Rhodiola rosea (R. rosea), a perennial herb from the Crassulaceae family, derives its name from the Greek words “rodia” or “rodion,” which signify its pink color when dried. It is also known by names such as “golden root” due to its shiny appearance after purification and “arctic root” because of its habitat in cold regions. This herb is resilient, thriving in harsh environmental conditions and low temperatures, and can be found in polar regions across North America, Europe, and Asia. The plant features compact stem leaves up to 40 cm tall and thick rhizomes that emit a distinct rosy fragrance when crushed. These rhizomes contain extracts responsible for the plant’s medicinal properties.
Medicinal Properties and Historical Usage
R. rosea is categorized as an adaptogen, containing active components that help the human body adjust to environmental stress factors. Its properties have been utilized for centuries to treat conditions such as chronic stress, fatigue, insomnia, and concentration problems. The plant has been the subject of numerous studies aimed at understanding its mechanisms of action and establishing its potential role in medicine. The medicinal properties of R. rosea are largely attributed to salidroside (SAL), a compound with various beneficial effects. SAL belongs to the group of Phenylethanoid glycosides and is distinguished by its high biological availability among compounds in this group due to its relatively simple structure. Additional compounds such as rosarin, rosin, and rosavin have been uncovered in subsequent studies and contribute to the unique properties of R. rosea. However, SAL continues to garner the most attention, with increasing research on its effects annually.
| Concept | Explanation |
|---|---|
| Rhodiola rosea (R. rosea) | A plant also known as “golden root” and “arctic root” found in cold regions, used for its medicinal properties. |
| Adaptogen | A natural substance that helps the body adapt to stress and promotes overall balance and health. |
| Salidroside (SAL) | The main active ingredient in Rhodiola rosea, known for its various health benefits. |
| Phenylethanoid glycosides | A group of chemical compounds that includes salidroside, known for being easily absorbed by the body. |
| Osteoblasts | Cells in the body that are responsible for bone formation. |
| Bone Morphogenetic Proteins (BMPs) | Proteins that help in the growth and development of bone and cartilage. |
| Alkaline Phosphatase (ALP) | An enzyme that is a marker of bone formation and health. |
| Adenosine Monophosphate-Activated Protein Kinase (AMPK) | An enzyme that plays a role in cellular energy balance and promotes bone health. |
| Endothelial Cells | Cells that line blood vessels and are important for blood vessel formation and health. |
| HIF-1α/VEGF Signaling Pathway | A pathway in the body that helps in the formation of new blood vessels, important for bone healing and growth. |
| Glucocorticoid-Induced Osteoporosis (OP) | Bone loss caused by long-term use of steroid medications, leading to weaker bones. |
| Antioxidant Activity | The ability of a substance to prevent or slow damage caused by free radicals, harmful molecules that can damage cells. |
| Oxidative Stress | An imbalance between free radicals and antioxidants in the body, which can lead to cell and tissue damage. |
| Ovariectomy (OVX)-Induced Osteoporosis Model | A research model that mimics postmenopausal osteoporosis in humans by removing the ovaries in animals. |
| Knee Osteoarthritis (KOA) | A condition where the cartilage in the knee joint wears down, causing pain and stiffness. |
| Trabecular Bone | The spongy part of the bone that is found at the ends of long bones and in the vertebrae, important for bone strength. |
| Mineralization | The process by which minerals are deposited in the bone, making it hard and strong. |
| Fracture Healing | The process by which broken bones repair themselves. |
| Bone Density | A measure of the amount of minerals (such as calcium) in a certain volume of bone, indicating bone strength. |
| Osteoclasts | Cells that break down bone tissue, which is a normal part of bone remodeling and healing. |
| Osteoprotegerin (OPG) and RANKL | Proteins that regulate bone remodeling; OPG inhibits bone breakdown while RANKL promotes it. |
| Apoptosis | The process of programmed cell death, which is a normal part of growth and development. |
| Reactive Oxygen Species (ROS) | Harmful molecules that can cause damage to cells if not balanced by antioxidants. |
| Nrf2 Pathway | A cellular pathway that helps protect cells from oxidative damage by activating antioxidant responses. |
| Micro-Computed Tomography (Micro-CT) | A high-resolution imaging technique used to visualize detailed bone structures. |
| Histological Analysis | The study of tissues under a microscope to observe the effects of treatments or diseases. |
| Transforming Growth Factor-beta (TGF-β)/Smad Pathway | A signaling pathway that helps regulate cell growth, differentiation, and repair. |
| Mitogen-Activated Protein Kinase (MAPK)/ERK Pathway | A pathway involved in cell division, growth, and survival, important for bone health. |
| Phosphoinositide 3-Kinase (PI3K)/Akt Pathway | A signaling pathway important for cell survival, growth, and metabolism. |
Biochemical Structure of Salidroside
SAL is a chemical compound classified in the group of phenylpropanoid glycosides with the molecular formula C14H20O7. Its full chemical name is 2-(4-hydroxyphenyl)ethyl O-β-D-glucopyranoside. The biochemical structure of SAL consists of an aglycone (tyrosol), which features a phenyl skeleton with a hydroxyl group (-OH) at the para position (4) and an ethyl group (-CH2CH2OH) attached to the phenyl ring. The aglycone is linked to a glucose molecule via a glycosidic bond, forming a β-D-glucopyranoside. Additionally, SAL is water-soluble.
Influence of Salidroside on Bone Metabolism
In Vitro Studies
Proliferation and Viability of Osteoblast Precursors
Studies have demonstrated that SAL positively affects the growth of C3H10T1/2 cells (mouse pluripotent mesenchymal stem cell-like fibroblasts) and MC3T3-E1 cells (osteoblast precursors derived from mouse calvariae). When cultured with varying levels of SAL for 48 hours, C3H10T1/2 cells showed a slight proliferation increase, while MC3T3-E1 cells exhibited significant growth increases. Notably, SAL also markedly enhanced the proliferation of other cells similar to osteoblasts derived from various rodent species, such as rat bone marrow-derived mesenchymal stem cells (rBMSCs).
Activation and Expression of Bone Morphogenetic Proteins
SAL has been evaluated as a potential activator of bone morphogenetic protein 2 (BMP-2), a crucial factor in osteoblast growth and maturation. Various concentrations of SAL added to MC3T3-E1 cells resulted in a clear enhancement in BMP-2 mRNA levels and triggered rapid phosphorylation of Smad1/5/8 and enhanced extracellular signal-regulated kinase 1/2 (ERK1/2) pathway stimulation. This indicates that SAL plays a role in osteoblast maturation and differentiation.
Alkaline Phosphatase Activity and Mineralization
Alkaline phosphatase (ALP) is an indicator of osteoblast maturation. Exposure of C3H10T1/2 cells to SAL led to a substantial rise in ALP activity and enhanced osteoblast mineralization. Additionally, SAL treatment resulted in increased mRNA expression of osteoblast indicators and bone-forming transcription factors, demonstrating its potential to promote bone formation.
Adenosine Monophosphate-Activated Protein Kinase Activation
Studies have shown that SAL activates adenosine monophosphate-activated protein kinase (AMPK) in osteoblast cultures, promoting cell expansion and differentiation. This activation enhances osteogenic differentiation markers and calcium nodule formation, highlighting SAL’s role in bone metabolism.
Cellular and Molecular Impact on Endothelial Cells
Endothelial progenitor cells (EPCs) play a critical role in bone regeneration by influencing the bone microenvironment. SAL has shown promise in enhancing angiogenic processes, promoting endothelial cell growth, viability, and migration. This effect is mediated through the HIF-1α/VEGF signaling pathway, essential for angiogenesis and bone tissue regeneration.
Effects on Glucocorticoid-Induced Osteoporosis
SAL has demonstrated protective effects against glucocorticoid-induced osteoporosis (OP). In studies, SAL mitigated the negative effects of dexamethasone on osteoblast proliferation, differentiation, and mineralization. It activated the TGF-β/Smad2/3 cellular route and reduced osteoblast apoptosis, indicating its potential in treating glucocorticoid-induced OP.
Role in Mitigating Osteoporosis through Antioxidant Activity
SAL exhibits protective effects against OP by inhibiting oxidative stress and encouraging osteogenesis. Studies have shown that SAL enhances antioxidant capacity, reduces apoptosis, and promotes osteogenic differentiation through the Nrf2 pathway, making it a potent agent for preventing bone loss due to oxidative stress.
In Vivo Studies
Protective Effects against Oxidative Stress
In vivo studies on OVX mice have shown that SAL administration significantly elevates antioxidant markers and improves bone quality. SAL treatment preserved bone microstructure parameters and mitigated trabecular thinning, indicating its potential in protecting against OP.
Effects on Knee Osteoarthritis in Mice
In knee osteoarthritis (KOA) models, SAL treatment reduced inflammation and preserved joint structure. It promoted osteogenic differentiation and reduced osteoclast activity, highlighting its therapeutic potential in treating KOA.
Angiogenesis in Mouse Embryonic Metatarsals
SAL has been shown to promote angiogenesis in mouse embryonic metatarsals through VEGF-dependent pathways. This pro-angiogenic effect is crucial for bone healing and regeneration.
Osteogenesis and Bone Healing
SAL significantly enhanced fracture healing in mouse models. It improved bone formation, mineralization, and angiogenesis within the callus, demonstrating its potential in accelerating fracture healing.
Effects on Osteoporosis Model in Rats
SAL has shown promising results in OVX-induced OP models in rats. It significantly increased bone density, improved bone microarchitecture, and reduced bone turnover markers. SAL treatment also enhanced the expression of HIF-1α and VEGF, supporting its role in bone healing and regeneration.
Rhodiola rosea and its key component, salidroside, have shown significant potential in promoting bone health and treating various bone-related disorders. The compound’s ability to enhance osteoblast proliferation, differentiation, and mineralization, along with its antioxidant and anti-inflammatory properties, makes it a promising therapeutic agent. Continued research and clinical trials are essential to further explore the therapeutic potential of salidroside in bone health and other medical applications.
resounce : https://www.mdpi.com/2072-6643/16/15/2387
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