A Natural Therapeutic Approach For Osteoporosis: Research Status And Future Perspectives Of Cistanche Glycosides

3.Related Signaling Pathways of GCs in Improving OP

3.1 Inhibiting Bone Resorption

Bone resorption is one of the important mechanisms in the occurrence of osteoporosis. Cathepsin K (CK) is a typical marker of bone resorption [51,52]. Research has found that GCs can inhibit the activity of CK, thereby inhibiting bone resorption and reducing bone loss [53]. Bone-tonifying Chinese medicines can treat osteoporosis by regulating the OPG/RANKL/RANK signaling pathway [54]. These Chinese medicines achieve the goal of inhibiting OC differentiation and reducing bone resorption by promoting osteoblast secretion of OPG or inhibiting the expression of RANKL. Cistanche extract can inhibit the expression of RANKL, thereby inhibiting the differentiation and activation of OC, downregulating the RANKL/OPG ratio in OC, exerting an inhibitory effect on bone resorption, tilting the balance between bone formation and bone resorption towards bone formation, which is beneficial for bone health [55].

3.2 Promoting Bone Formation

GCs exert anti-osteoporotic effects by upregulating the expression of bone matrix proteins such as BGP and OPN, thereby promoting the expression of OPG, and promoting the synthesis and mineralization of bone matrix. Bone morphogenetic proteins (BMPs) are the only soluble, low-molecular-weight transmembrane glycoproteins that can induce heterotopic osteogenesis. Among them, BMP-2 is the most important and highest osteogenic activity bone formation regulatory factor [56]. Alkaline phosphatase (ALP) is one of the specific markers of osteoblast differentiation. Osteoblasts secrete large amounts of ALP during bone formation to participate in bone mineralization. Therefore, ALP activity can serve as one of the indicators reflecting the activity status of OB [57-59]. Relevant studies have shown that using GCs to intervene in rapidly aging mice and observing the mechanism of GCs on the Wnt/β-catenin signaling pathway, GCs can upregulate the expression levels of BMP-2, BGP, and OPG, and decrease the expression of RANKL and p-β-catenin, thereby activating the Wnt/β-catenin signaling pathway. The bone microstructure damage in mice was improved, bone loss was slowed, bone formation was promoted, and thus OP was prevented [60, 61].

cistanche extract formula

4 Clinical Application and Toxicity Analysis

4.1 Clinical Application

Cistanche has been applied to some extent in the clinical treatment of OP. GCs have the effect of treating osteoporosis, mainly related to their ability to promote bone formation, inhibit bone absorption, effectively increase bone density, and also reduce fracture risk. GCs have anti-inflammatory effects, can inhibit the release of inflammatory mediators, reduce the level of inflammatory response, and have auxiliary effects in the treatment of inflammation-related diseases such as arthritis and cardiovascular diseases. GCs can regulate the body's immune function, enhance the body's resistance, and have a positive effect on improving the quality of life of patients. At the same time, GCs also have certain anti-aging effects, can delay cell senescence, and reduce oxidative stress damage to the body. Studies have found that GCs can promote the proliferation of mouse Leydig cells, improve sperm motility, improve sexual function, and have a certain protective effect on the male reproductive system [62]. Cistanche can bidirectionally regulate bone formation and bone resorption, simultaneously improve serum alkaline phosphatase, calcium and phosphorus metabolism, increase bone density, and thus effectively prevent and treat OP.

4.2 GCs Toxicity Analysis

Hu Yuming et al. [63] conducted acute and genetic toxicity tests on GCs, and the results were non-toxic and negative, respectively. Lu Wenting et al. [64] used rat acute oral toxicity tests and repeated dose 90-day oral toxicity tests. During the tests, the growth and development of the rats were not affected, and blood routine and biochemical indicators were all normal. At the end of the experiment, the weight and organ coefficients of the liver, kidney, and spleen of the rats were not significantly different from those of the control group, and no sample-related lesions were found in histopathological examinations.

GCs have shown certain application potential in the field of osteoporosis treatment. They can regulate bone metabolic balance through multiple targets and pathways, playing a key regulatory role in the activity and differentiation of osteoblasts and osteoclasts. Significant results have been achieved in animal experiments, bringing new ideas for the treatment of osteoporosis. However, there are still many urgent problems to be solved in current research on GCs. In terms of mechanism research, although some signaling pathways have been preliminarily revealed, the specific molecular regulatory network through which GCs affect bone metabolism has not been fully clarified and仍需进一步深入探究. In the future, with the help of cutting-edge technologies such as single-cell sequencing and gene editing, it is expected to systematically elucidate its molecular mechanism, laying a solid theoretical foundation for the precise treatment of OP. In the field of clinical application, the current number of clinical studies using GCs for OP treatment is limited, the sample size is small, and there is a lack of support from large-scale, multi-center, randomized controlled high-quality clinical trials. Therefore, the key task to promote the widespread application of GCs in clinical treatment is to carry out well-designed, scientifically standardized clinical trials to clarify the therapeutic effects, safety, and optimal medication regimen of GCs in humans. From the perspective of drug development, improving the purity and stability of GCs is an important current task. Furthermore, actively exploring and developing new formulations to significantly improve the bioavailability and efficacy of the drug is also a future work focus, hoping to provide patients with better and more diversified treatment experiences. Looking ahead, with continuous in-depth research, GCs are highly likely to become a safe and effective innovative drug for treating OP, opening up new treatment avenues for the majority of patients. At the same time, research on GCs will also inject new vitality into the field of traditional Chinese medicine for preventing and treating OP, provide innovative ideas and methods, vigorously promote the modernization of traditional Chinese medicine, and help traditional Chinese medicine showcase its unique charm on the international stage.

Conclusion

In recent years, GCs have shown significant therapeutic effects in the field of OP treatment. In promoting osteogenesis: GCs can have a positive effect on osteoblast proliferation and differentiation, increase bone density, and contribute to bone tissue formation. Mechanisms include activating BMP, promoting the expression of osteogenesis-related genes such as ALP and OPN, etc. In inhibiting osteoclastogenesis: GCs can inhibit osteoclast activity, reduce bone resorption, and inhibit the further development of OP. Mechanisms include inhibiting the production of inflammatory factors, downregulating osteoclast-related gene expression, reducing oxidative stress response, etc. In regulating hormones and calcium-phosphorus metabolism: GCs can also regulate sex hormone levels by exciting the HPG axis, regulate the metabolism of minerals such as calcium and phosphorus, increase the content of minerals such as calcium and phosphorus in bone tissue, improve bone strength and hardness, and promote

References

[1] MA M, ZENG H, YANG P, et al. Drug Delivery and Therapy Strategies for Osteoporosis Intervention[J]. Molecules, 2023, 28(18): 6652.
[2] ZOU Z, LIU W, CAO L, et al. Advances in the occurrence and biotherapy of osteoporosis[J]. Biochem Soc Trans, 2020, 48(4): 1623-1636.
[3] CAO Ying, YU Guo, WANG Yijun, et al. Investigation on Cognitive Function Status of Elderly Osteoporosis Patients[J]. Chinese Journal of Osteoporosis, 2021, 27(04): 569-575. (曹颖, 喻国, 王意君, 等. 老年骨质疏松症患者认知功能状况调查研究[J]. 中国骨质疏松杂志, 2021, 27(04) : 569-575.)
[4] Iolascon G, de Sire A, Curci C, et al. Osteoporosis guidelines from a rehabilitation perspective: systematic analysis and quality appraisal using AGREE III[J]. Eur J Phys Rehabil Med. 2021; 57(2): 273-279.
[5] QIAO Xiaochun. China's Population Development, Changes and Current Situation from the Perspective of the "Seventh Census" Data[J]. Population and Development, 2021, 27(04): 74-88. (乔晓春. 从"七普"数据看中国人口发展,变化和现状[J]. 人口与发展, 2021, 27(04): 74-88.)
[6] Release of Results from the Chinese Osteoporosis Epidemiology Survey and the "Healthy Bones" Special Campaign[J]. Chinese Journal of Osteoporosis and Bone Mineral Research, 2019, 12(04): 317-318. (中国骨质疏松症流行病学调查及"健康骨骼"专项行动结果发布[J]. 中华骨质疏松和骨矿盐疾病杂志, 2019, 12(04): 317-318.)
[7] LIU Guangzheng, ZHANG Hongmei, YANG Fan, et al. Research Progress on the Effects and Mechanisms of Traditional Chinese Medicine Polysaccharides in Preventing and Treating Osteoporosis[J]. Chinese Traditional and Herbal Drugs, 2022, 53(12): 3831-3841. (刘广正, 张红梅, 杨帆, 等. 中药多糖防治骨质疏松症作用及机制的研究进展[J]. 中草药, 2022, 53(12): 3831-3841.)
[8] HUANG Hongxing, WU Aijun, CHENG Qun, et al. Expert Consensus on the Construction of Osteoporosis Specialties in Medical Institutions[J]. Chinese Journal of Osteoporosis, 2024, 30(06): 781-789. (黄宏兴, 吴爱军, 程群, 等. 医疗机构骨质疏松专科建设专家共识[J]. 中国骨质疏松杂志, 2024, 30(06): 781-789.)
[9] PENG Congcong, PAN Ronggui, HUANG Peng. Research Progress on Ideas and Methods of Traditional Chinese Medicine Prevention and Treatment of Primary Osteoporosis Based on Modern Research[J]. World Latest Medicine Information, 2019, 19(82): 108-109. (彭聪聪, 盘荣贵, 黄鹏. 基于现代研究中医药防治原发性骨质疏松症思路与方法研究进展[J]. 世界最新医学信息文摘, 2019, 19(82): 108-109.)
[10] YANG Zongzheng. Desert Ginseng Cistanche[J]. Health Preservation Monthly, 2019, 40(4): 320-321. (杨宗正. 沙漠人参肉蓉[J]. 养生月刊, 2019, 40(4): 320-321.)