Conv. Plasma
Nigella Sativa

All andrographis studies
Meta analysis
study COVID-19 treatment researchAndrographisAndrographis (more..)
Melatonin Meta
Metformin Meta
Azvudine Meta
Bromhexine Meta Molnupiravir Meta
Budesonide Meta
Colchicine Meta
Conv. Plasma Meta Nigella Sativa Meta
Curcumin Meta Nitazoxanide Meta
Famotidine Meta Paxlovid Meta
Favipiravir Meta Quercetin Meta
Fluvoxamine Meta Remdesivir Meta
Hydroxychlor.. Meta Thermotherapy Meta
Ivermectin Meta

All Studies   Meta Analysis    Recent:   

The effects and mechanisms of the anti-COVID-19 traditional Chinese medicine, Dehydroandrographolide from Andrographis paniculata (Burm.f.) Wall, on acute lung injury by the inhibition of NLRP3-mediated pyroptosis

Pu et al., Phytomedicine, doi:10.1016/j.phymed.2023.154753
Jun 2023  
  Source   PDF   All Studies   Meta AnalysisMeta
In Vitro and mouse study investigating the potential therapeutic effects of dehydroandrographolide (Deh), a compound from the herb Andrographis paniculata, in models of acute lung injury caused by COVID-19 infection. Deh reduced inflammation, oxidative stress, and cell death in mouse and cell models. Mechanistically, Deh inhibited NLRP3 inflammasome-mediated pyroptosis, a form of inflammatory cell death, by preventing mitochondrial damage and reducing reactive oxygen species production. This effect involved activation of the Akt/Nrf2 cell signaling pathway and inhibition of the PDPK1 protein. By accelerating PDPK1 degradation, Deh promoted Akt signaling to suppress oxidative stress and mitochondrial dysfunction. Overall, the results suggest Deh may alleviate COVID-19 acute lung injury by targeting oxidative stress, inflammation, and cell death pathways.
6 preclinical studies support the efficacy of andrographis for COVID-19:
Pu et al., 30 Jun 2023, peer-reviewed, 6 authors. Contact:,
This PaperAndrographisAll
The effects and mechanisms of the anti-COVID-19 traditional Chinese medicine, Dehydroandrographolide from Andrographis paniculata (Burm.f.) Wall, on acute lung injury by the inhibition of NLRP3-mediated pyroptosis
Zhichen Pu, Bangzhi Sui, Xingwen Wang, Wusuan Wang, Lingling Li, Haitang Xie
Phytomedicine, doi:10.1016/j.phymed.2023.154753
Background: Dehydroandrographolide (Deh) from Andrographis paniculata (Burm.f.) Wall has strong antiinflammatory and antioxidant activities. Purpose: To explore the role of Deh in acute lung injury (ALI) of coronavirus disease 19 (COVID-19) and its inflammatory molecular mechanism. Methods: Liposaccharide (LPS) was injected into a C57BL/6 mouse model of ALI, and LPS + adenosine triphosphate (ATP) was used to stimulate BMDMs in an in vitro model of ALI. Results: In an in vivo and in vitro model of ALI, Deh considerably reduced inflammation and oxidative stress by inhibiting NLRP3-mediated pyroptosis and attenuated mitochondrial damage to suppress NLRP3-mediated pyroptosis through the suppression of ROS production by inhibiting the Akt/Nrf2 pathway. Deh inhibited the interaction between Akt at T308 and PDPK1 at S549 to promote Akt protein phosphorylation. Deh directly targeted PDPK1 protein and accelerated PDPK1 ubiquitination. 91-GLY, 111-LYS, 126-TYR, 162-ALA, 205-ASP and 223-ASP may be the reason for the interaction between PDPK1 and Deh. Conclusion: Deh from Andrographis paniculata (Burm.f.) Wall presented NLRP3-mediated pyroptosis in a model of ALI through ROS-induced mitochondrial damage through inhibition of the Akt/Nrf2 pathway by PDPK1 ubiquitination. Therefore, it can be concluded that Deh may be a potential therapeutic drug for the treatment of ALI in COVID-19 or other respiratory diseases.
The datasets used and/or analyzed of this study are from Authorship contribution statement The effects and mechanisms of the anti-covid-19 traditional Chinese medicine, Dehydroandrographolide from Andrographis paniculata (Burm.f.) Wall presented acute lung injury by the inhibition of NLRP3mediated pyroptosis. Zhichen Pu and Haitang Xie conceived the study, designed the study and prepared the manuscript. Zhichen Pu, Bangzhi Sui, Xingwen Wang, Wusan Wang, Lingling Li and Haitang Xie conducted the experiments and data analysis, involved in preparation of the figures and manuscript. All data were generated in-house, and no paper mill was used. All authors agree to be accountable for all aspects of work ensuring integrity and accuracy. Declaration of Competing Interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.
Albert, Torres, Bueno, Huntley, Molla et al., Field evaluation of a rapid antigen test (Panbio™ COVID-19 Ag Rapid Test Device) for COVID-19 diagnosis in primary healthcare centres, Clin. Microbiol. Infect
Amit, Beni, Biber, Grinberg, Leshem et al., Postvaccination COVID-19 among healthcare workers, Israel, Emerg. Infect. Dis
An, Heo, Kim, Lian, Lee et al., Tetraarsenic hexoxide enhances generation of mitochondrial ROS to promote pyroptosis by inducing the activation of caspase-3/GSDME in triplenegative breast cancer cells, Cell Death Dis
An, Zhang, Wang, Jiao, Xu et al., Activation of ROS/MAPKs/NF-κB/NLRP3 and inhibition of efferocytosis in osteoclast-mediated diabetic osteoporosis, FASEB J
Bonaventura, Vecchié, Dagna, Tangianu, Abbate et al., Colchicine for COVID-19: targeting NLRP3 inflammasome to blunt hyperinflammation, Inflamm. Res
Bora, Kamle, Hassan, Al-Emam, Chopra et al., Exploration of potent antiviral phytomedicines from lauraceae family plants against SARS-CoV-2 main protease, Viruses
Bordas-Martinez, Del Río, Molina-Molina, Multiple solid nodules at post-COVID-19 follow-up after mild pneumonia, Arch. Bronconeumol
Che, Hou, Zeng, Li, Zhang et al., Dehydroandrographolide inhibits IgE-mediated anaphylactic reactions via calcium signaling pathway, Toxicol. Appl. Pharmacol
Che, Zheng, Hou, Li, Du et al., Dehydroandrographolide targets CD300f and negatively regulated MRGPRX2-induced pseudo-allergic reaction, Phytother. Res
Chen, Xiao, Jiang, Jiang, Li et al., Schisandrin B Attenuates airway inflammation and airway remodeling in asthma by inhibiting NLRP3 inflammasome activation and reducing pyroptosis, Inflammation
Climans, Grunfeld, Mason, Chan, Effectiveness and safety of pneumocystis pneumonia prophylaxis for patients receiving temozolomide chemoradiotherapy, Neuro. Oncol
El-Twab, Hussein, Hozayen, Bin-Jumah, Mahmoud, Chicoric acid prevents methotrexate-induced kidney injury by suppressing NF-κB/ NLRP3 inflammasome activation and up-regulating Nrf2/ARE/HO-1 signaling, Inflamm. Res
Fenollar, Bouam, Ballouche, Fuster, Prudent et al., Evaluation of the panbio COVID-19 rapid antigen detection test device for the screening of patients with COVID-19, J. Clin. Microbiol
Gallo González, López-Padilla, Puente Maestú, Pulmonary calcifications as COVID-19 pneumonia sequelae, Arch
Guo, Liu, Zhang, Ma, Li et al., Dehydroandrographolide inhibits mastitis by activating autophagy without affecting intestinal flora, Aging
Gyebi, Elfiky, Ogunyemi, Ibrahim, Adegunloye et al., Structure-based virtual screening suggests inhibitors of 3-Chymotrypsin-Like Protease of SARS-CoV-2 from Vernonia amygdalina and Occinum gratissimum, Comput. Biol. Med
Huo, Wang, Feng, He, Qiu, Tracking the deprotonation site of dehydroandrographolide with electrospray ionization mass spectrometry by deuteration, Rapid Commun. Mass Spectrom
Jeong, Kim, Kim, Kim, Jeong et al., Mycetia cauliflora methanol extract exerts anti-inflammatory activity by directly targeting PDK1 in the NF-κB pathway, J. Ethnopharmacol
Jung, Lee, Korean Red Ginseng, a regulator of NLRP3 inflammasome, in the COVID-19 pandemic, J. Ginseng
Kim, Lee, Jung, Lee, Ha et al., Chicoric acid mitigates impaired insulin sensitivity by improving mitochondrial function, Biosci. Biotechnol. Biochem
Lara, Macías-Verde, Burgos-Burgos, Age-induced NLRP3 inflammasome over-activation increases lethality of SARS-CoV-2 pneumonia in elderly patients, Aging Dis
Li, Dai, Sun, Zhang, The activation of IL-17 signaling pathway promotes pyroptosis in pneumonia-induced sepsis, Ann. Transl. Med
Li, Dai, Zhang, Liu, Yu et al., Ulinastatin attenuates LPS-induced inflammation in mouse macrophage RAW264.7 cells by inhibiting the JNK/NF-κB signaling pathway and activating the PI3K/Akt/Nrf2 pathway, Acta Pharmacol. Sin
Li, Feng, Han, Ding, Shen et al., Chicoric acid ameliorate inflammation and oxidative stress in Lipopolysaccharide and d-galactosamine induced acute liver injury, J. Cell Mol. Med
Li, Li, Zhang, Zhuo, Zhang et al., Xuanfei Baidu decoction suppresses complement overactivation and ameliorates IgG immune complex-induced acute lung injury by inhibiting JAK2/STAT3/SOCS3 and NF-κB signaling pathway, Phytomedicine
Li, Pan, Yang, Chen, Wang et al., Xuanfei Baidu formula alleviates impaired mitochondrial dynamics and activated NLRP3 inflammasome by repressing NF-κB and MAPK pathways in LPS-induced ALI and inflammation models, Phytomedicine
Li, Zeng, Cheng, Han, Zhang et al., Acupuncture administration improves cognitive functions and alleviates inflammation and nuclear damage by regulating phosphatidylinositol 3 kinase (PI3K)/Phosphoinositol-Dependent Kinase 1 (PDK1)/Novel Protein Kinase C (nPKC)/Rac 1 signaling pathway in senescenceaccelerated prone 8 (SAM-P8) mice, Med. Sci. Monit
Lin, Li, Jiang, Shao, Zhang et al., PINK1-parkin pathway of mitophagy protects against contrast-induced acute kidney injury via decreasing mitochondrial ROS and NLRP3 inflammasome activation, Redox Biol
Liu, Deng, Jiang, Li, Zhang et al., Scoparone improves hepatic inflammation and autophagy in mice with nonalcoholic steatohepatitis by regulating the ROS/P38/Nrf2 axis and PI3K/AKT/mTOR pathway in macrophages, Biomed. Pharmacother
Liu, Fan, Xie, Zhang, Li et al., Dehydroandrographolide inhibits osteosarcoma cell growth and metastasis by targeting SATB2-mediated EMT, Anticancer Agents Med. Chem
Liu, Fang, Chen, Die, Wang et al., Chicoric acid improves neuron survival against inflammation by promoting mitochondrial function and energy metabolism, Food Funct
Liu, Liu, Sun, Zhou, Xue et al., Maxing Shigan decoction mitigates mycoplasma pneumonia-induced pyroptosis in A549 cells via the NLRP3 Inflammasome, Infect. Drug Resist
Lu, Wan, Wang, Zhang, Xu et al., Chicoric acid prevents PDGF-BB-induced VSMC dedifferentiation, proliferation and migration by suppressing ROS/NFκB/mTOR/P70S6K signaling cascade, Redox Biol
Lv, Zhao, Liu, Ye, Liang et al., Dysfunctional telomeres through mitostress-induced cGAS/STING activation to aggravate immune senescence and viral pneumonia, Aging Cell
Machado, Patente, Rouillé, Heumel, Melo et al., Acetate improves the killing of streptococcus pneumoniae by alveolar macrophages via NLRP3 inflammasome and glycolysis-HIF-1α axis, Front. Immunol
Majumder, Minko, Recent developments on therapeutic and diagnostic approaches for COVID-19, AAPS J
Mamidi, Mahmud, Maiti, Mendez, Fernandes et al., Idelalisib activates AKT via increased recruitment of PI3Kδ/PI3Kβ to BCR signalosome while reducing PDK1 in post-therapy CLL cells, Leukemia
Minutoli, Puzzolo, Rinaldi, Irrera, Marini et al., ROS-mediated NLRP3 inflammasome activation in brain, heart, kidney, and testis ischemia/reperfusion injury, Oxid. Med. Cell. Longev
Paul, Tao, West, Litzky, Feldman et al., Pulmonary vascular inflammation with fatal coronavirus disease 2019 (COVID-19): possible role for the NLRP3 inflammasome, Respir. Res
Piñeiro Roncal, García Luján, Siesto López, Tejedor Ortiz, Miguel Poch, Use of an endobronchial valve for management of a persistent air-Z. Pu et al. leak in a child with necrotising pneumonia, Arch. Bronconeumol
Pu, Liu, Li, Xu, Xie et al., Using network pharmacology for systematic understanding of geniposide in ameliorating inflammatory responses in colitis through suppression of NLRP3 inflammasome in macrophage by AMPK/Sirt1 dependent signaling, Am. J. Chin. Med
Pu, Shen, Zhang, Xie, Wang, Avenanthramide C from oats protects pyroptosis through dependent ROS-induced mitochondrial damage by PI3K ubiquitination and phosphorylation in pediatric pneumonia, J. Agric. Food Chem
Shin, Kim, Jeong, Shin, Kang et al., Nrf2-Heme oxygenase-1 attenuates high-glucose-induced epithelial-to-mesenchymal transition of renal tubule cells by inhibiting ROS-mediated PI3K/Akt/GSK-3β signaling, J. Diabetes Res
Sidiq, Hanif, Dwivedi, Chopra, Benefits and limitations of serological assays in COVID-19 infection, Indian J. Tuberc
Sun, Mao, Ji, LncRNA H19 activates cell pyroptosis via the miR-22-3p/ NLRP3 axis in pneumonia, Am. J. Transl. Res
To, Sridhar, Chiu, Hung, Li et al., Lessons learned 1 year after SARS-CoV-2 emergence leading to COVID-19 pandemic, Emerg. Microbes Infect
Van Lieshout, De Vos, Dessing, De Porto, De Boer et al., ASC and NLRP3 impair host defense during lethal pneumonia caused by serotype 3 Streptococcus pneumoniae in mice, Eur. J. Immunol
Visca, Migliori, Dinh-Xuan, Centis, Belli et al., The role of blood gas analysis in the post-acute phase of COVID-19 pneumonia, Arch. Bronconeumol
Wang, Liu, Zhao, Gao, Mitochondria regulation in ferroptosis, Eur. J. Cell Biol
Wang, Shi, Chen, Huang, Zou et al., Mitochondrial ROS promote macrophage pyroptosis by inducing GSDMD oxidation, J. Mol. Cell Biol
Wei, Chen, Cai, Lu, Xu et al., Rosmarinic acid regulates microglial M1/M2 polarization via the PDPK1/Akt/HIF pathway under conditions of neuroinflammation, Inflammation
Wu, Huang, Resveratrol alleviates Staphylococcus aureus pneumonia by inhibition of the NLRP3 inflammasome, Exp. Ther. Med
Xiao, Peng, Hong, Chen, Deng et al., PDGF promotes the warburg effect in pulmonary arterial smooth muscle cells via activation of the PI3K/AKT/mTOR/HIF-1α signaling pathway, Cell Physiol. Biochem
Xiao, Wang, Yuan, Xiao, Wang et al., Chicoric acid induces apoptosis in 3T3-L1 preadipocytes through ROS-mediated PI3K/Akt and MAPK signaling pathways, J. Agric. Food Chem
Xu, Che, Zhang, Huang, Ding et al., Apaf-1 pyroptosome senses mitochondrial permeability transition, Cell Metab
Yang, Li, Chen, Knockdown of phosphoinositide-dependent kinase 1 (PDK1) inhibits fibrosis and inflammation in lipopolysaccharide-induced acute lung injury rat model by attenuating NF-κB/p65 pathway activation, Ann. Transl. Med
Zeng, Wan, Liu, Xiong, Xiang et al., Chlorogenic acid ameliorates Klebsiella pneumoniae-induced pneumonia in immunosuppressed mice via inhibiting the activation of NLRP3 inflammasomes, Food Funct
Zhang, Guo, Zhang, Xu, Liu et al., Huashibaidu formula attenuates sepsis-induced acute lung injury via suppressing cytokine storm: implications for treatment of COVID-19, Phytomedicine
Zhang, Li, Guo, Zhou, Ming et al., Inhibition of PDK1 enhances radiosensitivity and reverses epithelial-mesenchymal transition in nasopharyngeal carcinoma, Head Neck
Zhang, Wang, Shen, Wang, Pu et al., Network pharmacology for systematic understanding of Schisandrin B reduces the epithelial cells injury of colitis through regulating pyroptosis by AMPK/Nrf2/NLRP3 inflammasome, Aging
Zhang, Wang, Vikash, Ye, Wu et al., ROS and ROSmediated cellular signaling, Oxid. Med. Cell. Longev
Zhuang, Wu, Wang, He, He et al., Resveratrol attenuates oxidative stress-induced intestinal barrier injury through PI3K/Akt-mediated Nrf2 signaling pathway, Oxid. Med. Cell. Longev
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Vaccines and treatments are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
  or use drag and drop