Chrysanthemum indicum L. flower reduces inflammation via the gut, in mouse model
Certain foods, such as chili, litchi, pepper, etc., are known as “heating” foods in traditional Chinese medicine. The excessive consumption of “heating” foods may cause a number of disorders, such as red and swollen eyes, acne, sore throat, yellow urine and constipation.
This condition is defined in modern medicine as a kind of systemic and chronic low-grade inflammation characterised by a significant increase in inflammatory factors such as tumor necrosis factor-α (TNF-α).
Prolonged systemic low-grade inflammation can cause substantial damage to the body and induce chronic diseases such as obesity, diabetes and depression.
Generally, nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat high-grade inflammation clinically but FSLI is a long-term condition and such long-term treatment with NSAIDs can induce a number of side effects in the gastrointestinal tract, liver, nervous system and other organs of the body.
Several reports have shown that The Chrysanthemum indicum L. flower (CIF) has antioxidant activity in vitro and previous animal studies have used direct LPS injection to induce systemic low-grade inflammation in laboratory animals such as mice. The drawback of this practice is that the inflammatory effects induced by LPS may not be the same as or accurately represent those induced by unhealthy diet.
In this study, capsaicin, a major component of chili, was used to establish a FSLI model by the oral gavage of mice for 7 days. The CIF were then orally administered to the mice at different doses as the treatment. Inflammatory factors, gut microbiota and SCFAs were analyzed to determine their correlations.
The objective of the study was to investigate the anti-inflammatory effect of CIF on capsaicin-induced FSLI and elucidate its mechanism of action, so as to provide a theoretical basis for the development of functional foods and nutritional supplements with efficient anti-systemic inflammation effects.
Mice were randomly divided into 5 treatment groups: model group (CHCB group), low-dose group (CHL group), medium-dose group (CHM group) and high-dose group (CHH group), along with a blank control group (CHCA group). Mice in treatment groups were treated with 14.4 g·kg−1·day−1 capsaicin (purity > 99%, Guangzhou Bosen Pharmaceutical Co., Ltd., Guangzhou, China) solution orally for 7 days. Starting from day 10, mice in the CHL, CHM and CHH groups were treated with 7, 14 and 28 g·kg−1·day−1 of CIF for 3 days. The lowest dose used in this study was 567 mg/kg as human dose.
AT the end of the treatment, blood and faecal samples were taken. The typical inflammatory factors TNF-α, IL-1β, IL-6 and IL-10 in the mouse serum were measured. Alpha (α) diversity in the faeces was analysed as indices reflecting the abundance, evenness and diversity of gut microbiota.
The resulting data reveal that high doses of oral capsaicin significantly increased the serum TNF-α levels in mice to almost twice those of the control group, indicating that excessive capsaicin can induce FSLI in mice.
Data also revealed exposure to medium and high doses of CIF significantly reduced the levels of the inflammatory factor TNF-α, implying that CIF was able to alleviate capsaicin-induced systemic inflammation.
Additionally, treatment with high-dose CIF led to significantly elevated levels of IL-6, restoring it to the levels in the control group. Furthermore, feeding capsaicin to mice significantly reduced their level of serum IL-10 (an anti-inflammatory factor that inhibits the synthesis of pro-inflammatory factors) but these levels significantly increased after the CIF intervention.
The authors conclude: "Taken together, these results demonstrated that CIF was able to reduce systemic low-grade inflammation induced by capsaicin by lowering the proinflammation factors such as TNF-α and increasing the level of anti-inflammation factors including IL-6 and IL-10.
"Treatments with medium and high doses of CIF can help restore the structure of gut microbiota, increase the production of SCFAs such as butyric acid, prevent the entry of LPS into the blood and inhibit FSLI.
"These findings provide scientific evidence to support the use of CIF for preventing and treating inflammation induced by unhealthy diet and are a foundation for the development of CIF-based functional foods and drinks for the prevention of chronic low-grade inflammation-related disorders."
Mechanism of action
Previous studies have shown that excessive Lipopolysaccharide (LPS) translocation into the blood is one of the main causes of systemic inflammation. The results obtained in this study showed that the concentration of LPS in the inflamed mice was more than twice that of the control group, suggesting that high-dose capsaicin promoted excessive LPS translocation into the blood and induced systemic inflammation. On the other hand, CIF treatments significantly decreased the levels of LPS in serum, indicating that CIF effectively prevented the release of a large amount of LPS into the blood, and thereby reduced the level of inflammation.
Gut microbiota have been reported to play a key role in the development of inflammation, and alterations of gut microbiota caused by capsaicin are a potential pathway for its inflammatory effects.
After the intervention with medium and high doses of CIF, the abundance of Lactobacillus became comparable to that of the control group, indicating that CIF can effectively rebalance the structure of gut microbiota by restoring the abundance of Lactobacillus. The main components of CIF are polyphenols; most polyphenols (90–95%) cannot be absorbed by the gastrointestinal tract directly, but are transported to the colon and synthesized by specific bacteria to synthesize SCFAs.
Short-chain fatty acids play a key regulatory role in a variety of metabolic functions of the host. Butyric acid can adjust tight junction proteins to enhance the function of the intestinal barrier, while acetic acid and butyric acid inhibit intestinal inflammation.
Medium and high doses of CIF significantly increase the concentrations of acetic acid and butyric acid in mouse faeces.
Further, CIF treatment significantly increased the abundance of Ruminococcaceae, which are a family of butyrate-producing bacteria, suggesting that CIF promotes the synthesis of butyric acid, with the consequent enhancement of the intestinal barrier function, which in turn can hinder the entry of LPS into the blood and reduces the level of inflammation.
"Water Extract of Chrysanthemum indicum L. Flower Inhibits Capsaicin-Induced Systemic Low-Grade Inflammation by Modulating Gut Microbiota and Short-Chain Fatty Acids"
Authors: Yang, B.; Sun, D.; Sun, L.; Cheng, Y.; Wang, C.; Hu, L.; Fang, Z.; Deng, Q.; Zhao, J.