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  1. Article ; Online: Inhibition of estrogen sulfation by Xian-Ling-Gu-Bao capsule.

    He, Liangliang / Chen, Chanjuan / Duan, Shuyi / Li, Yang / Li, Chuan / Yao, Xinsheng / Gonzalez, Frank J / Qin, Zifei / Yao, Zhihong

    The Journal of steroid biochemistry and molecular biology

    2022  Volume 225, Page(s) 106182

    Abstract: Xian-Ling-Gu-Bao capsule (XLGB) is a widely prescribed traditional Chinese medicine used ...

    Abstract Xian-Ling-Gu-Bao capsule (XLGB) is a widely prescribed traditional Chinese medicine used for the treatment of osteoporosis. However, it significantly elevates levels of serum estrogens. Here we aimed to assess the dominant contributors of sulfotransferase (SULT) enzymes to the sulfation of estrogens and identify the effective inhibitors of this pathway in XLGB. First, estrone, 17β-estradiol, and estriol underwent sulfation in human liver S9 extracts. Phenotyping reactions and enzyme kinetics assays revealed that SULT1A1, 1A2, 1A3, 1C4, 1E1, and 2A1 all participated in estrogen sulfation, with SULT1E1 and 1A1 as the most important contributors. The incubation system for these two active enzymes were optimized with Tris-HCl buffer, DL-Dithiothreitol (DTT), MgCl
    MeSH term(s) Humans ; Molecular Docking Simulation ; Sulfotransferases/metabolism ; Polyphenols ; Estrogens
    Chemical Substances Sulfotransferases (EC 2.8.2.-) ; Polyphenols ; Estrogens
    Language English
    Publishing date 2022-09-21
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1049188-0
    ISSN 1879-1220 ; 0960-0760
    ISSN (online) 1879-1220
    ISSN 0960-0760
    DOI 10.1016/j.jsbmb.2022.106182
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    Zs.A 708: Show issues Location:
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  2. Article: Identification of naturally occurring inhibitors in Xian-Ling-Gu-Bao capsule against the glucuronidation of estrogens.

    He, Liangliang / Xu, Chunxia / Wang, Ziying / Duan, Shuyi / Xu, Jinjin / Li, Chuan / Yao, Xinsheng / Gonzalez, Frank J / Qin, Zifei / Yao, Zhihong

    Frontiers in pharmacology

    2022  Volume 13, Page(s) 935685

    Abstract: Xian-Ling-Gu-Bao (XLGB) capsule, a well-known traditional Chinese medicine prescription, is widely ...

    Abstract Xian-Ling-Gu-Bao (XLGB) capsule, a well-known traditional Chinese medicine prescription, is widely used for the treatment of osteoporosis. It could significantly increase the levels of estrogen in ovariectomized rats and mice. However, this working mechanism has not been well elucidated. Considering that UDP-glucuronosyltransferase (UGT) enzymes are the important enzymes that inactivate and regulate estrogen activity
    Language English
    Publishing date 2022-08-04
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2022.935685
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  3. Article: Shen-Shuai-Ling Formulation Attenuates Renal Interstitial Fibrosis in Chronic Kidney Disease by Regulating SHH-Gli1 Signaling Pathway.

    Li, Ying / Tu, Haitao / Luo, Yan / Xiong, Weijian / Liu, Hong / Xiong, Yanying / Zhang, Qin / Li, Huihui / Gao, Xuan

    Evidence-based complementary and alternative medicine : eCAM

    2022  Volume 2022, Page(s) 3754985

    Abstract: Background: Shen-Shuai-Ling Formulation (SSLF) has apparent effects on improving renal function ...

    Abstract Background: Shen-Shuai-Ling Formulation (SSLF) has apparent effects on improving renal function, delaying the progression of chronic kidney disease (CKD).
    Methods: Fifty male SD rats were randomly divided into 5 groups: Sham group, Model group, SSLF group, CPN group, and C + S group. The morphological changes and the collagen fibers of the rat kidneys were observed by HE staining. The expression of
    Results: Compared with the Model group, the fibrosis in SSLF, CPN, and C + S groups was significantly alleviated. And, compared with those in the Model group, the expression of
    Conclusions: SSLF remarkably improves renal function and alleviates renal interstitial fibrosis in UUO rats.
    Language English
    Publishing date 2022-02-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2171158-6
    ISSN 1741-4288 ; 1741-427X
    ISSN (online) 1741-4288
    ISSN 1741-427X
    DOI 10.1155/2022/3754985
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    Zs.A 5995: Show issues Location:
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  4. Article ; Online: An UHPLC-MS/MS method for simultaneous determination of ten sex steroid hormones in ovariectomy-induced osteoporosis rat and its application in discovery of sex steroid hormones regulatory components of Xian-Ling-Gu-Bao capsule.

    Tang, Xi-Yang / Dai, Zi-Qin / Shi, Dan-Feng / Zeng, Jia-Xing / Wang, Xin-Luan / Li, Ling / Yao, Xin-Sheng / Dai, Yi

    Journal of pharmaceutical and biomedical analysis

    2021  Volume 195, Page(s) 113888

    Abstract: ... the action mechanism of anti-osteoporosis drugs. However, it is not clear whether Xian-Ling-Gu-Bao capsule ...

    Abstract Sex steroid hormones could directly affect the bone metabolism by regulating cell physiological functions. In female, it inevitably causes the abnormal levels of sex steroid hormones at post-menopause in vivo. Ovariectomized rats and mice are classic animal models of osteoporosis to better understand the action mechanism of anti-osteoporosis drugs. However, it is not clear whether Xian-Ling-Gu-Bao capsule (XLGB), a kidney-tonifying traditional Chinese medicine prescription, treat osteoporosis via regulating multiple sex steroid hormones. In the present study, a reliable method involving ultra high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC/TQ-XS-MS) was developed for simultaneous quantitative analysis of ten sex steroid hormones (three estrogens, five androgens and two progestogens) in rat and mouse serum. The results of methodology were acceptable. The validated method was then successfully applied in the determination of the levels of sex steroid hormones in ovariectomy-induced osteoporosis rats, as well as drug (17β-estradiol and XLGB) intervened rats. As a result, XLGB could not only significantly increase the level of 17β-estradiol, but also improve the levels of progesterone, 17α-hydroxyprogesterone and androstenedione. Combined with molecular docking results and pharmacokinetic parameters, psoralen, isopsoralen and sweroside were considered as the key effective components of XLGB to activate adenylyl cyclase on promoting the biosynthesis of multiple sex steroid hormones. It is the first time to evaluate the regulatory effect of kidney-tonifying traditional Chinese medicine prescription on the levels of steroids in ovariectomy-induced osteoporosis rat, as well as the potential substance basis and mechanism of steroid hormone regulation.
    MeSH term(s) Animals ; Chromatography, High Pressure Liquid ; Female ; Gonadal Steroid Hormones ; Humans ; Mice ; Molecular Docking Simulation ; Osteoporosis/drug therapy ; Osteoporosis/etiology ; Ovariectomy ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry
    Chemical Substances Gonadal Steroid Hormones
    Language English
    Publishing date 2021-01-02
    Publishing country England
    Document type Journal Article
    ZDB-ID 604917-5
    ISSN 1873-264X ; 0731-7085
    ISSN (online) 1873-264X
    ISSN 0731-7085
    DOI 10.1016/j.jpba.2020.113888
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    Zs.A 1850: Show issues Location:
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    ab Jg. 2022: Lesesaal (EG)

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  5. Article: Investigating the mechanism of Xian-ling-lian-xia-fang for inhibiting vasculogenic mimicry in triple negative breast cancer via blocking VEGF/MMPs pathway.

    Li, Feifei / Shi, Youyang / Zhang, Yang / Yang, Xiaojuan / Wang, Yi / Jiang, Kexin / Hua, Ciyi / Wu, Chunyu / Sun, Chenping / Qin, Yuenong / Liu, Sheng

    Chinese medicine

    2022  Volume 17, Issue 1, Page(s) 44

    Abstract: Background: Xian-ling-lian-xia-fang (XLLXF), a Chinese medicine decoction, is widely used ...

    Abstract Background: Xian-ling-lian-xia-fang (XLLXF), a Chinese medicine decoction, is widely used in the treatment of triple negative breast cancer (TNBC). However, the underlying mechanism of XLLXF in TNBC treatment has not been totally elucidated.
    Methods: Here, network pharmacology and molecular docking were used to explore the mechanism of Traditional Chinese medicine in the treatment of TNBC. Then, biological experiments were integrated to verify the results of network pharmacology.
    Results: Network pharmacology showed that the candidate active ingredients mainly included quercetin, kaempferol, stigmasterol, and β-sitosterol through the "XLLXF-active ingredients-targets" network. Vascular endothelial growth factor A (VEGFA) and matrix metalloproteinase (MMP) 2 were the potential therapeutic targets obtained through the protein-protein interaction (PPI) network. Molecular docking confirmed that quercetin, kaempferol, stigmasterol, and β-sitosterol could stably combine with VEGFA and MMP2. Experimental verification showed that XLLXF could inhibit proliferation, colony ability, and vasculogenic mimicry (VM) formation and promote cell apoptosis in TNBC. Laser confocal microscopy found that XLLXF impaired F-actin cytoskeleton organization and inhibited epithelial mesenchymal transition. Animal experiments also found that XLLXF could inhibit tumor growth and VM formation in TNBC xenograft model. Western blot analysis and immunohistochemical staining showed that XLLXF inhibited the protein expression of VEGFA, MMP2, MMP9, Vimentin, VE-cadherin, and Twist1 and increased that of E-cadherin, tissue inhibitors of metalloproteinase (TIMP)-1, and TIMP-3 in vitro and in vivo.
    Conclusions: Integrating the analysis of network pharmacology and experimental validation revealed that XLLXF could inhibit VM formation via downregulating the VEGF/MMPs signaling pathway.
    Language English
    Publishing date 2022-04-04
    Publishing country England
    Document type Journal Article
    ZDB-ID 2260322-0
    ISSN 1749-8546
    ISSN 1749-8546
    DOI 10.1186/s13020-022-00597-5
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  6. Article ; Online: Effects of Xian-Ling-Gu-Bao capsule on the gut microbiota in ovariectomized rats: Metabolism and modulation.

    Tang, Xi-Yang / Gao, Meng-Xue / Xiao, Hui-Hui / Dai, Zi-Qin / Yao, Zhi-Hong / Dai, Yi / Yao, Xin-Sheng

    Journal of chromatography. B, Analytical technologies in the biomedical and life sciences

    2021  Volume 1176, Page(s) 122771

    Abstract: Xian-Ling-Gu-Bao capsule (XLGB) has been proven to prevent and treat osteoporosis ...

    Abstract Xian-Ling-Gu-Bao capsule (XLGB) has been proven to prevent and treat osteoporosis. However, as a long-term oral formula, XLGB's effects on the metabolic capacity, structure and function of gut microbiota have yet to be elucidated in ovariectomized (OVX) rats. Our objectives were to evaluate the capacity of gut microbiota for metabolizing XLGB ingredients and to assess the effect of this prescription on gut microbiota. Herein, an integrated analysis that combined ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and ultrahigh-performance liquid chromatography tandem triple quadrupole mass spectrometry (UPLC-TQD-MS) was conducted to determine the metabolic capacity of gut microbiota. The effects of XLGB on gut microbiota were explored by metagenomic sequencing in OVX rats. Fecal samples from each group were collected after intragastric administration for three months. In total, 64 biotransformation products were fully characterized with rat gut microbiota from the OVX group and the XLGB group. The deglycosylation reaction was the main biotransformation pathway in core structures in the group that was incubated with XLGB. Compared with the OVX group, different biotransformation products and pathways of the XLGB group after incubation for 2 h and 8 h were described. After three months of feeding with XLGB, the domesticated gut microbiota was conducive to the production of active absorbed components via deglycosylation, such as icaritin, psoralen and isopsoralen. Comparisons of the gut microbiota of the OVX and XLGB groups showed differences in the relative abundances of the two dominant bacterial divisions, namely, Firmicutes and Bacteroidetes. The proportion of Firmicutes was significantly lower and that of Bacteroidetes was significantly higher in the XLGB group. This result demonstrated that XLGB could provide a basis for the treatment of osteoporosis by regulating lipid and bile acid metabolism. In addition, the increase in Lactobacillus, Bacteroides and Prevotella could be an important factor that led to easier production of active absorbed aglycones in the XLGB group. Our observation provided further evidence of the importance of gut microbiota in the metabolism and potential activity of XLGB.
    Language English
    Publishing date 2021-05-18
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1180823-8
    ISSN 1873-376X ; 0378-4347 ; 1570-0232 ; 1387-2273
    ISSN (online) 1873-376X
    ISSN 0378-4347 ; 1570-0232 ; 1387-2273
    DOI 10.1016/j.jchromb.2021.122771
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    Zs.A 813: Show issues Location:
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  7. Article ; Online: Shen-Shuai-Ling Formulation Attenuates Renal Interstitial Fibrosis in Chronic Kidney Disease by Regulating SHH-Gli1 Signaling Pathway

    Ying Li / Haitao Tu / Yan Luo / Weijian Xiong / Hong Liu / Yanying Xiong / Qin Zhang / Huihui Li / Xuan Gao

    Evidence-Based Complementary and Alternative Medicine, Vol

    2022  Volume 2022

    Abstract: Background. Shen-Shuai-Ling Formulation (SSLF) has apparent effects on improving renal function ...

    Abstract Background. Shen-Shuai-Ling Formulation (SSLF) has apparent effects on improving renal function, delaying the progression of chronic kidney disease (CKD). Methods. Fifty male SD rats were randomly divided into 5 groups: Sham group, Model group, SSLF group, CPN group, and C + S group. The morphological changes and the collagen fibers of the rat kidneys were observed by HE staining. The expression of α-SMA, Col I, SHH, Gli1, and snail1 was detected by Western blot and qPCR. Then, the cells were divided into the control group, SHH group, and SHH + SSLF serum group. Results. Compared with the Model group, the fibrosis in SSLF, CPN, and C + S groups was significantly alleviated. And, compared with those in the Model group, the expression of α-SMA, Col I, SHH, Gli1, Snail in SSLF, CPN, and C + S groups decreased remarkably. Conclusions. SSLF remarkably improves renal function and alleviates renal interstitial fibrosis in UUO rats.
    Keywords Other systems of medicine ; RZ201-999
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Hindawi Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article: Shen-Zhi-Ling oral liquid ameliorates cerebral glucose metabolism disorder in early AD via insulin signal transduction pathway in vivo and in vitro.

    Qin, Gaofeng / Dong, Yunfang / Liu, Zhenhong / Gong, Zhuoyan / Gao, Chenyan / Zheng, Mingcui / Tian, Meijing / He, Yannan / Zhong, Liqun / Wang, Pengwen

    Chinese medicine

    2021  Volume 16, Issue 1, Page(s) 128

    Abstract: Background: Shen-Zhi-Ling oral liquid (SZL) is an herbal formula known for its efficacy ...

    Abstract Background: Shen-Zhi-Ling oral liquid (SZL) is an herbal formula known for its efficacy of nourishing "heart and spleen", and is used for the treatment and prevention of middle- and early-stage dementia. This study investigated the effects of SZL on amelioration of AD, and examined whether the underlying mechanisms from the perspective of neuroprotection are related to brain glucose metabolism.
    Methods: Firstly, LC-MS/MS was used to analysis the SZL mainly enters the blood component. Then, the effects of SZL on cognitive and behavioral ability of APP/PS1 double transgenic mice and amyloid protein characteristic pathological changes were investigated by behavioral study and morphological observation. The effects of SZL on the ultrastructure of mitochondria, astrocytes, and micrangium related to cerebral glucose metabolism were observed using transmission electron microscopy. Then, micro-PET was also used to observe the effects of SZL on glucose uptake. Furthermore, the effects of SZL on insulin signaling pathway InR/PI3K/Akt and glucose transporters (GLUT1 and GLUT3) were observed by immunohistochemistry, Western-blot and RT-qPCR. Finally, the effects of SZL on brain glucose metabolism and key enzyme were observed. In vitro, the use of PI3K and/or GSK3β inhibitor to observe the effects of SZL drug-containing serum on GLUT1 and GLUT3.
    Results: In vivo, SZL could significantly ameliorate cognitive deficits, retarded the pathological damage, including neuronal degeneration, Aβ peptide aggregation, and ultrastructural damage of hippocampal neurons, improve the glucose uptake, transporters and glucolysis. Beyond that, SZL regulates the insulin signal transduction pathway the insulin signal transduction pathway InR/PI3K/Akt. Furthermore, 15% SZL drug-containing serum increased Aβ
    Conclusions: In summary, our results demonstrated that improving glucose uptake, transport, and glycolysis in the brain may underlie the neuroprotective effects of SZL, and its potential molecular mechanism may be related to regulate the insulin signal transduction pathway.
    Language English
    Publishing date 2021-12-02
    Publishing country England
    Document type Journal Article
    ZDB-ID 2260322-0
    ISSN 1749-8546
    ISSN 1749-8546
    DOI 10.1186/s13020-021-00540-0
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  9. Article ; Online: Network pharmacology studies on the effect of Chai-Ling decoction in coronavirus disease 2019

    Lu Yang / Yu-Ting Li / Jing Miao / Li Wang / Hui Fu / Qin Li / Wei-Bo Wen / Zhai-Yi Zhang / Rui-Wen Song / Xiang-Guo Liu / Hong-Wu Wang / Huan-Tian Cui

    Traditional Medicine Research, Vol 5, Iss 3, Pp 145-

    2020  Volume 159

    Abstract: Background: Chai-Ling decoction (CLD), derived from a modification of Xiao-Chai-Hu (XCH) decoction ... and Wu-Ling-San (WLS) decoction, has been used to treat the early-stage of coronavirus disease 2019 ...

    Abstract Background: Chai-Ling decoction (CLD), derived from a modification of Xiao-Chai-Hu (XCH) decoction and Wu-Ling-San (WLS) decoction, has been used to treat the early-stage of coronavirus disease 2019 (COVID-19). However, the mechanisms of CLD in COVID-19 remain unknown. In this study, the potential mechanisms of CLD in COVID-19 were preliminarily investigated based on network pharmacology and molecular docking method. Methods: Initially, the active components and targets of CLD were screened based on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and PharmMapper database. The targets of COVID-19 were obtained from GeneCards database. The protein-protein interaction network was established using STRING database to analyze the key targets. Gene Oncology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes analysis were also conducted to evaluate the pathways related to the targets of CLD on COVID-19. Moreover, the compound-target-pathway network was established using Cytoscape 3.2.7. Subsequently, the molecular docking method was performed to select the active compounds with high binding affinity on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and angiotensin-converting enzyme 2 (ACE2), which is the key target of SARS-CoV-2 in entering target cells. The possible binding sites were also visualized by a three-dimensional graph. Results: Network pharmacology analysis showed that there were 106 active components and 160 targets of CLD. Additionally, 251 targets related to COVID-19 were identified, and 24 candidates of CLD on COVID-19 were selected. A total of 283 GO terms of CLD on COVID-19 were identified, and 181 pathways were screened based on GO and Kyoto Encyclopedia of Genes and Genomes analyses. CLD might alleviate the inflammatory response and improve lung injury to treat COVID-19 through interleukin 17 signaling, T helper cell 17 differentiation, tumor necrosis factor signaling, and hypoxia inducible factor-1 signaling. Besides, molecular docking indicated that beta-sitosterol, kaempferol, and stigmasterol were the top three candidates in CLD with the highest affinity to SARS-CoV-2 and ACE2. Conclusion: Our study identifies the potential mechanisms of CLD on COVID-19 and beta-sitosterol, kaempferol, and stigmasterol may be the key compounds that exert antiviral effects against SARS-CoV-2.
    Keywords chai-ling decoction ; coronavirus disease 2019 ; network pharmacology ; molecular docking ; severe acute respiratory syndrome coronavirus 2 ; angiotensin-converting enzyme 2 ; Medicine ; R ; Miscellaneous systems and treatments ; RZ409.7-999 ; covid19
    Subject code 572
    Language English
    Publishing date 2020-04-01T00:00:00Z
    Publisher Hong Kong Gold Orchid Science and Technology Co., Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article: Network pharmacology studies on the effect of Chai-Ling decoction in coronavirus disease 2019

    Yang, Lu / Li, Yu-Ting / Miao, Jing / Wang, Li / Fu, Hui / Li, Qin / Wen, Wei-Bo / Zhang, Zhai-Yi / Song, Rui-Wen / Liu, Xiang-Guo / Wang, Hong-Wu / Cui, Huan-Tian

    Traditional Med.Res.

    Abstract: Background: Chai-Ling decoction (CLD), derived from a modification of Xiao-Chai-Hu (XCH) decoction ... and Wu-Ling-San (WLS) decoction, has been used to treat the early-stage of coronavirus disease 2019 ...

    Abstract Background: Chai-Ling decoction (CLD), derived from a modification of Xiao-Chai-Hu (XCH) decoction and Wu-Ling-San (WLS) decoction, has been used to treat the early-stage of coronavirus disease 2019 (COVID-19). However, the mechanisms of CLD in COVID-19 remain unknown. In this study, the potential mechanisms of CLD in COVID-19 were preliminarily investigated based on network pharmacology and molecular docking method. Methods: Initially, the active components and targets of CLD were screened based on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and PharmMapper database. The targets of COVID-19 were obtained from GeneCards database. The protein-protein interaction network was established using STRING database to analyze the key targets. Gene Oncology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes analysis were also conducted to evaluate the pathways related to the targets of CLD on COVID-19. Moreover, the compound-target-pathway network was established using Cytoscape 3.2.7. Subsequently, the molecular docking method was performed to select the active compounds with high binding affinity on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and angiotensin-converting enzyme 2 (ACE2), which is the key target of SARS-CoV-2 in entering target cells. The possible binding sites were also visualized by a three-dimensional graph. Results: Network pharmacology analysis showed that there were 106 active components and 160 targets of CLD. Additionally, 251 targets related to COVID-19 were identified, and 24 candidates of CLD on COVID-19 were selected. A total of 283 GO terms of CLD on COVID-19 were identified, and 181 pathways were screened based on GO and Kyoto Encyclopedia of Genes and Genomes analyses. CLD might alleviate the inflammatory response and improve lung injury to treat COVID-19 through interleukin 17 signaling, T helper cell 17 differentiation, tumor necrosis factor signaling, and hypoxia inducible factor-1 signaling. Besides, molecular docking indicated that beta-sitosterol, kaempferol, and stigmasterol were the top three candidates in CLD with the highest affinity to SARS-CoV-2 and ACE2. Conclusion: Our study identifies the potential mechanisms of CLD on COVID-19 and beta-sitosterol, kaempferol, and stigmasterol may be the key compounds that exert antiviral effects against SARS-CoV-2.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #176103
    Database COVID19

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