Naoxintong Capsule Alternates Gut Microbiota and Prevents Hyperlipidemia in High-Fat-Diet Fed Rats

Abstract

Background: Naoxintong Capsule (NXT) is a formulated Traditional Chinese Medicine (TCM) widely applied in the treatment of cardiovascular and metabolic diseases, most of which are closely related to hyperlipidemia as a major risk factor. Given the current limited understandings to the role of gut microbiota in the lipid-lowering effect of NXT and other TCM products, this study investigated the regulation of gut microbiota and lipid metabolism by NXT, and their potential relationship.Methods: The chemical components of NXT were firstly analyzed with HPLC-MS method. In high fat diet (HFD)-fed rat models, as well as normal rats as control, the histopathological and biochemical changes of serum and liver were examined, including total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C). In addition, the gut microbiota community was analyzed using 16S rRNA sequencing technique, the fecal levels of gut microbiota related metabolites, including bile acids (BAs) and short chain fatty acids (SCFAs) were determined with HPLC-MS. The correlations of the clinical indicators and gut microbiota related indicators were then investigated statistically.Results: The results showed that NXT exerted potential preventive effect on hyperlipidemia. Specifically, NXT significantly reduced the body weight, TC, TG and LDL-C in serum, increased HDL-C in serum, reduced the TC and TG in liver, as well as protected liver. The body weight, serum lipid levels and liver function were all significantly alleviated. The gut microbiota of the HFD-fed rats was reconstituted with supplementation of NXT. The fecal levels of gut microbiota related metabolites, including BAs and SCFAs were also altered. The correlation between the gut microbiota and clinical/metabolomic parameters was then studied. As the result, the amount of propionic aicd, Firmicutes/Bacteroidetes ratio (F/B) and the relative abundance of Collinsella in feces are the most possibly potential therapeutic biomarkers of NXT.Conclusion: NXT was effective in regulation of gut microbiota and prevention of hyperlipidemia in HFD fed rats. The present work might provide novel insights into the anti-hyperlipidemia effect of TCM and afford new scientific evidence for clinical application of TCM.

Gut microbiota mediates positive effects of liraglutide on dyslipidemia in mice fed a high-fat diet

“…The relationship between the gut microbiota and metabolic diseases, especially obesity, is one of the main foci of research in recent years. Emerging evidence has clarified that gut microbiota can regulate the lipid metabolism, which is closely associated with dyslipidemia ( 17 , 19 , 34 ).…”

“…In recent decades, the gut microbiota, dominated by Bacteroidetes and Firmicutes , has been reported to have a critical impact on the development of obesity ( 19 , 34 ). Firmicutes/Bacteroidetes (F/B) ratio is also commonly used to reflect the changes in microbial structure at the phylum level and is used as a marker to measure overweight and obesity ( 35 ).…”

“…Increasing the abundance of some beneficial bacteria could improve dyslipidemia. Therefore, modulating gut microbiota may be a beneficial strategy to prevent the development of dyslipidemia ( 19 ). On the other hand, there is evidence that GLP-1 may change the composition of gut microbiota by influencing the biological function of intestinal epithelium ( 20 ).…”

Intestinal flora: A new target for traditional Chinese medicine to improve lipid metabolism disorders

“…In addition, the effectiveness of TCM in reversing the elevated F/ B ratio in animals with a HFD has been experimentally confirmed. It was found that some natural medicine extracts, proprietary Chinese medicines and Chinese herbal formulas reduce F/B ratio by decreasing Firmicutes abundance and increasing Bacteroidetes abundance, such as Guizhi Tang (GZT) (Yuan et al, 2021), Naoxintong Capsule (NXT) (Lu et al, 2022), Huanglian Jiedu Decoction (HLJD) (Jiang et al, 2021), Quyu Huatan Tongmai Prescription (QYHTTM) (Miao et al, 2022), Danggui Shaoyao San (DGSY) (Yu et al, 2021), Laminaria japonica polysaccharide (LJP) (Zhang et al, 2021d), Porphyran-derived oligosaccharides (PYOs) , Ethyl Acetate Extract of Eleutherococcus senticosus (Rupr. & Maxim.)…”

“…To play its part in treating LMDs, TCM can control the prevalence of bacteria that produce SCFAs and encourage the generation of SCFAs. LC (Zhang et al, 2019), DLT (Sun et al, 2020), NXT (Lu et al, 2022), IPTS (Ba et al, 2022), LJP (Zhang et al, 2021d), LBPs (Gao et al, 2021), Zanthoxylum bungeanum Maxim. [Rutaceae; Zanthoxyli pericarpium] (ZB) (You, 2016), Ginkgo biloba extract (GbE) , Inulin (Bao, 2021;, NFP (Yang et al, 2020), TP (Wang et al, 2018), Bilberry anthocyanins (Nakano et al, 2020) and COSM (Feng et al, 2022) significantly improved serum lipid levels (TC, TG) as well as reducing lipid accumulation, which may be associated with modifying intestinal flora and increasing SCFAs levels.…”