Effects of kidney tonic herbs for primary osteoporosis: A systematic review and meta-analysis.

BACKGROUND: Primary osteoporosis (POP) is one of the most common orthopedic conditions with a high risk of fractures. Effective treatment of POP is crucial for reducing disability rates and improving quality of life. Kidney tonic therapy is a classical traditional Chinese medicine approach for treating POP. This study aims to provide a comprehensive and reliable assessment of the clinical evidence of kidney tonic herbs (KTH) in treating POP patients. METHODS: An extensive literature search was conducted in 8 electronic databases from their inception through September 30, 2022, to evaluate the efficacy and safety of KTH for POP. We included 43 randomized controlled trials with 4349 participants. The qualified studies will be chosen and evaluated separately by 2 researchers. The primary outcome measure was bone mineral density (BMD) of lumbar. RevMan 5.3 and Stata 16 were used to carry out the meta-analyses. RESULTS: Our meta-analysis showed 29 studies with significantly increased lumbar BMD (mean difference [MD] = 0.06; 95% confidence interval [CI]; I2 = 98%, P = .003), 18 studies with noticeably higher femoral neck BMD (MD = 0.08; 95% CI; I2 = 98%, P = .0005), 6 studies with significantly increased femoral trochanter BMD (MD = 0.10; 95% CI; I2 = 97%, P = .002), 4 studies with noticeably higher ward's triangle BMD (MD = 0.13; 95% CI; I2 = 100%, P = .04), and 3 studies with noticeably higher distal radius BMD (MD = 0.06; 95% CI; I2 = 86%, P = .009). One study showed 12 falls and 8 fallers in the intervention group, 28 falls and 17 fallers in the control group at 36 months. 3 studies showed a significant difference in fracture incidence between the intervention group and the control group (95% CI: 0.15-0.81; I2 = 0%, P = .01). Additionally, the meta-analysis demonstrated that KTH offered superior pain relief (8 trials, n = 980; 95% CI: -1.05 to -0.74; I2 = 94%, P < .00001). Besides, KTH found no serious harmful effects. DISCUSSION: KTH may increase BMD and decrease the likelihood of fractures in POP patients. However, further research is necessary to investigate the effectiveness of KTH in reducing falls and fractures.

Exploratory study of sea buckthorn enhancing QiangGuYin efficacy by inhibiting CKIP-1 and Notum activating the Wnt/ß-catenin signaling pathway and analysis of active ingredients by molecular docking.

Background: Sea buckthorn (SBT) is a traditional Chinese medicine (TCM), rich in calcium, phosphorus, and vitamins, which can potentially prevent and treat osteoporosis. However, no research has been conducted to confirm these hypotheses. QiangGuYin (QGY) is a TCM compound used to treat osteoporosis. There is a need to investigate whether SBT enhances QGY efficacy. Objectives: The aim of this study was to explore whether SBT enhances QGY efficacy by inhibiting CKIP-1 and Notum expression through the Wnt/ß-catenin pathway. The study also aimed to explore the active components of SBT. Methods: Experimental animals were divided into control, model, QGY, SBT, SBT + Eucommia ulmoides (EU), and SBT + QGY groups. After treatment, bone morphometric parameters, such as estrogen, PINP, and S-CTX levels, and Notum, CKIP-1, and ß-catenin expression were examined. Screening of SBT active components was conducted by molecular docking to obtain small molecules that bind Notum and CKIP-1. Results: The results showed that all the drug groups could elevate the estrogen, PINP, and S-CTX levels, improve femoral bone morphometric parameters, inhibit Notum and CKIP-1 expression, and promote ß-catenin expression. The effect of SBT + EU and SBT + QGY was superior to the others. Molecular docking identified that SBT contains seven small molecules (folic acid, rhein, quercetin, kaempferol, mandenol, isorhamnetin, and ent-epicatechin) with potential effects on CKIP-1 and Notum. Conclusion: SBT improves bone morphometric performance in PMOP rats by inhibiting CKIP-1 and Notum expression, increasing estrogen levels, and activating the Wnt/ß-catenin signaling pathway. Furthermore, SBT enhances the properties of QGY. Folic acid, rhein, quercetin, kaempferol, mandenol, isorhamnetin, and ent-epicatechin are the most likely active ingredients of SBT. These results provide insight into the pharmacological mechanisms of SBT in treating osteoporosis.

[Mechanism action of Chinese herbal compound and target network pharmacology of Yougui (YG) pill for the treatment of osteoporosis].

OBJECTIVE: To explore compounds, targets and mechanism of Yougui (YG) pill in treating osteoporosis based on systemic pharmacology of traditional Chinese medicine. METHODS: The known effective Chinese herbal compound of YG pill was searched from traditional Chinese medicine integrated database(TCMID). Bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine (BATMAN-TCM) was used to predict target of components;DisGeNET and artificial literature reading were used to obtain targets of osteoporosis and bone remodeling;Cytoscape 3.7.1 software and its plug-ins BiN-GO and ClueGO were used to enrich the GO annotation and pathwaysof the related targets, and validation of the predicted target of YG pill were validated by 87 differentially expressed proteins in postmenopausal osteoporosis and postmenopausal osteoporosis disease models in postmenopausal patients with normal bone mass from the previous serum proteomics data. RESULTS: Totally 392 compounds were retrieved from YG pill, including 83 sovereign drugs (monkshood, cinnamon, deerhorn gelatin), 127 ministerial drugs (prepared rehmannia root, dogwood, wolfberry fruit and Chinese yam) and 182 supplementary drugs (cuscuta chinensis, eucommia ulmoides and Chinese angelica). Among them, there were 4 same compounds between sovereign drug and ministerial drug, 1 same compound between sovereign drug and supplementary drug, and 14 same compounds between ministerial drug and supplementary drug. Totally 2 112 trusted targets were identified, included 775 sovereign drugs, 1 483 ministerial drugs and 1 491 supplementary drugs;227 targets were selected from YG pill for treating osteoporosis, which participate in nearly 20 process of metabolic process, cell differentiation and biology, and data mining revealed that the process involved bone remodeling and bone mineralization. Acting site of cell mainly inclded 9 kinds of cell which had 13 molecular function. Results of KEGG metabolic pathway enrichment analysis showed 137 signal passages were obviously enriched. Among them, classical osteoclast differentiation signal passages and relative estrogen regulates signaling pathways of menopause were widely distributed in 27 signal passages. Sixtargets were screened by target validation, such as AGT, FGA, APOE, DKK3, P4HB and RAB7A. CONCLUSION: The characteristics of multi-targets and multi-pathways of YG pill for the treatment of osteoporosis were clarified, which provided a clear direction for the in-depth research. The pharmacodynamic components of YG pill include 36 compounds, and their main action targets include FGA, AGT, APOE, DKK3, P4HB and RAB7A.

Berbamine suppresses cell proliferation and promotes apoptosis in ovarian cancer partially via the inhibition of Wnt/ß-catenin signaling.

Ovarian cancer is a common and lethal cancer affecting women globally. Berbamine is a natural compound from the plant Berberis amurensis, which is used in Chinese traditional medicine. Recent studies have shown the anti-tumor effects of berbamine in several types of cancers but not in ovarian cancer. In the present study, we investigated the potential anti-tumor effects of berbamine in ovarian cancer and explored the underlying molecular mechanisms. Berbamine suppressed the cell viability of ovarian cancer cells in a concentration-dependent manner as revealed by methyl thiazolyl tetrazolium assay. Berbamine also suppressed the cell growth and invasion of ovarian cancer cells as measured by colony formation and cell invasion assays, respectively. Flow cytometry experiments showed that berbamine increased cell apoptotic rate and induced cell cycle arrest at G0/G1 phase in ovarian cancer cells. Western blot analysis showed that berbamine increased the protein levels of cleaved caspase-3, cleaved caspase-9, Bax, and decreased the protein level of Bcl-2 in ovarian cancer cells. Quantitative real-time PCR and western blot analysis demonstrated that berbamine treatment inhibited the Wnt/ß-catenin signaling in ovarian cancer cells. The inhibitory effects of berbamine on cell viability and invasion of ovarian cancer cells can be partially reversed by lithium chloride (LiCl) treatment. Growth of tumors developed from SKOV3 cells was significantly suppressed in berbamine-treated group, and berbamine treatment enhanced caspase-3 and -9 cleavage and reduced ß-catenin protein level in tumor tissues. In summary, berbamine exerts its anti-cancer effects in vitro and in vivo via induction of apoptosis, partially associated with the inhibition of Wnt/ß-catenin signaling.

Beneficial effects of dietary soluble fiber supplementation in replacement gilts: Pubertal onset and subsequent performance.

The aim of this study was to examine the effects of soluble fiber supplementation prior to puberty on age at puberty and subsequent reproductive performance of gilts. A total of 136 gilts of similar body weight (BW, 60.59±7.02kg) and age (140±10 days) were fed a control diet (CON) or control diet supplemented with 0.8% soluble fiber (SF) until mating at the third estrus. Circulating concentrations of cholesterol, triglyceride, and estradiol in gilts fed the SF diet were lower than in CON gilts at 205d of age. Compared with CON-fed gilts, the SF-fed gilts attained observed puberty 15.6d earlier (P<0.05), at a 12.2kg lower body weight, and a 0.84mm lower backfat thickness at the P2 point (P<0.05). The total number of piglets born, the number born alive, and average birthweight, were not affected by diet (P>0.05). However, the incidence of intrauterine growth restriction (IUGR) was lower for SF gilts (4.62%) than for CON gilts (11.3%) (P<0.05). There was also a greater intra-litter uniformity (P<0.05) and a tendency for a higher number of piglets born in the SF gilts compared with the CON gilts (P=0.07). In summary, prepubescent dietary soluble fiber supplementation can reduce the age at puberty in gilts and increase their subsequent reproductive performance as sows.

Chinese Herbal Medicine for Osteoporosis: A Meta-analysis of Randomized Controlled Trials.

Osteoporosis is a major public health problem in the elderly population. Several studies have suggested that Chinese herbal medicine has antiosteoporotic activities that might be beneficial for osteoporosis. This study aimed to assess the effectiveness of Chinese herbal medicine in osteoporosis patients. We comprehensively searched for randomized controlled trials (until December 2016) that compared Chinese herbal medicine with Western medicine in adults with osteoporosis and reported bone mineral densities (BMDs). A total of 10 randomized controlled trials were included. The pooled results suggested that the increased spine BMD was lower but not significant in the Chinese herbal medicine group than in the Western drug group (standard mean difference [SMD] = -0.11, 95% confidence interval [CI]: -0.62 to 0.39, p > 0.05). In the subgroup analysis, in postmenopausal women, Chinese herbal medicine also showed a insignificantly higher increment in BMD than the control group (SMD = 0.22, 95% CI: -0.00 to 0.43, p = 0.05). For different treatment durations, subgroups over 6 mo (SMD = 0.09, 95% CI: -0.24 to 0.41, p > 0.05) and less than 6 mo (SMD = -0.25, 95% CI: -1.14 to 0.64, p > 0.05) showed comparable BMDs between the 2 therapies. Our study demonstrated that Chinese herbal medicine alone did not significantly increase lumbar spine BMD. Further studies with better adherence to the intervention are needed to confirm the results of this meta-analysis.

Effect of Traditional Chinese Medicine Product, QiangGuYin, on Bone Mineral Density and Bone Turnover in Chinese Postmenopausal Osteoporosis.

Introduction. The aim of this study was to investigate the efficacy of herbal formula QiangGuYin (QGY) in postmenopausal women. Materials and Methods. A total of 240 participants from six clinical centers were randomly to receive alendronate 70 mg/week, QGY granules 20 g/day, and placebo. Primary end points were BMD changes over 6 and 12 months; secondary end points were bone turnover markers changes at 3, 6, 9, and 12 months. Safety was monitored by clinical adverse events reported during the follow-up. Results. Of 240 women recruited, 218 completed the study. Significant BMD increases from baseline were observed over 6 and 12 months at each observed part both in QGY and alendronate compared with placebo (p < 0.01). Alendronate-treated subjects had significant decreases in ß-CTX compared to QGY-treated subjects at each time point assessed (p < 0.01). Reduction in t-P1NP was only observed in the QGY group at 3 and 6 months (-23.81% and -3.07%, resp.). No significant difference was observed in the overall incidence of clinical adverse events among the alendronate group and the QGY group (5.0% versus 7.5%, p = 0.513). Conclusion. 1-Year treatment with QGY demonstrated a safe statistical increase in BMD and new balance may be rebuilt after 9 months. This trail is registered with ChiCTR-POC-16008026.

Identification of human serum protein targets of Qianggu Decoction () in primary type I osteoporosis based on tandem mass tag labeling and liquid chromatography-tandem mass spectrometry technology.

OBJECTIVE: To investigate the serum protein targets of Qianggu Decoction (, QGD) on treating osteoporosis by the proteomics analysis using tandem mass tag (TMT) and liquid chromatographytandem mass spectrometry (LC-MS/MS). METHODS: Twenty serum protein samples were recruited (10 patients with primary type I osteoporosis before and after QGD treatment) and the high abundance ratios protein was removed, two serum samples were extracted and labeled with TMT reagent. Then, mass spectrometric detection, identification of differentially expressed proteins and bioinformatics analysis of differentially expressed proteins were carried out. RESULTS: A total of 60 proteins were identified, within a 99% confidence interval, to be differentially regulated of which, 34 proteins were up-regulated and 26 proteins were down-regulated. Differentially expressed proteins analyzed by Gene Ontology (GO) annotation mainly get involved in 12 different biological processes, 7 types of cellular components, and 6 kinds of molecular functions. Angiotensinogen (AGT), stromelysin-1 (MMP3), heparanase (HPSE) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were screened as candidate protein targets of QGD treatment, which were related to metabolic mechanism of bone remodeling and/or bone collagen of osteoporosis. By the utilization of the protein-protein interaction network analysis tool named STRING10.0, it showed that AGT, MMP3, HPSE and GAPDH were located in the key node of the protein-protein interactions network. Furthermore, AGT, MMP3, HPSE and GAPDH were found to be directly related to BMP, MAPK, Wnt, SMAD and tumor necrosis factor ligand superfamily member 11 (TNFSF11) families. CONCLUSIONS: The proteomics analysis by using TMT combined with LC-MS/MS was a feasible method for screening the potential therapeutic targets associated with QGD treatment. It suggests that AGT, MMP3, HPSE and GAPDH may be candidate protein targets of QGD treatment which can be used as therapeutic effect monitor and early diagnosis of primary type I osteoporosis.

Effects of electroacupuncture at GB points on markers of osteoporosis and bodyweight in ovariectomised rats.

BACKGROUND: Based on a description of acupuncture to treat a bone disease resembling osteoporosis in the ancient text of Huangdi Neijing, we aimed to assess the effects of electroacupuncture (EA) at GB points in ovariectomised (OVX) rats. METHODS: 40 female Wistar rats were randomly divided into four groups (n=10 each): ovariectomised model group (OVX); ovariectomised group treated with EA at GB points (OVX+GB); ovariectomised group treated with EA at non-GB points (OVX+N) in the hindlimb; and a sham surgery group (Sham). Three months after ovariectomy, rats in the OVX+GB and OVX+N groups received EA treatment for 3 months. Urine, blood and femur samples were collected from each animal for analysis. RESULTS: Bodyweight (BW) in the OVX+GB group decreased after EA treatment, reaching a minimum of ∼12% below the OVX and OVX+N groups at 1 month. Concentrations of urine deoxypyridinoline, a bone resorption marker, were significantly elevated in the OVX and OVX+N groups but not the OVX+GB group. Concentrations of serum bone specific alkaline phosphatase, a bone formation marker, were significantly higher in the OVX+GB group versus the Sham and OVX groups. Bone mineral density (BMD) did not differ between the OVX, OVX+GB and OVX+N groups, but was ∼10% lower than the Sham group. However, BMD/BW in the OVX+GB group was significantly higher than in the OVX and OVX+N groups and similar to the Sham group. Histological assessment of the femur showed that EA at GB points improved the bone architecture. CONCLUSIONS: EA treatment at GB points had anti-osteoporotic effects in a rat model of osteoporosis.

Interventional value of total flavonoids from Rhizoma Drynariae on Cathepsin K, a potential target of osteoporosis.

Osteoporosis, the sixth most common disease in the world, is bringing increasingly serious harm to people's health. Cathepsin K, which plays an important role in bone resorption, is a potential target in the treatment of osteoporosis. Total flavonoids, the active ingredients in Rhizoma Drynariae, have shown obvious, therapeutic effect on osteoporosis. In previous studies, it was presumed that the mechanism for the therapeutic effect was through inhibiting the expression of Cathepsin K. However, there are still no detailed reports on some key issues such as the specific inhibitory results of total flavonoids on Cathepsin K and the pathway of inhibition and so on. Based on previous studies on total flavonoids from Rhizoma Drynariae, the pathway for the effect of, total flavonoids inhibiting Cathepsin K and their interventional value on Cathepsin K were analyzed in this paper, so as to explore the interventional feasibility and value of total flavonoids in Rhizoma Drynariae on Cathepsin K.

[Effect of qianggu drink ([Chinese characters: see text]) on bone histomorphometry of lumbar vertebrae in ovariectomized rats].

OBJECTIVE: To observe the effect of Chinese herbal medicine Qianggu drink ([Chinese characters: see text]) on bone histomorphometry of lumbar vertebrae in ovariectomized rats and to explore its mechanism. METHODS: Sixty female SD rats (weight 230 to 280 gram) were randomized into three groups: Qianggu drink ([Chinese characters: see text]) group (treatment group), Miacalcic group (control group) and blank group. The osteoporosis model was established successfully after all rats were ovariectomized for 10 weeks. The treatment group was used intragastric infusion with Qianggu drink ([Chinese characters: see text]) 0.001 ml/kg once a day. The control group was used hypodermic injection once a day with Miacalcic 0.72 U/kg. Five rats were killed respectively and the lumbar specimens were taken and cut for bone histomorphometric analysis at 45, 90, 135 and 180 days after the treatment. RESULTS: The thickness of trabecular bone in treatment group had the statistical significance with control group at 135 days after ovariectomized rats were given the medicine. The data of BV/TV and the thickness and space of trabecular bone had statistical significance compared with control group and blank group 180 days later. CONCLUSION: Qianggu drink ([Chinese characters: see text]) could effectively improve the histomorphometry indexes. The mechanism probably plays by stimulating osteogenesis and inhibiting the cytoactive of osteoclast and the trend of bone transform.