TMEA, a Polyphenol in Sanguisorba officinalis, Promotes Thrombocytopoiesis by Upregulating PI3K/Akt Signaling

Abstract

Thrombocytopenia is closely linked with hemorrhagic diseases, for which induction of thrombopoiesis shows promise as an effective treatment. Polyphenols widely exist in plants and manifest antioxidation and antitumour activities. In this study, we investigated the thrombopoietic effect and mechanism of 3,3′,4′-trimethylellagic acid (TMEA, a polyphenol in Sanguisorba officinalis L.) using in silico prediction and experimental validation. A KEGG analysis indicated that PI3K/Akt signalling functioned as a crucial pathway. Furthermore, the virtual molecular docking results showed high-affinity binding (a docking score of 6.65) between TMEA and mTOR, suggesting that TMEA might target the mTOR protein to modulate signalling activity. After isolation of TMEA, in vitro and in vivo validation revealed that this compound could promote megakaryocyte differentiation/maturation and platelet formation. In addition, it enhanced the phosphorylation of PI3K, Akt, mTOR, and P70S6K and increased the expression of GATA-1 and NF-E2, which confirmed the mechanism prediction. In conclusion, our findings are the first to demonstrate that TMEA may provide a novel therapeutic strategy that relies on the PI3K/Akt/mTOR pathway to facilitate megakaryocyte differentiation and platelet production.

Methyl Gallate Alleviates Acute Ulcerative Colitis by Modulating Gut Microbiota and Inhibiting TLR4/NF-κB Pathway

“…Ulcerative colitis, a chronic and complicated inflammatory disease, is characterized by abdominal pain, diarrhea, rectal bleeding and hematochezia, which greatly affects the life quality of patients. UC has evolved into a global disease, posing major challenges to health care systems around the world [4,37,38]. Currently, clinical medications used for the treatment of UC include aminosalicylates and corticosteroids; however, some of them are expensive and have serious side effects.…”

The Application of Ethnomedicine in Modulating Megakaryocyte Differentiation and Platelet Counts

“…The researchers innovatively combined network pharmacology with traditional Chinese medicine pharmacology to systematically study the relationship between drugs and diseases and verified the accuracy of network pharmacology prediction through experiments. Therefore, a new idea of the relationship between the target and mechanism of botanical drugs in the treatment of diseases has been developed [ 49 , 50 , 51 , 52 ].…”

Anti-atherosclerosis mechanisms associated with regulation of non-coding RNAs by active monomers of traditional Chinese medicine

“…For example, a moderate dosage of marijuana proves highly efficient in alleviating chronic pain (Carter et al, 2015), but marijuana can also cause cardiovascular side effects, such as endothelial dysfunction and atherosclerosis (Feng et al, 2022). Proanthocyanidin A1 can promotes the production of platelets to ameliorate chemotherapy-induced thrombocytopenia (Wang et al, 2022) and TMEA, a polyphenol in Sanguisorba officinalis L., can facilitate megakaryocyte differentiation and platelet production (Li et al, 2021a). However, the increased platelets can raise the risk of blood clot formation in patients with atherosclerosis (Barrett et al, 2019).…”