presents an innovative approach to understanding the role of Nrf2 in the regulation of oxidative stress and inflammation, highlighting its potential in the prevention and treatment of various diseases, including cancer, neurodegenerative disorders, cardiovascular and pulmonary diseases, diabetes, inflammatory conditions, ageing, and infections such as COVID-19. The novelty of this study is to investigate the synergistic effects of bioactive compounds found in functional foods (such as polyphenols, flavonoids, and vitamins) and exercise-induced oxidative stress on the activation of the Nrf2 pathway. This combined approach reveals their potential to improve insulin sensitivity and lipid metabolism and reduce inflammation, offering a promising strategy for the management of chronic diseases. However, there are significant gaps in current research, particularly regarding the molecular mechanisms underlying the interaction between diet, physical activity, and Nrf2 activation, as well as their long-term effects in different populations, including those with chronic diseases. In addition, the interactions between Nrf2 and other critical signalling pathways, including AMPK, NF-κB, and PI3K/Akt, and their collective contributions to metabolic health are explored. Furthermore, novel biomarkers are presented to assess the impact of these synergistic strategies, such as the NAD+/NADH ratio, the GSH ratio, and markers of mitochondrial health. The findings provide valuable insights into how the integration of an antioxidant-rich diet and regular exercise can improve metabolic health by activating Nrf2 and related molecular pathways and represent promising strategies for the prevention and treatment of metabolic disorders. Further studies are needed to fully understand the therapeutic potential of these interventions in diseases related to oxidative stress, such as cardiovascular disease, neurodegenerative disease, diabetes, and cancer.

Helicobacter pylori-associated gastritis (HPAG) is a common condition of the gastrointestinal tract. However, extensive and long-term antibiotic use has resulted in numerous adverse effects, including increased resistance, gastrointestinal dysfunction, and increased recurrence rates. When these concerns develop, traditional Chinese medicine (TCM) may have advantages. TCM is based on the concept of completeness and aims to eliminate pathogens and strengthen the body. It has the potential to prevent this condition while also boosting the rate of Helicobacter pylori eradication. This review elaborates on the mechanism of TCM treatment for HPAG based on cellular signalling pathways, which reflects the flexibility of TCM in treating diseases and the advantages of multi-level, multi-pathway, and multi-target treatments for HPAG.

Cancer remains a formidable global health challenge, necessitating innovative therapeutic approaches to enhance treatment efficacy and reduce adverse effects. The traditional Chinese medicine (TCM), as an embodiment of ancient wisdom, has been validated to regulate the holistic human capacity against both internal and external "evils" in accordance with TCM principles. Therefore, it stands to reason to integrate TCM into current cancer therapy paradigms, such as chemotherapy, immunotherapy, and targeted therapy. This strategy conceptually intends to circumvent the inevitable side effects derived from present treatment, alleviate the discomfort, mollify the detrimental mood and synergize tumoricidal effects of distinct approaches. However, it is still vague whether TCM exert favorable function in cancer treatment. Therefore, it is imperative to retrieve and compile the existing literature on TCM in the realm of cancer, followed by a comprehensive recapitulation and synthesis of its core findings. Recently, with the advancement of contemporary biologic and medical theory and technology, it has become both feasible and imperative to elucidate the molecular signaling mechanisms and cellular biology underlying TCM. Specifically, leveraging TCM pharmaceutic components can not only directly impact tumor biology at the molecular level, but regulate the tumor immune environment through distinct pathways. Additionally, the administration of external TCM treatments such as acupuncture and moxibustion also demonstrates beneficial effects in cancer patients. Through comprehensive analysis, we demonstrated that TCM not only potentially increases the efficacy of conventional cancer treatments, but also significantly mitigates their toxic side effects, thereby prolonging patients' prognosis and improving their living quality. Furthermore, we have underscored the challenges and prospects associated with the integration of TCM into contemporary oncological practices, placing particular emphasis on the imperative for rigorous clinical trials and molecular investigations to substantiate the efficacy and safety of these combined therapeutic approaches. This synthesis aims to pave the way for a more integrated approach to cancer treatment rooted in both traditional wisdom and cutting-edge science.

This research investigated the possible shielding properties of BB (Berberrubine) against the harmful auditory effects of cisplatin, preliminarily delving into the underlying mechanisms responsible for this protection.

HEI-OC1 cell viability was determined using a Cell Counting Kit-8 (CCK-8). The impact of BB on cochlear hair cells was studied through in vitro cochlear explants culture. Apoptosis levels were measured through Annexin V-PI, Cleaved Caspase-3, and TUNEL staining. The level of ROS (reactive oxygen species) was measured through the application of DCFH-DA, MitoSOX, and JC-1 fluorescent dyes for staining. Immunofluorescence analysis of cochlear samples from mice was conducted to quantify the hair cell count, and concurrently, ABR (Auditory Brainstem Response) testing was utilized to evaluate auditory function. The mechanism of action of BB was explored using RNA-Seq and qRT-PCR analysis.

BB significantly improved cell survival rates under cisplatin treatment, reduced levels of apoptotic markers (TUNEL, Cleaved Caspase-3, Annexin V-PI), decreased ROS and MitoSOX levels, and improved JC-1 signals in both HEI-OC1 cells and cochlear hair cells in cochlear explants culture. Animal studies demonstrated that treatment with BB enhanced the survival of cochlear hair cells, reduced hearing impairment caused by cisplatin in mice. RNA-seq and qRT-PCR analysis revealed that BB influenced the expression levels of multiple genes (Ccnd2, Reln, Pgf, Mylk3, Ppplr12c, Thbsl), by promoting folate biosynthesis for hearing protection.

Our findings suggest that BB protects against cisplatin-induced hearing damage by enhancing folate biosynthesis, decreasing intracellular ROS levels, and inhibiting apoptosis.

Radix Codonopsis (Dangshen), derived from the dried root of plants in the Campanulaceae family, is a widely used Chinese herbal medicine. It is renowned for its pharmacological effects, including tonifying the middle qi, invigorating the spleen, benefiting the lungs, enhancing immunity, and nourishing the blood. Codonopsis extract is frequently incorporated into health products such as tablets and capsules, making it accessible for daily health maintenance. Additionally, it is commonly used in dietary applications like soups, teas, and porridges to nourish qi, enrich blood, and promote overall vitality. In recent years, increasing attention has been given to the anti-cancer potential of Radix Codonopsis. Studies have identified key active components such as luteolin, stigmasterol, polyacetylenes, lobetyolin, and glycitein, which exhibit anti-tumor properties through mechanisms like inhibiting cancer cell growth and proliferation, suppressing epithelial-mesenchymal transition (EMT), and inducing apoptosis. This review highlights the research progress on Radix Codonopsis, including its active constituents, anti-cancer mechanisms, and its role in the convergence of medicine and food in modern life. By doing so, it aims to provide valuable insights and references for future scientific studies and clinical applications of Radix Codonopsis.

Berberine (BBR) has been proved to inhibit the malignant progression of non-small cell lung cancer (NSCLC), but the underlying molecular mechanism still needs to be further revealed. NSCLC cells (A549 and H1299) were treated with BBR. CCK8 assay, colony formation assay, flow cytometry, TUNEL staining and transwell assay were used to examine cell proliferation, apoptosis and invasion. The levels of spindle pole body component 25 (SPC25) and NDC80 kinetochore complex component (NUF2) were detected by qRT-PCR or western blot. The interaction between SPC25 and NUF2 was confirmed by Co-IP assay and FISH assay. Xenograft tumors were constructed to assess the anti-tumor role of BBR in vivo. BBR inhibited NSCLC cell growth, invasion and glycolysis. SPC25 was upregulated in NSCLC tissues, and BBR could reduce SPC25 expression in NSCLC cells. SPC25 knockdown repressed NSCLC cell growth, invasion and glycolysis, and its overexpression also reversed the anti-tumor effect of BBR. SPC25 could interact with NUF2, and NUF2 overexpression abolished the inhibitory effect of SPC25 knockdown or BBR on NSCLC cell behaviors. In animal experiments, BBR could suppress NSCLC tumor growth by inhibiting SPC25/NUF2 axis in vivo. BBR mainly played an anti-NSCLC role by targeting SPC25/NUF2 axis, which provided a new idea for NSCLC treatment.