Search

Context α-Hederin, a potent bioactive compound of Pulsatilla chinensis (Bunge) Regel (Ranunculaceae), has many pharmacological uses, but its effect on cancer cell metabolism is still unclear. Objective To elucidate the role of α-hederin in the glucose metabolism of lung cancer cells. Materials and methods Cell Counting Kit 8 and colony formation assays were employed to assess the antiproliferative effects of α-hederin. Glucose uptake, ATP generation, and lactate production were measured. Glycolysis-related proteins were detected using western blotting, and a sirtuin 6 (SIRT6) inhibitor was used to verify A549 cell proliferation. Sixty male BALB/c nude mice were divided into normal control, 5-FU (25 mg/kg), and α-hederin (5 and 10 mg/kg) groups to assess the antitumor effect for 32 days. Glycolysis-related protein expression was evaluated using immunohistochemical analysis. Results α-Hederin inhibited A549 (IC50 = 13.75 μM), NCI-H460 (IC50 = 17.57 μM), and NCI-H292 (IC50 = 18.04 μM) proliferation; inhibited glucose uptake and ATP generation; and reduced lactate production. Furthermore, α-hederin (10 and 15 μM) markedly inhibited hexokinase 2, glucose transporter 1, pyruvate kinase M2, lactate dehydrogenase A, monocarboxylate transporter, c-Myc, hypoxia-inducible factor-1α, and activated SIRT6 protein expression. Using a SIRT6 inhibitor, we demonstrated that α-hederin inhibits glycolysis by activating SIRT6. A tumour xenograft mouse model of lung cancer confirmed that α-hederin (5 and 10 mg/kg) inhibits lung cancer growth by inhibiting glycolysis in vivo. Discussion and conclusions α-Hederin inhibits A549 cell growth by inhibiting SIRT6-dependent glycolysis. α-Hederin might serve as a potential agent to suppress cancer.

Anemoside B4 (B4) is a compound extracted from Pulsatilla chinensis(P. chinensis). Pharmacological studies have proved that it has certain anti-inflammatory activity. Acute ulcerative colitis (ulcerative colitis) is a non-specific inflammatory disease whose pathogenesis is not completely known, and there is no effective drugs. The purpose of this study was to investigate the protective effect of B4 on ulcerative colitis and its mechanism. In this study, the C57BL/6 mice model of ulcerative colitis was established by DSS [3% (w/v)] and treated with intraperitoneal injection of B4 and oral administration of mesalazine, respectively. During the experiment, the clinical symptoms of the mice were scored by the disease activity index (DAI). Histopathological changes were observed by HE staining. In addition, the effect of LPS on Raw264.7 cells was also studied. In vivo studies showed that B4 could prevent DSS-induced colitis mice from losing weight, shortening colon length and improving pathological changes of colon tissues. B4 significantly reduced levels of inflammatory cytokines IL-1β, IL-6, and TNF-α in colon tissues. In vitro experiments, B4 was almost nontoxic to Raw264.7 cells and could protect the Raw264.7 cells induced by LPS. In terms of mechanism, B4 significantly inhibited the activation of the TLR4 signaling pathway induced by DSS and down-regulate the expression of key proteins in the TLR4/NF-κB/MAPK signaling pathway in Raw264.7 cells induced by LPS. These findings suggest that the inhibition of B4 on ulcerative colitis may be through the TLR4/NF-κB/MAPK pathway. Therefore, B4 may be used as a potential drug for the treatment of ulcerative colitis.