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Objective: The present study aims to explore the application prospects of Citri Grandis Exocarpium for protecting against novel coronavirus pneumonia (COVID-19). Methods: The pharmacological effects, including expectorant, anti-acute lung injury, anti-inflammatory, anti-pulmonary fibrosis, relieving cough, anti-oxidation, anti-liver injury, anti-kidney injury effects and etc, of both Citri Grandis Exocarpium and its main chemical constituents were analyzed through literature review. The constituents of Citri Grandis Exocarpium were collected by using traditional Chinese medicine systems pharmacology (TCMSP) database and literature searching. The molecular docking study was performed to evaluate the binding ability between the chemical constituents and angiotensin converting enzyme 2 (ACE2), 3C-like main protease (Mpro), papain-like protease (PLP), and dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) to predict its potential activity in inhibiting the infection and replication of SARS-CoV-2 virus. Results: The literature review indicated that Citri Grandis Exocarpium possesses expectorant, anti-acute lung injury, anti-inflammatory, anti-pulmonary fibrosis, relieving cough, anti-oxidation, anti-liver injury, anti-kidney injury effects, and so on. Molecular docking results indicated that naringin, neohesperdin, rhoifolin, poncirin, and sitogluside were the main active flavonoids due to showing strong interactions with ACE2, MPro, PLP and DC-SIGN with potential activity in inhibiting the infection and replication of SARS-CoV-2 virus. Conclusion: Citri Grandis Exocarpium may probably delay the progression of COVID-19 through a variety of pharmacological activities and the inhibition of the infection and replication of SARS-CoV-2 due to targeting ACE2, MPro, PLP, and DC-SIGN, reminding that Citri Grandis Exocarpium may possess a potential capacity to protect against COVID-19.
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Objective To establish quantitative analysis of multi-components by single marker (QAMS) to compare five flavones in Citrus grandis “Tomentosa” and C. grandis. Methods Four relative correction factors (RCFs) of neohesperidin, rhoifolin, naringenin, apigenin were established in the HPLC method with the Naringin as internal standard, which were used to determine the content of four flavones in C. grandis “Tomentosa” and C. grandis. Meanwhile, external standard method (ESM) was employed to calculate the content of five flavones. The difference between ESM and QAMS were analyzed to evaluate the accuracy of QAMS. T-test was used to compare five flavones in C. grandis ‘Tomentosa’ and C. grandis. Results RCFs of neohesperidin, rhoifolin, naringenin, apigenin were 0.898, 1.519, 0.313, 0.406, and repeatability was good in different experimental conditions (RSD < 3.0 %). There were no significant differences in the quantitative analysis results of two methods. Content of naringin, rhoifolin and naringenin in two species were significant different. Conclusion The RCFs of neohesperidin, rhoifolin, naringenin, apigenin as reference to naringin are accurate and feasible. Content of flavones in Citrus grandis “Tomentosa” and C. grandis are obvious different. QASM can be applied as a strategy for quality control of C. grandis.
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Objective To develop and validate a LC-MS/MS method for determination of rhoifolin in rat plasma and investi?gate its pharmacokinetic properties after intravenous administration to rats. Methods The analyte was isolated from rat plasma by liq?uid-liquid extraction with ethyl acetate. Separation was performed on a Phenomenex C8 column(30 mm×2.00 mm,3μm)with gradient elution using water-methanol as mobile phase. Electrospray ionization(ESI)was adopted in the negative ion mode for multiple reaction monitoring(MRM). The mass transitions were m/z 577.6→269.1 for rhoifolin,and m/z 271.0→151.0 for naringenin(internal stan?dard),respectively. Results The method showed good linearity over the range of 1-2000μg/L. Intra and inter-day precisions were both less than 10%,the relative error was within ± 7%. The extraction recoveries of three concentrations (low,middle and high) ranged from 86.8%to 91.0%. Main pharmacokinetic parameters were calculated by DAS 2.0. AUC0-t was(72627.8± 18067.9)μg·min/L, t1/2 was(52.1±14.3)min and CLz was(0.07±0.02)L/(min·kg). Conclusion The established LC-MS/MS method is specific and sensi?tive,and can be applied to pharmacokinetic study of rhoifolin. The pharmacokinetic parameters show that rhoifolin is eliminated rapid?ly in rats.
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Objective To develop and validate a LC-MS/MS method for determination of rhoifolin in rat plasma and investigate its pharmacokinetic properties after intravenous administration to rats. Methods The analyte was isolated from rat plasma by liquid-liquid extraction with ethyl acetate. Separation was performed on a Phenomenex C8 column(30 mm×2.00 mm, 3 μm) with gradient elution using water-methanol as mobile phase. Electrospray ionization (ESI) was adopted in the negative ion mode for multiple reaction monitoring (MRM). The mass transitions were m/z 577.6→269.1 for rhoifolin, and m/z 271.0→151.0 for naringenin (internal standard), respectively. Results The method showed good linearity over the range of 1-2000 μg/L. Intra and inter-day precisions were both less than 10%, the relative error was within ±7%. The extraction recoveries of three concentrations (low, middle and high) ranged from 86.8% to 91.0%. Main pharmacokinetic parameters were calculated by DAS 2.0. AUC0-t was (72627.8± 18067.9) μg•min/L, 11/2 was (52.1 ±14.3) min and CLZ was(0.07±0.02)L/(min•kg). Conclusion The established LC-MS/MS method is specific and sensitive, and can be applied to pharmacokinetic study of rhoifolin. The pharmacokinetic parameters show that rhoifolin is eliminated rapidly in rats.
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【Objective】To observe the dynamic changes of flavonoids contents of Citrus grandis(L.)Osbeck var.tomentosa Hort..【Methods】The total flavonoid content was determined by spectral photometric analysis and naringin content by HPLC,and the fingerprints of Citrus grandis(L.)Osbeck var.tomentosa Hort.were studied by HPLC.【Results】With the increase of the fruit age,total flavonoid contents in the peel and the leaves of Citrus grandis(L.)Osbeck var.tomentosa Hort.decreased obviously.Fingerprints results showed that at the early fruit age the rhoifolin content in the peel increased with the fruit age and began to decrease 62 days later,while the rhoifolin content in the leaves showed no changes.【Conclusion】In terms of active components contents and economic value,the optimal collecting time for Citrus grandis(L.)Osbeck var.tomentosa Hort.is:young fruit,34 days,and immature fruit,55 days.
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Objective To investigate the dynamic variation of flavonoids contents in the flowers of Citrus grandis at different flowering periods. Methods The content of total flavonoids in the flowers of Citrus grandis was determined by means of ultraviolet-visible absorption spectroscopy ,and the contents of naringin and rhoifolin were determined by HPLC. Results The content of total flavonoids in the flowers during the flower withering period ,the young fruit period ,the blossom period,and the budding period was 306.90 mg.g-1,277.93 mg.g-1,215.55 mg.g-1 and 162.74 mg.g-1 respectively. The naringin content during the above four different periods was 246.31 mg.g-1,213.93 mg.g-1,175.94 mg.g-1 and 130.90 mg.g-1 respectively. The rhoifolin content during the four periods was unchanged. Conclusion The contents of total flavonoids and naringin in flowers of Citrus grandis during flower withering period are the highest.
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Objective To establish a method for the determination of Rhoifolin content in Exocarpium citri grandis (ECG). Methods The RP-HPLC method was operated on MACHEREY-NAGEL 100-5 C_(18), with methanol and wateracetic acid (61: 4) as mobile phase, gradient elution, flow rate at 1.0 mL/min, and detection wavelength at 345nm. Results In the range from 0.816 ?g to 13. 056?g, Rhoifolin is in a good linearity with chromatographic peaks area, r=0.9995, the average recovery ratio is 101.064%, RSD=3.10%(n=5). The content of Rhoifolin in Tomentulosus Exocarpium Citri Grandis(TECG) ranged from 1.33% to 0.177% and that in Glabrous Exocarpium Citri Grandis (GECG) is less than 0.17%. Conclusions RP-HPLC method is with accuracy and a good reproducibility for the determination of the Rhoifolin content in ECG; the difference of Rhoifolin content in TECG and GECG is significant.