Eucommia ulmoides leaf extract alters gut microbiota composition, enhances short‐chain fatty acids production, and ameliorates osteoporosis in the senescence‐accelerated mouse P6 (SAMP6) model

Abstract

The bark and the leaf of Eucommia ulmoides Oliv. content similar bioactive components, but the leaf of this medically important plant is mostly abandoned. In this study, we revealed that the aqueous extract of E. ulmoides leaf (EUL) can promote the growth of the probiotic Lactobacillus bulgaricus (LB) and inhibit the formation of osteoclast in vitro. This extract was next administrated to senescence‐accelerated mice P6 to evaluate examine its influence on the composition of gut microbiota (GM), short‐chain fatty acids (SCFAs), and osteoporosis (OP). The results showed that supplementation of the EUL aqueous extract to the mouse model: (a) increased bacterial diversity and Firmicutes/Bacteroidetes ratio in the gut, (b) increased SCFAs concentration in the feces and serum, and (c) ameliorated OP based on the results of bone mineral density (BMD), Dual‐energy X‐ray bone scan, and HE staining of distal femur.

Gut microbiome, parathyroid hormone, and bone

“…Probiotic dietary supplements improve bone health in osteoporotic patients [18,59]. The pro-biotic lactobacillus [16], kefir-fermented peptides (bioactive peptides produced from dairy milk proteins) [60], Dmannose and lactulose [61,62], and the medicinal herbs Daphnetin, Puerarin, Eucommia ulmoides leaf abstact, and Arecanut [62][63][64][65] have all been shown to increase cortical bone volume and trabecular bone microarchitecture by increasing fecal abundance of SCFA-producing Bacteroidetes, Firmicutes, and Proteobacteria, decreasing gut dysbiosis, increasing Tregs, and down-regulating osteoclastogenesis-related cytokines in mice with estrogendeficient and steroid-induced osteoporosis. How these agents might affect bone architecture and PTH sensitivity in CKD remains unknown and these knowledge gaps beg many questions, beginning with:…”

Traditional Chinese Medicine as a Promising Strategy for the Treatment of Alzheimer’s Disease Complicated With Osteoporosis

“…The leaves and seeds of EU may also be of potential benefit for the treatment of osteoporosis. In a combined estrogen deficiency-induced osteoporosis and obesity rodent model, EU leaf extract decreased rats’ body weight and body mass index (BMI) and increased the BMD and bone strength, which appeared to be beneficial for improving bone metabolism and restoring bone loss ( Zhao et al, 2020 ).…”

Traditional application and modern pharmacological research of Eucommia ulmoides Oliv.

“…Eucommia ulmoides has been unveiled to possess therapeutic effects on hypoestrogenemia after menopause result in osteoporosis, disuse-induced osteoporosis, senescence caused osteoporosis and lead affect bone composition and mineralization result in osteoporosis, and these therapeutic effects on osteoporotic models have been verified in ovariectomy (OVX) rats, hind limb suspension (HLS) rats, senescence-accelerated mice and lead acetate-induced bone loss rats. Mechanistic studies have revealed its anti-osteoporotic activities were referring to the modulation of the OPG/RANKL system in osteoblastic cells [ 22 – 27 ].…”

“…Another study has also demonstrated that ethanol extract (30 and 100 mg/kg) of the cortex administration into adolescent female rats increased longitudinal bone growth rate and growth plate height, characterized by increasing BMP-2 and IGF-1 expressions in the proliferative and hypertrophic zones [ 31 ]. Ethanol extract (495 and 990 mg/kg) of the leaf has also shown anti-osteoporotic effects in senescence-accelerated mice P6 [ 27 ]. In lead acetate-induced bone loss rats, ethanol extract (100 mg/kg) of the cortex has been demonstrated in vivo trails to be anti-osteoporosis and increased OPG expression and OPG/RANKL ratio, which were in line with the mentioned above in vitro study.…”