Polyacetylenic Compounds and Butanol Fraction fromBidens pilosacan Modulate the Differentiation of Helper T Cells and Prevent Autoimmune Diabetes in Non-Obese Diabetic Mice

Abstract

Compelling evidence suggests that infiltrating CD4+ type I helper T (Th1) cells in the pancreatic islets play a pivotal role in the progression of diabetes in non-obese diabetic (NOD) mice. We demonstrate in the present report that a butanol fraction of B. pilosa suppressed the development of diabetes, helped maintain levels of blood sugar and insulin in NOD mice in a dose-dependent manner and elevated the serum IgE levels regulated by Th2 cytokines in NOD mice. Moreover, the butanol fraction inhibited the differentiation of naive helper T (Th0) cells into Th1 cells but enhanced their transition into type II helper T (Th2) cells using an in vitro T cell differentiation assay. Two polyacetylenic compounds, 2-beta-D-glucopyranosyloxy-1-hydroxy-5(E)-tridecene-7,9,11-triyne and 3-beta-D-glucopyranosyloxy-1-hydroxy-6(E)-tetradecene-8,10,12-triyne, identified from the butanol fraction also prevented the onset of diabetes like the butanol fraction. The latter compound showed a stronger activity for T cell differentiation than the former. In summary, the butanol fraction of B. pilosa and its polyacetylenes can prevent diabetes plausibly via suppressing the differentiation of Th0 cells into Th1 cells and promoting that of Th0 cells into Th2 cells.

Botanical, Pharmacological, Phytochemical, and Toxicological Aspects of the Antidiabetic Plant Bidens pilosa L.

“…Accordingly, the butanol fraction of B. pilosa effectively prevented T1D in nonobese diabetic (NOD) mice [23]. Consistently, this prevention involved downregulation of Th1 cells or upregulation of Th2 cells.…”

“…To test the immunomodulatory effect of B. pilosa , one study showed that B. pilosa extract and its butanol fraction could decrease Th1 cells and cytokines and increase Th2 cells and cytokines [23]. This study indicated that IC 50 value of the butanol fraction was 200  μ g/mL.…”

“…This inhibition was reported to be partially attributed to cytotoxicity, because the butanol fraction at 180  μ g/mL could cause 50% death of Th1 cells. Using the bioactivity-directed isolation and identification approach (Figure 3), 3 active polyynes, 3- β -D-glucopyranosyl-1-hydroxy-6( E )-tetradecene-8,10,12-triyne ( 17 ), 2- β -D-glucopyranosyloxy-1-hydroxy-5( E )-tridecene-7,9,11-triyne ( 16 ), and 2- β -D-glucopyranosyloxy-1-hydroxytrideca-5,7,9,11-tetrayne (cytopiloyne, 19 ), as well as 2 index compounds, 4,5-Di- O -caffeoylquinic acid, 3,5-Di- O -caffeoylquinic acid, and 3,4-Di- O -caffeoylquinic acid, were isolated from the butanol extract using high pressure liquid chromatography (HPLC) and, in turns, were structurally identified by nuclear magnetic resonance (NMR) [23, 24]. Only the first three active compounds showed similar effects on Th cell differentiation as the B. pilosa butanol fraction.…”

“…Only the first three active compounds showed similar effects on Th cell differentiation as the B. pilosa butanol fraction. Moreover, compound 19 showed greater activity than compounds 17 and 16 in terms of enhancement (by 277% compared to 34% and 8%) of differentiation of Th0 to Th2 at 10  μ g/mL and inhibition (by 60% compared to 17% and 9%) of differentiation to Th1 at the same concentration (Table 3) [23, 24]. …”

“…Consistently, this prevention involved downregulation of Th1 cells or upregulation of Th2 cells. This was proven by intraperitoneal injection of the butanol fraction at a dose of 3 mg/kg body weight (BW), 3 times a week, to NOD mice from 4 to 27 weeks [23]. This dosage resulted in lower incidence of diabetes (33%).…”