Tongxinluo May Alleviate Inflammation and Improve the Stability of Atherosclerotic Plaques by Changing the Intestinal Flora

Abstract

Intestinal flora plays an important role in atherosclerosis. Tongxinluo, as a multi-target Chinese medicine to improve atherosclerosis, whether it can improve atherosclerosis by affecting the intestinal flora is worth exploring. We established a vulnerable plaque model of atherosclerosis in New Zealand white rabbits by high cholesterol diet and balloon injury (HCB), and performed Tongxinluo intervention. We detected the level of inflammation by immunohistochemistry, Western Blot, and ELISA, analyzed plaque characteristics by calculating the vulnerability index, and analyzed the changes of gut microbiota and metabolites by 16S rRNA gene sequencing and untargeted metabolomic sequencing. The results showed that Tongxinluo intervention improved plaque stability, reduced inflammatory response, inhibited NLRP3 inflammatory pathway, increased the relative abundance of beneficial bacteria such as Alistipes which reduced by HCB, and increased the content of beneficial metabolites such as trans-ferulic acid in feces. Through correlation analysis, we found that some metabolites were significantly correlated with some bacteria and some inflammatory factors. In particular, the metabolite trans-ferulic acid was also significantly positively correlated with plaque stability. Our further studies showed that trans-ferulic acid could also inhibit the NLRP3 inflammatory pathway. In conclusion, Tongxinluo can improve plaque stability and reduce inflammation in atherosclerotic rabbits, which may be achieved by modulating intestinal flora and intestinal metabolism. Our study provides new views for the role of Tongxinluo in improving atherosclerotic vulnerable plaque, which has important clinical significance.

Mitochondria as novel mediators linking gut microbiota to atherosclerosis that is ameliorated by herbal medicine: A review

“…Herbs are closely related to gut microbiota and mitochondria ( Zhou et al, 2022 ). Gut microbiota converts herbs into active metabolites with higher bioavailability, and herbs regulate gut microbiota biodiversity to ameliorate CVD in the host, similar to prebiotics ( Table 2 ) ( Ma et al, 2022 ; Qi et al, 2022 ).…”

Inflammatory Response: A Crucial Way for Gut Microbes to Regulate Cardiovascular Diseases

“…What is more, gastrodine was found to regulate gut microbial species and abundance, reducing the level of pro-inflammatory cytokines TNF-α and IL-6 and increasing that of anti-inflammatory factors IL-10 [ 79 ]. Tongxinluo intervention, a kind of Traditional Chinese Medicine, altered plaque stability by increasing the level of probiotics in the gut, thereby boosting the content of beneficial metabolites, such as trans-ferulic acid, which could inhibit the NLRP3-related inflammatory pathway in plaque and stabilize plaque [ 80 ]. In conclusion, there is a close relationship between gut microbiota and atherosclerosis, and modulating gut microbiota may be a new way for the treatment of atherosclerosis.…”

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

“…[Araliaceae, Acanthopanacis senticosi radix et rhizoma seu caulis] (Jia et al, 2022) and Lonicera caerulea L. berry polyphenols (LCBP) (Wu et al, 2018). In contrast, the abundance of Firmicutes and Bacteroidetes were not mentioned after applying interventions such as Jieyu Qutan Huazhuo Prescription (JYQTHZ) Li N. et al, 2022), Shenerjiangzhi formulation (SEJZ) (Zhang et al, 2022c), Jian Pi Tiao Gan Yin (JPTGY) (Dong et al, 2022), Shanmei (SM) Capsule (Du et al, 2022), Tongxinluo (TXL) Capsule (Qi et al, 2022), Hugan Qingzhi Tablet (HGQZ) (Tang et al, 2018;Tang, 2019), Compound Danshen Dripping Pills , Jiangan Jiangzhi Pill (JGJZ) (Zhao Z. et al, 2022), Jiangzhi Granules (JZG) , Procyanidin B2 (PB2) (Xing et al, 2019), Resistant starch (RS) (Shou, 2021), Tea polyphenol (TP) (Wang et al, 2018) and Gynostemma pentaphyllum (Thunb.) Makino [Cucurbitaceae;…”