The increasing rate of autoimmune disorders and cancer in recent years has been a controversial issue in all aspects of prevention, diagnosis, prognosis, and treatment. Among dietary factors, flavonoids have specific immunomodulatory effects that might be of importance to several cancers. Over different types of immune cells, T lymphocytes play a critical role in protecting the immune system as well as in the pathogenesis of specific autoimmune diseases. One of the important mediators of metabolism and immune system is mTOR, especially in T lymphocytes. In the current review, we assessed the effects of flavonoids on the immune system and then their impact on the mTOR pathway. Flavonoids can suppress mTOR activity and are consequently able to induce the T regulatory subset.

/pdf/immunomodulatory-effects-of-flavonoids-possible-induction-of-5269lkat63.pdf

Immunomodulatory Effects of Flavonoids: Possible Induction of T CD4+ Regulatory Cells Through Suppression of mTOR Pathway Signaling Activity.

Objectives: Luteolin is the active component of Perilla frutescens, an herb for the treatment of allergy in Asia. In this study, we aimed to investigate the effects and mechanisms of luteolin treatment. Methods: BALB/c mice sensitized with house dust mite (HDM) to induce allergic rhinitis (AR), and treated with dexamethasone or luteolin. In addition, mononuclear cells from peripheral blood (PBMC) of AR patients were co-cultured with dexamethasone or luteolin, and were re-stimulated with HDM. Results: Luteolin-treated mice had decreased allergic symptoms, and serum HDM-specific IgE when compared to the untreated group. Flow cytometric analyses of splenocytes and nasal lymphoid tissues from AR mice found that luteolin decreased CD4+ IL-4-secreting T cells when compared to those from vehicle treated AR mice. Histopathology sections showed reduced infiltration of eosinophils and decreased mucus secretion of mouse nasal epithelium. In the in vitro study, the results showed that luteolin reduced the percentage of CD4+ IL-4-secreting splenocytes expression was through reducing expression of pSTAT6 and GATA3. PBMCs from AR patients pretreated with luteolin could decrease percentage of CD4+ IL-4-secreting cells. Conclusion: Our study identified that luteolin attenuates allergic nasal inflammation via inhibition of IL-4 production, which supports the potential pharmaceutical application of luteolin treatment for AR.

/pdf/luteolin-attenuates-allergic-nasal-inflammation-via-544ko0xyz5.pdf

Luteolin Attenuates Allergic Nasal Inflammation via Inhibition of Interleukin-4 in an Allergic Rhinitis Mouse Model and Peripheral Blood From Human Subjects With Allergic Rhinitis.

Square wave voltammetric quantitative determination of flavonoid luteolin in peanut hulls and Perilla based on Au NPs loaded boron nitride nanosheets

Honey has exerted a high impact in the field of alternative medicine over many centuries. In addition to its wound healing, anti-microbial and antioxidant properties, several lines of evidence have highlighted the efficiency of honey and associated bioactive constituents as anti-tumor agents against a range of cancer types. Mechanistically, honey was shown to inhibit cancer cell growth through its pro-apoptotic, anti-proliferative and anti-metastatic effects. However, the potential of honey to regulate anti-tumor immune responses is relatively unexplored. A small number of in vitro and in vivo studies have demonstrated the ability of honey to modulate the immune system by inducing immunostimulatory as well as anti-inflammatory effects. In the present review, we summarize the findings from different studies that aimed to investigate the immunomodulatory properties of honey and its flavonoid components in relation to cancer. While these studies provide promising data, additional research is needed to further elucidate the immunomodulatory properties of honey, and to enable its utilization as an adjuvant therapy in cancer.

https://www.mdpi.com/2072-6643/13/4/1269/pdf

The Immunomodulatory Effects of Honey and Associated Flavonoids in Cancer

Flavonoids are low molecular weight, polyphenolic phytochemicals, obtained from secondary metabolism of various plant compounds. They have a spectrum of pharmacological efficacies, including potential anticancer efficacy. Natural flavonoids are present in fruits, vegetables, grains, bark, roots, stems, flowers, tea and wine. Flavonoids can attenuate or inhibit the initiation, promotion and progression of cancer by modulating various enzymes and receptors in diverse pathways that involve cellular proliferation, differentiation, apoptosis, inflammation, angiogenesis and metastasis. Furthermore, in vitro, flavonoids have been shown to reverse multidrug resistance when used as chemo-adjuvants. Flavonoids (both natural and synthetic analogues) interact with several oncogenic targets through dependent and independent mechanisms to mediate their anticancer efficacy in different types of cancer cells.

Flavonoids as Multi-Target Compounds: A Special Emphasis on their Potential as Chemo-adjuvants in Cancer Therapy.

Objective
To explore the regulatory effects of luteolin on airway inflammation in asthmatic rats.


Methods
A total of 48 male Sprague-Dawley (SD) rats were randomly divided into 3 groups of control, asthmatic and luteolin(n=16 each). The rat model of bronchial asthma was established in asthmatic and luteolin groups. The model was induced by intraperitoneally injecting a mixture of ovalbumin and aluminum hydroxide at Day 1 and 8. After two weeks, aomization excitation of normal saline (containing 1% ovalbumin) was induced thrice weekly. The treatment lasted 8 weeks. In control group, the mixture of ovalbumin, aluminum hydroxide and normal saline containing 1% ovalbumin was replaced by normal saline. At 30 min after aomization excitation, normal saline was given to rats in control and asthmatic groups, while 1 mg/kg luteolin was given intraperitoneally to luteolin group. The inflammatory cell number and level of interleukin-4 (IL-4) were measured in bronchoalveolar lavage fluid (BALF). The histopathological changes were observed under light microscope. The activities of peroxisome proliferator-activated receptors (PPARγ) and p38 mitogen-activated protein kinases (p38MAPK) in pulmonary tissues were detected by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR).


Results
The bronchial wall thickness of asthma group, along with smooth muscle thickness ((93.3±7.4), (34.9±2.3) μm) was more than that of control ((61.9±8.2), (19.3±1.5) μm) and luteolin ((76.6±6.7), (25.4±4.6) μm) groups (all P<0.05). The total cell count ((5.61±0.63)×109/L), neutrophil count ((1.83±0.09)×109/L), eosinophil count ((0.59±0.09)×109/L) and level of IL-4 ((78.23±12.73) pg/ml) in BALF of asthmatic group were markedly higher than those of control ((1.53±0.31)×109/L, (0.45±0.21)×109/L, (0.07±0.03)×109/L and (21.21±2.53)pg/ml) and luteolin ((3.24±0.25)×109/L, (1.54±0.10)×109/L, (0.33±0.05)×109/L and (43.24±8.65) pg/ml) groups (all P<0.05). The results of semi-quantitative immunohistochemical analysis showed that the p38 protein level in control group (0.143±0.017) and luteolin group (0.251±0.021) was significantly less than that in asthmatic group (0.362±0.008) (both P<0.01). As compared with asthmatic group, the expression of PPARγ protein markedly increased (0.247±0.034) in control (0.331±0.056) and luteolin (0.442±0.031) groups (all P<0.05). The level of p38 mRNA in asthmatic group (0.718±0.064) was significantly higher than that of control (0.312±0.052) and luteolin (0.426±0.067) groups (all P<0.01). However, the PPARγ mRNA level in asthmatic group (0.266±0.036) was much less than that in control (0.573±0.042) and luteolin (0.687±0.054) groups (all P<0.01).


Conclusion
The anti-inflammatory effects of luteolin may be associated with the regulation of PPARγ expression and p38MAPK signaling pathway in asthmatic rats.


Key words: 
Asthma; Luteolin; Peroxisome proliferator-activated raceptors; p38 Mitogen-activated protein kinases; Rats

Chengyun Wu

Papers

Regulatory effects of luteolin on airway inflammation in asthmatic rats