Medicinal Plant Research 2024, Vol.14, No.1, 57-70 http://hortherbpublisher.com/index.php/mpr 62 rabbits, reduce the mRNA levels of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF), and upregulate the mRNA level of type II collagen. HIF-1α and VEGF play an important regulatory role in cartilage development and reconstruction. HIF-1α may be one of the initiating factors in the development of KOA. Through HIF-1α, Achyranthes bidentata total saponins may enhance the tolerance of chondrocytes to hypoxia (Ma et al., 2019). 4.3 Effects on cartilage metabolism Achyranthes bidentata has been extensively used in Traditional Chinese Medicine for the treatment of osteoarthritis due to its positive effects on cartilage metabolism. The polysaccharides fromAchyranthes bidentata, such as ABPS, have been shown to activate the Wnt/β-catenin signaling pathway, promoting chondrocyte proliferation and increasing the expression of type II collagen in chondrocytes (Weng et al., 2014). Achyranthes bidentata polysaccharide can activate the Wnt/β-catenin signaling pathway, upregulate the expression of β-catenin and nuclear β-catenin, and downregulate the expression of p-β-catenin, thereby promoting the expression of downstream Runx2 and Osterix, increasing the bone density of rats with osteoporotic fractures, improving the level of bone metabolism in rats, and reducing the pathological damage of bone tissue in rats (Yang et al., 2021). Achyranthes bidentata total saponins and triterpenoid saponins can increase the levels of serum osteocalcin (BGP), alkaline phosphatase (ALP) and blood calcium in osteoporotic rat models, and can effectively inhibit the formation of osteoclasts (Ren et al., 2011; Yu et al., 2011). This suggests that Achyranthes bidentata can help in maintaining cartilage integrity and preventing cartilage degradation, which is essential for managing osteoarthritis. 4.4 Influence on immune responses The immunomodulatory effects of Achyranthes bidentata contribute to its efficacy in treating bone and joint disorders. Research has indicated that Achyranthes bidentata can regulate immune responses by reducing the accumulation of reactive oxygen species (ROS) and apoptosis in kidney cells, as well as modulating the expression of apoptosis marker proteins such as TLR4, Bcl-2, Bax, cleaved caspase 3, and cleaved caspase 9 (Wang et al., 2020). Additionally, network pharmacology studies have revealed that the active components of Achyranthes bidentata are involved in regulating immune and inflammatory responses, reducing chondrocyte apoptosis, and protecting the joint synovial membrane and cartilage (Figure 2) (Zhang et al., 2020). These immunomodulatory properties enhance the overall therapeutic potential of Achyranthes bidentata in bone and joint disorders. Zhang et al. (2020) presented a pathway diagram emphasizing the role of Radix Achyranthis Bidentatae (RAB) in the treatment of osteoarthritis through various signaling pathways and multiple target molecules, particularly the NF-κB and PI3K/AKT signaling pathways. The NF-κB signaling pathway is a crucial route for inflammation and immune responses. By targeting molecules within this pathway, RAB may alleviate inflammation caused by osteoarthritis. The PI3K/AKT signaling pathway plays an important role in cell survival and growth. RAB, by influencing targets within this pathway, may promote the survival and regeneration of joint cells. By regulating these pathways, RAB can effectively reduce inflammatory responses and inhibit cell apoptosis, thus achieving the therapeutic goal for osteoarthritis. 5 Clinical Studies and Trials 5.1 Overview of clinical trials 5.1.1 Study design and methodology Several clinical studies have been conducted to evaluate the efficacy of Achyranthes bidentata in treating bone and joint disorders. These studies typically involve animal models, such as ovariectomized (OVX) rats, to simulate conditions like osteoporosis and osteoarthritis. The methodologies often include the extraction and purification of specific polysaccharides or other active compounds fromAchyranthes bidentata, followed by their administration to the animal models. The effects are then measured using various techniques such as dual-energy X-ray absorptiometry (DEXA), microcomputed tomography (μCT), and biochemical markers analysis (Yan et al., 2019).
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