Integration of Multiple Analytical and Computational Tools for the Discovery of High‐Potency Enzyme Inhibitors from Herbal Medicines

Song, Hui‐Peng; Hong, Wei; Liang, Jin-Xiu; Qian, Cheng; Wu, Siqi; Xu, Wen-Jun; Wu, Bin; Liu, Xinguang; Li, Ping; Yang, Hua

doi:10.1002/cmdc.201600489

Cited by 14 publications

(5 citation statements)

References 43 publications

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“…Toxicity studies are considered vital components of herbal medicines' safety and provide evidence before further investigation in clinical trials. Although herbal extracts have been reported to possess multiple bioactivities and potential extensive applications (Gu et al, 2014 ; Chen et al, 2015 ; Song H. P. et al, 2016 ; Gao and Shen, 2017 ; Wu et al, 2017 ), the probable side effects are often neglected. For example, Arctigenin, the extract from Arctium lappa (burdock), a popular edible vegetable in China and Japan, is used as a general health tonic because of its multiple bioactivities in vivo and in vitro (Holetz et al, 2002 ; Liu et al, 2012 ; Fei et al, 2017 ), and this indiscriminate use lacks essential studies on its potential mild, moderate, and severe side effects and possible life-threatening effects.…”

Section: Discussionmentioning

confidence: 99%

28-Day Oral Chronic Toxicity Study of Arctigenin in Rats

et al. 2018

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Arctium lappa (burdock) is the most popular daily edible vegetable in China and Japan because of its general health tonic effects. Previous studies focused on the beneficial role of Arctigenin but neglected its potential side-effects and toxicities. In the present study, the sub-chronic toxicity profile of Arctigenin following 28 days of consecutive exposure was investigated in rats. The results showed that during the drug exposure period, Arctigenin-12 mg/kg administration resulted in focal necrosis and lymphocytes infiltration of heart ventricular septal muscle cells. In the kidney cortical zone, the renal tubular epithelial cells were swollen, mineralized, and lymphocyte infiltrated. In the liver, the partial hepatocyte cytoplasm showed vacuolation and fatty changes, focal necrosis, and interstitial lymphocyte infiltration. In the rats that underwent 36 mg/kg/day administration, there was bilateral testis and epididymis atrophy. In the lung and primary bronchus, erythrocytes and edema fluid were observed. Changes of proestrus or estrus were observed in the uterus, cervix, and vagina intimal epithelial cells. Lymphocytic focal infiltration occurred in the prostate mesenchyme. The high dosage of Arctigenin only decreased the body weight at day 4. At the end of the recovery period, histopathological changes were irreversible, even after withdrawal of the drug for 28 days. Focal necrosis still existed in the heart ventricular septal muscle cells and hepatocytes. Lymphocyte infiltrations were observed in the heart, renal cortex, hepatocyte, and pancreas exocrine gland. Meanwhile, atrophy occurred in the testicles and pancreas. In addition, in the Arctigenin-12 mg/kg group, creatinine (CREA) and brain weight were both significantly increased. The toxicokinetical study demonstrated that Arctigenin accumulated in the organs of rats. The food consumption, hematological, and biochemical parameters were not associated with the above results. These contradictory results might result from the lesions induced by Arctigenin, which were not sufficiently serious to change the parameters. These results suggest that Arctium lappa should be consumed daily with caution because of the potential toxicity induced by Arctigenin. According to all results, the lowest observed adverse effect level (LOAEL) was induced by 12 mg/kg daily exposure to Arctigenin, and the No-observed-adverse-effect-level (NOAEL) should be lower than 12 mg/kg.

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Section: Discussionmentioning

confidence: 99%

28-Day Oral Chronic Toxicity Study of Arctigenin in Rats

et al. 2018

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“…Table 1 shows some biologically active ingredients and their effects. In our previous summary of the various types of medicinal and edible plants, we briefly mentioned that some of these active substances can exert anti-HUA effects by inhibiting XOD activity and lowering serum uric acid levels ( 87 ). Therefore, in the next section, we will focus on summarizing the anti-hyperuricemia mechanism of various bioactive ingredients.…”

Section: Bioactive Substances and Their Uric Acid-lowering Mechanismmentioning

confidence: 99%

Research progress on the prevention and treatment of hyperuricemia by medicinal and edible plants and its bioactive components

Cheng-yuan,

Jian-gang

2023

Front. Nutr.

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Hyperuricemia is another common metabolic disease, which is considered to be closely related to the development of many chronic diseases, in addition to the “three highs.” Currently, although drugs show positive therapeutic effects, they have been shown to produce side effects that can damage the body. There is growing evidence that medicinal and edible plants and their bioactive components have a significant effect on hyperuricemia. In this paper, we review common medicinal and edible plants with uric acid-lowering effects and summarize the uric acid-lowering mechanisms of different bioactive components. Specifically, the bioactive components are divided into five categories: flavonoids, phenolic acids, alkaloids, polysaccharides, and saponins. These active substances exhibit positive uric acid-lowering effects by inhibiting uric acid production, promoting uric acid excretion, and improving inflammation. Overall, this review examines the potential role of medicinal and edible plants and their bioactive components as a means of combating hyperuricemia, with the hope of providing some reference value for the treatment of hyperuricemia.

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“…S6). By comparing the HPLC-MS/MS and NMR data with the reference [28], compound 2 was identified to be kaempferol 3-O-2''-(6 000 -p-coumaroyl) glucosylrhamnoside (KCGR). The chemical structures of compound 1 and 2 were shown in Fig.…”

Section: Pcsk9 Ligand Fishing Of Ginkgo Biloba Leaves and Hplc-q-tof-mentioning

confidence: 99%

A rapid strategy for screening high-efficiency PCSK9 inhibitors from Ginkgo biloba leaves by ligand fishing, HPLC-Q-TOF-MS and interdisciplinary assay

Li¹,

Fan²,

Li³

et al. 2020

Journal of Food and Drug Analysis

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Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an attractive target for new cholesterol-lowering drug development. Here, we developed a method integrating ligand fishing, HPLC-Q-TOF-MS and interdisciplinary assay, aiming to explore potential PCSK9 inhibitors from mixtures rapidly and accurately. PCSK9 was expressed and purified firstly, and then the recombined PCSK9 was coated on the surface of magnetic beads (MBs). The PCSK9-immobilized MBs (PCSK9-MBs) were used for ligand fishing combined with HPLC and Q-TOF-MS/MS. Ginkgo biloba leaves (GBL), an herbal medicine widely used in Asia and Europe with good efficacy in treatment of hypercholesterolemia, were chosen as an illustration for ligand fishing. Two PCSK9 ligands were discovered from GBL and identified as kaempferol-3-O-rutinoside (1) and kaempferol 3-O-2''-(6 000-p-coumaroyl) glucosylrhamnoside (KCGR) (2). In order to verify fishing results and pick out more powerful PCSK9 inhibitors, molecular docking assay was further performed and KCGR was optimized to be an excellent PCSK9 inhibitor by the confirmation of affinity and activity bioassay. These results suggested that the developed approach could be applied to screen and analysis potential bioactive constituents from mixtures, which may improve the efficiency of drug discovery. Moreover, KCGR separated from GBLwas expected to be a potential candidate of PCSK9 inhibitors.

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Integration of Multiple Analytical and Computational Tools for the Discovery of High‐Potency Enzyme Inhibitors from Herbal Medicines

Cited by 14 publications

References 43 publications

28-Day Oral Chronic Toxicity Study of Arctigenin in Rats

28-Day Oral Chronic Toxicity Study of Arctigenin in Rats

Research progress on the prevention and treatment of hyperuricemia by medicinal and edible plants and its bioactive components

A rapid strategy for screening high-efficiency PCSK9 inhibitors from Ginkgo biloba leaves by ligand fishing, HPLC-Q-TOF-MS and interdisciplinary assay

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