Mulberroside C

Mulberroside C is one of the main bioactive components in white mulberry (Morus alba L.). Mulberroside C exhibits antiplatelet, antiviral and neutrophil-regulating activities, and binds to EV-A71 VP1 with a K_d value of 1.289 nM. Mulberroside C reduces the phosphorylation level of ERK, promotes the phosphorylation of IP3RI at the Ser¹⁷⁵⁶ site, and decreases calcium influx and calcium mobilization. Mulberroside C inhibits the expression of P-selectin (P-selectin). Mulberroside C upregulates the cyclic nucleotide signaling pathway in human platelets. Mulberroside C binds to IL-23R, upregulates the expression of G-CSF, GM-CSF and RASGRP1, and activates the RAS/ERK signaling pathway. Mulberroside C promotes neutrophil maturation, accelerates the recovery of leukopenia, and enhances the antibacterial activity of neutrophils. Mulberroside C inhibits the replication of hepatitis C virus in replicon cells. Mulberroside C prevents the uncoating and genome release of EV-A71, and inhibits the synthesis of viral proteins and RNA. Mulberroside C can be used in studies related to thrombosis-mediated cardiovascular diseases, chemotherapy- and radiotherapy-induced leukopenia, hepatitis C virus infection, and hand, foot and mouth disease^[1][2][3]. In Vitro:Mulberroside C (50-150 μM; 2 min preincubation, 5 min aggregation) dose-dependently inhibits washed human platelet aggregation induced by Collagen (HY-NP003), Thrombin (HY-114164) and U46619 (HY-108566), with an IC₅₀ of 77.3 μM against collagen-induced aggregation, and shows no cytotoxicity at the tested concentrations^[1].
Mulberroside C (50-150 μM; 3 min preincubation) reduces collagen-induced intracellular Ca²⁺ mobilization in washed human platelets in a dose-dependent manner^[1].
Mulberroside C (50-150 μM; 2 min preincubation, 5 min Collagen stimulation) regulates platelet signaling pathways in washed human platelets by upregulating the phosphorylation levels of IP₃RI and VASP, and downregulating the phosphorylation levels of ERK, cPLA₂, p38 MAPK, PI3K, Akt and PLCγ₂^[1].
Mulberroside C (50-150 μM; 0-6 min) dose-dependently inhibits collagen-induced P-selectin expression (α-granule release), serotonin and ATP release (δ-granule secretion), and thromboxane A₂ production in washed human platelets. It also suppresses collagen-induced fibrinogen binding to αIIb/β₃ in washed human platelets, and elevates intracellular cAMP and cGMP levels in human platelets^[1].
Mulberroside C (50-150 μM; 30 min preincubation, 15 min clot reaction) dose-dependently inhibits thrombin-induced fibrin clot retraction in human platelet-rich plasma^[1].
Mulberroside C directly binds to human IL-23R with a binding score of 6.36 kcal/mol^[2].
Mulberroside C (5-20 μM; 5 days) dose-dependently increases the proportion of CD11b-positive differentiated myeloid cells in NB4 and HL-60 cell lines, induces morphological differentiation of cells into mature neutrophils, and promotes the functional differentiation of NB4 cells into mature neutrophils^[2].
Mulberroside C (5-20 μM; 5 days) dose-dependently enhances the bactericidal activity of differentiated NB4 cells against *Staphylococcus aureus*^[2].
Mulberroside C (5-20 μM; 5 days) dose-dependently upregulates the expression of IL-23R, G-CSF, GM-CSF and RASGRP1 in NB4 cells, as well as the expression of IL-23R, RASGRP1, RAS, phosphorylated ERK, and myeloid transcription factors PU.1, c-Fos, CEBPA and RUNX1 in NB4 cells^[2].
Mulberroside C (3.125-400 µM; 48 h) exhibits low cytotoxicity towards RD cells (CC₅₀ = 94.82 µM) and Vero cells (CC₅₀ = 257.1 µM)^[3].
Mulberroside C (1.5625-50 µM; 48 h) potently inhibits the cytopathic effects induced by EV-A71 (BrCr strain) in RD cells (IC₅₀ = 2.09 µM) and Vero cells (IC₅₀ = 35.48 µM)^[3].
Mulberroside C (12.5-50 µM; 4 days) reduces plaque formation of EV-A71 (BrCr strain) in Vero cells in a dose-dependent manner^[3].
Mulberroside C (12.5-50 µM; 24-48 h) dose-dependently inhibits EV-A71 (BrCr strain) RNA synthesis in RD cells, and at 48 h post-infection, the 50 µM concentration reduces viral RNA levels by more than 10,000-fold^[3].
Mulberroside C (12.5-50 µM; 24 h) dose-dependently inhibits the VP1 protein expression of EV-A71 (BrCr strain) in RD cells^[3].
Mulberroside C (25 µM, administered at post-infection (pi) -1 to 12 h, 0 to 12 h, 1 to 12 h, 3 to 12 h, 6 to 12 h, and 9 to 12 h) mainly inhibits the replication of EV-A71 (BrCr strain) at the early stage of RD cell infection, and significant antiviral activity is observed when it is added within 3 h post-infection^[3].
Mulberroside C (50 µM; mixed with virus for 1 h, followed by 1 h of cell incubation) significantly inhibits the adsorption of EV-A71 (BrCr strain) to RD cells^[3].
Mulberroside C (1.5625-50 µM; 48 h) inhibits the replication of EV-A71 (strain CC063) (IC₅₀ = 7.237 µM) and CV-A16 (strain CC045) (IC₅₀ = 15.24 µM) in RD cells^[3].
Mulberroside C (46.88-1500 µM; 30 s association, 30 s dissociation) binds to purified EV-A71 VP1 protein in a concentration-dependent manner, with a dissociation constant (K_d) of 1.289 nM^[3]. In Vivo:Mulberroside C (5-20 μM; immersion; continuous; from 3 dpf to 6 dpf) dose-dependently increases the neutrophil levels in zebrafish with irradiation- or chemotherapy-induced leukopenia and promotes the recovery from leukopenia^[2].
Mulberroside C (2-8 mg/kg, i.p.; once daily; for 11 consecutive days) dose-dependently restores white blood cell counts, promotes the proliferation and maturation of neutrophils, enhances bacterial clearance capacity, and exhibits favorable safety profiles in a mouse model of irradiation-induced leukopenia^[2].
Mulberroside C (2-8 mg/kg, i.p.; once daily for 7 consecutive days) dose-dependently promotes the recovery of peripheral blood leukocyte levels in mice with chemotherapy-induced leukopenia^[2].
Mulberroside C (25-50 mg/kg, i.p.; once daily; for 5 consecutive days) increases the survival rate of neonatal ICR mice to 30% at the dose of 50 mg/kg, reduces clinical scores, decreases viral loads in multiple tissues, and alleviates EV-A71-induced tissue damage; while the 25 mg/kg dose delays mouse death, as well as reduces viral loads and alleviates tissue damage^[3].