Immune and Metabolic Regulation Mechanism of Dangguiliuhuang Decoction against Insulin Resistance and Hepatic Steatosis

Abstract

Dangguiliuhuang decoction (DGLHD) is a traditional Chinese medicine (TCM) formula, which mainly consists of angelica, radix rehmanniae, radix rehmanniae praeparata, scutellaria baicalensis, coptis chinensis, astragalus membranaceus, and golden cypress, and used for the treatment of diabetes and some autoimmune diseases. In this study, we explored the potential mechanism of DGLHD against insulin resistance and fatty liver in vivo and in vitro. Our data revealed that DGLHD normalized glucose and insulin level, increased the expression of adiponectin, diminished fat accumulation and lipogenesis, and promoted glucose uptake. Metabolomic analysis also demonstrated that DGLHD decreased isoleucine, adenosine, and cholesterol, increased glutamine levels in liver and visceral adipose tissue (VAT) of ob/ob mice. Importantly, DGLHD promoted the shift of pro-inflammatory to anti-inflammatory cytokines, suppressed T lymphocytes proliferation, and enhanced regulatory T cells (Tregs) differentiation. DGLHD also inhibited dendritic cells (DCs) maturation, attenuated DCs-stimulated T cells proliferation and secretion of IL-12p70 cytokine from DCs, and promoted the interaction of DCs with Tregs. Further studies indicated that the changed PI3K/Akt signaling pathway and elevated PPAR-γ expression were not only observed with the ameliorated glucose and lipid metabolism in adipocytes and hepatocytes, but also exhibited in DCs and T cells by DGLHD. Collectively, our results suggest that DGLHD exerts anti-insulin resistant and antisteatotic effects by improving abnormal immune and metabolic homeostasis. And DGLHD may be a novel approach to the treatment of obesity-related insulin resistance and hepatic steatosis.

Exploring the Mechanism of Dangguiliuhuang Decoction Against Hepatic Fibrosis by Network Pharmacology and Experimental Validation

“…DGLHD has been used in clinic as alleviating diabetes, infection, myocarditis, and tuberculosis. Consistently, our previous studies have revealed that DGLHD possesses characteristics of anti-inflammation, immunosuppression, insulin sensitization, hypoglycemia, and hypolipidemia ( Liu et al, 2015 ; Cao et al, 2017 ). In the formula, AG, RR, and RRP are the primary components and exert anti-inflammatory and hepatoprotective effects; GC, CC, and SB act as the ministerial components to strengthen the efficacy of primary agents; AM is the adjunctive component and used to enhance the action or reduce the side effects of primary and ministerial components.…”

“…Dangguiliuhuang decoction (DGLHD) is a classical TCM formula recorded in “Lan Shi Mi Cang,” which composed of angelica (AG), radix rehmanniae (RR), radix rehmanniae praeparata (RRP), scutellaria baicalensis (SB), coptis chinensis (CC), golden cypress (GC), and astragalus membranaceus (AM) ( Cao et al, 2017 ), and is prepared in line with the China Pharmacopoeia standard of quality control. DGLHD has been used in clinic as alleviating diabetes, infection, myocarditis, and tuberculosis.…”

The Impacts of Herbal Medicines and Natural Products on Regulating the Hepatic Lipid Metabolism

“…Furthermore, it decreased T cells proliferation while increased regulatory T cells (Tregs) differentiation, reduced dendritic cells (DCs) maturation and secretion of IL-12p70 cytokine, decreased DCs-stimulated T cells proliferation, and promoted, the interaction of DCs with Tregs. In adipocytes and hepatocytes as well as DCs and T cells, Dangguiliuhuang Decoction treatment altered PI3K/Akt signaling pathway and increased PPAR-g expression, indicating the ameliorated glucose and lipid metabolism (Cao et al, 2017).…”

“…), Coptis chinensis Franch., Radix Rehmanniae Praeparata (Rehmannia root), Astragalus propinquus (the root of astragalus membranaceus), Chinese skullcap (Scutellaria baicalensis) and Phellodendron amurense (Phellodendron chinense Schneid. ), is used for the treatment of autoimmune diseases and diabetes (Cao et al, 2017;Cao et al, 2018). In a study of ob/ob mice model, it normalized glucose and insulin level, diminished fat accumulation and lipogenesis, increased the expression of adiponectin, and promoted glucose uptake (Cao et al, 2017).…”

“…), is used for the treatment of autoimmune diseases and diabetes (Cao et al, 2017;Cao et al, 2018). In a study of ob/ob mice model, it normalized glucose and insulin level, diminished fat accumulation and lipogenesis, increased the expression of adiponectin, and promoted glucose uptake (Cao et al, 2017). It showed modulation abilities on inflammation and immune response.…”