Kaempferitrin prevents bone lost in ovariectomized rats
Graphical abstract
Introduction
Osteoporosis is a kind of metabolic disorders characterized by the imbalance between osteoblastic formation and osteoclastic resorption. It is a stealthy and unpredictable disease that does not become symptomatic until the advanced stages, thus termed a “silent killer” (Kanis et al. 1994). The prevalence of this bone remodeling disease was estimated to be more than 200 million people worldwide in 2006 with attendant costs exceeding 10 billion dollars per annum (Reginster and Burlet 2006), which highlights the large medical input for new treatment options and strategies. Among those treatments, natural compounds with antiosteoporotic activity but few side effects are worth of exploring.
Flavonoids represent a large group of phenolic compounds commonly found in daily nutrition with proven health benefits as well as antiosteoporotic properties (Léotoing et al. 2014). Among this group, kaempferitrin (KN, 3,5,7,4′-tetrahydroxy-flavonoid 3,7-L-dirhamnoside) (Fig. 1A), a natural flavonoid glycoside, has been isolated from several edible and medicinal plants (Fang et al. 2005), suggested to possess antioxidant, antimicrobial, anti-inflammatory and anti-diabetic activities (Abdel-Ghani et al., 2001, Cazarolli et al., 2013). Recently, our lab performed bio-guided isolation on an antiosteoporotic plant, Podocarpium podocarpum (DC.) Yang et Huang, and found the abundance of KN (Ma et al. 2011), which implied that this natural flavonoid may be responsible for the antiosteoporotic activity of P. podocarpum and can be used as a potential agent to treat osteoporosis disease. Here we demonstrated the efficacy of KN on bone loss prevention both in ovariectomized rats of osteoporosis and in osteoclastic cell line. Futhermore, we revealed its effects on the phosphorylation of I-κB, JNK, p38 and ERK to elucidate the possible antiosteoporotic mechanisms.
Section snippets
Instruments and reagents
A total of 12.2 g KN (>95% pure) was isolated from P. podocarpum (DC.) Yang et Huang (13 kg) according to the method of our previous published paper (Urgaonkar and Shaw, 2007, Ye et al., 2015). The structure was elucidated mainly by NMR and MS spectra data analyses, which was consistent with reported data (Kader and Alqasoumi 2007). Its purity can be deduced by the HPLC area normalization method and evidenced by its clear 13C NMR spectrum (Fig. S1).
Estradiol valerate (1 mg, Delpharm Lille SAS,
Results and discussion
Low bone mass is a major risk factor for fractures. Ovariectomy significantly decreased trabecular structural parameters (Li et al. 2013). As showed in Fig. 1B, 12 weeks after ovariectomy, the total bone mineral density (BMD) of those OVX rats were declined by 7.4% in comparison to that of the Sham rats (P < 0.01). Administrated orally, the high dose of KN (KH, 16 mg/kg) increased the BMD by 6.4% (p < 0.01). And in micro-CT experiments, as shown in Fig. 1C1–C5, the bone mineral content (BMC),
Conclusion
In summary, our findings demonstrated that KN possessed significant antiosteoporotic activity mainly through bone resorption suppression, by inhibiting the I-κB phosphorylation and activation of NF-κB signal pathway. Combined with its limited estrogen-like side effect, KN may be regarded as an idealistic antiosteoporotic candidate for human osteoporosis diseases.
Conflict of interest
We confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.
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2018, PhytomedicineCitation Excerpt :However, many of these medicines have serious side effects as hypercalcemia, heart attack, breast and endometrial cancer (Gorman et al., 2002). Therefore, some novel drugs of plant origin, particularly phytochemical compounds, displayed high efficacy and less adverse effects, are worth of estimating for the prevention and therapy of osteoporosis (Li et al., 2013; Ma et al., 2015; Ye et al., 2015). Osteoporosis is called “silent killer” as no obvious symptoms were observed at the early stage, and thus always to be ignored.
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These authors contributed equally to this manuscript.