1.Mechanisms and benefits of phytochemicals as an alternative therapeutic strategy in female cancers.
Yufan ZHAO ; Shimenghui DENG ; Danli CAO ; Caiji LIN ; Mengzhi XU ; Jiaxing WANG ; Lingjie LUO ; Shulin LIU ; Huidi LIU
Chinese Herbal Medicines 2025;17(3):448-463
Cancer is a highly deadly disease, with breast cancer, cervical cancer, endometrial cancer, and ovarian cancer being the most prevalent in women. However, traditional cancer treatments present challenges due to their strong toxic side effects and adverse reactions. Numerous studies have demonstrated that natural products derived from various plants possess therapeutic and preventive properties against cancer. These phytochemicals have been extensively investigated as a potential alternative to conventional chemotherapy drugs, owing to their safety and efficacy. This article provides a comprehensive review of the recent advances in the chemoprevention and mechanisms of phytochemicals against the four major female cancers. The focus will be on how these phytochemicals regulate cancer cell proliferation, apoptosis, invasion, and metastasis to impede cancer progression. Given their extensive clinical applications, phytochemicals hold great promise in the field of cancer treatment. It hopes that this review will inspire more researchers to explore the potential of these natural compounds in combating female cancers.
2.Effects of Jianpi Bushen Jiedu Prescription regulating JAK2/STAT3 pathway on proliferation and migration of hepatocellular carcinoma cells
Huidi LI ; Yuanyuan FENG ; Youying LAI ; Ru JIA ; Pingping ZHANG ; Xiaojun ZHU ; Hongjie LIU
International Journal of Traditional Chinese Medicine 2024;46(2):186-190
Objective:To explore the effects of Jianpi Bushen Jiedu Prescription on the proliferation and migration of hepatocellular carcinoma cells; To discuss its possible mechanism.Methods:Using human highly metastatic liver cancer cell line (HCCLM3) as the research object, they were randomly divided into control group and TCM group (100, 200, 400, 800, 1 600, 3 200 μg/ml Jianpi Bushen Jiedu Prescription) and Western medicine group (2.5, 5, 10, 20, 40 μmol/L sorafenib) using a random number table method. Cell viability was detected using cell counting reagent (CCK-8) method; HCCLM3 cells were divided into control group and TCM (Jianpi Bushen Jiedu Prescription 800 μg/ml) group and combined group (Jianpi Bushen Jiedu Prescription 800 μg/ml +sorafenib 20 μmol/L). Western blot method was used to detect the protein expressions of kinase/signaling transducer and transcriptional activator (JAK2/STAT3) pathway related proteins (p-JAK2, JAK2, p-STAT3, STAT3) in each group.Results:Compared with the control group, viability and mobility of HCCLM cell in TCM group and Western medicine group decreased ( P<0.01 or P<0.05); compared with the control group, the protein expressions of P-JAK2, JAK2, P-STAT3 and STAT3 in the TCM group and the combined group decreased ( P<0.05), and the JAK2 protein expression in the combined group was lower than that in the TCM group ( P<0.05). Conclusion:Jianpi Bushen Jiedu Prescription can inhibit the proliferation and migration of HCC cells by regulating JAK2/STAT3 pathway.
3.Qidi Tangshen Prescription (QDTS) Regulate Akt1/HIF-1α/Bcl-xl Signaling Pathway to Improve Podocyte Autophagy in Diabetic Nephropathy
Fei GAO ; Huidi XIE ; Borui YU ; Ying ZHOU ; Yang SHI ; Xianhui ZHANG ; Hongfang LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(15):90-97
ObjectiveTo explore the mechanism of Qidi Tangshen prescription (QDTS) in alleviating podocyte injury and reducing urinary protein in diabetic nephropathy (DN). MethodUsing network pharmacology methods, we collected the chemical components and targets of QDTS, as well as the targets related to DN. Subsequently, we constructed a "drug-ingredient-target-disease" network for QDTS in the treatment of DN to systematically elucidate the mechanism. The db/db mice were assigned into the model, QDTS (3.34 g·kg-1), and losartan capsules (10.29 mg·kg-1) groups, and db/m mice served as the normal group. Each group consisted of 8 mice, and they underwent continuous intervention for 8 weeks. After the last administration, mice were euthanized, and the urinary albumin excretion rate (UAER) and renal pathological changes were measured and observed. The expression levels of protein kinase B1 (Akt1), hypoxia-inducible factor-1 alpha (HIF-1α), phosphorylated B-cell lymphoma-extra-large (p-Bcl-xl), as well as autophagy-related indicators microtubule-associated protein 1 light chain 3 (LC3), ubiquitin-binding protein p62 (p62), and autophagy-related gene 6 homolog (Beclin1), were determined. Furthermore, mouse podocytes were divided into the normal glucose (5.5 mmol·L-1), high glucose (35 mmol·L-1), DMSO (35 mmol·L-1 glucose+200 mg·L-1 DMSO), and QDTS (35 mmol·L-1 glucose+200 mg·L-1 QDTS freeze-dried powder) groups. After 48 h of intervention, the protein levels of Akt1, HIF-1α, p-Bcl-xl, LC3, p62, and Beclin1 in podocytes were measured. ResultQDTS had 34 active components acting on 143 targets in the treatment of DN, and 55 targets were related to autophagy, in which Akt1, HIF-1α, and Bcl-xl were the key targets. Compared with the normal group, mice in the model group exhibited significantly increased UAER, glomerular hypertrophy, deposition of blue collagen fibers, thickening of the glomerular basement membrane, and noticeable fusion of podocyte foot processes in some segments. Furthermore, the modeling up-regulated the protein levels of p-Akt1, HIF-1α, and p62 and down-regulating the protein levels of p-Bcl-xl, LC3, and Beclin1 in the renal tissue (P<0.05). Compared with the model group, QDTS and losartan decreased UAER (P<0.05) and alleviated the pathological damage in the renal tissue. Moreover, QDTS and losartan down-regulated the protein levels of p-Akt1, HIF-1α, and p62 and up-regulated the protein levels of p-Bcl-xl, LC3, and Beclin1 in the renal tissue (P<0.05). In comparison to the normal glucose group, the high glucose group displayed up-regulated protein levels of p-Akt1, HIF-1α, and p62 and down-regulated protein levels of p-Bcl-xl, LC3, and Beclin1 in podocytes (P<0.05). Compared with the high glucose group, QDTS down-regulated the protein levels of p-Akt1, HIF-1α, and p62 and up-regulated the protein levels of p-Bcl-xl, LC3, and Beclin1 in podocytes (P<0.05). ConclusionQDTS alleviates podocyte damage and reduced urinary protein in DN by regulating the Akt1/HIF-1α/Bcl-xl signaling pathway, thereby enhancing podocyte autophagy.
4.Implication of Qidi Tangshen Prescription (QDTS) on Podocyte Pyroptosis in Diabetes Nephropathy by Regulating MAPK14/RELA/Caspase-8 Signaling Pathway
Fei GAO ; Borui YU ; Huidi XIE ; Ying ZHOU ; Yang SHI ; Xianhui ZHANG ; Hongfang LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(13):67-75
ObjectiveTo explore the molecular mechanism of Qidi Tangshen prescription (QDTS) in regulating podocyte pyroptosis in diabetes nephropathy (DN). MethodThrough in vivo experiment, db/db mice were divided into the model group, QDTS group (3.34 g·kg-1), valsartan capsule group (10.29 mg·kg-1), with db/m mice serving as the normal control. Each group consisted of 8 mice, and they underwent continuous intervention for 8 weeks. After the last administration, mice were euthanized, and kidney pathological changes were observed. Additionally, the expression levels of pyroptosis-related indicators, including NOD-like receptor protein 3 (NLRP3), Gasdermin D protein (GSDMD), and interleukin-1β (IL-1β) protein, were examined. Through in vitro experiment, mouse podocytes were divided into the normal glucose group (5.5 mmol·L-1 glucose), high glucose group (35 mmol·L-1 glucose), DMSO group (35 mmol·L-1 glucose+200 mg·L-1 DMSO), and QDTS group (35 mmol·L-1 glucose+200 mg·L-1 QDTS freeze-dried powder). After 48 hours of intervention, the expression levels of NLRP3, GSDMD, and IL-1β proteins were measured in podocytes. A drug-ingredient-target-disease interaction network for QDTS in the treatment of DN was constructed by network pharmacology methods. The key signaling pathways regulating podocyte pyroptosis were analyzed, and validation was conducted through in vivo and in vitro experiments. ResultCompared with normal group, glomerular hyperplasia and glomerular basement membrane thickening were observed in model group, and some segments were accompanied by obvious podocellular process fusion. The protein expressions of NLRP3, GSDMD and IL-1β in mouse kidney were increased, the protein expressions of mitogen-activated protein kinase 14 (MAPK14), V-Rel reticuloendotheliosis virus oncogene homology A (RELA) and Caspase-8 in mouse kidney were increased (P<0.05). Compared with model group, kidney pathological injury of mice in QDTS group was significantly reduced, and the expressions of NLRP3, GSDMD and IL-1β in kidney of mice in QDTS group and valsartan group were decreased (P<0.05). The protein expressions of MAPK14, RELA and Caspase-8 in kidney of mice in QDTS group and valsartan group were decreased (P<0.05). Network pharmacology results showed that there were 16 targets for QDTS to regulate DN cell pyrodeath, among which MAPK14, RELA and Caspase-8 were the key targets. Compared with normal glucose group, the protein expressions of NLRP3, GSDMD and IL-1β in high glucose group were increased (P<0.05), and the protein expressions of MAPK14, RELA and Caspase-8 in mouse podocytes were increased (P<0.05). Compared with high glucose group, the expressions of NLRP3, GSDMD and IL-1β in podocytes of mice in QDTS group were decreased (P<0.05), and the expressions of MAPK14, RELA and Caspase-8 in podocytes of mice in QDTS group were decreased (P<0.05). ConclusionQDTS reduces damage to DN podocytes, which is associated with its regulation of the MAPK14/RELA/Caspase-8 signaling pathway and inhibition of podocyte pyroptosis.
5.Study on Jianpi Bushen Jiedu Decoction for inhibiting epithelial-mesenchymal transformation of hepatocellular carcinoma through JAK2/STAT3 pathway
Pingping ZHANG ; Huidi LI ; Hongjie LIU ; Xiaojun ZHU
International Journal of Traditional Chinese Medicine 2023;45(5):581-585
Objective:To study the effects of Jianpi Bushen Jiedu Decoction on the epithelial-mesenchymal transformation of nude mice with HCCLM3 subcutaneous transplanted tumor by regulating JAK2/STAT3 pathway.Methods:HCCLM3 subcutaneous transplanted tumor model was established in mice. After the successful modeling, 24 nude mice were divided into blank group, TCM group and combined group according to random number table method, with 8 mice in each group. Mice in the TCM group were given 0.68 mg/ml alcohol extract of Jianpi Bushen Jiedu Decoction for gavage, and the combined group were given sorafenib suspension plus alcohol extract of Jianpi Bushen Jiedu Decoction 3.5 mg/ml for gavage, once a day, for consecutive 4 weeks. The effects of Jianpi Bushen Jiedu Decoction on tumor volume, tumor weight of HCCLM3 subcutaneous transplanted tumor and mice body weight were observed; Western blot was used to detect the expressions of E-cadherin, N-cadherin, Vimentin and JAK2/STAT3 pathway-related proteins in subcutaneous transplanted tumor tissues of hepatocellular carcinoma of mice in each group.Results:Compared with the control group, the average tumor weight of subcutaneous transplanted tumor decreased significantly in the TCM group and the combined group ( P<0.05), and the expressions of JAK2, STAT3, p-JAK2, p-STAT3, N-cadherin, and Vimentin decreased significantly in subcutaneous transplanted tumor tissue ( P<0.05), while E-cadherin increased ( P<0.05). Conclusion:Jianpi Bushen Jiedu Decoction can inhibit the growth of subcutaneous transplanted tumor of hepatocellular carcinoma in mice. The mechanism may be related to inhibiting the activation of JAK2/STAT3 pathway, thereby inhibiting the epithelial-mesenchymal transformation of hepatocellular carcinoma.
6.Study on laterality of Parkinson's disease under transcranial ultrasound
Huidi TENG ; Ying LIU ; Yu WANG
Journal of Apoplexy and Nervous Diseases 2022;39(11):1019-1022
To explore the laterality of SN+ area in patients with PD under TCS,and to further analyze its correlation with clinical data,in order to have a more comprehensive understanding of Parkinson's disease.Methods 81 patients with Parkinson's disease were collected,and the differences between SN+O and SN+N,SN+L and SN+R under transcranial ultrasound,and the correlation between SN+O and S/M and clinical data in patients with EOPD and LOPD were analyzed.Nonparametric test was used for difference analysis and spearman correlation was used for correlation analysis.Results The SN+O of PD was significantly larger than that of SN+N,and there was no significant difference in SN+ between left and right substantia nigra.The SN+O of early-onset PD was negatively correlated with the age of onset.Conclusion The area of SN+ on both sides of Parkinson's disease was asymmetrical under transcranial ultrasound.SN+O in Parkinson's disease was significantly larger than that in SN+N.The larger S/M often occurred in patients with early-onset PD rather than in patients with late-onset PD.Subgroup analysis showed that the age of onset of EOPD was negatively correlated with SN+O.SN+O and S/M in Parkinson's disease are not affected by age,disease duration,severity,autonomic nervous dysfunction and depression,but their stability as biomarkers needs to be further studied.
7.Pathogenesis differentiation and treatments of gouty nephropathy
Xiangwei ZHANG ; Hongfang LIU ; Jiyuan HU ; Yixiu HU ; Qian NAN ; Huidi XIE
Journal of Beijing University of Traditional Chinese Medicine 2017;40(9):790-792
The obstruction of kidney collaterals by turbid and blood stasis is a characteristic pathogenesis of gouty nephropathy,which runs throughout the whole process of the disease.The pathogenesis of disease of gouty nephropathy is different from that of other chronic kidney diseases,determines the occurrence and development direction of patterns and symptoms,and is the common pathogenesis behind different patterns.The pathogenesis of pattern is the main body of pattern differentiation and treatment of gouty nephropathy,damp-heat obstruction and spleen-kidney deficiency and is the pathogenesis base of same treatment for different diseases.The pathogenesis of symptoms is a direct pathogenesis induced by symptoms.In treatment of gouty nephropathy,symptomatic treatment can improve the therapeutic effects based on disease and pattern differentiations.
8.The role of ADME evaluation in translation research of innovative drug.
Yao LIU ; Lan HONG ; Lushan YU ; Huidi JIANG ; Jianzhong CHEN ; Qin MENG ; Shuqing CHEN ; Su ZENG
Acta Pharmaceutica Sinica 2011;46(1):19-29
New Chemical Entities (NCEs) development is a systematic long-term project that involves multiple disciplines. The translation research will help to build an advanced R&D system from the basic laboratory research, preclinical studies and clinical evaluation to clinical application of drug, for the purpose of shortening the R&D cycle and accelerate the launch of new drugs. In new drug R&D and its clinical application, drug disposition (absorption, distribution, metabolism, excretion, ADME) properties are important criteria for assessing drug-likeness of candidates. ADME evaluation of NCEs plays an important role in the translation research throughout innovative drug R&D process. Therefore, ADME evaluation at the early stage of drug design and development will be helpful to improve the success rate and reduce costs, and further access to safe, effective drugs.
9.Sensitivity in typeⅠ hypersensitivity compared between BN rats and Wistar rats
Zhonggang LI ; Huidi QIN ; Huaishan WANG ; Yanqiu SHI ; Zhaoping LIU
Chinese Journal of Pharmacology and Toxicology 2010;24(1):30-34
OBJECTIVE To compare sensitivity in typeⅠ hypersensitivity between BN and Wistar rats, and to establish a sensitive and reliable determination system for typeⅠ hypersensitivity. METHODS BN and Wistar rats were sc given ovalbumin (OVA) 10, 20 and 40 μg·kg~(-1) every other day for 5 times and normal control group with sc normal saline. The total immunoglobulin E (IgE) levels in serum were determined with ELISA and the specific IgE levels in serum were determined by passive cutaneous anaphylaxis on the 21st day from the 1st injection. The blood pressure, serum histamine and tryptase levels were determined after challenge on the 22nd day. RESULTSTotal IgE, specific IgE, histamine and tryptase levels in serum significantly increased and blood pressure decreased in OVA 10, 20 and 40 μg·kg~(-1) BN rat groups compared with normal control group, while in Wistar rats these symptoms only appeared in OVA 40 μg·kg~(-1) group. CONCLUSION BN rats are more sensitive than Wistar rats in typeⅠ hypersensitivity. The blood pressure, serum total IgE, specific IgE, histamine and tryptase levels can be used as the important indicators in typeⅠ hypersensitivity.


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