PHYTOMEDICINE
·
2023
·
IF 7.9
Jun Jiang,Baixiu Zhao,Jianpeng Xiao,Liang Shi,Wei Shang,Ye Shu,Zhiming Zhao,Junyi Shen,Jingjuan Xu,Hui Cai
Background Clinical studies indicated that postmenopausal osteoporosis (PMOP) often accompanied by iron overload risk factor, which exacerbated bone metabolism disorders and accelerated PMOP. Previous research found that multicomponent in Ligustri Lucidi Fructus (FLL) or wine-steamed FLL (WFLL) acted on the common targets of iron overload and PMOP simultaneously, which indicated that FLL and WFLL probably regulated iron/bone metabolism dually. Additionally, WFLL had more superior effect according to the theory of Chinese medicine for thousands of years. Purpose To reveal the “superior multi-component structure (SMCS)” and its molecular mechanisms in parallelly down-regulating iron overload and rescuing bone metabolism by WFLL. Designs and methods HPLC fingerprinting was established to compare the chemical profiles of FLL and WFLL; Then, the chemical compositions and quality markers of FLL and WFLL were analyzed by UPLC-Orbitrap-MS/MS coupled with OPLS-DA; The dynamic contents of quality markers and the multi-component structure at different wine steaming times (WST) were simultaneously determined by HPLC-DAD; Meanwhile, the dynamic efficacy of FLL at different WST were hunt by systematic zebrafish model. Subsequently, potential mechanism of WFLL in treating PMOP accompanied with iron overload was obtained from network pharmacology (NP) and molecular docking (MD). Finally, zebrafish and ovariectomy rat model were carried out to validate this potential mechanism. Results HPLC fingerprints similarity of 15 batches in FLL and WFLL were among 0.9-1.0. 126 compositions were identified, including 58 iridoids, 25 terpenes, 30 phenylethanoids, 7 flavonoids and 6 others. 20 quality markers associated with WFLL was revealed, and the ratio of Phenylethanols: Iridoids: Triterpenes (P/I/T) was converted from 1: 15: 4.5 to 1: 0.8: 0.9 during steaming (0 - 24 h) calculated by the quantification of 11 quality markers; The bone mineralization and motor performance of zebrafish larvae indicated that the optimum efficacy of WFLL at 12 h ( P < 0.05) in which the SMCS of P/I/T was converted to 1: 4: 1.8. NP discovered that BMP-Smad pathway is one of the potential mechanisms of FLL in anti PMOP and then regulated bone formation and iron overload simultaneously. MD revealed that 17 active ingredients and 10 core targets genes could spontaneously bind with appropriate affinity. Rats model verified that FLL and WFLL significantly reversed PMOP, based on the improvement in bone formation indexes (ALP, OPG, OGN), iron metabolism indicators (hepcidin, ferritin), bone microstructure (BMD, BV/TV, Tb. Th, Tb. N); Moreover, WFLL significant enhanced reversal effect in anti-PMOP compared to FLL ( P < 0.05). FLL and WFLL increased genes and proteins expression (Hep, BMP-6, p-Smad1/5, Smad4) related to BMP-Smad pathway compared with model group, and WFLL was more superior than FLL ( P < 0.05). Conclusion The SMCS of FLL was optimized by wine-steam, WFLL represented a dual effect in downregulating iron overload and promoting bone formation, and the BMP-Smad pathway is one of the potential molecular mechanisms.
研究领域:
药理学
·
中药学
·
骨代谢
·
铁代谢
·
网络药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF FOOD SCIENCE
·
2022
·Vol. 87
·期 2
·651-663
·
IF 3.693
Hao-Xiang Gao,Heng-Yu Liang,Nan Chen,Bi Shi,Wei-Cai Zeng
Ligustrum robustum (Rxob.) Blume is traditionally served as a functional tea in China. In this work, the antioxidant activities of L. robustum (Rxob.) Blume extract (LRE) were evaluated and its inhibitory effect and mechanism on pancreatic lipase were further investigated. With the high contents of phenols (139.70 ± 1.41 mg gallic acid equivalent/g extract) and flavonoids (326.46 ± 7.36 mg rutin equivalent/g extract), LRE showed significant antioxidant activities ( p < 0.05) for scavenging free radicals and hydrogen peroxide, inhibiting lipid peroxidation and providing strong reducing power. Meanwhile, LRE displayed remarkable inhibitory activity on pancreatic lipase with a low half-effective inhibitory concentration (IC 50 ) of 2.469 ± 0.005 mg/ml which was further determined as non-competitive inhibition. The spectroscopic results showed that LRE inhibited the activity of pancreatic lipase by modifying the tertiary and secondary structures of lipase. Moreover, four phenolic compounds (acteoside, lipedoside A, oleuropein and ligurobustoside C) were identified from LRE by the high performance liquid chromatography-quadrupole- time of flight-mass spectrometry. In addition, according to molecular docking analysis, the four phenols could interact with pancreatic lipase by hydrogen bonds, so as to change the spatial structure of pancreatic lipase and inhibit its catalytic activity. The present results suggest that LRE not only exhibits strong antioxidant capacity but possesses effectively inhibitory activity on pancreatic lipase, which might have the potential to be developed as functional food and nutraceuticals for the prevention of metabolic diseases. Practical Application Ligustrum robustum (Rxob.) Blume extract has been confirmed to possess antioxidant activity and lipase inhibitory activity, which indicates that the L. robustum extract has the potential to prevent oxidative stress and regulate fat metabolism. This work suggests that L. robustum extract can be served as a novel resource to prepare nutraceuticals and functional food in food industries.
研究领域:
食品科学
·
药理学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2021
·
IF 4.36
Xuanhao Chen,Xiaoyan Wang,Lin Ma,Shiming Fang,Jin Li,Evans Owusu Boadi,Jun He,Xiu-mei Gao,Yu Wang,Yan-xu Chang
Ethnopharmacological relevance Viticis fructus ( VF ) has been widely used in alleviating the swelling and pain, owning to its pharmacologically active components including agnuside, 10- O -vanilloylaucubin, luteolin and casticin. Aim of the study The pharmacokinetic profiles of the absorbed components from aqueous and ethanolic extracts of VF in rat plasma were performed, and explored the molecular mechanisms of absorbed components via network pharmacology . Materials and methods Ultra-performance liquid chromatography-tandem mass spectroscopy (UHPLC-MS/MS) was employed to identify the absorbed components from rat plasma. Liquid-liquid extraction with ethyl acetate was used to purify the plasma samples. Plasma pharmacokinetics parameters of the components absorbed were analyzed after oral administration of both extracts. Network pharmacology was used to predict the biological functions and potential signaling pathways of VF . The anti-cancer effects of VF extract and absorbed components have been confirmed by in vitro experiments. Results The method was very sensitive with lower limit of quantification (LLOQ) of 1.0, 2.5, 0.2 and 0.5 ng/mL for agnuside, 10- O -vanilloylaucubin, luteolin and casticin, respectively. With the exception of 10- O- vanilloylaucubin which was not detected in the ethanolic extract of VF , all other components were detected in both extracts in plasma. The pharmacokinetic parameters of the four components from rat plasma were significantly different between the two extracts. According to the results of network pharmacology, the absorption components of VF are enriched in 32 key pathways, and 15 pathways are related to cancer. Ultimately, the anti-cancer effects, as well as the signaling pathways of VF ethanolic extract and absorbed components were verified by in vitro experiments. Conclusion The optimized, sensitive and validated UHPLC-MS/MS method was successfully applied for the plasma pharmacokinetics comparison analysis of the two VF extracts. The combination of network pharmacology and pharmacokinetics provides a useful method to elucidate the biological effects and molecular mechanism of the absorbed components of VF .
研究领域:
药理学
·
药代动力学
·
网络药理学
·
中药
·
癌症研究
✓ 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）