Table 3.
Alkaloid-SMAs and their molecular mechanisms of action
| Name | Source | Cell types | Function | Mechanisms | In vivo | Ref. |
|---|---|---|---|---|---|---|
| Neferine | Nelumbo nucifera (lotus) | BMMs(C57BL/6 mice) ; MC3T3 E1 |
OC↓ OB↑ |
Inhibits the NF-κB pathway | OVX | 153 |
| Nuciferine | Nelumbo nucifera (Lotus) | BMMs(Balb/c mice) | OC↓ | Inhibits the NF-κB and MAPK pathways | OVX; BCIO | 151,152 |
| Tetramethylpyrazine | Ligusticum chuanxiong Hort. | BMSCs; hPDLSCs; human chondrocytes; and human osteosarcoma cells |
OC↓ OB↑ |
Inhibits the NF-κB and mTOR pathways; inhibits RANKL and IL-6 signaling; activates the AMPK pathway |
GIOP | 25,131,186,187,264 |
| Tomatidine | Solanaceae | BMMs (C57BL/6 mice) |
OC↓ inflammation ↓ |
Inhibits the NF-κB pathway |
OVX | 154 |
| Neotuberostemonine | Stemona tuberosa | BMMs (C57BL/6 mice) | OC↓ |
Inhibits the NF-κB pathway |
— | 155 |
| Tetrandrine | Stephania tetrandra S. Moore | BMMs (C57BL/6 mice) |
OC↓ inflammation ↓ |
Inhibits the NF-κB, PI3K/AKT, and MAPK pathways |
OVX; SNM; TiP-IMAPO | 156–158 |
| Berberine | Berberis Linn. | MC3T3-E1 cells, hMSCs, RAW264.7 cells, etc. |
OC↓ OB↑ inflammation ↓ oxidative stress ↓ |
Inhibits the NF-κB, PI3K/Akt and NFAT pathways; activates the PKA, p38 MAPK, Wnt/β-catenin and AMPK pathways | SO(SAMP6); OVX; LIOP; GIOP | 188,265,266 |
| Sanguinarine | Sanguinaria Canadensis | BMMs, RAW264.7 cells, MC3T3-E1 cells | OC↓ |
Inhibits the NF-κB and ERK pathways; activates the AMPK/Smad1 pathway |
OVX | 106,136 |
| Vinpocetine | Catharanthus roseus (L.) G. Don, Gen. Hist | BMMs (C57BL/6 mice) |
OC↓ inflammation ↓ oxidative stress ↓ |
Inhibits the MAPK and NF-κB pathways | OVX | 33 |
| Norisoboldine | Lindera aggregata (Sims) Kosterm. | BMMs (male ICR mice); RAW264.7 cells | OC↓ | Inhibits the MAPKs/NF-κB/c-Fos/NFATc1 signaling and HIF pathways | OVX | 139,159 |
| Aconine | Aconitum carmichaelii Debx. | RAW264.7 cells | OC↓ | Inhibits the NF-κB pathway | - | 35 |
| Evodiamine | Tetradium ruticarpum (A.Jussieu) T. G. Hartley | BMMs (C57BL/6 mice) | OC↓ | Inhibits the NF-κB, MAPK, and calcium pathways | OVX; GIOP (zebrafish) | 34,71 |
| Rutaecarpine | Tetradium ruticarpum (A.Jussieu) T.G.Hartley | BMMs | OC↓ | Inhibits the NF-κB and NFATc1 pathways | - | 267 |
| Stachydrine |
Leonurus heterophyllus Sweet |
BMMs (C57BL/6 mice) | OC↓ | Inhibits the NF-κB and Akt pathways | LIOP | 164 |
| Dauricine | Menispermum dauricum DC. | BMMs (C57BL/6 mice) |
OC↓ oxidative stress ↓ |
Inhibits ROS/PP2A/NF-κB signaling | LIOP | 189 |
| Cytisine | Leguminosae (Fabaceae) | BMMs (C57BL/6 mice); RAW264.7 cells; BMSCs(C57BL/6) | OC↓ | Inhibits the JNK/ERK/p38-MAPK, IκB alpha/p65-NF-κB and PI3K/AKT pathways | OVX | 140 |
| l-Tetrahydropalmatine | Corydalis DC | BMMs (C57BL/6 mice); RAW264.7 cells | OC↓ | Inhibits the NF-κB and MAPKs pathways | OVX | 141 |
| Arecoline | Areca catechu Linn. |
BMMs (C57BL/6 mice); MC3T3-E1 cells |
OC↓ OB↑ |
Inhibits RANKL, NFATc1, and c-Fos signaling | LIOP | 132 |
| Piperine | Piper nigrum Linn. | RAW264.7 cells; MC3T3-E1 cells |
OC↓ OB↑ |
Inhibits p38/c-Fos/NFATc1 signaling; activates the Wnt and AMPK pathways |
OVX | 81,105,137 |
| Lycorine | Lycoris radiata (L’Her.) Herb. | BMMs (C57BL/6 mice) | OC↓ |
Inhibits mROS/TRPML1/TFEB signaling; inhibits the MAPK pathway |
OVX; TiP-IMAPO; LIOP | 268,269 |
| Sinomenine | Sinomenium acutum Rhed. et Wils. | RAW264.7 | OC↓ |
Activates caspase-3 activity; downregulates IL-8/CXCR1, TLR4/TRAF6 and c-Fos/NFATc1 signaling |
LIOP; BCIO | 270–272 |
| Diaporisoindole E | Diaporthe sp. SYSU-HQ3 | BMMs (C57BL/6 mice) | OC↓ | Inhibits the PI3K/AKT and MAPK pathways | - | 167 |
| Cinchonine | Cinchona ledgeriana (Howard) Moens ex Trim. | BMMs (C57BL/6 mice); RAW264.7 cells; BMSCs |
OC↓ OB↑ |
Inhibits the NF‐κB pathway | OVX; LIOP | 133 |
| Aminocoumarins | Streptomyces | BMMs (male ICR mice) | OC↓ |
Inhibits the MAPK pathway; inhibits IL-1β, TNF-α, and iNOS signaling |
LIOP | 273 |
| Nitensidine A | Pterogyne nitens | BMMs (male ddY mice) | OC↓ | - | — | 190 |
| Theobromine | Theobroma cacao L. | hMSCs | OB↑ | - |
Bone development (SD rats) during pregnancy, lactation, and the early growth period |
274 |
| Leonurine | Leonurus artemisia | RAW 264.7 cells; BMMs; MC3T3-E1 cells |
OC↓ OB↑ |
Inhibits the NF-κB and PI3K/Akt pathways; activates the PI3K/Akt/mTOR pathway |
OVX | 80,275 |
| Harmine | Peganum harmala L. | BMMs (male ddY mice); RAW264.7 cells;UAMS-32 cells; MC3T3-E1 cells |
OC↓ OB↑ |
Inhibits c-Fos and NFAT c1 signaling; activates the BMP and Runx2 pathways |
OVX | 120,276 |
| Vindoline | Catharanthus roseus (L.) G. Don | BMMs (C57BL/6 mice) |
OC↓ oxidative stress ↓ |
Inhibits the MAPK pathway | OVX | 209 |
| Matrine and its derivatives | Sophora flavescens Alt. | BMSCs (rats) |
OC↓ OB↑ |
Inhibits the NF-κB, AKT, and MAPKs pathways | OVX; RMEM | 277–279 |
| Securinine | Flueggea suffruticosa (Pall.) Baill. | BMMs (male ICR mice) | OC↓ | Inhibits the p38, Akt, JNK, IκB, c-Fos, and NFATc1 pathways | LIOP | 280 |
| Magnoflorine | Magnolia or Aristolochia | BMMs (C57BL/6 mice) | OC↓ | Inhibits the MAPK and NF-κB pathways | Ti particle-induced mice air pouch osteolysis | 281 |
| Nitidine chloride | Zanthoxylum nitidum (Rutacease) and Fagara zanthoxyloides | BMMs (C57BL/6 mice) | OC↓ | Inhibits the RANKL-induced NF-κB and NFATc1 pathways | OVX | 282 |
| Largazole | a cyanobacterium in the genus Symploca | C2C12 cells | OB↑ | Activates the Runx2 and BMPs pathways |
Mouse calvarial bone formation assay; rabbit calvarial bone fracture healing model |
283,284 |