A nutraceutical strategy for downregulating TGFβ signalling: prospects for prevention of fibrotic disorders, including post-COVID-19 pulmonary fibrosis

DiNicolantonio, James J.; McCarty, Mark F.; Barroso-Aranda, Jorge; Assanga, Simon Bernard Iloki; Luján, Lidianys María Lewis; O’Keefe, James H.

doi:10.1136/openhrt-2021-001663

Cited by 8 publications

(7 citation statements)

References 253 publications

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“…DiNicolantonio et al. (2021) discussed Spirulina extracts, rich in phycocyanobilin (PCB) as potential downregulators of TGFβ activity. PCB is reduced to phycocyanorubinin (PCR) by biliverdin reductase.…”

Section: Immunity Boosting Nutraceuticalsmentioning

confidence: 99%

Immunity boosting nutraceuticals: Current trends and challenges

Basak

Gokhale

2021

Journal of Food Biochemistry

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The immune function of the human body is highly influenced by the dietary intake of certain nutrients and bioactive compounds present in foods. The preventive effects of these bioactive ingredients against various diseases have been well investigated. Functional foods are consumed across various diverse cultures, in some form or the other, which provide benefits greater than the basic nutritional needs. Novel functional foods are being developed using novel bioactive ingredients such as probiotics, polyunsaturated fatty acids, and various phytoconstituents, which have a range of immunomodulatory properties. Apart from immunomodulation, these ingredients also affect immunity by their antioxidant, antibacterial, and antiviral properties. The global pandemic of Severe Acute Respiratory Syndrome Coronavirus‐2 has forced the scientific community to race against time to find a proper and effective drug or a vaccine. In this review, various non‐pharmacological interventions using nutraceuticals and functional foods have been discussed. Practical applications Despite a plethora of research being undertaken to understand the immunity boosting properties of the various bioactive present in food, the findings are not translating to nutraceutical products in the market. Immunity has proved to be one of the most important factors for the health and well‐being of an individual, especially when the world has been under the grip of the novel coronavirus Severe Acute Respiratory Syndrome Coronavirus‐2. The anti‐inflammatory properties of various nutraceuticals can come out as potential inhibitors of the various inflammatory processes such as cytokine storms, usually being observed in COVID 19. This review gives an insight into how various nutraceuticals can help in the prevention of various diseases through different mechanisms. The lack of awareness and proper clinical trials pose a challenge to the nutraceutical industry. This review will help and encourage researchers to further design and develop various functional foods, which might help in building immunity.

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Section: Immunity Boosting Nutraceuticalsmentioning

confidence: 99%

Immunity boosting nutraceuticals: Current trends and challenges

Basak

Gokhale

2021

Journal of Food Biochemistry

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“…Other supplements such as soy 61 and taurine 62 could be tapped for their roles in regulating TGF‐β action directly and indirectly. Lowering TGF‐β activity could slow down fibrosis in the lungs or myocardium.…”

Section: Resultsmentioning

confidence: 99%

Clinical trials on the pharmacological treatment of long COVID: A systematic review

Chee

Fan

Young

et al. 2022

Journal of Medical Virology

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The postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection (PASC), also known as post‐acute coronavirus disease 19 (COVID‐19) or the long COVID syndrome (long COVID) is an emerging public health concern. A substantial proportion of individuals may remain symptomatic months after initial recovery. An updated review of published and ongoing trials focusing on managing long COVID will help identify gaps and address the unmet needs of patients suffering from this potentially debilitating syndrome. A comprehensive literature search was conducted on the international databases and clinical trial registries from inception to 31 July 2022. This review included 6 published trials and 54 trial registration records. There is significant heterogeneity in the characterization of long COVID and ascertainment of primary outcomes. Most of the trials are focused on individual symptoms of long COVID or isolated organ dysfunction, classified according to cardiovascular, respiratory and functional capacity, neurological and psychological, fatigue, and olfactory dysfunction. Most of the interventions are related to the mechanisms causing the individual symptoms. Although the six published trials showed significant improvement in the symptoms or organ dysfunction studied, these initial studies lack internal and external validity limiting the generalizability. This review provides an update of the pharmacological agents that could be used to treat long COVID. Further standardization of the diagnostic criteria, inclusion of participants with concomitant chronic cardiometabolic diseases and standardization of outcomes will be essential in future clinical trials.

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“…Hormonal contraceptives are associated with reduced risk of fibromyalgia in women ( 146 ). Estrogen receptor-β, Sirt1, and hydrogen sulfide can diminish TGF-β signaling ( 45 ). A study conducted by survey sampled 616 individuals (77.4% women) found new onset of fibromyalgia symptoms after COVID-19 infection occur more often in males (OR: 9.95, 95% CI 6.02 to 16.43, p < 0.0001) and in obesity (OR: 41.20, 95% CI 18.00 to 98.88, p < 0.0001) ( 107 ), although one should take into account that online surveys have intrinsic limitations and biases such as self-selection bias ( 107 ).…”

Section: Discussionmentioning

confidence: 99%

“…Upon activation, TGF-β1 promotes the formation and activity of myofibroblasts ( 45 ). Most of the TGF-β molecules are not synthesized on demand but are present in the ECM in latent form and can be activated when required ( 36 ).…”

Section: The Theoretical Model Of “Fascial Armoring”mentioning

confidence: 99%

“Long COVID-19” and viral “fibromyalgia-ness”: Suggesting a mechanistic role for fascial myofibroblasts (Nineveh, the shadow is in the fascia)

Plaut

2023

Front. Med.

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The coronavirus pandemic has led to a wave of chronic disease cases; “Long COVID-19” is recognized as a new medical entity and resembles “fibromyalgia” which, likewise, lacks a clear mechanism. Observational studies indicate that up to 30%–40% of convalescent COVID-19 patients develop chronic widespread pain and fatigue and fulfill the 2016 diagnostic criteria for “fibromyalgia.” A recent study suggested a theoretical neuro-biomechanical model (coined “Fascial Armoring”) to help explain the pathogenesis and cellular pathway of fibromyalgia, pointing toward mechanical abnormalities in connective tissue and fascia, driven by contractile myo/fibroblasts and altered extracellular matrix remodeling with downstream corresponding neurophysiological aberrations. This may help explain several of fibromyalgia’s manifestations such as pain, distribution of pain, trigger points/tender spots, hyperalgesia, chronic fatigue, cardiovascular abnormalities, metabolic abnormalities, autonomic abnormalities, small fiber neuropathy, various psychosomatic symptoms, lack of obvious inflammation, and silent imaging investigations. Pro-inflammatory and pro-fibrotic pathways provide input into this mechanism via stimulation of proto/myofibroblasts. In this hypothesis and theory paper the theoretical model of Fascial Armoring is presented to help explain the pathogenesis and manifestations of “long COVID-19” as a disease of immuno-rheumo-psycho-neurology. The model is also used to make testable experimental predictions on investigations and predict risk and relieving factors.

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A nutraceutical strategy for downregulating TGFβ signalling: prospects for prevention of fibrotic disorders, including post-COVID-19 pulmonary fibrosis

Cited by 8 publications

References 253 publications

Immunity boosting nutraceuticals: Current trends and challenges

Immunity boosting nutraceuticals: Current trends and challenges

Clinical trials on the pharmacological treatment of long COVID: A systematic review

“Long COVID-19” and viral “fibromyalgia-ness”: Suggesting a mechanistic role for fascial myofibroblasts (Nineveh, the shadow is in the fascia)

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