Pyrrole-2-carboxaldehyde (Py-2-C) derivatives have been isolated from many natural sources, including fungi, plants (roots, leaves, and seeds), and microorganisms. The well-known diabetes molecular marker, pyrraline, which is produced after sequential reactions in vivo, has a Py-2-C skeleton. Py-2-Cs can be chemically produced by the strong acid-catalyzed condensation of glucose and amino acid derivatives in vitro. These observations indicate the importance of the Py-2-C skeleton in vivo and suggest that molecules containing this skeleton have various biological functions. In this review, we have summarized Py-2-C derivatives based on their origins. We also discuss the structural characteristics, natural sources, and physiological activities of isolated compounds containing the Py-2-C group.

Three pyrrole alkaloid derivatives were isolated from the edible mushroom Basidiomycetes-X (Echigoshirayukidake) by water extraction followed by ethyl acetate fractionation. The chemical structures determined by MS and NMR were 4-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl] butanoic acid (compound I), 4-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl] butanamide (compound II), and 5-(hydroxymethyl)-1H-pyrrole-2-carboxaldehyde (compound III). Compound I was found to be the major component, followed by compound II, and compound III was the minor component. The dry powder of Basidiomycetes-X contained approximately 825 μg g⁻¹ compound I and 484 μg g⁻¹ compound II. Compound II was found to be a novel pyrrole aldehyde homologue not previously reported and thus is a specific component of this mushroom.

Aging is a predominant risk factor for the development and progression of cardiovascular complications. Physiologically and anatomically, the heart undergoes numerous changes that result in poor cardiac function in the elderly population. Recently, several studies have provided promising results, confirming the ability of the senescence-accelerated mouse-prone 8 (SAMP8) model to accurately model age-related cardiovascular alterations. In this study, using a murine model of senescence, SAMP8, we aimed to investigate the effect of 3,4-dihydroxybenzalacetone (DBL), a catechol-containing phenylpropanoid derivative isolated from Inonotus obliquus (Chaga), on cardiac aging. DBL was administered at the doses of 10 mg/kg and 20 mg/kg by oral gavage to SAMP8 mice to examine aging-mediated cardiac changes, such as oxidative DNA damage, oxygen radical antioxidant capacity (ORAC) value, fibrosis, inflammation, and apoptosis. The treatment with DBL at both doses significantly reduced aging-mediated oxidative DNA damage, and simultaneously increased the ORAC value in the SAMP8 assay. Cardiac fibrosis was assessed with Azan-Mallory staining, and the number of cardiac remodeling markers was found to be significantly reduced after the treatment with DBL. We also observed a decrease in cardiomyocyte apoptosis as measured by the terminal transferase-mediated dUTP nick end labeling (TUNEL) staining method and the caspase-3 levels in SAMP8 mice compared with senescence-resistant control (SAMR1) mice. The findings from this study suggest that DBL has a potentially beneficial effect on aging-mediated myocardial alterations. Further studies are warranted to confirm the promising potential of this catechol compound against aging-associated myocardial dysfunction.

Mibyou has been defined in traditional oriental medicine as a certain physiological condition whereby an individual is not ill but not healthy; it is also often referred to as a sub-healthy condition. In a society focused on longevity, “Mibyou-care” becomes of primary importance for healthy lifespan expenditure. Functional foods can play crucial roles in Mibyou-care; thus, the search for novel resources of functional food is an important and attractive research field. Mushrooms are the target of such studies because of their wide variety of biological functions, such as immune modulation and anti-obesity and anticancer activities, in addition to their nutritional importance. Basidiomycetes-X (BDM-X; Shirayukidake in Japanese) is a mushroom which has several attractive beneficial health functions. A metabolome analysis revealed more than 470 components of both nutritional and functional interest in BDM-X. Further isolation and purification studies on its components using radical scavenging activity and UV absorbance identified ergosterol, (10E,12Z)-octadeca-10,12-dienoic acid (CLA), 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one (DDMP), formyl pyrrole analogues (FPA), including 4-[2-foemyl-5-(hydroxymethyl)-1H-pyrrole-1-yl] butanamide (FPAII), adenosine and uridine as major components. Biological activities attributed to these components were related to the observed biological functions of BDM-X, which suggest that this novel mushroom is a useful resource for Mibyou-care functional foods and medicines.

Inserting a sulfur atom into the 1,2-dithiolane ring of lipoic acid (LA racemate) is a promising approach for improving the diversity of lipoic acid (LA racemate). For this purpose, we prepared 1,2,3-trisulfur–lipoic acid derivatives (trisulfur lipoic acid (R-enantiomer, TR-LA, trisulfur lipoamide, racemate TLPA)) by the reaction of R-LA (lipoic acid R-enantiomer) or lipoamide (LPA) and H₂S and performed precise stereochemical studies. As a result, the 6-membered-1,2,3-trisulfur ring (TR-LA and TLPA) showed a completely different profile from that of the five-membered dithiolane compounds (R-LA and LPA) in ¹H- and ¹³C-NMR spectroscopy. Raman spectroscopy of TR-LA and TLPA showed a different profile to that of LA and LPA, which also indicates the uniqueness of the 6-membered 1,2,3-trisulfur ring chromophore. The regeneration of lipoic acid from 1,2,3-trisulfur lipoic acid (TR-LA) was achieved using a phosphine derivative and sodium cyanide while maintaining the stereochemistry of the chirality center, with an almost quantitative yield.