Therapeutic Effects of Citrus Flavonoids Neohesperidin, Hesperidin and Its Aglycone, Hesperetin on Bone Health

Abstract

Flavonoids are natural phytochemicals that have therapeutic effects and act in the prevention of several pathologies. These phytochemicals can be found in seeds, grains, tea, coffee, wine, chocolate, cocoa, vegetables and, mainly, in citrus fruits. Neohesperidin, hesperidin and hesperetin are citrus flavonoids from the flavanones subclass that have anti-inflammatory and antioxidant potential. Neohesperidin, in the form of neohesperidin dihydrochalcone (NHDC), also has dietary properties as a sweetener. In general, these flavanones have been investigated as a strategy to control bone diseases, such as osteoporosis and osteoarthritis. In this literature review, we compiled studies that investigated the effects of neohesperidin, hesperidin and its aglycone, hesperetin, on bone health. In vitro studies showed that these flavanones exerted an antiosteoclastic and anti- inflammatory effects, inhibiting the expression of osteoclastic markers and reducing the levels of reactive oxygen species, proinflammatory cytokines and matrix metalloproteinase levels. Similarly, such studies favored the osteogenic potential of preosteoblastic cells and induced the overexpression of osteogenic markers. In vivo, these flavanones favored the regeneration of bone defects and minimized inflammation in arthritis- and periodontitis-induced models. Additionally, they exerted a significant anticatabolic effect in ovariectomy models, reducing trabecular bone loss and increasing bone mineral density. Although research should advance to the clinical field, these flavanones may have therapeutic potential for controlling the progression of metabolic, autoimmune or inflammatory bone diseases.

Keywords: bone; bone health; bone repair; flavonoids; hesperetin; hesperidin; neohesperidin.

Figure 1

The integrity of bone tissue depends on the balance between bone formation and bone resorption processes. These processes are coordinated by the interactive action of specialized cells, such as osteoblasts and osteoclasts. Several biological factors also act in the process of physiological bone remodeling, such as cytokines, hormones, growth factors, transcriptional factors, ions and proteins of the extracellular matrix, in addition to other cell lines.

Figure 2

Flavonoids are polyphenolic compounds present in citrus fruits, grapes, raspberries, apples, vegetables, legumes and grains, as well as beverages, such as green tea, cocoa, coffee and red wine. These natural compounds have great nutritional value due to their therapeutic properties.

Figure 3

Flavonoids have an important therapeutic effect on the organism. The main benefits that flavonoids provide for health are related to their anti-inflammatory, antioxidant, antitumor and antimicrobial properties. Consumption of a diet containing flavonoids can also favor a reduction in triglycerides and cholesterol plasma levels, in addition to contributing to the prevention of neurodegenerative, cardiovascular, metabolic, inflammatory and bone diseases, such as osteoarthritis and osteoporosis.

Figure 4

Flavonoids contribute to the maintenance of the integrity of mineralized tissues. In bone, flavonoids exert an anticatabolic effect, reducing the resorption process and favoring bone formation. In dental tissue, flavonoids have anticollagenolytic activity on the dentin matrix, inhibiting the proteolytic activity of MMPs and acting as a natural collagen stabilizer. In addition, flavonoids may exert an antimicrobial effect, inhibiting the proliferation of oral bacterial strains.