Bisphosphonates (BPs) are used against diseases with enhanced bone resorption. Those classed as nitrogen-containing BPs (N-BPs) exhibit much stronger anti-bone-resorptive effects than non-nitrogen-containing BPs (non-N-BPs). However, N-BPs carry the risk of inflammatory/necrotic side effects. Depending on their side-chains, BPs are divided structurally into cyclic and non-cyclic types. We previously found in mice that etidronate and clodronate (both non-cyclic non-N-BPs) could reduce the inflammatory effects of all three N-BPs tested (cyclic and non-cyclic types), possibly by inhibiting their entry into soft-tissue cells via SLC20 and/or SLC34 phosphate transporters. Tiludronate is the only available cyclic non-N-BP, but its effects on N-BPs' side effects have not been examined. Here, we compared the effects of etidronate, clodronate, and tiludronate on the inflammatory effects of six N-BPs used in Japan [three cyclic (risedronate, zoledronate, minodronate) and three non-cyclic (pamidronate, alendronate, ibandronate)]. Inflammatory effects were evaluated in mice by measuring the hind-paw-pad swelling induced by subcutaneous injection of an N-BP (either alone or mixed with a non-N-BP) into the hind-paw-pad. All of six N-BPs tested induced inflammation. Etidronate, clodronate, and the SLC20/34 inhibitor phosphonoformate inhibited this inflammation. Tiludronate inhibited the inflammatory effects of all N-BPs except ibandronate and minodronate, which have higher molecular weights than the other N-BPs. The mRNAs of SLC20a1, SLC20a2, and SLC34a2 (but not of SLC34a1 and SLC34a3) were detected in the soft-tissues of hind-paw-pads. These results suggest that etidronate, clodronate, and phosphonoformate may act non-selectively on phosphate transporter members, while tiludronate may not act on those transporting N-BPs of higher molecular weights.
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http://dx.doi.org/10.1248/bpb.b16-00521 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Center for Nutritional Sciences, Food Science and Human Nutrition Department, College of Agricultural and Life Sciences, University of Florida, Gainesville, FL 32611.
Documented worldwide, impaired immunity is a cardinal signature resulting from loss of dietary zinc, an essential micronutrient. A steady supply of zinc to meet cellular requirements is regulated by an array of zinc transporters. Deletion of the transporter Zip14 (Slc39a14) in mice produced intestinal inflammation.
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January 2025
Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405.
Dysregulation of GABAergic inhibition is associated with pathological pain. Consequently, enhancement of GABAergic transmission represents a potential analgesic strategy. However, therapeutic potential of current GABA agonists and modulators is limited by unwanted side effects.
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Department of Bioengineering and Biotechnology, Birla Institute of Technology Mesra, Ranchi, Jharkhand 835215, India.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, extracellular amyloid-β (Aβ) plaque accumulation, and intracellular neurofibrillary tangles. Recent efforts to find effective therapies have increased interest in natural compounds with multifaceted effects on AD pathology. This study explores natural compounds for their potential to mitigate AD pathology using molecular docking, ADME screening, and assays, with ruscogenin─a steroidal sapogenin from emerging as a promising candidate.
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Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
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J Agric Food Chem
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Laboratory for Functional Food and Human Health, Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, North Carolina Research Campus, 500 Laureate Way, Kannapolis, North Carolina 28081, United States.
The health benefits of oats, particularly their enhanced nutritional and bioactive properties when sprouted, are well-documented. However, changes in steroidal saponins during germination and false germination are lacking. This study explored the influence of various temperatures (20, 25, and 30 °C) and durations (1, 3, 5, and 7 days) on the steroidal saponin profiles in both germinated and false-germinated oats and assessed their anti-inflammatory activities.
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