Kaempferol, as a representative of natural flavonoids, is widely found in a variety of herbs and vegetables—including spinach, watercress, mustard green, arugula, kale, green tee, and many others—and some fruits, such as apples, blueberry, or red grapes. This biologically active compound exhibits a variety of pharmacological effects, including antioxidant, anti-inflammatory, antimicrobial, antidiabetic, and anticancer activities.1–3 In this issue of the Journal of Cardiovascular Pharmacology, Du et al4 describe that kaempferol can attenuate angiotensin II–induced cardiac remodeling through reducing inflammation and oxidative stress in mice. These findings are in line with previous studies, extending observations showing that kaempferol alleviated angiotensin II–induced cardiac dysfunction and interstitial fibrosis in mice.5 Earlier experimental studies also showed that kaempferol attenuates myocardial ischemia/reperfusion injury in rats.6 Taking into account these previous investigations in combination with the current findings by Du et al, it seems that kaempferol's central cardiac mechanism of action in vitro seems to indeed relate to its effective capability of reducing oxidative stress and inflammation, which then leads to the beneficial net effects described. The key role of inflammation in the progression of cardiovascular disease has been effectively shown in a vast number of preclinical and clinical scenarios.7–12
Despite the various recent preclinical reports that highlighted the beneficial effects of kaempferol on the cardiovascular system, until now, there are only few epidemiological data suggesting that a high intake of kaempferol-containing foods effectively reduces the risk of cardiovascular or also other types of diseases in humans. Furthermore, clinical data are lacking, which generate sufficient evidence highlighting the specific protective or therapeutic effects of kaempferol versus additional bioactive constituents in kaempferol-containing foods—such as vitamins, minerals, and other phytochemicals—on cardiovascular diseases.
This gap between the reassuring findings in experimental studies and contemporary lack of sufficient epidemiologicaldata from patient studies might, most probably, originate from the low biological activity and/or high metabolism of kaempferol in humans if taken as an oral agent. This fact might be the huge obstacle to transform the promising in vitro effects to in vivo effects in humans (Figure 1). To overcome this obstacle, primarily additional efforts are warranted, which improve the pharmacokinetics of kaempferol in terms of favoring absorption and slowing down drug metabolism. Such an approach might be the essential, currently still missing, step to transform highly promising preclinical effects into clinical reality.
1. Wang J, Fang X, Ge L, et al. Antitumor, antioxidant and anti-inflammatory activities of kaempferol and its corresponding glycosides and the enzymatic preparation of kaempferol. PLoS One. 2018;13:e0197563.
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