Abstract
Metformin and Houttuynia cordata are representative anti-diabetic therapeutics in western and oriental medicine, respectively. The current study examined the synergistic anti-diabetic effect of Houttuynia cordata extraction (HCE) and metformin combination in Otsuka Long–Evans Tokushima Fatty (OLETF) rats. Fecal microbiota were analyzed by denaturing gradient gel electrophoresis (DGGE) and real-time PCR. Combining HCE + metformin resulted in significantly ameliorated glucose tolerance (oral glucose tolerance test (OGTT))—the same as metformin alone. Particularly, results of the insulin tolerance test (ITT) showed that combining HCE + metformin dramatically improved insulin sensitivity as compared to metformin treatment alone. Both fecal and serum endotoxin, as well as cytokines (tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6)) were significantly ameliorated by HCE + metformin compared to metformin alone. Meanwhile, the activation of AMPK (adenosine monophosphate-activated protein kinase) by metformin was distinctly enhanced by HCE. Both of HCE and metformin evidently changed the gut microbiota composition, causing the alteration of bacterial metabolite, like short-chain fatty acids. H. cordata, together with metformin, exerts intensive sensibilization to insulin; the corresponding mechanisms are associated with alleviation of endotoxemia via regulation of gut microbiota, particularly Roseburia, Akkermansia, and Gram-negative bacterium.
Highlights
According to World Health Organization (WHO) epidemiological data, 9% of adults had diabetes worldwide in 2014 among which 90% belong to type 2 diabetes (T2D) [1,2]
Exposure of OLEFT rats to either metformin alone or metformin + Houttuynia cordata extraction (HCE) did not produce any noticeable effect on the body weight gain (Figure S1A)
In an intraperitoneal insulin tolerance test (ipITT) test, treatment with metformin + HCE led to significant inhibition of the glucose level at 60 and 90 min (Figure 2A), suggesting improvement of insulin resistance, while in the oral glucose tolerance test (OGTT) test, treatment with metformin + HCE significantly reduced the glucose level at 0, 90, 120 min (Figure 2C)
Summary
According to World Health Organization (WHO) epidemiological data, 9% of adults had diabetes worldwide in 2014 among which 90% belong to type 2 diabetes (T2D) [1,2]. T2D is a chronic systemic progressive metabolic disease characterized by hyperglycaemia due to insulin insufficiency and/or reduction of insulin sensitivity. Development of T2D generally involves three pathological manifestations, insulin resistance, postprandial hyperglycemia, and fasting hyperglycemia. Despite its discovery more than 60 years ago in Europe as a suppressor of hepatic glucose production, so far metformin is still considered as a first-line therapeutic for T2D [3]. Genes 2017, 8, 239 metformin are not a negligible issue in the clinic. We attempted to explore an innovative agent which can act together with metformin for strengthening the therapeutic effectiveness and/or reducing the side effects
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