Chamomile as a potential remedy for obesity and metabolic syndrome

Abstract

Obesity is an increasing health concern related to many metabolic disorders, including metabolic syndrome, diabetes type 2 and cardiovascular diseases. Many studies suggest that herbal products can be useful dietary supplements for weight management due to the presence of numerous biologically active compounds, including antioxidant polyphenols that can counteract obesity-related oxidative stress. In this review we focus on Matricaria chamomilla, commonly known as chamomile, and one of the most popular medicinal plants in the world. Thanks to a high content of phenolic compounds and essential oils, preparations from chamomile flowers demonstrate a number of pharmacological effects, including antioxidant, anti-inflammatory, antimicrobial and sedative actions as well as improving gastrointestinal function. Several recent studies have shown certain positive effects of chamomile preparations in the prevention of obesity and complications of diabetes. These effects were associated with modulation of signaling pathways involving the AMP-activated protein kinase, NF-κB, Nrf2 and PPARγ transcription factors. However, the potential of chamomile in the management of obesity seems to be underestimated. This review summarizes current data on the use of chamomile and its individual components (apigenin, luteolin, essential oils) to treat obesity and related metabolic disorders in cell and animal models and in human studies. Special attention is paid to molecular mechanisms that can be involved in the anti-obesity effects of chamomile preparations. Limitation of chamomile usage is also analyzed.

Keywords: Chamomile; Nrf2; PPARgamma; inflammation; polyphenols; pro-oxidant.

Table 1. In vivo anti-obesity and anti-diabetic activities of whole chamomile flower extracts and apigenin, one of the main chamomile compounds

Figure 1. Mechanisms of development of obesity and metabolic syndrome

Chronic excessive energy intake especially in combination with low physical activity results in a positive energy balance that may increase insulin production with stimulation of lipogenesis in visceral white adipose tissue. Adipose tissue primarily responds to the higher demand for energy storage by increasing the size of adipocytes leading to adipocyte hypertrophy. As a first step, adipocytes produce higher ROS levels due to stimulation of glucose oxidation via mitochondrial respiration. Increased ROS levels induce activation of adipose AP-1 transcription factor, a regulator of adipose cell proliferation and differentiation, and NF-κB transcription factor, which trigger an acute inflammation response followed by releasing pro-inflammatory mediators, including interleukins (IL-6, IL-1β), TNF-α and MCP-1. The latter mediates macrophage infiltration in adipose tissue. Recruited macrophages produce high levels of ROS as a part of their protective function resulting in intensification of oxidative stress which further stimulates inflammation processes, forming a vicious cycle. Both chronic oxidative stress and inflammation lead to metabolic complications. NF-κB acts as a negative regulator of peroxisome proliferator activated receptor gamma PPARγ, which regulates expression of anti-inflammatory mediators and adiponectin. Adiponectin sensitizes adipocytes to insulin and stimulates lipogenesis. In the hypertrophied adipocytes, synthesis of adiponectin is decreased and that impairs the insulin signaling and stimulates lipolysis with the release of free fatty acids (FFAs) into the bloodstream. FFAs are adsorbed by liver and muscle causing a decrease in insulin sensitivity of these tissues. As a result, blood glucose level increases. Activated gluconeogenesis in insulin-insensitive liver also contributes to hyperglycemia. Liver increases synthesis and accumulation of triacylglycerols (TAG) that impairs its function and provokes atherogenic blood dyslipidemia. Together these processes characterize metabolic syndrome development.

Figure 2. The main constituents of chamomile flowers

Figure 3. General scheme of potential protective mechanisms of chamomile constituents in obesity

Chamomile phenolic compounds, especially flavonoids (apigenin, luteolin and quercetin) and their glycosides are able to slow down food digestion and absorption in the intestine by inhibition of enzymes involved in carbohydrate breakdown (amylase and maltase) and inhibition of transporters for monosaccharides. The chamomile analog of cholesterol sitosterol is supposed to decrease food cholesterol absorption via competitive mechanism. Chamomile phenolic compounds and essential oils possess antioxidant properties; therefore, they demonstrate the ability to protect against oxidative stress related to obesity. Аnti-inflammatory activity of chamomile compounds (dependent and independent one on antioxidant properties) could ameliorate obesity-induced inflammation. Direct modulation of PPARγ activity seems to be another protective mechanism that decreases lipotoxicity and improves insulin resistance of obesity. In addition, chamomile whole extracts and individual phenols can lead to activation of regulators of stress responsive Nrf2 and FOXO1 transcription factors suggesting a hormetic mechanism of the action. Green lines denote possible routes of chamomile action.