Tea Seed Kaempferol Triglycoside Attenuates LPS-Induced Systemic Inflammation and Ameliorates Cognitive Impairments in a Mouse Model

Abstract

(1) Background: The current research intended to obtain functional compounds from agricultural by-products. A functional tea seed flavonoid, kaempferol-3-O-[2-O-β-d-xylopyranosyl-6-O-α-L-rhanmopyranosyl]-β-d-glucopyranoside (KXRG), was isolated from tea seed dregs. We further determined its chemical structure and evaluated the protective effects of KXRG against local and systemic inflammation in vivo; (2) Methods: First, cytotoxicity and proinflammatory cytokine release were examined in a cell-culture system. The biological activities of KXRG were investigated in a mouse model of ear edema, and from inflammatory damage to organs as demonstrated by histologic examination, in addition to brain function evaluation using the Y-maze test. Serum biochemical analysis and western blotting were utilized to explore the related cellular factors; (3) Results: KXRG inhibited IL-6 in RAW264.7 cells at a non-toxic concentration. Further experiments confirmed that KXRG exerted a stronger effect than indomethacin in terms of the prevention of 12-O-tetradecanoylphorbol acetate (TPA)-induced ear inflammation in a mouse model. KXRG feeding significantly prevented LPS-induced small intestine, liver, and kidney inflammatory damage, as demonstrated by histologic examination. KXRG also significantly improved LPS-induced cognitive impairments. Serum biochemical analysis showed that KXRG elevated antioxidant capacity and reduced levels of proinflammatory cytokines. Western blotting revealed that KXRG reduced the COX-2 expression induced by LPS in mouse tissues; (4) Conclusions: KXRG can be purified from agricultural waste, and hence it is inexpensive, with large amounts of raw materials available. Thus, KXRG has strong potential for further development as a wide-use anti-systemic inflammation drug to prevent human disease.

A comprehensive and mechanistic review on protective effects of kaempferol against natural and chemical toxins: Role of NF‐κB inhibition and Nrf2 activation

“…Also, RAW264.7 cells were incubated with nontoxic concentrations of KXRG for 2 h then LPS was added for 24 h. KXRG had a protective effect against LPS in RAW264.7 cells at a nontoxic dose by suppressing IL‐6. Also, in vivo study revealed KXRG improved cognition following LPS via attenuation of serum pro‐inflammatory cytokines, decreasing COX‐2 expression in the cortex and hippocampus, and inhibition of IL‐6, TNF‐α, and IL‐1β 41 . In another study, BV2 cells were pretreated with kaempferol (10, 30, 50, and 100 μM) for 1 h then LPS was added at the dose of 1 μg/ml for 24 h. Kaempferol significantly reduced the generation of NO, PGE2, TNF‐α, IL‐1β, and ROS dose‐dependently.…”

“…Also, in vivo study revealed KXRG improved cognition following LPS via attenuation of serum pro-inflammatory cytokines, decreasing COX-2 expression in the cortex and hippocampus, and inhibition of IL-6, TNF-α, and IL-1β. 41 In another study, BV2 cells were pretreated with kaempferol (10, 30, 50, and 100 μM) for 1 h then LPS was added at the dose of 1 μg/ml for 24 h. Kaempferol significantly…”

Kaempferol improves acute kidney injury via inhibition of macrophage infiltration in septic mice

“…In context of sepsis model, kaempferol plays an important role in anti-inflammatory response. Kaempferol would improve liver injury in sepsis rat model by selective COX-2 inhibition [ 23 ]. Bian et al reported that kaempferol reduced excessive production of TNF-α, IL-1β, IL-6, ICAM-1, and VCAM-1 in LPS group [ 24 ].…”

“…In the context of inflammatory response, kaempferol could regulate the inflammatory response by controlling CD3+ T cell infiltration [ 20 ], CD4+FoxP3+ regulatory T cells [ 21 ], and Ag-specific T cells in both in vivo and in vitro experiments [ 20–22 ]. Moreover, kaempferol inhibited inflammatory markers such as Cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6), Intercellular cell adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) [ 23 , 24 ].…”

Potential Molecular Mechanisms of Ephedra Herb in the Treatment of Nephrotic Syndrome Based on Network Pharmacology and Molecular Docking

“…More and more studies have proved that quercetin exerts renal protective effects through a variety of ways, including inhibiting ferroptosis, preventing the aging of the kidney cells, alleviating renal fibrosis and apoptosis, and repressing oxidative stress and inflammation [ 36 , 37 ]. As a natural anti-inflammatory compound, kaempferol has been reported to exert curative effects on kidney inflammatory damage [ 38 ]. Recently, numerous studies have shown that kaempferol has salutary effects for anti-inflammatory, antioxidant, analgesic, and anticancer properties [ 39 ].…”