The protective effects of acteoside from cistanche on bones
Mar 05, 2022
Contact: emily.li@wecistanche.com
Part Ⅰ：Protective Effect Of Acteoside On Ovariectomy-Induced Bone Loss in Mice
Lingling Yang, Bo Zhang, Jingjing Liu, Yanhong Dong, Yanting Li, Nan Li, Xiaojun Zhao, Hunter Snooks, Changling Hu
Acteoside, an active phenylethanoid glycoside compound isolated from herbs of Cistanche, was chosen for the investigation of the anti-osteoporotic effect on postmenopausal osteoporosis by using an ovariectomized (OVX) mice model. The results from in vivo experiments showed that after daily oral administration of acteoside (20, 40, and 80 mg/kg body weight/day) for 12 weeks, bone mineral density and bone biomechanical properties of OVX mice were greatly enhanced, with significant improvement in bone microarchitecture. Furthermore, biochemical parameters of bone resorption markers as well as bone formation index, including tartrate-resistant acid phosphatase, cathepsin K, deoxypyridinoline, alkaline phosphatase, and bone GLA protein, were ameliorated by acteoside treatment, whereas the body, uterus, and vagina wet weights were seemingly not impacted by acteoside administration. Acteoside significantly affected osteoclastogenesis by attenuating nuclear factor kappa B (NF-kB) and stimulating phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signal pathways through down-regulated levels of tumor necrosis factor receptor-associated factor 6 (TRAF6), receptor activator of nuclear factor kappa B ligand (RANKL), RANK, NFKBIA, IkB kinase p, nuclear factor of activated T-cells c2 (NFAT2), and up-regulated expressions of PI3K, AKT, and c-Fos. Accordingly. the current research-validated our hypothesis that acteoside possesses potent anti-osteoporotic properties and may be a promising agent for the prevention of osteoporosis in the future. Therefore, more attention has been given to natural medicinal plants, especially some edible herbs and isolated active compounds, to treat this ailment. A series of medicinal herbs were discovered to possess anti-osteoporotic effects in the laboratory, which include Epimedium brevican, Ligustrum lucidum, Cistanche deserticola, etc. [4]. Unfortunately, the responsible bioactive components of these herbs, as well as the underlying molecular mechanisms, are still not clear.
Osteoporosis is a severe health threat defined as a systemic skeletal disease and characterized by low bone mass and deterioration of the trabecular bone structure, thereby being a significant risk factor for bone fracture [1]. Osteoporosis is becoming more prevalent as the elderly population is increasing worldwide, and it is estimated that 50% of women and 20% of men aged 50 years and over will suffer one or more fractures mainly caused by osteoporosis during their remaining life, thus posing a great challenge for the prevention and treatment of osteoporosis [2]. Although osteoporosis has received more attention lately and synthetic drugs used to treat this disease are indeed effective, various kinds of adverse effects which may be related to these agents make them far from ideal [3].
Osteoporosis is a significant risk factor for bone fracture
It is well known that bones are constantly undergoing a process of remodeling, including the formation of bone matrices and the resorption of bone, which are guided by osteoblasts and osteoclasts, respectively [5]. It is widely believed that the bone remodeling process is mainly dependent on the vitality and differentiation of osteoclasts [6]. The osteoclast is a unique myeloid-derived multinucleated giant cell, and colony-stimulating factors (M-CSF) as well as receptor activators of nuclear factor-kB (NF-kB) ligand (RANKL) are regarded as critical cytokines for the formation and activation of osteoclasts [7]. It was proven that osteoclastogenesis is activated when the receptor activator of NF-kB (RANK) interacts with its ligand RANKL, as well as when tumor-necrosis factor (TNF) receptor-associated factor 6 (TRAF6) is combined with this complex [8]. Consequently, the binding of TRAF6/RANKL/RANK activates a series of downstream signaling pathways including NF-kB and phosphatidylinositol 3-kinase AKT (PI3K/AKT) [9] and ultimately stimulates the activation of c-Fos and nuclear factor of activated T-cells c2 (NFAT2) [10].
bone remodeling: osteoblasts and osteoclasts
Acteoside, also called verbascoside, is one of the representative phenylethanoid glycoside (PhG) components existing in dozens of medicinal plants, including the herbs of genus Verbascum and Cistanche. In recent years, acteoside has garnered more attention due to its excellent biological activities including antioxidant [11], anti-inflammatory [12], neuronal protective [13], and improved muscle atrophy properties [14]. According to the record of the Chinese pharmacopeia, Cistanche deserticola is an edible traditional Chinese medicine (TCM) that was traditionally used to treat kidney deficiency symptoms including muscle weakness and lumbar debility, and PhGs including echinacoside and acteoside were established as the main bioactive constituents in this herb [15].
According to the TCM theory of “kidney dominates bone”, TCM possessing activities of nourishing and strengthening the kidney may be employed as anti-osteoporotic agents in clinical. In addition, published experiments using both osteoblasts in vitro and ovariectomized (OVX) mice in vivo proved the anti-osteoporotic effect of Cistanche deserticola [16-20], and acteoside was also reported to reduce bone loss by blocking osteoclast activation [21]. All the above evidence concurs with our hypothesis that acteoside may have bone protective and bone reparative properties. Therefore, the objective of this study is to determine the therapeutic effect of acteoside on OVX mice in vivo as well as the underlying molecular mechanism related to TRAF6/RANKL/RANK-mediated NF-kB and PI3K/AKT signals.
Acteoside from cistanche anti-osteoporosis
References
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