Immune checkpoint blockade (ICB) targeting PD-1/PD-L1 shows promising therapeutic potential in cancer patients. However, the efficacy of its antibody in colorectal cancer remains limited due to the immunosuppressive tumor microenvironment (TME) and related intestinal adverse effects. Plant-derived vesicle (PDV) is emerging natural nanomedicine treating various diseases, especially in cancer therapy. PDV is exhibited with high biocompatibility and low system toxicities, offering a novel strategy to treat colorectal cancer. In this work, we isolated and characterized Scutellaria baicalensis-derived vesicles (SBV). SBV exhibited typical vesicular morphology (~104.5 nm) and encapsulated several typical flavonoids, such as baicalin and baicalein, which showed high binding affinity to PD-L1 in silico. In vitro, SBV inhibited colorectal cancer cell viability and down-regulated the protein expression of PD-L1. Proteomic analysis indicated that SBV regulated multi-pathways including p53 signaling pathway, cell cycle, apoptosis, and endocytosis. In vivo, oral administration of SBV markedly suppressed tumor growth in a MC38 xenograft model. Furthermore, SBV down-regulated PD-L1 expression and enhanced tumor immunity with increased CD3+/CD8+ T cell population and granzyme E (GZME) expression. Notably, the combination treatment of SBV and TOR exhibited synergistic effects in tumor suppression and reduced the colon toxicity induced by Toripalimab (TOR). Our findings suggested SBV serves as a natural nanomedicine with dual potentials, not only could SBV inhibit PD-L1, but also could enhance the systemic anti-tumor immunity in colorectal cancer while reducing the colon toxicity related with PD-1 blockade, providing new insights into the potential application of PDV in cancer immunotherapy.

Malignant neoplasms are a leading cause of morbidity and mortality globally, with rising rates despite advancements in detection and treatment. This review examines the multifaceted role of MARCH6, an endoplasmic reticulum-resident E3 ubiquitin ligase, in cancer biology and disease regulation. MARCH6 exhibits a complex, context-dependent dual role: it functions as a pro-oncogenic driver in papillary thyroid carcinoma (PTC) and hepatocellular carcinoma (HCC), where it promotes cell proliferation and metastatic potential, yet simultaneously serves protective roles in non-malignant pathological conditions, including the regulation of ferroptosis, a form of iron-dependent lipid peroxidation-driven cell death, and antiviral immunity. In particular, emerging evidence suggests that MARCH6 can modulate ferroptosis through the selective degradation of key regulators such as p53 and ACSL4, thereby linking ubiquitin-mediated proteostasis to redox balance and lipid metabolism. The review synthesizes current understanding of MARCH6's structure, substrate specificity, and tissue-specific functional outcomes, emphasizing the molecular determinants of its context-dependent activity across different cellular contexts. Particular attention is given to MARCH6's regulatory impact on cholesterol and lipid metabolism, oxidative stress responses, and cell death mechanisms, with ferroptosis positioned as a central mechanistic axis through which MARCH6 may influence tumor progression and therapeutic response. Despite these mechanistic advances, critical knowledge gaps persist regarding substrate selectivity across diverse cancer types, the molecular basis of functional polarity, and therapeutic feasibility. This synthesis aims to guide future research toward harnessing MARCH6's potential as a biomarker and selective therapeutic target in cancer and stress-related diseases, particularly in the context of ferroptosis modulation, while acknowledging the inherent challenges in targeting its context-dependent functions.

Introduction:Abrus cantoniensis Hance (ACH), an edible traditional Chinese medicinal herb, has significant anti-inflammatory activity. However, there is limited research on the molecular targets of its active ingredients and their application in inflammatory bowel disease (IBD). Nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome plays a crucial role in IBD. Methods:Here, we explored the inhibitory activity of the 25 main ingredients from ACH on NLRP3 inflammasome using THP-1 and J774A.1 macrophage models, and the dextran sulfate sodium salt (DSS)-induced acute ulcerative colitis mouse model was used to investigate the therapeutic potential. 16S rRNA analysis was performed for gut microbiota assessment. Results:The results demonstrated that 2',4'-dihydroxychalcone (2',4'-DHC) exhibited the remarkable inhibitory effect on the activation of NLRP3 inflammasome. ELISA and western blotting analyses revealed that 2',4'-DHC effectively inhibited caspase-1 and Gasdermin D activation and IL-1β release but not TNF-α in macrophages. Furthermore, 2',4'-DHC significantly alleviated inflammation in IBD mice, which mitigated body weight loss, reduced DAI score, preserved colon length and protected the gut barrier by enhance the tight junction proteins occludin and ZO-1 expression. Importantly, 2',4'-DHC treatment inhibited NLRP3 inflammasome, while also balancing gut microbiota in colitis mice. The results showed that 2',4'-DHC reduced the abundance of Proteobacteria, reshaped the bacterial diversity and composition. Discussion:Overall, this study identified 2',4'-DHC in ACH that regulated the NLRP3 inflammasome activation to exert anti-inflammatory effects in IBD, highlighting its potential in treating NLRP3-related inflammatory diseases.

Abstract Gut microbiota metabolic remodeling is a pivotal determinant in irinotecan-induced enterotoxicity and epithelial damage, although the underlying mechanisms remain unclear. Herein, we discovered that Daikenchuto (DKT), a traditional Chinese prescription for intestinal disorders, alleviated irinotecan–induced enterotoxicity without compromising its anti-tumor efficacy by improving weight loss, diarrhea, intestinal inflammation, and barrier damage, and these effects were partially dependent on gut microbiota. DKT significantly restored microbial tryptophan metabolism in irinotecan-treated rats, which was characterized by the enrichment of Limosilactobacillus reuteri , and elevated levels of indole-3-ethanol (IE) and indole-3-propionic acid (IPA). Multi-omics analysis further revealed a positive correlation between L. reuteri and IE and IPA. Consistent with this, DKT promoted L. reuteri proliferation, leading to the conversion of tryptophan to IE and IPA, which improved epithelial barrier damage in the irinotecan-treated Caco-2 cells. In addition, DKT suppressed the growth of Loop 1 β-glucuronidase (β-GUS)-producing bacteria, such as Escherichia coli . Furthermore, the main constituents of DKT selectively inhibited Loop 1 β-GUS activity independent of the gut microbiota, which reduced the intra-luminal level of 7-ethyl-10-hydroxycamptothecin, the toxic metabolite of irinotecan. Taken together, this study reveals a dual gut microbiota–driven mechanism by which DKT mitigates irinotecan–induced enterotoxicity, which provides a promising strategy for managing chemotherapy-related enterotoxicity.

Objectives:Irinotecan(CPT-11)-induced delayed diarrhea is a major dose-limiting toxicity that restricts its clinical application.Gegen Qinlian decoction(GQD),a traditional Chinese herbal formula,has shown potential in alleviating CPT-11-induced intestinal injury,but its underlying mechanisms remain incompletely understood.This study aimed to systematically elucidate the protective effects and mechanisms of GQD against CPT-11 enterotoxicity. Methods:We integrated ultra-performance liquid chromatography-quadrupole-Orbitrap-mass spectrometry(UPLC-QE-Orbitrap-MS)for chemical profiling of GQD,along with network pharmacology,molecular docking,and molecular dynamics simulation to identify key bioactive constituents and potential targets.Furthermore,a CPT-11-treated mouse model and Caco-2 cell monolayers were employed to evaluate the effects of GQD.Quantitative proteomics and untargeted metabolomics were applied to explore pathway alterations,and biochemical,histological,and functional analyses were conducted to assess inflammatory responses,oxidative stress,barrier integrity,and drug transporter activity. Results:A total of 65 compounds were identified in GQD,with 17 prioritized as putative bioactive constituents.Network analysis highlighted the IL-6/IL-22/STAT3 inflammatory axis and ABC transporter pathways as central mechanisms.In vivo,GQD administration ameliorated diarrhea,preserved colonic architecture and mucin production,reduced pro-inflammatory cytokines and oxidative stress,and restored expression of tight-junction proteins.Multi-omics integration showed that GQD counteracted CPT-11-induced dysregulation in complement/coagulation cascades and metabolic pathways,while enriching ABC transporter-related functions.In Caco-2 monolayers,GQD promoted SN-38 efflux,upregulated MDR1 and MRP2 expression,and decreased intracellular SN-38 accumulation.Consistent with this,GQD enhanced colonic clearance of SN-38 in mice. Conclusions:GQD protects against CPT-11-induced enterotoxicity primarily through two mechanisms:suppressing the pro-inflammatory IL-6/IL-22/STAT3 signaling pathway and enhancing the epithelial efflux of SN-38 via upregulation of ABC transporters.These findings provide a mechanistic basis for the potential use of GQD as an adjuvant therapy to mitigate intestinal toxicity during irinotecan chemotherapy.

ABSTRACT Rosa roxburghii Tratt (Cili) is a vitamin C‐rich fruit with bioactive polyphenols and flavonoids. This study explored the components of Cili fruit juice and investigated its therapeutic potential in a dextran sodium sulfate (DSS)‐induced ulcerative colitis (UC) murine model. Our results revealed that Cili fruit juice and its components (vitamin C and kajiichigaside F1) significantly alleviated colitis symptoms. Notably, colitis symptoms improved even when vitamin C‐deficient Cili juice was administered. Specifically, Cili fruit juice restored intestinal barrier integrity, regulated inflammatory cytokines (TNF‐α, IL‐6, IL‐8, and IL‐12), and modulated gut microbiota dysbiosis by rebalancing Epsilonbacteraeota, Proteobacteria, and Lactobacillus abundances. Furthermore, Cili fruit juice positively modulated cellular metabolic processes and inflammatory pathways. These findings identify Cili fruit juice as a promising natural adjuvant therapy for UC, driven by the potent bioactivity of kajiichigaside F1, offering a novel strategy to enhance intestinal homeostasis and mitigate inflammation.

Ulcerative colitis (UC) is a condition with complex immune dysregulation and chronic intestinal inflammation. Currently, there are still a lack of natural and low-toxicity therapeutic approaches for UC. Emerging research has underscored the potential of plant-derived exosomes for UC treatment. In this study, it is found that Centella Asiatica-derived exosomes (CAEs) have anti-colitis effects. CAEs selectively accumulate in inflamed colons, enabling targeted delivery of RNA cargos. MicroRNA (miRNA)-enriched CAEs not only mitigate inflammation but also facilitate the reconstitution of a balanced gut microbiota, characterized by a deceased abundance of pathogenic bacteria (e.g., Salmonella enterica), as well as regulating 880 serum metabolites. Furthermore, the results indicate the remarkable impact of specific miRNAs from CAEs, such as aof-miR396b and fve-miR396c-3p, on Peak1 target. CAEs attenuate inflammatory responses and enhance the functions of immune cells in the intestinal milieu. Importantly, the safety profile of CAEs is exemplary, with no discernible adverse effects observed in both in vitro and in vivo assays. This study posits plant-derived exosomes as a potent, targeted, and safe therapeutic modality for UC, representing an alternative to conventional treatments by leveraging the inherent bioactive properties of botanically derived nanovesicles and the cross-kingdom regulatory potential of plant-derived miRNAs on mammalian genes.

Pinelliae Rhizoma(PR),known as Banxia in Chinese,Hange in Japanese,and Banha in Korean,is a renowned herbal medicine in East Asia derived from the dry tuber of Pinellia ternata(Thunb.)Breit.(PT).It is extensively utilized in dispensing granules,classical prescriptions,and herbal formulas to treat various conditions,including cough,infection,phlegm,nausea,asthma,and inflammation.Despite numerous studies on PR and its classical prescriptions over recent decades,a comprehensive synthesis of available evidence regarding its multifunc-tional roles and therapeutic potential is lacking.This review aims to address this gap by ex-amining emerging evidence from metabonomics,preclinical studies,and clinical trials,while exploring potential trends and prospects for future research.A systematic literature search was conducted across six electronic databases,including PubMed,Web of Science,Scopus,ScienceDirect,Wanfang,and China National Knowledge Infrastructure,to identify relevant articles on PR published until March 2023.PR contains 107 compounds with diverse pharma-cological activities,including anti-inflammatory,immune regulatory,anti-viral,anti-cancer,anti-asthma,antitussive and expectorant,antioxidant,anti-obesity,anti-atherosclerosis,anti-microbial,emetic and anti-emetic,anti-convulsant and anti-epileptic,sedative and hypnotic,learning and memory enhancement,and anti-depressant effects.Metabonomic studies sug-gest that raw PR may exhibit cardiotoxicity and pregnancy toxicity while showing no appar-ent hepatorenal toxicity.However,limited pharmacokinetic investigations on PR constrain its clinical translation.Furthermore,clinical safety data on PR is scarce,with only four clinical trials assessing its positive effects in pediatric epilepsy,nausea and vomiting,soft tissue in-jury,and chronic sinus tract.This review aims to enhance understanding of PR and provide valuable information and recommendations for further research and development of herbal medicine.

Bryopsis hypnoides, a unicellular multinucleate green alga in the genus Bryopsis, plays vital ecological roles and represents a key evolutionary link between unicellular and multicellular algae. However, its weak genetic baseline data have constrained the progress of evolutionary research. In this study, we successfully assembled and annotated the complete circular chloroplast and mitochondrial genomes of B. hypnoides. The chloroplast genome has a total length of 139,745 bp and contains 59 protein-coding genes, 2 rRNA genes, and 11 tRNA genes, with 31 genes associated with photosynthesis. The mitochondrial genome has a total length of 408,555 bp and contains 41 protein-coding genes, 3 rRNA genes, and 18 tRNA genes, with 18 genes involved in oxidative phosphorylation. Based on the data, we conducted a genetic comparison involving repeat sequences, phylogenetic relationships, codon usage preferences, and gene transfer between the two organellar genomes. The major results highlighted that (1) the chloroplast genome favors A/T repeats, whereas the mitochondrial genome prefers C/G repeats; (2) codon usage preference analysis indicated that both organellar genomes prefer codons ending in A/T, with a stronger bias observed in the chloroplast genome; and (3) sixteen fragments with high sequence identity were identified between the two organellar genomes, indicating potential gene transfer. These findings provide critical insights into the organellar genome characteristics and evolution of B. hypnoides.

Gut microbiota and bile acid metabolism play crucial roles in the progression of nonalcoholic fatty liver disease (NAFLD). Early evidence demonstrates that Ginsenoside Re (Re) possesses pharmacological effects on NAFLD, but its mechanisms of action are not well understood. This study aimed to investigate the hepatic protective effects of Re in NAFLD and elucidate relevant mechanisms. The effects of Re treatments (10, 20, or 40 mg/kg) against high-fat diet-induced NAFLD were initially tested on male C57BL/6 mice. Then, a separate mouse group received Re with or without antibiotics to confirm the regulatory role of microbiota in the effect of Re. Finally, another group of mice received fecal microbiota transplantation (FMT) from the initial experiment of NAFLD mice to further investigate the mechanistic role of gut microbiota. Re significantly improved liver function by reducing hepatic lipid accumulation, injury and hepatocyte steatosis, and inflammation. The liver protection was mediated by the regulation of gut microbiota as evidenced by restored intestinal barrier integrity, normalized Firmicutes/Bacteroidota ratio, enhanced abundances of Adlercreutzia equolifaciens , and reduced Faecalibaculum rodentium. Following that, Re reduced total and primary bile acids and downregulated bile acid synthesis genes and proteins such as farnesoid X receptor and cytochrome P450 family 7 subfamily A member 1. The co-administration of antibiotic cocktail counteracted the effect of Re against NAFLD. Further, the results obtained from the FMT animal study confirmed that Re's liver protective effects were at least partly driven by the regulation of gut microbiota. Re modulated bile salt hydrolase-related microbial genera to alter bile acid synthesis pathways, thereby inhibiting NAFLD progression.

Medicinal and edible plants (MEPs) have attracted increasing interest worldwide due to their natural origin, reliable efficacy, and minimal side effects in recent years. However, the complex and fluctuating levels of inherent chemical constituents and exogenous hazardous contaminants have triggered widespread concerns about their efficacy and safety. Developing analytical methods for both active components and exogenous contaminants concealed in these samples is central to the quality evaluation, in which sample preparation is crucial. This paper systematically reviewed the evolution of standard sample preparation methods, microextraction techniques based on novel solvents and nanomaterials, and innovative integrated techniques from 2019. Accordingly, their merits and weaknesses were discussed by showing fruitful applications in identifying and quantifying active components in these plants. Further, successful applications for analyzing exogenous contaminants were prominently showcased, highlighting the management of pesticides, heavy metals, mycotoxins, and polycyclic aromatic hydrocarbons (PAHs). Finally, forthcoming trends in sample preparation techniques were delineated to illuminate the development and implementation of more advanced sample preparation technologies.

ETHNOPHARMACOLOGICAL RELEVANCE:Curcuma kwangsiensis radix (CKR) is one of the most important herbs in traditional Chinese medicine. It effectively enhances blood circulation and eliminates stasis, which is highly associated with thrombosis. Furthermore, CKR is primarily produced in the Guangxi and Yunnan provinces of China. However, the quality control indicators of CKR in different production regions remain controversial. AIM:To explore the quality marker (Q-Marker) of CKR in different production regions. MATERIALS AND METHODS:First, we determined the UPLC fingerprints of CKR from different production regions. Second, in vitro, antiplatelet aggregation biopotency (AAB) was measured using a parallel-line assay based on the quantitative response method of the bioassay. We identified CKR components and their serum metabolism using UPLC-Q-TOF-MSE. Subsequently, molecular docking technology was used for Q-Marker analysis. Finally, we established a method for the quantitative analysis of Q-Marker. RESULTS:We observed significant differences of CKR between the Guangxi and Yunnan provinces according to the UPLC fingerprint and AAB results. Eight quality control-relevant components were screened using orthogonal partial least squares based on the spectrum-effect relationship. UPLC-Q-TOF-MSE identified 57 CKR components, and 10 prototype components and 11 metabolites, respectively, were detected during serum metabolism. Ultimately, curcumenone was screened as a Q-Marker using the spectrum-effect relationship integrated with serum metabolism, which positively correlated with the quality. The AAB results of the Q-Marker indicated that curcumenone exhibited significant anti-platelet aggregation activity. The results of the Q-Marker molecular docking revealed the strongest binding effect between curcumenone and the GP-IIb/IIIa receptor, whereas that between the P2Y12 receptor and the P2Y1 receptor was the weakest. In addition, quantitative analysis of the Q-Marker indicated that there were significant differences in the contents of the Q-Marker from different production regions. CONCLUSIONS:We identified a Q-Marker for CKR that can provide a foundation for quality evaluation research from different production regions.

Diabetes mellitus is a chronic metabolic disorder, which is characterized by high blood glucose levels, and this can lead to serious diabetic complications. According to the World Health Organization, approximately 830 million adults worldwide are living with diabetes in 2024, with its prevalence continuing to rise steadily over the years. To treat this disease, researchers have developed a variety of first-line drugs, such as sulfonylureas and thiazolidinediones. Despite their long clinical use, there are still many drawbacks and limitations. One of the main drawbacks is low bioavailability, this causes the diabetic patients to take the drugs frequently to lower the blood glucose levels continuously. Some patients may have to take multiple drugs to increase the effectiveness of lowering blood glucose levels. To address these limitations, nano-based drug delivery systems have emerged to overcome these problems. It has emerged as a promising approach for diabetes management, which offers controlled and localized release of anti-diabetic drugs, thus enhancing therapeutic efficacy. This review discusses recent advances in the field of nano-based drug delivery systems for diabetes management, safety and toxicity profiles of anti-diabetic drugs, and future perspectives for the development of nanomedicine in diabetic treatment. Literature search was conducted using electronic databases, and only English literatures were used and published between 2014 and 2024. Recent advancements in nanotechnology have facilitated the development of various nanocarriers, such as polymeric carrier nanoparticles, nanoliposomes, nanocrystals, nanosuspension and inorganic nanoparticles, which enhance drug stability, bioavailability, and efficacy. These systems can deliver anti-diabetic drugs and natural compounds more effectively, thereby minimizing side effects and improving patient compliance. As the field continues to evolve, the successful clinical implementation of nanodrugs could revolutionize the management of diabetes and improve the quality of life for millions of diabetic patients worldwide.

Lycium barbarum polysaccharides are considered the primary active ingredient of Lycium barbarum , and their therapeutic effects on retinal diseases have been extensively described. However, a systematic review and meta-analysis of these studies have not been conducted previously. This review aims to systematically review and meta-analyze published animal studies to investigate the mechanisms of the antioxidative, anti-inflammatory, anti-apoptotic, and neuroprotective effects of Lycium barbarum polysaccharides in rodent models of retinal diseases. To objectively and quantitatively compare the efficacy of Lycium barbarum polysaccharides in rodent models of retinal disease, a systematic review was conducted to search the PubMed and Web of Science databases (from inception to July 2024) for studies conducted in animals that met all a priori inclusion criteria. The included 27 studies reported outcomes on retinal structure (outer nuclear layer thickness) or function (electroretinogram b-wave amplitude). The methodological quality, assessed using the SYRCLE bias risk assessment tool, indicated that the overall risk of bias in the included literature was predominantly moderate. The results of the meta-analysis conducted using RevMan 5.4.1 software found that Lycium barbarum polysaccharides are protective against retinal injury in animal models, as evidenced by increases in the thickness of the outer nuclear layer and b-wave amplitude. The mechanisms involved include antioxidant effects, anti-inflammation, anti-apoptosis, and modulation of glia-driven neuroinflammation. Findings from this review confirm the protective actions of Lycium barbarum polysaccharides on retinal outer nuclear layer thickness and neuronal cells in rodent models of retinal diseases and may help propose strategies for future translational research on Lycium barbarum polysaccharides.

ETHNOPHARMACOLOGICAL RELEVANCE:Although several traditional Chinese medicine formulas have demonstrated remarkable outcomes in suppressing the severe gastrointestinal toxicity induced by irinotecan (CPT-11), few studies have investigated whether enhanced anti-cancer efficacy and reduced intestinal toxicity can be achieved through co-administration. CPT-11, as a first-line drug for treating colorectal cancer, has the side effect of intestinal toxicity. Previous studies have primarily focused on using traditional Chinese medicine to alleviate diarrhea caused by CPT-11. The combination of the classic Chinese medicine prescription Gegen Qinlian decoction (GQD) extract and CPT-11 can significantly reduce its intestinal toxicity. However, the mechanism by which it enhances anti-cancer effects remains to be elucidated. AIM OF STUDY:To investigate the combined effects of GQD and CPT-11 on colorectal cancer progression and intestinal toxicity. MATERIALS AND METHODS:The CT-26 xenograft tumor-bearing mouse model was established to evaluate the synergistic antitumor effects of GQD extract and CPT-11. Tumor size and tumor tissue changes were assessed, and flow cytometry was employed to analyze immune cell populations, thereby evaluating the impact of the combined treatment on tumor growth inhibition and immune modulation. Under anaerobic glycolysis conditions, glucose uptake and cell viability of CT26 cells were measured, and Western blotting analysis was used to determine the protein expression of PKM2 and GAPDH in tumors, assessing the metabolic impact of GQD extract on cancer cells. Flow cytometry was also used to assess the polarization of macrophages in colon tissue, and ELISA was employed to measure cytokine levels in colon tissue, evaluating the protective effect of GQD extract on the colon. RESULTS:The combination of GQD extract and CPT-11 significantly increased tumor growth suppression and decreased intestinal toxicity in the mouse model. The anti-cancer synergy was reduced Treg cell immunosuppression and increased CD4+ and CD8+ T cell populations. GQD extract regulated glucose uptake and cell viability in CT-26 cells under anaerobic glycolysis, potentially disrupting cancer cell glycolysis. GQD also alleviated intestinal toxicity by modulating cytokine levels and promoting macrophage polarization from M1 to M2 in colon tissues. CONCLUSION:The study indicates that GQD extract improves CPT-11 efficacy in treating colorectal cancer and provides insights into the synergistic effects of TCM formulas in cancer treatment.

Mammalian hair follicles undergo periodic regeneration, with recent research highlighting the immunological niche as a critical regulator of stem cell activity and hair follicle regeneration. Chemotactic signals from hair follicles attract macrophages and T cells, which, in turn, control the resting and differentiation of epithelial stem cells in both healthy and damaged conditions. T cells play a pivotal role in hair follicle regeneration, contributing to injury-induced hair neogenesis and physiologic hair cycling. However, disruption of this interaction can lead to clinically significant immune-mediated alopecia. Both scarring and non-scarring forms of alopecia arise from an imbalance in this dynamic system. In this review, we address the role of T cells in hair follicles, summarize related mechanisms, and highlight key genes involved in T cell differentiation and development. Our aim is to provide insights into the development of hair disorders linked to T cell immune homeostasis and hair follicle regeneration.

Curcumae Rhizoma, derived from the rhizome of Curcuma phaeocaulis, Curcuma kwangsiensis and Curcuma wenyujin, was called Ezhu in China. In the past, Curcumae Rhizoma extracts were obtained through water decoction or alternative methods, which showed significant anti-cancer effects. However, the mixed extracts contain various compound components of Curcumae Rhizoma, leading to an ambiguous mechanism of action for Curcumae Rhizoma extracts anti-cancer. Contemporary researchers have extracted the chemical components of Curcumae Rhizoma separately for experimental verification of its active ingredients in the anti-cancer field. Numerous studies demonstrated that curcumol, germacrone, β-elemene, and curcumin in Curcumae Rhizoma extracts have significant governing effects in anti-cancer activities. Pharmacological studies have shown that Curcumae Rhizoma suppresses cancer cell proliferation, invasion, and migration, triggering apoptosis and regulating cellular autophagy to achieve anticancer effects. Here, we summarized the research progress of Curcumae Rhizoma on anti-cancer effects from 2013 to 2022, aiming to explore the deeper molecular mechanisms of Curcumae Rhizoma's active components in cancer treatment.

The aberrant vasculature within the inflamed joint cavity of rheumatoid arthritis (RA) not only exacerbates joint pathology but also restricts the effective delivery of therapeutic drugs. Herein, we propose a strategy that involves the rapid and sustained vasculature repair alongside microenvironment-driven drug delivery to achieve multifaceted RA management. The transformable, self-assembling nanoplatform specifically accumulates in the inflamed joint cavity guided by a vascular targeting peptide (STP). Subsequently, STP detaches and undergoes shape transformation, forming nanofibers on the vascular endothelium, which serve as a rapid-acting physical barrier in the short term and facilitate sustained vascular normalization in the long term. Concurrently, the remaining nanoparticles undergo charge reversal and RGD exposure, enabling precise delivery of anti-RA agent triptolide and the immunomodulatory agent metformin. Collectively, this study provides a potent strategy for rapid, sustained, and precise spatiotemporal remodeling of RA using a simple yet intelligent self-assembling nanoplatform.

Anticancer photothermal therapy efficacy is currently restricted by heat shock protein (HSP90)-mediated thermoresistance, immunosuppressive microenvironment, and poor delivery efficiency of photosensitizers. At present, the “all-in-one” therapeutic system that can simultaneously achieve tumor-targeted delivery, efficient photothermal therapy, and tumor immune enhancement effects is desperately needed. We previously fabricated Glycyrrhizic acid (GL)-based lipid nanoparticles (GLPs) that possess hepatocellular carcinoma (HCC) targeting and improved membrane stability. Interestingly, GL exhibits the potential to inhibit the up-regulated HSP90 and regulate the immunosuppressive tumor microenvironment. Herein, the near-infrared photosensitizer IR780 was efficiently encapsulated into GLPs to promote photothermal enhancement and synergistic immunosuppressive anti-tumor effects. Under the irradiation of NIR light, the IR780 GLPs effectively enhance the PTT efficacy on the HCC-bearing mice model via suppressing HSP90 expression with the combination of GL. Furthermore, IR780 GLPs exhibited strong HCC targeting ability, effectively downregulating the expression of immunosuppressive Treg cells, promoting the repolarization of M2 macrophages to M1 macrophages, increasing the infiltration of cytotoxic CD8+T cells and downregulating the expression of TGF-β and IL-10, upregulating IL-12, TNF-α, and IFN-γ, reshaping the tumor immunosuppressive microenvironment. Overall, we developed a novel GL-based lipid nanoparticle system encapsulating IR780 to amplify the synergistic effects of chemo-PTT for HCC treatment.