Hesperidin, a Bioflavonoid in Cancer Therapy: A Review for a Mechanism of Action through the Modulation of Cell Signaling Pathways

Rahmani, Arshad Husain; Babiker, Ali Yousif; Anwar, Shehwaz

doi:10.3390/molecules28135152

Cited by 25 publications

(7 citation statements)

References 125 publications

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“…The radioprotective effects of flavonoids could be attributed to the presence of phenolic hydroxyl groups in their structures [ 59 ]. In addition, their effect could also be associated with their ability to downregulate PI3K/Akt/mTOR signaling, as reported by Rahmani et al [ 60 ] and Dong et al [ 61 ]. In the present study, cotreatment of salivary gland with hesperidin and rutin ameliorated the depression of antioxidant mechanisms, DNA damage, inflammation, vasculogenic responses, and PI3K/AKT/mTOR signaling induced by radiation and iron overload.…”

Section: Discussionmentioning

confidence: 81%

Iron overload induced submandibular glands toxicity in gamma irradiated rats with possible mitigation by hesperidin and rutin

Ahmed,

El-Maghraby,

Rashad

et al. 2024

BMC Pharmacol Toxicol

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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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Section: Discussionmentioning

confidence: 81%

Iron overload induced submandibular glands toxicity in gamma irradiated rats with possible mitigation by hesperidin and rutin

Ahmed,

El-Maghraby,

Rashad

et al. 2024

BMC Pharmacol Toxicol

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“…The significance of natural products lies in their unique chemical structures, which often serve as inspiration for the development of novel drugs with improved efficacy and few side effects [183]. Furthermore, natural products exhibit synergistic effects with anticancer drugs and other natural chemicals [184,185]. Some natural product-based glycolysis inhibitors for EGFR-TKI-resistant NSCLC such as apigenin, quercetin, capsaicin, catechin, curcumin, EGCG, leonurine, and sulforaphane have obtained FDA approval for their safety.…”

Section: Perspectives and Conclusionmentioning

confidence: 99%

Natural Product-Based Glycolysis Inhibitors as a Therapeutic Strategy for Epidermal Growth Factor Receptor–Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer

Park,

Han,

Wei

et al. 2024

IJMS

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Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths worldwide. Targeted therapy against the epidermal growth factor receptor (EGFR) is a promising treatment approach for NSCLC. However, resistance to EGFR tyrosine kinase inhibitors (TKIs) remains a major challenge in its clinical management. EGFR mutation elevates the expression of hypoxia-inducible factor-1 alpha to upregulate the production of glycolytic enzymes, increasing glycolysis and tumor resistance. The inhibition of glycolysis can be a potential strategy for overcoming EGFR-TKI resistance and enhancing the effectiveness of EGFR-TKIs. In this review, we specifically explored the effectiveness of pyruvate dehydrogenase kinase inhibitors and lactate dehydrogenase A inhibitors in combating EGFR-TKI resistance. The aim was to summarize the effects of these natural products in preclinical NSCLC models to provide a comprehensive understanding of the potential therapeutic effects. The study findings suggest that natural products can be promising inhibitors of glycolytic enzymes for the treatment of EGFR-TKI-resistant NSCLC. Further investigations through preclinical and clinical studies are required to validate the efficacy of natural product-based glycolytic inhibitors as innovative therapeutic modalities for NSCLC.

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“…With fewer negative effects, natural products and their bioactive components are important in managing disease. Many medicinal plants have been found to be quite helpful in the treatment and prevention of a wide range of illnesses [79]. Plants have been used as remedies to heal a variety of human ailments since time immemorial.…”

Section: Treatment Based On Plants and Other Natural Productsmentioning

confidence: 99%

A Review on Risk Factors, Diagnostic Innovations, and Plant Based Therapies for the Management of Erectile Dysfunction

Alrumaihi,

Raut,

Yahia

et al. 2024

Uro

Self Cite

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Men of all ages frequently experience erectile dysfunction (ED) or impotence, and it is a difficult health issue that adversely affects the quality of life of those who experience it. There are multiple types of treatment strategies for ED available, depending on the origin and severity of ED, as well as any underlying medical issues. However, these therapeutics are known to have a number of negative health effects. In contrast, plant-based treatments are more effective for managing diseases due to their ability to modulate biological processes like inflammation, oxidative stress, and cell signaling molecules. Many medicinal plants have been reported to be quite helpful in the improvement of ED. In this review, ED and its causes, diagnostic methods, treatment strategies, and some of the most potent plant-based interventions against ED are discussed in greater detail, along with a description of their mechanisms of action and a brief discussion of approaches to increase their efficacy, with a focus on the management of ED using herbal interventions as complementary and alternative medicines. While there is hope that medicinal plants could provide lead substances for erectile dysfunction medications, additional investigation is necessary to ascertain the efficacy and security of these prospective treatments.

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Hesperidin, a Bioflavonoid in Cancer Therapy: A Review for a Mechanism of Action through the Modulation of Cell Signaling Pathways

Cited by 25 publications

References 125 publications

Iron overload induced submandibular glands toxicity in gamma irradiated rats with possible mitigation by hesperidin and rutin

Iron overload induced submandibular glands toxicity in gamma irradiated rats with possible mitigation by hesperidin and rutin

Natural Product-Based Glycolysis Inhibitors as a Therapeutic Strategy for Epidermal Growth Factor Receptor–Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer

A Review on Risk Factors, Diagnostic Innovations, and Plant Based Therapies for the Management of Erectile Dysfunction

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