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Natural compounds show promise in modulating heme breakdown, offering latest therapeutic avenues

The technique of heme breakdown by heme oxygenase (HMOX) yields bilirubin (BR) and biliverdin (BV) as by-products. Yellow players (YP) are enzymes involved within the production of BR and BV. YP, together with BR and BV, are considered endogenous modulators of human health and, consequently, are widely studied for his or her potential role in the event of novel therapeutics.

A recent Biomolecules study discusses the efficacy of natural compounds targeting YP.

Study: Role of Natural Compounds Modulating Heme Catabolic Pathway in Gut, Liver, Cardiovascular, and Brain Diseases. Image Credit: cones /

Natural compounds affecting bilirubin and its enzymes

Treatment with silymarin, a seed extract of milk thistle, and flavonolignans leads to a slight elevation of total serum bilirubin (TSB) concentrations. Moreover, flavonoids help treat neurodegenerative diseases and are promising chemoadjuvants. 

Fisetin, for instance, has provided promising effects in a model of amyotrophic lateral sclerosis. Luteolin, which augments HMOX1 expression, can be considered a phototherapeutic agent for Parkinson’s Disease (PD) as a result of its anti-inflammatory and antioxidant properties.  

Curcumin, which originates from Curcuma longa, is a vital polyphenolic compound that induces HMOX1. Many studies investigating the prevention of neurodegeneration and neurotoxicity have explored using curcumin as a nutraceutical. 

Astragaloside IV (AST), an energetic ingredient of Astragalus membranaceus var. mongholicus, promoted neuroprotection in rats with ischemic stroke. In Alzheimer’s disease (AD) patients, oxidative stress may very well be reduced by the consumption of vitamins C and E for one month. There’s also emerging evidence that vitamin D deficiency can result in impaired brain processes, resembling cognition, and increase the chance of AD.

Other natural compounds that affect BR and its metabolic enzymes include green tea (leaf of Camellia sinensis), madecassoside (from Centella asiatica), S-Allyl Cysteine (from the garlic bulb Allium sativum), 20C (from Gastrodia elata), and Achyranthes bidentata from the Amaranthaceae family.

Natural compounds that duplicate products of the heme catabolic pathway

Phycocyanin, phycocyanobilin (PCB), and tetrapyrroles from Spirulina platensis are examples of natural compounds that mimic products of the heme catabolic pathway.

Spirulina (Arthrospira) platensis is wealthy in carotenoids, proteins, useful fatty acids, vitamin B complex, vitamin E, and plenty of minerals, including zinc, copper, iron, manganese, magnesium, and selenium. Spirulina can be a wealthy source of potent antioxidants and has been shown to have anti-atherosclerotic and anti-cancer properties.

Attributable to their antioxidant properties, phycocyanin and PCB are novel and viable therapeutic options for the prevention of diabetic nephropathy. Research on male albino rats treated with streptozotocin has highlighted the antidiabetic effects of PCB, phycocyanin, and S. platensis.

Chinese medicine has used artificial bezoar for hundreds of years in treating human diseases. To this end, pulverized bovine gallstones with not less than 25% BR by weight are used.

Several studies have similarly confirmed the neuroprotective effects of artificial bezoar. For instance, the remarkable reduction of ischemic damage to the brain was noted when pre-treated with An-GongNiu-Huang Wan, a Chinese medicine formulation containing bovine gallstones.

Chlorophyll is present in green leafy vegetables and is related to protection against cancer and other neurodegenerative diseases. Recent studies have documented the antioxidant and antiproliferative effects of chlorophyll, including pheophytin a, chlorophyll a/b, and chlorophyllin.

Natural compounds that focus on the heme catabolic pathway

Targeting specific parts of the heme catabolic pathway is a key option to augment BR levels in tissues. Modulation of HMOX1 will be achieved through various compounds, including flavonoids, curcuminoids, caffeic acid, resveratrol, and genistein, thus demonstrating their potential role within the treatment and prevention of many autoimmune and neurodegenerative diseases.

BR-reducing bacteria within the gut lumen can alter BR levels by impacting the enterosystemic and enterohepatic circulation of BR. Nonetheless, no data on potential modulation of the gut microbiome metabolizing BR are currently available.


HMOX and its metabolic checkpoints will be modulated, which makes this method a viable goal to combat various diseases while minimally altering food plan patterns. Nevertheless, more research is required to discover key natural food products and other compounds that may goal this pathway without causing any negative effects.

Journal reference:

  • Jayanti, S., Vitek, L., Dalla Verde, C., et al. (2024) Role of Natural Compounds Modulating Heme Catabolic Pathway in Gut, Liver, Cardiovascular, and Brain Diseases. Biomolecules 14(1); 63. doi:10.3390/biom14010063
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