INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2020
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IF 5.162
Jia-Qi He,Min-Xia Zheng,Hua-Zhong Ying,Yu-Sen Zhong,Huan-Huan Zhang,Min Xu,Chen-Huan Yu
Two polysaccharides (PRP1 and PRP2) were isolated from Platycodonis Radix . Preliminary structural analysis indicated that PRP1 was composed of glucose, fructose, and arabinose in a molar ratio of 1:1.91:1.59 with a molecular weight of 440 kDa, whereas PRP2 was composed of arabinose, fructose, and galactose in a molar ratio of 1:1.39:1.18 with a molecular weight of 2.85 kDa. Compared with PRP2, PRP1 exerted stronger anticancer activity in vitro. Treatment with 5–30 μg/ml of PRP1 significantly inhibited the proliferation of HepG2 cells in vitro, and oral administration at the doses of 75–300 mg/kg also reduced the tumor growth in vivo. The miRNA expression patterns of human liver cancer cells HepG2 in vivo under PRP1 treatment were established, and microRNA-21 (miR-21) as the onco-miRNA was appreciably downregulated. PRP1 repressed the expression of miR-21, which directly targeted and suppressed PTEN (a negative regulator of the PI3K/Akt signaling cascade), and subsequently upregulated the expression of PTEN but downregulated the PI3K/AKT pathway, thereby promoting liver cancer cell apoptosis. These findings indicated that PRP1 inhibited the proliferation and induced the apoptosis of HepG2 mainly via inactivating the miR-21/PI3K/AKT pathway. Therefore, PRP1 could be used as a food supplement and candidate for the treatment of liver cancer.
研究领域:
药理学
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肿瘤学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Shasha Han,Zichen Luo,Shihang Bao,Zihan Xiao,Weichen Xu,Tong Xie,Chen Shi,Jin Wang,Jinjun Shan
Ethnopharmacological relevance Platycodon grandiflorus root, is a widely used herb in East Asia for treating respiratory diseases, but research on its oral safety is limited. Aim of the study This study examines the potential adverse gastrointestinal reactions resulting from excessive consumption of Platycodon grandiflorus root (PR) and its effects on gut microbiota and host co-metabolism. Materials and methods This study evaluated the effects of different doses (1.5, 4.5, and 7.5 g/kg/day) of PR on ICR mice through gavage. Select the 7.5 g/kg/day dosage group and the control group to assess intestinal morphology and conduct histopathological studies. Examine inflammation-related factors and tight junction proteins using WB, qPCR, and ELISA. Additionally, perform 16S rDNA sequencing and metabolomic analyses to evaluate changes in gut microbiota and endogenous metabolites. Finally, the clearance of gut microbiota with antibiotics, the effects of excessive PR on mice were investigated. Results Excessive intake of PR can lead to mortality in mice, as well as symptoms such as intestinal flatulence and slowed intestinal transit, suggesting the occurrence of chronic intestinal pseudo-obstruction accompanied by endotoxemia. It altered both α-diversity and β-diversity in the gut microbiota of mice, with increased relative abundances of Pseudomonadota, Verrucomicrobiota, Escherichia-Shigella , Akkermansia , Bacteroides , and Klebsiella , closely linked to intestinal obstruction and bacterial overgrowth. Excessive intake of PR also resulted in metabolic disturbances in mice, particularly in the levels of metabolites such as bate-hydroxybutyrate, 5,6-dihydrouracil, uridine, isoleucine, mannitol, bate-alanine, L-cysteine, L-tyrosine, and orotic acid, which may provide insights into the side effects associated with excessive consumption of PR. Clearing the gut microbiota significantly mitigated adverse effects on the intestines and restored metabolite levels. Conclusions This study demonstrates that excessive PR induces gut microbiota and metabolic disruption in normal mice, with the overgrowth of Gram-negative bacteria releasing LPS that impair smooth muscle contraction, leading to adverse effects such as chronic intestinal pseudo-obstruction.
研究领域:
药理学
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微生物学
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代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2023
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IF 7.5
Tao Long,Xue Chen,Yue Zhang,Yu-Jia Zhou,Yan-Ni He,Yun-Fei Zhu,Hai-Jun Fu,Lu Yu,Chong-Lin Yu,Betty Yuen-Kwan Law,Jian-Ming Wu,Da-Lian Qin,An-Guo Wu,Xiao-Gang Zhou
Enhancing the clearance of proteins associated with Alzheimer's disease (AD) emerges as a promising approach for AD therapeutics. This study explores the potential of Radix Stellariae , a traditional Chinese medicine, in treating AD. Utilizing transgenic C. elegans models of AD, we demonstrated that a 75% ethanol extract of Radix Stellariae (RSE) (at 50 µg/mL) effectively diminishes Aβ and Tau protein expression, and alleviates their induced impairments including paralysis, behavioral dysfunction, neurotoxicity, and ROS accumulation. Additionally, RSE enhances the stress resistance of C. elegans . Further investigations revealed that RSE promotes autophagy, a critical cellular process for protein degradation, in these models. We found that inhibiting autophagy-related genes negated the neuroprotective effects of RSE, suggesting a central role for autophagy in the actions of RSE. In PC-12 cells, we observed that RSE not only inhibited Aβ fibril formation but also promoted the degradation of AD-related proteins and reduced their cytotoxicity. Mechanistically, RSE was found to induce autophagy via modulating PI3K/AKT/mTOR and AMPK/mTOR signaling pathways. Importantly, inhibiting autophagy counteracted the beneficial effects of RSE on the clearance of AD-associated proteins. Moreover, we identified Dichotomine B, a β-carboline alkaloid, as a key active constituent of RSE in mitigating AD pathology in C. elegans at concentrations ranging from 50 to 1000 µM. Collectively, our study presents novel discoveries that RSE alleviates AD pathology and toxicity primarily by inducing autophagy, both in vivo and in vitro. These findings open up new avenues for exploring the therapeutic potential of RSE and its active component, Dichotomine B, in treating neurodegenerative diseases like AD.
研究领域:
神经科学
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药理学
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中药学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）