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Marantodes pumilum (Blume) Kuntze (Kacip Fatimah) leaves aqueous extract prevents downregulation of Wnt/β-catenin pathway and upregulation of apoptosis in osteoblasts of estrogen-deficient, diabetes-induced rats

Kamarulzaman Karim 1Nelli Giribabu 2Naguib Salleh 3

J Ethnopharmacol doi: 10.1016/j.jep.2021.114236. 

Abstract

Ethnopharmacological relevance: Marantodes pumilum (Blume) Kuntze has been claimed to be beneficial in protecting the bone against loss in post-menopausal women. In view of increased incidence of diabetes mellitus (DM) in post-menopausal period, M. pumilum ability to overcome the detrimental effect of estrogen-deficiency and DM on the bones were identified.

Aim of the study: To identify the mechanisms underlying protective effect of MPLA on the bone in estrogen-deficient, diabetic condition.

Methods: Adult female, estrogen-deficient, diabetic rats (225±10 g) were divided into untreated group and treated with M. pumilum leaf aqueous extract (MPLA) (50 mg/kg/day and 100 mg/kg/day) and estrogen for 28 days (n=6 per group). Fasting blood glucose (FBG) levels were weekly monitored and at the end of treatment, rats were sacrificed and femur bones were harvested. Bone collagen distribution was observed by Masson’s trichome staining. Levels of bone osteoblastogenesis, apoptosis and proliferative markers were evaluated by Realtime PCR, Western blotting, immunofluorescence and immunohistochemistry.

Results: MPLA treatment was able to ameliorate the increased in FBG levels in estrogen deficient, diabetic rats. In these rats, decreased bone collagen content, expression level of osteoblastogenesis markers (Wnt3a, β-catenin, Frizzled, Dvl and LRP-5) and proliferative markers (PCNA and c-Myc) and increased expression of anti-osteoblastogenesis marker (Gsk-3β) and apoptosis markers (Caspase-3, Caspase-9 and Bax) but not Bcl-2 were ameliorated. Effects of 100 mg/kg/day MPLA were greater than estrogen.

Conclusion: MPLA was able to protect against bone loss, thus making it a promising agent for the treatment of osteoporosis in women with estrogen deficient, diabetic condition.