sulforaphane and Pulmonary Disease, Chronic Obstructive studies

sulforaphane: from Cardaria draba L.
sulforaphane : An isothiocyanate having a 4-(methylsulfinyl)butyl group attached to the nitrogen.

Pulmonary Disease, Chronic Obstructive: A disease of chronic diffuse irreversible airflow obstruction. Subcategories of COPD include CHRONIC BRONCHITIS and PULMONARY EMPHYSEMA.

Research Excerpts

Excerpt	Relevance	Reference
"Inflammation is a prominent feature of COPD and represents an important target for treatment."	5.62	Sulforaphane suppresses lipopolysaccharide- and Pam3CysSerLys4-mediated inflammation in chronic obstructive pulmonary disease via toll-like receptors. ( Bao, H; Liu, X; Zeng, X, 2021)
"Patients with chronic obstructive pulmonary disease (COPD) have high oxidative stress associated with the severity of the disease."	2.90	Compartmentalization of anti-oxidant and anti-inflammatory gene expression in current and former smokers with COPD. ( Berenson, CS; Biswal, S; Burke, A; Criner, GJ; Fahey, JW; Holbrook, JT; Jacobs, MR; Sethi, S; Sidhaye, VK; Sudini, KR; Thimmulappa, R; Wise, RA, 2019)
"Sulforaphane was absorbed in the patients as evident from their plasma metabolite levels."	2.82	Lack of Effect of Oral Sulforaphane Administration on Nrf2 Expression in COPD: A Randomized, Double-Blind, Placebo Controlled Trial. ( Berenson, CS; Biswal, S; Burke, A; Criner, G; Fahey, JW; Holbrook, JT; Jacobs, MR; Rayapudi, S; Sethi, S; Singh, A; Sudini, KR; Sugar, EA; Talalay, P; Thimmulappa, R; Wise, RA, 2016)
"Inflammation is a prominent feature of COPD and represents an important target for treatment."	1.62	Sulforaphane suppresses lipopolysaccharide- and Pam3CysSerLys4-mediated inflammation in chronic obstructive pulmonary disease via toll-like receptors. ( Bao, H; Liu, X; Zeng, X, 2021)
"Pretreatment with sulforaphane prevented OD-induced inflammation and AHR while increasing the uptake of OD in bronchial epithelial cells."	1.51	Organic dust, causing both oxidative stress and Nrf2 activation, is phagocytized by bronchial epithelial cells. ( Adner, M; Chen, M; Farahnak, S; Larsson, K; Martin, JG; McGovern, T, 2019)
"To examine the effect of COPD on AM phagocytic responses and identify the mechanisms, clinical consequences, and potential for therapeutic manipulation of these defects."	1.48	Opsonic Phagocytosis in Chronic Obstructive Pulmonary Disease Is Enhanced by Nrf2 Agonists. ( Barnes, PJ; Beech, G; Berbers, GAM; Bewley, MA; Brightling, CE; Budd, RC; Cole, J; Collini, P; Dockrell, DH; Donaldson, G; Donnelly, LE; Emes, RD; Kilty, I; Kolsum, U; Marshall, J; Rumsey, W; Ryan, E; Sanchez, Y; Singh, D; Tcherniaeva, I; Walmsley, SR; Wedzicha, JA; Whyte, MKB, 2018)
"Sulforaphane (SFN) is an antioxidant agent, which exerts protective effects against cell damage by activating the nuclear factor erythroid 2 like 2 (NFE2L2; Nrf2)."	1.46	Sulforaphane increases Nrf2 expression and protects alveolar epithelial cells against injury caused by cigarette smoke extract. ( Chang, J; Cui, H; Guo, D; Jiao, Z; Li, J; Nie, D, 2017)
"Chronic obstructive pulmonary disease (COPD) is currently the fifth leading cause of death worldwide."	1.37	Sulforaphane inhibits de novo synthesis of IL-8 and MCP-1 in human epithelial cells generated by cigarette smoke extract. ( Blake, DJ; Starrett, W, 2011)
"Sulforaphane treatment restored bacteria recognition and phagocytosis in alveolar macrophages from COPD patients."	1.37	Targeting Nrf2 signaling improves bacterial clearance by alveolar macrophages in patients with COPD and in a mouse model. ( Biswal, S; Brown, RH; Feller-Kopman, D; Harvey, CJ; Kong, X; Sethi, S; Thimmulappa, RK; Wise, R; Yarmus, L, 2011)
"Treatment with sulforaphane, a small-molecule activator of the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2), was also able to denitrosylate HDAC2, restoring dexamethasone sensitivity in alveolar macrophages from patients with COPD."	1.37	Denitrosylation of HDAC2 by targeting Nrf2 restores glucocorticosteroid sensitivity in macrophages from COPD patients. ( Barnes, P; Biswal, S; Feller-Kopman, D; Ito, K; Kombairaju, P; Kumar, S; Ma, J; Malhotra, D; Mercado, N; Thimmulappa, RK; Wise, R, 2011)

Research

Studies (10)

Authors

Clinical Trials (2)

Trial Overview

Trial Outcomes

Change From Baseline in Bronchial Epithelial Cell Expression of AKR1C1 at 4 Weeks

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	0 (0.00)	29.6817
2010's	9 (90.00)	24.3611
2020's	1 (10.00)	2.80

Authors	Studies
Sidhaye, VK	1
Holbrook, JT	2
Burke, A	2
Sudini, KR	2
Sethi, S	3
Criner, GJ	1
Fahey, JW	2
Berenson, CS	2
Jacobs, MR	2
Thimmulappa, R	2
Wise, RA	2
Biswal, S	4
Zeng, X	1
Liu, X	1
Bao, H	1
Jiao, Z	1
Chang, J	1
Li, J	1
Nie, D	1
Cui, H	1
Guo, D	1
Bewley, MA	1
Budd, RC	1
Ryan, E	1
Cole, J	1
Collini, P	1
Marshall, J	1
Kolsum, U	1
Beech, G	1
Emes, RD	1
Tcherniaeva, I	1
Berbers, GAM	1
Walmsley, SR	1
Donaldson, G	1
Wedzicha, JA	1
Kilty, I	1
Rumsey, W	1
Sanchez, Y	1
Brightling, CE	1
Donnelly, LE	1
Barnes, PJ	1
Singh, D	1
Whyte, MKB	1
Dockrell, DH	1
McGovern, T	1
Farahnak, S	1
Chen, M	1
Larsson, K	1
Martin, JG	1
Adner, M	1
Criner, G	1
Rayapudi, S	1
Sugar, EA	1
Singh, A	1
Talalay, P	1
Starrett, W	1
Blake, DJ	1
Harvey, CJ	1
Thimmulappa, RK	2
Kong, X	1
Yarmus, L	1
Brown, RH	1
Feller-Kopman, D	2
Wise, R	2
Malhotra, D	1
Mercado, N	1
Ito, K	1
Kombairaju, P	1
Kumar, S	1
Ma, J	1
Barnes, P	1
Garber, K	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
Enhancing Nrf2 by Sulforaphane Treatment in COPD[NCT01335971]	Phase 2	89 participants (Actual)	Interventional	2010-09-30	Completed
Analysis of Innate Immune Competence in People With Chronic Obstructive Pulmonary Disease (COPD)[NCT05743582]		189 participants (Anticipated)	Observational	2024-02-01	Not yet recruiting
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

The fifth primary design variable is the change from baseline in expression of Aldo-Keto Reductase Family 1 Member C1 (AKR1C1) in bronchial epithelial cells (BEC) at 4 weeks. Three participants - one from each treatment group - were unable to complete follow-up bronchoalveolar lavage for primary outcome data. (NCT01335971)
Timeframe: Baseline and 4 weeks

Change From Baseline in Bronchial Epithelial Cell Expression of AKR1C3 at 4 Weeks

Intervention	fold change (Median)
Placebo	1.45
Sulforaphane 25	1.08
Sulforaphane 150	0.79

The sixth primary design variable is the change from baseline in expression of Aldo-Keto Reductase Family 1 Member C3 (AKR1C3) in bronchial epithelial cells (BEC) at 4 weeks. Three participants - one from each treatment group - were unable to complete follow-up bronchoalveolar lavage for primary outcome data. (NCT01335971)
Timeframe: Baseline and 4 weeks

Change From Baseline in Bronchial Epithelial Cell Expression of HO1 at 4 Weeks

Intervention	fold change (Median)
Placebo	1.10
Sulforaphane 25	1.38
Sulforaphane 150	0.87

The fourth primary design variable is the change from baseline in expression of Heme Oxygenase 1 (HO1) in bronchial epithelial cells (BEC) at 4 weeks. Three participants - one from each treatment group - were unable to complete follow-up bronchoalveolar lavage for primary outcome data. (NCT01335971)
Timeframe: Baseline and 4 weeks

Change From Baseline in Bronchial Epithelial Cell Expression of Nrf2 at 4 Weeks

Intervention	fold change (Median)
Placebo	1.05
Sulforaphane 25	1.12
Sulforaphane 150	0.93

The second primary design variable is the change from baseline in nuclear factor erythroid 2 like 2 (Nrf2) expression in bronchial epithelial cells (BEC) at 4 weeks by analysing Nrf2 protein. Three participants - one from each treatment group - were unable to complete follow-up bronchoalveolar lavage for primary outcome data. (NCT01335971)
Timeframe: Baseline and 4 weeks

Fold-change in Isoprostane Concentrations (Follow-up to Baseline)

Intervention	fold change (Median)
Placebo	1.09
Sulforaphane 25	1.06
Sulforaphane 150	1.06

Isoprostane, an oxidant stress indicator, was measured in expired breath condensate at baseline and 4 weeks. (NCT01335971)
Timeframe: Baseline and 4 weeks

Change From Baseline in Alveolar Macrophage Expression of Nrf2 and Associated Genes at 4 Weeks

Intervention	fold change (Median)
Placebo	1.18
Sulforaphane 25	0.83
Sulforaphane 150	0.64

The first primary design variable is the change from baseline in nuclear factor erythroid 2 like 2 (Nrf2) expression in alveolar macrophages (AM) at 4 weeks by analysing Nrf2 protein and expression of a panel of Nrf2 regulated genes.Three participants - one from each treatment group - were unable to complete follow-up bronchoalveolar lavage for primary outcome data. (NCT01335971)
Timeframe: Baseline and 4 weeks

Change From Baseline in Bronchial Epithelial Cell Expression of NQ01 and Keap1 at 4 Weeks

Intervention	fold change (Median)
	NQ01	HO1	AKR1C1	AKR1C3	Nrf2	Keap1
Placebo	0.80	0.90	0.81	1.03	1.14	0.94
Sulforaphane 150	0.94	1.06	0.71	0.87	1.13	1.06
Sulforaphane 25	1.03	0.98	1.13	1.02	1.05	0.99

The third primary design variable is the change from baseline in NAD(P)H Quinone Dehydrogenase 1 (NQ01) and Kelch Like ECH Associated Protein 1 (Keap1) expression in bronchial epithelial cells (BEC) at 4 weeks. Three participants - one from each treatment group - were unable to complete follow-up bronchoalveolar lavage for primary outcome data. (NCT01335971)
Timeframe: Baseline and 4 weeks

Fold-change in Inflammatory Marker Concentrations in Bronchial Alveolar Lavage (Follow-up to Baseline) by Treatment Group

Intervention	fold change (Median)
	NQ01	KEAP1
Placebo	1.09	1.12
Sulforaphane 150	0.96	0.87
Sulforaphane 25	1.12	1.39

Inflammatory markers were measured in bronchial alveolar lavage samples at baseline and 4 weeks in the participants of this trial who had bronchoalveolar lavage samples obtained.Three participants - one from each treatment group - were unable to complete follow-up bronchoalveolar lavage. (NCT01335971)
Timeframe: Baseline and 4 weeks

Fold-change in Plasma Inflammatory Marker Concentrations (Follow-up to Baseline)

Intervention	fold change (Median)
	Interleukin-8 (pg/mg)	Secretory leukoprotease inhibitor (pg/mg)
Placebo	1.22	1.51
Sulforaphane 150	1.11	1.12
Sulforaphane 25	0.94	1.09

Inflammatory markers were measured in plasma at baseline and 4 weeks. Thiobarbituric acid reactive substances were measured in nmol malondialdehyde (MDA)/mL. (NCT01335971)
Timeframe: Baseline and 4 weeks

Fold-change in Serum Inflammatory Marker Concentrations (Follow-up to Baseline)

Intervention	fold change (Median)
	Isoprostane (ng/mg)	Thiobarbituric acid reactive substances	Total antioxidants (mM Trolox equivalents/L)
Placebo	0.89	0.96	0.97
Sulforaphane 150	0.88	1.06	0.97
Sulforaphane 25	0.90	1.05	0.92

Inflammatory markers were measured in serum samples derived from venipuncture at baseline and 4 weeks in the serum of the participants of the trial. (NCT01335971)
Timeframe: Baseline and 4 weeks

Trials

Other Studies

8 other studies available for sulforaphane and Pulmonary Disease, Chronic Obstructive

Article	Year
Compartmentalization of anti-oxidant and anti-inflammatory gene expression in current and former smokers with COPD. Respiratory research, 2019, Aug-20, Volume: 20, Issue:1 Topics: Aged; Antioxidants; Bronchi; Double-Blind Method; Epithelium; Female; Gene Expression; Humans; Infla	2019
Lack of Effect of Oral Sulforaphane Administration on Nrf2 Expression in COPD: A Randomized, Double-Blind, Placebo Controlled Trial. PloS one, 2016, Volume: 11, Issue:11 Topics: Administration, Oral; Aged; Double-Blind Method; Female; Gene Expression Regulation; Humans; Isothio	2016

Article	Year
Sulforaphane suppresses lipopolysaccharide- and Pam3CysSerLys4-mediated inflammation in chronic obstructive pulmonary disease via toll-like receptors. FEBS open bio, 2021, Volume: 11, Issue:5 Topics: Aged; Anti-Inflammatory Agents; China; Female; Humans; Inflammation; Inflammation Mediators; Isothio	2021
Sulforaphane increases Nrf2 expression and protects alveolar epithelial cells against injury caused by cigarette smoke extract. Molecular medicine reports, 2017, Volume: 16, Issue:2 Topics: Alveolar Epithelial Cells; Animals; Apoptosis; Cell Cycle; Cell Line; Cell Survival; Dose-Response R	2017
Opsonic Phagocytosis in Chronic Obstructive Pulmonary Disease Is Enhanced by Nrf2 Agonists. American journal of respiratory and critical care medicine, 2018, 09-15, Volume: 198, Issue:6 Topics: Adult; Aged; Case-Control Studies; Female; Humans; Isothiocyanates; Macrophages; Macrophages, Alveol	2018
Organic dust, causing both oxidative stress and Nrf2 activation, is phagocytized by bronchial epithelial cells. American journal of physiology. Lung cellular and molecular physiology, 2019, 09-01, Volume: 317, Issue:3 Topics: Animals; Antioxidants; Bronchi; Dust; Epithelial Cells; Inflammation; Isothiocyanates; Lung; Mice; N	2019
Sulforaphane inhibits de novo synthesis of IL-8 and MCP-1 in human epithelial cells generated by cigarette smoke extract. Journal of immunotoxicology, 2011, Volume: 8, Issue:2 Topics: Anticarcinogenic Agents; Cell Line; Chemokine CCL2; Epithelial Cells; Gene Expression Regulation; Gl	2011
Targeting Nrf2 signaling improves bacterial clearance by alveolar macrophages in patients with COPD and in a mouse model. Science translational medicine, 2011, Apr-13, Volume: 3, Issue:78 Topics: Aged; Animals; Cells, Cultured; Female; Haemophilus influenzae; Humans; Isothiocyanates; Macrophages	2011
Denitrosylation of HDAC2 by targeting Nrf2 restores glucocorticosteroid sensitivity in macrophages from COPD patients. The Journal of clinical investigation, 2011, Volume: 121, Issue:11 Topics: Adrenal Cortex Hormones; Aged; Animals; Cell Line; Dexamethasone; Drug Resistance; Glutathione; Hist	2011
Biochemistry: A radical treatment. Nature, 2012, Sep-27, Volume: 489, Issue:7417 Topics: Animals; Antioxidants; Clinical Trials as Topic; Disease Models, Animal; Free Radicals; Humans; Isot	2012

Intervention	fold change (Median)
	C-reactive protein (mg/L)	Interleukin-6 (pg/mL)	Interleukin-8 (pg/mL)
Placebo	0.99	0.75	1.06
Sulforaphane 150	1.01	1.12	1.03
Sulforaphane 25	0.90	0.90	1.04