PHYTOTHERAPY RESEARCH
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2026
·
IF 8.1
Jing Li,Yang-Chi-Dung Lin,Hsi-Yuan Huang,Jihang Chen,Huali Zuo,Yun Tang,Hsien-Da Huang
Obesity is a major risk factor for type 2 diabetes. Some traditional Chinese medicine (TCM) compounds can improve obesity by increasing energy consumption. This study aimed to identify and verify TCM compounds that promote adipose thermogenesis to alleviate obesity via transcriptomic analysis, molecular docking, network pharmacology, and Connectivity Map (CMap) analysis. Thirty-six TCMs related to adipose tissue thermogenesis were first collected to generate transcriptomic data. Then a ranking method based on integrated transcriptomic data was used to select emodin from the TCM Da Huang for network pharmacology to explore its potential mechanisms and further experimental validation. CMap analysis of thermogenesis signature genes from ProFAT and GEO datasets identified triptolide as another compound for improving obesity through enhanced thermogenesis. In vitro experiments with 3T3-L1 cells and in vivo experiments with zebrafish were conducted. The results showed that both emodin and triptolide could upregulate the NAD + /NADH ratio, increase AMPK and SIRT1 expression, suppress lipid accumulation, and promote lipolysis, as verified by both in vitro and in vivo experiments. They also upregulated thermogenesis-related genes (e.g., UCP1, PGC1α, and PRDM16), lipolysis-related genes (e.g., PKA, ATGL, and HSL), mitochondrial biogenesis-related genes (e.g., NRF1, NRF2, and TFAM), and β-oxidation-related genes (e.g., CPT1α and CPT1β). Meanwhile, they downregulated lipogenesis-related genes such as FASN, SREBP1, and ACC. These results provide a basis for understanding the effects of emodin and triptolide on obesity. The findings highlight the effectiveness of combined screening approaches in exploring compounds with beneficial metabolic effects.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2026
·
IF 8.7
Yang-Gang Yan,Xue Ma,Ze-Yu Wang,Jing Zhou,Hao-Zhe Yuan,Si-Qin Zhang,Jia-Xiang Fan,Yue Ren,Gang Wang,Jing-Hua Fu,Ru-Hao Chen,Ye Sun,Zhen-Yi Liu,Yu-Yao Jiang,Dai-Xu Wei,Yong Wang
In this study, we developed triptolide (TP)-loaded open-pore PBVHx microspheres (TP@OPMs) and compared their anticancer and embolization capabilities with those of TP-loaded sealed PBVHx microspheres (TP@SMs). TP@OPMs, characterized by an open surface and interconnected internal pores, showed higher water absorption (2860%) and porosity (79.69%), but slightly lower TP encapsulation efficiency (79 ± 0.32%) compared to TP@SMs, and achieved sustained TP release of 75.29% over 21 days. All PBVHx microspheres without TP demonstrated good biocompatibility, but TP@OPMs exhibited superior inhibitory effects on HepG2 cells compared to TP@SMs, with a hemolysis rate below 5%. In in vivo central arterial embolization experiments, TP@OPMs outperformed other microspheres and commercial gelatin microspheres, achieving the highest necrosis rate (50.70%). This resulted in the successful induction of ischemic necrosis and tissue detachment. These findings suggest that TP@OPMs are not only an effective drug delivery system but also have significant potential in embolization applications. This strategy provides a promising approach for the treatment of hepatocellular carcinoma and other malignant tumors.
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JOURNAL OF ETHNOPHARMACOLOGY
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2026
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IF 6.8
Ma-Long Qin,Yan-Ling Qian,Xi Wen,Yun-Li Zhao,Xiao-Dong Luo
Ethnopharmacological relevance Kadsura longipedunculata is a Yi ethnic herb for hepatic disorders treatment in China. However, its effects on herb- and chemical-induced liver injury remain unknown. Aim of the study To validate traditional ethnomedicinal applications of K. longipedunculata and characterize its bioactive constituents. Materials and methods The hepatoprotective effect was evaluated using a triptolide-induced mice liver injury model. Bio-guided isolates were screened in an acetaminophen (APAP)-induced HepG2 cell model. Underlying signaling pathways were investigated using transcriptomics, network pharmacology, molecular docking, molecular dynamics simulations, and subsequent Western blotting validation. Results Abnormal biochemical indices, antioxidant defenses, and liver pathological necrosis in triptolide-induced mice were all adjusted by treatment with K. longipedunculata extract, exhibiting effects superior to those of the positive control, silymarin. The PI3K/AKT/NF-κB signaling pathway was identified as a core therapeutic pathway through transcriptomic profiling, supported by the upregulation of phosphorylated AKT and MTOR concurrent with the downregulation of NF-κB and TNF-α. Four compounds were isolated, among which catechin-5- O -β-D-glucopyranoside (Catechin GP) showed potent anti-apoptotic and antioxidative bioactivities in APAP-induced hepatocytes through the same pathway. The formation of a stable Catechin GP-AKT1 complex was further supported by computational analyses of binding stability and safety. Conclusion The protective effect of K. longipedunculata and its bioactive compound, Catechin GP, against liver injury triggered by both herbal (triptolide) and chemical (acetaminophen) agents is regulated via the PI3K/AKT/NF-κB pathway.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2026
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IF 8.7
Pei Qiao,Shuang Chen,Mengqing Zhao,Zhiran Ju,Junxiang Chen,Wenhao Xu,Lichan Mao
Triptolide (TP) is a bioactive compound with anti-inflammatory, antitumor, and immunomodulatory effects. Its application, however, is limited due to poor aqueous solubility, low bioavailability, and organ toxicity. Based on the classical compatibility theory of Tripterygium and Polygonatum for toxicity reduction in traditional Chinese medicine, and the super-self-assembly behavior observed in the decoctions of these two herbs, a novel nano-delivery system (TP-PSP) was designed with Polygonatum Sibiricum Polysaccharide (PSP) as the carrier. TP-PSP achieved 6-fold enhancements in solubility and 3-fold enhancements in membrane permeability. The bioavailability of TP-PSP increased by 6.8/5.9-fold in AUC 0-t /AUC 0-∞ , significantly reducing gastrointestinal toxicity by shortening intestinal retention. In the diabetic nephropathy (DN) mouse model, TP-PSP achieved better therapeutic effects by enabling kidney-targeted delivery. TP-PSP reduced serum creatinine and urea nitrogen by 38.7% and 42.5%, respectively. It also alleviated TP-induced renal, cardiac, and hepatic toxicity. Physical characterization and molecular dynamic simulations revealed that TP and PSP form stable supramolecular aggregates via hydrogen bonding. TP-PSP activated the Nrf2/SLC7A11/GPX4 pathway, enhancing antioxidant defenses and suppressing lipid peroxidation/ferroptosis. This study not only reports a clinically viable TP delivery strategy but also highlights the application potential of traditional Chinese medicine principles in developing advanced nanomedicine with better effects but lower toxicity. Significance This work presents a significant advancement beyond classical Chinese medical principles to overcome the major clinical limitations of triptolide (TP), a potent yet therapeutically challenging compound. Guided by the “Sovereign-Minister-Assistant-Envoy” principle and systematic, detailed prescription research, we identified Polygonatum Sibiricum Polysaccharide (PSP) as a promising carrier to enhance the solubility and reduce the toxicity of TP. We developed an engineered nano-delivery system (TP-PSP) with improvements in TP's solubility, dissolution rate, and bioavailability while simultaneously reducing its systemic organ toxicity. The system demonstrates kidney-targeted delivery and a significant reduction in key nephropathy markers, revealing strong therapeutic potential for diabetic kidney disease. Furthermore, our integrated experimental and molecular dynamics approach elucidates the fundamental self-assembly mechanism between TP and PSP, which is driven by hydrogen bonding. Notably, we identified Nrf2 pathway activation and ferroptosis inhibition as a novel protective mechanism against TP-induced nephrotoxicity, effectively expanding its therapeutic window for clinical translation. This study successfully bridges traditional medicine wisdom with modern nanotechnology, addressing critical pharmacological and environmental challenges in drug development. Beyond the specific application of TP, this work validates a scientific principle from Chinese medicine for guiding the design of nanomedicine, offering a generalizable template for reformulating other potent but toxic herbal compounds.
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KAOHSIUNG JOURNAL OF MEDICAL SCIENCES
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2026
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IF 3.1
Shan-Shan Wang,Hong-Cheng Wei,Lin Jiang,Yi-Sen Shao
Tongue squamous cell carcinoma, the most aggressive subtype of oral squamous cell carcinoma, which is associated with high mortality, frequent recurrence, and early lymph-node metastasis. Triptolide, a bioactive diterpenoid from Tripterygium wilfordii , exhibits broad anticancer activity. Although its inhibitory action on OSCC has been established, its specific molecular regulatory mechanisms in TSCC, a distinct and aggressive subtype, remain largely underexplored. The present study investigates the regulatory role of triptolide in the PI3K–AKT signaling pathway, which is a critical axis intimately linked to tumor survival and metastasis. A network-pharmacology workflow was used to intersect triptolide putative targets with TSCC-related genes. Core hubs were identified with Cytoscape; KEGG and GO analyses highlighted the PI3K–AKT axis as the top enriched pathway. Binding kinetics were quantified by molecular docking and surface plasmon resonance (SPR). Cellular assays (CCK-8, Transwell, wound-healing, Western blot and immunofluorescence) validated the predictions. We retrieved 389 common targets and shortlisted eight key nodes (JUN, MAPK1, MAPK3, AKT1, TP53, BCL2, STAT3, MYC). SPR revealed high-affinity binding of triptolide to AKT1 and PI3K. Functionally, triptolide dose-dependently suppressed TSCC cell proliferation, invasion, and migration, downregulated PI3K–AKT signaling proteins, and reduced the colocalization and phosphorylation levels of p-PI3K and p-AKT. This study is the first to demonstrate the pivotal role of the PI3K–AKT signaling pathway in mediating the antitumor effects of triptolide in tongue squamous cell carcinoma. Our findings thereby provide a novel theoretical foundation for the development of traditional Chinese medicine-based therapeutic strategies targeting this malignancy.
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Frontiers in Pharmacology
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2021
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IF 5.811
Lin Jingpan,Gao Lu,Lin Yanke,Wang Shuai,Yang Zemin,Ren Shujing,Chen Min,Wu Baojian
Rheumatoid arthritis is a systemic autoimmune disease characterized by synovial inflammation and bone destruction. Identifying drugs with time-varying efficacy and toxicity, and elucidating the mechanisms would help to improve treatment efficacy and reduce adverse effects. Here, we aimed to determine the chronoefficacy of semen strychni (SS) and tripterygium glycoside tablet (TGT) against rheumatoid arthritis in mice, and to investigate a potential role of circadian pharmacokinetics in generating chronoefficacy. SS extract and TGT suspension were prepared with ultrasonication. Effects of SS and TGT on collagen-induced arthritis (CIA) were evaluated by measuring TNF-α and IL-6 levels. SS dosed at ZT18 was more effective in protecting against CIA than drug dosed at ZT6 (i.e., lower levels of key inflammatory factors at ZT18 than at ZT6). This was accompanied by higher systemic exposure levels of strychnine and brucine (two main putative active ingredients of SS) in ZT18-treated than in ZT6-treated CIA mice. TGT dosing at ZT2 showed a better efficacy against CIA as compared to herb doing at ZT14. Consistently, ZT2 dosing generated a higher exposure of triptolide (a main putative active ingredient of TGT) as compared to ZT14 dosing in CIA mice. Moreover, strychnine, brucine, and triptolide significantly inhibited the proliferation of fibroblast-like synoviocytes, and reduced the production of TNF-α and IL-6 and the mRNAs of TNF-α, IL-6, COX-2, and iNOS, suggesting that they possessed an anti-arthritis activity. In conclusion, SS and TGT display chronoefficacy against rheumatoid arthritis in mice, that is attributed to circadian pharmacokinetics of main active ingredients. Our findings have implications for improving treatment outcomes of SS and TGT via timed delivery.
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JOURNAL OF PHARMACY AND PHARMACOLOGY
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2020
·Vol. 72
·期 12
·1854-1864
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IF 2.571
Zhao Huan,Tong Yongbin,Lu Danyi,Wu Baojian
ObjectivesWe aimed to determine the diurnal rhythm of Tripterygium wilfordii (TW) hepatotoxicity and to investigate a potential role of metabolism and pharmacokinetics in generating chronotoxicity.MethodsHepatotoxicity was determined based on assessment of liver injury after dosing mice with TW at different circadian time points. Circadian clock control of metabolism, pharmacokinetics and hepatotoxicity was investigated using Clock-deficient (Clock−/−) mice.Key findingsHepatotoxicity of TW displayed a significant circadian rhythm (the highest level of toxicity was observed at ZT2 and the lowest level at ZT14). Pharmacokinetic experiments showed that oral gavage of TW at ZT2 generated higher plasma concentrations (and systemic exposure) of triptolide (a toxic constituent) compared with ZT14 dosing. This was accompanied by reduced formation of triptolide metabolites at ZT2. Loss of Clock gene sensitized mice to TW-induced hepatotoxicity and abolished the time-dependency of toxicity that was well correlated with altered metabolism and pharmacokinetics of triptolide. Loss of Clock gene also decreased Cyp3a11 expression in mouse liver and blunted its diurnal rhythm.ConclusionsTripterygium wilfordii chronotoxicity was associated with diurnal variations in triptolide pharmacokinetics and circadian expression of hepatic Cyp3a11 regulated by circadian clock. Our findings may have implications for improving TW treatment outcome with a chronotherapeutic approach.
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Communications Biology
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2019
·Vol. 2
·期 1
·1-11
·
IF 0
Lin Yanke,Wang Shuai,Zhou Ziyue,Guo Lianxia,Yu Fangjun,Wu Baojian
Metabolism is a major defense mechanism of the body against xenobiotic threats. Here we unravel a critical role of Bmal1 for circadian clock-controlled Cyp3a11 expression and xenobiotic metabolism. Bmal1 deficiency decreases the mRNA, protein and microsomal activity of Cyp3a11, and blunts their circadian rhythms in mice. A screen for Cyp3a11 regulators identifies two circadian genes Dbp and Hnf4α as potential regulatory mediators. Cell-based experiments confirm that Dbp and Hnf4α activate Cyp3a11 transcription by their binding to a D-box and a DR1 element in the Cyp3a11 promoter, respectively. Bmal1 binds to the P1 distal promoter to regulate Hnf4α transcriptionally. Cellular regulation of Cyp3a11 by Bmal1 is Dbp- and Hnf4α-dependent. Bmal1 deficiency sensitizes mice to toxicities of drugs such as aconitine and triptolide (and blunts circadian toxicity rhythmicities) due to elevated drug exposure. In summary, Bmal1 connects circadian clock and Cyp3a11 metabolism, thereby impacting drug detoxification as a function of daily time.
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ACS Biomaterials Science & Engineering
·
2019
·
IF 4.511
Caili Huang,Tao Zeng,Jiawen Li,Lishan Tan,Xiulong Deng,Yanchao Pan,Qi Chen,Aiqing Li,Jianqiang Hu
Triptolide (TP) has been widely used in clinical medicine; however, it has created a dilemma due to its toxicity and nonspecificity. Here, we reported a biocompatible and high-efficiency renal-targeting nanoplatform for renal ischemia/reperfusion injury (IRI) therapy, in which the toxic drug of TP was encapsulated into folate (FA)-modified Pluronic F127/P123 nanoparticles (FPNPs). The TP-loaded FPNPs (TP-FPNPs) had good stability and could effectively reduce the cytotoxicity of TP. Compared with the Pluronic nanoparticles (PNPs) group, cellular uptake ability of FPNPs significantly improved because of folate receptor-mediated endocytosis effect. Ex vivo organ imaging and pharmacokinetic results indicated that FPNPs possessed high kidney selectivity and long retention time. The therapeutic effect of TP-FPNPs on renal IRI was more superior to that of free TP, such as lower acute tubular injury index (2.9-fold), renal function indexes of serum creatinine (4.3-fold), urea nitrogen (2.0-fold), and Western blotting (2.4-fold). Systemic toxicity assay suggested that TP-FPNPs had much lower nephrotoxicity, hepatotoxicity, and genital system toxicity than free TP. Thus, renal-targeting FPNPs will be a potential delivery platform of hydrophobic drugs for treatment of renal diseases.
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RSC Advances
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2018
·Vol. 8
·期 39
·22062-22068
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IF 2.936
Bailing Ma,Mi Lu,Bo-Yang Yu,Jiangwei Tian
Drug-induced liver injury (DILI) is a serious concern in modern medicine due to its unpredictability. Currently, biochemical serum markers are being used in DILI detection. However, these biomarker-based methods lack sensitivity and specificity. A high intracellular level of hydroxyl radicals (˙OH) has been regarded as an early indicator of DILI. Therefore, we proposed an ˙OH-responsive and hepatocyte-targeted nanoprobe via conjugation of carboxyfluorescein-labeled DNA and pegylated galactose on the surface of gold nanoparticles. The nanoprobe could bind to a hepatocyte-specific asialoglycoprotein receptor through galactose, and it could be internalized into liver cells. In the presence of high levels of ˙OH in DILI, the DNA could be cleaved to release carboxyfluorescein, leading to remarkable fluorescence enhancement for ˙OH detection. Confocal fluorescence imaging demonstrated that the nanoprobe could be successfully applied in monitoring high ˙OH levels resulting from acetaminophen or triptolide-induced liver injury, which may provide a simple but powerful protocol for the prediction of DILI.
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Polymers
·
2024
·Vol. 16
·期 24
·3485
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IF 4.7
Meizhen Yin,Xinying Zhang,Tongguang Zhang,Zhiqiang Bao,Zhihui He
The present study aimed to explore an ideal delivery system for triptolide (TPL) by utilizing the thin-film hydration method to prepare drug-loaded, folate-modified mixed pluronic micelles (FA–F-127/F-68–TPL). Scanning electron microscopy and atomic force microscopy showed that the drug-loaded micelles had a spherical shape with a small particle size, with an average of 30.7 nm. Cell viability experiments showed that FA–F-127/F-68–TPL significantly reduced HepG2 cell viability, exhibiting strong cytotoxicity. Its cytotoxicity was markedly enhanced compared with bare TPL. Nile red (Nr) was used as a model drug to prepare FA–F-127/F-68–Nr to further validate its tumor-targeting and cellular uptake capability. After coincubation with HepG2 cells, a multifunctional microplate reader showed that intracellular fluorescence intensity significantly increased, indicating that FA–F-127/F-68–Nr could more effectively enter the cells. A nude mouse model of subcutaneous hepatocellular carcinoma was constructed. Following tail vein injection of FA–F-127/F-68–Nr, the fluorescence imaging system showed that FA–F127/F-68–Nr could significantly target tumor tissue, and even if entering the small-sized tumor was challenging, it could be excreted through urine. Nude mice with subcutaneous hepatocellular carcinoma were treated with tail vein injections of FA–F-127/F-68–TPL (45 µg/kg) every other day for 21 days. The results showed that the growth of the transplanted tumors was significantly slowed, with no significant difference compared with bare TPL. In summary, the FA–F-127/F-68–TPL exhibits the advantages of low cost, excellent biological properties, active/passive targeting capabilities, notable cytotoxicity against liver cancer cells, and significant inhibition of transplanted hepatocellular carcinoma growth. Significantly, the FA–F-127/F-68–TPL, despite challenges in targeting tumors with an insignificant EPR effect, can be efficiently excreted via the kidneys, thereby preventing the release of the drug during prolonged circulation and potential damage to normal tissues. Therefore, FA–F-127/F-68–TPL represents a promising antitumor drug delivery system.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2025
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IF 6.2
Wen-kui Li,Song Wang,Yong-hong Wang,Yu-zhen Wu,Jia Li,Tian-hua Chai,Kang Wang,GuangYou Chen,Zhiqing Ma
Nanoporous 3D-polyurethane (3D-PU) was prepared based on nano-CaCO3 templated controllably confined polymerization assembly and weak acid etching strategies. Nanopores with diameters ranging from 48 to 72 nm were distributed on 3D-PU, facilitating its high BET surface area of 468.0 m2/g. The 3D-PU exhibited enhanced adsorption selectivity to multi-H-bond donors and acceptors, multirings contained compounds based on pore filling, hydrogen-bonding, and π–π interactions; therefore, the novel 3D-PU had promising adsorption ability to toosendanin (TSN) with a maximum theoretical adsorption capacity of 361.6 mg/g. Adsorption isotherm, kinetic, and thermodynamic investigations revealed that the adsorption was heterogeneous and was supported by multiple adsorption sites, controlled by a chemical adsorption mechanism, endothermic, spontaneous, and with increased entropy. Based on the optimized adsorption, the loading capacity (LC) of 3D-PU toward TSN attained 23.4%. After encapsulation, the effective period of TSN was extended to 11 days, the photolysis half-life of TSN was increased 3.2 times, and the LC50 for Aphis citricola was reduced approximately 6.0 times, indicating that 3D-PU effectively improved the performance of TSN. The porous 3D-PU can serve as a promising carrier for more pesticide adsorption, encapsulation, safe, highly efficient, and environmentally friendly utilization.
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