TABLE 3.

Anti-osteoporotic effects of natural herbal medicines.

Drugs name	Source	Active ingredients	Mechanism of action	Signaling pathways	Efficacy (Based on in vitro and in vivo experiments, animal models or cellular models)	Bibliography
Epimedium	Dried leaves of Epimedium, family Berberidaceae	Total Flavonoids Epimedium icariin Epimedium polysaccharide	Promote bone marrow mesenchymal stem cells to osteogenic differentiation, inhibit osteoclast differentiation, and increase bone density	Wnt/β-catenin, MAPK, OPG/RANKL/RANK, BMP/RunX2/OSX, Notch signaling pathway	Nourishing the liver and kidneys, strengthening the muscles and bones, invigorating the blood	Zhao et al. (2019)
Bone tonic (Davallia trichomanoides Blume)	Dried rhizome of Quercus serrata, family Aquilariaceae	Total Flavonoids Naringenin New North American sage glucoside	Promote osteoblast proliferation and differentiation, regulate cytokines in bone metabolism, and reduce osteoclast activity	OPG/RANKL/RANK, histone K, Wnt/β-catenin, and Bone forming protein pathway	Tonifying the kidneys and strengthening the bones, invigorating the blood and dispelling bone wind	Lei et al. (2021)
Malaytea scurfpea fruit (Psoraleae Fructus)	Dried mature fruit of Psoralea vulgaris (Leguminosae)	Isoflavones Psoralen Isosplenetin	Promote osteoblast differentiation and inhibit osteoclast activity Phytoestrogen-like effects	Upward revision of OPG/RANKL ratio inhibition of NF-κB signaling pathway, the PI3k/AKT signaling pathway, activation of MAPK signaling pathway	Tonifies the kidneys and promotes bone healing	Wang et al. (2024)
Eucommia	Bark of Eucommia, family Eucommiaceae	Total Flavonoids Eucommia lignan	Regulation of bone metabolism Increased serum ALP levels, increased femur mass, and Phytoestrogen-like effects	Wnt/β-catenin, BMP/Smad MAPK, OPG/RANKL/RANK, estrogen signaling pathway	Benefiting Qi, strengthening the spleen, tonifying the muscles and bones, invigorating the blood	Feng et al. (2022)
Radix rehmanniae	Rehmannia concoctions	Sitosterol Stigmasterol	Increase osteoblast proliferation and differentiation, promote bone repair, regulate apoptosis, estrogen response process	Targeting IGF1, VEGFA core protein, PI3K-Akt, MAPK signaling pathway	Benefiting the essence and filling the marrow, nourishing Yin and replenishing blood	Xu et al. (2020b)
Radix achyranthis bidentatae	The root of the amaranth plant hyssop	Alkaloid Hyssop polysaccharides,ß-ecdyssterone	Protects bone minerals and increases osteoblast activity	PI3K/Akt JAK/STAT. NF-κB signaling pathway	Tonifying the liver and kidney, strengthening the waist and knees, invigorating blood circulation and removing blood stasis	Lee et al. (2022)
Lycium barbarum	Fruit of Lycium barbarum, family Solanaceae	Isoflavones Lycium barbarum polysaccharide	Enhancement of osteogenic activity and mineralization capacity of bone marrow mesenchymal stem cells	IL-17, TNF, AGE-RAGE, MAPK signaling pathway	Nourishes the liver and kidneys, strengthens the muscles and bones	Luo et al. (2023)
Astragalus	Roots of Astragalus mongolica or Astragalus membranaceus, family Leguminosae	Astragalus polysaccharide	Promotion of osteoblast proliferation and differentiation, inhibition of osteoclast resorption via estrogenic pathway, phytoestrogen-like effects	Osteoclast differentiation pathway, IL-17 factor pathway, AGE-RAGE signaling pathway, estrogen pathway BMP-2/Smads signaling pathway	Tonifying Qi and Blood	Kong et al. (2018)
Angelica sinensis	Dried root of Angelica sinensis, family Umbelliferae	Angelica polysaccharide	Improve bone density and quality, increase the number of osteoblasts	OPG/RANKL/RANK pathway, ERK pathway	Tonifying Qi and Blood	Lim and Kim (2014)
Salvia miltiorrhiza	The root of Salvia miltiorrhiza, family Labiatae	Salvia miltiorrhiza polysaccharides Tanshinone Salvia polyphenols	Promote differentiation of MSCs into osteoblasts, promote proliferation and mineralization of osteoblasts, and inhibit apoptosis of osteoblasts	BMP/Smads, Wnt/β-catenin, ERK/, PI3K/AKT signaling pathway, OPG/RANKL/RANK pathway	Promoting blood circulation and eliminating blood stasis, cooling the blood and eliminating carbuncles	Jiang et al. (2019)
Dipsaci Radix	Dried roots of the herbal plant himalayan teasel	Total Saponin	Promote differentiation of bone marrow mesenchymal stem cells towards osteoblasts, promote osteoblast differentiation and mineralization, and increase bone density	Promotes BMP-2 protein expression, OPG/RANKL/RANK pathway	Tonifying the liver and kidney, strengthening the muscles and bones, and renewing fractures	Zhang et al. (2019)
Antler	Young unossified densely antlered antlers of stags	Total Peptides Steroids Polyamines	Inhibits osteoclast differentiation and increases bone density	Wnt/β-catenin signaling pathway	Tonifies the vital energy and blood, benefits the essence and strengthens the muscles and bones	Liu et al. (2023)
Cornus officinalis	The dried, ripe pulp of the dogwood plant	Cornus neoside Total glycosides	Promote osteoblast proliferation and differentiation	Regulation of nuclear factor NF-κB TRPV6, TRPV5 channel protein expression	Tonifying the liver and kidney, astringing sperm and fixing deficiency	Tang et al. (2023)