Chlorella is a green unicellular alga that is commercially produced and distributed worldwide as a dietary supplement. Chlorella products contain numerous nutrients and vitamins, including D and B₁₂, that are absent in plant-derived food sources. Chlorella contains larger amounts of folate and iron than other plant-derived foods. Chlorella supplementation to mammals, including humans, has been reported to exhibit various pharmacological activities, including immunomodulatory, antioxidant, antidiabetic, antihypertensive, and antihyperlipidemic activities. Meta-analysis on the effects of Chlorella supplementation on cardiovascular risk factors have suggested that it improves total cholesterol levels, low-density lipoprotein cholesterol levels, systolic blood pressure, diastolic blood pressure, and fasting blood glucose levels but not triglycerides and high-density lipoprotein cholesterol levels. These beneficial effects of Chlorella might be due to synergism between multiple nutrient and antioxidant compounds. However, information regarding the bioactive compounds in Chlorella is limited.

High homocysteine (Hcy) levels, mainly caused by vitamin B₁₂ deficiency, have been reported to induce amyloid-β (Aβ) formation and tau hyperphosphorylation in mouse models of Alzheimer’s disease. However, the relationship between B₁₂ deficiency and Aβ aggregation is poorly understood, as is the associated mechanism. In the current study, we used the transgenic C. elegans strain GMC101, which expresses human Aβ_1–42 peptides in muscle cells, to investigate the effects of B₁₂ deficiency on Aβ aggregation–associated paralysis. C. elegans GMC101 was grown on nematode growth medium with or without B₁₂ supplementation or with 2-O-α-D-glucopyranosyl-L-ascorbic acid (AsA-2G) supplementation. The worms were age-synchronized by hypochlorite bleaching and incubated at 20 °C. After the worms reached the young adult stage, the temperature was increased to 25 °C to induce Aβ production. Worms lacking B₁₂ supplementation exhibited paralysis faster and more severely than those that received it. Furthermore, supplementing B₁₂-deficient growth medium with AsA-2G rescued the paralysis phenotype. However, AsA-2G had no effect on the aggregation of Aβ peptides. Our results indicated that B₁₂ supplementation lowered Hcy levels and alleviated Aβ toxicity, suggesting that oxidative stress caused by elevated Hcy levels is an important factor in Aβ toxicity.

Adenyl cobamide (commonly known as pseudovitamin B₁₂) is synthesized by intestinal bacteria or ingested from edible cyanobacteria. The effect of pseudovitamin B₁₂ on the activities of cobalamin-dependent enzymes in mammalian cells has not been studied well. This study was conducted to investigate the effects of pseudovitamin B₁₂ on the activities of the mammalian vitamin B₁₂-dependent enzymes methionine synthase and methylmalonyl-CoA mutase in cultured mammalian COS-7 cells to determine whether pseudovitamin B₁₂ functions as an inhibitor or a cofactor of these enzymes. Although the hydoroxo form of pseudovitamin B₁₂ functions as a coenzyme for methionine synthase in cultured cells, pseudovitamin B₁₂ does not activate the translation of methionine synthase, unlike the hydroxo form of vitamin B₁₂ does. In the second enzymatic reaction, the adenosyl form of pseudovitamin B₁₂ did not function as a coenzyme or an inhibitor of methylmalonyl-CoA mutase. Experiments on the cellular uptake were conducted with human transcobalamin II and suggested that treatment with a substantial amount of pseudovitamin B₁₂ might inhibit transcobalamin II-mediated absorption of a physiological trace concentration of vitamin B₁₂ present in the medium.

Pear juice concentrate prepared by boiling Japanese pear (Pyrus pyrifolia Nakai cv. Nijisseiki) juice can significantly inhibit the activity of tyrosinase, a key enzyme in melanin synthesis in human skin. Using the ethanol extract of pear juice concentrate, we homogeneously purified an active compound that was identified as 5-hydroxymethyl-2-furaldehyde (5-HMF) through 1H- and 13C-NMR and mass spectroscopy. We observed that 5-HMF inhibited the monophenolase and diphenolase activities of mushroom tyrosinase as a mixed-type inhibitor (Ki values of 3.81 and 3.70 mmol/L, respectively). In B16 mouse melanoma cells, treatment with 170 µmol/L of 5-HMF significantly reduced α-melanocyte-stimulated melanin synthesis by suppressing the cyclic adenosine monophosphate-dependent signaling pathway involved in melanogenesis. The results of our study indicated that 5-HMF can be potentially used as a skin-lightening agent in the cosmetic industry. Abbreviations: AC: adenylate cyclase; CREB: cAMP response element-binding protein; dhFAME: S-(−)-10,11-Dihydroxyfarnesoic acid methyl ester; DMEM: dulbecco′s modified eagle medium; l-DOPA: 3-(3,4-Dihydroxyphenyl)- l-alanine; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; HEPES: 4-(2-Hydroxyethyl)-1-piperazine ethane sulfonic acid; 5-HMF: 5-Hydroxymethyl-2-furaldehyde; MITF: microphthalmia-associated transcription factor; α-MSH: α-Melanocyte-stimulating hormone; PKA: protein kinase A; PVDF: polyvinylidene difluoride; SDS: sodium dodecyl sulfate; TRP1: tyrosinase-related protein 1; TRP2: tyrosinase-related protein 2