Anti-Osteoporosis Effect of Perilla frutescens Leaf Hexane Fraction through Regulating Osteoclast and Osteoblast Differentiation.

Kanokkarn Phromnoi,Komsak Pintha,Maitree Suttajit,Chalermpong Saenjum,Supachai Yodkeeree,Pornngarm Dejkriengkraikul,Sariya Mapoung

doi:10.3390/molecules27030824

Kanokkarn Phromnoi, Komsak Pintha + Show 5 more

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https://doi.org/10.3390/molecules27030824

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Abstract

Osteoporosis is the result of an imbalance in the bone-remodeling process via an increase in osteoclastic activity and a decrease in osteoblastic activity. Our previous studies have shown that Perilla frutescens seed meal has anti-osteoclastogenic activity. However, the role of perilla leaf hexane fraction (PLH) in osteoporosis has not yet been investigated and reported. In this study, we aimed to investigate the effects of PLH in osteoclast differentiation and osteogenic potential using cell-based experiments in vitro. From HPLC analysis, we found that PLH contained high luteolin and baicalein. PLH was shown to inhibit RANKL-induced ROS production and tartrate-resistant acid phosphatase (TRAP)-positive multi-nucleated osteoclasts. Moreover, PLH significantly downregulated the RANKL-induced MAPK and NF-κB signaling pathways, leading to the attenuation of NFATc1 and MMP-9 expression. In contrast, PLH enhanced osteoblast function by regulating alkaline phosphatase (ALP) and restoring TNF-α-suppressed osteoblast proliferation and osteogenic potential. Thus, luteolin and baicalein-rich PLH inhibits osteoclast differentiation but promotes the function of osteoblasts. Collectively, our data provide new evidence that suggests that PLH may be a valuable anti-osteoporosis agent.

Highlights

Bone remodeling is mediated by a balance between osteoblastic bone formation and osteoclastic bone resorption
To further identify the inhibitory effect of perilla leaf hexane fraction (PLH) on RANKL-induced osteoclastogenesis, we investigated the expression of this osteoclast-specific protein marker, matrix metalloproteinase-9 (MMP-9), using gelatin zymography assays
Our results indicate that PLH inhibited RANKL-induced osteoclast formation and differentiation from macrophage to multinucleated cells by tartrate-resistant acid phosphatase (TRAP) staining and colorimetric method, consistent with luteolin and baicalein treatment; these are the main active compounds of PLH

Summary

Introduction

Bone remodeling is mediated by a balance between osteoblastic bone formation and osteoclastic bone resorption. The disturbance of this balance results in several bone diseases, including arthritis, periodontitis, and osteoporosis [1,2]. Osteoporosis is a major worldwide health problem that affects mainly elderly and postmenopausal women. It leads to an increased risk of fractures and serious health concerns [3,4,5]. The current treatments for osteoporosis are anti-resorptive drugs (such as bisphosphonates, estrogen, selective estrogen receptor modulators, vitamin D, calcium, calcitonin, and denosumab) [6,7,8] and anabolic agents (abaloparatide and teriparatide) [9]. There was a hypothesis relating to the possibility that combination therapy with antiresorptive and anabolic drugs would provide even greater benefits than either drug alone [11]

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