Regulatory Effects of Quercetin on Bone Homeostasis: Research Updates and Future Perspectives.

The imbalance of bone homeostasis has become a major public medical problem amid the background of an aging population, which is closely related to the occurrence of osteoporosis, osteoarthritis, and fractures. Presently, most drugs used in the clinical treatment of bone homeostasis imbalance are bisphosphonates, calcitonin, estrogen receptor modulators, and biological agents that inhibit bone resorption or parathyroid hormone analogs that promote bone formation. However, there are many adverse reactions. Therefore, it is necessary to explore potential drugs. Quercetin, as a flavonol compound with various biological activities, is widely distributed in plants. Studies have found that quercetin can regulate bone homeostasis through multiple pathways and targets. An in-depth exploration of the pharmacological mechanism of quercetin is of great significance for the development of new drugs. This review discusses the therapeutic mechanisms of quercetin on bone homeostasis, such as regulating the expression of long non-coding RNA, signaling pathways of bone metabolism, various types of programmed cell death, bone nutrients supply pathways, anti-oxidative stress, anti-inflammation, and activation of Sirtuins. We also summarize recent progress in improving quercetin bioavailability and propose some issues worth paying attention to, which may help guide future research efforts.

HPF Modulates the Differentiation of BMSCs into HLCs and Promotes the Recovery of Acute Liver Injury in Mice.

Bone marrow-derived mesenchymal stem cells (BMSCs) can differentiate into hepatocyte-like cells (HLCs) to alleviate acute liver injury (ALI). Herpetfluorenone (HPF), as an active ingredient in the dried, mature seeds Herpetospermum caudigerum Wall, used in Tibetan medicine, has been proven to effectively alleviate ALI. Therefore, the purpose of this study was to determine whether HPF can promote the differentiation of BMSCs into HLCs and promote ALI recovery. Mouse BMSCs were isolated, and the BMSCs' differentiation into HLCs was induced by HPF and hepatocyte growth factor (HGF). Under the induction of HPF and HGF, the expression of hepatocellular specific markers and the accumulation of glycogen and lipids in the BMSCs increased, indicating that BMSCs successfully differentiated into HLCs. Then, the ALI mouse model was established, using carbon tetrachloride, followed by an intravenous injection of BMSCs. Then, only HPF was injected intraperitoneally, in order to verify the effect of HPF in vivo. In vivo imaging was used to detect the homing ability of HPF-BMSCs, and it was detected that HPF-BMSCs significantly increased the levels of serum AST, ALT and ALP in the liver of ALI mice, and alleviated liver cell necrosis, oxidative stress and liver pathology. In conclusion, HPF can promote the differentiation of BMSCs into HLCs and promote the recovery of ALI in mice.

Biosynthesis and Metabolism of Garlic Odor Compounds in Cultivated Chinese Chives (Allium tuberosum) and Wild Chinese Chives (Allium hookeri).

Chinese chives is a popular herb vegetable and medicine in Asian countries. Southwest China is one of the centers of origin, and the mountainous areas in this region are rich in wild germplasm. In this study, we collected four samples of germplasm from different altitudes: a land race of cultivated Chinese chives (Allium tuberosum), wide-leaf chives and extra-wide-leaf chives (Allium hookeri), and ovoid-leaf chives (Allium funckiaefolium). Leaf metabolites were detected and compared between A. tuberosum and A. hookeri. A total of 158 differentially accumulated metabolites (DAM) were identified by Gas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography-Mass Spectrometry (LC-MS), among which there was a wide range of garlic odor compounds, free amino acids, and sugars. A. hookeri contains a higher content of fructose, garlic odor compounds, and amino acids than A. tuberosum, which is supported by the higher expression level of biosynthetic genes revealed by transcriptome analysis. A. hookeri accumulates the same garlic odor compound precursors that A. tuberosum does (mainly methiin and alliin). We isolated full-length gene sequences of phytochelatin synthase (PCS), γ-glutamyltranspeptidases (GGT), flavin-containing monooxygenase (FMO), and alliinase (ALN). These sequences showed closer relations in phylogenetic analysis between A. hookeri and A. tuberosum (with sequence identities ranging from 86% to 90%) than with Allium cepa or Allium sativum (which had a lower sequence identity ranging from 76% to 88%). Among these assayed genes, ALN, the critical gene controlling the conversion of odorless precursors into odor compounds, was undetected in leaves, bulbs, and roots of A. tuberosum, which could account for its weaker garlic smell. Moreover, we identified a distinct FMO1 gene in extra-wide-leaf A. hookeri that is due to a CDS-deletion and frameshift mutation. These results above reveal the molecular and metabolomic basis of impressive strong odor in wild Chinese chives.

[Ershiwuwei Shanhu Pills regulate Akt/mTOR/GSK-3ß signaling pathway to alleviate Alzheimer's disease mice].

The present study investigated the mechanism of the Tibetan patent medicine Ershiwuwei Shanhu Pills(ESP) in alleviating Alzheimer's disease in mice via Akt/mTOR/GSK-3ß signaling pathway. BALB/c mice were randomly assigned into a blank control group, a model group, low(200 mg·kg~(-1)), medium(400 mg·kg~(-1)) and high(800 mg·kg~(-1)) dose groups of ESP, and donepezil hydrochloride group. Except the blank control group, the other groups were given 20 mg·kg~(-1) aluminum chloride by gavage and 120 mg·kg~(-1) D-galactose by intraperitoneal injection for 56 days to establish Alzheimer's disease model. Morris water maze was used to detect the learning and memory ability of mice. The level of p-tau protein in mouse hippocampus and the levels of superoxide dismutase(SOD), malondialdehyde(MDA), catalase(CAT), and total antioxidant capacity(T-AOC) in hippocampus and serum were detected. Hematoxylin-eosin staining and Nissl staining were performed for the pathological observation of whole brain in mice. TdT-mediated dUTP nick-end labeling(TUNEL) staining was employed for the observation of apoptosis in mouse cortex. Western blot was adopted to detect the protein levels of p-mTOR, p-Akt, and GSK-3ß in the hippocampus. Compared with the model group, the ESP groups showcased alleviated pathological damage of the whole brain, decreased TUNEL positive cells, reduced level of p-tau protein in hippocampus, and risen SOD, CAT, and T-AOC levels and declined MDA level in hippocampus and serum. Furthermore, the ESP groups had up-regulated protein levels of p-mTOR and p-Akt while down-regulated protein level of GSK-3ß in hippocampus. Therefore, ESP can alleviate the learning and memory decline and oxidative damage in mice with Alzheimer's disease induced by D-galactose combined with aluminum chloride, which may be related to Akt/mTOR/GSK-3ß signaling pathway.

Network Pharmacology and Molecular Docking Elucidate the Pharmacological Mechanism of the OSTEOWONDER Capsule for Treating Osteoporosis.

Background: Osteoporosis (OP) is a serious and common bone metabolic disease with bone mass loss and bone microarchitectural deterioration. The OSTEOWONDER capsule is clinically used to treat OP. However, the potential regulatory mechanism of the OSTEOWONDER capsule in treatment of OP remains largely unknown. Methods: The bioactive compounds of herbs and their targets were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. The speculative targets of OP were screened out based on GeneCards, DisGeNET, and Online Mendelian Inheritance in Man (OMIM) databases. The gene modules and hub genes of OP were identified using a weighted gene co-expression network analysis (WGCNA). Then, an herb-compound-target network was constructed based on the above analyses. The biological function of targets was subsequently investigated, and a protein-protein interaction (PPI) network was constructed to identify hub targets of OP. Finally, molecular docking was performed to explore the interaction between compounds and targets. Results: A total of 148 compounds of eight herbs and the corresponding 273 targets were identified based on the TCMSP database. A total of 4,929 targets of OP were obtained based on GeneCards, DisGeNET, and OMIM databases. In addition, six gene modules and 4,235 hub genes of OP were screened out based on WGCNA. Generally, an herb-compound-target network, including eight herbs, 84 compounds, and 58 targets, was constructed to investigate the therapeutic mechanism of the OSTEOWONDER capsule for OP. The biofunction analysis indicated 58 targets mainly associated with the bone metabolism, stimulation response, and immune response. EGFR, HIF1A, MAPK8, IL6, and PPARG were identified as the hub therapeutic targets in OP. Moreover, the interaction between EGFR, HIF1A, MAPK8, IL6, PPARG, and the corresponding compounds (quercetin and nobiletin) was analyzed using molecular docking. Conclusion: Our finding discovered the possible therapeutic mechanisms of the OSTEOWONDER capsule and supplied the potential therapeutic targets for OP.

Lycium barbarum (Wolfberry) Increases Retinal Ganglion Cell Survival and Affects both Microglia/Macrophage Polarization and Autophagy after Rat Partial Optic Nerve Transection.

The rat partial optic nerve transection (PONT) model has been used for studying secondary degeneration of retinal ganglion cells (RGCs) in recent years. In this study, we carried out PONT of the temporal side of rat optic nerves, whereas PONT was carried out of the superior side in the previous publication. We found that this surgery is better and easier than the previous method and can produce a repeatable and reliable model. We detected significant changes in the polarization of microglia/macrophages and the level of autophagy in optic nerves after PONT. We also used this model to detect the effects of the polysaccharides extracted from Lycium barbarum (LBP) on the survival of RGCs and the changes in the polarization of microglia/macrophages and the level of autophagy after PONT. We find that LBP can delay secondary degeneration of RGCs after temporal injury of optic nerves, promote the M2 polarization of microglia/macrophages, and down-regulate the level of autophagy after PONT. In conclusion, we find that the polarization of microglia/macrophages and the autophagy level change after PONT; LBP treatment delays secondary degeneration of RGCs; and the polarization of microglia/macrophages and the level of autophagy are also altered after LBP treatment.

[Cohort Study of EGFR-TKIs Combined with Traditional Chinese Medicine and Single EGFR-TKIs for Advanced NSCLC (Non₋small Cell Lung Cancer)].

OBJECTIVE: To explore the curative effect of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKIs) combined with Traditional Chinese Medicine (TCM) versus single EGFR-TKIs for Advanced non-small-cell lung cancer (NSCLC). METHODS: A total of 59 NSCLC patients with EGFR mutation were divided (2:1) into treatment group and control group. Patients in treatment group (39 cases) take EGFR-TKIs plus TCM and control group (20 cases) take EGFR-TKIs. Analysis the progression-free survival (PFS), disease control rate (DCR) and treatment-related adverse events of two groups. RESULTS: The DCR of the treatment group and control group was 94.1% and 84.2% respectively (P=0.24). In the total population, PFS was 12.1 months in treatment group and 9.1 months in control group [hazard ratio (HR) 0.46; 95%CI 0.23-0.9; P=0.025]. Among patients with exon 19 deletion (19-del), PFS between treatment group and control group was 10.5 months and 9.5 months respectively (P=0.17). For patients with exon Leu858Arg point mutation (L858R), PFS was significantly longer with treatment group than withcontrol group (median 13.2 months vs. 7.8 months; HR 0.32, 95%CI 0.10-0.97; P=0.046). Grade 3-4 treatment-related adverse events were less common withtreatment-group (8.33 %) than control group (15.00%) (P=0.65). CONCLUSION: For NSCLC patients with EGFR mutation, EGFR-TKIs combined with TCM has a certain effect to prolong PFS, especially for the patients with L858R.

Chemical properties and antioxidant activity of a water-soluble polysaccharide from Dendrobium officinale.

In this report, a water-soluble polysaccharide was obtained from the dried stems of Dendrobium officinale Kimura et Migo by hot-water (70-75°C) extraction and 85% ethanol precipitation, and successively purification by DEAE-cellulose anion-exchange chromatography and gel-permeation chromatography. The D. officinale polysaccharide (DOP) has a molecular weight of 8500Da. Monosaccharide composition analysis reveals that DOP is composed of mannose, glucose, and arabinose with a trace of galacturonic acid in a molar ratio of 6.2:2.3:2.1:0.1. Periodate oxidation-smith degradation and 1D and 2D NMR spectroscopy analysis suggest the predominance of mannose and glucose, and it contains a 2-O-acetylglucomannan and (1→4)-linked-ß-d-mannopyranosyl and (1→4)-linked-ß-d-glucopyranosyl residues. Atomic force microscope shows that DOP mainly exists as rod-shaped chains, supporting high degrees of polymerization. The antioxidant activities of the polysaccharide in vitro assay indicate that DOP has good scavenging activity of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, higher scavenging activity of hydroxyl radical, and metal chelating activities.

[Efficacy observation on Jin's three-needle therapy for allergic rhinitis of lung qi deficiency and cold syndrome].

OBJECTIVE: To compare the clinical efficacy in the treatment of allergic rhinitis (AR) of lung qi deficiency and cold syndrome between Jin's three-needle therapy and western medication. METHODS: Sixty-six patients were randomized into an acupuncture group and a western medication group, 33 cases in each one. In the acupuncture group, acupuncture was applied at three-nose points [Yingxiang (LI 20), Shangyingxiang (EX-HN 8) and Yintang (GV 29); Cuanzhu (BL 2) was added for frontal headache] and three-back points [Dazhu (BL 11), Fengmen (BL 12) and Feishu (BL 13)], once every day. Ten treatments made one session. Two sessions of treatment were required. In the western medication group, desloratadine oral suspension was prescribed, 5 mg each time, once a day, for 20 days. The scores of the symptoms and physical signs in AR patients as well as the clinical efficacy were observed between the two groups. RESULTS: The total effective rate was 93.9% (31/33) in the acupuncture group, which was better than 72.7% (24/33) in the western medication group (P < 0.05). After treatment, the scores of AR symptoms and physical signs as well as the total score were all reduced compared with those before treatment in the two groups (all P < 0.01). The score of every item in the acupuncture group was lower than that in the western medication group after treatment (score of symptoms: 4.70 +/- 2.07 vs 6.55 +/- 2. 69, score of physical signs: 0.85 +/- 0.67 vs 1.45 +/- +0.62, total score: 5.36 +/- 2.70 vs 8.00 +/- 2.91, all P < 0.01). CONCLUSION: Jin's three-needle therapy achieves superior efficacy on AR of lung-qi deficiency and cold syndrome, which is better than desloratadine oral suspension.

[Treatment of autism children: observation on efficacy of behavior training with retention of needles on head].

OBJECTIVE: To observe the effect difference of behavior training with head needling retention and behavior training after acupuncture for autism children. METHODS: Sixty qualified autism children were divided randomly into simultaneous head needling retention and behavior training group (trial group) and behavior training after acupuncture treatment group (control group) with 30 case in each group. Retention needles on the head with simultaneous behavior training was applied for the trial group. The main acupoints included Sishen Xue, Dingshen Sanxue (3 points for mental tranquilization), Nao Sanxue (3 points for the function of brain), Shou Zhisanxue (3 points for mental activities on hand) and Zozhi Sonxue (3 points for mental activities on foot). Other points were combined according to conditions of patients. Needles on the 4 extremities were withdrawn first after 30 minutes, needles on head were remained during behavior training. While behavior training was applied to the control group when acupuncture treatment was completely accomplished. Treatments were applied once a day to both groups. And 3 months was taken as one observation cycle. Estimation was made on therapeutic effect and developing level of autism children with CARS and PEP. RESULTS: The total effective rate of the trial group was 83.3% (25/30), better than 66.7% (20/30) of the control group (P < 0.05). The CARS scores of both groups declined after the treatment. And the score of trail group was lower than the control group (all P < 0.05). While the PEP scores of both groups increased, and the score of trail group was higher than the control group (all P < 0.05). The increasing level of scores of cognitive understanding and cognitive expression were all better than the control group (all P < 0.05). CONCLUSION: The effect of behavior training with head needle retention on autism children is better than behavior training after acupuncture treatment, especially in enhancing cognition understanding and cognition expression.

Two new prenylated isoflavones from Sedum aizoon L.

Investigation of a methanol extract from the Chinese endemic species Sedum aizoon L. led to the isolation of two new isoflavone derivatives that were named sedacin A and B (1 and 2). Their structures were elucidated by the basis of spectroscopic analysis. Two new isoflavone derivatives were isolated compounds were assayed for antioxidant activity.