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【Naringenin】Main Citrus Flavonoids with Antidiabetic Effects
【Naringenin 】Main Citrus Flavonoids with Antidiabetic Effects
(5,7-dihydroxy-2- (4-hydroxyphenyl) chroman-4-one) is a citrus flavanone mainly found in grapefruits, bergamots, and oranges. Numerous pharmacological activities of Naringenin
have already been reported in the scientific literature. It is widely used as a dietary supplement in different treatments, often in combination with other herbal preparations. Naringenin
(aglycone) and naringin are flavanones that display strong anti-inflammatory and antioxidant activities.
Since cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality in diabetic patients, Fallahi, Roghani, and Moghadami focused their study on investigating the cardiovascular potential of this natural flavonoid in diabetes. More specifically, the authors investigated its aortic reactivity, since increased serum glucose and ROS cause vascular endothelial dysfunction. Naringenin
prevented weight loss and lowered the increased plasma glucose concentration in diabetic animals, suggesting its cardioprotective effects. This bioflavonoid exhibited beneficial effects on the cardiovascular system by reducing the maximum contractile response of endothelium-intact rings and improving endothelium-dependent relaxation in response to acetylcholine (ACh). These effects seem to be dependent on modulating the NO pathway, since the pretreatment of endothelium-intact rings with the NOS inhibitor N (G)-nitro-l-arginine methyl ester (L-NAME) significantly attenuated the observed responses in diabetic rats.
Hasanein and Fazeli also investigated the antidiabetic effects of Naringenin
but with a special focus on its effectiveness in diabetes-induced hyperalgesia and allodynia. Naringenin
attenuated chemical and thermal hyperalgesia, as well as allodynia. Since oxidative stress and inflammation are also found in diabetic neuropathy, the study showed that Naringenin
administration increased the activity of SOD, an endogenous enzyme closely intertwined with oxidative stress during the diabetic condition.
Furthermore, using an HFD-induced obesity animal model (C57BL/6J Mice), Yoshida et al. evaluated the anti-inflammatory effects of Naringenin
and its mechanism of action. Naringenin
did not affect HFD-induced changes in serum biochemical parameters, such as glucose, TC, and TG levels. However, it was able to reduce the mRNA expression of the Mac-2 gene, an important macrophage marker. Reinforcing its anti-inflammatory effect, the administration of Naringenin
reduced monocyte chemoattractant protein 1 (MCP-1) expression in adipose tissue from HFD-fed mice, and in adipocyte and macrophage co-cultures, which is one of the key chemokines, one of its main roles being to suppress the migration and infiltration of monocytes/macrophages into adipose tissue. In addition, Naringenin
inhibited HFD-induced JNK phosphorylation but did not interfere in the expression of IκB-α, a member of a family of cellular proteins that function to inhibit the NF-κB transcription factor. In summary, these results suggest that Naringenin
suppresses macrophage infiltration and can modulate the chemoattraction of inflammatory cells via the regulation of MCP-1 expression in adipocytes via a JNK-dependent pathway in obesity-related metabolic disorders.
Tsuhako, Yoshida, Sugita, and Kurokawa conducted an in vivo experiment with a HFD-induced obese and insulin-resistant animal model, as well as with in vitro assays, using 3T3-L1 (adipocytes) and RAW264 (macrophages) cells to confirm their hypothesis that Naringenin
has effects on inflammatory cell infiltration into adipose tissue, in addition to being able to modulate vital chemokines and cytokines. The recruitment of immune cells was observed in obese adipose tissue, which contributes to the initiation and progression of obesity-linked diseases, such as insulin resistance and type 2 diabetes mellitus. They showed that Naringenin
suppressed the neutrophil infiltration into adipose tissue in obese mice. Naringenin
also produced an anti-inflammatory response in the adipose tissues in mice by reducing the levels of the chemokines and/or cytokines MCP-1, macrophage inflammatory protein (MIP)-1α, MIP-2, and MCP-3 and causing a noticeable reduction in the pro-inflammatory cytokine IL-6, although TNF-α was not affected. In the in vitro analyses, Naringenin
significantly reduced MCP-3 expression at the transcriptional and secretion levels in 3T3-L1 adipocytes, as well as in a co-culture of 3T3-L1 adipocytes and RAW264 macrophages. Thus, the authors suggest that Naringenin
suppresses neutrophil infiltration into adipose tissue via the regulation of vital inflammatory mediators connected to immune-cell functions.
Similar to other citrus flavonoids, Naringenin has also been observed to be a potent NF-κB pathway regulator that directly leads to the obstruction of ROS accumulation due to its ability to act as a scavenger of free radicals and up-regulate the activity of both prooxidant and antioxidant enzymes, which is the most remarkable dual property of this flavonoid. In addition, recent findings also point out that Naringenin can down-regulate vital chemokines, which have a significant role in the recruitment and infiltration of inflammatory cells into adipose tissue, and stop the advancement of metabolic disorders, such as insulin resistance and type 2 diabetes mellitus.
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