Thymosin Alpha-1 10mg

▎Thymosin Alpha-1 Structure

▎Thymosin Alpha-1 Research

Molecular Background

Thymosin α-1 (Tα1) is a thymus-derived peptide investigated for immunomodulatory activity and inflammation- and oxidative-stress-related responses in experimental systems. Published studies have examined its associations with T-cell differentiation, thymic-related markers, and the activity of dendritic cells and macrophages in defined research models^[1].

Research Progress

Xinmei Kang’s research reported in cellular and mouse experiments that the thymus-derived peptide thymosin α-1 (Tα1) may act as a non-classical ligand for the orexin receptor 1 (HCRTR1), a typical neuropeptide receptor on neurons. In the tested neuronal models, this interaction was associated with lower cell-death-related readouts and reduced activity of receptor-interacting protein kinase 3 (RIPK3), a mediator of necroptosis. The authors also reported an association between circulating Tα1 levels and ischemic-stroke severity in observational patient samples and mouse models; this association is not evidence of a therapeutic effect in humans. In the mouse model, Ptma deletion was associated with greater injury, whereas experimental Tα1 exposure was associated with differences in neuronal injury and functional outcomes^[2].

Fig1. Neuronal survival and functional outcome measurements in a mouse stroke model involving endogenous Tα1. WT and Ptma+/− male C57/Bl6 mice were subjected to 60 min of tMCAO and sacrificed at 3d or 14d after tMCAO^[2].
(A) Timeline of experimental design. (B) Survival of mice in each group was recorded at 0–14 days after tMCAO. N = 20 in each group. Exact p values are provided. compared with WT, by log-rank test. (C) Neurological deficit score was assessed at 0–3d after tMCAO. N = 10 in each group. compared with WT, **p < 0.01, by Two-way ANOVA (mean ± standard deviation). (D) Infarct volume was quantified with immunostaining of NeuN with coronal sections collected at 3d after tMCAO. Representative images were displayed. Dashed lines outlined the infarct area. N = 10 in each group.*p < 0.05, compared with WT, by Student's t test (mean ± standard deviation). (E) Neuronal injury in stroke penumbra was evaluated with co-immunostaining of NeuN (red) and TUNEL (green) at 3d after tMCAO. Representative images of NeuN+TUNEL+ neurons in stroke were displayed. N = 4 in each group. **p < 0.01, compared with WT, by Student's t test (mean ± standard deviation). (F) Infarct volume was quantified with immunostaining of NeuN with coronal sections collected at 14d after tMCAO. Representative images were displayed. Dashed lines outlined the infarct area. N = 10 in each group.**p < 0.01, compared with WT, by Student's t test (mean ± standard deviation). (G) Representative images and quantification of white matter damage in the corpus callosum (CC), external capsule (EC), striatum (STR), and cortex (CTX) at 14 days post-tMCAO. N = 4 in each group. *p < 0.05, **p < 0.01, compared with WT, by Two-way ANOVA (mean ± standard deviation). (H) Sensorimotor functions of the stroke models were evaluated by adhesive-removal test, foot-fault test and rotarod test at 3–14d after tMCAO. N = 12 in each group, *p < 0.05, **p < 0.01, compared with WT, by Two-way ANOVA (mean ± standard error). (I) Morris water maze test at 10–14 days after tMCAO. Representative images of the swim paths of mice in each group while the platform was present (learning phase) or removed (memory phase). N = 12 per group. **p < 0.01, ***p < 0.001. In the learning phase, Two-way ANOVA was used. In the memory phase, Student's t test and nonparametric test were used.

Yiting Wei found that after chemotherapy in observational patient samples and in tumor-bearing mice, circulating levels of thymosin α-1 (Tα-1)—a key endogenous peptide hormone with immunomodulatory activity—decreased. After antibodies (ABs) were internalized into the endolysosomal compartments of dendritic cells (DCs), Tα-1 bound to tumor-specific ABs and interacted with the microRNAs carried by the ABs, including miR146a-5p. In the reported experiments, interaction with Tα-1 was associated with reduced miR146a-5p degradation mediated by lysosomal ribonuclease A and with Toll-like receptor 7 (TLR7)-related dendritic-cell (DC) maturation, migration, and tumor-antigen presentation to CD8+ T cells. In mice bearing established tumors with high miR146a-5p expression, the researchers reported TLR7-dependent differences in tumor-related outcomes with experimental Tα-1 plus chemotherapy exposure; these findings do not establish clinical benefit^[3].

1. S. Espinar-Buitrago investigated in vitro immune-cell responses to Tα1 in a human cytomegalovirus (HCMV)-related experimental system. Dendritic cells (DCs) were isolated from peripheral blood mononuclear cells (PBMCs) by negative selection and cultured in the presence or absence of Tα1. The immunophenotype of the DCs was assessed by multiparameter flow cytometry, evaluating expression of CD40, CD80, TIM-3, and PDL-1, as well as intracellular TNF-α production. Subsequently, autologous CD4+ or CD8+ T lymphocytes (TLs) isolated from PBMCs via negative selection were co-cultured with DCs previously treated with Tα1. Regardless of the presence or absence of HCMV, intracellular TNF-α, IFN-γ, and IL-2 production, as well as CD40-L and PD-1 expression, were assessed via immunophenotyping, and the multifunctionality of total TLs and memory subsets was evaluated. The results showed changes in measured CD40, CD80, TIM-3, and TNF-α markers after Tα1 exposure, alongside lower PDL-1 expression in some cultured dendritic-cell subsets, particularly plasmacytoid dendritic cells (pDCs). Within these co-culture assays, the authors reported differences in TNF-α, IFN-γ, and IL-2 measurements in total and memory subsets of CD4+ and CD8+ TLs, together with changes in CD40/CD40-L and PDL-1/PD-1 expression^[4].

Fig.2. Culture and immunophenotyping of DCs. DCs were isolated from PBMCs and cultured (50.000 DCs) overnight in RPMI 10% with/without Tα1 treatment at 37 °C/5% CO2. Representative images were captured using a DMIL Leica microscope at 20X (Scale bar 100 µm). Black arrow indicates a region of aggregation and morphological changes towards a mature DCs phenotype in Tα1 treatment condition^[4].
(a). Scatter dots graphs represent the expression of each biomarker in total DCs (tDCs), myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs): CD40 (b), CD80 (c), TIM-3 (d), PDL-1 (e) and intracellular TNFα production (f). Medians with the interquartile ranges are shown. Ex-vivo: Ex-vivo condition; UT: Untreated condition; Tα1: Tα1 treated condition. Each dot represents an individual (n = 20). tDCs are highlighted with red triangle dots, mDCs with green circle dots, and pDCs with orange square dots. Statistical significance was determined using the Wilcoxon test to compare paired events (ns: not statistically significative, #0.05 ≤ p < 0.1; *p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001). Representative merged cytometry dot plots with Ex-vivo (grey), UT (green) and Tα1 (red) experimental condition for each biomarker: CD40 (b), CD80 (c), TIM-3 (d), PDL-1 (e); TNFα (f) in tDCs (left), mDCs (middle) and pDCs (right) are provided.

Indu Bala evaluated the cytotoxicity and nitric-oxide-related responses of Tα-1 on RAW 264.7 cells. The cytotoxic effect of Tα-1 was assessed using the MTT assay, which determined that its half-maximal inhibitory concentration (IC₅₀) for RAW 264.7 cells was 368.105 μg/mL. Morphological observations conducted at different concentrations of Tα-1 showed that cytotoxicity in RAW 264.7 cells increased and cell density decreased as the test concentration rose. Additionally, the nitric-oxide-related response to Tα-1 was evaluated by analyzing nitric oxide (NO) production in RAW 264.7 cells. Compared with the control group, NO production decreased as test concentrations increased during cell-culture exposure in the concentration range of 7.813 to 31.25 μg/mL^[5].

Chaoyu Chen’s study found that, in vitro, Tα1 stimulation of MoDCs was associated with differences in immune-cell measurements and the secretion of the interleukin-15/RA complex (p < 0.001). This interaction with the interleukin-2 Rβ/γ receptor on T cells was associated with higher measured levels of CCL3/5, interferon-γ, and tumor necrosis factor-α in CD8+ T cells (p < 0.05), was associated with lower p24 levels in CD4+ T cells (p = 0.002), and lower HIV-1 integrated DNA levels (p = 0.012). Furthermore, following co-culture, the secretion levels of interferon-γ, tumor necrosis factor-α, and granzyme B in NK cells, as well as the proportion of CD8+ T VM cells, increased significantly. In this in vitro system, these measures were negatively correlated with reservoir-size and reactivation readouts. However, these effects were observed in PBMCs from immunoresponders (CD4+ T-cell count > 350 cells/µL) but not in non-responders. The authors interpreted these cell-culture findings as evidence of altered dendritic-cell interleukin-15 signaling, CD8+ T-cell responses, and measures related to viral reservoir activity, without demonstrating clinical effects^[6].

Fig3. IL-15/RA complex secretion measured in an in vitro Tα1 experiment^[6].
(a) morphological differentiation from THP-1 to MoDCs after 4-6d (400x). (b) representative gate of mature CD14+CD11c+ MoDCs compared to THP-1. (c) morphological observation of MoDCs under a high-power microscope (1000x). (d) proportions of four surface markers of MoDCs (n = 3). (e) proportions of surface marker of THP-1 and MoDCs (n = 3). (f) ELISA results of IL-15 and IL-15/RA complex between groups (n = 9 for THP-1, n = 15 for MoDC). (g) intracellular IL-15 and IL-15RA of MoDCs (n = 3). (h) qPCR results of IL15 and IL15RA (n = 3). MoDCs: monocyte-derived dendritic cells; qPCR, quantitative polymerase chain reaction. Statistical method used in this figure was unpaired Student’s t-test.

María de la Sierra Espinar-Buitrago investigated the in vitro immunological effects of combined in vitro exposure to thymosin α1 (Tα1) and polyanionic carbosilane dendrimers (PCD) on peripheral blood mononuclear cells (PBMCs) during HCMV infection. The biocompatibility of PCD was assessed using MTT and LDH assays. PBMCs were first pretreated with the combined compounds and then exposed to HCMV for 48 hours. Morphological changes in PBMCs were observed using light microscopy, and total dendritic cells (tDCs), myeloid dendritic cells (mDCs), plasma cell-like dendritic cells (pDCs), as well as CD4⁺/CD8⁺ T cells and regulatory T cells (Tregs) were characterized using multiparameter flow cytometry. The results showed that exposure to Tα1 + PCD was associated with changes in dendritic-cell activation and maturation markers. Furthermore, exposure to Tα1 + G2 - S24P was associated with increased co-receptor expression and IFNγ measurements in T cells, together with changes in Treg-related and cell-state markers. In contrast, exposure to Tα1 + G2S16 was associated with lower co-receptor expression and cytokine measurements in T cells, alongside a different pattern of Treg-related and cell-state markers^[7].

Fengtian Wu established an in situ HCC model in aged C57BL/6 mice (22–26 months) and compared saline, IL-15, Tα1, and combined-exposure groups. Tumor progression was monitored via bioluminescence imaging, survival analysis, and histopathology, while the phenotype and function of CD8+ T cells in the liver were assessed using multicolor flow cytometry, immunofluorescence, transcriptomic sequencing, and Western blotting. Separate in vitro assays were performed using primary human CD8+ T cells co-cultured with Huh7 hepatocellular carcinoma cells. In this mouse model, the combined-exposure group showed lower tumor burden and longer survival than the comparison groups; experimental analyses also identified differences in hepatic CD8+ T-cell phenotypes, proliferation measures, and cytotoxic mediators including granzyme B, perforin, and interferon-γ. Transcriptomic and proteomic analyses indicated that the combined-exposure group differed in measures of activation of the phosphoinositide 3-kinase/protein kinase B signaling pathway in hepatic CD8+ T cells^[8].

Research Limitations

An important limitation in interpreting Tα1 research is that reported receptor interactions and downstream signaling depend on the experimental model and cellular context. A recent study reported an interaction with hypocretin (orexin) receptor 1 (HCRTR1) in neuronal models with RIPK3-related cell-death measurements, whereas studies of immune cells have described other pathways, including TLR7-related mechanisms in specific dendritic-cell experiments. These findings should not be generalized into a single established mechanism or a claim of clinical efficacy across cell types (e.g., dendritic cells, macrophages, and T cells)^{[2, 3]}.

Differences in the characterization and preparation of Tα1 materials across laboratories and manufacturers may limit comparability among experimental studies. Furthermore, the stability of Tα1 during storage cannot be overlooked; temperature fluctuations or prolonged storage may lead to peptide chain aggregation or degradation, thereby affecting experimental reproducibility and analytical interpretation^[1].

COCER Peptides presents Thymosin α-1 for laboratory research use only. Not for human or veterinary administration, consumption, or clinical use. The research discussed above summarizes findings reported in the cited literature and does not establish human clinical safety or efficacy, or provide directions for use; no FDA approval is claimed.

▎Relevant Citations

References

[1] Simonova M A, Ivanov I, Shoshina N S, et al. Aging and Thymosin Alpha-1[J]. International Journal of Molecular Sciences, 2025,26(23):11470.

DOI:10.3390/ijms262311470.

[2] Kang X, Wang S, Zhang L, et al. Thymosin Alpha‐1 Provides Direct Neuroprotection by Engaging the Orexin Receptor HCRTR1 to Suppress Neuronal Necroptosis[J]. Advanced Science, 2026.

DOI:10.1002/advs.202522372.

[3] Wei Y, Chen J, Zhang Y, et al. Thymosin Alpha-1 Restores Chemotherapy-Induced Antitumor Immunity by Chaperoning a MicroRNA Ligand of TLR7 in Dendritic Cells[J]. Cancer Research, 2026,86(17):4238-4254.

DOI:10.1158/0008-5472.can-25-5547.

[4] Espinar-Buitrago M S, Vazquez-Alejo E, Magro-Lopez E, et al. Immune modulation via dendritic cells by the effect of Thymosin-alpha-1 on immune synapse in HCMV infection[J]. International Immunopharmacology, 2023,125:111103.

DOI:10.1016/j.intimp.2023.111103.

[5] Indu Bala U, Navita Gupta U, Pranav Kumar Prabhakar U. The Effects of Thymosin Alpha-1 on Macrophages: A Cytological and Anti-Inflammatory Study[J]. Journal of Advanced Zoology, 2023,44:1720-1725.

DOI:10.17762/jaz.v44is-5.1428.

[6] Chen C, Xun J, Wang J, et al. Thymosin α1-induced secretion of IL-15/RA complex by THP-1 derived dendritic cells restrains HIV latency in vitro[J]. Virulence, 2026,17(1).

DOI:10.1080/21505594.2026.2645858.

[7] Espinar-Buitrago M D L S, Magro-López E, Vázquez-Alejo E, et al. Enhanced Immunomodulatory Effects of Thymosin-Alpha-1 in Combination with Polyanionic Carbosilane Dendrimers against HCMV Infection[J]. International Journal of Molecular Sciences, 2024,25(4):1952.

DOI:10.3390/ijms25041952.

[8] Wu F, Guo Z, Guan J, et al. IL-15 Plus Thymosin α1 Reduces Senescent Hepatic CD8+ T Cells in Hepatocellular Carcinoma via PI3K/AKT Suppression[J]. Journal of Gastroenterology and Hepatology, 2026,41(5):1600-1613.

DOI:10.1111/jgh.70359.

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