Shaofu Zhuyu decoction ameliorates obesity-mediated hepatic steatosis and systemic inflammation by regulating metabolic pathways

Abstract

Shaofu Zhuyu decoction (SFZYD, also known as Sobokchugeo-tang), a classical prescription drug in traditional East Asian medicine, has been used to treat blood stasis syndrome (BSS). Hepatic steatosis is the result of excess caloric intake, and its pathogenesis involves internal retention of phlegm and dampness, blood stasis, and liver Qi stagnation. To evaluate the effects of treatment with SFZYD on obesity-induced inflammation and hepatic steatosis, we fed male C57BL/6N mice a high fat diet (HFD) for 8 weeks and then treated them with SFZYD by oral gavage for an additional 4 weeks. The results of histological and biochemical examinations indicated that SFZYD treatment ameliorates systemic inflammation and hepatic steatosis. A partial least squares-discriminant analysis (PLS-DA) scores plot of serum metabolites showed that HFD mice began to produce metabolites similar to those of normal chow (NC) mice after SFZYD administration. We noted significant alterations in the levels of twenty-seven metabolites, alterations indicating that SFZYD regulates the TCA cycle, the pentose phosphate pathway and aromatic amino acid metabolism. Increases in the levels of TCA cycle intermediate metabolites, such as 2-oxoglutaric acid, isocitric acid, and malic acid, in the serum of obese mice were significantly reversed after SFZYD treatment. In addition to inducing changes in the above metabolites, treatment with SFZYD also recovered the expression of genes related to hepatic mitochondrial dysfunction, including Ucp2, Cpt1α, and Ppargc1α, as well as the expression of genes involved in lipid metabolism and inflammation, without affecting glucose uptake or insulin signaling. Taken together, these findings suggest that treatment with SFZYD ameliorated obesity-induced systemic inflammation and hepatic steatosis by regulating inflammatory cytokine and adipokine levels in the circulation and various tissues. Moreover, treatment with SFZYD also reversed alterations in the levels of metabolites of the TCA cycle, the pentose phosphate pathway and aromatic amino acid metabolism.

Letrozole and the Traditional Chinese Medicine, Shaofu Zhuyu Decoction, Reduce Endometriotic Disease Progression in Rats: A Potential Role for Gut Microbiota

“…This included reducing the Firmicutes/Bacteroidetes ratio and increasing the abundance of Ruminococcaceae , which could restore the impaired intestinal barrier function and indirectly alleviate the inflammatory response of rats with endometriosis as we have discussed above. It is worth noting that SFZYD has been shown to reduce inflammation and promote lipid metabolism in a high-fat diet mouse model [ 38 ]. In addition, the network pharmacology analysis showed that the lipid metabolism-related pathway constituted potential protein targets of SFZYD [ 39 ].…”

MDG-1, a Potential Regulator of PPARα and PPARγ, Ameliorates Dyslipidemia in Mice

“…In our previous study, MDG-1 treatment could up-regulate the levels of SCFAs (especially butanedioic acid) and slightly alter the contents of amino acids based on the GC-TOF/MS analysis of fecal samples [ 24 ]. Moreover, researches indicated that SCFAs [ 26 , 27 ] and some amino acids [ 28 , 29 ] have been proven to impact de novo synthesis of lipids and glucose. Taken together, the core signaling pathways which MDG-1 influenced might interact together, thus exerting beneficial effects on obesity and abnormal lipids in HF mice.…”

<p>The Mechanism of Traditional Chinese Medicine for the Treatment of Obesity</p>

“…Traditional Chinese medicine has been used for a long time for treating diseases, playing an important role in the treatment of obesity. 10,11 In this paper, we selected drugs that have been widely discussed in obesity-related metabolic studies and can be used in clinical practice without obvious toxic and side effects, such as ginsenoside (Ginseng), 12 celastrol (Tripterygium wilfordii), 13 berberine (Coptis chinensis), 14 curcumin (Turmeric), 15 and the Xiexin 16 and Danggui Buxue decoctions. 17 Considering that different organ tissues may play similar weight-reducing roles under the role of TCM or TCM extracts in the weight-reducing process, we will mainly generalize from the specific mechanisms (regulating fat metabolism, intestinal Microflora, and regulating hormone level, etc.…”

“…Traditional Chinese medicine has been used for a long time for treating diseases, playing an important role in the treatment of obesity. 10 , 11…”