“…It has also been indicated that HD (10, 15, 80 and 100 mg/kg) has shown anti-oxidant activity and plays a protective role against acrylamide (AA)-, concanavalin A (Con A)-, iron-, zinc oxide nanoparticle-induced oxidative damage and T cell activation in livers of rats by reducing the serum levels of liver function enzymes (alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP)) and malondialdehyde (MDA), elevating levels of glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and reducing the expression and release of high-mobility group box 1 (HMGB1) [ 37 – 40 ]. A later study has also confirmed the anti-oxidant and chemoprotective capacities of HD (50 mg/kg) in liver tissues through the reduction serum levels of progesterone, estradiol, ALT, AST, LDH, urea and creatinine in 7,12-Dimethylbenzanthracene (DMBA)-induced rats model [ 41 ]. Fig.…”
Section: Pharmacological Effects Of Flavonoids From Afi and Af In LIVmentioning
Background: Liver diseases and related complications are major sources of morbidity and mortality, which places a huge financial burden on patients and lead to nonnegligible social problems. Therefore, the discovery of novel therapeutic drugs for the treatment of liver diseases is urgently required. Aurantii Fructus Immaturus (AFI) and Aurantii Fructus (AF) are frequently used herbal medicines in traditional Chinese medicine (TCM) formulas for the treatment of diverse ailments. A variety of bioactive ingredients have been isolated and identified from AFI and AF, including alkaloids, flavonoids, coumarins and volatile oils. Main body: Emerging evidence suggests that flavonoids, especially hesperidin (HD), naringenin (NIN), nobiletin (NOB), naringin (NRG), tangeretin (TN), hesperetin (HT) and eriodictyol (ED) are major representative bioactive ingredients that alleviate diseases through multi-targeting mechanisms, including anti-oxidative stress, anti-cytotoxicity, anti-inflammation, anti-fibrosis and anti-tumor mechanisms. In the current review, we summarize the recent progress in the research of hepatoprotective effects of HD, NIN, NOB, NRG, TN, HT and ED and highlight the potential underlying molecular mechanisms. We also point out the limitations of the current studies and shed light on further in-depth pharmacological and pharmacokinetic studies of these bioactive flavonoids. Conclusion: This review outlines the recent advances in the literature and highlights the potential of these flavonoids isolated from AFI and AF as therapeutic agents for the treatment of liver diseases. Further pharmacological studies will accelerate the development of natural products in AFI and AF and their derivatives as medicines with tantalizing prospects in the clinical application.
“…It has also been indicated that HD (10, 15, 80 and 100 mg/kg) has shown anti-oxidant activity and plays a protective role against acrylamide (AA)-, concanavalin A (Con A)-, iron-, zinc oxide nanoparticle-induced oxidative damage and T cell activation in livers of rats by reducing the serum levels of liver function enzymes (alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP)) and malondialdehyde (MDA), elevating levels of glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and reducing the expression and release of high-mobility group box 1 (HMGB1) [ 37 – 40 ]. A later study has also confirmed the anti-oxidant and chemoprotective capacities of HD (50 mg/kg) in liver tissues through the reduction serum levels of progesterone, estradiol, ALT, AST, LDH, urea and creatinine in 7,12-Dimethylbenzanthracene (DMBA)-induced rats model [ 41 ]. Fig.…”
Section: Pharmacological Effects Of Flavonoids From Afi and Af In LIVmentioning
Background: Liver diseases and related complications are major sources of morbidity and mortality, which places a huge financial burden on patients and lead to nonnegligible social problems. Therefore, the discovery of novel therapeutic drugs for the treatment of liver diseases is urgently required. Aurantii Fructus Immaturus (AFI) and Aurantii Fructus (AF) are frequently used herbal medicines in traditional Chinese medicine (TCM) formulas for the treatment of diverse ailments. A variety of bioactive ingredients have been isolated and identified from AFI and AF, including alkaloids, flavonoids, coumarins and volatile oils. Main body: Emerging evidence suggests that flavonoids, especially hesperidin (HD), naringenin (NIN), nobiletin (NOB), naringin (NRG), tangeretin (TN), hesperetin (HT) and eriodictyol (ED) are major representative bioactive ingredients that alleviate diseases through multi-targeting mechanisms, including anti-oxidative stress, anti-cytotoxicity, anti-inflammation, anti-fibrosis and anti-tumor mechanisms. In the current review, we summarize the recent progress in the research of hepatoprotective effects of HD, NIN, NOB, NRG, TN, HT and ED and highlight the potential underlying molecular mechanisms. We also point out the limitations of the current studies and shed light on further in-depth pharmacological and pharmacokinetic studies of these bioactive flavonoids. Conclusion: This review outlines the recent advances in the literature and highlights the potential of these flavonoids isolated from AFI and AF as therapeutic agents for the treatment of liver diseases. Further pharmacological studies will accelerate the development of natural products in AFI and AF and their derivatives as medicines with tantalizing prospects in the clinical application.
“…Hesperidin also improved the follicular development in 3D culture of isolated preantral ovarian follicles and increased the concentration of progesterone and oestradiol in mice [93] . It has been reported that hesperidin supplementation in 7,12-Dimethylbenz (a) anthracene (DMBA)-and acrylamide-exposed adult Sprague Dawley female rats resulted in abrogation of toxicity and significant increase in serum progesterone and oestradiol levels, significantly lower malondialdehyde concentration, higher glutathione levels and superoxide dismutase activity [36,37] . Hesperidin supplementation also attenuated ovarian oxidative damage caused by ischaemia-reperfusion in Wistar female rats through decreasing the malondialdehyde levels and increase in the superoxide dismutase activity [4] .…”
Section: Hesperidin As a Potential Antioxidant In Enhancing Reproduct...mentioning
“…Hesperidin, a characteristic bioflavonoid of citrus fruits, is found in abundant quantities in orange, grapefruit, tangerine, lime, and lemon [ 12 ]. It has many biological and pharmacological properties including antioxidant [ 13 ], anti-inflammatory [ 12 ], anticancer [ 14 ], and radioprotective [ 15 ] effects.…”
Background
Radiation triggers salivary gland damage and excess iron accumulates in tissues induces cell injury. Flavonoids are found in some fruits and are utilized as potent antioxidants and radioprotective agents. This study aimed to evaluate the antioxidant and anti-inflammatory effects of hesperidin and rutin on gamma radiation and iron overload induced submandibular gland (SMG) damage and to evaluate their possible impact on mitigating the alteration in mTOR signaling pathway and angiogenesis.
Methods
Forty-eight adult male Wistar albino rats were randomly assigned to six groups: group C received a standard diet and distilled water; group H received hesperidin at a dose of 100 mg/kg; four times a week for four weeks; group U received rutin at a dose of 50 mg/kg; three times a week for three weeks; group RF received a single dose (5 Gy) of gamma radiation followed by iron at a dose of 100 mg/kg; five times a week for four weeks; group RFH received radiation and iron as group RF and hesperidin as group H; group RFU received radiation and iron as group RF and rutin as group U. SMG specimens from all groups were removed at the end of the experiment; and some were used for biochemical analysis, while others were fixed for histological and immunohistochemical examination.
Results
In the RF group, several genes related to antioxidants (Nrf-2 and SOD) and DNA damage (BRCA1) were significantly downregulated, while several genes related to inflammation and angiogenesis (TNFα, IL-1β and VEGF) and the mTOR signaling pathway (PIK3ca, AKT and mTOR) were significantly upregulated. Acinar cytoplasmic vacuolation, nuclear pyknosis, and interacinar hemorrhage with distinct interacinar spaces were observed as histopathological changes in SMGs. The duct system suffered significant damage, eventually degenerating entirely as the cells were shed into the lumina. VEGF and NF-κB were also significantly overexpressed. Hesperidin and rutin cotreatment generated partial recovery as indicated by significant upregulation of Nrf-2, SOD and BRCA1 and considerable downregulation of TNF-α, IL-1β, VEGF, PIK3ca, AKT, and mTOR. Although some acini and ducts continued to deteriorate, most of them had a normal appearance. There was a notable decrease in the expression of VEGF and NF-κB.
Conclusions
In γ-irradiated rats with iron overload, the administration of hesperidin and rutin may mitigate salivary gland damage.
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