Rat plasma protein binding of kaempferol‐3‐ O ‐rutinoside from Lu’an GuaPian tea and its anti‐inflammatory mechanism for cardiovascular protection

Abstract

Previous study found a high content of kaempferol‐3‐O‐rutinoside (KR) in Lu’an GuaPian tea, however, the rat plasma protein binding and mechanism of KR for cardiovascular protection are unclear. Thus, we studied plasma protein binding using ultrafiltration followed by UPLC, and screened its inhibition against LPS‐induced inflammation injury in vitro as well as the underlying mechanism by molecular docking and western blot. KR showed over 74% plasma protein binding ratio. Furthermore, KR may act on the toll‐like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88). In vitro experiments showed that KR decreases the overexpression of TLR4, MyD88, and nuclear factor‐κB (NF‐κB), which further validates the molecular docking results, suggesting that KR could block TLR4/MyD88/NF‐κB signaling. These results indicate that KR could be a potential active agent in the protection of myocardial injury. Practical applications Health benefits of tea are largely dependent on the intake of flavonoids. Flavonoids are a group of compounds beneficial to cardiovascular disease and an important part of “functional foods.” Lu’an GuaPian tea is mainly produced in Lu’an City, Anhui Province and is one of the top 10 famous teas in China. Kaempferol‐3‐O‐rutinoside in Lu’an GuaPian has good hypoglycemic effect, mainly manifested in a strong inhibition of α‐glucosidase and α‐amylase activities. Present study showed that kaempferol‐3‐O‐rutinoside could block TLR4/MyD88/NF‐κB signaling, suggesting that it could be a potential active agent in the protection of myocardial injury.

Pretreatment of kaempferol-3-O-rutinoside protects H9c2 cells against LPS-induced inflammation through the AMPK/SIRT1 pathway

“…KR has a protective effect on the TNFhuman umbilical vein endothelial cells (HUVEC) injury model established in vitro, and its mechanism is related to its anti-inflammatory and endothelial cell protection (Yu et al, 2021). Previous research has demonstrated that KR could decrease the protein expression levels of TLR4, MyD88, and NF-κB in LPS-induced H9c2 cell injury, indicating that it inhibits inflammatory response through TLR4/MyD88/NF-κB signaling pathway (Hua et al, 2021). Our latest finding has indicated that KR could decrease IL-1β level and inhibited the expression levels of NF-κB, NLRP3, ASC, Caspase-1 p20, GSDMD, and IL-1β, suggesting that the protective effect of KR was related to regulating the NF-κB/NLRP3/Caspase-1 signaling pathway (Hua et al, 2022).…”

Protective effects and molecular mechanisms of tea polyphenols on cardiovascular diseases

“…In obese mice fed a HFD, TPs reduced the serum levels of TNFα, IL-1β and IL-6 by inhibiting the activation of NF- κ B ( 28 ). Lu′an GuaPian tea, which is a green tea, is rich in kaempferol-3-O-rutinoside (KR), which can protect against cardiovascular disease by inhibiting TLR4/MyD88/NF- κ B signaling and protect against myocardial injury ( 112 ). In addition, endothelial cells control vascular tone and permeability and are important for maintaining vascular homeostasis ( 113 ).…”

The Role of Green Tea on the Regulation of Gut Microbes and Prevention of High-Fat Diet-Induced Metabolic Syndrome in Mice

“…Green tea is a popular non-alcoholic beverage known for its functional effects on humans and animals with functional components, such as tea polyphenols (TPP), caffeine (Caf), and L-theanine (Thea) [11,12]. Two major mechanisms have been identified in the functional effects of green tea: (1) decreasing the absorption of lipids and proteins in the intestine, thereby reducing calorie uptake [13,14], and (2) activating AMP-activated protein kinase via TPP that is bioavailable in the liver, skeletal muscle, and adipose tissues [15].…”