Publications by authors named "Hongda Sheng"

4 Publications

  • Page 1 of 1

Identification of bioactive ingredients from Babaodan using UPLC-QTOF-MS analysis combined with network pharmacology guided bioassays.

J Chromatogr B Analyt Technol Biomed Life Sci 2022 Aug 28;1206:123356. Epub 2022 Jun 28.

Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China; Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University, Hangzhou 310018, China. Electronic address:

Babaodan (BBD) is a traditional Chinese medicine (TCM) prescribed for various inflammatory diseases, including viral hepatitis and acute genitourinary tract infection. Like other TCMs, BBD is a multi-component formula whose chemical composition and mode of action are largely unknown. The current study identified the bioactive ingredients of BBD using ultrahigh-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) followed by mass spectrometry molecular networking analysis. Subsequently, network pharmacology analysis was performed to predict the potential targets and pathways regulated by BBD. Eventually, a panel of compounds was selected and examined for their anti-inflammatory effects using lipopolysaccharide-stimulated RAW264.7 cells. Eighty-six compounds, including saponins, bile acids, and fatty acids, were identified. Tumor necrosis factor-alpha was identified as a key molecule. Pathways in cancer, inflammatory bowel disease, and hepatitis were predicted to be the major regulatory pathways. The results from bioassays validated ginsenoside Rb1, ginsenoside Rd, deoxycholic acid, chenodeoxycholic acid, and taurochenodeoxycholic acid as novel bioactive ingredients in BBD with anti-inflammatory effects. In conclusion, our study explains the anti-inflammatory efficacy of BBD from both chemical and biological aspects, which provides a scientific basis for the clinical application of BBD in inflammation-related diseases.
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http://dx.doi.org/10.1016/j.jchromb.2022.123356DOI Listing
August 2022

Network pharmacology study to reveal active compounds of Qinggan Yin formula against pulmonary inflammation by inhibiting MAPK activation.

J Ethnopharmacol 2022 Oct 30;296:115513. Epub 2022 Jun 30.

State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China. Electronic address:

Ethnopharmacological Relevance: Pneumonia is common and frequently-occurred disease caused by pathogens which predisposes to lung parenchymal inflammation leading pulmonary dysfunction. To prevent and alleviate the symptoms of pneumonia, Qinggan Yin formula (QGY) was composed based on clinical experience and four classical traditional Chinese medicine prescriptions which frequently applied to treat infectious diseases.

Aim Of The Study: Traditional Chinese medicine is a complex mixture and it is difficult to distinguish the effective component molecules. The aim of this study is to identify the compounds of QGY with anti-inflammatory effects and investigate the molecular mechanism.

Materials And Methods: The high-resolution mass spectrometry and molecular networking were performed for comprehensive chemical profiling of QGY. Network pharmacology was used to generate "herbal-target-pathway" network for target predictions. The anti-inflammation effects of QGY were evaluated in mice model of lipopolysaccharide (LPS) induced acute inflammation. Tail transected zebrafish was also employed to validate macrophage migration reversed effect of QGY. Based on the molecular enrichment analysis, the active substances of QGY with anti-inflammatory effects were further identified in cellular model of macrophage activation. The mechanisms of active substances were investigated by testing their effects on the expression of correlated proteins by Western blot.

Results: In total, 71 compounds are identified as major substances of QGY. According to the results of network pharmacology, QGY shows moderate anti-inflammatory effects and inhibit pulmonary injury. MAPK signaling pathway was predicted as the most related pathway regulated by QGY. Moreover, QGY significantly inhibit LPS-induced pulmonary inflammation in mice, and reversed macrophage migration toward the injury site in zebrafish. We also validate that some major compounds in QGY significantly attenuated the release of IL-1β, IL-6 and TNF-α in LPS-stimulated macrophage. Those active substances including acacetin and arctiin can inhibit the phosphorylation of ERK/JNK and down-regulated the protein expression of BCL-2.

Conclusion: Collectively, QGY possessed pronounced anti-inflammation effects. The integration of network pharmacology and experimental results indicated arctiin, iridin, acacetin, liquiritin, and arctigenin are major active substances of QGY with anti-inflammatory effects. The underlying mechanism of QGY involves MAPK signaling pathway and oxidative stress pathway.
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http://dx.doi.org/10.1016/j.jep.2022.115513DOI Listing
October 2022

Guhong injection promotes post-stroke functional recovery via attenuating cortical inflammation and apoptosis in subacute stage of ischemic stroke.

Phytomedicine 2022 Mar 5;99:154034. Epub 2022 Mar 5.

Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Xihu District, Hangzhou 310012, China; State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Beihua South Road, Jinghai District, Tianjin 301617, China. Electronic address:

Background: As a leading cause of death and disability, alternative therapies for stroke are still limited by its complicated pathophysiological manifestations. Guhong injection (GHI), consisting of safflower aqueous extract and aceglutamide, has been widely applied for the clinical treatment of cerebrovascular diseases, especially ischemic stroke and post-stroke recovery, in China. Recently, a series of studies have reported the positive effect of GHI against cerebral ischemia/reperfusion injury via targeting various molecular mechanisms. However, questions remain on whether treatment with GHI contributes to better functional recovery after stroke and if so, the potential mechanisms and active substances.

Purpose: The aim of this work was to explore the potential therapeutic possibilities of GHI for the neurological and behavioral recovery after stroke and to investigate the underlying molecular mechanisms as well as active substances.

Methods: The neural and motor deficits as well as cortical lesions after GHI treatment were investigated in a mouse model of transient ischemic stroke. Based on the substance identification of GHI, network pharmacology combined with an experimental verification method was used to systematically decipher the biological processes and signaling pathways closely related to GHI intervention in response to post-stroke functional outcomes. Subsequently, ingenuity pathway analysis (IPA) analysis was performed to determine the anti-stroke active substances targeting to the hub targets involved in the significant molecular pathways regulated by GHI treatment.

Results: Therapeutically, administration of GHI observably ameliorated the post-stroke recovery of neural and locomotor function as well as reduced infarct volume and histopathological damage to the cerebral cortex in subacute stroke mice. According to 26 identified or tentatively characterized substances in GHI, the compound-target-pathway network was built. Bioinformatics analysis suggested that inflammatory and apoptotic pathways were tightly associated with the anti-stroke effect of GHI. Based on protein-protein interaction network analysis, the hub targets (such as NF-κB p65, TNF-α, IL-6, IL-1β, Bax, Bcl-2, and Caspase-3) involved in inflammation and apoptosis were selected. On the one hand, immunofluorescence and ELISA results showed that GHI (10 ml/kg) treatment obviously reduced NF-κB p65 nuclear translocation as well as decreased the abnormally elevated concentrations of proinflammatory cytokines (TNF-α, IL-6, and IL-1β) in damaged cortex tissues. On the other hand, GHI (10 ml/kg) treatment significantly downregulated the number of TUNEL-positive apoptotic cells in ischemic cortex and effectively restored the abnormal expression of Bax, Bcl-2, and Caspase-3. Based on the results of IPA, hydroxysafflor yellow A, baicalin, scutellarin, gallic acid, syringin, chlorogenic acid, kaempferol, kaempferol-3-O-β-rutinoside, and rutin acted synergistically on core targets, which could be considered as the active substances of GHI.

Conclusion: Overall, the current findings showed that the beneficial action of GHI on improving post-stroke functional recovery of subacute stroke mice partly via the modulation of cortical inflammation and apoptosis. These findings not only provide a reliable reference for the clinical application of GHI, but also shed light on a promising alternative therapeutic strategy for ischemic stroke patients.
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http://dx.doi.org/10.1016/j.phymed.2022.154034DOI Listing
March 2022

Discovery of tetrahydropalmatine and protopine regulate the expression of dopamine receptor D2 to alleviate migraine from Yuanhu Zhitong formula.

Phytomedicine 2021 Oct 8;91:153702. Epub 2021 Aug 8.

Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China; Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University, Hangzhou, China; State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China. Electronic address:

Background: Migraine is the third most common disease worldwide, leading to severely decreased quality of life for the patients. In spite of great efforts endeavored in pharmacological and nonpharmacological therapeutic strategies for treating migraine, the outcome is rather disappointing in terms of efficacy. Compelling evidence shows that the expression level of dopamine receptor D2 (DRD2) plays an essential role in progression of migraine.

Purpose: To explore potential therapeutical possibilities, the attention was paid to Yuanhu Zhitong formula (YHZTF), which is a classical traditional Chinese medicine prescription frequently applied to relieve pain. The aim of this study was to identify the promising compounds derived from YHZTF with anti-migraine effects and investigate the underlying molecular mechanism.

Methods: The high-resolution mass spectrometry and molecular networking were performed for comprehensive chemical profiling of YHZTF. Network pharmacology was used to generate herbal-component-target-pathway network. Based on the pathway enrichment analysis, the active substances of anti-migraine and the potential molecular mechanism were further determined by performing animal experiments combined with molecular docking strategy.

Results: In total, 31 substances were identified in YHZTF, including alkaloids such as tetrahydropalmatine and protopine. The analysis of herbal-component-target-pathway network suggests that the alkaloid substances (e.g. tetrahydropalmatine and protopine) from YHZTF target dopamine receptors, thus can be linked to neuroactive ligand-receptor interaction pathways. In a nitroglycerin-induced migraine animal model, pretreatment with tetrahydropalmatine or protopine substantially lessened the aberrant migraine-like symptoms. The results of molecular docking analysis showed that tetrahydropalmatine and protopine had strong affinities to dopamine receptor D2 (DRD2). Using RT-qPCR, the investigators found that DRD2 was significantly down-regulated at the mRNA level in brain tissues of tetrahydropalmatine and protopine-treated group compared to the control group.

Conclusion: Collectively, the results provide reliable evidence showing that the active substances tetrahydropalmatine and protopine from YHZTF lessens migraine symptoms in an in vivo mouse model suggestively via regulating expression of DRD2. These findings shed light on novel therapeutic strategies and targets to treat migraine using natural products.
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http://dx.doi.org/10.1016/j.phymed.2021.153702DOI Listing
October 2021
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