High-Performance NIR-II Fluorescent Type I/II Photosensitizer Enabling Augmented Mild Photothermal Therapy of Tumors by Disrupting Heat Shock Proteins.

NIR-II fluorescent photosensitizers as phototheranostic agents hold considerable promise in the application of mild photothermal therapy (MPTT) for tumors, as the reactive oxygen species generated during photodynamic therapy can effectively disrupt heat shock proteins. Nevertheless, the exclusive utilization of these photosensitizers to significantly augment the MPTT efficacy has rarely been substantiated, primarily due to their insufficient photodynamic performance. Herein, we present the utilization of high-performance NIR-II fluorescent type I/II photosensitizer (AS21:4) as a simple but effective nanoplatform derived from molecule AS2 to enhance the MPTT efficacy of tumors without any additional therapeutic components. By taking advantage of heavy atom effect, AS21:4 as a type I/II photosensitizer demonstrates superior efficacy in producing 1O2 (ΦΔ = 12.4%) and O2 •- among currently available NIR-II fluorescent photosensitizers with absorption exceeding 800 nm. In vitro and in vivo findings demonstrate that the 1O2 and O2 •- generated from AS21:4 induce a substantial reduction in the expression of HSP90, thereby improving the MPTT efficacy. The remarkable phototheranostic performance, substantial tumor accumulation, and prolonged tumor retention of AS21:4, establish it as a simple but superior phototheranostic agent for NIR-II fluorescence imaging-guided MPTT of tumors. This article is protected by copyright. All rights reserved.

[Charcoal-frying process and quality markers of Sanguisorbae Radix based on hemostatic effect].

Studies have reported that the hemostatic effect of Sanguisorbae Radix(SR) is significantly enhanced after processing with charcoal. However, the standard components(tannins and gallic acid) specified in the Chinese Pharmacopeia decrease in charcoal-fried Sanguisorbae Radix(CSR), which is contrast to the enhancement of the hemostatic effect. Therefore, this study aimed to optimize the charcoal-frying process of SR based on its hemostatic efficacy and comprehensively analyze the components of SR and its processed products, thus exploring the material basis for the hemostatic effect. The results indicated that SR processed at 250 ℃ for 14 min(14-min CSR) not only complied with the description in the Chinese Pharmacopeia but also demonstrated improved blood-coagulating and blood-adsorbing effects compared with raw SR(P<0.05). Moroever, 14-min CSR reduced the bleeding time in the rat models of tail snipping, liver bleeding, and muscle injury, surpassing both raw and excessively fried SR(16 min processed) as well as tranexamic acid(P<0.05). Ellagitannin, ellagic acid, methyl gallate, pyrogallic acid, protocatechuic acid, Mg, Ca, Mn, Cu, and Zn contributed to the hemostatic effect of CSR over SR. Among these substances, ellagitannin, ellagic acid, Mg, and Ca had high content in the 14 min CSR, reaching(106.73±14.87),(34.86±4.43),(2.81±0.23), and(1.21±0.23) mg·g~(-1), respectively. Additionally, the color difference value(ΔE~*ab) of SR processed to different extents was correlated with the content of the aforementioned hemostatic substances. In summary, this study optimized the charcoal-frying process as 250 ℃ for 14 min for SR based on its hemostatic effect. Furthermore, ellagic acid and/or the powder chromaticity are proposed as indicators for the processing and quality control of CSR.

Polyphenolic Nanoparticle-Modified Probiotics for Microenvironment Remodeling and Targeted Therapy of Inflammatory Bowel Disease.

Inflammatory bowel diseases (IBDs) refer to multifaceted disorders in the intestinal microenvironment and microbiota homeostasis. In view of the broad bioactivity and high compatibility of polyphenols, there is considerable interest in developing a polyphenol-based collaborative platform to remodel the IBD microenvironment and regulate microbiota. Here, we demonstrated the coordination assembly of nanostructured polyphenols to modify probiotics and simultaneously deliver drugs for IBD treatment. Inspired by the distinctive structure of tannic acid (TA), we fabricated nanostructured pBDT-TA by using a self-polymerizable aromatic dithiol (BDT) and TA, which exhibited excellent antioxidant and anti-inflammatory capability in vitro. We thus coated pBDT-TA and sodium alginate (SA) to the surface of Escherichia coli Nissle 1917 layer by layer to construct the collaborative platform EcN@SA-pBDT-TA. The modified probiotics showed improved resistance to oxidative and inflammatory stress, which resulted in superior colon accumulation and retention in IBD model mice. Further, EcN@SA-pBDT-TA could alleviate dextran sulfate sodium (DSS)-induced colitis by controlling the inflammatory response, repairing intestinal barriers, and modulating gut microbiota. Importantly, EcN@SA-pBDT-TA-mediated IBD drug delivery could achieve an improved therapeutic effect in DSS model mice. Given the availability and functionality of polyphenol and prebiotics, we expected that nanostructured polyphenol-modified probiotics provided a solution to develop a collaborative platform for IBD treatment.

Polydopamine-Mediated Metal-Organic Frameworks Modification for Improved Biocompatibility.

Engineered nanomaterials are promising in biomedical application. However, insufficient understanding of their biocompatibility at the cellular and organic levels prevents their widely biomedical applications. Metal-organic frameworks (MOFs) have attracted increasing attention in recent years. In this work, zeolitic imidazolate framework-8 (ZIF-8) and polydopamine (PDA)-modified ZIF-8 are chosen as model nanomaterials due to its emergent role in nanomedicine. In vitro, the results demonstrate that the PDA coating greatly alleviates the cytotoxicity of ZIF-8 to RAW264.7, LO2, and HST6, which represent three different cell types in liver organs. Mechanistically, ZIF-8 entering into the cells can greatly induce the reactive oxygen species generation, which subsequently induces cell cycle delay and autophagy, ultimately leads to enhanced cytotoxicity. Further, human umbilical vein endothelial cells model and zebrafish embryos assay also confirm that PDA can compromise the ZIF-8 toxicity significantly. This study reveals that PDA-coated MOFs nanomaterials show great potential in nano-based drug delivery systems .

Exposure to hexafluoropropylene oxide trimer acid (HFPO-TA) impairs 5-HT metabolism by impacting the brain-gut axis in mice.

Hexafluoropropylene oxide trimer acid (HFPO-TA) has been found to cause hepatotoxicity, lipotoxicity, and cytotoxicity. However, the effects of HFPO-TA exposure on nervous system toxicity are still unclear. Here, six-week-old male C57BL/6J mice were treated with 2, 20, and 200 µg/L HFPO-TA for six weeks. The untargeted transcriptome analysis was employed to identify differentially expressed mRNAs in the tissue of mouse hippocampi. Then, the levels of neurotransmitters were detected by ELISA analysis in hippocampal and colonic tissues. Real-time quantitative PCR and western blotting analysis were performed to detect the expression of genes associated with modulation of serotonin (5-HT) metabolism and blood-brain barrier. HFPO-TA exposure reduced the mRNA and protein expression of several tight junction protein-coded genes, including Occludin, Claudin-1, and ZO-1, in mice hippocampi, indicating that the blood-brain barrier was disrupted. Moreover, HFPO-TA exposure elevated the expression of neuroinflammatory factors, including TNF-α, IL-6, IL-1ß, TGF-α, and TGF-ß. Analysis of hippocampal transcriptomics suggested that HFPO-TA exposure would impair 5-HT generation and metabolic pathways. In keeping with this prediction, our findings confirmed that the levels of several neurotransmitters, including tryptophan (TRP), 5-HT, 5-HTP, and 5-HIAA, were all impaired by HFPO-TA exposure in the serum, colon, and hippocampus, as was the colonic and hippocampal expression of TRP and 5-HT metabolism-related genes such as SERT, MAO-A, and IDO. These results suggest that HFPO-TA nervous system toxicity in mice may be partly modulated by the brain-gut axis and that HFPO-TA exposure may negatively impact human mental health.

Poly(ethylenimine)-Cyclodextrin-Based Cationic Polymer Mediated HIF-1α Gene Delivery for Hindlimb Ischemia Treatment.

Hindlimb ischemia is a common disease worldwide featured by the sudden decrease in limb perfusion, which usually causes a potential threat to limb viability and even amputation or death. Revascularization has been defined as the gold-standard therapy for hindlimb ischemia. Considering that vascular injury recovery requires cellular adaptation to the hypoxia, hypoxia-inducible factor 1 α (HIF-1α) is a potential gene for tissue restoration and angiogenesis. In this manuscript, effective gene delivery vector PEI-ß-CD (PC) was reported for the first application in the hindlimb ischemia treatment to deliver HIF-1α plasmid in vitro and in vivo. Our in vitro finding demonstrated that PC/HIF-1α-pDNA could be successfully entered into the cells and mediated efficient gene transfection with good biocompatibility. More importantly, under hypoxic conditions, PC/HIF-1α-pDNA could up-regulate the HUEVC cell viability. In addition, the mRNA levels of VEGF, Ang-1, and PDGF were upregulated, and transcriptome results also demonstrated that the cell-related function of response to hypoxia was enhanced. The therapeutic effect of PC/HIF-1α-pDNA was further estimated in a murine acute hindlimb ischemia model, which demonstrated that intramuscular injection of PC/HIF-1α-pDNA resulted in significantly increased blood perfusion and alleviation in tissue damage, such as tissue fibrosis and inflammation. The results provide a rationale that HIF-1α-mediated gene therapy might be a practical strategy for the treatment of limb ischemia.

Sono-assembly of ellagic acid into nanostructures significantly enhances aqueous solubility and bioavailability.

INTRODUCTION: Ellagic acid (EA), commonly found in foods, offers significant health benefits in combating chronic diseases. However, its therapeutic potential is hindered by its extremely poor solubility and bioavailability. METHOD: In this study, EA nanoparticles (EA NPs) were produced using a sono-assembly method, without additional agents. RESULTS: EA NPs exhibited stick-like nanoparticle structures with an average size of 147.3 ± 0.73 nm. EA NPs likely adopt a tunnel-type solvate structure, with 4 water participating in disruption of intramolecular hydrogen bonds in EA and establishment of intermolecular hydrogen bonds between EAs. Importantly, EA NPs exhibited remarkable enhancements in water solubility, with 120.7-fold increase in water, and 97.8-fold increase in pH 6.8 buffer. Moreover, ex vivo intestinal permeability studies demonstrated significant improvements (P < 0.5). These findings were further supported by in vivo pharmacokinetic studies, where EA NPs significantly enhanced the relative bioavailability of EA by 4.69 times.

Polydopamine-Modified Zeolite Imidazole Framework Drug Delivery System for Photothermal Chemotherapy of Hepatocellular Carcinoma.

Metal-organic frameworks (MOFs) are promising drug-delivering platforms for their intrinsic capability of loading and releasing different cargoes. To further extend their biomedical practices, the development of collaborative MOF systems with good biocompatibility and synergistic efficacy is essential. Herein, the near-infrared and pH dual-response collaborative zeolitic imidazolate framework-8 (ZIF-8) platform SOR@ZIF-8@PDA (SZP) was constructed, in which the chemotherapeutic drug sorafenib (SOR) was encapsulated in ZIF-8 and via polydopamine (PDA) coating on ZIF-8 by hierarchical self-assembly. PDA coating serves as a photothermal agent for PPT while reducing the toxicity of ZIF-8. SZP achieves intelligent release of therapeutic drugs by responding to the lower pH of the tumor microenvironment and thermal stimulation generated by near-infrared light irradiation. In addition, under light irradiation, SZP could effectively realize treatment of cancer cells through synergistic chemo-photothermal therapy, as evidenced by the enhanced cell apoptosis, inhibited tumor cell proliferation and migration. This collaborative MOFs system showed excellent biocompatibility and antitumor ability in vivo on a mouse HepG2 tumor model. Our results demonstrated that PDA-modified MOFs exhibited a fantastic good development prospect in biomedical applications.

Near-Infrared-II Fluorophore with Inverted Dependence of Fluorescence Quantum Yield on Polarity as Potent Phototheranostics for Fluorescence-Image-Guided Phototherapy of Tumors.

Organic phototheranostics simultaneously having fluorescence in the second near-infrared (NIR-II, 1000-1700 nm) window, and photothermal and photodynamic functions possess great prospects in tumor diagnosis and therapy. However, such phototheranostics generally suffer from low brightness and poor photodynamic performance due to severe solvatochromism. Herein, an organic NIR-II fluorophore AS1, which possesses an inverted dependence of fluorescence quantum yield on polarity, is reported to serve as potent phototheranostics for tumor diagnosis and therapy. After encapsulation of AS1 into nanostructures, the obtained phototheranostics (AS1R ) exhibit high extinction coefficients (e.g., 68200 L mol-1  cm-1 at 808 nm), NIR-II emission with high fluorescence quantum yield up to 4.7% beyond 1000 nm, photothermal conversion efficiency of ≈65%, and 1 O2 quantum yield up to 4.1%. The characterization of photophysical properties demonstrates that AS1R is superior to other types of organic phototheranostics in brightness, photothermal effect, and photodynamic performance at the same mass concentration. The excellent phototheranostic performance of AS1R enables clear visualization and complete elimination of tumors using a single and low injection dose. This study demonstrates the merits and prospects of NIR-II fluorophore with inverted polarity dependence of fluorescence quantum yield as high-performance phototheranostic agents for fluorescence imaging and phototherapy of tumors.

Mitochondria Targeted Nanoparticles Potentiate Tumor Chemo-Phototherapy by Toxic Oxidative Stress Mediated Oxeiptosis.

Insufficient accumulation of drug at the tumor site and the low drug response are the main reason for the unsatisfactory effect of cancer therapy. Delivery drugs exquisitely to subcellular level can be employed to reduce side effects, and expand the therapeutic window. Herein, a triphenylphosphine (TPP) modified lipid nanoparticles is designed which are loaded with the photosensitizer indocyanine green (ICG) and chemotherapeutic paclitaxel (PTX) for mitochondria-targeted chemo-phototherapy. Owing to the movement of majority mitochondria along microtubules in cytoplasm, mitochondrial targeting may enable PTX to act more effectively. Meanwhile, the existence of chemo-drug potentiates the phototherapy to achieve synergistic anti-tumor activity. As expected, mitochondria targeting nanomedicine (M-ICG-PTX NPs) showed improved mitochondria targeted cellular distribution and enhanced cell cytotoxicity in vitro. Also, M-ICG-PTX NPs exhibited higher tumor growth inhibition ability by promoting cell apoptosis and oxeiptosis pathway, and high effective inhibition of primary tumor growth and tumor metastasis. Taken together, M-ICG-PTX NPs may be promising nanoplatforms to achieve potent therapeutic effect for the combination of chemo- and photo-therapy (PTT).

Effects of 2-ethylhexyl diphenyl phosphate exposure on the glucolipid metabolism and cardiac developmental toxicity in larval zebrafish based on transcriptomic analysis.

2-Ethylhexyl diphenyl phosphate (EHDPP) is an organophosphorus type of flame retardant. It is mainly used as a flame-retardant plasticizer in the production of flexible polyvinyl chloride. EHDPP is widely present in environment, particularly in aquatic environment. In this study, we reported that EHDPP exposure significantly affected glucose and lipid metabolism in zebrafish larvae, which was reflected by changes in the transcription of relevant genes and decreased levels of glucose, pyruvate, and triglycerides. In addition, the transcriptomic analysis revealed that the differentially expressed genes could enrich various endpoints in zebrafish larvae. Interestingly, EHDPP exposure could not only change the transcription of genes related to glucolipid metabolism but also cause cardiotoxicity by affecting the transcription of genes related to calcium signaling pathways in zebrafish larvae. To support these findings, we confirmed that these genes involved in cardiac morphology and development were significantly upregulated in zebrafish larvae after EHDPP exposure. More importantly, the distance and overlapping area of the atrium and ventricle were also changed in the EHDPP-exposed zebrafish larvae of transgenic Tg (myl7: EGFP). Overall, our study revealed that EHDPP exposure could affect various endpoints related to glucolipid metabolism and cardiac development in the early developmental stages of zebrafish.

Combined exposure to titanium dioxide and tetracycline induces neurotoxicity in zebrafish.

In aquatic environment, engineered materials may inevitably interact with the coexisted organic pollutants, which affect their bioavailability and toxicity. In this contribution, the combined impacts of tetracycline (TC) and titanium dioxide nanoparticles (TiO2 NPs) on the neurodevelopment of zebrafish larvae were investigated, and the underlying mechanisms were further elucidated. Firstly, it was confirmed that the co-existence of TC would increase the size and decrease the zeta potential of TiO2 NPs. Following, developmental indicators and motor behaviors were investigated. Our results indicated that co-exposure to TC and TiO2 NPs exhibited enhanced embryonic malformation rates and abnormal nervous system development in zebrafish embryos. Meanwhile, the locomotor behavior was increased upon treatment of TC and TiO2 NP. Further, pathway enrichment analyses of transcriptomic sequencing provided detailed information that either lipid metabolism or PPAR signaling pathway were significantly affected in the co-exposure group. Also, TC + TiO2 NP exposure significantly changed the mRNA expression of neural development-related genes and up-regulated the expression levels of neurotransmitters like 5-hydroxytryptamine, dopamine, acetylcholinesterase, and γ-aminobutyric acid. Taken together, our results demonstrated that the co-exposure of TC and TiO2 NPs had the potential to cause neurotoxicity in zebrafish embryos.

Supramolecular Theranostic Nanomedicine for In Situ Self-Boosting Cancer Photochemotherapy.

Although traditional nanomedicines have enhanced the therapeutic efficacy and improved the survival quality of cancer patients, random drug release and drug resistance are deep-rooted problems hindering their clinical application. A precise nanoplatform combing chemotherapy and photodynamic therapy (PDT) is developing as a new therapeutic strategy to overcome the above challenges. Herein, a novel supramolecular nanomedicine is ingeniously constructed for in situ self-boosting cancer photochemotherapy. Hydrophilic polyethylene glycol (PEG) chains or ß-cyclodextrin (ß-CD) hosts are first conjugated onto tetraphenyl porphyrin (TCPP) to improve the solubility of TCPP and decrease their π-π stacking interactions, guaranteeing a high-efficiency PDT. Then, two camptothecin (CPT) molecules are linked together via a reactive oxygen species (ROS)-responsive thioketal bond, which averts the premature burst release of CPT and realizes in situ drug release at the tumor site where PDT is performed, resulting in an enhanced chemotherapy. Benefiting from the collaboration of host-guest complexation between ß-CD and CPT, multiple intermolecular hydrogen bonds of ß-CD, π-π stacking interactions among CPT and TCPP as well as PEG shell protection, a prolonged blood circulation time, and a selective tumor accumulation are acquired, which facilitate the synergistic photochemotherapy and bring a pre-eminent antitumor response with a low systemic toxicity.

Cucurbit[10]uril-based supramolecular radicals: Powerful arms to kill facultative anaerobic bacteria.

Two water-soluble supramolecular complexes (CB[10]⊃PSA and CB[10]⊃TPE-cyc) are constructed based on the host-guest interaction between cucurbit[10]uril (CB[10]) and perylene diimide derivative (PSA) or tetracationic cyclophane (TPE-cyc). Attributing to the matched redox potential, both supramolecular complexes can be specifically reduced into corresponding supramolecular radical cations or anions by facultative anaerobic E. coli. Benefiting from the strong near-infrared (NIR) absorption, CB[10]⊃PSA radical anions and CB[10]⊃TPE-cyc radical cations act as efficient NIR photosensitizers and perform an excellent antimicrobial activity (close to 100%) via PTT. In addition, the biocompatibility of TPE-cyc is notably improved under the protection of CB[10], guaranteeing its biosafety for in vivo application. CB[10]⊃PSA radical anions and CB[10]⊃TPE-cyc radical cations are in situ generated in the E. coli-infected abscess of mice and effectively inhibit the bacterial infection without obvious system toxicity. It is anticipated that this supramolecular strategy may pave a new way for the selective bacteria inhibition to regulate the balance of different bacterial flora.

Hyperthermia-induced stellate cell deactivation to enhance dual chemo and pH-responsive photothermal therapy for pancreatic cancers.

For pancreatic ductal adenocarcinoma (PDAC) treatment, the deactivation of pancreatic stellate cells (PSCs) by blocking the transforming growth factor ß (TGF-ß) pathway is a promising strategy to inhibit stroma, enhance drug penetration, and greatly amplify chemotherapeutic efficacy. It is known that photothermal therapy (PTT) locally depletes stroma and enhances permeability but whether and how PTT reacts in the molecular pathway to induce PSC deactivation in PDAC has rarely been investigated so far. Herein, C-G NPs are synthesized by loading both acid-responsive photothermal molecules and gemcitabine for investigating both the combinatory chemophotothermal therapy and the interaction between the PTT and TGF-ß pathway in PDAC. Notably, C-G NPs exhibit tumoral acidic pH-activated PTT and succeeded in deactivating PSCs and suppressing the expression level for both TGF-ß and collagen fiber. Furthermore, hyperthermia remodels the tumoral extracellular matrix, significantly improves NP penetration, and boosts the ultimate synergistic chemophotothermal therapeutic efficacy. Importantly, the molecular biology study reveals that hyperthermia leads to the decrease in the mRNA expression of TGF-ß1, SMAD2, SMAD3, α-SMA, and Collagen I in the tumor tissue, which is the key to suppress tumor progression. This research demonstrates that combinatory chemophotothermal therapy holds great promise for PDAC treatment.

Engineering of small molecular organic nanoparticles for mitochondria-targeted mild photothermal therapy of malignant breast cancers.

Conventional photothermal therapy (PTT) often causes unwanted hyperthermia damage to the surrounding healthy tissues, and fails in the ablation of infiltrating and malignant tumors, which even leads to tumor recurrence. The main reasons for the suboptimal therapeutic efficacy of PTT include: (i) the heterogenous distribution of PTT agents in cancer cells, (ii) the limited penetration depth of irradiation light, and (iii) importantly, the difficulty in controlling the photothermal process which often leads to overheated hyperthermia and severe side effects, including inflammation, immune escape, metastasis and damage to normal tissues surrounding the tumor. It is envisioned that organelle targeted mild PTT would be a good strategy to overcome these shortcomings and significantly improve the therapeutic efficacy, decrease the therapeutic threshold for both the drug dosage and hyperthermia temperature, and diminish damage to the neighboring healthy tissues. Although small biocompatible organic photothermal agents are promising candidates for organelle targeted mild PTT, related research together with their therapeutic mechanism study has rarely been reported so far. In this contribution, we fabricate efficient small organic molecules (TD1) via donor-acceptor molecular engineering, and further package TD1 molecules into a lipid carrier to construct mitochondria-targeted nanoparticles (M-TD1 NPs) for mild PTT. The highly desirable photothermal performance of M-TD1 NPs dramatically improves the efficacy of photothermal cancer cell ablation. Benefiting from the excellent PTT effects of M-TD1 NPs, favorable antitumor efficacy and metastasis inhibition are achieved in vitro and in vivo. Mechanistically, the improved mitochondria-based mild thermal treatment triggers the apoptosis-dependent cell death and influences the autophagy of cancer cells, resulting in enhanced cancer elimination and suppressed cancer cell migration. This work demonstrates that sub-cellular targeted mild PTT is promising to control cell apoptosis and autophagy and has potential for future metastatic cancer therapy.

Amino-Functionalized Polystyrene Nano-Plastics Induce Mitochondria Damage in Human Umbilical Vein Endothelial Cells.

As emerging contaminants, nano-plastics have become a major cause for concern for their adverse effects on the ecosystem and human health. The nano-sized properties of nano-plastics enable their exposure risks to humans through the food chain or other ways. However, the fate and adverse impact of nano-plastics on the human cardiovascular system are lacking. In this regard, the human umbilical vein endothelial cell line HUVEC was applied as a cell model to investigate the biological effects of noncharged polystyrene nano-plastics (PS NPs) and amino-functionalized nano-plastics (NH2-PS NPs). The positively charged PS NPs exhibited higher cytotoxicity to HUVEC, as evidenced by the decreased cell viability, enhanced ROS generation, and decreased mitochondria membrane potential triggered by NH2-PS NPs. Importantly, RT-PCR analysis revealed that NH2-PS NPs dysregulated the mitochondrial dynamics, replication, and function-related gene expression. This study demonstrated that NH2-PS NPs presented higher risks to endothelial cells than non-charged nano-plastics by interfering with mitochondria, which supported the direct evidence and expanded the potential risks of PS NPs.

Investigation of Tannins Transformation in Sanguisorbae Radix Over Carbonizing by Stir-Frying.

Carbonizing by stir-frying (CSF) is the most common technology in botanical folk medicines to enhance the convergence, hemostasis, and antidiarrheal effects. Sanguisorbae Radix (SR), a well-known herbal medicine in China, has extensive therapeutic functions, while charred SR is known as an additional product obtained from SR after CSF. In this study, mass spectrometry was used to investigate the effect of charring on tannins transformation of SR. The findings showed that the content level of tannins in SR decreased significantly after carbonizing process, while their three categories, gallotannins, ellagitannins, and procyanidins, had downward trends in general. Moreover, CSF also induced the polyphenol in SR to release relevant monomers from its origins. Significant amount of hydrolyzable tannins were detected by mass spectrometry, including gallotannins and ellagitannins, suggesting that hydrolysis during CSF yielded gallic and ellagic acid and their derivatives, in addition to sugar moieties. Subsequently, gallic and ellagic acid can further polymerize to form sanguisorbic acid dilactone. The amount of proanthocyanidins, the oligomers of catechin, including procyanidin, procyanidin C2, procyanidin B3, and 3-O-galloylprocyanidin B3, decreased to form catechin and its derivatives, which may further degrade to protocatechualdehyde. Quantitative analysis illustrated that the amount of gallic, pyrogallic, and ellagic acid and methyl gallate, the essential effectors in SR, significantly increased after CSF, with increased ratios of 1.36, 4.28, 10.33, and 4.79, respectively. In contrast, the contents of cathechin and epigallocatechin dropped remarkably with increased ratios of 0.04 and 0.02. Tannins exhibit moderate absorption, while their relevant monomers have a higher bioavailability. Therefore, CSF is proved here to be an effective technique to the release of active monomers from the original polyphenol precursor. This study explored the mechanism by which tannins are transformed upon CSF of SR.