Table 5.
Brassicaceae-derived OSCs: effects on in vivo models of bone loss.
| Molecule tested | Experimental in vivo model description | Mode of administration, dose and duration | Main effect | Specific features | Authors | Ref |
|---|---|---|---|---|---|---|
| Sulforaphane | C57BL/6 mice, Mouse calvarial models treated with LPS (10 mg/kg body weight injected in calvaria) | Intraperitoneal injection, 10 mg/kg body weight, the day before LPS treatment for 6 days | Protection against LPS-induced calvarial bone erosion by inhibition of osteoclastogenesis | • ↑ BV/TV, Tb.N, ↓Tb.Sp (microCT) • ↓ osteoclasts (TRAP staining in histological samples) • ↓ CTSK (immunohistochemical and immunofluorescence analysis) |
Luo et al. | (103) |
| Sulforaphane | Ex vivo culture of calvariae explants of 2–3-day-old and 7-week-old, C57BL/6 mice | 3 μM | Promotes osteogenesis inhibits osteoclastogenesis | • ↑ ECM mineralization (alizarin red staining on calvaria tissue) • ↓ RANKL (RT-PCR on calvariae lysates) |
Thaler et al. | (97) |
| Sulforaphane | Mice model of OP (Female, 8-week-old, C57BL/6 mice, ovariectomy) | Intraperitoneal injection, 7.5 mM DL-SFN, every other day for 5 weeks | Prevention of bone loss | • ↑ BV/TV, Tb.N ↓Tb.Sp, no effect on Tb.Th or Co.Th in tibiae (micro CT) | Thaler et al. | (97) |
| SFX- 01® (a stable form of Sulforaphane) | Osteoarthritis model (Male, 26-week-old, STR/Ortmice) | Oral administration, 100 mg/kg, daily for 3 months | Improvements in cortical bone mass | • ↑ TV, BV and BV/TV of tibial epiphyseal trabecular bone and metaphyseal trabecular bone (micro CT) • ↑serum P1NP (ELISA) • ↓serum CTX-I (ELISA) |
Javaheri et al. | (105) |
| Brassica rapa L. root ethanol extract | Female, 3-week-old, Sprague- Dawley rats | Oral administration, 500 mg/kg/day, single daily dose for 6 weeks | Increased bone formation | • ↑ BMD, BV, BV/TV, Tb.N, Tb.Th., ↓Tb.Sp. (microCT) • ↑ serum OCN (immunoassay) |
Jeong et al. | (54) |
| Lepidum sativum seed extract | Rat model of OP (Female Wistar rats, ovariectomy) | Oral gavage 50 and 100 mg/kg | Prevention of bone loss and bone strengthening activity | • ↑ femur weight (weights were calculated as wet femur weight/body weight) • ↑ femur compression strength (hardness tester (Erweka GmbH, Heusen-stamm, Germany) • ↑ ALP, OCN serum levels; ↓ TRAP, CTX-I serum levels (ELISA) • ↓ RANKL, ↑ OPG mRNA (RT-PCR) |
Abdallah et al. | (59) |
| Lepidum sativum seed | Glucocorticoid-induced OP (GIO) model (Female Wistar rat, subcutaneous injection of methylprednisolone 3.5 mg/kg per day for 4 weeks) | Oral gavage, 6 g of LS seeds in diet daily | Prevention of GIO-dependent bone loss | • ↑ percentage of trabecular bone vs GIO (histopathological examination and Image J quantification) • ↓ serum TRAP vs GIO (commercial kit) • ↑ serum b-ALP (immunoassay), phosforous and calcium (automated analyser) vs GIO |
Elshal et al. | (106) |
| Lepidum sativum seed | Fracture-induced healing model (New Zealand White rabbits, induced fractures in the midshaft of the left femur) | Oral gavage, 6 g of Lepidum sativum seeds in their food daily after surgery | Increased healing of fractures | Increased callus formation in fractures (x-rays and quantification) | Juma et al. | (83) |
| Methanolic and aqueous extract of Lepidium sativum seeds | Fracture healing model (Charles foster rats, hand held three-point bending technique) | Oral administration, methanolic extracts 400 mg/kg or aqueous extracts 550 mg/kg, from the day of fracture induction for 2 months | Increased healing of fractures | • Larger callus formation (x-rays and quantification) • ↑ calcium, phosphorus, and ALP serum levels (commercial kits) |
Dixit Jr Iii et al. | (28) |
| Lepidium sativum seeds | Glucocorticoid-induced OP (Adult male guinea pigs, methyl prednisolone 3.5 mg/kg per day for 4 weeks subcutaneously) | Oral administration trough a gastric tube, 300 mg/kg, for 4 weeks | Prevention of bone loss in femur | • Prevention of caspase-3 activation (caspase-3 immunostaining) • Prevention of decrease of OPN (immunohystochemistry) • Prevention of decrease in osteoblast and Co.th. in femur (histomorphometric analysis) • Prevention of increase of osteoclasts in femur (histomorphometric analysis) |
EL-Haroun et al. | (107) |
| Ethanol extracts of Maca root (Lepidium meyenii Walp.) | Rat model of OP (Female, 90-day-old, Sprague-Dawley rats, ovariectomy) | Oral gavage, 0.096 and 0.24 g/kg, for 28 weeks | Prevention of estrogen deficient bone loss | • ↑ calcium content of femur (Atomic Absorption Spectrophotometer) • ↑ BMD and trabecular bone of the lumbar vertebrae (DEXA) • ↑ serum OCN (radioimmunoassay commercial kit) |
Zhang et al. | (108) |
| Hot water extract of Brassica oleracea (Bo) | Mice model of OP (Female, 7-week-old, C57BL/6 mice, ovariectomy) | Oral administration, 500 mg/kg, daily for 10 weeks | Inhibits OVX-induced bone loss | • ↑ BMD when in combination with Panax ginseng (DEXA) • ↓ osteoclast number when in combination with Panax ginseng (immunohistochemistry, TRAP staining) |
Kang et al. | (99) |
Most in vivo studies were conducted by using water or ethanol extracts of Brassica edible plants (8 studies; Brassica rapa, Lepidum sativum, Lepidum meyenii Walp, Brassica oleracea). A minority of studies used Brassicaceae-purified OSCs (3 studies; 4 models; SFN, SFX-01). Most studies were performed in osteoporosis mice showing prevention of bone loss. Notably, only the effects of purified OSCs (labeled with * in the table) can be attributable entirely to OSCs. The route of administration was mainly by oral administration. Markers of bone formation in serum: procollagen 1 intact N-terminal propeptide (P1NP); osteocalcin (OCN). Markers of bone resorption in serum: serum type I collagen breakdown product (CTX-I), tartrate-resistant acid phosphatase (TRAP), osteoprotegerin (OPG), cortical thickness (Co.Th). Bone microstructural parameters analyzed by microCT analysis: BMD (bone mineral density), bone volume (BV), bone volume/total volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular space (Tb.Sp.). Bone mineral density analyzed by Dual-energy X-ray absorptiometry (DEXA). Markers of bone formation in histological specimen: alkaline phosphatase (ALP), osteopontin (OPN). Markers of osteoclasts/bone resorption in histological specimen: tartrate-resistant acid phosphatase (TRAP), cathepsin K (CTSK). Measurements of bone strength: Erweka GmbH, Heusen-stamm Germany. Extracellular matrix (ECM). Markers of osteoclast in histological specimen: receptor activation of nuclear factor-kB ligand (RANKL). ↑ means up-regulation; ↓ means down-regulation. ↑ means up-regulation; ↓ means down-regulation.