Coffee consumption affects kidney function based on GCKR polymorphism in a Korean population.

Kidney function can be preserved through pharmacological interventions and nonpharmacological strategies, such as lifestyle and dietary adjustments. Among these, coffee has been linked to protective effects on kidney function. However, few studies have investigated the effect of coffee consumption on kidney function according to specific genes. We hypothesized that the impact of coffee consumption on kidney function might vary depending on GCKR polymorphism. GCKR rs1260326 polymorphism was examined using the Korean genome and epidemiology data from 656 chronic kidney disease (CKD) cases and 38,540 individuals without CKD (non-CKD). GCKR polymorphism has been previously associated with both coffee consumption and kidney function in Europeans. We replicated the associations between GCKR rs1260326 and coffee consumption and kidney function in Korean individuals. We also explored the effect of coffee consumption on kidney function by multivariate logistic regression analysis. Individuals with the rs1260326 (TC/CC) genotype did not experience significant changes in CKD risk based on their coffee consumption habits. In contrast, individuals with the TT genotype exhibited a significantly lower risk of CKD based on coffee consumption. Interestingly, in the non-CKD group, a beneficial effect on estimated glomerular filtration rate was observed in individuals with the T allele as coffee consumption increased. Our findings supported the hypothesis and revealed that the impact of coffee consumption habits on kidney function may vary based on the GCKR rs1260326 genotype of Korean individuals.

Osteoprotective Effects of Loganic Acid on Osteoblastic and Osteoclastic Cells and Osteoporosis-Induced Mice.

Osteoporosis is a common disease caused by an imbalance of processes between bone resorption by osteoclasts and bone formation by osteoblasts in postmenopausal women. The roots of Gentiana lutea L. (GL) are reported to have beneficial effects on various human diseases related to liver functions and gastrointestinal motility, as well as on arthritis. Here, we fractionated and isolated bioactive constituent(s) responsible for anti-osteoporotic effects of GL root extract. A single phytochemical compound, loganic acid, was identified as a candidate osteoprotective agent. Its anti-osteoporotic effects were examined in vitro and in vivo. Treatment with loganic acid significantly increased osteoblastic differentiation in preosteoblast MC3T3-E1 cells by promoting alkaline phosphatase activity and increasing mRNA expression levels of bone metabolic markers such as Alpl, Bglap, and Sp7. However, loganic acid inhibited osteoclast differentiation of primary-cultured monocytes derived from mouse bone marrow. For in vivo experiments, the effect of loganic acid on ovariectomized (OVX) mice was examined for 12 weeks. Loganic acid prevented OVX-induced bone mineral density loss and improved bone structural properties in osteoporotic model mice. These results suggest that loganic acid may be a potential therapeutic candidate for treatment of osteoporosis.

Scopolin Attenuates Osteoporotic Bone Loss in Ovariectomized Mice.

Bone remodeling is a renewal process regulated by bone synthesis (osteoblasts) and bone destruction (osteoclasts). A previous study demonstrated that Lycii radicis cortex (LRC) extract inhibited ovariectomized (OVX)-induced bone loss in mice. This study investigated the anti-osteoporotic effects of bioactive constituent(s) from the LRC extract. The effective compound(s) were screened, and a single compound, scopolin, which acts as a phytoalexin, was chosen as a candidate component. Scopolin treatment enhanced alkaline phosphatase activity and increased mineralized nodule formation in MC3T3-E1 pre-osteoblastic cells. However, osteoclast differentiation in primary-cultured monocytes was reduced by treatment with scopolin. Consistently, scopolin treatment increased osteoblast differentiation in the co-culture of monocytes (osteoclasts) and MC3T3-E1 (osteoblast) cells. Scopolin treatment prevented bone mineral density loss in OVX-induced osteoporotic mice. These results suggest that scopolin could be a therapeutic bioactive constituent for the treatment and prevention of osteoporosis.

Anti-Osteoporotic Effects of the Herbal Mixture of Cornus officinalis and Achyranthes japonica In Vitro and In Vivo.

Osteoporosis is a porous bone disease caused by bone density loss, which increases the risk of fractures. Cornus officinalis (CO) and Achyranthes japonica (AJ) have been used as traditional herbal medicine for various disorders in East Asia. Although the anti-osteoporotic effects of single extract of CO and AJ have already been reported, the synergistic effect of a combined mixture has not been studied. In this study, we investigated the effects of a CO and AJ herbal mixture on osteoporosis in in vitro and in vivo models. The results demonstrate that treatment with the CO and AJ mixture significantly promoted osteoblast differentiation of MC3T3-E1 mouse preosteoblasts through the upregulation of osteoblastic differentiation-associated genes such as alkaline phosphatase (Alpl), runt-related transcription factor 2 (Runx2), and bone gamma-carboxyglutamic acid-containing protein (Bglap), while the mixture significantly inhibited differentiation of osteoclasts isolated from primary-cultured mouse monocytes. In addition, oral administration of CO and AJ mixture significantly prevented bone mineral density loss and trabecular bone structures in an ovariectomy-induced osteoporotic mouse model. These results suggest that the combination treatment of CO and AJ mixture might be a beneficial therapy for osteoporosis.

Identifying Interactions between Dietary Sodium, Potassium, Sodium-Potassium Ratios, and FGF5 rs16998073 Variants and Their Associated Risk for Hypertension in Korean Adults.

Hypertension is affected by both genetic and dietary factors. This study aimed to examine the interaction between dietary sodium/potassium intake, sodium-potassium ratios, and FGF5 rs16998073 and link these with increased risk for developing hypertension. Using data from the Health Examinee (HEXA) Study of the Korean Genome and Epidemiologic Study (KoGES), we were able to identify a total of 17,736 middle-aged Korean adults who could be included in our genome-wide association study (GWAS) to confirm any associations between hypertension and the FGF5 rs16998073 variant. GWAS analysis revealed that the FGF5 rs16698073 variant demonstrated the strongest association with hypertension in this population. Multivariable logistic regression was used to examine the relationship between dietary intake of sodium, potassium, and sodium-potassium ratios and the FGF5 rs16998073 genotypes (AA, AT, TT) and any increased risk of hypertension. Carriers with at least one minor T allele for FGF5 rs16998073 were shown to be at significantly higher risk for developing hypertension. Male TT carriers with a daily sodium intake ≥2000 mg also demonstrated an increased risk for developing hypertension compared to the male AA carriers with daily sodium intake <2000 mg (adjusted odds ratio (AOR) = 2.41, 95% confidence intervals (CIs) = 1.84-3.15, p-interaction < 0.0001). Female AA carriers with a daily potassium intake ≥3500 mg showed a reduced risk for hypertension when compared to female AA carriers with a daily potassium intake <3500 mg (AOR = 0.75. 95% CIs = 0.58-0.95, p-interaction < 0.0001). Male TT carriers in the mid-tertile for sodium-potassium ratio values showed the highest odds ratio for hypertension when compared to male AA carriers in the lowest-tertile for sodium-potassium ratio values (AOR = 3.03, 95% CIs = 2.14-4.29, p-interaction < 0.0001). This study confirmed that FGF5 rs16998073 variants do place their carriers (men and women) at increased risk for developing hypertension. In addition, we showed that high daily intake of sodium exerted a synergistic effect for hypertension when combined with FGF5 rs16998073 variants in both genders and that dietary sodium, potassium, and sodium-potassium ratios all interact with FGF5 rs16998073 and alter the risk of developing hypertension in carriers of either gender among Koreans.

Anti-Osteoporotic Effects of Kukoamine B Isolated from Lycii Radicis Cortex Extract on Osteoblast and Osteoclast Cells and Ovariectomized Osteoporosis Model Mice.

Osteoporosis is an abnormal bone remodeling condition characterized by decreased bone density, which leads to high risks of fracture. Previous study has demonstrated that Lycii Radicis Cortex (LRC) extract inhibits bone loss in ovariectomized (OVX) mice by enhancing osteoblast differentiation. A bioactive compound, kukoamine B (KB), was identified from fractionation of an LRC extract as a candidate component responsible for an anti-osteoporotic effect. This study investigated the anti-osteoporotic effects of KB using in vitro and in vivo osteoporosis models. KB treatment significantly increased the osteoblastic differentiation and mineralized nodule formation of osteoblastic MC3T3-E1 cells, while it significantly decreased the osteoclast differentiation of primary-cultured monocytes derived from mouse bone marrow. The effects of KB on osteoblastic and osteoclastic differentiations under more physiological conditions were also examined. In the co-culture of MC3T3-E1 cells and monocytes, KB promoted osteoblast differentiation but did not affect osteoclast differentiation. In vivo experiments revealed that KB significantly inhibited OVX-induced bone mineral density loss and restored the impaired bone structural properties in osteoporosis model mice. These results suggest that KB may be a potential therapeutic candidate for the treatment of osteoporosis.

Effects of Dihydrophaseic Acid 3'-O-ß-d-Glucopyranoside Isolated from Lycii radicis Cortex on Osteoblast Differentiation.

Our previous study showed that ethanol extract of Lyciiradicis cortex (LRC) prevented the loss of bone mineral density in ovariectomized mice by promoting the differentiation of osteoblast linage cells. Here, we performed fractionation and isolation of the bioactive compound(s) responsible for the bone formation-enhancing effect of LRC extract. A known sesquiterpene glucoside, (1'R,3'S,5'R,8'S,2Z,4E)-dihydrophaseic acid 3'-O-ß-d-glucopyranoside (abbreviated as DPA3G), was isolated from LRC extract and identified as a candidate constituent. We investigated the effects of DPA3G on osteoblast and osteoclast differentiation, which play fundamental roles in bone formation and bone resorption, respectively, during bone remodeling. The DPA3G fraction treatment in mesenchymal stem cell line C3H10T1/2 and preosteoblast cell line MC3T3-E1 significantly enhanced cell proliferation and alkaline phosphatase activity in both cell lines compared to the untreated control cells. Furthermore, DPA3G significantly increased mineralized nodule formation and the mRNA expression of osteoblastogenesis markers, Alpl, Runx2, and Bglap, in MC3T3-E1 cells. The DPA3G treatment, however, did not influence osteoclast differentiation in primary-cultured monocytes of mouse bone marrow. Because osteoblastic and osteoclastic precursor cells coexist in vivo, we tested the DPA3G effects under the co-culture condition of MC3T3-E1 cells and monocytes. Remarkably, DPA3G enhanced not only osteoblast differentiation of MC3T3-El cells but also osteoclast differentiation of monocytes, indicating that DPA3G plays a role in the maintenance of the normal bone remodeling balance. Our results suggest that DPA3G may be a good candidate for the treatment of osteoporosis.

The effect of Lycii Radicis Cortex extract on bone formation in vitro and in vivo.

Osteoporosis is a common skeletal disease caused by decreased bone mass; it enhances the risk of bone fracture. This study aimed to discover novel herbal extract(s) for the treatment of osteoporosis. We screened 64 ethanol extracts of edible plants native to Korea for their ability to increase the cellular proliferation and differentiation of two osteoblastic cell lines: C3H10T1/2 and MC3T3-E1. We selected a Lycii Radicis Cortex (LRC), Lycium Chinese root bark as the primary candidate. Treatment with LRC extract showed enhanced alkaline phosphatase activity and increased expression of bone metabolic markers Alpl, Runx2, and Bglap genes in both osteoblastic cell lines. There was no effect on the osteoclastic differentiation of primary-cultured monocytes from the mouse bone marrows. Furthermore, the study examined the effect of LRC extract in vivo in ovariectomizd (OVX) mice for 8 weeks and 16 weeks, respectively. Bone mineral density (BMD) was significantly higher in LRC extract-administered group than in the non-LRC-administered OVX control group. The results indicated that LRC extract prevented the OVX-induced BMD loss in mice via promoting the differentiation of osteoblast linage cells. These results suggest that LRC extract may be a good natural herbal medicine candidate for the treatment of osteoporosis.