Thymalin

What it acts on

• ACE2 — bioinformatic cluster analysis in the cited work names ACE2 as a specific candidate target gene of the Glu-Trp (EW) dipeptide, and the same paper cites earlier evidence that EW reduces angiotensin-induced vasoconstriction through ACE2 inhibition.
• AKT1 and AKT2 — the predicted target genes of both active dipeptides converge on the AKT kinases, which the authors associate with the cytokine-storm programme; CHUK is named as a target specific to the Lys-Glu (KE) dipeptide.
• IL-1β, IL-6 and TNF-α output — in an LPS-stimulated model using human peripheral blood mononuclear cells, the complex and both of its dipeptides are reported to lower the secreted levels of all three cytokines on ELISA.
• CD44, CD117 and CD28 on human haematopoietic stem cells — a culture study reports lower stem-cell and intermediate-stage markers alongside a marked rise in CD28, which the authors take as indirect evidence of a shift toward a mature T-lymphocyte phenotype.
• Double-stranded DNA motifs — molecular docking places EW at a GGAG sequence in classical B-form DNA and KE at GCGC in the curved nucleosomal form; this is the proposed structural basis for an action at the level of gene expression, obtained by modelling rather than measurement.

What the studies report

Each item below summarises the paper it is numbered to, written from that paper's own abstract. The badge says how the evidence was produced.

1. 1.
   reviewNeuro Endocrinol Lett (2002)

   A programme review by the group that developed these organ-extract preparations, covering three decades of work on pineal, thymic and other tissue peptides. Thymalin occupies only a few lines of it: the authors state that its immunostimulating effects are the most prominent and link them to anticarcinogenic and geroprotective activity. No design, control groups or endpoints are given for the thymus-preparation experiments; the concrete data cited concern mainly the pineal preparation and the tetrapeptide Epitalon, and the paper closes by putting forward a general "peptide theory of ageing" rather than testing one.

2. 2.
   in vitroBull Exp Biol Med (2020)

   A culture study on human haematopoietic stem cells. Exposure to the complex is reported to lower CD44 (stem-cell marker) and CD117 (marker of an intermediate differentiation stage) by two- to three-fold, and to raise CD28 (mature T-lymphocyte marker) by 6.8-fold. The authors themselves call the differentiation conclusion indirect — it rests on marker expression, not on lineage tracing — and write that the targeted molecular mechanism still requires study; the closing suggestion about antiviral immunity is an inference drawn from published patient observations, not something this experiment tested.

3. 3.
   human studyAdv Gerontol (2002)

   A multi-year observation of 266 elderly participants, run jointly by the St Petersburg and Kyiv institutes, comparing thymus and pineal peptide preparations against a control group. The authors report a 2.0- to 2.4-fold lower incidence of acute respiratory illness among the peptide-treated participants taken together, and an approximately two-fold lower mortality rate over the follow-up in the thymus-preparation group, with the largest reported difference where both preparations were given. The abstract describes no randomisation, blinding or placebo; the paper is indexed as a review and reaches English only as the abstract of a Russian-language article, and every result comes from the same research programme that created the preparations. Nothing in this reference set replicates it independently.

4. 4.
   in vitroInt J Mol Sci (2023)

   The most mechanistic paper in the set, pairing modelling with a small experiment. Molecular docking assigns each active dipeptide a preferred double-stranded DNA motif, and promoter-database, pathway and protein-interaction analysis nominates AKT1/AKT2, ACE2, CYSLTR1 and CHUK as candidate targets. The experimental part is an LPS-induced inflammation model in human peripheral blood mononuclear cells, where the complex and both dipeptides lowered IL-1β, IL-6 and TNF-α by 1.4- to 6.0-fold on ELISA. The authors state the scale plainly: blood from four donors, with each cytokine assay repeated a handful of times, and the mechanism is described throughout as a potential one.

Used in research on