PHYTOMEDICINE
·
2016
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IF 2.937
Qin Tang,Fangling Ji,Wenhui Sun,Jingyun Wang,Jianli Guo,Lianying Guo,Yachen Li,Yongming Bao
Background 10-Hydroxy camptothecin (HCPT), a naturally occurring alkaloid, is a clinical drug for cancer chemotherapy . Baicalein (BA) is a flavonoid extracted from the root of Scutellaria baicalensis . The synergistic anti-cancer effect of BA and HCPT has not been reported. Purpose To explore whether and how BA enhances the anti-cancer effect of HCPT in BGC823 cells. Methods Cell viability was measured by MTT assay. Apoptosis and cell cycle were analyzed through flow cytometry and western blotting analysis. DNA damage was determined by a comet assay . The activity of topoisomerase I (Topo I) was detected by the plasmid DNA relaxation assay. The synergistic anti-cancer effect of BA and HCPT in vivo was tested by BGC823 xenografted tumor model. Results BA at non-toxic doses prominently enhanced the anti-cancer activities of HCPT in BGC823, MCF7 and SMMC7721 cells. Combination treatment of BA and HCPT induced BGC823 cells apoptosis mainly via intrinsic rather than extrinsic pathways, and preferentially arresting cell cycle in G1 and G2 phases with the aid of p21 . Of note, p53, the upstream regulator of cell apoptosis and cycle, was increased by 5 folds in combination group. It helped to further trigger DNA damage and inhibit Topo I catalytic activity after combination treatment of BA and HCPT. Moreover, the BGC823 xenografted tumor growth rate in nude mice was repressed in a greater degree ( P < 0.01) in the combinational group than the single-drug group. Conclusion HCPT and BA, a new and effective combination therapy, synergistically target Topo I and up-regulate p53 to induce cell apoptosis and cell cycle arrest.
研究领域:
肿瘤学
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药理学
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分子生物学
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细胞生物学
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PubMed
高影响因子
PHYTOMEDICINE
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2019
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IF 4.18
Hongjin Chen,Yali Zhang,Wenxin Zhang,Hui Liu,Chuchu Sun,Bing Zhang,Bin Bai,Di Wu,Zhongxiang Xiao,Hazel Lum,Jianmin Zhou,Ruijie Chen,Guang Liang
Background ALI/ARDS is characterized by severe hypoxemic respiratory failure attributed to inflammatory tissue injury. There are no treatment modalities able to prevent/reverse the dire pathological sequelae in these patients . Evidence links the inflammatory lung injury to uncontrolled activation of the immune signaling complex, TLR4-MD2 (Toll-like receptor-myeloid differentiation factor 2). Baicalein , a natural flavonoid , is reported to have robust anti-inflammatory properties, but its inhibition mechanism remains unclear. Hypothesis/Purpose This study investigated the protective mechanisms of baicalein on ALI/ARDS. Methods We used two experimental mouse models of LPS-induced ALI , pulmonary infection model (intratracheal LPS), and systemic infection model (intravenous LPS). Blood, BALF , lung and liver tissues were analyzed using routine methods. In vitro studies using peritoneal mouse macrophages or recombinant proteins were designed to elucidate inhibition mechanisms of baicalein. Results Our critical new findings revealed that Baicalein was an MD2 inhibitor, directly bound to MD2, effectively suppressing TLR4-MD2 activation and the subsequent MAPK and NF-κB signaling. The inhibited MD2 prevented development of inflammatory tissue injury and improved survival. The importance of MD2 in the inflammatory injury in ALI was corroborated by data obtained from MD2 −/− mice, which did not develop the characteristic LPS-induced lung tissue damage. Thus, the findings indicated that MD2 was critical for development of ALI, functioning as an early upstream signal driving the progression of inflammatory injury. Conclusion Baicalein, as a direct and selective MD2 inhibitor, inhibited the early upstream TLR4-MD2 signaling and is a promising therapeutic agent for the treatment of ALI/ARDS.
研究领域:
免疫学
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药理学
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肺科学
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分子生物学
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PubMed
高影响因子
Foods
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2022
·Vol. 11
·期 2
·168
·
IF 5.561
Yijing Liao,Xing Hu,Junhui Pan,Guowen Zhang
Alzheimer’s disease (AD) is the most prevalent chronic neurodegenerative disease in elderly individuals, causing dementia. Acetylcholinesterase (AChE) is regarded as one of the most popular drug targets for AD. Herbal secondary metabolites are frequently cited as a major source of AChE inhibitors. In the current study, baicalein, a typical bioactive flavonoid, was found to inhibit AChE competitively, with an associated IC50value of 6.42 ± 0.07 µM, through a monophasic kinetic process. The AChE fluorescence quenching by baicalein was a static process. The binding constant between baicalein and AChE was an order of magnitude of 104L mol−1, and hydrogen bonding and hydrophobic interaction were the major forces for forming the baicalein−AChE complex. Circular dichroism analysis revealed that baicalein caused the AChE structure to shrink and increased its surface hydrophobicity by increasing the α-helix and β-turn contents and decreasing the β-sheet and random coil structure content. Molecular docking revealed that baicalein predominated at the active site of AChE, likely tightening the gorge entrance and preventing the substrate from entering and binding with the enzyme, resulting in AChE inhibition. The preceding findings were confirmed by molecular dynamics simulation. The current study provides an insight into the molecular-level mechanism of baicalein interaction with AChE, which may offer new ideas for the research and development of anti-AD functional foods and drugs.Keywords:baicalein;acetylcholinesterase;inhibitory mechanism;conformational change;molecular docking;molecular dynamics simulation
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TOXICOLOGY AND APPLIED PHARMACOLOGY
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2017
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IF 3.791
Gang-Feng Ge,Wei-Wen Shi,Chen-Huan Yu,Xiao-Yin Jin,Huan-Huan Zhang,Wen-You Zhang,Lu-Chen Wang,Bing Yu
Chemotherapy is one of the major strategies for cancer treatment. Several antineoplastic drugs including vinorelbine (VRB) are commonly intravenously infused and liable to cause serious phlebitis. The therapeutic drugs for preventing this complication are limited. In this study, the mechanism of baicalein (BCN) was investigated on VRB-induced phlebitis in vivo and vascular endothelial cell injury in vitro . Treatment with BCN obviously attenuated vascular endothelial cell loss, edema, inflammatory cell infiltration and blood clots, and reduced the serum levels of TNF-α, IL-1β, IL-6 and ICAM-1 in the rabbit model of phlebitis induced by intravenous injection of VRB compared with vehicle. Further tests in vitro demonstrated that BCN lessened VRB-induced endothelial cell apoptosis, decreased intracellular ROS levels, suppressed phosphorylation of p38 and eventually inhibited activation of NF-κB signaling pathway. And these effects could be reversed by p38 agonist P79350. These results suggested that BCN exerted the protective effects against VRB-induced endothelial disruption in the rabbit model of phlebitis via inhibition of intracellular ROS generation and inactivation of p38/NF-κB pathway, leading to the decreased production of pro-inflammatory cytokines. Thus, BCN could be used as a potential agent for the treatment of phlebitis.
研究领域:
肿瘤学
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药理学
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分子生物学
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PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
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2023
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IF 3.6
Yujia Liu,Jun Qian,Xiufen Zhao,Tianyu Lan,Yongjun Luo,Qianqian Guo,Xiangchun Shen
Globally, due to the rapid development of bacterial resistance, bacterial infections lead to significant mortality and morbidity which require efficient strategies to eradicate these infections. Herein, we prepared a dual-responsive synergistic drug delivery nanoparticle carrier (NPS@Bai/Cip), which responds to sub-acid bacterial microenvironments and targets phosphatase or phospholipase at infection sites. Nanoparticles surfaces were positively (10.0 mV) charged under acidic conditions, leading to good bacterial adhesion and enhanced drug accumulation. NPS@Bai/Cip showed good antibacterial and anti-biofilm activity against drug-resistant Pseudomonas aeruginosa. NPS@Bai/Cip could inhibit the biofilm formation via affecting the swimming, swarming, and twitching motilities of P. aeruginosa. NPS@Bai/Cip was used to treat drug-resistance P. aeruginosa-induced infection in rats by improving wound healing and reducing inflammatory responses. Thus, NPS@Bai/Cip functioned as an antibacterial and antibiofilm agent with good potential for treating bacteria-induced infections.
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高影响因子
LIFE SCIENCES
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2020
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IF 3.647
Meifang Wang,Yinping Dong,Jing Wu,Hongyan Li,Yuanyang Zhang,Saijun Fan,Deguan Li
Aims Ionizing radiation (IR) induces injuries to the hematopoietic and intestinal systems, which are the leading cause of death. Baicalein, a plant-derived flavonoid, shows anti-oxidative stress, anti-apoptosis, anti-inflammation effects in many diseases. In this study, we evaluated the effects and mechanism of baicalein on IR induced intestinal and hematopoietic injuries. Main methods Mice were divided into three groups: Control, IR and IR + Baicalein. All of mice were intraperitoneally administered with 100 mg/kg baicalein or normal saline for 1 h before IR, and then a day post-IR. The changes in intestinal structure, function and molecular expression were observed by pathological experiments and western blot. 16S rRNA gene sequencing was performed to analyze gut microbiota and further predicted metabolic pathways through Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Hematopoietic function was evaluated by peripheral blood cells count and by flow cytometry analysis of hematopoietic cells composition. Key findings Baicalein improved intestinal structure and the ability of proliferation and regeneration after mice exposed to IR, in which the rebalance of gut microbial composition played an important role. KEGG results showed that p53-related apoptotic pathways played important roles in the composition changes of gut microbiota. Then we observed that baicalein inhibited the activation of p53 and p53 mediated mitochondrial apoptosis and death receptor apoptosis in the intestine. In addition, IR induced injuries to hematopoietic system also could be ameliorated by baicalein. Significance These results provide new insights into the mechanism of baicalein and support the potential of baicalein as a radioprotective medicine.
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高影响因子
JOURNAL OF FOOD SCIENCE
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2026
·Vol. 91
·期 2
·e70878
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IF 3.4
Naijun Dong,Nasha Wu,Shu Huang,Yuesheng Dong,Zhilong Xiu
Type 2 diabetes mellitus (T2DM), one of the most rapidly growing metabolic disorders globally, poses a substantial public health burden. In this study, a novel edible eutectogel was innovatively developed for the co-delivery of natural active ingredients, baicalein (Bai), and 1-deoxynojirimycin (DNJ). Utilizing a deep eutectic solvent (DES) system, the hydrophobic Bai and hydrophilic DNJ were co-dissolved and encapsulated within the eutectogel (Bai-DNJ/EG), enabling gastric protection and targeted intestinal release. Animal experimental demonstrated that the Bai-DNJ/EG significantly ameliorated multiple pathological features, including blood glucose reduction, improved insulin sensitivity, attenuated systemic inflammation, decreased fat accumulation, and mitigated organ damage. Compared with Bai/EG and DNJ/EG, Bai-DNJ/EG exhibited superior therapeutic efficacy across all parameters, indicating a synergistic effect between the Bai and DNJ. The dose of Bai in Bai-DNJ/EG was reduced by 50% relative to previous studies, and DNJ was 7.5 times less than that of clinical use in a Chinese herbal preparation for lowering blood glucose. In addition, comparison of lipid metabolism and inflammatory factors between Bai HG and Bai/EG groups indicated that DES enhanced the pharmacological activity of Bai by improving its solubility. Furthermore, 16S rRNA sequencing revealed that Bai-DNJ/EG positively regulates gut microbiota homeostasis and repairs the intestinal barrier. Bai-DNJ/EG inhibited deleterious bacteria including Methanobacteriaceae, Pseudomonadota , Campylobacterota , and Spirochaetota , while promoted the SCFA-producing bacteria, for example, Muribaculaceae and Butyricicoccaceae. This study presents a groundbreaking strategy for the synergistic delivery of natural bioactives and establishes a new paradigm for modernized traditional natural medicine formulations.
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高影响因子
JOURNAL OF DAIRY SCIENCE
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2026
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IF 4.7
Rongrong Wei,Jingyi Wang,Kui Li,Lu Yu,Ziyi Ye,Jiawei Du,Caixia Ru,Yanbin Gong,Chuang Xu
The timely onset of mammary involution during early dry period is important for subsequent udder health and productive performance. However, mammary involution is also accompanied by oxidative stress and inflammation, and existing strategies rarely boost involution while reducing related damage. Chitosan (CS) has the potential to promote involution, while Baicalein (BAI) can counter oxidative stress, yet their combined effects during early dry period in dairy cows remain unclear. Two independent cow experiments assessed a combined chitosan/baicalein formulation (C/B) for non-antibiotic intramammary use. In a preliminary trial, 15 Holstein cows (n = 3 per group) received Vehicle (solvent control without C or B), Ceftiofur Hydrochloride dry-cow therapy ( CEF ), CS, BAI or C/B via intramammary infusion immediately after the final milking at dry-off. Compared with Vehicle, C/B increased somatic cell count, bovine serum albumin, and lactoferrin concentrations in mammary secretions, indicating enhanced involution-associated changes. C/B also improved antioxidant and inflammatory profiles, as shown by increased superoxide dismutase activity and reduced malondialdehyde, interleukin-6, and tumor necrosis factor-α levels. In a validation experiment, 54 cows were assigned to C/B, CEF, or untreated abrupt dry-off control groups (n = 18 cows/group). Compared with control groups, C/B reduced post-dry-off milk leakage and clinical signs suggestive of new intramammary infection. It also promoted the resolution of udder distension and recovery of eating time, with overall responses comparable to CEF and no evident biochemical safety abnormalities. To investigate the underlying mechanisms, mammary epithelial cells were treated with C/B in vitro. C/B (30 μg/mL) reduced the expression of tight junction-associated proteins, impaired cell migratory capability, induced mitochondrial dysfunction, and triggered transcriptomic changes associated with epithelial remodeling and apoptosis. These findings suggest that C/B may facilitate physiological mammary involution while mitigating oxidative stress and inflammation, thereby supporting dry-off management and offering a potential non-antibiotic approach in dairy production.
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高影响因子
Heliyon
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2024
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IF 3.4
Guo-qiang Liang,Wei Mu,Chun-bo Jiang
Evidence indicates that Baicalein can ameliorate renal interstitial fibrosis by inducing myofibroblast apoptosis and inhibit the RLS3-induced ferroptosis in melanocytes. However, the relationship between renal interstitial fibrosis and anti-ferroptosis affected by Baicalein remains unclear. In our study, the anti-fibrosis and anti-ferroptosis effects of Baicalein were assessed in a rat model induced by the UUO method in vivo , and the effects of Baicalein on Erastin-induced ferroptosis of renal MPC-5 cells were examined by Western blot of fibrosis-related and ferroptosis-related proteins in vitro . In the UUO-induced rat model, Baicalein decreased kidney weight loss, improved renal function assessed the biomarks of urinary albumin excretion, serum creatine, and BUN levels, and reduced renal tubular injury. Furthermore, Baicalein inhibited renal ferroptosis by reducing ROS and MDA levels and increasing SOD and GSH levels in the UUO rat model. In addition, Baicalein potently reduced the expression of fibrosis-related proteins such as TGF-β1, a-SMA, and Smad-2 to prevent renal interstitial fibrosis, and increased the expression of ferroptosis-related proteins such as SLC7A11, GPX4, and FTH to inhibit ferroptosis both in vitro and in vivo . Taken together, Baicalein exerts anti-fibrosis activity by reducing the ferroptosis response on the UUO-induced rat model and renal MPC5 cells. Therefore, Baicalein, as a novel therapeutic method on kidney diseases with strong activity in suppressing ferroptosis, could be a potential alternative treatment for renal interstitial fibrosis.
研究领域:
药理学
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肾脏病学
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高影响因子
Food Bioscience
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2024
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IF 4.8
Qiuyan Jiang,Tiehua Zhang,Yuan Liang,Jie Zhang
The role of the pregnane X receptor (PXR) extended beyond regulating drug metabolism and transport, it also played a crucial part in lipid metabolism. Baicalein, a flavonoid derived from Scutellaria baicalensis , was demonstrated anti-inflammatory, anti-cancer, and anti-oxidative stress properties. Recent investigations reported its capacity to enhance lipid metabolism disorders. This study aimed to clarify the mechanism via which baicalein exerted its positive effects on lipid metabolism disorders by targeting PXR. The findings indicated that baicalein facilitated the nuclear translocation of PXR and controlled the expression of its target genes. In HepG2 cells with oleic acid and palmitic acid-induced lipid accumulation, baicalein treatment reduced the production of triglycerides, total cholesterol, and lipid droplets. In addition, it decreased the expression of sterol regulatory element-binding protein 1 (SREBP1), as well as lipogenic enzymes fatty acid synthase (FAS) and stearoyl-CoA desaturase-1 (SCD1). The results of computer simulation indicated that baicalein was a natural ligand of PXR. In conclusion, baicalein might potentially alleviate lipid metabolism disorders by targeting the PXR pathway.
研究领域:
药理学
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细胞生物学
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分子生物学
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高影响因子
Food Science and Technology
·
2021
·
IF 1.718
SHI Min,YIN Pengyi,GUO Xiaobo,LI Qian,SUN Lin,CAO Xiaohua
Baicalein has strong anti-inflammatory activity, but its efficacy and mechanism in pneumonia of mice is still unclear. Herein, RAW264.7 cells were infected with M. tuberculosis H37Rv (MOI 1:10) after pre-incubation with 50 μM baicalein, and the result found that baicalein incubation ameliorated the increase of bacterial load, and reduced the levels of ROS, IL-12p40, TLR2 protein, phosphorylated JNK protein and M1 polarization markers (iNOS and CD11c), and increased the levels of IL-10, M2 polarization markers (Arg1, Mrc1 and CD206) and NEDD4L protein in H37Rv infected-RAW264.7 cells. And lentivirus-mediated NEDD4L overexpression vector (LV-NEDD4L) transfection had the same effect as baicalein, while small interfering RNA target NEDD4L (si-NEDD4L) transfection or JNK pathway inhibitor IQ 3 treatment reversed the effects of baicalein, and ubiquitin inhibitor MG132 treatment reversed the effects of LV-NEDD4L. Co-immunoprecipitation (Co-IP) and TLR2 ubiquitination assays found that the binding of NEDD4L and TLR2 promoted the ubiquitination of TLR2. In vivo, C57BL/6 mice were nasal infected with H37Rv (1000 ± 150 CFU/mouse) to establish a mouse pneumonia model, and then administered with baicalein. The result found that baicalein improved H37Rv-induced pneumonia in mice. In conclusion, baicalein increased NEDD4L-mediated ubiquitination of TLR2, promoting macrophage M2 polarization and alleviating H37Rv-induced pneumonia.
研究领域:
免疫学
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药理学
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微生物学
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分子生物学
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DOI
高影响因子
PHYTOCHEMICAL ANALYSIS
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2026
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IF 2.9
Yu Xia,Xinyi Zhong,Chenggang Zhang
Background Hypoxia is a core pathological factor in myocardial injury and is involved in the development of various cardiovascular diseases. Although baicalein shows cardiovascular protective potential, its mechanism against hypoxic injury remains unclear. Methods H9c2 cardiomyocytes were exposed to sodium sulfite to establish a chemical hypoxia model. Network pharmacology, molecular docking, molecular dynamics simulation, and molecular biology assays were employed to predict the core target and investigate the underlying mechanism. Results Network pharmacology identified ESR1 as a core target, with stable binding to baicalein confirmed by molecular docking and dynamics simulations. Baicalein alleviated hypoxia-induced oxidative stress by elevating key antioxidant markers and reducing malondialdehyde levels. It also ameliorated energy metabolism disorders, reduced lactate dehydrogenase release, suppressed reactive oxygen species production, and decreased cell apoptosis. Furthermore, baicalein upregulated hypoxia-suppressed ESR1 protein expression and enhanced its co‑localization with the antiapoptotic protein BCL-XL. The cytoprotective effects were abolished by the ESR1 inhibitor fulvestrant. Conclusion These findings demonstrate that baicalein protects cardiomyocytes against hypoxic injury through an ESR1‑dependent mechanism by modulating the BCL‑XL/BAX apoptotic balance, mitigating oxidative stress, and improving energy metabolism.
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高影响因子
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