Therapeutic potential of Chinese medicinal herbs stimulating osteogenic differentiation of bone marrow-derived mesenchymal stem cells in osteoporosis

Osteoporosis (OP) is a standard and complicated continual metabolic illness, which continuously impacts middle-aged and aged individuals. Moreover, with an rising growing old inhabitants, the incidence price of OP can be rising (Khandelwal and Lane, 2023). Furthermore, it’s a bone metabolic illness with totally different etiologies, it develops slowly in years and is characterised by bone loss and brittle fractures. As a result of systemic nature of OP, the elevated danger of fractures impacts virtually all skeletal elements. Hip fractures are particularly harmful as they’re painful and scale back the bearing potential of the affected person, which requires surgical fixation and results in additional discount of practical standing and high quality of life, decreased mortality, and excessive medical prices (Compston et al., 2019). OP is a continual illness that impacts women and men of all races, considerably impacting their high quality of life and even mortality. At the moment, the first remedy medication embody anti-resorptive brokers (corresponding to calcitonin, estrogen, estrogen-receptor modulators, bisphosphonates, and vitamin D, and so on.) and anabolic brokers (corresponding to teriparatide, strontium ranelate, and romosozumab, and so on.). Nevertheless, though these medication have therapeutic advantages, their long-term use may cause hostile results (corresponding to nausea, vomiting, headache, insomnia, anxiousness, and so on.), which has prompted researchers to seek for alternate efficient and protected OP therapies (Ukon et al., 2019; Martiniakova et al., 2020).

The applying of stem cell expertise in medical follow has opened the trail for future medical growth (Zakrzewski et al., 2019). Mesenchymal stem cells (MSCs) are pluripotent stem cells discovered within the mesoderm, which have sturdy proliferation potential and multi-directional differentiation potential. MSCs have been noticed to repeatedly migrate from their authentic tissue to new tissue websites, the place they take part within the renewal and restore of tissues and organs beneath physiological or pathological circumstances, to take care of the integrity and practical stability of the physique’s tissue morphology. With steady technological progress and superior medical strategies, MSCs-based cell remedy has been more and more employed to deal with varied clinically refractory ailments, turning into one of many present analysis hotspots and essentially the most mature kind of cells in medical analysis and software (Yamanaka, 2020). Bone mesenchymal stem cells (BMSCs) are essential members of the stem cell household, which might differentiate into varied cell varieties corresponding to OBs, adipocytes, chondrocytes, and fibroblasts. Moreover, BMSCs are crucially concerned within the regulation of bone homeostasis. A examine on degenerative bone and joint ailments within the aged, corresponding to OP, indicated that MSCs have good bone and cartilage restore capabilities, highlighting a novel goal for the remedy of such ailments (Jiang et al., 2021). Conventional Chinese language medication (TCM) has been employed for hundreds of years for the prevention and remedy of OP. A number of research have indicated that TCM and its formulation can exert therapeutic results on OP by inducing the proliferation and osteogenic differentiation of BMSCs. This evaluate summarizes how TCM herbs stimulate osteogenic differentiation of BMSCs and discusses their software in treating OP.

The OP is a systemic illness characterised by low bone mass and destruction of bone microstructure, leading to elevated bone fragility and fracture susceptibility (Lane, 2006). The bone formation and resorption is a dynamic equilibrium course of and OP is often attributable to the imbalance on this equilibrium. This dynamic equilibrium is achieved by the mutual regulation of OB and osteoclasts (OC). The OBs secrete osteoid into the absorption cavity and are answerable for producing and processing new bone supplies, whereas OC promotes bone resorption by acidification and proteolytic digestion (Manolagas, 2000). When bone resorption exceeds bone formation, it results in bone loss and in the end OP. Ache is the most typical symptom of major OP, with decrease again ache being essentially the most frequent. The entrance of the vertebral physique carries a considerable amount of weight, subsequently, it’s vulnerable to compression and deformation, which causes the backbone to tilt ahead, forming a hunchback, and even fractures. Fractures are the most typical and extreme complication of degenerative OP (Aibar-Almazán et al., 2022). It has been indicated that age-related bone loss is the predominant reason for OP. In youngsters and adolescents, bone formation exceeds bone absorption, and bones develop in dimension, and power, and have elevated mineral content material. Throughout center age, in girls after 55 years (particularly after menopause) and in males after 65 years, the OB’s operate steadily decreases, and the OC’s bone absorption operate will increase, resulting in enhanced bone absorption and diminished bone formation (Compston et al., 2019). Due to this fact, because the age will increase, the mineral, natural matrix, and bone mass are likely to lower, lowering the mechanical power of bone and making it vulnerable to OP. In girls, OP is commonly related to elevated cancellous and cortical bone reworking, coupled with weight-bearing plastic steadiness, resulting in bone loss and bone microstructure destruction. In males, OP is especially associated to diminished bone formation, low bone turnover, adjustments within the matrix and mineral composition, and so on. (Liu et al., 2015). Along with age, genetic, endocrine, and dietary components, in addition to life-style, residing surroundings, oxidative stress, and inflammatory response are additionally thought of the chance components of OP. For instance, in white and Asian populations, the incidence price of OP in aged girls is increased, whereas in Hispanics, the incidence price of OP in males is increased than that of girls; nonetheless, after the age of 60, girls have increased OP incidence than males (Bohinc and Snyder, 2008). The cessation of ovarian operate and estrogen deficiency is the primary reason for OP in postmenopausal girls, and there can also be a relative improve in parathyroid hormones (Li and Wang, 2018). Calcium is a very powerful bone mineral, and its insufficiency inevitably impacts bone mineralization. In the course of the bone progress and growth interval, the calcium requirement will increase and inadequate consumption can induce OP (Weaver et al., 2016). As well as, smoking, extreme consuming, a excessive salt weight loss plan, extreme espresso consumption, and diminished mild publicity are all danger components for OP (Hannan et al., 2000).

BMSCs are pluripotent stem cells with the flexibility to distinguish into varied cell varieties and play an important function within the physiological and pathological processes of OP. Below regular physiological circumstances, BMSCs promote bone formation and regeneration by differentiating into OB after being stimulated by applicable progress components and cytokines (corresponding to bone morphogenetic proteins BMPs). These differentiated OBs then synthesize and secrete bone matrix, and mineralize to kind new bone (Lee et al., 2018). Nevertheless, in OP sufferers, the BMSC’s osteogenic differentiation potential is considerably diminished, thereby lowering bone formation price, which is perhaps related to growing old, hormone degree adjustments, continual inflammatory standing, and different metabolic problems. The result’s a lower in bone density, bone fragility, and an elevated danger of fractures (Zhang et al., 2022). In recent times, a number of research on the correlation between BMSCs and OP have indicated that osteogenesis induction BMSCs is a vital pathway for bone tissue renewal. Because the age will increase, the variety of BMSCs decreases, and their potential to induce additionally osteogenesis decreases, thereby lowering the OB proliferation and differentiation in addition to bone formation potential, thus rising the chance of OP incidence (Arthur and Gronthos, 2020; Jiang et al., 2021).

As well as, younger BMSCs have excessive proliferation and differentiation potential, subsequently, they’ll successfully take part in bone formation and restore. Nevertheless, with rising age, the proliferation and differentiation potential of BMSCs steadily decreases, and BMSC’s senescence is likely one of the essential components inflicting a lower in bone mass and the destruction of microarchitecture, particularly in senile OP, considered a frequent aging-related illness (Boz and Ozsarı, 2020). With age, not solely does the variety of BMSCs lower, however their differentiation potential can be diminished. BMSCs may differentiate into adipocytes. Below physiological circumstances, the “osteogenic-adipogenesis” differentiation of BMSCs is imbalanced, the place osteogenic differentiation is diminished and adipose differentiation is enhanced (Ivanovska et al., 2015). The buildup of adipocytes within the bone marrow not solely occupies the place of OB but additionally inhibits their operate by secreting adipokines corresponding to leptin and adiponectin, additional exacerbating OP. Moreover, the growing old cells secrete senescence-related secretory phenotype (SASP) components, which additional inhibit osteogenic differentiation and promote inflammatory response by autocrine and paracrine pathways, thereby exacerbating OP (Chen et al., 2016). Throughout bone formation, BMSCs are regulated by varied cytokines and signaling pathways. The Wnt/β-catenin, Notch, and mitogen-activated protein kinases (MAPK) signaling pathways play essential roles within the osteogenic differentiation of BMSCs. These signaling pathways preserve the dynamic steadiness of bone formation and resorption by regulating the proliferation, differentiation, and survival of BMSCs (Guo et al., 2021; Yang et al., 2023). The above information summarized how the molecular mechanisms modulate BMSC operate related to OP, highlighting that BMSC can be utilized as a therapeutic goal for OP remedy.

At the moment, OP is being handled with medication or hormonal remedy, which immediately stimulates bone formation to extend bone mass. Nevertheless, extended drug remedies have extreme unwanted effects. Contemplating that continual OP requires long-term and sustained intervention, stem cell regenerative medication expertise is a greater remedy various (Arjmand et al., 2020). For regenerative medication, BMSCs are potential candidates as they’ve fewer moral issues than different stem cells investigated for OP remedy. It has been noticed that MSCs can deal with OP by selling osteogenic differentiation, rising the variety of OB, inhibiting OC differentiation, and enhancing bone metabolism, and so on. (Hu et al., 2018). TCM has been really useful for bone regeneration and restore for hundreds of years. Lately, complete analysis on TCM and BMSCs has indicated that the TCM has a singular benefit of stimulating BMSCs for the prevention and remedy of OP, demonstrating a variety of software prospects.

Epimedii folium (Yinyanhuo in Chinese language) [Epimedium brevicornu Maxim] is among the many mostly used herbs for OP remedy. Its most important lively part, corresponding to icariin, has varied organic features, such because the stimulation of bone formation and sexual operate, safety of the nervous system, and prevention of degenerative ailments (Chen et al., 2015) (Table 1). Moreover, the entire flavonoids of Natural Epimedii folium (0.006–6 μg/mL) may regulate run-related transcription issue 2 (Runx2)-mediated osteogenesis and peroxisome proliferator-activated receptor gamma (PPARγ)-mediated adipogenesis in BMSCs, additional exhibit useful results to bone well being (Zhang et al., 2016). Furthermore, they (10 μg/mL) have additionally been noticed to control the steadiness between BMSC’s osteogenic and adipogenic differentiation in ovariectomized rats by down-regulating expression of Dickkopf-related protein 1 (DKK1) (Xu et al., 2011). Naturally remoted icariin has gained vital consideration instead part for OP remedy, which stimulates bone formation, inhibits bone resorption, and will increase angiogenesis (Zhang et al., 2014; Wang et al., 2018). Icariin (10⁻⁵ M) can induce osteogenic differentiation of pre-osteoblastic MC3T3-E1 cells and mouse major OB by upregulating the mRNA expression of Runx2, DNA binding inhibitor 1 (ID-1), and bone morphogenetic protein (BMP-4) (Zhao et al., 2008). Students have studied the dose-effect relationship of icariin and located that it has a dose-dependent impact (10⁻⁹ to 10⁻⁶ M) on the proliferation and osteogenic differentiation of human BMSCs inside the low focus vary. Due to this fact, icariin is extraordinarily low value and its excessive abundance has made it a horny remedy various for OP (Fan et al., 2011). Moreover, Icariin (10⁻⁹ M) additionally promotes osteogenesis by reversing the decreased proliferation, elevated ROS, decreased matrix metalloproteinases (MMPs), diminished osteogenesis, and enhanced adipogenesis of MSCs attributable to steroid-associated components (Sun et al., 2015; Kim et al., 2017). Icariin may inhibit glycogen synthase kinase-3beta (GSK3β) and PPARγ pathways, stimulate osteogenic differentiation, and inhibit adipogenesis in MSCs (Sheng et al., 2013). Furthermore, Epimedium herb has been noticed to stop OP attributable to ovariectomy in rats, which additional validated that icariin can improve osteogenic differentiation of rat major BMSCs in a concentration-dependent method (10⁻⁵ μM). It may possibly additionally enhance the expression of genes concerned in osteogenesis, corresponding to alkaline phosphatase, bone matrix protein (osteocalcin, osteopontin, and bone sialoprotein), and cytokines (TGF-β1 and IGF-I), and so on. (Chen et al., 2007). It has been noticed that sufferers with kind 2 diabetes mellitus (T2DM) are extra vulnerable to OP. Icariin has been indicated to advertise BMSC proliferation and osteogenic differentiation in OP sufferers with T2DM by up-regulating GLI-1 (Xia et al., 2023). Moreover, one other main part of Epimedium folium, maohuoside A (MHA), additionally promotes osteogenic differentiation of rat BMSCs through BMP, MAPK, and Wnt/β-catenin signaling pathways by enhancing the mRNA expression of BMP-2, BMP-4, Runx2, β-catenin, cyclinD1, ERK1/2, and p38 MAPK, and is perhaps more practical than icariin (Zhang et al., 2010; Yang et al., 2011; Xu et al., 2012). Pharmacokinetic evaluation has indicated that icaritin has a brief half-life within the blood and solely a hint quantity reaches the bone tissues. Due to this fact, to beat the restrictions of poor focusing on and metabolism of icaritin in vivo, researchers have developed a bone-targeting liposome that may encapsulate icaritin to additional promote bone formation and inhibit fats era in ovariectomy (OVX)-induced OP mice, probably through the Akt/GSK-3β/β-catenin signaling pathway (Huang et al., 2018). The above research indicated that Epimedii folium and its efficient medicinal elements exhibit their sturdy osteogenic exercise by enhancing the osteogenic differentiation of BMSCs and regulating oxidative stress, which partially explains their anti-OP results.

Desk 1. The primary efficient elements in single herb.

Ligustri lucidi fructus (Nvzhenzi in Chinese language) [Ligustrum lucidum Ait.] is a generally used TCM herb for stopping and treating OP by nourishing the liver and kidneys. Its lively compounds primarily embody ligustroside, oleanolic acid, oleanolic acid methyl ester and ursolic acid, and so on. Moreover, it and its compounds have a number of organic actions together with anti-fatigue, anti-oxidation, anti-tumor, and anti-aging properties, and so on. (Li et al., 2011). A number of complete research together with natural community pharmacology prediction mixed with in vitro experimental verifications, have confirmed that Ligustri lucidi fructus promotes osteogenic differentiation of BMSCs by activating the PI3K/AKT signaling pathway (Kong et al., 2022). Ligustri lucidi fructus can considerably improve bone mineral density (BMD) and bone microstructure, whereas reduces physique fats content material in postmenopausal OP (PMOP) mice. Furthermore, it will possibly scale back OC exercise, improve Runx2 inhibit PPARγ, and suppress adipocyte differentiation from BMSCs (Qin et al., 2023). The ethanol extract of Ligustri lucidi fructus has been noticed to upregulate the expression of osteogenic differentiation regulators (β-Catenin, BMP-2, Cyclin D1, MMPs, Osteoprotegerin, TBX3, and so on.), stimulate alkaline phosphatase (ALP) actions, shorten the time required for BMSC’s mineralization throughout osteogenic differentiation, and is employed for the remedy of OP (Li et al., 2010). The above research indicated that Ligustri lucidi fructus and its efficient medicinal elements can forestall bone loss and enhance bone microstructure by modulating bone and fats steadiness, which is perhaps a therapeutic agent for OP.

Psoralere fructus (Buguzhi in Chinese language) [Psoralea corylifolia L.] is a herbaceous plant of the leguminosae household, which is often consumed for the remedy of OP, bone fracture, osteomalacia, and leukoderma, and so on. (Yang et al., 2018). Psoralen, angelicin, bakuchiol, apigenin and kaempferol are the lively elements of Psoralere fructus. It’s reported that psoralen can activate the AKT/GSK-3β pathway and improve NRF2 expression to revive BMSCs stemness, thereby additional enhancing the radiation-induced OP (Yin et al., 2022). Furthermore, Psoralen may promote osteogenic differentiation of BMSCs by regulating the expression of osteogenic differentiation-related genes (BMP-4, osteopontin, Runx2, Osterix, and miR-488) and the TGF-β/Smad3 pathway related proteins (TGF-β1, TGF-β RI, p-Smad, and Smad3) (Huang et al., 2019, 2021). As well as, it has been indicated that Psoralen will increase the extent of osteogenic marker osteocalcin in ovariectomy (OVX)-induced OP rats, thereby considerably enhancing bone mass indicators, corresponding to elevated trabecular thickness and diminished trabecular area, which can be associated to the inhibition of Notch signaling pathway (Yang et al., 2012). Bergapten is a by-product of Psoralen, which belongs to linear furan coumarin and has protecting results in opposition to bone loss. The literature means that Bergapten can dose-dependently promote ALP, Runx2, and osteocalcin ranges in BMSCs in vitro. In OVX-induced OP mouse fashions, Bergapten has been noticed to upregulate Runx2 and osteocalcin, and additional enhance the parameters of bone metabolism corresponding to bone density, trabecular amount, and trabecular separation, which is perhaps related to the activation of WNT/β-catenin signaling that may promote BMSCs differentiation into OB (Xiao et al., 2015).

Drynariae rhizome (Gusuibu in Chinese language) [Drynaria fortune (Kunze) J. Sm.] can be a TCM herb, generally utilized by orthopedics and OP remedy. Moreover, it promotes an anti-osteoporotic impact by focusing on stem cells, OB, OC, and immune cells in addition to a number of signaling pathways (corresponding to PI3K/ATK, OC differentiation, WNT, and estrogen, and so on.) (Gan et al., 2019). Furthermore, whole flavonoids of Drynariae rhizome can upregulate the degrees of osteogenic-related components (ALP, OCN, and Runx2), improve the survival potential, and improve osteogenic differentiation of BMSCs in vitro, probably by activating the ERR1/2-Gga1-TGF-β/MAPK pathway (Han et al., 2024). Naringin is the primary efficient ingredient of Drynariae rhizome and has been discovered to advertise the proliferation and osteogenic differentiation of human BMSCs, thereby offering a foundation for the therapeutic mechanism of Drynariae rhizome in opposition to OP and bone nonunion (Zhang et al., 2009). As well as, naringin dose-dependently elevated ALP exercise, osteogenic genes mRNA ranges (ALP, BSP, and Cbfa1), and Notch1, whereas it decreases the mRNA ranges of PPARγ2, suggesting that the osteogenic impact of naringin is perhaps related to the Notch signaling pathway (Yu et al., 2016).

Morindae officinalis radix (Bajitian in Chinese language) [Morinda officinalis How] is a TCM herb that has been used for hundreds of years as tonics for nourishing the kidney, strengthening the bone, and enhancing the immune operate in OP remedy (Zhang et al., 2018). It incorporates potential anti-osteoporotic lively compounds corresponding to nystose that may regulate the proteins implicated in ovarian steroidogenesis-related pathways (Liu et al., 2020). Morinda officinalis polysaccharides (MOP) are lively elements remoted from Morindae officinalis radix. They’ve anti-OP medicinal potential and rat BMSCs pretreated with MOP have been noticed to advertise osteogenic differentiation (upregulating Runx2 and BMP2) or adipogenic differentiation (downregulating CEBPα and PPARγ). In OVX rats, MOP can activate the PTEN/PI3K/AKT pathway, upregulate BMD, bone-derived alkaline phosphatase (BALP), osteocalcin, and miR-21 (focusing on PTEN) ranges, in addition to partially alleviate OP signs (Wu P. et al., 2022). The exosomes are important for intracellular communication and may carry genetic info (miRNAs, mRNAs, DNA, proteins, and liquids) and act on the right track cells to exert their results. Moreover, they’ll have an effect on bone metabolism and modulate the OB and OC interplay (Shan et al., 2019). MOP has additionally been noticed to extend imply trabecular thickness and quantity, imply connectivity density, scale back imply trabecular separation/spacing, and improve cortical bone continuity in femoral tissue in glucocorticoid-induced OP rats. As well as, it additionally will increase Runx2 and RANK, whereas inhibits MMP 9 and cathepsin Ok ranges. In MOP-treated rats, BMSC-Exo can inhibit OC differentiation and proliferation, probably by upregulating miR-101-3p or inhibiting prostaglandin-endoperoxide synthase 2 (PTGS2) (Wu PY. et al., 2022). The emergence of exosomes gives new insights for mediating intercellular communication and knowledge alternate amongst BMSCs, OB, OC, and different cells. Due to this fact, additional analysis is warranted.

In TCM, Angelicae sinensis radix (Dangui in Chinese language) [Angelica sinensis Diels.] herb is consumed for “Qi-invigorating,” i.e., stimulating power metabolism (Chen et al., 2013). Ferulic acid, imperatorin and others are broadly obtainable and cheap plant extract remoted from A. sinensis radix, that has anti-oxidative and anti-apoptotic results (He et al., 2007). It has been indicated that imperatorin prompts Runx2, Col1a1, and osteocalcin in rat BMSCs by selling p-Ser9 of GSK3β and β-catenin nuclear translocation. Furthermore, it additionally promotes the secretion of the upstream issue p-AKT (Ser473) within the Akt/GSK3β/β-catenin pathway, thereby enhancing osteogenesis and inhibiting OC, assuaging OP signs (Yan et al., 2020).

For many years, TCM formulation have been used for stopping and treating OP and are considerably advantageous over single herbs. A examine ready Chinese language natural extracts from 9 TCM compounds with anti-fatigue and immune regulatory results, together with Astragalus, Cistanche deserticola, Dioscorea polystachya, Lycium barbarum, Epimedium, Cinnamomum cassia, Syzygium aromaticum, A. sinensis, and Curculigo orchioides. It was noticed that oral administration of this prescription alleviated alcohol-induced bone metabolism abnormalities in middle-aged and aged male mice, validating that conventional medicinal plant formulation have therapeutic potential in opposition to OP (Qian et al., 2021). Danggui Buxue Tang (DBT) is an natural combination comprising Astragalus membranaceus and A. sinensis. Compared with different natural extracts, DBT remedy considerably enhances OB with a rise in most respiration, reserve capability, glycolytic capability, and glycolytic reserve. Furthermore, DBT additionally modulates bioenergy metabolism through mobile Ca²⁺ and ROS signaling transduction, thus enhancing bone ailments corresponding to OP (Kwan et al., 2021). Research have additionally proven that the regulatory impact of TCM on OB and OC is achieved by stimulating BMSCs.

An anti-osteoporotic natural method containing Epimedii folium, Ligustri lucidi fructus, and Psoraleae fructus can improve bone formation and scale back bone reabsorption of BMSCs-derived osteoblastogenesis. This examine additionally indicated that Epimedii folium and Ligustri lucidi fructus are the primary herbs that promote OB differentiation, and their co-treatment had vital synergistic results (Siu et al., 2013; Ko et al., 2016). Liu’s Zhenggudan method comprising Rehmannia glutinosa, Caesalpinia sappan, S. aromaticum, Costustoot, and Acacia catechu has demonstrated good medical therapeutic efficacy in opposition to OP. Moreover, it has been discovered to induce osteogenic differentiation of MSCs and deal with OP by rising ALP and osteocalcin (Deng et al., 2022). Furthermore, the Qing’e method was ready from an historical Chinese language recipe comprising Cortex eucommiae, Fructus psoraleae, Semen juglandis, and Allium sativum. It has been noticed to control bone metabolism and enhance bone mineral density in OP sufferers. As well as, Qing’e formula-treated serum indicated elevated differentiation of BMSCs remoted from the proximal femurs of PMOP mice. Furthermore, it will possibly upregulate TGF-β1 mRNA degree and ALP exercise, in addition to improve the recombinant human bone morphogenetic protein-2 (rhBMP-2)-mediated adjustments in cell morphology, proliferation, and differentiation (Shuai et al., 2015). The Herba Epimedii, Fructus Ligustri Lucidi, and Fructus Psoraleae method and its part have indicated no cytotoxic impact on MSCs and may promote cell proliferation by upregulating the expression of Runx2, ALP, and OPN in MSCs (Siu et al., 2017). A TCM method, Jiawei Yanghe Tang (comprising Radix Rehmanniae Praeparata, Colla Cornus Cervi, Papaya, Mustard seed, Tetrandrine, C. cassia, Spatholobus stem, Baked ginger, Licorice, and Ephedra) was originated centuries in the past within the Qing Dynasty and has been used for treating OP. Its-treated serum and direct drug intervention can activate the bone morphogenetic protein-Drosophila moms in opposition to decapentaplegic (BMP-SMAD) signaling pathway, restore the differentiation potential of BMSCs, promote osteogenic differentiation of BMSCs and inhibit their adipogenic differentiation, thereby enhancing bone density, microstructure harm, and bone metabolism abnormalities in OVX rats (Luo et al., 2022). Taohong Siwu Decoction (THSWD) is a standard conventional Chinese language prescription that has been noticed to advertise blood circulation and alleviate blood stasis. Moreover, THSWD additionally promotes BMSC’s exercise, osteogenic differentiation, and migration in a time- and dose-dependent method. This is perhaps achieved by upregulating VEGF expression and phosphorylation of FAK (Tyr397) and Src (Tyr418) (Lu et al., 2023). One other TCM method is Er-Xian decoction which is broadly used for the remedy of postmenopausal OP. It has been discovered to extend bone mass in OVX-induced OP mice, improve osteocalcin ranges, and promote BMSC’s self-renewal and OB differentiation. Furthermore, it will possibly rescue a number of gene expressions (upregulating Col1a1, Cthrcl, Posten, and Igfals) related to OVX dysregulation (Liu et al., 2016). These information present the premise for additional analysis and proof for the applying of TCM formulation for OP remedy (Table 2).

Desk 2. Results and potential mechanisms of TCM prescriptions in OP.

Latest research have indicated that the BMSC differentiation into osteogenic lineages can promote bone formation and preserve bone homeostasis, which has develop into a promising technique for treating OP. Chinese language medicinal herbs are safer and more practical substitutes to trendy medication with vital unwanted effects and have been employed for hundreds of years for the remedy of assorted varieties of OP. Each in vivo and in vitro experiments have confirmed that TCM could exert therapeutic results by stimulating BMSCs differentiation, thereby restoring the steadiness between OB and OC, inhibiting adipocyte differentiation, and exerting anti-inflammatory, immune regulatory, antioxidant, and different results (Figure 1). Nevertheless, medical analysis to show their therapeutic results is at the moment inadequate. Some TCM herbs and prescriptions, corresponding to Dipsaci radix are generally utilized in medical follow to deal with OP and will induce the proliferation and differentiation of BMSCs. This evaluate helps to higher perceive the mechanism of TCM herbs and their efficient elements for treating OP, thereby offering a helpful and dependable foundation for creating more practical anti-OP medication.

Determine 1. Therapeutic potential of Chinese language medicinal herbs stimulating osteogenic differentiation of BMSCs in OP (Notice: Elements in pink are upregulated by TCM, whereas components in blue are downregulated by TCM).