HEALTHY BONE SUPPORT
Healthy Bone Support
Fluid, comfortable movement isn’t only the job of the joints. It requires bones strong enough to withstand bursts of physical activity or prolonged routine movement. Healthy bones require two coordinated actions: bone formation (by osteoblasts) and bone reabsorption (by osteoclasts). In the process of bone formation, osteoblasts produce a calcium and phosphate-based mineral that is deposited into bones. Almost the entire bone matrix is mineralized by the osteoblasts. An osteoclast is a type of bone cell that resorbs or breaks down bone tissue (see Figure 6). However, this healthy balance of bone formation and bone resorption tends to decline with age, particularly in postmenopausal women. Osteoporosis is the most common bone disorder and is caused by excessive bone resorption by osteoclasts without adequate bone formation by osteoblasts. Increased bone resorption, among other actions, are predominantly caused by the decline of estrogen production in postmenopausal women, who tend to develop porous bones more often than aging men.
Human Clinical Study 1
Andrographolide Inhibits Ovariectomy-Induced Bone Loss via the Suppression of RANKL Signaling Pathways
Tao Wang 1,2,3,†, Qian Liu 1,2,†, Lin Zhou 4, Jin Bo Yuan 4, Xixi Lin 1,2, Rong Zeng 1,2,
Xiaonan Liang 2, Jinmin Zhao 1,2,3 and Jiake Xu 1,2,4,*
Received: 30 August 2015 ; Accepted: 26 October 2015 ; Published: 17 November 2015 Academic Editor: Ge Zhang
ParActin® has been shown to help support healthy bone function. In research published in the International Journal of Molecular Sciences, a group of mice whose skeletons mimic postmenopausal osteoarthritis were treated with Andrographolide (5). The use of these ovariectomized (OVX) animals is a typical experimental model for the investigation of postmenopausal osteoporosis due to estrogen deficiency in women. The ParActin® group showed a significant increase in bone mass, trabecular thickness and number, and a decrease in trabecular separation compared to control mice (see Figure 7).
NF-kB activation is essential for RANKL (i.e., receptor activator of NF-kB ligand)-induced osteoclast formation. Andrographolide found in ParActin®—a natural NF-kB inhibitor—significantly decreased osteoclast formation in the bone marrow via suppression of RANKL, which are responsible for making osteoclasts (see Figure 8).
The authors concluded that Andrographolide inhibits estrogen deficiency-induced bone loss in mice and may have supplemental potential for osteoarthritis.
Human Clinical Study 2
In another unpublished study, Andrographolide induced osteoblast mineralization via COX-2 expression, showing a mineralizing effect on the bones with the increase of calcium deposits, thereby suggesting that ParActin® may have other supplemental effects for osteoarthritis (see Figure 9).
Human Clinical Study 3
British Journal of Pharmacology (2014) 171 663–675
Andrographolide suppresses RANKL-induced osteoclastogenesis in vitro and prevents inflammatory bone loss in vivo Z J Zhai1,*, H W Li1,*, G W Liu2,*, X H Qu1, B Tian1, W Yan3, Z Lin4,5, T T Tang1, A Qin1,5 and K R Dai1
BACKGROUND AND PURPOSE
Osteoclasts play a pivotal role in diseases such as osteoporosis, rheumatoid arthritis and tumour bone metastasis. Thus, searching for natural compounds that may suppress osteoclast formation and/or function is promising for the treatment of osteoclast-related diseases. Here, we examined changes in osteoclastogenesis and LPS-induced osteolysis in response to andrographolide (AP), a diterpenoid lactone isolated from the traditional Chinese and Indian medicinal plant Andrographis paniculata.
Effects of AP on osteoclast differentiation and bone resorption were measured in vitro. Western blots and RT-PCR techniques were used to examine the underlying molecular mechanisms. The bone protective activity of AP in vivo was assessed in a mouse model of osteolysis.
AP concentration-dependently suppressed RANKL-mediated osteoclast differentiation and bone resorption in vitro and reduced the expression of osteoclast-specific markers, including tartrate-resistant acid phosphatase, calcitonin receptors and cathepsin
K. Further molecular analysis revealed that AP impaired RANKL-induced NF-κB signalling by inhibiting the phosphorylation of TGF-β-activated kinase 1, suppressing the phosphorylation and degradation of IκBα, and subsequently preventing the nuclear translocation of the NF-κB p65 subunit. AP also inhibited the ERK/MAPK signalling pathway without affecting p38 or JNK signalling.
CONCLUSIONS AND IMPLICATIONS
AP suppressed RANKL-induced osteoclastogenesis through attenuating NF-κB and ERK/MAPK signalling pathways in vitro, thus preventing bone loss in vivo. These data indicated that AP is a promising natural compound for the treatment of osteoclast-related bone diseases.