Identification of potential anti-pneumonia pharmacological components of <i>Glycyrrhizae Radix</i> et Rhizoma after the treatment with Gan An He Ji oral liquid

Xiaojuan Jiang; Yihua Lin; Yunlong Wu; Caixia Yuan; Xuli Lang; Jiayun Chen; Chunyan Zhu; Xinyi Yang; Yu Huang; Hao Wang; Caisheng Wu

doi:10.1016/j.jpha.2022.07.004

Volume 12 Issue 6

Dec. 2022

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Article Navigation > Journal of Pharmaceutical Analysis > 2022 > 12(6): 839-851

Xiaojuan Jiang, Yihua Lin, Yunlong Wu, Caixia Yuan, Xuli Lang, Jiayun Chen, Chunyan Zhu, Xinyi Yang, Yu Huang, Hao Wang, Caisheng Wu. Identification of potential anti-pneumonia pharmacological components of Glycyrrhizae Radix et Rhizoma after the treatment with Gan An He Ji oral liquid[J]. Journal of Pharmaceutical Analysis, 2022, 12(6): 839-851. doi: 10.1016/j.jpha.2022.07.004

Citation:

Xiaojuan Jiang, Yihua Lin, Yunlong Wu, Caixia Yuan, Xuli Lang, Jiayun Chen, Chunyan Zhu, Xinyi Yang, Yu Huang, Hao Wang, Caisheng Wu. Identification of potential anti-pneumonia pharmacological components of Glycyrrhizae Radix et Rhizoma after the treatment with Gan An He Ji oral liquid[J]. Journal of Pharmaceutical Analysis, 2022, 12(6): 839-851. doi: 10.1016/j.jpha.2022.07.004

Citation:

Xiaojuan Jiang, Yihua Lin, Yunlong Wu, Caixia Yuan, Xuli Lang, Jiayun Chen, Chunyan Zhu, Xinyi Yang, Yu Huang, Hao Wang, Caisheng Wu. Identification of potential anti-pneumonia pharmacological components of Glycyrrhizae Radix et Rhizoma after the treatment with Gan An He Ji oral liquid[J]. Journal of Pharmaceutical Analysis, 2022, 12(6): 839-851. doi: 10.1016/j.jpha.2022.07.004

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Identification of potential anti-pneumonia pharmacological components of Glycyrrhizae Radix et Rhizoma after the treatment with Gan An He Ji oral liquid

doi: 10.1016/j.jpha.2022.07.004

a. Fujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cell Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, 361102, China;
b. Department of Respiratory and Critical Care Medicine, The Third Clinical Medical College, Fujian Medical University, Fuzhou, 350122, China;
c. Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, 361003, China;
d. Laboratory of Pharmacology/Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China;
e. School of Pharmacy, Ningxia Medical University, Yinchuan, 750004, China;
f. School of Pharmacy, Minzu University of China, Beijing, 100081, China;
g. Key Laboratory of Ethnomedicine (Minzu University of China), Ministry of Education, Beijing, 100081, China;
h. Institute of National Security, Minzu University of China, Beijing, 100081, China

Funds:

This research was funded by the National Natural Science Foundation of China (Grant Nos.: 82141215, 82173694, 82173779, 82222068, and U1903119), Fujian Province Science and Technology Project (Grant Nos.: 2021J011340 and 2020Y0013), and Xiamen Municipal Bureau of Science and Technology Planning Project (Grant No.: 3502Z2021YJ11).

Received Date: Feb. 22, 2022
Accepted Date: Jul. 20, 2022
Rev Recd Date: Jul. 16, 2022
Publish Date: Dec. 26, 2022

Abstract

Abstract

Glycyrrhizae Radix et Rhizoma, a traditional Chinese medicine also known as Gan Cao (GC), is frequently included in clinical prescriptions for the treatment of pneumonia. However, the pharmacological components of GC for pneumonia treatment are rarely explored. Gan An He Ji oral liquid (GAHJ) has a simple composition and contains GC liquid extracts and paregoric, and has been used clinically for many years. Therefore, GAHJ was selected as a compound preparation for the study of GC in the treatment of pneumonia. We conducted an in vivo study of patients with pneumonia undergoing GAHJ treatments for three days. Using the intelligent mass spectrometry data-processing technologies to analyze the metabolism of GC in vivo, we obtained 168 related components of GC in humans, consisting of 24 prototype components and 144 metabolites, with 135 compounds screened in plasma and 82 in urine. After analysis of the metabolic transformation relationship and relative exposure, six components (liquiritin, liquiritigenin, glycyrrhizin, glycyrrhetinic acid, daidzin, and formononetin) were selected as potential effective components. The experimental results based on two animal pneumonia models and the inflammatory cell model showed that the mixture of these six components was effective in the treatment of pneumonia and lung injury and could effectively downregulate the level of inducible nitric oxide synthase (iNOS). Interestingly, glycyrrhetinic acid exhibited the strongest inhibition on iNOS and the highest exposure in vivo. The following molecular dynamic simulations indicated a strong bond between glycyrrhetinic acid and iNOS. Thus, the current study provides a pharmaceutical basis for GC and reveals the possible corresponding mechanisms in pneumonia treatment.
- Glycyrrhizae Radix et Rhizoma,
- Pneumonia,
- Active components,
- Inducible nitric oxide synthase,
- Glycyrrhetinic acid

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References(41)

References

H. Liu, J. Wang, W. Zhou, et al., Systems approaches and polypharmacology for drug discovery from herbal medicines: an example using licorice, J. Ethnopharmacol. 146 (2013) 773-793

H.-X. Sun, H.-J. Pan, Immunological adjuvant effect of Glycyrrhiza uralensis saponins on the immune responses to ovalbumin in mice, Vaccine 24 (2006) 1914-1920

M. Jiang, S. Zhao, S. Yang, et al., An “essential herbal medicine”-licorice: a review of phytochemicals and its effects in combination preparations, J. Ethnopharmacol. 249 (2020), 112439

L. Wang, R. Yang, B. Yuan, et al., The antiviral and antimicrobial activities of licorice, a widely-used Chinese herb, Acta Pharm. Sin. B 5 (2015) 310-315

Y. Wang, X. Zhang, X. Ma, et al., Study on the kinetic model, thermodynamic and physicochemical properties of Glycyrrhiza polysaccharide by ultrasonic assisted extraction, Ultrason. Sonochem. 51 (2019) 249-257

R. Yang, L.Q. Wang, B.C. Yuan, et al., The pharmacological activities of licorice, Planta Med. 81 (2015) 1654-1669

J.Y. Yu, J.Y. Ha, K.M. Kim, et al., Anti-inflammatory activities of licorice extract and its active compounds, glycyrrhizic acid, liquiritin and liquiritigenin, in BV2 cells and mice liver, Molecules 20 (2015) 13041-13054

M. Ramalingam, H. Kim, Y. Lee, et al., Phytochemical and pharmacological role of liquiritigenin and isoliquiritigenin from Radix glycyrrhizae in human health and disease models, Front. Aging Neurosci. 10 (2018), 348

S. Pandit, S. Ponnusankar, A. Bandyopadhyay, et al., Exploring the possible metabolism mediated interaction of Glycyrrhiza glabra extract with CYP3A4 and CYP2D6, Phytother Res. 25 (2011) 1429-1434

T. Fukai, A. Marumo, K. Kaitou, et al., Anti-Helicobacter pylori flavonoids from licorice extract, Life Sci. 71 (2002) 1449-1463

J. Reuter, I. Merfort, C.M. Schempp, Botanicals in dermatology: an evidence-based review, Am. J. Clin. Dermatol. 11 (2010) 247-267

L. Luo, J. Jiang, C. Wang, et al., Analysis on herbal medicines utilized for treatment of COVID-19, Acta Pharm. Sin. B 10 (2020) 1192-1204

Y. Xian, J. Zhang, Z. Bian, et al., Bioactive natural compounds against human coronaviruses: a review and perspective, Acta Pharm. Sin. B 10 (2020) 1163-1174

J. Zhao, S. Tian, D. Lu, et al., Systems pharmacological study illustrates the immune regulation, anti-infection, anti-inflammation, and multi-organ protection mechanism of Qing-Fei-Pai-Du decoction in the treatment of COVID-19, Phytomedicine 85 (2021), 153315

J. Liu, W. Yang, Y. Liu, et al., Combination of Hua Shi Bai Du granule (Q-14) and standard care in the treatment of patients with coronavirus disease 2019 (COVID-19): A single-center, open-label, randomized controlled trial, Phytomedicine 91 (2021) 153671

Y.-F. Huang, C. Bai, F. He, et al., Review on the potential action mechanisms of Chinese medicines in treating Coronavirus Disease 2019 (COVID-19), Pharmacol. Res. 158 (2020), 104939

X. Chen, Y. Wu, C. Chen, et al., Identifying potential anti-COVID-19 pharmacological components of traditional Chinese medicine Lianhuaqingwen capsule based on human exposure and ACE2 biochromatography screening, Acta Pharm. Sin. B 11 (2021) 222-236

L. van de Sand, M. Bormann, M. Alt, et al., Glycyrrhizin effectively inhibits SARS-CoV-2 replication by inhibiting the viral main protease, Viruses 13 (2021), 609.

C. Zhu, T. Cai, Y. Jin, et al., Artificial intelligence and network pharmacology based investigation of pharmacological mechanism and substance basis of in treating diabetes, Pharmacol. Res. 159 (2020), 104935

X. Wang, A. Zhang, X. Zhou, et al., An integrated chinmedomics strategy for discovery of effective constituents from traditional herbal medicine, Sci. Rep. 6 (2016), 18997

T. Chen, X. Wang, P. Chen, et al., Chemical components analysis and in vivo metabolite profiling of Jian'er Xiaoshi oral liquid by UHPLC-Q-TOF-MS/MS, J. Pharm. Biomed. Anal. 211 (2022), 114629

W. Dong, P. Wang, X. Meng, et al., Ultra-performance liquid chromatography-high-definition mass spectrometry analysis of constituents in the root of Radix Stemonae and those absorbed in blood after oral administration of the extract of the crude drug, Phytochem. Anal. 23 (2012) 657-667

J. Shi, H. Wang, J. Liu, et al., Ganoderic acid B attenuates LPS-induced lung injury, Int. Immunopharm. 88 (2020), 106990

Q. Wu, H. Li, J. Qiu, et al., Betulin protects mice from bacterial pneumonia and acute lung injury, Microb. Pathog. 75 (2014) 21-28

R. Kapetanovic, G. Jouvion, C. Fitting, et al., Contribution of NOD2 to lung inflammation during Staphylococcus aureus-induced pneumonia, Microb. Infect. 12 (2010) 759-767

G. Jones, P. Willett, R.C. Glen, et al., Development and validation of a genetic algorithm for flexible docking, J. Mol. Biol. 267 (1997) 727-748

H.J. Yoon, M.E. Moon, H.S. Park, et al., Chitosan oligosaccharide (COS) inhibits LPS-induced inflammatory effects in RAW 264.7 macrophage cells, Biochem. Biophys. Res. Commun. 358 (2007) 954-959

S.J. Hwang, Y.W. Kim, Y. Park, et al., Anti-inflammatory effects of chlorogenic acid in lipopolysaccharide-stimulated RAW 264.7 cells, Inflamm. Res. 63 (2014) 81-90

E.D. Garcin, A.S. Arvai, R.J. Rosenfeld, et al., Anchored plasticity opens doors for selective inhibitor design in nitric oxide synthase, Nat. Chem. Biol. 4 (2008) 700-707

S. Kang, W. Tang, H. Li, et al., Nitric oxide synthase inhibitors that interact with both heme propionate and tetrahydrobiopterin show high isoform selectivity, J. Med. Chem. 57 (2014) 4382-4396

P.J. Kolodziejski, M.B. Rashid, N.T. Eissa, Intracellular formation of “undisruptable” dimers of inducible nitric oxide synthase, Proc. Natl. Acad. Sci. U. S. A. 100 (2003) 14263-14268

J.M. Perry, M.A. Marletta, Effects of transition metals on nitric oxide synthase catalysis, Proc. Natl. Acad. Sci. U. S. A. 95 (1998) 11101-11106

W. Hong, Y. Wang, Z. Chang, et al., The identification of novel Mycobacterium tuberculosis DHFR inhibitors and the investigation of their binding preferences by using molecular modelling, Sci. Rep. 5 (2015), 15328

C. Wu, H. Zhang, C. Wang, et al., An integrated approach for studying exposure, metabolism, and disposition of multiple component herbal medicines using high-resolution mass spectrometry and multiple data processing tools, Drug Metab. Dispos. 44 (2016) 800-808

T.J. Gross, K. Kremens, L.S. Powers, et al., Epigenetic silencing of the human NOS2 gene: rethinking the role of nitric oxide in human macrophage inflammatory responses, J. Immunol. 192 (2014) 2326-2338

X. Wang, Z. Gray, J. Willette-Brown, et al., Macrophage inducible nitric oxide synthase circulates inflammation and promotes lung carcinogenesis, Cell Death Dis. 4 (2018), 46

K. Vuolteenaho, A. Koskinen, M. Kukkonen, et al., Leptin enhances synthesis of proinflammatory mediators in human osteoarthritic cartilage - mediator role of NO in leptin-induced PGE₂, IL-6, and IL-8 production, Mediat. Inflamm. 2009 (2009), 345838

E.L. Feitosa, F.T.D.S. Júnior, J.A.O. Nery Neto, et al., COVID-19: rational discovery of the therapeutic potential of Melatonin as a SARS-CoV-2 main Protease Inhibitor, Int. J. Med. Sci. 17 (2020) 2133-2146

Q. Tang, C.I. Svensson, B. Fitzsimmons, et al., Inhibition of spinal constitutive NOS-2 by 1400W attenuates tissue injury and inflammation-induced hyperalgesia and spinal p38 activation, Eur. J. Neurosci. 25 (2007) 2964-2972

J.W. Coleman, Nitric oxide in immunity and inflammation, Int. Immunopharm. 1 (2001) 1397-1406

T. Okamoto, K. Gohil, E.I. Finkelstein, et al., Multiple contributing roles for NOS2 in LPS-induced acute airway inflammation in mice, Am. J. Physiol. Lung Cell Mol. Physiol. 286 (2004) L198-L209

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